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Sample records for excretory function induced

  1. Role of vegetative nervous system in regulation of excretory function of irradiated dog stomach

    International Nuclear Information System (INIS)

    Kostesha, N.Ya.

    1989-01-01

    Dogs and rats were exposed to γ/neutron- and X-radiation. The anterior part of dog's stomach was exposed to 10 Gy and 13 Gy respectively; rats were subjected to whole-body irradiation with absolutely lethal doses. Prior to irradiation, various parts of the vegetative nervous system of both types of animals were switched off pharmocologically. In addition to clinical investigation of radiation sickness the excretory function of the stomach was studied by the excretion of intravenously injected neutral red. The switching-off of the parasympathetic nervous system prior to irradiation stabilized the excretory processes in the stomach, increased the resistance of animals, and, vice wersa, the switching-off of the sympathetic nervous system destabilized the excetory processes and decreased the resistance of the organism

  2. Liver excretory function in patients with inflammatory diseases of the bile duct as reflected by radioimmunoassays of choleglycine

    International Nuclear Information System (INIS)

    Buyanov, V.M.; Orduyan, S.L.; Gidzev, M.Sh.; Kasimov, A.O.

    1989-01-01

    Radioimmunoassays of holeglycine in 41 healthy donors, 37 patients with gastroduodenal diseases and 41 ones with inflammatory diseases of the bile ducts have revealed that impaired excretory function of the liver is associated with a reduced coefficient of the bile acid extraction and a decreased bactericidal activity of the bile. The latter fact is conductive to active growth of microorganisms in the bile and thus promotes postoperative septic complications. Early detection of cholestasis resultant froom impaired excretory function with the use of choleglycine radioimmunoassays permits administration of early measures to restore the bile passage and of rational antibacterial therapy to prevent postoperative pyoseptic complications

  3. Effects of cryopreservation on excretory function, cellular adhesion molecules and vessel lumen formation in human umbilical vein endothelial cells.

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    Cai, Guoping; Lai, Binbin; Hong, Huaxing; Lin, Peng; Chen, Weifu; Zhu, Zhong; Chen, Haixiao

    2017-07-01

    Cryopreservation is widely used in regenerative medicine for tissue preservation. In the present study, the effects of cryopreservation on excretory function, cellular adhesion molecules and vessel lumen formation in human umbilical vein endothelial cells (HUVECs) were investigated. After 0, 4, 8, 12 or 24 weeks of cryopreservation in liquid nitrogen, the HUVECs were thawed. The excretory functions markers (endothelin‑1, prostaglandin E1, von Willebrand factor and nitric oxide) of HUVECs were measured by ELISA assay. The expression of intercellular adhesion molecule‑1 (ICAM‑1) in HUVECs was analyzed using flow cytometry. An angiogenesis assay was used to determine the angiogeneic capabilities of the thawed HUVECs. The results demonstrated that cryopreserved/thawed and recultivated HUVECs were unsuitable for tissue‑engineered microvascular construction. Specifically, the excretory function of the cells was significantly decreased in the post‑cryopreserved HUVECs at 24 weeks. In addition, the level of ICAM‑1 in HUVECs was significantly upregulated from the fourth week of cryopreservation. Furthermore, the tube‑like structure‑forming potential was weakened with increasing cryopreservation duration, and the numbers of lumen and the length of the pipeline were decreased in the thawed HUVECs, in a time‑dependent manner. In conclusion, the results of the present study revealed that prolonged cryopreservation may lead to HUVEC dysfunction and did not create stable cell lines for tissue‑engineered microvascular construction.

  4. Characterization of the effects of erythromycin estolate and erythromycin base on the excretory function of the isolated rat liver

    International Nuclear Information System (INIS)

    Gaeta, G.B.; Utili, R.; Adinolfi, L.E.; Abernathy, C.O.; Giusti, G.

    1985-01-01

    To investigate the mechanisms of erythromycin cholestasis, the effects of erythromycin estolate (EE) on the excretory function of the isolated perfused rat liver and on liver plasma membrane (LM) preparations were studied and compared to those of erythromycin base (EB) and lauryl sulfate (LS), added alone or in combination. EE (at 125 to 200 microM) caused dose-dependent reductions of bile and perfusate flows, bile acid (BA) excretion, and biliary BA concentration. The alterations of the excretory function were only in part due to the decreased perfusate flow. In contrast, both 200 and 300 microM concentrations of EB elicited similar choleretic responses, which were presumably related to the osmotic activity of the drug excreted in the bile. LS did not affect hepatic excretory functions. However, the simultaneous addition of EB and LS resulted in a rate of bile flow lower than that observed with EB alone. EE, but not EB, increased canalicular permeability to [ 14 C]sucrose as measured by bile to plasma (B:P) ratio. Neither drugs altered [ 14 C]erythritol B:P ratio. In LM preparations both Na+,K+- and Mg2+-ATPase activities were inhibited in a dose-dependent manner by EE, but not by EB. The data suggest that EE could affect bile flow by inhibiting cotransport of Na+ and BA and by altering LM permeability and support the view that the effect of erythromycins on the liver may be related to their surface activity

  5. Filarial excretory-secretory products induce human monocytes to produce lymphangiogenic mediators.

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    Tiffany Weinkopff

    2014-07-01

    Full Text Available The nematodes Wuchereria bancrofti and Brugia spp. infect over 120 million people worldwide, causing lymphedema, elephantiasis and hydrocele, collectively known as lymphatic filariasis. Most infected individuals appear to be asymptomatic, but many exhibit sub-clinical manifestations including the lymphangiectasia that likely contributes to the development of lymphedema and elephantiasis. As adult worm excretory-secretory products (ES do not directly activate lymphatic endothelial cells (LEC, we investigated the role of monocyte/macrophage-derived soluble factors in the development of filarial lymphatic pathology. We analyzed the production of IL-8, IL-6 and VEGF-A by peripheral blood mononuclear cells (PBMC from naïve donors following stimulation with filarial ES products. ES-stimulated PBMCs produced significantly more IL-8, IL-6 and VEGF-A compared to cells cultured in medium alone; CD14(+ monocytes appear to be the primary producers of IL-8 and VEGF-A, but not IL-6. Furthermore, IL-8, IL-6 and VEGF-A induced in vitro tubule formation in LEC Matrigel cultures. Matrigel plugs supplemented with IL-8, IL-6, VEGF-A, or with supernatants from ES-stimulated PBMCs and implanted in vivo stimulated lymphangiogenesis. Collectively, these data support the hypothesis that monocytes/macrophages exposed to filarial ES products may modulate lymphatic function through the secretion of soluble factors that stimulate the vessel growth associated with the pathogenesis of filarial disease.

  6. Excretory urogramm with angiotomography: Imaging of the renal arteries by excretory urogramm

    International Nuclear Information System (INIS)

    Binder, G.

    1982-01-01

    Excretory urography permits imaging of the renal arteries up to the intrarenal ramification if the contrast medium is injected as a bolus and the time of circulation between arm vein and abdominal aorta is determined with sufficient accuracy. Imaging of the vessel phase is done using simultaneous tomography. In the experimental part of the paper phantom tests are carried through to establish the contrast medium concentration to be expected in the renal arteries by means of microdensitometry. With the aid of 100 computerized tomograms of the abdomen the layer thickness required was determined to 4.5 cm; further phantom tests provided the necessary layer distances to image renal arteries that do not run in parallel to the plain of the film. The circulation time between arm vein and abdominal aorta was measured in 180 patients using the radioisotope method. It ranges between 9 and 22 seconds. Comparisons with the Decholin-method were made. 739 renal arteries were seen during the evaluation of 343 excretory urographies with angiotomograms, in 83 per cent of the cases these arteries were presented entirely. Provided perfect execution, simultaneous tomography is a very informative method. For 212 patients the side-effects of the bolar contrast medium injection were recorded. The importance of excretory urography with combined angiotomography for the diagnosis of arterial hypertension is discussed. (orig.) [de

  7. Effect of mammals’ excretory function on aspartate aminotransferase activity in Glechoma hederacea leaves in conditions of Cd pollution

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    O. M. Vasilyuk

    2014-07-01

    Full Text Available The paper includes analysis of research of Cd impact on the activity of the enzyme of aspartate aminotransferase (AST nitrogen metabolism and the content of water-soluble protein fraction (albumin in Glechoma hederacea L. leaves, which dominated in the research area (in natural floodplain oak forest with Stellaria holostea L.. Cd was introduced in the form of salts of Cd(NO32 in the range of concentrations of: 0.25, 1.25, 2.5 g/m2, equivalent to the inclusion of Cd in 1, 5, 10 doses of MAC. Increase (P < 0.05 in the activity of AST 2.6–3.0 times (with adding Cd salts at a dose of 1 and 5 МAС and albumin content by 37% (with adding Cd salts at a dose of 10 МAС compared to control (the area without Cd pollution and excretory activity of mammals was shown. Using of excreta of some representatives of mammals (for example, Capreolus capreolus L. contributed to reduction of Cd toxic effects and restoring of the functional metabolic activity of AST by 23% (with Cd 1 МAС and by 34% (Cd 5 МAС. It is the evidence of protective function of mammals and their normalization effect at the above concentrations of Cd. Whereas the adding of Cd salts at a dose of 10 МAС led to 3 times’ inhibition of AST activity, the toxic effect of metal by excretory function of mammals was not reduced. Observations revealed the albumin content normalization by 22% in the presence of Cd 1MAC respectively (with the introduction of C. capreolus excreta and to the control level (the area without Cd pollution and excretory activity of mammals with the excreta of Sus scrofa L. in the setting of Cd 10 MAC. It proves the need to use the different mammal species for integrated and comprehensive normalization of ecosystems under conditions of uncontrolled anthropogenic pollution.

  8. Clonorchis sinensis excretory-secretory products regulate migration and invasion in cholangiocarcinoma cells via extracellular signal-regulated kinase 1/2/nuclear factor-κB-dependent matrix metalloproteinase-9 expression.

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    Pak, Jhang Ho; Shin, Jimin; Song, In-Sung; Shim, Sungbo; Jang, Sung-Wuk

    2017-01-01

    Matrix metalloproteinase-9 plays an important role in the invasion and metastasis of various types of cancer cells. We have previously reported that excretory-secretory products from Clonorchis sinensis increases matrix metalloproteinase-9 expression. However, the regulatory mechanisms through which matrix metalloproteinase-9 expression affects cholangiocarcinoma development remain unclear. In the current study, we examined the potential role of excretory-secretory products in regulating the migration and invasion of various cholangiocarcinoma cell lines. We demonstrated that excretory-secretory products significantly induced matrix metalloproteinase-9 expression and activity in a concentration-dependent manner. Reporter gene and chromatin immunoprecipitation assays showed that excretory-secretory products induced matrix metalloproteinase-9 expression by enhancing the activity of nuclear factor-kappa B. Moreover, excretory-secretory products induced the degradation and phosphorylation of IκBα and stimulated nuclear factor-kappa B p65 nuclear translocation, which was regulated by extracellular signal-regulated kinase 1/2. Taken together, our findings indicated that the excretory-secretory product-dependent enhancement of matrix metalloproteinase-9 activity and subsequent induction of IκBα and nuclear factor-kappa B activities may contribute to the progression of cholangiocarcinoma. Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

  9. Renal malignancies with normal excretory urograms

    International Nuclear Information System (INIS)

    Kass, D.A.; Hricak, H.; Davidson, A.J.

    1983-01-01

    Four patients with malignant renal masses showed no abnormality of excretory urograms with tomography. Of the four lesions, two were primary renal cell carcinomas, one was a metastatic focus from a contralateral renal cell carcinoma, and one was a metastatic lesion from rectal adenocarcinoma. A normal excretory urogram should not be considered sufficient to exclude a clinically suspected malignant renal mass. In such an instance, diagnostic evaluation should be pursued using a method capable of topographic anatomic display, such as computed tomography or sonography

  10. Changing indications for excretory urography

    International Nuclear Information System (INIS)

    Kumar, R.; Schreiber, M.H.

    1985-01-01

    Most individuals suspected of having renovascular hypertension, men with benign prostatic enlargement, women with recurrent infections of the urinary tract or urinary stress incontinence, women undergoing hysterectomy, uremic and diabetic patients, and patients with renal transplant or adult polycystic kidney disease should not, as a rule, undergo routine excretory urography (EU). Possible morbidity and mortality and unwarranted cost do not justify the study, since the majority of individuals in any of these situations do not benefit from the information obtained from the study. Excretory urography must be performed selectively, rather than routinely, in such persons. As the authors emphasize, modified EU, often using only two to three films, may be performed under many clinical situations to reduce radiation exposure, toxic effects, and cost to the patient

  11. On the structure of fish gill, with special reference to its absorptive and excretory function

    International Nuclear Information System (INIS)

    Oguri, Mikio

    1981-01-01

    The gill of fish is not only the respiratory organ, but also the absorptive and excretory one of various substances, such as pesticides, anesthetics and minerals including radionuclides. Branchial absorption of Ca, Cr, Zn, Sr and Hg, and dieldrin (a pesticide) has been demonstrated by the gill-perfusion experiments using eel and rainbow trout. Also, branchial excretion of Cl, Ca and Sr has been ascertained by the same method using eel. Therefore, the gill is an important organ in relation to the accumulation and metabolism of radionuclides in fishes. Compared with the kidney, another excretory organ in fish, the structure of fish gill is rather simple. Histologically, the gill lamella, main functional portion of gill, is enveloped with simple squamous epithelium on each side. Between these two thin layers, pilaster cells and lacuna of branchial capillary are recognized as tissue components. In the gills of marine fishes, well-developed salt-secreting cells are detectable at the basal area of gill lamella. The cytoplasm of these cells are acidophilic and abundant in mitochondria and tubular endoplasmic reticulum. The cells are also called chloride cells and said to be involved in the extra-renal excretion of Na and Cl took in by marine fishes. The important problem is whether the salt-secreting cells in marine fishes are also concerned with the branchial excretion of another minerals such as Ca, Sr, I and so on, or these minerals are excreted across the ordinal epithelial cells of gill lamella. To elucidate this, detailed investigatios are awaited with interest. (author)

  12. Radiographic evaluation of experimentally induced nephrosis in goats

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    Kumar, R.; Pandey, N. N.; Singh, G. R.; Setia, H. C. [Indian Veterinary Research Institute, Izatnagar (India)

    1995-06-15

    Intravenous pyelography (IVP) with pneumoperitoneum (PP) was undertaken in normal and induced nephrotic goats. In normal goats, the technique provided visualization of both the kidneys, renal pelvis, ureter and urinary bladder at 10 min post-administration of sodium iothalamate (70%). In mercuric chloride- and oxytetracycline-induced nephrosis in goats, the urinary tract could not be visualized even 60 min post-administration of dye indicating sever failure of renal excretory function. However, in gentamicin-abused goats, renal excretory function was not significantly altered owing to a very mild renal damage. It was concluded that IVP with PP could be a dependable diagnostic test for varied degree of renal insufficiency in ruminants.

  13. Radiographic evaluation of experimentally induced nephrosis in goats

    International Nuclear Information System (INIS)

    Kumar, R.; Pandey, N.N.; Singh, G.R.; Setia, H.C.

    1995-01-01

    Intravenous pyelography (IVP) with pneumoperitoneum (PP) was undertaken in normal and induced nephrotic goats. In normal goats, the technique provided visualization of both the kidneys, renal pelvis, ureter and urinary bladder at 10 min post-administration of sodium iothalamate (70%). In mercuric chloride- and oxytetracycline-induced nephrosis in goats, the urinary tract could not be visualized even 60 min post-administration of dye indicating sever failure of renal excretory function. However, in gentamicin-abused goats, renal excretory function was not significantly altered owing to a very mild renal damage. It was concluded that IVP with PP could be a dependable diagnostic test for varied degree of renal insufficiency in ruminants

  14. Efficacy of the excretory urogram in the staging of gynecologic malignancies

    International Nuclear Information System (INIS)

    Hillman, B.J.; Clark, R.L.; Babbitt, G.

    1984-01-01

    It is common for patients suspected of having a gynecologic malignancy to be referred for excretory urography as part of their preoperative staging evaluation. This study investigated the efficacy of this practice using prospective and experimental retrospective interpretations of 88 urograms obtained for this clinical indication. The results indicate that excretory urography reliably depicts the ureters in most cases. However, the urogram is quite insensitive in demonstrating the extention of malignancy. The excretory urogram is useful for locating the position of the ureters and demonstrating the presence of obstruction or unsuspected urinary tract abnormalities. Nonetheless, this information also may be obtained by computed tomography, which can more accurately assess the primary mass and indicate the presence of malignant extension

  15. Antigenic analyses of tissues and excretory and secretory products from Strongylus vulgaris.

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    Wynne, E; Slocombe, J O; Wilkie, B N

    1981-07-01

    Rabbit antisera were prepared against veronal buffered saline extracts of L4 and L5 Strongylus vulgaris, adult S. vulgaris and adult Strongylus equinus retrieved from naturally infected horses. In agar gel diffusion with these antisera, adult S vulgaris and S. equinus each appeared to have at least one unique antigen; larval S. vulgaris appeared to have two species-specific and two stage-specific antigens. There were several common antigens. Excretory and secretory products were collected also from L4 and L5 an maintained over several days in tissue culture fluid. In agar gel diffusion against the above rabbit antisera, a stage-specific antigen was found also in excretory and secretory products. In addition, excretory and secretory products had three antigens in common with adult and larval S. vulgaris, but only one of these was common to adult S. equinus. The excretory and secretory products appear, therefore, to have two species-specific and one stage-specific antigens.

  16. Excretory/secretory products from Trichinella spiralis adult worms ameliorate DSS-induced colitis in mice.

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    Xiaodi Yang

    Full Text Available BACKGROUND: Many evidences show the inverse correlation between helminth infection and allergic or autoimmune diseases. Identification and characterization of the active helminth-derived products responsible for the beneficial effects on allergic or inflammatory diseases will provide another feasible approach to treat these diseases. METHODS AND FINDINGS: Colitis was induced in C57BL/6 mice by giving 3% DSS orally for 7 days. During this period, the mice were treated daily with the excretory/secretory products from T. spiralis adult worms (AES intraperitoneally. The severity of colitis was monitored by measuring body weight, stool consistency or bleeding, colon length and inflammation. To determine the T. spiralis AES product-induced immunological response, Th1, Th2, Th17 and regulatory cytokine profiles were measured in lymphocytes isolated from colon, mesenteric lymph nodes (MLN, and the spleen of treated mice. The CD4+ CD25+ FOXP3+ regulatory T cells (Tregs were also measured in the spleens and MLN of treated mice. Mice treated with AES significantly ameliorated the severity of the DSS-induced colitis indicated by the reduced disease manifestations, improved macroscopic and microscopic inflammation correlated with the up-regulation of Treg response (increased regulatory cytokines IL-10, TGF-beta and regulatory T cells and down-regulation of pro-inflammatory cytokines (IFN-gamma, IL-6 and IL-17 in the spleens, MLN and colon of treated mice. CONCLUSIONS: Our results provide direct evidences that T. spiralis AES have a therapeutic potential for alleviating inflammatory colitis in mice. This effect is possibly mediated by the immunomodulation of regulatory T cells to produce regulatory and anti-inflammatory cytokines and inhibit pro-inflammatory cytokines.

  17. Gd-BOPTA-enhanced excretory MR urography without administration of diuretics

    International Nuclear Information System (INIS)

    Allkemper, T.; Tombach, B.; Heindel, W.

    2001-01-01

    Purpose: To evaluate the feasibility and clinical utility of Gd-BOPTA enhanced excretory magnetic resonance urography without additional administration of diuretics in correlation with conventional urography. Method: 15 preoperative patients with pelvic tumors were examined at 1.5 T using a breath-hold high-resolution 3D-FLASH sequence during first-pass as well as 5, 10, 15 minutes after iv. injection of 0.05 mmol/kg BW Gd-BOPTA (MultiHance trademark ) without administration of diuretics. Post-processed coronal and multiplanar MIP reconstructions were compared to conventional excretory urography with regard to morphologic accuracy, anatomic variability, filling defects, cause and level of obstruction or compression, tumor visibility, and time-effectiveness by two independent radiologists. Results: Visualization of the urinary tract by MRU was comparable to conventional excretory urography in 14 of 15 cases. Caliceal fornices were better delineated on conventional urographies, whereas MRU was considered superior in the assessment of the inferior ureter sections, the urinary bladder and obstructive tumors, whose extents could be clearly marked out. Examination times of both techniques were comparable. Conclusion: These first results show that non-diuretic Gd-BOPTA enhanced MRU is comparable to conventional excretory urography for the preoperative diagnosis of pelvic tumors. Further improvements of this technique seem possible by optimization of examination intervals and injection doses. (orig.) [de

  18. DIAGNOSTICS AND TREATMENT OF EXCRETORY DEFICIENCY OF PANCREAS IN CHILDREN

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    S.V. Bel’mer

    2009-01-01

    Full Text Available Excretory pancreatic insufficiency is relatively frequent pathology in pediatric and therapeutic practice. It can be divided to primary and secondary, inborn and acquired, absolute and relative one. The causes of primary pancreatic insufficiency are agenesia or hypoplasia of pancreas, cystic fibrosis, Shwachman–Diamond syndrome. Secondary excretory pancreatic insufficiency can be caused by resection of pancreas, pancreatitis, pathology of mucous tunic of small intestine, abnormality of antitrypsinactivation with enterokinase deficiency, inactivation of enzymes by acid of duodenal contents in the presence of gastric hyper secretion and others. Excretory pancreatic deficiency has determined clinical signs and can be relatively easily diagnosed by simple laboratory methods: coprogramm and detection of elastase 1 in stool. The ways of its correction are determined by causes of disease, but modern high-active pancreatic enzymes medications must be necessary component of treatment in all cases.Key words: children, pancreatic insufficiency, celiac disease, pancreatic enzymes medications.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(2:114-118

  19. Diagnostic value of combined static-excretory MR Urography in children with hydroneph

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    Sally Emad-Eldin

    2015-03-01

    Full Text Available The aim of this study was to determine the feasibility, accuracy and diagnostic potential of combined static-excretory MR Urography in children with sonographically detected hydronephrosis. We prospectively evaluated 28 children (11 girls and 17 boys, mean age 8.3 years (range 2 months–16 years. Static-excretory MR Urography was performed in all cases. The results of MR Urography were compared with the results of other imaging modalities, cystoscopy and surgery. In 28 children, 61 renal units were evaluated by MR Urography (the renal unit is the kidney and its draining ureter. The final diagnoses included: normal renal units (n = 23; uretropelvic junction obstruction (n = 14; megaureter (n = 8; midureteric stricture (n = 1, complicated duplicated systems (n = 5, post ESWL non-obstructive dilation (n = 2, extrarenal pelvis (n = 4, dysplastic kidney (n = 4. Complex pathology and more than one disease entity in were found in 7 children. The MRI diagnosis correlated with the final diagnosis in 57 units, with diagnostic accuracy 93.4%. In conclusions static and excretory MRU give both morphological and functional information in a single examination without exposure to ionizing radiation and iodinated contrast agent. It is a valuable imaging technique for children with upper urinary tract dilatation; especially in cases of complex congenital pathologies and severely hydronephrotic kidney.

  20. The evaluation of kidney scan: On comparison with excretory urography

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    Choe, Yong Kyu; Kim, Chung Kyu; Choi, Byung Sook [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1970-10-15

    The kidney scan and the excretory urography of 21 cases in kidney disease proved clinically or pathologically at Yonsei University, Severance Hospital were reviewed and analysed briefly. Following were the results: 1. In all except 2 cases of pyelonephritis, changes on the kidney scan were noted with generalized motted density and cold area in the kidney, and with diffuse poor or non uptake density and various size or shape of the kidney. 2. On the excretory urogram, the demonstrable findings in the kidney parenchyma were discribed on the only 7 of 21 cases, hypernephroma, tuberculosis kidney, necrotizing papillits, medullary sponge kidney, and stenosis of renal artery. 3. Three of all cases, renal carbuncle, retroperitoneal hematoma with aberrant vessel and angiolipomyoma were no appreciable finding on the pyelography, but on the view of kidney scanning, there were apparently demonstrated abnormal cold area and some enlargement of kidney size. We concluded that the close correlation of the two techniques, kidney scanning and excretory urography on the kidney disease leads to more improved diagnostic accuracy.

  1. The evaluation of kidney scan: On comparison with excretory urography

    International Nuclear Information System (INIS)

    Choe, Yong Kyu; Kim, Chung Kyu; Choi, Byung Sook

    1970-01-01

    The kidney scan and the excretory urography of 21 cases in kidney disease proved clinically or pathologically at Yonsei University, Severance Hospital were reviewed and analysed briefly. Following were the results: 1. In all except 2 cases of pyelonephritis, changes on the kidney scan were noted with generalized motted density and cold area in the kidney, and with diffuse poor or non uptake density and various size or shape of the kidney. 2. On the excretory urogram, the demonstrable findings in the kidney parenchyma were discribed on the only 7 of 21 cases, hypernephroma, tuberculosis kidney, necrotizing papillits, medullary sponge kidney, and stenosis of renal artery. 3. Three of all cases, renal carbuncle, retroperitoneal hematoma with aberrant vessel and angiolipomyoma were no appreciable finding on the pyelography, but on the view of kidney scanning, there were apparently demonstrated abnormal cold area and some enlargement of kidney size. We concluded that the close correlation of the two techniques, kidney scanning and excretory urography on the kidney disease leads to more improved diagnostic accuracy

  2. Analysis of the effect of renal excretory system cooling during thermal radiofrequency ablation in an animal model

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    Andre Meireles

    2014-01-01

    Full Text Available Objective: Analysis of renal excretory system integrity and efficacy of radiofrequency ablation with and without irrigation with saline at 2 o C (SF2. Materials and Methods: The median third of sixteen kidneys were submitted to radiofrequency (exposition of 1 cm controlled by intra-surgical ultrasound, with eight minutes cycles and median temperature of 90 o C in eight female pigs. One excretory renal system was cooled with SF2, at a 30ml/min rate, and the other kidney was not. After 14 days of post-operatory, the biggest diameters of the lesions and the radiological aspects of the excretory system were compared by bilateral ascending pyelogram and the animals were sacrificed in order to perform histological analysis. Results: There were no significant differences between the diameters of the kidney lesions whether or not exposed to cooling of the excretory system. Median diameter of the cooled kidneys and not cooled kidneys were respectively (in mm: anteroposterior: 11.46 vs. 12.5 (p = 0.23; longitudinal: 17.94 vs. 18.84 (p = 0.62; depth: 11.38 vs. 12.25 (p = 0.47. There was no lesion of the excretory system or signs of leakage of contrast media or hydronephrosis at ascending pyelogram. Conclusion: Cooling of excretory system during radiofrequency ablation does not significantly alter generated coagulation necrosis or affect the integrity of the excretory system in the studied model.

  3. [Peculiarities of ultrastructure of excretory system in Bothrioplana semperi (Platyhelminthes, Turbellaria)].

    Science.gov (United States)

    Kornakova, E E

    2010-01-01

    Ultrastructural study of morphology of cirtocytes and excretory channels was performed in the free living turbellaria Bothrioplana semperi (Turbellaria, Seriata). It has been shown that cirtocytes of this species are formed by two cells--the terminal and the proximal cells of the channel. The fan is composed of two rod rows. The external row goes out from the terminal cell, the internal one is a derivate of the channel proximal cell. Inside each rod of the external row there runs a bundle of microfilaments; it originates in the cytoplasm of the channel proximal cell distal to bases of the external rods. On the internal rod membranes there are noted small electrondense granules disposed separately or fused in the solid layer continuing into a dense "membrane" connecting rods of the external and internal rows. Rare internal leptotrichiae go out from the cirtocyte cavity bottom. External leptotrichiae are absent. The septate desmosome at the level of the terminal cell is absent, but is present in the channel proximal cell at the level of terminal of cilia. The apical surface of the channel cell carries rare short microvilli. The basement membrane of cells of excretory channels forms deep invaginations almost reaching the apical membrane. Epithelium of excretory channels is deprived of cilia. Ultrastructure of cirtocytes and excretory channels of B. semperi is similar to those in representatives of the suborder Proseriata (Seriata). The significance of ultrastructure of the Proseriata cirtocytes, especially of the order of formation of versh, for construction of phylogeny of Platyhelminthes is discussed.

  4. Comprehensive renal scintillation procedures in spinal cord injury: comparison with excretory urography

    International Nuclear Information System (INIS)

    Lloyd, L.K.; Dubovsky, E.V.; Bueschen, A.J.; Witten, D.M.; Scott, J.W.; Kuhlemeier, K.; Stover, S.L.

    1981-01-01

    A 131 iodine orthoiodohippurate comprehensive renal scintillation procedure was performed and compared to results of excretory urography in 200 spinal cord injury patients. No severe urographic abnormalities were undetected by the comprehensive renal scintillation procedure. Only 1.4 per cent of renal units had greater than minimal pyelocaliectasis or ureterectasis in the presence of a normal radionuclide examination. A relatively large number of abnormalities were detected on the renal scintillation procedure when the excretory urogram was normal. Serial followup will be required to determine the significance of these findings but present data suggest that a comprehensive renal scintillation procedure and a plain film of the kidneys, ureters and bladder may be used for screening upper urinary tract abnormalities in lieu of an excretory urogram. This is particularly advantageous for the spinal cord injury population, since there have been no toxic or allergic reactions reported, no bowel preparation or dehydration is required and there is relatively low radiation exposure

  5. 99mtechnetium-dimercapto-succinic acid renal scanning and excretory urography in diagnosis of renal scars in children

    International Nuclear Information System (INIS)

    McLorie, G.A.; Aliabadi, H.; Churchill, B.M.; Ash, J.M.; Gilday, D.L.

    1989-01-01

    We compared the ability of excretory urography (without tomography) and 99mtechnetium-dimercapto-succinic acid renal scanning to detect renal scars in 32 children with primary vesicoureteral reflux. These children did not have hydronephrosis, renal failure or urinary tract obstruction. In all cases both studies were conducted within a 10-month period. The findings from both modalities were in agreement for 51 of the 64 renal units evaluated (80%). Evaluation of the excretory urogram indicated 6 cases of diffuse and 2 of focal scarring that were not detected by evaluation of the renal scan. The sensitivity of excretory urography to detect renal scars was 84% and the specificity was 83%. The 99mtechnetium-dimercapto-succinic acid renal scan showed 5 cases of focal renal scarring not detected by excretory urography. The sensitivity of the renal scan to detect renal scars was 77% and the specificity was 75%. We conclude that neither study alone could effectively replace the other for the detection of renal scars, and recommend that both be included in the initial evaluation and followup of patients with renal scars

  6. Excretory urography and ultrasonography in the diagnosis of bilateral ectopic ureters in a foal

    International Nuclear Information System (INIS)

    Blikslager, A.T.; Green, E.M.; MacFadden, K.E.; Fagin, B.; Johnson, G.C.

    1992-01-01

    A 7-week-old Appaloosa filly was admitted for persistent urinary incontinence since birth. Vaginal speculum examination revealed urine flowing from an opening in the right vaginal wall. Cytoscopy demonstrated that the ureters did not terminate at the bladder. The endoscope passed easily from the vagina directly into a dilated right ureter. An excretory urogram confirmed the vaginal termination of at least one ureter, based upon extensive filling of the vagina with contrast media in the absence of bladder filling. Bilateral hydroureter and dilated renal pelves were demonstrated both by excretory urography and by urtrasonography. Euthanasia was required by the owner in lieu of attempted surgical correction. At necroscopy, it was confirmed that the right ureter entered the vagina and the left ureter terminated at the urethra. The diagnosis of bilateral ectopic ureter in this foal was suggested by this history and clinical signs, supported by endoscopy and ultrasonography, and confirmed by excretory urography and necropsy. This case establishes the value of diagnostic imaging techniques in the antemortem diagnosis of ectopic ureter

  7. Three types of gall-bladder motility at men with chronic cholecystitis and pyelonephritis and accompanying their parameters of kidney excretory function as well as metabolism

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    Oksana M Ivanyts’ka

    2018-04-01

    Full Text Available Background. Previously it has been shown that balneotherapy in the spa Truskavets’ (Ukraїna in men with chronic cholecystitis combined with pyelonephritis causes changes in gall-bladder motility. This is combined with changes in diurese and urinary excretion of metabolites.Individual analysis revealed not only quantitative but also qualitative differences in the postprandial motility of the gall-bladder. The purpose of this study is to identify the parameters of kidney excretory function as well as metabolism under which three types of the gall-bladdermotility skills differ significantly from each other. Materialandmethods. The object of observationwere the same ones 22men aged24-70 years old,who cameto the spaTruskavets’ for the treatment of chronic cholecystitiscombined withpyelonephritis inremission. On thetone and motility of gall-bladder judged byits fasting and postprandial volume (echocamera “Radmir”. In the daily  determined content of oxalate and nitrogen metabolites: creatinine, urea and uric acid, electrolytes: phosphates, chloride, calcium, magnesium, potassium and sodium. Nitrogenous metabolites in plasma of venous blood were determined also. The survey was conducted twice, before and after balneotherapy. Results. The method of cluster analysis has formed three homogeneous cholekinetics groups, namely:normokinesia as well as hypertonic-hyperkinetic and hyperkinetic-hypertonic dyskinesia.The method of discriminatory analysis revealed 13 parameters of daily urine and three parameters of blood, as well as body weight and height, electrokinetic index and Kerdoe’s index, in the totality of which three types of cholekinetics are clearly delineated.Conclusion. The type of postprandial cholekinetics is naturally associated with a number of parameters of the excretory renal function and metabolism.

  8. Hidronefrosis prenatal en doble sistema excretor Prenatal hydronephrosis in double excretory system

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    Sandalio Durán Álvarez

    2007-12-01

    hydronephrosis were studied. The maternofetal ultrasound showed a double excretory system. To this end, all the newborns and infants with prenatally detected hydronephrosis and double excretory system diagnosed before or after birth were followed up by evolutive renal ultrasonography, micturition urethrocystography, static or dynamic scintigraphy and, in some cases, by excretory urogram. Double excretory system was found in 7 of the 182 patients (3.8 % with abnormalities of the urinary tract diagnosed before birth. Diagnosis was prenatal in just one of the fetuses (31 weeks of pregnancy. Hydronephrotic dilatation was mild in two fetuses and severe in five. Hydronephrosis had different causes. Upper polar nephrectomy was performed in those cases of ureteral ectopy and obstructed upper ureter, reimplantation in one ureterocele, whereas in another it was confirmed the spontaneous rupture by endoscopy. The rest of the patients were symptomatically treated. The hydronephrosis detected before birth by maternofetal ultrasonography may be associated with a double excretory system. Hydronephrotic dilatation associated with a double excretory system may have different causes, and it is necessary to study carefully and systematically these children and to treat them adequately, since each of them may need a different conduct.

  9. [Clinical application of high-pitch excretory phase images during dual-source CT urography with stellar photon detector].

    Science.gov (United States)

    Sun, Hao; Xue, Hua-dan; Jin, Zheng-yu; Wang, Xuan; Chen, Yu; He, Yong-lan; Zhang, Da-ming; Zhu, Liang; Wang, Yun; Qi, Bing; Xu, Kai; Wang, Ming

    2014-10-01

    To retrospectively evaluate the clinical feasibility of high-pitch excretory phase images during dual-source CT urography with Stellar photon detector. Totally 100 patients received dual-source CT high-pitch urinary excretory phase scanning with Stellar photon detector [80 kV, ref.92 mAs, CARE Dose 4D and CARE kV, pitch of 3.0, filter back projection reconstruction algorithm (FBP)] (group A). Another 100 patients received dual-source CT high-pitch urinary excretory phase scanning with common detector(100 kV, ref.140 mAs, CARE Dose 4D, pitch of 3.0, FBP) (group B). Quantitative measurement of CT value of urinary segments (Hounsfield units), image noise (Hounsfield units), and effective radiation dose (millisievert) were compared using independent-samples t test between two groups. Urinary system subjective opacification scores were compared using Mann-Whitney U test between two groups. There was no significant difference in subjective opacification score of intrarenal collecting system and ureters between two groups (all P>0.05). The group A images yielded significantly higher CT values of all urinary segments (all P0.05). The effective radiation dose of group A (1.1 mSv) was significantly lower than that of group B (3.79 mSv) (Ppitch low-tube-voltage during excretory phase dual-source CT urography with Stellar photon detector is feasible, with acceptable image noise and lower radiation dose.

  10. Chronic pyelonephritis as false interpretation in the excretory urogram

    International Nuclear Information System (INIS)

    Rieden, K.; Weber, M.

    1985-01-01

    Chronic pyelonephritis, which is largely diagnosed via imaging procedures, is characterised by defined parenchymal scars that become manifest in the excretory urogram as contour recessions of the kidney and result in deformations of the calyces and papillae. The authors describe other renal diseases, dysplasias, variations from the standard, and artifacts resulting in similar signs on X-ray film, thus leading to the wrong diagnosis of chronic pyelonephritis. The essential differential diagnostic criteria are explained. (orig.) [de

  11. The diagnostic effectiveness of contrast media in the excretory urography in dogs

    International Nuclear Information System (INIS)

    Velesova, M.; Ledecky, V.

    2005-01-01

    A clinical study was conducted to investigate the use of four different positive contrast media, Omnipaque (Nycomed Imaging As.), Optiray (Maliincrodt Medical GmbH), Ultravist (Schering AG), and Urografin (Schering AG) in normograde excretory urography. Investigations were carried out on thirteen dogs. Each group of dogs was administered a different contrast medium. Radiographs were obtained immediately after the administration of contrast media and after a lapse of 5, 10 and 15 minutes. The effectiveness of the application was evaluated by assessing the radiographs of abdominal cavities in ventro-dorsal and latero-lateral positions. None of the dogs showed pronounced side effect after the application of contrast media. Ectopic ureter was diagnosed in three and a prostate cyst in one of the patients. Our results showed that Omnipaque and Ultravist were the contrast agents most suitable for the examination of the urinary apparatus by intravenous contrast excretory urography. Their advantage is that visualisation of the kidneys and ureters achieved by these media are sufficiently long and contrastive

  12. Diagnostic value of 64-slice spiral computed tomography imaging of the urinary tract during the excretory phase for urinary tract obstruction.

    Science.gov (United States)

    Zhao, De-Li; Jia, Guang-Sheng; Chen, Peng; Liu, Xin-Ding; Shu, Sheng-Jie; Ling, Zai-Sheng; Fan, Ting-Ting; Shen, Xiu-Fen; Zhang, Jin-Ling

    2017-11-01

    The present study aimed to assess the diagnostic value of 64-slice spiral computed tomography (CT) imaging of the urinary tract during the excretory phase for urinary tract obstruction. CT imaging of the urinary tract during the excretory phase was performed in 46 patients that had been diagnosed with urinary tract obstruction by B-mode ultrasound imaging or clinical manifestations. It was demonstrated that out of the 46 patients, 18 had pelvic and ureteral calculi, 12 cases had congenital malformations, 3 had ureteral stricture caused by urinary tract infection and 13 cases had malignant tumors of the urinary tract. The average X-ray dose planned for the standard CT scan of the urinary tract group 1 was 14.11±5.45 mSv, while the actual X-ray dose administered for the CT scan during the excretory phase group 2 was 9.01±4.56 mSv. The difference between the two groups was statistically significant (t=15.36; Purinary tract during the excretory phase has a high diagnostic value for urinary tract obstruction.

  13. Toll-Like Receptor-Mediated Free Radical Generation in Clonorchis sinensis Excretory-Secretory Product-Treated Cholangiocarcinoma Cells.

    Science.gov (United States)

    Bahk, Young Yil; Pak, Jhang Ho

    2016-10-01

    Clonorchiasis, caused by direct contact with Clonorchis sinensis worms and their excretory-secretory products (ESPs), is associated with chronic inflammation, malignant changes in bile ducts, and even cholangiocarcinogenesis. Our previous report revealed that intracellular free radicals enzymatically generated by C. sinensis ESPs cause NF-κB-mediated inflammation in human cholangiocarcinoma cells (HuCCT1). Therefore, the present study was conducted to examine the role of upstream Toll-like receptors (TLRs) on the initial host innate immune responses to infection. We found that treatment of HuCCT1 cells with native ESPs induced changes in TLR mRNA levels in a time-dependent manner, concomitant with the generation of free radicals. ESP-mediated free radical generation was markedly attenuated by preincubation of the cells with TLR1-4-neutralizing antibodies, indicating that at least TLR1 through 4 participate in stimulation of the host innate immune responses. These findings indicate that free radicals triggered by ESPs are critically involved in TLR signal transduction. Continuous signaling by this pathway may function in initiating C. sinensis infection-associated inflammation cascades, a detrimental event leading to progression to more severe hepatobiliary diseases.

  14. Excretory/secretory-products of Echinococcus multilocularis larvae induce apoptosis and tolerogenic properties in dendritic cells in vitro.

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    Justin Komguep Nono

    Full Text Available BACKGROUND: Alveolar echinococcosis, caused by Echinococcus multilocularis larvae, is a chronic disease associated with considerable modulation of the host immune response. Dendritic cells (DC are key effectors in shaping the immune response and among the first cells encountered by the parasite during an infection. Although it is assumed that E.multilocularis, by excretory/secretory (E/S-products, specifically affects DC to deviate immune responses, little information is available on the molecular nature of respective E/S-products and their mode of action. METHODOLOGY/PRINCIPAL FINDINGS: We established cultivation systems for exposing DC to live material from early (oncosphere, chronic (metacestode and late (protoscolex infectious stages. When co-incubated with Echinococcus primary cells, representing the invading oncosphere, or metacestode vesicles, a significant proportion of DC underwent apoptosis and the surviving DC failed to mature. In contrast, DC exposed to protoscoleces upregulated maturation markers and did not undergo apoptosis. After pre-incubation with primary cells and metacestode vesicles, DC showed a strongly impaired ability to be activated by the TLR ligand LPS, which was not observed in DC pre-treated with protoscolex E/S-products. While none of the larvae induced the secretion of pro-inflammatory IL-12p70, the production of immunosuppressive IL-10 was elevated in response to primary cell E/S-products. Finally, upon incubation with DC and naïve T-cells, E/S-products from metacestode vesicles led to a significant expansion of Foxp3+ T cells in vitro. CONCLUSIONS: This is the first report on the induction of apoptosis in DC by cestode E/S-products. Our data indicate that the early infective stage of E. multilocularis is a strong inducer of tolerance in DC, which is most probably important for generating an immunosuppressive environment at an infection phase in which the parasite is highly vulnerable to host attacks. The

  15. Effect of Fasciola gigantica excretory secretory antigen on rat hematological indices

    Science.gov (United States)

    Ganga, G.; Sharma, R. L.

    2006-01-01

    The present study was undertaken to investigate the effect of Fasciola gigantica excretory secretory antigen (Fg-ESA) on rat hematological indices. Fg-ESA was prepared by keeping thoroughly washed 40 F. gigantica flukes in 100 ml phosphate buffer saline (PBS) for 2 h at 37℃, and centrifuging the supernatant at 12,000 g at 4℃ for 30 min. The protein content of Fg-ESA was adjusted to 1.8 mg/ml. The rats were randomly divided into two groups of six rats each. Rats in group A received 0.5 ml of Fg-ESA intraperitoneally (i.p.) for 7 days, whereas control rats in group B received 0.5 ml of PBS i.p. for 7 days. Hemograms of both groups were studied initially and on days 0, 2, 4, 14 and 21 after the final injection of Fg-ESA or PBS. Progressive and significant (p 0.05) changes in the values of mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, or mean corpuscular volume in group A. Thus, we conclude that Fg-ESA induces normocytic normochromic anemia in rats. PMID:16645335

  16. Gadolinium-enhanced excretory MR urography: comparison with MR urography using HASTE technique

    International Nuclear Information System (INIS)

    Jin, Gong Yong; Lee, Jeong Min; Han, Young Min; Cheong, Gyung Ho; Oh, Hee Sul; Kim, Chong Soo; Park, Sung Kwang; Kim, Young Gon

    2000-01-01

    To compare the feasibility of gadolinium-enhanced excretory MR urography (GEMRU) and conventional MR urography using the half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequence in patients with hydronephrosis or non-visualized kidney. Fifteen patients with hydronephrosis or non-visualized kidney, as demonstrated by ultrasonography or intravenous urography, were enrolled in this study. Nine were men and six were women, and their age ranged from 18 to 77 (mean, 60.6) years. For all MR examinations, a 1.5T MR unit was employed. For breath-hold MR urography, the HASTE technique (MRU) was used, and reconstruction involved the use of a maximum intensity-projection (MIP) algorithm. For gadolinium-enhanced excretory MR urography, the fast low angle shot (FLASH) 3-D method was used and images were obtained at 5, 10, 20, and 30 minutes, and reconstruction again involved the use of MIP algorithm. In some cases, additional GEMRU was obtained 24 hour after contrast material injection, and an MIP algorithm was used for reconstruction. MRU and GEMRU were independently interpreted by two radiologists who for quantitative analysis compared SNR with CNR, and at each anatomic level qualitatively analyzed morphologic accuracy and diagnostic value of the lesions. In quantitative analysis, SNR and CNR differences between the two sequences at the renal pelvis and the level of the ureter were not significant (p greater than 0.05). In qualitative analysis, GEMRU was superior to MRU for the assessment of evaluated ureter at each level (p less than 0.05), anatomic anomaly and intrinsic tumor. Ureteral stones, however, were more easily diagnosed with MRU. For assessment of the ureter GEMRU is superior to MRU and has the advantage of evaluating renal function. We believe that for evaluation of the urinary tract, especially the distal ureter, GEMRU may be a valuable adjunct to routine MR urography. (author)

  17. Static-dynamic MR urography. Comparison with excretory urography and scintigraphy in experimentally induced urinary tract obstruction (UTO); Statisch-dynamische MR-Urographie. Vergleich mit Ausscheidungsurographie und Szintigraphie bei experimentell induzierter Harntransportstoerung (HTS)

    Energy Technology Data Exchange (ETDEWEB)

    Rohrschneider, W.K.; Wunsch, R.; Troeger, J. [Paediatrische Radiologie, Univ. Heidelberg (Germany); Hoffend, J. [Nuklearmedizinische Klinik, Univ. Heidelberg (Germany); Becker, K. [Inst. fuer Versuchstierkunde, Univ. Heidelberg (Germany); Darge, K.; Clorius, J.H. [Kooperationseinheit Nuklearmedizin, Deutsches Krebsforschungszentrum, Heidelberg (Germany); Kooijman, H. [Philips Medizin-Systeme, Hamburg (Germany)

    2001-02-01

    Purpose: To assess the diagnostic value of combined static-dynamic MR urography (MRU) for the functional-morphological evaluation of experimentally induced urinary tract obstruction. Methods: Static-dynamic MRU - combination study with a respiratory-triggered 3D-IR-TSE sequence and a dynamic 2D-FFE sequence after Gd-DTPA and furosemide - was obtained in comparison with {sup 99m}Tc-MAG3 diuretic renal scintigraphy (DRS), excretory urography (EU) and ultrasound (US) in 29 healthy piglets and in 20 piglets with surgically induced ureteric stenosis (total of 50 postoperative examination blocks). Results: MRU allowed complete depiction of the urinary tract in all controls, in operated piglets the stenosis was always correctly identified. Quality of MRU was superior to EU in 36 to 43 comparative studies. Calculation of single kidney function from parenchymal renograms, and assessment of urinary excretion from whole-kidney renograms resulted in a highly significant agreement of MRU with DRS. Conclusion: Static-dynamic MR urography allows excellent depiction of experimentally induced urinary tract obstruction, and reliable assessment of individual renal function and urinary excretion. Two advantages of the method stand out, it does not require radiation and it permits a functional-morphological correlation. (orig.) [German] Ziel: Einschaetzung der Wertigkeit der kombinierten statisch-dynamischen MR-Urographie (MRU) zur umfassenden funktionell-morphologischen Diagnostik tierexperimentell induzierter Harntransportstoerungen. Methodik: Die statisch-dynamische MRU-Kombination aus einer atemgetriggerten 3D-IR-TSE-Sequenz und einer dynamischen 2D-FFE-Sequenz nach Gd-DTPA und Furosemid - wurde im Vergleich zu {sup 99m}Tc-MAG3-Diurese-Nierenszintigraphie (DNS), Ultraschall (US) und Ausscheidungsurographie (AUG) bei 29 gesunden Ferkeln sowie bei 20 Ferkeln mit operativ indizierter Harnwegsstenose (insgesamt 50 postoperative Untersuchungsbloecke) durchgefuehrt. Ergebnisse: Die MRU

  18. Comparison of Excretory-Secretory and Somatic Antigens of Ornithobilharzia turkestanicum in Agar Gel Diffusion Test

    Directory of Open Access Journals (Sweden)

    H Miranzadeh

    2008-12-01

    Full Text Available Background: Ornithobilharziosis as one of the parasitic infections may give rise to serious economic problems in animal husbandry. The Aim of the study was to prepare and compare the somatic and excretory-secretory (ES antigens of O. tur­kestanicum in gel diffusion test. Methods: Excretory-secretory (ES and somatic antigens of Ornithobilharzia turkestanicum were prepared from collected worms from mesentric blood vessels of infected sheep. The laboratory bred rabbits were immunized with antigens and then antisera were prepared. The reaction of antigens and antisera was observed in gel diffusion test. Results: ES antigens of this species showed positive reaction with antisera raised against ES and also somatic antigens. Somatic antigens also showed positive reaction with antisera raised against somatic and also ES antigens. Conclusion: The antigenicity of O. turkestanicum ES and somatic antigens is the same in gel diffusion test.

  19. Neural regulation of the kidney function in rats with cisplatin induced renal failure

    Science.gov (United States)

    Goulding, Niamh E.; Johns, Edward J.

    2015-01-01

    Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure. Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys. Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation. Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation. PMID:26175693

  20. Antigenic analyses of tissues and excretory and secretory products from Strongylus vulgaris.

    OpenAIRE

    Wynne, E; Slocombe, J O; Wilkie, B N

    1981-01-01

    Rabbit antisera were prepared against veronal buffered saline extracts of L4 and L5 Strongylus vulgaris, adult S. vulgaris and adult Strongylus equinus retrieved from naturally infected horses. In agar gel diffusion with these antisera, adult S vulgaris and S. equinus each appeared to have at least one unique antigen; larval S. vulgaris appeared to have two species-specific and two stage-specific antigens. There were several common antigens. Excretory and secretory products were collected als...

  1. Early report: Comparison of breath-hold MR excretory urography, Doppler ultrasound and isotope renography in evaluation of symptomatic hydronephrosis in pregnancy

    International Nuclear Information System (INIS)

    Spencer, J.A.; Tomlinson, A.J.; Weston, M.J.; Lloyd, S.N.

    2000-01-01

    AIM: To compare assessment by MR excretory urography (MREU), Doppler ultrasound and isotope renography of women with symptomatic hydronephrosis in pregnancy and to define its cause. MATERIALS AND METHODS: Eleven women at 19-34 weeks of gestation were studied prospectively with gadolinium-enhanced breath-hold gradient echo MREU and transabdominal Doppler ultrasound compared with a 'gold standard' of isotope renography employing frusemide challenge. All studies were performed within 24 h, were reported independently in a blinded fashion and employed clearly defined criteria. Obstetric and infant outcomes were obtained. RESULTS: There were no adverse reactions to gadolinium administration in pregnancy and no adverse obstetric or infant outcomes. Three of the 11 women were unable to tolerate the complete MREU protocol. Ultrasound indices could not be used to predict ureteric obstruction as shown by isotope renography. MREU agreed with renographic findings in five of the six cases with obstruction and in two without obstruction. MREU directly demonstrated hydronephrosis to result from extrinsic compression of the ureter between the gravid uterus and iliopsoas muscle. CONCLUSION: MR excretory urography is a promising technique which affords equivalent functional and additional anatomical information to isotope renography. It is more accurate than Doppler ultrasound in the assessment of ureteric obstruction in pregnancy. Spencer, J. A. (2000)

  2. Quantitative parameters of seminiferous epithelium in secretory and excretory oligoazoospermia.

    Science.gov (United States)

    Francavilla, S; Martini, M; Properzi, G; Cordeschi, G

    1990-01-01

    Testicular biopsy specimens from infertile men (sperm count, less than 10(6)/ml) were evaluated on 1-micron thick sections, and counts of stem cells and differentiated spermatogonia, primary spermatocytes, early and late spermatids, and Sertoli cells were compared to counts in six fertile men. Biopsy specimens were also compared for the appearance of seminiferous tubule wall, blood vessels, and interstitium. Infertile men were grouped according to the following diagnoses: hypospermatogenesis (n = 5), spermatocyte arrest of spermatogenesis (n = 5), and obstruction of the genital tract (n = 7). A low productivity of spermatogenesis in cases of hypospermatogenesis appeared to be due to an exaggerated degeneration of primary spermatocytes and to a yield of abnormal spermatids. A block of meiosis in spermatocyte arrest was associated with a degeneration of primary spermatocytes and with a reduced number of staminal spermatogonia. Abnormal spermiogenesis was observed in cases of obstruction of the genital tract and was associated with an increase in stem cell spermatogonia. A thickening of seminiferous tubule and blood vessel walls could be responsible for the limited functional capacity of Sertoli cells, causing altered spermiogenesis in cases of excretory azoospermia. A severe primitive failure of Sertoli cells in secretory oligoazoospermia could account for a deranged maturation and degeneration of premeiotic and postmeiotic germ cells.

  3. Combined static-dynamic MR urography for the simultaneous evaluation of morphology and function in urinary tract obstruction. II. Findings in experimentally induced ureteric stenosis

    International Nuclear Information System (INIS)

    Rohrschneider, W.K.; Becker, K.; Hoffend, J.; Clorius, J.H.; Darge, K.; Kooijman, H.; Troeger, J.

    2000-01-01

    Purpose. To assess the diagnostic value of combined static-dynamic MR urography (MRU) for the functional-morphological evaluation of experimentally induced urinary tract obstruction in the piglet. Materials and methods. In 20 piglets unilateral ureteric stenosis was created operatively. Post-surgery repeated comparative examinations were obtained with MRU, diuretic renal scintigraphy (DRS), excretory urography (EU) and ultrasound (US). MRU was performed as a combination study with a static 3D-IR-TSE sequence and a dynamic 2D-FFE sequence after Gd-DTPA with frusemide administration. Results. MRU allowed complete depiction of the prestenotic urinary tract and of the stenosis in all cases. In 43 comparative studies MRU was superior to EU in 36, EU to MRU in 2. When single kidney function was calculated with both MRU and DRS, results were highly correlated (r = 0.92). When urinary excretion was compared, significant agreement was achieved with concordant findings in 86 % and slightly discordant results in 12 %. Conclusions. Static-dynamic MR urography permits excellent depiction of experimentally induced urinary tract obstruction in piglets and reliable assessment of individual renal function and urinary excretion. Two advantages of the method stand out - it does not require radiation and it permits functional-morphological correlation. (orig.)

  4. Comparison of excretory urographic contrast effects of dimeric and monomeric non-ionic iodinated contrast media in dogs

    International Nuclear Information System (INIS)

    Kishimoto, M.; Yamada, K.; Watanabe, A.; Miyamoto, K.; Iwasaki, T.; Miyake, Y.

    2007-01-01

    In excretory urography, the osmolarity of contrast media has rarely been treated as important in veterinary medicine. In this study, the contrast effect of two contrast media (monomeric iohexol and dimeric iodixanol) in the renal cortex and aorta were compared using computed tomography (CT). Five beagle dogs were used and the study employed a cross-over method for each contrast media. The results showed that there was no difference between the media in the aorta, but iodixanol showed higher CT value and a longer contrast effect than iohexol in the renal cortex, in spite of having the same iodine dosage. It is believed that iodixanol, with its low osmolarity, is diluted less by osmotic diuresis than monomeric iohexol. It is important to consider the osmolarity of the contrast media when evaluating the contrast effect, and it is essential to use the same contrast media for each examination, or the renal excretory speed will be under/overestimated

  5. COX2 inhibition during nephrogenic period induces ANG II hypertension and sex-dependent changes in renal function during aging.

    Science.gov (United States)

    Reverte, Virginia; Tapia, Antonio; Loria, Analia; Salazar, Francisco; Llinas, M Teresa; Salazar, F Javier

    2014-03-01

    This study was performed to test the hypothesis that ANG II contributes to the hypertension and renal functional alterations induced by a decrease of COX2 activity during the nephrogenic period. It was also examined whether renal functional reserve and renal response to volume overload and high sodium intake are reduced in 3-4- and 9-11-mo-old male and female rats treated with vehicle or a COX2 inhibitor during nephrogenic period (COX2np). Our data show that this COX2 inhibition induces an ANG II-dependent hypertension that is similar in male and female rats. Renal functional reserve is reduced in COX2np-treated rats since their renal response to an increase in plasma amino acids levels is abolished, and their renal ability to eliminate a sodium load is impaired (P renal excretory ability is similar in both sexes during aging but does not induce the development of a sodium-sensitive hypertension. However, the prolonged high-sodium intake at 9-11 mo of age leads to a greater proteinuria in male than in female (114 ± 12 μg/min vs. 72 ± 8 μg/min; P Renal hemodynamic sensitivity to acute increments in ANG II is unaltered in both sexes and at both ages in COX2np-treated rats. In summary, these results indicate that the reduction of COX2 activity during nephrogenic period programs for the development of an ANG II-dependent hypertension, reduces renal functional reserve to a similar extent in both sexes, and increases proteinuria in males but not in females when there is a prolonged increment in sodium intake.

  6. Diagnostic value of diuretic-enhanced excretory MR urography in patients with obstructive uropathy

    Energy Technology Data Exchange (ETDEWEB)

    Karabacakoglu, Aydin E-mail: radaydin@hotmail.com; Karakose, Serdar; Ince, Ozlem; Cobankara, Osman Ege; Karalezli, Giray

    2004-12-01

    Purpose: Ultrasonography and conventional intravenous urography are most common methods in diagnosis of obstructive uropathies. The disadvantage of ultrasonography is inability of visualizing middle and lower one thirds of ureter, while intravenous urography is using radiation, also functionally extra loading effect on kidneys. In this study, the diagnostic value of MR urography on obstructive uropathy were investigated. Materials and methods: Forty five patients who were suffered from obstructive uropathy examined by ultrasonography, intravenous urography and diuretic-enhanced excretory MR urography by using MR-contrast-agent. Results: MR urography established accuracy rate of 92.8% for stone diseases which formed the largest group in this study, however, in other causes of obstructive uropathy, MR urography provide 100% correct diagnosis. Conclusion: MR urography provide high quality images for diagnosing and determining causes of urinary obstruction defining position and severity of dilatations as well as showing localization of the pathology. We think that MR urography should be a primary investigation in patients with obstructive uropathy who have contrast agent and X-ray contrindication.

  7. Diagnostic value of diuretic-enhanced excretory MR urography in patients with obstructive uropathy

    International Nuclear Information System (INIS)

    Karabacakoglu, Aydin; Karakose, Serdar; Ince, Ozlem; Cobankara, Osman Ege; Karalezli, Giray

    2004-01-01

    Purpose: Ultrasonography and conventional intravenous urography are most common methods in diagnosis of obstructive uropathies. The disadvantage of ultrasonography is inability of visualizing middle and lower one thirds of ureter, while intravenous urography is using radiation, also functionally extra loading effect on kidneys. In this study, the diagnostic value of MR urography on obstructive uropathy were investigated. Materials and methods: Forty five patients who were suffered from obstructive uropathy examined by ultrasonography, intravenous urography and diuretic-enhanced excretory MR urography by using MR-contrast-agent. Results: MR urography established accuracy rate of 92.8% for stone diseases which formed the largest group in this study, however, in other causes of obstructive uropathy, MR urography provide 100% correct diagnosis. Conclusion: MR urography provide high quality images for diagnosing and determining causes of urinary obstruction defining position and severity of dilatations as well as showing localization of the pathology. We think that MR urography should be a primary investigation in patients with obstructive uropathy who have contrast agent and X-ray contrindication

  8. Anatomical study of the renal excretory system in pigs. A review of its characteristics as compared to its human counterpart.

    Science.gov (United States)

    Gómez, F A; Ballesteros, L E; Estupiñán, H Y

    2017-01-01

    Despite the importance of the pyelocalyceal system in the pig as an experimental model, there is little information about this particular anatomical subject. We determined the morphological characteristics of the renal excretory system in pigs. This descriptive cross-sectional study evaluated 130 pairs of kidneys of pigs destined to slaughter. The pyelocalyceal system was subjected to injection technique - corrosion by infusion of polyester resin (85% Palatal and 15% Styrene) and subsequent infusion in potassium hydroxide (KOH) for 10 days. The significance level used was p renal excretory system is characterised by the presence of type A major cranial and caudal calyxes seen in 34.3% of the kidneys (type A1 in 30% and type A2 in 4.3%). type B calyxes, corresponding to minor calyxes draining directly into the renal pelvis, were present in 65.7% of the specimens (type B1 59.2%; type B2 6.5% of the cases). The number of minor calyxes in the collector system was 7.9 ± 2.27 with statistically significant differences in side (p = 0.0047). The morphometric characteristics of the kidneys in this study are slightly smaller than reported in humans. Similarly, the incidence of type A renal excretory system distribution is highest in humans and lowest in pigs. Due to its few morphological differences, the pig kidney is an excellent model for teaching- -learning processes, for research purposes, and for training of urologic applications.

  9. Comparison of excretory phase, helical computed tomography with intravenous urography in patients with painless haematuria

    International Nuclear Information System (INIS)

    O'Malley, M.E.; Hahn, P.F.; Yoder, I.C.; Gazelle, G.S.; McGovern, F.J.; Mueller, P.R.

    2003-01-01

    AIM: To compare excretory phase, helical computed tomography (CT) with intravenous (IV) urography for evaluation of the urinary tract in patients with painless haematuria. MATERIALS AND METHODS: Ninety-one out-patients had IV urography followed by helical CT limited to the urinary tract. Both IV urograms and CT images were evaluated for abnormalities of the urinary tract in a blinded, prospective manner. The clinical significance of abnormalities was scored subjectively and receiver operator characteristic curve analysis was performed. RESULTS: In 69 of 91 patients (76%), no cause of haematuria was identified. In 22 of 91 patients (24%), the cause of haematuria was identified as follows: transitional cell cancer of the bladder (n=15), urinary tract stones (n=3), cystitis (n=2), haemorrhagic pyelitis (n=1) and benign ureteral stricture (n=1). With IV urography, there were 15 true-positive, seven false-negative and three false-positive interpretations. With CT, there were 18 true-positive, four false-negative and two false-positive interpretations. There was no significant difference between IV and CT urography for the significance of the positive interpretations (n=0.47). CONCLUSION: Excretory phase CT urography was comparable with IV urography for evaluation of the urinary tract in patients with painless haematuria. However, the study population did not include any upper tract cancers. O'Malley M. E. et al. (2003). Clinical Radiology 58, 294-300

  10. Diuretic-enhanced gadolinium excretory MR urography: comparison of conventional gradient-echo sequences and echo-planar imaging

    Energy Technology Data Exchange (ETDEWEB)

    Nolte-Ernsting, C.C.A.; Tacke, J.; Adam, G.B.; Haage, P.; Guenther, R.W. [Univ. of Technology, Aachen (Germany). Dept. of Diagnostic Radiology; Jung, P.; Jakse, G. [Univ. of Technology, Aachen (Germany). Dept. of Urology

    2001-01-01

    The aim of this study was to investigate the utility of different gadolinium-enhanced T1-weighted gradient-echo techniques in excretory MR urography. In 74 urologic patients, excretory MR urography was performed using various T1-weighted gradient-echo (GRE) sequences after injection of gadolinium-DTPA and low-dose furosemide. The examinations included conventional GRE sequences and echo-planar imaging (GRE EPI), both obtained with 3D data sets and 2D projection images. Breath-hold acquisition was used primarily. In 20 of 74 examinations, we compared breath-hold imaging with respiratory gating. Breath-hold imaging was significantly superior to respiratory gating for the visualization of pelvicaliceal systems, but not for the ureters. Complete MR urograms were obtained within 14-20 s using 3D GRE EPI sequences and in 20-30 s with conventional 3D GRE sequences. Ghost artefacts caused by ureteral peristalsis often occurred with conventional 3D GRE imaging and were almost completely suppressed in EPI sequences (p < 0.0001). Susceptibility effects were more pronounced on GRE EPI MR urograms and calculi measured 0.8-21.7% greater in diameter compared with conventional GRE sequences. Increased spatial resolution degraded the image quality only in GRE-EPI urograms. (orig.)

  11. Excretory products of the cestode, Schistocephalus solidus, modulate in vitro responses of leukocytes from its specific host, the three-spined stickleback (Gasterosteus aculeatus).

    Science.gov (United States)

    Scharsack, Jörn Peter; Gossens, Anabel; Franke, Frederik; Kurtz, Joachim

    2013-12-01

    Helminth parasites have evolved remarkable strategies to manipulate the immune system of their hosts. During infections of three-spined stickleback (Gasterosteus aculeatus) with the cestode Schistocephalus solidus prominent immunological changes occur, presumably due to manipulative activity of the parasite. We hypothesise that excretory/secretory products of the parasite are involved in the manipulation of the stickleback's immune system and that this may depend on the individual parasite and its origin. We therefore produced S. solidus conditioned cell culture media (SSCM) with parasites from different origins (Norway, Spain and Germany) and exposed head kidney leukocytes (HKL) from un-infected sticklebacks in cell cultures to SSCM. After in vitro culture, HKL were subjected to differential cell counts (granulocytes/lymphocytes) by means of flow cytometry. Leukocyte sub-populations were analysed for cell viability and changes in cell morphology. The respiratory burst activity was measured with a luminescence assay. Exposure of HKL to SSCM induced an up-regulation of respiratory burst activity after already 1 h, which was still elevated at 24 h, but which was in some cases significantly down-regulated after 96 h. Respiratory burst was positively correlated with the number of live granulocytes in the culture, suggesting that the respiratory burst activity was changed by SSCM effects on granulocyte viability. After 1 h and 24 h of HKL culture, no lymphocyte responses to SSCM were detectable, but after 96 h lymphocyte viability was significantly decreased with SSCM from Spanish S. solidus. In these cultures, residual lymphocytes increased in size, suggesting that cell death and activation might have occurred in parallel. The highest respiratory burst activity was induced by SSCM from Spanish parasites, in particular when they were grown in sympatric sticklebacks. The in vitro HKL responses to SSCM depended on the individual parasite and its population of origin

  12. Gd-BOPTA-enhanced excretory MR urography without administration of diuretics; Gd-BOPTA-gestuetzte MR-Ausscheidungsurographie ohne Diuretikagabe

    Energy Technology Data Exchange (ETDEWEB)

    Allkemper, T.; Tombach, B.; Heindel, W. [Muenster Univ. (Germany). Inst. fuer Klinische Radiologie

    2001-02-01

    Purpose: To evaluate the feasibility and clinical utility of Gd-BOPTA enhanced excretory magnetic resonance urography without additional administration of diuretics in correlation with conventional urography. Method: 15 preoperative patients with pelvic tumors were examined at 1.5 T using a breath-hold high-resolution 3D-FLASH sequence during first-pass as well as 5, 10, 15 minutes after iv. injection of 0.05 mmol/kg BW Gd-BOPTA (MultiHance {sup trademark}) without administration of diuretics. Post-processed coronal and multiplanar MIP reconstructions were compared to conventional excretory urography with regard to morphologic accuracy, anatomic variability, filling defects, cause and level of obstruction or compression, tumor visibility, and time-effectiveness by two independent radiologists. Results: Visualization of the urinary tract by MRU was comparable to conventional excretory urography in 14 of 15 cases. Caliceal fornices were better delineated on conventional urographies, whereas MRU was considered superior in the assessment of the inferior ureter sections, the urinary bladder and obstructive tumors, whose extents could be clearly marked out. Examination times of both techniques were comparable. Conclusion: These first results show that non-diuretic Gd-BOPTA enhanced MRU is comparable to conventional excretory urography for the preoperative diagnosis of pelvic tumors. Further improvements of this technique seem possible by optimization of examination intervals and injection doses. (orig.) [German] Ziel: Abschaetzung der Durchfuehrbarkeit und des klinischen Nutzens der Gd-BOPTA-gestuetzten MR-Ausscheidungsurographie (MRU) ohne zusaetzliche Diuretikagabe im Vergleich zur konventionellen Ausscheidungsurographie. Methoden: 15 Patienten mit Beckentumoren wurden praeoperativ an einem 1.5 T-Ganzkoerpersystem mit Hilfe einer atemgehaltenen, hochaufloesenden 3D-FLASH-Sequenz unmittelbar nach intra-venoeser Applikation von 0,05 mmol/kg KG Gd-BOPTA (MultiHance {sup

  13. Antigravity suit inflation - Kidney function and cardiovascular and hormonal responses in men

    Science.gov (United States)

    Geelen, Ghislaine; Kravik, Stein E.; Hadj-Aissa, Aoumeur; Leftheriotis, Georges; Vincent, Madeleine

    1989-01-01

    The effect of the lower body positive pressure (LBPP) on kidney function in normal men was investigated in experiments in which the subjects underwent 30 min of sitting and then were subjected to 4.5 h of 70-deg head-up tilt. During the last 3 h of the tilt period, an antigravity suit (60 T legs, 30 T abdomen) was applied. The results showed that LBPP induces a significant increase in effective renal plasma flow and significant changes in the kidney excretory patterns, which were similar to those observed during a water immersion or the early phase of bed rest.

  14. Serum Symmetric Dimethylarginine as an Early Marker of Excretory Dysfunction in Canine Leishmaniosis (L. infantum Induced Nephropathy

    Directory of Open Access Journals (Sweden)

    Esther Torrent

    2018-01-01

    Full Text Available The aims of the study were to determine whether symmetric dimethylarginine (SDMA was increased in dogs with leishmaniosis and to assess its relationship with creatinine concentration and urinary protein : creatinine ratio (UPC to determine its utility as a marker of early excretory dysfunction. Fifty-three dogs with leishmaniosis classified according to the LeishVet clinical staging (stage I, n=5, stage II, n=30; stage III, n=12; stage IV, n=6 were selected and compared with 41 clinically healthy dogs. Thirty-nine dogs with leishmaniosis were also followed up for six months. SDMA concentrations on the day of diagnosis were significantly higher in dogs with leishmaniosis with respect to control dogs and in dogs from LeishVet stage IV when compared with the other stages. Increased UPC (>0.5, SDMA (>19 μg/dL, and creatinine concentrations (≥1.4 mg/dL were found in 47.1%, 15.1%, and 9.4% of dogs with leishmaniosis, respectively. SDMA concentration was increased in 24% of proteinuric dogs, in 7% of nonproteinuric dogs, and in four of five dogs with increased creatinine. SDMA concentration ≥ 25 μg/dL was associated with clinical chronic kidney disease (CKD after six months. Our results did not demonstrate advantages in using SDMA concentration as an early marker of CKD when compared to creatinine and UPC in canine leishmaniosis.

  15. Studies on the influence on the excretory kinetics of 125I-Adipiodon

    International Nuclear Information System (INIS)

    Koenig, H.

    1982-01-01

    The possibility of influencing distribution and elimination of 125 I-Adipiodon ( 125 I-iodipamide meglumine) by a preceding administration of Falignost (iomeglamic acid) as well as by dose-time variants of the mechanic intravenous application of contrast medium was tested in 55 anicteric and 2 icteric patients within clinically indicated cholegraphic examination with the aim of methodical optimization. For the detection of principal regularities comparative studies with 125 I-Adipiodon and Falignost in rats as well as examinations of protein binding of 125 I-Adipiodon in the plasm of rats and in the plasm and in mixed serum (application in vitro) of patients by gel filtration with Epidex B 2 coarse and batch operation on more than 1,200 samples were additionally carried out. For combined cholecystography with intravenous infusion of Adipiodon in immediate temporal connection with the administration of Falignost a reduced visibility of the biliary tract in the X-ray picture is not to be expected as the consequence of the mutual influence of the contrast media. For intact excretory function of liver and kidneys the combined cholecystography can be recommended. The effects of a dose increase, of protracted infusion of Adipiodon and of the intravenous administration of 0.01 g metroclopramide on the demonstration of the biliary tract in the intravenous cholegram are outlined. (author)

  16. Genome analysis of Excretory/Secretory proteins in Taenia solium reveals their Abundance of Antigenic Regions (AAR).

    Science.gov (United States)

    Gomez, Sandra; Adalid-Peralta, Laura; Palafox-Fonseca, Hector; Cantu-Robles, Vito Adrian; Soberón, Xavier; Sciutto, Edda; Fragoso, Gladis; Bobes, Raúl J; Laclette, Juan P; Yauner, Luis del Pozo; Ochoa-Leyva, Adrián

    2015-05-19

    Excretory/Secretory (ES) proteins play an important role in the host-parasite interactions. Experimental identification of ES proteins is time-consuming and expensive. Alternative bioinformatics approaches are cost-effective and can be used to prioritize the experimental analysis of therapeutic targets for parasitic diseases. Here we predicted and functionally annotated the ES proteins in T. solium genome using an integration of bioinformatics tools. Additionally, we developed a novel measurement to evaluate the potential antigenicity of T. solium secretome using sequence length and number of antigenic regions of ES proteins. This measurement was formalized as the Abundance of Antigenic Regions (AAR) value. AAR value for secretome showed a similar value to that obtained for a set of experimentally determined antigenic proteins and was different to the calculated value for the non-ES proteins of T. solium genome. Furthermore, we calculated the AAR values for known helminth secretomes and they were similar to that obtained for T. solium. The results reveal the utility of AAR value as a novel genomic measurement to evaluate the potential antigenicity of secretomes. This comprehensive analysis of T. solium secretome provides functional information for future experimental studies, including the identification of novel ES proteins of therapeutic, diagnosis and immunological interest.

  17. Influence of drugs with antioxidant properties on the state of the sperm antioxidant system in men with excretory-toxic forms of infertility

    Directory of Open Access Journals (Sweden)

    O.K. Onufrovych

    2013-10-01

    Full Text Available Since the development of many disorders of the reproductive function in men involves processes of free radical oxidation, the purpose of this study was to form an evaluation of the pro- and antioxidant status of sperm and to restore its biological usefulness in men with excretory-toxic forms of infertility by using drugs with antioxidant properties. It is shown that excretory-toxic forms of infertility in men are mostly caused by such infectious agents as Chlamydia (22%, Chlamydia + Ureaplasma (16%, Chlamydia + Trichomonas (13%, Ureaplasma (10%. This reduces the total number of sperm in the ejaculate by 2.7 times, and motility by 1.8 times. The number of abnormal forms increases by 1.75 times. With the development of chronic inflammation of the male sex organs sperm lipid peroxidation increases by 1.3 times while the activity of glutathione peroxidase decreases (by 2.3 times and that of glutathione reductase (by 1.7 times. We observed a close correlation between the low biological quality of sperm (low concentration, low number and motility of sperm in the ejaculate with activation of lipid peroxidation and inhibition of activity of the glutathione antioxidant system. In the case of superoxide dismutase, the negative impact of reactive oxygen species on this enzyme was not observed. A course of drugs with antioxidant properties – vitamin E, vitamin C and zinc sulfate leads to improvement in the indicators on the spermagram (mostly sperm mobility and morphology, to reduction of the number of peroxide compounds and activation of the glutathione antioxidant system. In this case, the activity of glutathione peroxidase is increased by 1.5 times and the activity of glutathione reductase by 1.3 times. The activity of superoxide dismutase at the same time approaches the norm for zoospermia. The data obtained show that one of the pathogenic factors of the chronic inflammation of male sex organs, considered as a main developmental reason for infertility

  18. In vivo thermoluminescent dosimetry in studies of helicoid computed tomography and excretory urogram

    International Nuclear Information System (INIS)

    Cruz C, D.; Azorin N, J.; Saucedo A, V.M.; Barajas O, J.L.

    2005-01-01

    The dosimetry is the field of measurement of the ionizing radiations. It final objective is to determine the 'absorbed dose' for people. The dosimetry is vital in the radiotherapy, the radiological protection and the treatment technologies by irradiation. Presently work, we develop 'In vivo' dosimetry, in exposed patients to studies of helical computed tomography and excretory urogram. The dosimetry 'in vivo' was carried out in 20 patients selected aleatorily, for each medical study. The absorbed dose was measured in points of interest located in crystalline, thyroid, chest and abdomen of each patient, by means of thermoluminescent dosemeters (TLD) LiF: Mg,Cu,P + Ptfe of national fabrication. Also it was quantified the dose in the working area. (Author)

  19. Assessment of the function of the nervus intermedius by means of functional salivary gland-scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, J.P.; Bertram, G.; Moedder, G.

    1982-01-01

    Using functional scintigraphy of the salivary glands, the function of the nervus intermedius can be assessed by estimating excretory quotients for both submandibular glands. This method is preferred to the standard salivation test method of Magielski and Blatt, despite a minimal exposure of the patient to radiation from the injected Natriumpertechnetat. The technical course of this investigation, along with the indications for its use, will be presented.

  20. Helminth-induced regulatory T cells and suppression of allergic responses.

    Science.gov (United States)

    Logan, Jayden; Navarro, Severine; Loukas, Alex; Giacomin, Paul

    2018-05-28

    Infection with helminths has been associated with lower rates of asthma and other allergic diseases. This has been attributed, in part, to the ability of helminths to induce regulatory T cells that suppress inappropriate immune responses to allergens. Recent compelling evidence suggests that helminths may promote regulatory T cell expansion or effector functions through either direct (secretion of excretory/secretory molecules) or indirect mechanisms (regulation of the microbiome). This review will discuss key findings from human immunoepidemiological observations, studies using animal models of disease, and clinical trials with live worm infections, discussing the therapeutic potential for worms and their secreted products for treating allergic inflammation. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  1. Diagnostic potential of low molecular weight excretory secretory proteins of Paramphistomum epiclitum for caprine amphistomosis.

    Science.gov (United States)

    Jaiswal, Amit Kumar; Shanker, Daya; Sudan, Vikrant; Singh, Amit

    2018-06-15

    In the present study, the 75% alcoholic fractionation of excretory-secretory (ES) antigen isolated from 200 to 300 live P. epiclitum was assessed for its diagnostic potential for the detection of caprine amphistomosis by using antibody detection enzyme immunoassay. Prior to enzyme immunoassay, 75% alcoholic fractionation of excretory-secretory (ES) antigen was subjected to SDS- PAGE and western blot analysis for the presence of immunoreactive polypeptides. SDS-PAGE analysis of ES antigen resolved a total 7 polypeptides bands of size 56, 27, 25, 22.5, 12, 11 and 10 kDa. Western blot analysis revealed only two immunoreactive polypeptides (11 kDa and 12 kDa) when polypeptides resolved in SDS-PAGE were probed with known positive pooled serum. None of the polypeptides showed reactions with pooled known negative serum. The working dilutions of antigen, sera and conjugates were determined by checkerboard titration for employing ELISA and cut-off O.D. was calculated 0.616 by using the mean absorbance value of 11 negative kid sera. The sensitivity and specificity of ELISA was found to be 100% and 86.76%, respectively. As per kappa value estimation, the strength of agreement was found to be good. Antibodies to 75% alcoholic fractionation of ES antigen was detected in 20% goats (n = 160) of either sex, although faecal examination detected 10.6% goats to be infected with amphistomosis. The study confirmed that 75% alcoholic fractionation of ES antigen of P. epiclitum based ELISA had good value for serodiagnosis of caprine amphistomosis. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Adrenoceptors of the medial septal area modulate water intake and renal excretory function induced by central administration of angiotensin II

    Directory of Open Access Journals (Sweden)

    Saad W.A.

    2002-01-01

    Full Text Available We investigated the role of alpha-adrenergic antagonists and clonidine injected into the medial septal area (MSA on water intake and the decrease in Na+, K+ and urine elicited by ANGII injection into the third ventricle (3rdV. Male Holtzman rats with stainless steel cannulas implanted into the 3rdV and MSA were used. ANGII (12 nmol/µl increased water intake (12.5 ± 1.7 ml/120 min. Clonidine (20 nmol/µl injected into the MSA reduced the ANGII-induced water intake (2.9 ± 0.5 ml/120 min. Pretreatment with 80 nmol/µl yohimbine or prazosin into the MSA also reduced the ANGII-induced water intake (3.0 ± 0.4 and 3.1 ± 0.2 ml/120 min, respectively. Yohimbine + prazosin + clonidine injected into the MSA abolished the ANGII-induced water intake (0.2 ± 0.1 and 0.2 ± 0.1 ml/120 min, respectively. ANGII reduced Na+ (23 ± 7 µEq/120 min, K+ (27 ± 3 µEq/120 min and urine volume (4.3 ± 0.9 ml/120 min. Clonidine increased the parameters above. Clonidine injected into the MSA abolished the inhibitory effect of ANGII on urinary sodium. Yohimbine injected into the MSA also abolished the inhibitory effects of ANGII. Yohimbine + clonidine attenuated the inhibitory effects of ANGII. Prazosin injected into the MSA did not cause changes in ANGII responses. Prazosin + clonidine attenuated the inhibitory effects of ANGII. The results showed that MSA injections of alpha1- and alpha2-antagonists decreased ANGII-induced water intake, and abolished the Na+, K+ and urine decrease induced by ANGII into the 3rdV. These findings suggest the involvement of septal alpha1- and alpha2-adrenergic receptors in water intake and electrolyte and urine excretion induced by central ANGII.

  3. Excretory MR urography using breathhold three-dimensional FISP: comparison with MR urography using HASTE technique

    Energy Technology Data Exchange (ETDEWEB)

    Song, Won Kue; Lee, Jeong Min; Jin, Kong Young; Hwang, Ho keung; Han, Young Min [Chonbuk Narional University Hospital, Chonju (Korea, Republic of); Ym, Seong Hee [Namwon Medical Center, Chonju (Korea, Republic of)

    2000-09-01

    To compare the usefulness of gadolinium-enhanced excretory MR urography using breath-hold three-dimensional fast imaging with steady state precession (3-D FISP) with conventional MR urography using the half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequence in the evaluation of obstructive uropathy. Twenty-three patients in whom ultrasonography (US) and/or intravenous urography (IVU) revealed signs of urinary obstruction were enrolled in this study. Fifteen were men and eight were women, and their mean age was 54 (range, 21-80) years. All MR images were obtained using a 1.5T MR unit. MR urography using the HASTE technique (MRU) and gadolinium-enhanced excretory MR urography using the 3D-FISP technique were performed, and in all cases, reconstructions involved maximum intensity projection. For contrast-enhanced MR urography(CEMRU), images were obtained 3, 5, 20, and 30 minutes after the administration of intravenous contrast media, and for selected cases, additional images were obtained until 24 hours after contrast media injection. For qualitative analysis, two experienced radiologists compared CEMRU and MRU in terms of their diagnostic value as regards the level and cause of urinary obstruction, and morphologic accuracy. In addition, signal to noise ration(SNR) and contrast to noise ration (CNR) of the urinary tract at each anatomic level were quantitatively analysed. Quantitative analysis showed that in terms of SNR and CNR of the urinary tract at the level of the mid and distal ureter, CEMRU using 3-D FISP was better than MRU using HASTE (p less than 0.05). Qualitative analysis indicated that for the depiction of the whole length of normal ureter, and detection of the level of obstruction, anatomic anomalies and intrinsic tumors, 3-D FISP was superior to HASTE. There was, however, no difference between these two modalities in the diagnosis of ureteral stone and the degree of hydronephrosis. In addition, 3-D FISP was better than HASTE for the

  4. Excretory MR urography using breathhold three-dimensional FISP: comparison with MR urography using HASTE technique

    International Nuclear Information System (INIS)

    Song, Won Kue; Lee, Jeong Min; Jin, Kong Young; Hwang, Ho keung; Han, Young Min; Ym, Seong Hee

    2000-01-01

    To compare the usefulness of gadolinium-enhanced excretory MR urography using breath-hold three-dimensional fast imaging with steady state precession (3-D FISP) with conventional MR urography using the half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequence in the evaluation of obstructive uropathy. Twenty-three patients in whom ultrasonography (US) and/or intravenous urography (IVU) revealed signs of urinary obstruction were enrolled in this study. Fifteen were men and eight were women, and their mean age was 54 (range, 21-80) years. All MR images were obtained using a 1.5T MR unit. MR urography using the HASTE technique (MRU) and gadolinium-enhanced excretory MR urography using the 3D-FISP technique were performed, and in all cases, reconstructions involved maximum intensity projection. For contrast-enhanced MR urography(CEMRU), images were obtained 3, 5, 20, and 30 minutes after the administration of intravenous contrast media, and for selected cases, additional images were obtained until 24 hours after contrast media injection. For qualitative analysis, two experienced radiologists compared CEMRU and MRU in terms of their diagnostic value as regards the level and cause of urinary obstruction, and morphologic accuracy. In addition, signal to noise ration(SNR) and contrast to noise ration (CNR) of the urinary tract at each anatomic level were quantitatively analysed. Quantitative analysis showed that in terms of SNR and CNR of the urinary tract at the level of the mid and distal ureter, CEMRU using 3-D FISP was better than MRU using HASTE (p less than 0.05). Qualitative analysis indicated that for the depiction of the whole length of normal ureter, and detection of the level of obstruction, anatomic anomalies and intrinsic tumors, 3-D FISP was superior to HASTE. There was, however, no difference between these two modalities in the diagnosis of ureteral stone and the degree of hydronephrosis. In addition, 3-D FISP was better than HASTE for the

  5. The assessment of the function of the nervus intermedius by means of functional salivary gland-scintigraphy

    International Nuclear Information System (INIS)

    Thomas, J.P.; Bertram, G.; Moedder, G.

