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Sample records for serum limitation induced

  1. A model for mild traumatic brain injury that induces limited transient memory impairment and increased levels of axon related serum biomarkers

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    Elham eRostami

    2012-07-01

    Full Text Available Mild traumatic brain injury (mTBI is one of the most common neuronal insults and can lead to long-term disabilities. mTBI occurs when the head is exposed to a rapid acceleration-deceleration movement triggering axonal injuries. Our limited understanding of the underlying pathological changes makes it difficult to predict the outcome of mTBI. In this study we used a scalable rat model for rotational acceleration TBI, previously characterized for the threshold of axonal pathology. We have analyzed whether a TBI just above the defined threshold would induce any detectable behavioral changes and/or changes in serum biomarkers. The effect of injury on sensory motor functions, memory and anxiety were assessed by beam walking, radial arms maze and elevated plus maze at 3 to 7 days following TBI. The only behavioral deficits found were transient impairments in working and reference memory. Blood serum was analyzed at 1, 3 and 14 days after injury for changes in selected protein biomarkers. Serum levels of neurofilament heavy chain (NF-H and Tau, as well as S100B and myelin basic protein (MBP showed significant increases in the injured animals at all time points. No signs of macroscopic injuries such as intracerebral hematomas or contusions were found. Amyloid precursor protein (APP immunostaining indicated axonal injuries at all time points analyzed. In summary, this model mimics some of the key symptoms of mTBI, such as transient memory impairment, which is paralleled by an increase in serum biomarkers. Our findings suggest that serum biomarkers may be used to detect mTBI. The model provides a suitable foundation for further investigation of the underlying pathology of mTBI.

  2. LIMITED ELEVATIONS IN ANTITUBERCULOSIS DRUG-INDUCED SERUM ALANINE AMINOTRANSFERASE (ALT) LEVELS IN A COHORT OF NIGERIANS ON TREATMENT FOR PULMONARY TUBERCULOSIS AND HIV INFECTION IN YENAGOA

    NARCIS (Netherlands)

    Ikuabe, Peter Ogie; Ebuenyi, Ikenna Desmond; Harry, Tubonye Clement

    2015-01-01

    BACKGROUND: This study, undertaken in a major tertiary hospital in the Niger Delta region of Nigeria was designed to examine the incidence of elevation in serum alanine aminotransference (ALT) in our patients who were on treatment for HIV/AIDS with some of them on antituberculosis drugs. METHOD:

  3. Al cation induces aggregation of serum proteins.

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    Chanphai, P; Kreplak, L; Tajmir-Riahi, H A

    2017-07-15

    Al cation is known to induce protein fibrillation and causes several neurodegenerative disorders. We report the spectroscopic, thermodynamic analysis and AFM imaging for the Al cation binding process with human serum albumin (HSA), bovine serum albumin (BSA) and milk beta-lactoglobulin (b-LG) in aqueous solution at physiological pH. Hydrophobicity played a major role in Al-protein interactions with more hydrophobic b-LG forming stronger Al-protein complexes. Thermodynamic parameters ΔS, ΔH and ΔG showed Al-protein bindings occur via hydrophobic and H-bonding contacts for b-LG, while van der Waals and H-bonding interactions prevail in HSA and BSA adducts. AFM clearly indicated that aluminum cations are able to force BSA and b-LG into larger or more robust aggregates than HSA, with HSA 4±0.2 (SE, n=801) proteins per aggregate, for BSA 17±2 (SE, n=148), and for b-LG 12±3 (SE, n=151). Thioflavin T test showed no major protein fibrillation in the presence of Al cation. Al complexation induced major alterations of protein conformations with the order of perturbations b-LG>BSA>HSA. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Anaerobic exercise - Induced changes in serum mineral ...

    African Journals Online (AJOL)

    Anaerobic exercise, a non 02 – dependent energy metabolism leads to transient metabolic changes, which are corrected gradually by homestatic mechanism. We investigated in eight male subjects, the effects of anaerobic exercise after a day sedentary activity on serum mineral concentration. There was significant ...

  5. Study of serum lipid profile in pregnancy induced hypertension in ...

    African Journals Online (AJOL)

    At recent times, there has been a great interest on the role of lipid metabolism in the development of pregnancy induced hypertension and pre-eclampsia ... Results: Mean serum triglyceride was higher in (Group 1) pregnant women with pregnancy induced hypertension than in Groups 2 and 3, this was however not ...

  6. Serum gastrin: interests and limitations of radio-immunoassay

    International Nuclear Information System (INIS)

    Rougier, P.; Linhart, N.; Bok, B.

    1980-01-01

    Radio-immunoassay of serum gastrin may now be carried out in all laboratories of radio-immunology. Comparison of two commercial kits A: Schwartz-Mann and B: CEA-SORIN according to criteria of specificity, sensitivity and reproducibility within and between systems, shows that they both permit the detection of pathological hypergastrinemias (Zollinger Ellison and atropic gastritis). Both kits have an identical intrasystem coefficient of variation (10 p. cent and 7 p. cent fort A, 5 p. cent and 8 p. cent for B) on the other hand, the inter-system coefficient of variation is better for kit B (22.4 p. cent and 37 p. cent for kit A, and 11.5 p. cent and 14.2 p. cent for kit B). The normal values for each kit are quite different: 97 . 64 pg.ml -1 for A and 51 . 23 pg.ml -1 for B preventing one from comparing estimations carried out with two different kits [fr

  7. Limited interlaboratory comparison of Schmallenberg virus antibody detection in serum samples

    DEFF Research Database (Denmark)

    van der Poel, W. H. M.; Cay, B.; Zientara, S.

    2014-01-01

    Eight veterinary institutes in seven different countries in Europe participated in a limited interlaboratory comparison trial to evaluate laboratory performances of Schmallenberg virus (SBV) antibody detection in serum. Seven different sheep sera and three different cattle sera were circulated, a...

  8. Reproducibility of biomarkers in induced sputum and in serum from chronic smokers.

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    Zuiker, Rob G J A; Kamerling, Ingrid M C; Morelli, Nicoletta; Calderon, Cesar; Boot, J Diderik; de Kam, Marieke; Diamant, Zuzana; Burggraaf, Jacobus; Cohen, Adam F

    2015-08-01

    Soluble inflammatory markers obtained from non-invasive airway sampling such as induced sputum may be useful biomarkers for targeted pharmaceutical interventions. However, before these soluble markers can be used as potential targets, their variability and reproducibility need to be established in distinct study populations. This study aimed to assess the reproducibility of biomarkers obtained from induced sputum and serum in chronic smokers and non-smokers. Sputum and serum samples were obtained from 16 healthy non-smokers and 16 asymptomatic chronic smokers (for both groups: 8M/8F, 30-52 years, FEV1 ≥80% pred.; ≥10 pack years for the smokers) on 2 separate visits 4-10 days apart. Soluble markers in serum and sputum were analysed by ELISA. The differences between smokers vs non-smokers were analysed with a t-test and variability was assessed on log-transformed data by a mixed model ANOVA. Analysable sputum samples could be obtained from all 32 subjects. In both study populations neutrophils and macrophages were the predominant cell types. Serum Pulmonary Surfactant Associated Protein D had favourable reproducibility criteria for reliability ratio (0.99), intra-subject coefficient of variation (11.2%) and the Bland Altman limits of agreement. Furthermore, chronic smokers, compared to non-smokers, had significantly higher sputum concentrations of IL-8 (1094.6 pg/mL vs 460.8 pg/mL, p = 0.006)), and higher serum concentrations of Pulmonary Surfactant Associated Protein D (110.9 pg/mL vs 64.7 pg/mL, p = 0.019), and lower concentrations of Serum Amyloid A (1352.4 pg/mL vs 2297.5 pg/mL, p = 0.022). Serum Pulmonary Surfactant Associated Protein D proved to be a biomarker that fulfilled the criteria for reproducibility in both study groups. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Photoexcited riboflavin induces oxidative damage to human serum albumin

    Science.gov (United States)

    Hirakawa, Kazutaka; Yoshioka, Takuto

    2015-08-01

    Photoexcited riboflavin induced damage of human serum albumin (HSA), a water soluble protein, resulting in the diminishment of fluorescence from the tryptophan residue. Because riboflavin hardly photosensitized singlet oxygen generation and sodium azide, a singlet oxygen quencher, did not inhibit protein damage, electron transfer-mediated oxidation of HSA was speculated. Fluorescence lifetime of riboflavin was not affected by HSA, suggesting that the excited triplet state of riboflavin is responsible for protein damage through electron transfer. In addition, the preventive effect of xanthone derivatives, triplet quenchers, on photosensitized protein damage could be evaluated using this photosensitized reaction system of riboflavin and HSA.

  10. Analysis of the NTPDase and ecto-5'-nucleotidase profiles in serum-limited Trichomonas vaginalis

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    Amanda Piccoli Frasson

    2012-03-01

    Full Text Available Trichomonas vaginalis is a parasite of the human urogenital tract that causes trichomonosis, the most prevalent non-viral sexually transmitted disease. Ectonucleoside triphosphate diphosphohydrolase (NTPDase family members, which hydrolyse extracellular ATP and ADP and ecto-5′-nucleotidase, which hydrolyses AMP, have been characterised in T. vaginalis. For trichomonad culture, the growth medium is supplemented with 10% serum, which is an important source of nutrients, such as adenosine. Here, we investigated the ATP metabolism of T. vaginalis trophozoites from long-term cultures and clinical isolates under limited bovine serum conditions (1% serum. The specific enzymatic activities were expressed as nmol inorganic phosphate (Pi released/min/mg protein, the gene expression patterns were determined by reverse transcriptase-polymerase chain reaction, the extracellular adenine nucleotide hydrolysis was analysed by high performance liquid chromatography and the cell cycle analysis was assessed by flow cytometry. Serum limitation led to the profound activation of NTPDase and ecto-5'-nucleotidase activities. Furthermore, the levels of NTPDase A and B transcripts increased and extracellular ATP metabolism was activated, which led to enhanced ATP hydrolysis and the formation of ADP and AMP. Moreover, the cell cycle was arrested at the G0/G1 stage, which suggested adenosine uptake. Our data suggest that under conditions of serum limitation, NTPDase and ecto-5'-nucleotidase play a role in providing the adenosine required for T. vaginalis growth and that this process contributes to the establishment of parasitism.

  11. Study of the levels of serum cortisol and gastrin in dogs with vibration-induced injury

    International Nuclear Information System (INIS)

    Wei Zikun

    2005-01-01

    Objective: To study the changes of levels of serum cortisol and gastrin in dogs with vibration-induced injury for providing better treatment regimen. Methods: In this experiment, 8 or 10 domestic dogs were placed on each of four sites away from explosion center about 0, 100, 200, 300 meters respectively. The dogs were standing uncontrolled or lying right side down under anesthesia. Serum cortisol and gastrin levels were detected with RIA both before and after explosion. Results: The levels of serum cortisol and gastrin began to fall about 24 hours after explosion. The serum levels of cortisol were still decreased significantly after 9 days and 17 days. Conclusion: The levels of the serum cortisol declined when the animals were injured by vibration. Detection of serum cortisol levels might lead to definitive diagnosis and supplemental treatment with cortical hormones for vibration-induced injury. (authors)

  12. Serum Protein Profile Study of Clinical Samples Using High Performance Liquid Chromatography-Laser Induced Fluorescence

    DEFF Research Database (Denmark)

    Karemore, Gopal Raghunath; Ukendt, Sujatha; Rai, Lavanya

    2009-01-01

    The serum protein profiles of normal subjects, patients diagnosed with cervical cancer, and oral cancer were recorded using High Performance Liquid Chromatography combined with Laser Induced Fluorescence detection (HPLC-LIF). Serum protein profiles of the above three classes were tested for estab...

  13. Conditions and limits of serum LH radioimmunoassay in normal, hypophysectomised or castred rats

    International Nuclear Information System (INIS)

    Andre, M.; Boucher, D.; Thieblot, L.

    1976-01-01

    Serum LH was measured by radioimmunoassay (NIAMD Kits) free and linked hormones were separated by double antibodies method. Influence of concentration on antibody-hormone complex is studied. Hypophysectomised rats serum does not modify results. The standard (rat LH-RPl) has the same action as serum LH. Rat serum LH contents are measured in normal or castred rats [fr

  14. Serum glucose and lipid levels in alloxan-induced diabetic rats ...

    African Journals Online (AJOL)

    Effect of Aloe barbadensis Miller juice extract on serum glucose and lipids in alloxan-induced diabetic rats was investigated. Diabetes was induced by intraperitoneal injection of 150mg/kg alloxan in 5% solution. Diabetes was confirmed 72 hours after alloxan injection, if fasting blood glucose (FBG) was equal to or greater ...

  15. Proposition of decision limits for serum lipids in Brazilian children aged one to 13 years.

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    Slhessarenko, Natasha; Fontes, Cor J F; Slhessarenko, Maria Eduarda; Azevedo, Raymundo S; Andriolo, Adagmar

    2018-03-09

    To determine decision limits for total cholesterol, LDL-cholesterol, non-HDL cholesterol, HDL-cholesterol, and triglycerides in healthy children and adolescents from Cuiabá, Brazil. This was a cross-sectional study of 1866 healthy children and adolescents randomly selected from daycare centers and public schools in Cuiabá. The desirable levels of serum lipids were defined using the classic criteria, i.e., total cholesterol, LDL-cholesterol, non-HDL cholesterol, and triglycerides levels below the P75 percentile, and HDL-c above the P10 percentile. For CT, P75 was: 160mg/dL for the age range of 1 to <3 years, 170mg/dL for ≥3 to <9 years, and 176mg/dL for ≥9 to <13 years. For non-HDL cholesterol, it was 122mg/dL for the age range of 1 to <13 years. For LDL-c, it was 104mg/dL at the age range of 1 to <9 years and 106mg/dL from ≥9 to <13 years. For TG, it was 127mg/dL from 1 to <2 years; 98mg/dL from ≥2 to <6 years; and 92mg/dL from ≥6 to <13 years. As for HDL-cholesterol, P10 was 24mg/dL, 28mg/dL, 32mg/dL, and 36mg/dL, for the age ranges of 1 to <2 years, ≥2 to <3 years, ≥3 to <4 years, and ≥4 to <13 years, respectively. The decision limits for the serum lipid levels defined in this study differed from those observed in the current Brazilian and North-American guidelines, especially because it differentiates between the age ranges. Using these decision limits in clinical practice will certainly contribute to improve the diagnostic accuracy for dyslipidemia in this population group. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  16. Fasting induces the generation of serum thyronine-binding globulin in Zucker rats

    International Nuclear Information System (INIS)

    Young, R.A.; Rajatanavin, R.; Moring, A.F.; Braverman, L.E.

    1985-01-01

    Five-month-old lean and obese Zucker rats were fasted for up to 7 days (lean rats) or 28 days (obese rats), and serum total and free T4 and T3 concentrations, percent free T4 and T3 by equilibrium dialysis, and the binding of [ 125 I] T4 to serum proteins by gel electrophoresis were measured. In the lean rats, a 4- or 7-day fast resulted in significant decreases in serum total and free T4 and T3 concentrations. There was a decrease in the percent free T3 after 7 days of starvation. In contrast, a 4- or 7-day fast did not alter any of these variables in the obese rats. However, after 14 or more days of starvation, serum total T4 and T3 concentrations increased, and the percent free T4 and T3 decreased, resulting in no change in the serum free T4 or T3 concentrations in the obese rats. The percent of [ 125 I]T4 bound to serum thyronine-binding globulin increased and the percent bound to thyronine-binding prealbumin decreased with the duration of the fast in both the lean and obese rats. The increase in serum thyronine-binding globulin binding of T4 can explain the increase in serum total T4 and T3 concentrations, the decrease in percent free T4 and T3, and the normal free hormone concentration in the long term fasted obese rats. The findings in the lean rats appear to be due to a combination of the known central hypothyroidism that occurs during 4-7 days of fasting and the fasting-induced changes in T4 binding in serum. Changes in T4 and T3 binding in serum during fasting in the rat must be considered when the effects of fasting on serum concentrations of the thyroid hormones, thyroid hormone kinetics, and the peripheral action of the thyroid hormones are evaluated

  17. A comparison of definitions of contrast-induced nephropathy in patients with normal serum creatinine

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    Mohammad Reza Khatami

    2016-01-01

    Full Text Available Contrast-induced nephropathy (CIN is the third leading cause of acute kidney injury in hospitalized patients. The prevalence of CIN is reported to range from 0% to 50%, depending not only on patient condition and the procedure used but also the definition of CIN applied. We aimed to determine the best diagnostic indicator of CIN in patients with normal serum creatinine. This study included 206 patients with normal serum creatinine who underwent coronary angiography/angioplasty. Serum creatinine level and glomerular filtration rate (GFR were measured before and on the second and fifth days after contrast administration. The incidence of CIN based on a 25% increase in serum creatinine was calculated and compared with the incidence based on a 25% decrease in GFR or an increase of at least 0.5 mg/dL in serum creatinine. Of 206 patients, 127 were male (61.7% and 79 were female (38.3%; the mean age was 59.56 ± 10.3 years. The prevalence of CIN was 30% based on a 25% increase in serum creatinine, 23% based on a 25% decrease in GFR (P <0.012 and 3.8% based on a serum creatinine increase of at least 0.5 mg/dL (P <0.0001. The serum creatinine levels remained within the normal range in the majority of patients with CIN based on the different definitions. In patients with normal serum creatinine, the absolute increase in serum creatinine may describe the prevalence of CIN more accurately than the relative increase in serum creatinine or relative decrease in GFR.

  18. Serum-induced G0/G1 transition in chemically transformed 3T3 cells

    International Nuclear Information System (INIS)

    Gray, H.E.; Buchou, T.; Mester, J.

    1987-01-01

    Quiescent, chemically transformed (benzo-a-pyrene) BALB/c 3T3 cells (BP A31) enter the cell division cycle when exposed to complete medium containing 10% fetal calf serum (FCS); the number of cells recruited is a function of the duration of serum exposure. The recruitment of cells by short (<4 h) serum pulses is not inhibited by simultaneous exposure to cycloheximide (CH), and therefore the initial commitment does not require protein synthesis. The cells enter S phase with a constant delay following the removal of CH, even if CH exposure has been continued for as long as 20 h after the end of the serum pulse. The cell recruitment by serum pulses was inhibited by 5,6-dichloro-1-β-D-ribofuranosyl-benzimidazole (DRB), an inhibitor of cytoplasmic mRNA accumulation. These data suggest that serum exposure produces a stable memory that is necessary and sufficient for the eventual progression through G1 to S phase that occurs when protein synthesis is resumed after the removal of CH; this memory probably consists of mRNA species that are induced by serum and that are stable in the absence of protein synthesis. Unexpectedly, pretreatment of quiescent BP A31 cells with CH (8-24 h) dramatically increased the fraction of the total cell population that is recruited by a serum pulse of fixed duration

  19. Urinary estrogen excretion and concentration of serum human placental lactogen in pregnancies following legally induced abortion

    DEFF Research Database (Denmark)

    Obel, E B; Madsen, Mette

    1980-01-01

    Feto-placental function was assessed by 24-hour excretion of estrogen in urine and by the concentration of human Placental Lactogen (hPL) in serum in pregnant women whose previous pregnancy was terminated by legally induced abortion. The mean 24-hour excretion of estrogens in urine and the mean...... an increased frequency of dysfunction of the feto-placental unit during the last part of pregnancy in women with previous legally induced abortion. These findings indicate that legal abortion does not seem to increase the frequency of retarded intrauterine growth in a subsequent pregnancy....... concentration of hPL in serum were no lower in this group than in women without previous induced abortion. Neither was the frequency of a low 24-hour excretion of estrogens in urine or low concentration of hPL in serum (values less than mean - 1.96 s) found to be increased. This study could not demonstrate...

  20. Inulin significantly improves serum magnesium levels in proton pump inhibitor-induced hypomagnesaemia.

    Science.gov (United States)

    Hess, M W; de Baaij, J H F; Broekman, M; Bisseling, T M; Haarhuis, B; Tan, A; Te Morsche, R; Hoenderop, J G J; Bindels, R J M; Drenth, J P H

    2016-06-01

    Proton pump inhibitors (PPI) are among the most widely prescribed drugs to treat gastric acid-related disorders. PPI-induced hypomagnesaemia, a defect in intestinal absorption of Mg(2+) , can be a severe side effect of chronic PPI use. To restore serum Mg(2+) concentrations in PPI-induced hypomagnesaemia patients by dietary supplementation with inulin fibres. Eleven patients with PPI-induced hypomagnesaemia and 10 controls were treated with inulin (20 g/day). Each trial consisted of two cycles of 14-day inulin treatment followed by a washout period of 14 days. Patients continued to use their PPI. Serum Mg(2+) levels served as the primary endpoint. Inulin significantly enhanced serum Mg(2+) levels from 0.60 to 0.68 mmol/L in PPI-induced hypomagnesaemia patients, and from 0.84 to 0.93 mmol/L in controls. As a consequence 24 h urinary Mg(2+) excretion was significantly increased in patients with PPI-induced hypomagnesaemia (0.3-2.2 mmol/day). Symptoms related to hypomagnesaemia, including muscle cramps and paraesthesia, were reduced during intervention with inulin. Inulin increases serum Mg(2+) concentrations under PPI maintenance in patients with PPI-induced hypomagnesaemia. © 2016 John Wiley & Sons Ltd.

  1. Effect of Jiangzhi tablet on serum indexes of mice with fatty liver induced by CCL4

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    Geng, Xiuli; Kong, Xuejun; Li, Chongxian; Hao, Shaojun; Wang, Hongyu; Chen, Weiliang; Zhang, Zhengchen

    2018-04-01

    To investigate the effect of Jiangzhi tablet on serum indexes of mice with fatty liver induced by CCL4, 60 mice were randomly divided into blank control group, model group, positive group, high, middle and low dose group. High fat diet fed mice for 2 weeks, in second the beginning of the weekend, each group of experimental animal except the blank group in the afternoon 1:00 subcutaneous injection of 40% CCl4 of edible oil (0.05 mL/10g, 2 times / week) for modeling; at the same time, 9:00 in the morning to lipid-lowering tablets LARGEMEDTUM and small dose group (0.1125g/ml, 0.05625g/ml, 0.02815g/ml) and Gantai tablet group (0.045g/ml) mice fed with corresponding drugs, the model group received the same volume of physiological saline. At the end of the fifth week, the eyeballs were collected and the serum was separated. The levels of serum triglyceride, high density lipoprotein, low density lipoprotein, serum AST, ALT and ALP were detected. Compared with the model group, Dongbao Gantai group, Jiangzhi tablets, high dose group had significantly decreased TG and LDL content in serum of mice (ptablets low dose group can significantly reduce TG and LDL content in serum (ptablet high dose group and middle dose group could significantly reduce the content of ALT, ALP, AST in serum of mice (ptablets in small dose group can significantly reduce ALP and AST content in serum (ptablets have a better intervention effect on the mice model of fatty liver induced by small dose of carbon tetrachloride.

  2. Proton induced X-ray emission analysis of trace elements in human blood serum

    International Nuclear Information System (INIS)

    Cheek, D.B.; Hay, H.J.; Newton, C.S.

    1979-01-01

    Proton induced x-ray emission has been used for quantitative analyses of trace elements in blood serum samples. This work is part of a survey concerned with Zn, Cu, Fe, Cr, Mn and Se in Australian Aboriginal people not receiving optimal diet. Special attention is being directed to Cr because of the high incidence of diabetes mellitus in these people

  3. Human Umbilical Cord Blood Serum Has Higher Potential in Inducing Proliferation of Fibroblast than Fetal Bovine Serum

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    Ferry Sandra

    2017-09-01

    Full Text Available Background: Cytokines and growth factors were reported to play an important role in stimulating fibroblast proliferation. In vitro culture, fibroblast is mostly culture in medium containing fetal bovine serum (FBS.  Human umbilical cord blood (hUCB has been reported to have low immunogenic property and potential in wound healing, so therefore hUCB serum (hUCBS could be potential and were investigated in current study. Materials and Methods: Five hUCBs were collected from healthy volunteers with normal delivering procedure. hUCB was ex utero immediately collected from umbilical vein in vacutainers and processed. NIH3T3 cells were cultured in DMEM with 10% FBS or 5-20% hUCBS for 48 hours. Cells were then quantified using MTT assay. Protein concentration of FBS and hUCBS were quantified using Bradford assay. Results: NIH3T3 cells density grown in DMEM with 10% FBS was the lowest. NIH3T3 cells densities were increased along with the increment of hUCBS concentrations. MTT results showed that average number of NIH3T3 cells grown in DMEM with 10% FBS was 6,185±1,243. Meanwhile average numbers of NIH3T3 cells grown in DMEM with 5%, 10% and 20% hUCBS were 8,126±628, 9,685±313 and 12,200±304, respectively. Average numbers of NIH3T3 cells grown in DMEM with 5% hUCBS were significantly higher than the ones with 10% FBS (p=0.000. Bradford results showed that concentration of hUCBS was significantly higher than the one of FBS (p=0.000. Conclusion: hUCBS could induce higher proliferation rate of NIH3T3 cells than FBS. Hence hUCBS could be suggested as an alternate of FBS in inducing fibroblast. Keywords: NIH3T3, fibroblast, UCB, serum, FBS, proliferation

  4. Protection from radiation induced changes in liver and serum transaminase of whole body gamma irradiated rats

    International Nuclear Information System (INIS)

    Elkashef, H.S.; Roushdy, H.M.; Saada, H.N.; Abdelsamie, M.

    1986-01-01

    Whole body gamma irradiation of rats with a dose of 5.5 Gy induced significant changes in the activity of liver and serum transaminase. The results indicated that this radiation dose caused a significant increase in the activity of serum Got and GPT on the third and seventh days after irradiation. This was followed by significant decreases on the fourteenth post-irradiation day. The activity of Got returned to is control activity, while the activity of GPT was significantly above the control on the twenty ones post-irradiation day. The activity of Got, in the liver of irradiated rats was elevated during the post-irradiation days, but on the twenty one day activity was about the normal value. The activity of liver GPT firstly decreased and then increased very much but attained the control level on the fourteenth after irradiation. The intraperitoneal injection of testosterone-vitamin E mixture 10 days before whole body gamma irradiation caused complete recovery for the activity of liver and serum Got. No indication of remarkable recovery in the case of GPT activity was recorded either in liver or in serum of irradiated rats. The applied mixture could protect against radiation induced changes in Got activity of liver and serum but could not protect or ameliorate the changes which occurred in the activity of GPT of the two tissues. 2 tab

  5. Is rosuvastatin protective against on noise-induced oxidative stress in rat serum?

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    Emine Rabia Koc

    2015-01-01

    Full Text Available Noise, one of the main components of modern society, has become an important environmental problem. Noise is not only an irritating sound, but also a stress factor leading to serious health problems. In this study, we have investigated possible effects of rosuvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, thought to have an antioxidant effect, on noise-induced oxidative stress in the serum of rat models. Thirty-two male Wistar albino rats were used. In order to ease their adaptation, 2 weeks before the experiment, the rats were divided into four groups (with eight rats per each group: Noise exposure plus rosuvastatin usage, only noise exposure, only rosuvastatin usage and control. After the data had been collected, oxidant (Malondialdehyde, nitric oxide [NO], protein carbonyl [PC] and antioxidant (superoxide dismutase [SOD], glutathione peroxidase [GSH-PX], catalase [CAT] parameters were analyzed in the serum. Results indicated that SOD values were found to be significantly lower, while PC values in serum were remarkably higher in the group that was exposed to only noise. GSH-Px values in serum dramatically increased in the group on which only rosuvastatin was used. During noise exposure, the use of rosuvastatin caused significantly increased CAT values, whereas it resulted in reduced PC and NO values in serum. In conclusion, our data show that noise exposure leads to oxidative stress in rat serum; however, rosuvastatin therapy decreases the oxidative stress caused by noise exposure.

  6. Alteration of human serum albumin binding properties induced by modifications: A review

    Science.gov (United States)

    Maciążek-Jurczyk, Małgorzata; Szkudlarek, Agnieszka; Chudzik, Mariola; Pożycka, Jadwiga; Sułkowska, Anna

    2018-01-01

    Albumin, a major transporting protein in the blood, is the main target of modification that affects the binding of drugs to Sudlow's site I and II. These modification of serum protein moderates its physiological function, and works as a biomarker of some diseases. The main goal of the paper was to explain the possible alteration of human serum albumin binding properties induced by modifications such as glycation, oxidation and ageing, their origin, methods of evaluation and positive and negative meaning described by significant researchers.

  7. Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal

    DEFF Research Database (Denmark)

    Parkinson, C; Kassem, M; Heickendorff, Lene

    2003-01-01

    Active acromegaly is associated with increased biochemical markers of bone turnover. Pegvisomant is a GH receptor antagonist that normalizes serum IGF-I in 97% of patients with active acromegaly. We evaluated the effects of pegvisomant-induced serum IGF-I normalization on biochemical markers...... of bone and soft tissue turnover, as well as levels of PTH and vitamin D metabolites, in 16 patients (nine males; median age, 52 yr; range, 28-78 yr) with active acromegaly (serum IGF-I at least 30% above upper limit of an age-related reference range). Serum procollagen III amino-terminal propeptide...... (PIIINP) and type I procollagen amino-terminal propeptide, osteocalcin (OC), bone-related alkaline phosphatase, C-terminal cross-linked telopeptide of type I collagen (CTx), albumin-corrected calcium, intact PTH, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D [1,25-(OH)(2) vit D], urinary type 1 collagen...

  8. Phosphate limitation induces sporulation in the chytridiomycete Blastocladiella emersonii.

    Science.gov (United States)

    Bongiorno, Vagner Alexandre; Ferreira da Cruz, Angela; Nunis da Silva, Antonio; Corrêa, Luiz Carlos

    2012-09-01

    The cell cycle is controlled by numerous mechanisms that ensure correct cell division. If growth is not possible, cells may eventually promote autophagy, differentiation, or apoptosis. Microorganisms interrupt their growth and differentiate under general nutrient limitation. We analyzed the effects of phosphate limitation on growth and sporulation in the chytridiomycete Blastocladiella emersonii using kinetic data, phase-contrast, and laser confocal microscopy. Under phosphate limitation, zoospores germinated and subsequently formed 2-4 spores, regardless of the nutritional content of the medium. The removal of phosphate at any time during growth induced sporulation of vegetative cells. If phosphate was later added to the same cultures, growth was restored if the cells were not yet committed to sporulation. The cycles of addition and withdrawal of phosphate from growth medium resulted in cycles of germination-growth, germination-sporulation, or germination-growth-sporulation. These results show that phosphate limitation is sufficient to interrupt cell growth and to induce complete sporulation in B. emersonii. We concluded that the determination of growth or sporulation in this microorganism is linked to phosphate availability when other nutrients are not limiting. This result provides a new tool for the dissection of nutrient-energy and signal pathways in cell growth and differentiation.

  9. O2-mediated oxidation of ferrous nitrosylated human serum heme-albumin is limited by nitrogen monoxide dissociation

    International Nuclear Information System (INIS)

    Ascenzi, Paolo; Gullotta, Francesca; Gioia, Magda; Coletta, Massimo; Fasano, Mauro

    2011-01-01

    Research highlights: → Human serum heme-albumin displays globin-like properties. → O 2 -mediated oxidation of ferrous nitrosylated human serum heme-albumin. → Allosteric modulation of human serum heme-albumin reactivity. → Rifampicin is an allosteric effector of human serum heme-albumin. → Human serum heme-albumin is a ROS and NOS scavenger. -- Abstract: Human serum heme-albumin (HSA-heme-Fe) displays globin-like properties. Here, kinetics of O 2 -mediated oxidation of ferrous nitrosylated HSA-heme-Fe (HSA-heme-Fe(II)-NO) is reported. Values of the first-order rate constants for O 2 -mediated oxidation of HSA-heme-Fe(II)-NO (i.e., for ferric HSA-heme-Fe formation) and for NO dissociation from HSA-heme-Fe(II)-NO (i.e., for NO replacement by CO) are k = 9.8 x 10 -5 and 8.3 x 10 -4 s -1 , and h = 1.3 x 10 -4 and 8.5 x 10 -4 s -1 , in the absence and presence of rifampicin, respectively, at pH = 7.0 and T = 20.0 o C. The coincidence of values of k and h indicates that NO dissociation represents the rate limiting step of O 2 -mediated oxidation of HSA-heme-Fe(II)-NO. Mixing HSA-heme-Fe(II)-NO with O 2 does not lead to the formation of the transient adduct(s), but leads to the final ferric HSA-heme-Fe derivative. These results reflect the fast O 2 -mediated oxidation of ferrous HSA-heme-Fe and highlight the role of drugs in modulating allosterically the heme-Fe-atom reactivity.

  10. Limitations of the radioimmunoprecipitation polyethylene glycol assay (RIPEGA) for detection of filarial antigens in serum

    International Nuclear Information System (INIS)

    Hamilton, R.G.; Alexander, E.; Adkinson, N.F.

    1984-01-01

    The performance of the radioimmunoprecipitation polyethylene glycol assay (RIPEGA) was examined for quantitation of filarial antigens (Brugia malayi and Dirofilaria immitis) in serum from infected human and animal hosts and non-infected controls. Multiple PEG concentrations were employed to determine the level of non-specific binding (NSB) in non-exposed human sera (NEHS) containing no filarial antigen. The NSB observed when 3 different 125 I-labelled IgG antibodies were added to 26 NEHS varied 3-fold and was correlated significantly with total serum IgM (r = 0.80, P 2 fragment of the 125 I-labelled antibody was used, but the correlation of NSB with total serum IgM remained significant (r = 0.57, P < 0.01). The presence of rheumatoid factor in NEHS sera also significantly increased NSB by an average of 3-fold. These effects eliminated the assay's ability to detect in sera from infected hosts filarial antigen the presence of which could be readily demonstrated by an immunoradiometric assay. The RIPEGA's precision (intra-assay coefficient of variation (CV) = 21% at 35% Bsub(max)) and reproducibility (inter-assay CV = 29% at 35% Bsub(max)) are less satisfactory than many alternative immunoassays. (Auth.)

  11. Reference limits and behaviour of serum transferrin receptor in children 6-10 years of age.

    Science.gov (United States)

    Danise, P; Maconi, M; Morelli, G; Di Palma, A; Rescigno, G; Esposito, C; Avino, D; Talento, B

    2008-08-01

    Serum transferrin receptor (sTfR) originates mostly from erythroblasts and lesser from reticulocytes. The usefulness of sTfR has been implicated in several clinical situations, mainly as a marker of accelerated erythropoiesis or iron deficiency. The assessment of sTfR may be useful in the period of rapid growth during infancy, childhood and adolescence. We evaluated sTfR and the other quantitative and qualitative parameters of the erythropoiesis (Hb, MCV, CHr, Ret-He) and of the iron storage (serum ferritin, sTfR/ferritin index) in a total of 916 children aged 6-10 years. Children were divided into three groups: (A) healthy children, (B) with storage iron deficiency (serum ferritin 3.3). We determined reference intervals by sex and by age in healthy children. sTfR showed a slight but statistically significant age related increase but did not show significant sex differences. We compared sTfR and the other parameters investigated in the three groups of children. sTfR is not a decisive parameter that can be utilized alone in discriminating the border-line situations between normal and pathologic ones but can help in completing the panel of tests in iron deficiency and in thalassaemia Beta trait carriers.

  12. Normal human serum (HS) prevents oxidant-induced lysis of cultured endothelial cells (ECs)

    International Nuclear Information System (INIS)

    Callahan, K.S.; Harlan, J.M.

    1986-01-01

    Most studies demonstrating oxidant lysis of cultured ECs are performed in serum-free media or media containing low concentrations of bovine serum. The authors found that HS protects human and bovine ECs from lysis caused by reagent H 2 O 2 or glucose/glucose oxidase (GO)-generated H 2 O 2 . EC injury was assessed by 51 Cr release, cell detachment, or trypan blue dye exclusion. Protective HS activity was dose-dependent with concentrations greater than or equal to 25% preventing lethal injury. Cytotoxicity at 24 hrs, induced by 20 mU/ml GO, was 90.1 +/- 5.2% without HS vs 1.7 +/- 4.6% with 25% HS present (20 exp). Similar protection was observed with heparinized plasma. Of note, comparable concentrations of bovine serum were devoid of protective activity. Addition of fatty acid-free albumin to the media was also without protective effect. Preliminary characterization showed HS activity was stable to 60 0 C for 30 min, non-dialyzable at 25,000 MW cutoff, and retained in delipidated serum. The HS protection was not merely due to scavenging of exogenous H 2 O 2 as A23187-induced EC lysis was also prevented by HS. Protective activity was not reproduced by purified cerruloplasmin or transferrin. In conclusion, unidentified factor(s) present in HS protect cultured ECs from oxidant-induced lysis. Since endothelium is normally exposed to 100% plasma, the authors suggest that in vitro studies of oxidant-mediated injury be performed in the presence of HS. Factor(s) in HS may play an important role in modulating oxidant-induced vascular injury in vivo

  13. Study of vitamin D serum level in patients with epilepsy treated with enzyme-inducing and non enzyme-inducing medications

    Directory of Open Access Journals (Sweden)

    sima Hashemipour

    2014-01-01

    Full Text Available Background : Changes of serum minerals and vitamin D have been reported in anticonvulsant drugs user patients. The present study aimed at comparing the changes of serum minerals and vitamin D among two groups of enzyme-inducing and non enzyme-inducing anticonvulsant drug users. Methods: In this study 22 patients treated with enzyme-inducing drugs (carbamazepin, phenytoin, phenobarbital were compared to 25 patients of matched sex, age, and BMI treated with non enzyme-inducing drugs (sodium evaporate, lamotrigine. Serum calcium, phosphate, parathormone, and 25-hydroxy vitamin D were calculated in both groups. Calcium was measured by Calorimetery method. Parathormone and vitamin D were measured using ELISA method. Results: The mean serum vitamin D level was lower in enzyme-inducing than non enzyme-inducing drugs users (15.9±8.3 and 24.2±14.8, P=0.02. Frequency of vitamin D deficiency was higher in enzyme-inducing compared to non enzyme-inducing drugs users, 84% and 48% , respectively (P=0.016. The mean serum calcium level was significantly lower in enzyme-inducing drugs users. (8.7±0.2 vs. 9.0± 0.7, p= 0.05. Four percent in enzyme-inducing group compared to twenty four percent of non enzyme-inducing group had secondary hyperparathyroidism (P=0.016. Conclusion: While vitamin D deficiency is more frequent in enzyme-inducing drug users, secondary hyperparathyroidism is less frequent.

  14. Neurokinin B and serum albumin limit copper binding to mammalian gonadotropin releasing hormone.

    Science.gov (United States)

    Gul, Ahmad Samir; Tran, Kevin K; Jones, Christopher E

    2018-02-26

    Gonadotropin releasing hormone (GnRH) triggers secretion of luteinizing hormone and follicle stimulating hormone from gonadotropic cells in the anterior pituitary gland. GnRH is able to bind copper, and both in vitro and in vivo studies have suggested that the copper-GnRH complex is more potent at triggering gonadotropin release than GnRH alone. However, it remains unclear whether copper-GnRH is the active species in vivo. To explore this we have estimated the GnRH-copper affinity and have examined whether GnRH remains copper-bound in the presence of serum albumin and the neuropeptide neurokinin B, both copper-binding proteins that GnRH will encounter in vivo. We show that GnRH has a copper dissociation constant of ∼0.9 × 10 -9  M, however serum albumin and neurokinin B can extract metal from the copper-GnRH complex. It is therefore unlikely that a copper-GnRH complex will survive transit through the pituitary portal circulation and that any effect of copper must occur outside the bloodstream in the absence of neurokinin B. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Inhaled ozone (O3)-induces changes in serum metabolomic and liver transcriptomic profiles in rats

    International Nuclear Information System (INIS)

    Miller, Desinia B.; Karoly, Edward D.; Jones, Jan C.; Ward, William O.; Vallanat, Beena D.; Andrews, Debora L.; Schladweiler, Mette C.; Snow, Samantha J.; Bass, Virginia L.; Richards, Judy E.; Ghio, Andrew J.; Cascio, Wayne E.; Ledbetter, Allen D.; Kodavanti, Urmila P.

    2015-01-01

    Air pollution has been linked to increased incidence of diabetes. Recently, we showed that ozone (O 3 ) induces glucose intolerance, and increases serum leptin and epinephrine in Brown Norway rats. In this study, we hypothesized that O 3 exposure will cause systemic changes in metabolic homeostasis and that serum metabolomic and liver transcriptomic profiling will provide mechanistic insights. In the first experiment, male Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or O 3 at 0.25, 0.50, or 1.0 ppm, 6 h/day for two days to establish concentration-related effects on glucose tolerance and lung injury. In a second experiment, rats were exposed to FA or 1.0 ppm O 3 , 6 h/day for either one or two consecutive days, and systemic metabolic responses were determined immediately after or 18 h post-exposure. O 3 increased serum glucose and leptin on day 1. Glucose intolerance persisted through two days of exposure but reversed 18 h-post second exposure. O 3 increased circulating metabolites of glycolysis, long-chain free fatty acids, branched-chain amino acids and cholesterol, while 1,5-anhydroglucitol, bile acids and metabolites of TCA cycle were decreased, indicating impaired glycemic control, proteolysis and lipolysis. Liver gene expression increased for markers of glycolysis, TCA cycle and gluconeogenesis, and decreased for markers of steroid and fat biosynthesis. Genes involved in apoptosis and mitochondrial function were also impacted by O 3 . In conclusion, short-term O 3 exposure induces global metabolic derangement involving glucose, lipid, and amino acid metabolism, typical of a stress–response. It remains to be examined if these alterations contribute to insulin resistance upon chronic exposure. - Highlights: • Ozone, an ubiquitous air pollutant induces acute systemic metabolic derangement. • Serum metabolomic approach provides novel insights in ozone-induced changes. • Ozone exposure induces leptinemia, hyperglycemia, and glucose intolerance

  16. Persistent tumor-induced osteomalacia confirmed by elevated postoperative levels of serum fibroblast growth factor-23 and 5-year follow-up of bone density changes.

    Science.gov (United States)

    Zimering, Mark B; Caldarella, Felice A; White, Kenneth E; Econs, Michael J

    2005-01-01

    To describe a case of persistent tumor-induced osteomalacia, determine whether serum fibroblast growth factor-23 (FGF-23) levels postoperatively indicate incomplete tumor resection, and report lumbar spine and forearm bone mineral density (BMD) changes during 5 years of follow-up. We present clinical, radiologic, histologic, and bone densitometry data as well as serum FGF-23 levels (determined with use of a novel C-terminal enzyme-linked immunosorbent assay) from the study patient and discuss these findings in the context of previous literature. A 52-year-old man, who presented with muscle weakness and multiple fractures, was found to have low values for serum phosphorus, serum 1,25-dihydroxyvitamin D, and maximal tubular reabsorption of phosphate per glomerular filtration rate, a high level of serum alkaline phosphatase, and a normal serum concentration of parathyroid hormone, characteristic of tumor-induced osteomalacia. Magnetic resonance imaging to evaluate an abnormality of the left foot revealed a soft tissue mass, biopsy of which confirmed the presence of a benign, phosphaturic, mesenchymal tumor. The baseline serum FGF-23 level (2,050 RU/mL) was more than 17 times the upper limit of normal for adults (23 to 118 RU/mL) and decreased substantially within 1 day after partial resection of the tumor but remained above normal postoperatively. BMD changes indicated rapid substantial recovery of vertebral BMD but ongoing loss of forearm bone density. The serum FGF-23 level is high in a substantial proportion of patients with tumor-induced osteomalacia. The postoperative above normal levels of serum FGF-23 correlated with known persistence of tumor in our study patient. In a patient with normal renal function, such as our study patient, levels of serum FGF-23 studied with use of the C-terminal enzyme-linked immunosorbent assay reached their nadir within 24 hours postoperatively. This result suggests that this assay can provide clinicians with rapid prognostic

  17. Identification of biomarkers for radiation-induced acute intestinal symptoms (RIAISs) in cervical cancer patients by serum protein profiling

    International Nuclear Information System (INIS)

    Chai Yanlan; Wang Juan; Gao Ying

    2015-01-01

    Radiation-induced acute intestinal symptoms (RIAISs) are the most frequent complication of radiotherapy that causes great pain and limits the treatment efficacy. The aim of this study was to identify serum biomarkers of RIAISs in cervical cancer patients by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Serum samples were collected from 66 cervical cancer patients prior to pelvic radiotherapy. In our study, RIAISs occurred in 11 patients. An additional 11 patients without RIAISs were selected as controls, whose age, stage, histological type and treatment methods were matched to RIAISs patients. The 22 sera were subsequently analyzed by SELDI-TOF MS, and the resulting protein profiles were evaluated to identify biomarkers using appropriate bioinformatics tools. Comparing the protein profiles of serum samples from the RIAIS group and the control group, it was found that 22 protein peaks were significantly different (P < 0.05), and six of these peaks with mass-to-charge (m/z) ratios of 7514.9, 4603.94, 6887.41, 2769.21, 3839.72 and 4215.7 were successfully identified. A decision tree model of biomarkers was constructed based on three biomarkers (m/z 1270.88, 1503.23 and 7514.90), which separated RIAIS-affected patients from the control group with an accuracy of 81%. This study suggests that serum proteomic analysis by SELDI-TOF MS can identify cervical cancer patients that are susceptible to RIAISs prior to pelvic radiotherapy. (author)

  18. Limited Investigation of the Effects of Elevator Rate Limiting and Stick Dynamics on Longitudinal Pilot Induced Oscillations (HAVE GRIP)

    National Research Council Canada - National Science Library

    Peters, Patrick

    1996-01-01

    This report presents the results of the HAVE GRIP flight test program. This program performed a limited investigation of the effects of stick dynamics and elevator rate limiting on longitudinal pilot induced oscillations (PIOs...