    1982-01-01

    Using functional scintigraphy of the salivary glands, the function of the nervus intermedius can be assessed by estimating excretory quotients for both submandibular glands. This method is preferred to the standard salivationtest method of Magielski and Blatt, despite a minimal exposure of the patient to radiation from the injected Natriumpertechnetat. The technical course of this investigation, along with the indications for its use, will be presented. (orig.) [de

  6. Stage- and gender-specific proteomic analysis of Brugia malayi excretory-secretory products.

    Directory of Open Access Journals (Sweden)

    Yovany Moreno

    Full Text Available INTRODUCTION: While we lack a complete understanding of the molecular mechanisms by which parasites establish and achieve protection from host immune responses, it is accepted that many of these processes are mediated by products, primarily proteins, released from the parasite. Parasitic nematodes occur in different life stages and anatomical compartments within the host. Little is known about the composition and variability of products released at different developmental stages and their contribution to parasite survival and progression of the infection. METHODOLOGY/PRINCIPAL FINDINGS: To gain a deeper understanding on these aspects, we collected and analyzed through 1D-SDS PAGE and LC-MS/MS the Excretory-Secretory Products (ESP of adult female, adult male and microfilariae of the filarial nematode Brugia malayi, one of the etiological agents of human lymphatic filariasis. This proteomic analysis led to the identification of 228 proteins. The list includes 76 proteins with unknown function as well as also proteins with potential immunoregulatory properties, such as protease inhibitors, cytokine homologues and carbohydrate-binding proteins. Larval and adult ESP differed in composition. Only 32 proteins were shared between all three stages/genders. Consistent with this observation, different gene ontology profiles were associated with the different ESP. CONCLUSIONS/SIGNIFICANCE: A comparative analysis of the proteins released in vitro by different forms of a parasitic nematode dwelling in the same host is presented. The catalog of secreted proteins reflects different stage- and gender-specific related processes and different strategies of immune evasion, providing valuable insights on the contribution of each form of the parasite for establishing the host-parasite interaction.

  7. Excretory/secretory products from two Fasciola hepatica isolates induce different transcriptional changes and IL-10 release in LPS-activated bovine "BOMA" macrophages.

    Science.gov (United States)

    Bąska, Piotr; Norbury, Luke James; Zawistowska-Deniziak, Anna; Wiśniewski, Marcin; Januszkiewicz, Kamil

    2017-10-01

    Fasciola hepatica are trematodes that reside in the bile ducts of mammals. Infection causes US$3 billion in losses annually in animal production and is considered a zoonosis of growing importance. An under-represented area in F. hepatica research has been the examination of the different immunomodulatory abilities of various parasite isolates on the host immune system. In this paper, this issue was explored, with the bovine macrophage cell line "BOMA". The cells were matured by LPS treatment and stimulated with excretory/secretory antigens (ES) from two Fasciola hepatica isolates: a laboratory isolate "Weybridge" (Fh-WeyES) and a wild isolate (Fh-WildES). As expected, stimulation with antigen mixtures with highly similar compositions resulted in mild transcriptomic differences. However, there were significant differences in cytokine levels. Compared to Fh-WeyES, exposure to Fh-WildES upregulated 27 and downregulated 30 genes. Fh-ES from both isolates diminished the release of TNF-α, whereas only Fh-WildES decreased IL-10 secretion. Neither Fh-WeyES nor Fh-WildES had an impact on IL-12 release. Our results indicate that various isolates can have different immunomodulatory abilities and impacts on the bovine immune system.

  8. Dietary creatine supplementation during pregnancy: a study on the effects of creatine supplementation on creatine homeostasis and renal excretory function in spiny mice.

    Science.gov (United States)

    Ellery, Stacey J; LaRosa, Domenic A; Kett, Michelle M; Della Gatta, Paul A; Snow, Rod J; Walker, David W; Dickinson, Hayley

    2016-08-01

    Recent evidence obtained from a rodent model of birth asphyxia shows that supplementation of the maternal diet with creatine during pregnancy protects the neonate from multi-organ damage. However, the effect of increasing creatine intake on creatine homeostasis and biosynthesis in females, particularly during pregnancy, is unknown. This study assessed the impact of creatine supplementation on creatine homeostasis, body composition, capacity for de novo creatine synthesis and renal excretory function in non-pregnant and pregnant spiny mice. Mid-gestation pregnant and virgin spiny mice were fed normal chow or chow supplemented with 5 % w/w creatine for 18 days. Weight gain, urinary creatine and electrolyte excretion were assessed during supplementation. At post mortem, body composition was assessed by Dual-energy X-ray absorptiometry, or tissues were collected to assess creatine content and mRNA expression of the creatine synthesising enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT) and the creatine transporter (CrT1). Protein expression of AGAT and GAMT was also assessed by Western blot. Key findings of this study include no changes in body weight or composition with creatine supplementation; increased urinary creatine excretion in supplemented spiny mice, with increased sodium (P < 0.001) and chloride (P < 0.05) excretion in pregnant dams after 3 days of supplementation; lowered renal AGAT mRNA (P < 0.001) and protein (P < 0.001) expressions, and lowered CrT1 mRNA expression in the kidney (P < 0.01) and brain (P < 0.001). Creatine supplementation had minimal impact on creatine homeostasis in either non-pregnant or pregnant spiny mice. Increasing maternal dietary creatine consumption could be a useful treatment for birth asphyxia.

  9. Functional dynamic MR imaging and pharmacokinetics of Gd-DTPA in patients with renal failure

    International Nuclear Information System (INIS)

    Krestin, G.P.; Neufang, K.F.R.; Friedmann, G.; Clauss, W.; Schuhmann-Giampieri, G.; Stoeckl, B.

    1989-01-01

    This paper reports excretion of Gd-DTPA analyzed in 20 patients with renal parenchymal disease and decreased creatinine clearance (20-80 mL/min) and compared with excretion in five patients with normal renal function. All 25 underwent a dynamic MR study that employed fast gradient-echo sequences with single images during breath holding. The time between appearance of the contrast agent in the renal cortex and signal intensity drop in the medulla was an indicator of glomerular filtration rate and correlated well with creatinine clearance values. Fractionate urine collection and serum analysis up to 120 hours showed a prolonged but complete (98%) elimination of Gd-DTPA. Renal functional parameters did not change after administration of Gd-DTPA, and no nephrotoxic effects were observed. Thus, MR imaging provides a good quantitative evaluation of the glomerular filtration rate; moreover, administration of Gd-DTPA in patients with renal failure does not impair excretory function and can therefore be safely applied in patients with reduced excretory function

  10. Anti-inflammatory Potentials of Excretory/Secretory (ES and Somatic Products of Marshallagia marshalli on Allergic Airway Inflammation in BALB/c Mice

    Directory of Open Access Journals (Sweden)

    Sima PARANDE SHIRVAN

    2016-12-01

    Full Text Available Background: Inverse relationship between helminths infection and immune-mediated diseases has inspired researchers to investigate therapeutic potential of helminths in allergic asthma. Helminth unique ability to induce immunoregulatory responses has already been documented in several experimental studies. This study was designed to investigate whether excretory/secretory (ES and somatic products of Marshallagia marshalli modulate the development of ovalbumin-induced airway inflammation in a mouse model.Methods: This study was carried out at the laboratories of Immunology and Parasitology of Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran during spring and summer 2015. Allergic airway inflammation was induced in mice by intraperitoneal (IP injection with ovalbumin (OVA. The effects of ES and somatic products of M. marshalli were analyzed by inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF, pathological changes and IgE response.Results: Treatment with ES and somatic products of M. marshalli decreased cellular infiltration into BALF when they were administered during sensitization with allergen. Pathological changes were decreased in helminth-treated group, as demonstrated by reduced inflammatory cell infiltration, goblet cell hyperplasia, epithelial lesion and smooth muscle hypertrophy. However, no significant differences were observed in IgE serum levels, cytokines and eosinophil counts between different groups.Conclusion: This study provides new insights into anti-inflammatory effects of ES and somatic products of M. marshalli, during the development of non-eosinophilic model of asthma. Further study is necessary to characterize immunomodulatory molecules derived from M. marshalli as a candidate for the treatment of airway inflammation.

  11. Ancylostoma ceylanicum Excretory-Secretory Protein 2 Adopts a Netrin-Like Fold and Defines a Novel Family of Nematode Proteins

    Energy Technology Data Exchange (ETDEWEB)

    K Kucera; L Harrison; M Cappello; Y Modis

    2011-12-31

    Hookworms are human parasites that have devastating effects on global health, particularly in underdeveloped countries. Ancylostoma ceylanicum infects humans and animals, making it a useful model organism to study disease pathogenesis. A. ceylanicum excretory-secretory protein 2 (AceES-2), a highly immunoreactive molecule secreted by adult worms at the site of intestinal attachment, is partially protective when administered as a mucosal vaccine against hookworm anemia. The crystal structure of AceES-2 determined at 1.75 {angstrom} resolution shows that it adopts a netrin-like fold similar to that found in tissue inhibitors of matrix metalloproteases (TIMPs) and in complement factors C3 and C5. However, recombinant AceES-2 does not significantly inhibit the 10 most abundant human matrix metalloproteases or complement-mediated cell lysis. The presence of a highly acidic surface on AceES-2 suggests that it may function as a cytokine decoy receptor. Several small nematode proteins that have been annotated as TIMPs or netrin-domain-containing proteins display sequence homology in structurally important regions of AceES-2's netrin-likefold. Together, our results suggest that AceES-2 defines a novel family of nematode netrin-like proteins, which may function to modulate the host immune response to hookworm and other parasites.

  12. Excretory urography by subcutaneous injection of iodixanol in Persian squirrel (Sciurus anomalous)

    International Nuclear Information System (INIS)

    Veshkini, A.; Tavana, M.; Haghdost, I.S.; Masouleh, M.N.; Savojbolaghi, S.H.

    2011-01-01

    There are many indications for excretory urography in humans and animals. Intravenous urography (IVU) is the most practical method about other urography techniques are used because of difficulties for finding veins in IVU, due to small size of the patients. This study was performed to evaluate the feasibility of subcutaneous injection of iodixanol in providing a safe and diagnostic urogram in Persian squirrel. Twelve clinically healthy adult Persian squirrels were prepared and kept for two weeks prior to study. Blood tests were performed 7 days prior to the study. After eighteen hour fasting, animals were sedated by using xylazine/diazepam cocktail (xylazine 5mg/kg, diazepam 30mg/kg). Lateral and ventrodorsal control radiographs were taken. Thirteen hundred and 1800 mg iodine per kilogram body weight of iodixanol was injected subcutaneously over shoulder area in Persian squirrels (each dose for six Persian squirrels). Lateral and ventrodorsal radiographs were taken every 5 m

  13. The roles of supernatant of macrophage treated by excretory-secretory products from muscle larvae of Trichinella spiralis on the differentiation of C2C12 myoblasts

    Science.gov (United States)

    The excretory-secretory products (ESPs) released by the muscle-larvae (ML) stage of Trichinella spiralis have been suggested to be involved in nurse cell formation. However, the molecular mechanisms by which ML-ESPs modulate nurse cell formation remain unclear. Macrophages exert either beneficial or...

  14. Comparative assay of glutathione S-transferase (GSTs) activity of excretory-secretory materials and somatic extract of Fasciola spp parasites.

    Science.gov (United States)

    Alirahmi, Heshmatollah; Farahnak, Ali; Golmohamadi, Taghi; Esharghian, Mohammad Reza

    2010-01-01

    Fascioliasis is a worldwide parasitic disease in human and domestic animals. The causative agents of fascioliasis are Fasciola hepatica and Fasciola gigantica. In the recent years, fasciola resistance to drugs has been reported in the many of publications. Fasciola spp has detoxification system including GST enzyme which may be responsible for its resistance. Therefore , the aim of the study was to assay of GST enzyme activity in fasciola parasites. Fasciola gigantica and Fasciola hepatica helminths were collected from abattoir as a live and cultured in buffer media for 4 h at 37 °C. Excretory-Secretory products were collected and stored in -80◦C. F. gigantica and Fasciola hepatica were homogenized with homogenizing buffer in a glass homogenizer to prepare of somatic extract. Suspension was then centrifuged and supernatant was stored at -80°C. In order to assay the enzyme activity, excretory-secretory and somatic extracts in the form of cocktails (potassium phosphate buffer, reduced glutathione and 1-chloro-2,4-dinitrobenzene substrates) were prepared and their absorbance recorded for 5 minutes at 340 nm. The total and specific GST activity of F. gigantica somatic and ES products were obtained as 2916.00, 272.01 micromole/minute and 1.33, 1.70 micromole/minute/mg protein, respectively. Fasciola hepatica also showed 2705.00, 276.86 micromole/minute and 1.33, 1.52 micromole/minute/mg protein, respectively. These results are important for analysis of parasite survival / resistance to drugs which use for treatment of fascioliasis.

  15. Excretory function of salivary gland during static salivary scintigraphy using technetium-99m pertechnetate: a correlation study with salivary flow rate in sjogrens syndrome

    International Nuclear Information System (INIS)

    Jang, S. J.; Lee, W. W.; Lee, Y. J.; So, Y.; Jeong, J. G.; Lee, M. C.; Kim, S. E.

    2005-01-01

    Salivary scintigraphy is useful in the evaluation of xerostomia. To identify the relevant and clinically applicable parameter for the evaluation of xerostomia, we performed static salivary scintigraphy using Tc-99m and compared it with salivary flow rate in patients with xerostomia. Twenty-three female patients (age 51.2±10.4 years) who suffered from xerostomia were investigated. Nine patients were classified as Sjogrens syndrome (SS) by clinical criteria, and 14 patients were classified as non-Sjogrens syndrome. Un-stimulated salivary flow rate and simulated salivary flow rate were checked. Salivary scintigraphy was performed with injection of 25 mCi Tc-99m pertechnetate after injection anterior static image was obtained over face as basal uptake. ROIs were drawn over each salivary gland with background subtraction by square ROI drawn over skull. We used the mean data of right and left salivary glands for analysis. Percent excretion of salivary gland was calculated. Un-stimulated salivary flow rates(SFR) were different between groups (p 0.05): 5.88±4.07 ml/15 min in SS, and 10.31±6.49 ml/15 min in non-SS. The uptake value in submandibular gland revealed significant difference between the groups. The percent excretion of submandibular gland had positive correlation with un-stimulated salivary flow rate (r=0.534, p=0.009), and that of parotid gland was also positive correlation (r=0.437, p=0.037). The result of multiple regression analysis revealed only percent excretion of submandibular gland was single determinant of unstimulated SFR. Percent excretion of submandibular gland had positive correlation with un-stimulated SFR. Thus, excretory function of submandibular gland assessed by salivary scintigraphy appears more related with xerostomia than parotid gland

  16. Radionuclide determination of individual kidney function in the treatment of chronic renal obstruction

    International Nuclear Information System (INIS)

    Belis, J.A.; Belis, T.E.; Lai, J.C.; Goodwin, C.A.; Gabriele, O.F.

    1982-01-01

    Differential radionuclide renal scans can be useful in the management of patients with chronic partial obstruction of 1 kidney. The /sup 99m/Tc diethylenetriaminepentaacetic acid perfusion scan can be used to assess glomerular blood flow. The 131 I orthoiodohippurate renal scan provides qualitative functional information from scintigrams and quantitative evaluation of effective renal plasma flow to each kidney, as well as a total excretory index. Sequential /sup 99m/Tc diethylenetriaminepentaacetic acid and 131 I orthoiodohippurate renal scans were used to assess individual renal function before and after surgical correction of unilateral chronic renal obstruction in 31 patients. The preservation of cortical perfusion on /supb 99m/Tc diethylenetriaminepentaacetic acid scans indicated that potential existed for partial recovery of renal function. Effective renal plasma flow and excretory index determined in conjunction with the 131 I orthoiodohippurate scans provided a quantitative assessment of preoperative renal function, an evaluation of the effect of surgery and a sensitive method for long-term evaluation of differential renal function. Correction of ureteropelvic junction obstruction usually resulted in improvement in unilateral renal function. Neither nephrolithotomy nor extended pyelolithotomy diminished renal function in the kidney subjected to an operation and often improved it. Patients with long-standing distal ureteral obstruction had the least improvement in renal function postoperatively

  17. Comparative Assay of Glutathione S- Transferase (GSTs Activity of Excretory-Secretory Materials and Somatic Extract of Fasciola spp Parasites

    Directory of Open Access Journals (Sweden)

    Heshmatollah Alirahmi

    2010-12-01

    Full Text Available Fascioliasis is a worldwide parasitic disease in human and domestic animals. The causative agents of fascioliasis are Fasciola hepatica and Fasciola gigantica. In the recent years, fasciola resistance to drugs has been reported in the many of publications. Fasciola spp has detoxification system including GST enzyme which may be responsible for its resistance. Therefore , the aim of the study was to assay of GST enzyme activity in fasciola parasites. Fasciola gigantica and Fasciola hepatica helminths were collected from abattoir as a live and cultured in buffer media for 4 h at 37 °C. Excretory-Secretory products were collected and stored in -80◦C. F. gigantica and Fasciola hepatica were homogenized with homogenizing buffer in a glass homogenizer to prepare of somatic extract. Suspension was then centrifuged and supernatant was stored at -80°C. In order to assay the enzyme activity, excretory-secretory and somatic extracts in the form of cocktails (potassium phosphate buffer, reduced glutathione and 1-chloro-2,4-dinitrobenzene substrates were prepared and their absorbance recorded for 5 minutes at 340 nm. The total and specific GST activity of F. gigantica somatic and ES products were obtained as 2916.00, 272.01 micromole/minute and 1.33, 1.70 micromole/minute/mg protein, respectively. Fasciola hepatica also showed 2705.00, 276.86 micromole/minute and 1.33, 1.52 micromole/minute/mg protein, respectively. These results are important for analysis of parasite survival / resistance to drugs which use for treatment of fascioliasis.

  18. Comparative Assay of Glutathione S- Transferase (GSTs Activity of Excretory-Secretory Materials and Somatic Extract of Fasciola spp Parasites

    Directory of Open Access Journals (Sweden)

    Taghi Golmohamadi

    2010-11-01

    Full Text Available Fascioliasis is a worldwide parasitic disease in human and domestic animals. The causative agents of fascioliasis are Fasciola hepatica and Fasciola gigantica. In the recent years, fasciola resistance to drugs has been reported in the many of publications. Fasciola spp has detoxification system including GST enzyme which may be responsible for its resistance. Therefore , the aim of the study was to assay of GST enzyme activity in fasciola parasites. Fasciola gigantica and Fasciola hepatica helminths were collected from abattoir as a live and cultured in buffer media for 4 h at 37 °C. Excretory-Secretory products were collected and stored in -80◦C. F. gigantica and Fasciola hepatica were homogenized with homogenizing buffer in a glass homogenizer to prepare of somatic extract. Suspension was then centrifuged and supernatant was stored at -80°C. In order to assay the enzyme activity, excretory-secretory and somatic extracts in the form of cocktails (potassium phosphate buffer, reduced glutathione and 1-chloro-2,4-dinitrobenzene substrates were prepared and their absorbance recorded for 5 minutes at 340 nm. The total and specific GST activity of F. gigantica somatic and ES products were obtained as 2916.00, 272.01 micromole/minute and 1.33, 1.70 micromole/minute/mg protein, respectively. Fasciola hepatica also showed 2705.00, 276.86 micromole/minute and 1.33, 1.52 micromole/minute/mg protein, respectively. These results are important for analysis of parasite survival / resistance to drugs which use for treatment of fascioliasis.

  19. Renal morphology and function immediately after extracorporeal shock-wave lithotripsy

    Energy Technology Data Exchange (ETDEWEB)

    Kaude, J.V.; Williams, C.M.; Millner, M.R.; Scott, K.N.; Finlayson, B.

    1985-08-01

    The acute effects of extracorporeal shock-wave lithotripsy (ESWL) on morphology and function of the kidney were evaluated by excretory urography, quantitative radionuclide renography (QRR), and magnetic resonance imaging (MRI) in 33 consecutive patients. Excretory urograms demonstrated an enlarged kidney in seven (18%) of 41 treatments and partial or complete obstruction of the ureter by stone fragments after 15 (37%) of 41 treatments. Total effective renal plasma flow (ERPF) was not changed after ESWL, but the percentage ERPF of the treated kidney was decreased by more than 5% in 10 (30%) of 33 cases. QRR images showed partial parenchymal obstruction in 10 (25%) of 41 teated kidneys and total parenchymal obstruction in 9 (22%). MRI disclosed one or more abnormalities in 24 (63%) of 38 treated kidneys. Treated kidneys were normal by all three imaging methods in 26% and abnormal by one or more tests in 74% of cases. The morphologic and functional changes are attributed to renal contusion resulting in edema and extravasation of urine and blood into the interstitial, subcapsular, and perirenal spaces.

  20. Trichinella britovi human infection in Spain : antibody response to surface, excretory/secretory and somatic antigens

    Directory of Open Access Journals (Sweden)

    Rodríguez-Osorio M.

    2003-06-01

    Full Text Available A third outbreak of Trichinella britovi with 140 people involved, occurred in Granada Spain (December 1998. The source of infection was sausage made from uninspected wild boar meat. Fifty-two patients agreed to participated in this study. An elevated eosinophil level (> 5 % was detected in 59.6 % of patients, and persisted in most of these cases for two months. A moderate IgG response was observed. At the onset of symptoms, Western blot (WB test detected more positive cases than Enzyme linked immunosorbent assay (ELISA and indirect immunofluorescence (IIF. Six months from infection, ELISA revealed fewer positive cases than the other two tests. It would appear that the response to somatic antigens starts earlier than those to cuticular and excretory/secretory (ES antigens and that the response to ES antigens is the first to decrease.

  1. P-glycoprotein-deficient mice have proximal tubule dysfunction but are protected against ischemic renal injury

    NARCIS (Netherlands)

    Huls, M.; Kramers, C.; Levtchenko, E.N.; Wilmer, M.J.G.; Dijkman, H.B.P.M.; Kluijtmans, L.A.J.; Hoorn, J.W.A. van der; Russel, F.G.M.; Masereeuw, R.

    2007-01-01

    The multidrug resistance gene 1 product, P-glycoprotein (P-gp), is expressed in several excretory organs, including the apical membrane of proximal tubules. After inducing acute renal failure, P-gp expression is upregulated and this might be a protective function by pumping out toxicants and harmful

  2. MDCT urography: experience with a bi-phasic excretory phase examination protocol

    International Nuclear Information System (INIS)

    Meindl, Thomas; Coppenrath, Eva; Degenhart, Christoph; Reiser, Maximilian F.; Mueller-Lisse, Ullrich G.; Mueller-Lisse, Ulrike L.

    2007-01-01

    The benefit of multidetector computed tomographic urography (MDCTU) for visualising early and late excretory phase (EP) upper urinary tract (UUT) opacification has been studied. UUT opacification was retrospectively evaluated in 45 bi-phasic four-row MDCTU examinations. The UUT was divided into intrarenal collecting system (IRCS), proximal, middle and distal ureter. Two independent readers rated opacification: 1, none; 2, partial; 3, complete. Numbers of segments and percentages of UUTs at each score were calculated for each EP and two EPs combined. Results of a single EP and of combined EPs were compared by Wilcoxon matched-pairs signed-ranks. IRCS and proximal ureter were at least partially opacified in each EP in >95%. The middle ureter was at least partially opacified in the early and late EP in 85% and 93%, respectively. The distal ureter was opacified in 65% (49/75) in the early EP and in 78% (59/75) in the late EP. Combining two EPs, non-opacified distal segments decreased to 9% (7/75). Significant improvement between a single EP and combining two EPs were found for the middle and distal ureter (P < 0.03). Bi-phasic MDCTU substantially improved opacification of the middle and distal ureter. IRCS and proximal ureter are reliably opacified with one EP. (orig.)

  3. Sequential hepato-biliary scintigraphy of the patients with constitutional jaundices and ICG excretory defect disease with sup(99m)Tc-HIDA and sup(99m)Tc-PI

    International Nuclear Information System (INIS)

    Ueda, Hideo; Asahara, Akira; Hishinuma, Sanpei; Toogin, Masayuki; Takagi, Masao

    1979-01-01

    The hepato-biliary scintigraphy with sup(99m)Tc-HIDA and sup(99m)Tc-PI and the measurement of hepatic clearance have been studied on constitutional hyperbilirubinemia and ICG excretory defect disease. The results obtained are as follows: 1) In Dubin-Johnson's syndrome cases, the hepatic uptake of sup(99m)Tc-HIDA was faster, but the excretion was extremely slower than in normal cases. 2) Hepatic uptake and excretion of sup(99m)Tc-PI were both almost normal in Dubin-Johnson's syndrome. 3) In Rotor's disease, hepatic uptake of sup(99m)Tc-HIDA was very poor, showing almost no hepatic image. 4) In Gilbert's disease and ICG excretory defect disease, hepatic uptake and excretion of sup(99m)Tc-HIDA were both within normal limit. From these results it can be presumed that Dubin-Johnson's syndrome and Rotor's disease differ in morbid condition. Dubin-Johnson's syndrome, Rotor's disease and Gilbert's disease show the different patterns between hepatic uptake and excretion on sup(99m)Tc-HIDA hepatoscintigraphy and the patterns contribute to the differential diagnosis of constitutional jaundice. (author)

  4. Comparison of excretory-secretory antigen and positive faecal supernatant antigen in the detection of Echinococcus granulosus infection in dogs by CIEP

    Directory of Open Access Journals (Sweden)

    P. R. Prathiush

    Full Text Available Coproantigen detection of Echinococcosis in dogs by counter immunoelectrophoresis was standardized. Adult Echinococcus granulosus worms were obtained from intestine of a necropsied positive dog. Excretory-secretory antigen was prepared by culturing adult worms in Medium 199 (pH 7.4. Faeces of positive dog were collected and fecal supernatant was prepared and used for coproantigen detection. CIEP was carried out using tris-borate buffer (pH 8.0 at a constant current of 8mA/slide for 60 minutes. CIEP detected infection with both the antigens. [Vet World 2009; 2(11.000: 421-422

  5. Renal ultrasound and excretory urography in infants and young children with urinary tract infection

    International Nuclear Information System (INIS)

    Kenda, R.; Kenig, T.; Silc, M.; Zupancic, Z.

    1989-01-01

    The main purpose of the study was to see whether excretory urography (EU) can be safely replaced by ultrasound (US) in children with urinary tract infection (UTI) younger than 6 years. 101 hospitalised children were admitted to the prospective study. They were all diagnosed as having UTI and were treated accordingly. All children had voiding cystography (VCU), EU and US done. US and EU correlated well in 94% of the cases. In all 6 cases with discrepancy between EU and US, the VCU was abnormal. Our results confirm the data from other authors, that VCU and US should be sufficient as an initial work-up on children with UTI, while EU should be done only in the cases with abnormal findings on either one or both of the former investigations. However, it should be kept in mind that some cases of parenchymal involvement or mild subpelvic stenosis can be missed using this protocol. If EU is obtained only in the cases with abnormal US and/or VCU, only 55 children (54%) in our group would have had an EU done. (orig.)

  6. Clonorchis sinensis excretory-secretory products promote the migration and invasion of cholangiocarcinoma cells by activating the integrin β4-FAK/Src signaling pathway.

    Science.gov (United States)

    Pak, Jhang Ho; Bashir, Qudsia; Kim, In Ki; Hong, Sung-Jong; Maeng, Sejung; Bahk, Young Yil; Kim, Tong-Soo

    2017-06-01

    Cholangiocarcinoma (CCA) is a slow-growing but highly metastatic cancer. Its metastatic potential largely explains its high mortality rate. A recognized risk factor for CCA development is infection with the liver flukes Opisthorchis viverrini and Clonorchis sinensis. We previously reported that the excretory-secretory products (ESPs) of C. sinensis promoted the three-dimensional aggregation and invasion of CCA cells. In the present study, a quantitative real-time PCR array of extracellular matrix (ECM) and adhesion molecules was used to examine the regulatory mechanism of ESP-mediated CCA cell migration and invasion. In particular, the expression levels of integrin α isoforms and β4 were upregulated in response to ESPs. Increased expression of integrin β4 was probably correlated with activation of focal adhesion kinase (FAK) and the steroid receptor coactivator (Src) family kinase and the subsequent activation of two downstream focal adhesion molecules, paxillin and vinculin. Moreover, inhibition of FAK/Src activation reduced paxillin and vinculin phosphorylation and attenuated ESP-induced CCA cell migration and invasion. These findings suggest that the integrin β4-FAK/Src signaling axis may play a crucial role in clonorchiasis-associated CCA metastasis during tumor progression. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Age-related features of renal function (on radiorenographic data)

    International Nuclear Information System (INIS)

    Korkushko, O.V.; Frajfel'd, V.Eh.; Belyj, A.A.

    1986-01-01

    Renal function of 91 healthy subjects aged 18-91 has been evaluated at radionuclide renography with the use of 131 I-Hippuran. Renal excretory function, effective renal plasma and blood flows were found to decrease annually by 0.09 ml/kg in ageing men and by 0.08 ml/kg in women. The use of new indices may be useful for evaluation of renal blood circulation, especially during hypo- or hypervolaemia is proposed. These are the index of renal circulation efficiency and the mean time of circulating blood volume transfer through renal blood vessels

  8. Transporter function and cyclic AMP turnover in normal colonic mucosa from patients with and without colorectal neoplasia

    Directory of Open Access Journals (Sweden)

    Kleberg Karen

    2012-06-01

    Full Text Available Abstract Background The pathogenesis of colorectal neoplasia is still unresolved but has been associated with alterations in epithelial clearance of xenobiotics and metabolic waste products. The aim of this study was to functionally characterize the transport of cyclic nucleotides in colonic biopsies from patients with and without colorectal neoplasia. Methods Cyclic nucleotides were used as model substrates shared by some OATP- and ABC-transporters, which in part are responsible for clearance of metabolites and xenobiotics from the colonic epithelium. On colonic biopsies from patients with and without colorectal neoplasia, molecular transport was electrophysiologically registered in Ussing-chamber set-ups, mRNA level of selected transporters was quantified by rt-PCR, and subcellular location of transporters was determined by immunohistochemistry. Results Of four cyclic nucleotides, dibuturyl-cAMP induced the largest short circuit current in both patient groups. The induced short circuit current was significantly lower in neoplasia-patients (p = 0.024. The observed altered transport of dibuturyl-cAMP in neoplasia-patients could not be directly translated to an observed increased mRNA expression of OATP4A1 and OATP2B1 in neoplasia patients. All other examined transporters were expressed to similar extents in both patient groups. Conclusions OATP1C1, OATP4A1, OATP4C1 seem to be involved in the excretory system of human colon. ABCC4 is likely to be involved from an endoplasmic-Golgi complex and basolateral location in goblet cells. ABCC5 might be directly involved in the turnover of intracellular cAMP at the basolateral membrane of columnar epithelial cells, while OATP2B1 is indirectly related to the excretory system. Colorectal neoplasia is associated with lower transport or sensitivity to cyclic nucleotides and increased expression of OATP2B1 and OATP4A1 transporters, known to transport PGE2.

  9. The mythology of renal function measurement

    International Nuclear Information System (INIS)

    Britton, K.E.

    2003-01-01

    The kidney is a conservative organ. In principle it retains what the body needs, and what is not needed is excreted. It has a number of basic properties. It has the ability to take solutes up from the blood whether by filtration or secretion, which is best called its Uptake function. In the special circumstance where the kidneys are the only exit for the solute from the body, then the rate of loss from the blood is equal to the rate of uptake by the kidney. It has the ability to move solutes among its nephrons, which is its Transit function. The solutes may be absorbed in whole or part and be retained or returned to the blood, its Reabsorption function. In the special case where the solute is non- reabsorbable, then, if there is an increase in salt and water reabsorption as in functionally significant renovascular disease or obstructive nephropathy, the transit function is altered and the transit time through the parenchyme is prolonged. In renovascular disorder the transit time is prolonged through both cortical and juxta-medullary nephrons and collecting ducts. In obstructive nephropathy the transit time is prolonged through the cortical nephrons, but usually is shortened through the juxta-medullary nephrons and collecting ducts due to loss of medullary concentrating ability. After transit through the kidney, the solutes move through the pelvis and ureter, its Excretory function. No more can come out of the kidney then went in previously. If less comes out than what went in, then an increased resistance to outflow is predicted. The balance between excretory function and uptake function is measurable by the Output (Outflow) Efficiency. The kidney also has receptors for hormones, which may modify its reabsorptive functions, for example increased Vasopressin binding decreases the permeability of the collecting duct to water. The kidney also has the ability through enzymes to modify solutes, such as the activation of Vitamin D

  10. Nociceptin/orphanin FQ peptide receptor agonist Ac-RYYRWKKKKKKK-NH2 (ZP120) induces antinatriuresis in rats by stimulation of amiloride-sensitive sodium reabsorption

    DEFF Research Database (Denmark)

    van Deurs, Ulla S K; Hadrup, Niels; Petersen, Jørgen Søberg

    2008-01-01

    receptors are expressed in the distal convoluted tubules, the connecting tubules, and the collecting ducts. Using clearance techniques, we evaluated renal excretory function during acute administration of ZP120 (1 nmol/kg/min) in chronically catheterized, conscious rats (n = 8/group). To examine...

  11. Tranilast reduces serum IL-6 and IL-13 and protects against thioacetamide-induced acute liver injury and hepatic encephalopathy.

    Science.gov (United States)

    Abdelaziz, Rania R; Elkashef, Wagdi F; Said, Eman

    2015-07-01

    Hepatic encephalopathy is a serious neuropsychiatric disorder usually affecting either acute or chronic hepatic failure patients. Hepatic encephalopathy was replicated in a validated rat model to assess the potential protective efficacy of tranilast against experimentally induced hepatic encephalopathy. Thioacetamide injection significantly impaired hepatic synthetic, metabolic and excretory functions with significant increase in serum NO, IL-6 and IL-13 levels and negative shift in the oxidant/antioxidant balance. Most importantly, there was a significant increase in serum ammonia levels with significant astrocytes' swelling and vacuolization; hallmarks of hepatic encephalopathy. Tranilast administration (300 mg/kg, orally) for 15 days significantly improved hepatic functions, restored oxidant/antioxidant balance, reduced serum NO, IL-6 and IL-13 levels. Meanwhile, serum ammonia significantly declined with significant reduction in astrocytes' swelling and vacuolization. Several mechanisms can be implicated in the observed hepato- and neuroprotective potentials of tranilast, such as its anti-inflammatory potential, its antioxidant potential as well as its immunomodulatory properties. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Characterisation of proteolytic activity of excretory-secretory products from adult Strongylus vulgaris.

    Science.gov (United States)

    Caffrey, C R; Ryan, M F

    1994-04-01

    An excretory-secretory (ES) preparation derived from adult Strongylus vulgaris in vitro was assessed for proteolytic activity using azocasein and synthetic, fluorogenic, peptide substrates. Fractionation was by molecular sieve fast protein liquid chromatography (molecular sieve FPLC) and resolution by gelatin-substrate sodium dodecyl sulphate-polyacrylamide gel electrophoresis (gelatin-substrate SDS-PAGE). The cysteine proteinase activator, dithiothreitol (DTT), enhanced azocaseinolysis and hydrolysis of carbobenzoxy-phenylalanyl-arginine-7-amido-4-methylcoumarin (Z-Phe-Arg-NMec) by the ES preparation and was a requirement for the detection of carbobenzoxy-arginyl-arginine-7-amido-4-methylcoumarin (Z-Arg-Arg-NMec) hydrolysis. Assays of FPLC-eluted fractions, with DTT, detected a broad peak of azocaseinolytic activity (22-24 kDa) and two peaks (24 and 18 kDa) of hydrolysis using the synthetic substrates. Hydrolysis by these peaks of Z-Phe-Arg-NMec was 50-fold greater than that of Z-Arg-Arg-NMec suggesting that their specificities are more like papain or cathepsin L rather than cathepsin B. In gelatin-substrate SDS-PAGE, DTT was required to detect proteolysis by the ES preparation which was optimal at pH 6.0 and resolved into eight bands (87-29 kDa). Cysteine proteinase inhibitors were the most effective in all assays. Collectively, these data indicate that cysteine-class proteolytic activity predominates in the ES preparation of adult S. vulgaris.

  13. Effects of excretory/secretory products from Anisakis simplex (Nematoda) on immune gene expression in rainbow trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Bahlool, Qusay Zuhair Mohammad; Skovgaard, Alf; Kania, Per Walter

    2013-01-01

    Excretory/secretory (ES) products are molecules produced by parasitic nematodes, including larval Anisakis simplex, a parasite occurring in numerous marine fish hosts. The effects of these substances on host physiology have not been fully described. The present work elucidates the influence of ES...... substances on the fish immune system by measuring immune gene expression in spleen and liver of rainbow trout (Oncorhynchus mykiss) injected intraperitoneally with ES products isolated from A. simplex third stage larvae. The overall gene expression profile of exposed fish showed a generalized down....... This type of hydrolytic enzyme activity may play a role in nematode penetration of host tissue. In addition, based on the notion that A. simplex ES products may have an immune-depressive effect (by minimizing immune gene expression) it could also be suggested that worm enzymes directly target host immune...

  14. Radioisotope examination of kidney function in lead intoxication

    International Nuclear Information System (INIS)

    Klimentova, G.; Buchancova, J.; Galikova, E.; Lepej, J.

    1982-01-01

    The renal function was assessed of 12 patients with professional lead intoxication by radioisotope examination methods. In six patients changes on the radionephrographic curve were observed, showing flattening and shift of the peak of the curve, and prolongation of the secretory and excretory phases. The phase scintiscan displayed a slowed down uptake of the radioactive substance and pathological persistance of activity in the kidneys. The impairment of renal functions proved to be reversible. The authors consider rad+oisotope examinations to be an appropriate approach permitting evaluation of renal functions during lead intoxication, as well as helping to assess the deployment of persons who had suffered from intoxication, to workplaces where there is danger of exposure to lead. (author)

  15. Thymus function in drug-induced lupus.

    Science.gov (United States)

    Rubin, R L; Salomon, D R; Guerrero, R S

    2001-01-01

    Autoimmunity develops when a lupus-inducing drug is introduced into the thymus of normal mice, but the relevance of this model to the human disorder is unclear in part because it is widely assumed that the thymus is non-functional in the adult. We compared thymus function in 10 patients with symptomatic procainamide-induced lupus to that in 13 asymptomatic patients who only developed drug-induced autoantibodies. T cell output from the thymus was quantified using a competitive polymerase chain reaction that detects T cell receptor DNA excision circles in peripheral blood lymphocytes. Despite the advanced age of the patient population under study, newly generated T cells were detected in all subjects. Although there was no overall quantitative difference between the symptomatic and asymptomatic patients, we found a positive correlation between the level of T cell receptor excision circles in peripheral lymphocytes and serum IgG anti-chromatin antibody activity in patients with drug-induced lupus. The association between autoantibodies and nascent peripheral T cells supports the requirement for T cells in autoantibody production. Our observations are consistent with findings in mice in which autoreactive T cells derived from drug-induced abnormalities in T cell development in the thymus.

  16. Development of indirect sandwich ELISA for determination of excretory-secretory antigens of Fasciola hepatica

    Directory of Open Access Journals (Sweden)

    Libertad Alzamora-Gonzales

    2016-05-01

    Full Text Available Fasciolosis is a cosmopolitan parasitosis medical-veterinary importance caused by Fasciola hepatica, which affects sheep, goats and cattle; and it affects man accidentally causing an epidemic-endemic infection difficult to diagnose. The aim was to develop an indirect sandwich ELISA with 3 antibodies for detecting excretory-secretory antigens of Fasciola hepatica (ESFh. For the development of indirect sandwich ELISA were used, as capture antibody, mouse polyclonal antibodies anti ESFh and polyclonal antibodies rabbit anti-ESFh as detection antibody, at the concentrations of 10 and 5 µg/mL respectively. The conjugate used was mouse monoclonal anti- total immunoglobulins rabbit linked to peroxidase (1/1000. Were analized 31 sheep fecal samples, and the results were compared with those obtained by direct coproparasitological examination (DC and counterimmunoelectrophoresis (CIEP. The detection limit obtained for indirect sandwich ELISA was 100 ng/mL. The test had a 100% sensitivity, 96.6% specificity, positive and negative predictive values of 50% and 96.6% respectively, in relation to DC test. Comparing with CIEP the specificity obtained for indirect sandwich ELISA was 93.5% and a negative predictive value of 100%. We concluded that indirect sandwich ELISA designed is able to detect metabolic antigens in ovine feces samples and can be used for Fasciola hepatica diagnosis.

  17. The skin function: a factor of anti-metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Zhou Shi-Sheng

    2012-04-01

    Full Text Available Abstract The body’s total antioxidant capacity represents a sum of the antioxidant capacity of various tissues/organs. A decrease in the body’s antioxidant capacity may induce oxidative stress and subsequent metabolic syndrome, a clustering of risk factors for type 2 diabetes and cardiovascular disease. The skin, the largest organ of the body, is one of the major components of the body’s total antioxidant defense system, primarily through its xenobiotic/drug biotransformation system, reactive oxygen species-scavenging system, and sweat glands- and sebaceous glands-mediated excretion system. Notably, unlike other contributors, the skin contribution is variable, depending on lifestyles and ambient temperature or seasonal variations. Emerging evidence suggests that decreased skin’s antioxidant and excretory functions (e.g., due to sedentary lifestyles and low ambient temperature may increase the risk for metabolic syndrome. This review focuses on the relationship between the variability of skin-mediated detoxification and elimination of exogenous and endogenous toxic substances and the development of metabolic syndrome. The potential role of sebum secretion in lipid and cholesterol homeostasis and its impact on metabolic syndrome, and the association between skin disorders (acanthosis nigricans, acne, and burn and metabolic syndrome are also discussed.

  18. Molecular characterization of severin from Clonorchis sinensis excretory/secretory products and its potential anti-apoptotic role in hepatocarcinoma PLC cells.

    Directory of Open Access Journals (Sweden)

    Xueqing Chen

    Full Text Available BACKGROUND: Clonorchiasis, caused by the infection of Clonorchis sinensis (C. sinensis, is a kind of neglected tropical disease, but it is highly related to cholangiocarcinoma and hepatocellular carcinoma (HCC. It has been well known that the excretory/secretory products of C. sinensis (CsESPs play key roles in clonorchiasis associated carcinoma. From genome and transcriptome of C. sinensis, we identified one component of CsESPs, severin (Csseverin, which had three putative gelsolin domains. Its homologues are supposed to play a vital role in apoptosis resistance of tumour cell. METHODOLOGY/PRINCIPAL FINDINGS: There was significant similarity in tertiary structures between human gelsolin and Csseverin by bioinformatics analysis. We identified that Csseverin expressed at life stage of adult worm, metacercaria and egg by the method of quantitative real-time PCR and western blotting. Csseverin distributed in vitellarium and intrauterine eggs of adult worm and tegument of metacercaria by immunofluorence assay. We obtained recombinant Csseverin (rCsseverin and confirmed that rCsseverin could bind with calciumion in circular dichroism spectrum analysis. It was demonstrated that rCsseverin was of the capability of actin binding by gel overlay assay and immunocytochemistry. Both Annexin V/PI assay and mitochondrial membrane potential assay of human hepatocarcinoma cell line PLC showed apoptosis resistance after incubation with different concentrations of rCsseverin. Morphological analysis, apoptosis-associated changes of mitochondrial membrane potential and Annexin V/PI apoptosis assay showed that co-incubation of PLC cells with rCsseverin in vitro led to an inhibition of apoptosis induced by serum-starved for 24 h. CONCLUSIONS/SIGNIFICANCE: Collectively, the molecular properties of Csseverin, a molecule of CsESPs, were characterized in our study. rCsseverin could cause obvious apoptotic inhibition in human HCC cell line. Csseverin might exacerbate the

  19. Molecular Characterization of Severin from Clonorchis sinensis Excretory/Secretory Products and Its Potential Anti-apoptotic Role in Hepatocarcinoma PLC Cells

    Science.gov (United States)

    He, Lei; Wang, Xiaoyun; Liang, Pei; Chen, Wenjun; Bian, Meng; Ren, Mengyu; Lin, Jinsi; Liang, Chi; Xu, Jin; Wu, Zhongdao; Li, Xuerong; Huang, Yan; Yu, Xinbing

    2013-01-01

    Background Clonorchiasis, caused by the infection of Clonorchis sinensis (C. sinensis), is a kind of neglected tropical disease, but it is highly related to cholangiocarcinoma and hepatocellular carcinoma (HCC). It has been well known that the excretory/secretory products of C. sinensis (CsESPs) play key roles in clonorchiasis associated carcinoma. From genome and transcriptome of C. sinensis, we identified one component of CsESPs, severin (Csseverin), which had three putative gelsolin domains. Its homologues are supposed to play a vital role in apoptosis resistance of tumour cell. Methodology/Principal Findings There was significant similarity in tertiary structures between human gelsolin and Csseverin by bioinformatics analysis. We identified that Csseverin expressed at life stage of adult worm, metacercaria and egg by the method of quantitative real-time PCR and western blotting. Csseverin distributed in vitellarium and intrauterine eggs of adult worm and tegument of metacercaria by immunofluorence assay. We obtained recombinant Csseverin (rCsseverin) and confirmed that rCsseverin could bind with calciumion in circular dichroism spectrum analysis. It was demonstrated that rCsseverin was of the capability of actin binding by gel overlay assay and immunocytochemistry. Both Annexin V/PI assay and mitochondrial membrane potential assay of human hepatocarcinoma cell line PLC showed apoptosis resistance after incubation with different concentrations of rCsseverin. Morphological analysis, apoptosis-associated changes of mitochondrial membrane potential and Annexin V/PI apoptosis assay showed that co-incubation of PLC cells with rCsseverin in vitro led to an inhibition of apoptosis induced by serum-starved for 24 h. Conclusions/Significance Collectively, the molecular properties of Csseverin, a molecule of CsESPs, were characterized in our study. rCsseverin could cause obvious apoptotic inhibition in human HCC cell line. Csseverin might exacerbate the process of HCC

  20. Proteomic analysis of the excretory/secretory products and antigenic proteins of Echinococcus granulosus adult worms from infected dogs.

    Science.gov (United States)

    Wang, Ying; Xiao, Di; Shen, Yujuan; Han, Xiuming; Zhao, Fei; Li, Xiaohong; Wu, Weiping; Zhou, Hejun; Zhang, Jianzhong; Cao, Jianping

    2015-05-21

    Cystic echinococcosis, which is caused by Echinococcus granulosus, is one of the most widespread zoonotic helminth diseases that affects humans and livestock. Dogs, which harbor adult worms in their small intestines, are a pivotal source of E. granulosus infection in humans and domestic animals. Therefore, novel molecular approaches for the prevention and diagnosis of this parasite infection in dogs need to be developed. In this study, we performed proteomic analysis to identify excretory/secretory products (ES) and antigenic proteins of E. granulosus adult worms using two-dimensional electrophoresis, tandem matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF/TOF), and Western blotting of sera from infected dogs. This study identified 33 ES product spots corresponding to 9 different proteins and 21 antigenic protein spots corresponding to 13 different proteins. Six antigenic proteins were identified for the first time. The present study extended the existing proteomic data of E. granulosus and provides further information regarding host-parasite interactions and survival mechanisms. The results of this study contribute to vaccination and immunodiagnoses for E. granulosus infections.

  1. Bacterial diversity of bacteriomes and organs of reproductive, digestive and excretory systems in two cicada species (Hemiptera: Cicadidae).

    Science.gov (United States)

    Zheng, Zhou; Wang, Dandan; He, Hong; Wei, Cong

    2017-01-01

    Cicadas form intimate symbioses with bacteria to obtain nutrients that are scarce in the xylem fluid they feed on. The obligate symbionts in cicadas are purportedly confined to specialized bacteriomes, but knowledge of bacterial communities associated with cicadas is limited. Bacterial communities in the bacteriomes and organs of reproductive, digestive and excretory systems of two cicada species (Platypleura kaempferi and Meimuna mongolica) were investigated using different methods, and the bacterial diversity and distribution patterns of dominant bacteria in different tissues were compared. Within each species, the bacterial communities of testes are significantly different from those of bacteriomes and ovaries. The dominant endosymbiont Candidatus Sulcia muelleri is found not only in the bacteriomes and reproductive organs, but also in the "filter chamber + conical segment" of both species. The transmission mode of this endosymbiont in the alimentary canal and its effect on physiological processes merits further study. A novel bacterium of Rhizobiales, showing ~80% similarity to Candidatus Hodgkinia cicadicola, is dominant in the bacteriomes and ovaries of P. kaempferi. Given that the genome of H. cicadicola exhibits rapid sequence evolution, it is possible that this novel bacterium is a related endosymbiont with beneficial trophic functions similar to that of H. cicadicola in some other cicadas. Failure to detect H. cicadicola in M. mongolica suggests that it has been subsequently replaced by another bacterium, a yeast or gut microbiota which compensates for the loss of H. cicadicola. The distribution of this novel Rhizobiales species in other cicadas and its identification require further investigation to help establish the definition of the bacterial genus Candidatus Hodgkinia and to provide more information on sequence divergence of related endosymbionts of cicadas. Our results highlight the complex bacterial communities of cicadas, and are informative for

  2. Bacterial diversity of bacteriomes and organs of reproductive, digestive and excretory systems in two cicada species (Hemiptera: Cicadidae.

    Directory of Open Access Journals (Sweden)

    Zhou Zheng

    Full Text Available Cicadas form intimate symbioses with bacteria to obtain nutrients that are scarce in the xylem fluid they feed on. The obligate symbionts in cicadas are purportedly confined to specialized bacteriomes, but knowledge of bacterial communities associated with cicadas is limited. Bacterial communities in the bacteriomes and organs of reproductive, digestive and excretory systems of two cicada species (Platypleura kaempferi and Meimuna mongolica were investigated using different methods, and the bacterial diversity and distribution patterns of dominant bacteria in different tissues were compared. Within each species, the bacterial communities of testes are significantly different from those of bacteriomes and ovaries. The dominant endosymbiont Candidatus Sulcia muelleri is found not only in the bacteriomes and reproductive organs, but also in the "filter chamber + conical segment" of both species. The transmission mode of this endosymbiont in the alimentary canal and its effect on physiological processes merits further study. A novel bacterium of Rhizobiales, showing ~80% similarity to Candidatus Hodgkinia cicadicola, is dominant in the bacteriomes and ovaries of P. kaempferi. Given that the genome of H. cicadicola exhibits rapid sequence evolution, it is possible that this novel bacterium is a related endosymbiont with beneficial trophic functions similar to that of H. cicadicola in some other cicadas. Failure to detect H. cicadicola in M. mongolica suggests that it has been subsequently replaced by another bacterium, a yeast or gut microbiota which compensates for the loss of H. cicadicola. The distribution of this novel Rhizobiales species in other cicadas and its identification require further investigation to help establish the definition of the bacterial genus Candidatus Hodgkinia and to provide more information on sequence divergence of related endosymbionts of cicadas. Our results highlight the complex bacterial communities of cicadas, and

  3. Proteinases in excretory-secretory products of Toxocara canis second-stage larvae: zymography and modeling insights.

    Science.gov (United States)

    González-Páez, Gonzalo Ernesto; Alba-Hurtado, Fernando; García-Tovar, Carlos Gerardo; Argüello-García, Raúl

    2014-01-01

    Components released in excretory-secretory products of Toxocara canis larvae (TES) include phosphatidylethanolamine-binding proteins (TES26), mucins (TES120, MUC2-5), and C-type lectins (TES32, TES70) and their biochemical, immunological, and diagnostic properties have been extensively studied albeit proteinase activities towards physiological substrates are almost unknown. Proteolytic activities in TES samples were first analyzed by gel electrophoresis with gelatin as substrate. Major activities of ~400, 120, and 32 kDa in TES were relatively similar over a broad pH range (5.5-9.0) and all these were of the serine-type as leupeptin abolished gelatinolysis. Further, the ~400 kDa component degraded all physiological substrates tested (laminin, fibronectin, albumin, and goat IgG) and the 120 kDa component degraded albumin and goat IgG while proteinases of lower MW (45, 32, and 26 kDa) only degraded laminin and fibronectin, preferentially at alkaline pH (9.0). By protein modeling approaches using the known sequences of TES components, only TES26 and MUC4 displayed folding patterns significantly related to reference serine proteinases. These data suggest that most of serine proteinase activities secreted in vitro by infective larvae of T. canis have intriguing nature but otherwise help the parasite to affect multiple components of somatic organs and bodily fluids within the infected host.

  4. Clinical Case of Newly Diagnosed Hypoglycemic Paroxysm Complicated by Severe Neurological Disorders

    Directory of Open Access Journals (Sweden)

    L.V. Shkala

    2013-02-01

    Full Text Available The paper presents a case of hypoglycemic paroxysm, manifested as epilepsy, in 53-year-old man, suffering from diabetes mellitus type 1, complicated by steatohepatosis following excretory and endocrine pancreatic insufficiency, disorders of renal excretory function, triggered by the lack of food after insulin administration.

  5. Inducible tertiary lymphoid structures, autoimmunity, and exocrine dysfunction in a novel model of salivary gland inflammation in C57BL/6 mice.

    Science.gov (United States)

    Bombardieri, Michele; Barone, Francesca; Lucchesi, Davide; Nayar, Saba; van den Berg, Wim B; Proctor, Gordon; Buckley, Christopher D; Pitzalis, Costantino

    2012-10-01

    Salivary glands in patients with Sjögren's syndrome (SS) develop ectopic lymphoid structures (ELS) characterized by B/T cell compartmentalization, the formation of high endothelial venules, follicular dendritic cell networks, functional B cell activation with expression of activation-induced cytidine deaminase, as well as local differentiation of autoreactive plasma cells. The mechanisms that trigger ELS formation, autoimmunity, and exocrine dysfunction in SS are largely unknown. In this article, we present a novel model of inducible ectopic lymphoid tissue formation, breach of humoral self-tolerance, and salivary hypofunction after delivery of a replication-deficient adenovirus-5 in submandibular glands of C57BL/6 mice through retrograde excretory duct cannulation. In this model, inflammation rapidly and consistently evolves from diffuse infiltration toward the development of SS-like periductal lymphoid aggregates within 2 wk from AdV delivery. These infiltrates progressively acquire ELS features and support functional GL7(+)/activation-induced cytidine deaminase(+) germinal centers. Formation of ELS is preceded by ectopic expression of lymphoid chemokines CXCL13, CCL19, and lymphotoxin-β, and is associated with development of anti-nuclear Abs in up to 75% of mice. Finally, reduction in salivary flow was observed over 3 wk post-AdV infection, consistent with exocrine gland dysfunction as a consequence of the inflammatory response. This novel model has the potential to unravel the cellular and molecular mechanisms that regulate ELS formation and their role in exocrine dysfunction and autoimmunity in SS.

  6. Immunolocalization and immunodetection of the excretory/secretory (ES) antigens of Fasciola gigantica.

    Science.gov (United States)

    Khan, M A Hannan; Ullah, Rizwan; Rehman, Abdur; Rehman, Lubna; P A, Ahammed Shareef; Abidi, S M A

    2017-01-01

    The digenetic trematode Fasciola gigantica is a parasite of great agricultural and economic importance. Along with Fasciola hepatica, F. gigantica incurs huge economic losses to the agricultural sector. Because of unavailability of an effective and commercial vaccine, the earliest diagnosis of the disease is the only way to control the disease. The conventional coprological techniques are able to detect the disease only after the parasites get matured and starts releasing their eggs with the faeces of host, therefore prepatent infection remain undiagnosed. The alternative method is by serological tests that uses circulatory antigens. Despite high sensitivity, their reliability is quite low because of the common antigens shared between different helminth parasites. To overcome this, investigation was shifted to identify the copro-antigens which could be more sensitive and reliable. In the present study, we tried to identify some of the immunodominant proteins from the Excretory Secretory (ES) product of F. gigantica which can be further characterized and used for early detection of infection and also as drug and vaccine candidates. The ES products of F. gigantica were collected and used for raising the polyclonal antibody in rabbit. The polypeptide profile was generated as well as immunogenic polypeptides were identified. The Source of ES antigen was immunolocalized using confocal microscopy and dot blot assay was performed to diagnose field infection. The polypeptide profile of ES products revealed a total of 24 polypeptides out of which 12 immunogenic polypeptides were identified by western blotting. Confocal micrographs showed the immunolocalization of antigens in the intestinal caecae, vitalline glands, gonads as well as in the tegument of the worm. The dot blot assay confirmed the utility of ES products for the detection of field infection. Subsequently, cross reactivity was found negative with Gigantocotyle explanatum; an amphitome parasite of same habitat

  7. Immunolocalization and immunodetection of the excretory/secretory (ES antigens of Fasciola gigantica.

    Directory of Open Access Journals (Sweden)

    M A Hannan Khan

    Full Text Available The digenetic trematode Fasciola gigantica is a parasite of great agricultural and economic importance. Along with Fasciola hepatica, F. gigantica incurs huge economic losses to the agricultural sector. Because of unavailability of an effective and commercial vaccine, the earliest diagnosis of the disease is the only way to control the disease. The conventional coprological techniques are able to detect the disease only after the parasites get matured and starts releasing their eggs with the faeces of host, therefore prepatent infection remain undiagnosed. The alternative method is by serological tests that uses circulatory antigens. Despite high sensitivity, their reliability is quite low because of the common antigens shared between different helminth parasites. To overcome this, investigation was shifted to identify the copro-antigens which could be more sensitive and reliable. In the present study, we tried to identify some of the immunodominant proteins from the Excretory Secretory (ES product of F. gigantica which can be further characterized and used for early detection of infection and also as drug and vaccine candidates. The ES products of F. gigantica were collected and used for raising the polyclonal antibody in rabbit. The polypeptide profile was generated as well as immunogenic polypeptides were identified. The Source of ES antigen was immunolocalized using confocal microscopy and dot blot assay was performed to diagnose field infection. The polypeptide profile of ES products revealed a total of 24 polypeptides out of which 12 immunogenic polypeptides were identified by western blotting. Confocal micrographs showed the immunolocalization of antigens in the intestinal caecae, vitalline glands, gonads as well as in the tegument of the worm. The dot blot assay confirmed the utility of ES products for the detection of field infection. Subsequently, cross reactivity was found negative with Gigantocotyle explanatum; an amphitome parasite

  8. Androgenic function of the adrenal cortex in external gamma-irradiation

    International Nuclear Information System (INIS)

    Kirkov, N.; Jordanov, J.

    1987-01-01

    Urinary 17-ketosteroid (17-KS) excretion served to evaluate the androgenic function of the adrenal cortex and the gonads of male albino Wistar rats, following single external gamma-irradiation ( 137 Cs) with dose 4 Gy. A three-phase undulant dynamics in 17-KS excretion was established after irradiation at a high level of significance (p<0,001): a fall down to 19% during the first two days; a rise on day 15 up to 185% and a second fall down to 70% on day 25. On day 30 urinary 17-KS excretion returned to normal. The reduced 17-KS excretion during the first two days may be due to blocking of androgenic hormone secretion and excretion, to inhibited excretory renal function and to changes in the liver metabolic function

  9. Radionuclide assessment of renal function in patients with oncogynecological diseases

    International Nuclear Information System (INIS)

    Vlakhov, N.; Penkova, D.; Kovachev, A.

    1989-01-01

    Results of 131 I-hippuran (0.74 MBq) nephrography and 99m Tc DMCA (55.6 MBq) scintigraphy of the kidneys in 204 women from 21 to 75 years of age are analyzed. All patients were examined before and after treatment (surgical, radiation, hormonal). It was found that combined radiotherapy of patients with cervix uteri cancer and surgical treatment of patients with corpus uteri cancer resulted in aggravation of the secretory and excretory renal disorders, as compared to the pre-treatment state. It was not until after the second year of treatment that normal renal function was reestablished. Radionuclide methods furnish the opportunity both for early detection of renal function disorders and for their dynamic control and treatment. 1 tab., 4 refs

  10. Trichomonas vaginalis Metalloproteinase Induces mTOR Cleavage of SiHa Cells

    Science.gov (United States)

    Quan, Juan-Hua; Choi, In-Wook; Yang, Jung-Bo; Zhou, Wei; Cha, Guang-Ho; Zhou, Yu; Ryu, Jae-Sook

    2014-01-01

    Trichomonas vaginalis secretes a number of proteases which are suspected to be the cause of pathogenesis; however, little is understood how they manipulate host cells. The mammalian target of rapamycin (mTOR) regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription. We detected various types of metalloproteinases including GP63 protein from T. vaginalis trophozoites, and T. vaginalis GP63 metalloproteinase was confirmed by sequencing and western blot. When SiHa cells were stimulated with live T. vaginalis, T. vaginalis excretory-secretory products (ESP) or T. vaginalis lysate, live T. vaginalis and T. vaginalis ESP induced the mTOR cleavage in both time- and parasite load-dependent manner, but T. vaginalis lysate did not. Pretreatment of T. vaginalis with a metalloproteinase inhibitor, 1,10-phenanthroline, completely disappeared the mTOR cleavage in SiHa cells. Collectively, T. vaginalis metallopeptidase induces host cell mTOR cleavage, which may be related to survival of the parasite. PMID:25548410

  11. Delineation of upper urinary tract segments at MDCT urography in patients with extra-urinary mass lesions: retrospective comparison of standard and low-dose protocols for the excretory phase of imaging

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Lisse, Ulrike L. [University of Munich, Department of Urology, Munich (Germany); University of Munich Medical School, Department of Urology, Muenchen (Germany); Coppenrath, Eva M.; Meindl, Thomas; Degenhart, Christoph; Scherr, Michael K.; Reiser, Maximilian F.; Mueller-Lisse, Ullrich G. [University of Munich, Department of Radiology, Munich (Germany); Stief, Christian G. [University of Munich, Department of Urology, Munich (Germany)

    2011-02-15

    Excretory-phase CT urography (CTU) may replace excretory urography in patients without urinary tumors. However, radiation exposure is a concern. We retrospectively compared upper urinary tract (UUT) delineation in low-dose and standard CTU. CTU (1-2 phases, 120 KV, 4 x 2.5 mm, pitch 0.875, i.v. non-ionic contrast media, iodine 36 g) was obtained with standard (14 patients, n = 27 UUTs, average 175.6 mAs/slice, average delay 16.8 min) or low-dose (26 patients, n = 86 UUTs, 29 mAs/slice, average delay 19.6 min) protocols. UUT was segmented into intrarenal collecting system (IRCS), upper, middle, and lower ureter (UU,MU,LU). Two independent readers (R1,R2) graded UUT segments as 1-not delineated, 2-partially delineated, 3-completely delineated (noisy margins), 4-completely delineated (clear margins). Chi-square statistics were calculated for partial versus complete delineation and complete delineation (clear margins), respectively. Complete delineation of UUT was similar in standard and low-dose CTU (R1, p > 0.15; R2, p > 0.2). IRCS, UU, and MU clearly delineated similarly often in standard and low-dose CTU (R1, p > 0.25; R2, p > 0.1). LU clearly delineated more often in standard protocols (R1, 18/6 standard, 38/31 low-dose, p > 0.1; R2 18/6 standard, 21/48 low-dose, p < 0.05). Low-dose CTU sufficiently delineated course of UUT and may locate obstruction/dilation, but appears unlikely to find intraluminal LU lesions. (orig.)

  12. In vivo thermoluminescent dosimetry in studies of helicoid computed tomography and excretory urogram; Dosimetria termoluminiscente In vivo en estudios de tomografia computada helicoidal y urograma excretor

    Energy Technology Data Exchange (ETDEWEB)

    Cruz C, D.; Azorin N, J. [UAM-I, 09340 Mexico D.F. (Mexico); Saucedo A, V.M.; Barajas O, J.L. [Unidad de Especialidades Medicas, Secretaria de la Defensa Nacional, 11500 Mexico D.F. (Mexico)

    2005-07-01

    The dosimetry is the field of measurement of the ionizing radiations. It final objective is to determine the 'absorbed dose' for people. The dosimetry is vital in the radiotherapy, the radiological protection and the treatment technologies by irradiation. Presently work, we develop 'In vivo' dosimetry, in exposed patients to studies of helical computed tomography and excretory urogram. The dosimetry 'in vivo' was carried out in 20 patients selected aleatorily, for each medical study. The absorbed dose was measured in points of interest located in crystalline, thyroid, chest and abdomen of each patient, by means of thermoluminescent dosemeters (TLD) LiF: Mg,Cu,P + Ptfe of national fabrication. Also it was quantified the dose in the working area. (Author)

  13. Biochemical and immunological characterization of annexin B30 from Clonorchis sinensis excretory/secretory products.

    Science.gov (United States)

    He, Lei; Ren, Mengyu; Chen, Xueqing; Wang, Xiaoyun; Li, Shan; Lin, Jinsi; Liang, Chi; Liang, Pei; Hu, Yue; Lei, Huali; Bian, Meng; Huang, Yan; Wu, Zhongdao; Li, Xuerong; Yu, Xinbing

    2014-07-01

    Clonorchis sinensis has been classified as group I biological carcinogen for cholangiocarcinoma by the World Health Organization. Biological studies on excretory/secretory products (ESPs) enabled us to understand the pathogenesis mechanism of C. sinensis and develop new strategies for the prevention of clonorchiasis. In this study, sequence analysis showed that annexin B30 from C. sinensis (CsANXB30) is composed of four annexin repeats which were characterized by type II and III Ca(2+)-binding sites or KGD motif with the capability of Ca(2+)-binding. In addition, immunoblot assay revealed that recombinant CsANXB30 (rCsANXB30) could be recognized by the sera from rats infected with C. sinensis and the sera from rats immunized by CsESPs. Real-time PCR showed that its transcriptional level was the highest at the stage of metacercaria. Immunofluorescence assay was employed to confirm that CsANXB30 was distributed in the tegument, intestine, and egg of adult worms, as well as the tegument and vitellarium of metacercaria. rCsANXB30 was able to bind phospholipid in a Ca(2+)-dependent manner and human plasminogen in a dose-dependent manner. Moreover, cytokine and antibody measurements indicated that rats subcutaneously immunized with rCsANXB30 developed a strong IL-10 production in spleen cells and a high level of IgG1 isotype, indicating that rCsANXB30 could trigger specific humoral and cellular immune response in rats. The present results implied that CsANXB30 might be involved in a host-parasite interaction and affected the immune response of the host during C. sinensis infection.

  14. Antigravity suit inflation: kidney function and cardiovascular and hormonal responses in men.

    Science.gov (United States)

    Geelen, G; Kravik, S E; Hadj-Aissa, A; Leftheriotis, G; Vincent, M; Bizollon, C A; Sem-Jacobsen, C W; Greenleaf, J E; Gharib, C

    1989-02-01

    To investigate the effects of lower body positive pressure (LBPP) on kidney function while controlling certain cardiovascular and endocrine responses, seven men [35 +/- 2 (SE) yr] underwent 30 min of sitting and then 4.5 h of 70 degrees head-up tilt. An antigravity suit was applied (60 Torr legs, 30 Torr abdomen) during the last 3 h of tilt. A similar noninflation experiment was conducted where the suited subjects were tilted for 3.5 h. To provide adequate urine flow, the subjects were hydrated during the course of both experiments. Immediately after inflation, mean arterial pressure increased by 8 +/- 3 Torr and pulse rate decreased by 16 +/- 3 beats/min. Plasma renin activity and aldosterone were maximally suppressed (P less than 0.05) after 2.5 h of inflation. Plasma vasopressin decreased by 40-50% (P less than 0.05) and plasma sodium and potassium remained unchanged during both experiments. Glomerular filtration rate was not increased significantly by inflation, whereas inflation induced marked increases (P less than 0.05) in effective renal plasma flow (ERPF), urine flow, osmolar and free water clearances, and total and fractional sodium excretion. No such changes occurred during control. Thus, LBPP induces 1) a significant increase in ERPF and 2) significant changes in kidney excretory patterns similar to those observed during water immersion or the early phase of bed rest, situations that also result in central vascular volume expansion.

  15. Sequential hepatobiliary scintigraphy of the patients with constitutional jaundice, ICG excretory defect disease and hepatocellular carcinoma with 99mTc-PI, 99mTc-HIDA and 99mTc-EHIDA

    International Nuclear Information System (INIS)

    Mitani, Tsuyoshi

    1987-01-01

    Sequential 2 min scintiphotos were obtained with a scintilation camera after intravenous injection of 3 mCi of 99m Tc-HIDA or 99m Tc-PI. Digital matrix images were simultaneously recorded with computer. Sequential samples for the blood clearance of 99m Tc-HIDA or 99m Tc-PI were obtained for 120 min following injection to the patient of constitutional hyperbilirubinemia and ICG excretory defect disease. In Dubin-Johnson syndrome, the hepatic uptake of 99m Tc-HIDA was faster or normal but the excretion was extremely slower than in normal cases. Both hepatic uptake and excretion of 99m Tc-PI were almost normal. In Rotor's disease, hepatic uptake of 99m Tc-HIDA or 99m Tc-PI was very poor, showing almost no hepatic images in all time. In Gilbert's disease and ICG excretory defect disease, hepatic uptake and excretion of 99m Tc-HIDA or 99m Tc-PI were within normal limit. From these results, Dubin-Johnson syndrome, Rotor's disease and Gilbert's disease show the different patterns between hepatic uptake and excretion of 99m Tc-HIDA and 99m Tc-PI hepatobiliary scintigraphy and these patterns contribute to the differential diagnosis of constitutional jaundice. The usefulness of hepatobiliary imaging with 99m Tc-EHIDA in diagnosis of hepatocellular carcinoma was studied in 15 patients with histologically verified HCC. In 15 patients, 3 patients (20 %) showed increased radioactivity with 99m Tc-EHIDA image, where liver scan with 99m Tc-Sn colloid showed filling defect. These results indicate that use of 99m Tc-EHIDA scan and 67 Ga-citrate imaging is useful for positive visualization of HCC. (author)

  16. TO THE QUESTION ON THE CHOICE OF RADIOTRACER FOR THE DINAMIC NEPHROSCINTIGRAPHY WITH FUNCTIONAL TESTS

    Directory of Open Access Journals (Sweden)

    D.K. Fomin

    2008-01-01

    Full Text Available The comparison of quality of the images at various stages complex dynamic nephroscintigraphy of the urinary tract received with use of various types of radiotracers. To all patients has been executed dynamic nephroscintigraphy with orthostatic sign and indirect radionuclide cystography, also the analysis of quality of images is lead by a method of expert estimations. It was established, that the best opportunities of a visual estimation of a condition of collective system of kidneys and ureters are provided with application tubular radiotraceres, and for an estimation parenchymatous phases of research — glomerular traceres.Key words: vesicoureteral reflux, secretory function of kidneys, excretory function of kidneys, dinamic scintigraphy, radionuclide cystography.

  17. Constraint-induced movement therapy promotes brain functional reorganization in stroke patients with hemiplegia

    Science.gov (United States)

    Wang, Wenqing; Wang, Aihui; Yu, Limin; Han, Xuesong; Jiang, Guiyun; Weng, Changshui; Zhang, Hongwei; Zhou, Zhiqiang

    2012-01-01

    Stroke patients with hemiplegia exhibit flexor spasms in the upper limb and extensor spasms in the lower limb, and their movement patterns vary greatly. Constraint-induced movement therapy is an upper limb rehabilitation technique used in stroke patients with hemiplegia; however, studies of lower extremity rehabilitation are scarce. In this study, stroke patients with lower limb hemiplegia underwent conventional Bobath therapy for 4 weeks as baseline treatment, followed by constraint-induced movement therapy for an additional 4 weeks. The 10-m maximum walking speed and Berg balance scale scores significantly improved following treatment, and lower extremity motor function also improved. The results of functional MRI showed that constraint-induced movement therapy alleviates the reduction in cerebral functional activation in patients, which indicates activation of functional brain regions and a significant increase in cerebral blood perfusion. These results demonstrate that constraint-induced movement therapy promotes brain functional reorganization in stroke patients with lower limb hemiplegia. PMID:25337108

  18. Molecular characterization of cathepsin B from Clonorchis sinensis excretory/secretory products and assessment of its potential for serodiagnosis of clonorchiasis

    Directory of Open Access Journals (Sweden)

    Zhou Chenhui

    2011-07-01

    Full Text Available Abstract Background Cathepsin cysteine proteases play multiple roles in the life cycle of parasites such as food uptake, immune invasion and pathogenesis, making them valuable targets for diagnostic assays, vaccines and drugs. The purpose of this study was to identify a cathepsin B of Clonorchis sinensis (CsCB and to investigate its diagnostic value for human helminthiases. Results The predicted amino acid sequence of the cathepsin B of C. sinensis shared 63%, 52%, 50% identity with that of Schistosoma japonicum, Homo sapiens and Fasciola hepatica, respectively. Sequence encoding proenzyme of CsCB was overexpressed in Escherichia coli. Reverse transcription PCR experiments revealed that CsCB transcribed in both adult worm and metacercaria of C. sinensis. CsCB was identified as a C. sinensis excretory/secretory product by immunoblot assay, which was consistent with immunohistochemical localization showing that CsCB was especially expressed in the intestine of C. sinensis adults. Both ELISA and western blotting analysis showed recombinant CsCB could react with human sera from clonorchiasis and other helminthiases. Conclusions Our findings revealed that secreted CsCB may play an important role in the biology of C. sinensis and could be a diagnostic candidate for helminthiases.

  19. Inducible tertiary lymphoid structures, autoimmunity and exocrine dysfunction in a novel model of salivary gland inflammation in C57BL/6 mice§

    Science.gov (United States)

    Bombardieri, Michele; Barone, Francesca; Lucchesi, Davide; Nayar, Saba; van den Berg, Wim B; Proctor, Gordon; Buckley, Christopher D; Pitzalis, Costantino

    2012-01-01

    Salivary glands in patients with Sjögren’s syndrome (SS) develop ectopic lymphoid structures (ELS) characterized by B/T cell compartmentalization, the formation of high endothelial venules (HEV), follicular dendritic cell networks (FDCs), functional B cell activation with expression of activation-induced cytidine deaminase (AID) as well as local differentiation of autoreactive plasma cells. The mechanisms triggering ELS formation, autoimmunity and exocrine dysfunction in SS are largely unknown. Here we present a novel model of inducible ectopic lymphoid tissue formation, breach of humoral self-tolerance and salivary hypofunction following delivery of a replication-deficient adenovirus-5 (AdV5) in submandibular glands of C57BL/6 mice through retrograde excretory duct cannulation. In this model, inflammation rapidly and consistently evolves from diffuse infiltration towards the development of SS-like periductal lymphoid aggregates within 2 weeks from AdV delivery. These infiltrates progressively acquire ELS features and support functional GL7+/AID+ germinal centers. Formation of ELS is preceded by ectopic expression of lymphoid chemokines CXCL13, CCL19 and lymphotoxin-β and is associated with development of anti-nuclear antibodies in up to 75% of mice. Finally, reduction in salivary flow was observed over 3 weeks post AdV infection consistent with exocrine gland dysfunction as a consequence of the inflammatory response. This novel model has the potential to unravel the cellular and molecular mechanisms regulating ELS formation and their role in exocrine dysfunction and autoimmunity in SS. PMID:22942425

  20. Comparative renal anatomy of exotic species.

    Science.gov (United States)

    Holz, Peter H; Raidal, Shane R

    2006-01-01

    All living organisms consume nutrients that are required for the production of both tissue and energy. The waste products of this process include nitrogenous materials and inorganic salts. They are removed from the body by excretory organs, which in vertebrate shave developed into kidneys and into salt glands in some birds and reptiles. Many invertebrates use a series of excretory organs called nephridia to perform the same function. Even though they perform similar functions, there is no evolutionary connection between invertebrate nephridia and vertebrate kidneys. Both evolved independently.

  1. Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes.

    Directory of Open Access Journals (Sweden)

    Benjamin R Jack

    2016-05-01

    Full Text Available Functional residues in proteins tend to be highly conserved over evolutionary time. However, to what extent functional sites impose evolutionary constraints on nearby or even more distant residues is not known. Here, we report pervasive conservation gradients toward catalytic residues in a dataset of 524 distinct enzymes: evolutionary conservation decreases approximately linearly with increasing distance to the nearest catalytic residue in the protein structure. This trend encompasses, on average, 80% of the residues in any enzyme, and it is independent of known structural constraints on protein evolution such as residue packing or solvent accessibility. Further, the trend exists in both monomeric and multimeric enzymes and irrespective of enzyme size and/or location of the active site in the enzyme structure. By contrast, sites in protein-protein interfaces, unlike catalytic residues, are only weakly conserved and induce only minor rate gradients. In aggregate, these observations show that functional sites, and in particular catalytic residues, induce long-range evolutionary constraints in enzymes.

  2. 活性氧清除剂 NAC 抑制阴道毛滴虫排泄分泌物诱导的 SiHa 细胞凋亡%REACTIVE OXYGEN SPECIES SCAVENGER PROTECTS SIHA CELL APOPTOSIS INDUCED BY TRICHOMONAS VAGINALIS EXCRETORY-SECRETORY PRODUCTS

    Institute of Scientific and Technical Information of China (English)

    全娟花; 李鹏; 黄瑞; 楚佳奇

    2015-01-01

    本研究旨在探讨活性氧( ROS)清除剂N-乙酰-L-半胱氨酸( NAC)能否抑制滴虫排泄分泌物( Tv ESP)诱导的人子宫颈癌SiHa细胞凋亡。体外培养阴道毛滴虫并制备Tv ESP,分别用100μg/mL Tv ESP和PBS处理SiHa细胞, Tv ESP处理SiHa细胞30 min前加入NAC,进行预处理。使用CellTiter 96 AQueous单溶液细胞增殖检测试剂盒检测细胞存活率;利用2′,7′-二氯荧光黄双乙酸盐( DCFH-DA)进行荧光探针标记测定胞内ROS水平;免疫印迹法检测cleaved caspase-3和PARP-1蛋白表达。结果显示, NAC预处理可降低Tv ESP的细胞毒性作用。 Tv ESP作用SiHa细胞16 h后,细胞内ROS水平升高,但经过NAC预处理后胞内ROS生成显著降低。此外, NAC预处理后能显著下调Tv ESP诱导的cleaved caspase-3和cleaved PARP-1的表达水平。%This study intends to investigate whether the reactive oxygen species ( ROS ) scavenger N-aeetyl-L-cysteine ( NAC ) can inhibit Trichomonas vaginalis excretory-secretory products ( Tv ESP ) induced apoptosis of human cervical cancer ( SiHa) cells.T.vaginalis were in vitro cultured and Tv ESP were prepared.SiHa cells were treated with 100 μg/mL Tv ESP, PBS and NAC was pretreated with SiHa cells 30 min prior to exposure to 100 μg/mL Tv ESP.The cell viability was evaluated using CellTiter 96 AQueous One Solution Cell Proliferation Assay kit, and the intercellular ROS level was measured by fluorescent probe 2′, 7′-dichlorfluorescein-diacetate ( DCFH-DA ) .Cleaved caspase-3 and PARP-1 protein levels were detected by Western blot.Our results demonstrate that pretreatment of NAC reduced Tv ESP induced SiHa cell cytotoxicity.Intracellular ROS levels were highly induced after exposure to 100 μg/mL Tv ESP for 16 h, however, intracellular ROS levels were significantly reduced by pretreatment of NAC.In addition, pretreatment of NAC, significantly reduced cleaved caspase-3 and cleaved PARP-1

  3. Triclabendazole Effect on Protease Enzyme Activity in the Excretory- Secretory Products of Fasciola hepatica in Vitro.

    Directory of Open Access Journals (Sweden)

    Yosef Shrifi

    2014-03-01

    Full Text Available Fasciola hepatica is one of the most important helminthes parasites and triclabendazole (TCBZ is routinely used for treatment of infected people and animals. Secreted protease enzymes by the F. hepatica plays a critical role in the invasion, migration, nutrition and the survival of parasite and are key targets for novel drugs and vaccines. The aim of study was to determine the protease activity of excretory- secretory products (ESP of F. hepatica in the presence of TCBZ anthelmintic.F. hepatica helminthes were collected and cultured within RPMI 1640 [TCBZ treated (test and untreated (control] for 6 h at 37 °C. ESP of treated and control were collected, centrifuged and supernatants were stored at -20°C. Protein concentrations were measured according to Bradford method. Protease enzymes activities of ESP samples were estimated by using sigma's non-specific protease activity assay. ESP protein bands were detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE.Mean protein concentrations in control and treated of ESP samples were determined 196.1 ±14.52 and 376.4 ±28.20 μg/ml, respectively. Mean protease enzymes activities in control and treated were 0.37 ±0.1 and 0.089 ±0.03 U/ml, respectively. Significant difference between proteins concentrations and protease enzymes activities of two groups was observed (P<0.05. SDS-PAGE showed different patterns of protein bands between treated and control samples.The TCBZ reduced secreted protease enzymes activities and possibly effects on invasion, migration, nutrition and particularly survival of the parasite in the host tissues.

  4. The renal quantitative scintillation camera study for determination of renal function

    International Nuclear Information System (INIS)

    Thompson, I.M. Jr.; Boineau, F.G.; Evans, B.B.; Schlegel, J.U.

    1983-01-01

    The renal quantitative scintillation camera study assesses glomerular filtration rate and effective renal plasma flow based upon renal uptake of 99mtechnetium-iron ascorbate and 131iodine-hippuran, respectively. The method was compared to inulin, para-aminohippuric acid and creatinine clearance studies in 7 normal subjects and 9 patients with various degrees of reduced renal function. The reproducibility of the technique was determined in 15 randomly selected pediatric patients. The values of glomerular filtration rate and effective renal plasma flow were not significantly different from those of inulin and para-aminohippuric acid studies. The reproducibility of the technique was comparable to that of inulin and para-aminohippuric acid studies. Patient acceptance of the technique is excellent and the cost is minimal. Renal morphology and excretory dynamics also are demonstrated. The technique is advocated as a clinical measure of renal function

  5. Radiation effects on regeneration and T-cell-inducing function of the thymus

    International Nuclear Information System (INIS)

    Hirokawa, K.; Sado, T.

    1984-01-01

    Radiation effects on regeneration and T-cell-inducing function of the thymus were studied in three sets of experiments. When TXB mice were grafted with 1-week-old thymus which had been previously irradiated at various doses, an exponential decrease was observed in the morphological regeneration of the thymus grafts and in their T-cell-inducing function at doses of 600 R and over, showing about 10% that of the control at 1500 R. When in situ thymus of adult mice was locally irradiated, the radiation effect on T-cell-inducing function was less pronounced as compared with the first experiment; i.e., about 40% of the control at 1797 R. When in situ thymus of 1-day-old newborn mice was locally irradiated, regeneration potential of 1-day-old newborn thymus was highly resistant to radiation exposure and no effect on immunological functions was observed even by local irradiation of 2000 R

  6. A Comparative Study of 131I-Hippuran Renogram, 131I-Hippuran Urinary Excretion Test and Intravenous Pyelogram in Obstructive Uropathy due to Cancerous Invasion

    International Nuclear Information System (INIS)

    Park, Kee Bok; Rhee, Chong Heon; Hong, Chang Gi; Park, Soo Seong; Koh, Chang Soon

    1968-01-01

    A comparative study of 131 I-hippuran renogram, 131 I-hippuran excretion test and intravenous pyelogram were performed in 61 cases of gynecological cancer. The following were the results: 1) Among 40 cases of cervix cancer showing normal excretory urography 7 cases (17.5%) were found to have unilateral or bilateral delayed excretory pattern on 131 I-hippuran renogram and on the contrary only 2 cases (5.7%) showed a mild caliectatic change on excretory urography among 35 cases of gynecological cancer showing normal pattern of 131 I-hippuran renogram. 2) In the group showing unilateral of bilateral delayed excretory pattern of 131 I-hippuran renogram there was a reduction of 131 I-hippuran excretion in the first 20 minutes, but there was no significant difference of 131 I-hippuran excretion in 60 minutes compared with that of normal renogram group. 3) In the group showing unilateral non-functioning pattern of 131 I-hippuran renogram in one side and normal pattern in the other side there was found to be no difference in 131 I-hippuran excretion amount compared with that of normal renogram group. 4) It was evident from these experimental study that 131 I-hippuran renogram was considered as a good examination method for the evaluation of obstructive uropathy, and if one side kidney was intact it might compensate for the other diseased kidney so far as to renal excretory function. It was also shown that the more severe the cancerous spread in the pelvic wall the more changes on 131 I-hippuran renogram.

  7. Distinct Cell Guidance Pathways Controlled by the Rac and Rho GEF Domains of UNC-73/TRIO in Caenorhabditis elegans

    Science.gov (United States)

    Marcus-Gueret, Nancy; Schmidt, Kristopher L.; Stringham, Eve G.

    2012-01-01

    The cytoskeleton regulator UNC-53/NAV2 is required for both the anterior and posterior outgrowth of several neurons as well as that of the excretory cell while the kinesin-like motor VAB-8 is essential for most posteriorly directed migrations in Caenorhabditis elegans. Null mutations in either unc-53 or vab-8 result in reduced posterior excretory canal outgrowth, while double null mutants display an enhanced canal extension defect, suggesting the genes act in separate pathways to control this posteriorly directed outgrowth. Genetic analysis of putative interactors of UNC-53 or VAB-8, and cell-specific rescue experiments suggest that VAB-8, SAX-3/ROBO, SLT-1/Slit, and EVA-1 are functioning together in the outgrowth of the excretory canals, while UNC-53 appears to function in a parallel pathway with UNC-71/ADAM. The known VAB-8 interactor, the Rac/Rho GEF UNC-73/TRIO operates in both pathways, as isoform specific alleles exhibit enhancement of the phenotype in double-mutant combination with either unc-53 or vab-8. On the basis of these results, we propose a bipartite model for UNC-73/TRIO activity in excretory canal extension: a cell autonomous function that is mediated by the Rho-specific GEF domain of the UNC-73E isoform in conjunction with UNC-53 and UNC-71 and a cell nonautonomous function that is mediated by the Rac-specific GEF domain of the UNC-73B isoform, through partnering with VAB-8 and the receptors SAX-3 and EVA-1. PMID:21996675

  8. Capsaicin induced histological and ultrastructural changes in the submandibular salivary gland of albino rats

    Directory of Open Access Journals (Sweden)

    Ahmed Mahmoud Halawa

    2016-06-01

    From the present work, it could be concluded that chronic capsaicin intake was associated with noticeable histological and ultrastructural changes in acini, granular convoluted tubules and excretory ducts of the SMSG in albino rats.

  9. A Model for Microcontroller Functionality Upset Induced by External Pulsed Electromagnetic Irradiation

    Science.gov (United States)

    2016-11-21

    AFRL-RD-PS- AFRL-RD-PS- TN-2016-0003 TN-2016-0003 A Model for Microcontroller Functionality Upset Induced by External Pulsed Electromagnetic...TYPE Technical Note 3. DATES COVERED (From - To) 22-11-2015 – 21-11-2016 4. TITLE AND SUBTITLE A Model for Microcontroller Functionality Upset Induced by... microcontroller (µC) subjected to external irradiation by a narrowband electromagnetic (EM) pulse. In our model, the state of a µC is completely specified by

  10. Maintenance of exercise-induced benefits in physical functioning and bone among elderly women.

    Science.gov (United States)

    Karinkanta, S; Heinonen, A; Sievänen, H; Uusi-Rasi, K; Fogelholm, M; Kannus, P

    2009-04-01

    This study showed that about a half of the exercise-induced gain in dynamic balance and bone strength was maintained one year after cessation of the supervised high-intensity training of home-dwelling elderly women. However, to maintain exercise-induced gains in lower limb muscle force and physical functioning, continued training seems necessary. Maintenance of exercise-induced benefits in physical functioning and bone structure was assessed one year after cessation of 12-month randomized controlled exercise intervention. Originally 149 healthy women 70-78 years of age participated in the 12-month exercise RCT and 120 (81%) of them completed the follow-up study. Self-rated physical functioning, dynamic balance, leg extensor force, and bone structure were assessed. During the intervention, exercise increased dynamic balance by 7% in the combination resistance and balance-jumping training group (COMB). At the follow-up, a 4% (95% CI: 1-8%) gain compared with the controls was still seen, while the exercise-induced isometric leg extension force and self-rated physical functioning benefits had disappeared. During the intervention, at least twice a week trained COMB subjects obtained a significant 2% benefit in tibial shaft bone strength index compared to the controls. A half of this benefit seemed to be maintained at the follow-up. Exercise-induced benefits in dynamic balance and rigidity in the tibial shaft may partly be maintained one year after cessation of a supervised 12-month multi-component training in initially healthy elderly women. However, to maintain the achieved gains in muscle force and physical functioning, continued training seems necessary.

  11. A Comparative Study of {sup 131}I-Hippuran Renogram, {sup 131}I-Hippuran Urinary Excretion Test and Intravenous Pyelogram in Obstructive Uropathy due to Cancerous Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Park, Kee Bok; Rhee, Chong Heon; Hong, Chang Gi; Park, Soo Seong; Koh, Chang Soon [Radiological Research Institue, Seoul (Korea, Republic of)

    1968-03-15

    A comparative study of {sup 131}I-hippuran renogram, {sup 131}I-hippuran excretion test and intravenous pyelogram were performed in 61 cases of gynecological cancer. The following were the results: 1) Among 40 cases of cervix cancer showing normal excretory urography 7 cases (17.5%) were found to have unilateral or bilateral delayed excretory pattern on {sup 131}I-hippuran renogram and on the contrary only 2 cases (5.7%) showed a mild caliectatic change on excretory urography among 35 cases of gynecological cancer showing normal pattern of {sup 131}I-hippuran renogram. 2) In the group showing unilateral of bilateral delayed excretory pattern of {sup 131}I-hippuran renogram there was a reduction of {sup 131}I-hippuran excretion in the first 20 minutes, but there was no significant difference of {sup 131}I-hippuran excretion in 60 minutes compared with that of normal renogram group. 3) In the group showing unilateral non-functioning pattern of {sup 131}I-hippuran renogram in one side and normal pattern in the other side there was found to be no difference in {sup 131}I-hippuran excretion amount compared with that of normal renogram group. 4) It was evident from these experimental study that {sup 131}I-hippuran renogram was considered as a good examination method for the evaluation of obstructive uropathy, and if one side kidney was intact it might compensate for the other diseased kidney so far as to renal excretory function. It was also shown that the more severe the cancerous spread in the pelvic wall the more changes on {sup 131}I-hippuran renogram.

  12. Reversible cold-induced abnormalities in myocardial perfusion and function in systemic sclerosis

    International Nuclear Information System (INIS)

    Alexander, E.L.; Firestein, G.S.; Weiss, J.L.; Heuser, R.R.; Leitl, G.; Wagner, H.N. Jr.; Brinker, J.A.; Ciuffo, A.A.; Becker, L.C.

    1986-01-01

    The effects of peripheral cold exposure on myocardial perfusion and function were studied in 13 patients with scleroderma without clinically evident myocardial disease. Ten patients had at least one transient, cold-induced, myocardial perfusion defect visualized by thallium-201 scintigraphy, and 12 had reversible, cold-induced, segmental left ventricular hypokinesis by two-dimensional echocardiography. The 10 patients with transient perfusion defects all had anatomically corresponding ventricular wall motion abnormalities. No one in either of two control groups (9 normal volunteers and 7 patients with chest pain and normal coronary arteriograms) had cold-induced abnormalities. This study is the first to show the simultaneous occurrence of cold-induced abnormalities in myocardial perfusion and function in patients with scleroderma. The results suggest that cold exposure in such patients may elicit transient reflex coronary vasoconstriction resulting in reversible myocardial ischemia and dysfunction. Chronic recurrent episodes of coronary spasm may lead to focal myocardial fibrosis

  13. Effects of hyperthermia on the normal liver using scintigraphic methods. Functional changes of the rabbit whole-liver by local hyperthermia

    International Nuclear Information System (INIS)

    Ryu, Kiyotaka; Shinotsuka, Akira; Takenaka, Hiroki; Hirono, Yoshisada

    1995-01-01

    An experimental study was conducted to investigate effect of hyperthermia to the liver in rabbits. The whole liver was heated at 43degC for 30 min by a RF capacitive heating device, and subsequent changes were observed by scintigraphy using 99m Tc-EHIDA and 99m Tc-Sn-colloid. The excretory ratio (Ke value) of 99m Tc-EHIDA and the uptake ratio (K value) of 99m Tc-Sn-colloid were measured to estimate hyperthermia induced hepatic injury for a month. Blood chemistry analysis was also conducted during this period. Also, the uptake of 3 H-methyl-thymidine into the DNA of hepatocyted was assayed 2 and 5 days after heating. Concurrently, histopathological changes were observed. The Ke value showed a transient increase and returned to the level prior to heating after approximately one week. A distinct increase in GPT was observed. The uptake of 3 H-methyl-thymidine showed a marked rise 2 days after hyperthermia, which demonstrated regeneration of the previously damaged hepatocytes. Pathologically, overall liver congestion and hepatocytes necrosis were noted. Also, both enlargement of the nuclei and binuclear hepatocytes were present, pathologically proving hepatocytes regeneration. The K value showed a transient decrease, showing that the reticuloendothelial function and blood flow of the liver were temporarily reduced. These results indicate the whole liver function damaged by hyperthermia is reversible. (author)

  14. Characterization of the secreted cathepsin B cysteine proteases family of the carcinogenic liver fluke Clonorchis sinensis.

    Science.gov (United States)

    Chen, Wenjun; Wang, Xiaoyun; Lv, Xiaoli; Tian, Yanli; Xu, Yanquan; Mao, Qiang; Shang, Mei; Li, Xuerong; Huang, Yan; Yu, Xinbing

    2014-09-01

    Clonorchis sinensis excretory/secretory products (ESP) have gained high attentions because of their potential to be vaccine candidates and drug targets in C. sinensis prevention. In this study, we extensively profiled the characteristics of four C. sinensis cathepsin B cysteine proteases (CsCB1, CsCB2, CsCB3, and CsCB4). Bioinformatics analysis showed all CsCBs contained signal peptides at the N-terminal. Functional domains and residues were found in CsCB sequences. We expressed four CsCBs and profiled immune responses followed by vaccine trials. Recombinant CsCBs could induce high IgG titers, indicating high immunogenicity of CsCB family. Additionally, ELISA results showed that both IgG1 and IgG2a levels apparently increased post-immunization with all four CsCBs, showing that combined Th1/Th2 immune responses were triggered by CsCB family. Both Real-time polymerase chain reaction (RT-PCR) and Western blotting confirmed that four CsCBs have distinct expression patterns in C. sinensis life stages. More importantly, we validated our hypothesis that CsCBs were C. sinensis excretory/secretory products. CsCBs could be recognized by C. sinensis-infected sera throughout the infection period, indicating that secreted CsCBs are immune triggers during C. sinensis infection. The protective effect was assessed by comparing the worm burden and egg per gram (EPG) between CsCB group and control group, showing that worm burden (P sinensis excretory/secretory products that may regulate host immune responses.

  15. Increasing fetal ovine number per gestation alters fetal plasma clinical chemistry values.

    Science.gov (United States)

    Zywicki, Micaela; Blohowiak, Sharon E; Magness, Ronald R; Segar, Jeffrey L; Kling, Pamela J

    2016-08-01

    Intrauterine growth restriction (IUGR) is interconnected with developmental programming of lifelong pathophysiology. IUGR is seen in human multifetal pregnancies, with stepwise rises in fetal numbers interfering with placental nutrient delivery. It remains unknown whether fetal blood analyses would reflect fetal nutrition, liver, and excretory function in the last trimester of human or ovine IUGR In an ovine model, we hypothesized that fetal plasma biochemical values would reflect progressive placental, fetal liver, and fetal kidney dysfunction as the number of fetuses per gestation rose. To determine fetal plasma biochemical values in singleton, twin, triplet, and quadruplet/quintuplet ovine gestation, we investigated morphometric measures and comprehensive metabolic panels with nutritional measures, liver enzymes, and placental and fetal kidney excretory measures at gestational day (GD) 130 (90% gestation). As anticipated, placental dysfunction was supported by a stepwise fall in fetal weight, fetal plasma glucose, and triglyceride levels as fetal number per ewe rose. Fetal glucose and triglycerides were directly related to fetal weight. Plasma creatinine, reflecting fetal renal excretory function, and plasma cholesterol, reflecting placental excretory function, were inversely correlated with fetal weight. Progressive biochemical disturbances and growth restriction accompanied the rise in fetal number. Understanding the compensatory and adaptive responses of growth-restricted fetuses at the biochemical level may help explain how metabolic pathways in growth restriction can be predetermined at birth. This physiological understanding is important for clinical care and generating interventional strategies to prevent altered developmental programming in multifetal gestation. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  16. Effect of acute moderate exercise on induced inflammation and arterial function in older adults.

    Science.gov (United States)

    Ranadive, Sushant Mohan; Kappus, Rebecca Marie; Cook, Marc D; Yan, Huimin; Lane, Abbi Danielle; Woods, Jeffrey A; Wilund, Kenneth R; Iwamoto, Gary; Vanar, Vishwas; Tandon, Rudhir; Fernhall, Bo

    2014-04-01

    Acute inflammation reduces flow-mediated vasodilatation and increases arterial stiffness in young healthy individuals. However, this response has not been studied in older adults. The aim of this study, therefore, was to evaluate the effect of acute induced systemic inflammation on endothelial function and wave reflection in older adults. Furthermore, an acute bout of moderate-intensity aerobic exercise can be anti-inflammatory. Taken together, we tested the hypothesis that acute moderate-intensity endurance exercise, immediately preceding induced inflammation, would be protective against the negative effects of acute systemic inflammation on vascular function. Fifty-nine healthy volunteers between 55 and 75 years of age were randomized to an exercise or a control group. Both groups received a vaccine (induced inflammation) and sham (saline) injection in a counterbalanced crossover design. Inflammatory markers, endothelial function (flow-mediated vasodilatation) and measures of wave reflection and arterial stiffness were evaluated at baseline and at 24 and 48 h after injections. There were no significant differences in endothelial function and arterial stiffness between the exercise and control group after induced inflammation. The groups were then analysed together, and we found significant differences in the inflammatory markers 24 and 48 h after induction of acute inflammation compared with sham injection. However, flow-mediated vasodilatation, augmentation index normalized for heart rate (AIx75) and β-stiffness did not change significantly. Our results suggest that acute inflammation induced by influenza vaccination did not affect endothelial function in older adults.

  17. Biliary copper excretion by hepatocyte lysosomes in the rat. Major excretory pathway in experimental copper overload

    International Nuclear Information System (INIS)

    Gross, J.B. Jr.; Myers, B.M.; Kost, L.J.; Kuntz, S.M.; LaRusso, N.F.

    1989-01-01

    We investigated the hypothesis that lysosomes are the main source of biliary copper in conditions of hepatic copper overload. We used a rat model of oral copper loading and studied the relationship between the biliary output of copper and lysosomal hydrolases. Male Sprague-Dawley rats were given tap water with or without 0.125% copper acetate for up to 36 wk. Copper loading produced a 23-fold increase in the hepatic copper concentration and a 30-65% increase in hepatic lysosomal enzyme activity. Acid phosphatase histochemistry showed that copper-loaded livers contained an increased number of hepatocyte lysosomes; increased copper concentration of these organelles was confirmed directly by both x ray microanalysis and tissue fractionation. The copper-loaded rats showed a 16-fold increase in biliary copper output and a 50-300% increase in biliary lysosomal enzyme output. In the basal state, excretory profiles over time were similar for biliary outputs of lysosomal enzymes and copper in the copper-loaded animals but not in controls. After pharmacologic stimulation of lysosomal exocytosis, biliary outputs of copper and lysosomal hydrolases in the copper-loaded animals remained coupled: injection of colchicine or vinblastine produced an acute rise in the biliary output of both lysosomal enzymes and copper to 150-250% of baseline rates. After these same drugs, control animals showed only the expected increase in lysosomal enzyme output without a corresponding increase in copper output. We conclude that the hepatocyte responds to an increased copper load by sequestering excess copper in an increased number of lysosomes that then empty their contents directly into bile. The results provide direct evidence that exocytosis of lysosomal contents into biliary canaliculi is the major mechanism for biliary copper excretion in hepatic copper overload

  18. Dexamethasone impairs hypoxia-inducible factor-1 function

    International Nuclear Information System (INIS)

    Wagner, A.E.; Huck, G.; Stiehl, D.P.; Jelkmann, W.; Hellwig-Buergel, T.

    2008-01-01

    Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription-factor composed of α- and β-subunits. HIF-1 is not only necessary for the cellular adaptation to hypoxia, but it is also involved in inflammatory processes and wound healing. Glucocorticoids (GC) are therapeutically used to suppress inflammatory responses. Herein, we investigated whether GC modulate HIF-1 function using GC receptor (GR) possessing (HepG2) and GR deficient (Hep3B) human hepatoma cell cultures as model systems. Dexamethasone (DEX) treatment increased HIF-1α levels in the cytosol of HepG2 cells, while nuclear HIF-1α levels and HIF-1 DNA-binding was reduced. In addition, DEX dose-dependently lowered the hypoxia-induced luciferase activity in a reporter gene system. DEX suppressed the hypoxic stimulation of the expression of the HIF-1 target gene VEGF (vascular endothelial growth factor) in HepG2 cultures. DEX did not reduce hypoxically induced luciferase activity in HRB5 cells, a Hep3B derivative lacking GR. Transient expression of the GR in HRB5 cells restored the susceptibility to DEX. Our study discloses the inhibitory action of GC on HIF-1 dependent gene expression, which may be important with respect to the impaired wound healing in DEX-treated patients

  19. Diet-induced obesity: dopamine transporter function, impulsivity and motivation.

    Science.gov (United States)

    Narayanaswami, V; Thompson, A C; Cassis, L A; Bardo, M T; Dwoskin, L P

    2013-08-01

    A rat model of diet-induced obesity (DIO) was used to determine dopamine transporter (DAT) function, impulsivity and motivation as neurobehavioral outcomes and predictors of obesity. To evaluate neurobehavioral alterations following the development of DIO induced by an 8-week high-fat diet (HF) exposure, striatal D2-receptor density, DAT function and expression, extracellular dopamine concentrations, impulsivity, and motivation for high- and low-fat reinforcers were determined. To determine predictors of DIO, neurobehavioral antecedents including impulsivity, motivation for high-fat reinforcers, DAT function and extracellular dopamine were evaluated before the 8-week HF exposure. Striatal D2-receptor density was determined by in vitro kinetic analysis of [(3)H]raclopride binding. DAT function was determined using in vitro kinetic analysis of [(3)H]dopamine uptake, methamphetamine-evoked [(3)H]dopamine overflow and no-net flux in vivo microdialysis. DAT cell-surface expression was determined using biotinylation and western blotting. Impulsivity and food-motivated behavior were determined using a delay discounting task and progressive ratio schedule, respectively. Relative to obesity-resistant (OR) rats, obesity-prone (OP) rats exhibited 18% greater body weight following an 8-week HF-diet exposure, 42% lower striatal D2-receptor density, 30% lower total DAT expression, 40% lower in vitro and in vivo DAT function, 45% greater extracellular dopamine and twofold greater methamphetamine-evoked [(3)H]dopamine overflow. OP rats exhibited higher motivation for food, and surprisingly, were less impulsive relative to OR rats. Impulsivity, in vivo DAT function and extracellular dopamine concentration did not predict DIO. Importantly, motivation for high-fat reinforcers predicted the development of DIO. Human studies are limited by their ability to determine if impulsivity, motivation and DAT function are causes or consequences of DIO. The current animal model shows that

  20. Immobilisation-induced hypercalcemia following spinal cord injury affecting the kidney function in two young native Greenlanders

    DEFF Research Database (Denmark)

    Linstow, Michael V; Biering-Sørensen, Fin

    2017-01-01

    INTRODUCTION: Immobilisation-induced hypercalcemia following SCI affecting the kidney function, is a rare but potentially serious condition. We report immobilisation-induced hypercalcemia affecting the kidney function in two young native Greenlanders with spinal cord injury (SCI). CASE...... PRESENTATIONS: Two 15- and 24-year-old male native Greenlanders, both with traumatic C5 SCI were admitted to our spinal cord unit. They were non-smokers without history of daily alcohol intake pre- or immediately post-injury. No physical demanding activities pre-injury. Due to complaints of nausea/vomiting 10...... the last 20 years our spinal cord unit has only experienced immobilisation-induced hypercalcemia following SCI affecting the kidney function in two young male native Greenlanders. This finding of immobilisation-induced hypercalcemia following SCI affecting the kidney function in two young native...

  1. EFFECT OF MODIFIED CONSTRAINT INDUCED THERAPY ON UPPERLIMB FUNCTIONAL RECOVERY IN YOUNG STROKE SUBJECTS

    Directory of Open Access Journals (Sweden)

    Kiran Prakash Pappala

    2014-10-01

    Full Text Available Background: The aim of this study is to evaluate the effect of modified constraint induced therapy on upper limb functional recovery in young stroke subjects. Most of the stroke rehabilitation units following conventional rehabilitation methods for treatment of the stroke patients where these methods have been proved to be less useful especially in the young stroke subjects. Hence the purpose of this study is to see the effect of modified constraint induced therapy which is a task specific training method for upperlimb in young stroke subjects. Methods: Total of 40 young stroke subjects who is having minimal motor criterion and met other inclusion criteria were recruited from department of physiotherapy, g.s.l.general hospital. Pre and post intervention measures were taken using Wolf motor function test and Jebsen Taylor hand function test. Results: In this study had shown significant improvements in the modified constraint induced therapy group when compared to the conventional rehabilitation alone. P value between groups was < 0.05. Conclusion: In this study concludes that addition of 15 minutes modified constraint induced movement therapy to conventional physiotherapy is a useful adjunct in functional recovery of upper limb among young stroke subjects

  2. Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats.

    Directory of Open Access Journals (Sweden)

    Tsung-I Chen

    Full Text Available In obstructive sleep apnea (OSA, recurrent obstruction of the upper airway leads to intermittent hypoxia (IH during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON or to a group receiving 10 weeks of exercise training (EXE. During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE, whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl ethylenediamine (TPEN, or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect.

  3. Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats

    Science.gov (United States)

    Chen, Michael Yu-Chih

    2016-01-01

    In obstructive sleep apnea (OSA), recurrent obstruction of the upper airway leads to intermittent hypoxia (IH) during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON) or to a group receiving 10 weeks of exercise training (EXE). During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE), whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect. PMID:27977796

  4. Extracellular Enzyme Composition and Functional Characteristics of Aspergillus niger An-76 Induced by Food Processing Byproducts and Based on Integrated Functional Omics.

    Science.gov (United States)

    Liu, Lin; Gong, Weili; Sun, Xiaomeng; Chen, Guanjun; Wang, Lushan

    2018-02-07

    Byproducts of food processing can be utilized for the production of high-value-added enzyme cocktails. In this study, we utilized integrated functional omics technology to analyze composition and functional characteristics of extracellular enzymes produced by Aspergillus niger grown on food processing byproducts. The results showed that oligosaccharides constituted by arabinose, xylose, and glucose in wheat bran were able to efficiently induce the production of extracellular enzymes of A. niger. Compared with other substrates, wheat bran was more effective at inducing the secretion of β-glucosidases from GH1 and GH3 families, as well as >50% of proteases from A1-family aspartic proteases. Compared with proteins induced by single wheat bran or soybean dregs, the protein yield induced by their mixture was doubled, and the time required to reach peak enzyme activity was shortened by 25%. This study provided a technical platform for the complex formulation of various substrates and functional analysis of extracellular enzymes.

  5. [X-ray evaluation of renal function in children with hydronephrosis as a criterion in the selection of therapeutic tactics].

    Science.gov (United States)

    Bosin, V Iu; Murvanidze, D D; Sturua, D G; Nabokov, A K; Soloshenko, V N

    1989-01-01

    The anatomic parameters of the kidneys and the rate of glomerular filtration were measured in 77 children with unilateral hydronephrosis and in 27 children with nonobstructive diseases of the urinary tract according to the clearance of an opaque medium during excretory urography. Alterations in the anatomic parameters of the kidneys in obstructive affection did not reflect the gravity of functional disorders. It has been established that there is a possibility of carrying out a separate assessment of filtration function of the hydronephrotic and contralateral kidneys. A new diagnostic criterion is offered, namely an index of relative clearance, which enables one to measure the degree of compensatory phenomena in the preserved glomeruli and the extent of sclerotic process. It has been demonstrated that accurate measurement of the functional parameters of the affected kidney should underlie the treatment choice in children with unilateral hydronephrosis.

  6. Impaired atrial electromechanical function and atrial fibrillation promotion in alloxan-induced diabetic rabbits.

    Science.gov (United States)

    Fu, Huaying; Liu, Changle; Li, Jian; Zhou, Changyu; Cheng, Lijun; Liu, Tong; Li, Guangping

    2013-01-01

    Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF). However, the underlying mechanisms are still not clearly elucidated. The aim of this study was to evaluate the atrial electromechanical function, atrial electrophysiological changes and AF inducibility in alloxan-induced diabetic rabbits. In 8 alloxan-induced diabetic rabbits and 8 controls, we evaluated atrial electromechanical function by tissue Doppler imaging. Isolated Langendorff-perfused rabbit hearts were prepared to measure atrial refractory effective period (AERP) and its dispersion (AERPD), interatrial conduction time (IACT) and vulnerability to AF. Atrial interstitial fibrosis was evaluated by Sirius-Red staining. Compared with controls, left atrial lateral wall Pa'-start interval (Pastart) and right atrial wall Pastart were increased in diabetic rabbits. AERPD was increased and IACT was prolonged in diabetic rabbits. Inducibility of AF in diabetic group was significant higher than controls (6/8 vs. 1/8, p TEMA); left atrial lateral wall Papeak and TEMA, left atrial posterior wall TEMA, and IACT were correlated with atrial areas of fibrosis. Atrial electromechanical function is impaired in diabetic rabbits, and is associated with atrial fibrosis and interatrial electrical conduction delay.

  7. Measurement-induced decoherence and Gaussian smoothing of the Wigner distribution function

    International Nuclear Information System (INIS)

    Chun, Yong-Jin; Lee, Hai-Woong

    2003-01-01

    We study the problem of measurement-induced decoherence using the phase-space approach employing the Gaussian-smoothed Wigner distribution function. Our investigation is based on the notion that measurement-induced decoherence is represented by the transition from the Wigner distribution to the Gaussian-smoothed Wigner distribution with the widths of the smoothing function identified as measurement errors. We also compare the smoothed Wigner distribution with the corresponding distribution resulting from the classical analysis. The distributions we computed are the phase-space distributions for simple one-dimensional dynamical systems such as a particle in a square-well potential and a particle moving under the influence of a step potential, and the time-frequency distributions for high-harmonic radiation emitted from an atom irradiated by short, intense laser pulses

  8. Doxycycline Impairs Mitochondrial Function and Protects Human Glioma Cells from Hypoxia-Induced Cell Death: Implications of Using Tet-Inducible Systems.

    Science.gov (United States)

    Luger, Anna-Luisa; Sauer, Benedikt; Lorenz, Nadja I; Engel, Anna L; Braun, Yannick; Voss, Martin; Harter, Patrick N; Steinbach, Joachim P; Ronellenfitsch, Michael W

    2018-05-17

    Inducible gene expression is an important tool in molecular biology research to study protein function. Most frequently, the antibiotic doxycycline is used for regulation of so-called tetracycline (Tet)-inducible systems. In contrast to stable gene overexpression, these systems allow investigation of acute and reversible effects of cellular protein induction. Recent reports have already called for caution when using Tet-inducible systems as the employed antibiotics can disturb mitochondrial function and alter cellular metabolism by interfering with mitochondrial translation. Reprogramming of energy metabolism has lately been recognized as an important emerging hallmark of cancer and is a central focus of cancer research. Therefore, the scope of this study was to systematically analyze dose-dependent metabolic effects of doxycycline on a panel of glioma cell lines with concomitant monitoring of gene expression from Tet-inducible systems. We report that doxycycline doses commonly used with inducible expression systems (0.01⁻1 µg/mL) substantially alter cellular metabolism: Mitochondrial protein synthesis was inhibited accompanied by reduced oxygen and increased glucose consumption. Furthermore, doxycycline protected human glioma cells from hypoxia-induced cell death. An impairment of cell growth was only detectable with higher doxycycline doses (10 µg/mL). Our findings describe settings where doxycycline exerts effects on eukaryotic cellular metabolism, limiting the employment of Tet-inducible systems.

  9. Mechanochemistry Induced Using Force Exerted by a Functionalized Microscope Tip

    DEFF Research Database (Denmark)

    Zhang, Yajie; Wang, Yongfeng; Lü, Jing-Tao

    2017-01-01

    Atomic-scale mechanochemistry is realized from force exerted by a C60 -functionalized scanning tunneling microscope tip. Two conformers of tin phthalocyanine can be prepared on coinage-metal surfaces. A transition between these conformers is induced on Cu(111) and Ag(100). Density...

  10. The role of some radionuclide tests in assessment of lithium-induced nephropathy

    International Nuclear Information System (INIS)

    Petrov, T.; Vretenarska, M.; Svrakova, E.; Stoyanova, V.

    1998-01-01

    The purpose of the study was to compare some radionuclide tests as possibility for assessment of Li-induced nephropathy and to make recommendations for the routine clinical practice. Gamma-renogram (as assessment of nephron activity) as well as the clearance of 131 I-hippuran and 199 Yb-EDTA (as assessment of effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were used. A group of 110 patients (57 men and 53 women), aged 22-73 years (44.95 ± 12.87), treated for affective mental disease with Li-carbonate monotherapy for a period 1-20 years, was examined. Serum Li-levels were in the range 0.450-0.860 mmol/l. All patients had polyuria more than 2000 ml/24 h and decreased renal concentrating ability under 800 mOsm/kg. No other renal diseases were found. Radionuclide tests were done two or three times at an average interval 5.1 years at 69 of the patients. At 23.53% of them slightly disturbed secretory and excretory functions with gamma-renogram were established. The values of GRF were slightly diminished in 21% of the cases. A clear tendency to reducing of the values of ERPF was established. 5.1 years later 131 I-hippuran clearance was normal only at 34.37% of the patients. The rate of the disturbance of the tubular function depended on the duration of thr Li-therapy and the age. At 10.6% of the cases treated longer than 10 years ERPF decreasing was more significant. 131 I-hippuran clearance investigation was recommended as the most sensitive method for early renal disturbances assessment at patients on long-term Li-therapy

  11. Functional MR urography in patients with renal transplants

    International Nuclear Information System (INIS)

    Knopp, M.V.; Doersam, J.; Oesingmann, N.; Piesche, S.; Hawighorst, H.; Wiesel, M.; Schad, L.R.; Kaick, G. van

    1997-01-01

    Purpose: To assess the value of functional magnetic resonance urography for the noninvasive postoperative evaluation of renal transplants. Methods: A saturation inversion projection sequence allows the selective imaging of strongly T1 weighted signal from the MR contrast agent. A coronal slab leads to images comparable to conventional urography which can be acquired as a sequence with four images per minute. Results: 15 patients with urologic questionable findings after renal transplantation were studied. FMRU revealed in 6 patients normal findings, in 6 moderate dilatation of the renal pelvis without any urodynamic relevant obstruction. 3 pathologic findings, ureteral leak, ureteropelvic-junction obstruction and ureteral stenosis were diagnosed and consequently surgically treated. The imaging quality in all studies was diagnostic and urologically relevant. Conclusion: FMRU can be used as a noninvasive technique for the assessment of renal transplant in cases with suspicion of complication in the excretory system. (orig.) [de

  12. Non-verbal emotion communication training induces specific changes in brain function and structure.

    Science.gov (United States)

    Kreifelts, Benjamin; Jacob, Heike; Brück, Carolin; Erb, Michael; Ethofer, Thomas; Wildgruber, Dirk

    2013-01-01

    The perception of emotional cues from voice and face is essential for social interaction. However, this process is altered in various psychiatric conditions along with impaired social functioning. Emotion communication trainings have been demonstrated to improve social interaction in healthy individuals and to reduce emotional communication deficits in psychiatric patients. Here, we investigated the impact of a non-verbal emotion communication training (NECT) on cerebral activation and brain structure in a controlled and combined functional magnetic resonance imaging (fMRI) and voxel-based morphometry study. NECT-specific reductions in brain activity occurred in a distributed set of brain regions including face and voice processing regions as well as emotion processing- and motor-related regions presumably reflecting training-induced familiarization with the evaluation of face/voice stimuli. Training-induced changes in non-verbal emotion sensitivity at the behavioral level and the respective cerebral activation patterns were correlated in the face-selective cortical areas in the posterior superior temporal sulcus and fusiform gyrus for valence ratings and in the temporal pole, lateral prefrontal cortex and midbrain/thalamus for the response times. A NECT-induced increase in gray matter (GM) volume was observed in the fusiform face area. Thus, NECT induces both functional and structural plasticity in the face processing system as well as functional plasticity in the emotion perception and evaluation system. We propose that functional alterations are presumably related to changes in sensory tuning in the decoding of emotional expressions. Taken together, these findings highlight that the present experimental design may serve as a valuable tool to investigate the altered behavioral and neuronal processing of emotional cues in psychiatric disorders as well as the impact of therapeutic interventions on brain function and structure.

  13. Dammarane Sapogenins Ameliorates Neurocognitive Functional Impairment Induced by Simulated Long-Duration Spaceflight

    Directory of Open Access Journals (Sweden)

    Xiaorui Wu

    2017-05-01

    Full Text Available Increasing evidence indicates the occurrence of cognitive impairment in astronauts under spaceflight compound conditions, but the underlying mechanisms and countermeasures need to be explored. In this study, we found that learning and memory abilities were significantly reduced in rats under a simulated long-duration spaceflight environment (SLSE, which includes microgravity, isolation confinement, noises, and altered circadian rhythms. Dammarane sapogenins (DS, alkaline hydrolyzed products of ginsenosides, can enhance cognition function by regulating brain neurotransmitter levels and inhibiting SLSE-induced neuronal injury. Bioinformatics combined with experimental verification identified that the PI3K-Akt-mTOR pathway was inhibited and the MAPK pathway was activated during SLSE-induced cognition dysfunction, whereas DS substantially ameliorated the changes in brain. These findings defined the characteristics of SLSE-induced cognitive decline and the mechanisms by which DS improves it. The results provide an effective candidate for improving cognitive function in spaceflight missions.

  14. Radionuclide assessment of renal function in the transplanted kidney

    International Nuclear Information System (INIS)

    Kawasaki, Yukiko; Maki, Masako; Nara, Shigeko; Hiroe, Michiaki; Kusakabe, Kiyoko; Shigeta, Akiko; Toma, Hiroshi; Kohno, Hiroko

    1985-01-01

    The ability of radionuclide renal function to detect rejection and to presume the prognosis of the transplanted kidney was evaluated in 70 patients. Effective renal plasma flow (ERPF), excretory index (EI) and perfusion index (PI) were examined by I-123 OIH and Tc-99 m DTPA. Numbers of the study in various status were as follows; 51 studies in good function, 43 in acute rejection and 18 in chronic rejection. Significant reduction in ERPF and EI and increase of PI were observed in the acute rejection (p<0.01). In the chronic rejection, there was a progressive decrease of ERPF (p<0.01). The patients were divided into two groups: group A; 46 patients with good function more than 9 months after transplantation and group B; 20 patients of whom recurrence of hemodialysis or nephectomy was done. In living transplantation, ERPF of group B at the first week after transplantation was remarkably lower than group A (p<0.05). In cadaveric transplantation, ERPF of group B at the sixth week was lower than that of group B (p<0.05). This study indicates that serial measurements of renal function by radionuclide methods may provide the state of rejection and prognosis of the transplanted kidney. (author)

  15. Generation of functional podocytes from human induced pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Osele Ciampi

    2016-07-01

    Full Text Available Generating human podocytes in vitro could offer a unique opportunity to study human diseases. Here, we describe a simple and efficient protocol for obtaining functional podocytes in vitro from human induced pluripotent stem cells. Cells were exposed to a three-step protocol, which induced their differentiation into intermediate mesoderm, then into nephron progenitors and, finally, into mature podocytes. After differentiation, cells expressed the main podocyte markers, such as synaptopodin, WT1, α-Actinin-4, P-cadherin and nephrin at the protein and mRNA level, and showed the low proliferation rate typical of mature podocytes. Exposure to Angiotensin II significantly decreased the expression of podocyte genes and cells underwent cytoskeleton rearrangement. Cells were able to internalize albumin and self-assembled into chimeric 3D structures in combination with dissociated embryonic mouse kidney cells. Overall, these findings demonstrate the establishment of a robust protocol that, mimicking developmental stages, makes it possible to derive functional podocytes in vitro.

  16. Assessing and inducing neuroplasticity with transcranial magnetic stimulation and robotics for motor function.

    Science.gov (United States)

    O'Malley, Marcia K; Ro, Tony; Levin, Harvey S

    2006-12-01

    To describe 2 new ways of assessing and inducing neuroplasticity in the human brain--transcranial magnetic stimulation (TMS) and robotics--and to investigate and promote the recovery of motor function after brain damage. We identified recent articles and books directly bearing on TMS and robotics. Articles using these tools for purposes other than rehabilitation were excluded. From these studies, we emphasize the methodologic and technical details of these tools as applicable for assessing and inducing plasticity. Because both tools have only recently been used for rehabilitation, the majority of the articles selected for this review have been published only within the last 10 years. We used the PubMed and Compendex databases to find relevant peer-reviewed studies for this review. The studies were required to be relevant to rehabilitation and to use TMS or robotics methodologies. Guidelines were applied via independent extraction by multiple observers. Despite the limited amount of research using these procedures for assessing and inducing neuroplasticity, there is growing evidence that both TMS and robotics can be very effective, inexpensive, and convenient ways for assessing and inducing rehabilitation. Although TMS has primarily been used as an assessment tool for motor function, an increasing number of studies are using TMS as a tool to directly induce plasticity and improve motor function. Similarly, robotic devices have been used for rehabilitation because of their suitability for delivery of highly repeatable training. New directions in robotics-assisted rehabilitation are taking advantage of novel measurements that can be acquired via the devices, enabling unique methods of assessment of motor recovery. As refinements in technology and advances in our knowledge continue, TMS and robotics should play an increasing role in assessing and promoting the recovery of function. Ongoing and future studies combining TMS and robotics within the same populations may

  17. Androgens Exert a Cysticidal Effect upon Taenia crassiceps by Disrupting Flame Cell Morphology and Function

    Science.gov (United States)

    Ambrosio, Javier R.; Valverde-Islas, Laura; Nava-Castro, Karen E.; Palacios- Arreola, M. Isabel; Ostoa-Saloma, Pedro; Reynoso-Ducoing, Olivia; Escobedo, Galileo; Ruíz-Rosado, Azucena; Dominguez-Ramírez, Lenin; Morales-Montor, Jorge

    2015-01-01

    The effects of testosterone (T4) and dihydrotestosterone (DHT) on the survival of the helminth cestode parasite Taenia crassiceps, as well as their effects on actin, tubulin and myosin expression and their assembly into the excretory system of flame cells are described in this paper. In vitro evaluations on parasite viability, flow cytometry, confocal microscopy, video-microscopy of live flame cells, and docking experiments of androgens interacting with actin, tubulin, and myosin were conducted. Our results show that T4 and DHT reduce T. crassiceps viability in a dose- and time-dependent fashion, reaching 90% of mortality at the highest dose used (40 ng/ml) and time exposed (10 days) in culture. Androgen treatment does not induce differences in the specific expression pattern of actin, tubulin, and myosin isoforms as compared with control parasites. Confocal microscopy demonstrated a strong disruption of the parasite tegument, with reduced assembly, shape, and motion of flame cells. Docking experiments show that androgens are capable of affecting parasite survival and flame cell morphology by directly interacting with actin, tubulin and myosin without altering their protein expression pattern. We show that both T4 and DHT are able to bind actin, tubulin, and myosin affecting their assembly and causing parasite intoxication due to impairment of flame cell function. Live flame cell video microscopy showing a reduced motion as well changes in the shape of flame cells are also shown. In summary, T4 and DHT directly act on T. crassiceps cysticerci through altering parasite survival as well as the assembly and function of flame cells. PMID:26076446

  18. Determination of Immunogenic Relevant Antigens in the Excretory-Secretory (ES Products and the Lysates of Ascaridia galli Larvae

    Directory of Open Access Journals (Sweden)

    S Saffi

    2008-04-01

    Full Text Available Background: Ascaridia galli, the largest nematode of small intestine of birds, especially the native poultry, may give rise to serious illness, pathological defects and economical losses even in modern poultry production systems. Although various measures have been undertaken to vaccinate poultry against A.galli, no satisfactory results were obtained so far. However, there is no report on the efficacy of excretory-secretory (ES proteins of A.galli larvae in immunization of poultry. Thus, the aim of the present research project was based on the use of the ES products of the larvae, in order to find the protective anti­gens.Methods: Five hundred native poultry were autopsied and adult A.galli was removed form their intestines. The eggs were harvested form the uterus of female worms and cultured at 25 ˚C in water containing 0.1 N sulphuric acid for almost a fort­night. The larvae were then freed mechanically and kept in Earl's salt solution for a few days. The supernatant solution of alive larvae containing the ES products of the larvae, as well as the sonicated alive and dead larvae, was analyzed by SDS-PAGE.Result: Many protein fractions of 15 kDa up to 200 kDa were demonstrated in lysate of these larvae. Using the serum of a hen, infected with a high numbers of A.galli, an immunogenic antigen was identified between 55 kDa to 72 kDa by Western blotting procedure.Conclusion: Finding the protein band between 55 and 72 kDa can be promising for preparation of vaccine, though more investigations are needed to prove the protective ability of this antigen.

  19. Gravity induced wave function collapse

    Science.gov (United States)

    Gasbarri, G.; Toroš, M.; Donadi, S.; Bassi, A.

    2017-11-01

    Starting from an idea of S. L. Adler [in Quantum Nonlocality and Reality: 50 Years of Bell's Theorem, edited by M. Bell and S. Gao (Cambridge University Press, Cambridge, England 2016)], we develop a novel model of gravity induced spontaneous wave function collapse. The collapse is driven by complex stochastic fluctuations of the spacetime metric. After deriving the fundamental equations, we prove the collapse and amplification mechanism, the two most important features of a consistent collapse model. Under reasonable simplifying assumptions, we constrain the strength ξ of the complex metric fluctuations with available experimental data. We show that ξ ≥10-26 in order for the model to guarantee classicality of macro-objects, and at the same time ξ ≤10-20 in order not to contradict experimental evidence. As a comparison, in the recent discovery of gravitational waves in the frequency range 35 to 250 Hz, the (real) metric fluctuations reach a peak of ξ ˜10-21.

  20. Application of radiation-induced graft polymerization to preparation of functional materials

    International Nuclear Information System (INIS)

    Sugo, Takanobu

    2010-01-01

    Radiation-induced graft polymerization is a powerful method for appending various functionalities onto existing fabrics, nonwoven fabrics, fibers, membranes, and beads while maintaining the shape and mechanical strength. By using this method, the author has developed and commercialized functional polymeric materials over 45 years. The materials produced by the fruits of radiation chemistry contributed to the improvement of our lives and environments and the collection of rare metal resources. (author)

  1. Rethinking platelet function: thrombocytopenia induced immunodeficiency in critical illness

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Johansson, Per Ingemar

    2011-01-01

    Thrombocytopenia in critical illness predicts a poor clinical outcome. Apart from its role in microvascular thrombus formation, it is widely anticipated that this association is indirect rather than causal. Emerging evidence however indicates that platelets are also immune competent cells. Like...... per se results in immunodeficiency through loss of platelet-mediated immune functions, and propose that thrombocytopenia induced immunodeficiency in critical illness in part explain the negative predictive value of low or declining platelet count. We propose that rethinking the risks...... of thrombocytopenia to include not only bleeding but also immunodeficiency and immune dysregulation along with the conduct of studies investigating mechanisms contributing to thrombocytopenia induced poor non-hemorrhagic outcome in critical illness, may be means to improve outcome in these patients through...

  2. Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

    Science.gov (United States)

    Shin, Sun; Lee, Yun Jung; Kim, Eun Ju; Lee, An Sook; Kang, Dae Gill; Lee, Ho Sub

    2011-01-01

    The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

  3. Oxidative stress induced inflammation initiates functional decline of tear production.

    Directory of Open Access Journals (Sweden)

    Yuichi Uchino

    Full Text Available Oxidative damage and inflammation are proposed to be involved in an age-related functional decline of exocrine glands. However, the molecular mechanism of how oxidative stress affects the secretory function of exocrine glands is unclear. We developed a novel mev-1 conditional transgenic mouse model (Tet-mev-1 using a modified tetracycline system (Tet-On/Off system. This mouse model demonstrated decreased tear production with morphological changes including leukocytic infiltration and fibrosis. We found that the mev-1 gene encodes Cyt-1, which is the cytochrome b(560 large subunit of succinate-ubiquinone oxidoreductase in complex II of mitochondria (homologous to succinate dehydrogenase C subunit (SDHC in humans. The mev-1 gene induced excessive oxidative stress associated with ocular surface epithelial damage and a decrease in protein and aqueous secretory function. This new model provides evidence that mitochondrial oxidative damage in the lacrimal gland induces lacrimal dysfunction resulting in dry eye disease. Tear volume in Tet-mev-1 mice was lower than in wild type mice and histopathological analyses showed the hallmarks of lacrimal gland inflammation by intense mononuclear leukocytic infiltration and fibrosis in the lacrimal gland of Tet-mev-1 mice. These findings strongly suggest that oxidative stress can be a causative factor for the development of dry eye disease.

  4. Fast-twitch glycolytic skeletal muscle is predisposed to age-induced impairments in mitochondrial function

    DEFF Research Database (Denmark)

    Jacobs, Robert A; Díaz, Víctor; Soldini, Lavinia

    2013-01-01

    The etiology of mammalian senescence is suggested to involve the progressive impairment of mitochondrial function; however, direct observations of age-induced alterations in actual respiratory chain function are lacking. Accordingly, we assessed mitochondrial function via high-resolution respirom......The etiology of mammalian senescence is suggested to involve the progressive impairment of mitochondrial function; however, direct observations of age-induced alterations in actual respiratory chain function are lacking. Accordingly, we assessed mitochondrial function via high......-resolution respirometry and mitochondrial protein expression in soleus, quadricep, and lateral gastrocnemius skeletal muscles, which represent type 1 slow-twitch oxidative muscle (soleus) and type 2 fast-twitch glycolytic muscle (quadricep and gastrocnemius), respectively, in young (10-12 weeks) and mature (74-76 weeks......) mice. Electron transport through mitochondrial complexes I and III increases with age in quadricep and gastrocnemius, which is not observed in soleus. Mitochondrial coupling efficiency during respiration through complex I also deteriorates with age in gastrocnemius and shows a tendency (p = .085...

  5. Bovine colostrum improves intestinal function following formula-induced gut inflammation in preterm pigs

    DEFF Research Database (Denmark)

    Støy, Ann Cathrine Findal; Heegaard, Peter M. H.; Thymann, Thomas

    2014-01-01

    Background & aims Only few hours of formula feeding may induce proinflammatory responses and predispose to necrotizing enterocolitis (NEC) in preterm pigs. We hypothesized that bovine colostrum, rich in bioactive factors, would improve intestinal function in preterm pigs following an initial...... exposure to formula feeding after some days of total parenteral nutrition (TPN). Methods After receiving TPN for 2 days, preterm pigs were fed formula (FORM, n = 14), bovine colostrum (COLOS, n = 6), or formula (6 h) followed by bovine colostrum (FCOLOS, n = 14). Intestinal lesions, function, and structure...... and FCOLOS pigs, relative to FORM pigs. Intestinal gene expression of serum amyloid A, IL-1β, -6 and -8, and bacterial abundance, correlated positively with NEC severity of the distal small intestine. Conclusions Bovine colostrum restores intestinal function after initial formula-induced inflammation...

  6. Adjoint method provides phase response functions for delay-induced oscillations.

    Science.gov (United States)

    Kotani, Kiyoshi; Yamaguchi, Ikuhiro; Ogawa, Yutaro; Jimbo, Yasuhiko; Nakao, Hiroya; Ermentrout, G Bard

    2012-07-27

    Limit-cycle oscillations induced by time delay are widely observed in various systems, but a systematic phase-reduction theory for them has yet to be developed. Here we present a practical theoretical framework to calculate the phase response function Z(θ), a fundamental quantity for the theory, of delay-induced limit cycles with infinite-dimensional phase space. We show that Z(θ) can be obtained as a zero eigenfunction of the adjoint equation associated with an appropriate bilinear form for the delay differential equations. We confirm the validity of the proposed framework for two biological oscillators and demonstrate that the derived phase equation predicts intriguing multimodal locking behavior.

  7. MR-urography and CT-urography: principles, examination techniques, applications

    International Nuclear Information System (INIS)

    Nolte-Ernsting, C.; Adam, G.; Staatz, G.; Wildberger, J.

    2003-01-01

    MR-urography (MRU) and CT-urography (CTU) provide refined imaging of the upper urinary tract not achievable with conventional intravenous urography (IVU). The traditional MR-urographic technique utilizes unenhanced, heavily T 2 -weighted turbo spin-echo sequences for obtaining static fluid images of the urinary tract independent of the excretory renal function. T 2 -weighted MR-urograms have proved to be excellent in visualizing the dilated urinary tract, even in non-excreting kidneys. In contrast, T 1 -weighted MRU reflects the excretory renal function and displays the urine flow through the upper tract after renal excretion of an intravenously administered gadolinium chelate. The gadolinium-enhanced urine is visualized with fast T 1 -weighted 3D-gradient-echo sequences. The combination of gadolinium and low-dose furosemide (5-10 mg) is the key for achieving a uniform distribution of gadolinium in the collecting system and for avoiding susceptibility artifacts (T 2 *-effects) in the urine. T 1 -weighted excretory MRU provides impressive urograms of both non-dilated and obstructed collecting systems in patients with normal or moderately impaired renal function. Multislice-CT-urography (MS-CTU) is also an excretory urography like T 1 -weighted MRU. Furthermore, MS-CTU can be combined with low-dose furosemide for accelerated passage of excreted contrast material obviating the need for abdominal compression. CT-urography is limited by its radiation burden and the nephrotoxicity of radiographic contrast media. Combining MRU or MS-CTU with conventional MRI or CT offers several applications, e.g., diagnosis of intrinsic and extrinsic tumors. Meanwhile, MRU has replaced IVU in pediatric uroradiology and is also recommended for the assessment of renal transplants. MS-CTU may provide valuable information in chronic urolithiasis, especially if associated with a distorted urinary tract anatomy. Both MRU and MS-CTU will play an important role in modern uroradiology. (orig

  8. Glucose-induced effects and joker function of glucose: endocrine or genotoxic prevalence?

    Science.gov (United States)

    Berstein, L M; Vasilyev, D A; Poroshina, T E; Kovalenko, I G

    2006-10-01

    The steady increase in chronic "glycemic load" is characteristic for modern times. Among myriad of glucose functions, two principals can be emphasized: first, endocrine (in particular, ability to induce insulin secretion) and second, DNA-damaging related to formation of reactive oxygen species (ROS). It was suggested by us earlier that a shift in the ratio of mentioned functions reflects a possible "joker" role of glucose as an important modifier of human pathology. Therefore, we embarked on a study to investigate an individual effect of peroral glucose challenge on serum insulin level and ROS generation by mononuclears (luminol-dependent/latex-induced chemiluminescence) in 20 healthy people aged between 28-75. Concentrations of glucose, blood lipids, carbonylated proteins, malondialdehyde, leptin and TNF-alpha were determined as well. On the basis of received data two separate groups could be distinguished: one (n=8), in which glucose stimulation of ROS generation by mononuclears was increased and relatively prevailed over induction of insulin secretion (state of the so called glucose-induced genotoxicity, GIGT), and another (n=12), in which signs of GIGT were not revealed. People who belonged to the first group were characterized with a tendency to lower body mass index, blood leptin and cholesterol and to higher TNF-alpha concentration. Thus, if joker function of glucose is realized in "genotoxic mode", the phenotype (and probably genotype) of subjects may be rather distinctive to the one discovered in glucose-induced "endocrine prevalence". Whether such changes may serve as a pro-mutagenic or pro-endocrine basis for the rise of different chronic diseases or, rather, different features/aggressiveness of the same disease warrants further study.

  9. Analysis of functional failure mode of commercial deep sub-micron SRAM induced by total dose irradiation

    International Nuclear Information System (INIS)

    Zheng Qi-Wen; Cui Jiang-Wei; Zhou Hang; Yu De-Zhao; Yu Xue-Feng; Lu Wu; Guo Qi; Ren Di-Yuan

    2015-01-01

    Functional failure mode of commercial deep sub-micron static random access memory (SRAM) induced by total dose irradiation is experimentally analyzed and verified by circuit simulation. We extensively characterize the functional failure mode of the device by testing its electrical parameters and function with test patterns covering different functional failure modes. Experimental results reveal that the functional failure mode of the device is a temporary function interruption caused by peripheral circuits being sensitive to the standby current rising. By including radiation-induced threshold shift and off-state leakage current in memory cell transistors, we simulate the influence of radiation on the functionality of the memory cell. Simulation results reveal that the memory cell is tolerant to irradiation due to its high stability, which agrees with our experimental result. (paper)

  10. Prevention of shockwave induced functional and morphological alterations: an overview.

    Science.gov (United States)

    Sarica, Kemal; Yencilek, Faruk

    2008-03-01

    Experimental as well as clinical findings reported in the literature suggest that treatment with shock wave lithotripsy (SWL) causes renal parenchymal damage mainly by generating free radicals through ischaemia/reperfusion injury mechanism. Although SWL-induced renal damage is well tolerated in the majority of healthy cases with no permanent functional and/or morphologic side effects, a subset of patients with certain risk factors requires close attention on this aspect among which the ones with pre-existing renal disorders, urinary tract infection, previous lithotripsy history and solitary kidneys could be mentioned. It is clear that in such patients lowering the number of shock waves (per session) could be beneficial and has been applied by the physicians as the first practical step of diminishing SWL induced parenchymal damage. On the other hand, taking the injurious effects of high energy shock wave (HESW) induced free radical formation on renal parenchyma and subsequent histopathologic alterations into account, physicians searched for some protective agents in an attempt to prevent or at least to limit the extent of the functional as well as the morphologic alterations. Among these agents calcium channel blocking agents (verapamil and nifedipine), antioxidant agents (allopurinol, vitamin E and selenium) and potassium citrate have been used to minimize these adverse effects. Additionally, therapeutic application of these agents on reducing stone recurrence particularly after SWL will gain more importance in the future in order to limit new stone formation in these cases. Lastly, as experimental and clinical studies have demonstrated, combination of anti-oxidants with free radical scavengers may provide superior renal protection against shock wave induced trauma. However, we believe that further investigations are certainly needed to determine the dose-response relationship between the damaging effects of SWL application and the protective role of these agents.

  11. TiO{sub 2} nanoparticle-induced ROS correlates with modulated immune cell function

    Energy Technology Data Exchange (ETDEWEB)

    Maurer-Jones, Melissa A.; Christenson, Jenna R.; Haynes, Christy L., E-mail: chaynes@umn.edu [University of Minnesota, Department of Chemistry (United States)

    2012-12-15

    Design of non-toxic nanoparticles will be greatly facilitated by understanding the nanoparticle-cell interaction mechanism on a cell function level. Mast cells are important cells for the immune system's first line of defense, and we can utilize their exocytotic behavior as a model cellular function as it is a conserved process across cell types and species. Perturbations in exocytosis can also have implications for whole organism health. One proposed mode of toxicity is nanoparticle-induced reactive oxygen species (ROS), particularly for titanium dioxide (TiO{sub 2}) nanoparticles. Herein, we have correlated changes in ROS with the perturbation of the critical cell function of exocytosis, using UV light to induce greater levels of ROS in TiO{sub 2} exposed cells. The primary culture mouse peritoneal mast cells (MPMCs) were exposed to varying concentrations of TiO{sub 2} nanoparticles for 24 h. ROS content was determined using 2,7-dihydrodichlorofluorescein diacetate (DCFDA). Cellular viability was determined with the MTT and Trypan blue assays, and exocytosis was measured by the analytical electrochemistry technique of carbon-fiber microelectrode amperometry. MPMCs exposed to TiO{sub 2} nanoparticles experienced a dose-dependent increase in total ROS content. While there was minimal impact of ROS on cellular viability, there is a correlation between ROS amount and exocytosis perturbation. As nanoparticle-induced ROS increases, there is a significant decrease (45 %) in the number of serotonin molecules being released during exocytosis, increase (26 %) in the amount of time for each exocytotic granule to release, and decrease (28 %) in the efficiency of granule trafficking and docking. This is the first evidence that nanoparticle-induced ROS correlates with chemical messenger molecule secretion, possibly making a critical connection between functional impairment and mechanisms contributing to that impairment.

  12. Investigating Gene Function in Cereal Rust Fungi by Plant-Mediated Virus-Induced Gene Silencing.

    Science.gov (United States)

    Panwar, Vinay; Bakkeren, Guus

    2017-01-01

    Cereal rust fungi are destructive pathogens, threatening grain production worldwide. Targeted breeding for resistance utilizing host resistance genes has been effective. However, breakdown of resistance occurs frequently and continued efforts are needed to understand how these fungi overcome resistance and to expand the range of available resistance genes. Whole genome sequencing, transcriptomic and proteomic studies followed by genome-wide computational and comparative analyses have identified large repertoire of genes in rust fungi among which are candidates predicted to code for pathogenicity and virulence factors. Some of these genes represent defence triggering avirulence effectors. However, functions of most genes still needs to be assessed to understand the biology of these obligate biotrophic pathogens. Since genetic manipulations such as gene deletion and genetic transformation are not yet feasible in rust fungi, performing functional gene studies is challenging. Recently, Host-induced gene silencing (HIGS) has emerged as a useful tool to characterize gene function in rust fungi while infecting and growing in host plants. We utilized Barley stripe mosaic virus-mediated virus induced gene silencing (BSMV-VIGS) to induce HIGS of candidate rust fungal genes in the wheat host to determine their role in plant-fungal interactions. Here, we describe the methods for using BSMV-VIGS in wheat for functional genomics study in cereal rust fungi.

  13. Radioisotope examination of the renal function in gravidic pyelonephritis

    Energy Technology Data Exchange (ETDEWEB)

    Voigt, R; Stoll, W; Arndt, J [Friedrich-Schiller-Universitaet, Jena (German Democratic Republic). Radiologische Klinik und Poliklinik

    1980-08-01

    By means of the results of combined renal sequence scintigraphy and /sup 131/I-hippurate clearance in 18 pregnant women with gravidic pyelonephritis as well as in 22 voluntary healthy pregnant women of the corresponding duration of pregnancy and in 13 non-pregnant women without hormonal anticonception as control groups the detection of the renal function with the clinical picture of gravidic pyelonephritis is discussed. The clearance equivalents are represented globally as well as subdivided to the single kidney. Besides typical activity-time curves of the control groups are demonstrated. It was shown that at the time of the most frequent occurrence of gravidic pyelonephritis in the 7th-8th month of pregnancy the clearance equivalents are decreased compared to those of uncomplicated pregnancy. The changes in the course of activity-time curves manifest themselves in a decreased initial phase as well as in an increased excretory phase. Conclusions are drawn for the clinical preliminary diagnosis of risky pregnancies from the results discussed regarding further references.

  14. Radioisotope examination of the renal function in gravidic pyelonephritis

    International Nuclear Information System (INIS)

    Voigt, R.; Stoll, W.; Arndt, J.

    1980-01-01

    By means of the results of combined renal sequence scintigraphy and 131 I-hippurate clearance in 18 pregnant women with gravidic pyelonephritis as well as in 22 voluntary healthy pregnant women of the corresponding duration of pregnancy and in 13 non-pregnant women without hormonal anticonception as control groups the detection of the renal function with the clinical picture of gravidic pyelonephritis is discussed. The clearance equivalents are represented globally as well as subdivided to the single kidney. Besides typical activity-time curves of the control groups are demonstrated. It was shown that at the time of the most frequent occurrence of gravidic pyelonephritis in the 7th-8th month of pregnancy the clearance equivalents are decreased compared to those of uncomplicated pregnancy. The changes in the course of activity-time curves manifest themselves in a decreased initial phase as well as in an increased excretory phase. Conclusions are drawn for the clinical preliminary diagnosis of risky pregnancies from the results discussed regarding further references. (author)

  15. Bobath Concept versus constraint-induced movement therapy to improve arm functional recovery in stroke patients: a randomized controlled trial.

    Science.gov (United States)

    Huseyinsinoglu, Burcu Ersoz; Ozdincler, Arzu Razak; Krespi, Yakup

    2012-08-01

    To compare the effects of the Bobath Concept and constraint-induced movement therapy on arm functional recovery among stroke patients with a high level of function on the affected side. A single-blinded, randomized controlled trial. Outpatient physiotherapy department of a stroke unit. A total of 24 patients were randomized to constraint-induced movement therapy or Bobath Concept group. The Bobath Concept group was treated for 1 hour whereas the constraint-induced movement therapy group received training for 3 hours per day during 10 consecutive weekdays. Main measures were the Motor Activity Log-28, the Wolf Motor Function Test, the Motor Evaluation Scale for Arm in Stroke Patients and the Functional Independence Measure. The two groups were found to be homogeneous based on demographic variables and baseline measurements. Significant improvements were seen after treatment only in the 'Amount of use' and 'Quality of movement' subscales of the Motor Activity Log-28 in the constraint-induced movement therapy group over the the Bobath Concept group (P = 0.003; P = 0.01 respectively). There were no significant differences in Wolf Motor Function Test 'Functional ability' (P = 0.137) and 'Performance time' (P = 0.922), Motor Evaluation Scale for Arm in Stroke Patients (P = 0.947) and Functional Independence Measure scores (P = 0.259) between the two intervention groups. Constraint-induced movement therapy and the Bobath Concept have similar efficiencies in improving functional ability, speed and quality of movement in the paretic arm among stroke patients with a high level of function. Constraint-induced movement therapy seems to be slightly more efficient than the Bobath Concept in improving the amount and quality of affected arm use.

  16. Ethylbenzene-induced hearing loss, neurobehavioral function, and neurotransmitter alterations in petrochemical workers.

    Science.gov (United States)

    Zhang, Ming; Wang, Yanrang; Wang, Qian; Yang, Deyi; Zhang, Jingshu; Wang, Fengshan; Gu, Qing

    2013-09-01

    To estimate hearing loss, neurobehavioral function, and neurotransmitter alteration induced by ethylbenzene in petrochemical workers. From two petrochemical plants, 246 and 307 workers exposed to both ethylbenzene and noise were recruited-290 workers exposed to noise only from a power station plant and 327 office personnel as control group, respectively. Hearing and neurobehavioral functions were evaluated. Serum neurotransmitters were also determined. The prevalence of hearing loss was much higher in petrochemical groups than that in power station and control groups (P workers (P hearing loss, neurobehavioral function impairment, and imbalance of neurotransmitters.

  17. Conservation of a microRNA cluster in parasitic nematodes and profiling of miRNAs in excretory-secretory products and microvesicles of Haemonchus contortus.

    Directory of Open Access Journals (Sweden)

    Henry Y Gu

    2017-11-01

    Full Text Available microRNAs are small non-coding RNAs that are important regulators of gene expression in a range of animals, including nematodes. We have analysed a cluster of four miRNAs from the pathogenic nematode species Haemonchus contortus that are closely linked in the genome. We find that the cluster is conserved only in clade V parasitic nematodes and in some ascarids, but not in other clade III species nor in clade V free-living nematodes. Members of the cluster are present in parasite excretory-secretory products and can be detected in the abomasum and draining lymph nodes of infected sheep, indicating their release in vitro and in vivo. As observed for other parasitic nematodes, H. contortus adult worms release extracellular vesicles (EV. Small RNA libraries were prepared from vesicle-enriched and vesicle-depleted supernatants from both adult worms and L4 stage larvae. Comparison of the miRNA species in the different fractions indicated that specific miRNAs are packaged within vesicles, while others are more abundant in vesicle-depleted supernatant. Hierarchical clustering analysis indicated that the gut is the likely source of vesicle-associated miRNAs in the L4 stage, but not in the adult worm. These findings add to the growing body of work demonstrating that miRNAs released from parasitic helminths may play an important role in host-parasite interactions.

  18. Development of radiation-induced mutation techniques and functional genomics studies

    International Nuclear Information System (INIS)

    Kim, Dong Sub; Kang, Si Yong; Kim, Jin Baek

    2012-01-01

    This project has been performed to develop plant genetic resources using radiation (gamma-rays, ion-beam, space environments), to conduct functional genomics studies with mutant resources, and to develop new radiation plant breeding techniques using various radiation sources during 3 years. In the first section, we developed flower genetic resources, functional crop resources, and bio-industrial plant resources. In the second section, we cloned several mutated genes and studied mechanisms of gene expression and genetic diversity of mutations induced by gamma-rays. In the third section, we developed new plant breeding techniques using gamma-phytotron, heavy ion-beam, and space environments. Based on these results, a total of 8 cultivars containing Chrysanthemum, Hibiscus, kenaf, rice, and soybean were applied for plant variety protection (PVP) and a total of 4 cultivars were registered for PVP. Also, license agreement for the dwarf type Hibiscus mutant 'Ggoma' was conducted with Supro co. and the manufacturing technology for natural antioxidant pear-grape vinegar was transferred into Enzenic co. Also, 8 gene sequences, such as F3'H and LDOX genes associated with flower color in Chrysanthemum and EPSPS gene from Korean lawn grass, were registered in the database of National Center for Biotechnology Information (NCBI). In the future study, we will develop new radiation mutation breeding techniques through the mutation spectrum induced by various radiation sources, the studies for mechanism of the cellular response to radiation, and the comparative·structural·functional genomics studies for useful traits

  19. Monosodium glutamate neonatal treatment induces cardiovascular autonomic function changes in rodents

    Directory of Open Access Journals (Sweden)

    Signorá Peres Konrad

    2012-10-01

    Full Text Available OBJECTIVES: The aim of this study was to evaluate cardiovascular autonomic function in a rodent obesity model induced by monosodium glutamate injections during the first seven days of life. METHOD: The animals were assigned to control (control, n = 10 and monosodium glutamate (monosodium glutamate, n = 13 groups. Thirty-three weeks after birth, arterial and venous catheters were implanted for arterial pressure measurements, drug administration, and blood sampling. Baroreflex sensitivity was evaluated according to the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine infusion, respectively. Sympathetic and vagal effects were determined by administering methylatropine and propranolol. RESULTS: Body weight, Lee index, and epididymal white adipose tissue values were higher in the monosodium glutamate group in comparison to the control group. The monosodium glutamate-treated rats displayed insulin resistance, as shown by a reduced glucose/insulin index (-62.5%, an increased area under the curve of total insulin secretion during glucose overload (39.3%, and basal hyperinsulinemia. The mean arterial pressure values were higher in the monosodium glutamate rats, whereas heart rate variability (>7 times, bradycardic responses (>4 times, and vagal (~38% and sympathetic effects (~36% were reduced as compared to the control group. CONCLUSION: Our results suggest that obesity induced by neonatal monosodium glutamate treatment impairs cardiac autonomic function and most likely contributes to increased arterial pressure and insulin resistance.

  20. Electron Beam Induced Functionalization of Fluoropolymers

    International Nuclear Information System (INIS)

    Lappan, U.

    2006-01-01

    Ionizing radiation affects the properties of polymers by chain scission and cross-linking reactions. One process will usually predominate, depending on the chemical structure of the polymer and the irradiation conditions such as temperature and atmosphere. Poly(tetrafluoroethylene) (PTFE) and the perfluorinated copolymers poly(tetrafluoroethylene-co-hexafluoropropylene) (FEP) and poly(tetrafluoroethylene-co-perfluoropropylvinyl ether) (PFA) undergo predominantly chain scission, if the irradiation is performed at room temperature. This shortcoming is exploited by converting PTFE into low molecular weight micropowders. The irradiation of PTFE in the presence of air results in micropowders functionalized with oxygen-containing groups. The concentration of end groups was investigated by FTIR and 19F solid-state NMR. The data were used to calculate number-average molecular weights. It was demonstrated that PTFE can be cross-linked by irradiation above its crystalline melting temperature in an oxygen-free atmosphere. Evidence for cross-links in PTFE was derived directly from structural information using 19 F solid-state NMR. FEP is understood to undergo cross-linking by irradiation above the glass transition temperature. It was found that also PFA can be branched and cross-linked by irradiation under special conditions. Radiation-induced grafting of styrene into fluoropolymer films and subsequent sulfonation offers an attractive way to prepare proton exchange membranes. Recently, radiation-induced grafting into cross-linked PTFE was reported. Modified FEP, PFA and ETFE films have been used as base material in this study. The modified films have been prepared by irradiation in nitrogen atmosphere at different temperatures up to temperatures above the melting temperature of the fluoropolymer

  1. Results of the use of a kinetic model of radiohippuran transport in the human body for quantitative assessment of summary and isolated renal function

    International Nuclear Information System (INIS)

    Ryabov, S.I.; Degtereva, O.A.; Klemina, I.K.; Degterev, B.V.; Senchik, R.V.

    1986-01-01

    The results of a method for the interpretation of commonly used methods of the determination of blood clearance and radionephrography with 131 I-hipuran based on a mathematical model of its transport in the human body are presented. Empirical values of model parameters were obtained in 120 patients with chronic glomerulo- and pyelonephritides verified morphologically and roentgenologically. The use of computational-interpretation algorithms made it possible to determine the volume of circulating plasma (blood), values of true summary and isolated effective renal plasma flow (blood flow) by means of a single i.v. hippuran administration. New indicators for assessment of isolated excretory-transport function and renal hemodynamics as well as indicators of the symmetry of renal function were proposed. The results of a statistical analysis made it possible to recommend some of them as criteria of early diagnosis of preuremic disorder of renal function. Radionuclide indicators of renal function showed good correlation with biochemical, morphological and roentgenological characteristics of renal damage in renal

  2. Hydraulic Function in Australian Tree Species during Drought-Induced Mortality

    Science.gov (United States)

    Tissue, D.; Maier, C.; Creek, D.; Choat, B.

    2016-12-01

    Drought induced tree mortality and decline are key issues facing forest ecology and management. Here, we primarily investigated the hydraulic limitations underpinning drought-induced mortality in three Australian tree species. Using field-based large rainout shelters, three angiosperm species (Casuarina cunninghamiana, Eucalyptus sideroxylon, Eucalyptus tereticornis) were subjected to two successive drought and recovery cycles, prior to a subsequent long and extreme drought to mortality; total duration of experiment was 2.5 years. Leaf gas exchange, leaf and stem hydraulics, and carbon reserves were monitored during the experiment. Trees died as a result of failure in the hydraulic transport system, primarily related to water stress induced embolism. Stomatal closure occurred prior to the induction of significant embolism in the stem xylem of all species. Nonetheless, trees suffered a rapid decline in xylem water potential and increase in embolism during the severe drought treatment. Trees died at water potentials causing greater than 90% loss of hydraulic conductivity in the stem, providing support for the theory that lethal water potential is correlated with complete loss of hydraulic function in the stem xylem of angiosperms.

  3. Functional Analysis of the Unique Cytochrome P450 of the Liver Fluke Opisthorchis felineus.

    Directory of Open Access Journals (Sweden)

    Mariya Y Pakharukova

    2015-12-01

    Full Text Available The basic metabolic cytochrome P450 (CYP system is essential for biotransformation of sterols and xenobiotics including drugs, for synthesis and degradation of signaling molecules in all living organisms. Most eukaryotes including free-living flatworms have numerous paralogues of the CYP gene encoding heme monooxygenases with specific substrate range. Notably, by contrast, the parasitic flatworms have only one CYP gene. The role of this enzyme in the physiology and biochemistry of helminths is not known. The flukes and tapeworms are the etiologic agents of major neglected tropical diseases of humanity. Three helminth infections (Opisthorchis viverrini, Clonorchis sinensis and Schistosoma haematobium are considered by the International Agency for Research on Cancer (IARC as definite causes of cancer. We focused our research on the human liver fluke Opisthorchis felineus, an emerging source of biliary tract disease including bile duct cancer in Russia and central Europe. The aims of this study were (i to determine the significance of the CYP activity for the morphology and survival of the liver fluke, (ii to assess CYP ability to metabolize xenobiotics, and (iii to localize the CYP activity in O. felineus tissues. We observed high constitutive expression of CYP mRNA (Real-time PCR in O. felineus. This enzyme metabolized xenobiotics selective for mammalian CYP2E1, CYP2B, CYP3A, but not CYP1A, as determined by liquid chromatography and imaging analyses. Tissue localization studies revealed the CYP activity in excretory channels, while suppression of CYP mRNA by RNA interference was accompanied by morphological changes of the excretory system and increased mortality rates of the worms. These results suggest that the CYP function is linked to worm metabolism and detoxification. The findings also suggest that the CYP enzyme is involved in vitally important processes in the organism of parasites and is a potential drug target.

  4. Dietary Chlorella vulgaris Ameliorates Altered Immunomodulatory Functions in Cyclophosphamide-Induced Immunosuppressive Mice

    Science.gov (United States)

    Cheng, Dai; Wan, Zhaodong; Zhang, Xinyu; Li, Jian; Li, He; Wang, Chunling

    2017-01-01

    Based on the well-known toxicity of cyclophosphamide (CYP) on the immune system, this research investigated the modulating effects of the long-term dietary Chlorella vulgaris (CV) supplementation on the immunosuppression induced by CYP in mice, in order to provide a novel dietary design to mitigate the side effects of CYP therapy. Control, CYP-treated, CYP + CV (6%), CYP + CV (12%) and CYP + CV (24%) were used for 6 weeks, CV supplement in diet recovered the significantly reduced immunological function in CYP treated mice. As CV may have a modulating function through the inducible expression of cytokines, we assayed the expressions of interleukin-2 (IL-2), interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Our results suggested that CYP significantly reduced the lymphocytes proliferation and phagocytic activities of macrophages, and stimulated the production of IL-2, IL-12, TNF-α and IFN-γ and that this impairment has been successfully adjusted by CV supplementation. Treatment with the algae also enhanced the natural killer (NK) cells cytotoxicity, and ameliorate histological changes of the spleen in CYP-treated mice. Therefore, as we found in this study, a diet supplemented with whole CV has beneficial effects on CVP-induced immunosuppression, through its immunomodulatory potential. PMID:28684674

  5. Development of radiation-induced mutation techniques and functional genomics studies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Sub; Kang, Si Yong; Kim, Jin Baek [KAERI, Daejeon (Korea, Republic of); and others

    2012-01-15

    This project has been performed to develop plant genetic resources using radiation (gamma-rays, ion-beam, space environments), to conduct functional genomics studies with mutant resources, and to develop new radiation plant breeding techniques using various radiation sources during 3 years. In the first section, we developed flower genetic resources, functional crop resources, and bio-industrial plant resources. In the second section, we cloned several mutated genes and studied mechanisms of gene expression and genetic diversity of mutations induced by gamma-rays. In the third section, we developed new plant breeding techniques using gamma-phytotron, heavy ion-beam, and space environments. Based on these results, a total of 8 cultivars containing Chrysanthemum, Hibiscus, kenaf, rice, and soybean were applied for plant variety protection (PVP) and a total of 4 cultivars were registered for PVP. Also, license agreement for the dwarf type Hibiscus mutant 'Ggoma' was conducted with Supro co. and the manufacturing technology for natural antioxidant pear-grape vinegar was transferred into Enzenic co. Also, 8 gene sequences, such as F3'H and LDOX genes associated with flower color in Chrysanthemum and EPSPS gene from Korean lawn grass, were registered in the database of National Center for Biotechnology Information (NCBI). In the future study, we will develop new radiation mutation breeding techniques through the mutation spectrum induced by various radiation sources, the studies for mechanism of the cellular response to radiation, and the comparative{center_dot}structural{center_dot}functional genomics studies for useful traits.

  6. CD44 plays a functional role in Helicobacter pylori-induced epithelial cell proliferation.

    Directory of Open Access Journals (Sweden)

    Nina Bertaux-Skeirik

    2015-02-01

    Full Text Available The cytotoxin-associated gene (Cag pathogenicity island is a strain-specific constituent of Helicobacter pylori (H. pylori that augments cancer risk. CagA translocates into the cytoplasm where it stimulates cell signaling through the interaction with tyrosine kinase c-Met receptor, leading cellular proliferation. Identified as a potential gastric stem cell marker, cluster-of-differentiation (CD CD44 also acts as a co-receptor for c-Met, but whether it plays a functional role in H. pylori-induced epithelial proliferation is unknown. We tested the hypothesis that CD44 plays a functional role in H. pylori-induced epithelial cell proliferation. To assay changes in gastric epithelial cell proliferation in relation to the direct interaction with H. pylori, human- and mouse-derived gastric organoids were infected with the G27 H. pylori strain or a mutant G27 strain bearing cagA deletion (∆CagA::cat. Epithelial proliferation was quantified by EdU immunostaining. Phosphorylation of c-Met was analyzed by immunoprecipitation followed by Western blot analysis for expression of CD44 and CagA. H. pylori infection of both mouse- and human-derived gastric organoids induced epithelial proliferation that correlated with c-Met phosphorylation. CagA and CD44 co-immunoprecipitated with phosphorylated c-Met. The formation of this complex did not occur in organoids infected with ∆CagA::cat. Epithelial proliferation in response to H. pylori infection was lost in infected organoids derived from CD44-deficient mouse stomachs. Human-derived fundic gastric organoids exhibited an induction in proliferation when infected with H. pylori that was not seen in organoids pre-treated with a peptide inhibitor specific to CD44. In the well-established Mongolian gerbil model of gastric cancer, animals treated with CD44 peptide inhibitor Pep1, resulted in the inhibition of H. pylori-induced proliferation and associated atrophic gastritis. The current study reports a unique

  7. Proteomic analysis of Fasciola hepatica excretory and secretory products (FhESPs) involved in interacting with host PBMCs and cytokines by shotgun LC-MS/MS.

    Science.gov (United States)

    Liu, Qing; Huang, Si-Yang; Yue, Dong-Mei; Wang, Jin-Lei; Wang, Yujian; Li, Xiangrui; Zhu, Xing-Quan

    2017-02-01

    Fasciola hepatica is a helminth parasite with a worldwide distribution, which can cause chronic liver disease, fasciolosis, leading to economic losses in the livestock and public health in many countries. Control is mostly reliant on the use of drugs, and as a result, drug resistance has now emerged. The identification of F. hepatica genes involved in interaction between the parasite and host immune system is utmost important to elucidate the evasion mechanisms of the parasite and develop more effective strategies against fasciolosis. In this study, we aimed to identify molecules in F. hepatica excretory and secretory products (FhESPs) interacting with the host peripheral blood mononuclear cells (PBMCs), Th1-like cytokines (IL2 and IFN-γ), and Th17-like cytokines (IL17) by Co-IP combined with tandem mass spectrometry. The results showed that 14, 16, and 9 proteins in FhESPs could bind with IL2, IL17, and IFN-γ, respectively, which indicated that adult F. hepatica may evade the host immune responses through directly interplaying with cytokines. In addition, nine proteins in FhESPs could adhere to PBMCs. Our findings provided potential targets as immuno-regulators, and will be helpful to elucidate the molecular basis of host-parasite interactions and search for new potential proteins as vaccine and drug target candidates.

  8. Common effects of lithium and valproate on mitochondrial functions: protection against methamphetamine-induced mitochondrial damage.

    Science.gov (United States)

    Bachmann, Rosilla F; Wang, Yun; Yuan, Peixiong; Zhou, Rulun; Li, Xiaoxia; Alesci, Salvatore; Du, Jing; Manji, Husseini K

    2009-07-01

    Accumulating evidence suggests that mitochondrial dysfunction plays a critical role in the progression of a variety of neurodegenerative and psychiatric disorders. Thus, enhancing mitochondrial function could potentially help ameliorate the impairments of neural plasticity and cellular resilience associated with a variety of neuropsychiatric disorders. A series of studies was undertaken to investigate the effects of mood stabilizers on mitochondrial function, and against mitochondrially mediated neurotoxicity. We found that long-term treatment with lithium and valproate (VPA) enhanced cell respiration rate. Furthermore, chronic treatment with lithium or VPA enhanced mitochondrial function as determined by mitochondrial membrane potential, and mitochondrial oxidation in SH-SY5Y cells. In-vivo studies showed that long-term treatment with lithium or VPA protected against methamphetamine (Meth)-induced toxicity at the mitochondrial level. Furthermore, these agents prevented the Meth-induced reduction of mitochondrial cytochrome c, the mitochondrial anti-apoptotic Bcl-2/Bax ratio, and mitochondrial cytochrome oxidase (COX) activity. Oligoarray analysis demonstrated that the gene expression of several proteins related to the apoptotic pathway and mitochondrial functions were altered by Meth, and these changes were attenuated by treatment with lithium or VPA. One of the genes, Bcl-2, is a common target for lithium and VPA. Knock-down of Bcl-2 with specific Bcl-2 siRNA reduced the lithium- and VPA-induced increases in mitochondrial oxidation. These findings illustrate that lithium and VPA enhance mitochondrial function and protect against mitochondrially mediated toxicity. These agents may have potential clinical utility in the treatment of other diseases associated with impaired mitochondrial function, such as neurodegenerative diseases and schizophrenia.

  9. Functional and Structural Neuroplasticity Induced by Short-Term Tactile Training Based on Braille Reading.

    Science.gov (United States)

    Debowska, Weronika; Wolak, Tomasz; Nowicka, Anna; Kozak, Anna; Szwed, Marcin; Kossut, Malgorzata

    2016-01-01

    Neuroplastic changes induced by sensory learning have been recognized within the cortices of specific modalities as well as within higher ordered multimodal areas. The interplay between these areas is not fully understood, particularly in the case of somatosensory learning. Here we examined functional and structural changes induced by short-term tactile training based of Braille reading, a task that requires both significant tactile expertise and mapping of tactile input onto multimodal representations. Subjects with normal vision were trained for 3 weeks to read Braille exclusively by touch and scanned before and after training, while performing a same-different discrimination task on Braille characters and meaningless characters. Functional and diffusion-weighted magnetic resonance imaging sequences were used to assess resulting changes. The strongest training-induced effect was found in the primary somatosensory cortex (SI), where we observed bilateral augmentation in activity accompanied by an increase in fractional anisotropy (FA) within the contralateral SI. Increases of white matter fractional anisotropy were also observed in the secondary somatosensory area (SII) and the thalamus. Outside of somatosensory system, changes in both structure and function were found in i.e., the fusiform gyrus, the medial frontal gyri and the inferior parietal lobule. Our results provide evidence for functional remodeling of the somatosensory pathway and higher ordered multimodal brain areas occurring as a result of short-lasting tactile learning, and add to them a novel picture of extensive white matter plasticity.

  10. Lesion-induced pseudo-dominance at functional magnetic resonance imaging: implications for preoperative assessments.

    Science.gov (United States)

    Ulmer, John L; Hacein-Bey, Lotfi; Mathews, Vincent P; Mueller, Wade M; DeYoe, Edgar A; Prost, Robert W; Meyer, Glenn A; Krouwer, Hendrikus G; Schmainda, Kathleen M

    2004-09-01

    To illustrate how lesion-induced neurovascular uncoupling at functional magnetic resonance imaging (fMRI) can mimic hemispheric dominance opposite the side of a lesion preoperatively. We retrospectively reviewed preoperative fMRI mapping data from 50 patients with focal brain abnormalities to establish patterns of hemispheric dominance of language, speech, visual, or motor system functions. Abnormalities included gliomas (31 patients), arteriovenous malformations (AVMs) (11 patients), other congenital lesions (4 patients), encephalomalacia (3 patients), and tumefactive encephalitis (1 patient). A laterality ratio of fMRI hemispheric dominance was compared with actual hemispheric dominance as verified by electrocortical stimulation, Wada testing, postoperative and posttreatment deficits, and/or lesion-induced deficits. fMRI activation maps were generated with cross-correlation (P frontal gyrus gliomas and in one patient with focal tumefactive meningoencephalitis, fMRI incorrectly suggested strong right hemispheric speech dominance. In two patients with lateral precentral gyrus region gliomas and one patient with a left central sulcus AVM, the fMRI pattern incorrectly suggested primary corticobulbar motor dominance contralateral to the side of the lesion. In a patient with a right superior frontal gyrus AVM, fMRI revealed pronounced left dominant supplementary motor area activity in response to a bilateral complex motor task, but right superior frontal gyrus perilesional hemorrhage and edema subsequently caused left upper-extremity plegia. Pathophysiological factors that might have caused neurovascular uncoupling and facilitated pseudo-dominance at fMRI in these patients included direct tumor infiltration, neovascularity, cerebrovascular inflammation, and AVM-induced hemodynamic effects. Sixteen patients had proven (1 patient), probable (2 patients), or possible (13 patients) but unproven lesion-induced homotopic cortical reorganization. Lesion-induced neurovascular

  11. Naringin Improves Neuronal Insulin Signaling, Brain Mitochondrial Function, and Cognitive Function in High-Fat Diet-Induced Obese Mice.

    Science.gov (United States)

    Wang, Dongmei; Yan, Junqiang; Chen, Jing; Wu, Wenlan; Zhu, Xiaoying; Wang, Yong

    2015-10-01

    The epidemic and experimental studies have confirmed that the obesity induced by high-fat diet not only caused neuronal insulin resistance, but also induced brain mitochondrial dysfunction as well as learning impairment in mice. Naringin has been reported to posses biological functions which are beneficial to human cognitions, but its protective effects on HFD-induced cognitive deficits and underlying mechanisms have not been well characterized. In the present study Male C57BL/6 J mice were fed either a control or high-fat diet for 20 weeks and then randomized into four groups treated with their respective diets including control diet, control diet + naringin, high-fat diet (HFD), and high-fat diet + naringin (HFDN). The behavioral performance was assessed by using novel object recognition test and Morris water maze test. Hippocampal mitochondrial parameters were analyzed. Then the protein levels of insulin signaling pathway and the AMP-activated protein kinase (AMPK) in the hippocampus were detected by Western blot method. Our results showed that oral administration of naringin significantly improved the learning and memory abilities as evidenced by increasing recognition index by 52.5% in the novel object recognition test and inducing a 1.05-fold increase in the crossing-target number in the probe test, and ameliorated mitochondrial dysfunction in mice caused by HFD consumption. Moreover, naringin significantly enhanced insulin signaling pathway as indicated by a 34.5% increase in the expression levels of IRS-1, a 47.8% decrease in the p-IRS-1, a 1.43-fold increase in the p-Akt, and a 1.89-fold increase in the p-GSK-3β in the hippocampus of the HFDN mice versus HFD mice. Furthermore, the AMPK activity significantly increased in the naringin-treated (100 mg kg(-1) d(-1)) group. These findings suggest that an enhancement in insulin signaling and a decrease in mitochondrial dysfunction through the activation of AMPK may be one of the mechanisms that naringin

  12. Flavanol-rich cocoa consumption enhances exercise-induced executive function improvements in humans.

    Science.gov (United States)

    Tsukamoto, Hayato; Suga, Tadashi; Ishibashi, Aya; Takenaka, Saki; Tanaka, Daichi; Hirano, Yoshitaka; Hamaoka, Takafumi; Goto, Kazushige; Ebi, Kumiko; Isaka, Tadao; Hashimoto, Takeshi

    2018-02-01

    Aerobic exercise is known to acutely improve cognitive functions, such as executive function (EF) and memory function (MF). Additionally, consumption of flavanol-rich cocoa has been reported to acutely improve cognitive function. The aim of this study was to determine whether high cocoa flavanol (CF; HCF) consumption would enhance exercise-induced improvement in cognitive function. To test this hypothesis, we examined the combined effects of HCF consumption and moderate-intensity exercise on EF and MF during postexercise recovery. Ten healthy young men received either an HCF (563 mg of CF) or energy-matched low CF (LCF; 38 mg of CF) beverage 70 min before exercise in a single-blind counterbalanced manner. The men then performed moderate-intensity cycling exercise at 60% of peak oxygen uptake for 30 min. The participants performed a color-word Stroop task and face-name matching task to evaluate EF and MF, respectively, during six time periods throughout the experimental session. EF significantly improved immediately after exercise compared with before exercise in both conditions. However, EF was higher after HCF consumption than after LCF consumption during all time periods because HCF consumption improved EF before exercise. In contrast, HCF consumption and moderate-intensity exercise did not improve MF throughout the experiment. The present findings demonstrated that HCF consumption before moderate-intensity exercise could enhance exercise-induced improvement in EF, but not in MF. Therefore, we suggest that the combination of HCF consumption and aerobic exercise may be beneficial for improving EF. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Charles Edward Isaacs (1811-1860): exploring the details of nephron structure and function in the post-Bowman period.