  19. Multiplex assessment of serum cytokine and chemokine levels in idiopathic morphea and vitamin K1-induced morphea.

    Science.gov (United States)

    Cox, Lori Ann; Webster, Guy F; Piera-Velazquez, Sonsoles; Jimenez, Sergio A

    2017-05-01

    The levels of 63 cytokines, chemokines, and growth factors were measured in the serum of four patients with idiopathic morphea and of one patient with vitamin K 1 -induced morphea employing a multiplex assay to identify the role of inflammatory/immunologic events in their pathogenesis. Full-thickness skin biopsies of affected skin were analyzed by histopathology. Luminex assays for 63 cytokines, chemokines, and growth factors were performed in the sera from four patients with idiopathic morphea and in two different samples of serum obtained in two separate occasions from one patient with vitamin K 1 -induced morphea. The serum values of numerous inflammatory cytokines and growth factors including IL-2, IL-4, IL-6, and IFNβ were markedly increased in the serum of patients with idiopathic morphea, whereas, these values were normal in the serum of the patient with vitamin K 1 -induced morphea. In contrast, serum eotaxin levels were greater than threefold higher in the patient with vitamin K 1 -induced morphea compared to patients with idiopathic morphea. The results demonstrated remarkable increases in the levels of numerous cytokines and chemokines in the serum samples of all patients with idiopathic morphea indicative of a prominent role of inflammatory/immunologic events in its pathogenesis. The results also showed statistically significant differences between idiopathic morphea and vitamin K 1 -induced morphea suggesting that their development involves different pathogenetic mechanisms.

  20. Toxicoproteomics: serum proteomic pattern diagnostics for early detection of drug induced cardiac toxicities and cardioprotection.

    Science.gov (United States)

    Petricoin, Emanuel F; Rajapaske, Vinodh; Herman, Eugene H; Arekani, Ali M; Ross, Sally; Johann, Donald; Knapton, Alan; Zhang, J; Hitt, Ben A; Conrads, Thomas P; Veenstra, Timothy D; Liotta, Lance A; Sistare, Frank D

    2004-01-01

    Proteomics is more than just generating lists of proteins that increase or decrease in expression as a cause or consequence of pathology. The goal should be to characterize the information flow through the intercellular protein circuitry which communicates with the extracellular microenvironment and then ultimately to the serum/plasma macroenvironment. The nature of this information can be a cause, or a consequence, of disease and toxicity based processes as cascades of reinforcing information percolate through the system and become reflected in changing proteomic information content of the circulation. Serum Proteomic Pattern Diagnostics is a new type of proteomic platform in which patterns of proteomic signatures from high dimensional mass spectrometry data are used as a diagnostic classifier. While this approach has shown tremendous promise in early detection of cancers, detection of drug-induced toxicity may also be possible with this same technology. Analysis of serum from rat models of anthracycline and anthracenedione induced cardiotoxicity indicate the potential clinical utility of diagnostic proteomic patterns where low molecular weight peptides and protein fragments may have higher accuracy than traditional biomarkers of cardiotoxicity such as troponins. These fragments may one day be harvested by circulating nanoparticles designed to absorb, enrich and amplify the diagnostic biomarker repertoire generated even at the critical initial stages of toxicity.

  1. The utility of serum tryptase in the diagnosis of food-induced anaphylaxis.

    Science.gov (United States)

    Wongkaewpothong, Patcharaporn; Pacharn, Punchama; Sripramong, Chaweewan; Boonchoo, Siribangon; Piboonpocanun, Surapon; Visitsunthorn, Nualanong; Vichyanond, Pakit; Jirapongsananuruk, Orathai

    2014-07-01

    This study investigates the utility of serum tryptase for the confirmation of shrimp-induced anaphylaxis. Patients with a history of shrimp allergy and positive skin prick tests (SPT) to commercial shrimp extract were recruited for shrimp challenges. Serum total tryptase was obtained at baseline and 60 min (peak) after the onset of symptoms. Thirty-nine patients were challenged. There were 12 patients with anaphylaxis, 20 with mild reactions and 7 without symptoms (control group). Characteristic features and baseline tryptase were not different among the 3 groups. The peak tryptase levels were higher than the baseline in anaphylaxis and mild reaction groups (P11.4 µg/L with 17% sensitivity, 100% specificity, infinity positive LR and 0.83 negative LR. The best cut-off for delta-tryptase was ≥0.8 µg/L with 83% sensitivity, 93% specificity, 11.86 positive LR and 0.18 negative LR. The best cut-off for tryptase ratio was ≥1.5 with 92% sensitivity, 96% specificity, 23 positive LR and 0.08 negative LR. The peak tryptase level should be compared with the baseline value to confirm anaphylaxis. The tryptase ratio provide the best sensitivity, specificity, positive and negative LR than a single peak serum tryptase for the confirmation of shrimp-induced anaphylaxis.

  2. Changes of serum lipid for patients with subclinical hypothyroidism induced by post-radiotherapy nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Shao Qian; Zhao Baohua; Liang Chaoqian; Li Jianbing; Tian Shiyu; Fan Tingyong

    2007-01-01

    Objective: To study the changes of serum lipid of pre-and post-treatment by Levothyroxine(LT 4 ) for patients with subclinical hypothyroidism (SHT) induced by post-radiotherapy nasopharyngeal carcinoma(NPC). Methods: From Nov. 1998 to Nov. 2002, 76 NPC pathologically confirmed patients were treated by radiotherapy. The total dose of thy- ;old was 45Gy-60Gy and the median dose was 50Gy. There were 40 patients with normal thyroid function(NC group) and 36 patients with subclinical hypothyroidism(SHT group). The SHT patients received LT 4 treatment from 25 μg/day with the does gyadually increased till thyrotropin(TSH) was normal. The serum levels of TSH, free thyroxine (FT 4 ), free triiodothyronine (FT 3 ), total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) in NC group and SHT group was measured and compared before and after LT4 treatment. Results: The serum levels of TSH, FT 3 , FT 4 , TC, TG, HDL-C, LDL-C in pre-and post-treatment SHT group and NC group were significantly different between those in the pre-and post-treatment SHT group was measured aha compared, and pre-treatment SHT group and NC group except HDL-C (P<0.001 or 0.05). Conclusions: Radiotherapy on NPC patients can induce SHT, and LT4 treatment for SHT patients can ameliorates the function of thyroid and metabolism of serum lipid. (authors)

  3. MicroRNA changes in rat mesentery and serum associated with drug-induced vascular injury

    International Nuclear Information System (INIS)

    Thomas, Roberta A.; Scicchitano, Marshall S.; Mirabile, Rosanna C.; Chau, Nancy T.; Frazier, Kendall S.; Thomas, Heath C.

    2012-01-01

    Regulatory miRNAs play a role in vascular biology and are involved in biochemical and molecular pathways dysregulated during vascular injury. Collection and integration of functional miRNA data into these pathways can provide insight into pathogenesis at the site of injury; the same technologies applied to biofluids may provide diagnostic or surrogate biomarkers. miRNA was analyzed from mesentery and serum from rats given vasculotoxic compounds for 4 days. Fenoldopam, dopamine and midodrine each alter hemodynamics and are associated with histologic evidence of vascular injury, while yohimbine is vasoactive but does not cause histologic evidence of vascular injury in rat. There were 38 and 35 miRNAs altered in a statistically significant manner with a fold change of 2 or greater in mesenteries of fenoldopam- and dopamine-dosed rats, respectively, with 9 of these miRNAs shared. 10 miRNAs were altered in rats given midodrine; 6 were shared with either fenoldopam or dopamine. In situ hybridization demonstrated strong expression and co-localization of miR-134 in affected but not in adjacent unaffected vessels. Mesenteric miRNA expression may provide clarity or avenues of research into mechanisms involved in vascular injury once the functional role of specific miRNAs becomes better characterized. 102 miRNAs were altered in serum from rats with drug-induced vascular injury. 10 miRNAs were commonly altered in serum from dopamine and either fenoldopam or midodrine dosed rats; 18 of these 102 were also altered in mesenteries from rats with drug-induced vascular injury, suggesting their possible utility as peripheral biomarkers. -- Highlights: ► Mesentery and serum were examined from rats given vasoactive compounds for 4 days. ► 72 miRNAs were altered in mesenteries from rats with vascular injury. ► miR-134 was localized to affected but not adjacent unaffected vessels. ► 102 miRNAs were changed in serum from rats with vascular injury. ► 18 miRNAs changed in both

  4. TVP1022 and propargylamine protect neonatal rat ventricular myocytes against doxorubicin-induced and serum starvation-induced cardiotoxicity.

    Science.gov (United States)

    Kleiner, Yana; Bar-Am, Orit; Amit, Tamar; Berdichevski, Alexandra; Liani, Esti; Maor, Gila; Reiter, Irina; Youdim, Moussa B H; Binah, Ofer

    2008-09-01

    We recently reported that propargylamine derivatives such as rasagiline (Azilect) and its S-isomer TVP1022 are neuroprotective. The aim of this study was to test the hypothesis that the neuroprotective agents TVP1022 and propargylamine (the active moiety of propargylamine derivatives) are also cardioprotective. We specifically investigated the protective efficacy of TVP1022 and propargylamine in neonatal rat ventricular myocytes (NRVM) against apoptosis induced by the anthracycline chemotherapeutic agent doxorubicin and by serum starvation. We demonstrated that pretreatment of NRVM cultures with TVP1022 or propargylamine attenuated doxorubicin-induced and serum starvation-induced apoptosis, inhibited the increase in cleaved caspase 3 levels, and reversed the decline in Bcl-2/Bax ratio. These cytoprotective effects were shown to reside in the propargylamine moiety. Finally, we showed that TVP1022 neither caused proliferation of the human cancer cell lines HeLa and MDA-231 nor interfered with the anti-cancer efficacy of doxorubicin. These results suggest that TVP1022 should be considered as a novel cardioprotective agent against ischemic insults and against anthracycline cardiotoxicity and can be coadministered with doxorubicin in the treatment of human malignancies.

  5. Serum deprivation induces glucose response and intercellular coupling in human pancreatic adenocarcinoma PANC-1 cells.

    Science.gov (United States)

    Hiram-Bab, Sahar; Shapira, Yuval; Gershengorn, Marvin C; Oron, Yoram

    2012-03-01

    This study aimed to investigate whether the previously described differentiating islet-like aggregates of human pancreatic adenocarcinoma cells (PANC-1) develop glucose response and exhibit intercellular communication. Fura 2-loaded PANC-1 cells in serum-free medium were assayed for changes in cytosolic free calcium ([Ca]i) induced by depolarization, tolbutamide inhibition of K(ATP) channels, or glucose. Dye transfer, assayed by confocal microscopy or by FACS, was used to detect intercellular communication. Changes in messenger RNA (mRNA) expression of genes of interest were assessed by quantitative real-time polymerase chain reaction. Proliferation was assayed by the MTT method. Serum-deprived PANC-1 cell aggregates developed [Ca]i response to KCl, tolbutamide, or glucose. These responses were accompanied by 5-fold increase in glucokinase mRNA level and, to a lesser extent, of mRNAs for K(ATP) and L-type calcium channels, as well as increase in mRNA levels of glucagon and somatostatin. Trypsin, a proteinase-activated receptor 2 agonist previously shown to enhance aggregation, modestly improved [Ca]i response to glucose. Glucose-induced coordinated [Ca]i oscillations and dye transfer demonstrated the emergence of intercellular communication. These findings suggest that PANC-1 cells, a pancreatic adenocarcinoma cell line, can be induced to express a differentiated phenotype in which cells exhibit response to glucose and form a functional syncytium similar to those observed in pancreatic islets.

  6. Fibre and components induced limitations in high capacity optical networks

    DEFF Research Database (Denmark)

    Peucheret, Christophe

    2003-01-01

    The design of future all-optical networks relies on the knowledge of the physical layer transport properties. In this thesis, we focus on two types of system impairments: those induced by the non-ideal transfer functions of optical filters to be found in network elements such as optical add...... design in order to maximise the spectral efficiency in a four add-drop node ring network. The concept of "normalised transmission sections" is introduced in order to ease the dimensioning of transparent domains in future all-optical networks. Normalised sections based on standard single mode fibre (SMF......-drop multiplexers (OADM) and optical cross-connects (OXC), as well as those due to the interaction of group-velocity dispersion, optical fibre non-linearities and accumulation of amplifier noise in the transmission path. The dispersion of fibre optics components is shown to limit their cascadability. Dispersion...

  7. Dynamics and Predictors of Serum TSH and fT4 Reference Limits in Early Pregnancy

    DEFF Research Database (Denmark)

    Laurberg, Peter; Andersen, Stine Linding; Hindersson, Peter

    2016-01-01

    CONTEXT: Thyroid hormones are important developmental factors and levels should be adequate both in the pregnant woman and in the fetus. However, there is no consensus on maternal thyroid test reference limits in early pregnancy. OBJECTIVE: Estimation of week-to-week changes in and predictors of ...

  8. Serum drug level-related sodium valproate-induced hair loss.

    Science.gov (United States)

    Ramakrishnappa, Suresh K; Belhekar, Mahesh N

    2013-01-01

    Sodium valproate is a well-established treatment in epilepsy and mood disorders. Its utility is compromised by its adverse effects such as tremor, weight gain, hair loss, and liver dysfunction. Hair loss may occur when drug is used in higher dose. Drug-induced hair loss is diffused and non-scarring, which is reversible upon withdrawal. But there are no case reports showing relation between serum levels of valproate and occurrence of hair loss. So we took interest in reporting this case report.

  9. Limits of recovery against slip-induced falls while walking.

    Science.gov (United States)

    Yang, Feng; Bhatt, Tanvi; Pai, Yi-Chung

    2011-10-13

    Slip-induced falls in gait often have devastating consequences. The purposes of this study were 1) to select the determinants that can best discriminate the outcomes (recoveries or falls) of an unannounced slip induced in gait (and to find their corresponding threshold, i.e., the limits of recovery, which can clearly separate these two outcomes), and 2) to verify these results in a subset of repeated-slip trials. Based on the data collected from 69 young subjects during a slip induced in gait, nine different ways of combining the center of mass (COM) stability, the hip height, and its vertical velocity were investigated with the aid of logistic regression. The results revealed that the COM stability (s) and limb support (represented by the quotient of hip vertical velocity to hip height, S(hip)) recorded at the instant immediately prior to the recovery step touchdown were sufficiently sensitive to account for all (100%) variance in falls, and specific enough to account for nearly all (98.3%) variability in recoveries. This boundary (S(hip)=-0.22s-0.25), which quantifies the risk of falls in the stability-limb support quotient (s-S(hip)) domain, was fully verified using second-slip and third-slip trials (n=76) with classification of falls at 100% and recoveries at 98.6%. The severity of an actual fall is likely to be greater further below the boundary, while the likelihood of a fall diminishes above it. Finally, the slope of the boundary also indicates the tradeoff between the stability and limb support, whereby high stability can compensate for the insufficiency in limb support, or vice versa. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Physiological serum copper concentrations found in malignancies cause unfolding induced aggregation of human serum albumin in vitro.

    Science.gov (United States)

    Rizvi, Asim; Furkan, Mohd; Naseem, Imrana

    2017-12-15

    Malignancies are characterized by several drastic metabolic changes, one of which is a progressive rise in the levels of serum copper. This rise in serum copper is documented across all malignancies and across malignancies in several species. This study aims to explore in vitro the effect of increased copper levels on the structure of the blood protein human serum albumin. Exposure of human serum albumin to physiologically relevant copper concentrations for 21 days resulted in structural modifications in the protein which were evident by changes in the intrinsic florescence. A loss of the predominantly alpha helical structure of human serum albumin was recorded along with a tendency to form protein aggregates. This aggregation was characterized by Thioflavin T and Congo Red assays. Rayleigh light scattering and turbidity assays confirmed aggregation. The aggregates were visually confirmed using transmission electron microscopy. This is the first report implicating increased copper levels as a cause of aggregation of blood proteins in malignancies. The physiological and biochemical implications of this phenomenon are discussed. Copyright © 2017. Published by Elsevier Inc.

  11. Effect of melatonin on serum glucose and body weights in streptozotocin induced diabetes in albino rats

    International Nuclear Information System (INIS)

    Hidayat, M.

    2015-01-01

    It has been demonstrated in experimental animal models that oxidative stress causes persistent and chronic hyperglycaemia, causing reduction in antioxidant defence system, ultimately leading to accumulation of free radicals.This study was performed to observe the effect of melatonin on serum glucose and body weights in streptozotocin induced diabetes in albino rats. Methods: Forty healthy adult male albino rats were included in the study and divided equally into 4 groups for 6 weeks. Group-A was taken as control. Group-B received streptozotocin I/P in a dose of 37 mg/kg body weight. Group-C received 10 mg/100 ml melatonin in drinking water and Group-D received only melatonin. Results: Streptozotocin significantly increased serum glucose and decreased weight in group B animals, whereas in group C, melatonin significantly restored serum glucose but could not restore the body weights reduced by streptozotocin. There was a significant reduction in body weight in melatonin treated group D animals. Conclusion: Melatonin decreases oxidative stress and hyperglycemia, but cannot restore the body weight reduced by streptozotocin. In fact, it further reduces body weight both in diabetic and normal state. (author)

  12. Mobile phone specific electromagnetic fields induce transient DNA damage and nucleotide excision repair in serum-deprived human glioblastoma cells.

    Science.gov (United States)

    Al-Serori, Halh; Ferk, Franziska; Kundi, Michael; Bileck, Andrea; Gerner, Christopher; Mišík, Miroslav; Nersesyan, Armen; Waldherr, Monika; Murbach, Manuel; Lah, Tamara T; Herold-Mende, Christel; Collins, Andrew R; Knasmüller, Siegfried

    2018-01-01

    Some epidemiological studies indicate that the use of mobile phones causes cancer in humans (in particular glioblastomas). It is known that DNA damage plays a key role in malignant transformation; therefore, we investigated the impact of the UMTS signal which is widely used in mobile telecommunications, on DNA stability in ten different human cell lines (six brain derived cell lines, lymphocytes, fibroblasts, liver and buccal tissue derived cells) under conditions relevant for users (SAR 0.25 to 1.00 W/kg). We found no evidence for induction of damage in single cell gel electrophoresis assays when the cells were cultivated with serum. However, clear positive effects were seen in a p53 proficient glioblastoma line (U87) when the cells were grown under serum free conditions, while no effects were found in p53 deficient glioblastoma cells (U251). Further experiments showed that the damage disappears rapidly in U87 and that exposure induced nucleotide excision repair (NER) and does not cause double strand breaks (DSBs). The observation of NER induction is supported by results of a proteome analysis indicating that several proteins involved in NER are up-regulated after exposure to UMTS; additionally, we found limited evidence for the activation of the γ-interferon pathway. The present findings show that the signal causes transient genetic instability in glioma derived cells and activates cellular defense systems.

  13. Radiation therapy induces circulating serum Hsp72 in patients with prostate cancer

    International Nuclear Information System (INIS)

    Hurwitz, Mark D.; Kaur, Punit; Nagaraja, Ganachari M.; Bausero, Maria A.; Manola, Judith; Asea, Alexzander

    2010-01-01

    Background and purpose: Hsp72 found in the extracellular milieu has been shown to play an important role in immune regulation. The impact of common cancer therapies on extracellular release of Hsp72 however, has been to date undefined. Materials and methods: Serum from 13 patients undergoing radiation therapy (XRT) for prostate cancer with or without hormonal therapy (ADT) was measured for levels of circulating serum Hsp72 and pro-inflammatory cytokines (IL-6 and TNF-α) using the classical sandwich ELISA technique and the relative expression of CD8 + T lymphocytes and natural killer (NK) cells was measured using flow cytometry. Mouse orthotopic xenograft of human prostate cancer tumors (DU-145 and PC-3) were used to validate and further characterize the response noted in the clinical setting. The biological significance of tumor released Hsp72 was studied in human dendritic cells (DC) in vitro. Results: Circulating serum Hsp72 levels increased an average of 3.5-fold (median per patient 4.8-fold) with XRT but not with ADT (p = 0.0002). Increases in IL-6 (3.3-fold), TNF-α (1.8-fold), CD8 + CTL (2.1-fold) and NK cells (3.2-fold) also occurred. Using PC-3 and DU-145 human prostate cancer xenograft models in mice, we confirmed that XRT induces Hsp72 release primarily from implanted tumors. In vitro studies using supernatant recovered from irradiated human prostate cancer cells point to exosomes containing Hsp72 as a possible stimulator of pro-inflammatory cytokine production and costimulatory molecules expression in human DC. Conclusions: The current study confirms for the first time in an actual clinical setting elevation of circulating serum Hsp72 with XRT. The accompanying studies in mice and in vitro identify the released exosomes containing Hsp72 as playing a pivotal role in stimulating pro-inflammatory immune responses. These findings, if validated, may lead to new treatment paradigms for common human malignancies.

  14. Limited hair cell induction from human induced pluripotent stem cells using a simple stepwise method.

    Science.gov (United States)

    Ohnishi, Hiroe; Skerleva, Desislava; Kitajiri, Shin-ichiro; Sakamoto, Tatsunori; Yamamoto, Norio; Ito, Juichi; Nakagawa, Takayuki

    2015-07-10

    Disease-specific induced pluripotent stem cells (iPS) cells are expected to contribute to exploring useful tools for studying the pathophysiology of inner ear diseases and to drug discovery for treating inner ear diseases. For this purpose, stable induction methods for the differentiation of human iPS cells into inner ear hair cells are required. In the present study, we examined the efficacy of a simple induction method for inducing the differentiation of human iPS cells into hair cells. The induction of inner ear hair cell-like cells was performed using a stepwise method mimicking inner ear development. Human iPS cells were sequentially transformed into the preplacodal ectoderm, otic placode, and hair cell-like cells. As a first step, preplacodal ectoderm induction, human iPS cells were seeded on a Matrigel-coated plate and cultured in a serum free N2/B27 medium for 8 days according to a previous study that demonstrated spontaneous differentiation of human ES cells into the preplacodal ectoderm. As the second step, the cells after preplacodal ectoderm induction were treated with basic fibroblast growth factor (bFGF) for induction of differentiation into otic-placode-like cells for 15 days. As the final step, cultured cells were incubated in a serum free medium containing Matrigel for 48 days. After preplacodal ectoderm induction, over 90% of cultured cells expressed the genes that express in preplacodal ectoderm. By culture with bFGF, otic placode marker-positive cells were obtained, although their number was limited. Further 48-day culture in serum free media resulted in the induction of hair cell-like cells, which expressed a hair cell marker and had stereocilia bundle-like constructions on their apical surface. Our results indicate that hair cell-like cells are induced from human iPS cells using a simple stepwise method with only bFGF, without the use of xenogeneic cells. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Trimetazidine Protects Umbilical Cord Mesenchymal Stem Cells Against Hypoxia and Serum Deprivation Induced Apoptosis by Activation of Akt

    Directory of Open Access Journals (Sweden)

    Xuhe Gong

    2014-12-01

    Full Text Available Background: Mesenchymal stem cell (MSC transplantation is a promising therapy for cardiac repair. However, the efficacy is limited by the poor viability of MSCs in the infarcted heart. Recent findings have implicated that trimetazidine (TMZ enhanced the survival of the stem cells under various conditions. However, as the stem cells in these studies were animal-derived, little information is available about the effects of TMZ on human MSCs. Herein, we propose that TMZ may protect human MSCs against apoptosis induced by Hypoxia/Serum deprivation (H/SD. Methods: Human umbilical cord MSCs (UC-MSCs from Wharton's jelly were pretreated with 10µM TMZ of H/SD with or without the Akt inhibitor LY294002. The morphological changes were assessed using Hoechst 33342. Apoptosis was evaluated via Annexin V/PI staining; and apoptosis-related proteins were detected using Western-blot. Protein chip technology was used to screen for differences between the cell supernatants. Results: TMZ had a significant protective effect against H/SD-induced apoptosis, accompanied by an increase in Bcl-2 and p-Akt. The TMZ-mediated anti-apoptotic effect on MSCs could be attenuated by treatment with LY294002. Moreover, protein chip assays showed that TMZ treatment increased the paracrine functions of MSCs. Conclusion: Trimetazidine protects human UC-MSCs from H/SD-induced apoptosis via the Akt pathway and may therefore be a potentially useful therapeutic adjunct for transplanting MSCs into damaged heart after myocardial infarction.

  16. Selected serum oxidative stress biomarkers in dogs with non-food-induced and food-induced atopic dermatitis.

    Science.gov (United States)

    Almela, Ramón M; Rubio, Camila P; Cerón, José J; Ansón, Agustina; Tichy, Alexander; Mayer, Ursula

    2018-06-01

    Oxidative stress (OS) has been shown to be involved in the pathogenesis of human and canine atopic dermatitis (AD) through several distinct mechanisms. Selected serum biomarkers of OS (sbOS) have been validated in normal dogs and studied in several canine diseases. To the best of the authors' knowledge, the sbOS evaluated in this study have not previously been described in canine AD. The aims of the study were to evaluate a panel of sbOS in dogs with food-induced (FIAD) and non-food-induced (NFIAD) AD: cupric reducing antioxidant capacity (CUPRAC), ferrous oxidation-xylenol orange (FOX), ferric reducing ability of the plasma (FRAP), paraoxonase-1 (PON1), trolox equivalent antioxidant capacity (TEAC) and serum total thiol (THIOL). The aim was to compare these metabolites with those in healthy control dogs, and to correlate sbOS with validated pruritus and CADESI-04 severity scales in dogs with AD. Forty six healthy, nine NFIAD and three FIAD client-owned dogs were included. The study was designed as a cohort study. There were significant differences in atopic dogs when compared to healthy dogs for all of the sbOS analysed. These findings suggest that OS could play a role in the pathogenesis of canine NFIAD and FIAD. In addition, the evaluation of sbOS could be useful for precision medicine to help to detect atopic dogs that might benefit from antioxidant-targeted therapies. © 2018 ESVD and ACVD.

  17. Pregnancy-induced rise in serum C-peptide concentrations in women with type 1 diabetes

    DEFF Research Database (Denmark)

    Nielsen, Lene Ringholm; Rehfeld, Jens F; Pedersen-Bjergaard, Ulrik

    2009-01-01

    OBJECTIVE: The purpose of this study was to investigate whether pregnancy induces increased insulin production as a marker of improved beta-cell function in women with long-term type 1 diabetes. RESEARCH DESIGN AND METHODS: This was a prospective study of 90 consecutive pregnant women with type 1.......85). Multivariate regression analysis revealed a positive association between the absolute increase in C-peptide concentrations during pregnancy and decreased A1C from 8 to 33 weeks (P = 0.003). CONCLUSIONS: A pregnancy-induced increase in C-peptide concentrations in women with long-term type 1 diabetes...... in 35 women. RESULTS: C-peptide concentrations gradually increased throughout pregnancy regardless of serum glucose concentrations in the 90 women with a median duration of diabetes of 17 years (range 1-36 years). Among 35 women with paired recordings of stimulated C-peptide, C-peptide production...

  18. Knockout Serum Replacement Promotes Cell Survival by Preventing BIM from Inducing Mitochondrial Cytochrome C Release.

    Directory of Open Access Journals (Sweden)

    Yuki Ishii

    Full Text Available Knockout serum replacement (KOSR is a nutrient supplement commonly used to replace serum for culturing stem cells. We show here that KOSR has pro-survival activity in chronic myelogenous leukemia (CML cells transformed by the BCR-ABL oncogene. Inhibitors of BCR-ABL tyrosine kinase kill CML cells by stimulating pro-apoptotic BIM and inhibiting anti-apoptotic BCL2, BCLxL and MCL1. We found that KOSR protects CML cells from killing by BCR-ABL inhibitors--imatinib, dasatinib and nilotinib. The protective effect of KOSR is reversible and not due to the selective outgrowth of drug-resistant clones. In KOSR-protected CML cells, imatinib still inhibited the BCR-ABL tyrosine kinase, reduced the phosphorylation of STAT, ERK and AKT, down-regulated BCL2, BCLxL, MCL1 and up-regulated BIM. However, these pro-apoptotic alterations failed to cause cytochrome c release from the mitochondria. With mitochondria isolated from KOSR-cultured CML cells, we showed that addition of recombinant BIM protein also failed to cause cytochrome c release. Besides the kinase inhibitors, KOSR could protect cells from menadione, an inducer of oxidative stress, but it did not protect cells from DNA damaging agents. Switching from serum to KOSR caused a transient increase in reactive oxygen species and AKT phosphorylation in CML cells that were protected by KOSR but not in those that were not protected by this nutrient supplement. Treatment of KOSR-cultured cells with the PH-domain inhibitor MK2206 blocked AKT phosphorylation, abrogated the formation of BIM-resistant mitochondria and stimulated cell death. These results show that KOSR has cell-context dependent pro-survival activity that is linked to AKT activation and the inhibition of BIM-induced cytochrome c release from the mitochondria.

  19. Inhaled ozone (O3)-induces changes in serum metabolomic and liver transcriptomic profiles in rats☆

    Science.gov (United States)

    Miller, Desinia B.; Karoly, Edward D.; Jones, Jan C.; Ward, William O.; Vallanat, Beena D.; Andrews, Debora L.; Schladweiler, Mette C.; Snow, Samantha J.; Bass, Virginia L.; Richards, Judy E.; Ghio, Andrew J.; Cascio, Wayne E.; Ledbetter, Allen D.; Kodavanti, Urmila P.

    2016-01-01

    Air pollution has been linked to increased incidence of diabetes. Recently, we showed that ozone (O3) induces glucose intolerance, and increases serum leptin and epinephrine in Brown Norway rats. In this study, we hypothesized that O3 exposure will cause systemic changes in metabolic homeostasis and that serum metabolomic and liver transcriptomic profiling will provide mechanistic insights. In the first experiment, male Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or O3 at 0.25, 0.50, or 1.0 ppm, 6 h/day for two days to establish concentration-related effects on glucose tolerance and lung injury. In a second experiment, rats were exposed to FA or 1.0 ppm O3, 6 h/day for either one or two consecutive days, and systemic metabolic responses were determined immediately after or 18 h post-exposure. O3 increased serum glucose and leptin on day 1. Glucose intolerance persisted through two days of exposure but reversed 18 h-post second exposure. O3 increased circulating metabolites of glycolysis, long-chain free fatty acids, branched-chain amino acids and cholesterol, while 1,5-anhydroglucitol, bile acids and metabolites of TCA cycle were decreased, indicating impaired glycemic control, proteolysis and lipolysis. Liver gene expression increased for markers of glycolysis, TCA cycle and gluconeogenesis, and decreased for markers of steroid and fat biosynthesis. Genes involved in apoptosis and mitochondrial function were also impacted by O3. In conclusion, short-term O3 exposure induces global metabolic derangement involving glucose, lipid, and amino acid metabolism, typical of a stress–response. It remains to be examined if these alterations contribute to insulin resistance upon chronic exposure. PMID:25838073

  20. Serum phosphate is an early predictor of outcome in severe acetaminophen-induced hepatotoxicity

    DEFF Research Database (Denmark)

    Schmidt, Lars E; Dalhoff, Kim

    2002-01-01

    Hypophosphatemia is frequently observed in acetaminophen-induced hepatotoxicity and may be involved in the pathogenesis of hepatic failure. The aim of the study was to evaluate the prognostic value of serial measurements of serum phosphate in patients with severe acetaminophen poisoning. Prospect......Hypophosphatemia is frequently observed in acetaminophen-induced hepatotoxicity and may be involved in the pathogenesis of hepatic failure. The aim of the study was to evaluate the prognostic value of serial measurements of serum phosphate in patients with severe acetaminophen poisoning...... Hospital (KCH) criteria. Phosphate concentrations were significantly higher in nonsurvivors than in survivors at 48 to 72 hours after overdose (mean 2.65 +/- 1.18 mmol/L vs. 0.68 +/- 0.22 mmol/L, P L vs. 0.59 +/- 0.23 mmol/L, P ...). A threshold phosphate concentration of 1.2 mmol/L at 48 to 96 hours after overdose had sensitivity 89%, specificity 100%, accuracy 98%, positive predictive value 100%, and negative predictive value 98%. The phosphate criteria had higher sensitivity, accuracy, and positive and negative predictive values than...

  1. Serum Proteases Potentiate BMP-Induced Cell Cycle Re-entry of Dedifferentiating Muscle Cells during Newt Limb Regeneration

    NARCIS (Netherlands)

    Wagner, Ines; Wang, Heng; Weissert, Philipp M.; Straube, Werner L.; Shevchenko, Anna; Gentzel, Marc; Brito, Goncalo; Tazaki, Akira; Oliveira, Catarina; Sugiura, Takuji; Shevchenko, Andrej; Simon, Andras; Drechsel, David N.; Tanaka, Elly M.

    2017-01-01

    Limb amputation in the newt induces myofibers to dedifferentiate and re-enter the cell cycle to generate proliferative myogenic precursors in the regeneration blastema. Here we show that bone morphogenetic proteins (BMPs) and mature BMPs that have been further cleaved by serum proteases induce cell

  2. Limitations to CO2-induced growth enhancement in pot studies.

    Science.gov (United States)

    McConnaughay, K D M; Berntson, G M; Bazzaz, F A

    1993-07-01

    Recently, it has been suggested that small pots may reduce or eliminate plant responses to enriched CO 2 atmospheres due to root restriction. While smaller pot volumes provide less physical space available for root growth, they also provide less nutrients. Reduced nutrient availability alone may reduce growth enhancement under elevated CO 2 . To investigate the relative importance of limited physical rooting space separate from and in conjunction with soil nutrients, we grew plants at ambient and double-ambient CO 2 levels in growth containers of varied volume, shape, nutrient concentration, and total nutrient content. Two species (Abutilon theophrasti, a C 3 dicot with a deep tap root andSetaria faberii, a C 4 monocot with a shallow diffuse root system) were selected for their contrasting physiology and root architecture. Shoot demography was determined weekly and biomass was determined after eight and ten weeks of growth. Increasing total nutrients, either by increasing nutrient concentration or by increasing pot size, increased plant growth. Further, increasing pot size while maintaining equal total nutrients per pot resulted in increased total biomass for both species. CO 2 -induced growth and reproductive yield enhancements were greatest in pots with high nutrient concentrations, regardless of total nutrient content or pot size, and were also mediated by the shape of the pot. CO 2 -induced growth and reproductive yield enhancements were unaffected by pot size (growth) or were greater in small pots (reproductive yield), regardless of total nutrient content, contrary to predictions based on earlier studies. These results suggest that several aspects of growth conditions within pots may influence the CO 2 responses of plants; pot size, pot shape, the concentration and total amount of nutrient additions to pots may lead to over-or underestimates of the CO 2 responses of real-world plants.

  3. Retinal Damage Induced by Internal Limiting Membrane Removal

    Directory of Open Access Journals (Sweden)

    Rachel Gelman

    2015-01-01

    Full Text Available The internal limiting membrane (ILM, the basement membrane of the Müller cells, serves as the interface between the vitreous body and the retinal nerve fiber layer. It has a fundamental role in the development, structure, and function of the retina, although it also is a pathologic component in the various vitreoretinal disorders, most notably in macular holes. It was not until understanding of the evolution of idiopathic macular holes and the advent of idiopathic macular hole surgery that the idea of adjuvant ILM peeling in the treatment of tractional maculopathies was explored. Today intentional ILM peeling is a commonly applied surgical technique among vitreoretinal surgeons as it has been found to increase the rate of successful macular hole closure and improve surgical outcomes in other vitreoretinal diseases. Though ILM peeling has refined surgery for tractional maculopathies, like all surgical procedures it is not immune to perioperative risk. The essential role of the ILM to the integrity of the retina and risk of trauma to retinal tissue spurs suspicion with regard to its routine removal. Several authors have investigated the retinal damage induced by ILM peeling and these complications have been manifested across many different diagnostic studies.

  4. Limits for Beam Induced Damage: Reckless or too Cautious?

    CERN Document Server

    Bertarelli, A; Carra, F; Cerutti, F; Dallocchio, A; Mariani, N; Peroni, L; Scapin, M

    2011-01-01

    Accidental events implying direct beam impacts on collimators are of the utmost importance as they may lead to serious limitations of the overall LHC Performance. In order to assess damage threshold of components impacted by high energy density beams, entailing changes of phase and extreme pressures, state-of-the-art numerical simulation methods are required. In this paper, a review of the different dynamic response regimes induced by particle beams is given along with an indication of the most suited tools to treat each regime. Particular attention is paid to the most critical case, that of shock waves, for which standard Finite Element codes are totally unfit. A novel category of numerical tools, named Hydrocodes, has been adapted and used to analyse the consequences of an asynchronous beam abort on Phase 1 Tertiary Collimators (TCT). A number of simulations has been carried out with varying beam energy, number of bunches and bunch sizes allowing to identify different damage levels for the TCT up to catastr...

  5. Serum glycine is associated with regional body fat and insulin resistance in functionally-limited older adults.

    Directory of Open Access Journals (Sweden)

    Michael S Lustgarten

    Full Text Available Metabolic profiling may provide insight into biologic mechanisms related to age-related increases in regional adiposity and insulin resistance.The objectives of the current study were to characterize the association between mid-thigh intermuscular and subcutaneous adipose tissue (IMAT, SCAT, respectively and, abdominal adiposity with the serum metabolite profile, to identify significant metabolites as further associated with the homeostasis model assessment of insulin resistance (HOMA-IR, and, to develop a HOMA-IR associated metabolite predictor set representative of regional adiposity, in 73 functionally-limited (short physical performance battery ≤10; SPPB older adults (age range, 70-85 y.Fasting levels of 181 total metabolites, including amino acids, fatty acids and acylcarnitines were measured with use of an untargeted mass spectrometry-based metabolomic approach. Multivariable-adjusted linear regression was used in all analyses.Thirty-two, seven and one metabolite(s were found to be associated with IMAT, abdominal adiposity and, SCAT, respectively, including the amino acid glycine, which was positively associated with SCAT and, negatively associated with both IMAT and abdominal adiposity. Glycine and four metabolites found to be significantly associated with regional adiposity were additionally associated with HOMA-IR. Separate stepwise regression models identified glycine as a HOMA-IR associated marker of both IMAT (model R(2 = 0.51, p<0.0001 and abdominal adiposity (model R(2 = 0.41, p<0.0001.Our findings for a positive association between glycine with SCAT but, a negative association between glycine with IMAT and abdominal adiposity supports the hypothesis that SCAT metabolic processes are different from that found in other fat depots. In addition, because of the significant associations found between glycine with HOMA-IR, IMAT, SCAT and abdominal adiposity, our results suggest glycine as a serum biomarker of both insulin sensitivity

  6. Glucose-induced serum- and glucocorticoid-regulated kinase activation in oncofetal fibronectin expression

    International Nuclear Information System (INIS)

    Khan, Zia A.; Barbin, Yousef P.; Farhangkhoee, Hana; Beier, Norbert; Scholz, Wolfgang; Chakrabarti, Subrata

    2005-01-01

    Preferential expression of oncofetal extra domain-B fibronectin (EDB + FN), a proposed angiogenic marker, has been shown in proliferative diabetic retinopathy. High levels of glucose also increase EDB + FN expression in endothelial cells (ECs) via transforming growth factor-β1 (TGF-β1) and endothelin-1 (ET-1). The present study was aimed at elucidating the role of serum- and glucocorticoid-regulated kinase (SGK-1) in glucose-induced EDB + FN expression. Using human macro- and microvascular ECs, we show that high levels of glucose, TGF-β1, and ET-1 increase the EDB + FN expression via SGK-1 alteration at the mRNA, protein, and activity levels. Inhibition of TGF-β1 and ET-1 prevented glucose-induced SGK-1 activation and the EDB + FN expression. Furthermore, using siRNA-mediated SGK-1 gene silencing, we show that glucose-induced EDB + FN expression can be completely prevented. These findings provide first evidence of glucose-induced SGK-1 activation in altered EDB + FN expression and provide novel avenues for therapeutic modalities

  7. Relation cellular- molecular between serum IL10 levels and hyperalgesia variation in adjuvant- induced arthritis

    Directory of Open Access Journals (Sweden)

    Zenab Akhtari

    2015-01-01

    Full Text Available Background: Regarding to the important anti-inflammatory role of IL10 during inflammation process and hyperalgesia and edema variation during CFA-induced arthritis and also the increase of Spinal mu opioid receptor (mOR expression, in this study researchers investigate the role of serum IL10 level on mOR expression and edema and hyperalgesia variation during different stages of Complete Freund`s Adjuvant (CFA - induced arthritis in male Wistar rats. Materials and Methods: Mono-arthritis was induced by CFA and inflammatory symptoms (hyperalgesia and edema were assessed on 0, 3, 7, 14th and 21st days of study. Anti-IL10 was administered during the 21 days of study in different experimental groups. mOR expression were detected by western blotting on 0, 3,7, 14th and 21st days of study. Data was analyzed by SPSS statistical software version 19 with using one way ANOVA (post hoc Tokey's. Results: Our results showed that anti-IL10 administration in AA group (Adjuvant Arthritis caused an increase in the paw volume and hyperalgesia until 21st of study. Our study stated that there were no significant differences in spinal mOR expression between AA and AA+anti-IL10rats. Conclusion: Our study confirmed that anti-IL10administration caused to hyperalgesia and edema during AA inflammation. Also these findings suggested that mOR expression increased in chronic phase of AA inflammation, however an increase in the level of spinal mu opioid receptor (mOR expression during AA inflammation is not mediated directly via the effect of serum IL-10.

  8. Comparison of biomarkers in serum and induced sputum of patients with occupational asthma and chronic obstructive pulmonary disease.

    Science.gov (United States)

    Kleniewska, Aneta; Walusiak-Skorupa, Jolanta; Piotrowski, Wojciech; Nowakowska-Świrta, Ewa; Wiszniewska, Marta

    2016-07-22

    Occupational asthma and chronic obstructive pulmonary disease (COPD) are associated with the airway inflammatory process. The aim of this study was to compare the sputum and serum markers of inflammation in patients with occupational asthma and COPD. The study group included 20 patients with stable COPD, 24 patients with asthma, and 22 healthy subjects. Interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, matrix metalloproteinase (MMP)-9 levels in serum and induced sputum as well as fibrinogen and CRP in serum were determined in all the subjects. Higher concentrations of IL-1β, IL-6, TNF-α, and MMP-9 in induced sputum and an increased concentration of acute-phase proteins in serum were observed in COPD patients compared with healthy subjects. Higher concentrations of IL-1β and MMP-9 in induced sputum and a higher concentration of C-reactive protein (CRP) were detected in COPD patients than in asthmatic subjects. Never smokers with COPD had significantly higher levels of IL-1β and MMP-9 in induced sputum than never smoker controls. There was no significant difference between the serum and sputum levels of cytokines and MMP-9 of never smokers and smokers with COPD. Higher concentrations of IL-1β and MMP-9 in induced sputum and a higher concentration of CRP in serum allow distinguishing between biomarker profiles of COPD patients and asthmatic patients. Occupational exposure induces a systemic proinflammatory state with increased levels of acute-phase proteins in stable COPD patients. MMP-9 and IL-1β concentrations are increased in induced sputum of never smokers with COPD, which is associated with occupational exposure.