    Science.gov (United States)

    Fine, Leon G

    2003-01-01

    Charles Edward Isaacs (1811-1860), an anatomist working in New York, undertook a series of studies which attempted to define the microscopic structure of the nephrons in a variety of species. Given that he published his findings 15 years after William Bowman's seminal paper on the subject, he was able to add only a few of the finer details to the picture. He observed the continuity of the epithelium of the glomerular capsule with that of the proximal tubule and he demonstrated that the glomerular tuft is covered by a layer of epithelial cells. In a series of studies on human renal function he erroneously concluded that the glomerulus must have an excretory function in addition to its filtration function and that diuretics act primarily on the glomerlus. The latter conclusion was based upon observations of substances not currently categorized as being diuretic agents. The absence of a major conceptual advance in the writings of Isaacs probably accounts for that fact that his contribution has been largely forgotten.

  14. Imaging

    International Nuclear Information System (INIS)

    Kellum, C.D.; Fisher, L.M.; Tegtmeyer, C.J.

    1987-01-01

    This paper examines the advantages of the use of excretory urography for diagnosis. According to the authors, excretory urography remains the basic radiologic examination of the urinary tract and is the foundation for the evaluation of suspected urologic disease. Despite development of the newer diagnostic modalities such as isotope scanning, ultrasonography, CT, and magnetic resonsance imaging (MRI), excretory urography has maintained a prominent role in ruorradiology. Some indications have been altered and will continue to change with the newer imaging modalities, but the initial evaluation of suspected urinary tract structural abnormalities; hematuria, pyuria, and calculus disease is best performed with excretory urography. The examination is relatively inexpensive and simple to perform, with few contraindictions. Excretory urography, when properly performed, can provide valuable information about the renal parenchyma, pelvicalyceal system, ureters, and urinary bladder

  15. Apoptosis-Inducing-Factor-Dependent Mitochondrial Function Is Required for T Cell but Not B Cell Function.

    Science.gov (United States)

    Milasta, Sandra; Dillon, Christopher P; Sturm, Oliver E; Verbist, Katherine C; Brewer, Taylor L; Quarato, Giovanni; Brown, Scott A; Frase, Sharon; Janke, Laura J; Perry, S Scott; Thomas, Paul G; Green, Douglas R

    2016-01-19

    The role of apoptosis inducing factor (AIF) in promoting cell death versus survival remains controversial. We report that the loss of AIF in fibroblasts led to mitochondrial electron transport chain defects and loss of proliferation that could be restored by ectopic expression of the yeast NADH dehydrogenase Ndi1. Aif-deficiency in T cells led to decreased peripheral T cell numbers and defective homeostatic proliferation, but thymic T cell development was unaffected. In contrast, Aif-deficient B cells developed and functioned normally. The difference in the dependency of T cells versus B cells on AIF for function and survival correlated with their metabolic requirements. Ectopic Ndi1 expression rescued homeostatic proliferation of Aif-deficient T cells. Despite its reported roles in cell death, fibroblasts, thymocytes and B cells lacking AIF underwent normal death. These studies suggest that the primary role of AIF relates to complex I function, with differential effects on T and B cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Analysis of the excitation functions for 3He- and α-induced reactions on 107Ag and 109Ag

    International Nuclear Information System (INIS)

    Misaelides, P.

    1976-06-01

    Excitation functions of 32 3 He- and α-induced nuclear reactions on 107 Ag and 109 Ag have been measured. The incident projectile energies ranged from 10 to 40 MeV for the 3 He-ions and 10 to 100 MeV for the α-particles. The recoil range of some 3 He-induced reaction products and the isomeric ratio values indicate the predominance of a precompound-compound nucleous mechanism. The experimental cross sections were compared with the excitation functions calculated on the basis of the compound nucleus and hybrid models. Using the values n 0 ( 3 He) = 5 and n 0 (α) = 4 for the initial exciton number and a = A/12.5 for the level density parameter a satisfactory reproduction of the experimental results for the α-induced reactions was achieved, whereas the calculated excitation functions for the 3 He-induced reactions are about a factor of two higher. (orig.) [de

  17. Dextran sulfate sodium-induced acute colitis impairs dermal lymphatic function in mice.

    Science.gov (United States)

    Agollah, Germaine D; Wu, Grace; Peng, Ho-Lan; Kwon, Sunkuk

    2015-12-07

    To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium (DSS)-induced acute colitis. Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence (NIRF) imaging following intradermal injection of indocyanine green (ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSS administration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin (BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest (ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI. Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels, indicating impaired

  18. AMPKγ3 is dispensable for skeletal muscle hypertrophy induced by functional overload.

    Science.gov (United States)

    Riedl, Isabelle; Osler, Megan E; Björnholm, Marie; Egan, Brendan; Nader, Gustavo A; Chibalin, Alexander V; Zierath, Juleen R

    2016-03-15

    Mechanisms regulating skeletal muscle growth involve a balance between the activity of serine/threonine protein kinases, including the mammalian target of rapamycin (mTOR) and 5'-AMP-activated protein kinase (AMPK). The contribution of different AMPK subunits to the regulation of cell growth size remains inadequately characterized. Using AMPKγ3 mutant-overexpressing transgenic Tg-Prkag3(225Q) and AMPKγ3-knockout (Prkag3(-/-)) mice, we investigated the requirement for the AMPKγ3 isoform in functional overload-induced muscle hypertrophy. Although the genetic disruption of the γ3 isoform did not impair muscle growth, control sham-operated AMPKγ3-transgenic mice displayed heavier plantaris muscles in response to overload hypertrophy and underwent smaller mass gain and lower Igf1 expression compared with wild-type littermates. The mTOR signaling pathway was upregulated with functional overload but unchanged between genetically modified animals and wild-type littermates. Differences in AMPK-related signaling pathways between transgenic, knockout, and wild-type mice did not impact muscle hypertrophy. Glycogen content was increased following overload in wild-type mice. In conclusion, our functional, transcriptional, and signaling data provide evidence against the involvement of the AMPKγ3 isoform in the regulation of skeletal muscle hypertrophy. Thus, the AMPKγ3 isoform is dispensable for functional overload-induced muscle growth. Mechanical loading can override signaling pathways that act as negative effectors of mTOR signaling and consequently promote skeletal muscle hypertrophy. Copyright © 2016 the American Physiological Society.

  19. Artificial stone dust-induced functional and inflammatory abnormalities in exposed workers monitored quantitatively by biometrics.

    Science.gov (United States)

    Ophir, Noa; Shai, Amir Bar; Alkalay, Yifat; Israeli, Shani; Korenstein, Rafi; Kramer, Mordechai R; Fireman, Elizabeth

    2016-01-01

    The manufacture of kitchen and bath countertops in Israel is based mainly on artificial stone that contains 93% silica as natural quartz, and ∼3500 workers are involved in cutting and processing it. Artificial stone produces high concentrations of silica dust. Exposure to crystalline silica may cause silicosis, an irreversible lung disease. Our aim was to screen exposed workers by quantitative biometric monitoring of functional and inflammatory parameters. 68 exposed artificial stone workers were compared to 48 nonexposed individuals (controls). Exposed workers filled in questionnaires, and all participants underwent pulmonary function tests and induced sputum analyses. Silica was quantitated by a Niton XL3 X-ray fluorescence spectrometer. Pulmonary function test results of exposed workers were significantly lower and induced sputa showed significantly higher neutrophilic inflammation compared to controls; both processes were slowed down by the use of protective measures in the workplace. Particle size distribution in induced sputum samples of exposed workers was similar to that of artificial stone dust, which contained aluminium, zirconium and titanium in addition to silica. In conclusion, the quantitation of biometric parameters is useful for monitoring workers exposed to artificial stone in order to avoid deterioration over time.

  20. Pacing-induced chronic atrial fibrillation impairs sinus node function in dogs. Electrophysiological remodeling.

    Science.gov (United States)

    Elvan, A; Wylie, K; Zipes, D P

    1996-12-01

    We assessed the effects of pacing-induced chronic atrial fibrillation (AF) on sinus node function, intra-atrial conduction, and atrial refractoriness. In 15 mongrel dogs (20 to 30 kg), AV nodal block was produced by radiofrequency catheter ablation, and a ventricular-inhibited (VVI) pacemaker (Minix 8330, Medtronic) was implanted and programmed to pace at 80 pulses per minute. In 11 of these dogs, right atrial endocardial pacing leads were connected to a pulse generator (Itrel 7432, Medtronic) and set at a rate of 20 Hz to induce AF. Corrected sinus node recovery time, P-wave duration, 24-hour Holter ECG to assess AF duration, maximal heart rate in response to isoproterenol (10 micrograms/min), intrinsic heart rate after administration of atropine (0.04 mg/kg) and propranolol (0.1 mg/kg), and atrial effective refractory periods (ERPs) were obtained at baseline (EPS-1) and after 2 to 6 weeks (EPS-2) of VVI pacing alone (n = 4) or VVI pacing and rapid atrial pacing (n = 11). At EPS-2, corrected sinus node recovery time and P-wave duration were prolonged, maximal heart rate and intrinsic heart rate were decreased, atrial ERPs were shortened, and the duration of AF was increased significantly compared with EPS-1. These changes partially reversed toward baseline 1 week after conversion to sinus rhythm. Sinus node function and AF inducibility observed in the control dogs that underwent ventricular pacing alone (n = 4) did not change. Pacing-induced chronic AF induces sinus node dysfunction, prolongs intra-atrial conduction time, shortens atrial refractoriness, and perpetuates AF, changes that reverse gradually after termination of AF.

  1. Differences in the gene expression profiles of haemocytes from schistosome-susceptible and -resistant biomphalaria glabrata exposed to Schistosoma mansoni excretory-secretory products.

    Directory of Open Access Journals (Sweden)

    Zahida Zahoor

    Full Text Available During its life cycle, the helminth parasite Schistosoma mansoni uses the freshwater snail Biomphalaria glabrata as an intermediate host to reproduce asexually generating cercariae for infection of the human definitive host. Following invasion of the snail, the parasite develops from a miracidium to a mother sporocyst and releases excretory-secretory products (ESPs that likely influence the outcome of host infection. To better understand molecular interactions between these ESPs and the host snail defence system, we determined gene expression profiles of haemocytes from S. mansoni-resistant or -susceptible strains of B. glabrata exposed in vitro to S. mansoni ESPs (20 μg/ml for 1 h, using a 5K B. glabrata cDNA microarray. Ninety-eight genes were found differentially expressed between haemocytes from the two snail strains, 57 resistant specific and 41 susceptible specific, 60 of which had no known homologue in GenBank. Known differentially expressed resistant-snail genes included the nuclear factor kappa B subunit Relish, elongation factor 1α, 40S ribosomal protein S9, and matrilin; known susceptible-snail specific genes included cathepsins D and L, and theromacin. Comparative analysis with other gene expression studies revealed 38 of the 98 identified genes to be uniquely differentially expressed in haemocytes in the presence of ESPs, thus identifying for the first time schistosome ESPs as important molecules that influence global snail host-defence cell gene expression profiles. Such immunomodulation may benefit the schistosome, enabling its survival and successful development in the snail host.

  2. Differentiation-inducing factor-1 and -2 function also as modulators for Dictyostelium chemotaxis.

    Directory of Open Access Journals (Sweden)

    Hidekazu Kuwayama

    Full Text Available BACKGROUND: In the early stages of development of the cellular slime mold Dictyostelium discoideum, chemotaxis toward cAMP plays a pivotal role in organizing discrete cells into a multicellular structure. In this process, a series of signaling molecules, such as G-protein-coupled cell surface receptors for cAMP, phosphatidylinositol metabolites, and cyclic nucleotides, function as the signal transducers for controlling dynamics of cytoskeleton. Differentiation-inducing factor-1 and -2 (DIF-1 and DIF-2 were originally identified as the factors (chlorinated alkylphenones that induce Dictyostelium stalk cell differentiation, but it remained unknown whether the DIFs had any other physiologic functions. METHODOLOGY/PRINCIPAL FINDINGS: To further elucidate the functions of DIFs, in the present study we investigated their effects on chemotaxis under various conditions. Quite interestingly, in shallow cAMP gradients, DIF-1 suppressed chemotaxis whereas DIF-2 promoted it greatly. Analyses with various mutants revealed that DIF-1 may inhibit chemotaxis, at least in part, via GbpB (a phosphodiesterase and a decrease in the intracellular cGMP concentration ([cGMP](i. DIF-2, by contrast, may enhance chemotaxis, at least in part, via RegA (another phosphodiesterase and an increase in [cGMP](i. Using null mutants for DimA and DimB, the transcription factors that are required for DIF-dependent prestalk differentiation, we also showed that the mechanisms for the modulation of chemotaxis by DIFs differ from those for the induction of cell differentiation by DIFs, at least in part. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that DIF-1 and DIF-2 function as negative and positive modulators for Dictyostelium chemotaxis, respectively. To our knowledge, this is the first report in any organism of physiologic modulators (small molecules for chemotaxis having differentiation-inducing activity.

  3. Hepatorenal dysfunction in patients with metabolic syndrome according to radionuclide findings

    International Nuclear Information System (INIS)

    Zubkova, G.A.; Luchits'kij, Je.V.; Slavnov, V.M.; Ribal'chenko, V.M.; Luchits'kij, V.Je.; Markov, V.V.; Pospelov, S.V.

    2010-01-01

    Ukrainian scintillation tomographic gamma-camera was used to investigate the functional state of the kidneys and liver in patients with metabolic syndrome. In men with MS, inconsiderable delay in the kidney filtration function and significant delay of excretory function, according to renoangiography - significant delay of arterial in-flow time and a tendency to delay of venous out-flow time, were noted.

  4. Response function for the characterization of photo-induced anisotropy in azobenzene containing polymers

    DEFF Research Database (Denmark)

    Sajti, S.; Kerekes, Á.; Ramanujam, P.S.

    2002-01-01

    A response function is derived for the description of photo-induced birefringence and dichroism in case of materials where the underlying process is photo-isomerization. Our result explains the usefulness of the theoretical formulae derived earlier by Kakichashvili for photo-anisotropic materials...

  5. Blockade of cannabinoid CB receptor function protects against in vivo disseminating brain damage following NMDA-induced excitotoxicity

    DEFF Research Database (Denmark)

    Hansen, H.H.; Ramos, J.A.; Fernández-Ruiz, J.

    2002-01-01

    -induced excitotoxic damage in the ipsilateral forebrain was not influenced by agonist-stimulated CB receptor function. In contrast, blockade of CB, but not CB, receptor activity evoked a robust neuroprotective response by reducing the infarct area and the number of cortical degenerating neurons. These results suggest...... receptor function on NMDA-induced excitotoxicity. Neonatal (6-day-old) rat pups received a systemic injection of a mixed CB/CB receptor agonist (WIN55,212-2) or their respective antagonists (SR141716A for CB and SR144528 for CB) prior to an unilateral intrastriatal microinjection of NMDA. The NMDA...... a critical involvement of CB receptor tonus on neuronal survival following NMDA receptor-induced excitotoxicity in vivo....

  6. Function and regulation of ATF 3 expression induced by ionizing radiation

    International Nuclear Information System (INIS)

    Fan, Feiyue; Wang, Yong; Du, Liqin; Zhan, Qimin

    2008-01-01

    Full text: Ionizing radiation results in a series of damages of mammalian cells as a genotoxic stress. There are some genes expressed after cells damaged, in which ATF 3, a member of ATF/CREB family of transcription factors, is one of them. In this report, we demonstrate that ATF 3 can be induced by ionizing radiation. The induction of ATF 3 protein requires normal status of p53 function in cells. There are some quantitative relationships between ATF 3 induction and dosages of radiation or time post-irradiation. In another word, ATF 3 expression induced by ionizing radiation present dose- and time-dependent. The regulation of ATF 3 expression refers to program of promoter and transcription. Radiation induces ATF 3 expression by activating the promoter and RNA transcription. In method of tetracycline-inducible system (tet-off), we have found that over-expression of ATF 3 protein brings caspase/PARP proteins into cleavage, which induces cell programmed death, and suppresses cell growth. Meanwhile, it was found that ATF 3 expression could slow down progression of cell from G 1 to S phase. It indicates ATF 3 protein might play a negative role in the control of cell cycle progression. It is very excited that expression of ATF 3 protein did not only suppress cell growth, but also demonstrated protecting effect of cell growth suppression resulting from ionizing radiation. It is suggested that ATF 3 protein might take part in the damage repair process of cells. (author)

  7. Temperature-induced changes in neuromuscular function: central and peripheral mechanisms.

    Science.gov (United States)

    Goodman, D; Hancock, P A; Runnings, D W; Brown, S L

    1984-10-01

    Three series of experimental tests were conducted on subjects under both elevated and depressed thermal conditions. Tripartite series consisted of whole-body immersion excepting the head, whole-body immersion excepting the head and response limb, and immersion of the discrete-response limb. Measures of physiological and behavioural responses were made at sequential .4 degrees C changes during whole-body immersions and approximately 5 degrees C changes of water temperature during the immersion of a limb only. Results suggested that velocity of nerve conduction decreased with thermal depression. Premotor, motor, simple, and choice reaction times varied differentially as a function of the hot and cold conditions. Implications of these differential effects on neuromuscular function are examined with respect to person-machine performance in artificially induced or naturally occurring extremes of ambient temperature.

  8. SIRT1 Functions as an Important Regulator of Estrogen-Mediated Cardiomyocyte Protection in Angiotensin II-Induced Heart Hypertrophy

    Directory of Open Access Journals (Sweden)

    Tao Shen

    2014-01-01

    Full Text Available Background. Sirtuin 1 (SIRT1 is a member of the sirtuin family, which could activate cell survival machinery and has been shown to be protective in regulation of heart function. Here, we determined the mechanism by which SIRT1 regulates Angiotensin II- (AngII- induced cardiac hypertrophy and injury in vivo and in vitro. Methods. We analyzed SIRT1 expression in the hearts of control and AngII-induced mouse hypertrophy. Female C57BL/6 mice were ovariectomized and pretreated with 17β-estradiol to measure SIRT1 expression. Protein synthesis, cardiomyocyte surface area analysis, qRT-PCR, TUNEL staining, and Western blot were performed on AngII-induced mouse heart hypertrophy samples and cultured neonatal rat ventricular myocytes (NRVMs to investigate the function of SIRT1. Results. SIRT1 expression was slightly upregulated in AngII-induced mouse heart hypertrophy in vivo and in vitro, accompanied by elevated cardiomyocyte apoptosis. SIRT1 overexpression relieves AngII-induced cardiomyocyte hypertrophy and apoptosis. 17β-Estradiol was able to protect cardiomyocytes from AngII-induced injury with a profound upregulation of SIRT1 and activation of AMPK. Moreover, estrogen receptor inhibitor ICI 182,780 and SIRT1 inhibitor niacinamide could block SIRT1’s protective effect. Conclusions. These results indicate that SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection during AngII-induced heart hypertrophy and injury.

  9. Monocytes can be induced by lipopolysaccharide-triggered T lymphocytes to express functional factor VII/VIIa protease activity

    OpenAIRE

    1984-01-01

    In the present study we demonstrate that human monocytes can be induced by the model stimulus, lipopolysaccharide (LPS), to produce and assemble on their surface functional Factor VII/VIIa. This protease was not induced in relatively purified monocytes alone following exposure to LPS; but was induced in the presence of Leu-3a positive helper/inducer T cells. The Factor VII/VIIa protease activity represented 35-40% of the potential initiating activity for the extrinsic coagulation pathway and ...

  10. DISTINCT FUNCTIONS OF JNK AND C-JUN IN OXIDANT-INDUCED HEPATOCYTE DEATH

    Science.gov (United States)

    Amir, Muhammad; Liu, Kun; Zhao, Enpeng; Czaja, Mark J.

    2013-01-01

    Overactivation of c-Jun N-terminal kinase (JNK)/c-Jun signaling is a central mechanism of hepatocyte injury and death including that from oxidative stress. However, the functions of JNK and c-Jun are still unclear, and this pathway also inhibits hepatocyte death. Previous studies of menadione-induced oxidant stress demonstrated that toxicity resulted from sustained JNK/c-Jun activation as death was blocked by the c-Jun dominant negative TAM67. To further delineate the function of JNK/c-Jun signaling in hepatocyte injury from oxidant stress, the effects of direct JNK inhibition on menadione-induced death were examined. In contrast to the inhibitory effect of TAM67, pharmacological JNK inhibition by SP600125 sensitized the rat hepatocyte cell line RALA255-10G to death from menadione. SP600125 similarly sensitized mouse primary hepatocytes to menadione toxicity. Death from SP600125/menadione was c-Jun dependent as it was blocked by TAM67, but independent of c-Jun phosphorylation. Death occurred by apoptosis and necrosis and activation of the mitochondrial death pathway. Short hairpin RNA knockdowns of total JNK or JNK2 sensitized to death from menadione, whereas a jnk1 knockdown was protective. Jnk2 null mouse primary hepatocytes were also sensitized to menadione death. JNK inhibition magnified decreases in cellular ATP content and β-oxidation induced by menadione. This effect mediated cell death as chemical inhibition of β-oxidation also sensitized cells to death from menadione, and supplementation with the β-oxidation substrate oleate blocked death. Components of the JNK/c-Jun signaling pathway have opposing functions in hepatocyte oxidant stress with JNK2 mediating resistance to cell death and c-Jun promoting death. PMID:22644775

  11. Agmatine improves renal function in gentamicin-induced nephrotoxicity in rats.

    Science.gov (United States)

    El-Kashef, Dalia H; El-Kenawi, Asmaa E; Abdel Rahim, Mona; Suddek, Ghada M; Salem, Hatem A

    2016-03-01

    The present study was designed to explore the possible protective effects of agmatine, a known nitric oxide (NO) synthase inhibitor, against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of agmatine on gentamicin-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was evaluated. Twenty-four male Wistar albino rats were randomly divided into 3 groups, namely control, gentamicin (100 mg/kg, i.p.), and gentamicin plus agmatine (40 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood and urine samples and kidneys were taken. Administration of agmatine significantly decreased kidney/body mass ratio, serum creatinine, lactate dehydrogenase (LDH), renal malondialdehyde (MDA), myeloperoxidase (MPO), NO, and tumor necrosis factor-alpha (TNF-α) while it significantly increased creatinine clearance and renal superoxide dismutase (SOD) activity when compared with the gentamicin-treated group. Additionally, agmatine ameliorated tissue morphology as evidenced by histological evaluation and reduced the responses of isolated bladder rings to ACh. Our study indicates that agmatine administration with gentamicin attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation, restoring NO level and inhibiting inflammatory mediators such as TNF-α.

  12. Changes of liver function and serum hepatic fibrosis markers levels in patients with trichloroethylene induced drugrash-like dermatitis

    International Nuclear Information System (INIS)

    Li Senhua; Xie Guoqiang; Zeng Zeming

    2004-01-01

    Objective: To investigate the liver function damage and serum hepatic fibrosis markers levels changes in patients suffering from trichloroethylene induced drugrash-like dermatitis. Methods: Serum hyaluronic acid (HA), laminin (LN), procollagen type III (PC III), type IV collagen ( IV C) levels (with RIA), mono-amine oxidase (MAO) activity (with chemo-colorimetry) and liver function tests (including ALT, AGT, total protein, albumin, total bile acid, with automated biochemical analysis system) were determined in 30 controls and 30 patients with trichloroethylene induced drugrash-like dermatitis. Results: Severe liver function damage was demonstrated in all the patients. The serum hepatic fibrosis markers levels were significantly increased (vs controls, P<0.01) and correlated well with the degree of hepatic damage. Conclusion: Liver damage occurred early in patients with trichloroethylene induced dermatitis, accompanied with laboratory evidence of hepatic fibrosis. (authors)

  13. Limonene inhibits methamphetamine-induced locomotor activity via regulation of 5-HT neuronal function and dopamine release.

    Science.gov (United States)

    Yun, Jaesuk

    2014-05-15

    Methamphetamine is a psychomotor stimulant that produces hyperlocomotion in rodents. Limonene (a cyclic terpene from citrus essential oils) has been reported to induce sedative effects. In this study, we demonstrated that limonene administration significantly inhibited serotonin (5-hydroxytryptamine, 5-HT)-induced head twitch response in mice. In rats, pretreatment with limonene decreased hyperlocomotion induced by methamphetamine injection. In addition, limonene reversed the increase in dopamine levels in the nucleus accumbens of rats given methamphetamine. These results suggest that limonene may inhibit stimulant-induced behavioral changes via regulating dopamine levels and 5-HT receptor function. Copyright © 2013 Elsevier GmbH. All rights reserved.

  14. Decreased proteasomal function accelerates cigarette smoke-induced pulmonary emphysema in mice.

    Science.gov (United States)

    Yamada, Yosuke; Tomaru, Utano; Ishizu, Akihiro; Ito, Tomoki; Kiuchi, Takayuki; Ono, Ayako; Miyajima, Syota; Nagai, Katsura; Higashi, Tsunehito; Matsuno, Yoshihiro; Dosaka-Akita, Hirotoshi; Nishimura, Masaharu; Miwa, Soichi; Kasahara, Masanori

    2015-06-01

    Chronic obstructive pulmonary disease (COPD) is a disease common in elderly people, characterized by progressive destruction of lung parenchyma and chronic inflammation of the airways. The pathogenesis of COPD remains unclear, but recent studies suggest that oxidative stress-induced apoptosis in alveolar cells contributes to emphysematous lung destruction. The proteasome is a multicatalytic enzyme complex that plays a critical role in proteostasis by rapidly destroying misfolded and modified proteins generated by oxidative and other stresses. Proteasome activity decreases with aging in many organs including lungs, and an age-related decline in proteasomal function has been implicated in various age-related pathologies. However, the role of the proteasome system in the pathogenesis of COPD has not been investigated. Recently, we have established a transgenic (Tg) mouse model with decreased proteasomal chymotrypsin-like activity, showing age-related phenotypes. Using this model, we demonstrate here that decreased proteasomal function accelerates cigarette smoke (CS)-induced pulmonary emphysema. CS-exposed Tg mice showed remarkable airspace enlargement and increased foci of inflammation compared with wild-type controls. Importantly, apoptotic cells were found in the alveolar walls of the affected lungs. Impaired proteasomal activity also enhanced apoptosis in cigarette smoke extract (CSE)-exposed fibroblastic cells derived from mice and humans in vitro. Notably, aggresome formation and prominent nuclear translocation of apoptosis-inducing factor were observed in CSE-exposed fibroblastic cells isolated from Tg mice. Collective evidence suggests that CS exposure and impaired proteasomal activity coordinately enhance apoptotic cell death in the alveolar walls that may be involved in the development and progression of emphysema in susceptible individuals such as the elderly.

  15. Clinical and Functional Assays of Radiosensitivity and Radiation-Induced Second Cancer

    Directory of Open Access Journals (Sweden)

    Mohammad Habash

    2017-10-01

    Full Text Available Whilst the near instantaneous physical interaction of radiation energy with living cells leaves little opportunity for inter-individual variation in the initial yield of DNA damage, all the downstream processes in how damage is recognized, repaired or resolved and therefore the ultimate fate of cells can vary across the population. In the clinic, this variability is observed most readily as rare extreme sensitivity to radiotherapy with acute and late tissue toxic reactions. Though some radiosensitivity can be anticipated in individuals with known genetic predispositions manifest through recognizable phenotypes and clinical presentations, others exhibit unexpected radiosensitivity which nevertheless has an underlying genetic cause. Currently, functional assays for cellular radiosensitivity represent a strategy to identify patients with potential radiosensitivity before radiotherapy begins, without needing to discover or evaluate the impact of the precise genetic determinants. Yet, some of the genes responsible for extreme radiosensitivity would also be expected to confer susceptibility to radiation-induced cancer, which can be considered another late adverse event associated with radiotherapy. Here, the utility of functional assays of radiosensitivity for identifying individuals susceptible to radiotherapy-induced second cancer is discussed, considering both the common mechanisms and important differences between stochastic radiation carcinogenesis and the range of deterministic acute and late toxic effects of radiotherapy.

  16. The role of multi-detector computed

    Directory of Open Access Journals (Sweden)

    Nasr Mohamed Mohamed Osman

    2016-03-01

    Conclusion: MDCT is the modality of choice in evaluation and grading of renal trauma with high sensitivity (90–100%. CT detects site and extension of renal trauma and assesses the excretory function. CT is advantageous for the selection of best patient treatment.

  17. Dopamine natriuresis in salt-repleted, water-loaded humans

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Olsen, M H; Bonde, J

    1997-01-01

    The purpose of the present study was to define the dose-response relationship between exogenous dopamine and systemic haemodynamics, renal haemodynamics, and renal excretory function at infusion rates in the range 0 to 12.5 microg kg(-1) min(-1) in normal volunteers....

  18. Rescue of the apoptotic-inducing function of mutant p53 by small molecule RITA.

    Science.gov (United States)

    Zhao, Carolyn Y; Grinkevich, Vera V; Nikulenkov, Fedor; Bao, Wenjie; Selivanova, Galina

    2010-05-01

    Expression of mutant p53 correlates with poor prognosis in many tumors, therefore strategies aimed at reactivation of mutant p53 are likely to provide important benefits for treatment of tumors that are resistant to chemotherapy and radiotherapy. We have previously identified and characterized a small molecule RITA which binds p53 and induces a conformational change which prevents the binding of p53 to several inhibitors, including its own destructor MDM2. In this way, RITA rescues the tumor suppression function of wild type p53. Here, we demonstrate that RITA suppressed the growth and induced apoptosis in human tumor cell lines of a diverse origin carrying mutant p53 proteins. RITA restored transcriptional transactivation and transrepression function of several hot spot p53 mutants. The ability of RITA to rescue the activity of different p53 mutants suggests its generic mechanism of action. Thus, RITA is a promising lead for the development of anti-cancer drugs that reactivate the tumor suppressor function of p53 in cancer cells irrespective whether they express mutant or wild type p53.

  19. Measurement by means of sup(99m)Tc-pertechnetate of the function of salivary glands before and after stimulation with pilocarpine in cases of sicca-syndrome of the parotidic glands

    International Nuclear Information System (INIS)

    Gelinsky, P.

    1979-01-01

    Judgement on xerostomia in systemic diseases of the salivary glands and on the sicca-syndrome as a side-effect of radiation therapy or of a treatment with psychopharmaca has been improved by the function test of the parotidic glands for each side individually with sup(99m)Tc-pertechnetate, particularly in view of the detection of lateral differences. Measurements of the salivation volume and activity are completive of the function test, yielding knowledge of the total excretory power of all the salivary glands. Functional remainders and reserves can be visualized objectively by additional utilization of the pilocarpine stimulation test (today performed with carbachol). The findings will be still more precise if the parotide salivation is collected and measured for each side separately. This exploration method is appropriate for frequent controls in the course of a disease and for the forming of an opinion upon therapeutic effects of sialogogic agents. (orig.) [de

  20. Carbide induced reconstruction of monatomic steps on Ni(111) - A density functional study

    DEFF Research Database (Denmark)

    Andersson, Martin; Abild-Pedersen, Frank

    2007-01-01

    We present density functional calculations for carbon adsorption at the two types of monatomic steps on a Ni(111) surface. We show that it is thermodynamically favourable to make a carbon induced clock-type reconstruction at the close-packed step with a [111] step geometry, which creates fourfold...

  1. Study of induced functions by UV in Staphylococcus

    International Nuclear Information System (INIS)

    Silva, B.S. da.

    1982-01-01

    SOS functions induced by ultraviolet (UV) radiation were studied using S. aureus and S. epidermidis. Comparing the results obtained from these two organisms with those described in the literature for E. coli allows us to conclude: the difference in UV sensibility between the lysogenic and non-lysogenic strains of Staphylococcus is extremely large; the dose of UV radiation which results in the maximum induction of the lysogenic strains lead to 99% inactivation of the lysogenic strains; the kinetics of prophage liberation in lysogenic cultures of Staphylococcus is more rapid than those described for E. coli; the dose of UV radiation is much lower than the dose described for E. coli; the maximum W-reactivatio and W-mutagenesis are obtained immediately after the irradiation or within the 15 minutes allowed for the phage adsorption. (author)

  2. A model-independent comparison of the rates of uptake and short term retention of 47Ca and 85Sr by the skeleton.

    Science.gov (United States)

    Reeve, J; Hesp, R

    1976-12-22

    1. A method has been devised for comparing the impulse response functions of the skeleton for two or more boneseeking tracers, and for estimating the contribution made by measurement errors to the differences between any pair of impulse response functions. 2. Comparisons were made between the calculated impulse response functions for 47Ca and 85Sr obtained in simultaneous double tracer studies in sixteen subjects. Collectively the differences between the 47Ca and 85Sr functions could be accounted for entirely by measurement errors. 3. Because the calculation of an impulse response function requires fewer a priori assumptions than other forms of mathematical analysis, and automatically corrects for differences induced by recycling of tracer and non-identical rates of excretory plasma clearance of tracer, it is concluded that differences shown in previous in vivo studies between the fluxes of Ca and Sr into bone can be fully accounted for by undetermined oversimplifications in the various mathematical models used to analyse the results of those studies. 85Sr is therefore an adequate tracer for bone calcium in most in vivo studies.

  3. Flow-induced vibration test of an advanced water reactor model. Pt. 1. Turbulence-induced forcing function

    International Nuclear Information System (INIS)

    Au-Yang, M.K.; Brenneman, B.; Raj, D.

    1995-01-01

    A 1:9 scale model of a proposed advanced water reactor was tested for flow-induced vibration. The main objectives of this test were: (1) to derive an empirical equation for the turbulence forcing function which can be applied to the full-sized prototype; (2) to study the effect of viscosity on the turbulence; (3) to verify the ''superposition'' assumption widely used in dynamic analysis of weakly coupled fluid-shell systems; and (4) to measure the shell responses to verify methods and computer programs used in the flow-induced vibration analysis of the prototype. This paper describes objectives (1), (2), and (3); objective (4) will be discussed in a companion paper.The turbulence-induced fluctuating pressure was measured at 49 locations over the surface of a thick-walled, non-responsive scale model of the reactor vessel/core support cylinders. An empirical equation relating the fluctuating pressure, the frequency, and the distance from the inlet nozzle center line was derived to fit the test data. This equation involves only non-dimensional, fluid mechanical parameters that are postulated to represent the full-sized, geometrically similar prototype. While this postulate cannot be verified until similar measurements are taken on the full-sized unit, a similar approach using a 1:6 scale model of a commercial pressurized water reactor was verified in the mid-1970s by field measurements on the full-sized reactor. (orig.)

  4. Excitation functions of radionuclides produced by proton induced reactions on gadolinium targets

    International Nuclear Information System (INIS)

    Challana, M.B.; Comsana, M.N.H.; Moawadb, G.S.; Abou-Zeid, M.A.

    2008-01-01

    Cross section study for proton induced reaction on natural Gadolinium targets were performed. Excitation functions for the reactions n atGd(p,x) 152m+g , 154m,154g Tb from threshold up to E p = 18 MeV have been measured employing the stacked foil activation technique, and using high resolution HPGe gamma spectrometry. Utilizing the simultaneous measurement of the excitation function of n atCu(p,x) 62 Zn, n atCu(p,x) 63 Zn, and n atCu(p,x) 65 Zn as monitor reactions. The theoretical analysis of the excitation functions has been done employing both ALICE-91 and EMPIRE-II codes. In general, theoretical calculations agree well with the experimental data. A significant contribution of pre-equilibrium component has been observed at these energies

  5. "Purification and evaluation of somatic, excretory-secretory and Cysteine proteinase antigens of Fasciola Hepatica using IgG-ELISA in diagnosing Fascioliasis "

    Directory of Open Access Journals (Sweden)

    "Rokni MB

    2001-08-01

    Full Text Available Fasciolosis, or liver fluke disease, caused by parasites of the genus Fasciola is emerging as an important disease in man and animals, in the world and Iran, particularly in nortern parts. The economical losses in domestic animals are considerable. In the recent decade there were two major outbreaks of human fasciolosis in the Caspian region, northern part of Iran with 7000-10000 infected cases. Sicne it is impossible to diagnose fasciolosis in acute phase using coprological methods and even in chronic phases its sensitivity is low, evaluating and establishing a reliable and cost-effetive test is indispensable and notewortly.In the present survey, we produced and examined the sensitivity and specificity of liver fluke homogenate (LFH , excretory-secetory (ES and cysteine proteinase (CP antigens of F. hepatica using IgG-ELISA test. A 25-27 kilo Dalton coomassie blue-stained band was observed and using of specific inhibitors indicated that this antigen belongs to the class of cysteine proteinase. The sensitivity of LFH, ES and CP antigen in IgG-ELISa was 100% for each, while their specificity was 97.8%, 98.8% and 98.8% respectively. There was a significant difference in mean OD values between cases of proven fasciolosis and other true negative cases, including healthy control individuals and patients with other parasitic diseases.This present report is the first to demonstrate the purification and evaluation of F. hepatica cysteine proteinase antigen by IgG-ELISA test for the diagnosis of fasciolosis in Iran. In conclusion, the IgG-ELISa using ES and CP show high sensitivity and specificity and would be a valuable tool to diagnose human fasciolosis in Iran, particularly in endemic areas.

  6. Production of Monoclonal Antibody Against Excretory-Secretory Antigen of Fasciola hepatica and Evaluation of Its Efficacy in the Diagnosis of Fascioliasis.

    Science.gov (United States)

    Abdolahi Khabisi, Samaneh; Sarkari, Bahador; Moshfe, Abdolali; Jalali, Sedigheh

    2017-02-01

    Parasitological methods are not helpful for the diagnosis of fascioliasis in acute and invasive periods of the disease. Detection of coproantigens seems to be a suitable alternative approach in the diagnosis of fascioliasis. The present study aimed to develop a reliable antigen detection system, using monoclonal antibodies raised against excretory-secretory (ES) antigen of Fasciola hepatica, for the diagnosis of fascioliasis. Fasciola adult worms were collected from the bile ducts of infected animals. Species of the fluke was determined by polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR). ES antigen of F. hepatica was prepared. For production of monoclonal antibodies, mice were immunized with ES antigens of F. hepatica. Spleen cells from the immunized mice were fused with NS-1 myeloma cells, using polyethylene glycol. Hybridoma cells secreting specific antibody were expanded and cloned by limiting dilution. Moreover, polyclonal antibody was produced against F. hepatica ES antigen in rabbits. A capture enzyme-linked immunosorbent assay (ELISA) system, using produced monoclonal antibody, was designed and stool samples of infected animals along with control samples were tested by the system. The capture ELISA detected the coproantigen in 27 of 30 (90%) parasitologically confirmed fascioliasis cases, while 4 of 39 (10.25%) samples infected with other parasitic infections showed a positive reaction in this system. No positive reactivity was found with healthy control samples. Accordingly, sensitivity of 90% and specificity of 94.2% were obtained for the capture ELISA system. The results were compared with those obtained with commercial BIO-X ELISA, and a very good (kappa = 0.9) agreement was found between the commercial kit and the developed capture ELISA. Findings of this study showed that the produced monoclonal antibody has appropriate performance for the detection of Fasciola coproantigen in stool samples and can be appropriately

  7. The excretory-secretory products of Echinococcus granulosus protoscoleces directly regulate the differentiation of B10, B17 and Th17 cells.

    Science.gov (United States)

    Pan, Wei; Hao, Wen-Ting; Shen, Yu-Juan; Li, Xiang-Yang; Wang, Yan-Juan; Sun, Fen-Fen; Yin, Jian-Hai; Zhang, Jing; Tang, Ren-Xian; Cao, Jian-Ping; Zheng, Kui-Yang

    2017-07-21

    Excretory-secretory products (ESPs) released by helminths are well-known to regulate T cell responses in the host. However, their direct influence in the differentiation of naïve T cells, and especially B cells, remains largely unknown. This study investigated the effects of Echinococcus granulosus protoscoleces ESPs (EgPSC-ESPs) on the differentiation of IL-10-producing B cells (B10), IL-17A-producing B cells (B17) and Th17 cells. BALB/c mice injected with EgPSC were used to evaluate the in vivo profiles of B10, B17 and Th17 cells. In vitro purified CD19 + B and naïve CD4 + T cells were cultured in the presence of native, heat-inactivated or periodate-treated EgPSC-ESPs, and the differentiation of these cell subsets were compared. In contrast to the control group, infected mice showed higher frequencies of B10, B17 and Th17 cells, and higher levels of IL-10 and IL-17A in the sera. Interestingly, B17 cells were first identified to express CD19 + CD1d high . In vitro, B cells cultured with native ESPs exhibited a higher percentage of B10 cells but lower percentage of B17 and Th17 cells compared to the PBS group. Moreover, the relative expression of IL-10 and IL-17A mRNA were consistent with the altered frequencies. However, ESPs subjected to heat-inactivation or periodate treatment exhibited an inverse effect on the induction of these cell subsets. Our findings indicate that ESPs released by EgPSC can directly regulate the differentiation of B10, B17 and Th17 cells, which appear to be heat-labile and carbohydrate-dependent.

  8. α-Synuclein fibril-induced paradoxical structural and functional defects in hippocampal neurons.

    Science.gov (United States)

    Froula, Jessica M; Henderson, Benjamin W; Gonzalez, Jose Carlos; Vaden, Jada H; Mclean, John W; Wu, Yumei; Banumurthy, Gokulakrishna; Overstreet-Wadiche, Linda; Herskowitz, Jeremy H; Volpicelli-Daley, Laura A

    2018-05-01

    Neuronal inclusions composed of α-synuclein (α-syn) characterize Parkinson's Disease (PD) and Dementia with Lewy bodies (DLB). Cognitive dysfunction defines DLB, and up to 80% of PD patients develop dementia. α-Syn inclusions are abundant in the hippocampus, yet functional consequences are unclear. To determine if pathologic α-syn causes neuronal defects, we induced endogenous α-syn to form inclusions resembling those found in diseased brains by treating hippocampal neurons with α-syn fibrils. At seven days after adding fibrils, α-syn inclusions are abundant in axons, but there is no cell death at this time point, allowing us to assess for potential alterations in neuronal function that are not caused by neuron death. We found that exposure of neurons to fibrils caused a significant reduction in mushroom spine densities, adding to the growing body of literature showing that altered spine morphology is a major pathologic phenotype in synucleinopathies. The reduction in spine densities occurred only in wild type neurons and not in neurons from α-syn knockout mice, suggesting that the changes in spine morphology result from fibril-induced corruption of endogenously expressed α-syn. Paradoxically, reduced postsynaptic spine density was accompanied by increased frequency of miniature excitatory postsynaptic currents (EPSCs) and presynaptic docked vesicles, suggesting enhanced presynaptic function. Action-potential dependent activity was unchanged, suggesting compensatory mechanisms responding to synaptic defects. Although activity at the level of the synapse was unchanged, neurons exposed to α-syn fibrils, showed reduced frequency and amplitudes of spontaneous Ca 2+ transients. These findings open areas of research to determine the mechanisms that alter neuronal function in brain regions critical for cognition at time points before neuron death.

  9. Early uneven ear input induces long-lasting differences in left-right motor function.

    Science.gov (United States)

    Antoine, Michelle W; Zhu, Xiaoxia; Dieterich, Marianne; Brandt, Thomas; Vijayakumar, Sarath; McKeehan, Nicholas; Arezzo, Joseph C; Zukin, R Suzanne; Borkholder, David A; Jones, Sherri M; Frisina, Robert D; Hébert, Jean M

    2018-03-01

    How asymmetries in motor behavior become established normally or atypically in mammals remains unclear. An established model for motor asymmetry that is conserved across mammals can be obtained by experimentally inducing asymmetric striatal dopamine activity. However, the factors that can cause motor asymmetries in the absence of experimental manipulations to the brain remain unknown. Here, we show that mice with inner ear dysfunction display a robust left or right rotational preference, and this motor preference reflects an atypical asymmetry in cortico-striatal neurotransmission. By unilaterally targeting striatal activity with an antagonist of extracellular signal-regulated kinase (ERK), a downstream integrator of striatal neurotransmitter signaling, we can reverse or exaggerate rotational preference in these mice. By surgically biasing vestibular failure to one ear, we can dictate the direction of motor preference, illustrating the influence of uneven vestibular failure in establishing the outward asymmetries in motor preference. The inner ear-induced striatal asymmetries identified here intersect with non-ear-induced asymmetries previously linked to lateralized motor behavior across species and suggest that aspects of left-right brain function in mammals can be ontogenetically influenced by inner ear input. Consistent with inner ear input contributing to motor asymmetry, we also show that, in humans with normal ear function, the motor-dominant hemisphere, measured as handedness, is ipsilateral to the ear with weaker vestibular input.

  10. Surgical treatment reduces blood pressure in children with unilateral congenital hydronephrosis.

    Science.gov (United States)

    Al-Mashhadi, Ammar; Nevéus, Tryggve; Stenberg, Arne; Karanikas, Birgitta; Persson, A Erik G; Carlström, Mattias; Wåhlin, Nils

    2015-04-01

    Renal disorders can cause hypertension, but less is known about the influence of hydronephrosis on blood pressure. Hydronephrosis due to pelvo-ureteric junction obstruction (PUJO) is a fairly common condition (incidence in newborns of 0.5-1%). Although hypertensive effects of hydronephrosis have been suggested, this has not been substantiated by prospective studies in humans [1-3]. Experimental studies with PUJO have shown that animals with induced hydronephrosis develop salt-sensitive hypertension, which strongly correlate to the degree of obstruction [4-7]. Moreover, relief of the obstruction normalized blood pressure [8]. In this first prospective study our aim was to study the blood pressure pattern in pediatric patients with hydronephrosis before and after surgical correction of the ureteral obstruction. Specifically, we investigated if preoperative blood pressure is reduced after surgery and if split renal function and renographic excretion curves provide any prognostic information. Twelve patients with unilateral congenital hydronephrosis were included in this prospective study. Ambulatory blood pressure (24 h) was measured preoperatively and six months after surgery. Preoperative evaluations of bilateral renal function by Tc99m-MAG3 scintigraphy, and renography curves, classified according to O'Reilly, were also performed. As shown in the summary figure, postoperative systolic (103 ± 2 mmHg) and diastolic (62 ± 2 mmHg) blood pressure were significantly lower than those obtained preoperatively (110 ± 4 and 69 ± 2 mmHg, respectively), whereas no changes in circadian variation or pulse pressure were observed. Renal functional share of the hydronephrotic kidney ranged from 11 to 55%. There was no correlation between the degree of renal function impairment and the preoperative excretory pattern, or between the preoperative excretory pattern and the blood pressure reduction postoperatively. However, preoperative MAG3 function of the affected kidney correlated

  11. Reprogrammed Functional Brown Adipocytes Ameliorate Insulin Resistance and Dyslipidemia in Diet-Induced Obesity and Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Tsunao Kishida

    2015-10-01

    Full Text Available Brown adipocytes (BAs play important roles in body temperature regulation, energy balance, and carbohydrate and lipid metabolism. Activities of BAs are remarkably diminished in obese and diabetic patients, providing possibilities of transplanting functional BAs resulting in therapeutic benefit. Here, we show generation of functional BAs by cellular reprogramming procedures. Transduction of the PRDM16 gene into iPSC-derived embryoid bodies induced BA phenotypes (iBAs. Moreover, normal human fibroblasts were directly converted into BAs (dBAs by C/EBP-β and C-MYC gene transduction. Approximately 90% of the fibroblasts were successfully converted within 12 days. The dBAs were highly active in mitochondrial biogenesis and oxidative metabolism. Mouse dBAs were induced by Prdm16, C/ebp-β, and L-myc genes, and after transplantation, they significantly reduced diet-induced obesity and insulin resistance in an UCP1-dependent manner. Thus, highly functional BAs can be generated by cellular reprogramming, suggesting a promising tailor-made cell therapy against metabolic disorders including type 2 diabetes mellitus.

  12. Reprogrammed Functional Brown Adipocytes Ameliorate Insulin Resistance and Dyslipidemia in Diet-Induced Obesity and Type 2 Diabetes.

    Science.gov (United States)

    Kishida, Tsunao; Ejima, Akika; Yamamoto, Kenta; Tanaka, Seiji; Yamamoto, Toshiro; Mazda, Osam

    2015-10-13

    Brown adipocytes (BAs) play important roles in body temperature regulation, energy balance, and carbohydrate and lipid metabolism. Activities of BAs are remarkably diminished in obese and diabetic patients, providing possibilities of transplanting functional BAs resulting in therapeutic benefit. Here, we show generation of functional BAs by cellular reprogramming procedures. Transduction of the PRDM16 gene into iPSC-derived embryoid bodies induced BA phenotypes (iBAs). Moreover, normal human fibroblasts were directly converted into BAs (dBAs) by C/EBP-β and C-MYC gene transduction. Approximately 90% of the fibroblasts were successfully converted within 12 days. The dBAs were highly active in mitochondrial biogenesis and oxidative metabolism. Mouse dBAs were induced by Prdm16, C/ebp-β, and L-myc genes, and after transplantation, they significantly reduced diet-induced obesity and insulin resistance in an UCP1-dependent manner. Thus, highly functional BAs can be generated by cellular reprogramming, suggesting a promising tailor-made cell therapy against metabolic disorders including type 2 diabetes mellitus. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Dopamine D(3) receptors contribute to methamphetamine-induced alterations in dopaminergic neuronal function: role of hyperthermia.

    Science.gov (United States)

    Baladi, Michelle G; Newman, Amy H; Nielsen, Shannon M; Hanson, Glen R; Fleckenstein, Annette E

    2014-06-05

    Methamphetamine administration causes long-term deficits to dopaminergic systems that, in humans, are thought to be associated with motor slowing and memory impairment. Methamphetamine interacts with the dopamine transporter (DAT) and increases extracellular concentrations of dopamine that, in turn, binds to a number of dopamine receptor subtypes. Although the relative contribution of each receptor subtype to the effects of methamphetamine is not fully known, non-selective dopamine D2/D3 receptor antagonists can attenuate methamphetamine-induced changes to dopamine systems. The present study extended these findings by testing the role of the dopamine D3 receptor subtype in mediating the long-term dopaminergic, and for comparison serotonergic, deficits caused by methamphetamine. Results indicate that the dopamine D3 receptor selective antagonist, PG01037, attenuated methamphetamine-induced decreases in striatal DAT, but not hippocampal serotonin (5HT) transporter (SERT), function, as assessed 7 days after treatment. However, PG01037 also attenuated methamphetamine-induced hyperthermia. When methamphetamine-induced hyperthermia was maintained by treating rats in a warm ambient environment, PG01037 failed to attenuate the effects of methamphetamine on DAT uptake. Furthermore, PG01037 did not attenuate methamphetamine-induced decreases in dopamine and 5HT content. Taken together, the present study demonstrates that dopamine D3 receptors mediate, in part, the long-term deficits in DAT function caused by methamphetamine, and that this effect likely involves an attenuation of methamphetamine-induced hyperthermia. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Dopamine D3 receptors contribute to methamphetamine-induced alterations in dopaminergic neuronal function: Role of hyperthermia

    Science.gov (United States)

    Baladi, Michelle G.; Newman, Amy H.; Nielsen, Shannon M.; Hanson, Glen R.; Fleckenstein, Annette E.

    2014-01-01

    Methamphetamine administration causes long-term deficits to dopaminergic systems that, in humans, are thought to be associated with motor slowing and memory impairment. Methamphetamine interacts with the dopamine transporter (DAT) and increases extracellular concentrations of dopamine that, in turn, binds to a number of dopamine receptor subtypes. Although the relative contribution of each receptor subtype to the effects of methamphetamine is not fully known, non-selective dopamine D2/D3 receptor antagonists can attenuate methamphetamine-induced changes to dopamine systems. The present study extended these findings by testing the role of the dopamine D3 receptor subtype in mediating the long-term dopaminergic, and for comparison serotonergic, deficits caused by methamphetamine. Results indicate that the dopamine D3 receptor selective antagonist, PG01037, attenuated methamphetamine-induced decreases in striatal DAT, but not hippocampal serotonin (5HT) transporter (SERT), function, as assessed 7 days after treatment. However, PG01037 also attenuated methamphetamine-induced hyperthermia. When methamphetamine-induced hyperthermia was maintained by treating rats in a warm ambient environment, PG01037 failed to attenuate the effects of methamphetamine on DAT uptake. Furthermore, PG01037 did not attenuate methamphetamine-induced decreases in dopamine and 5HT content. Taken together, the present study demonstrates that dopamine D3 receptors mediate, in part, the long-term deficits in DAT function caused by methamphetamine, and that this effect likely involves an attenuation of methamphetamine-induced hyperthermia. PMID:24685638

  15. Music-induced changes in functional cerebral asymmetries.

    Science.gov (United States)

    Hausmann, Markus; Hodgetts, Sophie; Eerola, Tuomas

    2016-04-01

    After decades of research, it remains unclear whether emotion lateralization occurs because one hemisphere is dominant for processing the emotional content of the stimuli, or whether emotional stimuli activate lateralised networks associated with the subjective emotional experience. By using emotion-induction procedures, we investigated the effect of listening to happy and sad music on three well-established lateralization tasks. In a prestudy, Mozart's piano sonata (K. 448) and Beethoven's Moonlight Sonata were rated as the most happy and sad excerpts, respectively. Participants listened to either one emotional excerpt, or sat in silence before completing an emotional chimeric faces task (Experiment 1), visual line bisection task (Experiment 2) and a dichotic listening task (Experiment 3 and 4). Listening to happy music resulted in a reduced right hemispheric bias in facial emotion recognition (Experiment 1) and visuospatial attention (Experiment 2) and increased left hemispheric bias in language lateralization (Experiments 3 and 4). Although Experiments 1-3 revealed an increased positive emotional state after listening to happy music, mediation analyses revealed that the effect on hemispheric asymmetries was not mediated by music-induced emotional changes. The direct effect of music listening on lateralization was investigated in Experiment 4 in which tempo of the happy excerpt was manipulated by controlling for other acoustic features. However, the results of Experiment 4 made it rather unlikely that tempo is the critical cue accounting for the effects. We conclude that listening to music can affect functional cerebral asymmetries in well-established emotional and cognitive laterality tasks, independent of music-induced changes in the emotion state. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Functional polymorphisms of interferon-gamma affect pneumonia-induced sepsis.

    Directory of Open Access Journals (Sweden)

    Ding Wang

    Full Text Available Sepsis is an inflammatory syndrome caused by infection, and both its incidence and mortality are high. Because interferon-gamma (IFN-γ plays an important role in inflammation, this work assessed IFN-γ single nucleotide polymorphism (SNPs that may be associated with sepsis.A total of 196 patients with pneumonia-induced sepsis and 213 age- and sex-matched healthy volunteers participated in our study from July 2012 to July 2013 in Guangzhou, China. Patient clinical information was collected. Clinical pathology was assessed in subgroups defined based on clinical criteria, APACHE II (acute physiology and chronic health evaluation and SOFA (sepsis-related organ failure assessment scores and discharge rate. Four functional SNPs, -1616T/C (rs2069705, -764G/C (rs2069707, +874A/T (rs2430561 and +3234C/T (rs2069718, were genotyped by Snapshot in both sepsis patients and healthy controls. Pearson's chi-square test or Fisher's exact test were used to analyze the distribution of the SNPs, and the probability values (P values, odds ratios (OR and 95% confidence intervals (CIs were calculated.No mutations in the IFN-γ -764G/C SNP were detected among the participants in our study. The +874A/T and +3234C/T SNPs were in strong linkage disequilibrium (LD (r(2 = 0.894. The -1616 TC+TT, +874 AT+AA genotype and the TAC haplotype were significantly associated with sepsis susceptibility, while the CTT haplotype was associated with protection against sepsis incidence. Genotype of -1616 TT wasn't only protective against severity of sepsis, but also against higher APACHE II and SOFA scores as +874 AA and +3234 CC. The TAC haplotype was was protective against progression to severe sepsis either.Our results suggest that functional IFN-γ SNPs and their haplotypes are associated with pneumonia-induced sepsis.

  17. Platelet-derived growth factor (PDGF)-signaling mediates radiation-induced apoptosis in human prostate cancer cells with loss of p53 function

    International Nuclear Information System (INIS)

    Kim, Harold E.; Han, Sue J.; Kasza, Thomas; Han, Richard; Choi, Hyeong-Seon; Palmer, Kenneth C.; Kim, Hyeong-Reh C.

    1997-01-01

    Platelet-derived growth factor (PDGF) signals a diversity of cellular responses in vitro, including cell proliferation, survival, transformation, and chemotaxis. PDGF functions as a 'competence factor' to induce a set of early response genes expressed in G 1 including p21 WAF1/CIP1 , a functional mediator of the tumor suppressor gene p53 in G 1 /S checkpoint. For PDGF-stimulated cells to progress beyond G 1 and transit the cell cycle completely, progression factors in serum such as insulin and IGF-1 are required. We have recently shown a novel role of PDGF in inducing apoptosis in growth-arrested murine fibroblasts. The PDGF-induced apoptosis is rescued by insulin, suggesting that G 1 /S checkpoint is a critical determinant for PDGF-induced apoptosis. Because recent studies suggest that radiation-induced signal transduction pathways interact with growth factor-mediated signaling pathways, we have investigated whether activation of the PDGF-signaling facilitates the radiation-induced apoptosis in the absence of functional p53. For this study we have used the 125-IL cell line, a mutant p53-containing, highly metastatic, and hormone-unresponsive human prostate carcinoma cell line. PDGF signaling is constitutively activated by transfection with a p28 v-sis expression vector, which was previously shown to activate PDGF α- and β- receptors. Although the basal level of p21 WAF1/CIP1 expression and radiation-induced apoptosis were not detectable in control 125-IL cells as would be predicted in mutant p53-containing cells, activation of PDGF-signaling induced expression of p21 WAF1/CIP1 and radiation-induced apoptosis. Our study suggests that the level of 'competence' growth factors including PDGF may be one of the critical determinants for radiation-induced apoptosis, especially in cells with loss of p53 function at the site of radiotherapy in vivo

  18. Functional response of cerebral blood flow induced by somatosensory stimulation in rats with subarachnoid hemorrhage

    Science.gov (United States)

    Li, Zhiguo; Huang, Qin; Liu, Peng; Li, Pengcheng; Ma, Lianting; Lu, Jinling

    2015-09-01

    Subarachnoid hemorrhage (SAH) is often accompanied by cerebral vasospasm (CVS), which is the phenomenon of narrowing of large cerebral arteries, and then can produce delayed ischemic neurological deficit (DIND) such as lateralized sensory dysfunction. CVS was regarded as a major contributor to DIND in patients with SAH. However, therapy for preventing vasospasm after SAH to improve the outcomes may not work all the time. It is important to find answers to the relationship between CVS and DIND after SAH. How local cerebral blood flow (CBF) is regulated during functional activation after SAH still remains poorly understood, whereas, the regulation of CBF may play an important role in weakening the impact of CVS on cortex function. Therefore, it is worthwhile to evaluate the functional response of CBF in the activated cortex in an SAH animal model. Most evaluation of the effect of SAH is presently carried out by neurological behavioral scales. The functional imaging of cortical activation during sensory stimulation may help to reflect the function of the somatosensory cortex more locally than the behavioral scales do. We investigated the functional response of CBF in the somatosensory cortex induced by an electrical stimulation to contralateral forepaw via laser speckle imaging in a rat SAH model. Nineteen Sprague-Dawley rats from two groups (control group, n=10 and SAH group, n=9) were studied. SAH was induced in rats by double injection of autologous blood into the cisterna magna after CSF aspiration. The same surgical procedure was applied in the control group without CSF aspiration or blood injection. Significant CVS was found in the SAH group. Meanwhile, we observed a delayed peak of CBF response in rats with SAH compared with those in the control group, whereas no significant difference was found in magnitude, duration, and areas under curve of relative CBF changes between the two groups. The results suggest that the regulation function of local CBF during

  19. High fat diet-induced glucose intolerance impairs myocardial function, but not myocardial perfusion during hyperaemia: a pilot study

    Directory of Open Access Journals (Sweden)

    van den Brom Charissa E

    2012-06-01

    Full Text Available Abstract Background Glucose intolerance is a major health problem and is associated with increased risk of progression to type 2 diabetes mellitus and cardiovascular disease. However, whether glucose intolerance is related to impaired myocardial perfusion is not known. The purpose of the present study was to study the effect of diet-induced glucose intolerance on myocardial function and perfusion during baseline and pharmacological induced hyperaemia. Methods Male Wistar rats were randomly exposed to a high fat diet (HFD or control diet (CD (n = 8 per group. After 4 weeks, rats underwent an oral glucose tolerance test. Subsequently, rats underwent (contrast echocardiography to determine myocardial function and perfusion during baseline and dipyridamole-induced hyperaemia (20 mg/kg for 10 min. Results Four weeks of HFD feeding resulted in glucose intolerance compared to CD-feeding. Contractile function as represented by fractional shortening was not altered in HFD-fed rats compared to CD-fed rats under baseline conditions. However, dipyridamole increased fractional shortening in CD-fed rats, but not in HFD-fed rats. Basal myocardial perfusion, as measured by estimate of perfusion, was similar in CD- and HFD-fed rats, whereas dipyridamole increased estimate of perfusion in CD-fed rats, but not in HFD-fed rats. However, flow reserve was not different between CD- and HFD-fed rats. Conclusions Diet-induced glucose intolerance is associated with impaired myocardial function during conditions of hyperaemia, but myocardial perfusion is maintained. These findings may result in new insights into the effect of glucose intolerance on myocardial function and perfusion during hyperaemia.

  20. Cognitive functions in methamphetamine induced psychosis compared to schizophrenia and normal subjects.

    Directory of Open Access Journals (Sweden)

    Zahra Ezzatpanah

    2014-09-01

    Full Text Available The purpose of this research was to study the cognitive functions in patients with methamphetamine-induced psychosis (MIP in comparison with schizophrenia patients and normal subjects.This was a cross-sectional study, 30 patients with MIP, 30 patients with schizophrenia and 30 normal individuals were selected via convenient sampling and were matched on age, sex and education. Wisconsin Cards Sorting, Stroop, Visual Search and Attention and Wechsler Memory Tests were used to assess the subjects.The study showed that patients with MIP and schizophrenia have more deficits in executive functions, selective attention, sustained attention and memory than normal subjects. There were no significant differences in cognitive functions between patients with MIP and schizophrenia except for visual search and attention that showed more impairment in patients with schizophrenia.Although, cognitive dysfunctions of patients with MIP are mostly similar to patients with schizophrenia, some differences seem to exist, especially in those functions that are not primarily dependent on frontal lobe.

  1. Integral excitation functions for proton and alpha induced reactions on target elements 22 <= Z <= 28

    International Nuclear Information System (INIS)

    Brinkmann, G.

    1979-01-01

    In the framework of a systematic study which is also important for certain cosmological questions a series of integral excitation functions of p- and α-induced nuclear reactions on target elements 22 [de

  2. Excitation functions for some Ne induced reactions with Holmium: incomplete fusion vs complete fusion

    International Nuclear Information System (INIS)

    Agarwal, Avinash; Kumar, Munish; Sharma, Anjali; Rizvi, I.A.; Ahamad, Tauseef; Ghugre, S.S.; Sinha, A.K.; Chaubey, A.K.

    2010-01-01

    Reactions induced by 20 Ne are expected to be considerably more complex than those of 12 C, and 16 O. As a part of the ongoing program to understand CF and ICF reaction mechanisms, it is of great interest to see whether the same experimental technique yield similarly valuable information for 20 Ne induced reactions. In this present work an attempt has been made to measure the excitation functions for fifteen evaporation residues (ERs) identified in the interaction of 20 Ne + 165 Ho system in the energy range 4 -7 MeV/A

  3. Sequential Tc-99m gluconate scintigraphy following renal transplantation: clinical study in twenty-five cases

    International Nuclear Information System (INIS)

    Lucsko, M.; Akerman, M.; Tovar, G. de; Aubert, P.; Chaignon, M.; Le Duc, A.; Guedon, J.; Beaufils, H.

    1981-01-01

    The value of sequential Tc-99m gluconate scintigraphy investigations following renal transplantation is illustrated with reference to 25 cases. Scintigraphy images are recorded on instantaneous photographic paper and radiological film (early vascular images, early and late static images). Results in various clinical situations are analysed: functioning renal transplants, acute postoperative tubulopathy, reversible acute reject hyperacute reject, chronic reject, lower pole arterial thrombosis, renal artery stenosis, ruptured excretory pathway. Isotopic exploration of this type is simple to conduct, and can be repeated without provoking excessive irradiation of the organism. Comparative analysis of several scintigraphic recordings from the same patient is of diagnostic value in cases of acute rejection, renal artery thrombosis, and ruptured excretory pathways. Renal artery stenosis is poorly demonstrated by this type of investigation [fr

  4. Thymoquinone supplementation ameliorates lead-induced testis function impairment in adult rats.

    Science.gov (United States)

    Mabrouk, Aymen; Ben Cheikh, Hassen

    2016-06-01

    This study was realized to investigate the possible beneficial effect of thymoquinone (TQ), the major active component of volatile oil of Nigella sativa seeds, against lead (Pb)-induced inhibition of rat testicular functions. Adult rats were randomized into four groups: a control group receiving no treatment; a Pb group exposed to 2000 parts per million (ppm) of Pb acetate in drinking water; a Pb-TQ group co-treated with Pb (as in Pb group) plus TQ (5 mg/kg body weight (b.w.)/day, per orally (p.o.)); and a TQ group receiving TQ (5 mg/kg b.w./day, p.o.). All treatments were for 5 weeks. No significant differences were observed for the body weight gain or for relative testes weight among the four groups of animals. Testicular Pb content significantly increased in metal-intoxicated rats compared with that in control rats. TQ supplementation had no effect on this testicular Pb accumulation. Interestingly, when coadministrated with Pb, TQ significantly improved the low plasma testosterone level and the decreased epididymal sperm count caused by Pb. In conclusion, the results suggest, for the first time, that TQ protects against Pb-induced impairment of testicular steroidogenic and spermatogenic functions. This study will open new perspectives for the clinical use of TQ in Pb intoxication. © The Author(s) 2014.

  5. Diagnostic efficacy of monoclonal antibody based sandwich enzyme linked immunosorbent assay (ELISA for detection of Fasciola gigantica excretory/secretory antigens in both serum and stool

    Directory of Open Access Journals (Sweden)

    Zoheiry Mona K

    2011-09-01

    Full Text Available Abstract Background This research was carried out to develop a reliable monoclonal antibody (MoAb-based sandwich enzyme linked immunosorbent assay (ELISA for the diagnosis of active Fasciola gigantica infection in both serum and stool for comparative purposes. Methods From a panel of MoAbs raised against F. gigantica excretory/secretory antigens (ES Ags, a pair (12B/11D/3F and 10A/9D/10G was chosen due to its high reactivity and strict specificity to F. gigantica antigen by indirect ELISA. Results The two MoAbs were of the IgG1 and IgG2a subclasses, respectively. Using SDS-PAGE and EITB, the selected MoAbs recognized 83, 64, 45 and 26 kDa bands of ES Ags. The lower detection limit of ELISA assay was 3 ng/ml. In stool, the sensitivity, specificity and diagnostic efficacy of ELISA was 96%, 98.2 and 97.1%; while in serum they were 94%, 94.6% and 94.3%, respectively. Moreover, a positive correlation was found between ova count in stool of F. gigantica infected patients and the OD readings of ELISA in both stool and serum samples (r = 0.730, p Conclusions These data showed that the use of MoAb-based sandwich ELISA for the detection of F. gigantica coproantigens in stool specimens was superior to serum samples; it provides a highly efficient, non-invasive technique for the diagnosis of active F. gigantica infection.

  6. Distinct Shifts in Microbiota Composition during Drosophila Aging Impair Intestinal Function and Drive Mortality

    Directory of Open Access Journals (Sweden)

    Rebecca I. Clark

    2015-09-01

    Full Text Available Alterations in the composition of the intestinal microbiota have been correlated with aging and measures of frailty in the elderly. However, the relationships between microbial dynamics, age-related changes in intestinal physiology, and organismal health remain poorly understood. Here, we show that dysbiosis of the intestinal microbiota, characterized by an expansion of the Gammaproteobacteria, is tightly linked to age-onset intestinal barrier dysfunction in Drosophila. Indeed, alterations in the microbiota precede and predict the onset of intestinal barrier dysfunction in aged flies. Changes in microbial composition occurring prior to intestinal barrier dysfunction contribute to changes in excretory function and immune gene activation in the aging intestine. In addition, we show that a distinct shift in microbiota composition follows intestinal barrier dysfunction, leading to systemic immune activation and organismal death. Our results indicate that alterations in microbiota dynamics could contribute to and also predict varying rates of health decline during aging in mammals.

  7. Fluoride-induced modulation of ionic transport in asymmetric nanopores functionalized with "caged" fluorescein moieties.

    Science.gov (United States)

    Ali, Mubarak; Ahmed, Ishtiaq; Ramirez, Patricio; Nasir, Saima; Cervera, Javier; Niemeyer, Christof M; Ensinger, Wolfgang

    2016-04-28

    We demonstrate experimentally and theoretically a nanofluidic fluoride sensing device based on a single conical pore functionalized with "caged" fluorescein moieties. The nanopore functionalization is based on an amine-terminated fluorescein whose phenolic hydroxyl groups are protected with tert-butyldiphenylsilyl (TBDPS) moieties. The protected fluorescein (Fcn-TBDPS-NH2) molecules are then immobilized on the nanopore surface via carbodiimide coupling chemistry. Exposure to fluoride ions removes the uncharged TBDPS moieties due to the fluoride-promoted cleavage of the silicon-oxygen bond, leading to the generation of negatively charged groups on the fluorescein moieties immobilized onto the pore surface. The asymmetrical distribution of these groups along the conical nanopore leads to the electrical rectification observed in the current-voltage (I-V) curve. On the contrary, other halides and anions are not able to induce any significant ionic rectification in the asymmetric pore. In each case, the success of the chemical functionalization and deprotection reactions is monitored through the changes observed in the I-V curves before and after the specified reaction step. The theoretical results based on the Nernst-Planck and Poisson equations further demonstrate the validity of an experimental approach to fluoride-induced modulation of nanopore current rectification behaviour.

  8. Urinary stone detection and characterisation with dual-energy CT urography after furosemide intravenous injection: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Botsikas, Diomidis; Hansen, Catrina; Stefanelli, Salvatore; Becker, Christoph D.; Montet, Xavier [Geneva University Hospital, Radiology Department, Geneva (Switzerland)

    2014-03-15

    To investigate the added advantage of IV furosemide injection and the subsequent urine dilution in the detection of urinary calculi in the excretory phase of dual-source dual-energy (DE) computed tomography (CT) urography, and to investigate the feasibility of characterising the calculi through diluted urine. Twenty-three urinary calculi were detected in 116 patients who underwent DECT urography for macroscopic haematuria with a split bolus two- or three-acquisition protocol, including a true unenhanced series and at least a mixed nephrographic excretory phase. Virtual unenhanced images were reconstructed from contrast-enhanced DE data. Calculi were recorded on all series and characterised based on their X-ray absorption characteristics at 100 kVp and 140 kVp in both true unenhanced and nephrographic excretory phase series. All calculi with a diameter more than 2 mm were detected in the virtual unenhanced phase and in the nephrographic excretory phase. Thirteen of these calculi could be characterised in the true unenhanced phase and in the mixed nephrographic excretory phase. The results were strictly identical for both phases, six of them being recognised as non-uric acid calculi and seven as uric acid calculi. Mixed nephrographic excretory phase DECT after furosemide administration allows both detection and characterisation of clinically significant calculi, through the diluted urine. (orig.)

  9. Postural Effect on Renal Function In Cases of Pregnancy-Induced Hypertension

    OpenAIRE

    丸山, 晋司; Maruyama, Shinji

    1989-01-01

    Postual effect on renal function was analysed on the cases of pregnancy-induced hypertension (PIH) (n=11) compared with cases of normotensive pregnancies (n=12) and non-pregnant women (n=9). In non-pregnant women, GFR, RBF and RPF showed no changes in relation to the changing posture (supine and left lateral). In normal pregnant women and cases of PIH, GFR, RBF and RPF significantly increased on changing their posture from supine to left lateral at third trimester. Especially, patients with P...

  10. Thrombospondin-4 knockout in hypertension protects small-artery endothelial function but induces aortic aneurysms

    NARCIS (Netherlands)

    Palao, Teresa; Rippe, Catarina; van Veen, Henk; VanBavel, Ed; Swärd, Karl; Bakker, Erik N. T. P.

    2016-01-01

    Thrombospondin-4 (TSP-4) is a multidomain calcium-binding protein that has both intracellular and extracellular functions. As an extracellular matrix protein, it is involved in remodeling processes. Previous work showed that, in the cardiovascular system, TSP-4 expression is induced in the heart in

  11. Inhomogeneity induced and appropriately parameterized semilocal exchange and correlation energy functionals in two-dimensions

    Science.gov (United States)

    Patra, Abhilash; Jana, Subrata; Samal, Prasanjit

    2018-04-01

    The construction of meta generalized gradient approximations based on the density matrix expansion (DME) is considered as one of the most accurate techniques to design semilocal exchange energy functionals in two-dimensional density functional formalism. The exchange holes modeled using DME possess unique features that make it a superior entity. Parameterized semilocal exchange energy functionals based on the DME are proposed. The use of different forms of the momentum and flexible parameters is to subsume the non-uniform effects of the density in the newly constructed semilocal functionals. In addition to the exchange functionals, a suitable correlation functional is also constructed by working upon the local correlation functional developed for 2D homogeneous electron gas. The non-local effects are induced into the correlation functional by a parametric form of one of the newly constructed exchange energy functionals. The proposed functionals are applied to the parabolic quantum dots with a varying number of confined electrons and the confinement strength. The results obtained with the aforementioned functionals are quite satisfactory, which indicates why these are suitable for two-dimensional quantum systems.

  12. The metabolic enhancer piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by beta-amyloid peptide.

    Science.gov (United States)

    Kurz, C; Ungerer, I; Lipka, U; Kirr, S; Schütt, T; Eckert, A; Leuner, K; Müller, W E

    2010-05-01

    beta-Amyloid peptide (Abeta) is implicated in the pathogenesis of Alzheimer's disease by initiating a cascade of events from mitochondrial dysfunction to neuronal death. The metabolic enhancer piracetam has been shown to improve mitochondrial dysfunction following brain aging and experimentally induced oxidative stress. We used cell lines (PC12 and HEK cells) and murine dissociated brain cells. The protective effects of piracetam in vitro and ex vivo on Abeta-induced impairment of mitochondrial function (as mitochondrial membrane potential and ATP production), on secretion of soluble Abeta and on neurite outgrowth in PC12 cells were investigated. Piracetam improves mitochondrial function of PC12 cells and acutely dissociated brain cells from young NMRI mice following exposure to extracellular Abeta(1-42). Similar protective effects against Abeta(1-42) were observed in dissociated brain cells from aged NMRI mice, or mice transgenic for mutant human amyloid precursor protein (APP) treated with piracetam for 14 days. Soluble Abeta load was markedly diminished in the brain of those animals after treatment with piracetam. Abeta production by HEK cells stably transfected with mutant human APP was elevated by oxidative stress and this was reduced by piracetam. Impairment of neuritogenesis is an important consequence of Abeta-induced mitochondrial dysfunction and Abeta-induced reduction of neurite growth in PC12 cells was substantially improved by piracetam. Our findings strongly support the concept of improving mitochondrial function as an approach to ameliorate the detrimental effects of Abeta on brain function.

  13. Functional and structural changes in internal pudendal arteries underlie erectile dysfunction induced by androgen deprivation

    Directory of Open Access Journals (Sweden)

    Rhéure Alves-Lopes

    2017-01-01

    Full Text Available Androgen deficiency is strongly associated with erectile dysfunction (ED. Inadequate penile arterial blood flow is one of the major causes of ED. The blood flow to the corpus cavernosum is mainly derived from the internal pudendal arteries (IPAs; however, no study has evaluated the effects of androgen deprivation on IPA′s function. We hypothesized that castration impairs IPAs reactivity and structure, contributing to ED. In our study, Wistar male rats, 8-week-old, were castrated and studied 30 days after orchiectomy. Functional and structural properties of rat IPAs were determined using wire and pressure myograph systems, respectively. Protein expression was determined by Western blot and immunohistochemistry. Plasma testosterone levels were determined using the IMMULITE 1000 Immunoassay System. Castrated rats exhibited impaired erectile function, represented by decreased intracavernosal pressure/mean arterial pressure ratio. IPAs from castrated rats exhibited decreased phenylephrine- and electrical field stimulation (EFS-induced contraction and decreased acetylcholine- and EFS-induced vasodilatation. IPAs from castrated rats exhibited decreased internal diameter, external diameter, thickness of the arterial wall, and cross-sectional area. Castration decreased nNOS and α-actin expression and increased collagen expression, p38 (Thr180/Tyr182 phosphorylation, as well as caspase 3 cleavage. In conclusion, androgen deficiency is associated with impairment of IPA reactivity and structure and increased apoptosis signaling markers. Our findings suggest that androgen deficiency-induced vascular dysfunction is an event involving hypotrophic vascular remodeling of IPAs.

  14. Functional MRI neurofeedback training on connectivity between two regions induces long-lasting changes in intrinsic functional network

    Directory of Open Access Journals (Sweden)

    Fukuda eMegumi

    2015-03-01

    Full Text Available Motor or perceptual learning is known to influence functional connectivity between brain regions and induce short-term changes in the intrinsic functional networks revealed as correlations in slow blood-oxygen-level dependent (BOLD signal fluctuations. However, no cause-and-effect relationship has been elucidated between a specific change in connectivity and a long-term change in global networks. Here, we examine the hypothesis that functional connectivity (i.e. temporal correlation between two regions is increased and preserved for a long time when two regions are simultaneously activated or deactivated. Using the connectivity-neurofeedback training paradigm, subjects successfully learned to increase the correlation of activity between the lateral parietal and primary motor areas, regions that belong to different intrinsic networks and negatively correlated before training under the resting conditions. Furthermore, whole-brain hypothesis-free analysis as well as functional network analyses demonstrated that the correlation in the resting state between these areas as well as the correlation between the intrinsic networks that include the areas increased for at least two months. These findings indicate that the connectivity-neurofeedback training can cause long-term changes in intrinsic connectivity and that intrinsic networks can be shaped by experience-driven modulation of regional correlation.

  15. Diabetes-induced hyperglycemia impairs male reproductive function: a systematic review.

    Science.gov (United States)

    Maresch, Constanze C; Stute, Dina C; Alves, Marco G; Oliveira, Pedro F; de Kretser, David M; Linn, Thomas

    2018-01-01

    Hyperglycemia can result from a loss of pancreatic beta-cells or a decline in their function leading to decreased insulin secretion or may arise from insulin resistance and variable degrees of inadequate insulin secretion resulting in diabetes and related comorbidities. To date several reviews have addressed the issue of diabetes-related male infertility but most have focused on how metabolic syndrome causes the decline in male fertility. However, a comprehensive overview as to how diabetes-induced hyperglycemia impairs male fertility is missing. Impaired regulation of glucose and the resultant hyperglycemia are major threats to the health of individuals in modern societies especially given the rapidly rising prevalence affecting an increasing number of men in their reproductive years. Consequently, diabetes-induced hyperglycemia is likely to contribute to a decline in global birth rates especially in those societies with a high diabetic prevalence. This systematic review addresses and summarizes the impact of hyperglycemia on male reproductive health with a particular emphasis on the molecular mechanisms that influence the testis and other parts of the male reproductive tract. A systematic search of the literature published in the MEDLINE-Pubmed database (http://www.ncbi.nlm.nih.gov/pubmed) and Cochrane Library (http://www.cochranelibrary.com) was performed, as well as hand searching reference lists, from the earliest available online indexing year until May 2017, using diabetes- and male fertility-related keywords in combination with other search phrases relevant to the topic of hyperglycemia. Inclusion criteria were: clinical studies on type 1 diabetic (T1D) men and studies on T1D animal models with a focus on reproductive parameters. Case reports/series, observational studies and clinical trials were included. Studies on patients with type 2 diabetes (T2D) or animal models of T2D were excluded to distinguish hyperglycemia from other metabolic effects. A total

  16. Predictive value of excretory urography, ultrasonography, computerized tomography, and liver and bone scan in the staging of bilharzial bladder cancer in Saudi Arabia

    International Nuclear Information System (INIS)

    Hanash, K.A.; Bissada, N.K.; Abla, A.; Esmail, D.; Dowling, A.

    1984-01-01

    The role of ultrasonography, computed tomography (CT), and radioisotopic scanning in the staging of bilharzial bladder cancer has not been reported previously. Forty patients with invasive bladder cancer seen at the King Faisal Specialist Hospital and Research Centre between January 1978 and June 1981 underwent complete preoperative workup for staging of their tumors prior to radical cystectomy. The preoperative radiologic investigations included excretory urography (IVP), ultrasonography (US), CT of the pelvis, and liver and bone scans. The results of these investigations were compared with the operative and pathologic staging. Ninety-three percent of the patients with bilharzial cancer had evidence of ureteric obstruction on IVP compared with 22% of the nonbilharzial cancer patients. The presence of ureteric obstruction in these patients did not correlate with the stage of the disease with 83% of the patients with superficial tumors (T1 and T2) having hydroureteronephrosis. Ultrasonography and CT had an 83% accuracy in the staging of superficial tumors. Stage T3 tumors were understaged in 14% of the cases. Ultrasonography did not differentiate Stages T3 and T4 tumors while CT scan differentiated these two stages in 57% of the cases. Bone scan failed to reveal evidence of metastatic disease in any of the bilharzial cancer patients. Liver scan was suspicious for liver metastases in two patients with bilharzial cancers in whom open liver biopsy revealed only hepatic bilharziasis. Of all the radiographic studies, US or preferably CT scan seem to be of some value in the staging of bilharzial tumors localized to the bladder. Bone and liver scans are probably of no cost effective benefit

  17. Role of epithelial-mesenchymal transition (EMT) and fibroblast function in cerium oxide nanoparticles-induced lung fibrosis

    International Nuclear Information System (INIS)

    Ma, Jane; Bishoff, Bridget; Mercer, R.R.; Barger, Mark; Schwegler-Berry, Diane; Castranova, Vincent

    2017-01-01

    The emission of cerium oxide nanoparticles (CeO 2 ) from diesel engines, using cerium compounds as a catalyst to lower the diesel exhaust particles, is a health concern. We have previously shown that CeO 2 induced pulmonary inflammation and lung fibrosis. The objective of the present study was to investigate the modification of fibroblast function and the role of epithelial-mesenchymal transition (EMT) in CeO 2 -induced fibrosis. Male Sprague-Dawley rats were exposed to CeO 2 (0.15 to 7 mg/kg) by a single intratracheal instillation and sacrificed at various times post-exposure. The results show that at 28 days after CeO 2 (3.5 mg/kg) exposure, lung fibrosis was evidenced by increased soluble collagen in bronchoalveolar lavage fluid, elevated hydroxyproline content in lung tissues, and enhanced sirius red staining for collagen in the lung tissue. Lung fibroblasts and alveolar type II (ATII) cells isolated from CeO 2 -exposed rats at 28 days post-exposure demonstrated decreasing proliferation rate when compare to the controls. CeO 2 exposure was cytotoxic and altered cell function as demonstrated by fibroblast apoptosis and aggregation, and ATII cell hypertrophy and hyperplasia with increased surfactant. The presence of stress fibers, expressed as α-smooth muscle actin (SMA), in CeO 2 -exposed fibroblasts and ATII cells was significantly increased compared to the control. Immunohistofluorescence analysis demonstrated co-localization of TGF-β or α-SMA with prosurfactant protein C (SPC)-stained ATII cells. These results demonstrate that CeO 2 exposure affects fibroblast function and induces EMT in ATII cells that play a role in lung fibrosis. These findings suggest potential adverse health effects in response to CeO 2 nanoparticle exposure. - Highlights: • CeO 2 exposure induced lung fibrosis. • CeO 2 were detected in lung tissue, alveolar type II (ATII) cells and fibroblasts. • CeO 2 caused ATII cell hypertrophy and hyperplasia and altered fibroblast function

  18. Role of epithelial-mesenchymal transition (EMT) and fibroblast function in cerium oxide nanoparticles-induced lung fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Jane [Health Effects Laboratory Division, NIOSH, Morgantown, WV (United States); Bishoff, Bridget [Mylan Pharmaceuticals, Morganntown, WV (United States); Mercer, R.R.; Barger, Mark; Schwegler-Berry, Diane [Health Effects Laboratory Division, NIOSH, Morgantown, WV (United States); Castranova, Vincent, E-mail: vcastran@hsc.wvu.edu [School of Pharmacy, West Virginia University, Morgantown, WV (United States)

    2017-05-15

    The emission of cerium oxide nanoparticles (CeO{sub 2}) from diesel engines, using cerium compounds as a catalyst to lower the diesel exhaust particles, is a health concern. We have previously shown that CeO{sub 2} induced pulmonary inflammation and lung fibrosis. The objective of the present study was to investigate the modification of fibroblast function and the role of epithelial-mesenchymal transition (EMT) in CeO{sub 2}-induced fibrosis. Male Sprague-Dawley rats were exposed to CeO{sub 2} (0.15 to 7 mg/kg) by a single intratracheal instillation and sacrificed at various times post-exposure. The results show that at 28 days after CeO{sub 2} (3.5 mg/kg) exposure, lung fibrosis was evidenced by increased soluble collagen in bronchoalveolar lavage fluid, elevated hydroxyproline content in lung tissues, and enhanced sirius red staining for collagen in the lung tissue. Lung fibroblasts and alveolar type II (ATII) cells isolated from CeO{sub 2}-exposed rats at 28 days post-exposure demonstrated decreasing proliferation rate when compare to the controls. CeO{sub 2} exposure was cytotoxic and altered cell function as demonstrated by fibroblast apoptosis and aggregation, and ATII cell hypertrophy and hyperplasia with increased surfactant. The presence of stress fibers, expressed as α-smooth muscle actin (SMA), in CeO{sub 2}-exposed fibroblasts and ATII cells was significantly increased compared to the control. Immunohistofluorescence analysis demonstrated co-localization of TGF-β or α-SMA with prosurfactant protein C (SPC)-stained ATII cells. These results demonstrate that CeO{sub 2} exposure affects fibroblast function and induces EMT in ATII cells that play a role in lung fibrosis. These findings suggest potential adverse health effects in response to CeO{sub 2} nanoparticle exposure. - Highlights: • CeO{sub 2} exposure induced lung fibrosis. • CeO{sub 2} were detected in lung tissue, alveolar type II (ATII) cells and fibroblasts. • CeO{sub 2} caused ATII

  19. DISORDERS OF ACID-BASE STATE

    Directory of Open Access Journals (Sweden)

    P. F. Litvitskiy

    2011-01-01

    Full Text Available The lecture describes modern data on disorders of acid-base state (ABS: their types, etiology, key stages of pathogenesis, main symptoms, and principles of treatment. The first part of the lecture in present journal characterizes main conception, parameters of ABS in normal state, buffer systems, common mechanisms of BS shifts elimination, etiology and pathogenesis of gas-induced (respiratory disorders of ABS. The second part of the lecture in following journal will describe not gas-induced (metabolic, excretory and exogenous disorders of ABS and principles of their treatment.

  20. Serum IgE and IgG4 against muscle larva excretory-secretory products during the early and late phases of human trichinellosis.

    Science.gov (United States)

    Calcagno, Marcela A; Forastiero, María A; Saracino, María P; Vila, Cecilia C; Venturiello, Stella M

    2017-11-01

    In human trichinellosis, the relevance of the presence and persistence of specific serum IgE and IgG4 during the early and late phases of infection is still controversial.The aim of this work was to determine the percentage of human sera presenting IgE and IgG4 against Trichinella spiralis muscle larvae excretory-secretory products as well as their levels during the early and late phases of the infection. The antigen recognition pattern by serum total immunoglobulins (IgGAM), IgE, and IgG4 was assessed over time. Serum samples during early and late phases were analyzed by ELISA and immunoelectrotransfer blot (IETB).Results showed that (a)-IgE and IgG4 are present at constant levels in both phases; (b)-IgE recognized the glycoproteins of ~ 45 and ~ 55 kDa and IgG4 only the ~ 45 kDa; (c)-in the late phase, the percentage of specific IgE positive sera was higher than that of specific IgG4 by IETB; while in serum samples taken during the early phase, no differences were found between both isotypes; (d)-both isotypes displayed different glycoprotein recognition patterns: the pattern corresponding to IgE was coincident with that of IgGAM, comprising seven glycoproteins (ranging from ~ 116 to ~ 29 kDa), whereas IgG4 revealed four glycoproteins (ranging from ~ 97 to ~ 45 kDa), showing a different sera recognition percentage depending on the phase studied.In conclusion, IgE and IgG4 cannot be considered exclusive isotypes of neither the early nor the late phase of infection and they are as useful as the detection of total antibodies in the early diagnosis.

  1. Effects of modified constraint-induced movement therapy on reach-to-grasp movements and functional performance after chronic stroke: a randomized controlled study.

    Science.gov (United States)

    Lin, K-C; Wu, C-Y; Wei, T-H; Lee, C-Y; Liu, J-S

    2007-12-01

    To evaluate changes in (1) motor control characteristics of the hemiparetic hand during the performance of a functional reach-to-grasp task and (2) functional performance of daily activities in patients with stroke treated with modified constraint-induced movement therapy. Two-group randomized controlled trial with pretreatment and posttreatment measures. Rehabilitation clinics. Thirty-two chronic stroke patients (21 men, 11 women; mean age=57.9 years, range=43-81 years) 13-26 months (mean 16.3 months) after onset of a first-ever cerebrovascular accident. Thirty-two patients were randomized to receive modified constraint-induced movement therapy (restraint of the unaffected limb combined with intensive training of the affected limb) or traditional rehabilitation for three weeks. Kinematic analysis was used to assess motor control characteristics as patients reached to grasp a beverage can. Functional outcomes were evaluated using the Motor Activity Log and Functional Independence Measure. There were moderate and significant effects of modified constraint-induced movement therapy on some aspects of motor control of reach-to-grasp and on functional ability. The modified constraint-induced movement therapy group preplanned reaching and grasping (P=0.018) more efficiently and depended more on the feedforward control of reaching (P=0.046) than did the traditional rehabilitation group. The modified constraint-induced movement therapy group also showed significantly improved functional performance on the Motor Activity Log (Pcontrol strategy during goal-directed reaching, a possible mechanism for the improved movement performance of stroke patients undergoing this therapy.

  2. Long distance run induced hydration and kidney function changes in marathoners

    Directory of Open Access Journals (Sweden)

    Luiz Guilherme Cruz Gonçalves

    2015-09-01

    Full Text Available AbstractThe aim of the study was to verify the hydration status and the kidney function in marathoners during the training season and after a marathon race. Nine male runners were investigated during 12 weeks of training. Urine was collected in four moments; in the beginning (C1 and during (C2 the training program, before (C3 and after (C4 the competition. Urine pH was measured using reagent tapes, urine density with a refractometer, protein excretion by Bradford assay and erythrocytes and leucocytes by microscopy. Changes were observed when C-4 was compared to the other collection times for all variables investigated. It is possible to conclude that physical exertion induced important changes in the hydration status and glomerular membrane selectivity to macromolecules, modifying the kidney function of the marathoners in C4.

  3. Sulforaphane Protects against High Cholesterol-Induced Mitochondrial Bioenergetics Impairments, Inflammation, and Oxidative Stress and Preserves Pancreatic β-Cells Function

    Directory of Open Access Journals (Sweden)

    Catalina Carrasco-Pozo

    2017-01-01

    Full Text Available Cholesterol plays an important role in inducing pancreatic β-cell dysfunction, leading to an impaired insulin secretory response to glucose. This study aimed to determine the protective effects of sulforaphane, a natural isothiocyanate Nrf2-inducer, against cholesterol-induced pancreatic β-cells dysfunction, through molecular and cellular mechanisms involving mitochondrial bioenergetics. Sulforaphane prevented cholesterol-induced alterations in the coupling efficiency of mitochondrial respiration, improving ATP turnover and spare capacity, and averted the impairment of the electron flow at complexes I, II, and IV. Sulforaphane also attenuated the cholesterol-induced activation of the NFκB pathway, normalizing the expression of pro- and anti-inflammatory cytokines. In addition, it also inhibited the decrease in sirtuin 1 expression and greatly increased Pgc-1α expression in Min6 cells. Sulforaphane increased the expression of antioxidant enzymes downstream of the Nrf2 pathway and prevented lipid peroxidation induced by cholesterol. The antioxidant and anti-inflammatory properties of sulforaphane and its ability to protect and improve mitochondrial bioenergetic function contribute to its protective action against cholesterol-induced pancreatic β-cell dysfunction. Our data provide a scientifically tested foundation upon which sulforaphane can be developed as nutraceutical to preserve β-cell function and eventually control hyperglycemia.

  4. TVP1022 Protects Neonatal Rat Ventricular Myocytes against Doxorubicin-Induced Functional Derangements

    Science.gov (United States)

    Berdichevski, Alexandra; Meiry, Gideon; Milman, Felix; Reiter, Irena; Sedan, Oshra; Eliyahu, Sivan; Duffy, Heather S.; Youdim, Moussa B.; Binah, Ofer

    2010-01-01

    Our recent studies demonstrated that propargylamine derivatives such as rasagiline (Azilect, Food and Drug Administration-approved anti-Parkinson drug) and its S-isomer TVP1022 protect cardiac and neuronal cell cultures against apoptotic-inducing stimuli. Studies on structure-activity relationship revealed that their neuroprotective effect is associated with the propargylamine moiety, which protects mitochondrial viability and prevents apoptosis by activating Bcl-2 and protein kinase C-ε and by down-regulating the proapoptotic protein Bax. Based on the established cytoprotective and neuroprotective efficacies of propargylamine derivatives, as well as on our recent study showing that TVP1022 attenuates serum starvation-induced and doxorubicin-induced apoptosis in neonatal rat ventricular myocytes (NRVMs), we tested the hypothesis that TVP1022 will also provide protection against doxorubicin-induced NRVM functional derangements. The present study demonstrates that pretreatment of NRVMs with TVP1022 (1 μM, 24 h) prevented doxorubicin (0.5 μM, 24 h)-induced elevation of diastolic [Ca2+]i, the slowing of [Ca2+]i relaxation kinetics, and the decrease in the rates of myocyte contraction and relaxation. Furthermore, pretreatment with TVP1022 attenuated the doxorubicin-induced reduction in the protein expression of sarco/endoplasmic reticulum calcium (Ca2+) ATPase, Na+/Ca2+ exchanger 1, and total connexin 43. Finally, TVP1022 diminished the inhibitory effect of doxorubicin on gap junctional intercellular coupling (measured by means of Lucifer yellow transfer) and on conduction velocity, the amplitude of the activation phase, and the maximal rate of activation (dv/dtmax) measured by the Micro-Electrode-Array system. In summary, our results indicate that TVP1022 acts as a novel cardioprotective agent against anthracycline cardiotoxicity, and therefore potentially can be coadmhence, the inistered with doxorubicin in the treatment of malignancies in humans. PMID:19915070

  5. Semipermeable membrane devices concentrate mixed function oxygenase inducers from oil sands and refinery wastewaters

    International Nuclear Information System (INIS)

    Parrott, J.L.; Hewitt, L.M.

    2002-01-01

    The health of fish in the Athabasca River was examined to determine the effects of both natural and anthropogenic oil sands exposure on liver mixed function oxygenase (MFO) enzymes. Semipermeable membrane devices (SPMD) were used to concentrate bioavailable compounds that may result in MFO induction. The SPMDs were used for a period of 2 weeks in the Steepbank River as well as in oil refinery wastewater and intake ponds. They were then tested to see if they induced ethoxyresorufin-O-deethylase (EROD) activity in hepatoma cells, a cell line derived from a liver cancer of a small fish. SPMDs from the wastewater pond contained potent EROD inducers in fish liver cells. SPMDs from the Athabasca River exhibited some EROD inducers, but they were 1/100 as potent as those of the refinery wastewater. The characteristics of MFO inducers from refinery wastewater were different from natural inducers from the oil sands in the Athabasca and Steepbank Rivers. For instance, log Kow was less than 5 for refinery wastewater, but it was greater than 5 for Athabasca River wastewater and from natural oil sands exposure. In the case of the Steepbank River, the pattern of MFO induction was similar to the MFO induction seen in wild fish.The highest MFO inducers were found to be in the area of the mine, suggesting and anthropogenic pollution source. The less potent inducers were in the area of the natural and undisturbed oil sands. Very few inducers were found outside of the oil sands formation

  6. Memory function approach to the line shape problem in collision-induced light scattering

    International Nuclear Information System (INIS)

    Balucani, U.; Tognetti, V.; Vallauri, R.

    1980-01-01

    This article mainly deals with the problem of the shape of the spectrum due to interacting pairs of atoms at low and moderate densities. A memory function approach is used which permits to obtain in a consistent way the shape of the scattered spectrum. In order to obtain 'exact' time correlation functions and spectral shapes, molecular-dynamics 'experiments' in Lennard-Jones argon at two different densities were also performed. The dipole-induced dipole (DID) polarizabilities have been used to ascertain the validity of the theoretical approach in a well-defined physical model. The theoretical shapes and correlation functions can be then directly compared with computer simulations. Finally, a comparison with the data of real experiments clarifies the relevance of other-than-DID polarizability mechanisms as far as the spectrum is concerned. (KBE)

  7. Induction of UV-resistant DNA replication in Escherichia coli: Induced stable DNA replication as an SOS function

    International Nuclear Information System (INIS)

    Kogoma, T.; Torrey, T.A.; Connaughton, M.J.

    1979-01-01

    The striking similarity between the treatments that induce SOS functions and those that result in stable DNA replication (continuous DNA replication in the absence of protein synthesis) prompted us to examine the possibility of stable DNA replication being a recA + lexA + -dependent SOS function. In addition to the treatments previously reported, ultraviolet (UV) irradiation or treatment with mitomycin C was also found to induce stable DNA replication. The thermal treatment of tif-1 strains did not result in detectable levels of stable DNA replication, but nalidixic acid readily induced the activity in these strains. The induction of stable DNA replication with nalidixic acid was severely suppressed in tif-1 lex A mutant strains. The inhibitory activity of lexA3 was negated by the presence of the spr-5l mutation, an intragenic suppressor of lexA3. Induced stable DNA replication was found to be considerably more resistant to UV irradiation than normal replication both in a uvr A6 strain and a uvr + strain. The UV-resistant replication occurred mostly in the semiconservative manner. The possible roles of stable DNA replication in repair of damaged DNA are discussed. (orig.)

  8. Neuropathic pain-like alterations in muscle nociceptor function associated with vibration-induced muscle pain.

    Science.gov (United States)

    Chen, Xiaojie; Green, Paul G; Levine, Jon D

    2010-11-01

    We recently developed a rodent model of the painful muscle disorders induced by occupational exposure to vibration. In the present study we used this model to evaluate the function of sensory neurons innervating the vibration-exposed gastrocnemius muscle. Activity of 74 vibration-exposed and 40 control nociceptors, with mechanical receptive fields in the gastrocnemius muscle, were recorded. In vibration-exposed rats ∼15% of nociceptors demonstrated an intense and long-lasting barrage of action potentials in response to sustained suprathreshold mechanical stimulation (average of 2635 action potentials with frequency of ∼44Hz during a 1min suprathreshold stimulus) much greater than that has been reported to be produced even by potent inflammatory mediators. While these high-firing nociceptors had lower mechanical thresholds than the remaining nociceptors, exposure to vibration had no effect on conduction velocity and did not induce spontaneous activity. Hyperactivity was not observed in any of 19 neurons from vibration-exposed rats pretreated with intrathecal antisense for the IL-6 receptor subunit gp130. Since vibration can injure peripheral nerves and IL-6 has been implicated in painful peripheral neuropathies, we suggest that the dramatic change in sensory neuron function and development of muscles pain, induced by exposure to vibration, reflects a neuropathic muscle pain syndrome. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  9. Usefulness of zebrafish larvae to evaluate drug-induced functional and morphological renal tubular alterations.

    Science.gov (United States)

    Gorgulho, Rita; Jacinto, Raquel; Lopes, Susana S; Pereira, Sofia A; Tranfield, Erin M; Martins, Gabriel G; Gualda, Emilio J; Derks, Rico J E; Correia, Ana C; Steenvoorden, Evelyne; Pintado, Petra; Mayboroda, Oleg A; Monteiro, Emilia C; Morello, Judit

    2018-01-01

    Prediction and management of drug-induced renal injury (DIRI) rely on the knowledge of the mechanisms of drug insult and on the availability of appropriate animal models to explore it. Zebrafish (Danio rerio) offers unique advantages for assessing DIRI because the larval pronephric kidney has a high homology with its human counterpart and it is fully mature at 3.5 days post-fertilization. Herein, we aimed to evaluate the usefulness of zebrafish larvae as a model of renal tubular toxicity through a comprehensive analysis of the renal alterations induced by the lethal concentrations for 10% of the larvae for gentamicin, paracetamol and tenofovir. We evaluated drug metabolic profile by mass spectrometry, renal function with the inulin clearance assay, the 3D morphology of the proximal convoluted tubule by two-photon microscopy and the ultrastructure of proximal convoluted tubule mitochondria by transmission electron microscopy. Paracetamol was metabolized by conjugation and oxidation with further detoxification with glutathione. Renal clearance was reduced with gentamicin and paracetamol. Proximal tubules were enlarged with paracetamol and tenofovir. All drugs induced mitochondrial alterations including dysmorphic shapes ("donuts", "pancakes" and "rods"), mitochondrial swelling, cristae disruption and/or loss of matrix granules. These results are in agreement with the tubular effects of gentamicin, paracetamol and tenofovir in man and demonstrate that zebrafish larvae might be a good model to assess functional and structural damage associated with DIRI.

  10. Functionalized Surface Geometries Induce: “Bone: Formation by Autoinduction”

    Directory of Open Access Journals (Sweden)

    Ugo Ripamonti

    2018-02-01

    Full Text Available The induction of tissue formation, and the allied disciplines of tissue engineering and regenerative medicine, have flooded the twenty-first century tissue biology scenario and morphed into high expectations of a fulfilling regenerative dream of molecularly generated tissues and organs in assembling human tissue factories. The grand conceptualization of deploying soluble molecular signals, first defined by Turing as forms generating substances, or morphogens, stemmed from classic last century studies that hypothesized the presence of morphogens in several mineralized and non-mineralized mammalian matrices. The realization of morphogens within mammalian matrices devised dissociative extractions and chromatographic procedures to isolate, purify, and finally reconstitute the cloned morphogens, found to be members of the transforming growth factor-β (TGF-β supergene family, with insoluble signals or substrata to induce de novo tissue induction and morphogenesis. Can we however construct macroporous bioreactors per se capable of inducing bone formation even without the exogenous applications of the osteogenic soluble molecular signals of the TGF-β supergene family? This review describes original research on coral-derived calcium phosphate-based macroporous constructs showing that the formation of bone is independent of the exogenous application of the osteogenic soluble signals of the TGF-β supergene family. Such signals are the molecular bases of the induction of bone formation. The aim of this review is to primarily describe today's hottest topic of biomaterials' science, i.e., to construct and define osteogenetic biomaterials' surfaces that per se, in its own right, do initiate the induction of bone formation. Biomaterials are often used to reconstruct osseous defects particularly in the craniofacial skeleton. Edentulism did spring titanium implants as tooth replacement strategies. No were else that titanium surfaces require functionalized

  11. Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy.

    Science.gov (United States)

    Thoonen, Robrecht; Ernande, Laura; Cheng, Juan; Nagasaka, Yasuko; Yao, Vincent; Miranda-Bezerra, Alexandre; Chen, Chan; Chao, Wei; Panagia, Marcello; Sosnovik, David E; Puppala, Dheeraj; Armoundas, Antonis A; Hindle, Allyson; Bloch, Kenneth D; Buys, Emmanuel S; Scherrer-Crosbie, Marielle

    2015-07-01

    Brown adipose tissue (BAT) has well recognized thermogenic properties mediated by uncoupling protein 1 (UCP1); more recently, BAT has been demonstrated to modulate cardiovascular risk factors. To investigate whether BAT also affects myocardial injury and remodeling, UCP1-deficient (UCP1(-/-)) mice, which have dysfunctional BAT, were subjected to catecholamine-induced cardiomyopathy. At baseline, there were no differences in echocardiographic parameters, plasma cardiac troponin I (cTnI) or myocardial fibrosis between wild-type (WT) and UCP1(-/-) mice. Isoproterenol infusion increased cTnI and myocardial fibrosis and induced left ventricular (LV) hypertrophy in both WT and UCP1(-/-) mice. UCP1(-/-) mice also demonstrated exaggerated myocardial injury, fibrosis, and adverse remodeling, as well as decreased survival. Transplantation of WT BAT to UCP1(-/-) mice prevented the isoproterenol-induced cTnI increase and improved survival, whereas UCP1(-/-) BAT transplanted to either UCP1(-/-) or WT mice had no effect on cTnI release. After 3 days of isoproterenol treatment, phosphorylated AKT and ERK were lower in the LV's of UCP1(-/-) mice than in those of WT mice. Activation of BAT was also noted in a model of chronic ischemic cardiomyopathy, and was correlated to LV dysfunction. Deficiency in UCP1, and accompanying BAT dysfunction, increases cardiomyocyte injury and adverse LV remodeling, and decreases survival in a mouse model of catecholamine-induced cardiomyopathy. Myocardial injury and decreased survival are rescued by transplantation of functional BAT to UCP1(-/-) mice, suggesting a systemic cardioprotective role of functional BAT. BAT is also activated in chronic ischemic cardiomyopathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Study on the effect of micro-gravity on bio-functions; Seitai kino eno bisho juryoku no eikyo ni kansuru kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    The effect of micro-gravity on bio-functions and vital reaction was studied using the facility of Underground Gravity-free Experiment Center Co. On the effect on osteoblast shape and gene expression, although fluorochrome reacting with Ca was well taken into cells, no significant difference in Ca content in cells was observed before/after falling. Expression of genes related to cell propagation was controlled under micro-gravity. Protoplast fusion of Lentinus was unaffected by micro-gravity. The mRNA fragments of gravity sensitive mutant of rice plant were affected by micro-gravity. Paramecium was set swimming in solutions with different specific gravities. The reaction behavior of Paramecium was affected by the difference in specific gravity between cell bodies and solutions. The water content metabolism functions of a mouse with needle stimulus, in particular excretory, were slightly promoted by micro- gravity. The cortisol level in blood of a falling mouse group rose showing strong stress. As the preliminary study on the geotaxis of insects, motion of bagworm was observed. 12 refs., 38 figs., 4 tabs.

  13. ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function.

    Science.gov (United States)

    Sharma, Aarti; Lyashchenko, Alexander K; Lu, Lei; Nasrabady, Sara Ebrahimi; Elmaleh, Margot; Mendelsohn, Monica; Nemes, Adriana; Tapia, Juan Carlos; Mentis, George Z; Shneider, Neil A

    2016-02-04

    Mutations in FUS cause amyotrophic lateral sclerosis (ALS), including some of the most aggressive, juvenile-onset forms of the disease. FUS loss-of-function and toxic gain-of-function mechanisms have been proposed to explain how mutant FUS leads to motor neuron degeneration, but neither has been firmly established in the pathogenesis of ALS. Here we characterize a series of transgenic FUS mouse lines that manifest progressive, mutant-dependent motor neuron degeneration preceded by early, structural and functional abnormalities at the neuromuscular junction. A novel, conditional FUS knockout mutant reveals that postnatal elimination of FUS has no effect on motor neuron survival or function. Moreover, endogenous FUS does not contribute to the onset of the ALS phenotype induced by mutant FUS. These findings demonstrate that FUS-dependent motor degeneration is not due to loss of FUS function, but to the gain of toxic properties conferred by ALS mutations.

  14. Uroradiographic manifestations of Burkitt's lymphoma in children

    International Nuclear Information System (INIS)

    Fernbach, S.K.; Glass, R.B.

    1986-01-01

    The radiological studies of 18 children with biopsy proved Burkitt's lymphoma were analyzed retrospectively. Before therapy the genitourinary tract was evaluated in 15 children by excretory urography, sonography, computerized tomography and/or gallium citrate scintigraphy. Genitourinary abnormalities were detected in 9 children. Changes due to tumor included renal or ureteral displacement in 4 children, hydronephrosis in 3 and intraparenchymal masses in 4. Extrinsic compression of the bladder causing no compromise of function was seen in only 2 children. Gonadal involvement occurred in 2 boys and 1 girl. The modality of choice for evaluating the genitourinary tract in patients with Burkitt's lymphoma has been excretory urography. Since ultrasound and computerized tomography provide more direct information about tumor deposits within the kidney and retroperitoneum, either should be performed in this population before initiation of chemotherapy

  15. Obestatin regulates adipocyte function and protects against diet-induced insulin resistance and inflammation.

    Science.gov (United States)

    Granata, Riccarda; Gallo, Davide; Luque, Raul M; Baragli, Alessandra; Scarlatti, Francesca; Grande, Cristina; Gesmundo, Iacopo; Córdoba-Chacón, Jose; Bergandi, Loredana; Settanni, Fabio; Togliatto, Gabriele; Volante, Marco; Garetto, Stefano; Annunziata, Marta; Chanclón, Belén; Gargantini, Eleonora; Rocchietto, Stefano; Matera, Lina; Datta, Giacomo; Morino, Mario; Brizzi, Maria Felice; Ong, Huy; Camussi, Giovanni; Castaño, Justo P; Papotti, Mauro; Ghigo, Ezio

    2012-08-01

    The metabolic actions of the ghrelin gene-derived peptide obestatin are still unclear. We investigated obestatin effects in vitro, on adipocyte function, and in vivo, on insulin resistance and inflammation in mice fed a high-fat diet (HFD). Obestatin effects on apoptosis, differentiation, lipolysis, and glucose uptake were determined in vitro in mouse 3T3-L1 and in human subcutaneous (hSC) and omental (hOM) adipocytes. In vivo, the influence of obestatin on glucose metabolism was assessed in mice fed an HFD for 8 wk. 3T3-L1, hSC, and hOM preadipocytes and adipocytes secreted obestatin and showed specific binding for the hormone. Obestatin prevented apoptosis in 3T3-L1 preadipocytes by increasing phosphoinositide 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK)1/2 signaling. In both mice and human adipocytes, obestatin inhibited isoproterenol-induced lipolysis, promoted AMP-activated protein kinase phosphorylation, induced adiponectin, and reduced leptin secretion. Obestatin also enhanced glucose uptake in either the absence or presence of insulin, promoted GLUT4 translocation, and increased Akt phosphorylation and sirtuin 1 (SIRT1) protein expression. Inhibition of SIRT1 by small interfering RNA reduced obestatin-induced glucose uptake. In HFD-fed mice, obestatin reduced insulin resistance, increased insulin secretion from pancreatic islets, and reduced adipocyte apoptosis and inflammation in metabolic tissues. These results provide evidence of a novel role for obestatin in adipocyte function and glucose metabolism and suggest potential therapeutic perspectives in insulin resistance and metabolic dysfunctions.

  16. cDNA cloning and transcriptional controlling of a novel low dose radiation-induced gene and its function analysis

    International Nuclear Information System (INIS)

    Zhou Pingkun; Sui Jianli

    2002-01-01

    Objective: To clone a novel low dose radiation-induced gene (LRIGx) and study its function as well as its transcriptional changes after irradiation. Methods: Its cDNA was obtained by DDRT-PCR and RACE techniques. Northern blot hybridization was used to investigate the gene transcription. Bioinformatics was employed to analysis structure and function of this gene. Results: LRIGx cDNA was cloned. The sequence of LRIGx was identical to a DNA clone located in human chromosome 20 q 11.2-12 Bioinformatics analysis predicted an encoded protein with a conserved helicase domain. Northern analysis revealed a ∼8.5 kb transcript which was induced after 0.2 Gy as well as 0.02 Gy irradiation, and the transcript level was increased 5 times at 4 h after 0.2 Gy irradiation. The induced level of LRIGx transcript by 2.0 Gy high dose was lower than by 0.2 Gy. Conclusion: A novel low dose radiation-induced gene has been cloned. It encodes a protein with a conserved helicase domain that could involve in DNA metabolism in the cellular process of radiation response

  17. Functioning of spontaneous and induced Con A regulators of T-cell proliferation. Modifying factors

    International Nuclear Information System (INIS)

    Kuz'mina, E.G.

    1989-01-01

    It is shown that active spontaneous non-specific regulators of T-cell proliferation are activated in peripheral blood ''in vivo'' by endogenous metabolites; non-specific regulator action can be induced ''in vitro'' by Con A, FGA. Non-specific regulators suppress and increase lymphocyte proliferation. Cyclic character of their functioning is revealed. 4 refs.; 1 tab

  18. Pretreatment with mixed-function oxidase inducers increases the sensitivity of the hepatocyte/DNA repair assay

    International Nuclear Information System (INIS)

    Shaddock, J.G.; Heflich, R.H.; McMillan, D.C.; Hinson, J.A.; Casciano, D.A.

    1989-01-01

    A recent National Toxicology Program evaluation indicates that the rat hepatocyte/DNA repair assay has a high false-negative rate and that it is insensitive to some genotoxic hepatocarcinogens as well as other species and organ-specific carcinogens. In this study, the authors examined whether the sensitivity of the hepatocyte/DNA repair assay might be increased through animal pretreatment with various hepatic mixed-function oxidase inducers, i.e., Aroclor 1254, phenobarbital, and 3,3',4,4'-tetrachloroazobenzene (TCAB). The effects on unscheduled DNA synthesis (UDS), a measured of DNA damage and repair, were studied in cultures exposed to known and/or potential carcinogens that had been evaluated as negative or questionable or that produced conflicting results with hepatocytes isolated from uninduced animals. 4,4'-Oxydianiline, 1-nitropy-rene, and TCAB produced concentration-dependent increases in UDS in hepatocytes from rats pretreated with Aroclor 1254. 4,4'-Oxydianiline and TCAB also induced a dose-dependent increase in DNA repair in hepatocytes from rats pretreated with phenobarbital, whereas 1-nitropyrene was negative. These data indicate that the limited sensitivity to chemical carcinogens displayed by the hepatocyte/DNA repair assay may be increased by using hepatocytes isolated from animals exposed to hepatic mixed-function oxidase inducers

  19. Pretreatment with mixed-function oxidase inducers increases the sensitivity of the hepatocyte/DNA repair assay

    Energy Technology Data Exchange (ETDEWEB)

    Shaddock, J.G.; Heflich, R.H.; McMillan, D.C.; Hinson, J.A.; Casciano, D.A. (National Center for Toxicological Research, Jefferson, AK (USA) Univ. of Arkansas for Medical Sciences, Little Rock (USA))

    1989-01-01

    A recent National Toxicology Program evaluation indicates that the rat hepatocyte/DNA repair assay has a high false-negative rate and that it is insensitive to some genotoxic hepatocarcinogens as well as other species and organ-specific carcinogens. In this study, the authors examined whether the sensitivity of the hepatocyte/DNA repair assay might be increased through animal pretreatment with various hepatic mixed-function oxidase inducers, i.e., Aroclor 1254, phenobarbital, and 3,3{prime},4,4{prime}-tetrachloroazobenzene (TCAB). The effects on unscheduled DNA synthesis (UDS), a measured of DNA damage and repair, were studied in cultures exposed to known and/or potential carcinogens that had been evaluated as negative or questionable or that produced conflicting results with hepatocytes isolated from uninduced animals. 4,4{prime}-Oxydianiline, 1-nitropy-rene, and TCAB produced concentration-dependent increases in UDS in hepatocytes from rats pretreated with Aroclor 1254. 4,4{prime}-Oxydianiline and TCAB also induced a dose-dependent increase in DNA repair in hepatocytes from rats pretreated with phenobarbital, whereas 1-nitropyrene was negative. These data indicate that the limited sensitivity to chemical carcinogens displayed by the hepatocyte/DNA repair assay may be increased by using hepatocytes isolated from animals exposed to hepatic mixed-function oxidase inducers.

  20. Polarization-induced local pore-wall functionalization for biosensing: from micropore to nanopore.

    Science.gov (United States)

    Liu, Jie; Pham, Pascale; Haguet, Vincent; Sauter-Starace, Fabien; Leroy, Loïc; Roget, André; Descamps, Emeline; Bouchet, Aurélie; Buhot, Arnaud; Mailley, Pascal; Livache, Thierry

    2012-04-03

    The use of biological-probe-modified solid-state pores in biosensing is currently hindered by difficulties in pore-wall functionalization. The surface to be functionalized is small and difficult to target and is usually chemically similar to the bulk membrane. Herein, we demonstrate the contactless electrofunctionalization (CLEF) approach and its mechanism. This technique enables the one-step local functionalization of the single pore wall fabricated in a silica-covered silicon membrane. CLEF is induced by polarization of the pore membrane in an electric field and requires a sandwich-like composition and a conducting or semiconducting core for the pore membrane. The defects in the silica layer of the micropore wall enable the creation of an electric pathway through the silica layer, which allows electrochemical reactions to take place locally on the pore wall. The pore diameter is not a limiting factor for local wall modification using CLEF. Nanopores with a diameter of 200 nm fabricated in a silicon membrane and covered with native silica layer have been successfully functionalized with this method, and localized pore-wall modification was obtained. Furthermore, through proof-of-concept experiments using ODN-modified nanopores, we show that functionalized nanopores are suitable for translocation-based biosensing.

  1. Redox-Triggered Bonding-Induced Emission of Thiol-Functionalized Gold Nanoclusters for Luminescence Turn-On Detection of Molecular Oxygen.

    Science.gov (United States)

    Ao, Hang; Feng, Hui; Zhao, Mengting; Zhao, Meizhi; Chen, Jianrong; Qian, Zhaosheng

    2017-11-22

    Most optical sensors for molecular oxygen were developed based on the quenching effect of the luminescence of oxygen-sensitive probes; however, the signal turn-off mode of these probes is undesirable to quantify and visualize molecular oxygen. Herein, we report a novel luminescence turn-on detection strategy for molecular oxygen via the specific oxygen-triggered bonding-induced emission of thiol-functionalized gold nanoclusters. Thiol-functionalized gold nanoclusters were prepared by a facile one-step synthesis, and as-prepared gold nanoclusters possess significant aggregation-induced emission (AIE) property. It is the first time to discover the oxygen-triggered bonding-induced emission (BIE) behavior of gold nanoclusters, which results in disulfide-linked covalent bonding assemblies with intensely red luminescence. This specific redox-triggered BIE is capable of quantitatively detecting dissolved oxygen in aqueous solution in a light-up manner, and trace amount of dissolved oxygen at ppb level is achieved based on this detection method. A facile and convenient test strip for oxygen detection was also developed to monitor molecular oxygen in a gas matrix. Covalent bonding-induced emission is proven to be a more efficient way to attain high brightness of AIEgens than a physical aggregation-induced emission process, and provides a more convenient and desirable detection method for molecular oxygen than the previous sensors.

  2. Cyclophilin B as a co-regulator of prolactin-induced gene expression and function in breast cancer cells.

    Science.gov (United States)

    Fang, Feng; Zheng, Jiamao; Galbaugh, Traci L; Fiorillo, Alyson A; Hjort, Elizabeth E; Zeng, Xianke; Clevenger, Charles V

    2010-06-01

    The effects of prolactin (PRL) during the pathogenesis of breast cancer are mediated in part though Stat5 activity enhanced by its interaction with its transcriptional inducer, the prolyl isomerase cyclophilin B (CypB). We have demonstrated that knockdown of CypB decreases cell growth, proliferation, and migration, and CypB expression is associated with malignant progression of breast cancer. In this study, we examined the effect of CypB knockdown on PRL signaling in breast cancer cells. CypB knockdown with two independent siRNAs was shown to impair PRL-induced reporter expression in breast cancer cell line. cDNA microarray analysis was performed on these cells to assess the effect of CypB reduction, and revealed a significant decrease in PRL-induced endogenous gene expression in two breast cancer cell lines. Parallel functional assays revealed corresponding alterations of both anchorage-independent cell growth and cell motility of breast cancer cells. Our results demonstrate that CypB expression levels significantly modulate PRL-induced function in breast cancer cells ultimately resulting in enhanced levels of PRL-responsive gene expression, cell growth, and migration. Given the increasingly appreciated role of PRL in the pathogenesis of breast cancer, the actions of CypB detailed here are of biological significance.

  3. Lysosomal Exoglycosidase Profile and Secretory Function in the Salivary Glands of Rats with Streptozotocin-Induced Diabetes.

    Science.gov (United States)

    Maciejczyk, Mateusz; Kossakowska, Agnieszka; Szulimowska, Julita; Klimiuk, Anna; Knaś, Małgorzata; Car, Halina; Niklińska, Wiesława; Ładny, Jerzy Robert; Chabowski, Adrian; Zalewska, Anna

    2017-01-01

    Before this study, there had been no research evaluating the relationship between a lysosomal exoglycosidase profile and secretory function in the salivary glands of rats with streptozotocin- (STZ-) induced type 1 diabetes. In our work, rats were divided into 4 groups of 8 animals each: control groups (C2, C4) and diabetic groups (STZ2, STZ4). The secretory function of salivary glands-nonstimulated and stimulated salivary flow, α -amylase, total protein-and salivary exoglycosidase activities-N-acetyl- β -hexosaminidase (HEX, HEX A, and HEX B), β -glucuronidase, α -fucosidase, β -galactosidase, and α -mannosidase-was estimated both in the parotid and submandibular glands of STZ-diabetic and control rats. The study has demonstrated that the activity of most salivary exoglycosidases is significantly higher in the parotid and submandibular glands of STZ-diabetic rats as compared to the healthy controls and that it increases as the disease progresses. Reduced secretory function of diabetic salivary glands was also observed. A significant inverse correlation between HEX B, α -amylase activity, and stimulated salivary flow in diabetic parotid gland has also been shown. Summarizing, STZ-induced diabetes leads to a change in the lysosomal exoglycosidase profile and reduced function of the salivary glands.

  4. Lysosomal Exoglycosidase Profile and Secretory Function in the Salivary Glands of Rats with Streptozotocin-Induced Diabetes

    Directory of Open Access Journals (Sweden)

    Mateusz Maciejczyk

    2017-01-01

    Full Text Available Before this study, there had been no research evaluating the relationship between a lysosomal exoglycosidase profile and secretory function in the salivary glands of rats with streptozotocin- (STZ- induced type 1 diabetes. In our work, rats were divided into 4 groups of 8 animals each: control groups (C2, C4 and diabetic groups (STZ2, STZ4. The secretory function of salivary glands—nonstimulated and stimulated salivary flow, α-amylase, total protein—and salivary exoglycosidase activities—N-acetyl-β-hexosaminidase (HEX, HEX A, and HEX B, β-glucuronidase, α-fucosidase, β-galactosidase, and α-mannosidase—was estimated both in the parotid and submandibular glands of STZ-diabetic and control rats. The study has demonstrated that the activity of most salivary exoglycosidases is significantly higher in the parotid and submandibular glands of STZ-diabetic rats as compared to the healthy controls and that it increases as the disease progresses. Reduced secretory function of diabetic salivary glands was also observed. A significant inverse correlation between HEX B, α-amylase activity, and stimulated salivary flow in diabetic parotid gland has also been shown. Summarizing, STZ-induced diabetes leads to a change in the lysosomal exoglycosidase profile and reduced function of the salivary glands.

  5. Sustained NMDA receptor hypofunction induces compromised neural systems integration and schizophrenia-like alterations in functional brain networks.

    Science.gov (United States)

    Dawson, Neil; Xiao, Xiaolin; McDonald, Martin; Higham, Desmond J; Morris, Brian J; Pratt, Judith A

    2014-02-01

    Compromised functional integration between cerebral subsystems and dysfunctional brain network organization may underlie the neurocognitive deficits seen in psychiatric disorders. Applying topological measures from network science to brain imaging data allows the quantification of complex brain network connectivity. While this approach has recently been used to further elucidate the nature of brain dysfunction in schizophrenia, the value of applying this approach in preclinical models of psychiatric disease has not been recognized. For the first time, we apply both established and recently derived algorithms from network science (graph theory) to functional brain imaging data from rats treated subchronically with the N-methyl-D-aspartic acid (NMDA) receptor antagonist phencyclidine (PCP). We show that subchronic PCP treatment induces alterations in the global properties of functional brain networks akin to those reported in schizophrenia. Furthermore, we show that subchronic PCP treatment induces compromised functional integration between distributed neural systems, including between the prefrontal cortex and hippocampus, that have established roles in cognition through, in part, the promotion of thalamic dysconnectivity. We also show that subchronic PCP treatment promotes the functional disintegration of discrete cerebral subsystems and also alters the connectivity of neurotransmitter systems strongly implicated in schizophrenia. Therefore, we propose that sustained NMDA receptor hypofunction contributes to the pathophysiology of dysfunctional brain network organization in schizophrenia.

  6. Constraint-Induced Movement Therapy Combined with Transcranial Direct Current Stimulation over Premotor Cortex Improves Motor Function in Severe Stroke: A Pilot Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Suellen M. Andrade

    2017-01-01

    Full Text Available Objective. We compared the effects of transcranial direct current stimulation at different cortical sites (premotor and motor primary cortex combined with constraint-induced movement therapy for treatment of stroke patients. Design. Sixty patients were randomly distributed into 3 groups: Group A, anodal stimulation on premotor cortex and constraint-induced movement therapy; Group B, anodal stimulation on primary motor cortex and constraint-induced movement therapy; Group C, sham stimulation and constraint-induced movement therapy. Evaluations involved analysis of functional independence, motor recovery, spasticity, gross motor function, and muscle strength. Results. A significant improvement in primary outcome (functional independence after treatment in the premotor group followed by primary motor group and sham group was observed. The same pattern of improvement was highlighted among all secondary outcome measures regarding the superior performance of the premotor group over primary motor and sham groups. Conclusions. Premotor cortex can contribute to motor function in patients with severe functional disabilities in early stages of stroke. This study was registered in ClinicalTrials.gov database (NCT 02628561.

  7. Lateralized kappa opioid receptor signaling from the amygdala central nucleus promotes stress-induced functional pain.

    Science.gov (United States)

    Nation, Kelsey M; De Felice, Milena; Hernandez, Pablo I; Dodick, David W; Neugebauer, Volker; Navratilova, Edita; Porreca, Frank

    2018-05-01

    The response of diffuse noxious inhibitory controls (DNIC) is often decreased, or lost, in stress-related functional pain syndromes. Because the dynorphin/kappa opioid receptor (KOR) pathway is activated by stress, we determined its role in DNIC using a model of stress-induced functional pain. Male, Sprague-Dawley rats were primed for 7 days with systemic morphine resulting in opioid-induced hyperalgesia. Fourteen days after priming, when hyperalgesia was resolved, rats were exposed to environmental stress and DNIC was evaluated by measuring hind paw response threshold to noxious pressure (test stimulus) after capsaicin injection in the forepaw (conditioning stimulus). Morphine priming without stress did not alter DNIC. However, stress produced a loss of DNIC in morphine-primed rats in both hind paws that was abolished by systemic administration of the KOR antagonist, nor-binaltorphimine (nor-BNI). Microinjection of nor-BNI into the right, but not left, central nucleus of the amygdala (CeA) prevented the loss of DNIC in morphine-primed rats. Diffuse noxious inhibitory controls were not modulated by bilateral nor-BNI in the rostral ventromedial medulla. Stress increased dynorphin content in both the left and right CeA of primed rats, reaching significance only in the right CeA; no change was observed in the rostral ventromedial medulla or hypothalamus. Although morphine priming alone is not sufficient to influence DNIC, it establishes a state of latent sensitization that amplifies the consequences of stress. After priming, stress-induced dynorphin/KOR signaling from the right CeA inhibits DNIC in both hind paws, likely reflecting enhanced descending facilitation that masks descending inhibition. Kappa opioid receptor antagonists may provide a new therapeutic strategy for stress-related functional pain disorders.

  8. Bladder function in 17β-estradiol-induced nonbacterial prostatitis model in Wistar rat.

    Science.gov (United States)

    Matsumoto, Seiji; Kawai, Yuko; Oka, Michiko; Oyama, Tatsuya; Hashizume, Kazumi; Wada, Naoki; Hori, Jun-ichi; Tamaki, Gaku; Kita, Masafumi; Iwata, Tatsuya; Kakizaki, Hidehiro

    2013-06-01

    To investigate bladder function in a model of nonbacterial prostatitis (NBP) induced in castrated rats by 17β-estradiol injection. Ten-month-old male Wistar rats were divided into two groups, sham and NBP (both N = 8). NBP was induced by castration followed by daily subcutaneous injection of 17β-estradiol for 30 days. On the 31st day after surgery, we investigated (1) voiding behavior, (2) bladder blood flow (BBF), (3) prostate and bladder weight, and proinflammatory cytokines (TNF-α and CXCL1) levels and (4) bladder contractile responses to electrical field stimulation (EFS), carbachol and KCl. (1) Voiding behavior (average micturition volume, total urine volume and number of micturitions) and (2) BBF were not significantly different between the sham and NBP groups. (3) NBP led to a significant decrease in prostatic weight and increase in proinflammatory cytokine levels in the prostate, but NBP did not cause a significant change in bladder weight or proinflammatory cytokine levels in the bladder. (4) Bladder contractile forces in response to EFS, carbachol and KCl were not significantly affected by NBP. In this rat model, NBP did not cause a significant change in the level of proinflammatory cytokines in the bladder and affect bladder function.

  9. Ultrastructural aspects of feeding and secretion-excretion by the equine parasite Strongylus vulgaris.

    Science.gov (United States)

    Mobarak, M S; Ryan, M F

    1999-06-01

    Light, scanning, and transmission electron microscopy were employed to provide further data on the putative origins of the immunogenic secretory-excretory product (ESP) of Strongylus vulgaris (Looss 1900). The sharply delineated but superficial attachment to the equine caecum by the mouth leaves behind an oval area devoid of epithelial cells. Attachment does not extend deeply enough to reach the muscularis mucosa layer of the equine intestine. The progressive digestion of the ingested plug of tissue (epithelial cells, blood cells and mucous) was visualized. The coelomocytes, floating cells and membranous structures located in the pseudocoelom and intimately associated with the digestive, excretory and reproductive systems, and with the somatic muscles are described. The secretory-excretory system comprises two, ventrally-located, secretory-excretory glands connected to tubular elements. These glands synthesize granules of various sizes and densities that are delineated.

  10. Study of sympathetic nervous function under effort induced ischemia in patients with angina pectoris with I-123 metaiodobenzylguanidine (MIBG) myocardial SPECT images

    International Nuclear Information System (INIS)

    Tanaka, Takeshi; Aizawa, Tadanori; Kato, Kazuzo; Ogasawara, Ken; Sakuma, Toru; Kirigaya, Hajime; Hirosaka, Akira; Igarashi, Masaki

    1990-01-01

    I-123 metaiodobenzylguanidine (MIBG) is a norepinephrine analog, which can be used to study the sympathetic nervous function of the heart. With MIBG myocardial SPECT images sympathetic nervous function under effort induced ischemia were studied in 18 patients with significant coronary artery lesions. In 5 patients with effort induced ischemic region in stress Tl-201 myocardial images rest MIBG images were collected and then exercise stress test was performed. Patients continued exercising for 3 minutes after onset of symptom. Post-stress MIBG images were collected. Definite ischemic region was noted in stress Tl-201 myocardial images, however no differences were noted between rest and post-stress MIBG images. These results suggested that exercise induced ischemia did not enhance release of uptaken MIBG. In 13 patients with significant coronary artery lesions symptom-limited exercise stress test was performed MIBG and Tl-201 were simultaneously injected at onset of symptom and patients continued exercising for an additional one minute. In 6 cases (46%, 6/13) MIBG defects with Tl-201 uptake were noted. These results showed that exercise induced ischemia depressed net MIBG uptake and that sympathetic nervous function (MIBG images) may be more sensitive to ischemic damage than muscle (Tl-201 images). It is suggested that exercise induced ischemia depressed reuptake of norepinephrine at sympathetic nervous endings. MIBG myocardial SPECT images may be useful for evaluating sympathetic nervous function under ischemia. (author)

  11. Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats

    NARCIS (Netherlands)

    L. Zafrani (Lara); B. Ergin (Bulent); Kapucu, A. (Aysegul); C. Ince (Can)

    2016-01-01

    textabstractBackground: The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Methods: Twenty-seven Wistar

  12. Caenorhabditis elegans as a model to study renal development and disease: sexy cilia.

    Science.gov (United States)

    Barr, Maureen M

    2005-02-01

    The nematode Caenorhabditis elegans has no kidney per se, yet "the worm" has proved to be an excellent model to study renal-related issues, including tubulogenesis of the excretory canal, membrane transport and ion channel function, and human genetic diseases including autosomal dominant polycystic kidney disease (ADPKD). The goal of this review is to explain how C. elegans has provided insight into cilia development, cilia function, and human cystic kidney diseases.

  13. Functional properties of nisin–carbohydrate conjugates formed by radiation induced Maillard reaction

    International Nuclear Information System (INIS)

    Muppalla, Shobita R.; Sonavale, Rahul; Chawla, Surinder P.; Sharma, Arun

    2012-01-01

    Nisin–carbohydrate conjugates were prepared by irradiating nisin either with glucose or dextran. Increase in browning and formation of intermediate products was observed with a concomitant decrease in free amino and reducing sugar groups indicating occurrence of the Maillard reaction catalyzed by irradiation. Nisin–carbohydrate conjugates showed a broad spectrum antibacterial activity against Gram negative bacteria (Escherichia coli, Pseudomonas fluorescence) as well as Gram positive bacteria (Staphylococcus aureus, Bacillus cereus). Results of antioxidant assays, including that of DPPH radical-scavenging activity and reducing power, showed that the nisin–dextran conjugates possessed better antioxidant potential than nisin–glucose conjugate. These results suggested that it was possible to enhance the functional properties of nisin by preparing radiation induced conjugates suitable for application in food industry. - Highlights: ► Nisin–carbohydrate conjugates were prepared using radiation induced Maillard reaction. ► Conjugation of nisin with dextran/glucose resulted in improvement of antibacterial spectrum. ► Conjugates of nisin with dextran/glucose had significant radical scavenging activity.

  14. Role of reactive nitrogen species generated via inducible nitric oxide synthase in vesicant-induced lung injury, inflammation and altered lung functioning

    Energy Technology Data Exchange (ETDEWEB)

    Sunil, Vasanthi R., E-mail: sunilvr@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy Piscataway, NJ (United States); Shen, Jianliang; Patel-Vayas, Kinal; Gow, Andrew J. [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy Piscataway, NJ (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Ernest Mario School of Pharmacy Piscataway, NJ (United States)

    2012-05-15

    Pulmonary toxicity induced by sulfur mustard and related vesicants is associated with oxidative stress. In the present studies we analyzed the role of reactive nitrogen species (RNS) generated via inducible nitric oxide synthase (iNOS) in lung injury and inflammation induced by vesicants using 2-chloroethyl ethyl sulfide (CEES) as a model. C57Bl/6 (WT) and iNOS −/− mice were sacrificed 3 days or 14 days following intratracheal administration of CEES (6 mg/kg) or control. CEES intoxication resulted in transient (3 days) increases in bronchoalveolar lavage (BAL) cell and protein content in WT, but not iNOS −/− mice. This correlated with expression of Ym1, a marker of oxidative stress in alveolar macrophages and epithelial cells. In contrast, in iNOS −/− mice, Ym1 was only observed 14 days post-exposure in enlarged alveolar macrophages, suggesting that they are alternatively activated. This is supported by findings that lung tumor necrosis factor and lipocalin Lcn2 expression, mediators involved in tissue repair were also upregulated at this time in iNOS −/− mice. Conversely, CEES-induced increases in the proinflammatory genes, monocyte chemotactic protein-1 and cyclooxygenase-2, were abrogated in iNOS −/− mice. In WT mice, CEES treatment also resulted in increases in total lung resistance and decreases in compliance in response to methacholine, effects blunted by loss of iNOS. These data demonstrate that RNS, generated via iNOS play a role in the pathogenic responses to CEES, augmenting oxidative stress and inflammation and suppressing tissue repair. Elucidating inflammatory mechanisms mediating vesicant-induced lung injury is key to the development of therapeutics to treat mustard poisoning. -- Highlights: ► Lung injury, inflammation and oxidative stress are induced by the model vesicant CEES ► RNS generated via iNOS are important in the CEES-induced pulmonary toxicity ► iNOS −/− mice are protected from CEES-induced lung toxicity and

  15. Functional significance of metastasis-inducing S100A4(Mts1) in tumor-stroma interplay

    DEFF Research Database (Denmark)

    Schmidt-Hansen, Birgitte; Klingelhöfer, Jörg; Grum-Schwensen, Birgitte

    2004-01-01

    Causal implication of S100A4 in inducing metastases was convincingly shown previously. However, the mechanisms that associate S100A4 with tumor progression are not well understood. S100A4 protein, as a typical member of the S100 family, exhibits dual, intracellular and extracellular, functions. T...

  16. Child and parent perceived food-induced gastrointestinal symptoms and quality of life in children with functional gastrointestinal disorders.

    Science.gov (United States)

    Carlson, Michelle J; Moore, Carolyn E; Tsai, Cynthia M; Shulman, Robert J; Chumpitazi, Bruno P

    2014-03-01

    It is unknown whether children with functional gastrointestinal (GI) disorders identify specific foods that exacerbate their GI symptoms. The objectives of this study were to determine the perceived role of food on GI symptoms and to determine the impact of food-induced symptoms on quality of life (QOL) in children with functional GI disorders. Between August and November 2010, 25 children ages 11 to 17 years old with functional GI disorders and a parent completed a food symptom association questionnaire and validated questionnaires assessing FGID symptoms and QOL. In addition, children completed a 24-hour food recall, participated in focus groups to identify problematic foods and any coping strategies, and discussed how their QOL was affected. Statistical analyses were conducted using χ2, t test, Mann-Whitney U test, Wilcoxon signed rank, and Spearman's ρ. Children identified a median of 11 (range=2 to 25) foods as exacerbating a GI symptom, with the most commonly identified foods being spicy foods, cow's milk, and pizza. Several coping strategies were identified, including consuming smaller portions, modifying foods, and avoiding a median of 8 (range=1 to 20) foods. Children reported that food-induced symptoms interfered with school performance, sports, and social activities. Although the parent's assessment of their child's QOL negatively correlated with the number of perceived symptom-inducing foods in their child, this relationship was not found in the children. Findings suggest that specific foods are perceived to exacerbate GI symptoms in children with functional GI disorders. In addition, despite use of several coping strategies, food-induced symptoms can adversely impact children's QOL in several important areas. Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  17. Physical exercise prevents cognitive impairment by enhancing hippocampal neuroplasticity and mitochondrial function in doxorubicin-induced chemobrain.

    Science.gov (United States)

    Park, Hye-Sang; Kim, Chang-Ju; Kwak, Hyo-Bum; No, Mi-Hyun; Heo, Jun-Won; Kim, Tae-Woon

    2018-05-01

    Although chemotherapy increases the survival rate of patients with various cancers, such treatment can induce acute or long-term cognitive dysfunction a phenomenon known as post-chemotherapy cognitive impairment (PCCI) or "chemobrain." Exercise is known to positively affect brain function. Thus, the present study aimed to determine whether symptoms of chemobrain and disruptions in the neuroplasticity and functioning of hippocampal mitochondria can be prevented or relieved by exercise. Wistar rats were separated into the following groups: control, control plus exercise, chemobrain, and chemobrain plus exercise. For chemobrain induction, 2 mg/kg of doxorubicin (DOX) a widely utilized chemotherapeutic agent among patients with breast cancer was dissolved in saline and directly injected to the abdomen once every 4 weeks. The exercise groups were subjected to low-intensity treadmill, 6 days per week for 4 weeks. The Morris water maze and step-down avoidance tests were conducted to evaluate cognitive function, while neuroplasticity and mitochondrial function were assessed in the hippocampus and dentate gyrus. Decreased cognitive function were observed in the chemobrain group, along with decreases in levels of neurogenesis, brain derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), Ca 2+ retention in hippocampus. Rats of the chemobrain group also exhibited an increase in apoptosis, H 2 O 2 emission and permeability transition pore by hippocampal mitochondria. However, exercise attenuated impairments in cognitive function, neuroplasticity, and mitochondrial function induced by DOX treatment. Therefore, the findings of the present study indicate that low-intensity exercise may assist in preventing cognitive dysfunction during or after chemotherapy in patients with various cancers, including breast cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Effects of exercise and diet change on cognition function and synaptic plasticity in high fat diet induced obese rats

    Science.gov (United States)

    2013-01-01

    Background Nutritional imbalance-induced obesity causes a variety of diseases and in particular is an important cause of cognitive function decline. This study was performed on Sprague Dawley (SD) rats with 13-weeks of high fat diet-induced obesity in connection to the effects of regular exercise and dietary control for 8 weeks on the synaptic plasticity and cognitive abilities of brain. Methods Four weeks-old SD rats were adopted classified into normal-normal diet-sedentary (NNS, n = 8), obesity-high fat diet-sedentary (OHS, n = 8), obesity-high fat diet-training (OHT, n = 8), obesity-normal diet-sedentary (ONS, n = 8) and obesity- normal diet-training (ONT, n = 8). The exercise program consisted of a treadmill exercise administered at a speed of 8 m/min for 1–4 weeks, and 14 m/min for 5–8 weeks. The Western blot method was used to measure the expression of NGF, BDNF, p38MAPK and p-p38MAPK proteins in hippocampus of the brain, and expressions of NGF, BDNF, TrkA, TrkB, CREB and synapsin1 mRNA were analyzed through qRT-PCR. Results The results suggest cognitive function-related protein levels and mRNA expression to be significantly decreased in the hippocampus of obese rats, and synaptic plasticity as well as cognitive function signaling sub-pathway factors were also significantly decreased. In addition, 8-weeks exercises and treatment by dietary change had induced significant increase of cognitive function-related protein levels and mRNA expression as well as synaptic plasticity and cognitive function signaling sub-pathway factors in obese rats. In particular, the combined treatment had presented even more positive effect. Conclusions Therefore, it was determined that the high fat diet-induced obesity decreases plasticity and cognitive function of the brain, but was identified as being improved by exercises and dietary changes. In particular, it is considered that regular exercise has positive effects on memory span and learning

  19. Heligmosomoides polygyrus Venom Allergen-like Protein-4 (HpVAL-4) is a sterol binding protein

    NARCIS (Netherlands)

    Asojo, Oluwatoyin A.; Darwiche, Rabih; Gebremedhin, Selam; Smant, Geert; Lozano-Torres, Jose L.; Drurey, Claire; Pollet, Jeroen; Maizels, Rick M.; Schneiter, Roger; Wilbers, Ruud H.P.

    2018-01-01

    Heligmosomoides polygyrus bakeri is a model parasitic hookworm used to study animal and human helminth diseases. During infection, the parasite releases excretory/secretory products that modulate the immune system of the host. The most abundant protein family in excretory/secretory products

  20. Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats

    NARCIS (Netherlands)

    Zafrani, Lara; Ergin, Bulent; Kapucu, Aysegul; Ince, Can

    2016-01-01

    The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Twenty-seven Wistar albino rats were randomized into

  1. Repair of radiation-induced DNA damage in rat epidermis as a function of age

    International Nuclear Information System (INIS)

    Sargent, E.V.; Burns, F.J.

    1985-01-01

    The rate of repair of radiation-induced DNA damage in proliferating rat epidermal cells diminished progressively with increasing age of the animal. The dorsal skin was irradiated with 1200 rad of 0.8 MeV electrons at various ages, and the amount of DNA damage was determined as a function of time after irradiation by the method of alkaline unwinding followed by S 1 nuclease digestion. The amount of DNA damage immediately after irradiation was not age dependent, while the rate of damage removal from the DNA decreased with increasing age. By fitting an exponential function to the relative amount of undamaged DNA as a function of time after irradiation, DNA repair halftimes of 20, 27, 69, and 107 min were obtained for 28, 100-, 200-, and 400-day-old animals, respectively

  2. Effect of Child Friendly Constraint Induced Movement Therapy on Unimanual and Bimanual Functions in Children with Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Seyyed Mohammad Sadegh Hosseini

    2013-07-01

    Full Text Available Objective: Effectiveness of Constraint Induced Movement Therapy (CIMT has been approved in adult persons, while it seems that we need many researches with higher levels of evidences in children. This research aimed to identify the efficacy of CIMT on unimanual and bimanual functions in children with Cerebral Palsy. Materials & Methods: In this interventional study, twenty eight participants were selected that had the inclusion and exclusion criteria and then divided into two groups ofCIMT and control. The intervention was provided on 10 out of 12 consecutive days in CIMT group and another group was received occupational therapy services. Assessment tools which were utilized in the survey were Bruininks-Oseretsky Motor Proficiency Test, Caregiver Functional Use Survey (CFUS, Jebsen-Taylor Test in Hand Function. In order to compare two groups Independent t-test was used and to compare each group from pre-test to post-test paired t-test was utilized. Results: Data showed significant differences between two groups in dexterity, bilateral coordination, bimanual coordination, bimanual function, unimanual function and Caregiver Functional Use Survey (how well & how frequently (P<0.05. Also comparison between pre-test and post-test in each group showed improvement in most of variables in research. Conclusion: protocol of child friendly Constraint Induced Movement Therapywas lead to improvement in either unimanual or bimanual hand functions in children with cerebral palsy.

  3. Lysosomal Exoglycosidase Profile and Secretory Function in the Salivary Glands of Rats with Streptozotocin-Induced Diabetes

    OpenAIRE

    Maciejczyk, Mateusz; Kossakowska, Agnieszka; Szulimowska, Julita; Klimiuk, Anna; Knaś, Małgorzata; Car, Halina; Niklińska, Wiesława; Ładny, Jerzy Robert; Chabowski, Adrian; Zalewska, Anna

    2017-01-01

    Before this study, there had been no research evaluating the relationship between a lysosomal exoglycosidase profile and secretory function in the salivary glands of rats with streptozotocin- (STZ-) induced type 1 diabetes. In our work, rats were divided into 4 groups of 8 animals each: control groups (C2, C4) and diabetic groups (STZ2, STZ4). The secretory function of salivary glands—nonstimulated and stimulated salivary flow, α-amylase, total protein—and salivary exoglycosidase activities—N...

  4. Functionalization of embedded thiol-ene waveguides for evanescent wave induced fluorescence detection in a microfluidic device

    DEFF Research Database (Denmark)

    Feidenhans'l, Nikolaj Agentoft; Jensen, Thomas Glasdam; Lafleur, Josiane P.

    2013-01-01

    We demonstrate the use of functional surface groups inherently present on off-stoichiometric thiol−ene polymers, for site-specific immobilization of biomolecules and detection by evanescent wave-induced fluorescence. An optofluidic chip featuring an embedded thiol−ene waveguide was selectively...... functionalized with biotin using photografting. The biotin was used for immobilization of fluorescently labelled streptavidin, and experiments revealed a linear correlation between streptavidin concentration and fluorescent intensity. To further demonstrate the attractiveness of using thiol−ene for optofluidic...

  5. The role of MAC1 in diesel exhaust particle-induced microglial activation and loss of dopaminergic neuron function.

    Science.gov (United States)

    Levesque, Shannon; Taetzsch, Thomas; Lull, Melinda E; Johnson, Jo Anne; McGraw, Constance; Block, Michelle L

    2013-06-01

    Increasing reports support that air pollution causes neuroinflammation and is linked to central nervous system (CNS) disease/damage. Diesel exhaust particles (DEP) are a major component of urban air pollution, which has been linked to microglial activation and Parkinson's disease-like pathology. To begin to address how DEP may exert CNS effects, microglia and neuron-glia cultures were treated with either nanometer-sized DEP (neuron function was assessed. All three treatments showed enhanced ameboid microglia morphology, increased H2 O2 production, and decreased DA uptake. Mechanistic inquiry revealed that the scavenger receptor inhibitor fucoidan blocked DEP internalization in microglia, but failed to alter DEP-induced H2 O2 production in microglia. However, pre-treatment with the MAC1/CD11b inhibitor antibody blocked microglial H2 O2 production in response to DEP. MAC1(-/-) mesencephalic neuron-glia cultures were protected from DEP-induced loss of DA neuron function, as measured by DA uptake. These findings support that DEP may activate microglia through multiple mechanisms, where scavenger receptors regulate internalization of DEP and the MAC1 receptor is mandatory for both DEP-induced microglial H2 O2 production and loss of DA neuron function. © 2013 International Society for Neurochemistry.

  6. Processing Semblances Induced through Inter-Postsynaptic Functional LINKs, Presumed Biological Parallels of K-Lines Proposed for Building Artificial Intelligence

    Science.gov (United States)

    Vadakkan, Kunjumon I.

    2011-01-01

    The internal sensation of memory, which is available only to the owner of an individual nervous system, is difficult to analyze for its basic elements of operation. We hypothesize that associative learning induces the formation of functional LINK between the postsynapses. During memory retrieval, the activation of either postsynapse re-activates the functional LINK evoking a semblance of sensory activity arriving at its opposite postsynapse, nature of which defines the basic unit of internal sensation – namely, the semblion. In neuronal networks that undergo continuous oscillatory activity at certain levels of their organization re-activation of functional LINKs is expected to induce semblions, enabling the system to continuously learn, self-organize, and demonstrate instantiation, features that can be utilized for developing artificial intelligence (AI). This paper also explains suitability of the inter-postsynaptic functional LINKs to meet the expectations of Minsky’s K-lines, basic elements of a memory theory generated to develop AI and methods to replicate semblances outside the nervous system. PMID:21845180

  7. High efficient differentiation of functional hepatocytes from porcine induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Ying Ao

    Full Text Available Hepatocyte transplantation is considered to be a promising therapy for patients with liver diseases. Induced pluripotent stem cells (iPSCs provide an unlimited source for the generation of functional hepatocytes. In this study, we generated iPSCs from porcine ear fibroblasts (PEFs by overexpressing Sox2, Klf4, Oct4, and c-Myc (SKOM, and developed a novel strategy for the efficient differentiation of hepatocyte-like cells from porcine iPSCs by following the processes of early liver development. The differentiated cells displayed the phenotypes of hepatocytes, exhibited classic hepatocyte-associated bio-functions, such as LDL uptake, glycogen storage and urea secretion, as well as possessed the metabolic activities of cytochrome P-450 (CYP 3A and 2C. Furthermore, we compared the hepatocyte differentiation efficacy of our protocol with another published method, and the results demonstrated that our differentiation strategy could significantly improve the generation of morphological and functional hepatocyte-like cells from porcine iPSCs. In conclusion, this study establishes an efficient method for in vitro generation of functional hepatocytes from porcine iPSCs, which could represent a promising cell source for preclinical testing of cell-based therapeutics for liver failure and for pharmacological applications.

  8. A tamoxifen inducible knock-in allele for investigation of E2A function

    Directory of Open Access Journals (Sweden)

    Kondo Motonari

    2009-10-01

    Full Text Available Abstract Background E-proteins are transcription factors important for the development of a variety of cell types, including neural, muscle and lymphocytes of the immune system. E2A, the best characterized E-protein family member in mammals, has been shown to have stage specific roles in cell differentiation, lineage commitment, proliferation, and survival. However, due to the complexity of E2A function, it is often difficult to separate these roles using conventional genetic approaches. Here, we have developed a new genetic model for reversible control of E2A protein activity at physiological levels. This system was created by inserting a tamoxifen-responsive region of the estrogen receptor (ER at the carboxyl end of the tcfe2a gene to generate E2AER fusion proteins. We have characterized and analyzed the efficiency and kinetics of this inducible E2AER system in the context of B cell development. Results B cell development has been shown previously to be blocked at an early stage in E2A deficient animals. Our E2AER/ER mice demonstrated this predicted block in B cell development, and E2AER DNA binding activity was not detected in the absence of ligand. In vitro studies verified rapid induction of E2AER DNA binding activity upon tamoxifen treatment. While tamoxifen treatment of E2AER/ER mice showed inefficient rescue of B cell development in live animals, direct exposure of bone marrow cells to tamoxifen in an ex vivo culture was sufficient to rescue and support early B cell development from the pre-proB cell stage. Conclusion The E2AER system provides inducible and reversible regulation of E2A function at the protein level. Many previous studies have utilized over-expression systems to induce E2A function, which are complicated by the toxicity often resulting from high levels of E2A. The E2AER model instead restores E2A activity at an endogenous level and in addition, allows for tight regulation of the timing of induction. These features make

  9. Intracavernous Delivery of a Designed Angiopoietin-1 Variant Rescues Erectile Function by Enhancing Endothelial Regeneration in the Streptozotocin-Induced Diabetic Mouse

    Science.gov (United States)

    Jin, Hai-Rong; Kim, Woo Jean; Song, Jae Sook; Piao, Shuguang; Choi, Min Ji; Tumurbaatar, Munkhbayar; Shin, Sun Hwa; Yin, Guo Nan; Koh, Gou Young; Ryu, Ji-Kan; Suh, Jun-Kyu

    2011-01-01

    OBJECTIVE Patients with diabetic erectile dysfunction often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase-5 inhibitors. We examined the effectiveness of the potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1, in promoting cavernous endothelial regeneration and restoring erectile function in diabetic animals. RESEARCH DESIGN AND METHODS Four groups of mice were used: controls; streptozotocin (STZ)-induced diabetic mice; STZ-induced diabetic mice treated with repeated intracavernous injections of PBS; and STZ-induced diabetic mice treated with COMP-Ang1 protein (days −3 and 0). Two and 4 weeks after treatment, we measured erectile function by electrical stimulation of the cavernous nerve. The penis was harvested for histologic examinations, Western blot analysis, and cGMP quantification. We also performed a vascular permeability test. RESULTS Local delivery of the COMP-Ang1 protein significantly increased cavernous endothelial proliferation, endothelial nitric oxide (NO) synthase (NOS) phosphorylation, and cGMP expression compared with that in the untreated or PBS-treated STZ-induced diabetic group. The changes in the group that received COMP-Ang1 restored erectile function up to 4 weeks after treatment. Endothelial protective effects, such as marked decreases in the expression of p47phox and inducible NOS, in the generation of superoxide anion and nitrotyrosine, and in the number of apoptotic cells in the corpus cavernosum tissue, were noted in COMP-Ang1–treated STZ-induced diabetic mice. An intracavernous injection of COMP-Ang1 completely restored endothelial cell-cell junction proteins and decreased cavernous endothelial permeability. COMP-Ang1–induced promotion of cavernous angiogenesis and erectile function was abolished by the NOS inhibitor, N-nitro-L-arginine methyl ester, but not by the NADPH oxidase inhibitor, apocynin. CONCLUSIONS These findings support the concept of cavernous

  10. Functional Toll-like receptor 4 expressed in lactotrophs mediates LPS-induced proliferation in experimental pituitary hyperplasia

    International Nuclear Information System (INIS)

    Sabatino, María Eugenia; Sosa, Liliana del Valle; Petiti, Juan Pablo; Mukdsi, Jorge Humberto; Mascanfroni, Iván Darío; Pellizas, Claudia Gabriela; Gutiérrez, Silvina; Torres, Alicia Inés; De Paul, Ana Lucía

    2013-01-01

    Toll like receptor 4 (TLR4) has been characterized for its ability to recognize bacterial endotoxin lipopolysaccharide (LPS). Considering that infections or inflammatory processes might contribute to the progression of pituitary tumors, we analyzed the TLR4 functional role by evaluating the LPS effect on lactotroph proliferation in primary cultures from experimental pituitary tumors, and examined the involvement of PI3K-Akt and NF-κB activation in this effect. In addition, the role of 17β-estradiol as a possible modulator of LPS-induced PRL cell proliferation was further investigated. In estrogen-induced hyperplasic pituitaries, LPS triggered lactotroph cell proliferation. However, endotoxin failed to increase the number of lactotrophs taking up BrdU in normal pituitaries. Moreover, incubation with anti-TLR4 antibody significantly reduced LPS-induced lactotroph proliferation, suggesting a functional role of this receptor. As a sign of TLR4 activation, an LPS challenge increased IL-6 release in normal and tumoral cells. By flow cytometry, TLR4 baseline expression was revealed at the plasma membrane of tumoral lactotrophs, without changes noted in the percentage of double PRL/TLR4 positive cells after LPS stimulus. Increases in TLR4 intracellular expression were detected as well as rises in CD14, p-Akt and NF-κB after an LPS challenge, as assessed by western blotting. The TLR4/PRL and PRL/NF-κB co-localization was also corroborated by immunofluorescence and the involvement of PI3K/Akt signaling in lactotroph proliferation and IL-6 release was revealed through the PI3K inhibitor Ly-294002. In addition, 17β-estradiol attenuated the LPS-evoked increase in tumoral lactotroph proliferation and IL-6 release. Collectively these results demonstrate the presence of functional TLR4 in lactotrophs from estrogen-induced hyperplasic pituitaries, which responded to the proliferative stimulation and IL-6 release induced by LPS through TLR4/CD14, with a contribution of the PI3K

  11. Functional Toll-like receptor 4 expressed in lactotrophs mediates LPS-induced proliferation in experimental pituitary hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    Sabatino, María Eugenia; Sosa, Liliana del Valle; Petiti, Juan Pablo; Mukdsi, Jorge Humberto [Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Av. Enrique Barros y Enfermera Gordillo, Ciudad Universitaria, CP 5000, Córdoba (Argentina); Mascanfroni, Iván Darío; Pellizas, Claudia Gabriela [Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Av. Haya de la Torre y Medina Allende, Ciudad Universitaria, CP 5000, Córdoba (Argentina); Gutiérrez, Silvina; Torres, Alicia Inés [Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Av. Enrique Barros y Enfermera Gordillo, Ciudad Universitaria, CP 5000, Córdoba (Argentina); De Paul, Ana Lucía, E-mail: adepaul@cmefcm.uncor.edu [Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Av. Enrique Barros y Enfermera Gordillo, Ciudad Universitaria, CP 5000, Córdoba (Argentina)

    2013-11-15

    Toll like receptor 4 (TLR4) has been characterized for its ability to recognize bacterial endotoxin lipopolysaccharide (LPS). Considering that infections or inflammatory processes might contribute to the progression of pituitary tumors, we analyzed the TLR4 functional role by evaluating the LPS effect on lactotroph proliferation in primary cultures from experimental pituitary tumors, and examined the involvement of PI3K-Akt and NF-κB activation in this effect. In addition, the role of 17β-estradiol as a possible modulator of LPS-induced PRL cell proliferation was further investigated. In estrogen-induced hyperplasic pituitaries, LPS triggered lactotroph cell proliferation. However, endotoxin failed to increase the number of lactotrophs taking up BrdU in normal pituitaries. Moreover, incubation with anti-TLR4 antibody significantly reduced LPS-induced lactotroph proliferation, suggesting a functional role of this receptor. As a sign of TLR4 activation, an LPS challenge increased IL-6 release in normal and tumoral cells. By flow cytometry, TLR4 baseline expression was revealed at the plasma membrane of tumoral lactotrophs, without changes noted in the percentage of double PRL/TLR4 positive cells after LPS stimulus. Increases in TLR4 intracellular expression were detected as well as rises in CD14, p-Akt and NF-κB after an LPS challenge, as assessed by western blotting. The TLR4/PRL and PRL/NF-κB co-localization was also corroborated by immunofluorescence and the involvement of PI3K/Akt signaling in lactotroph proliferation and IL-6 release was revealed through the PI3K inhibitor Ly-294002. In addition, 17β-estradiol attenuated the LPS-evoked increase in tumoral lactotroph proliferation and IL-6 release. Collectively these results demonstrate the presence of functional TLR4 in lactotrophs from estrogen-induced hyperplasic pituitaries, which responded to the proliferative stimulation and IL-6 release induced by LPS through TLR4/CD14, with a contribution of the PI3K

  12. Interaction between graviception and carotid baroreflex function in humans during parabolic flight-induced microgravity.

    Science.gov (United States)

    Ogoh, Shigehiko; Marais, Michaël; Lericollais, Romain; Denise, Pierre; Raven, Peter B; Normand, Hervé

    2018-05-10

    The aim of the present study was to assess carotid baroreflex (CBR) during acute changes in otolithic activity in humans. To address this question, we designed a set of experiments to identify the modulatory effects of microgravity on CBR function at a tilt angle of -2{degree sign}, which was identified to minimize changes in central blood volume during parabolic flight. During parabolic flight at 0g and 1g, CBR function curves were modelled from the heart rate (HR) and mean arterial pressure (MAP) responses to rapid pulse trains of neck pressure (NP) and neck suction (NS) ranging from +40 to -80 Torr; CBR control of HR (carotid-HR) and MAP (carotid-MAP) baroreflex function curves, respectively. The maximal gain (G max ) of both carotid-HR and carotid-MAP baroreflex function curves were augmented during microgravity compared to 1g (carotid-HR, -0.53 to -0.80 beats/min/mmHg, Pflight-induced acute change of otolithic activity may modify CBR function and identifies that the vestibular system contributes to blood pressure regulation under fluctuations in gravitational forces.

  13. Effects of mesenchymal stem cells from human induced pluripotent stem cells on differentiation, maturation, and function of dendritic cells.

    Science.gov (United States)

    Gao, Wen-Xiang; Sun, Yue-Qi; Shi, Jianbo; Li, Cheng-Lin; Fang, Shu-Bin; Wang, Dan; Deng, Xue-Quan; Wen, Weiping; Fu, Qing-Ling

    2017-03-02

    Mesenchymal stem cells (MSCs) have potent immunomodulatory effects on multiple immune cells and have great potential in treating immune disorders. Induced pluripotent stem cells (iPSCs) serve as an unlimited and noninvasive source of MSCs, and iPSC-MSCs have been reported to have more advantages and exhibit immunomodulation on T lymphocytes and natural killer cells. However, the effects of iPSC-MSCs on dendritic cells (DCs) are unclear. The aim of this study is to investigate the effects of iPSC-MSCs on the differentiation, maturation, and function of DCs. Human monocyte-derived DCs were induced and cultured in the presence or absence of iPSC-MSCs. Flow cytometry was used to analyze the phenotype and functions of DCs, and enzyme-linked immunosorbent assay (ELISA) was used to study cytokine production. In this study, we successfully induced MSCs from different clones of human iPSCs. iPSC-MSCs exhibited a higher proliferation rate with less cell senescence than BM-MSCs. iPSC-MSCs inhibited the differentiation of human monocyte-derived DCs by both producing interleukin (IL)-10 and direct cell contact. Furthermore, iPSC-MSCs did not affect immature DCs to become mature DCs, but modulated their functional properties by increasing their phagocytic ability and inhibiting their ability to stimulate proliferation of lymphocytes. More importantly, iPSC-MSCs induced the generation of IL-10-producing regulatory DCs in the process of maturation, which was mostly mediated by a cell-cell contact mechanism. Our results indicate an important role for iPSC-MSCs in the modulation of DC differentiation and function, supporting the clinical application of iPSC-MSCs in DC-mediated immune diseases.

  14. Orally active multi-functional antioxidants are neuroprotective in a rat model of light-induced retinal damage.

    Directory of Open Access Journals (Sweden)

    James Randazzo

    Full Text Available Progression of age-related macular degeneration has been linked to iron dysregulation and oxidative stress that induce apoptosis of neural retinal cells. Since both antioxidants and chelating agents have been reported to reduce the progression of retinal lesions associated with AMD in experimental animals, the present study evaluates the ability of multi-functional antioxidants containing functional groups that can independently chelate redox metals and quench free radicals to protect the retina against light-induced retinal degeneration, a rat model of dry atrophic AMD.Proof of concept studies were conducted to evaluate the ability of 4-(5-hydroxypyrimidin-2-yl-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 4 and 4-(5-hydroxy-4,6-dimethoxypyrimidin-2-yl-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 8 to reduce retinal damage in 2-week dark adapted Wistar rats exposed to 1000 lx of light for 3 hours. Assessment of the oxidative stress markers 4- hydroxynonenal and nitrotyrosine modified proteins and Thioredoxin by ELISA and Western blots indicated that these compounds reduced the oxidative insult caused by light exposure. The beneficial antioxidant effects of these compounds in providing significant functional and structural protection were confirmed by electroretinography and quantitative histology of the retina.The present study suggests that multi-functional compounds may be effective candidates for preventive therapy of AMD.

  15. Evidence of changes in alpha-1/AT1 receptor function generated by diet-induced obesity.

    Science.gov (United States)

    Juarez, Esther; Tufiño, Cecilia; Querejeta, Enrique; Bracho-Valdes, Ismael; Bobadilla-Lugo, Rosa A

    2017-11-01

    To study whether hypercaloric diet-induced obesity deteriorates vascular contractility of rat aorta through functional changes in α 1 adrenergic and/or AT1 Angiotensin II receptors. Angiotensin II- or phenylephrine-induced contraction was tested on isolated aorta rings with and without endothelium from female Wistar rats fed for 7 weeks with hypercaloric diet or standard diet. Vascular expression of Angiotensin II Receptor type 1 (AT1R), Angiotensin II Receptor type 2 (AT2R), Cyclooxygenase-1 (COX-1), Cyclooxygenase-2 (COX-2), inducible Nitric Oxide Synthase (iNOS) and endothelial Nitric Oxide Synthase (eNOS), as well as blood pressure, glucose, insulin and angiotensin II blood levels were measured. Diet-induced obesity did not significantly change agonist-induced contractions (Emax and pD 2 hypercaloric diet vs standard diet n.s.d.) of both intact (e+) or endothelium free (e-) vessels but significantly decrease both phenylephrine and angiotensin II contraction (Emax p obesity did not change angiotensin II AT1, AT2 receptor proteins expression but reduced COX-1 and NOS2 ( p obesity produces alterations in vascular adrenergic and angiotensin II receptor dynamics that suggest an endothelium-dependent adrenergic/angiotensin II crosstalk. These changes reflect early-stage vascular responses to obesity.

  16. Dibutyltin disrupts glucocorticoid receptor function and impairs glucocorticoid-induced suppression of cytokine production.

    Directory of Open Access Journals (Sweden)

    Christel Gumy

    Full Text Available BACKGROUND: Organotins are highly toxic and widely distributed environmental chemicals. Dibutyltin (DBT is used as stabilizer in the production of polyvinyl chloride plastics, and it is also the major metabolite formed from tributyltin (TBT in vivo. DBT is immunotoxic, however, the responsible targets remain to be defined. Due to the importance of glucocorticoids in immune-modulation, we investigated whether DBT could interfere with glucocorticoid receptor (GR function. METHODOLOGY: We used HEK-293 cells transiently transfected with human GR as well as rat H4IIE hepatoma cells and native human macrophages and human THP-1 macrophages expressing endogenous receptor to study organotin effects on GR function. Docking of organotins was used to investigate the binding mechanism. PRINCIPAL FINDINGS: We found that nanomolar concentrations of DBT, but not other organotins tested, inhibit ligand binding to GR and its transcriptional activity. Docking analysis indicated that DBT inhibits GR activation allosterically by inserting into a site close to the steroid-binding pocket, which disrupts a key interaction between the A-ring of the glucocorticoid and the GR. DBT inhibited glucocorticoid-induced expression of phosphoenolpyruvate carboxykinase (PEPCK and tyrosine-aminotransferase (TAT and abolished the glucocorticoid-mediated transrepression of TNF-alpha-induced NF-kappaB activity. Moreover, DBT abrogated the glucocorticoid-mediated suppression of interleukin-6 (IL-6 and TNF-alpha production in lipopolysaccharide (LPS-stimulated native human macrophages and human THP-1 macrophages. CONCLUSIONS: DBT inhibits ligand binding to GR and subsequent activation of the receptor. By blocking GR activation, DBT may disturb metabolic functions and modulation of the immune system, providing an explanation for some of the toxic effects of this organotin.

  17. A hypercrosslinking-induced self-assembly strategy for preparation of advanced hierarchical porous polymers with customizable functional components.

    Science.gov (United States)

    Xu, Hongji; Wu, Jinlun; Zheng, Bingna; Mai, Weicong; Xu, Fei; Chen, Luyi; Liu, Hao; Fu, Ruowen; Wu, Dingcai; Matyjaszewski, Krzysztof

    2017-05-09

    The fabrication of advanced hierarchical porous polymers with a unique 3D nanonetwork structure composed of functional core-microporous shell nanoparticles was reported based on the development of a simple and efficient hypercrosslinking-induced self-assembly strategy.

  18. Effects of atomic bomb radiation on differentiation of B lymphocytes and on the function of concanavalin A-induced suppressor T lymphocytes

    International Nuclear Information System (INIS)

    Yamada, Y.; Neriishi, S.; Ishimaru, T.; Shimba, N.; Hamilton, H.B.; Ohgushi, Y.; Koyanagi, M.; Ichimaru, M.

    1985-01-01

    The differentiation of peripheral blood B lymphocytes into immunoglobulin-producing cells (Ig-PC) by pokeweed mitogen (PWM) and the function of concanavalin A (Con A)-induced suppressor T lymphocytes were examined to elucidate the late effects of atomic bomb radiation. A total of 140 individuals, 70 with an exposure dose of 100 rad or more and an equal number with an exposure dose of 0 rad matched by sex and age, were selected from the Nagasaki Adult Health Study (AHS) sample. Both the differentiation of peripheral blood B lymphocytes into Ig-PC by PWM and the function of Con A-induced suppressor T lymphocytes tended to be more depressed in the exposed group than in the control group, but a statistically significant difference could not be observed between the two groups. The function of Con A-induced suppressor T lymphocytes tended to decrease with age, but a statistical significance was detected only for percentage suppression against IgM-PC

  19. Comparative analysis of excretory-secretory antigens of Trichinella spiralis and Trichinella britovi muscle larvae by two-dimensional difference gel electrophoresis and immunoblotting.

    Science.gov (United States)

    Bien, Justyna; Näreaho, Anu; Varmanen, Pekka; Gozdzik, Katarzyna; Moskwa, Bozena; Cabaj, Wladyslaw; Nyman, Tuula A; Savijoki, Kirsi

    2012-02-11

    Trichinellosis is a zoonotic disease in humans caused by Trichinella spp. The present study was undertaken to discover excretory-secretory (E-S) proteins from T. spiralis and T. britovi muscle larvae (ML) that hold promise for species-specific diagnostics. To that end, the purified E-S proteins were analyzed by fluorescent two-dimensional difference gel electrophoresis (2-D DIGE) coupled with protein identification by liquid chromatography-tandem mass spectrometry (LC-MS/MS). To search for immunoreactive proteins that are specifically recognized by host antibodies the E-S proteins were subjected to two-dimensional (2-DE) immunoblotting with antisera derived from pigs experimentally infected with T. spiralis or T. britovi. According to 2-D DIGE analysis, a total of twenty-two proteins including potentially immunogenic proteins and proteins produced only by one of the two Trichinella species were subjected to LC-MS/MS for protein identification. From these proteins seventeen could be identified, of which many were identified in multiple spots, suggesting that they have undergone post-translational modification, possibly involving glycosylation and/or proteolysis. These proteins included 5'-nucleotidase, serine-type protease/proteinase, and p43 glycoprotein (gp43) as well as 49 kDa E-S protein (p49). Our findings also suggest that some of the commonly identified proteins were post-translationally modified to different extents, which in certain cases seemed to result in species-specific modification. Both commonly and specifically recognized immunoreactive proteins were identified by 2-DE immunoblotting; shared antigens were identified as gp43 and different protease variants, whereas those specific to T. britovi included multiple isoforms of the 5'-nucleotidase. Both 2-D DIGE and 2-DE immunoblotting approaches indicate that T. spiralis and T. britovi produce somewhat distinctive antigen profiles, which contain E-S antigens with potential as species-specific diagnostic

  20. Accelerated Testing and Modeling of Potential-Induced Degradation as a Function of Temperature and Relative Humidity

    DEFF Research Database (Denmark)

    Hacke, Peter; Spataru, Sergiu; Terwilliger, Kent

    2015-01-01

    An acceleration model based on the Peck equation was applied to power performance of crystalline silicon cell modules as a function of time and of temperature and humidity, which are the two main environmental stress factors that promote potential-induced degradation (PID). This model was derived...