  9. Dynamically observing the value of the changes of serum sex hormone levels of early pregnancy after drug-induced abortion

    International Nuclear Information System (INIS)

    Zhao Honggang; Dong Hua; Gu Yan; Zhang Zuncheng

    2009-01-01

    Objective: To observe the value of the changes of serum β-human chorionic gonadotropin (β-HCG), estradiol (E), progesterone (P) Levels of early pregnancy after drug-induced abortion dynamically. Methods: Assessing 55 women proved pregnant by urine or blood HCG retrospecticly, who had terminated their pregnancy by mifepristonr and misoprostol. Meanwhile the serum levels of β-HCG, E, P were monitored dynamically. Results: Among the 55 patients, the levels of β-HCG, E and P had significant decreased (t β-HCG =4.845, t E =7.655, t P =11.390, P E =9.089, P P =2.910, P<0.05). Conclusion: Detectint the serum hormone's levels after drug-induced abortion by chemiluminescent immunoassay, we can assess indirectly the value of administration of mifepristone and misoprostol, predict the prolonged vaginal bleeding after drug-induced abortion, and the outcome of the treatment, which determine wether need another curestage. (authors)

  10. 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)

  11. Radiation-induced Changes in the Electrophoretic Profile of Serum Albumin

    Directory of Open Access Journals (Sweden)

    Celso Vieira Lima

    2018-01-01

    Full Text Available ABSTRACT Albumin protein profiles were investigated in electrophoresis system in relation to the whole body exposition to the radiation. Two groups of rats Wistar were set up as the control (CG and the irradiated one (IG. The IG was exposed to Co-60 at a dose of 5 Gy. After a 72-hour exposition, 300 μL of blood was collected in the inferior vena cava, renal, jugular, hepatic, and pulmonary veins and the serum separated. The albumin protein was identified by vertical electrophoresis in acrylamide Commassi blue or silver stained. The calibration procedure was applied to albumin samples with well-known concentrations. The mathematical correlation was developed involving electrophoretic parameters of band intensities and sizes from gel representation, providing values of protein concentrations in comparison with standard bands with known concentrations. There were significant differences in the physiological concentrations in the jugular and pulmonary sites in relation to renal and cava regional sites. Significant differences induced by radiation in serum albumin concentration were also found in hepatic and jugular sites. Alteration of albumin concentration was found as a nearly effect from whole body irradiation. This phenomenon points out to alterations in cell metabolism in the liver justified by a possible indication of proteomics damage from radiation.

  12. Serum Metabonomics of Articular Cartilage Destruction Induced by T-2 Toxin in Wistar Rats.

    Science.gov (United States)

    Zhu, Lei; Zhao, Zhi Jun; Ren, Xiao Bin; Li, Qiang; Ding, Hua; Sun, Zhou; Kao, Qing Jun; Wang, Li Hua

    2018-01-01

    The molecular pathogenesis of T-2 toxin-induced cartilage destruction has not been fully unraveled yet. The aim of this study was to detect changes in serum metabolites in a rat anomaly model with articular cartilage destruction. Thirty healthy male Wistar rats were fed a diet containing T-2 toxin (300 ng/kg chow) for 3 months. Histopathological changes in femorotibial cartilage were characterized in terms of chondrocyte degeneration/necrosis and superficial cartilage defect, and the endogenous metabolite profile of serum was determined by UPLC/Q-TOF MS. Treated rats showed extensive areas of chondrocyte necrosis and superficial cartilage defect in the articular cartilage. In addition, 8 metabolites were found to change significantly in these rats compared to the control group, including lysoPE (18:0/0:0), lysoPC(14:0), lysoPC[18:4 (6Z,9Z,12Z,15Z)], lysoPC[(16:1(9Z)], lysoPC(16:0), L-valine, hippuric acid, and asparaginyl-glycine. These 8 metabolites associated with cartilage injury are mainly involved in phospholipid and amino acid metabolic pathways. Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  13. Ghrelin Alleviates MDMA-Induced Disturbance of Serum Glucose and Lipids Levels in the Rat

    Directory of Open Access Journals (Sweden)

    Ravieh Golchoobian

    2018-01-01

    Full Text Available Hepatotoxicity is one of the clinically adverse effects of ecstasy (3, 4-methylenedioxymethamphetamine; MDMA consumption. The detoxification tissue, liver, plays a central role in maintaining circulating levels of glucose and lipid. Hypoglycemia and hypotriglyceridemia have been reported due to ecstasy abuse. Ghrelin is a 28-amino-acid peptide secreted predominantly from the stomach. It has been demonstrated that ghrelin has hepatoprotective effects and is able to increase blood glucose concentration. In the current study, we explored the effect of hepatotoxic dose of MDMA and therapeutic use of exogenous ghrelin on the serum levels of glucose and lipids in four groups of rats. MDMA caused a severe and transient reduction in circulating levels of glucose and triglyceride and increased serum LDL. However, cholesterol and HDL levels remained unchanged. Meanwhile, altered hepatic architecture was observed with intracellular vacuolation that may indicate intracellular accumulation of lipid droplets. In addition, following ghrelin administration, the blood sugar levels improved and LDL levels returned to the baseline value, and ghrelin treatment did not improve triglycerides levels. These results showed that MDMA causes hypoglycemia, hypotriglyceridemia, and hyper LDL-cholesterolemia. To our knowledge, this is the first report showing ghrelin administration could improve hypoglycemia and normalize LDL levels induced by MDMA and partially restore hepatic architecture.

  14. Immunotherapy of murine leukemia. Efficacy of passive serum therapy of Friend leukemia virus-induced disease in immunocompromised mice

    International Nuclear Information System (INIS)

    Genovesi, E.V.; Livnat, D.; Collins, J.J.

    1983-01-01

    Previous studies have demonstrated that the passive therapy of Friend murine leukemia virus (F-MuLV)-induced disease with chimpanzee anti-F-MuLV serum is accompanied by the development of host antiviral humoral and cellular immunity, the latter measurable in adoptive transfer protocols and by the ability of serum-protected mice to resist virus rechallenge. The present study was designed to further examine the contribution of various compartments of the host immune system to serum therapy itself, as well as to the acquired antiviral immunity that develops in serum-protected mice, through the use of naturally immunocompromised animals [e.g., nude athymic mice and natural killer (NK)-deficient beige mutant mice] or mice treated with immunoabrogating agents such as sublethal irradiation, cyclophosphamide [Cytoxan (Cy)], cortisone, and 89 Sr. The studies in nude mice indicate that while mature T-cells are not needed for effective serum therapy, they do appear to be necessary for the long-term resistance of serum-protected mice to virus rechallenge and for the generation of the cell population(s) responsible for adoptive transfer of antiviral immunity. Furthermore, this acquired resistance is not due to virus neutralization by serum antibodies since antibody-negative, Cy-treated, serum-protected mice still reject the secondary virus infection. Lastly, while the immunocompromise systems examined did effect various host antiviral immune responses, none of them, including the NK-deficient beige mutation, significantly diminished the efficacy of the passive serum therapy of F-MuLV-induced disease

  15. Dietary Compound Kaempferol Inhibits Airway Thickening Induced by Allergic Reaction in a Bovine Serum Albumin-Induced Model of Asthma.

    Science.gov (United States)

    Shin, Daekeun; Park, Sin-Hye; Choi, Yean-Jung; Kim, Yun-Ho; Antika, Lucia Dwi; Habibah, Nurina Umy; Kang, Min-Kyung; Kang, Young-Hee

    2015-12-16

    Asthma is characterized by aberrant airways including epithelial thickening, goblet cell hyperplasia, and smooth muscle hypertrophy within the airway wall. The current study examined whether kaempferol inhibited mast cell degranulation and prostaglandin (PG) release leading to the development of aberrant airways, using an in vitro model of dinitrophenylated bovine serum albumin (DNP-BSA)-sensitized rat basophilic leukemia (RBL-2H3) mast cells and an in vivo model of BSA-challenged asthmatic mice. Nontoxic kaempferol at 10-20 μM suppressed β-hexosaminidase release and cyclooxygenase 2 (COX2)-mediated production of prostaglandin D2 (PGD2) and prostaglandin F2α (PGF2α) in sensitized mast cells. Oral administration of ≤20 mg/kg kaempferol blocked bovine serum albumin (BSA) inhalation-induced epithelial cell excrescence and smooth muscle hypertrophy by attenuating the induction of COX2 and the formation of PGD2 and PGF2α, together with reducing the anti-α-smooth muscle actin (α-SMA) expression in mouse airways. Kaempferol deterred the antigen-induced mast cell activation of cytosolic phospholipase A2 (cPLA2) responsive to protein kinase Cμ (PKCμ) and extracellular signal-regulated kinase (ERK). Furthermore, the antigen-challenged activation of Syk-phospholipase Cγ (PLCγ) pathway was dampened in kaempferol-supplemented mast cells. These results demonstrated that kaempferol inhibited airway wall thickening through disturbing Syk-PLCγ signaling and PKCμ-ERK-cPLA2-COX2 signaling in antigen-exposed mast cells. Thus, kaempferol may be a potent anti-allergic compound targeting allergic asthma typical of airway hyperplasia and hypertrophy.

  16. Study of deutero-isotopomer-induced inhibition of caffeine and phenobarbitone binding to human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Cherrah, Y.; Falconnet, J.B.; Desage, M.; Brazier, J.L.; Zini, R.; Tillement, J.P.

    1988-01-01

    The present study of inhibition provides confirmation to previously observed deuterium isotope effects on in vitro caffeine and phenobarbitone binding to human serum albumin (HSA). Addition of either 3,7(C(/sup 2/H)/sub 3/)/sub 2/ or 1,3,7(C(/sup 2/H)/sub 3/)/sub 3/ caffeine induces a 50% loss in both the extent of binding and binding parameters of the unlabelled analog. As concerns caffeine displacement from its HSA sites, it is shown that phenobarbitone and its 5-pentadeuterophenyl analog are equally potent inhibitors of caffeine binding, though individual HSA binding profiles differ. As for HSA binding interactions between phenobarbitone isotopomers, a 50% decrease in unlabelled phenobarbitone extent of binding is observed in the presence of its 5-pentadeuterophenyl analog. Results favor the hypothesis of differing binding sites for each isotopomer.

  17. Proteomic biomarkers predicting lymph node involvement in serum of cervical cancer patients. Limitations of SELDI-TOF MS

    Directory of Open Access Journals (Sweden)

    Van Gorp Toon

    2012-06-01

    Full Text Available Abstract Background Lymph node status is not part of the staging system for cervical cancer, but provides important information for prognosis and treatment. We investigated whether lymph node status can be predicted with proteomic profiling. Material & methods Serum samples of 60 cervical cancer patients (FIGO I/II were obtained before primary treatment. Samples were run through a HPLC depletion column, eliminating the 14 most abundant proteins ubiquitously present in serum. Unbound fractions were concentrated with spin filters. Fractions were spotted onto CM10 and IMAC30 surfaces and analyzed with surface-enhanced laser desorption time of flight (SELDI-TOF mass spectrometry (MS. Unsupervised peak detection and peak clustering was performed using MASDA software. Leave-one-out (LOO validation for weighted Least Squares Support Vector Machines (LSSVM was used for prediction of lymph node involvement. Other outcomes were histological type, lymphvascular space involvement (LVSI and recurrent disease. Results LSSVM models were able to determine LN status with a LOO area under the receiver operating characteristics curve (AUC of 0.95, based on peaks with m/z values 2,698.9, 3,953.2, and 15,254.8. Furthermore, we were able to predict LVSI (AUC 0.81, to predict recurrence (AUC 0.92, and to differentiate between squamous carcinomas and adenocarcinomas (AUC 0.88, between squamous and adenosquamous carcinomas (AUC 0.85, and between adenocarcinomas and adenosquamous carcinomas (AUC 0.94. Conclusions Potential markers related with lymph node involvement were detected, and protein/peptide profiling support differentiation between various subtypes of cervical cancer. However, identification of the potential biomarkers was hampered by the technical limitations of SELDI-TOF MS.

  18. Comparative evaluation of hmopolesis and serum proteins from dogs with transmissible venereal tumor by natural ocorrence and induced by alogenic transplant

    International Nuclear Information System (INIS)

    Aptekmann, K.P.; Costa, M.T.; Fabeni, R. de C.; Santana, A.E.

    2005-01-01

    The objective of this study was to evaluate the haemopoiesis and total serum proteins of dogs with canine Transmissible Venereal Tumour (TVT) (naturally occurring or induced by allogenic transplant). Complete haemogram, bone marrow evaluation, total serum protein, albumin determination and electrophoretic fractionation of serum proteins were performed. Results revealed normocytic normochromic anaemia and thrombocytopenia in dogs with naturally occurring TVT

  19. Enzymatic-induced upconversion photoinduced electron transfer for sensing tyrosine in human serum.

    Science.gov (United States)

    Wu, Qiongqiong; Fang, Aijin; Li, Haitao; Zhang, Youyu; Yao, Shouzhuo

    2016-03-15

    This paper reports a novel nanosensor for tyrosine based on photoinduced electron-transfer (PET) between NaYF4:Yb, Tm upconversion nanoparticles (UCNPs) and melanin-like polymers. Melanin-like films were obtained from catalytic oxidation of tyrosine by tyrosinase, and deposited on the surface of UCNPs, and then quenched the fluorescence of UCNPs. Under the optimized conditions, the fluorescence quenching of UCNPs showed a good linear response to tyrosine concentration in the range of 0.8-100 μΜ with a detection limit of 1.1 μΜ. Meanwhile, it showed good sensitivity, stability and has been successfully applied to the detection of tyrosine in human serum. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Physical Performance and Serum 25(OH)vitamin D Status in Community Dwelling Old Mobility Limited Adults: A Cross-Sectional Study.

    Science.gov (United States)

    von Berens, Å; Cederholm, T; Fielding, R A; Gustafsson, T; Kirn, D; Laussen, J; Nydahl, M; Travison, T G; Reid, K; Koochek, A

    2018-01-01

    To examine the potential association between serum 25(OH) vitamin D and the performance on the Short Physical Performance Battery (SPPB) including the sub-components; five repeated chair stands test, 4 meters walk test and balance in older mobility-limited community-dwelling men and women. A cross sectional study was performed in American and Swedish subjects who were examined for potential participation in a combined exercise and nutrition intervention trial. Logistic regression analysis and linear regression analyses were performed to evaluate the association for 25(OH)D with the overall score on the SBBP, chair stand, gait speed and balance. Community-dwelling (mean age 77.6 ± 5.3 years) mobility limited American (n=494) and Swedish (n=116) females (59%) and males. The SPPB (0-12 points) includes chair stand (s), gait speed (m/s) and a balance test. Mobility limitation i.e., SPPB score ≤ 9 was an inclusion criterion. A blood sample was obtained to measure serum 25(OH)vitamin D concentrations. No clear association of 25(OH)D with SPPB scores was detected either when 25(OH)D was assessed as a continuous variable or when categorized according to serum concentrations of <50, 50-75 or <75 nmol/L. However, when analyzing the relationship between 25(OH)D and seconds to perform the chair stands, a significant quadratic relationship was observed. Thus, at serum levels of 25(OH)D above 74 nmol/L, higher concentrations appeared to be advantageous for the chair stand test, whereas for serum levels below 74 nmol/L this association was not observed. This cross- sectional study lacked clear association between serum 25(OH)D and physical performance in mobility limited adults. A potentially interesting observation was that at higher serum levels of 25(OH)D a better performance on the chair stand test was indicated.

  1. [Effects of intermittent hypoxic exposure on the parameter of erythrocyte and serum hypoxia inducible factor-1 alpha and erythropoietin levels].

    Science.gov (United States)

    Zhang, Cheng-yan; Zhang, Ji-xin; Lü, Xiao-tao; Li, Bao-yu

    2009-10-01

    To investigate the effects of intermittent hypoxic exposure and normoxic convalescence on the parameter of erythrocyte and serum hypoxia inducible factor-1 alpha (HIF-1alpha) and erythropoietin (EPO) levels. Rat models of intermittent hypoxic exposure were established, combined with the clinical research on volunteers experiencing the intermittent plateau work. Blood samples for red blood cell (RBC) counts, hemoglobin (Hb) and hematocrit (HCT) were collected, serum HIF-1alpha and EPO levels were measured using enzyme linked immunosorbent assay. RBC counts, Hb concentration and HCT were significantly higher than the normoxic group (P hypoxic exposure can enhance serum hypoxia inducible factor-1 alpha and erythropointin levels and the generation of red blood cells, which leads to an increase in hemoglobin concentration and hematocrit. The results have changed with the hypoxic exposure period prolonged. Normoxic convalescence after intermittent hypoxic exposure can make the related indexes reduced, and contribute to the organism recovery.

  2. Protective effect of Hibiscus sabdariffa against serum/glucose deprivation-induced PC12 cells injury

    Science.gov (United States)

    Bakhtiari, Elham; Hosseini, Azar; Mousavi, Seyed Hadi

    2015-01-01

    Objectives: Findings natural products with antioxidant and antiapoptotic properties has been one of the interesting challenges in the search for the treatment of neurodegenerative diseases including ischemic stroke. Serum/glucose deprivation (SGD) has been used as a model for the understanding of the molecular mechanisms of neuronal damage during ischemia in vitro and for the expansion of neuroprotective drugs against ischemia-induced brain injury. Recent studies showed that Hibiscus sabdariffa exert pharmacological actions such as potent antioxidant. Therefore, in this study we investigated the protective effect of extract of H. sabdariffa against SGD-induced PC12 cells injury. Materials and Methods: Cells were pretreated with different concentrations of H. sabdariffa extract (HSE) for 2 hr, and then exposed to SGD condition for 6, 12 and 18 hr. Results: SGD caused a major reduction in cell viability after 6, 12, and 18 hr as compared with control cells (psabdariffa has the potential to be used as a new therapeutic approach for neurodegenerative disorders. PMID:26101756

  3. Globular Adiponectin Inhibits the Apoptosis of Mesenchymal Stem Cells Induced by Hypoxia and Serum Deprivation via the AdipoR1-Mediated Pathway

    OpenAIRE

    Xia-Qiu Tian; Yue-Jin Yang; Qing Li; Pei-Sen Huang; Xiang-Dong Li; Chen Jin; Kang Qi; Lei-Pei Jiang; Gui-Hao Chen

    2016-01-01

    Background/Aims: Poor viability of transplanted mesenchymal stem cells (MSCs) within the ischemic heart limits their therapeutic potential for cardiac repair. Globular adiponectin (gAPN) exerts anti-apoptotic effects on several types of stem cells. Herein, we investigated the effect of gAPN on the MSCs against apoptosis induced by hypoxia and serum deprivation (H/SD). Methods: MSCs exposed to H/SD conditions were treated with different concentrations of gAPN. To identify the main type of rece...

  4. High Serum Pepsinogen I and beta Helicobacter pylori Infection Are Risk Factors for Aspirin-Induced Gastroduodenal Injury.

    Science.gov (United States)

    Shan, Jing; Lei, Hongjun; Shi, Wei; Sun, Xiaobin; Tang, Yu; Ren, Chunrong

    2018-01-01

    Whether gastric hyperchlorhydria and Helicobacter pylori infection contribute to aspirin-induced gastroduodenal injury still lacks evidence. Because serum pepsinogens (PGs) and gastrin-17 (G17) can reflect gastric acid secretion, this study intended to elucidate whether serum PGs, serum G17, and H. pylori infection are associated with aspirin-induced gastrointestinal injury. A total of 60 patients taking low-dose aspirin for more than 1 month were enrolled in this study. Serum PG I, PG II, and G17 were determined using ELISA. A 14C-urea breath test was used for the detection of an H. pylori infection. The modified Lanza score was used to evaluate the degree of gastroduodenal injury under endoscopy. The median serum PG I level was significantly higher in the intensive gastroduodenal injury (IGI) group compared to that in the mild gastroduodenal injury group (155.0 vs. 116.6 ng/mL, p = 0.006). The H. pylori infection rate was significantly higher in the IGI group (73 vs. 40%, p = 0.037). Receiver operator characteristic curves analysis revealed that the cutoff value of PG I was 123 ng/mL, with 80% sensitivity and 61.4% specificity. H. pylori infection combined with PG I at >123 ng/mL had an OR (95% CI) of 15.8 (2.4 ± 104.5) for the prediction of aspirin-induced gastroduodenal injury. Key Messages: Serum PG I and H. pylori infection could be used to identify potential high-risk aspirin-induced gastroduodenal injury patients. © 2017 S. Karger AG, Basel.

  5. Assessment of chronic spontaneous urticaria by serum-induced tumor necrosis factor alpha and matrix metalloproteinase-9 release

    DEFF Research Database (Denmark)

    Falkencrone, Sidsel; Bindslev-Jensen, Carsten; Skov, Per Stahl

    BACKGROUND Previous studies from our group have demonstrated that IgE-mediated basophil activation leads to release of TNFα that in turn can induce matrix metallo-proteinase-9 (MMP-9) release from monocytes. We wished to investigate if serum from chronic spontaneous urticaria-patients with auto-a...

  6. The Protective and Therapeutic Roles of Hexamethylenetetramine and N-Acetyl-Cysteine on Sulfur Mustard-Induced Oxidative Stress in Rat Serum

    Directory of Open Access Journals (Sweden)

    M Jafari

    2016-04-01

    Conclusion: The study findings revealed that SM induces oxidative stress in rat serum. HMT and NAC can ameliorate SM-induced oxidative stress by altering antioxidant defense system in serum. The protective effect of HMT against the toxicity of SM is higher than NAC.

  7. Relationship between serum hypoxia-inducible factor-1α and carotid plaque in patients with type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    E Weiqin; Shi Bimin

    2012-01-01

    Objective: To observe the changes of type 2 diabetes mellitus (T2DM) patients' serum hypoxia inducible factor-1α (HIF-1α), and evaluate the relationship between serum HIF-1α and vascular lesions of atherosclerosis. Methods: The serum level of HIF-1α in 32 T2DM with carotid plaques (T2DM+CP group), 24 T2DM without macrovascular complications (T2DM group), and 24 controls was studied with ELISA method. Results: The serum HIF-1α level in T2DM with and without carotid plaque group was significantly higher than that in the controls (all P<0.01). Furthermore, among T2DM, the level of HIF-1α was higher in patients with carotid plaque than that without carotid plaque (P<0.05) . The serum HIF-1α was positively correlated with fasting plasma glucose, HbAlc and HOMA-IR (all P<0.05). Multiple linear stepwise regression analysis showed that HbAlc was the independent determinants of HIF-1α. Conclusion: High level of serum HIF-1α in T2DM patients concerns with blood glucose and insulin resistance, which plays an important role in the development of macrovascular complications. (authors)

  8. Recovery from radiation induced changes in some protein end-products in the liver and blood serum of irradiated rats

    International Nuclear Information System (INIS)

    Elkashef, H.S.; Roushdy, H.M.; Saada, H.N.; Abdelsamie, M.A.

    1989-01-01

    When rats were subjected to whole body gamma-irradiation at the dose of 5.5 Gy it caused significant changes in the content of urea and creatine the serum at 7 and 14 days postirradiation. In the liver significant changes were observed in the content of urea, creatine and creatinine at all post-irradiation days except the third day for urea and seventh day for creatine. Ten days pre-irradiation of the rats a mixture of 5 mg testosterone propionate and 10 mg of vitamin E was intraperitoneally injected. The results indicated that this mixture could help in obtaining complete recovery for radiation induced changes in the content of urea in both liver and serum of irradiated protected rats. Also this mixture provided good protection and caused recovery from radiation induced changes in the liver creatine on the third and seventh days after irradiation. But for serum creatine, the recovery was observed only on the third post irradiation day. The applied radiation dose did not induce any significant changes in the level of serum creatinine, while a partial recovery was noticed for liver creatinine in irradiated protected rats. The recovery process seems to be related to the radiosensitivity of the animal tissue, with the chemical structure of the radioprotector substances and the estimated compounds as well as the post-irradiation time intervals.3 tab

  9. Nucleation speed limit on remote fluid induced earthquakes

    Science.gov (United States)

    Parsons, Thomas E.; Akinci, Aybige; Malignini, Luca

    2017-01-01

    Earthquakes triggered by other remote seismic events are explained as a response to long-traveling seismic waves that temporarily stress the crust. However, delays of hours or days after seismic waves pass through are reported by several studies, which are difficult to reconcile with the transient stresses imparted by seismic waves. We show that these delays are proportional to magnitude and that nucleation times are best fit to a fluid diffusion process if the governing rupture process involves unlocking a magnitude-dependent critical nucleation zone. It is well established that distant earthquakes can strongly affect the pressure and distribution of crustal pore fluids. Earth’s crust contains hydraulically isolated, pressurized compartments in which fluids are contained within low-permeability walls. We know that strong shaking induced by seismic waves from large earthquakes can change the permeability of rocks. Thus, the boundary of a pressurized compartment may see its permeability rise. Previously confined, overpressurized pore fluids may then diffuse away, infiltrate faults, decrease their strength, and induce earthquakes. Magnitude-dependent delays and critical nucleation zone conclusions can also be applied to human-induced earthquakes.

  10. Nucleation speed limit on remote fluid-induced earthquakes

    Science.gov (United States)

    Parsons, Tom; Malagnini, Luca; Akinci, Aybige

    2017-01-01

    Earthquakes triggered by other remote seismic events are explained as a response to long-traveling seismic waves that temporarily stress the crust. However, delays of hours or days after seismic waves pass through are reported by several studies, which are difficult to reconcile with the transient stresses imparted by seismic waves. We show that these delays are proportional to magnitude and that nucleation times are best fit to a fluid diffusion process if the governing rupture process involves unlocking a magnitude-dependent critical nucleation zone. It is well established that distant earthquakes can strongly affect the pressure and distribution of crustal pore fluids. Earth’s crust contains hydraulically isolated, pressurized compartments in which fluids are contained within low-permeability walls. We know that strong shaking induced by seismic waves from large earthquakes can change the permeability of rocks. Thus, the boundary of a pressurized compartment may see its permeability rise. Previously confined, overpressurized pore fluids may then diffuse away, infiltrate faults, decrease their strength, and induce earthquakes. Magnitude-dependent delays and critical nucleation zone conclusions can also be applied to human-induced earthquakes. PMID:28845448

  11. 1H NMR-based serum metabolomics reveals erythromycin-induced liver toxicity in albino Wistar rats

    Directory of Open Access Journals (Sweden)

    Atul Rawat

    2016-01-01

    Full Text Available Introduction: Erythromycin (ERY is known to induce hepatic toxicity which mimics other liver diseases. Thus, ERY is often used to produce experimental models of drug-induced liver-toxicity. The serum metabolic profiles can be used to evaluate the liver-toxicity and to further improve the understanding of underlying mechanism. Objective: To establish the serum metabolic patterns of Erythromycin induced hepatotoxicity in albino wistar rats using 1H NMR based serum metabolomics. Experimental: Fourteen male rats were randomly divided into two groups (n = 7 in each group: control and ERY treated. After 28 days of intervention, the metabolic profiles of sera obtained from ERY and control groups were analyzed using high-resolution 1D 1H CPMG and diffusion-edited nuclear magnetic resonance (NMR spectra. The histopathological and SEM examinations were employed to evaluate the liver toxicity in ERY treated group. Results: The serum metabolic profiles of control and ERY treated rats were compared using multivariate statistical analysis and the metabolic patterns specific to ERY-induced liver toxicity were established. The toxic response of ERY was characterized with: (a increased serum levels of Glucose, glutamine, dimethylamine, malonate, choline, phosphocholine and phospholipids and (b decreased levels of isoleucine, leucine, valine, alanine, glutamate, citrate, glycerol, lactate, threonine, circulating lipoproteins, N-acetyl glycoproteins, and poly-unsaturated lipids. These metabolic alterations were found to be associated with (a decreased TCA cycle activity and enhanced fatty acid oxidation, (b dysfunction of lipid and amino acid metabolism and (c oxidative stress. Conclusion and Recommendations: Erythromycin is often used to produce experimental models of liver toxicity; therefore, the established NMR-based metabolic patterns will form the basis for future studies aiming to evaluate the efficacy of anti-hepatotoxic agents or the hepatotoxicity of new

  12. Temperature dependent rapid annealing effect induces amorphous aggregation of human serum albumin.

    Science.gov (United States)

    Ishtikhar, Mohd; Ali, Mohd Sajid; Atta, Ayman M; Al-Lohedan, Hammad; Badr, Gamal; Khan, Rizwan Hasan

    2016-01-01

    This study represents an analysis of the thermal aggregation of human serum albumin (HSA) induced by novel rosin modified compounds. The aggregation process causes conformational alterations in the secondary and tertiary structures of the proteins. The conversion of globular protein to amorphous aggregates was carried out by spectroscopic, calorimetric and microscopic techniques to investigate the factors that are responsible for the structural, conformational and morphological alteration in the protein. Our outcome results show that the aggregation of HSA was dependent on the hydrophobicity, charge and temperature, because the formation of amorphous aggregates occurs in the presence of a novel cationic rosin compound, quaternary amine of rosin diethylaminoethyl ester (QRMAE), at 40°C and pH 7.4 (but at 25°C on similar pH value, there was no evidence of aggregate formation). In addition, the parent compound of QRMAE, i.e., abietic acid, and other derivatives such as nonionic rosin compounds [(RMPEG-750) and (RMA-MPEG-750)] do not shows the aggregating property. This work provides precise and necessary information that aid in the understanding the effects of rosin derivative compounds on HSA. This study also restrains important information for athletes, health providers, pharmaceutical companies, industries, and soft drink-processing companies. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Urea-induced binding between diclofenac sodium and bovine serum albumin: a spectroscopic insight.

    Science.gov (United States)

    Dohare, Neeraj; Khan, Abbul Bashar; Athar, Fareeda; Thakur, Sonu Chand; Patel, Rajan

    2016-06-01

    We investigated the interaction of diclofenac sodium (Dic.Na) with bovine serum albumin (BSA) in the absence and presence of urea using different spectroscopic techniques. A fluorescence quenching study revealed that the Stern-Volmer quenching constant decreases in the presence of urea, decreasing further at higher urea concentrations. The binding constant and number of binding sites were also evaluated for the BSA-Dic.Na interaction system in the absence and presence of urea using a modified Stern-Volmer equation. The binding constant is greater at high urea concentrations, as shown by the fluorescence results. In addition, for the BSA-Dic.Na interaction system, a static quenching mechanism was observed, which was further confirmed using time-resolved fluorescence spectroscopy. UV-vis spectroscopy provided information about the formation of a complex between BSA and Dic.Na. Circular dichroism was carried out to explain the conformational changes in BSA induced by Dic.Na in the absence and presence of urea. The presence of urea reduced the α-helical content of BSA as the Dic.Na concentration varied. The distance r between the donor (BSA) and acceptor (Dic.Na) was also obtained in the absence and presence of urea, using fluorescence resonance energy transfer. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  14. Heparin-induced increase in serum levels of aminotranferases. A controlled clinical trial.

    Science.gov (United States)

    Nielsen, H K; Husted, S E; Koopmann, H D; Fasting, H; Simonsen, O; Andersen, K; Husegaard, H C; Petersen, T K

    1984-01-01

    Sixty-four patients over the age of 40 years, undergoing elective surgery of at least one hour's duration, were randomized to treatment with either a thromboembolic deterrent ( TED ) stocking (Kendall Co.) or subcutaneous low-dose heparin 5 000 IU every 12 hours. Serum levels of alanine aminotransferase (S-ALAT), aspartate aminotransferase (S-ASAT), gamma-glutamyl transpeptidase (S-gamma-GT) and alkaline phosphatase (S-ALP) were measured. S-ALAT increased significantly on the 5th and 10th postoperative day, from 27 +/- 2 (x +/- SE) to 40 +/- 4 (p less than 0.01) and 55 +/- 7 U/l (p less than 0.001), respectively, in the heparin group and was significantly higher in the heparin than in the TED group both on the 5th (p less than 0.01) and 10th (p less than 0.05) postoperative day. S-ASAT and S-gamma-GT increased significantly during heparin treatment, but did not differ significantly from the values of the TED group. No change in S-ALP was registered in either group. It is concluded that prophylactic treatment with low-dose heparin induces a significant increase in S-aminotransferase levels, especially in S-ALAT. The phenomenon has profound differential diagnostic implications in conditions such as pulmonary embolism and acute myocardial infarction.

  15. Coexistence induced by pollen limitation in flowering-plant species.

    OpenAIRE

    Ishii, R; Higashi, M

    2001-01-01

    We report a novel mechanism for species coexistence that does not invoke a trade-off relationship in the case of outbreeding flowering plants. Competition for pollination services may lead to interspecific segregation of the timing of flowering among plants. This, in turn, sets limits on the pollination services, which restrain the population growth of a competitively superior species, thereby allowing an inferior species to sustain its population in the habitat. This explains the often-obser...

  16. Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

    Science.gov (United States)

    Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

    2015-01-01

    In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type.

  17. Effect of L-ascorbic acid on nickel-induced alterations in serum lipid profiles and liver histopathology in rats.

    Science.gov (United States)

    Das, Kusal K; Gupta, Amrita Das; Dhundasi, Salim A; Patil, Ashok M; Das, Swastika N; Ambekar, Jeevan G

    2006-01-01

    Nickel exposure greatly depletes intracellular ascorbate and alters ascorbate-cholesterol metabolism. We studied the effect of the simultaneous oral treatment with L-ascorbic acid (50 mg/100 g body weight (BW) and nickel sulfate (2.0 mg/100 g BW, i.p) on nickelinduced changes in serum lipid profiles and liver histopathology. Nickel-treated rats showed a significant increase in serum low-density lipoprotein-cholesterol, total cholesterol, triglycerides, and a significant decrease in serum high-density lipoprotein-cholesterol. In the liver, nickel sulfate caused a loss of normal architecture, fatty changes, extensive vacuolization in hepatocytes, eccentric nuclei, and Kupffer cell hypertrophy. Simultaneous administration of L-ascorbic acid with nickel sulfate improved both the lipid profile and liver impairments when compared with rats receiving nickel sulfate only. The results indicate that L-ascorbic acid is beneficial in preventing nickel-induced lipid alterations and hepatocellular damage.

  18. Evaluation of Trace Elements in Augmentation of Statin-Induced Cytotoxicity in Uremic Serum-Exposed Human Rhabdomyosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Hitoshi Uchiyama

    2018-01-01

    Full Text Available Patients with end-stage kidney disease (ESKD are at higher risk for rhabdomyolysis induced by statin than patients with normal kidney function. Previously, we showed that this increase in the severity of statin-induced rhabdomyolysis was partly due to uremic toxins. However, changes in the quantity of various trace elements in ESKD patients likely contribute as well. The purpose of this study is to determine the effect of trace elements on statin-induced toxicity in rhabdomyosarcoma cells exposed to uremic serum (US cells for a long time. Cell viability, apoptosis, mRNA expression, and intracellular trace elements were assessed by viability assays, flow cytometry, real-time RT-PCR, and ICP-MS, respectively. US cells exhibited greater simvastatin-induced cytotoxicity than cells long-time exposed with normal serum (NS cells (non-overlapping 95% confidence intervals. Intracellular levels of Mg, Mn, Cu, and Zn were significantly less in US cells compared to that in NS cells (p < 0.05 or 0.01. Pre-treatment with TPEN increased simvastatin-induced cytotoxicity and eliminated the distinction between both cells of simvastatin-induced cytotoxicity. These results suggest that Zn deficiencies may be involved in the increased risk for muscle complaints in ESKD patients. In conclusion, the increased severity of statin-induced rhabdomyolysis in ESKD patients may be partly due to trace elements deficiencies.

  19. The effect of weight loss on serum concentrations of nitric oxide induced by short - term exercise in obese women

    Directory of Open Access Journals (Sweden)

    M Olszanecka-Glinianowicz

    2009-07-01

    Full Text Available Objective: The aim of present study was to examine the effect of weight loss comprising regular moderate physical activity on resting serum concentrations of nitric oxide metabolites and exercise induced NO release. Materials and Methods: The study was carried out in 43 obese women without additional diseases (age 41.8±11.9y, body weight 94.5±15.1kg, BMI 36.5±4.6kg/m2. All obese patients participated in a 3-month weight reduction programme that consisted of 1 a group instruction in behavioural and dietary methods of weight control every two weeks; 2 1000-1400kcal/day balanced diet, and 3 moderate physical exercises (30 minutes, 3 times a week. Before and after treatment body mass and height were measured, body mass index (BMI was calculated. Body composition was determined by impedance analysis using a Bodystat analyser. The serum concentration of nitric oxide metabolites before and after exercise was measured using spectrophotometry method by Griess. The serum concentrations of lactate before and after exercise were measured with the use of strip test (ACCUSPORT analyzer. Serum concentration of insulin was measured with the use of RIA. Plasma glucose, cholesterol, HDL cholesterol and triglicerydes were determined by enzymatic procedure. Results: The mean weight loss during treatment was 8.3±4.3 kg. We did not observe differences between resting serum concentrations of NO and lactate before and after weight loss. During exercise serum NO concentrations increased significantly both before and after weight loss treatment. After the weight reduction treatment, the time of exercise test increased significantly P<0.005, but there were no significant differences between the value of NO before and after weight loss. Conclusion: 3 – month regular physical activity and weight loss did not influence exercise-induced nitric oxide production.

  20. INDUCED SCATTERING LIMITS ON FAST RADIO BURSTS FROM STELLAR CORONAE

    Energy Technology Data Exchange (ETDEWEB)

    Lyubarsky, Yuri [Physics Department, Ben-Gurion University, P.O.B. 653, Beer-Sheva 84105 (Israel); Ostrovska, Sofiya [Department of Mathematics, Atilim University, Incek 06836, Ankara (Turkey)

    2016-02-10

    The origin of fast radio bursts remains a puzzle. Suggestions have been made that they are produced within the Earth’s atmosphere, in stellar coronae, in other galaxies, or at cosmological distances. If they are extraterrestrial, the implied brightness temperature is very high, and therefore the induced scattering places constraints on possible models. In this paper, constraints are obtained on flares from coronae of nearby stars. It is shown that the radio pulses with the observed power could not be generated if the plasma density within and in the nearest vicinity of the source is as high as is necessary to provide the observed dispersion measure. However, one cannot exclude the possibility that the pulses are generated within a bubble with a very low density and pass through the dense plasma only in the outer corona.

  1. Serum depletion induces changes in protein expression in the trophoblast-derived cell line HTR-8/SVneo.

    Science.gov (United States)

    Novoa-Herran, Susana; Umaña-Perez, Adriana; Canals, Francesc; Sanchez-Gomez, Myriam

    2016-01-01

    serum depletion induces specific changes in protein expression concordant with main cell metabolic adaptations and EMT, resembling the progression to a malignant phenotype.

  2. Serum IgE Induced Airway Smooth Muscle Cell Remodeling Is Independent of Allergens and Is Prevented by Omalizumab

    Science.gov (United States)

    Roth, Michael; Zhao, Feng; Zhong, Jun; Lardinois, Didier; Tamm, Michael

    2015-01-01

    Background Airway wall remodeling in allergic asthma is reduced after treatment with humanized anti-IgE-antibodies. We reported earlier that purified IgE, without the presence of allergens, is sufficient to induce airway wall remodeling due to airway smooth muscle cell (ASMC) activity deposing extracellular matrix. Objective We postulate that IgE contained in serum of allergic asthma patients, in the absence of allergens, stimulates ASMC remodeling activities and can be prevented by anti-IgE antibodies. Methods Isolated human ASMC were exposed to serum obtained from: (i) healthy controls, or patients with (ii) allergic asthma, (iii) non-allergic asthma, and (iv) atopic non-asthma patients. Proliferation and the deposition of collagens and fibronectin were determined after 3 and 5 days. Results Serum from patients with allergies significantly stimulated: (i) ASMC proliferation, (ii) deposition of collagen type-I (48 hours) and (iii) of fibronectin (24 hours). One hour pre-incubation with Omalizumab prevented these three effects of allergic serum, but had no significant effect on serum from healthy donors or non-allergic asthma patients. Interestingly, the addition of allergens did not further increase any of the IgE effects. Conclusion and Clinical Relevance Our data provides experimental evidence that the beneficial effect of Omalizumab on airway wall remodeling and improved lung function may be due to its direct action on IgE bound ASMC. PMID:26332463

  3. Serum IgE Induced Airway Smooth Muscle Cell Remodeling Is Independent of Allergens and Is Prevented by Omalizumab.

    Directory of Open Access Journals (Sweden)

    Michael Roth

    Full Text Available Airway wall remodeling in allergic asthma is reduced after treatment with humanized anti-IgE-antibodies. We reported earlier that purified IgE, without the presence of allergens, is sufficient to induce airway wall remodeling due to airway smooth muscle cell (ASMC activity deposing extracellular matrix.We postulate that IgE contained in serum of allergic asthma patients, in the absence of allergens, stimulates ASMC remodeling activities and can be prevented by anti-IgE antibodies.Isolated human ASMC were exposed to serum obtained from: (i healthy controls, or patients with (ii allergic asthma, (iii non-allergic asthma, and (iv atopic non-asthma patients. Proliferation and the deposition of collagens and fibronectin were determined after 3 and 5 days.Serum from patients with allergies significantly stimulated: (i ASMC proliferation, (ii deposition of collagen type-I (48 hours and (iii of fibronectin (24 hours. One hour pre-incubation with Omalizumab prevented these three effects of allergic serum, but had no significant effect on serum from healthy donors or non-allergic asthma patients. Interestingly, the addition of allergens did not further increase any of the IgE effects.Our data provides experimental evidence that the beneficial effect of Omalizumab on airway wall remodeling and improved lung function may be due to its direct action on IgE bound ASMC.

  4. Effect of eplerenone on serum TNF-α levels in adriamycin induced heart failure male rat models

    International Nuclear Information System (INIS)

    Xuan Nan; Song Liping; Xing Haiyan

    2009-01-01

    Objective: To investigate the effect of eplerenone on serum TNF-α levels in adriamycin induced heart failure male rat models. Methods: Forty male rat models of adriamycin-induced heart failure were prepared with weekly intraperitoneal injection of adriamycin (4/mg/kg) for six weeks. Twenty surviving models were randomly divided into two groups: (1)eplerenone-treated group, n=10, treated with garage of eplerenone 200mg/kg/d for 12 weeks (2) non-treated group n=10. All the surviving models (group (1) n=8, group (2) n=6) were sacrificed after 12 weeks with left ventricular hemodynamic function parameters tested and serum TNF-α levels measured. Ten male rats without adriamycin administration served as controls. Results: Left ventricular hemodynamic parameters in the non-treated group were significantly worse than those in controls (P<0.05). The parameters in the eplerenone treated group were significantly better than those in the non-treated group (P<0.05). The serum TNF-α levels in the non-treated group were significantly higher than those in controls (P<0.05). TNF-α levels in the eplerenone group were significantly lower than those in the non-treated group (P<0.05). Conclusion: Eplerenone could reduce the serum TNF-α levels in the rat models of heart failure. (authors)

  5. Effect of soluble calcium and lactose on limiting flux and serum protein removal during skim milk microfiltration.

    Science.gov (United States)

    Adams, Michael C; Hurt, Emily E; Barbano, David M

    2015-11-01

    The tendency of calcium to promote microfiltration (MF) membrane fouling is well documented, but the role of lactose has not been studied. Milk protein concentrate that is 85% protein on a dry basis (MPC85) contains less calcium and lactose than skim milk. Our objectives were to determine the effects of skim milk soluble calcium and lactose concentrations on the limiting fluxes (LF) and serum protein (SP) removal factors of 0.1-µm ceramic graded permeability membranes. The MF was fed with 3 different milks: skim milk, liquid MPC85 that had been standardized to the protein content of skim milk with reverse osmosis water (MPC), and liquid MPC85 that had been standardized to the protein and lactose contents of skim milk with reverse osmosis water and lactose monohydrate (MPC+L). Retentate and permeate were continuously recycled to the feed tank. The LF for each feed was determined by increasing flux once per hour from 55 kg·m(-2)·h(-1) until flux did not increase with increasing transmembrane pressure. Temperature, pressure drop across the membrane length, and protein concentration in the retentate recirculation loop were maintained at 50°C, 220 kPa, and 8.77 ± 0.2%, respectively. Experiments were replicated 3 times and the Proc GLM procedure of SAS was used for statistical analysis. An increase in LF between skim milk (91 kg·m(-2)·h(-1)) and MPC+L (124 kg·m(-2)·h(-1)) was associated with a reduction in soluble calcium. The LF of MPC+L was lower than the LF of MPC (137 kg·m(-2)·h(-1)) due to the higher viscosity contributed by lactose. Permeates produced from the MPC and MPC+L contained more protein than the skim milk permeate due to the transfer of caseins from the micelles into the reduced-calcium sera of the MPC and MPC+L. A SP removal factor was calculated by dividing true protein in the permeate by SP in the permeate portion of the feed to describe the ease of SP passage through the membrane. No differences in SP removal factors were detected among the

  6. Limiting Accretion onto Massive Stars by Fragmentation-Induced Starvation

    Energy Technology Data Exchange (ETDEWEB)

    Peters, Thomas; /ZAH, Heidelberg; Klessen, Ralf S.; /ZAH, Heidelberg /KIPAC, Menlo Park; Mac Low, Mordecai-Mark; /Amer. Museum Natural Hist.; Banerjee, Robi; /ZAH, Heidelberg

    2010-08-25

    Massive stars influence their surroundings through radiation, winds, and supernova explosions far out of proportion to their small numbers. However, the physical processes that initiate and govern the birth of massive stars remain poorly understood. Two widely discussed models are monolithic collapse of molecular cloud cores and competitive accretion. To learn more about massive star formation, we perform simulations of the collapse of rotating, massive, cloud cores including radiative heating by both non-ionizing and ionizing radiation using the FLASH adaptive mesh refinement code. These simulations show fragmentation from gravitational instability in the enormously dense accretion flows required to build up massive stars. Secondary stars form rapidly in these flows and accrete mass that would have otherwise been consumed by the massive star in the center, in a process that we term fragmentation-induced starvation. This explains why massive stars are usually found as members of high-order stellar systems that themselves belong to large clusters containing stars of all masses. The radiative heating does not prevent fragmentation, but does lead to a higher Jeans mass, resulting in fewer and more massive stars than would form without the heating. This mechanism reproduces the observed relation between the total stellar mass in the cluster and the mass of the largest star. It predicts strong clumping and filamentary structure in the center of collapsing cores, as has recently been observed. We speculate that a similar mechanism will act during primordial star formation.

  7. Identification of serum biomarkers for occupational medicamentosa-like dermatitis induced by trichloroethylene using mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Wen-Xu; Liu, Wei [Key Laboratory of Modern Toxicology of Shenzhen, Medical Key Laboratory of Guangdong Province, Medical Key Laboratory of Health Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055 (China); Zhang, Yanfang [Shenzhen Prevention and Treatment Center for Occupational Disease, Shenzhen 518001 (China); Huang, Peiwu; Yang, Xifei; Ren, Xiaohu; Ye, Jinbo; Huang, Haiyan [Key Laboratory of Modern Toxicology of Shenzhen, Medical Key Laboratory of Guangdong Province, Medical Key Laboratory of Health Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055 (China); Tang, Haiyan [Shenzhen Prevention and Treatment Center for Occupational Disease, Shenzhen 518001 (China); Zhou, Guifeng [Medical School of Hunan Normal University, Changsha 410006 (China); Huang, Xinfeng; Zhuang, Zhixiong [Key Laboratory of Modern Toxicology of Shenzhen, Medical Key Laboratory of Guangdong Province, Medical Key Laboratory of Health Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055 (China); Liu, Jianjun, E-mail: bio-research@hotmail.com [Key Laboratory of Modern Toxicology of Shenzhen, Medical Key Laboratory of Guangdong Province, Medical Key Laboratory of Health Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055 (China)

    2013-11-15

    Occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) is an autoimmune disease and it has become a serious occupational health hazard. In the present study, we collected fasting blood samples from patients with OMLDT (n = 18) and healthy volunteers (n = 33) to explore serum peptidome patterns. Peptides in sera were purified using weak cation exchange magnetic beads (MB-WCX), and analyzed by matrix-assisted laser desorption ionization time-of-flight-mass spectrometry (MALDI-TOF-MS) and ClinProTools bioinformatics software. The intensities of thirty protein/peptide peaks were significantly different between the healthy control and OMLDT patients. A pattern of three peaks (m/z 2106.3, 2134.5, and 3263.67) was selected for supervised neural network (SNN) model building to separate the OMLDT patients from the healthy controls with a sensitivity of 95.5% and a specificity of 73.8%. Furthermore, two peptide peaks of m/z 4091.61 and 4281.69 were identified as fragments of ATP-binding cassette transporter family A member 12 (ABCA12), and cationic trypsinogen (PRRS1), respectively. Our findings not only show that specific proteomic fingerprints in the sera of OMLDT patients can be served as a differentiated tool of OMLDT patients with high sensitivity and high specificity, but also reveal the novel correlation between OMLDT with ABC transports and PRRS1, which will be of potential value for clinical and mechanistic studies of OMLDT. - Highlights: • Identify 30 differential protein/peptide peaks between OMLDT and healthy control • The test sensitivity and test specificity were 95.5% and 73.8%, respectively. • ABCA12 and PRSS1 were identified as potential biomarkers in OMLDT patients.

  8. Serum Acetyl Cholinesterase as a Biomarker of Arsenic Induced Neurotoxicity in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Paul B. Tchounwou

    2005-04-01

    Full Text Available Arsenic is an environmental toxicant, and one of the major mechanisms by which it exerts its toxic effect is through an impairment of cellular respiration by inhibition of various mitochondrial enzymes, and the uncoupling of oxidative phosphorylation. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Recent studies have pointed out that arsenic toxicity is associated with the formation of reactive oxygen species, which may cause severe injury/damage to the nervous system. The main objective of this study was to conduct biochemical analysis to determine the effect of arsenic trioxide on the activity of acetyl cholinesterase; a critical important nervous system enzyme that hydrolyzes the neurotransmitter acetylcholine. Four groups of six male rats each weighing an average 60 + 2 g were used in this study. Arsenic trioxide was intraperitoneally administered to the rats at the doses of 5, 10, 15, 20mg/kg body weight (BW, one dose per 24 hour given for five days. A control group was also made of 6 animals injected with distilled water without chemical. Following anaesthesia, blood specimens were immediately collected using heparinized syringes, and acetyl cholinesterase detection and quantification were performed in serum samples by spectrophotometry. Arsenic trioxide exposure significantly decreased the activity of cholinesterase in the Sprague-Dawley rats. Acetyl cholinesterase activities of 6895 + 822, 5697 + 468, 5069 + 624, 4054 + 980, and 3158 + 648 U/L were recorded for 0, 5, 10, 15, and 20 mg/kg, respectively; indicating a gradual decrease in acetyl cholinesterase activity with increasing doses of arsenic. These findings indicate that acetyl

  9. Identification of serum biomarkers for occupational medicamentosa-like dermatitis induced by trichloroethylene using mass spectrometry

    International Nuclear Information System (INIS)

    Hong, Wen-Xu; Liu, Wei; Zhang, Yanfang; Huang, Peiwu; Yang, Xifei; Ren, Xiaohu; Ye, Jinbo; Huang, Haiyan; Tang, Haiyan; Zhou, Guifeng; Huang, Xinfeng; Zhuang, Zhixiong; Liu, Jianjun

    2013-01-01

    Occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) is an autoimmune disease and it has become a serious occupational health hazard. In the present study, we collected fasting blood samples from patients with OMLDT (n = 18) and healthy volunteers (n = 33) to explore serum peptidome patterns. Peptides in sera were purified using weak cation exchange magnetic beads (MB-WCX), and analyzed by matrix-assisted laser desorption ionization time-of-flight-mass spectrometry (MALDI-TOF-MS) and ClinProTools bioinformatics software. The intensities of thirty protein/peptide peaks were significantly different between the healthy control and OMLDT patients. A pattern of three peaks (m/z 2106.3, 2134.5, and 3263.67) was selected for supervised neural network (SNN) model building to separate the OMLDT patients from the healthy controls with a sensitivity of 95.5% and a specificity of 73.8%. Furthermore, two peptide peaks of m/z 4091.61 and 4281.69 were identified as fragments of ATP-binding cassette transporter family A member 12 (ABCA12), and cationic trypsinogen (PRRS1), respectively. Our findings not only show that specific proteomic fingerprints in the sera of OMLDT patients can be served as a differentiated tool of OMLDT patients with high sensitivity and high specificity, but also reveal the novel correlation between OMLDT with ABC transports and PRRS1, which will be of potential value for clinical and mechanistic studies of OMLDT. - Highlights: • Identify 30 differential protein/peptide peaks between OMLDT and healthy control • The test sensitivity and test specificity were 95.5% and 73.8%, respectively. • ABCA12 and PRSS1 were identified as potential biomarkers in OMLDT patients

  10. Metabolic Profiling Analysis of the Alleviation Effect of Treatment with Baicalin on Cinnabar Induced Toxicity in Rats Urine and Serum

    OpenAIRE

    Guangyue Su; Guangyue Su; Gang Chen; Gang Chen; Xiao An; Haifeng Wang; Haifeng Wang; Yue-Hu Pei; Yue-Hu Pei

    2017-01-01

    Objectives: Baicalin is the main bioactive flavonoid constituent isolated from Scutellaria baicalensis Georgi. The mechanisms of protection of liver remain unclear. In this study, 1H NMR-based metabonomics approach has been used to investigate the alleviation effect of Baicalin.Method:1H NMR metabolomics analyses of urine and serum from rats, was performed to illuminate the alleviation effect of Baicalin on mineral medicine (cinnabar)-induced liver and kidney toxicity.Results: The metabolic p...

  11. Metabolic Profiling Analysis of the Alleviation Effect of Treatment with Baicalin on Cinnabar Induced Toxicity in Rats Urine and Serum

    OpenAIRE

    Su, Guangyue; Chen, Gang; An, Xiao; Wang, Haifeng; Pei, Yue-Hu

    2017-01-01

    Objectives: Baicalin is the main bioactive flavonoid constituent isolated from Scutellaria baicalensis Georgi. The mechanisms of protection of liver remain unclear. In this study, 1H NMR-based metabonomics approach has been used to investigate the alleviation effect of Baicalin. Method: 1H NMR metabolomics analyses of urine and serum from rats, was performed to illuminate the alleviation effect of Baicalin on mineral medicine (cinnabar)-induced liver and kidney toxicity. Results: The me...

  12. Lithography-induced limits to scaling of design quality

    Science.gov (United States)

    Kahng, Andrew B.

    2014-03-01

    Quality and value of an IC product are functions of power, performance, area, cost and reliability. The forthcoming 2013 ITRS roadmap observes that while manufacturers continue to enable potential Moore's Law scaling of layout densities, the "realizable" scaling in competitive products has for some years been significantly less. In this paper, we consider aspects of the question, "To what extent should this scaling gap be blamed on lithography?" Non-ideal scaling of layout densities has been attributed to (i) layout restrictions associated with multi-patterning technologies (SADP, LELE, LELELE), as well as (ii) various ground rule and layout style choices that stem from misalignment, reliability, variability, device architecture, and electrical performance vs. power constraints. Certain impacts seem obvious, e.g., loss of 2D flexibility and new line-end placement constraints with SADP, or algorithmically intractable layout stitching and mask coloring formulations with LELELE. However, these impacts may well be outweighed by weaknesses in design methodology and tooling. Arguably, the industry has entered a new era in which many new factors - (i) standard-cell library architecture, and layout guardbanding for automated place-and-route: (ii) performance model guardbanding and signoff analyses: (iii) physical design and manufacturing handoff algorithms spanning detailed placement and routing, stitching and RET; and (iv) reliability guardbanding - all contribute, hand in hand with lithography, to a newly-identified "design capability gap". How specific aspects of process and design enablements limit the scaling of design quality is a fundamental question whose answer must guide future RandD investment at the design-manufacturing interface. terface.

  13. Bone morphogenic protein-2 regulates the myogenic differentiation of PMVECs in CBDL rat serum-induced pulmonary microvascular remodeling

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chang; Chen, Lin; Zeng, Jing; Cui, Jian; Ning, Jiao-nin [Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038 (China); Wang, Guan-song [Institute of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037 (China); Belguise, Karine; Wang, Xiaobo [Université P. Sabatier Toulouse III and CNRS, LBCMCP, 31062 Toulouse Cedex 9 (France); Qian, Gui-sheng [Institute of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037 (China); Lu, Kai-zhi [Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038 (China); Yi, Bin, E-mail: yibin1974@163.com [Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038 (China)

    2015-08-01

    Hepatopulmonary syndrome (HPS) is characterized by an arterial oxygenation defect induced by intrapulmonary vasodilation (IPVD) that increases morbidity and mortality. In our previous study, it was determined that both the proliferation and the myogenic differentiation of pulmonary microvascular endothelial cells (PMVECs) play a key role in the development of IPVD. However, the molecular mechanism underlying the relationship between IPVD and the myogenic differentiation of PMVECs remains unknown. Additionally, it has been shown that bone morphogenic protein-2 (BMP2), via the control of protein expression, may regulate cell differentiation including cardiomyocyte differentiation, neuronal differentiation and odontoblastic differentiation. In this study, we observed that common bile duct ligation (CBDL)-rat serum induced the upregulation of the expression of several myogenic proteins (SM-α-actin, calponin, SM-MHC) and enhanced the expression levels of BMP2 mRNA and protein in PMVECs. We also observed that both the expression levels of Smad1/5 and the activation of phosphorylated Smad1/5 were significantly elevated in PMVECs following exposure to CBDL-rat serum, which was accompanied by the down-regulation of Smurf1. The blockage of the BMP2/Smad signaling pathway with Noggin inhibited the myogenic differentiation of PMVECs, a process that was associated with relatively low expression levels of both SM-α-actin and calponin in the setting of CBDL-rat serum exposure, although SM-MHC expression was not affected. These findings suggested that the BMP2/Smad signaling pathway is involved in the myogenic differentiation of the PMVECs. In conclusion, our data highlight the pivotal role of BMP2 in the CBDL-rat serum-induced myogenic differentiation of PMVECs via the activation of both Smad1 and Smad5 and the down-regulation of Smurf1, which may represent a potential therapy for HPS-induced pulmonary vascular remodeling. - Highlights: • CBDL-rat serum promotes the myogenic

  14. Serum apolipoprotein A1 and haptoglobin, in patients with suspected drug-induced liver injury (DILI as biomarkers of recovery.

    Directory of Open Access Journals (Sweden)

    Valentina Peta

    Full Text Available There is a clear need for better biomarkers of drug-induced-liver-injury (DILI.We aimed to evaluate the possible prognostic value of ActiTest and FibroTest proteins apoliprotein-A1, haptoglobin and alpha-2-macroglobulin, in patients with DILI.We analyzed cases and controls included in the IMI-SAFE-T-DILI European project, from which serum samples had been stored in a dedicated biobank. The analyses of ActiTest and FibroTest had been prospectively scheduled. The primary objective was to analyze the performance (AUROC of ActiTest components as predictors of recovery outcome defined as an ALT <2x the upper limit of normal (ULN, and BILI <2x ULN.After adjudication, 154 patients were considered to have DILI and 22 were considered to have acute liver injury without DILI. A multivariate regression analysis (ActiTest-DILI patent pending combining the ActiTest components without BILI and ALT (used as references, apolipoprotein-A1, haptoglobin, alpha-2-macroglobulin and GGT, age and gender, resulted in a significant prediction of recovery with 67.0% accuracy (77/115 and an AUROC of 0.724 (P<0.001 vs. no prediction 0.500. Repeated apolipoprotein-A1 and haptoglobin remained significantly higher in the DILI cases that recovered (n = 65 versus those that did not (n = 16, at inclusion, at 4-8 weeks and at 8-12 weeks. The same results were observed after stratification on APAP cases and non-APAP cases.We identified that apolipoprotein-A1 and haptoglobin had significant predictive values for the prediction of recovery at 12 weeks in DILI, enabling the construction of a new prognostic panel, the DILI-ActiTest, which needs to be independently validated.

  15. The Serum Anion Gap in the Evaluation of Acid-Base Disorders: What Are Its Limitations and Can Its Effectiveness Be Improved?

    OpenAIRE

    Kraut, Jeffrey A.; Nagami, Glenn T.

    2013-01-01

    The serum anion gap has been utilized to identify errors in the measurement of electrolytes, to detect paraproteins, and, most relevant to the nephrologist, to evaluate patients with suspected acid-base disorders. In regard to the latter purpose, traditionally an increased anion gap is identified when it exceeds the upper limit of normal for a particular clinical laboratory measurement. However, because there is a wide range of normal values (often 8–10 mEq/L), an increase in anion concentrat...

  16. Inhaled ozone (O{sub 3})-induces changes in serum metabolomic and liver transcriptomic profiles in rats

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Desinia B. [Curriculum in Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, NC (United States); Karoly, Edward D.; Jones, Jan C. [Metabolon Incorporation, Durham, NC (United States); Ward, William O.; Vallanat, Beena D.; Andrews, Debora L. [Research Cores Unit, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Schladweiler, Mette C.; Snow, Samantha J. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Bass, Virginia L. [Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC (United States); Richards, Judy E.; Ghio, Andrew J.; Cascio, Wayne E.; Ledbetter, Allen D. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Kodavanti, Urmila P., E-mail: kodavanti.urmila@epa.gov [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States)

    2015-07-15

    Air pollution has been linked to increased incidence of diabetes. Recently, we showed that ozone (O{sub 3}) induces glucose intolerance, and increases serum leptin and epinephrine in Brown Norway rats. In this study, we hypothesized that O{sub 3} exposure will cause systemic changes in metabolic homeostasis and that serum metabolomic and liver transcriptomic profiling will provide mechanistic insights. In the first experiment, male Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or O{sub 3} at 0.25, 0.50, or 1.0 ppm, 6 h/day for two days to establish concentration-related effects on glucose tolerance and lung injury. In a second experiment, rats were exposed to FA or 1.0 ppm O{sub 3}, 6 h/day for either one or two consecutive days, and systemic metabolic responses were determined immediately after or 18 h post-exposure. O{sub 3} increased serum glucose and leptin on day 1. Glucose intolerance persisted through two days of exposure but reversed 18 h-post second exposure. O{sub 3} increased circulating metabolites of glycolysis, long-chain free fatty acids, branched-chain amino acids and cholesterol, while 1,5-anhydroglucitol, bile acids and metabolites of TCA cycle were decreased, indicating impaired glycemic control, proteolysis and lipolysis. Liver gene expression increased for markers of glycolysis, TCA cycle and gluconeogenesis, and decreased for markers of steroid and fat biosynthesis. Genes involved in apoptosis and mitochondrial function were also impacted by O{sub 3}. In conclusion, short-term O{sub 3} exposure induces global metabolic derangement involving glucose, lipid, and amino acid metabolism, typical of a stress–response. It remains to be examined if these alterations contribute to insulin resistance upon chronic exposure. - Highlights: • Ozone, an ubiquitous air pollutant induces acute systemic metabolic derangement. • Serum metabolomic approach provides novel insights in ozone-induced changes. • Ozone exposure induces leptinemia

  17. Serum Oxidative Stress-Induced Repression of Nrf2 and GSH Depletion: A Mechanism Potentially Involved in Endothelial Dysfunction of Young Smokers

    Science.gov (United States)

    Fratta Pasini, Anna; Albiero, Anna; Stranieri, Chiara; Cominacini, Mattia; Pasini, Andrea; Mozzini, Chiara; Vallerio, Paola; Cominacini, Luciano; Garbin, Ulisse

    2012-01-01

    Background Although oxidative stress plays a major role in endothelial dysfunction (ED), the role of glutathione (GSH), of nuclear erythroid-related factor 2 (Nrf2) and of related antioxidant genes (ARE) are yet unknown. In this study we combined an in vivo with an in vitro model to assess whether cigarette smoking affects flow-mediated vasodilation (FMD), GSH concentrations and the Nrf2/ARE pathway in human umbilical vein endothelial cells (HUVECs). Methods and Results 52 healthy subjects (26 non-smokers and 26 heavy smokers) were enrolled in this study. In smokers we demonstrated increased oxidative stress, i.e., reduced concentrations of GSH and increased concentrations of oxidation products of the phospholipid 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (oxPAPC) in serum and in peripheral blood mononuclear cells (PBMC), used as in vivo surrogates of endothelial cells. Moreover we showed impairment of FMD in smokers and a positive correlation with the concentration of GSH in PBMC of all subjects. In HUVECs exposed to smokers' serum but not to non-smokers' serum we found that oxidative stress increased, whereas nitric oxide and GSH concentrations decreased; interestingly the expression of Nrf2, of heme oxygenase-1 (HO-1) and of glutamate-cysteine ligase catalytic (GCLC) subunit, the rate-limiting step of synthesis of GSH, was decreased. To test the hypothesis that the increased oxidative stress in smokers may have a causal role in the repression of Nrf2/ARE pathway, we exposed HUVECs to increasing concentrations of oxPAPC and found that at the highest concentration (similar to that found in smokers' serum) the expression of Nrf2/ARE pathway was reduced. The knockdown of Nrf2 was associated to a significant reduction of HO-1 and GCLC expression induced by oxPAPC in ECs. Conclusions In young smokers with ED a novel further consequence of increased oxidative stress is a repression of Nrf2/ARE pathway leading to GSH depletion. PMID:22272327

  18. Serum oxidative stress-induced repression of Nrf2 and GSH depletion: a mechanism potentially involved in endothelial dysfunction of young smokers.

    Directory of Open Access Journals (Sweden)

    Anna Fratta Pasini

    Full Text Available Although oxidative stress plays a major role in endothelial dysfunction (ED, the role of glutathione (GSH, of nuclear erythroid-related factor 2 (Nrf2 and of related antioxidant genes (ARE are yet unknown. In this study we combined an in vivo with an in vitro model to assess whether cigarette smoking affects flow-mediated vasodilation (FMD, GSH concentrations and the Nrf2/ARE pathway in human umbilical vein endothelial cells (HUVECs.52 healthy subjects (26 non-smokers and 26 heavy smokers were enrolled in this study. In smokers we demonstrated increased oxidative stress, i.e., reduced concentrations of GSH and increased concentrations of oxidation products of the phospholipid 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (oxPAPC in serum and in peripheral blood mononuclear cells (PBMC, used as in vivo surrogates of endothelial cells. Moreover we showed impairment of FMD in smokers and a positive correlation with the concentration of GSH in PBMC of all subjects. In HUVECs exposed to smokers' serum but not to non-smokers' serum we found that oxidative stress increased, whereas nitric oxide and GSH concentrations decreased; interestingly the expression of Nrf2, of heme oxygenase-1 (HO-1 and of glutamate-cysteine ligase catalytic (GCLC subunit, the rate-limiting step of synthesis of GSH, was decreased. To test the hypothesis that the increased oxidative stress in smokers may have a causal role in the repression of Nrf2/ARE pathway, we exposed HUVECs to increasing concentrations of oxPAPC and found that at the highest concentration (similar to that found in smokers' serum the expression of Nrf2/ARE pathway was reduced. The knockdown of Nrf2 was associated to a significant reduction of HO-1 and GCLC expression induced by oxPAPC in ECs.In young smokers with ED a novel further consequence of increased oxidative stress is a repression of Nrf2/ARE pathway leading to GSH depletion.

  19. [Detection of fps tumor antigen with mono-specific anti-fps serum in tumors induced by acute transforming ALV].

    Science.gov (United States)

    Wang, Yixin; Chen, Hao; Zhao, Peng; Li, Jianliang; Cui, Zhizhong

    2013-03-04

    To prepare anti-fps mono-specific serum, and detect the fps antigen in tumors induced by acute transforming avian leukosis/sarcoma virus containing v-fps oncogene. Two part of v-fps gene was amplified by RT-PCR using the Fu-J viral RNA as the template. Mono-specific serum was prepared by immuning Kunming white mouse with both two recombinant infusion proteins expressed by the prokaryotic expression system. Indirect immunofluorescent assay was used to detect fps antigen in tumor tissue suspension cells and CEF infected by sarcoma supernatant. Immunohistochemical method was used to detect fps antigen in tumor tissue. The mouse mono-specific serum was specific as it had no cross reaction with classical ALV-J strains. The result reveals that the tumor tissue suspension cells, the CEF infected by sarcoma supernatant, and the slice immunohistochemistry of the sarcoma showed positive results. The anti-fps mono-specific serum was prepared, and the detection method was established, which laid the foundation for the study of viral biological characteristics and mechanism of tumourgenesis of acute transforming avian leukosis/sarcoma virus containing v-fps oncogene.

  20. 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.

  1. Limitations in SELDI-TOF MS whole serum proteomic profiling with IMAC surface to specifically detect colorectal cancer

    International Nuclear Information System (INIS)

    Wang, Qi; Gu, Jin; Shen, Jing; Li, Zhen-fu; Jie, Jian-zheng; Wang, Wen-yue; Wang, Jin; Zhang, Zhong-tao; Li, Zhi-xia; Yan, Li

    2009-01-01

    Surface enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF-MS) analysis on serum samples was reported to be able to detect colorectal cancer (CRC) from normal or control patients. We carried out a validation study of a SELDI-TOF MS approach with IMAC surface sample processing to identify CRC. A retrospective cohort of 338 serum samples including 154 CRCs, 67 control cancers and 117 non-cancerous conditions was profiled using SELDI-TOF-MS. No CRC 'specific' classifier was found. However, a classifier consisting of two protein peaks separates cancer from non-cancerous conditions with high accuracy. In this study, the SELDI-TOF-MS-based protein expression profiling approach did not perform to identify CRC. However, this technique is promising in distinguishing patients with cancer from a non-cancerous population; it may be useful for monitoring recurrence of CRC after treatment

  2. Two Classifiers Based on Serum Peptide Pattern for Prediction of HBV-Induced Liver Cirrhosis Using MALDI-TOF MS

    Directory of Open Access Journals (Sweden)

    Yuan Cao

    2013-01-01

    Full Text Available Chronic infection with hepatitis B virus (HBV is associated with the majority of cases of liver cirrhosis (LC in China. Although liver biopsy is the reference method for evaluation of cirrhosis, it is an invasive procedure with inherent risk. The aim of this study is to discover novel noninvasive specific serum biomarkers for the diagnosis of HBV-induced LC. We performed bead fractionation/MALDI-TOF MS analysis on sera from patients with LC. Thirteen feature peaks which had optimal discriminatory performance were obtained by using support-vector-machine-(SVM- based strategy. Based on the previous results, five supervised machine learning methods were employed to construct classifiers that discriminated proteomic spectra of patients with HBV-induced LC from those of controls. Here, we describe two novel methods for prediction of HBV-induced LC, termed LC-NB and LC-MLP, respectively. We obtained a sensitivity of 90.9%, a specificity of 94.9%, and overall accuracy of 93.8% on an independent test set. Comparisons with the existing methods showed that LC-NB and LC-MLP held better accuracy. Our study suggests that potential serum biomarkers can be determined for discriminating LC and non-LC cohorts by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. These two classifiers could be used for clinical practice in HBV-induced LC assessment.

  3. Serum Fetuin-A Levels Related with Microalbuminuria in Diet-Induced Obese Rats

    Directory of Open Access Journals (Sweden)

    Yanyan Li

    2013-01-01

    Full Text Available The aim of the study was to investigate the association between elevated serum fetuin-A and increased urine albumin excretion in obese rats, and whether increased urine albumin excretion was modified by improving hepatic steatosis and lipid metabolism disorder. Male Wistar rats 4 weeks in age were randomly divided into three groups and fed with normal chow (control group, high-fat chow (obesity group, or high-fat chow plus fenofibrate (fenofibrate group. After 24 weeks, both body weight and visceral fat/body weight ratio in obese rats were higher than in controls. A difference in serology markers and pathology associated with hepatic steatosis was also found among the three groups. Serum fetuin-A and the expression of NF-κB in the liver were increased, while serum adiponectin was decreased in obese rats in comparison to controls (. Urinary albumin/creatinine ratio (ACR was increased in the obesity group compared to controls (. The fenofibrate intervention reduced serum fetuin-A and NF-κB expression in the liver and increased serum adiponectin compared to obese rats and was accompanied by decrease in ACR. A positive correlation was found between ACR and fetuin-A (, , and a negative correlation was found between ACR and adiponectin (, . We conclude that elevated fetuin-A levels are associated with microalbuminuria in obese rats, and abnormal albuminuria is reversible by improving hepatic steatosis.

  4. Protective effect of Nigella sativa extract and thymoquinone on serum/glucose deprivation-induced PC12 cells death.

    Science.gov (United States)

    Mousavi, S H; Tayarani-Najaran, Z; Asghari, M; Sadeghnia, H R

    2010-05-01

    The serum/glucose deprivation (SGD)-induced cell death in cultured PC12 cells represents a useful in vitro model for the study of brain ischemia and neurodegenerative disorders. Nigella sativa L. (family Ranunculaceae) and its active component thymoquinone (TQ) has been known as a source of antioxidants. In the present study, the protective effects of N. sativa and TQ on cell viability and reactive oxygen species (ROS) production in cultured PC12 cells were investigated under SGD conditions. PC12 cells were cultured in DMEM medium containing 10% (v/v) fetal bovine serum, 100 units/ml penicillin, and 100 microg/ml streptomycin. Cells were seeded overnight and then deprived of serum/glucose for 6 and 18 h. Cells were pretreated with different concentrations of N. sativa extract (15.62-250 microg/ml) and TQ (1.17-150 microM) for 2 h. Cell viability was quantitated by MTT assay. Intracellular ROS production was measured by flow cytometry using 2',7'-dichlorofluorescin diacetate (DCF-DA) as a probe. SGD induced significant cells toxicity after 6, 18, or 24 h (P < 0.001). Pretreatment with N. sativa (15.62-250 microg/ml) and TQ (1.17-37.5 microM) reduced SGD-induced cytotoxicity in PC12 cells after 6 and 18 h. A significant increase in intracellular ROS production was seen following SGD (P < 0.001). N. sativa (250 microg/ml, P < 0.01) and TQ (2.34, 4.68, 9.37 microM, P < 0.01) pretreatment reversed the increased ROS production following ischemic insult. The experimental results suggest that N. sativa extract and TQ protects the PC12 cells against SGD-induced cytotoxicity via antioxidant mechanisms. Our findings might raise the possibility of potential therapeutic application of N. sativa extract and TQ for managing cerebral ischemic and neurodegenerative disorders.

  5. Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy

    DEFF Research Database (Denmark)

    Sun, S; Henriksen, K; Karsdal, M A

    2014-01-01

    used to assess biological and clinical relevance. RESULTS: A technically robust ELISA measuring the Titin fragment was developed against a Titin peptide fragment identified in human urine. The fragment was shown to be produced primarily by MMP-2 cleavage of Titin. In the rat muscle DEX induced atrophy...... model, Titin-MMP2 fragment was decreased in the beginning of DEX treatment, and then significantly increased later on during DEX administration. In the human bed rest study, the Titin-MMP2 fragment was initially decreased 11.9 (±3.7) % after 1day of bed rest, and then gradually increased ending up...... at a 16.4 (±4.6) % increase at day 47. CONCLUSIONS: We developed a robust ELISA measuring a muscle derived MMP-2 generated Titin degradation fragment in rat and human serum. Importantly, the fragment can be measured in serum and that these levels are related to induction of skeletal muscle atrophy....

  6. Analysis of serum microRNA expression in male workers with occupational noise-induced hearing loss

    Directory of Open Access Journals (Sweden)

    Y.H. Li

    2018-01-01

    Full Text Available Occupational noise-induced hearing loss (ONIHL is a prevalent occupational disorder that impairs auditory function in workers exposed to prolonged noise. However, serum microRNA expression in ONIHL subjects has not yet been studied. We aimed to compare the serum microRNA expression profiles in male workers of ONIHL subjects and controls. MicroRNA microarray analysis revealed that four serum microRNAs were differentially expressed between controls (n=3 and ONIHL subjects (n=3. Among these microRNAs, three were upregulated (hsa-miR-3162-5p, hsa-miR-4484, hsa-miR-1229-5p and one was downregulated (hsa-miR-4652-3p in the ONIHL group (fold change >1.5 and Pbon value <0.05. Real time quantitative PCR was conducted for validation of the microRNA expression. Significantly increased serum levels of miR-1229-5p were found in ONIHL subjects compared to controls (n=10 for each group; P<0.05. A total of 659 (27.0% genes were predicted as the target genes of miR-1229-5p. These genes were involved in various pathways, such as mitogen-activated protein kinase (MAPK signaling pathway. Overexpression of miR-1229-5p dramatically inhibited the luciferase activity of 3′ UTR segment of MAPK1 (P<0.01. Compared to the negative control, HEK293T cells expressing miR-1229-5p mimics showed a significant decline in mRNA levels of MAPK1 (P<0.05. This preliminary study indicated that serum miR-1229-5p was significantly elevated in ONIHL subjects. Increased miR-1229-5p may participate in the pathogenesis of ONIHL through repressing MAPK1 signaling.

  7. Analysis of serum microRNA expression in male workers with occupational noise-induced hearing loss.

    Science.gov (United States)

    Li, Y H; Yang, Y; Yan, Y T; Xu, L W; Ma, H Y; Shao, Y X; Cao, C J; Wu, X; Qi, M J; Wu, Y Y; Chen, R; Hong, Y; Tan, X H; Yang, L

    2018-01-11

    Occupational noise-induced hearing loss (ONIHL) is a prevalent occupational disorder that impairs auditory function in workers exposed to prolonged noise. However, serum microRNA expression in ONIHL subjects has not yet been studied. We aimed to compare the serum microRNA expression profiles in male workers of ONIHL subjects and controls. MicroRNA microarray analysis revealed that four serum microRNAs were differentially expressed between controls (n=3) and ONIHL subjects (n=3). Among these microRNAs, three were upregulated (hsa-miR-3162-5p, hsa-miR-4484, hsa-miR-1229-5p) and one was downregulated (hsa-miR-4652-3p) in the ONIHL group (fold change >1.5 and Pbon value <0.05). Real time quantitative PCR was conducted for validation of the microRNA expression. Significantly increased serum levels of miR-1229-5p were found in ONIHL subjects compared to controls (n=10 for each group; P<0.05). A total of 659 (27.0%) genes were predicted as the target genes of miR-1229-5p. These genes were involved in various pathways, such as mitogen-activated protein kinase (MAPK) signaling pathway. Overexpression of miR-1229-5p dramatically inhibited the luciferase activity of 3' UTR segment of MAPK1 (P<0.01). Compared to the negative control, HEK293T cells expressing miR-1229-5p mimics showed a significant decline in mRNA levels of MAPK1 (P<0.05). This preliminary study indicated that serum miR-1229-5p was significantly elevated in ONIHL subjects. Increased miR-1229-5p may participate in the pathogenesis of ONIHL through repressing MAPK1 signaling.

  8. The serum anion gap in the evaluation of acid-base disorders: what are its limitations and can its effectiveness be improved?

    Science.gov (United States)

    Kraut, Jeffrey A; Nagami, Glenn T

    2013-11-01

    The serum anion gap has been utilized to identify errors in the measurement of electrolytes, to detect paraproteins, and, most relevant to the nephrologist, to evaluate patients with suspected acid-base disorders. In regard to the latter purpose, traditionally an increased anion gap is identified when it exceeds the upper limit of normal for a particular clinical laboratory measurement. However, because there is a wide range of normal values (often 8-10 mEq/L), an increase in anion concentration can be present in the absence of an increased anion gap. In addition, the type of retained anion can affect the magnitude of the increase in anion gap relative to change in serum [HCO3(-)] being greater with lactic acidosis compared with ketoacidosis. This review examines the methods of calculation of the serum anion gap in textbooks and published literature, the effect of perturbations other than changes in acid-base balance, and its effectiveness in identifying mild and more severe disturbances in acid-base balance. Limitations of the present methods of determining the normal anion gap and change in the anion gap are highlighted. The possibility of identifying the baseline value for individuals to optimize the use of the calculation in the detection of metabolic acidosis is suggested.

  9. Lymphocyte cytotoxicity induced by preincubation with serum from patients with Hashimoto thyroiditis

    Science.gov (United States)

    Calder, Elizabeth A.; McLeman, Dena; Irvine, W. J.

    1973-01-01

    Lymphocytes from healthy donors were incubated with serum samples from nine patients with Hashimoto thyroiditis and subsequently shown to be cytotoxic to chicken red blood cells (Ch. RBC) coated with thyroglobulin. Target cell death was estimated using a standard 51Cr release assay system. Lymphocytes pre-incubated with Hashimoto serum caused a mean% 51Cr release of 13·11±2·83 (SEM) from thyroglobulin-coated Ch. RBC and a mean% 51Cr release of 1·22±0·65 from uncoated Ch. RBC. Untreated lymphocytes caused no significant isotope release from either uncoated or thyroglobulin coated target cells. PMID:4800956

  10. On the limits of toxicant-induced tolerance testing: cotolerance and response variation of antibiotic effects.

    NARCIS (Netherlands)

    Schmitt, Heike; Martinali, Bennie; Beelen, Patrick van; Seinen, Willem

    2006-01-01

    Pollution-induced community tolerance (PICT) as an ecotoxicological test system has been claimed to detect pollutant effects highly specifically and sensitively. However, the specificity might be limited by the occurrence of cotolerance. Another limitation of the application of any ecotoxicological

  11. Limit of probability of causation in the compensation of radiation induced malignant diseases

    International Nuclear Information System (INIS)

    Sun Shiquan

    1989-01-01

    Etiological relationship between previous radiation exposure and malignant diseases concerned could be estimated from NIH Epidemiological Tables expressed as Probability of Causation (PC). But the limit of PC in the compensation of radiation induced malignant diseases has not been decided definitely. In this paper PC calculations were made for populations of occupational exposure with typical distribution of individual doses and levels of exposure. The results show that it is feasible to choice PC ≥ 50% as a limit of compensation for leukemia and radon induced lung cancer. Some lenient limits may be taken for other radiation related solid carcinomas

  12. Iron Dextran treatment does not induce serum protein carbonyls in the newborn pig

    Science.gov (United States)

    Oxidation of serum proteins can lead to carbonyl formation which alters their function and is often associated with stress-related diseases. Since it is recommended that all pigs reared in modern production facilities be given supplemental iron at birth to prevent anemia, and metals can catalyze th...

  13. Cartap and carbofuran induced alterations in serum lipid profile of Wistar rats.

    Science.gov (United States)

    Rai, Devendra K; Rai, Prashant Kumar; Gupta, Aradhna; Watal, Geeta; Sharma, Bechan

    2009-04-01

    Wistar rats of 6-8 weeks in age weighing between 120-150 g were exposed to the fixed doses of each of the carbamate pesticides such as cartap (50% LD(50)) and carbofuran (50% LD(50)) as well as a combination of these two with 25% LD(50) of each for one week. The effect of treatments was studied in terms of serum lipid parameters such as high-density lipoprotein, total cholesterol, triglyceride, low-density lipoprotein and very low-density lipoprotein. Treatment with individual doses of carbofuran (50% LD(50)) and cartap (50 % LD(50)) caused significant alterations in the levels of serum lipid parameters. The pesticides treatment resulted in marked decrease in the level of serum high-density lipoprotein where as that of other lipids got significantly elevated. Further, the rats exhibited relatively higher impact of pesticides when treated with the compounds in combination (25 % LD(50) of each). The results indicated that these compounds when used together may exert enhanced effect on the levels of serum lipids in rat.

  14. Effect of raised serum uric acid level on perinatal and maternal outcome in cases of pregnancy-induced hypertension

    Directory of Open Access Journals (Sweden)

    Qumrun Nassa Ahmed

    2017-05-01

    Full Text Available The aim of this study was to find out the effects of raised serum uric acid level on perinatal and maternal outcome in cases of pregnancy-induced hypertension. One hundred pregnant women with gestational period beyond 28 weeks with pregnancy-induced hypertension-preeclampsia and eclampsia were included in this study and divided into two groups. Group A (n=65 patients with a serum uric acid level >6 mg/dL was compared to Group B (n=35 patients with a uric acid level <6 gm/dL. It revealed that high uric acid level in patients with pregnancy-induced hypertension was a risk factor for several maternal complications like postpartum hemorrhage (Group A, 17.4%; Group B, 22.6%, postpartum eclampsia (Group A, 10.1%; Group B, 9.7%, abruptio placentae (Group A, 8.7%; Group B, 6.4%, HELLP syndrome (Group A, 2.9%; Group B, 0% and pulmonary edema (Group A, 4.3%; Group B, 0%. In case of perinatal outcome, the birth weight, intrauterine growth retardation, intrauterine death, stillbirth and neonatal death rate were worse in Group A 1.9 kg, 66.7, 19, 7 and 8% in comparison to Group B, where those were 2.1, 13, 6, 2, and 2% respectively. In conclusion, high uric acid in blood in patient with hypertensive disorders in pregnancy is a risk factor for several maternal complications.

  15. Serum Proteases Potentiate BMP-Induced Cell Cycle Re-entry of Dedifferentiating Muscle Cells during Newt Limb Regeneration.

    Science.gov (United States)

    Wagner, Ines; Wang, Heng; Weissert, Philipp M; Straube, Werner L; Shevchenko, Anna; Gentzel, Marc; Brito, Goncalo; Tazaki, Akira; Oliveira, Catarina; Sugiura, Takuji; Shevchenko, Andrej; Simon, András; Drechsel, David N; Tanaka, Elly M

    2017-03-27

    Limb amputation in the newt induces myofibers to dedifferentiate and re-enter the cell cycle to generate proliferative myogenic precursors in the regeneration blastema. Here we show that bone morphogenetic proteins (BMPs) and mature BMPs that have been further cleaved by serum proteases induce cell cycle entry by dedifferentiating newt muscle cells. Protease-activated BMP4/7 heterodimers that are present in serum strongly induced myotube cell cycle re-entry with protease cleavage yielding a 30-fold potency increase of BMP4/7 compared with canonical BMP4/7. Inhibition of BMP signaling via muscle-specific dominant-negative receptor expression reduced cell cycle entry in vitro and in vivo. In vivo inhibition of serine protease activity depressed cell cycle re-entry, which in turn was rescued by cleaved-mimic BMP. This work identifies a mechanism of BMP activation that generates blastema cells from differentiated muscle. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Relation between serum xenobiotic induced receptor activities and sperm DNA damage and sperm apoptotic markers in European and Inuit populations

    DEFF Research Database (Denmark)

    Long, Manhai; Stronati, Alessanda; Bizzaro, Davide

    2007-01-01

    Persistent organic pollutants (POPs) can interfere with hormone activities and are suspected as endocrine disrupters involved in disorders, e.g. reproductive disorders. We investigated the possible relation between the actual integrated serum xenoestrogenic, xenoandrogenic and aryl hydrocarbon......, but higher xenoandrogenic activity. In contrast, in the European groups, xenobiotic-induced receptor activities were found to be positively correlated with the DNA damage. Further research must elucidate whether altered receptor activities in concerted action with genetic and/or nutrient factors may have...... protecting effect on sperm DNA damage of the Inuit population....

  17. Features of blood serum protein spectrum and cytokine spectrum of rats with chronic carrageenan-induced intestinal inflammation

    Directory of Open Access Journals (Sweden)

    A. S. Tkachenko

    2014-04-01

    Full Text Available It has been established that features of modern diet might be considered as a possible source of inflammatory diseases of gastrointestinal tract. Particular attention is paid to the role of different food additives in the development of intestinal inflammation, including the food additive E407, known as carrageenan. A model of chronic carrageenan-induced gastroenterocolitis of moderate severity has been elaborated, which allows us to study carrageenan-induced intestinal inflammation. In particular, the features of blood serum protein spectrum and cytokine spectrum in chronic carrageenan-induced intestinal inflammation are not studied. The female Wistar rats have been used for the experiment. Chronic carrageenan-induced gastroenterocolitis has been reproduced by the free access of animals to 1% solution of carrageenan in drinking water. Laboratory animals have been divided into 3 groups. Group № 1 consisted of experimental animals, who consumed food additive carrageenan during 2 weeks and group № 2 included experimental animals, who consumed food additive carrageenan during 4 weeks. Group № 3 consisted of intact healthy animals. The development of gastroenterocolitis has been proved morphologically and biochemically. Manipulations with animals have been carried out in accordance with the provisions of the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Strasbourg, 1986. It has been established that the disease has been associated with dysproteinemia. The level of α1-globulins increased after 2 weeks of carrageenan consumption and has been normalized in animals, who consumed carrageenan during 4 weeks. The similar changes have been observed for α2-globulins level. It could be explained by production of acute phase proteins, such as α1-acid glycoprotein, C-reactive protein, fibrinogen, α2-macroglobulin, ceruloplasmin, etc. The intake of carrageenan also caused

  18. Serum reactome induced by Bordetella pertussis infection and Pertussis vaccines: qualitative differences in serum antibody recognition patterns revealed by peptide microarray analysis.