  1. Accelerated Testing and Modeling of Potential-Induced Degradation as a Function of Temperature and Relative Humidity

    DEFF Research Database (Denmark)

    Hacke, Peter; Spataru, Sergiu; Terwilliger, Kent

    2015-01-01

    An acceleration model based on the Peck equation was applied to power performance of crystalline silicon cell modules as a function of time and of temperature and humidity, the two main environmental stress factors that promote potential-induced degradation. This model was derived from module pow...

  2. Clinical studies on Bell's palsy

    International Nuclear Information System (INIS)

    Yamada, Yoshio

    1985-01-01

    The purpose of this study was to evaluate the diagnostic value of the salivary gland scintigraphy using sup(99m)Tc-pertechnetate for the prognosis of Bell's palsy. The salivary gland scintigraphy was performed in 40 patients with Bell's palsy and 15 normal subjects. After intravenous injection of 10 mCt of sup(99m)Tc-pertechnetate, sequential scintigrams were taken with a scintillation camera every one minute for 25 minutes. At 15 minutes after injection, both of normal subjects and patients were given ascorbic acid to stimulate the secretion of saliva. By the present method, the time activity curve was examined for the regions of interest over the parotid and submandibular glands and backgrounds. In normal subjects, values of the concentration and excretory ratio between the right and left sides of the parotid and submandibular glands were more than 80%. Some patients with Bell's palsy showed a decreased concentration and/or excretory ratio less than 80% between the normal and affected sides of the parotid glands. This suggests a functional involvement of the facial nerve in the salivary secretion from the parotid glands. On examination within 10 days of the onset of Bell's palsy, 31 cases with complete recovery showed values of the concentration ratio and/or excretory ratio more than 80% between the normal and affected sides of the submandibular glands. In contrast, 9 cases with imcomplete recovery showed low values of the concentration ratio and excretory ratio less than 80%. In the latter, more active treatments such as decompression operation should be considerd in the early stage of the palsy. The salivary scintigraphy using sup(99m)Tc-pertechnetate is more valuable as an early prognostic indicator for Bell's palsy compared with other prognostic tests such as the lid vibration test, the stapedial reflex test, the electrogustometry, the nerve excitability test and the evoked electromyography. (author)

  3. Chronic exposure to Tributyltin induces brain functional damage in juvenile common carp (Cyprinus carpio.

    Directory of Open Access Journals (Sweden)

    Zhi-Hua Li

    Full Text Available The aim of the present study was to investigate the effect of Tributyltin (TBT on brain function and neurotoxicity of freshwater teleost. The effects of long-term exposure to TBT on antioxidant related indices (MDA, malondialdehyde; SOD, superoxide dismutase; CAT, catalase; GR, glutathione reductase; GPx, glutathione peroxidase, Na+-K+-ATPase and neurological parameters (AChE, acetylcholinesterase; MAO, monoamine oxidase; NO, nitric oxide in the brain of common carp were evaluated. Fish were exposed to sublethal concentrations of TBT (75 ng/L, 0.75 μg/L and 7.5 μg/L for 15, 30, and 60 days. Based on the results, a low level and short-term TBT-induced stress could not induce the notable responses of the fish brain, but long-term exposure (more than 15 days to TBT could lead to obvious physiological-biochemical responses (based on the measured parameters. The results also strongly indicated that neurotoxicity of TBT to fish. Thus, the measured physiological responses in fish brain could provide useful information to better understand the mechanisms of TBT-induced bio-toxicity.

  4. Chronic Exposure to Tributyltin Induces Brain Functional Damage in Juvenile Common Carp (Cyprinus carpio)

    Science.gov (United States)

    Li, Zhi-Hua; Li, Ping; Shi, Ze-Chao

    2015-01-01

    The aim of the present study was to investigate the effect of Tributyltin (TBT) on brain function and neurotoxicity of freshwater teleost. The effects of long-term exposure to TBT on antioxidant related indices (MDA, malondialdehyde; SOD, superoxide dismutase; CAT, catalase; GR, glutathione reductase; GPx, glutathione peroxidase), Na+-K+-ATPase and neurological parameters (AChE, acetylcholinesterase; MAO, monoamine oxidase; NO, nitric oxide) in the brain of common carp were evaluated. Fish were exposed to sublethal concentrations of TBT (75 ng/L, 0.75 μg/L and 7.5 μg/L) for 15, 30, and 60 days. Based on the results, a low level and short-term TBT-induced stress could not induce the notable responses of the fish brain, but long-term exposure (more than 15 days) to TBT could lead to obvious physiological-biochemical responses (based on the measured parameters). The results also strongly indicated that neurotoxicity of TBT to fish. Thus, the measured physiological responses in fish brain could provide useful information to better understand the mechanisms of TBT-induced bio-toxicity. PMID:25879203

  5. Chronic exposure to Tributyltin induces brain functional damage in juvenile common carp (Cyprinus carpio).

    Science.gov (United States)

    Li, Zhi-Hua; Li, Ping; Shi, Ze-Chao

    2015-01-01

    The aim of the present study was to investigate the effect of Tributyltin (TBT) on brain function and neurotoxicity of freshwater teleost. The effects of long-term exposure to TBT on antioxidant related indices (MDA, malondialdehyde; SOD, superoxide dismutase; CAT, catalase; GR, glutathione reductase; GPx, glutathione peroxidase), Na+-K+-ATPase and neurological parameters (AChE, acetylcholinesterase; MAO, monoamine oxidase; NO, nitric oxide) in the brain of common carp were evaluated. Fish were exposed to sublethal concentrations of TBT (75 ng/L, 0.75 μg/L and 7.5 μg/L) for 15, 30, and 60 days. Based on the results, a low level and short-term TBT-induced stress could not induce the notable responses of the fish brain, but long-term exposure (more than 15 days) to TBT could lead to obvious physiological-biochemical responses (based on the measured parameters). The results also strongly indicated that neurotoxicity of TBT to fish. Thus, the measured physiological responses in fish brain could provide useful information to better understand the mechanisms of TBT-induced bio-toxicity.

  6. Baroreflex deficiency induces additional impairment of vagal tone, diastolic function and calcium handling proteins after myocardial infarction

    Science.gov (United States)

    Mostarda, Cristiano; Rodrigues, Bruno; Medeiros, Alessandra; Moreira, Edson D; Moraes-Silva, Ivana C; Brum, Patricia C; Angelis, Katia De; Irigoyen, Maria-Cláudia

    2014-01-01

    Baroreflex dysfunction has been considered an important mortality predictor after myocardial infarction (MI). However, the impact of baroreflex deficiency prior to MI on tonic autonomic control and cardiac function, and on the profile of proteins associated with intracellular calcium handling has not yet been studied. The aim of the present study was to analyze how the impairment of baroreflex induced by sinoaortic denervation (SAD) prior to MI in rats affects the tonic autonomic control, ventricular function and cardiomyocyte calcium handling proteins. After 15 days of following or SAD surgery, rats underwent MI. Echocardiographic, hemodynamic, autonomic and molecular evaluations were performed 90 days after MI. Baroreflex impairment led to additional damage on: left ventricular remodeling, diastolic function, vagal tonus and intrinsic heart rate after MI. The loss of vagal component of the arterial baroreflex and vagal tonus were correlated with changes in the cardiac proteins involved in intracellular calcium homeostasis. Furthermore, additional increase in sodium calcium exchanger expression levels was associated with impaired diastolic function in experimental animals. Our findings strongly suggest that previous arterial baroreflex deficiency may induce additional impairment of vagal tonus, which was associated with calcium handling proteins abnormalities, probably triggering ventricular diastolic dysfunction after MI in rats. PMID:24936224

  7. Ginger extract inhibits LPS induced macrophage activation and function

    Directory of Open Access Journals (Sweden)

    Bruch David

    2008-01-01

    Full Text Available Abstract Background Macrophages play a dual role in host defence. They act as the first line of defence by mounting an inflammatory response to antigen exposure and also act as antigen presenting cells and initiate the adaptive immune response. They are also the primary infiltrating cells at the site of inflammation. Inhibition of macrophage activation is one of the possible approaches towards modulating inflammation. Both conventional and alternative approaches are being studied in this regard. Ginger, an herbal product with broad anti inflammatory actions, is used as an alternative medicine in a number of inflammatory conditions like rheumatic disorders. In the present study we examined the effect of ginger extract on macrophage activation in the presence of LPS stimulation. Methods Murine peritoneal macrophages were stimulated by LPS in presence or absence of ginger extract and production of proinflammatory cytokines and chemokines were observed. We also studied the effect of ginger extract on the LPS induced expression of MHC II, B7.1, B7.2 and CD40 molecules. We also studied the antigen presenting function of ginger extract treated macrophages by primary mixed lymphocyte reaction. Results We observed that ginger extract inhibited IL-12, TNF-α, IL-1β (pro inflammatory cytokines and RANTES, MCP-1 (pro inflammatory chemokines production in LPS stimulated macrophages. Ginger extract also down regulated the expression of B7.1, B7.2 and MHC class II molecules. In addition ginger extract negatively affected the antigen presenting function of macrophages and we observed a significant reduction in T cell proliferation in response to allostimulation, when ginger extract treated macrophages were used as APCs. A significant decrease in IFN-γ and IL-2 production by T cells in response to allostimulation was also observed. Conclusion In conclusion ginger extract inhibits macrophage activation and APC function and indirectly inhibits T cell activation.

  8. Suggestion-Induced Modulation of Semantic Priming during Functional Magnetic Resonance Imaging

    Science.gov (United States)

    Ulrich, Martin; Kiefer, Markus; Bongartz, Walter; Grön, Georg; Hoenig, Klaus

    2015-01-01

    Using functional magnetic resonance imaging during a primed visual lexical decision task, we investigated the neural and functional mechanisms underlying modulations of semantic word processing through hypnotic suggestions aimed at altering lexical processing of primes. The priming task was to discriminate between target words and pseudowords presented 200 ms after the prime word which was semantically related or unrelated to the target. In a counterbalanced study design, each participant performed the task once at normal wakefulness and once after the administration of hypnotic suggestions to perceive the prime as a meaningless symbol of a foreign language. Neural correlates of priming were defined as significantly lower activations upon semantically related compared to unrelated trials. We found significant suggestive treatment-induced reductions in neural priming, albeit irrespective of the degree of suggestibility. Neural priming was attenuated upon suggestive treatment compared with normal wakefulness in brain regions supporting automatic (fusiform gyrus) and controlled semantic processing (superior and middle temporal gyri, pre- and postcentral gyri, and supplementary motor area). Hence, suggestions reduced semantic word processing by conjointly dampening both automatic and strategic semantic processes. PMID:25923740

  9. Suggestion-Induced Modulation of Semantic Priming during Functional Magnetic Resonance Imaging.

    Directory of Open Access Journals (Sweden)

    Martin Ulrich

    Full Text Available Using functional magnetic resonance imaging during a primed visual lexical decision task, we investigated the neural and functional mechanisms underlying modulations of semantic word processing through hypnotic suggestions aimed at altering lexical processing of primes. The priming task was to discriminate between target words and pseudowords presented 200 ms after the prime word which was semantically related or unrelated to the target. In a counterbalanced study design, each participant performed the task once at normal wakefulness and once after the administration of hypnotic suggestions to perceive the prime as a meaningless symbol of a foreign language. Neural correlates of priming were defined as significantly lower activations upon semantically related compared to unrelated trials. We found significant suggestive treatment-induced reductions in neural priming, albeit irrespective of the degree of suggestibility. Neural priming was attenuated upon suggestive treatment compared with normal wakefulness in brain regions supporting automatic (fusiform gyrus and controlled semantic processing (superior and middle temporal gyri, pre- and postcentral gyri, and supplementary motor area. Hence, suggestions reduced semantic word processing by conjointly dampening both automatic and strategic semantic processes.

  10. Biological function of activation-induced cytidine deaminase (AID

    Directory of Open Access Journals (Sweden)

    Ritu Kumar

    2014-10-01

    Full Text Available Activation-induced Cytidine Deaminase (AID is an essential regulator of B cell diversification, but its full range of action has until recently been an enigma. Based on homology, it was originally proposed to be an RNA-editing enzyme, but so far, no RNA substrates are known. Rather, it functions by deaminating cytidine, and in this manner, coupled with base-excision repair or mismatch repair machinery, it is a natural mutator. This allows it to play a central role in adaptive immunity, whereby it initiates the processes of class switch recombination and somatic hypermutation to help generate a diverse and high-affinity repertoire of immunoglobulin isotypes. More recently, it has been appreciated that methylated cytidine, already known as a key epigenetic mark on DNA controlling gene expression, can also be a target for AID modification. Coupled with repair machinery, this can facilitate the active removal of methylated DNA. This activity can impact the process of cellular reprogramming, including transition of a somatic cell to pluripotency, which requires major reshuffling of epigenetic memory. Thus, seemingly disparate roles for AID in controlling immune diversity and epigenetic memory have a common mechanistic basis. However, the very activity that is so useful for B cell diversity and cellular reprogramming is dangerous for the integrity of the genome. Thus, AID expression and activity is tightly regulated, and deregulation is associated with diseases including cancer. Here, we review the range of AID functions with a focus on its mechanisms of action and regulation. Major questions remain to be answered concerning how and when AID is targeted to specific loci and how this impacts development and disease.

  11. Remeasurement and compilation of excitation function of proton induced reactions on iron for activation techniques

    International Nuclear Information System (INIS)

    Takacs, S.; Vasvary, L.; Tarkanyi, F.

    1994-01-01

    Excitation functions of proton induced reactions on nat Fe(p, xn) 56 Co have been remeasured in the energy region up to 18 MeV using stacked foil technique and standard high resolution gamma-ray spectrometry at the Debrecen MGC-20E cyclotron. Compilation of the available data measured between 1959 and 1993 has been made. The corresponding excitation functions have been reviewed, critical comparison of all the available data was done to obtain the most accurate data set. The feasibility of the evaluated data set was checked by reproducing experimental calibration curves for TLA by calculation. (orig.)

  12. Combined static-dynamic MR urography for the simultaneous evaluation of morphology and function in urinary tract obstruction. I. Evaluation of the normal status in an animal model

    International Nuclear Information System (INIS)

    Rohrschneider, W.K.; Hoffend, J.; Becker, K.; Clorius, J.H.; Darge, K.; Kooijman, H.; Troeger, J.

    2000-01-01

    Objective. A new approach, combined static-dynamic MR urography is evaluated to determine its potential utility for the functional-morphological diagnosis of paediatric urinary tract obstruction. In this initial investigation we sought to evaluate the procedure by imaging the urinary tract of piglets. Materials and methods. Twenty-nine healthy piglets were studied with MR urography (MRU), 99 m Tc-MAG3 diuretic renal scintigraphy (DRS), ultrasound (US) and excretory urography (EU). The functional and morphological findings were compared. For MRU we combined a respiration-triggered 3D-IR-TSE sequence and a dynamic 2D-FFE sequence after Gd-DTPA injection. Results. MRU depicted the complete urinary tract with superior image quality compared to EU. Calculation of time-intensity curves from the dynamic sequence permitted determination of single kidney function from parenchymal ROIs and urinary excretion using the whole kidney ROI. MRU and DRS showed significant agreement in the assessment of both single kidney function and urinary excretion. Disturbances of urinary drainage were generally caused by an overfilled bladder. Conclusions. Combined static-dynamic MRU is well suited for the depiction of the complete urinary tract and for the determination of individual kidney function and urinary excretion in the piglet. (orig.)

  13. Quantitative Classification of Quartz by Laser Induced Breakdown Spectroscopy in Conjunction with Discriminant Function Analysis

    Directory of Open Access Journals (Sweden)

    A. Ali

    2016-01-01

    Full Text Available A responsive laser induced breakdown spectroscopic system was developed and improved for utilizing it as a sensor for the classification of quartz samples on the basis of trace elements present in the acquired samples. Laser induced breakdown spectroscopy (LIBS in conjunction with discriminant function analysis (DFA was applied for the classification of five different types of quartz samples. The quartz plasmas were produced at ambient pressure using Nd:YAG laser at fundamental harmonic mode (1064 nm. We optimized the detection system by finding the suitable delay time of the laser excitation. This is the first study, where the developed technique (LIBS+DFA was successfully employed to probe and confirm the elemental composition of quartz samples.

  14. Enhanced thermomechanical stability on laser-induced damage by functionally graded layers in quasi-rugate filters

    Science.gov (United States)

    Pu, Yunti; Ma, Ping; Lv, Liang; Zhang, Mingxiao; Lu, Zhongwen; Qiao, Zhao; Qiu, Fuming

    2018-05-01

    Ta2O5-SiO2 quasi-rugate filters with a reasonable optimization of rugate notch filter design were prepared by ion-beam sputtering. The optical properties and laser-induced damage threshold are studied. Compared with the spectrum of HL-stacks, the spectrum of quasi-rugate filters have weaker second harmonic peaks and narrower stopbands. According to the effect of functionally graded layers (FGLs), 1-on-1 and S-on-1 Laser induced damage threshold (LIDT) of quasi-rugate filters are about 22% and 50% higher than those of HL stacks, respectively. Through the analysis of the damage morphologies, laser-induced damage of films under nanosecond multi-pulse are dominated by a combination of thermal shock stress and thermomechanical instability due to nodules. Compared with catastrophic damages, the damage sits of quasi-rugate filters are developed in a moderate way. The damage growth behavior of defect-induced damage sites have been effectively restrained by the structure of FGLs. Generally, FGLs are used to reduce thermal stress by the similar thermal-expansion coefficients of neighboring layers and solve the problems such as instability and cracking raised by the interface discontinuity of nodular boundaries, respectively.

  15. Possible Contribution of Zerumbone-Induced Proteo-Stress to Its Anti-Inflammatory Functions via the Activation of Heat Shock Factor 1.

    Directory of Open Access Journals (Sweden)

    Yoko Igarashi

    Full Text Available Zerumbone is a sesquiterpene present in Zinger zerumbet. Many studies have demonstrated its marked anti-inflammatory and anti-carcinogenesis activities. Recently, we showed that zerumbone binds to numerous proteins with scant selectivity and induces the expression of heat shock proteins (HSPs in hepatocytes. To dampen proteo-toxic stress, organisms have a stress-responsive molecular machinery, known as heat shock response. Heat shock factor 1 (HSF1 plays a key role in this protein quality control system by promoting activation of HSPs. In this study, we investigated whether zerumbone-induced HSF1 activation contributes to its anti-inflammatory functions in stimulated macrophages. Our findings showed that zerumbone increased cellular protein aggregates and promoted nuclear translocation of HSF1 for HSP expression. Interestingly, HSF1 down-regulation attenuated the suppressive effects of zerumbone on mRNA and protein expressions of pro-inflammatory genes, including inducible nitric oxide synthase and interlukin-1β. These results suggest that proteo-stress induced by zerumbone activates HSF1 for exhibiting its anti-inflammatory functions.

  16. Age-dependent methamphetamine-induced alterations in vesicular monoamine transporter-2 function: implications for neurotoxicity.

    Science.gov (United States)

    Truong, Jannine G; Wilkins, Diana G; Baudys, Jakub; Crouch, Dennis J; Johnson-Davis, Kamisha L; Gibb, James W; Hanson, Glen R; Fleckenstein, Annette E

    2005-09-01

    Tens of thousands of adolescents and young adults have used illicit methamphetamine. This is of concern since its high-dose administration causes persistent dopaminergic deficits in adult animal models. The effects in adolescents are less studied. In adult rodents, toxic effects of methamphetamine may result partly from aberrant cytosolic dopamine accumulation and subsequent reactive oxygen species formation. The vesicular monoamine transporter-2 (VMAT-2) sequesters cytoplasmic dopamine into synaptic vesicles for storage and perhaps protection against dopamine-associated oxidative consequences. Accordingly, aberrant VMAT-2 function may contribute to the methamphetamine-induced persistent dopaminergic deficits. Hence, this study examined effects of methamphetamine on VMAT-2 in adolescent (postnatal day 40) and young adult (postnatal day 90) rats. Results revealed that high-dose methamphetamine treatment caused greater acute (within 1 h) decreases in vesicular dopamine uptake in postnatal day 90 versus 40 rats, as determined in a nonmembrane-associated subcellular fraction. Greater basal levels of VMAT-2 at postnatal day 90 versus 40 in this purified fraction seemed to contribute to the larger effect. Basal tissue dopamine content was also greater in postnatal day 90 versus 40 rats. In addition, postnatal day 90 rats were more susceptible to methamphetamine-induced persistent dopaminergic deficits as assessed by measuring VMAT-2 activity and dopamine content 7 days after treatment, even if drug doses were adjusted for age-related pharmacokinetic differences. Together, these data demonstrate dynamic changes in VMAT-2 susceptibility to methamphetamine as a function of development. Implications with regard to methamphetamine-induced dopaminergic deficits, as well as dopamine-associated neurodegenerative disorders such as Parkinson's disease, are discussed.

  17. Salivary function in patients with chronic renal failure undergoing hemodialysis

    International Nuclear Information System (INIS)

    Kaya, M.; Cermik, T.F.; Uestuen, F.; Sen, S.; Berkarda, S.

    2002-01-01

    The aim of this study was to evaluate the changes in salivary gland function in patients with chronic renal failure (CRF) undergoing hemodialysis. The group consisted of 23 patients with CRF (13 female, 10 male; mean age: 40±13 yr) and 14 healthy control subjects (mean age: 40±13 yr). All underwent dynamic salivary gland scintigraphy with gustatory stimulation. After intravenous administration of 99m Tc pertechnetate, first, perfusion images at 2 seconds per frame were acquired for 1 minute, then dynamic images at 1 minute per frame were acquired for 45 minutes. At 30 minutes after injection , 10 ml lemon juice was given for 15 minutes as a gustatory stimulus. We obtained time-activity curves derived from regions of interest centered over the four major salivary glands. The following functional indices were calculated for each gland: the time of maximum radioactivity (T max ) for the prestimulated period, the time of minimum radioactivity (T min ), as an indicator of velocity of secretion after stimulation, and the Lem E 5 % value as an indicator of the secretion function. When the patients with CRF undergoing hemodialysis were compared to the controls, there were statistically significant differences in T max , T min and Lem E 5 % values for bilateral parotid glands, and T min values for bilateral submandibular glands (p max and Lem E 5 % values for bilateral submandibular glands. There were also significant differences in T max and Lem E 5 % values for bilateral parotid glands between mild oral problems and severe oral problems in patients with CRF (undergoing hemodialysis). In this study, prolonged T max and T min values, and decreased Lem E 5 % values for parotid glands and prolonged T min values for submandibular glands on salivary scintigraphy pointed out decreased parenchymatous and excretory function in patients with CRF undergoing hemodialysis. (author)

  18. Effect of tributyltin (TBT) on ATP levels in human natural killer (NK) cells: relationship to TBT-induced decreases in NK function.

    Science.gov (United States)

    Dudimah, Fred D; Odman-Ghazi, Sabah O; Hatcher, Frank; Whalen, Margaret M

    2007-01-01

    The purpose of this study was to investigate the role that tributyltin (TBT)-induced decreases in ATP levels may play in TBT-induced decreases in the tumor lysing (lytic) function of natural killer (NK) cells. NK cells are a subset of lymphocytes that act as an initial immune defense against tumor cells and virally infected cells. TBT is an environmental contaminant that has been detected in human blood, which has been shown to interfere with ATP synthesis. Previous studies have shown that TBT is able to decrease very significantly the lytic function of NK cells. In this study NK cells were exposed to various concentrations of TBT and to two other compounds that interfere with ATP synthesis (rotenone a complex I inhibitor and oligomycin an ATP synthase inhibitor) for various lengths of time before determining the levels of ATP and lytic function. Exposures of NK cells to 10, 25, 50 and 100 nm TBT did not significantly reduce ATP levels after 24 h. However, these same exposures caused significant decreases in cytotoxic function. Studies of brief 1 h exposures to a range of TBT, rotenone and oligomycin concentrations followed by 24 h, 48 h and 6 day periods in compound-free media prior to assaying for ATP levels or cytotoxic function showed that each of the compounds caused persistent decreases in ATP levels and lytic function of NK cells. Exposures to 0.05-5 microm rotenone or oligomycin for 1 h reduced ATP levels by 20-25% but did not have any measurable effect on the ability of NK cells to lyse tumor cells. ATP levels were also decreased by about 20-25% after 24 h or 48 h exposures to rotenone or oligomycin (0.5 microm ), and the lytic function was decreased by about 50%. The results suggest that TBT-induced decreases in ATP levels were not responsible for the loss of cytotoxic function seen at 1 h and 24 h. However, TBT-induced decreases of NK-ATP levels may be at least in part responsible for losses of NK-cytotoxic function seen after 48 h and 6 day exposures

  19. The metabolic enhancer piracetam ameliorates the impairment of mitochondrial function and neurite outgrowth induced by ß-amyloid peptide

    Science.gov (United States)

    Kurz, C; Ungerer, I; Lipka, U; Kirr, S; Schütt, T; Eckert, A; Leuner, K; Müller, WE

    2010-01-01

    Background and purpose: β-Amyloid peptide (Aβ) is implicated in the pathogenesis of Alzheimer's disease by initiating a cascade of events from mitochondrial dysfunction to neuronal death. The metabolic enhancer piracetam has been shown to improve mitochondrial dysfunction following brain aging and experimentally induced oxidative stress. Experimental approach: We used cell lines (PC12 and HEK cells) and murine dissociated brain cells. The protective effects of piracetam in vitro and ex vivo on Aβ-induced impairment of mitochondrial function (as mitochondrial membrane potential and ATP production), on secretion of soluble Aβ and on neurite outgrowth in PC12 cells were investigated. Key results: Piracetam improves mitochondrial function of PC12 cells and acutely dissociated brain cells from young NMRI mice following exposure to extracellular Aβ1-42. Similar protective effects against Aβ1-42 were observed in dissociated brain cells from aged NMRI mice, or mice transgenic for mutant human amyloid precursor protein (APP) treated with piracetam for 14 days. Soluble Aβ load was markedly diminished in the brain of those animals after treatment with piracetam. Aβ production by HEK cells stably transfected with mutant human APP was elevated by oxidative stress and this was reduced by piracetam. Impairment of neuritogenesis is an important consequence of Aβ-induced mitochondrial dysfunction and Aβ-induced reduction of neurite growth in PC12 cells was substantially improved by piracetam. Conclusion and implications: Our findings strongly support the concept of improving mitochondrial function as an approach to ameliorate the detrimental effects of Aβ on brain function. This article is commented on by Moncada, pp. 217–219 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2010.00706.x and to view related papers by Pravdic et al. and Puerta et al. visit http://dx.doi.org/10.1111/j.1476-5381.2010.00698.x and http://dx.doi.org/10.1111/j

  20. Alloxan-induced diabetes reduces sarcolemmal Na+-K+ pump function in rabbit ventricular myocytes.

    Science.gov (United States)

    Hansen, Peter S; Clarke, Ronald J; Buhagiar, Kerrie A; Hamilton, Elisha; Garcia, Alvaro; White, Caroline; Rasmussen, Helge H

    2007-03-01

    The effect of diabetes on sarcolemmal Na(+)-K(+) pump function is important for our understanding of heart disease associated with diabetes and design of its treatment. We induced diabetes characterized by hyperglycemia but no other major metabolic disturbances in rabbits. Ventricular myocytes isolated from diabetic rabbits and controls were voltage clamped and internally perfused with the whole cell patch-clamp technique. Electrogenic Na(+)-K(+) pump current (I(p), arising from the 3:2 Na(+)-to-K(+) exchange ratio) was identified as the shift in holding current induced by Na(+)-K(+) pump blockade with 100 micromol/l ouabain in most experiments. There was no effect of diabetes on I(p) recorded when myocytes were perfused with pipette solutions containing 80 mmol/l Na(+) to nearly saturate intracellular Na(+)-K(+) pump sites. However, diabetes was associated with a significant decrease in I(p) measured when pipette solutions contained 10 mmol/l Na(+). The decrease was independent of membrane voltage but dependent on the intracellular concentration of K(+). There was no effect of diabetes on the sensitivity of I(p) to extracellular K(+). Pump inhibition was abolished by restoration of euglycemia or by in vivo angiotensin II receptor blockade with losartan. We conclude that diabetes induces sarcolemmal Na(+)-K(+) pump inhibition that can be reversed with pharmacological intervention.

  1. Functional magnetic resonances imaging of psychological functions with experimentally induced emotion

    International Nuclear Information System (INIS)

    Grodd, W.; Schneider, F.; Klose, U.; Naegele, T.

    1995-01-01

    In this study a T 2 * FLASH sequence (TR 240 ms, TE 60 ms, slice thickness 4 mm, α=40 , matrix 64x128) was used to investigate changes in signal intensity within the temporal lobe and the amygdala during experimentally induced emotions. Visual stimuli of happy [sad] facial portraits were presented to volunteers to induce changes in the subjects' mood while lying in the tomograph. In agreement with a previous PET study, a significant increase in signal intensity in the left amygdala was found during induction of a sad mood, while no comparable effect was visible during induction of a happy mood. (orig.) [de

  2. Multidetector computed tomography with triple-bolus contrast medium administration protocol for preoperative anatomical and functional assessment of potential living renal donors

    International Nuclear Information System (INIS)

    Knox, Matthew K.; Rivers-Bowerman, Michael D.; Bardgett, Harry P.; Cowan, Nigel C.

    2010-01-01

    To evaluate multidetector computed tomography (MDCT) with a triple-bolus contrast administration protocol for preoperative anatomical and functional assessment of living renal donors. Fifty-five potential living renal donors underwent MDCT of which 27 proceeded to donor nephrectomy. A triple-bolus contrast administration protocol was used for simultaneous acquisition of arterial, nephrographic, and excretory phases. MDCT images were independently reviewed in random order by two radiologists blinded to surgical anatomy findings. Diagnostic accuracy for anatomical variants was quantified by sensitivity and specificity. Differential renal function (DRF) was derived from MDCT for 54 patients and compared with technetium-99 m dimercaptosuccinic acid renography (Tc-99 m DMSA). All triple-bolus MDCT examinations were technically adequate. Accessory renal arteries and veins were identified at surgery in 33% (n = 9/27) and 22% (n = 6/27) of donor kidneys. The mean difference between MDCT-derived DRF and DMSA was 0.8% (95% CI 0.1-1.6) with 95% limits of agreement of -4.6% (95% CI -3.3 to -5.9) to 6.3% (95% CI 5.0-7.6). MDCT delivered a mean (SD, range) radiation dose of 9.5 (3.6, 3.6-17.3) mSv. MDCT with a triple-bolus contrast administration provides accurate anatomical and functional evaluation of living renal donors. (orig.)

  3. Multidetector computed tomography with triple-bolus contrast medium administration protocol for preoperative anatomical and functional assessment of potential living renal donors

    Energy Technology Data Exchange (ETDEWEB)

    Knox, Matthew K. [University of Calgary, Faculty of Medicine, UME Office, Health Sciences Centre, Calgary, Alberta (Canada); Rivers-Bowerman, Michael D. [University of British Columbia, Faculty of Medicine, MD Undergraduate Program, Diamond Health Care Centre, Vancouver, British Columbia (Canada); Bardgett, Harry P. [Bradford Teaching Hospitals, Department of Radiology, Bradford (United Kingdom); Cowan, Nigel C. [The Churchill Hospital, Department of Radiology, Oxford (United Kingdom)

    2010-11-15

    To evaluate multidetector computed tomography (MDCT) with a triple-bolus contrast administration protocol for preoperative anatomical and functional assessment of living renal donors. Fifty-five potential living renal donors underwent MDCT of which 27 proceeded to donor nephrectomy. A triple-bolus contrast administration protocol was used for simultaneous acquisition of arterial, nephrographic, and excretory phases. MDCT images were independently reviewed in random order by two radiologists blinded to surgical anatomy findings. Diagnostic accuracy for anatomical variants was quantified by sensitivity and specificity. Differential renal function (DRF) was derived from MDCT for 54 patients and compared with technetium-99 m dimercaptosuccinic acid renography (Tc-99 m DMSA). All triple-bolus MDCT examinations were technically adequate. Accessory renal arteries and veins were identified at surgery in 33% (n = 9/27) and 22% (n = 6/27) of donor kidneys. The mean difference between MDCT-derived DRF and DMSA was 0.8% (95% CI 0.1-1.6) with 95% limits of agreement of -4.6% (95% CI -3.3 to -5.9) to 6.3% (95% CI 5.0-7.6). MDCT delivered a mean (SD, range) radiation dose of 9.5 (3.6, 3.6-17.3) mSv. MDCT with a triple-bolus contrast administration provides accurate anatomical and functional evaluation of living renal donors. (orig.)

  4. Bone Morphogenic Protein 4-Smad-Induced Upregulation of Platelet-Derived Growth Factor AA Impairs Endothelial Function.

    Science.gov (United States)

    Hu, Weining; Zhang, Yang; Wang, Li; Lau, Chi Wai; Xu, Jian; Luo, Jiang-Yun; Gou, Lingshan; Yao, Xiaoqiang; Chen, Zhen-Yu; Ma, Ronald Ching Wan; Tian, Xiao Yu; Huang, Yu

    2016-03-01

    Bone morphogenic protein 4 (BMP4) is an important mediator of endothelial dysfunction in cardio-metabolic diseases, whereas platelet-derived growth factors (PDGFs) are major angiogenic and proinflammatory mediator, although the functional link between these 2 factors is unknown. The present study investigated whether PDGF mediates BMP4-induced endothelial dysfunction in diabetes mellitus. We generated Ad-Bmp4 to overexpress Bmp4 and Ad-Pdgfa-shRNA to knockdown Pdgfa in mice through tail intravenous injection. SMAD4-shRNA lentivirus, SMAD1-shRNA, and SMAD5 shRNA adenovirus were used for knockdown in human and mouse endothelial cells. We found that PDGF-AA impaired endothelium-dependent vasodilation in aortas and mesenteric resistance arteries. BMP4 upregulated PDGF-AA in human and mouse endothelial cells, which was abolished by BMP4 antagonist noggin or knockdown of SMAD1/5 or SMAD4. BMP4-impared relaxation in mouse aorta was also ameliorated by PDGF-AA neutralizing antibody. Tail injection of Ad-Pdgfa-shRNA ameliorates endothelial dysfunction induced by Bmp4 overexpression (Ad-Bmp4) in vivo. Serum PDGF-AA was elevated in both diabetic patients and diabetic db/db mice compared with nondiabetic controls. Pdgfa-shRNA or Bmp4-shRNA adenovirus reduced serum PDGF-AA concentration in db/db mice. PDGF-AA neutralizing antibody or tail injection with Pdgfa-shRNA adenovirus improved endothelial function in aortas and mesenteric resistance arteries from db/db mice. The effect of PDGF-AA on endothelial function in mouse aorta was also inhibited by Ad-Pdgfra-shRNA to inhibit PDGFRα. The present study provides novel evidences to show that PDGF-AA impairs endothelium-dependent vasodilation and PDGF-AA mediates BMP4-induced adverse effect on endothelial cell function through SMAD1/5- and SMAD4-dependent mechanisms. Inhibition of PGDF-AA ameliorates vascular dysfunction in diabetic mice. © 2016 American Heart Association, Inc.

  5. The Impact of a Non-Functional Thyroid Receptor Beta upon Triiodotironine-Induced Cardiac Hypertrophy in Mice

    Directory of Open Access Journals (Sweden)

    Güínever Eustáquio do Império

    2015-08-01

    Full Text Available Background/Aims: Thyroid hormone (TH signalling is critical for heart function. The heart expresses thyroid hormone receptors (THRs; THRα1 and THRβ1. We aimed to investigate the regulation mechanisms of the THRβ isoform, its association with gene expression changes and implications for cardiac function. Methods: The experiments were performed using adult male mice expressing TRβΔ337T, which contains the Δ337T mutation of the human THRB gene and impairs ligand binding. Cardiac function and RNA expression were studied after hypo-or hyperthyroidism inductions. T3-induced cardiac hypertrophy was not observed in TRβΔ337T mice, showing the fundamental role of THRβ in cardiac hypertrophy. Results: We identified a group of independently regulated THRβ genes, which includes Adrb2, Myh7 and Hcn2 that were normally regulated by T3 in the TRβΔ337T group. However, Adrb1, Myh6 and Atp2a2 were regulated via THRβ. The TRβΔ337T mice exhibited a contractile deficit, decreased ejection fraction and stroke volume, as assessed by echocardiography. In our model, miR-208a and miR-199a may contribute to THRβ-mediated cardiac hypertrophy, as indicated by the absence of T3-regulated ventricular expression in TRβΔ337T mice. Conclusion: THRβ has important role in the regulation of specific mRNA and miRNA in T3-induced cardiac hypertrophic growth and in the alteration of heart functions.

  6. Hypercholesterolemia Induced by a PCSK9 Gain-of-Function Mutation Augments Angiotensin II-Induced Abdominal Aortic Aneurysms in C57BL/6 Mice-Brief Report.

    Science.gov (United States)

    Lu, Hong; Howatt, Deborah A; Balakrishnan, Anju; Graham, Mark J; Mullick, Adam E; Daugherty, Alan

    2016-09-01

    Gain-of-function mutations of PCSK9 (proprotein convertase subtilisin/kexin type 9) lead to hypercholesterolemia. This study was to determine whether infection of normocholesterolemic mice with an adeno-associated viral (AAV) vector expressing a gain-of-function mutation of mouse PCSK9 increased angiotensin II (AngII)-induced abdominal aortic aneurysms. In an initial study, male C57BL/6 mice were injected intraperitoneally with either an empty vector or PCSK9 gain-of-function mutation (D377Y). AAV at 3 doses and fed a saturated fat-enriched diet for 6 weeks. Two weeks after AAV injection, mice were infused with AngII for 4 weeks. Plasma PCSK9 concentrations were increased dose dependently in mice injected with AAV containing PCSK9D377Y mutation and positively associated with elevations of plasma cholesterol concentrations. Infection with intermediate and high doses of PCSK9D377Y.AAV led to equivalent increases of maximal width of abdominal aortas in C57BL/6 mice infused with AngII. Therefore, the intermediate dose was used in subsequent experiments. We then determined effects of PCSK9D377Y.AAV infection on 5 normolipidemic mouse strains, demonstrating that C57BL/6 mice were the most susceptible to this AAV infection. PCSK9D377Y.AAV infected male C57BL/6 mice were also compared with age-matched male low-density lipoprotein receptor(-/-) mice. Although plasma cholesterol concentrations were lower in mice infected with PCSK9D377Y.AAV, these mice had equivalent abdominal aortic aneurysmal formation, compared to low-density lipoprotein receptor(-/-) mice. In a separate study, reduced plasma PCSK9 concentrations by PCSK9 antisense oligonucleotides in male low-density lipoprotein receptor(-/-) mice did not influence AngII-induced abdominal aortic aneurysms. AAV-mediated infection with a mouse PCSK9 gain-of-function mutation is a rapid, easy, and efficient approach for inducing hypercholesterolemia and promoting abdominal aortic aneurysms in C57BL/6 mice infused with Ang

  7. Tartary buckwheat improves cognition and memory function in an in vivo amyloid-β-induced Alzheimer model.

    Science.gov (United States)

    Choi, Ji Yeon; Cho, Eun Ju; Lee, Hae Song; Lee, Jeong Min; Yoon, Young-Ho; Lee, Sanghyun

    2013-03-01

    Protective effects of Tartary buckwheat (TB) and common buckwheat (CB) on amyloid beta (Aβ)-induced impairment of cognition and memory function were investigated in vivo in order to identify potential therapeutic agents against Alzheimer's disease (AD) and its associated progressive memory deficits, cognitive impairment, and personality changes. An in vivo mouse model of AD was created by injecting the brains of ICR mice with Aβ(25-35), a fragment of the full-length Aβ protein. Damage of mice recognition ability through following Aβ(25-35) brain injections was confirmed using the T-maze test, the object recognition test, and the Morris water maze test. Results of behavior tests in AD model showed that oral administration of the methanol (MeOH) extracts of TB and CB improved cognition and memory function following Aβ(25-35) injections. Furthermore, in groups receiving the MeOH extracts of TB and CB, lipid peroxidation was significantly inhibited, and nitric oxide levels in tissue, which are elevated by injection of Aβ(25-35), were also decrease. In particular, the MeOH extract of TB exerted a stronger protective activity than CB against Aβ(25-35)-induced memory and cognition impairment. The results indicate that TB may play a promising role in preventing or reversing memory and cognition loss associated with Aβ(25-35)-induced AD. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Neuropathic Pain-like Alterations in Muscle Nociceptor Function Associated with Vibration-induced Muscle Pain

    OpenAIRE

    Chen, Xiaojie; Green, Paul G.; Levine, Jon D.

    2010-01-01

    We recently developed a rodent model of the painful muscle disorders induced by occupational exposure to vibration. In the present study we used this model to evaluate the function of sensory neurons innervating the vibration-exposed gastrocnemius muscle. Activity of 74 vibration-exposed and 40 control nociceptors, with mechanical receptive fields in the gastrocnemius muscle, were recorded. In vibration-exposed rats ~15% of nociceptors demonstrated an intense and long-lasting barrage of actio...

  9. Regular voluntary exercise cures stress-induced impairment of cognitive function and cell proliferation accompanied by increases in cerebral IGF-1 and GST activity in mice.

    Science.gov (United States)

    Nakajima, Sanae; Ohsawa, Ikuroh; Ohta, Shigeo; Ohno, Makoto; Mikami, Toshio

    2010-08-25

    Chronic stress impairs cognitive function and hippocampal neurogenesis. This impairment is attributed to increases in oxidative stress, which result in the accumulation of lipid peroxide. On the other hand, voluntary exercise enhances cognitive function, hippocampal neurogenesis, and antioxidant capacity in normal animals. However, the effects of voluntary exercise on cognitive function, neurogenesis, and antioxidants in stressed mice are unclear. This study was designed to investigate whether voluntary exercise cures stress-induced impairment of cognitive function accompanied by improvement of hippocampal neurogenesis and increases in antioxidant capacity. Stressed mice were exposed to chronic restraint stress (CRS), which consisted of 12h immobilization daily and feeding in a small cage, for 8 weeks. Exercised mice were allowed free access to a running wheel during their exposure to CRS. At the 6th week, cognitive function was examined using the Morris water maze (MWM) test. Daily voluntary exercise restored stress-induced impairment of cognitive function and the hippocampal cell proliferation of newborn cells but not cell survival. Voluntary exercise increased insulin-like growth factor 1 (IGF-1) protein and mRNA expression in the cerebral cortex and liver, respectively. In addition, CRS resulted in a significant increase in the number of 4-hydrosynonenal (4-HNE)-positive cells in the hippocampal dentate gyrus; whereas, voluntary exercise inhibited it and enhanced glutathione s-transferases (GST) activity in the brain. These findings suggest that voluntary exercise attenuated the stress-induced impairment of cognitive function accompanied by improvement of cell proliferation in the dentate gyrus. This exercise-induced improvement was attributed to exercise-induced enhancement of IGF-1 protein and GST activity in the brain. Copyright 2010 Elsevier B.V. All rights reserved.

  10. Radiation-induced genomic instability, and the cloning and functional analysis of its related gene

    International Nuclear Information System (INIS)

    Muto, Masahiro; Kanari, Yasuyoshi; Kubo, Eiko; Yamada, Yutaka

    2000-01-01

    Exposure to ionizing radiation produces a number of biological consequences including gene mutations, chromosome aberrations, cellular transformation and cell death. The classical view has been that mutations occur at the sites of DNA damage, that is, damage produced by radiation is converted into a mutation during subsequent DNA replication or as a consequence of enzymatic repair processes. However, many investigators have presented evidence for an alternative mechanism to explain these biological effects. This evidence suggests that radiation may induce a process of genomic instability that is transmissible over many generations of cell replication and that serves to enhance the probability of the occurrence of such genetic effects among the progeny of the irradiated cell after many generations of cell replication. If such a process exists in vivo, it could have significant implications for mechanisms of carcinogenesis. Exposure of B10 mice to fractionated X-irradiation induces a high incidence of thymic lymphomas, whereas the incidence in STS/A mice is very low. Such strain differences are presumably determined genetically, and various genetic factors have been reported to be involved in radiation-induced lymphomagenesis. The mechanism of radiation-induced lymphomagenesis appears to develop through a complex and multistep process. Using this experimental system, we characterized the prelymphoma cells induced by radiation, and identified the genetic changes preceding the development of thymic lymphomas by comparing the oncogenic alterations with the pattern of T cell receptor (TCR) γ rearrangements. In these studies, the latent expression of some chromosomal aberrations and p53 mutations in irradiated progeny has been interpreted to be a manifestation of genomic instability. In the present report we review the results of in vivo studies conducted in our laboratory that support the hypothesis of genomic instability induced by radiation, and we describe the

  11. Probiotics and Probiotic Metabolic Product Improved Intestinal Function and Ameliorated LPS-Induced Injury in Rats.

    Science.gov (United States)

    Deng, Bo; Wu, Jie; Li, Xiaohui; Men, Xiaoming; Xu, Ziwei

    2017-11-01

    In the present study, we sought to determine the effects of Bacillus subtilis (BAS) and Bacillus licheniformis (BAL) in rats after lipopolysaccharide (LPS)-induced acute intestinal inflammation. We also determined whether the B. subtilis metabolic product (BASM) is as effective as the live-cell probiotic. 60 male SD rats were randomly assigned to five groups and administered a diet containing 0.05% B. licheniformis (BAL group), 0.05% B. subtilis (BAS group), 0.5% B. subtilis metabolic product (BASM group), or a basic diet (PC group and NC group) for 40 days. On day 40, BAL, BAS, BASM, and NC groups were injected with 4 mg/kg body weight LPS. 4 h later, all rats were anesthetized and sacrificed. The results showed that the administration of B. licheniformis and B. subtilis improved intestinal function as evidenced by histology, increased enzyme activity, and mucosal thickness. They also increased the number of intraepithelial lymphocytes and decreased mucosal myeloperoxidase activity and plasma TNF-α. In addition, the cecal content of B. subtilis-treated rats had significantly increased microbial diversity, decreased numbers of Firmicutes, and increased numbers of Bacteroidetes as compared to rats fed basic diets. Similar to BAS group, the cecal content of B. licheniformis-treated rats decreased the number of Firmicutes. Administration of B. subtilis metabolic product had similar effects on intestinal function, inflammation response, and microbial diversity as B. subtilis but these effects were attenuated. In conclusion, administration of probiotic strains B. licheniformis or B. subtilis improved intestinal function, ameliorated the inflammation response, and modulated microflora after LPS-induced acute inflammation in rats. Non-living cells also exerted probiotic properties but live cells tended to function better.

  12. Hyperthermia-induced disruption of functional connectivity in the human brain network.

    Directory of Open Access Journals (Sweden)

    Gang Sun

    executive control reaction time. CONCLUSIONS/SIGNIFICANCE: We first identified the hyperthermia-induced altered functional connectivity patterns. The changes in the functional connectivity network might be a possible explanation for the cognitive performance and work behavior alteration.

  13. Myocardial Perfusion and Function Are Distinctly Altered by Sevoflurane Anesthesia in Diet-Induced Prediabetic Rats.

    Science.gov (United States)

    van den Brom, Charissa E; Boly, Chantal A; Bulte, Carolien S E; van den Akker, Rob F P; Kwekkeboom, Rick F J; Loer, Stephan A; Boer, Christa; Bouwman, R Arthur

    2016-01-01

    Preservation of myocardial perfusion during surgery is particularly important in patients with increased risk for perioperative complications, such as diabetes. Volatile anesthetics, like sevoflurane, have cardiodepressive effects and may aggravate cardiovascular complications. We investigated the effect of sevoflurane on myocardial perfusion and function in prediabetic rats. Rats were fed a western diet (WD; n = 18) or control diet (CD; n = 18) for 8 weeks and underwent (contrast) echocardiography to determine perfusion and function during baseline and sevoflurane exposure. Myocardial perfusion was estimated based on the product of microvascular filling velocity and blood volume. WD-feeding resulted in a prediabetic phenotype characterized by obesity, hyperinsulinemia, hyperlipidemia, glucose intolerance, and hyperglycemia. At baseline, WD-feeding impaired myocardial perfusion and systolic function compared to CD-feeding. Exposure of healthy rats to sevoflurane increased the microvascular filling velocity without altering myocardial perfusion but impaired systolic function. In prediabetic rats, sevoflurane did also not affect myocardial perfusion; however, it further impaired systolic function. Diet-induced prediabetes is associated with impaired myocardial perfusion and function in rats. While sevoflurane further impaired systolic function, it did not affect myocardial perfusion in prediabetic rats. Our findings suggest that sevoflurane anesthesia leads to uncoupling of myocardial perfusion and function, irrespective of the metabolic state.

  14. Multidetector computed tomography has replaced conventional intravenous excretory urography in imaging of the kidneys: A scoping review of multidetector computed tomography findings in renal tuberculosis

    Directory of Open Access Journals (Sweden)

    Ntombizakhona B.A. Mthalane

    2018-02-01

    Full Text Available Background: Tuberculosis (TB is a worldwide infectious disease burden, especially in non-developed countries, with increased morbidity and mortality among human immunodeficiency virus (HIV-infected patients. Extrapulmonary TB is rare and renal TB is one of the commonest manifestations. The end result of renal TB is end-stage renal disease; however, this can be avoided if the diagnosis is made early. The diagnosis of renal TB is challenging because of the non-specific presentation and low sensitivity of clinical tests. Although the sequel of TB infection in the kidney causes varying manifestations depending on the stage of the disease, multidetector computed tomography (MDCT is capable of demonstrating early findings. We performed a 20-year scoping review of MDCT findings in renal TB to promote awareness. Aim: To identify specific MDCT imaging characteristics of renal TB, promote early diagnosis and increase awareness of the typical imaging features. Methods and material: We searched published and unpublished literature from 1997 to 2017 using a combination of search terms on electronic databases. We followed the Joanna Briggs Institute guidelines. Results: A total of 150 articles were identified, of which 145 were found through electronic search engines and 5 were obtained from grey literature. Seventy-nine articles that fulfilled our inclusion criteria were reviewed. These included original research, case reports, literature review, organisational reports and grey literature. Conclusion: Multidetector computed tomography can reproduce images comparable with intravenous excretory urography; together with advantages of being able to better assess the renal parenchyma and surrounding spaces, it is important in suggesting the diagnosis of renal TB and clinicians should consider including MDCT when investigating patients with recurrent urinary tract infection not responding to usual antimicrobial therapy.

  15. Induction of Functional 3D Ciliary Epithelium-Like Structure From Mouse Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Kinoshita, Hirofumi; Suzuma, Kiyoshi; Kaneko, Jun; Mandai, Michiko; Kitaoka, Takashi; Takahashi, Masayo

    2016-01-01

    To generate ciliary epithelium (CE) from mouse induced pluripotent stem (iPS) cells. Recently, a protocol for self-organizing optic cup morphogenesis in three-dimensional culture was reported, and it was suggested that ocular tissue derived from neural ectoderm could be differentiated. We demonstrated that a CE-like double-layered structure could be induced in simple culture by using a modified Eiraku differentiation protocol. Differentiation of a CE-like double-layered structure could be promoted by glycogen synthase kinase 3β (GSK-3β) inhibitor. Connexin43 and aquaporin1 were expressed in both thin layers, and induced CE-like cells expressed ciliary marker genes, such as cyclinD2, zic1, tgfb2, aldh1a3, wfdc1, otx1, BMP4, and BMP7. Increases in cytoplasmic and nuclear β-catenin in aggregates of the CE-like double-layered structure were confirmed by Western blot analysis. In addition, tankyrase inhibitor prevented the induction of the CE-like double-layered structure by GSK-3β inhibitor. Dye movement from pigmented cells to nonpigmented cells in the mouse iPS cell-derived CE-like structure was observed in a fluid movement experiment, consistent with the physiological function of CE in vivo. We could differentiate CE from mouse iPS cells in the present study. In the future, we hope that this CE-like complex will become useful as a graft for transplantation therapy in pathologic ocular hypotension due to CE dysfunction, and as a screening tool for the development of drugs for diseases associated with CE function.

  16. Central pain processing in chronic chemotherapy-induced peripheral neuropathy: a functional magnetic resonance imaging study.

    Directory of Open Access Journals (Sweden)

    Elaine G Boland

    Full Text Available Life expectancy in multiple myeloma has significantly increased. However, a high incidence of chemotherapy induced peripheral neuropathy (CIPN can negatively influence quality of life during this period. This study applied functional magnetic resonance imaging (fMRI to compare areas associated with central pain processing in patients with multiple myeloma who had chemotherapy induced peripheral neuropathy (MM-CIPN with those from healthy volunteers (HV. Twenty-four participants (n = 12 MM-CIPN, n = 12 HV underwent Blood Oxygen Level-Dependent (BOLD fMRI at 3T whilst noxious heat-pain stimuli were applied to the foot and then thigh. Patients with MM-CIPN demonstrated greater activation during painful stimulation in the precuneus compared to HV (p = 0.014, FWE-corrected. Patients with MM-CIPN exhibited hypo-activation of the right superior frontal gyrus compared to HV (p = 0.031, FWE-corrected. Significant positive correlation existed between the total neuropathy score (reduced version and activation in the frontal operculum (close to insular cortex during foot stimulation in patients with MM-CIPN (p = 0.03, FWE-corrected; adjusted R2 = 0.87. Painful stimuli delivered to MM-CIPN patients evoke differential activation of distinct cortical regions, reflecting a unique pattern of central pain processing compared with healthy volunteers. This characteristic activation pattern associated with pain furthers the understanding of the pathophysiology of painful chemotherapy induced peripheral neuropathy. Functional MRI provides a tool for monitoring cerebral changes during anti-cancer and analgesic treatment.

  17. Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats.

    Science.gov (United States)

    Zafrani, Lara; Ergin, Bulent; Kapucu, Aysegul; Ince, Can

    2016-12-20

    The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Twenty-seven Wistar albino rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 7), a LPS group that received fluid resuscitation (n = 7), and a LPS group that received blood transfusion (n = 7). The mean arterial blood pressure, renal blood flow, and renal microvascular oxygenation within the kidney cortex were recorded. Acute kidney injury was assessed using the serum creatinine levels, metabolic cost, and histopathological lesions. Nitrosative stress (expression of endothelial (eNOS) and inducible nitric oxide synthase (iNOS)) within the kidney was assessed by immunohistochemistry. Hemoglobin levels, pH, serum lactate levels, and liver enzymes were measured. Fluid resuscitation and blood transfusion both significantly improved the mean arterial pressure and renal blood flow after LPS infusion. Renal microvascular oxygenation, serum creatinine levels, and tubular damage significantly improved in the LPS group that received blood transfusion compared to the group that received fluids. Moreover, the renal expression of eNOS was markedly suppressed under endotoxin challenge. Blood transfusion, but not fluid resuscitation, was able to restore the renal expression of eNOS. However, there were no significant differences in lactic acidosis or liver function between the two groups. Blood transfusion significantly improved renal function in endotoxemic rats. The specific beneficial effect of blood transfusion on the kidney could have been mediated in part by the improvements in renal microvascular oxygenation and sepsis-induced endothelial dysfunction via the restoration of eNOS expression within the kidney.

  18. Human monocytes undergo functional re-programming during sepsis mediated by hypoxia-inducible factor-1α.

    Science.gov (United States)

    Shalova, Irina N; Lim, Jyue Yuan; Chittezhath, Manesh; Zinkernagel, Annelies S; Beasley, Federico; Hernández-Jiménez, Enrique; Toledano, Victor; Cubillos-Zapata, Carolina; Rapisarda, Annamaria; Chen, Jinmiao; Duan, Kaibo; Yang, Henry; Poidinger, Michael; Melillo, Giovanni; Nizet, Victor; Arnalich, Francisco; López-Collazo, Eduardo; Biswas, Subhra K

    2015-03-17

    Sepsis is characterized by a dysregulated inflammatory response to infection. Despite studies in mice, the cellular and molecular basis of human sepsis remains unclear and effective therapies are lacking. Blood monocytes serve as the first line of host defense and are equipped to recognize and respond to infection by triggering an immune-inflammatory response. However, the response of these cells in human sepsis and their contribution to sepsis pathogenesis is poorly understood. To investigate this, we performed a transcriptomic, functional, and mechanistic analysis of blood monocytes from patients during sepsis and after recovery. Our results revealed the functional plasticity of monocytes during human sepsis, wherein they transited from a pro-inflammatory to an immunosuppressive phenotype, while enhancing protective functions like phagocytosis, anti-microbial activity, and tissue remodeling. Mechanistically, hypoxia inducible factor-1α (HIF1α) mediated this functional re-programming of monocytes, revealing a potential mechanism for their therapeutic targeting to regulate human sepsis. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Processing semblances induced through inter-postsynaptic functional LINKs, presumed biological parallels of K-lines proposed for building artificial intelligence

    Directory of Open Access Journals (Sweden)

    Kunjumon I Vadakkan

    2011-07-01

    Full Text Available The internal sensation of memory, which is available only to the owner of an individual nervous system, is difficult to analyze for its basic elements of operation. We hypothesize that associative learning induces the formation of functional LINK between the postsynapses. During memory retrieval, the activation of either postsynapse re-activates the functional LINK evoking a semblance of sensory activity arriving at its opposite postsynapse, nature of which defines the basic unit of virtual internal sensation - namely, semblion. Neuronal networks that undergo continuous oscillatory activity at certain levels of their organization induce semblions enabling the system to continuously learn, self-organize, and demonstrate instantiation, features that can be utilized for developing artificial intelligence (AI. Suitability of the inter-postsynaptic functional LINKs to meet the expectations of Minsky’s K-lines, basic elements of a memory theory generated to develop AI and methods to replicate semblances outside the nervous system are explained.

  20. Assaying the character and stenosis of the pyeloureteric segment in nephrolithiasis through pharmacologic modification of the imaging methods

    International Nuclear Information System (INIS)

    Yudin, L.; Reznichenko, A.; Budkevich, Yu.; Shejretova, E.

    1994-01-01

    The study is performed with 17 patients presenting nephrolithiasis and 6 - hydronephrosis with stenosis of the pyeloureteric segment, confirmed intraoperatively. The character of stenosis (reversible or irreversible) is determined by ultrasonography with furosemide, dynamic scintigraphy with furosemide and progesterone, and excretory urography with progesterone. As shown by the obtained results, the pharmacologic modifications of imaging methods prove more informative in hydronephrosis, and to a lesser extent in nephrolithiasis patients. Dynamic scintigraphy with furosemide and excretory urography with progesterone yields less information, in comparison to ultrasonography with forosemid and excretory urography with progesterone. However, the comparatively limited number of patients investigated should be borne in mind. 2 tabs., 5 refs

  1. Oncostatin M induces upregulation of claudin-2 in rodent hepatocytes coinciding with changes in morphology and function of tight junctions

    International Nuclear Information System (INIS)

    Imamura, Masafumi; Kojima, Takashi; Lan, Mengdong; Son, Seiichi; Murata, Masaki; Osanai, Makoto; Chiba, Hideki; Hirata, Koichi; Sawada, Norimasa

    2007-01-01

    In rodent livers, integral tight junction (TJ) proteins claudin-1, -2, -3, -5 and -14 are detected and play crucial roles in the barrier to keep bile in bile canaculi away from the blood circulation. Claudin-2 shows a lobular gradient increasing from periportal to pericentral hepatocytes, whereas claudin-1 and -3 are expressed in the whole liver lobule. Although claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells, the physiological functions and regulation of claudin-2 in hepatocytes remain unclear. Oncostatin M (OSM) is a multifunctional cytokine implicated in the differentiation of hepatocytes that induces formation of E-cadherin-based adherens junctions in fetal hepatocytes. In this study, we examined whether OSM could induce expression and function of claudin-2 in rodent hepatocytes, immortalized mouse and primary cultured proliferative rat hepatocytes. In the immortalized mouse and primary cultured proliferative rat hepatocytes, treatment with OSM markedly increased mRNA and protein of claudin-2 together with formation of developed networks of TJ strands. The increase of claudin-2 enhanced the paracellular barrier function which depended on molecular size. The increase of claudin-2 expression induced by OSM in rodent hepatocytes was regulated through distinct signaling pathways including PKC. These results suggest that expression of claudin-2 in rodent hepatocytes may play a specific role as controlling the size of paracellular permeability in the barrier to keep bile in bile canaculi

  2. Exkretionssystem und systematische Stellung Kubanischer Fledermaustrematoden

    NARCIS (Netherlands)

    Odening, Klaus

    1969-01-01

    1. Eight species of Cuban bat trematodes have been examined, and their excretory system established. 2. In Urotrema scabridum Braun a small V-shaped excretory bladder and the flame cell formula 2[(2+ 2+2) + (2+2+2)] were ascertained. This enabled us to affiliate the family Urotrematidae to the

  3. Cytokine-induced differentiation of multipotent adult progenitor cells into functional smooth muscle cells.

    Science.gov (United States)

    Ross, Jeffrey J; Hong, Zhigang; Willenbring, Ben; Zeng, Lepeng; Isenberg, Brett; Lee, Eu Han; Reyes, Morayma; Keirstead, Susan A; Weir, E Kenneth; Tranquillo, Robert T; Verfaillie, Catherine M

    2006-12-01

    Smooth muscle formation and function are critical in development and postnatal life. Hence, studies aimed at better understanding SMC differentiation are of great importance. Here, we report that multipotent adult progenitor cells (MAPCs) isolated from rat, murine, porcine, and human bone marrow demonstrate the potential to differentiate into cells with an SMC-like phenotype and function. TGF-beta1 alone or combined with PDGF-BB in serum-free medium induces a temporally correct expression of transcripts and proteins consistent with smooth muscle development. Furthermore, SMCs derived from MAPCs (MAPC-SMCs) demonstrated functional L-type calcium channels. MAPC-SMCs entrapped in fibrin vascular molds became circumferentially aligned and generated force in response to KCl, the L-type channel opener FPL64176, or the SMC agonists 5-HT and ET-1, and exhibited complete relaxation in response to the Rho-kinase inhibitor Y-27632. Cyclic distention (5% circumferential strain) for 3 weeks increased responses by 2- to 3-fold, consistent with what occurred in neonatal SMCs. These results provide evidence that MAPC-SMCs are phenotypically and functionally similar to neonatal SMCs and that the in vitro MAPC-SMC differentiation system may be an ideal model for the study of SMC development. Moreover, MAPC-SMCs may lend themselves to tissue engineering applications.

  4. Histamine and TNF-α release by rat peritoneal mast cells stimulated with Trichomonas vaginalis

    Directory of Open Access Journals (Sweden)

    Im S.J.

    2011-02-01

    Full Text Available Mast cells have been reported to be predominant in the vaginal smears of patients infected with T. vaginalis. In this study, we investigated whether T. vaginalis could induce mast cells to migrate and to produce TNF-α and histamine. Rat peritoneal mast cells (RPMC, a primary mast cell, were used for the study. T. vaginalis induced an increase in chemotactic migration of the mast cells toward excretory and secretory product (ESP of T. vaginalis, and the mast cells activated with T. vaginalis showed an increased release of histamine and TNF-α. Therefore, mast cells may be involved in the inflammatory response caused by T. vaginalis.

  5. Vitamin D Can Ameliorate Chlorhexidine Gluconate-Induced Peritoneal Fibrosis and Functional Deterioration through the Inhibition of Epithelial-to-Mesenchymal Transition of Mesothelial Cells

    Directory of Open Access Journals (Sweden)

    Yi-Che Lee

    2015-01-01

    Full Text Available Background. Peritoneal dialysis (PD can induce fibrosis and functional alterations in PD patients’ peritoneal membranes, due to long-term unphysiological dialysate exposure, partially occurring via triggering of epithelial-to-mesenchymal transition (EMT in peritoneal mesothelial cells (MCs. Vitamin D can ameliorate these negative effects; however, the mechanism remains unexplored. Therefore, we investigated its possible links to MCs EMT inhibition. Methods. Peritoneal fibrosis was established in Sprague-Dawley rats by chlorhexidine gluconate (CG intraperitoneal injection for 21 days, with and without 1α,25(OH2D3 treatment. Morphological and functional evaluation and western blot analysis of EMT marker were performed upon peritoneum tissue. In vitro study was also performed in a primary human peritoneal MC culture system; MCs were incubated with transforming growth factor-β1 (TGF-β1 in the absence or presence of 1α,25(OH2D3. EMT marker expression, migration activities, and cytoskeleton redistribution of MCs were determined. Results. 1α,25(OH2D3 ameliorated CG-induced morphological and functional deterioration in animal model, along with CG-induced upregulation of α-SMA and downregulation of E-cadherin expression. Meanwhile, 1α,25(OH2D3 also ameliorated TGF-β1-induced decrease in E-cadherin expression, increase in Snai1 and α-SMA expression, intracellular F-actin redistribution, and migration activity in vitro. Conclusion. 1α,25(OH2D3 can ameliorate CG-induced peritoneal fibrosis and attenuate functional deterioration through inhibiting MC EMT.

  6. Immunohistochemical sweat gland profiles.

    Science.gov (United States)

    Noël, Fanchon; Piérard, Gérald E; Delvenne, Philippe; Quatresooz, Pascale; Humbert, Philippe; Piérard-Franchimont, Claudine

    2013-09-01

    Human sweat glands are heterogeneous in their structures and functions. Accordingly, eccrine, apocrine, and apoeccrine glands are distinguished. Some immunohistochemical markers are expected to distinguish the sweat gland types in their secretory and excretory parts. This study used two sets of antibodies. The first panel was composed of antibodies directed to well-defined sweat gland structures. The molecular targets included the low-molecular-weight cytokeratins CAM 5.2, the S100-B protein, the epithelial membrane antigen (EMA), the carcinoembryonic antigen (CEA), and the lectin Ulex europaeus agglutinin-1 (UEA-1). A second exploratory panel of antibodies targeted syndecan-1 (CD138), NKI-C3 (CD63), and CD68. They were used to disclose some undescribed antigen expressions in human sweat glands. The first set of antibodies confirmed previous findings. The immunoreactivities of the three sweat gland types were similar in the excretory ducts. By contrast, they were distinguished in the deeper coiled secretory portions of the glands. Clues supporting their distinction and probably their functional activity were obtained by immunohistochemistry using the S100-B protein, CEA and CD63 antibodies. The immunoreactivity to the S100-B protein, CEA and CD63 possibly help identifying apoeccrine sweat glands or a peculiar functional activity of eccrine sweat glands. © 2013 Wiley Periodicals, Inc.

  7. Functional consequences of climate change-induced plant species loss in a tallgrass prairie.

    Science.gov (United States)

    Craine, Joseph M; Nippert, Jesse B; Towne, E Gene; Tucker, Sally; Kembel, Steven W; Skibbe, Adam; McLauchlan, Kendra K

    2011-04-01

    Future climate change is likely to reduce the floristic diversity of grasslands. Yet the potential consequences of climate-induced plant species losses for the functioning of these ecosystems are poorly understood. We investigated how climate change might alter the functional composition of grasslands for Konza Prairie, a diverse tallgrass prairie in central North America. With species-specific climate envelopes, we show that a reduction in mean annual precipitation would preferentially remove species that are more abundant in the more productive lowland positions at Konza. As such, decreases in precipitation could reduce productivity not only by reducing water availability but by also removing species that inhabit the most productive areas and respond the most to climate variability. In support of this prediction, data on species abundance at Konza over 16 years show that species that are more abundant in lowlands than uplands are preferentially reduced in years with low precipitation. Climate change is likely to also preferentially remove species from particular functional groups and clades. For example, warming is forecast to preferentially remove perennials over annuals as well as Cyperaceae species. Despite these predictions, climate change is unlikely to unilaterally alter the functional composition of the tallgrass prairie flora, as many functional traits such as physiological drought tolerance and maximum photosynthetic rates showed little relationship with climate envelope parameters. In all, although climatic drying would indirectly alter grassland productivity through species loss patterns, the insurance afforded by biodiversity to ecosystem function is likely to be sustained in the face of climate change.

  8. Effect of selective inhibition of renal inducible nitric oxide synthase on renal blood flow and function in experimental hyperdynamic sepsis.

    Science.gov (United States)

    Ishikawa, Ken; Calzavacca, Paolo; Bellomo, Rinaldo; Bailey, Michael; May, Clive N

    2012-08-01

    Nitric oxide plays an important role in the control of renal blood flow and renal function. In sepsis, increased levels of inducible nitric oxide synthase produce excessive nitric oxide, which may contribute to the development of acute kidney injury. We, therefore, examined the effects of intrarenal infusion of selective inducible nitric oxide synthase inhibitors in a large animal model of hyperdynamic sepsis in which acute kidney injury occurs in the presence of increased renal blood flow. Prospective crossover randomized controlled interventional studies. University-affiliated research institute. Twelve unilaterally nephrectomized Merino ewes. Infusion of a selective (1400W) and a partially selective inducible nitric oxide synthase inhibitor (aminoguanidine) into the renal artery for 2 hrs after the induction of sepsis, and comparison with a nonselective inhibitor (Nω-nitro-L-arginine methyl ester). In sheep with nonhypotensive hyperdynamic sepsis, creatinine clearance halved (32 to 16 mL/min, ratio [95% confidence interval] 0.51 [0.28-0.92]) despite increased renal blood flow (241 to 343 mL/min, difference [95% confidence interval] 102 [78-126]). Infusion of 1400W did not change renal blood flow, urine output, or creatinine clearance, whereas infusion of Nω-nitro-L-arginine methyl ester and a high dose of aminoguanidine normalized renal blood flow, but did not alter creatinine clearance. In hyperdynamic sepsis, intrarenal infusion of a highly selective inducible nitric oxide synthase inhibitor did not reduce the elevated renal blood flow or improve renal function. In contrast, renal blood flow was reduced by infusion of a nonselective NOS inhibitor or a high dose of a partially selective inducible nitric oxide synthase inhibitor. The renal vasodilatation in septic acute kidney injury may be due to nitric oxide derived from the endothelial and neural isoforms of nitric oxide synthase, but their blockade did not restore renal function.

  9. The Impaired Function of Macrophages Induced by Strenuous Exercise Could Not Be Ameliorated by BCAA Supplementation.

    Science.gov (United States)

    Xiao, Weihua; Chen, Peijie; Liu, Xiaoguang; Zhao, Linlin

    2015-10-21

    The aim of this study was to evaluate the effect of strenuous exercise on the functions of peritoneal macrophages in rats and to test the hypothesis that branched-chain amino acid (BCAA) supplementation will be beneficial to the macrophages of rats from strenuous exercise. Forty male Wistar rats were randomly divided into five groups: (C) Control, E) Exercise, (E1) Exercise with one week to recover, (ES) Exercise + Supplementation and (ES1) Exercise + Supplementation with 1 week to recover. All rats except those of the sedentary control were subjected to four weeks of strenuous exercise. Blood hemoglobin, serum testosterone and BCAA levels were tested. Peritoneal macrophages functions were also determined at the same time. The data showed that hemoglobin, testosterone, BCAA levels, and body weight in group E decreased significantly as compared with that of group C. Meanwhile, phagocytosis capacity (decreased by 17.07%, p = 0.031), reactive oxygen species (ROS) production (decreased by 26%, p = 0.003) and MHC II mRNA (decreased by 22%, p = 0.041) of macrophages decreased in the strenuous exercise group as compared with group C. However, the chemotaxis of macrophages did not change significantly. In addition, BCAA supplementation could slightly increase the serum BCAA levels of rats from strenuous exercise (increased by 6.70%, p > 0.05). Moreover, the body weight, the blood hemoglobin, the serum testosterone and the function of peritoneal macrophages in group ES did not change significantly as compared with group E. These results suggest that long-term intensive exercise impairs the function of macrophages, which is essential for microbicidal capability. This may represent a novel mechanism of immunosuppression induced by strenuous exercise. Moreover, the impaired function of macrophage induced by strenuous exercise could not be ameliorated by BCAA supplementation in the dosing and timing used for this study.

  10. The Impaired Function of Macrophages Induced by Strenuous Exercise Could Not Be Ameliorated by BCAA Supplementation

    Directory of Open Access Journals (Sweden)

    Weihua Xiao

    2015-10-01

    Full Text Available The aim of this study was to evaluate the effect of strenuous exercise on the functions of peritoneal macrophages in rats and to test the hypothesis that branched-chain amino acid (BCAA supplementation will be beneficial to the macrophages of rats from strenuous exercise. Forty male Wistar rats were randomly divided into five groups: (C Control, E Exercise, (E1 Exercise with one week to recover, (ES Exercise + Supplementation and (ES1 Exercise + Supplementation with 1 week to recover. All rats except those of the sedentary control were subjected to four weeks of strenuous exercise. Blood hemoglobin, serum testosterone and BCAA levels were tested. Peritoneal macrophages functions were also determined at the same time. The data showed that hemoglobin, testosterone, BCAA levels, and body weight in group E decreased significantly as compared with that of group C. Meanwhile, phagocytosis capacity (decreased by 17.07%, p = 0.031, reactive oxygen species (ROS production (decreased by 26%, p = 0.003 and MHC II mRNA (decreased by 22%, p = 0.041 of macrophages decreased in the strenuous exercise group as compared with group C. However, the chemotaxis of macrophages did not change significantly. In addition, BCAA supplementation could slightly increase the serum BCAA levels of rats from strenuous exercise (increased by 6.70%, p > 0.05. Moreover, the body weight, the blood hemoglobin, the serum testosterone and the function of peritoneal macrophages in group ES did not change significantly as compared with group E. These results suggest that long-term intensive exercise impairs the function of macrophages, which is essential for microbicidal capability. This may represent a novel mechanism of immunosuppression induced by strenuous exercise. Moreover, the impaired function of macrophage induced by strenuous exercise could not be ameliorated by BCAA supplementation in the dosing and timing used for this study.

  11. VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity.

    Science.gov (United States)

    Malykhina, Anna P; Lei, Qi; Erickson, Chris S; Epstein, Miles L; Saban, Marcia R; Davis, Carole A; Saban, Ricardo

    2012-12-19

    This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF) modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity.In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) and cholinergic nerves (ChAT) was studied one week after one or two intravesical instillations of the growth factor.To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG) neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments. In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment) reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation) caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na(+) channels (VGSC) in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation. For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a key modulator of neural plasticity in the pelvis and

  12. VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity

    Directory of Open Access Journals (Sweden)

    Malykhina Anna P

    2012-12-01

    Full Text Available Abstract Background This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity. In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1 and cholinergic nerves (ChAT was studied one week after one or two intravesical instillations of the growth factor. To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments. Results In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na+ channels (VGSC in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation. Conclusions For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a

  13. Opposite variations in maternal and neonatal thyroid function induced by iodine supplementation during pregnancy

    DEFF Research Database (Denmark)

    Nøhr, S B; Laurberg, P

    2000-01-01

    pregnancy, and 95 took no artificial iodine supplementation. Iodine supplementation (+I) induced opposite variations in thyroid function in the mother and the fetus. In +I mothers, TSH was 7.6% lower than in mothers with no supplementation (P ... in the +I group (P caused by opposite shifts in TSH frequency distribution in mothers and neonates. The association between iodine supplementation and high serum TSH in the neonates was further substantiated by an inverse correlation between thyroglobulin and TSH in cord blood...

  14. Gain-of-function assays in the axolotl (Ambystoma mexicanum) to identify signaling pathways that induce and regulate limb regeneration.

    Science.gov (United States)

    Lee, Jangwoo; Aguilar, Cristian; Gardiner, David

    2013-01-01

    The adult salamander has been studied as a model for regeneration of complex tissues for many decades. Only recently with the development of gain-of-function assays for regeneration, has it been possible to screen for and assay the function of the multitude of signaling factors that have been identified in studies of embryonic development and tumorigenesis. Given the conservation of function of these regulatory pathways controlling growth and pattern formation, it is now possible to use the functional assays in the salamander to test the ability of endogenous as well as small-molecule signaling factors to induce a regenerative response.

  15. Videogame training strategy-induced change in brain function during a complex visuomotor task.

    Science.gov (United States)

    Lee, Hyunkyu; Voss, Michelle W; Prakash, Ruchika Shaurya; Boot, Walter R; Vo, Loan T K; Basak, Chandramallika; Vanpatter, Matt; Gratton, Gabriele; Fabiani, Monica; Kramer, Arthur F

    2012-07-01

    Although changes in brain function induced by cognitive training have been examined, functional plasticity associated with specific training strategies is still relatively unexplored. In this study, we examined changes in brain function during a complex visuomotor task following training using the Space Fortress video game. To assess brain function, participants completed functional magnetic resonance imaging (fMRI) before and after 30 h of training with one of two training regimens: Hybrid Variable-Priority Training (HVT), with a focus on improving specific skills and managing task priority, or Full Emphasis Training (FET), in which participants simply practiced the game to obtain the highest overall score. Control participants received only 6 h of FET. Compared to FET, HVT learners reached higher performance on the game and showed less brain activation in areas related to visuo-spatial attention and goal-directed movement after training. Compared to the control group, HVT exhibited less brain activation in right dorsolateral prefrontal cortex (DLPFC), coupled with greater performance improvement. Region-of-interest analysis revealed that the reduction in brain activation was correlated with improved performance on the task. This study sheds light on the neurobiological mechanisms of improved learning from directed training (HVT) over non-directed training (FET), which is related to visuo-spatial attention and goal-directed motor planning, while separating the practice-based benefit, which is related to executive control and rule management. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. [TCD functional test for vertigo induced by ischemic cerebrovascular disorders].

    Science.gov (United States)

    Li, Q; Zhong, N; Xue, X

    1999-04-01

    To diagnose differentially the vetigo induced by some ischemic cerebrovascular disorder. Patients with vertebrobasilar artery transient ischemic vertigo (group A), migraine (group B), hyperventilation syndrome (group C), hypertension (group D) are measured by using TCD functional examination which included blood peak velocity of systolic (Vs) and diastolic (Vd) end-period of vertibrobasilar artery of routine TCD (TCD-R), one minute hyperventilation TCD (TCD-HV) and one minute voluntary apnea TCD (TCD-B) respectively. It showed that the Vs, Vd are decreased under the three conditions in A, B and D groups. The most apparent decrease are obversed in D group. The values of the decrease are similar between group A and B. No changes are found in C group. The abnormal Vs incidences of TCD-B measurement in group A are higher than those in group B and C, but significant lower than those in group D; and in TCD-HV test lower than group D and C, higher than group B; in TCD-R test, lower than group D, and no difference with group B and C. The abnormal incidences of Vd in group A are lower than group D and higher than group B in TCD-B test. In TCD-HV test, the group A abnormol incidences are lower than group D but higher than group B and C. In TCD-R test, the abnormal incidences are lower than group D and no difference between group B and C. The TCD measuremen is useful for differential diagnosis of vertigo induced by ischemic cerebrovascular disorders.

  17. Diet-Induced Obesity Is Associated with an Impaired NK Cell Function and an Increased Colon Cancer Incidence

    Directory of Open Access Journals (Sweden)

    Ina Bähr

    2017-01-01

    Full Text Available Obesity is associated with an increased colon cancer incidence, but underlying mechanisms remained unclear. Previous studies showed altered Natural killer (NK cell functions in obese individuals. Therefore, we studied the impact of an impaired NK cell functionality on the increased colon cancer risk in obesity. In vitro investigations demonstrated a decreased IFN-γ secretion and cytotoxicity of human NK cells against colon tumor cells after NK cell preincubation with the adipokine leptin. In addition, leptin incubation decreased the expression of activating NK cell receptors. In animal studies, colon cancer growth was induced by injection of azoxymethane (AOM in normal weight and diet-induced obese rats. Body weight and visceral fat mass were increased in obese animals compared to normal weight rats. AOM-treated obese rats showed an increased quantity, size, and weight of colon tumors compared to the normal weight tumor group. Immunohistochemical analyses demonstrated a decreased number of NK cells in spleen and liver in obesity. Additionally, the expression levels of activating NK cell receptors were lower in spleen and liver of obese rats. The results show for the first time that the decreased number and impaired NK cell function may be one cause for the higher colon cancer risk in obesity.

  18. Effect of Time Constraind Induced Therapy on Function, Coordination and Movements of Upper Limb on Hemiplegic Adults

    Directory of Open Access Journals (Sweden)

    Masoud Gharib

    2011-10-01

    Full Text Available Objectives: Stroke, is one of the major causes of disability in adults. So, the patient may prefer to use the non-involved limb to perfom selfcare & named this phenomen learned non used. Constraint induced therapy is one of the rehabilitative interventions that can be effective in restoration of the function of the involved limb in some hemiparetic post stroke patients. purpose of this study was to investigate effect of time constraind induced therapy on function, coordination and movements of upper limb on hemiplegic adults. Methods: In an interventional design, 15 hemiplegic patients attended in stracture exrcises for 2 hours a day, 5 days a week for 12 weeks in during while for 5 hours a day, 5 days a week for 12 weeks, the sound limb was restricted within an arm sling for movement & dextrity assessment were used Fugl-Meyer & Minnesota Manual Dexterity Test. Results: the results of Fugl-Meyer & Minnesota Manual Dexterity Test were significantly improved in patients, after the intervention (P<0.05. Discussion: Our study shows that using CIT in involved limb encouraged the patients to use their involved limb and improved function by conquering learned non-use of the limb. more research is necessary to define baselines or golden times for rehabilitation of the patients using CIT method.

  19. Roles of Sensory Nerves in the Regulation of Radiation-Induced Structural and Functional Changes in the Heart

    Energy Technology Data Exchange (ETDEWEB)

    Sridharan, Vijayalakshmi; Tripathi, Preeti [Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Sharma, Sunil [Department of Radiation Oncology, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Moros, Eduardo G. [Department of Radiation Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida (United States); Zheng, Junying [Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Hauer-Jensen, Martin [Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Surgical Service, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas (United States); Boerma, Marjan, E-mail: mboerma@uams.edu [Department of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States)

    2014-01-01

    Purpose: Radiation-induced heart disease (RIHD) is a chronic severe side effect of radiation therapy of intrathoracic and chest wall tumors. The heart contains a dense network of sensory neurons that not only are involved in monitoring of cardiac events such as ischemia and reperfusion but also play a role in cardiac tissue homeostasis, preconditioning, and repair. The purpose of this study was to examine the role of sensory nerves in RIHD. Methods and Materials: Male Sprague-Dawley rats were administered capsaicin to permanently ablate sensory nerves, 2 weeks before local image-guided heart x-ray irradiation with a single dose of 21 Gy. During the 6 months of follow-up, heart function was assessed with high-resolution echocardiography. At 6 months after irradiation, cardiac structural and molecular changes were examined with histology, immunohistochemistry, and Western blot analysis. Results: Capsaicin pretreatment blunted the effects of radiation on myocardial fibrosis and mast cell infiltration and activity. By contrast, capsaicin pretreatment caused a small but significant reduction in cardiac output 6 months after irradiation. Capsaicin did not alter the effects of radiation on cardiac macrophage number or indicators of autophagy and apoptosis. Conclusions: These results suggest that sensory nerves, although they play a predominantly protective role in radiation-induced cardiac function changes, may eventually enhance radiation-induced myocardial fibrosis and mast cell activity.

  20. Roles of Sensory Nerves in the Regulation of Radiation-Induced Structural and Functional Changes in the Heart

    International Nuclear Information System (INIS)

    Sridharan, Vijayalakshmi; Tripathi, Preeti; Sharma, Sunil; Moros, Eduardo G.; Zheng, Junying; Hauer-Jensen, Martin; Boerma, Marjan

    2014-01-01

    Purpose: Radiation-induced heart disease (RIHD) is a chronic severe side effect of radiation therapy of intrathoracic and chest wall tumors. The heart contains a dense network of sensory neurons that not only are involved in monitoring of cardiac events such as ischemia and reperfusion but also play a role in cardiac tissue homeostasis, preconditioning, and repair. The purpose of this study was to examine the role of sensory nerves in RIHD. Methods and Materials: Male Sprague-Dawley rats were administered capsaicin to permanently ablate sensory nerves, 2 weeks before local image-guided heart x-ray irradiation with a single dose of 21 Gy. During the 6 months of follow-up, heart function was assessed with high-resolution echocardiography. At 6 months after irradiation, cardiac structural and molecular changes were examined with histology, immunohistochemistry, and Western blot analysis. Results: Capsaicin pretreatment blunted the effects of radiation on myocardial fibrosis and mast cell infiltration and activity. By contrast, capsaicin pretreatment caused a small but significant reduction in cardiac output 6 months after irradiation. Capsaicin did not alter the effects of radiation on cardiac macrophage number or indicators of autophagy and apoptosis. Conclusions: These results suggest that sensory nerves, although they play a predominantly protective role in radiation-induced cardiac function changes, may eventually enhance radiation-induced myocardial fibrosis and mast cell activity

  1. Rhynchophylline suppresses soluble Aβ1-42-induced impairment of spatial cognition function via inhibiting excessive activation of extrasynaptic NR2B-containing NMDA receptors.