    Science.gov (United States)

    Valentini, Davide; Ferrara, Giovanni; Advani, Reza; Hallander, Hans O; Maeurer, Markus J

    2015-07-01

    Pertussis (whooping cough) remains a public health problem despite extensive vaccination strategies. Better understanding of the host-pathogen interaction and the detailed B. pertussis (Bp) target recognition pattern will help in guided vaccine design. We characterized the specific epitope antigen recognition profiles of serum antibodies ('the reactome') induced by whooping cough and B. pertussis (Bp) vaccines from a case-control study conducted in 1996 in infants enrolled in a Bp vaccine trial in Sweden (Gustafsson, NEJM, 1996, 334, 349-355). Sera from children with whooping cough, vaccinated with Diphtheria Tetanus Pertussis (DTP) whole-cell (wc), acellular 5 (DPTa5), or with the 2 component (a2) vaccines and from infants receiving only DT (n=10 for each group) were tested with high-content peptide microarrays containing 17 Bp proteins displayed as linear (n=3175) peptide stretches. Slides were incubated with serum and peptide-IgG complexes detected with Cy5-labeled goat anti-human IgG and analyzed using a GenePix 4000B microarray scanner, followed by statistical analysis, using PAM (Prediction Analysis for Microarrays) and the identification of uniquely recognized peptide epitopes. 367/3,085 (11.9%) peptides were recognized in 10/10 sera from children with whooping cough, 239 (7.7%) in DTPwc, 259 (8.4%) in DTPa5, 105 (3.4%) DTPa2, 179 (5.8%) in the DT groups. Recognition of strongly recognized peptides was similar between whooping cough and DPTwc, but statistically different between whooping cough vs. DTPa5 (p<0.05), DTPa2 and DT (p<0.001 vs. both) vaccines. 6/3,085 and 2/3,085 peptides were exclusively recognized in (10/10) sera from children with whooping cough and DTPa2 vaccination, respectively. DTPwc resembles more closely the whooping cough reactome as compared to acellular vaccines. We could identify a unique recognition signature common for each vaccination group (10/10 children). Peptide microarray technology allows detection of subtle differences in

  19. Serum of patients with antiphospholipid syndrome induces adhesion molecules in endothelial cells.

    Science.gov (United States)

    Engel, Bettina; Müller, Gregor; Roch, Beate; Schröder, Hans-Egbert; Aringer, Martin; Bornstein, Stefan R; Morawietz, Henning

    2017-11-01

    The antiphospholipid syndrome (APS) is a systemic auto-immune disease with an unclear pathophysiology. The aim of our study was to understand the development of APS on a cellular level. Therefore, we analyzed the influence of human serum of APS patients on endothelial expression of specific genes and proteins in comparison to a control group. In this study, we analyzed the expression of ICAM-1, VCAM-1, E-selectin and annexin V in primary cultures of human umbilical vein endothelial cells (HUVEC) in response to 10% (v/v) serum of control patients (n = 6), patients with systemic lupus erythematosus (SLE) and no APS (n = 4) or APS patients (n = 9) for 24 h. Total RNA was prepared from confluent endothelial cell layers and mRNA expression of ICAM-1, VCAM-1 and E-selectin was analyzed by reverse transcription polymerase-chain reaction (RT-PCR). The protein expression was determined by Western blot. Serum protein concentrations of soluble forms of adhesion molecules sICAM-1 and sVCAM-1 were quantified by ELISA. Gene expression data were correlated with clinical parameters. The mRNA expression of ICAM-1 was increased in cells incubated with serum from APS patients (166 ± 22% of control; P = 0.023). Serum of patients with (SLE)/no APS caused a 1.4-fold higher ICAM-1 mRNA level. Western blot analysis showed an increase in protein expression of adhesion molecules ICAM-1 (260 ± 49%; P = 0.011) and VCAM-1 (357 ± 97%; P = 0.023) in cells that were incubated with serum from APS patients. Plasma analysis showed elevated levels of sVCAM-1 in APS patients (189 ± 34%; P = 0.045) compared to the levels measured in the control group. The sVCAM-1 plasma level was correlating with the frequency of abortions. An augmented expression of endothelial adhesion molecules is involved in the pathophysiology of patients with antiphospholipid syndrome. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Serum induced degradation of 3D DNA box origami observed by high speed atomic force microscope

    DEFF Research Database (Denmark)

    Jiang, Zaixing; Zhang, Shuai; Yang, Chuanxu

    2015-01-01

    3D DNA origami holds tremendous potential to encapsulate and selectively release therapeutic drugs. Observations of real-time performance of 3D DNA origami structures in physiological environment will contribute much to its further applications. Here, we investigate the degradation kinetics of 3D...... DNA box origami in serum using high-speed atomic force microscope optimized for imaging 3D DNA origami in real time. The time resolution allows characterizing the stages of serum effects on individual 3D DNA box origami with nanometer resolution. Our results indicate that the whole digest process...... is a combination of a rapid collapse phase and a slow degradation phase. The damages of box origami mainly happen in the collapse phase. Thus, the structure stability of 3D DNA box origami should be further improved, especially in the collapse phase, before clinical applications...

  1. Thyroid iodine content and serum thyroglobulin: cues to the natural history of destruction-induced thyroiditis

    International Nuclear Information System (INIS)

    Smallridge, R.C.; De Keyser, F.M.; Van Herle, A.J.; Butkus, N.E.; Wartofsky, L.

    1986-01-01

    Twenty-eight patients with destructive thyroiditis were followed to study the natural history of healing of thyroid gland injury. All had sequential measurements of thyroidal iodine [ 127 I] content by fluorescent scanning (normal mean, 10.1 mg), 17 had serial serum thyroglobulin (Tg) measurements (normal, less than 21 ng/ml), and 13 had perchlorate discharge studies during the recovery phase. Seventeen patients had painful subacute thyroiditis (SAT), 9 had painless thyroiditis with thyrotoxicosis (PTT), and 2 had postpartum thyroiditis with thyrotoxicosis (PPT). Thyroidal iodine content decreased from a mean of 9.8 to a nadir of 3.8 mg in patients with SAT and from 8.5 to a nadir of 3.5 mg in patients with PTT. Mean serum Tg concentrations were highest (approximately 165 ng/ml) in both groups 1-3 months after the onset of symptoms. Abnormalities in both 127 I content and Tg levels persisted for 2 or more yr in some individuals. No patient had detectable Tg antibodies by hemagglutination, but low titers were detected intermittently by sensitive RIA in 5 PTT patients. Microsomal antibodies were positive in only 1 of 16 SAT patients, but in 4 of 7 PTT patients and in both PPT patients. Three patients had positive perchlorate discharge tests (2 of 8 with SAT, 0 of 4 with PTT, and 1 of 1 with PPT). Permanent hypothyroidism occurred in 3 patients (2 with PTT; 1 with SAT and positive antibodies), but did not correlate with perchlorate results. HLA typing and serum immunoglobulin measurements were not useful for predicting the clinical course. These data indicate that several years may be necessary for complete resolution of destructive thyroiditis; many patients have evidence of thyroid injury persisting long after serum thyroid hormone and TSH levels become normal

  2. Magnesium sulfate reduces formalin-induced orofacial pain in rats with normal magnesium serum levels.

    Science.gov (United States)

    Srebro, Dragana P; Vučković, Sonja M; Dožić, Ivan S; Dožić, Branko S; Savić Vujović, Katarina R; Milovanović, Aleksandar P; Karadžić, Branislav V; Prostran, Milica Š

    2018-02-01

    In humans, orofacial pain has a high prevalence and is often difficult to treat. Magnesium is an essential element in biological a system which controls the activity of many ion channels, neurotransmitters and enzymes. Magnesium produces an antinociceptive effect in neuropathic pain, while in inflammatory pain results are not consistent. We examined the effects of magnesium sulfate using the rat orofacial formalin test, a model of trigeminal pain. Male Wistar rats were injected with 1.5% formalin into the perinasal area, and the total time spent in pain-related behavior (face rubbing) was quantified. We also spectrophotometrically determined the concentration of magnesium and creatine kinase activity in blood serum. Magnesium sulfate administered subcutaneously (0.005-45mg/kg) produced significant antinociception in the second phase of the orofacial formalin test in rats at physiological serum concentration of magnesium. The effect was not dose-dependent. The maximum antinociceptive effect of magnesium sulfate was about 50% and was achieved at doses of 15 and 45mg/kg. Magnesium did not affect increase the levels of serum creatine kinase activity. Preemptive systemic administration of magnesium sulfate as the only drug can be used to prevent inflammatory pain in the orofacial region. Its analgesic effect is not associated with magnesium deficiency. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

  3. Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy.

    Science.gov (United States)

    Sun, S; Henriksen, K; Karsdal, M A; Armbrecht, G; Belavý, D L; Felsenberg, D; Rittweger, J; Wang, Y; Zheng, Q; Nedergaard, A F

    2014-10-01

    In this study we sought to determine whether a Titin peptide fragment can serve as a clinical biomarker for changes in muscle mass. Mass spectrometry was used to identify Titin fragment in urine. An antibody against this Titin sequence was raised and used to develop a competitive ELISA assay for measurement in serum. Rat tissue extractions in the presence or absence of a series of proteases of interest were used to identify its enzymatic origin. A rat model of dexamethasone (DEX) induced muscle atrophy and a human 56-day bed rest study with and without vibration therapy were used to assess biological and clinical relevance. A technically robust ELISA measuring the Titin fragment was developed against a Titin peptide fragment identified in human urine. The fragment was shown to be produced primarily by MMP-2 cleavage of Titin. In the rat muscle DEX induced atrophy model, Titin-MMP2 fragment was decreased in the beginning of DEX treatment, and then significantly increased later on during DEX administration. In the human bed rest study, the Titin-MMP2 fragment was initially decreased 11.9 (±3.7) % after 1day of bed rest, and then gradually increased ending up at a 16.4 (±4.6) % increase at day 47. We developed a robust ELISA measuring a muscle derived MMP-2 generated Titin degradation fragment in rat and human serum. Importantly, the fragment can be measured in serum and that these levels are related to induction of skeletal muscle atrophy. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Effect of Urtica Dioica Decoction on Serum Glucose and Lipid Profile in Stereptozotocin Induced Diabetic Male Rats

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Sahraki

    Full Text Available Background: Since Urtica dioica is a traditional treatment plant and is used for antihypertensive, antilipidemic and antidiabetic agents, this survey was carried out to evaluate the effect of Urtica dioica decoction on serum glucose and lipid profile in diabetic male rats induced by stereptozotocin (STZ. Materials and Methods: This experiment was performed on 30 Wistar-Albino male rats, weighing 200-250 g, which were divided in sham control (A, diabetic control (B and diabetic test groups (C randomly (N=10. Type I diabetes was induced by single intraperitoneal injection of STZ (65 mg/kg. Test group received 0.40-0.60 ml of Urtica dioica decoction for a month by gavages, control group (B received the same volume of distill water. Group (A did not receive any agent during the experiment period. Finally, animals were anesthetized, sacrificed and blood samples were collected from the cervical vein. Then, serum glucose and lipid profiles were measured by ordinary methods. Data were analyzed by SPSS-11, using ANOVA and post hoc Tukey tests. Results were expressed as mean±SD, and statistical difference was considered significant by p<0.05.Results: Results in the present study showed that fasting blood glucose (FBS, total cholesterol (TCho, triglyceride (TG, LDL, food and water intake were significantly decreased in group C compared with those of group B, but body weight gain was significantly increased compared with that of control group (B.Conclusion: These results indicated that Urtica dioica decoction caused decreased FBS and improved serum lipids in diabetic male rats. Some more studies have shown the same mechanism.

  5. 25-hydroxy-Vitamin D status: limitations in comparison and clinical interpretation of serum-levels across different assay methods.

    Science.gov (United States)

    Enko, Dietmar; Fridrich, Leo; Rezanka, Erwin; Stolba, Robert; Ernst, Juliane; Wendler, Iris; Fabian, Daniel; Hauptlorenz, Susanne; Halwachs-Baumann, Gabriele

    2014-01-01

    Background: Over the last decade, clinical interest to evaluate human 25-hydroxy-vitamin D (25[OH]D) serum levels has increased exponentially. In the present study, four chemiluminescence immunoassays (CLIA), one radioimmunoassy (RIA), and one high performance liquid chromatography (HPLC) method were compared and also with the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in view of 25(OH)D serum level determination. Methods: For the method comparison, blood samples from 133 consecutive patients were prospectively collected. All participants gave written informed consent for their blood samples to be used in this study. They came to the Department of Nuclear Medicine of the Central Hospital Steyr (Austria) for osteodensidometric measurement as part of their preventive medical check-up. Pearson's correlation coefficients, Bland-Altman plots, and paired t-tests were calculated. Assay-specific reference ranges were considered using blood samples from persons with normal parathormone, calcium, and total-protein values (n = 97). Results: The highest correlation was between the HPLC and the LC-MS/MS method (r = 0.96). The lowest correlation was between the cobas Vitamin D3 assay (Roche) and any of the evaluated assays (r = 0.46 - 0.63). Bland-Altman plots revealed a big negative mean bias in three assays (cobas Vitamin D3 assay [Roche]: -22.8; DiaSorin LIAISON [25[OH]D total CLIA [Diasorin]: -18.4; Diasorin 25[OH]D125 I RIA [Diasorin]: -23.8 [nmol/L]) and a much smaller positive mean bias in the other assays (ClinRep complete 25[OH]D2/D3 HPLC kit [Recipe]: 2.7; ADVIA Centaur Vitamin D total assay [Siemens]: 8.2; IDS total vitamin D assay [Immunodiagnostic Systems]: 12.1 [nmol/L]) compared to the LC-MS/MS method. Meanwhile, the manufacturer has withdrawn the cobas Vitamin D3 assay from the market. Conclusions: Poor antibody specificity with cross-reactivity to other vitamin D metabolites, incomplete extraction of the 25(OH)D analyte from the vitamin D

  6. The effect of Stevia rebaudiana on serum omentin and visfatin level in STZ-induced diabetic rats.

    Science.gov (United States)

    Akbarzadeh, Samad; Eskandari, Fatemeh; Tangestani, Hadis; Bagherinejad, Somaieh Tangerami; Bargahi, Afshar; Bazzi, Parviz; Daneshi, Adel; Sahrapoor, Azam; O'Connor, William J; Rahbar, Ali Reza

    2015-03-01

    Recently the role of adipocytokines in relationship to incidence of diabetes has been demonstrated. One of the medicinal plants that are used in the treatment of diabetes is stevia. This study investigates the effect of stevia on serum omentin and visfatin levels as novel adipocytokines in diabetic induced rats to find potential mechanisms for the anti hyperglycemic effect of stevia. Forty male wistar rats weighing 180-250 g were induced with diabetes by intraperitoneal injection of streptozotocin (STZ). The animals were divided into 5 groups of 8. Rats in group 1 (non-diabetic control) and group 2 (diabetic control) were treated with distilled water, and the rats in the treated groups, group 3 (T250), group 4 (T500), and group 5 (T750) were treated with stevia, gavaged every day at 9 a.m. in doses of 250, 500, and 750 mg/kg, respectively. At the end of the study significant reductions in fasting blood sugar (FBS), the homeostasis model assessment insulin resistance (HOMA-IR), triglyceride (TG), alkaline phosphatase (ALP), and Omentin level were found in groups 3 and 4 in comparison with group 2. Pancreatic histopathology slides demonstrated that stevia extract did not induce any increase in the number of β-cells. The conclusion is that prescription of stevia in the doses of 250 and 500 mg/kg/d decreases the omentin level indirectly via activating insulin sensitivity and lowering blood glucose in STZ-induced diabetic rats.

  7. Serum and mucosal immune responses to an inactivated influenza virus vaccine induced by epidermal powder immunization.

    Science.gov (United States)

    Chen, D; Periwal, S B; Larrivee, K; Zuleger, C; Erickson, C A; Endres, R L; Payne, L G

    2001-09-01

    Both circulating and mucosal antibodies are considered important for protection against infection by influenza virus in humans and animals. However, current inactivated vaccines administered by intramuscular injection using a syringe and needle elicit primarily circulating antibodies. In this study, we report that epidermal powder immunization (EPI) via a unique powder delivery system elicits both serum and mucosal antibodies to an inactivated influenza virus vaccine. Serum antibody responses to influenza vaccine following EPI were enhanced by codelivery of cholera toxin (CT), a synthetic oligodeoxynucleotide containing immunostimulatory CpG motifs (CpG DNA), or the combination of these two adjuvants. In addition, secretory immunoglobulin A (sIgA) antibodies were detected in the saliva and mucosal lavages of the small intestine, trachea, and vaginal tract, although the titers were much lower than the IgG titers. The local origin of the sIgA antibodies was further shown by measuring antibodies released from cultured tracheal and small intestinal fragments and by detecting antigen-specific IgA-secreting cells in the lamina propria using ELISPOT assays. EPI with a single dose of influenza vaccine containing CT or CT and CpG DNA conferred complete protection against lethal challenges with an influenza virus isolated 30 years ago, whereas a prime and boost immunizations were required for protection in the absence of an adjuvant. The ability to elicit augmented circulating antibody and mucosal antibody responses makes EPI a promising alternative to needle injection for administering vaccines against influenza and other diseases.

  8. Friction induced hunting limit cycles : a comparison between the LuGre and switch friction model

    NARCIS (Netherlands)

    Hensen, R.H.A.; Molengraft, van de M.J.G.; Steinbuch, M.

    2003-01-01

    In this paper, friction induced limit cycles are predicted for a simple motion system consisting of a motor-driven inertia subjected to friction and a PID-controlled regulator task. The two friction models used, i.e., (i) the dynamic LuGre friction model and (ii) the static switch friction model,

  9. Limiting of photo induced changes in amorphous chalcogenide/alumino-silicate nanomultilayers

    International Nuclear Information System (INIS)

    Charnovych, S.; Nemec, P.; Nazabal, V.; Csik, A.; Allix, M.; Matzen, G.; Kokenyesi, S.

    2011-01-01

    Highlights: → Amorphous chalcogenides were investigated in this work. → Photo-induced effects were investigated in the created thin films. → Limiting of photo induced changes in amorphous chalcogenide/alumino-silicate nanomultilayers have been studied. - Abstract: Photo induced changes in amorphous As 20 Se 80 /alumino-silicate nanomultilayers (NML) produced by pulsed laser deposition (PLD) method have been studied in this work. The aim was to investigate the photo induced optical and surface relief changes due to the band gap illumination under the size- and hard cover limited conditions. It was observed that the hard cover layer on the surface of the uniform film or alumino-silicate sub-layers in the NML structure influences the photo darkening and restricts surface relief formations in As 20 Se 80 film or in the related NML compared with this effect in a pure chalcogenide layer. The influence of hard layers is supposed to be connected with limiting the free volume formation at the initial stage of the transformation process, which in turn limits the atomic movement and so the surface relief formation.

  10. Antioxidative phytochemicals from Rhododendron oldhamii Maxim. leaf extracts reduce serum uric acid levels in potassium oxonate-induced hyperuricemic mice.

    Science.gov (United States)

    Tung, Yu-Tang; Lin, Lei-Chen; Liu, Ya-Ling; Ho, Shang-Tse; Lin, Chi-Yang; Chuang, Hsiao-Li; Chiu, Chien-Chao; Huang, Chi-Chang; Wu, Jyh-Horng

    2015-12-01

    Some of the genus Rhododendron was used in traditional medicine for arthritis, acute and chronic bronchitis, asthma, pain, inflammation, rheumatism, hypertension and metabolic diseases and many species of the genus Rhododendron contain a large number of phenolic compounds and antioxidant properties that could be developed into pharmaceutical products. In this study, the antioxidative phytochemicals of Rhododendron oldhamii Maxim. leaves were detected by an online HPLC-DPPH method. In addition, the anti-hyperuricemic effect of the active phytochemicals from R. oldhamii leaf extracts was investigated using potassium oxonate (PO)-induced acute hyperuricemia. Six phytochemicals, including (2R, 3R)-epicatechin (1), (2R, 3R)-taxifolin (2), (2R, 3R)-astilbin (3), hyposide (4), guaijaverin (5), and quercitrin (6), were isolated using the developed screening method. Of these, compounds 3, 4, 5, and 6 were found to be major bioactive phytochemicals, and their contents were determined to be 130.8 ± 10.9, 105.5 ± 8.5, 104.1 ± 4.7, and 108.6 ± 4.0 mg per gram of EtOAc fraction, respectively. In addition, the four major bioactive phytochemicals at the same dosage (100 mmol/kg) were administered to the abdominal cavity of potassium oxonate (PO)-induced hyperuricemic mice, and the serum uric acid level was measured after 3 h of administration. H&E staining showed that PO-induced kidney injury caused renal tubular epithelium nuclear condensation in the cortex areas or the appearance of numerous hyaline casts in the medulla areas; treatment with 100 mmol/kg of EtOAc fraction, (2R, 3R)-astilbin, hyposide, guaijaverin, and quercitrin significantly reduced kidney injury. In addition, the serum uric acid level was significantly suppressed by 54.1, 35.1, 56.3, 56.3, and 53.2 %, respectively, by the administrations of 100 mmol/kg EtOAc fraction and the derived major phytochemicals, (2R, 3R)-astilbin, hyposide, guaijaverin, and quercitrin, compared to the PO group. The administration

  11. Serum adiposity-induced biomarkers in obese and lean children with recently diagnosed autoimmune type 1 diabetes.

    Science.gov (United States)

    Redondo, M J; Rodriguez, L M; Haymond, M W; Hampe, C S; Smith, E O; Balasubramanyam, A; Devaraj, S

    2014-12-01

    Obesity increases the risk of cardiovascular disease and diabetic complications in type 1 diabetes. Adipokines, which regulate obesity-induced inflammation, may contribute to this association. We compared serum adipokines and inflammatory cytokines in obese and lean children with new-onset autoimmune type 1 diabetes. We prospectively studied 32 lean and 18 obese children (age range: 2-18 yr) with new-onset autoimmune type 1 diabetes and followed them for up to 2 yr. Serum adipokines [leptin, total and high molecular weight (HMW) adiponectin, omentin, resistin, chemerin, visfatin], cytokines [interferon (IFN)-gamma, interleukin (IL)-10, IL-12, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha] and C-reactive protein (CRP) were measured at a median of 7 wk after diagnosis (range: 3-16 wk). Lean children were 71.9% non-Hispanic White, 21.9% Hispanic, and 6.3% African-American, compared with 27.8, 55.6, and 16.7%, respectively, for obese children (p = 0.01). Compared with lean children, obese children had significantly higher serum leptin, visfatin, chemerin, TNF-alpha and CRP, and lower total adiponectin and omentin after adjustment for race/ethnicity and Tanner stage. African-American race was independently associated with higher leptin among youth ≥10 yr (p = 0.007). Leptin levels at onset positively correlated with hemoglobin A1c after 1-2 yr (p = 0.0001) independently of body mass index, race/ethnicity, and diabetes duration. Higher TNF-alpha was associated with obesity and female gender, after adjustment for race/ethnicity (p = 0.0003). Obese children with new-onset autoimmune type 1 diabetes have a proinflammatory profile of circulating adipokines and cytokines that may contribute to the development of cardiovascular disease and diabetic complications. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Clinical significance of measurement of changes of serum TNF-α, IL-6 and IL-8 centent after treatment in patients with pregnancy induced hypertension (PIH)

    International Nuclear Information System (INIS)

    Wang Guiying

    2008-01-01

    Objective: To explore the clinical significance of changes of serum TNF-α, IL-6 and IL-8 levels in patients with pregnancy induced hypertension. Methods: Serum TNF-α, IL-6 and IL-8 levels were measured with RIA in 36 patients with pregnancy induced hypertension both before and after 2 weeks of treatment as well as in 35 controls. Results: Before treatment, the serum TNF-α, IL-6 and IL-8 levels were significantly higher in patients with PIH than those in the controls (P 0.05). Conclusion: The inflammatory cytokines such as TNF-α, IL-6 and IL-8 may play important roles in the pathogenesis of pregnancy induced hypertension. (authors)

  13. Carbonate radical anion-induced electron transfer in bovine serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Joshi, Ravi [Chemistry Group, Bhabha Atomic Research Centre, Mumbai 400 085 (India)]. E-mail: rjudrin@yahoo.com; Mukherjee, T. [Chemistry Group, Bhabha Atomic Research Centre, Mumbai 400 085 (India)

    2006-07-15

    Reaction of native and thermally denatured bovine serum albumin (BSA) with carbonate radical anion (CO{sub 3}{sup -} radical) has been studied using pulse radiolysis technique. Scavenging of CO{sub 3}{sup -} radical by native BSA and consequent electron transfer from tyrosine to tryptophan radical has been observed to occur with almost same rate constant (k{approx}1.7x10{sup 8} dm{sup 3} mol{sup -1} s{sup -1}) at pH 8.8. Effect of structural changes, due to thermal denaturation, on scavenging of CO{sub 3}{sup -} radical and the electron transfer process have been studied and discussed in this paper.

  14. Brain-derived neurotrophic factor (BDNF) serum basal levels is not affected by power training in mobility-limited older adults - A randomized controlled trial.

    Science.gov (United States)

    Hvid, L G; Nielsen, M K F; Simonsen, C; Andersen, M; Caserotti, P

    2017-07-01

    Brain-derived neurotrophic factor (BDNF) is a potential important factor involved in neuroplasticity, and may be a mediator for eliciting adaptations in neuromuscular function and physical function in older individuals following physical training. As power training taxes the neural system to a very high extent, it may be particularly effective in terms of eliciting increases in systemic BDNF levels. We examined the effects of 12weeks of power training on mature BDNF (mBDNF) and total BDNF (tBDNF) in mobility-limited older adults from the Healthy Ageing Network of Competence (HANC) study. We included 47 older men and women: n=22 in the training group (TG: progressive high intensity power training, 2 sessions per week; age 82.7±5.4years, 55% women) and n=25 in the control group (CG: no interventions; age 82.2±4.5years, 76% women). Following overnight fasting, basal serum levels of mBDNF and tBDNF were assessed (human ELISA kits) at baseline and post-intervention. At baseline, mBDNF and tBDNF levels were comparable in the two groups, TG and CG. Post-intervention, no significant within-group or between-group changes were observed in mBDNF or tBDNF. Moreover, when divided into responder tertiles based upon changes in mBDNF and tBDNF (i.e. decliners, maintainers, improvers), respectively, comparable findings were observed for TG and CG. Altogether, basal systemic levels of serum mBDNF and tBDNF are not affected in mobility-limited older adults following 12-weeks of power training, and do not appear to be a major mechanistic factor mediating neuroplasticity in mobility-limited older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Globular Adiponectin Inhibits the Apoptosis of Mesenchymal Stem Cells Induced by Hypoxia and Serum Deprivation via the AdipoR1-Mediated Pathway

    Directory of Open Access Journals (Sweden)

    Xia-Qiu Tian

    2016-02-01

    Full Text Available Background/Aims: Poor viability of transplanted mesenchymal stem cells (MSCs within the ischemic heart limits their therapeutic potential for cardiac repair. Globular adiponectin (gAPN exerts anti-apoptotic effects on several types of stem cells. Herein, we investigated the effect of gAPN on the MSCs against apoptosis induced by hypoxia and serum deprivation (H/SD. Methods: MSCs exposed to H/SD conditions were treated with different concentrations of gAPN. To identify the main type of receptor, MSCs were transfected with siRNA targeting adiponectin receptor 1 or 2 (AdipoR1 or AdipoR2. To elucidate the downstream pathway, MSCs were pre-incubated with AMPK inhibitor Compound C. Apoptosis, caspase-3 activity and mitochondrial membrane potential were evaluated. Results: H/SD-induced MSCs apoptosis and caspase-3 activation were attenuated by gAPN in a concentration-dependent manner. gAPN increased Bcl-2 and decreased Bax expressions. The loss of mitochondrial membrane potential induced by H/SD was also abolished by gAPN. The protective effect of gAPN was significantly attenuated after the knockdown of AdipoR1 rather than AdipoR2. Moreover, Compound C partly suppressed the anti-apoptotic effect of gAPN. Conclusions: gAPN inhibits H/SD-induced apoptosis in MSCs via AdipoR1-mediated pathway, possibly linked to the activation of AMPK. gAPN may be a novel survival factor for MSCs in the ischemic engraftment environment.

  16. Globular Adiponectin Inhibits the Apoptosis of Mesenchymal Stem Cells Induced by Hypoxia and Serum Deprivation via the AdipoR1-Mediated Pathway.

    Science.gov (United States)

    Tian, Xia-Qiu; Yang, Yue-Jin; Li, Qing; Huang, Pei-Sen; Li, Xiang-Dong; Jin, Chen; Qi, Kang; Jiang, Lei-Pei; Chen, Gui-Hao

    2016-01-01

    Poor viability of transplanted mesenchymal stem cells (MSCs) within the ischemic heart limits their therapeutic potential for cardiac repair. Globular adiponectin (gAPN) exerts anti-apoptotic effects on several types of stem cells. Herein, we investigated the effect of gAPN on the MSCs against apoptosis induced by hypoxia and serum deprivation (H/SD). MSCs exposed to H/SD conditions were treated with different concentrations of gAPN. To identify the main type of receptor, MSCs were transfected with siRNA targeting adiponectin receptor 1 or 2 (AdipoR1 or AdipoR2). To elucidate the downstream pathway, MSCs were pre-incubated with AMPK inhibitor Compound C. Apoptosis, caspase-3 activity and mitochondrial membrane potential were evaluated. H/SD-induced MSCs apoptosis and caspase-3 activation were attenuated by gAPN in a concentration-dependent manner. gAPN increased Bcl-2 and decreased Bax expressions. The loss of mitochondrial membrane potential induced by H/SD was also abolished by gAPN. The protective effect of gAPN was significantly attenuated after the knockdown of AdipoR1 rather than AdipoR2. Moreover, Compound C partly suppressed the anti-apoptotic effect of gAPN. gAPN inhibits H/SD-induced apoptosis in MSCs via AdipoR1-mediated pathway, possibly linked to the activation of AMPK. gAPN may be a novel survival factor for MSCs in the ischemic engraftment environment. © 2016 The Author(s) Published by S. Karger AG, Basel.

  17. Chemoradiation-induced changes in serum CEA and plasma TIMP-1 in patients with locally advanced rectal cancer

    DEFF Research Database (Denmark)

    Aldulaymi, Bahir; Christensen, Ib J; Sölétormos, György

    2010-01-01

    BACKGROUND: Preoperative biomarkers serum CEA and plasma TIMP-1 have been shown to have prognostic and predictive value in patients with colorectal cancer. The aim of the present study was to evaluate the possible impact of chemoradiotherapy (CRT) on preoperative biomarker levels in patients...... with rectal cancer. PATIENTS AND METHODS: Thirty-three patients with rectal cancer were prospectively included. The patients received CRT for 6-8 weeks. Blood samples were collected before CRT (pre-CRT) and preoperatively (post-CRT). RESULTS: Median CEA was 3.5 (range 0.6-36.1) µg/l and 2.4 (range 0.......0-10.2) µg/l (p=0.002) and median plasma TIMP-1 was 132.1 (range 77.8-342.7) µg/l and 140.0 (range 82.6-440.9) µg/l (p=0.04) in the pre- and post-CRT measurements, respectively. CONCLUSION: CRT induced a significant decrease in serum CEA and increase in plasma TIMP-1 levels. Therefore, the preoperative...

  18. Role of pH-induced structural change in protein aggregation in foam fractionation of bovine serum albumin

    Directory of Open Access Journals (Sweden)

    Rui Li

    2016-03-01

    Full Text Available For reducing protein aggregation in foam fractionation, the role of pH-induced structural change in the interface-induced protein aggregation was analyzed using bovine serum albumin (BSA as a model protein. The results show that the decrease in pH from 7.0 to 3.0 gradually unfolded the BSA structure to increase the molecular size and the relative content of β-sheet and thus reduced the stability of BSA in the aqueous solution. At the isoelectric point (pH 4.7, BSA suffered the lowest level in protein aggregation induced by the gas–liquid interface. In the pH range from 7.0 to 4.7, most BSA aggregates were formed in the defoaming process while in the pH range from 4.7 to 3.0, the BSA aggregates were formed at the gas–liquid interface due to the unfolded BSA structure and they further aggregated to form insoluble ones in the desorption process.

  19. Kaempferol-human serum albumin interaction: Characterization of the induced chirality upon binding by experimental circular dichroism and TDDFT calculations

    Science.gov (United States)

    Matei, Iulia; Ionescu, Sorana; Hillebrand, Mihaela

    2012-10-01

    The experimental induced circular dichroism (ICD) and absorption spectra of the achiral flavonoid kaempferol upon binding to human serum albumin (HSA) were correlated to electronic CD and UV-vis spectra theoretically predicted by time-dependent density functional theory (TDDFT). The neutral and four anionic species of kaempferol in various conformations were considered in the calculations. The appearance of the experimental ICD signal was rationalized in terms of kaempferol binding to HSA in a distorted, chiral, rigid conformation. The comparison between the experimental and simulated spectra allowed for the identification of the kaempferol species that binds to HSA, namely the anion generated by deprotonation of the hydroxyl group in position 7. This approach constitutes a convenient method for evidencing the binding species and for determining its conformation in the binding pocket of the protein. Its main advantage over the UV-vis absorption method lays in the fact that only the bound ligand species gives an ICD signal.

  20. Cadmium-induced bone effect is not mediated via low serum 1,25-dihydroxy vitamin D

    International Nuclear Information System (INIS)

    Engstroem, Annette; Skerving, Staffan; Lidfeldt, Jonas; Burgaz, Ann; Lundh, Thomas; Samsioe, Goeran; Vahter, Marie; Akesson, Agneta

    2009-01-01

    Cadmium is a widespread environmental pollutant, which is associated with increased risk of osteoporosis. It has been proposed that cadmium's toxic effect on bone is exerted via impaired activation of vitamin D, secondary to the kidney effects. To test this, we assessed the association of cadmium-induced bone and kidney effects with serum 1,25-dihydroxyvitamin D (1,25(OH) 2 D); measured by enzyme immunoassay. For the assessment, we selected 85 postmenopausal women, based on low (0.14-0.39 μg/L) or high (0.66-2.1 μg/L) urinary cadmium, within a cross-sectional population-based women's health survey in Southern Sweden. We also measured 25-hydroxy vitamin D, cadmium in blood, bone mineral density and several markers of bone remodeling and kidney effects. Although there were clear differences in both kidney and bone effect markers between women with low and high cadmium exposure, the 1,25(OH) 2 D concentrations were not significantly different (median, 111 pmol/L (5-95th percentile, 67-170 pmol/L) in low- and 125 pmol/L (66-200 pmol/L) in high-cadmium groups; p=0.08). Also, there was no association between 1,25(OH) 2 D and markers of bone or kidney effects. It is concluded that the low levels of cadmium exposure present in the studied women, although high enough to be associated with lower bone mineral density and increased bone resorption, were not associated with lower serum concentrations of 1,25(OH) 2 D. Hence, decreased circulating levels of 1,25(OH) 2 D are unlikely to be the proposed link between cadmium-induced effects on kidney and bone

  1. Influenza Virus Induces Inflammatory Response in Mouse Primary Cortical Neurons with Limited Viral Replication

    Directory of Open Access Journals (Sweden)

    Gefei Wang

    2016-01-01

    Full Text Available Unlike stereotypical neurotropic viruses, influenza A viruses have been detected in the brain tissues of human and animal models. To investigate the interaction between neurons and influenza A viruses, mouse cortical neurons were isolated, infected with human H1N1 influenza virus, and then examined for the production of various inflammatory molecules involved in immune response. We found that replication of the influenza virus in neurons was limited, although early viral transcription was not affected. Virus-induced neuron viability decreased at 6 h postinfection (p.i. but increased at 24 h p.i. depending upon the viral strain. Virus-induced apoptosis and cytopathy in primary cortical neurons were not apparent at 24 h p.i. The mRNA levels of inflammatory cytokines, chemokines, and type I interferons were upregulated at 6 h and 24 h p.i. These results indicate that the influenza virus induces inflammatory response in mouse primary cortical neurons with limited viral replication. The cytokines released in viral infection-induced neuroinflammation might play critical roles in influenza encephalopathy, rather than in viral replication-induced cytopathy.

  2. Effects of limited concentrate feeding on growth and blood and serum variables, and on nutrient digestibility and gene expression of hepatic gluconeogenic enzymes in dairy calves.

    Science.gov (United States)

    Lohakare, J D; van de Sand, H; Gerlach, K; Hosseini, A; Mielenz, M; Sauerwein, H; Pries, M; Südekum, K-H

    2012-02-01

    This study elucidated the effects of limited concentrate feeding on growth, nutrient digestibility, blood profile and gene expression of gluconeogenic enzymes in the liver of dairy calves. The study utilized 36 German Holstein dairy calves (5-7 days of age) divided into two groups of 18 calves each for 150 days. Control group calves received 2 kg/(calf × day) of concentrate, whereas calves in the restricted group received only 1 kg/(calf × day). Good quality forage (mixture of maize and grass silages) was available for ad libitum consumption to both groups. The intake of milk replacer before weaning, and of concentrate were recorded daily per calf; however, the consumption of forages was quantified as daily average of the group. Body weights (BW) were recorded at start and on days 35, 70, 112 and 150. Blood and serum samples and spot urinary and faecal samples were also collected at similar time points. On days 70 and 150, liver biopsies were collected from seven animals in each group. The BW was not different between the groups at all times. Total BW gain in the control group was 124 kg as opposed to 111 kg in restricted group that led to average BW gain of 827 g/day and 739 g/day in respective groups, and the differences were significant (p = 0.018). As planned, the control group had higher concentrate and lower forage intake than the restricted group. The blood haemoglobin, haematocrit and serum variables (glucose, total protein, albumin and urea) were within the normal range in both groups, but serum glucose was higher (p < 0.05) in control than in restricted group at 70 days. There was no difference between groups in organic matter (OM) digestibility which declined (p < 0.001) with increasing age in both groups. Microbial crude protein (MCP) synthesis estimated from urinary allantoin excretion increased (p < 0.001) in both groups with increasing age but was not different between groups. The mRNA expressions for the gluconeogenic enzymes, cytosolic and

  3. Amino acid limitation induces down-regulation of WNT5a at transcriptional level

    International Nuclear Information System (INIS)

    Wang Zuguang; Chen Hong

    2009-01-01

    An aberrant WNT signaling contributes to the development and progression of multiple cancers. WNT5a is one of the WNT signaling molecules. This study was designed to test the hypothesis that amino acid deprivation induces changes in the WNT signaling pathway in colon cancer cells. Results showed that targets of the amino acid response pathway, ATF3 and p21, were induced in the human colon cancer cell line SW480 during amino acid limitation. There was a significant decrease in the WNT5a mRNA level following amino acid deprivation. The down-regulation of WNT5a mRNA by amino acid deprivation is not due to mRNA destabilization. There is a reduction of nuclear β-catenin protein level by amino acid limitation. Under amino acid limitation, phosphorylation of ERK1/2 was increased and the blockage of ERK1/2 by the inhibitor U0126 partially restored WNT5a mRNA level. In conclusion, amino acid limitation in colon cancer cells induces phosphorylation of ERK1/2, which then down-regulates WNT5a expression.

  4. Reproducibility of biomarkers in induced sputum and in serum from chronic smokers

    NARCIS (Netherlands)

    Zuiker, Rob G. J. A.; Kamerling, Ingrid M. C.; Morelli, Nicoletta; Calderon, Cesar; Boot, J. Diderik; de Kam, Marieke; Diamant, Zuzana; Burggraaf, Jacobus; Cohen, Adam F.

    Rationale: Soluble inflammatory markers obtained from non-invasive airway sampling such as induced sputum may be useful biomarkers for targeted pharmaceutical interventions. However, before these soluble markers can be used as potential targets, their variability and reproducibility need to be

  5. Limited Link between Oxidative Stress and Ochratoxin A—Induced Renal Injury in an Acute Toxicity Rat Model

    Directory of Open Access Journals (Sweden)

    Liye Zhu

    2016-12-01

    Full Text Available Ochratoxin A (OTA displays nephrotoxicity and hepatotoxicity. However, in the acute toxicity rat model, there is no evidence on the relationship between OTA and nephrotoxicity and hepatotoxicity. Based on this, the integrated analysis of physiological status, damage biomarkers, oxidative stress, and DNA damage were performed. After OTA treatment, the body weight decreased and AST, ALP, TP, and BUN levels in serum increased. Hydropic degeneration, swelling, vacuolization, and partial drop occurred in proximal tubule epithelial cells. PCNA and Kim-1 were dose-dependently increased in the kidney, but Cox-2 expression and proliferation were not found in the liver. In OTA-treated kidneys, the mRNA expressions of Kim-1, Cox-2, Lcn2, and Clu were dose-dependently increased. The mRNA expressions of Vim and Cox-2 were decreased in OTA-treated livers. Some oxidative stress indicators were altered in the kidneys (ROS and SOD and livers (SOD and GSH. DNA damage and oxidative DNA damage were not found. In conclusion, there is a limited link between oxidative stress and OTA-induced renal injury in an acute toxicity rat model.

  6. Clinical significance of determination of changes of serum Hcy, ET and BNP levels After treatment in patients with pregnancy induced hypertension (PIH)

    International Nuclear Information System (INIS)

    He Hongling

    2010-01-01

    Objective: To study the clinical significance of changes of serum Hcy, ET and BNP levels after treatment in patients with pregnancy induced hypertension(PIH). Methods: Serum Hcy (with ELISA), ET and BNP (with RIA) levels were determined in 32 patients with PIH both before and after treatment as well as in 35 controls. Results: Before treatment, serum Hcy, ET and BNP levels in patients with PIH were significantly higher than those in controls (P < 0.01). After 1 month of treatment the levels dropped markedly, but still remained significantly higher(P < 0.05). Conclusion: Serum Hcy, ET and BNP levels were closely related to the diseases process of PIH and were of prognostic values. (authors)

  7. Validation of basophil histamine release against the autologous serum skin test and outcome of serum-induced basophil histamine release studies in a large population of chronic urticaria patients

    DEFF Research Database (Denmark)

    Platzer, M H; Grattan, C E H; Poulsen, Lars K.

    2005-01-01

    the immunoglobulin E (IgE) or the high affinity IgE receptor (FcepsilonRI) and serum-induced histamine release (HR) from basophils and mast cells. We have examined the correlation between the ASST and a new basophil histamine-releasing assay (the HR-Urtikaria test) in a group of well-characterized CU patients...... and subsequently determined the frequency of HR-Urticaria-positive sera from a larger population of CU patients....

  8. The Stringent Response Induced by Phosphate Limitation Promotes Purine Salvage in Agrobacterium fabrum.

    Science.gov (United States)

    Sivapragasam, Smitha; Deochand, Dinesh K; Meariman, Jacob K; Grove, Anne

    2017-10-31

    Agrobacterium fabrum induces tumor growth in susceptible plant species. The upregulation of virulence genes that occurs when the bacterium senses plant-derived compounds is enhanced by acidic pH and limiting inorganic phosphate. Nutrient starvation may also trigger the stringent response, and purine salvage is among the pathways expected to be favored under such conditions. We show here that phosphate limitation induces the stringent response, as evidenced by production of (p)ppGpp, and that the xdhCSML operon encoding the purine salvage enzyme xanthine dehydrogenase is upregulated ∼15-fold. The xdhCSML operon is under control of the TetR family transcription factor XdhR; direct binding of ppGpp to XdhR attenuates DNA binding, and the enhanced xdhCSML expression correlates with increased cellular levels of (p)ppGpp. Xanthine dehydrogenase may also divert purines away from salvage pathways to form urate, the ligand for the transcription factor PecS, which in the plant pathogen Dickeya dadantii is a key regulator of virulence gene expression. However, urate levels remain low under conditions that produce increased levels of xdhCSML expression, and neither acidic pH nor limiting phosphate results in induction of genes under control of PecS. Instead, expression of such genes is induced only by externally supplemented urate. Taken together, our data indicate that purine salvage is favored during the stringent response induced by phosphate starvation, suggesting that control of this pathway may constitute a novel approach to modulating virulence. Because bacterial purine catabolism appears to be unaffected, as evidenced by the absence of urate accumulation, we further propose that the PecS regulon is induced by only host-derived urate.

  9. Serum pentraxin-3 and tumor necrosis factor-like weak inducer of apoptosis (TWEAK predict severity of infections in acute decompensated cirrhotic patients

    Directory of Open Access Journals (Sweden)

    Wen-Chien Fan

    2017-12-01

    Full Text Available Background: Pentraxin-3 (PTX3 and soluble tumor necrosis factor (TNF-like weak inducer of apoptosis (sTWEAK are new candidate prognostic markers for comorbidities and mortality in various inflammatory diseases. Acute decompensation of cirrhosis is characterized by acute exacerbation of chronic systemic inflammation. Recently, increased circulating PTX3 levels have been reported in nonalcoholic steatohepatitis patients and positively correlated with disease severity. This study aims to explore serum PTX3/sTWEAK levels and their relationship with clinical outcomes in cirrhotic patients with acute decompensation. Methods: We analyzed serum PTX3/sTWEAK levels in relation to inhospital and 3-month new clinical events and survivals in cirrhotic patients with acute decompensation. Results: During admission, serum PTX3/sTWEAK levels were significantly higher in acute decompensated cirrhotic patients than controls and positively correlated with protein-energy wasting (PEW, new infections, long hospital stays, high medical costs, and high mortality. During a 3-month follow-up, acute decompensated cirrhotic patients with high serum PTX3/sTWEAK levels had more episodes of unplanned readmission and high 3-month mortality. On multivariate analysis, high PTX3/sTWEAK levels and PEW were independent risk factors for high mortality. Conclusion: High serum PTX3/sTWEAK levels and PEW are common in cirrhotic patients with acute decompensation. As compared with low serum PTX3 and sTWEAK cases, cirrhotic patients with high serum PTX3/sTWEAK levels a have higher probability of new severe infections, severe sepsis, septic shock, type 1 hepatorenal syndrome, in-hospital, and 3-month follow-up mortalities. Therefore, high serum PTX3/sTWEAK levels on hospital admission predict disease severity and case fatality in cirrhotic patients with acute decompensation. Keywords: pentraxin-3, protein-energy wasting, soluble TNF-like weak inducer of apoptosis

  10. Mangiferin binding to serum albumin is non-saturable and induces conformational changes at high concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Freitas, P.G.; Barbosa, A.F. [Biochemistry Laboratory, Institute of Exact Sciences, Federal University of Alfenas, Unifal-MG, R. Gabriel Monteiro da Silva, 700, 37130-000 Alfenas, MG (Brazil); Saraiva, L.A. [Phytochemistry and Medicinal Chemistry Laboratory, Institute of Exact Sciences, Unifal-MG (Brazil); Camps, I. [Physics Laboratory, Institute of Exact Sciences, Unifal-MG (Brazil); Silveira, N.J.F. da [Bioinformatics Laboratory, Institute of Exact Sciences, Unifal-MG (Brazil); Veloso, M.P. [Phytochemistry and Medicinal Chemistry Laboratory, Institute of Exact Sciences, Unifal-MG (Brazil); Santos, M.H., E-mail: poliany.santos@gmail.com [Phytochemistry and Medicinal Chemistry Laboratory, Institute of Exact Sciences, Unifal-MG (Brazil); Schneedorf, J.M., E-mail: zemasfs@gmail.com [Biochemistry Laboratory, Institute of Exact Sciences, Federal University of Alfenas, Unifal-MG, R. Gabriel Monteiro da Silva, 700, 37130-000 Alfenas, MG (Brazil)

    2012-11-15

    The binding interaction between mangiferin (MGF), which a natural xanthone isolated from mangoes, and bovine serum albumin (BSA) was studied with absorbance and fluorescence spectroscopy, cyclic voltammetry and molecular modeling. The data were analyzed to assess the binding mechanism, effect of pH and ionic strength, conformational changes in the protein and electrical charge transfer involved. The MGF-BSA complex exhibited positive cooperativity with a 1:1 stoichiometry (K{sub d}=0.38 mmol L{sup -1}) for the first binding site and a non-saturable binding at high ligand concentrations. Furthermore, the data also suggest an increase in drug bioavailability in the acidic region and relatively low ionic strength values, which are close to physiological levels. The data suggest a specific electrostatic interaction together with hydrophobic effects and H-bonding displayed in MGF binding to the BSA IIA subdomain. Synchronous fluorescence spectra indicate that there are conformational changes in the polypeptide backbone upon ligand binding. Cyclic voltammetry indicates that there is an irreversible charge transfer between MGF and BSA that is modulated by diffusion on the electrode surface, where two electrons are transferred. These results can help the knowledge of the pharmacokinetic activities of natural or chemical xanthone-based drugs. - Highlights: Black-Right-Pointing-Pointer The MGF-BSA complex exhibited positive cooperativity beyond 1:1 stoichiometry. Black-Right-Pointing-Pointer The interaction of MGF with BSA is non-saturable at higher ligand concentration. Black-Right-Pointing-Pointer The binding was accomplished by H-bonding, hydrophobic and electrostatic forces. Black-Right-Pointing-Pointer The apparent binding constant for MGF-BSA was 0.38 mmol L{sup -1}. Black-Right-Pointing-Pointer MGF binds electrostatically to BSA, different from a hydrophobic interaction to HSA.

  11. A microculture system for the measurement of antigen-induced murine lymphocyte proliferation: advantages of 5% horse serum and 5 X 10(-5) M mercaptoethanol.

    Science.gov (United States)

    Brummer, E; Vris, T W; Lawrence, H S

    1977-01-01

    Short term microculture systems which measure murine lymphocyte proliferative responses to mitogens are well established. We demonstrate here that these microculture methods are not suitable for antigen-induced responses because of the high levels of murine lymphocyte proliferation in control cultures associated with the use of fetal calf serum or human serum. We also show that this problem can be eliminated with the use of a combination of 5% horse serum and 5 X 10(-5) M mercaptoethanol. We describe an antigen-induced murine lymphocyte proliferation microculture system in which good stimulation indices are achieved and the lymphocyte proliferation in control cultures remain at a low level throughout the 7 day culture period.

  12. Protective Effect of Diospyros kaki against Glucose-Oxygen-Serum Deprivation-Induced PC12 Cells Injury

    Directory of Open Access Journals (Sweden)

    Fatemeh Forouzanfar

    2016-01-01

    Full Text Available Ischemic cerebrovascular disease is one of the most common causes of death in the world. Recent interests have been focused on natural antioxidants and anti-inflammatory agents as potentially useful neuroprotective agents. Diospyros kaki (persimmon has been shown to exert anti-inflammatory, antioxidant, and antineoplastic effects. However, its effects on ischemic damage have not been evaluated. Here, we used an in vitro model of cerebral ischemia and studied the effects of hydroalcoholic extract of peel (PeHE and fruit pulp (PuHE of persimmon on cell viability and markers of oxidative damage mainly intracellular reactive oxygen species (ROS induced by glucose-oxygen-serum deprivation (GOSD in PC12 cells. GOSD for 6 h produced significant cell death which was accompanied by increased levels of ROS. Pretreatment with different concentrations of PeHE and PuHE (0–500 μg/mL for 2 and 24 h markedly restored these changes only at high concentrations. However, no significant differences were seen in the protection against ischemic insult between different extracts and the time of exposure. The experimental results suggest that persimmon protects the PC12 cells from GOSD-induced injury via antioxidant mechanisms. Our findings might raise the possibility of potential therapeutic application of persimmon for managing cerebral ischemic and other neurodegenerative disorders.

  13. Metabolic Profiling Analysis of the Alleviation Effect of Treatment with Baicalin on Cinnabar Induced Toxicity in Rats Urine and Serum

    Directory of Open Access Journals (Sweden)

    Guangyue Su

    2017-05-01

    Full Text Available Objectives: Baicalin is the main bioactive flavonoid constituent isolated from Scutellaria baicalensis Georgi. The mechanisms of protection of liver remain unclear. In this study, 1H NMR-based metabonomics approach has been used to investigate the alleviation effect of Baicalin.Method:1H NMR metabolomics analyses of urine and serum from rats, was performed to illuminate the alleviation effect of Baicalin on mineral medicine (cinnabar-induced liver and kidney toxicity.Results: The metabolic profiles of groups receiving Baicalin at a dose of 80 mg/kg were remarkably different from cinnabar, and meanwhile, the level of endogenous metabolites returned to normal compared to group cinnabar. PLS-DA scores plots demonstrated that the variation tendency of control and Baicalein are apart from Cinnabar. The metabolic profiles of group Baicalein were similar to those of group control. Statistics results were confirmed by the histopathological examination and biochemical assay.Conclusion: Baicalin have the alleviation effect to the liver and kidney damage induced by cinnabar. The Baicalin could regulate endogenous metabolites associated with the energy metabolism, choline metabolism, amino acid metabolism, and gut flora.

  14. Immunomodulatory response of mice splenocytes induced by RcaL, a lectin isolated from cobia fish (Rachycentron canadum) serum.

    Science.gov (United States)

    Coriolano, Marília Cavalcanti; Silva, Cynarha Daysy Cardoso da; Melo, Cristiane Moutinho Lagos de; Bezerra, Ranilson de Souza; Santos, Athiê Jorge Guerra; Pereira, Valéria Rêgo Alves; Coelho, Luana Cassandra Breitenbach Barroso

    2012-11-01

    This work reports the isolation of a serum lectin from cobia fish (Rachycentron canadum) named RcaL. Immunomodulatory activity on mice splenocyte experimental cultures through cytotoxic assays and cytokine production were also performed. RcaL was obtained through precipitation with ammonium sulphate and affinity chromatography on a Concanavalin A-Sepharose 4B column. The ammonium sulphate fraction F3 showed the highest specific hemagglutinating activity and was applied to affinity chromatography. The lectin was eluted with methyl-α-D-mannopyranoside. RcaL showed highest affinity for methyl-α-D-mannopyranoside and D-mannose; eluted fractions of RcaL agglutinated rabbit erythrocytes (titre, 128(-1)) retained 66 % of chromatographed lectin activity, and the obtained purification factor was 1.14. Under reducing conditions, a polypeptide band of 19.2 kDa was revealed in sodium dodecyl sulphate polyacrylamide gel electrophoresis (PAGE). PAGE confirmed RcaL as an acidic protein revealed in a single band. Cytotoxic and immunomodulatory assays with RcaL in mice splenocyte cultures showed that the lectin was not cytotoxic and induced higher interferon gamma and nitric oxide production in splenocyte cultures. Purified RcaL induced preferential Th1 response, suggesting that it acts as an immunomodulatory compound.

  15. Effects of combinations of curcumin, linalool, rutin, safranal, and thymoquinone on glucose/serum deprivation-induced cell death

    Directory of Open Access Journals (Sweden)

    Bagher Alinejad

    2013-07-01

    Full Text Available Objective: Several phytochemical agents have been known to exhibit a neuroprotective effect. Among them, curcumin, linalool, rutin, safranal, and thymoquinonewere widely investigated and neuroprotective activity of each of them was shown by several studies. This work was planned to investigate whether different combinations of them could induce better neuroprotective effect against glucose/serum deprivation (GSD-induced cytotoxicity. Materials and Methods: PC12 cells were cultivated for 8 h in GSD condition in both the absence and presence of curcumin, linalool, rutin, safranal, thymoquinone, or combinations of them. At the end of the experiment, the cell viability was determined using MTT assay. Results: The cells cultured in GSD condition showed a significant decrease in viability (28±1% as compared with those cultured in standard condition (100±2%. In the presence of curcumin (10 µg/ml, linalool (16 µg/ml, rutin (200 µg/ml, safranal (50 µg/ml, and thymoquinone (1 µg/ml, the cell viability increased to 69±3.4% (p

  16. Effect of dietary supplementation on the prognostic value of urinary and serum 8-isoprostaglandin F2α in chemically-induced mammary carcinogenesis in the rat

    Directory of Open Access Journals (Sweden)

    Białek Sławomir

    2011-03-01

    Full Text Available Abstract Backround The aim of the present study was to assess the effects of zinc or copper and polyphenolic compounds on the 8-isoprostaglandin F2α concentration in the serum and urine of rats with mammary cancer (adenocarcinoma induced with 7,12-dimethylbenz[a]antracene. The research focused on the kinetics of alterations in urinary 8-isoPGF2α at the early stage of carcinogenesis as well as the influence of dietary factors on the process. The impact of selected compounds on the intensity of DMBA - induced carcinogenesis was also assessed. Result and conclusions Administration of DMBA, a compound that inducers mammary tumors in experimental animals, increased the serum and urinary 8-isoPGF2α levels in study rats. In the rat model, diet supplementation with zinc, combined with selected polyphenolic compounds (resveratrol or genistein yielded a statistically significant decrease in the rat serum and urinary biomarker concentration with a simultaneously significant stimulation of carcinogenesis. The results indicate that there is an inverse correlation between the intensity of DMBA-induced carcinogenicity and the level of 8-isoPGF2α in urine and serum of rats.

  17. Statistical methods for assays with limits of detection: Serum bile acid as a differentiator between patients with normal colons, adenomas, and colorectal cancer

    Directory of Open Access Journals (Sweden)

    Bonnie LaFleur

    2011-01-01

    Full Text Available In analytic chemistry a detection limit (DL is the lowest measurable amount of an analyte that can be distinguished from a blank; many biomedical measurement technologies exhibit this property. From a statistical perspective, these data present inferential challenges because instead of precise measures, one only has information that the value is somewhere between 0 and the DL (below detection limit, BDL. Substitution of BDL values, with 0 or the DL can lead to biased parameter estimates and a loss of statistical power. Statistical methods that make adjustments when dealing with these types of data, often called left-censored data, are available in many commercial statistical packages. Despite this availability, the use of these methods is still not widespread in biomedical literature. We have reviewed the statistical approaches of dealing with BDL values, and used simulations to examine the performance of the commonly used substitution methods and the most widely available statistical methods. We have illustrated these methods using a study undertaken at the Vanderbilt-Ingram Cancer Center, to examine the serum bile acid levels in patients with colorectal cancer and adenoma. We have found that the modern methods for BDL values identify disease-related differences that are often missed, with statistically naive approaches.

  18. Distinct roles of two anaplerotic pathways in glutamate production induced by biotin limitation in Corynebacterium glutamicum.

    Science.gov (United States)

    Sato, Hiroki; Orishimo, Keita; Shirai, Tomokazu; Hirasawa, Takashi; Nagahisa, Keisuke; Shimizu, Hiroshi; Wachi, Masaaki

    2008-07-01

    Corynebacterium glutamicum is a biotin auxotrophic bacterium in which glutamate production is induced under biotin-limited conditions. During glutamate production, anaplerotic reactions catalyzed by phosphoenolpyruvate carboxylase (PEPC) and a biotin-containing enzyme pyruvate carboxylase (PC) are believed to play an important role in supplying oxaloacetate in the tricarboxylic acid cycle. To understand the distinct roles of PEPC and PC on glutamate production by C. glutamicum, we observed glutamate production induced under biotin-limited conditions in the disruptants of the genes encoding PEPC (ppc) and PC (pyc), respectively. The pyc disruptant retained the ability to produce high amounts of glutamate, and lactate was simultaneously produced probably due to the increased intracellular pyruvate levels. On the other hand, the ppc knockout mutant could not produce glutamate. Additionally, glutamate production in the pyc disruptant was enhanced by overexpression of ppc rather than disruption of the lactate dehydrogenase gene (ldh), which is involved in lactate production. Metabolic flux analysis based on the 13C-labeling experiment and measurement of 13C-enrichment in glutamate using nuclear magnetic resonance spectroscopy revealed that the flux for anaplerotic reactions in the pyc disruptant was lower than that in the wild type, concomitantly increasing the flux for lactate formation. Moreover, overexpression of ppc increased this flux in both the pyc disruptant and the wild type. Our results suggest that the PEPC-catalyzed anaplerotic reaction is necessary for glutamate production induced under biotin-limited conditions, because PC is not active during glutamate production, and overexpression of ppc effectively enhances glutamate production under biotin-limited conditions.

  19. Effect of Resistance Exercise Training Associated with Skeletal Muscle Hypertrophy on Serum Pro-Inflammatory Cytokines in STZ-induced Diabetes

    Directory of Open Access Journals (Sweden)

    Mahdieh Molanouri Shamsi

    2016-06-01

    Full Text Available Skeletal muscle atrophy is associated with type 1 diabetes. Effects of resistance exercise training associated with skeletal muscle hypertrophy on serum inflammatory cytokines was exactly not clarified. Protein levels of inflammatory cytokines IL-6, TNF-α, and interleukin-1beta (IL-1β in serum of healthy and streptozotocin (STZ- induced diabetic rats subjected to resistance exercise training were assessed in this study. Rats were divided into the control, training, control diabetic and diabetic training groups. Training groups performed the resistance training consisted of climbing a 1 m ladder with increasing weight added to the tail. Proteins levels of IL-6, TNF-α and IL-1β in serum were measured by the ELIZA method. The results of this study indicated that resistance training induced skeletal muscle hypertrophy in diabetic samples (P<0.05. Also, Resistance training decrease IL-6 protein levels in serum. Inflammatory cytokines could act as stress factors in diabetes. It seems that this kind of exercise training individually could not change cytokines levels in serum.

  20. The determination of trace elements in commercial human serum albumin solutions by proton-induced X-ray emission spectrometry and neutron activation analysis

    International Nuclear Information System (INIS)

    Maenhaut, W.; De Reu, L.; Tomza, U.; Versieck, J.

    1982-01-01

    Particle induced X-ray emission (p.i.x.e.) and neutron activation analysis (n.a.a.) are proposed for determining the trace element content of human serum albumin. Application of these methods to some commercial albumin solutions provided concentration data for up to 19 elements, most of which were present at a level below a few μg ml -1 . The precision of the p.i.x.e. technique, as determined by irradiating up to 20 targets from one sample, was about 3% for those elements where counting statistics were good. A comparison between the p.i.x.e. and n.a.a. results showed close agreement, indicating that p.i.x.e. can yield data which are accurate to within 10%. Neutron activation showed very good sensitivity for the elements producing long-lived nuclides (tsub(1/2) >= 3 days), but had rather high detection limits for the other elements, unless radiochemical separations were used. (Auth.)

  1. MFGE8 inhibits inflammasome-induced IL-1β production and limits postischemic cerebral injury.

    Science.gov (United States)

    Deroide, Nicolas; Li, Xuan; Lerouet, Dominique; Van Vré, Emily; Baker, Lauren; Harrison, James; Poittevin, Marine; Masters, Leanne; Nih, Lina; Margaill, Isabelle; Iwakura, Yoichiro; Ryffel, Bernhard; Pocard, Marc; Tedgui, Alain; Kubis, Nathalie; Mallat, Ziad

    2013-03-01

    Milk fat globule-EGF 8 (MFGE8) plays important, nonredundant roles in several biological processes, including apoptotic cell clearance, angiogenesis, and adaptive immunity. Several recent studies have reported a potential role for MFGE8 in regulation of the innate immune response; however, the precise mechanisms underlying this role are poorly understood. Here, we show that MFGE8 is an endogenous inhibitor of inflammasome-induced IL-1β production. MFGE8 inhibited necrotic cell-induced and ATP-dependent IL-1β production by macrophages through mediation of integrin β(3) and P2X7 receptor interactions in primed cells. Itgb3 deficiency in macrophages abrogated the inhibitory effect of MFGE8 on ATP-induced IL-1β production. In a setting of postischemic cerebral injury in mice, MFGE8 deficiency was associated with enhanced IL-1β production and larger infarct size; the latter was abolished after treatment with IL-1 receptor antagonist. MFGE8 supplementation significantly dampened caspase-1 activation and IL-1β production and reduced infarct size in wild-type mice, but did not limit cerebral necrosis in Il1b-, Itgb3-, or P2rx7-deficient animals. In conclusion, we demonstrated that MFGE8 regulates innate immunity through inhibition of inflammasome-induced IL-1β production.

  2. Limited role of murine ATM in oncogene-induced senescence and p53-dependent tumor suppression.

    Directory of Open Access Journals (Sweden)

    Alejo Efeyan

    Full Text Available Recent studies in human fibroblasts have provided a new general paradigm of tumor suppression according to which oncogenic signaling produces DNA damage and this, in turn, results in ATM/p53-dependent cellular senescence. Here, we have tested this model in a variety of murine experimental systems. Overexpression of oncogenic Ras in murine fibroblasts efficiently induced senescence but this occurred in the absence of detectable DNA damage signaling, thus suggesting a fundamental difference between human and murine cells. Moreover, lung adenomas initiated by endogenous levels of oncogenic K-Ras presented abundant senescent cells, but undetectable DNA damage signaling. Accordingly, K-Ras-driven adenomas were also senescent in Atm-null mice, and the tumorigenic progression of these lesions was only modestly accelerated by Atm-deficiency. Finally, we have examined chemically-induced fibrosarcomas, which possess a persistently activated DNA damage response and are highly sensitive to the activity of p53. We found that the absence of Atm favored genomic instability in the resulting tumors, but did not affect the persistent DNA damage response and did not impair p53-dependent tumor suppression. All together, we conclude that oncogene-induced senescence in mice may occur in the absence of a detectable DNA damage response. Regarding murine Atm, our data suggest that it plays a minor role in oncogene-induced senescence or in p53-dependent tumor suppression, being its tumor suppressive activity probably limited to the maintenance of genomic stability.

  3. Serum cobalt status during pregnancy and the risks of pregnancy-induced hypertension syndrome: A prospective birth cohort study.

    Science.gov (United States)

    Liang, Chunmei; Wang, Jianqing; Xia, Xun; Wang, Qunan; Li, Zhijuan; Tao, Ruiwen; Tao, Yiran; Xiang, Haiyun; Tong, Shilu; Tao, Fangbiao

    2018-03-01

    Cobalt (Co) is an essential trace element and has been suggested to be involved in blood pressure regulation, but few studies have focused on serum Co status during pregnancy and the risks of pregnancy-induced hypertension syndrome (PIH). The aim of this study was to prospectively assess the association between serum Co levels during pregnancy and the risks of PIH, and to explore how the maternal Co status contributes to the incidence of PIH. 3260 non-hypertensive women before pregnancy with singleton births in Ma'anShan birth cohort study (MABC) were recruited with the assessment of maternal Co concentrations, additionally, the levels of 7 inflammatory factors and 3 stress factors in placentas were also determined. Relative risks (RRs) [95% confidence intervals (CIs)] for the risks of PIH were assessed and the relationships between 10 factors and maternal Co status during pregnancy were evaluated as well. A total of 194 (5.95%) women were diagnosed with PIH. The concentrations of Co varied from the first trimester to the second trimester, and maternal serum Co concentrations during pregnancy were negatively associated with the incidence of PIH in a linear fashion. There was a clear trend in RRs according to decreasing exposure to Co levels in the second trimester (RR a =1.80, 95% CI (1.26, 2.56); RR b =1.73, 95% CI (1.21, 2.46) and RR c =1.43, 95% CI (1.02, 2.04) when low Co levels comparing with high Co levels before and after adjustment for confounders; and RR a =1.29, 95% CI (0.88, 1.88); RR b =1.28, 95% CI (0.87, 1.87) and RR c =1.25, 95% CI (0.86, 1.82) when medium Co levels comparing with high Co levels before and after adjustment for confounders). In addition, the trend for the first trimester was nearly identifical to those for the second trimester (RR a =1.35, 95% CI (0.94, 1.93); RR b =1.33, 95% CI (0.93, 1.91); RR c =1.22, 95%CI (0.86, 1.73) when low Co levels comparing with high Co levels before and after adjustment for confounders; and RR a =1.10, 95

  4. Peripheral Blood Cells from Patients with Autoimmune Addison's Disease Poorly Respond to Interferons In Vitro, Despite Elevated Serum Levels of Interferon-Inducible Chemokines.

    Science.gov (United States)

    Edvardsen, Kine; Bjånesøy, Trine; Hellesen, Alexander; Breivik, Lars; Bakke, Marit; Husebye, Eystein S; Bratland, Eirik

    2015-10-01

    Autoimmune Addison's disease (AAD) is a disorder caused by an immunological attack on the adrenal cortex. The interferon (IFN)-inducible chemokine CXCL10 is elevated in serum of AAD patients, suggesting a peripheral IFN signature. However, CXCL10 can also be induced in adrenocortical cells stimulated with IFNs, cytokines, or microbial components. We therefore investigated whether peripheral blood mononuclear cells (PBMCs) from AAD patients display an enhanced propensity to produce CXCL10 and the related chemokine CXCL9, after stimulation with type I or II IFNs or the IFN inducer poly (I:C). Although serum levels of CXCL10 and CXCL9 were significantly elevated in patients compared with controls, IFN stimulated patient PBMC produced significantly less CXCL10/CXCL9 than control PBMC. Low CXCL10 production was not significantly associated with medication, disease duration, or comorbidities, but the low production of poly (I:C)-induced CXCL10 among patients was associated with an AAD risk allele in the phosphatase nonreceptor type 22 (PTPN22) gene. PBMC levels of total STAT1 and -2, and IFN-induced phosphorylated STAT1 and -2, were not significantly different between patients and controls. We conclude that PBMC from patients with AAD are deficient in their response to IFNs, and that the adrenal cortex itself may be responsible for the increased serum levels of CXCL10.

  5. Peripheral Blood Cells from Patients with Autoimmune Addison's Disease Poorly Respond to Interferons In Vitro, Despite Elevated Serum Levels of Interferon-Inducible Chemokines

    Science.gov (United States)

    Bjånesøy, Trine; Hellesen, Alexander; Breivik, Lars; Bakke, Marit; Husebye, Eystein S.; Bratland, Eirik

    2015-01-01

    Autoimmune Addison's disease (AAD) is a disorder caused by an immunological attack on the adrenal cortex. The interferon (IFN)-inducible chemokine CXCL10 is elevated in serum of AAD patients, suggesting a peripheral IFN signature. However, CXCL10 can also be induced in adrenocortical cells stimulated with IFNs, cytokines, or microbial components. We therefore investigated whether peripheral blood mononuclear cells (PBMCs) from AAD patients display an enhanced propensity to produce CXCL10 and the related chemokine CXCL9, after stimulation with type I or II IFNs or the IFN inducer poly (I:C). Although serum levels of CXCL10 and CXCL9 were significantly elevated in patients compared with controls, IFN stimulated patient PBMC produced significantly less CXCL10/CXCL9 than control PBMC. Low CXCL10 production was not significantly associated with medication, disease duration, or comorbidities, but the low production of poly (I:C)-induced CXCL10 among patients was associated with an AAD risk allele in the phosphatase nonreceptor type 22 (PTPN22) gene. PBMC levels of total STAT1 and -2, and IFN-induced phosphorylated STAT1 and -2, were not significantly different between patients and controls. We conclude that PBMC from patients with AAD are deficient in their response to IFNs, and that the adrenal cortex itself may be responsible for the increased serum levels of CXCL10. PMID:25978633

  6. Transcriptome analysis documents induced competence of Bacillus subtilis during nitrogen limiting conditions

    DEFF Research Database (Denmark)

    Jarmer, Hanne Østergaard; Berka, R.; Knudsen, Steen

    2002-01-01

    DNA microarrays were used to analyze the changes in gene expression in Bacillus subtilis strain 168 when nitrogen limiting (glutamate) and nitrogen excess (ammonium plus glutamate) growth conditions were compared. Among more than 100 genes that were significantly induced during nitrogen starvation...... we detected the comG, comF, comE, nin-nucA and comK transcription units together with recA. DNA was added to B. subtilis grown in minimal medium with glutamate as the sole nitrogen source and it was demonstrated that the cells were competent. Based on these observations we propose a simplification...

  7. Proteomic profiling of occupational medicamentosa-like dermatitis induced by trichloroethylene in serum based on MALDI-TOF MS.

    Science.gov (United States)

    Liu, Wei; Hong, Wen-Xu; Zhang, Yanfang; Huang, Peiwu; Yang, Xifei; Ren, Xiaohu; Huang, Haiyan; Liu, Jianjun

    2015-11-01

    Trichloroethylene (TCE) has long been well known as a major pollutant that affects both occupational and general environments. Occupational medicamentosa-like dermatitis induced by TCE (OMLDT) is an autoimmune disease, which has become one of the critical occupational health issues in China. In this study, we analyzed 18 OMLDT patients and 29 professional TCE contact people on serum proteomic analysis by matrix-assisted laser desorption ionization time-of-flight mass spectrometry and ClinProTools bioinformatics software. The intensities of 35 protein/peptide peaks were significantly different between TCE contact controls and OMLDT patients. A pattern of six peaks (m/z 1,450.33, 1,866.16, 3,262.39, 4,109.55, 5,064.85 and 5,956.57) were selected to construct a diagnostic model to discriminate the OMLDT patients from controls with sensitivity and specificity of both 93.8 %. Our findings provide an alternative proteomic approach to differentiate the OMLDT patients from TCE contact workers with high sensitivity and high specificity, which will be of potential value in clinical diagnosis for occupational disease.

  8. UPLC-Q-TOF/MS based metabolomic profiling of serum and urine of hyperlipidemic rats induced by high fat diet

    Directory of Open Access Journals (Sweden)

    Qiong Wu

    2014-12-01

    Full Text Available Hyperlipidemia is considered to be a high lipid level in blood, can induce metabolic disorders and dysfunctions of the body, and results in some severe complications. Therefore, hunting for some metabolite markers and clarifying the metabolic pathways in vivo will be an important strategy in the treatment and prevention of hyperlipidemia. In this study, a rat model of hyperlipidemia was constructed according to histopathological data and biochemical parameters, and the metabolites of serum and urine were analyzed by UPLC-Q-TOF/MS. Combining pattern recognition and statistical analysis, 19 candidate biomarkers were screened and identified. These changed metabolites indicated that during the development and progression of hyperlipidemia, energy metabolism, lipid metabolism, amino acid metabolism and nucleotide metabolism were mainly disturbed, which are reported to be closely related to diabetes, cardiovascular diseases, etc. This study demonstrated that a UPLC-Q-TOF/MS based metabolomic approach is useful to profile the alternation of endogenous metabolites of hyperlipidemia. Keywords: UPLC-Q-TOF/MS, Hyperlipidemia, Metabolomic, Pattern recognition

  9. APPLIED OPTICS. Overcoming Kerr-induced capacity limit in optical fiber transmission.

    Science.gov (United States)

    Temprana, E; Myslivets, E; Kuo, B P-P; Liu, L; Ataie, V; Alic, N; Radic, S

    2015-06-26

    Nonlinear optical response of silica imposes a fundamental limit on the information transfer capacity in optical fibers. Communication beyond this limit requires higher signal power and suppression of nonlinear distortions to prevent irreversible information loss. The nonlinear interaction in silica is a deterministic phenomenon that can, in principle, be completely reversed. However, attempts to remove the effects of nonlinear propagation have led to only modest improvements, and the precise physical mechanism preventing nonlinear cancellation remains unknown. We demonstrate that optical carrier stability plays a critical role in canceling Kerr-induced distortions and that nonlinear wave interaction in silica can be substantially reverted if optical carriers possess a sufficient degree of mutual coherence. These measurements indicate that fiber information capacity can be notably increased over previous estimates. Copyright © 2015, American Association for the Advancement of Science.

  10. Brain-derived neurotrophic factor (BDNF) serum basal levels is not affected by power training in mobility-limited older adults - A randomized controlled trial

    DEFF Research Database (Denmark)

    Hvid, Lars G; Nielsen, Martin KF; Simonsen, Casper

    2017-01-01

    high extent, it may be particularly effective in terms of eliciting increases in systemic BDNF levels. We examined the effects of 12 weeks of power training on mature BDNF (mBDNF) and total BDNF (tBDNF) in mobility-limited older adults from the Healthy Ageing Network of Competence (HANC) study. We......Brain-derived neurotrophic factor (BDNF) is a potential important factor involved in neuroplasticity, and may be a mediator for eliciting adaptations in neuromuscular function and physical function in older individuals following physical training. As power training taxes the neural system to a very...... included 47 older men and women: n = 22 in the training group (TG: progressive high intensity power training, 2 sessions per week; age 82.7 ± 5.4 years, 55% women) and n = 25 in the control group (CG: no interventions; age 82.2 ± 4.5 years, 76% women). Following overnight fasting, basal serum levels of m...

  11. Selenium and other elements in human maternal and umbilical serum, as determined simultaneously by proton-induced X-ray emission

    International Nuclear Information System (INIS)

    Hyvoenen-Dabek, M.; Nikkinen-Vilkki, P.; Dabek, J.T.

    1984-01-01

    Using PIXE (proton-induced X-ray emission), we simultaneously determined the concentrations of Se, Ca, Fe, Cu, Zn, Br, and Pb in blood serum from 56 pregnant women, 25 healthy controls, and 31 others with twin pregnancy or some complicating condition (diabetes, hypertension, epilepsy, hepatosis gravidarum, pre-eclampsia, small baby), and in cord-blood serum from 21 newborns. Pellets, pressed from the serum samples after addition of yttrium as an internal standard, mixing, and evaporating at 30 degrees C with or without reduced pressure (less than 1 kPa), were bombarded by 2.2 MeV protons from a Van de Graaff accelerator in the air and the induced X-rays collected by a Ge(Li) detector. Relative to mean Se values for early six- to 12-week pregnancy (0.045 ppm), those for 35-42 week pregnancy (0.028 ppm) were low (p less than 0.001). Umbilical cord blood serum showed even lower values (0.016 ppm, p less than 0.001)--findings in harmony with the incidence pattern of Keshan cardiomyopathy. Pb crossed the placenta; values for cord serum were not significantly different from those in pregnancy serum. Cu, Zn, Fe, and Ca showed the significant expected patterns in the different groups. Compared with the late-pregnancy controls, Fe was high in mothers of small-birth-weight babies (1.70 ppm, p less than 0.02). Br was high in pre-eclampsia (3.59 ppm, p less than 0.05) and mothers with twins (3.61 ppm, p less than 0.05)

  12. The role of Omi/HtrA2 protease in neonatal postasphyxial serum-induced apoptosis in human kidney proximal tubule cells

    Directory of Open Access Journals (Sweden)

    Zhang Yong

    2012-01-01

    Full Text Available Omi/HtrA2, a proapoptotic mitochondrial serine protease, is involved in both caspase-dependent and caspaseindependent apoptosis. A growing body of evidence indicates that Omi/HtrA2 plays an important role in the pathogenesis of a variety of ischemia-reperfusion (I/R injuries. However, the role of Omi/HtrA2 in renal injuries that occur in neonates with asphyxia remains unknown. The present study was designed to investigate whether Omi/HtrA2 plays an important role in the types of renal injuries that are induced by neonatal postasphyxial serum. Human renal proximal tubular cell line (HK-2 cells were used as targets. A 20% serum taken from neonates one day after asphyxia was applied to target cells as an attacking factor. We initially included control and postasphyxial serum-attacked groups and later included a ucf-101 group in the study. In the postasphyxial serum-treated group, cytosolic Omi/HtrA2 and caspase-3 expression in HK-2 cells was significantly higher than in the control group. Moreover, the concentration of cytosolic caspase-3 was found to be markedly decreased in HK-2 cells in the ucf-101 group. Our results suggest both that postasphyxial serum has a potent apoptosis-inducing effect on HK-2 cells and that this effect can be partially blocked by ucf-101. Taken together, our results demonstrate for the first time that postasphyxial serum from neonates results in Omi/HtrA2 translocation from the mitochondria to the cytosol, where it promotes HK-2 cell apoptosis via a protease activity-dependent, caspase-mediated pathway.

  13. Simple serum markers for significant liver inflammation in chronic hepatitis B patients with an alanine aminotransferase level lower than 2 times upper limit of normal

    Directory of Open Access Journals (Sweden)

    LI Qiang

    2016-06-01

    Full Text Available ObjectiveTo investigate the simple serum markers for significant liver inflammation in chronic hepatitis B (CHB patients with an alanine aminotransferase (ALT level of <2 times upper limit of normal (ULN. MethodsThe clinical data of 278 CHB patients with ALT <2×ULN (ULN=40 U/L were analyzed retrospectively. Significant liver inflammation was defined as a liver inflammatory activity grade (G ≥2. The t-test was used for comparison of normally distributed continuous data between groups, and the Kruskal-Wallis rank sum test was used for non-normally distributed continuous data; the chi-square test was used for comparison of categorical data between groups. Multivariate logistic regression analysis was used to identify independent predictors for significant liver inflammation in CHB patients with ALT <2×ULN. The receiver operating characteristic (ROC curve was used to evaluate the diagnostic value of serum markers in significant liver inflammation. ResultsOf the 278 CHB patients enrolled, 175 (62.9% had no significant liver inflammation (G0-1 group and 103 (37.1% had significant liver inflammation (G2-4 group. There were significant differences in ALT, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase (GGT, albumin, globulin, prothrombin time (PT, platelet, absolute neutrophil count, hyaluronic acid (HA, glycocholic acid, precollagen Ⅲ, and collagen type Ⅳ(ⅣC between the two groups (all P<0.05. The multivariate regression analysis showed that GGT, PT, ⅣC, and HA were independent predictors for significant liver inflammation in CHB patients with ALT<2×ULN (OR=1.015, 1.600, 1.151, and 1.014, P=0.008, 0.021, 0.003, and 0.018. The areas under the ROC curve for GGT, PT, IVC, and HA to diagnose significant liver inflammation were 0.804, 0.722, 0.707, and 0.632, respectively. The cut-off value of 48.5 U/L for GGT to predict significant liver inflammation had a specificity of 90.3% and a negative

  14. Epigenetics of drought-induced trans-generational plasticity: consequences for range limit development

    Science.gov (United States)

    Alsdurf, Jacob; Anderson, Cynthia; Siemens, David H.

    2016-01-01

    Genetic variation gives plants the potential to adapt to stressful environments that often exist beyond their geographic range limits. However, various genetic, physiological or developmental constraints might prevent the process of adaptation. Alternatively, environmentally induced epigenetic changes might sustain populations for several generations in stressful areas across range boundaries, but previous work on Boechera stricta, an upland mustard closely related to Arabidopsis, documented a drought-induced trans-generational plastic trade-off that could contribute to range limit development. Offspring of parents who were drought treated had higher drought tolerance, but lower levels of glucosinolate toxins. Both drought tolerance and defence are thought to be needed to expand the range to lower elevations. Here, we used methylation-sensitive amplified fragment length polymorphisms to determine whether environmentally induced DNA methylation and thus epigenetics could be a mechanism involved in the observed trans-generational plastic trade-off. We compared 110 offspring from the same self-fertilizing lineages whose parents were exposed to experimental drought stress treatments in the laboratory. Using three primer combinations, 643 polymorphic epi-loci were detected. Discriminant function analysis (DFA) on the amount of methylation detected resulted in significant combinations of epi-loci that distinguished the parent drought treatments in the offspring. Principal component (PC) and univariate association analyses also detected the significant differences, even after controlling for lineage, planting flat, developmental differences and multiple testing. Univariate tests also indicated significant associations between the amount of methylation and drought tolerance or glucosinolate toxin concentration. One epi-locus that was implicated in DFA, PC and univariate association analysis may be directly involved in the trade-off because increased methylation at this

  15. Epigenetics of drought-induced trans-generational plasticity: consequences for range limit development.

    Science.gov (United States)

    Alsdurf, Jacob; Anderson, Cynthia; Siemens, David H

    2015-12-18

    Genetic variation gives plants the potential to adapt to stressful environments that often exist beyond their geographic range limits. However, various genetic, physiological or developmental constraints might prevent the process of adaptation. Alternatively, environmentally induced epigenetic changes might sustain populations for several generations in stressful areas across range boundaries, but previous work on Boechera stricta, an upland mustard closely related to Arabidopsis, documented a drought-induced trans-generational plastic trade-off that could contribute to range limit development. Offspring of parents who were drought treated had higher drought tolerance, but lower levels of glucosinolate toxins. Both drought tolerance and defence are thought to be needed to expand the range to lower elevations. Here, we used methylation-sensitive amplified fragment length polymorphisms to determine whether environmentally induced DNA methylation and thus epigenetics could be a mechanism involved in the observed trans-generational plastic trade-off. We compared 110 offspring from the same self-fertilizing lineages whose parents were exposed to experimental drought stress treatments in the laboratory. Using three primer combinations, 643 polymorphic epi-loci were detected. Discriminant function analysis (DFA) on the amount of methylation detected resulted in significant combinations of epi-loci that distinguished the parent drought treatments in the offspring. Principal component (PC) and univariate association analyses also detected the significant differences, even after controlling for lineage, planting flat, developmental differences and multiple testing. Univariate tests also indicated significant associations between the amount of methylation and drought tolerance or glucosinolate toxin concentration. One epi-locus that was implicated in DFA, PC and univariate association analysis may be directly involved in the trade-off because increased methylation at this

  16. Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

    International Nuclear Information System (INIS)

    Qi, Xiaozhe; Yu, Tao; Zhu, Liye; Gao, Jing; He, Xiaoyun; Huang, Kunlun; Luo, Yunbo; Xu, Wentao

    2014-01-01

    Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected in the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation

  17. Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Xiaozhe; Yu, Tao; Zhu, Liye; Gao, Jing [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); He, Xiaoyun; Huang, Kunlun; Luo, Yunbo [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Xu, Wentao, E-mail: xuwentao@cau.edu.cn [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China)

    2014-11-01

    Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected in the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation.

  18. The phantom menace. Determination of the true Method Detection Limit (MDL) for background levels of PCDDs, PCDFs, and cPCBs in human serum by high-resolution mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Turner, W.; Welch, S.; DiPietro, E.; Cash, T.; McClure, C.; Needham, L.; Patterson, D. [CDC/ATSDR, Atlanta, GA (United States)

    2004-09-15

    The recent worldwide decline in background serum levels of polychlorinated dibenzo-p-dioxins, furans, and coplanar biphenyls (PCDDs/PCDFs/cPCBs) is unquestionably an important finding. However, as serum levels continue to diminish, our analytical methods for measuring these toxicants will continue to be ''pushed to their limit''. In a previous article, we investigated some of the variables that influence the quantification of ''ultra-trace'' (fg/g) concentrations of PCDDs/PCDFs and cPCBs in human serum. In this report, we continue to explore parameters that can affect the determination of the ''true'' detection limit of our method (MDL), using both analytical standards and matrix-based samples.

  19. Bile acids induce arrhythmias in human atrial myocardium--implications for altered serum bile acid composition in patients with atrial fibrillation.

    Science.gov (United States)

    Rainer, Peter P; Primessnig, Uwe; Harenkamp, Sandra; Doleschal, Bernhard; Wallner, Markus; Fauler, Guenter; Stojakovic, Tatjana; Wachter, Rolf; Yates, Ameli; Groschner, Klaus; Trauner, Michael; Pieske, Burkert M; von Lewinski, Dirk

    2013-11-01

    High bile acid serum concentrations have been implicated in cardiac disease, particularly in arrhythmias. Most data originate from in vitro studies and animal models. We tested the hypotheses that (1) high bile acid concentrations are arrhythmogenic in adult human myocardium, (2) serum bile acid concentrations and composition are altered in patients with atrial fibrillation (AF) and (3) the therapeutically used ursodeoxycholic acid has different effects than other potentially toxic bile acids. Multicellular human atrial preparations ('trabeculae') were exposed to primary bile acids and the incidence of arrhythmic events was assessed. Bile acid concentrations were measured in serum samples from 250 patients and their association with AF and ECG parameters analysed. Additionally, we conducted electrophysiological studies in murine myocytes. Taurocholic acid (TCA) concentration-dependently induced arrhythmias in atrial trabeculae (14/28 at 300 µM TCA, pursodeoxycholic acid did not. Patients with AF had significantly decreased serum levels of ursodeoxycholic acid conjugates and increased levels of non-ursodeoxycholic bile acids. In isolated myocytes, TCA depolarised the resting membrane potential, enhanced Na(+)/Ca(2+) exchanger (NCX) tail current density and induced afterdepolarisations. Inhibition of NCX prevented arrhythmias in atrial trabeculae. High TCA concentrations induce arrhythmias in adult human atria while ursodeoxycholic acid does not. AF is associated with higher serum levels of non-ursodeoxycholic bile acid conjugates and low levels of ursodeoxycholic acid conjugates. These data suggest that higher levels of toxic (arrhythmogenic) and low levels of protective bile acids create a milieu with a decreased arrhythmic threshold and thus may facilitate arrhythmic events.

  20. Conversion to Sirolimus Ameliorates Cyclosporine-Induced Nephropathy in the Rat: Focus on Serum, Urine, Gene, and Protein Renal Expression Biomarkers

    Directory of Open Access Journals (Sweden)

    José Sereno

    2014-01-01

    Full Text Available Protocols of conversion from cyclosporin A (CsA to sirolimus (SRL have been widely used in immunotherapy after transplantation to prevent CsA-induced nephropathy, but the molecular mechanisms underlying these protocols remain nuclear. This study aimed to identify the molecular pathways and putative biomarkers of CsA-to-SRL conversion in a rat model. Four animal groups (n=6 were tested during 9 weeks: control, CsA, SRL, and conversion (CsA for 3 weeks followed by SRL for 6 weeks. Classical and emergent serum, urinary, and kidney tissue (gene and protein expression markers were assessed. Renal lesions were analyzed in hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome stains. SRL-treated rats presented proteinuria and NGAL (serum and urinary as the best markers of renal impairment. Short CsA treatment presented slight or even absent kidney lesions and TGF-β, NF-κβ, mTOR, PCNA, TP53, KIM-1, and CTGF as relevant gene and protein changes. Prolonged CsA exposure aggravated renal damage, without clear changes on the traditional markers, but with changes in serums TGF-β and IL-7, TBARs clearance, and kidney TGF-β and mTOR. Conversion to SRL prevented CsA-induced renal damage evolution (absent/mild grade lesions, while NGAL (serum versus urine seems to be a feasible biomarker of CsA replacement to SRL.