    Science.gov (United States)

    Yang, Yang; Ji, Wei-Gang; Zhu, Zhi-Ru; Wu, Yu-Ling; Zhang, Zhi-Yang; Qu, Shao-Chen

    2018-06-01

    Rhynchophylline (RIN) is a significant active component isolated from the Chinese herbal medicine Uncaria rhynchophylla. The overproduction of soluble amyloid β protein (Aβ) oligomers in the hippocampus is closely involved in impairments in cognitive function at the early stage of Alzheimer's disease (AD). Growing evidences show that RIN possesses neuroprotective effects against Aβ-induced neurotoxicity. However, whether RIN can prevent soluble Aβ 1-42 -induced impairments in spatial cognitive function and synaptic plasticity is still unclear. Using the combined methods of behavioral tests, immunofluorescence and electrophysiological recordings, we characterized the key neuroprotective properties of RIN and its possible cellular and molecular mechanisms against soluble Aβ 1-42 -related impairments in rats. Our findings are as follows: (1) RIN efficiently rescued the soluble Aβ 1-42 -induced spatial learning and memory deficits in the Morris water maze test and prevented soluble Aβ 1-42 -induced suppression in long term potentiation (LTP) in the entorhinal cortex (EC)-dentate gyrus (DG) circuit. (2) Excessive activation of extrasynaptic GluN2B-NMDAR and subsequent Ca 2+ overload contributed to the soluble Aβ 1-42 -induced impairments in spatial cognitive function and synaptic plasticity. (3) RIN prevented Aβ 1-42 -induced excessive activation of extrasynaptic NMDARs by reducing extrasynaptic NMDARs -mediated excitatory postsynaptic currents and down regulating GluN2B-NMDAR expression in the DG region, which inhibited Aβ 1-42 -induced Ca 2+ overload mediated by extrasynanptic NMDARs. The results suggest that RIN could be an effective therapeutic candidate for cognitive impairment in AD. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Gemfibrozil-induced myositis in a patient with normal renal function.

    Science.gov (United States)

    Hahn, Martin; Sriharan, Kalavally; McFarland, M Shawn

    2010-01-01

    To describe a case of gemfibrozil monotherapy-induced myositis in a patient with normal renal function A 68-year-old white man presented to his primary care clinic complaining of a 6-month history of total body pain. His past medical history was significant for hypertension, diabetes mellitus, hyperlipidemia, gastroesophageal reflux disease, benign prostatic hypertrophy, arthritis, impotence, and pancreatic cancer that required excision of part of his pancreas. His home drug regimen included bupropion 75 mg twice daily, gemfibrozil 600 mg twice daily for the past 8 months, glimiperide 1 mg daily, insulin glargine 5 units at bedtime, insulin aspart 5 units in the evening, lisinopril 10 mg daily, omeprazole 40 mg daily, pregabalin 100 mg daily, and sildenafil 100 mg as needed. Laboratory test results were significant for elevated aspartate aminotransferase (AST) 78 U/L (reference range 15-46 U/L), alanine aminotransferase (ALT) 83 U/L (13-69 U/L), and creatine kinase (CK) 3495 U/L (55-170 U/L). Serum creatinine was normal at 1.19 mg/dL. The physician determined that the elevated CK indicated myositis secondary to gemfibrozil use, and gemfibrozil was subsequently discontinued. The patient returned 1 week later to repeat the laboratory tests. Results were CK 220 U/L, AST 26 U/L, ALT 43 U/L, and serum creatinine 1.28 mg/dL. The patient was asked to return in 3 weeks to repeat the laboratory tests. At that time, CK had continued to decrease to 142 U/L, and the AST and ALT had returned to normal, at 22 and 29 U/L, respectively. The patient reported complete resolution of total body pain 3 weeks after discontinuation of gemfibrozil. Follow-up 5 weeks after discontinuation revealed no change compared to the 3-week follow-up. Myositis most often produces weakness and elevated CK levels more than 10 times the upper limit of normal. The risk of developing myositis, myopathy, or rhabdomyolysis is low (1%) when fibrates such as gemfibrozil are used as monotherapy. Evaluation of

  3. Mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion-induced injury by improving lysosomal function and autophagic flux.

    Science.gov (United States)

    Zhou, Tianen; Liang, Lian; Liang, Yanran; Yu, Tao; Zeng, Chaotao; Jiang, Longyuan

    2017-09-15

    Mild hypothermia has been proven to be useful to treat brain ischemia/reperfusion injury. However, the underlying mechanisms have not yet been fully elucidated. The present study was undertaken to determine whether mild hypothermia protects hippocampal neurons against oxygen-glucose deprivation/reperfusion(OGD/R)-induced injury via improving lysosomal function and autophagic flux. The results showed that OGD/R induced the occurrence of autophagy, while the acidic environment inside the lysosomes was altered. The autophagic flux assay with RFP-GFP tf-LC3 was impeded in hippocampal neurons after OGD/R. Mild hypothermia recovered the lysosomal acidic fluorescence and the lysosomal marker protein expression of LAMP2, which decreased after OGD/R.Furthermore, we found that mild hypothermia up-regulated autophagic flux and promoted the fusion of autophagosomes and lysosomes in hippocampal neurons following OGD/R injury, but could be reversed by treatment with chloroquine, which acts as a lysosome inhibitor. We also found that mild hypothermia improved mitochondrial autophagy in hippocampal neurons following OGD/R injury. Finally,we found that chloroquine blocked the protective effects of mild hypothermia against OGD/R-induced cell death and injury. Taken together, the present study indicates that mild hypothermia protects hippocampal neurons against OGD/R-induced injury by improving lysosomal function and autophagic flux. Copyright © 2017. Published by Elsevier Inc.

  4. Adenovirus vector expressing keratinocyte growth factor using CAG promoter impairs pulmonary function of mice with elastase-induced emphysema.

    Science.gov (United States)

    Oki, Hiroshi; Yazawa, Takuya; Baba, Yasuko; Kanegae, Yumi; Sato, Hanako; Sakamoto, Seiko; Goto, Takahisa; Saito, Izumu; Kurahashi, Kiyoyasu

    2017-07-01

    Pulmonary emphysema impairs quality of life and increases mortality. It has previously been shown that administration of adenovirus vector expressing murine keratinocyte growth factor (KGF) before elastase instillation prevents pulmonary emphysema in mice. We therefore hypothesized that therapeutic administration of KGF would restore damage to lungs caused by elastase instillation and thus improve pulmonary function in an animal model. KGF expressing adenovirus vector, which prevented bleomycin-induced pulmonary fibrosis in a previous study, was constructed. Adenovirus vector (1.0 × 10 9 plaque-forming units) was administered intratracheally one week after administration of elastase into mouse lungs. One week after administration of KGF-vector, exercise tolerance testing and blood gas analysis were performed, after which the lungs were removed under deep anesthesia. KGF-positive pneumocytes were more numerous, surfactant protein secretion in the airspace greater and mean linear intercept of lungs shorter in animals that had received KGF than in control animals. Unexpectedly, however, arterial blood oxygenation was worse in the KGF group and maximum running speed, an indicator of exercise capacity, had not improved after KGF in mice with elastase-induced emphysema, indicating that KGF-expressing adenovirus vector impaired pulmonary function in these mice. Notably, vector lacking KGF-expression unit did not induce such impairment, implying that the KGF expression unit itself may cause the damage to alveolar cells. Possible involvement of the CAG promoter used for KGF expression in impairing pulmonary function is discussed. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  5. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders

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    Ignacio Negrón-Oyarzo

    2016-01-01

    Full Text Available Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders.

  6. Functional photoacoustic imaging to observe regional brain activation induced by cocaine hydrochloride

    Science.gov (United States)

    Jo, Janggun; Yang, Xinmai

    2011-09-01

    Photoacoustic microscopy (PAM) was used to detect small animal brain activation in response to drug abuse. Cocaine hydrochloride in saline solution was injected into the blood stream of Sprague Dawley rats through tail veins. The rat brain functional change in response to the injection of drug was then monitored by the PAM technique. Images in the coronal view of the rat brain at the locations of 1.2 and 3.4 mm posterior to bregma were obtained. The resulted photoacoustic (PA) images showed the regional changes in the blood volume. Additionally, the regional changes in blood oxygenation were also presented. The results demonstrated that PA imaging is capable of monitoring regional hemodynamic changes induced by drug abuse.

  7. Anti-tachycardia therapy can improve altered cardiac adrenergic function in tachycardia-induced cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Ohkusu, Yasuo; Takahashi, Nobukazu; Ishikawa, Toshiyuki [Yokohama City Univ. (Japan). School of Medicine] [and others

    2002-11-01

    We investigated whether anti-tachycardia therapy might improve the altered cardiac adrenergic and systolic function in tachycardia-induced cardiomyopathy (TC) in contrast to dilated cardiomyopathy (DCM). The subjects were 23 patients with heart failure, consisting of 8 patients with TC (43.6{+-}10.0 yrs) and 15 with DCM (45.3{+-}8.2 yrs). TC was determined as impairment of left ventricular function secondary to chronic or very frequent arrhythmia during more than 10% of the day. All patients were receiving anti-tachycardia treatment. Cardiac {sup 123}I-MIBG uptake was assessed as the heart/mediastinum activity ratio (H/M) before and after treatment. Left ventricular ejection fraction (LVEF) was also assessed. In the baseline study, H/M and LVEF showed no difference between TC and DCM (2.21{+-}0.44 vs. 2.10{+-}0.42, 35.3{+-}13.1 vs. 36.0{+-}10.9%, respectively). After treatment, the degree of change in H/M and LVEF differed significantly (0.41{+-}0.34 vs. 0.08{+-}0.20, 20.5{+-}14.4 vs. -2.1{+-}9.6%, p<0.01). In TC, heart failure improved after a shorter duration of treatment (p<0.05). In conclusion, anti-tachycardia therapy can improve altered cardiac adrenergic function and systolic function in patients with TC over a shorter period than in those with DCM. (author)

  8. Effect of Child Friendly Constraint Induced Movement Therapy on Unimanual and Bimanual Function in Hemiplegia

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    Seyed Mohammad Sadegh Hosseini

    2010-10-01

    Full Text Available Objectives: Hemiplegia is a non-progressive damage in premature growing brain which causes movement disorders in one side of the body. The objective of present research is to study the method of modified constraints induced movement therapy (CIMT which can be appropriate on unimanual and bimanual functions of children with Hemiplegia. Methods: This single-blinded, randomized, control trial study performed on twenty-eight participants who were selected based on specific inclusion criteria and divided into two groups of CIMT and conventional therapy. Intervention at CIMT was done six hours every day, for 10 days, whereas another group received conventional occupational therapy. Results: To analyze the data, independent-sample t-test and paired-sample t-test were used. Results showed that significant differences in variables of unimanual function, Jebson Taylor test and dexterity of involved hand in CIMT group, but, these variables did not show any difference in conventional group. Also bimanual functions in CIMT demonstrated significant difference in variables of bimanual function, bilateral coordination, and caregivers’ perception (how much and (how well, whereas this variables did not show any difference in pre-test and post-test of conventional therapy. Discussion: Child friendly CIMT has fairly good effects on unimanual function and some variables of bimanual function of children with hemiplegia.

  9. Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

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    Magdalena Cristóbal-García

    2015-01-01

    Full Text Available We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks and short-term (3 weeks effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW, OA+Allopurinol (AP, 150 mg/L drinking water, OA+Tempol (T, 15 mg/kg BW, or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase and oxidative stress markers (lipid and protein oxidation along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.

  10. MR urography: examination techniques and clinical applications

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    Nolte-Ernsting, C.C.A.; Adam, G.B.; Guenther, R.W. [Technische Hochschule Aachen (Germany). Klinik fuer Radiologische Diagnostik

    2001-03-01

    Modern MR urography is performed on the basis of two different imaging strategies, which can be used complementarily to cover almost all aspects in the diagnosis of upper urinary tract diseases. The first technique utilizes unenhanced, heavily T2-weighted pulse sequences to obtain static-fluid images of the urinary tract. T2-weighted MR urograms have proved to be excellent in the visualization of the markedly dilated urinary tract, even if the renal excretory function is quiescent. Static-fluid MR urography is less suitable for imaging of disorders that occur in the nondilated collecting system. The second MR urography technique is analogous to the methodology of conventional intravenous pyelography and is, therefore, designated as excretory MR urography. For this purpose, a non-nephrotoxic gadolinium chelate is intravenously administered and after its renal excretion, the gadolinium-enhanced urine is visualized using fast T1-weighted gradient-echo sequences. The combination of gadolinium and low-dose furosemide (5-10 mg) is the key for achieving a uniform distribution of the contrast material inside the entire urinary tract and, secondly, to avoid high endoluminal gadolinium concentrations, which cause signal loss of the urine due to T2{sup *} effects. Gadolinium excretory MR urography allows to obtain high-quality images of both nondilated and obstructed urinary tracts in patients with normal or moderately impaired renal function. This article reviews the principles of T2- and T1-weighted MR urography in detail and informs how to use these techniques safely in potential clinical applications such as chronic urolithiasis, intrinsic and extrinsic tumor diseases, and congenital anomalies. Magnetic resonance urography performed in combination with standard MR imaging offers a potential to reduce the need for invasive retrograde pyelography. Although the economic aspect is still problematic, it is obvious that MR urography will continue to increase its role in

  11. Lipocalins Are Required for Apical Extracellular Matrix Organization and Remodeling in Caenorhabditis elegans.

    Science.gov (United States)

    Forman-Rubinsky, Rachel; Cohen, Jennifer D; Sundaram, Meera V

    2017-10-01

    A lipid and glycoprotein-rich apical extracellular matrix (aECM) or glycocalyx lines exposed membranes in the body, and is particularly important to protect narrow tube integrity. Lipocalins ("fat cups") are small, secreted, cup-shaped proteins that bind and transport lipophilic cargo and are often found in luminal or aECM compartments such as mammalian plasma, urine, or tear film. Although some lipocalins can bind known aECM lipids and/or matrix metalloproteinases, it is not known if and how lipocalins affect aECM structure due to challenges in visualizing the aECM in most systems. Here we show that two Caenorhabditis elegans lipocalins, LPR-1 and LPR-3, have distinct functions in the precuticular glycocalyx of developing external epithelia. LPR-1 moves freely through luminal compartments, while LPR-3 stably localizes to a central layer of the membrane-anchored glycocalyx, adjacent to the transient zona pellucida domain protein LET-653 Like LET-653 and other C. elegans glycocalyx components, these lipocalins are required to maintain the patency of the narrow excretory duct tube, and also affect multiple aspects of later cuticle organization. lpr-1 mutants cannot maintain a continuous excretory duct apical domain and have misshapen cuticle ridges (alae) and abnormal patterns of cuticular surface lipid staining. lpr-3 mutants cannot maintain a passable excretory duct lumen, properly degrade the eggshell, or shed old cuticle during molting, and they lack cuticle barrier function. Based on these phenotypes, we infer that both LPR-1 and LPR-3 are required to build a properly organized aECM, while LPR-3 additionally is needed for aECM clearance and remodeling. The C. elegans glycocalyx provides a powerful system, amenable to both genetic analysis and live imaging, for investigating how lipocalins and lipids affect aECM structure. Copyright © 2017 by the Genetics Society of America.

  12. Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function

    Science.gov (United States)

    McNamee, Eóin N.; Johnson, Darlynn Korns; Homann, Dirk

    2014-01-01

    Oxygen is a molecule that is central to cellular respiration and viability, yet there are multiple physiologic and pathological contexts in which cells experience conditions of insufficient oxygen availability, a state known as hypoxia. Given the metabolic challenges of a low oxygen environment, hypoxia elicits a range of adaptive responses at the cellular, tissue, and systemic level to promote continued survival and function. Within this context, T lymphocytes are a highly migratory cell type of the adaptive immune system that frequently encounters a wide range of oxygen tensions in both health and disease. It is now clear that oxygen availability regulates T cell differentiation and function, a response orchestrated in large part by the hypoxia-inducible factor transcription factors. Here, we discuss the physiologic scope of hypoxia and hypoxic signaling, the contribution of these pathways in regulating T cell biology, and current gaps in our understanding. Finally, we discuss how emerging therapies that modulate the hypoxic response may offer new modalities to alter T cell function and the outcome of acute and chronic pathologies. PMID:22961658

  13. Conjugated Linoleic Acid Administration Induces Amnesia in Male Sprague Dawley Rats and Exacerbates Recovery from Functional Deficits Induced by a Controlled Cortical Impact Injury.

    Directory of Open Access Journals (Sweden)

    Rastafa I Geddes

    Full Text Available Long-chain polyunsaturated fatty acids like conjugated linoleic acids (CLA are required for normal neural development and cognitive function and have been ascribed various beneficial functions. Recently, oral CLA also has been shown to increase testosterone (T biosynthesis, which is known to diminish traumatic brain injury (TBI-induced neuropathology and reduce deficits induced by stroke in adult rats. To test the impact of CLA on cognitive recovery following a TBI, 5-6 month old male Sprague Dawley rats received a focal injury (craniectomy + controlled cortical impact (CCI; n = 17 or Sham injury (craniectomy alone; n = 12 and were injected with 25 mg/kg body weight of Clarinol® G-80 (80% CLA in safflower oil; n = 16 or saline (n = 13 every 48 h for 4 weeks. Sham surgery decreased baseline plasma progesterone (P4 by 64.2% (from 9.5 ± 3.4 ng/mL to 3.4 ± 0.5 ng/mL; p = 0.068, T by 74.6% (from 5.9 ± 1.2 ng/mL to 1.5 ± 0.3 ng/mL; p 0.05 animals by post-injury day 29, but rapidly reversed by post-injury day 1 the hypoadrenalism in Sham (11-DOC: 372.6 ± 36.6 ng/mL; corticosterone: 202.6 ± 15.6 ng/mL and CCI-injured (11-DOC: 384.2 ± 101.3 ng/mL; corticosterone: 234.6 ± 43.8 ng/mL animals. In Sham surgery animals, CLA did not alter body weight, but did markedly increase latency to find the hidden Morris Water Maze platform (40.3 ± 13.0 s compared to saline treated Sham animals (8.8 ± 1.7 s. In CCI injured animals, CLA did not alter CCI-induced body weight loss, CCI-induced cystic infarct size, or deficits in rotarod performance. However, like Sham animals, CLA injections exacerbated the latency of CCI-injured rats to find the hidden MWM platform (66.8 ± 10.6 s compared to CCI-injured rats treated with saline (30.7 ± 5.5 s, p < 0.05. These results indicate that chronic treatment of CLA at a dose of 25 mg/kg body weight in adult male rats over 1-month 1 does not reverse craniectomy- and craniectomy + CCI-induced hypogonadism, but does reverse

  14. Vacancy-induced magnetism in BaTiO3(001) thin films based on density functional theory.

    Science.gov (United States)

    Cao, Dan; Cai, Meng-Qiu; Hu, Wang-Yu; Yu, Ping; Huang, Hai-Tao

    2011-03-14

    The origin of magnetism induced by vacancies on BaTiO(3)(001) surfaces is investigated systematically by first-principles calculations within density-functional theory. The calculated results show that O vacancy is responsible for the magnetism of the BaO-terminated surface and the magnetism of the TiO(2)-terminated surface is induced by Ti vacancy. For the BaO-terminated surface, the magnetism mainly arises from the unpaired electrons that are localized in the O vacancy basin. In contrast, for the TiO(2)-terminated surface, the magnetism mainly originates from the partially occupied O-2p states of the first nearest neighbor O atoms surrounding the Ti vacancy. These results suggest the possibility of implementing magneto-electric coupling in conventional ferroelectric materials.

  15. Transcriptome analysis of the Cryptocaryon irritans tomont stage identifies potential genes for the detection and control of cryptocaryonosis

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    Wan Kiew-Lian

    2010-01-01

    Full Text Available Abstract Background Cryptocaryon irritans is a parasitic ciliate that causes cryptocaryonosis (white spot disease in marine fish. Diagnosis of cryptocaryonosis often depends on the appearance of white spots on the surface of the fish, which are usually visible only during later stages of the disease. Identifying suitable biomarkers of this parasite would aid the development of diagnostic tools and control strategies for C. irritans. The C. irritans genome is virtually unexplored; therefore, we generated and analyzed expressed sequence tags (ESTs of the parasite to identify genes that encode for surface proteins, excretory/secretory proteins and repeat-containing proteins. Results ESTs were generated from a cDNA library of C. irritans tomonts isolated from infected Asian sea bass, Lates calcarifer. Clustering of the 5356 ESTs produced 2659 unique transcripts (UTs containing 1989 singletons and 670 consensi. BLAST analysis showed that 74% of the UTs had significant similarity (E-value -5 to sequences that are currently available in the GenBank database, with more than 15% of the significant hits showing unknown function. Forty percent of the UTs had significant similarity to ciliates from the genera Tetrahymena and Paramecium. Comparative gene family analysis with related taxa showed that many protein families are conserved among the protozoans. Based on gene ontology annotation, functional groups were successfully assigned to 790 UTs. Genes encoding excretory/secretory proteins and membrane and membrane-associated proteins were identified because these proteins often function as antigens and are good antibody targets. A total of 481 UTs were classified as encoding membrane proteins, 54 were classified as encoding for membrane-bound proteins, and 155 were found to contain excretory/secretory protein-coding sequences. Amino acid repeat-containing proteins and GPI-anchored proteins were also identified as potential candidates for the development of

  16. A functional MRI study of the brain in stroke patients with upper-limb paralysis treated with constraint-induced movement therapy

    International Nuclear Information System (INIS)

    Wen Bo; Ma Lin; Weng Changshui; Zheng Zhixin; Sun Tong

    2009-01-01

    Objective: To investigate and compare the activation patterns of stroke patients with upper-limb paralysis using functional MRI before and after treatment with constraint-induced movement therapy (CIMT) so as to explore the mechanism of CIMT. Methods: Six patients in chronic stage of brain infarction who have functional disturbance in right upper-limb and 9 normal controls were entered into the study. All of the patients were asked to perform the thumb-to-index finger tapping task and underwent functional MRI before and two weeks after CIMT. The controls underwent fMRI of same protocol once. The patients' upper-limb function scores before and after CIMT were analyzed with SPSS 11.5 by paired t test. The fMRI data were analyzed with analysis of functional neurolmages (AFNI) software. The percentage of blood oxygenation level dependent (BOLD) signal change for the normal control was analyzed by one-sample t test to indentify the activated brain regions. The percentage change of BOLD signal for the patients before and after CIMT was compared to control's data by independent-samples t test. The percentage change of BOLD signal for the patients before and after CIMT was analyzed by paired-samples t test. The significant difference level was set P<0.05. Results: The fMRI showed the patients' activated brain regions before CIMT were similar to that of the controls', while the activation level was lower. There were wide areas activated to compensate the impaired function especially for the fight upper-limb. Before CIMT, the patients' score for fight upper-limb on the action research arm test was 27±4. After CIMT, the patients' score was 40±3, and the difference was significant (t=14.626, P<0.05), which indicated the improved function. These subjects also displayed cortical reorganization after CIMT on fMRI. The areas responsible for the right hand movement showed increased activation and the activation level at bilateral corpora striata thalami, and cerebella increased

  17. Radiation-induced heterogeneity of chymotrypsin of mus musculus. On the characterization of structurally and functionally in vitro modified enzyme forms

    International Nuclear Information System (INIS)

    Amneus, H.

    1976-01-01

    The distribution of in vitro induced 60 Co-γ (structural heterogeneity of mouse chymotrypsin has been studied in terms of molecular weight, catalytic activity and net charge distribution. It was found that the enzyme stucture, with retained molecular weight, could partly accumulate structural changes subsequently not leading to modification of catalytic properties. Loss of petide fragments (0 < Mw (lt 6000) the enzyme showed native function but also modified as well as total loss of function. Further loss of peptide fragments results in modified function and total loss of function. These results indicate the capability of the enzyme to accumulate in vitro changes partly without a total loss of function. (author)

  18. Amphetamine-induced dopamine release and neurocognitive function in treatment-naive adults with ADHD.

    Science.gov (United States)

    Cherkasova, Mariya V; Faridi, Nazlie; Casey, Kevin F; O'Driscoll, Gillian A; Hechtman, Lily; Joober, Ridha; Baker, Glen B; Palmer, Jennifer; Dagher, Alain; Leyton, Marco; Benkelfat, Chawki

    2014-05-01

    Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [(11)C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87 ± 8.65) and 18 healthy male controls (age: 25.44 ± 6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a battery of neurocognitive tests. Relative to the healthy controls, the ADHD patients, as a group, showed greater d-amphetamine-induced decreases in striatal [(11)C]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [(11)C]raclopride binding potential was associated with poorer performance on measures of response inhibition and ADHD symptoms. Our findings suggest an augmented striatal dopaminergic response in treatment-naive ADHD. Though in contrast to results of a previous study, this finding appears consistent with a model proposing exaggerated phasic dopamine release in ADHD. A susceptibility to increased phasic dopamine responsivity may contribute to such characteristics of ADHD as poor inhibition and impulsivity.

  19. Functional role of CCCTC binding factor (CTCF) in stress-induced apoptosis

    International Nuclear Information System (INIS)

    Li Tie; Lu Luo

    2007-01-01

    CTCF, a nuclear transcriptional factor, is a multifunctional protein and involves regulation of growth factor- and cytokine-induced cell proliferation/differentiation. In the present study, we investigated the role of CTCF in protecting stress-induced apoptosis in various human cell types. We found that UV irradiation and hyper-osmotic stress induced human corneal epithelial (HCE) and hematopoietic myeloid cell apoptosis detected by significantly increased caspase 3 activity and decreased cell viability. The stress-induced apoptotic response in these cells requires down-regulation of CTCF at both mRNA and protein levels, suggesting that CTCF may play an important role in downstream events of stress-induced signaling pathways. Inhibition of NFκB activity prevented stress-induced down-regulation of CTCF and increased cell viability against stress-induced apoptosis. The anti-apoptotic effect of CTCF was further studied by manipulating CTCF activities in HCE and hematopoietic cells. Transient transfection of cDNAs encoding full-length human CTCF markedly suppressed stress-induced apoptosis in these cells. In contrast, knocking down of CTCF mRNA using siRNA specific to CTCF significantly promoted stress-induced apoptosis. Thus, our results reveal that CTCF is a down stream target of stress-induced signaling cascades and it plays a significant anti-apoptotic role in regulation of stress-induced cellular responses in HCE and hematopoietic myeloid cells

  20. Functional and molecular characterization of hyposensitive underactive bladder tissue and urine in streptozotocin-induced diabetic rat.

    Directory of Open Access Journals (Sweden)

    Jayabalan Nirmal

    Full Text Available The functional and molecular alterations of nerve growth factor (NGF and Prostaglandin E2 (PGE2 and its receptors were studied in bladder and urine in streptozotocin (STZ-induced diabetic rats.Diabetes mellitus was induced with a single dose of 45 mg/kg STZ Intraperitoneally (i.p in female Sprague-Dawley rats. Continuous cystometrogram were performed on control rats and STZ treated rats at week 4 or 12 under urethane anesthesia. Bladder was then harvested for histology, expression of EP receptors and NGF by western blotting, PGE2 levels by ELISA, and detection of apoptosis by TUNEL staining. In addition, 4-hr urine was collected from all groups for urine levels of PGE2, and NGF assay. DM induced progressive increase of bladder weight, urine production, intercontraction interval (ICI and residual urine in a time dependent fashion. Upregulation of Prostaglandin E receptor (EP1 and EP3 receptors and downregulation of NGF expression, increase in urine NGF and decrease levels of urine PGE2 at week 12 was observed. The decrease in ICI by intravesical instillation of PGE2 was by 51% in control rats and 31.4% in DM group at week 12.DM induced hyposensitive underactive bladder which is characterized by increased inflammatory reaction, apoptosis, urine NGF levels, upregulation of EP1 and EP3 receptors and decreased bladder NGF and urine PGE2. The data suggest that EP3 receptor are potential targets in the treatment of diabetes induced underactive bladder.

  1. Long-term activation of TLR3 by Poly(I:C induces inflammation and impairs lung function in mice

    Directory of Open Access Journals (Sweden)

    Alexopoulou Lena

    2009-06-01

    Full Text Available Abstract Background The immune mechanisms associated with infection-induced disease exacerbations in asthma and COPD are not fully understood. Toll-like receptor (TLR 3 has an important role in recognition of double-stranded viral RNA, which leads to the production of various inflammatory mediators. Thus, an understanding of TLR3 activation should provide insight into the mechanisms underlying virus-induced exacerbations of pulmonary diseases. Methods TLR3 knock-out (KO mice and C57B6 (WT mice were intranasally administered repeated doses of the synthetic double stranded RNA analog poly(I:C. Results There was a significant increase in total cells, especially neutrophils, in BALF samples from poly(I:C-treated mice. In addition, IL-6, CXCL10, JE, KC, mGCSF, CCL3, CCL5, and TNFα were up regulated. Histological analyses of the lungs revealed a cellular infiltrate in the interstitium and epithelial cell hypertrophy in small bronchioles. Associated with the pro-inflammatory effects of poly(I:C, the mice exhibited significant impairment of lung function both at baseline and in response to methacholine challenge as measured by whole body plethysmography and an invasive measure of airway resistance. Importantly, TLR3 KO mice were protected from poly(I:C-induced changes in lung function at baseline, which correlated with milder inflammation in the lung, and significantly reduced epithelial cell hypertrophy. Conclusion These findings demonstrate that TLR3 activation by poly(I:C modulates the local inflammatory response in the lung and suggest a critical role of TLR3 activation in driving lung function impairment. Thus, TLR3 activation may be one mechanism through which viral infections contribute toward exacerbation of respiratory disease.

  2. Improved mitochondrial function with diet-induced increase in either docosahexaenoic acid or arachidonic acid in membrane phospholipids.

    Directory of Open Access Journals (Sweden)

    Ramzi J Khairallah

    Full Text Available Mitochondria can depolarize and trigger cell death through the opening of the mitochondrial permeability transition pore (MPTP. We recently showed that an increase in the long chain n3 polyunsaturated fatty acids (PUFA docosahexaenoic acid (DHA; 22:6n3 and depletion of the n6 PUFA arachidonic acid (ARA; 20:4n6 in mitochondrial membranes is associated with a greater Ca(2+ load required to induce MPTP opening. Here we manipulated mitochondrial phospholipid composition by supplementing the diet with DHA, ARA or combined DHA+ARA in rats for 10 weeks. There were no effects on cardiac function, or respiration of isolated mitochondria. Analysis of mitochondrial phospholipids showed DHA supplementation increased DHA and displaced ARA in mitochondrial membranes, while supplementation with ARA or DHA+ARA increased ARA and depleted linoleic acid (18:2n6. Phospholipid analysis revealed a similar pattern, particularly in cardiolipin. Tetralinoleoyl cardiolipin was depleted by 80% with ARA or DHA+ARA supplementation, with linoleic acid side chains replaced by ARA. Both the DHA and ARA groups had delayed Ca(2+-induced MPTP opening, but the DHA+ARA group was similar to the control diet. In conclusion, alterations in mitochondria membrane phospholipid fatty acid composition caused by dietary DHA or ARA was associated with a greater cumulative Ca(2+ load required to induced MPTP opening. Further, high levels of tetralinoleoyl cardiolipin were not essential for normal mitochondrial function if replaced with very-long chain n3 or n6 PUFAs.

  3. EFFECT OF FUROSTANOL GLYCOSIDES FROM CULTURED DIOSCOREA DELTOIDEA CELLS ON REGULATORY FUNCTION OF ENDOTHELIUM IN A RAT MODEL OF HYPOESTROGEN-INDUCED ENDOTHELIAL DYSFUNCTION

    Directory of Open Access Journals (Sweden)

    E. B. Artyushkova

    2008-01-01

    Full Text Available Aim. To study the effects of furostanol glycosides from cultured Dioscorea Deltoidea cells (DM-05, Institute of Plant Physiology, RAS on physiological and biochemical markers of endothelial function in rats with hypoestrogen-induced endothelial dysfunction.Material and methods. 10 female rats of Wistar line, with body mass 200-300 g have been included in the experiment. The bilateral ovariectomy was performed in rats to produce the model of hypoestrogen-induced endothelial dysfunction. Rats were treated with the injections of DM-05 during 6 weeks. False ovariectomy was performed in rats of control group (n=10.Results. DM-05 restored the levels of stable metabolites of nitric oxide (NO which reflex endothelial NO-synthase activity. Besides DM-05 corrected blood pressure and endothelial function. Experiments on open heart showed that DM-05 protects the cardiac tissue from hypoestrogen-induced hyperadrenoreactivity.Conclusion. Treatment with plant origin substances with estrogen-like activity can be a perspective approach to the correction of endothelial function and decrease in cardiovascular risk in menopause women.

  4. Functional properties of nisin-carbohydrate conjugates formed by radiation induced Maillard reaction

    Science.gov (United States)

    Muppalla, Shobita R.; Sonavale, Rahul; Chawla, Surinder P.; Sharma, Arun

    2012-12-01

    Nisin-carbohydrate conjugates were prepared by irradiating nisin either with glucose or dextran. Increase in browning and formation of intermediate products was observed with a concomitant decrease in free amino and reducing sugar groups indicating occurrence of the Maillard reaction catalyzed by irradiation. Nisin-carbohydrate conjugates showed a broad spectrum antibacterial activity against Gram negative bacteria (Escherichia coli, Pseudomonas fluorescence) as well as Gram positive bacteria (Staphylococcus aureus, Bacillus cereus). Results of antioxidant assays, including that of DPPH radical-scavenging activity and reducing power, showed that the nisin-dextran conjugates possessed better antioxidant potential than nisin-glucose conjugate. These results suggested that it was possible to enhance the functional properties of nisin by preparing radiation induced conjugates suitable for application in food industry.

  5. Separation of photo-induced radical pair in cryptochrome to a functionally critical distance

    DEFF Research Database (Denmark)

    Solov'yov, Ilia; Domratcheva, Tatiana; Schulten, Klaus

    2014-01-01

    Cryptochrome is a blue light receptor that acts as a sensor for the geomagnetic field and assists many animals in long-range navigation. The magnetoreceptor function arises from light-induced formation of a radical pair through electron transfer between a flavin cofactor (FAD) and a triad...... of tryptophan residues. Here, this electron transfer is investigated by quantum chemical and classical molecular dynamics calculations. The results reveal how sequential electron transfer, assisted by rearrangement of polar side groups in the cryptochrome interior, can yield a FAD-Trp radical pair state...... step can overcome in speed both recombination (electron back-transfer) and proton transfer involving the radical pair reached after primary electron transfer....

  6. Excitation functions for quasi-elastic transfer reactions induced with heavy ions in bismuth

    International Nuclear Information System (INIS)

    Gardes, D.; Bimbot, R.; Maison, J.; Reilhac, L. de; Rivet, M.F.; Fleury, A.; Hubert, F.; Llabador, Y.

    1977-01-01

    The excitation functions for the production of 210 Bi, 210 Po, sup(207-211)At and 211 Rn through quasi-elastic transfer reactions induced with heavy ions in 209 Bi have been measured. The corresponding reactions involved the transfer of one neutron, one proton, two and three charges from projectile to target. The projectiles used were 12 C, 14 N, 16 O, 19 F, 20 Ne, 40 Ca, 56 Fe and 63 Cu. The experimental techniques involved target irradiations and off-line α and γ activity measurements. Chemical separations were used to solve specific problems. Careful measurements of incident energies and cross sections were performed close to the reaction thresholds

  7. Functionalized nanoparticles for AMF-induced gene and drug delivery

    Science.gov (United States)

    Biswas, Souvik

    The properties and broad applications of nano-magnetic colloids have generated much interest in recent years. Specially, Fe3O4 nanoparticles have attracted a great deal of attention since their magnetic properties can be used for hyperthermia treatment or drug targeting. For example, enhanced levels of intracellular gene delivery can be achieved using Fe3O4 nano-vectors in the presence of an external magnetic field, a process known as 'magnetofection'. The low cytotoxicity, tunable particle size, ease of surface functionalization, and ability to generate thermal energy using an external alternating magnetic field (AMF) are properties have propelled Fe3O4 research to the forefront of nanoparticle research. The strategy of nanoparticle-mediated, AMF-induced heat generation has been used to effect intracellular hyperthermia. One application of this 'magnetic hyperthermia' is heat activated local delivery of a therapeutic effector (e.g.; drug or polynucleotide). This thesis describes the development of a magnetic nano-vector for AMF-induced, heat-activated pDNA and small molecule delivery. The use of heat-inducible vectors, such as heat shock protein ( hsp) genes, is a promising mode of gene therapy that would restrict gene expression to a local region by focusing a heat stimulus only at a target region. We thus aimed to design an Fe3O4 nanoparticle-mediated gene transfer vehicle for AMF-induced localized gene expression. We opted to use 'click' oximation techniques to assemble the magnetic gene transfer vector. Chapter 2 describes the synthesis, characterization, and transfection studies of the oxime ether lipid-based nano-magnetic vectors MLP and dMLP. The synthesis and characterization of a novel series of quaternary ammonium aminooxy reagents (2.1--2.4) is described. These cationic aminooxy compounds were loaded onto nanoparticles for ligation with carbonyl groups and also to impart a net positive charge on the nanoparticle surface. Our studies indicated that the

  8. Far infra-red therapy promotes ischemia-induced angiogenesis in diabetic mice and restores high glucose-suppressed endothelial progenitor cell functions

    Directory of Open Access Journals (Sweden)

    Huang Po-Hsun

    2012-08-01

    Full Text Available Abstract Background Far infra-red (IFR therapy was shown to exert beneficial effects in cardiovascular system, but effects of IFR on endothelial progenitor cell (EPC and EPC-related vasculogenesis remain unclear. We hypothesized that IFR radiation can restore blood flow recovery in ischemic hindlimb in diabetic mice by enhancement of EPCs functions and homing process. Materials and methods Starting at 4 weeks after the onset of diabetes, unilateral hindlimb ischemia was induced in streptozotocine (STZ-induced diabetic mice, which were divided into control and IFR therapy groups (n = 6 per group. The latter mice were placed in an IFR dry sauna at 34°C for 30 min once per day for 5 weeks. Results Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio in the thermal therapy group was significantly increased beyond that in controls, and significantly greater capillary density was seen in the IFR therapy group. Flow cytometry analysis showed impaired EPCs (Sca-1+/Flk-1+ mobilization after ischemia surgery in diabetic mice with or without IFR therapy (n = 6 per group. However, as compared to those in the control group, bone marrow-derived EPCs differentiated into endothelial cells defined as GFP+/CD31+ double-positive cells were significantly increased in ischemic tissue around the vessels in diabetic mice that received IFR radiation. In in-vitro studies, cultured EPCs treated with IFR radiation markedly augmented high glucose-impaired EPC functions, inhibited high glucose-induced EPC senescence and reduced H2O2 production. Nude mice received human EPCs treated with IFR in high glucose medium showed a significant improvement in blood flow recovery in ischemic limb compared to those without IFR therapy. IFR therapy promoted blood flow recovery and new vessel formation in STZ-induced diabetic mice. Conclusions Administration of IFR therapy promoted collateral flow recovery and new vessel formation in STZ-induced

  9. Age-related functional changes and susceptibility to eccentric contraction-induced damage in skeletal muscle cell.

    Science.gov (United States)

    Choi, Seung-Jun

    2016-09-01

    Depending upon external loading conditions, skeletal muscles can either shorten, lengthen, or remain at a fixed length as they produce force. Fixed-end or isometric contractions stabilize joints and allow muscles to act as active struts during locomotion. Active muscles dissipate energy when they are lengthened by an external force that exceeds their current force producing capacity. These unaccustomed eccentric activities often lead to muscle weakness, soreness, and inflammation. During aging, the ability to produce force under these conditions is reduced and appears to be due to not only reductions in muscle mass but also to alterations in the basic mechanisms of contraction. These alterations include impairments in the excitation-contraction process, and the action of the cross-bridges. Also, it is well known that age-related skeletal muscle atrophy is characterized by a preferential atrophy of fast fibers, and increased susceptibility to fast muscle fiber when aged muscles are exposed to eccentric contraction followed by the impaired recovery process has been reported. Taken together, the selective loss of fast muscle fiber in aged muscle could be affected by eccentric-induced muscle damage, which has significant implication to identify the etiology of the age-related functional changes. Therefore, in this review the alteration of age-related muscle function and its impact to/of eccentric induced muscle damage and recovery will be addressed in detail.

  10. Age-related functional changes and susceptibility to eccentric contraction-induced damage in skeletal muscle cell

    Directory of Open Access Journals (Sweden)

    Seung-Jun Choi

    2016-09-01

    Full Text Available Depending upon external loading conditions, skeletal muscles can either shorten, lengthen, or remain at a fixed length as they produce force. Fixed-end or isometric contractions stabilize joints and allow muscles to act as active struts during locomotion. Active muscles dissipate energy when they are lengthened by an external force that exceeds their current force producing capacity. These unaccustomed eccentric activities often lead to muscle weakness, soreness, and inflammation. During aging, the ability to produce force under these conditions is reduced and appears to be due to not only reductions in muscle mass but also to alterations in the basic mechanisms of contraction. These alterations include impairments in the excitation–contraction process, and the action of the cross-bridges. Also, it is well known that age-related skeletal muscle atrophy is characterized by a preferential atrophy of fast fibers, and increased susceptibility to fast muscle fiber when aged muscles are exposed to eccentric contraction followed by the impaired recovery process has been reported. Taken together, the selective loss of fast muscle fiber in aged muscle could be affected by eccentric-induced muscle damage, which has significant implication to identify the etiology of the age-related functional changes. Therefore, in this review the alteration of age-related muscle function and its impact to/of eccentric induced muscle damage and recovery will be addressed in detail.

  11. Mixtures of xenoestrogens disrupt estradiol-induced non-genomic signaling and downstream functions in pituitary cells.

    Science.gov (United States)

    Viñas, René; Watson, Cheryl S

    2013-03-26

    Our study examines the effects of xenoestrogen mixtures on estradiol-induced non-genomic signaling and associated functional responses. Bisphenol-A, used to manufacture plastic consumer products, and nonylphenol, a surfactant, are estrogenic by a variety of assays, including altering many intracellular signaling pathways; bisphenol-S is now used as a bisphenol-A substitute. All three compounds contaminate the environment globally. We previously showed that bisphenol-S, bisphenol-A, and nonylphenol alone rapidly activated several kinases at very low concentrations in the GH3/B6/F10 rat pituitary cell line. For each assay we compared the response of individual xenoestrogens at environmentally relevant concentrations (10-15 -10-7 M), to their mixture effects on 10-9 M estradiol-induced responses. We used a medium-throughput plate immunoassay to quantify phosphorylations of extracellular signal-regulated kinases (ERKs) and c-Jun-N-terminal kinases (JNKs). Cell numbers were assessed by crystal violet assay to compare the proliferative effects. Apoptosis was assessed by measuring caspase 8 and 9 activities via the release of the fluorescent product 7-amino-4-trifluoromethylcoumarin. Prolactin release was measured by radio-immunoassay after a 1 min exposure to all individual and combinations of estrogens. Individual xenoestrogens elicited phospho-activation of ERK in a non-monotonic dose- (fM-nM) and mostly oscillating time-dependent (2.5-60 min) manner. When multiple xenoestrogens were combined with nM estradiol, the physiologic estrogen's response was attenuated. Individual bisphenol compounds did not activate JNK, while nonylphenol did; however, the combination of two or three xenoestrogens with estradiol generated an enhanced non-monotonic JNK dose-response. Estradiol and all xenoestrogen compounds induced cell proliferation individually, while the mixtures of these compounds with estradiol suppressed proliferation below that of the vehicle control, suggesting a

  12. Non-thermal plasma instabilities induced by deformation of the electron energy distribution function

    Science.gov (United States)

    Dyatko, N. A.; Kochetov, I. V.; Napartovich, A. P.

    2014-08-01

    Non-thermal plasma is a key component in gas lasers, microelectronics, medical applications, waste gas cleaners, ozone generators, plasma igniters, flame holders, flow control in high-speed aerodynamics and others. A specific feature of non-thermal plasma is its high sensitivity to variations in governing parameters (gas composition, pressure, pulse duration, E/N parameter). This sensitivity is due to complex deformations of the electron energy distribution function (EEDF) shape induced by variations in electric field strength, electron and ion number densities and gas excitation degree. Particular attention in this article is paid to mechanisms of instabilities based on non-linearity of plasma properties for specific conditions: gas composition, steady-state and decaying plasma produced by the electron beam, or by an electric current pulse. The following effects are analyzed: the negative differential electron conductivity; the absolute negative electron mobility; the stepwise changes of plasma properties induced by the EEDF bi-stability; thermo-current instability and the constriction of the glow discharge column in rare gases. Some of these effects were observed experimentally and some of them were theoretically predicted and still wait for experimental confirmation.

  13. Dual AAV therapy ameliorates exercise-induced muscle injury and functional ischemia in murine models of Duchenne muscular dystrophy.

    Science.gov (United States)

    Zhang, Yadong; Yue, Yongping; Li, Liang; Hakim, Chady H; Zhang, Keqing; Thomas, Gail D; Duan, Dongsheng

    2013-09-15

    Neuronal nitric oxide synthase (nNOS) membrane delocalization contributes to the pathogenesis of Duchenne muscular dystrophy (DMD) by promoting functional muscle ischemia and exacerbating muscle injury during exercise. We have previously shown that supra-physiological expression of nNOS-binding mini-dystrophin restores normal blood flow regulation and prevents functional ischemia in transgenic mdx mice, a DMD model. A critical next issue is whether systemic dual adeno-associated virus (AAV) gene therapy can restore nNOS-binding mini-dystrophin expression and mitigate muscle activity-related functional ischemia and injury. Here, we performed systemic gene transfer in mdx and mdx4cv mice using a pair of dual AAV vectors that expressed a 6 kb nNOS-binding mini-dystrophin gene. Vectors were packaged in tyrosine mutant AAV-9 and co-injected (5 × 10(12) viral genome particles/vector/mouse) via the tail vein to 1-month-old dystrophin-null mice. Four months later, we observed 30-50% mini-dystrophin positive myofibers in limb muscles. Treatment ameliorated histopathology, increased muscle force and protected against eccentric contraction-induced injury. Importantly, dual AAV therapy successfully prevented chronic exercise-induced muscle force drop. Doppler hemodynamic assay further showed that therapy attenuated adrenergic vasoconstriction in contracting muscle. Our results suggest that partial transduction can still ameliorate nNOS delocalization-associated functional deficiency. Further evaluation of nNOS binding mini-dystrophin dual AAV vectors is warranted in dystrophic dogs and eventually in human patients.

  14. Bisphenol S impairs blood functions and induces cardiovascular risks in rats

    Directory of Open Access Journals (Sweden)

    Sanghamitra Pal

    Full Text Available Bisphenol S (BPS is an industrial chemical which is recently used to replace the potentially toxic Bisphenol A (BPA in making polycarbonate plastics, epoxy resins and thermal receipt papers. The probable toxic effects of BPS on the functions of haemopoietic and cardiovascular systems have not been reported till to date. We report here that BPS depresses haematological functions and induces cardiovascular risks in rat. Adult male albino rats of Sprague-Dawley strain were given BPS at a dose level of 30, 60 and 120 mg/kg BW/day respectively for 30 days. Red blood cell (RBC count, white blood cell (WBC count, Hb concentration, and clotting time have been shown to be significantly (*P < 0.05 reduced in a dose dependent manner in all exposed groups of rats comparing to the control. It has also been shown that BPS increases total serum glucose and protein concentration in the exposed groups of rats. We have observed that BPS increases serum total cholesterol, triglyceride, glycerol free triglyceride, low density lipoprotein (LDL and very low density lipoprotein (VLDL concentration, whereas high density lipoprotein (HDL concentration has been found to be reduced in the exposed groups. BPS significantly increases serum aspartate aminotransferase (AST, alanine aminotransferase (ALT and alkaline phosphatase (ALP activities dose dependently. Moreover, serum calcium, bilirubin and urea concentration have been observed to be increased in all exposed groups. In conclusion, BPS probably impairs the functions of blood and promotes cardiovascular risks in rats. Keywords: Bisphenol S, Red blood cell count, White blood cell count, Clotting time, LDL cholesterol, HDL cholesterol, Cardiovascular risks

  15. Freeze-thaw lysates of Plasmodium falciparum-infected red blood cells induce differentiation of functionally competent regulatory T cells from memory T cells.

    Science.gov (United States)

    Finney, Olivia C; Lawrence, Emma; Gray, Alice P; Njie, Madi; Riley, Eleanor M; Walther, Michael

    2012-07-01

    In addition to naturally occurring regulatory T (nTreg) cells derived from the thymus, functionally competent Treg cells can be induced in vitro from peripheral blood lymphocytes in response to TCR stimulation with cytokine costimulation. Using these artificial stimulation conditions, both naïve as well as memory CD4(+) T cells can be converted into induced Treg (iTreg) cells, but the cellular origin of such iTreg cells in vivo or in response to more physiologic stimulation with pathogen-derived antigens is less clear. Here, we demonstrate that a freeze/thaw lysate of Plasmodium falciparum schizont extract (PfSE) can induce functionally competent Treg cells from peripheral lymphocytes in a time- and dose-dependent manner without the addition of exogenous costimulatory factors. The PfSE-mediated induction of Treg cells required the presence of nTreg cells in the starting culture. Further experiments mixing either memory or naïve T cells with antigen presenting cells and CFSE-labeled Treg cells identified CD4(+) CD45RO(+) CD25(-) memory T cells rather than Treg cells as the primary source of PfSE-induced Treg cells. Taken together, these data suggest that in the presence of nTreg cells, PfSE induces memory T cells to convert into iTreg cells that subsequently expand alongside PfSE-induced effector T cells. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Mice with diet-induced obesity demonstrate a relative prothrombotic factor profile and a thicker aorta with reduced ex-vivo function.

    Science.gov (United States)

    Uner, Aykut G; Unsal, Cengiz; Unsal, Humeyra; Erdogan, Mumin A; Koc, Ece; Ekici, Mehmet; Avci, Hamdi; Balkaya, Muharrem; Belge, Ferda; Tarin, Lokman

    2018-04-01

    : Classical risk factors such as cholesterol and lipoproteins are currently not sufficient to explain all physiopathological processes of obesity-related vascular dysfunction as well as atherosclerosis and arteriosclerosis. Therefore, the discovery of potential markers involved in vascular dysfunction in the obese state is still needed. Disturbances in hemostatic factors may be involved in the developmental processes associated with obesity-related cardiovascular disorders. We hypothesized that alterations of several hemostatic factors in the obese state could correlate with the function and morphology of the aorta and it could play an important role in the development of vascular dysfunction. To test this, we fed mice with a high-fat diet for 18 weeks and investigated the relationships between selected hemostatic factors (in either plasma or in the liver), metabolic hormones and morphology, and ex-vivo function of the aorta. Here, we show that 18-week exposure to a high-fat diet results in a higher plasma fibrinogen and prolonged prothrombin time in diet-induced obese mice compared to the controls. In addition, liver levels or activities of FII, FX, activated protein C, AT-III, and protein S are significantly different in diet-induced obese mice as compared to the controls. Curiously, FII, FVIII, FX, activated protein C, PTT, and protein S are correlated with both the aorta histology (aortic thickness and diameter) and ex-vivo aortic function. Notably, ex-vivo studies revealed that diet-induced obese mice show a marked attenuation in the functions of the aorta. Taken together, aforementioned hemostatic factors may be considered as critical markers for obesity-related vascular dysfunction and they could play important roles in diagnosing of the dysfunction.

  17. Divergent effects of 17-β-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-α-induced neointima formation

    International Nuclear Information System (INIS)

    Nintasen, Rungrat; Riches, Kirsten; Mughal, Romana S.; Viriyavejakul, Parnpen; Chaisri, Urai; Maneerat, Yaowapa; Turner, Neil A.; Porter, Karen E.

    2012-01-01

    Highlights: ► TNF-α augments neointimal hyperplasia in human saphenous vein. ► TNF-α induces detrimental effects on endothelial and smooth muscle cell function. ► Estradiol exerts modulatory effects on TNF-induced vascular cell functions. ► The modulatory effects of estradiol are discriminatory and cell-type specific. -- Abstract: Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α). TNF-α can induce vascular endothelial cell (EC) and smooth muscle cell (SMC) dysfunction, central events in development of neointimal lesions. The reduced incidence of CHD in young women is believed to be due to the protective effects of estradiol (E2). We therefore investigated the effects of TNF-α on human neointima formation and SMC/EC functions and any modulatory effects of E2. Saphenous vein (SV) segments were cultured in the presence of TNF-α (10 ng/ml), E2 (2.5 nM) or both in combination. Neointimal thickening was augmented by incubation with TNF-α, an effect that was abolished by co-culture with E2. TNF-α increased SV–SMC proliferation in a concentration-dependent manner that was optimal at 10 ng/ml (1.5-fold increase), and abolished by E2 at all concentrations studied (1–50 nM). Surprisingly, E2 itself at low concentrations (1 and 5 nM) stimulated SV–SMC proliferation to a level comparable to that of TNF-α alone. SV–EC migration was significantly impaired by TNF-α (42% of control), and co-culture with E2 partially restored the ability of SV–EC to migrate and repair the wound. In contrast, TNF-α increased SV–SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-α potently induced ICAM-1 and VCAM-1 expression in both SV–EC and SV–SMC. However there was no modulation by E2 in either cell-type. In conclusion, TNF-α induced SV neointima formation, increased SMC proliferation and migration, impaired

  18. Functional computed tomography imaging of tumor-induced angiogenesis. Preliminary results of new tracer kinetic modeling using a computer discretization approach

    International Nuclear Information System (INIS)

    Kaneoya, Katsuhiko; Ueda, Takuya; Suito, Hiroshi

    2008-01-01

    The aim of this study was to establish functional computed tomography (CT) imaging as a method for assessing tumor-induced angiogenesis. Functional CT imaging was mathematically analyzed for 14 renal cell carcinomas by means of two-compartment modeling using a computer-discretization approach. The model incorporated diffusible kinetics of contrast medium including leakage from the capillary to the extravascular compartment and back-flux to the capillary compartment. The correlations between functional CT parameters [relative blood volume (rbv), permeability 1 (Pm1), and permeability 2 (Pm2)] and histopathological markers of angiogenesis [microvessel density (MVD) and vascular endothelial growth factor (VEGF)] were statistically analyzed. The modeling was successfully performed, showing similarity between the mathematically simulated curve and the measured time-density curve. There were significant linear correlations between MVD grade and Pm1 (r=0.841, P=0.001) and between VEGF grade and Pm2 (r=0.804, P=0.005) by Pearson's correlation coefficient. This method may be a useful tool for the assessment of tumor-induced angiogenesis. (author)

  19. [EFFECT OF ACETYLCYSTEINE, CORVITIN AND THEIR COMBINATION ON THE FUNCTIONAL STATE OF LIVER IN RATS WITH PARACETAMOL INDUCED TOXIC HEPATITIS].

    Science.gov (United States)

    Ghonghadze, M; Antelava, N; Liluashvili, K; Okujava, M; Pachkoria, K

    2017-02-01

    Nowadays drug-induced hepatotoxicity is urgent problem worldwide. Currently more than 1000 drugs are hepatotoxic and most often are the reason of acute fulminant hepatitis and hepatocellular failure, the states requiring liver transplantation. The paracetamol induced liver toxicity is related with accumulation of its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), which is the free radical and enhances peroxidation of lipids, disturbs the energy status and causes death of hepatocytes. During our research we investigated and assessed the efficacy of acetylcysteine, corvitin and their combination in rat model of paracetamol induced acute toxic hepatitis. The study was performed on mature white male Wistar rates with body mass 150-180 g. 50 rats were randomly divided into 5 groups (10 rats in each group). To get the model of acute toxic hepatitis single intraperitoneal injection of paracetamol solution was used (750 mg/kg). Toxic hepatitis was treated with intrapertoneal administration of 40mg/kg acetylcysteine or 100mg/kg corvitin, as well as with combination of these drugs. Monotherapy with acetylcysteine and corvitin of paracetamol induced toxic hepatitis improved the liver function, decreased relative mass of the liver and animal mortality. The treatment of toxic hepatitis was most effective in the case of simultaneous administration of acetylcysteine and corvitin. The normal value of laboratory tests (ALT, ACT, alkaline phosphatase, total and unconjugated bilirubin) was reached and mortality was not more observed. On the bases of obtained data was concluded that acetylcysteine and corvitin have almost equal hepatoprotective activity. The combination of two drugs actually improves the liver function. The most pronounced hepatoprotective effect may be due to synergic action of acetylcysteine and corvitin and such regime can be recommended for correction of liver function.

  20. A functional MRI study of happy and sad affective states induced by classical music.

    Science.gov (United States)

    Mitterschiffthaler, Martina T; Fu, Cynthia H Y; Dalton, Jeffrey A; Andrew, Christopher M; Williams, Steven C R

    2007-11-01

    The present study investigated the functional neuroanatomy of transient mood changes in response to Western classical music. In a pilot experiment, 53 healthy volunteers (mean age: 32.0; SD = 9.6) evaluated their emotional responses to 60 classical musical pieces using a visual analogue scale (VAS) ranging from 0 (sad) through 50 (neutral) to 100 (happy). Twenty pieces were found to accurately induce the intended emotional states with good reliability, consisting of 5 happy, 5 sad, and 10 emotionally unevocative, neutral musical pieces. In a subsequent functional magnetic resonance imaging (fMRI) study, the blood oxygenation level dependent (BOLD) signal contrast was measured in response to the mood state induced by each musical stimulus in a separate group of 16 healthy participants (mean age: 29.5; SD = 5.5). Mood state ratings during scanning were made by a VAS, which confirmed the emotional valence of the selected stimuli. Increased BOLD signal contrast during presentation of happy music was found in the ventral and dorsal striatum, anterior cingulate, parahippocampal gyrus, and auditory association areas. With sad music, increased BOLD signal responses were noted in the hippocampus/amygdala and auditory association areas. Presentation of neutral music was associated with increased BOLD signal responses in the insula and auditory association areas. Our findings suggest that an emotion processing network in response to music integrates the ventral and dorsal striatum, areas involved in reward experience and movement; the anterior cingulate, which is important for targeting attention; and medial temporal areas, traditionally found in the appraisal and processing of emotions. Copyright 2006 Wiley-Liss, Inc.

  1. Functionalization of Polymer Surfaces by Radiation-Induced Grafting for Separation of Heavy Metal Ions

    Energy Technology Data Exchange (ETDEWEB)

    Przybytniak, G; Kornacka, E M; Fuks, L; Walo, M; Lyczko, K; Mirkowski, K [Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland)

    2012-09-15

    The reported investigations were focused on the elucidation of the most important factors influencing radiation-induced grafting; particularly (1) the effect of radical population generated in polymeric matrix on degree of grafting, (2) parameters determined grafting and its procedure, (3) correlation between layer structure formed via copolymerization and content of monomers in the initial solution. Sorption capacity of the adsorbants was evaluated using {sup 152}Eu{sup 3+} as a marker monitoring depletion of the radioisotope from the initial solution by gamma radiometer. Electron spin resonance spectroscopy (EPR) and gas chromatography (GC) studies confirmed that yield of radiation-induced radicals increases in the following order polystyrene (PS) < polypropylene (PP) < polyethylene (PE). The same relationship was found for efficiency of radiation grafting. It was concluded that under comparable conditions the content of radicals in polymeric matrices determines grafting degree. It was found that application of the simultaneous method of grafting introduces to the grafted layers crosslinking or/and branching as well as degradation of functional groups. All these phenomena reduce access of Eu{sup 3+} to the studied sorbent therefore sorption capacity of the polyamide functionalized via pre-irradiation (indirect) method is higher than that determined for the sorbent prepared by simultaneous method of grafting. When two monomers, acrylic acid (AAc) and acrylamide (AAm) , contributed in the formation of grafted layer, their input into copolymerization was not proportional to the concentrations in the feed solution. It was confirmed that grafting of the monomers shows synergetic effect as the yield of copolymerization exceeds degree of grafting achieved for individual components. (author)

  2. Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats

    Directory of Open Access Journals (Sweden)

    Fernando B. R. da Silva

    2018-05-01

    Full Text Available Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures’ morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF, pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.

  3. Transcriptomic and functional analysis of NaCl-induced stress in Enterococcus faecalis.

    Directory of Open Access Journals (Sweden)

    Margrete Solheim

    Full Text Available The robust physiology of Enterococcus faecalis facilitates tolerance to various stresses. We here report the transcriptional response of E. faecalis V583 to growth in the presence of 6.5% NaCl. Among the early responses observed was an immediate down-regulation of mscL, accompanied by an up-regulation of genes predicted to be involved in uptake of extracellular potassium and glycine betaine. The high NaCl concentration also induced expression of chaperons and cell envelope related traits, such as the enterococcal polysaccharide antigen (epa locus. Functional genetic analysis revealed reduced salt stress resistance in both epaB and epaE mutants. The reduced salt resistance phenotype associated with the epaB mutant was restored by complementation, hence demonstrating a role of Epa in the physiological robustness of E. faecalis. Furthermore, we demonstrate that Epa confers increased resistance towards multiple cell envelope stress-inducing factors. Accordingly, these findings delineate a potential link between the robust nature of E. faecalis and its ability to perform as a human pathogen, and provide a new perspective on the mechanisms by which Epa contributes to virulence. Notably, the high NaCl concentration also resulted in strict repression of the gelE-sprE operon and impaired gelatinase activity. We demonstrate that NaCl antagonize the GBAP-pheromone dependent induction in a concentration dependent manner.

  4. A functional RG equation for the c-function

    DEFF Research Database (Denmark)

    Codello, A.; D'Odorico, G.; Pagani, C.

    2014-01-01

    , local potential approximation and loop expansion. In each case we construct the relative approximate c-function and find it to be consistent with Zamolodchikov's c-theorem. Finally, we present a relation between the c-function and the (matter induced) beta function of Newton's constant, allowing us...... to use heat kernel techniques to compute the RG running of the c-function....

  5. Contribution of High-Pressure-Induced Protein Modifications to the Microenvironment and Functional Properties of Rabbit Meat Sausages.

    Science.gov (United States)

    Xue, Siwen; Yu, Xiaobo; Yang, Huijuan; Xu, Xinglian; Ma, Hanjun; Zhou, Guanghong

    2017-06-01

    Rabbit meat batters were subjected to high pressure (HP, 100 to 300 MPa for 3, 9, or 15 min) to elucidate their effects on proteins structures, the microenvironment, and the resulting functionalities of the subsequently heated products. To determine these effects, we investigated structural and microenvironmental changes using Raman spectroscopy and also expressible moisture content, textural characteristics, and dynamic rheological properties of batters during heating (20 to 80 °C). Untreated samples served as controls. Analysis of specific Raman spectral regions demonstrated that applications of HP to rabbit meat batters tended to induce the transformation of the all-gauche S-S conformation to gauche-gauche-trans in the batter system. HP treatment higher than 100 MPa for 9 min promoted secondary structural rearrangements, and molecular polarity enhancement in the proteins prior to cooking. Also, increases of O-H stretching intensities of rabbit meat sausages were obtained by HP treatment, denoting the strengthening of water-holding capacity. These HP-induced alterations resulted in improved texture and, perhaps, improved juiciness of rabbit meat sausages (P functionalities of gel-type products through modification of meat proteins. © 2017 Institute of Food Technologists®.

  6. Single-phase DECT with VNCT compared with three-phase CTU in patients with haematuria

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jung Jae; Park, Byung Kwan; Kim, Chan Kyo [Sungkyunkwan University School of Medicine, Department of Radiology, Samsung Medical Center, Seoul (Korea, Republic of)

    2016-10-15

    To retrospectively evaluate the diagnostic performance of single-phase dual-energy CT (DECT) with virtual non-contrast CT (VNCT) compared with three-phase CT urography (CTU) in patients with haematuria. A total of 296 patients underwent three-phase CTU (NCT at 120 kVp; nephrographic phase and excretory phase DECTs at 140 kVp and 80 kVp) owing to haematuria. Diagnostic performances of CT scans were compared for detecting urothelial tumours and urinary stones. Dose-length product (DLP) was compared in relation to single-phase DECT and three-phase CTU Dose-length product (DLP) was compared in relation to single-phase DECT and three-phase CTU. Sensitivity and specificity for tumour were 95 % (19/20) and 98.9 % (273/276) on CTU, 95 % (19/20) and 98.2 % (271/276) on nephrographic phase DECT, and 90 % (18/20) and 98.2 % (271/276) on excretory phase DECT (P > 0.1). Of the 148 stones detected on NCT, 108 (73 %) and 100 (67.6 %) were detected on nephrographic phase and excretory phase VNCTs, respectively. The mean size of stones undetected on nephrographic and excretory VNCTs was measured as 1.5 ± 0.5 mm and 1.6 ± 0.6 mm, respectively. The mean DLPs of three-phase CTU, nephrographic phase DECT and excretory phase DECT were 1076 ± 248 mGy . cm, 410 ± 98 mGy . cm, and 360 ± 87 mGy . cm, respectively (P < 0.001). Single-phase DECT has a potential to replace three-phase CTU for detecting tumours with a lower radiation dose. (orig.)

  7. Protein kinase C and extracellular signal-regulated kinase regulate movement, attachment, pairing and egg release in Schistosoma mansoni.

    Directory of Open Access Journals (Sweden)

    Margarida Ressurreição

    2014-06-01

    Full Text Available Protein kinases C (PKCs and extracellular signal-regulated kinases (ERKs are evolutionary conserved cell signalling enzymes that coordinate cell function. Here we have employed biochemical approaches using 'smart' antibodies and functional screening to unravel the importance of these enzymes to Schistosoma mansoni physiology. Various PKC and ERK isotypes were detected, and were differentially phosphorylated (activated throughout the various S. mansoni life stages, suggesting isotype-specific roles and differences in signalling complexity during parasite development. Functional kinase mapping in adult worms revealed that activated PKC and ERK were particularly associated with the adult male tegument, musculature and oesophagus and occasionally with the oesophageal gland; other structures possessing detectable activated PKC and/or ERK included the Mehlis' gland, ootype, lumen of the vitellaria, seminal receptacle and excretory ducts. Pharmacological modulation of PKC and ERK activity in adult worms using GF109203X, U0126, or PMA, resulted in significant physiological disturbance commensurate with these proteins occupying a central position in signalling pathways associated with schistosome muscular activity, neuromuscular coordination, reproductive function, attachment and pairing. Increased activation of ERK and PKC was also detected in worms following praziquantel treatment, with increased signalling associated with the tegument and excretory system and activated ERK localizing to previously unseen structures, including the cephalic ganglia. These findings support roles for PKC and ERK in S. mansoni homeostasis, and identify these kinase groups as potential targets for chemotherapeutic treatments against human schistosomiasis, a neglected tropical disease of enormous public health significance.

  8. Protective effect of S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721) on irradiation-induced inhibition of intestinal transport function

    International Nuclear Information System (INIS)

    Chen, T.S.; Ando, M.

    1983-01-01

    The purpose of this study was to investigate the protective effect of S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721) on whole-body irradiation-induced inhibition of intestinal transport function. The jejunal transport of fluid and sugars was studied in male Swiss-Webster mice before and 3 days after whole-body irradiation (1000 rads). The rates of glucose and water transport were decreased by 86 and 70%, respectively, in irradiated animals. However, the rate of transport of 3-O-methyl-D-glucose (3MG) was not affected. In mice receiving WR-2721 (500 mg/kg, ip) 15 to 30 min prior to whole-body irradiation, net water flux was unaffected and the rate of D-glucose transport was decreased only 8%. WR-2721 administered alone (500 mg/kg, ip) had no effect on either D-glucose transport or net water flux across the jejunal mucosa. The results suggest that WR-2721 protects against irradiation-induced inhibition of some intestinal transport functions

  9. Combined Cognitive-Psychological-Physical Intervention Induces Reorganization of Intrinsic Functional Brain Architecture in Older Adults

    Directory of Open Access Journals (Sweden)

    Zhiwei Zheng

    2015-01-01

    Full Text Available Mounting evidence suggests that enriched mental, physical, and socially stimulating activities are beneficial for counteracting age-related decreases in brain function and cognition in older adults. Here, we used functional magnetic resonance imaging (fMRI to demonstrate the functional plasticity of brain activity in response to a combined cognitive-psychological-physical intervention and investigated the contribution of the intervention-related brain changes to individual performance in healthy older adults. The intervention was composed of a 6-week program of combined activities including cognitive training, Tai Chi exercise, and group counseling. The results showed improved cognitive performance and reorganized regional homogeneity of spontaneous fluctuations in the blood oxygen level-dependent (BOLD signals in the superior and middle temporal gyri, and the posterior lobe of the cerebellum, in the participants who attended the intervention. Intriguingly, the intervention-induced changes in the coherence of local spontaneous activity correlated with the improvements in individual cognitive performance. Taken together with our previous findings of enhanced resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe regions following a combined intervention program in older adults, we conclude that the functional plasticity of the aging brain is a rather complex process, and an effective cognitive-psychological-physical intervention is helpful for maintaining a healthy brain and comprehensive cognition during old age.

  10. Edaravone Improves Septic Cardiac Function by Inducing an HIF-1α/HO-1 Pathway

    Directory of Open Access Journals (Sweden)

    Chao He

    2018-01-01

    Full Text Available Septic myocardial dysfunction remains prevalent and raises mortality rate in patients with sepsis. During sepsis, tissues undergo tremendous oxidative stress which contributes critically to organ dysfunction. Edaravone, a potent radical scavenger, has been proved beneficial in ischemic injuries involving hypoxia-inducible factor- (HIF- 1, a key regulator of a prominent antioxidative protein heme oxygenase- (HO- 1. However, its effect in septic myocardial dysfunction remains unclarified. We hypothesized that edaravone may prevent septic myocardial dysfunction by inducing the HIF-1/HO-1 pathway. Rats were subjected to cecal ligation and puncture (CLP with or without edaravone infusion at three doses (50, 100, or 200 mg/kg, resp. before CLP and intraperitoneal injection of the HIF-1α antagonist, ME (15 mg/kg, after CLP. After CLP, rats had cardiac dysfunction, which was associated with deformed myocardium, augmented lipid peroxidation, and increased myocardial apoptosis and inflammation, along with decreased activities of catalase, HIF-1α, and HO-1 in the myocardium. Edaravone pretreatment dose-dependently reversed the changes, of which high dose most effectively improved cardiac function and survival rate of septic rats. However, inhibition of HIF-1α by ME demolished the beneficial effects of edaravone at high dose, reducing the survival rate of the septic rats without treatments. Taken together, edaravone, by inducing the HIF-1α/HO-1 pathway, suppressed oxidative stress and protected the heart against septic myocardial injury and dysfunction.

  11. Laser-induced surface modification of biopolymers – micro/nanostructuring and functionalization

    Science.gov (United States)

    Stankova, N. E.; Atanasov, P. A.; Nedyalkov, N. N.; Tatchev, Dr; Kolev, K. N.; Valova, E. I.; Armyanov, St. A.; Grochowska, K.; Śliwiński, G.; Fukata, N.; Hirsch, D.; Rauschenbach, B.

    2018-03-01

    The medical-grade polydimethylsiloxane (PDMS) elastomer is a widely used biomaterial in medicine for preparation of high-tech devices because of its remarkable properties. In this paper, we present experimental results on surface modification of PDMS elastomer by using ultraviolet, visible, and near-infrared ns-laser system and investigation of the chemical composition and the morphological structure inside the treated area in dependence on the processing parameters – wavelength, laser fluence and number of pulses. Remarkable chemical transformations and changes of the morphological structure were observed, resulting in the formation of a highly catalytically active surface, which was successfully functionalized via electroless Ni and Pt deposition by a sensitizing-activation free process. The results obtained are very promising in view of applying the methods of laser-induced micro- and nano-structuring and activation of biopolymers’ surface and further electroless metal plating to the preparation of, e.g., multielectrode arrays (MEAs) devices in neural and muscular surface interfacing implantable systems.

  12. Pharmacological activation of the EDA/EDAR signaling pathway restores salivary gland function following radiation-induced damage.

    Directory of Open Access Journals (Sweden)

    Grace Hill

    Full Text Available Radiotherapy of head and neck cancers often results in collateral damage to adjacent salivary glands associated with clinically significant hyposalivation and xerostomia. Due to the reduced capacity of salivary glands to regenerate, hyposalivation is treated by substitution with artificial saliva, rather than through functional restoration of the glands. During embryogenesis, the ectodysplasin/ectodysplasin receptor (EDA/EDAR signaling pathway is a critical element in the development and growth of salivary glands. We have assessed the effects of pharmacological activation of this pathway in a mouse model of radiation-induced salivary gland dysfunction. We report that post-irradiation administration of an EDAR-agonist monoclonal antibody (mAbEDAR1 normalizes function of radiation damaged adult salivary glands as determined by stimulated salivary flow rates. In addition, salivary gland structure and homeostasis is restored to pre-irradiation levels. These results suggest that transient activation of pathways involved in salivary gland development could facilitate regeneration and restoration of function following damage.

  13. Radiation induced functionalism of polyethylene and ground tire rubber for their reactive compatibility in thermoplastic elastomers

    Energy Technology Data Exchange (ETDEWEB)

    Fainleib, A.; Grigoryeva, O. [Institute of Macromolecular Chemistry, National Academy of Sciences of Ukraine, Kiev 02160 (Ukraine); Martinez B, G. [Laboratorio de Investigacion y Desarrollo de Materiales Avanzados, Facultad de Quimica, Universidad Autonoma del Estado de Mexico, Km. 12 Carretera Toluca-Atlacomulco, San Cayetano 50200, Estado de Mexico (Mexico)], e-mail: fainleib@i.kiev.ua

    2009-07-01

    Reactive compatibility of recycled low-or high-density polyethylenes (LDPE and HDPE, respectively) and ground tire rubber (GTR) via chemical interactions of pre-functionalized components in their blend interface has been carried out. Polyethylene component was functionalized with maleic anhydride (MAH) as well as the rubber component was modified via functionalism with MAH or acrylamide using chemically or irradiation ({gamma} rays) induced grafting techniques. Additional coupling agents such as-p-phenylene diamine (PDA) and polyamide fiber (PAF, from fiber wastes) were used for some thermoplastic elastomer (TPE) producing. The grafting degree and molecular mass distribution of the chromatography analyses, respectively. TPE materials based on synthesized reactive polyethylenes and GTR as well as ethylene-propylene-diene monomer rubber were prepared by dynamic vulcanization of the rubber phase inside thermoplastic (polyethylene) matrix and their phase structure, and main properties have been studied using DSC, TGA, DMTA and mechanical testing. As a final result, the high performance TPE with improved mechanical properties has been developed. (Author)

  14. Causal Correlation Functions and Fourier Transforms: Application in Calculating Pressure Induced Shifts

    Science.gov (United States)

    Ma, Q.; Tipping, R. H.; Lavrentieva, N. N.

    2012-01-01

    By adopting a concept from signal processing, instead of starting from the correlation functions which are even, one considers the causal correlation functions whose Fourier transforms become complex. Their real and imaginary parts multiplied by 2 are the Fourier transforms of the original correlations and the subsequent Hilbert transforms, respectively. Thus, by taking this step one can complete the two previously needed transforms. However, to obviate performing the Cauchy principal integrations required in the Hilbert transforms is the greatest advantage. Meanwhile, because the causal correlations are well-bounded within the time domain and band limited in the frequency domain, one can replace their Fourier transforms by the discrete Fourier transforms and the latter can be carried out with the FFT algorithm. This replacement is justified by sampling theory because the Fourier transforms can be derived from the discrete Fourier transforms with the Nyquis rate without any distortions. We apply this method in calculating pressure induced shifts of H2O lines and obtain more reliable values. By comparing the calculated shifts with those in HITRAN 2008 and by screening both of them with the pair identity and the smooth variation rules, one can conclude many of shift values in HITRAN are not correct.

  15. Zoledronate inhibits ischemia-induced neovascularization by impairing the mobilization and function of endothelial progenitor cells.

    Directory of Open Access Journals (Sweden)

    Shih-Hung Tsai

    Full Text Available BACKGROUND: Bisphosphonates are a class of pharmacologic compounds that are commonly used to treat postmenopausal osteoporosis and malignant osteolytic processes. Studies have shown that bone marrow-derived endothelial progenitor cells (EPCs play a significant role in postnatal neovascularization. Whether the nitrogen-containing bisphosphonate zoledronate inhibits ischemia-induced neovascularization by modulating EPC functions remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Unilateral hindlimb ischemia was surgically induced in wild-type mice after 2 weeks of treatment with vehicle or zoledronate (low-dose: 30 μg/kg; high-dose: 100 μg/kg. Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio was significantly lower in wild-type mice treated with low-dose zoledronate and in mice treated with high-dose zoledronate than in controls 4 weeks after ischemic surgery (control vs. low-dose vs. high-dose: 87±7% vs. *61±18% vs. **49±17%, *p<0.01, **p<0.005 compared to control. Capillary densities were also significantly lower in mice treated with low-dose zoledronate and in mice treated with high-dose zoledronate than in control mice. Flow cytometry analysis showed impaired mobilization of EPC-like cells (Sca-1(+/Flk-1(+ after surgical induction of ischemia in mice treated with zoledronate but normal levels of mobilization in mice treated with vehicle. In addition, ischemic tissue from mice that received zoledronate treatment exhibited significantly lower levels of the active form of MMP-9, lower levels of VEGF, and lower levels of phosphorylated eNOS and phosphorylated Akt than ischemic tissue from mice that received vehicle. Results of the in vitro studies showed that incubation with zoledronate inhibited the viability, migration, and tube-forming capacities of EPC. CONCLUSIONS/SIGNIFICANCE: Zoledronate inhibited ischemia-induced neovascularization by impairing EPC mobilization and angiogenic functions

  16. [Effect of inducers and inhibitors of mixed function oxidases on body resistance to endotoxins of gram-negative bacteria].

    Science.gov (United States)

    Liniuchev, M N; Zubik, T M; Kovelenov, A Iu; Bulyko, V I; Sergeev, V V

    1989-06-01

    Experimental typhoid intoxication in white mice leads to the inhibition of microsomal oxidation in the liver, which is manifested by the prolongation of hexenal-induced sleep and a decrease in the toxic action of parathion. Phenobarbital, capable of inducing oxidases with mixed function (OMF), enhances the process of the detoxification of endotoxin injected into the animals, which is manifested by the increase of its LD50. Soluble levomycetin succinate, widely used for the treatment of typhoid-paratyphoid infections, is a powerful inhibitor of OMF (as shown by the hexenal test). Benzonal, the analog of phenobarbital, removes the inhibitory effect of the antibiotic. Experimental studies carried out in the course of this investigation make it possible to substantiate the clinical trial of these preparations (OMF inducers) used in the complex therapy of typhoid-paratyphoid infections for the stimulation of natural detoxification mechanisms of the body. Benzonal is the preparation of choice for use in clinical practice.

  17. Activation of p44/42 MAPK plays a role in the TBT-induced loss of human natural killer (NK) cell function.

    Science.gov (United States)

    Dudimah, Fred D; Griffey, Denisha; Wang, Xiaofei; Whalen, Margaret M

    2010-10-01

    Natural killer (NK) cells destroy (lyse) tumor cells, virally infected cells, and antibody-coated cells. Previous studies indicated that exposure to the environmental contaminant tributyltin (TBT) decreases the lytic function of NK cells and activates mitogen-activated protein kinases (MAPK), including p44/42 (Aluoch and Whalen Toxicology 209:263-277, 2005). If activation of p44/42 is required for TBT-induced decreases of lytic function, then activation of p44/42 to similar extents by pharmacological agents such as phorbol 12-myristate 13-acetate (PMA) should mimic to some extent changes induced in NK cells with TBT exposures. NK cells were exposed to PMA concentrations between 0.25 and 10 nM for 10 min, 1 h, and 6 h before determining the lytic function ((51)Cr release assay) and phosphorylation state of MAPKs (Western blot). A 1-h exposure of NK cells to 5 nM PMA resulted in a loss of lytic function of 47%. Western blot analysis showed that a 1-h exposure to 5 nM PMA caused a sixfold increase in phospho-p44/42 levels. Previous studies showed a fivefold increase in phospho-p44/42 in response to a 1-h exposure to 300 nM TBT. Exposure to 300 nM TBT caused about a 40% decrease in lytic function. This study supports the hypothesis that p44/42 activation (as seen with TBT exposures) can cause a loss of NK-cell lytic function.

  18. Activation of p44/42 MAPK Plays a Role in the TBT-induced Loss of Human Natural Killer (NK) Cell Function

    Science.gov (United States)

    Dudimah, Fred D.; Griffey, Denisha; Wang, Xiaofei; Whalen, Margaret M.

    2009-01-01

    Natural Killer (NK) cells destroy (lyse) tumor cells, virally infected cells and antibody-coated cells. Previous studies indicated that exposure to the environmental contaminant tributyltin (TBT) decreases the lytic function of NK cells and activates mitogen activated protein kinases (MAPK), including p44/42 (Aluoch and Whalen, 2005). If activation of p44/42 is required for TBT-induced decreases of lytic function, then activation of p44/42 to similar extents by pharmacological agents such as Phorbol 12-myristate 13-acetate (PMA) should mimic to some extent changes induced in NK cells with TBT exposures. NK cells were exposed to PMA concentrations between 0.25 and 10 nM for 10 min, 1 h, and 6 h before determining the lytic function (51Cr release assay) and phosphorylation state of MAPKs (Western blot). A 1 h exposure of NK cells to 5 nM PMA resulted in a loss of lytic function of 47%. Western blot analysis showed that a 1 h exposure to 5 nM PMA caused a 6 fold increase in phospho-p44/42 levels. Previous studies showed a 5 fold increase in phospho-p44/42 in response to a 1 h exposure to 300 nM TBT. Exposure to 300 nM TBT caused about a 40% decrease in lytic function. This study supports the hypothesis that p44/42 activation (as seen with TBT exposures) can cause a loss of NK-cell lytic function. PMID:20213532

  19. Inducible indirect defence of plants : from mechanisms to ecological functions

    NARCIS (Netherlands)

    Dicke, M.; Poecke, van R.M.P.; Boer, de J.G.

    2003-01-01

    Inducible defences allow plants to be phenotypically plastic. Inducible indirect defence of plants by attracting carnivorous enemies of herbivorous arthropods can vary with plant species and genotype, with herbivore species or instar and potentially with other environmental conditions. So far,

  20. Divergent effects of 17-{beta}-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-{alpha}-induced neointima formation

    Energy Technology Data Exchange (ETDEWEB)

    Nintasen, Rungrat [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom); Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University (Thailand); Riches, Kirsten; Mughal, Romana S. [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom); Viriyavejakul, Parnpen; Chaisri, Urai; Maneerat, Yaowapa [Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University (Thailand); Turner, Neil A. [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom); Porter, Karen E., E-mail: medkep@leeds.ac.uk [Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom); Multidisciplinary Cardiovascular Research Center (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} augments neointimal hyperplasia in human saphenous vein. Black-Right-Pointing-Pointer TNF-{alpha} induces detrimental effects on endothelial and smooth muscle cell function. Black-Right-Pointing-Pointer Estradiol exerts modulatory effects on TNF-induced vascular cell functions. Black-Right-Pointing-Pointer The modulatory effects of estradiol are discriminatory and cell-type specific. -- Abstract: Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-{alpha} (TNF-{alpha}). TNF-{alpha} can induce vascular endothelial cell (EC) and smooth muscle cell (SMC) dysfunction, central events in development of neointimal lesions. The reduced incidence of CHD in young women is believed to be due to the protective effects of estradiol (E2). We therefore investigated the effects of TNF-{alpha} on human neointima formation and SMC/EC functions and any modulatory effects of E2. Saphenous vein (SV) segments were cultured in the presence of TNF-{alpha} (10 ng/ml), E2 (2.5 nM) or both in combination. Neointimal thickening was augmented by incubation with TNF-{alpha}, an effect that was abolished by co-culture with E2. TNF-{alpha} increased SV-SMC proliferation in a concentration-dependent manner that was optimal at 10 ng/ml (1.5-fold increase), and abolished by E2 at all concentrations studied (1-50 nM). Surprisingly, E2 itself at low concentrations (1 and 5 nM) stimulated SV-SMC proliferation to a level comparable to that of TNF-{alpha} alone. SV-EC migration was significantly impaired by TNF-{alpha} (42% of control), and co-culture with E2 partially restored the ability of SV-EC to migrate and repair the wound. In contrast, TNF-{alpha} increased SV-SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-{alpha} potently induced ICAM-1 and VCAM-1 expression in both SV-EC and SV-SMC. However there

  1. QiShenYiQi Pills, a Compound Chinese Medicine, Prevented Cisplatin Induced Acute Kidney Injury via Regulating Mitochondrial Function

    Directory of Open Access Journals (Sweden)

    Li Zhou

    2017-12-01

    Full Text Available Nephrotoxicity is a serious adverse effect of cisplatin chemotherapy that limits its clinical application, to deal with which no effective management is available so far. The present study was to investigate the potential protective effect of QiShenYiQi Pills (QSYQ, a compound Chinese medicine, against cisplatin induced nephrotoxicity in mice. Pretreatment with QSYQ significantly attenuated the cisplatin induced increase in plasma urea and creatinine, along with the histological damage, such as tubular necrosis, protein cast, and desquamation of epithelial cells, improved the renal microcirculation disturbance as indicated by renal blood flow, microvascular flow velocity, and the number of adherent leukocytes. Additionally, QSYQ prevented mitochondrial dysfunction by preventing the cisplatin induced downregulation of mitochondrial complex activity and the expression of NDUFA10, ATP5D, and Sirt3. Meanwhile, the cisplatin-increased renal thiobarbituric acid-reactive substances, caspase9, cleaved-caspase9, and cleaved-caspase3 were all diminished by QSYQ pretreatment. In summary, the pretreatment with QSYQ remarkably ameliorated the cisplatin induced nephrotoxicity in mice, possibly via the regulation of mitochondrial function, oxidative stress, and apoptosis.