  1. Effect of Age-Related Cartilage Turnover on Serum C-Telopeptide of Collagen Type II and Osteocalcin Levels in Growing Rabbits with and without Surgically Induced Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Chung-Cheng Huang

    2014-01-01

    Full Text Available This study aims to determine the effect of age-related cartilage turnover on the serum C-telopeptide of type II collagen (CTX-II and osteocalcin (OC levels in growing rabbits with and without surgically induced osteoarthritis. Twenty-four New Zealand male 3-month-old rabbits were randomized into three operated groups (n = 6 per group, with surgically induced osteroarthritis in the right knee; after blood sampling, the knees were harvested following euthanization at 2, 3, and 6 months after surgery and a control group (n = 6, blood samples were obtained monthly between 3 and 15 months. Histomorphologically, the medial femoral condyles, particularly the central parts, harbored the most severe osteoarthritic changes among the operated rabbits. The serum levels of CTX-II and OC decreased in the controls from 3 to 11 months and then remained stable. No significant differences in the serum CTX-II and OC levels between the osteoarthritic rabbits and controls were observed. The osteoarthritic-to-normal ratios (ONRs, the ratios of serum CTX-II or OC levels in osteoarthritic rabbits to those of the controls at same ages enabled an overall assessment of osteoarthritis and age-related cartilage turnover. Elevated CTX-II ONRs were observed in rabbits with mild to advanced osteoarthritis. However, the OC ONRs were unhelpful in assessing osteoarthritic growing rabbits.

  2. [Role of phosphoinositide 3 kinase/protein kinase B signal pathway in monocyte-endothelial adhesion induced by serum of rats with electrical burn].

    Science.gov (United States)

    Ruan, Qiongfang; Zhao, Chaoli; Ye, Ziqing; Zhang, Weidong; Xie, Qionghui; Xie, Weiguo

    2014-06-01

    To observe the change in phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signal pathway in monocytes as induced by serum of rats with electrical burn, and to explore the effects of PI3K/Akt pathway on monocyte-endothelial cell adhesion. Sixty-four SD rats of clean grade were inflicted with electrical burn for the collection of serum of rats with electrical burn; another group of twenty-four SD rats were used to obtain normal serum without treatment. (1) Human monocyte line THP-1 was routinely cultured. The THP-1 cells in logarithmic phase were divided into normal serum group (resuspended in RPMI 1640 medium with 20% normal rat serum) and burn serum group (resuspended with RPMI 1640 medium with 20% serum of rats with electrical burn) according to the random number table, with 6 wells in each group. Morphology of THP-1 cells in normal serum group was observed at post culture hour (PCH) 24, and that in burn serum group at PCH 3, 6, 24. The contents of TNF-α in culture supernatant were determined by double-antibody sandwich ELISA at the corresponding time point in each group. The state of Akt activation was determined by Western blotting at PCH 3, 6, 24. (2) Another portion of THP-1 cells were divided into 4 groups according to the random number table, with 6 wells in each group. Cells in normal serum group and burn serum group were given with the same culture condition as above; cells in normal serum+inhibitor group and burn serum+inhibitor group were cultured with the same culture conditions as in the former two groups correspondingly with addition of 100 nmol/L wortmannin in the nutrient solution. At PCH 3 and 6, THP-1 cells were added into the well with a monolayer of endothelial cell line EA.hy926 to observe the monocyte-endothelial cell adhesion. Data were processed with one-way analysis of variance and LSD- t test. (1) In normal serum group, THP-1 cells showed growth in suspension, with uniform shape at PCH 24. In burn serum group, the cell shape became

  3. Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal

    DEFF Research Database (Denmark)

    Parkinson, C; Kassem, M; Heickendorff, Lene

    2003-01-01

    of bone and soft tissue turnover, as well as levels of PTH and vitamin D metabolites, in 16 patients (nine males; median age, 52 yr; range, 28-78 yr) with active acromegaly (serum IGF-I at least 30% above upper limit of an age-related reference range). Serum procollagen III amino-terminal propeptide...... (PIIINP) and type I procollagen amino-terminal propeptide, osteocalcin (OC), bone-related alkaline phosphatase, C-terminal cross-linked telopeptide of type I collagen (CTx), albumin-corrected calcium, intact PTH, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D [1,25-(OH)(2) vit D], urinary type 1 collagen...... (CTx and urinary type 1 collagen cross-linked N-telopeptide/creatinine ratio). 1,25-(OH)(2) vit D decreased and intact PTH increased significantly, but 25-hydroxy vitamin D was unaffected. A significant decline in calculated calcium clearance was observed. The decrease in serum IGF-I correlated...

  4. Fast-food-based hyper-alimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects.

    Science.gov (United States)

    Kechagias, S; Ernersson, A; Dahlqvist, O; Lundberg, P; Lindström, T; Nystrom, F H

    2008-05-01

    To study the effect of fast-food-based hyper-alimentation on liver enzymes and hepatic triglyceride content (HTGC). Prospective interventional study with parallel control group. University Hospital of Linköping, Sweden. 12 healthy men and six healthy women with a mean (SD) age of 26 (6.6) years and a matched control group. Subjects in the intervention group aimed for a body weight increase of 5-15% by eating at least two fast-food-based meals a day with the goal to double the regular caloric intake in combination with adoption of a sedentary lifestyle for 4 weeks. Weekly changes of serum aminotransferases and HTGC measured by proton nuclear magnetic resonance spectroscopy at baseline and after the intervention. Subjects in the intervention group increased from 67.6 (9.1) kg to 74.0 (11) kg in weight (p19 U/l, men >30 U/l) during the intervention. Sugar (mono- and disaccharides) intake during week 3 correlated with the maximal ALT/baseline ALT ratio (r = 0.62, p = 0.006). HTGC increased from 1.1 (1.9)% to 2.8 (4.8)%, although this was not related to the increase in ALT levels. ALT levels were unchanged in controls. Hyper-alimentation per se can induce profound ALT elevations in less than 4 weeks. Our study clearly shows that in the evaluation of subjects with elevated ALT the medical history should include not only questions about alcohol intake but also explore whether recent excessive food intake has occurred.

  5. The effect of sulforaphane on the levels of serum cystatin-c in acetaminophen- induced nephrotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Eda Dokumacioglu

    2016-09-01

    Full Text Available Objective: The exposure of living creatures to drugs and chemicals often results in toxicity of liver and kidney. Drugs constitute an important and big part of the commu­nity and hospital-acquired kidney diseases. In this study, we investigated the effect of sulforaphane (SFN on the levels of cystatin-C and lipid peroxidation on acetamino­phen (APAP- induced nephrotoxicity in rats. Methods: Thirty-six Sprague-Dawley rats were separat­ed equally into four experimental groups: control group, SFN group, APAP group, and APAP + SFN group. In the experimental treatment groups APAP was administered oral gavage at 1 g/kg 3 h after SFN treatment in last day and, in the APAP + SFN group, SFN was administered oral gavage at a dose of 500 μg/kg exactly for three days. Rats were euthanized and sacrificed 24 h after APAP ad­ministration. Results: APAP administration showed to significant in­crease in serum BUN, creatinine, urea and LDH concen­trations as compared to the control datas indicating the induction of severe nephrotoxicity (p<0.001. SFN treat­ment significantly decreased the cystatin-C levels and lipid peroxidation compared to APAP group (p<0.05. Conclusion: The present study demonstrate that the at­tachment of SFN to the nephrotoxicity treatment protocol will be beneficial and further studies should be conducted for cystatin C which plays an important role in kidney tox­icity and disease to be routinized as a biomarker.

  6. Is serum level of CC chemokine ligand 18 a biomarker for the prediction of radiation induced lung toxicity (RILT)?

    Science.gov (United States)

    Gkika, Eleni; Vach, Werner; Adebahr, Sonja; Schimek-Jasch, Tanja; Brenner, Anton; Brunner, Thomas Baptist; Kaier, Klaus; Prasse, Antje; Müller-Quernheim, Joachim; Grosu, Anca-Ligia; Zissel, Gernot; Nestle, Ursula

    2017-01-01

    The CC chemokine ligand 18 (CCL18) is produced by alveolar macrophages in patients with fibrosing lung disease and its concentration is increased in various fibrotic lung diseases. Furthermore CCL18 is elevated in several malignancies as it is produced by tumor associated macrophages. In this study we aimed to analyze the role of CCL18 as a prognostic biomarker for the development of early radiation induced lung toxicity (RILT), i.e. radiation pneumonitis after thoracic irradiation and its significance in the course of the disease. Sixty seven patients were enrolled prospectively in the study. Patients were treated with irradiation for several thoracic malignancies (lung cancer, esophageal cancer, thymoma), either with conventionally fractionated or hypo-fractionated radiotherapy. The CCL18 serum levels were quantified with ELISA (enzyme-linked immunosorbent assay) at predefined time points: before, during and at the end of treatment as well as in the first and second follow-up. Treatment parameters and functional tests were also correlated with the development of RILT.Fifty three patients were evaluable for this study. Twenty one patients (39%) developed radiologic signs of RILT Grade >1 but only three of them (5.6%) developed clinical symptoms (Grade 2). We could not find any association between the different CCL18 concentrations and a higher incidence of RILT. Statistical significant factors were the planning target volume (odds ratio OR: 1.003, p = 0.010), the volume of the lung receiving > 20 Gy (OR: 1.132 p = 0.004) and age (OR: 0.917, p = 0.008). There was no association between serial CCL18 concentrations with tumor response and overall survival.In our study the dosimetric parameters remained the most potent predictors of RILT. Further studies are needed in order to estimate the role of CCL18 in the development of early RILT.

  7. Is serum level of CC chemokine ligand 18 a biomarker for the prediction of radiation induced lung toxicity (RILT?

    Directory of Open Access Journals (Sweden)

    Eleni Gkika

    Full Text Available The CC chemokine ligand 18 (CCL18 is produced by alveolar macrophages in patients with fibrosing lung disease and its concentration is increased in various fibrotic lung diseases. Furthermore CCL18 is elevated in several malignancies as it is produced by tumor associated macrophages. In this study we aimed to analyze the role of CCL18 as a prognostic biomarker for the development of early radiation induced lung toxicity (RILT, i.e. radiation pneumonitis after thoracic irradiation and its significance in the course of the disease. Sixty seven patients were enrolled prospectively in the study. Patients were treated with irradiation for several thoracic malignancies (lung cancer, esophageal cancer, thymoma, either with conventionally fractionated or hypo-fractionated radiotherapy. The CCL18 serum levels were quantified with ELISA (enzyme-linked immunosorbent assay at predefined time points: before, during and at the end of treatment as well as in the first and second follow-up. Treatment parameters and functional tests were also correlated with the development of RILT.Fifty three patients were evaluable for this study. Twenty one patients (39% developed radiologic signs of RILT Grade >1 but only three of them (5.6% developed clinical symptoms (Grade 2. We could not find any association between the different CCL18 concentrations and a higher incidence of RILT. Statistical significant factors were the planning target volume (odds ratio OR: 1.003, p = 0.010, the volume of the lung receiving > 20 Gy (OR: 1.132 p = 0.004 and age (OR: 0.917, p = 0.008. There was no association between serial CCL18 concentrations with tumor response and overall survival.In our study the dosimetric parameters remained the most potent predictors of RILT. Further studies are needed in order to estimate the role of CCL18 in the development of early RILT.

  8. Effects of metformin treatment on Iron, Zinc and Copper status concentration in the serum of female rats with induced polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Muhsin S. G. Al-Moziel

    2013-07-01

    Full Text Available This study conducted to investigate the effects of metformin drug on serum Iron, Zinc and Copper concentration in Estradiol Valerate(EV induced polycystic ovary syndrome(PCOS in virgin rats. Thirty virgin rats were randomly allotted to constitute Normal control (NC-I group and induced polycystic ovary (PCO-I and PCO-II groups having 10 rats in each group. Rats from NC-I group were administered intramuscularly with 0.2 ml of corn oil whereas polycystic ovary was induced in rats from PCO-I and PCO-II groups by administering single intra-muscular injection of estradiol Valerate 4mg/rat. The rats from PCO-I and PCO-II groups were left for 60 days for development of polycystic ovary syndrome. Animals from PCO-I group were then administered with 0.2 ml normal saline as oral gavage for 15 days, these animals were kept as PCO control group animals whereas those from PCO-II groups received metformin (50mg/kg B.wt as oral gavage for 15 days, these animals served as metformin treated PCO group animals. All the rats were thereafter sacrificed for collecting blood from inferior vena-cava. Serum samples from each rat were assessed for iron, zinc and copper status in each experimental group. The results revealed a significant (p≤0.05 increase in serum Fe and Zn and a significant (p≤0.05 decrease in serum Cu concentration in PCO group 1 compared with control non-treated group. The PCO group2 treated with metformin showed a significant (p≤0.05 decrease in serum Fe concentration as compared with those in animals from group NC-I and PCO-I. While, no significant differences were found in serum Zn concentration between all treated groups. On the other hand, a significant (p≤0.05 increase in serum Cu concentration appeared in metformin treated group compared with PCO group 1 which appears significant decrease compared with control group.

  9. Stress-induced change in serum BDNF is related to quantitative family history of alcohol use disorder and age at first alcohol use.

    Science.gov (United States)

    Sharma, Shobhit; Graham, Reiko; Rohde, Rodney; Ceballos, Natalie A

    2017-02-01

    Previous research in animal models suggests that brain-derived neurotrophic factor (BDNF) is involved in stress-modulated alcohol consumption. However, relatively few studies have investigated this issue in humans, and results of existing studies have been heterogeneous. The primary aim of the current study was to examine the within-subjects effect of acute stress (timed math plus cold pressor) on serum BDNF levels (ΔBDNF: post- minus pre-stress) in healthy social drinkers (N=68, 20 male). A secondary aim was to explore which heritable and environmental factors in our limited sample might exert the greatest influences on ΔBDNF. Importantly, presence versus absence of the BDNF Val 66 Met polymorphism (rs6265), which has often been discounted in studies of human serum BDNF, was included as a between-subjects control variable in all statistical analyses. Our results indicated that acute stress decreased serum BDNF. Further, multiple regression analyses revealed that quantitative family history of alcohol use disorder (qFH) and age at first alcohol use together accounted for 15% of the variance in ΔBDNF. Thus, the influences of qFH and age at first alcohol use may explain some of the heterogeneity that exists in previous studies of human serum BDNF. These results parallel findings in animal models and suggest that stress-related changes in serum BDNF are influenced by both heritable (qFH) and environmental (early alcohol consumption) factors. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Passive transfer with serum and IgG antibodies of irradiated cercaria-induced resistance against Schistosoma mansoni in mice

    International Nuclear Information System (INIS)

    Mangold, B.L.; Dean, D.A.

    1986-01-01

    The role of humoral immunity to Schistosoma mansoni infection in C57BL/6J mice was examined by employing a passive transfer system. Sera from highly resistant mice that had been exposed to two or three immunizations with 50-kilorad-gamma-irradiated cercariae were tested for their ability to transfer protection against S. mansoni challenge. All five batches of serum tested were observed to have protective activity. Immune serum recipients exhibited statistically significant reductions in challenge worm burdens of 20 to 50% compared with recipients of normal serum or no serum. The most consistent level of resistance was obtained when immune serum was administered several days post-challenge, i.e., at a time coincident with schistosomulum residence in the lungs. Furthermore, it was shown that the protective activity in immune serum was associated with factors that bind to staphylococcal protein A and that are precipitated by 50% ammonium sulfate; thus it appears that the protective factors in immune serum are IgG antibodies

  11. Buyang Huanwu Decoction Vigorously Rescues PC12 Cells Against 6-OHDA-Induced Neurotoxicity via Akt/GSK3β Pathway Based on Serum Pharmacology Methodology.

    Science.gov (United States)

    Li, Zeyan; Wang, Hui; Wang, Qian; Sun, Jinhao

    2016-12-01

    Buyang Huanwu decoction (BYHWD), as a popular traditional Chinese medicine formula, was widely used for treating ischemic diseases. However, in the area of neurodegenerative diseases, the researches focused on BYHWD are rare but promising, and molecular mechanisms underlying are largely elusive. 6-Hydroxydopamine (6-OHDA), a dopaminergic-specific neurotoxin, is extensively used to establish neurotoxic model in vivo and in vitro. In our present study, we prepared drug-containing serum of BYHWD (Buyang Huanwu drug-containing serum [BYHWS]) based on serum pharmacology methodology. Neurotoxic model in vitro was established in PC12 cells, and innovative experimental grouping method was adopted to investigate neuroprotective effects of BYHWS on neurotoxicity induced by 6-OHDA exposure. Remarkably, BYHWS vigorously rescued PC12 cells from 6-OHDA-induced neurotoxicity even to surpass 100% in cell viability. Moreover, Hoechst/propidium iodide (PI) staining revealed that cell apoptotic rate was reduced significantly after incubation of BYHWS. Besides, BYHWS effectively restored the disruption of mitochondrial membrane potential and attenuated the elevation of intracellular reactive oxygen species level caused by 6-OHDA insult. Furthermore, BYHWS remarkably reversed the dephosphorylation of Akt (protein kinase B) and glycogen synthase kinase-3β (GSK3β) evoked by 6-OHDA. The above protective effects were attenuated by coculturing with Akt inhibitor LY294002. In summary, we concluded that the BYHWS vigorously blocked 6-OHDA-induced neurotoxicity via Akt/GSK3β pathway and provided a novel insight into roles of BYHWD in the clinical practices on neurodegenerative diseases.

  12. Plasma-induced surface degradation in 304 stainless steel used for TRIAM-1M limiter

    International Nuclear Information System (INIS)

    Tsukuda, N.; Kuramoto, E.; Tokunaga, K.; Muroga, T.; Yoshida, N.; Itoh, S.

    1994-01-01

    Surface degradation in a 304 stainless steel limiter of TRIAM-1M by long-pulse discharge during long period operation has been examined by means of X-ray diffraction, scanning electron microscopy and dynamical microindentation tests. Particular exfoliation and hardening of the surface of the electron drift side were observed. These result from the formation of α prime martensite induced by hydrogen in the plasma. The stability of the martensitic phase has been studied by annealing experiments on the cathodically hydrogen charged 316 stainless steel by X-ray diffraction. Both ε and α prime martensites were formed by 22 h cathodic charging. The former reverts to γ-phase and/or converts to α prime martensite below 723 K and the latter reverts to γ-phase below 923 K, repectively. ((orig.))

  13. DC current in the collisionless limit induced by a travelling wave

    International Nuclear Information System (INIS)

    Midzuno, Yukio; Fukuda, Masaji.

    1977-03-01

    The DC current induced by a Travelling Wave is calculated on the basis of the assumption that the distribution function of electrons in the collisionless limit should be determined by a condition derived from the nature of the collision operator, as in the case of the calculation of the neoclassical transport in a torus. The resultant net current is found to have the same parameter dependence as the one derived in a previous analysis, in which we assumed the initial distribution of electrons to be uniform and isotropic Maxwellian. The numerical coefficient is found, however, to be a little different from the previous one. The importance of the accurate matching of the distribution function of untrapped particles to the Maxwellian one for large velocity is demonstrated. (auth.)

  14. Potential role of peroxisome proliferator activated receptor gamma activation on serum visfatin and trace elements in high fat diet induced type 2 diabetes mellitus.

    Science.gov (United States)

    Tabassum, Arshia; Zaidi, Syeda Nuzhat Fatima; Yasmeen, Kausar; Mahboob, Tabassum

    2018-07-15

    Electrolytes and trace elements dysregulation play an important role in the progression of obesity and diabetes complications. The present study was designed to evaluate the insulin sensitizing effects of peroxisomes proliferators activated receptor gamma (PPAR-γ) agonist on trace elements in obesity induced type 2 diabetes mellitus and correlate with serum visfatin. Wistar rats were categorized into five groups. Group I served as control; Group II fed on high fat diet (HFD); Group III fed on HFD and treated with rosiglitazone (3 mg/kg) for 7 days; Group IV were T2DM rats induce by HFD and low dose of streptozotocin (i.p. 35 mg/kg); Group V was T2DM rats treated with rosiglitazone (3 mg/kg) for 7 days. Serum and tissues electrolytes levels and renal, hepatic and cardiac tissues trace elements were estimated by flame photometer and atomic absorption spectroscopy. Serum visfatin was estimated by ELISA. Pearson correlations were analyzed among fasting blood glucose (FBG), serum visfatin and tissues trace elements. Results of the current study showed hyponatremia, hyperkalemia, hypomagnesemia and hypercalcemia in HFD and T2DM groups. HFD and T2DM also showed elevated copper and iron levels; however, zinc and selenium levels were decreased. Rosiglitazone treatment increased the insulin sensitization and altered these changes. A Strong association was observed among FBG, serum visfatin and trace elements levels of HFD and T2DM. Obesity and diabetes mellitus disturbed visfatin, electrolytes and trace elements homeostasis. Rosiglitazone treatment restored these changes. The results of the study could serve as a basis for further studies for the prevention of diabetic complications. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Bulk-Like Electrical Properties Induced by Contact-Limited Charge Transport in Organic Diodes: Revised Space Charge Limited Current

    KAUST Repository

    Xu, Guangwei

    2018-02-22

    Charge transport governs the operation and performance of organic diodes. Illuminating the charge-transfer/transport processes across the interfaces and the bulk organic semiconductors is at the focus of intensive investigations. Traditionally, the charge transport properties of organic diodes are usually characterized by probing the current–voltage (I–V) curves of the devices. However, to unveil the landscape of the underlying potential/charge distribution, which essentially determines the I–V characteristics, still represents a major challenge. Here, the electrical potential distribution in planar organic diodes is investigated by using the scanning Kelvin probe force microscopy technique, a method that can clearly separate the contact and bulk regimes of charge transport. Interestingly, by applying to devices based on novel, high mobility organic materials, the space-charge-limited-current-like I–V curves, which are previously believed to be a result of the bulk transport, are surprisingly but unambiguously demonstrated to be caused by contact-limited conduction. A model accounting is developed for the transport properties of both the two metal/organic interfaces and the bulk. The results indicate that pure interface-dominated transport can indeed give rise to I–V curves similar to those caused by bulk transport. These findings provide a new insight into the charge injection and transport processes in organic diodes.

  16. Serum Creatinine: Not So Simple!

    OpenAIRE

    DELANAYE, Pierre; Cavalier, Etienne; Pottel, Hans

    2017-01-01

    Measuring serum creatinine is cheap and commonly done in daily practice. However, interpretation of serum creatinine results is not always easy. In this review, we will briefly remind the physiological limitations of serum creatinine due notably to its tubular secretion and the influence of muscular mass or protein intake on its concentration. We mainly focus on the analytical limitations of serum creatinine, insisting on important concept such as reference intervals, standardization (and IDM...

  17. Degalactosylated/desialylated human serum containing GcMAF induces macrophage phagocytic activity and in vivo antitumor activity.

    Science.gov (United States)

    Kuchiike, Daisuke; Uto, Yoshihiro; Mukai, Hirotaka; Ishiyama, Noriko; Abe, Chiaki; Tanaka, Daichi; Kawai, Tomohito; Kubo, Kentaro; Mette, Martin; Inui, Toshio; Endo, Yoshio; Hori, Hitoshi

    2013-07-01

    The group-specific component protein-derived macrophage-activating factor (GcMAF) has various biological activities, such as macrophage activation and antitumor activity. Clinical trials of GcMAF have been carried out for metastatic breast cancer, prostate cancer, and metastatic colorectal cancer. In this study, despite the complicated purification process of GcMAF, we used enzymatically-treated human serum containing GcMAF with a considerable macrophage-stimulating activity and antitumor activity. We detected GcMAF in degalactosylated/desialylated human serum by western blotting using an anti-human Gc globulin antibody, and Helix pomatia agglutinin lectin. We also found that GcMAF-containing human serum significantly enhanced the phagocytic activity of mouse peritoneal macrophages and extended the survival time of mice bearing Ehrlich ascites tumors. We demonstrated that GcMAF-containing human serum can be used as a potential macrophage activator for cancer immunotherapy.

  18. RCRA materials analysis by laser-induced breakdown spectroscopy: Detection limits in soils

    International Nuclear Information System (INIS)

    Koskelo, A.; Cremers, D.A.

    1994-01-01

    The goal of the Technical Task Plan (TTP) that this report supports is research, development, testing and evaluation of a portable analyzer for RCRA and other metals. The instrumentation to be built will be used for field-screening of soils. Data quality is expected to be suitable for this purpose. The data presented in this report were acquired to demonstrate the detection limits for laser-induced breakdown spectroscopy (LIBS) of soils using instrument parameters suitable for fieldable instrumentation. The data are not expected to be the best achievable with the high pulse energies available in laboratory lasers. The report presents work to date on the detection limits for several elements in soils using LIBS. The elements targeted in the Technical Task Plan are antimony, arsenic, beryllium, cadmium, chromium, lead, selenium, and zirconium. Data for these elements are presented in this report. Also included are other data of interest to potential customers for the portable LIBS apparatus. These data are for barium, mercury, cesium and strontium. Data for uranium and thorium will be acquired during the tasks geared toward mixed waste characterization

  19. Interleukin-17 limits hypoxia-inducible factor 1α and development of hypoxic granulomas during tuberculosis.

    Science.gov (United States)

    Domingo-Gonzalez, Racquel; Das, Shibali; Griffiths, Kristin L; Ahmed, Mushtaq; Bambouskova, Monika; Gopal, Radha; Gondi, Suhas; Muñoz-Torrico, Marcela; Salazar-Lezama, Miguel A; Cruz-Lagunas, Alfredo; Jiménez-Álvarez, Luis; Ramirez-Martinez, Gustavo; Espinosa-Soto, Ramón; Sultana, Tamanna; Lyons-Weiler, James; Reinhart, Todd A; Arcos, Jesus; de la Luz Garcia-Hernandez, Maria; Mastrangelo, Michael A; Al-Hammadi, Noor; Townsend, Reid; Balada-Llasat, Joan-Miquel; Torrelles, Jordi B; Kaplan, Gilla; Horne, William; Kolls, Jay K; Artyomov, Maxim N; Rangel-Moreno, Javier; Zúñiga, Joaquín; Khader, Shabaana A

    2017-10-05

    Mycobacterium tuberculosis (Mtb) is a global health threat, compounded by the emergence of drug-resistant strains. A hallmark of pulmonary tuberculosis (TB) is the formation of hypoxic necrotic granulomas, which upon disintegration, release infectious Mtb. Furthermore, hypoxic necrotic granulomas are associated with increased disease severity and provide a niche for drug-resistant Mtb. However, the host immune responses that promote the development of hypoxic TB granulomas are not well described. Using a necrotic Mtb mouse model, we show that loss of Mtb virulence factors, such as phenolic glycolipids, decreases the production of the proinflammatory cytokine IL-17 (also referred to as IL-17A). IL-17 production negatively regulates the development of hypoxic TB granulomas by limiting the expression of the transcription factor hypoxia-inducible factor 1α (HIF1α). In human TB patients, HIF1α mRNA expression is increased. Through genotyping and association analyses in human samples, we identified a link between the single nucleotide polymorphism rs2275913 in the IL-17 promoter (-197G/G), which is associated with decreased IL-17 production upon stimulation with Mtb cell wall. Together, our data highlight a potentially novel role for IL-17 in limiting the development of hypoxic necrotic granulomas and reducing disease severity in TB.

  20. The influence of folate serum levels on depressive mood and mental processing in patients with epilepsy treated with enzyme-inducing anti-epileptic drugs.

    Science.gov (United States)

    Rösche, J; Uhlmann, C; Weber, R; Fröscher, W

    2003-04-01

    Folate deficiency is common in patients with epilepsy and also occurs in patients with depression or cognitive deficits. This study investigates whether low serum folate levels may contribute to depressive mood and difficulties in mental processing in patients with epilepsy treated with anti-epileptic drugs inducing the cytochrome P450. We analysed the serum folate levels, the score in the Self Rating Depression Scale (SDS) and the results of a bedside test in mental processing in 54 patients with epilepsy. There was a significant negative correlation between the serum folate levels and the score in SDS and significant positive correlations between the score in SDS and the time needed to process an interference task or a letter-reading task. Low serum folate levels may contribute to depressive mood and therefore to difficulties in mental processing. Further studies utilizing total plasma homocysteine as a sensitive measure of functional folate deficiency and more elaborate tests of mental processing are required to elucidate the impact of folate metabolism on depressive mood and cognitive function in patients with epilepsy.

  1. Protection of Human Podocytes from Shiga Toxin 2-Induced Phosphorylation of Mitogen-Activated Protein Kinases and Apoptosis by Human Serum Amyloid P Component

    Science.gov (United States)

    Dettmar, Anne K.; Binder, Elisabeth; Greiner, Friederike R.; Liebau, Max C.; Kurschat, Christine E.; Jungraithmayr, Therese C.; Saleem, Moin A.; Schmitt, Claus-Peter; Feifel, Elisabeth; Orth-Höller, Dorothea; Kemper, Markus J.; Pepys, Mark; Würzner, Reinhard

    2014-01-01

    Hemolytic uremic syndrome (HUS) is mainly induced by Shiga toxin 2 (Stx2)-producing Escherichia coli. Proteinuria can occur in the early phase of the disease, and its persistence determines the renal prognosis. Stx2 may injure podocytes and induce proteinuria. Human serum amyloid P component (SAP), a member of the pentraxin family, has been shown to protect against Stx2-induced lethality in mice in vivo, presumably by specific binding to the toxin. We therefore tested the hypothesis that SAP can protect against Stx2-induced injury of human podocytes. To elucidate the mechanisms underlying podocyte injury in HUS-associated proteinuria, we assessed Stx2-induced activation of mitogen-activated protein kinases (MAPKs) and apoptosis in immortalized human podocytes and evaluated the impact of SAP on Stx2-induced damage. Human podocytes express Stx2-binding globotriaosylceramide 3. Stx2 applied to cultured podocytes was internalized and then activated p38α MAPK and c-Jun N-terminal kinase (JNK), important signaling steps in cell differentiation and apoptosis. Stx2 also activated caspase 3, resulting in an increased level of apoptosis. Coincubation of podocytes with SAP and Stx2 mitigated the effects of Stx2 and induced upregulation of antiapoptotic Bcl2. These data suggest that podocytes are a target of Stx2 and that SAP protects podocytes against Stx2-induced injury. SAP may therefore be a useful therapeutic option. PMID:24566618

  2. Serum Creatinine in Patients with Advanced Liver Disease Is of Limited Value for Identification of Moderate Renal Dysfunction: Are the Equations for Estimating Renal Function Better?

    Directory of Open Access Journals (Sweden)

    Jillian MacAulay

    2006-01-01

    Full Text Available BACKGROUND: The Cockcroft-Gault formula (CGF is used to estimate the glomerular filtration rate (GFR based on serum creatinine (Cr levels, age and sex. A new formula developed by the Modification of Diet in Renal Disease (MDRD Study Group, based on the patient’s Cr levels, age, sex, race and serum urea nitrogen and serum albumin levels, has shown to be more accurate. However, the best formula to identify patients with advanced liver disease (ALD and moderate renal dysfunction (GFR 60 mL/min/1.73 m2 or less is not known. The aim of the present study was to compare calculations of GFR, using published formulas (excluding those requiring urine collections with standard radionuclide measurement of GFR in patients with ALD.

  3. Effect of ceramic membrane channel geometry and uniform transmembrane pressure on limiting flux and serum protein removal during skim milk microfiltration.

    Science.gov (United States)

    Adams, Michael C; Hurt, Emily E; Barbano, David M

    2015-11-01

    Our objectives were to determine the effects of a ceramic microfiltration (MF) membrane's retentate flow channel geometry (round or diamond-shaped) and uniform transmembrane pressure (UTP) on limiting flux (LF) and serum protein (SP) removal during skim milk MF at a temperature of 50°C, a retentate protein concentration of 8.5%, and an average cross-flow velocity of 7 m·s(-1). Performance of membranes with round and diamond flow channels was compared in UTP mode. Performance of the membrane with round flow channels was compared with and without UTP. Using UTP with round flow channel MF membranes increased the LF by 5% when compared with not using UTP, but SP removal was not affected by the use of UTP. Using membranes with round channels instead of diamond-shaped channels in UTP mode increased the LF by 24%. This increase was associated with a 25% increase in Reynolds number and can be explained by lower shear at the vertices of the diamond-shaped channel's surface. The SP removal factor of the diamond channel system was higher than the SP removal factor of the round channel system below the LF. However, the diamond channel system passed more casein into the MF permeate than the round channel system. Because only one batch of each membrane was tested in our study, it was not possible to determine if the differences in protein rejection between channel geometries were due to the membrane design or random manufacturing variation. Despite the lower LF of the diamond channel system, the 47% increase in membrane module surface area of the diamond channel system produced a modular permeate removal rate that was at least 19% higher than the round channel system. Consequently, using diamond channel membranes instead of round channel membranes could reduce some of the costs associated with ceramic MF of skim milk if fewer membrane modules could be used to attain the required membrane area. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All

  4. Limited ability of DNA polymerase kappa to suppress benzo[a]pyrene-induced genotoxicity in vivo.

    Science.gov (United States)

    Masumura, Kenichi; Toyoda-Hokaiwado, Naomi; Niimi, Naoko; Grúz, Petr; Wada, Naoko A; Takeiri, Akira; Jishage, Kou-Ichi; Mishima, Masayuki; Nohmi, Takehiko

    2017-12-01

    DNA polymerase kappa (Polk) is a specialized DNA polymerase involved in translesion DNA synthesis. To understand the protective roles against genotoxins in vivo, we established inactivated Polk knock-in gpt delta (inactivated Polk KI) mice that possessed reporter genes for mutations and expressed inactive Polk. In this study, we examined genotoxicity of benzo[a]pyrene (BP) to determine whether Polk actually suppressed BP-induced genotoxicity as predicted by biochemistry and in vitro cell culture studies. Seven-week-old inactivated Polk KI and wild-type (WT) mice were treated with BP at doses of 5, 15, or 50 mg/(kg·day) for three consecutive days by intragastric gavage, and mutations in the colon and micronucleus formation in the peripheral blood were examined. Surprisingly, no differences were observed in the frequencies of mutations and micronucleus formation at 5 or 50 mg/kg doses. Inactivated Polk KI mice exhibited approximately two times higher gpt mutant frequency than did WT mice only at the 15 mg/kg dose. The frequency of micronucleus formation was slightly higher in inactivated Polk KI than in WT mice at the same dose, but it was statistically insignificant. The results suggest that Polk has a limited ability to suppress BP-induced genotoxicity in the colon and bone marrow and also that the roles of specialized DNA polymerases in mutagenesis and carcinogenesis should be examined not only by in vitro assays but also by in vivo mouse studies. We also report the spontaneous mutagenesis in inactivated Polk KI mice at young and old ages. Environ. Mol. Mutagen. 58:644-653, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Intranasal administration of a proteosome-influenza vaccine is well-tolerated and induces serum and nasal secretion influenza antibodies in healthy human subjects.

    Science.gov (United States)

    Treanor, John; Nolan, Carrie; O'Brien, Diane; Burt, David; Lowell, George; Linden, Janine; Fries, Louis

    2006-01-16

    Two randomized, blinded, active comparator-controlled trials of a prototype monovalent A/Beijing/262/95 (H1N1) - proteosome vaccine delivered by intranasal spray were performed in healthy adults. Overall, the intranasal proteosome-adjuvanted vaccine was well-tolerated with only mild stuffy nose and rhinorrhea seen more frequently in recipients of vaccine than in recipients of intranasal saline, and there were no serious adverse events. The intranasal proteosome-adjuvanted vaccine induced serum hemagglutination inhibiting (HAI) and nasal secretory IgA (sIgA) responses specific for the influenza antigen. Serum HAI responses were most influenced by the dosage level, whereas mucosal sIgA responses, although demonstrable with both single-dose and two-dose vaccine regimens, appeared to be greater in response to two-dose regimens (regardless of dose level). Further evaluation of mucosal influenza immunization using the proteosome adjuvant/delivery system is clearly warranted.

  6. Brain-derived neurotrophic factor and interleukin-6 levels in the serum and cerebrospinal fluid of children with viral infection-induced encephalopathy.

    Science.gov (United States)

    Morichi, Shinichiro; Yamanaka, Gaku; Ishida, Yu; Oana, Shingo; Kashiwagi, Yasuyo; Kawashima, Hisashi

    2014-11-01

    We investigated changes in the brain-derived neurotrophic factor (BDNF) and interleukin (IL)-6 levels in pediatric patients with central nervous system (CNS) infections, particularly viral infection-induced encephalopathy. Over a 5-year study period, 24 children hospitalized with encephalopathy were grouped based on their acute encephalopathy type (the excitotoxicity, cytokine storm, and metabolic error types). Children without CNS infections served as controls. In serum and cerebrospinal fluid (CSF) samples, BDNF and IL-6 levels were increased in all encephalopathy groups, and significant increases were noted in the influenza-associated and cytokine storm encephalopathy groups. Children with sequelae showed higher BDNF and IL-6 levels than those without sequelae. In pediatric patients, changes in serum and CSF BDNF and IL-6 levels may serve as a prognostic index of CNS infections, particularly for the diagnosis of encephalopathy and differentiation of encephalopathy types.

  7. Mitochondrial ribosomal protein L41 mediates serum starvation-induced cell-cycle arrest through an increase of p21WAF1/CIP1

    International Nuclear Information System (INIS)

    Kim, Mi Jin; Yoo, Young A.; Kim, Hyung Jung; Kang, Seongman; Kim, Yong Geon; Kim, Jun Suk; Yoo, Young Do

    2005-01-01

    Ribosomal proteins not only act as components of the translation apparatus but also regulate cell proliferation and apoptosis. A previous study reported that MRPL41 plays an important role in p53-dependent apoptosis. It also showed that MRPL41 arrests the cell cycle by stabilizing p27 Kip1 in the absence of p53. This study found that MRPL41 mediates the p21 WAF1/CIP1 -mediated G1 arrest in response to serum starvation. The cells were released from serum starvation-induced G1 arrest via the siRNA-mediated blocking of MRPL41 expression. Overall, these results suggest that MRPL41 arrests the cell cycle by increasing the p21 WAF1/CIP1 and p27 Kip1 levels under the growth inhibitory conditions

  8. Chest wall restriction limits high airway pressure-induced lung injury in young rabbits.

    Science.gov (United States)

    Hernandez, L A; Peevy, K J; Moise, A A; Parker, J C

    1989-05-01

    High peak inspiratory pressures (PIP) during mechanical ventilation can induce lung injury. In the present study we compare the respective roles of high tidal volume with high PIP in intact immature rabbits to determine whether the increase in capillary permeability is the result of overdistension of the lung or direct pressure effects. New Zealand White rabbits were assigned to one of three protocols, which produced different degrees of inspiratory volume limitation: intact closed-chest animals (CC), closed-chest animals with a full-body plaster cast (C), and isolated excised lungs (IL). The intact animals were ventilated at 15, 30, or 45 cmH2O PIP for 1 h, and the lungs of the CC and C groups were placed in an isolated lung perfusion system. Microvascular permeability was evaluated using the capillary filtration coefficient (Kfc). Base-line Kfc for isolated lungs before ventilation was 0.33 +/- 0.31 ml.min-1.cmH2O-1.100g-1 and was not different from the Kfc in the CC group ventilated with 15 cmH2O PIP. Kfc increased by 850% after ventilation with only 15 cmH2O PIP in the unrestricted IL group, and in the CC group Kfc increased by 31% after 30 cmH2O PIP and 430% after 45 cmH2O PIP. Inspiratory volume limitation by the plaster cast in the C group prevented any significant increase in Kfc at the PIP values used. These data indicate that volume distension of the lung rather than high PIP per se produces microvascular damage in the immature rabbit lung.

  9. Serum miR-451a Levels Are Significantly Elevated in Women With Endometriosis and Recapitulated in Baboons ( Papio anubis) With Experimentally-Induced Disease.

    Science.gov (United States)

    Nothnick, Warren B; Falcone, Tommaso; Joshi, Niraj; Fazleabas, Asgerally T; Graham, Amanda

    2017-08-01

    We have previously demonstrated that human microRNA-451a (miR-451a) endometriotic lesion expression is significantly higher compared to that of the corresponding eutopic endometrium. The objective of the current study was to examine the relationship between lesion and serum content of miR-451a and to determine the utility of serum miR-451a in distinguishing between women with and without visible signs of endometriosis. Eighty-one participants were enrolled in this study, 41 with confirmed endometriosis and 40 without visible signs of endometriosis at laparoscopy (n = 20) or symptoms of endometriosis (pain, infertility n = 20). Experimental endometriosis was also induced in 8 baboons. Blood, endometriotic lesions, and eutopic endometrial samples were collected from women undergoing laparoscopy for surgical removal of endometriosis. Blood was also collected from control participants with no signs and symptoms associated with the disease as well as from baboons prior to, and then 1, 3, 6, 9, and 15 months postinduction of endometriosis. MicroRNA-451a was assessed by quantitative real-time polymerase chain reaction in all samples. In humans, serum miR-451a levels positively correlated with endometriotic lesion miR-451a content, and sera levels were significantly higher in these participants compared to controls. The area under the curve (AUC) for miR-451a was 0.8599. In baboons, serum miR-451a reached statistically significant peak levels at 6 months postinduction of endometriosis. We conclude from this study that sera miR-451a levels positively correlated with endometriotic lesion content and are significantly greater compared to sera levels in women without visible signs or symptoms of endometriosis. MicroRNA-451a may serve as a serum diagnostic marker for endometriosis.

  10. EFFECTS OF L-ASCORBIC ACID AND ALPHA-TOCOPHEROL ON BIOCHEMICAL PARAMETERS OF SWIMMING-INDUCED OXIDATIVE STRESS IN SERUM OF GUINEA PIGS.

    Science.gov (United States)

    Bursać-Mitrović, Marija; Milovanović, Dragan R; Mitić, Radoslav; Jovanović, Danijela; Sovrlić, Miroslav; Vasiljević, Perica; Tomović, Jovica; Manojlović, Nedeljko

    2016-01-01

    The purpose of this study is to determine the effect of L-ascorbic acid and alpha-tocopherol as well as combination of these vitamins with or without exposure to physical exercise on intensity of lipid peroxidation, activity of xanthine oxidase, activity of total antioxidative system, concentration of glutathione, and activity of catalase in the serum of guinea pigs. The experimental measurements of intensity of lipid peroxidation, activity of xanthine oxidase, activity of total antioxidative system, concentration of glutathione, and activity of catalase were done in the serum of guinea pigs. The animals were exposed to the test load to achieve exhaustion and the test was terminated when the animal for the third time to sink into the water. The results of this study demonstrated that endurance exercise of guinea pigs induced oxidative stress response in terms of increased lipid peroxidation and activity of xanthine oxidase in the serum of experimental animals. Our study investigated the antioxidant activity of L-ascorbic acid and alpha-tocopherol also measuring three protective markers in the serum: total antioxidant activity, content of glutathione and activity of catalase. The results obtained show that the vitamins influence the concentrations of above mentioned biochemical parameters, which points out their protective effect of swimming-induced oxidative stress. Single or combined administration of L-ascorbic acid and alpha-tocopherol caused significant inhibition of these markers indicating the important antioxidant activity of the vitamins. Results lead to conclude that the combined treatments with vitamins with or without exposure to physical exercise showed the clear synergistic effect..

  11. Effects of chicory inulin on serum metabolites of uric acid, lipids, glucose, and abdominal fat deposition in quails induced by purine-rich diets.

    Science.gov (United States)

    Lin, Zhijian; Zhang, Bing; Liu, Xiaoqing; Jin, Rui; Zhu, Wenjing

    2014-11-01

    Inulin, a group of dietary fibers, is reported to improve the metabolic disorders. In the present study, we investigated the effects of chicory inulin on serum metabolites of uric acid (UA), lipids, glucose, and abdominal fat deposition in quail model induced by a purine-rich diet. In this study, 60 male French quails were randomly allocated to five groups: CON (control group), MOD (model group), BEN (benzbromarone-treated group), CHI-H (high-dosage chicory inulin-treated group), and CHI-L (low-dosage chicory inulin-treated group). The serum UA level was significantly increased in the model group from days 7 to 28, as well as triglyceride (TG) and free fatty acid (FFA) increased later in the experimental period. The abdominal fat ratio was increased on day 28. Benzbromarone can decrease UA levels on days 14 and 28. The high and low dosage of chicory inulin also decreased serum UA levels on days 7, 14, and 28. The abdominal fat ratio, activity, and protein of acetyl-CoA carboxylase (ACC) were decreased in chicory inulin-treated groups. The activities of xanthine oxidase (XOD) and fatty acid synthase (FAS) were increased in the model group and decreased in the benzbromarone and chicory inulin groups. This study evaluated a quail model of induced hyperuricemia with other metabolic disorders caused by a high-purine diet. The results indicated that a purine-rich diet might contribute to the development of hyperuricemia, hypertriglyceridemia, and abdominal obesity. Chicory inulin decreased serum UA, TG, and abdominal fat deposition in a quail model of hyperuricemia by altering the ACC protein expression and FAS and XOD activities.