  2. Pattern of retinal morphological and functional decay in a light-inducible, rhodopsin mutant mouse.

    Science.gov (United States)

    Gargini, Claudia; Novelli, Elena; Piano, Ilaria; Biagioni, Martina; Strettoi, Enrica

    2017-07-18

    Hallmarks of Retinitis Pigmentosa (RP), a family of genetic diseases, are a typical rod-cone-degeneration with initial night blindness and loss of peripheral vision, followed by decreased daylight sight and progressive visual acuity loss up to legal blindness. Great heterogeneity in nature and function of mutated genes, variety of mutations for each of them, variability in phenotypic appearance and transmission modality contribute to make RP a still incurable disease. Translational research relies on appropriate animal models mimicking the genetic and phenotypic diversity of the human pathology. Here, we provide a systematic, morphological and functional analysis of Rho Tvrm4 /Rho + rhodopsin mutant mice, originally described in 2010 and portraying several features of common forms of autosomal dominant RP caused by gain-of-function mutations. These mice undergo photoreceptor degeneration only when exposed briefly to strong, white light and allow controlled timing of induction of rod and cone death, which therefore can be elicited in adult animals, as observed in human RP. The option to control severity and retinal extent of the phenotype by regulating intensity and duration of the inducing light opens possibilities to exploit this model for multiple experimental purposes. Altogether, the unique features of this mutant make it an excellent resource for retinal degeneration research.

  3. Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice.

    Science.gov (United States)

    Zhang, Yiqiang; Fischer, Kathleen E; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B

    2015-06-15

    Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality, leading some to suggest this condition represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers of function and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal, functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. Published by Elsevier Inc.

  4. Functionalization of PCL-3D Electrospun Nanofibrous Scaffolds for Improved BMP2-Induced Bone Formation.

    Science.gov (United States)

    Miszuk, Jacob M; Xu, Tao; Yao, Qingqing; Fang, Fang; Childs, Josh D; Hong, Zhongkui; Tao, Jianning; Fong, Hao; Sun, Hongli

    2018-03-01

    Bone morphogenic protein 2 (BMP2) is a key growth factor for bone regeneration, possessing FDA approval for orthopedic applications. BMP2 is often required in supratherapeutic doses clinically, yielding adverse side effects and substantial treatment costs. Considering the crucial role of materials for BMPs delivery and cell osteogenic differentiation, we devote to engineering an innovative bone-matrix mimicking niche to improve low dose of BMP2-induced bone formation. Our previous work describes a novel technique, named thermally induced nanofiber self-agglomeration (TISA), for generating 3D electrospun nanofibrous (NF) polycaprolactone (PCL) scaffolds. TISA process could readily blend PCL with PLA, leading to increased osteogenic capabilities in vitro , however, these bio-inert synthetic polymers produced limited BMP2-induced bone formation in vivo. We therefore hypothesize that functionalization of NF 3D PCL scaffolds with bone-like hydroxyapatite (HA) and BMP2 signaling activator phenamil will provide a favorable osteogenic niche for bone formation at low doses of BMP2. Compared to PCL-3D scaffolds, PCL/HA-3D scaffolds demonstrated synergistically enhanced osteogenic differentiation capabilities of C2C12 cells with phenamil. Importantly, in vivo studies showed this synergism was able to generate significantly increased new bone in an ectopic mouse model, suggesting PCL/HA-3D scaffolds act as a favorable synthetic extracellular matrix for bone regeneration.

  5. CT urography in the urinary bladder: To compare excretory phase images using a low noise index and a high noise index with adaptive noise reduction filter

    International Nuclear Information System (INIS)

    Takeyama, Nobuyuki; Hayashi, Takaki; Ohgiya, Yoshimitsu

    2011-01-01

    Background: Although CT urography (CTU) is widely used for the evaluation of the entire urinary tract, the most important drawback is the radiation exposure. Purpose: To evaluate the effect of a noise reduction filter (NRF) using a phantom and to quantitatively and qualitatively compare excretory phase (EP) images using a low noise index (NI) with those using a high NI and postprocessing NRF (pNRF). Material and Methods: Each NI value was defined for a slice thickness of 5 mm, and reconstructed images with a slice thickness of 1.25 mm were assessed. Sixty patients who were at high risk of developing bladder tumors (BT) were divided into two groups according to whether their EP images were obtained using an NI of 9.88 (29 patients; group A) or an NI of 20 and pNRF (31 patients; group B). The CT dose index volume (CTDI vol ) and the contrast-to-noise ratio (CNR) of the bladder with respect to the anterior pelvic fat were compared in both groups. Qualitative assessment of the urinary bladder for image noise, sharpness, streak artifacts, homogeneity, and the conspicuity of polypoid or sessile-shaped BTs with a short-axis diameter greater than 10 mm was performed using a 3-point scale. Results: The phantom study showed noise reduction of approximately 40% and 76% dose reduction between group A and group B. CTDI vol demonstrated a 73% reduction in group B (4.6 ± 1.1 mGy) compared with group A (16.9 ± 3.4 mGy). The CNR value was not significantly different (P = 0.60) between group A (16.1 ± 5.1) and group B (16.6 ± 7.6). Although group A was superior (P < 0.01) to group B with regard to image noise, other qualitative analyses did not show significant differences. Conclusion: EP images using a high NI and pNRF were quantitatively and qualitatively comparable to those using a low NI, except with regard to image noise

  6. Cisplatin Induces a Mitochondrial-ROS Response That Contributes to Cytotoxicity Depending on Mitochondrial Redox Status and Bioenergetic Functions

    Science.gov (United States)

    Marullo, Rossella; Werner, Erica; Degtyareva, Natalya; Moore, Bryn; Altavilla, Giuseppe; Ramalingam, Suresh S.; Doetsch, Paul W.

    2013-01-01

    Cisplatin is one of the most effective and widely used anticancer agents for the treatment of several types of tumors. The cytotoxic effect of cisplatin is thought to be mediated primarily by the generation of nuclear DNA adducts, which, if not repaired, cause cell death as a consequence of DNA replication and transcription blockage. However, the ability of cisplatin to induce nuclear DNA (nDNA) damage per se is not sufficient to explain its high degree of effectiveness nor the toxic effects exerted on normal, post-mitotic tissues. Oxidative damage has been observed in vivo following exposure to cisplatin in several tissues, suggesting a role for oxidative stress in the pathogenesis of cisplatin-induced dose-limiting toxicities. However, the mechanism of cisplatin-induced generation of ROS and their contribution to cisplatin cytotoxicity in normal and cancer cells is still poorly understood. By employing a panel of normal and cancer cell lines and the budding yeast Saccharomyces cerevisiae as model system, we show that exposure to cisplatin induces a mitochondrial-dependent ROS response that significantly enhances the cytotoxic effect caused by nDNA damage. ROS generation is independent of the amount of cisplatin-induced nDNA damage and occurs in mitochondria as a consequence of protein synthesis impairment. The contribution of cisplatin-induced mitochondrial dysfunction in determining its cytotoxic effect varies among cells and depends on mitochondrial redox status, mitochondrial DNA integrity and bioenergetic function. Thus, by manipulating these cellular parameters, we were able to enhance cisplatin cytotoxicity in cancer cells. This study provides a new mechanistic insight into cisplatin-induced cell killing and may lead to the design of novel therapeutic strategies to improve anticancer drug efficacy. PMID:24260552

  7. Experimental studies on excitation functions of the proton-induced activation reactions on silver

    International Nuclear Information System (INIS)

    Uddin, M.S.; Hagiwara, M.; Baba, M.; Tarkanyi, F.; Ditroi, F.

    2005-01-01

    Excitation functions were measured for the production of 106m,105 Ag, 103,101,100 Pd, 105,102,101m,100,99 Rh and 97 Ru via proton-induced activation reactions on natural silver using a stacked foil technique in the energy range 11-80 MeV. The residual activity measurements were carried out nondestructively by the high-resolution HPGe γ-ray spectroscopy. Thick target integral yields were deduced using the measured cross-sections from the respective threshold energies of the investigated reactions up to 80 MeV. The present work gives new results for the investigated radionuclides. The data in MENDL-2P deduced with the theoretical model code ALICE-IPPE are consistent in shape with the measured values, but show disagreement in magnitude

  8. Self-Organized Patterns Induced by Neimark-Sacker, Flip and Turing Bifurcations in a Discrete Predator-Prey Model with Lesie-Gower Functional Response

    Directory of Open Access Journals (Sweden)

    Feifan Zhang

    2017-06-01

    Full Text Available The formation of self-organized patterns in predator-prey models has been a very hot topic recently. The dynamics of these models, bifurcations and pattern formations are so complex that studies are urgently needed. In this research, we transformed a continuous predator-prey model with Lesie-Gower functional response into a discrete model. Fixed points and stability analyses were studied. Around the stable fixed point, bifurcation analyses including: flip, Neimark-Sacker and Turing bifurcation were done and bifurcation conditions were obtained. Based on these bifurcation conditions, parameters values were selected to carry out numerical simulations on pattern formation. The simulation results showed that Neimark-Sacker bifurcation induced spots, spirals and transitional patterns from spots to spirals. Turing bifurcation induced labyrinth patterns and spirals coupled with mosaic patterns, while flip bifurcation induced many irregular complex patterns. Compared with former studies on continuous predator-prey model with Lesie-Gower functional response, our research on the discrete model demonstrated more complex dynamics and varieties of self-organized patterns.

  9. Methylmercury-induced alterations in astrocyte functions are attenuated by ebselen.

    Science.gov (United States)

    Yin, Zhaobao; Lee, Eunsook; Ni, Mingwei; Jiang, Haiyan; Milatovic, Dejan; Rongzhu, Lu; Farina, Marcelo; Rocha, Joao B T; Aschner, Michael

    2011-06-01

    Methylmercury (MeHg) preferentially accumulates in glia of the central nervous system (CNS), but its toxic mechanisms have yet to be fully recognized. In the present study, we tested the hypothesis that MeHg induces neurotoxicity via oxidative stress mechanisms, and that these effects are attenuated by the antioxidant, ebselen. Rat neonatal primary cortical astrocytes were pretreated with or without 10 μM ebselen for 2h followed by MeHg (0, 1, 5, and 10 μM) treatments. MeHg-induced changes in astrocytic [(3)H]-glutamine uptake were assessed along with changes in mitochondrial membrane potential (ΔΨ(m)), using the potentiometric dye tetramethylrhodamine ethyl ester (TMRE). Western blot analysis was used to detect MeHg-induced ERK (extracellular-signal related kinase) phosphorylation and caspase-3 activation. MeHg treatment significantly decreased (pEbselen fully reversed MeHg's (1 μM) effect on [(3)H]-glutamine uptake at 1 min. At higher MeHg concentrations, ebselen partially reversed the MeHg-induced astrocytic inhibition of [(3)H]-glutamine uptake [at 1 min (5 and 10 μM) (pEbselen fully reversed the effect of 1 μM MeHg treatment for 1h on astrocytic ΔΨ(m) and partially reversed the effect of 5 and 10 μM MeHg treatments for 1h on ΔΨ(m). In addition, ebselen inhibited MeHg-induced phosphorylation of ERK (pebselen reinforce the idea that organic selenocompounds represent promising strategies to counteract MeHg-induced neurotoxicity. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. From the HINDAS Project: Excitation Functions for Residual Nuclide Production by Proton-Induced Reactions

    International Nuclear Information System (INIS)

    Michel, R.; Gloris, M.; Protoschill, J.; Uosif, M.A.M.; Weug, M.; Herpers, U.; Kuhnhenn, J.; Kubik, P.-W.; Schumann, D.; Synal, H.-A.; Weinreich, R.; Leya, I.; David, J.C.; Leray, S.; Duijvestijn, M.; Koning, A.; Kelic, A.; Schmidt, K.H.; Cugnon, J.

    2005-01-01

    A survey is given about efforts undertaken during the HINDAS project to investigate the energy dependence of residual nuclide production by proton-induced reactions from thresholds up to 2.6 GeV. For proton-induced reactions, our experiments aimed to further develop and complete the cross-section database that was established by our collaboration in recent years. It was extended to the heavy-target elements Ta, W, Pb, and Bi for energies up to 2.6 GeV. In addition, new measurements for the target element iron were performed up to 2.6 GeV and for natural uranium for energies from 21 MeV to 69 MeV. For the target element lead, a comprehensive set of excitation functions published recently was completed by AMS-measurements of cross sections for the production of the long-lived radionuclides Be-10, Al-26, Cl-36, and I-129 and by mass spectrometric measurements for stable and radioactive rare gas isotopes of He, Ne, Ar, Kr, and Xe. Comprehensive tests of the nuclear-reaction codes TALYS and INCL4+ABLA, which were developed within the HINDAS project, were performed with the new experimental results over the entire energy range

  11. Velocity Induced by a Plane Uniform Vortex Having the Schwarz Function of Its Boundary with Two Simple Poles

    Directory of Open Access Journals (Sweden)

    G. Riccardi

    2008-01-01

    Full Text Available The velocity induced by a plane, uniform vortex is investigated through the use of an integral relation between Schwarz function of the vortex boundary and conjugate of the velocity. The analysis is restricted to a certain class of vortices, the boundaries of which are described through conformal maps onto the unit circle and the corresponding Schwarz functions possess two poles in the plane of the circle. The dependence of the velocity field on the vortex shape is investigated by comparing velocity and streamfunction with the ones of the equivalent Rankine vortex (which has the same vorticity, area, and center of vorticity. By changing the parameters of the Schwarz function (poles and corresponding residues, rather complicated vortex shapes can be easily analyzed, some of them mimicing an incipient filamentation of the vortex boundary.

  12. Earthworms and their Nephridial Symbionts: Co-diversification and Maintenance of the Symbiosis

    DEFF Research Database (Denmark)

    Lund, Marie Braad; Holmstrup, Martin; Davidson, Seana K.

    Earthworms harbor in their nephridia (excretory organs) symbiotic bacteria which densely colonize a specific part of the nephridia, called the ampulla [1]. The symbiosis is species-specific and the symbionts form their own monophyletic genus Verminephrobacter (β-proteobacteria) [2] and are vertic......,J. 1926. Z Morph Ökol Tiere, 6(3):588-624. [2] Schramm,A. et al. 2003. Environ Microbiol 5(9):804-809. [3] Davidson,S.K. & Stahl,D.A. 2006. Appl Environ Microbiol 72(1):769-775. [4] Pandazis,G. 1931. Zentralbl Bakteriol 120:440-453.......Earthworms harbor in their nephridia (excretory organs) symbiotic bacteria which densely colonize a specific part of the nephridia, called the ampulla [1]. The symbiosis is species-specific and the symbionts form their own monophyletic genus Verminephrobacter (β-proteobacteria) [2...... showed no significant differences in growth rate and fecundity between symbiotic and aposymbiotic worms. Thus the symbionts do not appear to have an effect on worm fitness, under growth conditions tested. The underlying functional and maintaining mechanisms of this symbiosis remain a conundrum. [1] Knop...

  13. Dicranostiga leptopodu (Maxim.) Fedde extracts attenuated CCl4-induced acute liver damage in mice through increasing anti-oxidative enzyme activity to improve mitochondrial function.

    Science.gov (United States)

    Tang, Deping; Wang, Fang; Tang, Jinzhou; Mao, Aihong; Liao, Shiqi; Wang, Qin

    2017-01-01

    Dicranostiga Leptodu (Maxim.) fedde (DLF), a poppy plant, has been reported have many benefits and medicinal properties, including free radicals scavenging and detoxifying. However, the protective effect of DLF extracts against carbon tetrachloride (CCl 4 )-induced damage in mice liver has not been elucidated. Here, we demonstrated that DLF extracts attenuated CCl 4 -induced liver damage in mice through increasing anti-oxidative enzyme activity to improve mitochondrial function. In this study, the mice liver damage evoked by CCl 4 was marked by morphology changes, significant rise in lipid peroxidation, as well as alterations of mitochondrial respiratory function. Interestingly, pretreatment with DLF extracts attenuated CCl 4 -induced morphological damage and increasing of lipid peroxidation in mice liver. Additionally, DLF extracts improved mitochondrial function by preventing the disruption of respiratory chain and suppression of mitochondrial Na + K + -ATPase and Ca 2+ -ATPase activity. Furthermore, administration with DLF extracts elevated superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels and maintained the balance of redox status. This results showed that toxic protection effect of DLF extracts on mice liver is mediated by improving mitochondrial respiratory function and keeping the balance of redox status, which suggesting that DLF extracts could be used as potential toxic protection agent for the liver against hepatotoxic agent. Copyright © 2016. Published by Elsevier Masson SAS.

  14. Multi-detector CT urography: effect of oral hydration and contrast medium volume on renal parenchymal enhancement and urinary tract opacification - a quantitative and qualitative analysis

    International Nuclear Information System (INIS)

    Szolar, Dieter H.; Tillich, Manfred; Preidler, Klaus W.

    2010-01-01

    To assess the effect of oral hydration and contrast-medium volume on renal enhancement and urinary tract opacification in multi-detector CT urography. A total of 192 patients were assigned to different protocols with varying doses of contrast agent with and without oral hydration. The attenuation was measured in the renal parenchyma in the unenhanced, nephrographic and excretory phase, and in the urinary tract in excretory phase imaging, respectively. Opacification of the urinary tract was graded on volume rendered images. Oral hydration did not significantly alter renal parenchymal enhancement in both the nephrographic and the excretory phase (p > 0.001), but significantly decreased mean attenuation of the urinary tract in the excretory phase (p ≤ 0.001), and improved continuous opacification of all ureter segments (p < 0.01). Higher volumes of contrast medium improved renal parenchymal enhancement (p ≤ 0.001) and continuous opacification of the urinary tract (p ≤ 0.01). Oral hydration leads to lower attenuation values in the urinary tract but improves the continuous opacification of the tract. Increase in contrast medium volume leads to higher renal parenchymal enhancement as well as to an increased continuous opacification of the urinary tract. Decrease in contrast medium volume cannot be compensated for by oral hydration in terms of parenchymal enhancement. (orig.)

  15. The salt glands of Tamarix usneoides E. Mey. ex Bunge (South African Salt Cedar).

    Science.gov (United States)

    Wilson, Hayden; Mycock, David; Weiersbye, Isabel M

    2017-06-03

    Tamarix usneoides is a halophyte tree endemic to south-western Africa. This species is known to excrete a range of ions from specialized glandular structures on its leaves. To understand the mechanisms involved in the transport, sequestration and excretion of ions by the glands, a study was performed on salt gland distribution and ultrastructure. The glands are vesiculated trichomes, comprised of eight cells viz. two basal collecting cells and six excretory cells, partially bounded by a secondary cell wall that could serve as an impermeable barrier, forcing excess ions to move from the apoplast of the surrounding tissue into the cytoplasm of the basal excretory cells. It was hypothesized that the ions are moved across the excretory cells in endocytotic vesicles that fuse with the plasmalemma or form junctional complexes, allowing ion movement from one excretory cell to the next. In the apical cell, the vesicles fuse with the plasmalemma, releasing the ions into the network of cell wall ingrowths which channel the ions to the outside surface of the cell. This study shows that there are distinct structural adaptations for the processing of ions for excretion, although the mechanism by which ions enter the cells still needs to be determined.

  16. Retinoic acid-induced alveolar cellular growth does not improve function after right pneumonectomy.

    Science.gov (United States)

    Dane, D Merrill; Yan, Xiao; Tamhane, Rahul M; Johnson, Robert L; Estrera, Aaron S; Hogg, Deborah C; Hogg, Richard T; Hsia, Connie C W

    2004-03-01

    To determine whether all-trans retinoic acid (RA) treatment enhances lung function during compensatory lung growth in fully mature animals, adult male dogs (n = 4) received 2 mg x kg(-1) x day(-1) po RA 4 days/wk beginning the day after right pneumonectomy (R-PNX, 55-58% resection). Litter-matched male R-PNX controls (n = 4) received placebo. After 3 mo, transpulmonary pressure (TPP)-lung volume relationship, diffusing capacities for carbon monoxide and nitric oxide, cardiac output, and septal volume (V(tiss-RB)) were measured under anesthesia by a rebreathing technique at two lung volumes. Lung air and tissue volumes (V(air-CT) and V(tiss-CT)) were also measured from high-resolution computerized tomographic (CT) scans at a constant TPP. In RA-treated dogs compared with controls, TPP-lung volume relationships were similar. Diffusing capacities for carbon monoxide and nitric oxide were significantly impaired at a lower lung volume but similar at a high lung volume. Whereas V(tiss-RB) was significantly lower at both lung volumes in RA-treated animals, V(air-CT) and V(tiss-CT) were not different between groups; results suggest uneven distribution of ventilation consistent with distortion of alveolar geometry and/or altered small airway function induced by RA. We conclude that RA does not improve resting pulmonary function during the early months after R-PNX despite histological evidence of its action in enhancing alveolar cellular growth in the remaining lung.

  17. Secreted products of Fasciola hepatica inhibit the induction of T cell responses that mediate allergy.

    Science.gov (United States)

    Finlay, C M; Stefanska, A M; Coleman, M M; Jahns, H; Cassidy, J P; McLoughlin, R M; Mills, K H G

    2017-10-01

    There is evidence from epidemiology studies of a negative association between infection with helminth parasites and the development of allergy and asthma. Here, we demonstrate that the excretory/secretory products of the helminth Fasciola hepatica (FHES) protected mice against ovalbumin (OVA)-induced allergic asthma when administered at time of allergen sensitization. FHES reduced the accumulation of mucus, eosinophils and lymphocytes into the airways of allergen-challenged mice. Furthermore, FHES treatment suppressed Th2 responses in the airways. Interestingly, systemic administration of FHES at allergen challenge had no effect on airway inflammation, demonstrating that alum-induced Th2 response is set following initial allergen sensitization. Our findings highlight the immunomodulatory potential of molecules secreted by F. hepatica. © 2017 John Wiley & Sons Ltd.

  18. Imaging of hematuria.

    LENUS (Irish Health Repository)

    O'Connor, Owen J

    2010-10-01

    OBJECTIVE: In this article, we will discuss the current status of imaging in patients with hematuria of urologic origin. Issues impacting evaluation of these patients with radiography, excretory urography, retrograde pyelography, and sonography will be discussed. CONCLUSION: Conventional radiography has no role in the detection of renal or urothelial carcinoma. Low-dose CT offers much greater sensitivities for the detection of urinary tract calculi than radiography at doses equivalent to conventional radiography. Ultrasound alone is insufficient for imaging of hematuria. Using ultrasound alone, it is often difficult to differentiate renal transitional cell carcinoma from other causes of filling defects of the renal collecting system such as blood clots, sloughed papillae, or fungus balls. The prominence of the role of excretory urography in the evaluation of patients with hematuria has diminished, and MDCT urography is now preferred to excretory urography in most cases.

  19. Diuretic Scintigraphy of kidneys using lazex

    International Nuclear Information System (INIS)

    Yudin, L.; Reznichenko, A.; Uskov, I.; Budkevich, Yu.; Shejretova, E.; Sultanov, S.

    1993-01-01

    Diuretic scintigraphy performed in 59 patients with hydronephrosis, nephrolithiasis, chronic pyelonephritis and ureteral hydronephrosis, discloses 99m Tc-DTPA retention in the urinary tract - prolongation and absence of excretory segment on the nephrogram to appearance of an obstructive type curve. As shown by the data from 19 operatively verified patients with hydronephrosis and nephrolithiasis diagnosed as stenosis of the pelviureteral segment, a high sensitivity and accuracy of stenosis demonstration is recorded in the absence of excretory segment in the initial nephrogram regardless of whether or not it appears later, after Lazex administration. Stenosis of the pelviureteral segment may be likewise observed in the presence of excretory segment in the initial nephrogram with a prolonged half-period of excretion. A two-fold shortening of the latter is documented in the diuretic nephrogram. 12 refs., 3 figs. (orig.)

  20. Inducible Activation of ERK5 MAP Kinase Enhances Adult Neurogenesis in the Olfactory Bulb and Improves Olfactory Function

    Science.gov (United States)

    Wang, Wenbin; Lu, Song; Li, Tan; Pan, Yung-Wei; Zou, Junhui; Abel, Glen M.; Xu, Lihong; Storm, Daniel R.

    2015-01-01

    Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function and have more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury. PMID:25995470

  1. The Regulatory Roles of Toll-Like Receptor 4 in Secretions of Type 1/Type 2 Relative Cytokines by Splenocytes and Dendritic Cells Exposed to Clonorchis sinensis Excretory/Secretory Products.

    Science.gov (United States)

    Hua, Hui; Du, Ying; Ma, Rui; Zhang, Bei-Bei; Yu, Qian; Li, Bo; Xu, Jiang-Tao; Li, Xiang-Yang; Tang, Ren-Xian; Yan, Chao; Zheng, Kui-Yang

    2018-02-01

    The roles of TLR4 in mediation of innate immune response and in regulation of adaptive immune responses triggered by Clonorchis sinensis remain unknown. In the present study, splenocytes derived from C3H/HeN (TLR4 wild ) and C3H/Hej mice (TLR4 mut ) that were infected with 45 metacercariae of C. sinensis were harvested, then stimulated by C. sinensis excretory/secretory products (ESP) or medium (control) for 48 h, respectively. Meanwhile, bone marrow-derived dendritic cells (BMDCs) from normal C3H/HeN and C3H/Hej mice were prepared and stimulated with medium, ESP, LPS, or ESP+LPS for 24 h, respectively. The supernatants were collected, and the concentrations of type 1 and type 2 relative cytokines were determined by ELISA. The maturation of BMDCs indicated by surface markers of CD80, CD86, and MHC II was evaluated by flow cytometry. The results showed that the levels of IFN-γ, IL-6, TNF-α, and IL-10 in the splenocytes from C. sinensis-infected TLR4 mut mice were significantly lower than those from TLR4 wild mice when they were further exposed to ESP. For BMDCs, the productions of the cytokines IL-12p70 and IL-10, but not IL-4, in the BMDCs from TLR4 mutation mice were predominantly decreased compared with those from TLR4 wild mice when the BMDCs were co-stimulated by ESP combined with LPS. Flow cytometry analysis showed that ESP could significantly decrease the high levels of CD80, CD86, and MHC II which were elevated by LPS. In conclusion, these data suggest that TLR4 may play a regulatory role in type 1 immune responses during C. sinensis infection.

  2. Multiplexed quantitative high content screening reveals that cigarette smoke condensate induces changes in cell structure and function through alterations in cell signaling pathways in human bronchial cells

    International Nuclear Information System (INIS)

    Carter, Charleata A.; Hamm, Jonathan T.

    2009-01-01

    Human bronchial cells are one of the first cell types exposed to environmental toxins. Toxins often activate nuclear factor-κB (NF-κB) and protein kinase C (PKC). We evaluated the hypothesis that cigarette smoke condensate (CSC), the particulate fraction of cigarette smoke, activates PKC-α and NF-κB, and concomitantly disrupts the F-actin cytoskeleton, induces apoptosis and alters cell function in BEAS-2B human bronchial epithelial cells. Compared to controls, exposure of BEAS-2B cells to doses of 30 μg/ml CSC significantly activated PKC-α, while CSC doses above 20 μg/ml CSC significantly activated NF-κB. As NF-κB was activated, cell number decreased. CSC treatment of BEAS-2B cells induced a decrease in cell size and an increase in cell surface extensions including filopodia and lamellipodia. CSC treatment of BEAS-2B cells induced F-actin rearrangement such that stress fibers were no longer prominent at the cell periphery and throughout the cells, but relocalized to perinuclear regions. Concurrently, CSC induced an increase in the focal adhesion protein vinculin at the cell periphery. CSC doses above 30 μg/ml induced a significant increase in apoptosis in BEAS-2B cells evidenced by an increase in activated caspase 3, an increase in mitochondrial mass and a decrease in mitochondrial membrane potential. As caspase 3 increased, cell number decreased. CSC doses above 30 μg/ml also induced significant concurrent changes in cell function including decreased cell spreading and motility. CSC initiates a signaling cascade in human bronchial epithelial cells involving PKC-α, NF-κB and caspase 3, and consequently decreases cell spreading and motility. These CSC-induced alterations in cell structure likely prevent cells from performing their normal function thereby contributing to smoke-induced diseases.

  3. Protection by sulforaphane from type 1 diabetes-induced testicular apoptosis is associated with the up-regulation of Nrf2 expression and function

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Xin; Bai, Yang; Zhang, Zhiguo [The First Hospital of Jilin University, Changchun 130021 (China); KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202 (United States); Xin, Ying, E-mail: xiny@jlu.edu.cn [KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202 (United States); Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021 (China); Cai, Lu, E-mail: l0cai001@louisville.edu [The First Hospital of Jilin University, Changchun 130021 (China); KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202 (United States)

    2014-09-01

    Diabetes-induced testicular apoptosis is predominantly due to increased oxidative stress. The nuclear factor-erythroid 2-related factor 2 (Nrf2), as a master transcription factor in controlling anti-oxidative systems, is able to be induced by sulforaphane (SFN). To examine whether SFN prevents testicular apoptosis, type 1 diabetic mouse model was induced with multiple low-dose streptozotocin. Diabetic and age-matched control mice were treated with and without SFN at 0.5 mg/kg daily in five days of each week for 3 months and then kept until 6 months. Diabetes significantly increased testicular apoptosis that was associated with endoplasmic reticulum stress and mitochondrial cell death pathways, shown by the increased expression of C/EBP homologous protein (CHOP), cleaved caspase-12, Bax to Bcl2 expression ratio, and cleaved caspase-3. Diabetes also significantly increased testicular oxidative damage, inflammation and fibrosis, and decreased germ cell proliferation. All these diabetic effects were significantly prevented by SFN treatment for the first 3 months, and the protective effect could be sustained at 3 months after SFN treatment. SFN was able to up-regulate Nrf2 expression and function. The latter was reflected by the increased phosphorylation of Nrf2 at Ser40 and expression of Nrf2 downstream antioxidants at mRNA and protein levels. These results suggest that type 1 diabetes significantly induced testicular apoptosis and damage along with increasing oxidative stress and cell death and suppressing Nrf2 expression and function. SFN is able to prevent testicular oxidative damage and apoptosis in type 1 diabetes mice, which may be associated with the preservation of testicular Nrf2 expression and function under diabetic condition. - Highlights: • Sulforaphane (SFN) could attenuate diabetes-induced germ cell apoptosis. • SFN could preserve germ cell proliferation under diabetic conditions. • SFN testicular protection was sustained until 3 months after

  4. Protection by sulforaphane from type 1 diabetes-induced testicular apoptosis is associated with the up-regulation of Nrf2 expression and function

    International Nuclear Information System (INIS)

    Jiang, Xin; Bai, Yang; Zhang, Zhiguo; Xin, Ying; Cai, Lu

    2014-01-01

    Diabetes-induced testicular apoptosis is predominantly due to increased oxidative stress. The nuclear factor-erythroid 2-related factor 2 (Nrf2), as a master transcription factor in controlling anti-oxidative systems, is able to be induced by sulforaphane (SFN). To examine whether SFN prevents testicular apoptosis, type 1 diabetic mouse model was induced with multiple low-dose streptozotocin. Diabetic and age-matched control mice were treated with and without SFN at 0.5 mg/kg daily in five days of each week for 3 months and then kept until 6 months. Diabetes significantly increased testicular apoptosis that was associated with endoplasmic reticulum stress and mitochondrial cell death pathways, shown by the increased expression of C/EBP homologous protein (CHOP), cleaved caspase-12, Bax to Bcl2 expression ratio, and cleaved caspase-3. Diabetes also significantly increased testicular oxidative damage, inflammation and fibrosis, and decreased germ cell proliferation. All these diabetic effects were significantly prevented by SFN treatment for the first 3 months, and the protective effect could be sustained at 3 months after SFN treatment. SFN was able to up-regulate Nrf2 expression and function. The latter was reflected by the increased phosphorylation of Nrf2 at Ser40 and expression of Nrf2 downstream antioxidants at mRNA and protein levels. These results suggest that type 1 diabetes significantly induced testicular apoptosis and damage along with increasing oxidative stress and cell death and suppressing Nrf2 expression and function. SFN is able to prevent testicular oxidative damage and apoptosis in type 1 diabetes mice, which may be associated with the preservation of testicular Nrf2 expression and function under diabetic condition. - Highlights: • Sulforaphane (SFN) could attenuate diabetes-induced germ cell apoptosis. • SFN could preserve germ cell proliferation under diabetic conditions. • SFN testicular protection was sustained until 3 months after

  5. Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2

    Energy Technology Data Exchange (ETDEWEB)

    Eum, Sung Yong, E-mail: seum@miami.edu; Jaraki, Dima; András, Ibolya E.; Toborek, Michal

    2015-09-15

    Occludin is an essential integral transmembrane protein regulating tight junction (TJ) integrity in brain endothelial cells. Phosphorylation of occludin is associated with its localization to TJ sites and incorporation into intact TJ assembly. The present study is focused on the role of lipid rafts in polychlorinated biphenyl (PCB)-induced disruption of occludin and endothelial barrier function. Exposure of human brain endothelial cells to 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) induced dephosphorylation of threonine residues of occludin and displacement of occludin from detergent-resistant membrane (DRM)/lipid raft fractions within 1 h. Moreover, lipid rafts modulated the reduction of occludin level through activation of matrix metalloproteinase 2 (MMP-2) after 24 h PCB153 treatment. Inhibition of protein phosphatase 2A (PP2A) activity by okadaic acid or fostriecin markedly protected against PCB153-induced displacement of occludin and increased permeability of endothelial cells. The implication of lipid rafts and PP2A signaling in these processes was further defined by co-immunoprecipitation of occludin with PP2A and caveolin-1, a marker protein of lipid rafts. Indeed, a significant MMP-2 activity was observed in lipid rafts and was increased by exposure to PCB153. The pretreatment of MMP-2 inhibitors protected against PCB153-induced loss of occludin and disruption of lipid raft structure prevented the increase of endothelial permeability. Overall, these results indicate that lipid raft-associated processes, such as PP2A and MMP-2 activation, participate in PCB153-induced disruption of occludin function in brain endothelial barrier. This study contributes to a better understanding of the mechanisms leading to brain endothelial barrier dysfunction in response to exposure to environmental pollutants, such as ortho-substituted PCBs. - Highlights: • PCB153 disturbed human brain endothelial barrier through disruption of occludin. • Lipid raft-associated PP

  6. Combination of exercise training and diet restriction normalizes limited exercise capacity and impaired skeletal muscle function in diet-induced diabetic mice.

    Science.gov (United States)

    Suga, Tadashi; Kinugawa, Shintaro; Takada, Shingo; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Masaki, Yoshihiro; Furihata, Takaaki; Takahashi, Masashige; Sobirin, Mochamad A; Ono, Taisuke; Hirabayashi, Kagami; Yokota, Takashi; Tanaka, Shinya; Okita, Koichi; Tsutsui, Hiroyuki

    2014-01-01

    Exercise training (EX) and diet restriction (DR) are essential for effective management of obesity and insulin resistance in diabetes mellitus. However, whether these interventions ameliorate the limited exercise capacity and impaired skeletal muscle function in diabetes patients remains unexplored. Therefore, we investigated the effects of EX and/or DR on exercise capacity and skeletal muscle function in diet-induced diabetic mice. Male C57BL/6J mice that were fed a high-fat diet (HFD) for 8 weeks were randomly assigned for an additional 4 weeks to 4 groups: control, EX, DR, and EX+DR. A lean group fed with a normal diet was also studied. Obesity and insulin resistance induced by a HFD were significantly but partially improved by EX or DR and completely reversed by EX+DR. Although exercise capacity decreased significantly with HFD compared with normal diet, it partially improved with EX and DR and completely reversed with EX+DR. In parallel, the impaired mitochondrial function and enhanced oxidative stress in the skeletal muscle caused by the HFD were normalized only by EX+DR. Although obesity and insulin resistance were completely reversed by DR with an insulin-sensitizing drug or a long-term intervention, the exercise capacity and skeletal muscle function could not be normalized. Therefore, improvement in impaired skeletal muscle function, rather than obesity and insulin resistance, may be an important therapeutic target for normalization of the limited exercise capacity in diabetes. In conclusion, a comprehensive lifestyle therapy of exercise and diet normalizes the limited exercise capacity and impaired muscle function in diabetes mellitus.

  7. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Kathrin Hemmer

    2014-09-01

    Full Text Available Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]. iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

  8. Enhanced response to radiotherapy in tumours deficient in the function of hypoxia-inducible factor-1

    International Nuclear Information System (INIS)

    Williams, Kaye J.; Telfer, Brian A.; Xenaki, Dia; Sheridan, Mary R.; Desbaillets, Isabelle; Peters, Hans J.W.; Honess, Davina; Harris, Adrian L.; Dachs, Gabi U.; Kogel, Albert van der; Stratford, Ian J.

    2005-01-01

    Background and purpose: To test the hypothesis that deficiency in expression of the transcription factor, HIF-1, renders tumours more radioresponsive than HIF-1 proficient tumours. Patients and methods: Tumours comprising mouse hepatoma cells lacking HIF-1β (and thereby HIF-1 function) were grown in nude mice and radiation-induced growth delay compared with that seen for wild-type tumours and tumours derived from HIF-1β negative cells where HIF-1 function had been restored. Results: The xenografts that lack HIF-1 activity take longer to establish their growth and are more radioresponsive than both parental xenografts and those with restored HIF-1 function. Pre-treatment of the HIF-1 deficient xenografts with the hypoxic radiosensitizer misonidazole, had little effect on radioresponse. In contrast this treatment radiosensitized the parental xenografts. In spite of this, no difference in oxygenation status was found between the tumour types as measured by Eppendorf O 2 -electrodes and by binding of the hypoxic cell marker NITP. Admixing wild type and HIF-1 deficient cells in the same tumour at ratios of 1 in 10 and 1 in 100 restores the growth of the mixed tumours to that of a 100% HIF-1 proficient cell population. However, when comparing the effects of radiation on the mixed tumours, radioresponsiveness is maintained in those tumours containing the high proportion of HIF-1 deficient cells. Conclusions: The differences in radioresponse do not correlate with tumour oxygenation, suggesting that the hypoxic cells within the HIF-1 deficient tumours do not contribute to the outcome of radiotherapy. Thus, hypoxia impacts on tumour radioresponsiveness not simply because of the physio-chemical mechanism of oxygen with radiation-induced radicals causing damage 'fixation', but also because hypoxia/HIF-1 promotes expression of genes that allow tumour cells to survive under these adverse conditions. Further, the results from the cell mixing experiments uncouple the growth

  9. Evaluation of ubiquinone concentration and mitochondrial function relative to cerivastatin-induced skeletal myopathy in rats

    International Nuclear Information System (INIS)

    Schaefer, William H.; Lawrence, Jeffery W.; Loughlin, Amy F.; Stoffregen, Dana A.; Mixson, Lori A.; Dean, Dennis C.; Raab, Conrad E.; Yu, Nathan X.; Lankas, George R.; Frederick, Clay B.

    2004-01-01

    As a class, hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors can potentially cause skeletal myopathy. One statin, cerivastatin, has recently been withdrawn from the market due to an unacceptably high incidence of rhabdomyolysis. The mechanism underlying statin-induced myopathy is unknown. This paper sought to investigate the relationship among statin-induced myopathy, mitochondrial function, and muscle ubiquinone levels. Rats were administered cerivastatin at 0.1, 0.5, and 1.0 (mg/kg)/day or dose vehicle (controls) by oral gavage for 15 days. Samples of type I-predominant skeletal muscle (soleus) and type II-predominant skeletal muscle [quadriceps and extensor digitorum longus (EDL)], and blood were collected on study days 5, 10, and 15 for morphological evaluation, clinical chemistry, mitochondrial function tests, and analysis of ubiquinone levels. No histological changes were observed in any of the animals on study days 5 or 10, but on study day 15, mid- and high-dose animals had necrosis and inflammation in type II skeletal muscle. Elevated creatine kinase (CK) levels in blood (a clinical marker of myopathy) correlated with the histopathological diagnosis of myopathy. Ultrastructural characterization of skeletal muscle revealed disruption of the sarcomere and altered mitochondria only in myofibers with degeneration, while adjacent myofibers were unaffected and had normal mitochondria. Thus, mitochondrial effects appeared not to precede myofiber degeneration. Mean coenzyme Q9 (CoQ9) levels in all dose groups were slightly decreased relative to controls in type II skeletal muscle, although the difference was not significantly different in most cases. Mitochondrial function in skeletal muscle was not affected by the changes in ubiquinone levels. The ubiquinone levels in high-dose-treated animals exhibiting myopathy were not significantly different from low-dose animals with no observable toxic effects. Furthermore, ubiquinone levels did not correlate

  10. Bifidobacterium breve alters immune function and ameliorates DSS-induced inflammation in weanling rats.

    Science.gov (United States)

    Izumi, Hirohisa; Minegishi, Mario; Sato, Yohei; Shimizu, Takashi; Sekine, Kazunori; Takase, Mitsunori

    2015-10-01

    Bifidobacterium breve M-16V (M16V) is a probiotic bacterial strain with a long tradition of use in neonatal intensive care units in some countries. Previous study showed that the effects of M16V administration on gene expression were greater during the weaning period than in the neonatal period and were greater in the colon than in the small intestine and spleen, suggesting that M16V has anti-inflammatory effects. In this study, we evaluated the effects of inflammation during the weaning period and the effects of M16V on normal and inflammatory conditions. From postnatal day (PD) 21 to 34, weanling rats were administered of 2.5 × 10(9) of M16V daily, and colitis was induced by administration of 2% dextran sulfate sodium from PD28 to 35. Colitis severity, immune function, and microbiota were investigated. Colitis caused a reduction in body weight gain, colon shortening, poor nutritional status, anemia, changes in blood and spleen lymphocyte populations, spleen T-cell malfunctions, and alterations in colon microbiota. M16V administration improved some but not all of the changes induced by colitis. M16V could suppress inflammation and, therefore, can be considered a safe strain to use not only during the neonatal period but also the weaning period.

  11. Thujone inhibits the function of α7-nicotinic acetylcholine receptors and impairs nicotine-induced memory enhancement in one-trial passive avoidance paradigm.

    Science.gov (United States)

    Sultan, Ahmed; Yang, Keun-Hang Susan; Isaev, Dmitro; Nebrisi, Eslam El; Syed, Nurulain; Khan, Nadia; Howarth, Christopher F; Sadek, Bassem; Oz, Murat

    2017-06-01

    Effects of thujone, a major ingredient of absinthe, wormwood oil and some herbal medicines, were tested on the function of α 7 subunit of the human nicotinic acetylcholine (α 7 nACh) receptor expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Thujone reversibly inhibited ACh (100μM)-induced currents with an IC 50 value of 24.7μM. The effect of thujone was not dependent on the membrane potential and did not involve Ca 2+ -dependent Cl - channels expressed endogenously in oocytes. Inhibition by thujone was not reversed by increasing ACh concentrations. Moreover, specific binding of [ 125 I] α-bungarotoxin was not altered by thujone. Further experiments in SH-EP1 cells expressing human α 7 nACh receptor indicated that thujone suppressed choline induced Ca 2+ transients in a concentration-dependent manner. In rat hippocampal CA3-dentate gyrus synapses, nicotine-induced enhancement of long-term potentiation was also inhibited by thujone. Furthermore, the results observed in in-vivo one-trial passive avoidance paradigm show that thujone (1.25mg/kg, i.p.) significantly impaired nicotine-induced enhancement of learning and memory in Wistar rats. Collectively, our results indicate that thujone inhibits the function of the α7-nACh receptor and impairs cellular and behavioral correlates of cholinergic modulation of learning and memory. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Thujone inhibits the function of α7-nicotinic acetylcholine receptors and impairs nicotine-induced memory enhancement in one-trial passive avoidance paradigm

    International Nuclear Information System (INIS)

    Sultan, Ahmed; Yang, Keun-Hang Susan; Isaev, Dmitro; Nebrisi, Eslam El; Syed, Nurulain; Khan, Nadia; Howarth, Christopher F.; Sadek, Bassem; Oz, Murat

    2017-01-01

    Effects of thujone, a major ingredient of absinthe, wormwood oil and some herbal medicines, were tested on the function of α 7 subunit of the human nicotinic acetylcholine (α 7 nACh) receptor expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Thujone reversibly inhibited ACh (100 μM)-induced currents with an IC 50 value of 24.7 μM. The effect of thujone was not dependent on the membrane potential and did not involve Ca 2+ -dependent Cl − channels expressed endogenously in oocytes. Inhibition by thujone was not reversed by increasing ACh concentrations. Moreover, specific binding of [ 125 I] α-bungarotoxin was not altered by thujone. Further experiments in SH-EP1 cells expressing human α 7 nACh receptor indicated that thujone suppressed choline induced Ca 2+ transients in a concentration-dependent manner. In rat hippocampal CA3-dentate gyrus synapses, nicotine-induced enhancement of long-term potentiation was also inhibited by thujone. Furthermore, the results observed in in-vivo one-trial passive avoidance paradigm show that thujone (1.25 mg/kg, i.p.) significantly impaired nicotine-induced enhancement of learning and memory in Wistar rats. Collectively, our results indicate that thujone inhibits the function of the α7-nACh receptor and impairs cellular and behavioral correlates of cholinergic modulation of learning and memory.

  13. Radiation-induced cell mutations as a function of dose rate

    International Nuclear Information System (INIS)

    Kiefer, J.

    1987-01-01

    A brief review of the data in the literature is presented and forms the background of the experimental data given by the author obtained with exponential long-term cultures of V79 hamster cells exposed over a period of up to 35 days to different dose rates of gamma radiation. The experimental results show that at a dose rate of 40 mGy/hour the number of induced mutations is reduced, - which is in agreement with literature data - , but a dose rate of less than 30 mGy/hour makes the induced mutations leap to a value clearly higher than those induced by acute irradiation. As in addition to the mutations recombination is a significant factor of the radiation risk, experiments with a heterozygotic yeast strain have been made, as there is to date no reliable mammalian cell system available for this kind of research. Long-term radiation exposure of the yeast cells over a period of six weeks drastically increased the rate of recombinations, to a value higher by a factor of about 4 than that induced by acute irradiation. (orig.) [de

  14. Cognitive tutoring induces widespread neuroplasticity and remediates brain function in children with mathematical learning disabilities.

    Science.gov (United States)

    Iuculano, Teresa; Rosenberg-Lee, Miriam; Richardson, Jennifer; Tenison, Caitlin; Fuchs, Lynn; Supekar, Kaustubh; Menon, Vinod

    2015-09-30

    Competency with numbers is essential in today's society; yet, up to 20% of children exhibit moderate to severe mathematical learning disabilities (MLD). Behavioural intervention can be effective, but the neurobiological mechanisms underlying successful intervention are unknown. Here we demonstrate that eight weeks of 1:1 cognitive tutoring not only remediates poor performance in children with MLD, but also induces widespread changes in brain activity. Neuroplasticity manifests as normalization of aberrant functional responses in a distributed network of parietal, prefrontal and ventral temporal-occipital areas that support successful numerical problem solving, and is correlated with performance gains. Remarkably, machine learning algorithms show that brain activity patterns in children with MLD are significantly discriminable from neurotypical peers before, but not after, tutoring, suggesting that behavioural gains are not due to compensatory mechanisms. Our study identifies functional brain mechanisms underlying effective intervention in children with MLD and provides novel metrics for assessing response to intervention.

  15. Tartrazine induces structural and functional aberrations and genotoxic effects in vivo

    Directory of Open Access Journals (Sweden)

    Latifa Khayyat

    2017-02-01

    Full Text Available Tartrazine is a synthetic organic azo dye widely used in food and pharmaceutical products. The current study aimed to evaluate the possible adverse effect of this coloring food additive on renal and hepatic structures and functions. Also, the genotoxic potential of tartrazine on white blood cells was investigated using comet assay. Twenty adult male Wistar rats were grouped into two groups of 10 each, control- and tartrazine-treated groups. The control group was administered orally with water alone. The experimental group was administered orally with tartrazine (7.5 mg/kg, b.wt.. Our results showed a marked increase in the levels of ALT, AST, ALP, urea, uric acid, creatinine, MDA and NO, and a decreased level of total antioxidants in the serum of rats dosed with tartrazine compared to controls. On the other hand, administration of tartrazine was associated with severe histopathological and cellular alterations of rat liver and kidney tissues and induced DNA damage in leucocytes as detected by comet assay. Taken together, the results showed that tartrazine intake may lead to adverse health effects.

  16. Tartrazine induces structural and functional aberrations and genotoxic effects in vivo.

    Science.gov (United States)

    Khayyat, Latifa; Essawy, Amina; Sorour, Jehan; Soffar, Ahmed

    2017-01-01

    Tartrazine is a synthetic organic azo dye widely used in food and pharmaceutical products. The current study aimed to evaluate the possible adverse effect of this coloring food additive on renal and hepatic structures and functions. Also, the genotoxic potential of tartrazine on white blood cells was investigated using comet assay. Twenty adult male Wistar rats were grouped into two groups of 10 each, control- and tartrazine-treated groups. The control group was administered orally with water alone. The experimental group was administered orally with tartrazine (7.5 mg/kg, b.wt.). Our results showed a marked increase in the levels of ALT, AST, ALP, urea, uric acid, creatinine, MDA and NO, and a decreased level of total antioxidants in the serum of rats dosed with tartrazine compared to controls. On the other hand, administration of tartrazine was associated with severe histopathological and cellular alterations of rat liver and kidney tissues and induced DNA damage in leucocytes as detected by comet assay. Taken together, the results showed that tartrazine intake may lead to adverse health effects.

  17. L-carnitine protects against nickel-induced neurotoxicity by maintaining mitochondrial function in Neuro-2a cells

    International Nuclear Information System (INIS)

    He Mindi; Xu Shangcheng; Lu Yonghui; Li Li; Zhong Min; Zhang Yanwen; Wang Yuan; Li Min; Yang Ju; Zhang Guangbin; Yu Zhengping; Zhou Zhou

    2011-01-01

    Mitochondrial dysfunction is thought to be a part of the mechanism underlying nickel-induced neurotoxicity. L-carnitine (LC), a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine in all mammalian species, manifests its neuroprotective effects by improving mitochondrial energetics and function. The purpose of this study was to investigate whether LC could efficiently protect against nickel-induced neurotoxicity. Here, we exposed a mouse neuroblastoma cell line (Neuro-2a) to different concentrations of nickel chloride (NiCl 2 ) (0.25, 0.5, 1, and 2 mM) for 24 h, or to 0.5 mM and 1 mM NiCl 2 for various periods (0, 3, 6, 12, or 24 h). We found that nickel significantly increased the cell viability loss and lactate dehydrogenase (LDH) release in Neuro-2a cells. In addition, nickel exposure significantly elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels, disrupted the mitochondrial membrane potential (ΔΨ m ), reduced adenosine-5'-triphosphate (ATP) concentrations and decreased mitochondrial DNA (mtDNA) copy numbers and mtRNA transcript levels. However, all of the cytotoxicities and mitochondrial dysfunctions that were triggered by nickel were efficiently attenuated by pretreatment with LC. These protective effects of LC may be attributable to its role in maintaining mitochondrial function in nickel-treated cells. Our results suggest that LC may have great pharmacological potential in protecting against the adverse effects of nickel in the nervous system.

  18. Intravenous superoxide dismutase as a protective agent to prevent impairment of lung function induced by high tidal volume ventilation.

    Science.gov (United States)

    Wu, Nan-Chun; Liao, Fan-Ting; Cheng, Hao-Min; Sung, Shih-Hsien; Yang, Yu-Chun; Wang, Jiun-Jr

    2017-07-26

    Positive-pressure mechanical ventilation is essential in assisting patients with respiratory failure in the intensive care unit and facilitating oxygenation in the operating room. However, it was also recognized as a primary factor leading to hospital-acquired pulmonary dysfunction, in which pulmonary oxidative stress and lung inflammation had been known to play important roles. Cu/Zn superoxide dismutase (SOD) is an important antioxidant, and possesses anti-inflammatory capacity. In this study, we aimed to study the efficacy of Cu/Zn SOD, administered intravenously during high tidal volume (HTV) ventilation, to prevent impairment of lung function. Thirty-eight male Sprague-Dawley rats were divided into 3 groups: 5 h ventilation with (A) low tidal volume (LTV; 8 mL/kg; n = 10), (B) high tidal volume (HTV; 18 mL/kg; n = 14), or (C) HTV and intravenous treatment of Cu/Zn SOD at a dose of 1000 U/kg/h (HTV + SOD; n = 14). Lung function was evaluated both at baseline and after 5-h ventilation. Lung injury was assessed by histological examination, lung water and protein contents in the bronchoalveolar lavage fluid (BALF). Pulmonary oxidative stress was examined by concentrations of methylguanidine (MG) and malondialdehyde (MDA) in BALF, and antioxidative activity by protein expression of glutathione peroxidase-1 (GPx-1) in the lung. Severity of lung inflammation was evaluated by white blood cell and differential count in BALF, and protein expression of inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), and mRNA expression of nuclear factor-κB (NF-κB) in the lung. We also examined protein expression of surfactant protein (SP)-A and D and we measured hourly changes in serum nitric oxide (NO) level. Five hours of LTV ventilation did not induce a major change in lung function, whereas 5 h of HTV ventilation induced apparent combined restrictive and

  19. Thin-plate spline analysis of mandibular shape changes induced by functional appliances in Class II malocclusion : A long-term evaluation.

    Science.gov (United States)

    Franchi, Lorenzo; Pavoni, Chiara; Faltin, Kurt; Bigliazzi, Renato; Gazzani, Francesca; Cozza, Paola

    2016-09-01

    The purpose of this work was to evaluate the long-term morphological mandibular changes induced by functional treatment of Class II malocclusion with mandibular retrusion. Forty patients (20 females, 20 males) with Class II malocclusion consecutively treated with either a Bionator or an Activator followed by fixed appliances were compared with a control group of 40 subjects (19 females, 21 males) with untreated Class II malocclusion. Lateral cephalograms were available at the start of treatment (T1, mean age 9.9 years), at the end of treatment with functional appliances (T2, mean age 12.2 years), and for long-term follow-up (T3, mean age 18.3 years). Mandibular shape changes were analyzed on lateral cephalograms of the subjects in both groups via thin-plate spline (TPS) analysis. Shape differences were statistically analyzed by conducting permutation tests on Goodall F statistics. In the long term, both the treated and control groups exhibited significant longitudinal mandibular shape changes characterized by upward and forward dislocation of point Co associated with a vertical extension in the gonial region and backward dislocation of point B. Functional appliances induced mandible's significant posterior morphogenetic rotation over the short term. The treated and control groups demonstrated similar mandibular shape over the long term.

  20. Afferent thermosensory function in relapsing-remitting multiple sclerosis following exercise-induced increases in body temperature.

    Science.gov (United States)

    Filingeri, Davide; Chaseling, Georgia; Hoang, Phu; Barnett, Michael; Davis, Scott L; Jay, Ollie

    2017-08-01

    What is the central question of this study? Between 60 and 80% of multiple sclerosis (MS) patients experience transient worsening of symptoms with increased body temperature (heat sensitivity). As sensory abnormalities are common in MS, we asked whether afferent thermosensory function is altered in MS following exercise-induced increases in body temperature. What is the main finding and its importance? Increases in body temperature of as little as ∼0.4°C were sufficient to decrease cold, but not warm, skin thermosensitivity (∼10%) in MS, across a wider temperature range than in age-matched healthy individuals. These findings provide new evidence on the impact of heat sensitivity on afferent function in MS, which could be useful for clinical evaluation of this neurological disease. In multiple sclerosis (MS), increases in body temperature result in transient worsening of clinical symptoms (heat sensitivity or Uhthoff's phenomenon). Although the impact of heat sensitivity on efferent physiological function has been investigated, the effects of heat stress on afferent sensory function in MS are unknown. Hence, we quantified afferent thermosensory function in MS following exercise-induced increases in body temperature with a new quantitative sensory test. Eight relapsing-remitting MS patients (three men and five women; 51.4 ± 9.1 years of age; Expanded Disability Status Scale score 2.8 ± 1.1) and eight age-matched control (CTR) subjects (five men and three women; 47.4 ± 9.1 years of age) rated the perceived magnitude of two cold (26 and 22°C) and two warm stimuli (34 and 38°C) applied to the dorsum of the hand before and after 30 min cycling in the heat (30°C air; 30% relative humidity). Exercise produced similar increases in mean body temperature in MS [+0.39°C (95% CI: +0.21, +0.53) P = 0.001] and CTR subjects [+0.41°C (95% CI: +0.25, +0.58) P = 0.001]. These changes were sufficient to decrease thermosensitivity significantly to all cold [26

  1. Ion-Exchange-Induced Selective Etching for the Synthesis of Amino-Functionalized Hollow Mesoporous Silica for Elevated-High-Temperature Fuel Cells.

    Science.gov (United States)

    Zhang, Jin; Liu, Jian; Lu, Shanfu; Zhu, Haijin; Aili, David; De Marco, Roland; Xiang, Yan; Forsyth, Maria; Li, Qingfeng; Jiang, San Ping

    2017-09-20

    As differentiated from conventional synthetic processes, amino-functionalized hollow mesoporous silica (NH 2 -HMS) has been synthesized using a new and facile strategy of ion-exchange-induced selective etching of amino-functionalized mesoporous silica (NH 2 -meso-silica) by an alkaline solution. Nuclear magnetic resonance (NMR) spectroscopy and in situ time-resolved small-angle X-ray scattering (SAXS) reveal that ion-exchange-induced selective etching arises from the gradient distribution of OH - in the NH 2 -meso-silica nanospheres. Moreover, the ion-exchange-induced selective etching mechanism is verified through a successful synthesis of hollow mesoporous silica. After infiltration with phosphotungstic acid (PWA), PWA-NH 2 -HMS nanoparticles are dispersed in the poly(ether sulfone)-polyvinylpyrrolidone (PES-PVP) matrix, forming a hybrid PWA-NH 2 -HMS/PES-PVP nanocomposite membrane. The resultant nanocomposite membrane with an optimum loading of 10 wt % of PWA-NH 2 -HMS showed an enhanced proton conductivity of 0.175 S cm -1 and peak power density of 420 mW cm -2 at 180 °C under anhydrous conditions. Excellent durability of the hybrid composite membrane fuel cell has been demonstrated at 200 °C. The results of this study demonstrated the potential of the facile synthetic strategy in the fabrication of NH 2 -HMS with controlled mesoporous structure for application in nanocomposite membranes as a technology platform for elevated-temperature proton exchange membrane fuel cells.

  2. Monocyte-lymphocyte fusion induced by the HIV-1 envelope generates functional heterokaryons with an activated monocyte-like phenotype

    International Nuclear Information System (INIS)

    Martínez-Méndez, David; Rivera-Toledo, Evelyn; Ortega, Enrique; Licona-Limón, Ileana; Huerta, Leonor

    2017-01-01

    Enveloped viruses induce cell-cell fusion when infected cells expressing viral envelope proteins interact with target cells, or through the contact of cell-free viral particles with adjoining target cells. CD4"+ T lymphocytes and cells from the monocyte-macrophage lineage express receptors for HIV envelope protein. We have previously reported that lymphoid Jurkat T cells expressing the HIV-1 envelope protein (Env) can fuse with THP-1 monocytic cells, forming heterokaryons with a predominantly myeloid phenotype. This study shows that the expression of monocytic markers in heterokaryons is stable, whereas the expression of lymphoid markers is mostly lost. Like THP-1 cells, heterokaryons exhibited FcγR-dependent phagocytic activity and showed an enhanced expression of the activation marker ICAM-1 upon stimulation with PMA. In addition, heterokaryons showed morphological changes compatible with maturation, and high expression of the differentiation marker CD11b in the absence of differentiation-inducing agents. No morphological change nor increase in CD11b expression were observed when an HIV-fusion inhibitor blocked fusion, or when THP-1 cells were cocultured with Jurkat cells expressing a non-fusogenic Env protein, showing that differentiation was not induced merely by cell-cell interaction but required cell-cell fusion. Inhibition of TLR2/TLR4 signaling by a TIRAP inhibitor greatly reduced the expression of CD11b in heterokaryons. Thus, lymphocyte-monocyte heterokaryons induced by HIV-1 Env are stable and functional, and fusion prompts a phenotype characteristic of activated monocytes via intracellular TLR2/TLR4 signaling. - Highlights: • Jurkat T cells expressing the HIV-1 envelope fuse with THP-1 monocytes. • Heterokaryons display a dominant myeloid phenotype and monocyte function. • Heterokaryons exhibit activation features in the absence of activation agents. • Activation is not due to cell-cell interaction but requires cell-cell fusion. • The

  3. Organophosphate-Induced Changes in the PKA Regulatory Function of Swiss Cheese/NTE Lead to Behavioral Deficits and Neurodegeneration

    Science.gov (United States)

    Kretzschmar, Doris

    2014-01-01

    Organophosphate-induced delayed neuropathy (OPIDN) is a Wallerian-type axonopathy that occurs weeks after exposure to certain organophosphates (OPs). OPs have been shown to bind to Neuropathy Target Esterase (NTE), thereby inhibiting its enzymatic activity. However, only OPs that also induce the so-called aging reaction cause OPIDN. This reaction results in the release and possible transfer of a side group from the bound OP to NTE and it has been suggested that this induces an unknown toxic function of NTE. To further investigate the mechanisms of aging OPs, we used Drosophila, which expresses a functionally conserved orthologue of NTE named Swiss Cheese (SWS). Treating flies with the organophosporous compound tri-ortho-cresyl phosphate (TOCP) resulted in behavioral deficits and neurodegeneration two weeks after exposure, symptoms similar to the delayed effects observed in other models. In addition, we found that primary neurons showed signs of axonal degeneration within an hour after treatment. Surprisingly, increasing the levels of SWS, and thereby its enzymatic activity after exposure, did not ameliorate these phenotypes. In contrast, reducing SWS levels protected from TOCP-induced degeneration and behavioral deficits but did not affect the axonopathy observed in cell culture. Besides its enzymatic activity as a phospholipase, SWS also acts as regulatory PKA subunit, binding and inhibiting the C3 catalytic subunit. Measuring PKA activity in TOCP treated flies revealed a significant decrease that was also confirmed in treated rat hippocampal neurons. Flies expressing additional PKA-C3 were protected from the behavioral and degenerative phenotypes caused by TOCP exposure whereas primary neurons were not. In addition, knocking-down PKA-C3 caused similar behavioral and degenerative phenotypes as TOCP treatment. We therefore propose a model in which OP-modified SWS cannot release PKA-C3 and that the resulting loss of PKA-C3 activity plays a crucial role in developing

  4. Monocyte-lymphocyte fusion induced by the HIV-1 envelope generates functional heterokaryons with an activated monocyte-like phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Martínez-Méndez, David; Rivera-Toledo, Evelyn; Ortega, Enrique; Licona-Limón, Ileana; Huerta, Leonor, E-mail: leonorhh@biomedicas.unam.mx

    2017-03-01

    Enveloped viruses induce cell-cell fusion when infected cells expressing viral envelope proteins interact with target cells, or through the contact of cell-free viral particles with adjoining target cells. CD4{sup +} T lymphocytes and cells from the monocyte-macrophage lineage express receptors for HIV envelope protein. We have previously reported that lymphoid Jurkat T cells expressing the HIV-1 envelope protein (Env) can fuse with THP-1 monocytic cells, forming heterokaryons with a predominantly myeloid phenotype. This study shows that the expression of monocytic markers in heterokaryons is stable, whereas the expression of lymphoid markers is mostly lost. Like THP-1 cells, heterokaryons exhibited FcγR-dependent phagocytic activity and showed an enhanced expression of the activation marker ICAM-1 upon stimulation with PMA. In addition, heterokaryons showed morphological changes compatible with maturation, and high expression of the differentiation marker CD11b in the absence of differentiation-inducing agents. No morphological change nor increase in CD11b expression were observed when an HIV-fusion inhibitor blocked fusion, or when THP-1 cells were cocultured with Jurkat cells expressing a non-fusogenic Env protein, showing that differentiation was not induced merely by cell-cell interaction but required cell-cell fusion. Inhibition of TLR2/TLR4 signaling by a TIRAP inhibitor greatly reduced the expression of CD11b in heterokaryons. Thus, lymphocyte-monocyte heterokaryons induced by HIV-1 Env are stable and functional, and fusion prompts a phenotype characteristic of activated monocytes via intracellular TLR2/TLR4 signaling. - Highlights: • Jurkat T cells expressing the HIV-1 envelope fuse with THP-1 monocytes. • Heterokaryons display a dominant myeloid phenotype and monocyte function. • Heterokaryons exhibit activation features in the absence of activation agents. • Activation is not due to cell-cell interaction but requires cell-cell fusion. • The

  5. Exercise training-induced different improvement profile of endothelial progenitor cells function in mice with or without myocardial infarction.

    Science.gov (United States)

    Guo, Yuan; Peng, Ran; Liu, Qiong; Xu, Danyan

    2016-10-15

    Neovascularization in response to ischemia after myocardial infarction (MI) has been widely considered as being initiated by endothelial progenitor cells (EPCs). Well-documented evidences in recent years have proved exercise training (ET) improving EPC function. However, whether ET-induced improvement of EPC function under or without ischemic state is different has not been reported. Mice performed ET following an exercise prescription 1week after MI or non-MI surgery respectively. Bone marrow-derived EPCs were isolated at 0day, 3days, 1week, 2weeks, 4weeks, and 8weeks of ET. After 7days cultivation, EPC functions including proliferation, adhesion, migration, and in vitro angiogenesis were measured. AKT/glycogen synthase kinase 3β (GSK3β) signaling pathway was tested by western blotting. EPC function in mice underwent non-MI surgery was attenuated overtime, while ET ameliorated this tendency. EPC function was peaked at 4weeks ET in non-MI surgery mice and maintained with an extended exercise time. Besides, simple ischemia was sufficient to enhanced EPC function, with a maximum at 2weeks of MI surgery. In MI mice, ET further improved EPC function and achieved peak at 2weeks exercise. Furthermore, AKT/GSK3β signaling pathway activation was consistent with EPC function change after ischemia, which was further promoted by 4weeks exercise. ET significantly increased EPC function in mice both with and without MI, but the time points of peak function were different. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Modulate function and effect of 60Co γ-rays on ConA-induced CD4+ and CD8+ subpopulations of lymphocytes

    International Nuclear Information System (INIS)

    Xu Yujie; Su Liaoyuan; Liu Keliang

    1991-03-01

    The monocyte-depleted peripheral blood mononuclear cells were separated into B, CD 4 + and CD 8 + subpopulations by a Panning technique with McAb CD 4 and CD 8 . The purity of the B, CD 4 + and CD 8 + subpopulations was 82.7%, 90.4% and 90.8% respectively, which was estimated by an indirect immunofluorescence technique. More than 92% of the three subpopulations were viable according to the trypan blue exclusion test. The radiosensitivities of ConA-induced CD 4 + and CD 8 + cells were assessed by 3 H-TdR incorporation. Experiment demonstrated that a part of ConA-induced CD 4 + and CD 8 + cells was radiosensitive but the rest of them was radioresistant. There was no significant difference between the sensitive part both in the ConA-induced CD 4 + and CD 8 + cells while there was great significant difference between the resistant one in the both cell lines. The modulate functions of ConA-induced CD 4 + and CD 8 + cells and the effect of 10 Gy 60 Co γ-rays on them were investigated by the technique of 3 H-TdR incorporation. It was demonstrated that the transformation of LPS-induced B lymphocytes was suppressed by the ConA-induced CD 4 + and CD 8 + cells. After irradiation, the suppressor activity of ConA-induced CD 4 + and CD 8 + cells didn't decrease. The suppressor activity of ConA-induced CD 8 + cells were enhanced by the ConA-induced CD 4 + cells significantly, and the suppressor activity of ConA-induced CD 4 + cells was also enhanced by the ConA-induced CD 8 + cells. After irradiation, the enhancement effects of the ConA-induced CD 4 + and CD 8 + cells disappeared

  7. Estimation of adsorption-induced pore pressure and confinement in a nanoscopic slit pore by a density functional theory

    Science.gov (United States)

    Grégoire, David; Malheiro, Carine; Miqueu, Christelle

    2018-03-01

    This study aims at characterising the adsorption-induced pore pressure and confinement in nanoscopic pores by molecular non-local density functional theory (DFT). Considering its important potential industrial applications, the adsorption of methane in graphitic slit pores has been selected as the test case. While retaining the accuracy of molecular simulations at pore scale, DFT has a very low computational cost that allows obtaining highly resolved pore pressure maps as a function of both pore width and thermodynamic conditions. The dependency of pore pressure on these parameters (pore width, pressure and temperature) is carefully analysed in order to highlight the effect of each parameter on the confined fluid properties that impact the solid matrix.

  8. Generation of Functional Lentoid Bodies From Human Induced Pluripotent Stem Cells Derived From Urinary Cells.

    Science.gov (United States)

    Fu, Qiuli; Qin, Zhenwei; Jin, Xiuming; Zhang, Lifang; Chen, Zhijian; He, Jiliang; Ji, Junfeng; Yao, Ke

    2017-01-01

    The pathological mechanisms underlying cataract formation remain largely unknown on account of the lack of appropriate in vitro cellular models. The aim of this study is to develop a stable in vitro system for human lens regeneration using pluripotent stem cells. Isolated human urinary cells were infected with four Yamanaka factors to generate urinary human induced pluripotent stem cells (UiPSCs), which were induced to differentiate into lens progenitor cells and lentoid bodies (LBs). The expression of lens-specific markers was examined by real-time PCR, immunostaining, and Western blotting. The structure and magnifying ability of LBs were investigated using transmission electron microscopy and observing the magnification of the letter "X," respectively. We developed a "fried egg" differentiation method to generate functional LBs from UiPSCs. The UiPSC-derived LBs exhibited crystalline lens-like morphology and a transparent structure and expressed lens-specific markers αA-, αB-, β-, and γ-crystallin and MIP. During LB differentiation, the placodal markers SIX1, EYA1, DLX3, PAX6, and the specific early lens markers SOX1, PROX1, FOXE3, αA-, and αB-crystallin were observed at certain time points. Microscopic examination revealed the presence of lens epithelial cells adjacent to the lens capsule as well as both immature and mature fiber-like cells. Optical analysis further demonstrated the magnifying ability (1.7×) of the LBs generated from UiPSCs. Our study provides the first evidence toward generating functional LBs from UiPSCs, thereby establishing an in vitro system that can be used to study human lens development and cataractogenesis and perhaps even be useful for drug screening.

  9. Biphasic functional regulation in hippocampus of rat with chronic cerebral hypoperfusion induced by permanent occlusion of bilateral common carotid artery.

    Directory of Open Access Journals (Sweden)

    Jihye Bang

    Full Text Available BACKGROUND: Chronic cerebral hypoperfusion induced by permanent occlusion of the bilateral common carotid artery (BCCAO in rats has been commonly used for the study of Alzheimer's disease and vascular dementia. Despite the apparent cognitive dysfunction in rats with BCCAO, the molecular markers or pathways involved in the pathological alternation have not been clearly identified. METHODS: Temporal changes (sham, 21, 35, 45, 55 and 70 days in gene expression in the hippocampus of rats after BCCAO were measured using time-course microarray analysis. Gene Ontology (GO and pathway analyses were performed to identify the functional involvement of temporally regulated genes in BCCAO. RESULTS: Two major gene expression patterns were observed in the hippocampus of rats after BCCAO. One pattern, which was composed of 341 early up-regulated genes after the surgical procedure, was dominantly involved in immune-related biological functions (false discovery rate [FDR]<0.01. Another pattern composed of 182 temporally delayed down-regulated genes was involved in sensory perception such as olfactory and cognition functions (FDR<0.01. In addition to the two gene expression patterns, the temporal change of GO and the pathway activities using all differentially expressed genes also confirmed that an immune response was the main early change, whereas sensory functions were delayed responses. Moreover, we identified FADD and SOCS3 as possible core genes in the sensory function loss process using text-based mining and interaction network analysis. CONCLUSIONS: The biphasic regulatory mechanism first reported here could provide molecular evidence of BCCAO-induced impaired memory in rats as well as mechanism of the development of vascular dementia.

  10. Anion induced conformational preference of Cα NN motif residues in functional proteins.

    Science.gov (United States)

    Patra, Piya; Ghosh, Mahua; Banerjee, Raja; Chakrabarti, Jaydeb

    2017-12-01

    Among different ligand binding motifs, anion binding C α NN motif consisting of peptide backbone atoms of three consecutive residues are observed to be important for recognition of free anions, like sulphate or biphosphate and participate in different key functions. Here we study the interaction of sulphate and biphosphate with C α NN motif present in different proteins. Instead of total protein, a peptide fragment has been studied keeping C α NN motif flanked in between other residues. We use classical force field based molecular dynamics simulations to understand the stability of this motif. Our data indicate fluctuations in conformational preferences of the motif residues in absence of the anion. The anion gives stability to one of these conformations. However, the anion induced conformational preferences are highly sequence dependent and specific to the type of anion. In particular, the polar residues are more favourable compared to the other residues for recognising the anion. © 2017 Wiley Periodicals, Inc.

  11. Repeated electroacupuncture attenuating of apelin expression and function in the rostral ventrolateral medulla in stress-induced hypertensive rats.

    Science.gov (United States)

    Zhang, Cheng-Rong; Xia, Chun-Mei; Jiang, Mei-Yan; Zhu, Min-Xia; Zhu, Ji-Min; Du, Dong-Shu; Liu, Min; Wang, Jin; Zhu, Da-Nian

    2013-08-01

    Studies have revealed that apelin is a novel multifunctional peptide implicated both in blood pressure (BP) regulation and cardiac function control. Evidence shows that apelin and its receptor (APJ) in the rostral ventrolateral medulla (RVLM) may play an important role in central BP regulation; however, its role is controversial and very few reports have shown the relationship between acupuncture and apelin. Our study aims to both investigate the apelinergic system role in stress-induced hypertension (SIH) and determine whether acupuncture therapy effects on hypertension involve the apelinergic system in the RVLM. We established the stress-induced hypertensive rat (SIHR) model using electric foot-shock stressors with noise interventions. The expression of both apelin and the APJ receptor in the RVLM neurons was examined by immunohistochemical staining and Western blots. The results showed apelin expression increased remarkably in SIHR while APJ receptor expression showed no significant difference between control and SIHR groups. Microinjection of apelin-13 into the RVLM of control rats or SIHR produced pressor and tachycardic effects. Furthermore, effects induced by apelin-13 in SIHR were significantly greater than those of control rats. In addition, repetitive electroacupuncture (EA) stimulation at the Zusanli (ST-36) acupoint attenuated hypertension and apelin expression in the RVLM in SIHR; it also attenuated the pressor effect elicited by exogenous apelin-13 microinjection in SIHR. The results suggest that augmented apelin in the RVLM was part of the manifestations of SIH; the antihypertensive effects of EA might be associated with the attenuation of apelin expression and function in the RVLM, which might be a novel role for EA in SIH setting. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Inducible activation of ERK5 MAP kinase enhances adult neurogenesis in the olfactory bulb and improves olfactory function.

    Science.gov (United States)

    Wang, Wenbin; Lu, Song; Li, Tan; Pan, Yung-Wei; Zou, Junhui; Abel, Glen M; Xu, Lihong; Storm, Daniel R; Xia, Zhengui

    2015-05-20

    Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function and have more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury. Copyright © 2015 the authors 0270-6474/15/357833-17$15.00/0.

  13. Enhancing the smoothness of joint motion induced by functional electrical stimulation using co-activation strategies

    Directory of Open Access Journals (Sweden)

    Ruppel Mirjana

    2017-09-01

    Full Text Available The motor precision of today’s neuroprosthetic devices that use artificial generation of limb motion using Functional Electrical Stimulation (FES is generally low. We investigate the adoption of natural co-activation strategies as present in antagonistic muscle pairs aiming to improve motor precision produced by FES. In a test in which artificial knee-joint movements were generated, we could improve the smoothness of FES-induced motion by 513% when applying co-activation during the phases in which torque production is switched between muscles – compared to no co-activation. We further demonstrated how the co-activation level influences the joint stiffness in a pendulum test.

  14. A temperature induced ferrocene–ferrocenium interconversion in a ferrocene functionalized μ3-O chromium carboxylate

    International Nuclear Information System (INIS)

    Mereacre, Valeriu; Schlageter, Martin; Powell, Annie K.

    2015-01-01

    The infrared spectra and 57 Fe Mössbauer measurements of a ferrocenecarboxylate functionalized {Cr 3 O} complex in solid state are reported. It was established that conjugation of ferrocene Cp orbitals with the π orbitals of the adjacent carboxylic group stabilizes the trapped mixed-valence state leading to an intriguing coexistence of ferrocene and ferrocenium species giving rise to a new type of compound showing valence tautomerism in the solid state. - Highlights: • A stabilized ferrocene trapped mixed-valence state is reported. • New type of compound showing valence tautomerism in solid state. • A thermally induced electron transfer and a mixed-valence state near room temperature

  15. Evaluation of effects of various drugs on platelet functions using phorbol 12-myristate 13-acetate-induced megakaryocytic human erythroid leukemia cells

    Directory of Open Access Journals (Sweden)

    Tada T

    2016-09-01

    Full Text Available Tomoki Tada,1 Kensaku Aki,2 Wataru Oboshi,1,3 Kazuyoshi Kawazoe,4 Toshiyuki Yasui,5 Eiji Hosoi2 1Subdivision of Biomedical Laboratory Sciences, Graduate School of Health Sciences, Tokushima University, 2Department of Cells and Immunity Analytics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 3Department of Medical Technology, Kagawa Prefectural University of Health Sciences, Kagawa, 4Department of Clinical Pharmacy Practice Pedagogy, Institute of Biomedical Sciences, 5Department of Reproductive and Menopausal Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan Background: The hyperfunction and activation of platelets have been strongly implicated in the development and recurrence of arterial occlusive disease, and various antiplatelet drugs are used to treat and prevent such diseases. New antiplatelet drugs and many other drugs have been developed, but some drugs may have adverse effects on platelet functions. Objective: The aim of this study was to establish an evaluation method for evaluating the effect and adverse effect of various drugs on platelet functions. Materials and methods: Human erythroid leukemia (HEL cells were used after megakaryocytic differentiation with phorbol 12-myristate 13-acetate as an alternative to platelets. Drugs were evaluated by changes in intracellular Ca2+ concentration ([Ca2+]i mobilization in Fura2-loaded phorbol 12-myristate 13-acetate-induced HEL cells. Aspirin and cilostazol were selected as antiplatelet drugs and ibuprofen and sodium valproate as other drugs. Results: There was a positive correlation between [Ca2+]i and platelet aggregation induced by thrombin. Aspirin (5.6–560 µM and cilostazol (5–10 µM significantly inhibited thrombin-induced increases in [Ca2+]i in a concentration-dependent manner. On the other hand, ibuprofen (8–200 µM and sodium valproate (50–1,000 µg/mL also significantly inhibited

  16. Role of protein kinase C in TBT-induced inhibition of lytic function and MAPK activation in human natural killer cells.

    Science.gov (United States)

    Abraha, Abraham B; Rana, Krupa; Whalen, Margaret M

    2010-11-01

    Human natural killer (NK) cells are lymphocytes that destroy tumor and virally infected cells. Previous studies have shown that exposure of NK cells to tributyltin (TBT) greatly diminishes their ability to destroy tumor cells (lytic function) while activating mitogen-activated protein kinases (MAPK) (p44/42, p38, and JNK) in NK cells. The signaling pathway that regulates NK lytic function appears to include activation of protein kinase C(PKC) as well as MAPK activity. TBT-induced activation of MAPKs would trigger a portion of the NK lytic signaling pathway, which would then leave the NK cell unable to trigger this pathway in response to a subsequent encounter with a target cell. In the present study we evaluated the involvement of PKC in inhibition of NK lysis of tumor cells and activation of MAPKs caused by TBT exposure. TBT caused a 2–3-fold activation of PKC at concentrations ranging from 50 to 300 nM (16–98 ng/ml),indicating that activation of PKC occurs in response to TBT exposure. This would then leave the NK cell unable to respond to targets. Treatment with the PKC inhibitor, bisindolylmaleimide I, caused an 85% decrease in the ability of NK cells to lyse tumor cells, validating the involvement of PKC in the lytic signaling pathway. The role of PKC in the activation of MAPKs by TBT was also investigated using bisindolylmaleimide I. The results indicated that, in NK cells where PKC activation was blocked, there was no activation of the MAPK, p44/42 in response to TBT.However, TBT-induced activation of the MAPKs, p38 and JNK did not require PKC activation. These results indicate the pivotal role of PKC in the TBT-induced loss of NK lytic function including activation of p44/42 by TBT in NK cells.

  17. Lysosomal function is involved in 17β-estradiol-induced estrogen receptor α degradation and cell proliferation.

    Science.gov (United States)

    Totta, Pierangela; Pesiri, Valeria; Marino, Maria; Acconcia, Filippo

    2014-01-01

    The homeostatic control of the cellular proteome steady-state is dependent either on the 26S proteasome activity or on the lysosome function. The sex hormone 17β-estradiol (E2) controls a plethora of biological functions by binding to the estrogen receptor α (ERα), which is both a nuclear ligand-activated transcription factor and also an extrinsic plasma membrane receptor. Regulation of E2-induced physiological functions (e.g., cell proliferation) requires the synergistic activation of both transcription of estrogen responsive element (ERE)-containing genes and rapid extra-nuclear phosphorylation of many different signalling kinases (e.g., ERK/MAPK; PI3K/AKT). Although E2 controls ERα intracellular content and activity via the 26S proteasome-mediated degradation, biochemical and microscopy-based evidence suggests a possible cross-talk among lysosomes and ERα activities. Here, we studied the putative localization of endogenous ERα to lysosomes and the role played by lysosomal function in ERα signalling. By using confocal microscopy and biochemical assays, we report that ERα localizes to lysosomes and to endosomes in an E2-dependent manner. Moreover, the inhibition of lysosomal function obtained by chloroquine demonstrates that, in addition to 26S proteasome-mediated receptor elimination, lysosome-based degradation also contributes to the E2-dependent ERα breakdown. Remarkably, the lysosome function is further involved in those ERα activities required for E2-dependent cell proliferation while it is dispensable for ERα-mediated ERE-containing gene transcription. Our discoveries reveal a novel lysosome-dependent degradation pathway for ERα and show a novel biological mechanism by which E2 regulates ERα cellular content and, as a consequence, cellular functions.

  18. WRNIP1 functions upstream of DNA polymerase η in the UV-induced DNA damage response

    Energy Technology Data Exchange (ETDEWEB)

    Yoshimura, Akari, E-mail: akari_yo@stu.musashino-u.ac.jp [Molecular Cell Biology Laboratory, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585 (Japan); Kobayashi, Yume [Molecular Cell Biology Laboratory, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585 (Japan); Tada, Shusuke [Department of Medical Biochemistry, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi-shi, Chiba 274-8510 (Japan); Seki, Masayuki [Department of Biochemistry, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai-shi, Miyagi 981-8558 (Japan); Enomoto, Takemi [Molecular Cell Biology Laboratory, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585 (Japan)

    2014-09-12

    Highlights: • The UV sensitivity of POLH{sup −/−} cells was suppressed by disruption of WRNIP1. • In WRNIP1{sup −/−/−}/POLH{sup −/−} cells, mutation frequencies and SCE after irradiation reduced. • WRNIP1 defect recovered rate of fork progression after irradiation in POLH{sup −/−} cells. • WRNIP1 functions upstream of Polη in the translesion DNA synthesis pathway. - Abstract: WRNIP1 (WRN-interacting protein 1) was first identified as a factor that interacts with WRN, the protein that is defective in Werner syndrome (WS). WRNIP1 associates with DNA polymerase η (Polη), but the biological significance of this interaction remains unknown. In this study, we analyzed the functional interaction between WRNIP1 and Polη by generating knockouts of both genes in DT40 chicken cells. Disruption of WRNIP1 in Polη-disrupted (POLH{sup −/−}) cells suppressed the phenotypes associated with the loss of Polη: sensitivity to ultraviolet light (UV), delayed repair of cyclobutane pyrimidine dimers (CPD), elevated frequency of mutation, elevated levels of UV-induced sister chromatid exchange (SCE), and reduced rate of fork progression after UV irradiation. These results suggest that WRNIP1 functions upstream of Polη in the response to UV irradiation.

  19. Quantitative renal cinescintigraphy with iodine-123 hippuran methodological aspects, kit for labeling of hippuran

    International Nuclear Information System (INIS)

    Mehdaoui, A.; Pecking, A.; Delorme, G.; Mathonnat, F.; Debaud, B.; Bardy, A.; Coornaert, S.; Merlin, L.; Vinot, J.M.; Desgrez, A.; Gambini, D.; Vernejoul, P. de.

    1981-08-01

    The development of an extemporaneous kit for the labeling of ortho-iodo-hippuric acid (Hippuran) with iodine 123 allows the performance of a routine quantitative renal cinescintigraphy providing in 20 minutes, and in an absolutely non-traumatic way, a very complete renal morphofunctional study including: a cortical renal scintigraphy, sequential scintigraphies of excretory tract, renal functional curves, tubular, global, and separate clearances for each kidney. This functional quantitative investigation method should take a preferential place in the routine renal balance. The methodology of the technique is explained and compared to classical methods for estimation of tubular, global and separate clearances [fr

  20. 3D ion velocity distribution function measurement in an electric thruster using laser induced fluorescence tomography

    Science.gov (United States)

    Elias, P. Q.; Jarrige, J.; Cucchetti, E.; Cannat, F.; Packan, D.

    2017-09-01

    Measuring the full ion velocity distribution function (IVDF) by non-intrusive techniques can improve our understanding of the ionization processes and beam dynamics at work in electric thrusters. In this paper, a Laser-Induced Fluorescence (LIF) tomographic reconstruction technique is applied to the measurement of the IVDF in the plume of a miniature Hall effect thruster. A setup is developed to move the laser axis along two rotation axes around the measurement volume. The fluorescence spectra taken from different viewing angles are combined using a tomographic reconstruction algorithm to build the complete 3D (in phase space) time-averaged distribution function. For the first time, this technique is used in the plume of a miniature Hall effect thruster to measure the full distribution function of the xenon ions. Two examples of reconstructions are provided, in front of the thruster nose-cone and in front of the anode channel. The reconstruction reveals the features of the ion beam, in particular on the thruster axis where a toroidal distribution function is observed. These findings are consistent with the thruster shape and operation. This technique, which can be used with other LIF schemes, could be helpful in revealing the details of the ion production regions and the beam dynamics. Using a more powerful laser source, the current implementation of the technique could be improved to reduce the measurement time and also to reconstruct the temporal evolution of the distribution function.