  12. Significance of determination of serum IL-8 and interferon induced protein-10 (IP-10) contents in patients with psoriasis

    International Nuclear Information System (INIS)

    Yang Shijun; Cui Jianhe; Xue Mei

    2005-01-01

    Objective: To explore the roles played by IL-8 and IP-10 in the development and pathogenesis of psoriasis. Methods: Serum IL-8 (with RIA) and IP-10 (with ELISA) contents were measured in 47 patients with psoriasis and 42 controls. Results: The serum contents of IL-8 and IP-10 were significantly higher in the patients with psoriasis than those in the controls (P<0.01). Conclusion: IL-8 and IP-10 participated in the pathogenesis of psoriasis. Possible mechanisms were discussed. (authors)

  13. Drought-induced trans-generational tradeoff between stress tolerance and defence: consequences for range limits?

    Science.gov (United States)

    Alsdurf, Jacob D; Ripley, Tayler J; Matzner, Steven L; Siemens, David H

    2013-01-01

    Areas just across species range boundaries are often stressful, but even with ample genetic variation within and among range-margin populations, adaptation towards stress tolerance across range boundaries often does not occur. Adaptive trans-generational plasticity should allow organisms to circumvent these problems for temporary range expansion; however, range boundaries often persist. To investigate this dilemma, we drought stressed a parent generation of Boechera stricta (A.Gray) A. Löve & D. Löve, a perennial wild relative of Arabidopsis, representing genetic variation within and among several low-elevation range margin populations. Boechera stricta is restricted to higher, moister elevations in temperate regions where generalist herbivores are often less common. Previous reports indicate a negative genetic correlation (genetic tradeoff) between chemical defence allocation and abiotic stress tolerance that may prevent the simultaneous evolution of defence and drought tolerance that would be needed for range expansion. In growth chamber experiments, the genetic tradeoff became undetectable among offspring sib-families whose parents had been drought treated, suggesting that the stress-induced trans-generational plasticity may circumvent the genetic tradeoff and thus enable range expansion. However, the trans-generational effects also included a conflict between plastic responses (environmental tradeoff); offspring whose parents were drought treated were more drought tolerant, but had lower levels of glucosinolate toxins that function in defence against generalist herbivores. We suggest that either the genetic or environmental tradeoff between defence allocation and stress tolerance has the potential to contribute to range limit development in upland mustards.

  14. Growth decline linked to warming-induced water limitation in hemi-boreal forests.

    Directory of Open Access Journals (Sweden)

    Xiuchen Wu

    Full Text Available Hemi-boreal forests, which make up the transition from temperate deciduous forests to boreal forests in southern Siberia, have experienced significant warming without any accompanying increase in precipitation during the last 80 years. This climatic change could have a profound impact on tree growth and on the stability of forest ecosystems in this region, but at present evidence for these impacts is lacking. In this study, we report a recent dramatic decline in the growth of hemi-boreal forests, based on ring width measurements from three dominant tree-species (Pinus sylvestris, Larix sibirica and Larix gmelinii, sampled from eight sites in the region. We found that regional tree growth has become increasingly limited by low soil water content in the pre- and early-growing season (from October of the previous year to July of the current year over the past 80 years. A warming-induced reduction in soil water content has also increased the climate sensitivity of these three tree species. Beginning in the mid-1980s, a clear decline in growth is evident for both the pine forests and the larch forests, although there are increasing trends in the proxy of soil water use efficiencies. Our findings are consistent with those from other parts of the world and provide valuable insights into the regional carbon cycle and vegetation dynamics, and should be useful for devising adaptive forest management strategies.

  15. Growth decline linked to warming-induced water limitation in hemi-boreal forests.

    Science.gov (United States)

    Wu, Xiuchen; Liu, Hongyan; Guo, Dali; Anenkhonov, Oleg A; Badmaeva, Natalya K; Sandanov, Denis V

    2012-01-01

    Hemi-boreal forests, which make up the transition from temperate deciduous forests to boreal forests in southern Siberia, have experienced significant warming without any accompanying increase in precipitation during the last 80 years. This climatic change could have a profound impact on tree growth and on the stability of forest ecosystems in this region, but at present evidence for these impacts is lacking. In this study, we report a recent dramatic decline in the growth of hemi-boreal forests, based on ring width measurements from three dominant tree-species (Pinus sylvestris, Larix sibirica and Larix gmelinii), sampled from eight sites in the region. We found that regional tree growth has become increasingly limited by low soil water content in the pre- and early-growing season (from October of the previous year to July of the current year) over the past 80 years. A warming-induced reduction in soil water content has also increased the climate sensitivity of these three tree species. Beginning in the mid-1980s, a clear decline in growth is evident for both the pine forests and the larch forests, although there are increasing trends in the proxy of soil water use efficiencies. Our findings are consistent with those from other parts of the world and provide valuable insights into the regional carbon cycle and vegetation dynamics, and should be useful for devising adaptive forest management strategies.

  16. Confocal laser-induced fluorescence detector for narrow capillary system with yoctomole limit of detection.

    Science.gov (United States)

    Weaver, Mitchell T; Lynch, Kyle B; Zhu, Zaifang; Chen, Huang; Lu, Joann J; Pu, Qiaosheng; Liu, Shaorong

    2017-04-01

    Laser-induced fluorescence (LIF) detectors for low-micrometer and sub-micrometer capillary on-column detection are not commercially available. In this paper, we describe in details how to construct a confocal LIF detector to address this issue. We characterize the detector by determining its limit of detection (LOD), linear dynamic range (LDR) and background signal drift; a very low LOD (~70 fluorescein molecules or 12 yoctomole fluorescein), a wide LDR (greater than 3 orders of magnitude) and a small background signal drift (~1.2-fold of the root mean square noise) are obtained. For detecting analytes inside a low-micrometer and sub-micrometer capillary, proper alignment is essential. We present a simple protocol to align the capillary with the optical system and use the position-lock capability of a translation stage to fix the capillary in position during the experiment. To demonstrate the feasibility of using this detector for narrow capillary systems, we build a 2-μm-i.d. capillary flow injection analysis (FIA) system using the newly developed LIF prototype as a detector and obtain an FIA LOD of 14 zeptomole fluorescein. We also separate a DNA ladder sample by bare narrow capillary - hydrodynamic chromatography and use the LIF prototype to monitor the resolved DNA fragments. We obtain not only well-resolved peaks but also the quantitative information of all DNA fragments. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Limitations on the use of the planar laser induced exciplex fluorescence technique in diesel sprays

    Energy Technology Data Exchange (ETDEWEB)

    J.M. Desantes; J.V. Pastor; J.M. Pastor; J.E. Julia [Universidad Politecnica de Valencia, Valencia (Spain). CMT Motores Termicos

    2005-12-01

    The Planar Laser Induced Exciplex Fluorescence (PLIEF) technique is widely used to visualize and measure the fuel concentration fields in both liquid and vapor phases of DI Diesel sprays. However, the real limitations of the PLIEF technique in Diesel sprays and the accuracy of the results obtained are still a source of controversy. In this work, a complete methodology for maximum penetration and fuel concentration measurements in evaporating conditions in Diesel sprays has been developed and the reliability of the results obtained has been investigated. The methodology includes new procedures for measuring both liquid and vapor phases, adapting, when necessary, correlations available in the literature for calibration. An experimental matrix of nine test points with different injection pressures and combustion chamber densities has been performed. A critical analysis of the different error sources for proper quantification is made. Results have shown that macroscopic features can be accurately determined using the PLIEF technique, but for fuel concentration measurements special considerations have to be taken into account, particularly in the regions where liquid and vapor coexist. 37 refs., 15 figs., 2 tabs.

  18. High-energy limit of collision-induced false vacuum decay

    Energy Technology Data Exchange (ETDEWEB)

    Demidov, Sergei; Levkov, Dmitry [Institute for Nuclear Research of the Russian Academy of Sciences,60-th October Anniversary Prospect 7a, Moscow, 117312 (Russian Federation)

    2015-06-17

    We develop a consistent semiclassical description of field-theoretic collision-induced tunneling at arbitrary high collision energies. As a playground we consider a (1+1)-dimensional false vacuum decay initiated by a collision of N particles at energy E, paying special attention to the realistic case of N=2 particles. We demonstrate that the cross section of this process is exponentially suppressed at all energies. Moreover, the respective suppressesion exponent F{sub N}(E) exhibits a specific behavior which is significant for our semiclassical method and assumed to be general: it decreases with energy, reaches absolute minimum F=F{sub min}(N) at a certain threshold energy E=E{sub rt}(N), and stays constant at higher energies. We show that the minimal suppression F{sub min}(N) and threshold energy can be evaluated using a special class of semiclassical solutions which describe exponentially suppressed transitions but nevertheless evolve in real time. Importantly, we argue that the cross section at energies above E{sub rt}(N) is computed perturbatively in the background of the latter solutions, and the terms of this perturbative expansion stay bounded in the infinite-energy limit. Transitions in the high-energy regime proceed via emission of many soft quanta with total energy E{sub rt}; the energy excess E−E{sub rt} remains in the colliding particles till the end of the process.

  19. Dietary induced serum phenolic acids promote bone growth via p38 MAPK / Beta-Catenin Canonical Wnt signaling

    Science.gov (United States)

    Diet and nutritional status are critical factors that influences bone development. In this report, we demonstrate that a mixture of phenolic acids found in the serum of young rats fed blueberries (BB), significantly stimulated osteoblast differentiation, resulting in significantly increased bone mas...

  20. 3-Keto-1,5-bisphosphonates Alleviate Serum-Oxidative Stress in the High-fat Diet Induced Obesity in Rats.

    Science.gov (United States)

    Lahbib, Karima; Aouani, Iyadh; Cavalier, Jean-François; Touil, Soufiane

    2015-09-01

    Obesity has become a leading global health problem owing to its strong association with a high incidence of oxidative stress. Many epidemiologic studies showed that an antioxidant supplementation decreases the state of oxidative stress. In the present work, a HFD-induced rat obesity and oxidative stress were used to investigate the link between fat deposition and serum-oxidative stress markers. We also studied the effect of a chronic administration of 3-keto-1,5-bisphosphonates 1 (a & b) (40 μg/kg/8 weeks/i.p.). Exposure of rats to HFD during 16 weeks induced fat deposition, weight gain and metabolic disruption characterized by an increase in cholesterol, triglyceride and glycemia levels, and a decrease in ionizable calcium and free iron concentrations. HFD also induced serum-oxidative stress status vocalized by an increase in ROS (H2 O2 ), MDA and PC levels, with a decrease in antioxidant enzyme activity (CAT, GPx, SOD). Importantly, 3-keto-1,5-bisphosphonates corrected all the deleterious effects of HFD treatment in vivo, but it failed to inhibit lipases in vitro and in vivo. These studies suggest that 3-keto-1,5-bisphosphonates 1 could be considered as safe antioxidant agents that should also find other potential biological applications. © 2014 John Wiley & Sons A/S.

  1. Simultaneous radioimmunoassay for corticosterone and deoxycortisol in human serum: Sex differences in the mean serum concentrations

    International Nuclear Information System (INIS)

    Schoeneshoefer, M.; Harendt, H.; Vecsei, P.

    1977-01-01

    A specific radioimmunoassay is described which allows the simultaneous determination of serum corticosterone and deoxycortisol. The normal serum concentration of both steroids were found to be dependent on sex and menstrual cycle. Mean concentrations (+-S.D.) in males, females (follicular phase) and females (luteal phase) were 4210 +- 2170 ng/l, 2410 +- 1480 ng/l and 4390 +- 2320 ng/l for corticosterone and 499 +- 273 ng/l, 207 +- 152 ng/l and 335 +- 182 ng/l for deoxycortisol. After adrenal stimulation by corticotropin itself or by insulin induced hypoglycemia, the serum concentrations of corticosterone became significantly higher than those of deoxycortisol. After oral administration of dexamethasone serum concentrations of both steroids were suppressed to levels below the limit of the normal range. One hour after oral metyrapone administration at midnight, serum corticosterone decreased, while serum deoxycortisol increased by a factor of about five. After eight hours serum concentrations of both steroids were increased considerably. Corticosterone attained levels slightly higher than the normal range and deoxycortisol rose to levels which were higher than the normal mean concentrations by a factor of about 500. (orig./AS) [de

  2. Effects of adjunctive eslicarbazepine acetate on serum lipids in patients with partial-onset seizures: Impact of concomitant statins and enzyme-inducing antiepileptic drugs.

    Science.gov (United States)

    Mintzer, Scott; Wechsler, Robert T; Rogin, Joanne B; Gidal, Barry E; Schwab, Matthias; Ben-Menachem, Elinor; Carreño, Mar; da Silva, Patrício Soares; Moreira, Joana; Li, Yan; Blum, David; Grinnell, Todd

    2018-03-01

    To evaluate the effects of eslicarbazepine acetate (ESL) on lipid metabolism and to determine whether reduced statin exposure during ESL therapy has clinical consequences. We conducted a post-hoc analysis of pooled data for serum lipids (laboratory values) from three phase III, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive ESL therapy (400, 800, or 1200 mg once daily) in patients with treatment-refractory partial-onset seizures. Changes from baseline in serum lipid levels were analyzed according to use of statins and/or enzyme-inducing antiepileptic drugs (EIAEDs) during the baseline period. In total, 426 and 1021 placebo- and ESL-treated patients, respectively, were included in the analysis. With regard to the changes from baseline in serum concentrations, there were statistically significant differences between the placebo and ESL 1200 mg QD groups, for both total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), but the effect sizes were small (+4.1 mg/dL and +1.8 mg/dL, respectively). A small but significant difference in low-density lipoprotein cholesterol (LDL-C; -5.0 mg/dL) was observed between the ESL 400 mg QD group and the placebo group. In patients not taking a concomitant EIAED, there were no changes with ESL 400 mg QD, but modest and statistically significant increases in cholesterol fractions (TC, LDL-C and HDL-C) with ESL 800 mg QD (ESL 1200 mg QD (ESL had no consistent effect on lipids in patients taking a concomitant EIAED. In patients taking statins during baseline, there were no clinically relevant changes in serum lipids during use of ESL, although the subgroups were small. These results suggest that ESL does not appear to have clinically significant effects on serum lipids, nor does the pharmacokinetic interaction between ESL and statins have an impact on serum lipid concentrations. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Newly divided eosinophils limit ozone-induced airway hyperreactivity in nonsensitized guinea pigs.

    Science.gov (United States)

    Wicher, Sarah A; Jacoby, David B; Fryer, Allison D

    2017-06-01

    Ozone causes vagally mediated airway hyperreactivity and recruits inflammatory cells, including eosinophils, to lungs, where they mediate ozone-induced hyperreactivity 1 day after exposure but are paradoxically protective 3 days later. We aimed to test the role of newly divided eosinophils in ozone-induced airway hyperreactivity in sensitized and nonsensitized guinea pigs. Nonsensitized and sensitized guinea pigs were treated with 5-bromo-2-deoxyuridine (BrdU) to label newly divided cells and were exposed to air or ozone for 4 h. Later (1 or 3 days later), vagally induced bronchoconstriction was measured, and inflammatory cells were harvested from bone marrow, blood, and bronchoalveolar lavage. Ozone induced eosinophil hematopoiesis. One day after ozone, mature eosinophils dominate the inflammatory response and potentiate vagally induced bronchoconstriction. However, by 3 days, newly divided eosinophils have reached the lungs, where they inhibit ozone-induced airway hyperreactivity because depleting them with antibody to IL-5 or a TNF-α antagonist worsened vagally induced bronchoconstriction. In sensitized guinea pigs, both ozone-induced eosinophil hematopoiesis and subsequent recruitment of newly divided eosinophils to lungs 3 days later failed to occur. Thus mature eosinophils dominated the ozone-induced inflammatory response in sensitized guinea pigs. Depleting these mature eosinophils prevented ozone-induced airway hyperreactivity in sensitized animals. Ozone induces eosinophil hematopoiesis and recruitment to lungs, where 3 days later, newly divided eosinophils attenuate vagally mediated hyperreactivity. Ozone-induced hematopoiesis of beneficial eosinophils is blocked by a TNF-α antagonist or by prior sensitization. In these animals, mature eosinophils are associated with hyperreactivity. Thus interventions targeting eosinophils, although beneficial in atopic individuals, may delay resolution of airway hyperreactivity in nonatopic individuals. Copyright

  4. Drugs elevating extracellular adenosine administered in vivo induce serum colony-stimulating activity and interleukin-6 in mice

    Czech Academy of Sciences Publication Activity Database

    Weiterová, Lenka; Hofer, Michal; Pospíšil, Milan; Znojil, V.; Štreitová, Denisa

    2007-01-01

    Roč. 56, č. 4 (2007), s. 463-473 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GP305/03/D050 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : extracellular adenosine * serum colony-stimulating activity * interleukin-6 Subject RIV: BO - Biophysics Impact factor: 1.505, year: 2007

  5. Lentiviral-mediated RNAi targeting caspase-3 inhibits apoptosis induced by serum deprivation in rat endplate chondrocytes in vitro

    International Nuclear Information System (INIS)

    Ding, L.; Wu, J.P.; Xu, G.; Zhu, B.; Zeng, Q.M.; Li, D.F.; Lu, W.

    2014-01-01

    Current studies find that degenerated cartilage endplates (CEP) of vertebrae, with fewer diffusion areas, decrease nutrient supply and accelerate intervertebral disc degeneration. Many more apoptotic cells have been identified in degenerated than in normal endplates, and may be responsible for the degenerated grade. Previous findings suggest that inhibition of apoptosis is one possible approach to improve disc regeneration. It is postulated that inhibition of CEP cell apoptosis may be responsible for the regeneration of endplates. Caspase-3, involved in the execution phase of apoptosis, is a candidate for regulating the apoptotic process. In the present study, CEP cells were incubated in 1% fetal bovine serum. Activated caspases were detected to identify the apoptotic pathway, and apoptosis was quantified by flow cytometry. Lentiviral caspase-3 short hairpin RNA (shRNA) was employed to study its protective effects against serum deprivation. Silencing of caspase-3 expression was quantified by reverse transcription-polymerase chain reaction and Western blots, and inhibition of apoptosis was quantified by flow cytometry. Serum deprivation increased apoptosis of rat CEP cells through activation of a caspase cascade. Lentiviral caspase-3 shRNA was successfully transduced into CEP cells, and specifically silenced endogenous caspase-3 expression. Surviving cells were protected by the downregulation of caspase-3 expression and activation. Thus, lentiviral caspase-3 shRNA-mediated RNAi successfully silenced endogenous caspase-3 expression, preventing inappropriate or premature apoptosis

  6. Lentiviral-mediated RNAi targeting caspase-3 inhibits apoptosis induced by serum deprivation in rat endplate chondrocytes in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ding, L.; Wu, J.P. [Fudan University, Jinshan Hospital, Department of Orthopaedics, Shanghai, China, Department of Orthopaedics, Jinshan Hospital, Fudan University, Shanghai (China); Xu, G. [Fudan University, Jinshan Hospital, Center Laboratory, Shanghai, China, Center Laboratory, Jinshan Hospital, Fudan University, Shanghai (China); Zhu, B.; Zeng, Q.M.; Li, D.F.; Lu, W. [Fudan University, Jinshan Hospital, Department of Orthopaedics, Shanghai, China, Department of Orthopaedics, Jinshan Hospital, Fudan University, Shanghai (China)

    2014-05-09

    Current studies find that degenerated cartilage endplates (CEP) of vertebrae, with fewer diffusion areas, decrease nutrient supply and accelerate intervertebral disc degeneration. Many more apoptotic cells have been identified in degenerated than in normal endplates, and may be responsible for the degenerated grade. Previous findings suggest that inhibition of apoptosis is one possible approach to improve disc regeneration. It is postulated that inhibition of CEP cell apoptosis may be responsible for the regeneration of endplates. Caspase-3, involved in the execution phase of apoptosis, is a candidate for regulating the apoptotic process. In the present study, CEP cells were incubated in 1% fetal bovine serum. Activated caspases were detected to identify the apoptotic pathway, and apoptosis was quantified by flow cytometry. Lentiviral caspase-3 short hairpin RNA (shRNA) was employed to study its protective effects against serum deprivation. Silencing of caspase-3 expression was quantified by reverse transcription-polymerase chain reaction and Western blots, and inhibition of apoptosis was quantified by flow cytometry. Serum deprivation increased apoptosis of rat CEP cells through activation of a caspase cascade. Lentiviral caspase-3 shRNA was successfully transduced into CEP cells, and specifically silenced endogenous caspase-3 expression. Surviving cells were protected by the downregulation of caspase-3 expression and activation. Thus, lentiviral caspase-3 shRNA-mediated RNAi successfully silenced endogenous caspase-3 expression, preventing inappropriate or premature apoptosis.

  7. Lentiviral-mediated RNAi targeting caspase-3 inhibits apoptosis induced by serum deprivation in rat endplate chondrocytes in vitro

    Directory of Open Access Journals (Sweden)

    L. Ding

    2014-06-01

    Full Text Available Current studies find that degenerated cartilage endplates (CEP of vertebrae, with fewer diffusion areas, decrease nutrient supply and accelerate intervertebral disc degeneration. Many more apoptotic cells have been identified in degenerated than in normal endplates, and may be responsible for the degenerated grade. Previous findings suggest that inhibition of apoptosis is one possible approach to improve disc regeneration. It is postulated that inhibition of CEP cell apoptosis may be responsible for the regeneration of endplates. Caspase-3, involved in the execution phase of apoptosis, is a candidate for regulating the apoptotic process. In the present study, CEP cells were incubated in 1% fetal bovine serum. Activated caspases were detected to identify the apoptotic pathway, and apoptosis was quantified by flow cytometry. Lentiviral caspase-3 short hairpin RNA (shRNA was employed to study its protective effects against serum deprivation. Silencing of caspase-3 expression was quantified by reverse transcription-polymerase chain reaction and Western blots, and inhibition of apoptosis was quantified by flow cytometry. Serum deprivation increased apoptosis of rat CEP cells through activation of a caspase cascade. Lentiviral caspase-3 shRNA was successfully transduced into CEP cells, and specifically silenced endogenous caspase-3 expression. Surviving cells were protected by the downregulation of caspase-3 expression and activation. Thus, lentiviral caspase-3 shRNA-mediated RNAi successfully silenced endogenous caspase-3 expression, preventing inappropriate or premature apoptosis.

  8. A superoxide anion-scavenger, 1,3-selenazolidin-4-one suppresses serum deprivation-induced apoptosis in PC12 cells by activating MAP kinase

    International Nuclear Information System (INIS)

    Nishina, Atsuyoshi; Kimura, Hirokazu; Kozawa, Kunihisa; Sommen, Geoffroy; Nakamura, Takao; Heimgartner, Heinz; Koketsu, Mamoru; Furukawa, Shoei

    2011-01-01

    Synthetic organic selenium compounds, such as ebselen, may show glutathione peroxidase-like antioxidant activity and have a neurotrophic effect. We synthesized 1,3-selenazolidin-4-ones, new types of synthetic organic selenium compounds (five-member ring compounds), to study their possible applications as antioxidants or neurotrophic-like molecules. Their superoxide radical scavenging effects were assessed using the quantitative, highly sensitive method of real-time kinetic chemiluminescence. At 166 μM, the O 2 − scavenging activity of 1,3-selenazolidin-4-ones ranged from 0 to 66.2%. 2-[3-(4-Methoxyphenyl)-4-oxo-1,3-selenazolidin-2-ylidene]malononitrile (compound b) showed the strongest superoxide anion-scavenging activity among the 6 kinds of 2-methylene-1,3-selenazolidin-4-ones examined. Compound b had a 50% inhibitory concentration (IC 50 ) at 92.4 μM and acted as an effective and potentially useful O 2 − scavenger in vitro. The effect of compound b on rat pheochromocytome cell line PC12 cells was compared with that of ebselen or nerve growth factor (NGF) by use of the MTT [3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] assay. When ebselen was added at 100 μM or more, toxicity toward PC12 cells was evident. On the contrary, compound b suppressed serum deprivation-induced apoptosis in PC12 cells more effectively at a concentration of 100 μM. The activity of compound b to phosphorylate mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK) 1/2 (MAP kinase) in PC12 cells was higher than that of ebselen, and the former at 100 μM induced the phosphorylation of MAP kinase to a degree similar to that induced by NGF. From these results, we conclude that this superoxide anion-scavenger, compound b, suppressed serum deprivation-induced apoptosis by promoting the phosphorylation of MAP kinase. -- Highlights: ► We newly synthesized 1,3-selenazolidin-4-ones to study their possible applications. ► Among new

  9. A superoxide anion-scavenger, 1,3-selenazolidin-4-one suppresses serum deprivation-induced apoptosis in PC12 cells by activating MAP kinase

    Energy Technology Data Exchange (ETDEWEB)

    Nishina, Atsuyoshi, E-mail: nishina@yone.ac.jp [Yonezawa Women' s Junior College, 6-15-1 Tohrimachi, Yonezawa, Yamagata 992-0025 (Japan); Kimura, Hirokazu; Kozawa, Kunihisa [Gunma Prefectural Institute of Public Health and Environmental Sciences, 378 Kamioki, Maebashi, Gunma 371-0052 (Japan); Sommen, Geoffroy [Lonza Braine SA, Chaussee de Tubize 297, B-1420 Braine l' Alleud (Belgium); Nakamura, Takao [Department of Biomedical Information Engineering, Graduate School of Medical Science, Yamagata University, Yamagata 990-9585 (Japan); Heimgartner, Heinz [University of Zuerich, Institut of Organic Chemistry, Winterthurerstrasse 190, CH-8057 Zuerich (Switzerland); Koketsu, Mamoru [Department of Materials Science and Technology, Faculty of Engineering, Gifu University, Gifu 501-1193 (Japan); Furukawa, Shoei [Laboratory of Molecular Biology, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585 (Japan)

    2011-12-15

    Synthetic organic selenium compounds, such as ebselen, may show glutathione peroxidase-like antioxidant activity and have a neurotrophic effect. We synthesized 1,3-selenazolidin-4-ones, new types of synthetic organic selenium compounds (five-member ring compounds), to study their possible applications as antioxidants or neurotrophic-like molecules. Their superoxide radical scavenging effects were assessed using the quantitative, highly sensitive method of real-time kinetic chemiluminescence. At 166 {mu}M, the O{sub 2}{sup -} scavenging activity of 1,3-selenazolidin-4-ones ranged from 0 to 66.2%. 2-[3-(4-Methoxyphenyl)-4-oxo-1,3-selenazolidin-2-ylidene]malononitrile (compound b) showed the strongest superoxide anion-scavenging activity among the 6 kinds of 2-methylene-1,3-selenazolidin-4-ones examined. Compound b had a 50% inhibitory concentration (IC{sub 50}) at 92.4 {mu}M and acted as an effective and potentially useful O{sub 2}{sup -} scavenger in vitro. The effect of compound b on rat pheochromocytome cell line PC12 cells was compared with that of ebselen or nerve growth factor (NGF) by use of the MTT [3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] assay. When ebselen was added at 100 {mu}M or more, toxicity toward PC12 cells was evident. On the contrary, compound b suppressed serum deprivation-induced apoptosis in PC12 cells more effectively at a concentration of 100 {mu}M. The activity of compound b to phosphorylate mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK) 1/2 (MAP kinase) in PC12 cells was higher than that of ebselen, and the former at 100 {mu}M induced the phosphorylation of MAP kinase to a degree similar to that induced by NGF. From these results, we conclude that this superoxide anion-scavenger, compound b, suppressed serum deprivation-induced apoptosis by promoting the phosphorylation of MAP kinase. -- Highlights: Black-Right-Pointing-Pointer We newly synthesized 1,3-selenazolidin-4-ones to

  10. Self-limiting atypical antipsychotics-induced edema: Clinical cases and systematic review

    OpenAIRE

    Musa Usman Umar; Aminu Taura Abdullahi

    2016-01-01

    A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect.

  11. Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review.

    Science.gov (United States)

    Umar, Musa Usman; Abdullahi, Aminu Taura

    2016-01-01

    A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect.

  12. Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review

    Science.gov (United States)

    Umar, Musa Usman; Abdullahi, Aminu Taura

    2016-01-01

    A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect. PMID:27335511

  13. Effects of paternal deprivation on cocaine-induced behavioral response and hypothalamic oxytocin immunoreactivity and serum oxytocin level in female mandarin voles.

    Science.gov (United States)

    Wang, Jianli; Fang, Qianqian; Yang, Chenxi

    2017-09-15

    Early paternal behavior plays a critical role in behavioral development in monogamous species. The vast majority of laboratory studies investigating the influence of parental behavior on cocaine vulnerability focus on the effects of early maternal separation. However, comparable studies on whether early paternal deprivation influences cocaine-induced behavioral response are substantially lacking. Mandarin vole (Microtus mandarinus) is a monogamous rodent with high levels of paternal care. After mandarin vole pups were subjected to early paternal deprivation, acute cocaine- induced locomotion, anxiety- like behavior and social behavior were examined in 45day old female pups, while hypothalamic oxytocin immunoreactivity and serum oxytocin level were also assessed. We found that cocaine increased locomotion and decreased social investigation, contact behavior and serum oxytocin level regardless of paternal care. Cocaine increased anxiety levels and decreased oxytocin immunoreactive neurons of the paraventricular nuclei and supraoptic nuclei in the bi-parental care group, whilst there were no specific effects in the paternal deprivation group. These results indicate that paternal deprivation results in different behavioral response to acute cocaine exposure in adolescents, which may be in part associated with the alterations in oxytocin immunoreactivity and peripheral OT level. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Piper sarmentosum Effects on 11β-Hydroxysteroid Dehydrogenase Type 1 Enzyme in Serum and Bone in Rat Model of Glucocorticoid-Induced Osteoporosis.

    Science.gov (United States)

    Mohamad Asri, Siti Fadziyah; Mohd Ramli, Elvy Suhana; Soelaiman, Ima Nirwana; Mat Noh, Muhamad Alfakry; Abdul Rashid, Abdul Hamid; Suhaimi, Farihah

    2016-11-15

    Glucocorticoid-induced osteoporosis is one of the common causes of secondary osteoporosis. Piper sarmentosum ( Ps ) extract possesses antioxidant and anti-inflammatory activities. In this study, we determined the correlation between the effects of Ps leaf water extract with the regulation of 11β-hydroxysteroid dehydrogenase (HSD) type 1 enzyme activity in serum and bone of glucocorticoid-induced osteoporotic rats. Twenty-four Sprague-Dawley rats were grouped into following: G1: sham-operated group administered with intramuscular vehicle olive oil and vehicle normal saline orally; G2: adrenalectomized (adrx) control group given intramuscular dexamethasone (120 μg/kg/day) and vehicle normal saline orally; G3: adrx group given intramuscular dexamethasone (120 μg/kg/day) and water extract of Piper sarmentosum (125 mg/kg/day) orally. After two months, the femur and serum were taken for ELISA analysis. Results showed that Ps leaf water extract significantly reduced the femur corticosterone concentration ( p < 0.05). This suggests that Ps leaf water extract was able to prevent bone loss due to long-term glucocorticoid therapy by acting locally on the bone cells by increasing the dehydrogenase action of 11β-HSD type 1. Thus, Ps may have the potential to be used as an alternative medicine against osteoporosis and osteoporotic fracture in patients on long-term glucocorticoid treatment.

  15. Limitations of polyethylene glycol-induced precipitation as predictive tool for protein solubility during formulation development.

    Science.gov (United States)

    Hofmann, Melanie; Winzer, Matthias; Weber, Christian; Gieseler, Henning

    2018-05-01

    Polyethylene glycol (PEG)-induced protein precipitation is often used to extrapolate apparent protein solubility at specific formulation compositions. The procedure was used for several fields of application such as protein crystal growth but also protein formulation development. Nevertheless, most studies focused on applicability in protein crystal growth. In contrast, this study focuses on applicability of PEG-induced precipitation during high-concentration protein formulation development. In this study, solubility of three different model proteins was investigated over a broad range of pH. Solubility values predicted by PEG-induced precipitation were compared to real solubility behaviour determined by either turbidity or content measurements. Predicted solubility by PEG-induced precipitation was confirmed for an Fc fusion protein and a monoclonal antibody. In contrast, PEG-induced precipitation failed to predict solubility of a single-domain antibody construct. Applicability of PEG-induced precipitation as indicator of protein solubility during formulation development was found to be not valid for one of three model molecules. Under certain conditions, PEG-induced protein precipitation is not valid for prediction of real protein solubility behaviour. The procedure should be used carefully as tool for formulation development, and the results obtained should be validated by additional investigations. © 2017 Royal Pharmaceutical Society.

  16. The Differences in Serum Quantitative Specific IgE Levels Induced by Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis Sensitization in Intermittent and Persistent Allergic Asthma

    Directory of Open Access Journals (Sweden)

    Agus Joko Susanto

    2018-01-01

    Full Text Available Background: house dust mites (HDM are an important inhalant allergen in allergic asthma. However, molecular diagnostic study of specific IgE to HDM allergens has not been done in Indonesia. In addition, the association of quantitative specific IgE measurement with asthma severity has not been investigatedd. This study aimed to investigate the difference of serum quantitative specific IgE levels induced by Dermatophagoides (D. pteronyssinus, D. farinae and Blomia tropicalis sensitization in intermittent and persistent allergic asthma. Methods: this was a cross-sectional study on adult allergic asthma patients who were invited for serum specific IgE testing. This study was a part of a larger study within the Division of Allergy and Immunology, Cipto Mangunkusumo Hospital. Asthma severity was defined based on Global Initiative on Asthma (GINA 2015 criteria and were grouped as intermittent or persistent. Quantitative specific IgE testing was done on blood serum using a multiple allergosorbent test (Polycheck Allergy, Biocheck GmbH, Munster, Germany. The HDM allergens tested were D. pteronyssinus, D. farinae, and Blomia tropicalis. Difference between two groups were analyze using Mann-Whitney test. Results: a total of 87 subjects were enrolled in this study; 69 (79.3% were women. Mean patients’ age was 40, 2 years. Sixty-three (72.4% subjects had asthma and allergic rhinitis. Fifty-eight (66.7% subjects were classified as persistent asthma. The prevalence of sensitization was 62.1% for D. farinae, 51.7% for D. pteronyssinus, and 48.3% for Blomia tropicalis. The median of specific IgE levels were significantly higher in persistent asthma compares to intermittent asthma induced by D. farinae (median 1.30 vs. 0.0 kU/L; p=0.024 and B. tropicalis (median 0.57 vs. 0.0 kU/L; p=0.015 sensitization. Level of Specific IgE  D. pteronyssinus was also to be higher in persistent asthma than the level measured in intermittent asthma (0.67 vs. 0.00 kU/L; p=0

  17. Melatonin limits paclitaxel‐induced mitochondrial dysfunction in vitro and protects against paclitaxel‐induced neuropathic pain in the rat

    OpenAIRE

    Galley, Helen F.; McCormick, Barry; Wilson, Kirsten L.; Lowes, Damon A.; Colvin, Lesley; Torsney, Carole

    2017-01-01

    Chemotherapy-induced neuropathic pain is a debilitating and common side effect of cancer treatment. Mitochondrial dysfunction associated with oxidative stress in peripheral nerves has been implicated in the underlying mechanism. We investigated the potential of melatonin, a potent antioxidant that preferentially acts within mitochondria, to reduce mitochondrial damage and neuropathic pain resulting from the chemotherapeutic drug paclitaxel. In vitro, paclitaxel caused a 50% reduction of mitoc...

  18. Serum androgen and gonadotropin levels decline after progestogen-induced withdrawal bleeding in oligomenorrheic women with or without polycystic ovaries.

    Science.gov (United States)

    Anttila, L; Koskinen, P; Kaihola, H L; Erkkola, R; Irjala, K; Ruutiainen, K

    1992-10-01

    To examine the effect of short-term progestogen treatment on androgen, gonadotropin, and sex hormone-binding globulin (SHBG) levels in oligomenorrheic women. Comparative study of changes in hormonal parameters in patients with or without ultrasonographically diagnosed polycystic ovarian disease (PCOD). Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. Seventy-five oligomenorrheic women with (n = 51) or without (n = 24) PCOD. Serum concentrations of testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and SHBG. The levels of T, A, LH, and the LH:FSH ratios decreased significantly after oral treatment with medroxyprogesterone acetate (10 mg/d for 10 days) in non-PCOD women and in women with PCOD decreasing the frequencies of pathological laboratory findings, in particular elevated levels of LH:FSH ratio and A in PCOD women and of LH:FSH ratio in non-PCOD women. The levels of T, A, and LH as well as the LH:FSH ratio were significantly higher in women with PCOD. Obesity was associated with high free androgen indices, low LH:FSH ratios, and low concentrations of LH, A, and SHBG. The serum samples for hormonal analyses used as an aid in diagnosing PCOD should be obtained without pretreatment with progestogen because it masks the biochemical findings of PCOD.

  19. Clinical significance of changes of plasma endothelin vasoactive factors (ET and NO) as well as serum related interleukin (IL-6 and IL-8) levels in patients with pregnancy induced hypertension (PIH)

    International Nuclear Information System (INIS)

    Chen Ying

    2009-01-01

    Objective: To investigate the clinical etiological significance of changes of plasma endothelin (ET) and nitric oxide (NO) as well as serum interleukin-6 (IL-6) and interleukin-8 (IL-8) levels in patients with pregnancy induced hypertension. Methods: Plasma ET (with RIA), NO (with biochemistry) and serum IL-6, IL-8 (with RIA) levels were measured in 32 pregnant women with PIH, 35 normal pregnant women without PIH and 35 non-pregnant women (as controls). Results: The plasma ET, NO level were significantly higher in normal pregnant women than those in the non-pregnant women controls, while serum levels of IL-6 and IL-8 levels were only slightly higher without significance (P>0.05). Before treatment, the blood ET, IL-6 and IL- 8 levels were significantly higher in patients with pregnancy induced hypertension than those in the control (P<0.01), while plasma levels of NO were significantly decreased (P<0.01), Two weeks after treatment, the plasma ET, NO and serum IL-6 and IL-8 levels were markedly corrected with no significantly differences from those in controls. The ET levels and serum IL-6, IL-8 levels were mutually positively correlated (r=0.6097, 0.7213, P<0.01). Conclusion: Determination of changes of plasma ET and NO, serum IL-6 and IL-8 levels in patients with pregnancy induced hypertension was helpful for outcome prediction. (authors)

  20. Ethnicity influences BMI as evaluated from reported serum lipid values in Inuit and non-Inuit: raised upper limit of BMI in Inuit?

    Science.gov (United States)

    Noahsen, Paneeraq; Andersen, Stig

    2013-01-01

    To identify thresholds of BMI at which similar levels of serum lipids occur in Inuit and in non-Inuit as the impact of obesity on metabolic risk factors differ in Inuit compared to other ethnic groups. Published comparative data among Inuit and non-Inuit whites on BMI and HDL-cholesterol and triglyceride were identified for analysis. A literature search was done for BMI, lipids, Inuit and Greenland or Canada. Studies with data on triglycerides and HDL-cholesterol in Inuit and non-Inuit Caucasians were selected and data were retrieved. Regression equations were computed for BMI and HDL-cholesterol and BMI and triglycerides. BMI for similar levels of lipids in Inuit and non-Inuit and ratios of Inuit/non-Inuit BMI's were calculated. At BMI 25 kg/m2 HDL-cholesterol was 1.7/1.6 mM in Greenland Inuit/non-Inuit women and 1.7/1.5 mM in men in a major comparative study. HDL cholesterol decreased by 0.09 for each 1 kg/m2 increase in BMI. Serum triglycerides were 1.0/1.1 mM for Greenland Inuit/non-Inuit women and 0.9/ 1.4 mM for men at BMI 25 kg/m2. Slopes were around 0.1. A comparative study in Canadian Inuit/non-Inuit gave similar results. The BMI levels required for similar HDL-cholesterol or triglycerides were around 27.5 kg/m2, and Inuit/non-Inuit BMI-ratios were around 1.1. The same degree of dyslipidaemia was seen when Inuit had a 10% higher BMI compared to non-Inuit. This may support the establishment of Inuit-specific BMI cut-offs for the purposes of health screening and population health surveillance.

  1. Fitness declines towards range limits and local adaptation to climate affect dispersal evolution during climate‐induced range shifts

    DEFF Research Database (Denmark)

    Hargreaves, Anna; Bailey, Susan; Laird, Robert

    2015-01-01

    Dispersal ability will largely determine whether species track their climatic niches during climate change, a process especially important for populations at contracting (low-latitude/low-elevation) range limits that otherwise risk extinction. We investigate whether dispersal evolution....... We simulate a species distributed continuously along a temperature gradient using a spatially explicit, individual-based model. We compare range-wide dispersal evolution during climate stability vs. directional climate change, with uniform fitness vs. fitness that declines towards range limits (RLs...... at contracting range limits is facilitated by two processes that potentially enable edge populations to experience and adjust to the effects of climate deterioration before they cause extinction: (i) climate-induced fitness declines towards range limits and (ii) local adaptation to a shifting climate gradient...

  2. Phosphate limitation induces the intergeneric inhibition of Pseudomonas aeruginosa by Serratia marcescens isolated from paper machines

    Science.gov (United States)

    Kuo, Pei-An; Kuo, Chih-Horng; Lai, Yiu-Kay; Graumann, Peter L; Tu, Jenn

    2013-01-01

    Phosphate is an essential nutrient for heterotrophic bacteria, affecting bacterioplankton in aquatic ecosystems and bacteria in biofilms. However, the influence of phosphate limitation on bacterial competition and biofilm development in multispecies populations has received limited attention in existing studies. To address this issue, we isolated 13 adhesive bacteria from paper machine aggregates. Intergeneric inhibition of Pseudomonas aeruginosa WW5 by Serratia marcescens WW4 was identified under phosphate-limited conditions, but not in Luria–Bertani medium or M9 minimal medium. The viable numbers of the pure S. marcescens WW4 culture decreased over 3 days in the phosphate-limited medium; however, the mortality of S. marcescens WW4 was significantly reduced when it was co-cultured with P. aeruginosa WW5, which appeared to sustain the S. marcescens WW4 biofilm. In contrast, viable P. aeruginosa WW5 cells immediately declined in the phosphate-limited co-culture. To identify the genetic/inhibitory element(s) involved in this process, we inserted a mini-Tn5 mutant of S. marcescens WW4 that lacked inhibitory effect. The results showed that an endonuclease bacteriocin was involved in this intergeneric inhibition by S. marcescens WW4 under phosphate limitation. In conclusion, this study highlights the importance of nutrient limitation in bacterial interactions and provides a strong candidate gene for future functional characterisation. PMID:23398522

  3. Clinical significance of determination of changes of serum TNF-α levels, peripheral B lymphocyte count and T lymphocyte subsets distribution pattern in patients with pregnancy induced hypertension syndrome

    International Nuclear Information System (INIS)

    Zhao Wenjuan

    2006-01-01

    Objective: To explore the changes of serum TNF-α levels, peripheral B cell count and T subsets distribution pattern in patients with pregnancy induced hypertension syndrome. Methods: Serum TNF-α levels (with RIA), peripheral B cell count as well as T subsets (with monoclonal technique) were examined in 34 patients with pregnancy induced hypertension syndrome and 35 controls. Results: The serum TNF-α levels and B lymphocytes count were significantly higher than those in controls (P 3 , CD 4 , CD4/CD8 ratio were significantly lower than those in controls (P<0.01). Conclusion: Pregnancy induced hY- pertension syndrome is a kind of autoimmune diseases with abnormal immunoregulation. (authors)

  4. Impact of high glucose concentration on aspirin-induced acetylation of human serum albumin: An in vitro study

    Directory of Open Access Journals (Sweden)

    Francesco Finamore

    2014-06-01

    Full Text Available Aspirin (ASA plays a key role in protecting high risk cardiovascular patients from ischaemic events. The modifications underlying its effects are the results of the trans-acetylation that occurs between ASA and the amino groups made up of lysine and N-terminal residues. ASA's effects have also been demonstrated on several plasma proteins, including human serum albumin (HSA. However, its beneficial effects seem to be lower in diabetic patients, suggesting that protein glycation may impair ASA's acetylation process. Using immunoblotting and mass spectrometry, this study characterized the degree of HSA acetylation mediated by ASA in vitro, as well as the impact of high glucose concentrations. Glycation's influence on HSA acetylation might impair the latter's biological functions, leading to a potential failure of ASA to prevent cardiovascular complications in diabetes.

  5. Severe tremor after cotrimoxazole-induced elevation of venlafaxine serum concentrations in a patient with major depressive disorder.

    Science.gov (United States)

    Geber, Christian; Ostad Haji, Elnaz; Schlicht, Konrad; Hiemke, Christoph; Tadić, André

    2013-06-01

    : We describe a female patient who was an extensive metabolizer of cytochrome P450 isoenzyme (CYP) 2D6 and an intermediate metabolizer of CYP2C19 (genotype: CYP2C19 *1/*2). She exhibited high serum concentrations of venlafaxine and O-desmethylvenlafaxine and developed severe tremor after comedication with cotrimoxazole (sulfamethazole/trimethoprim). Venlafaxine is mainly metabolized by O- and N-demethylation. O-demethylation is catalyzed by the highly polymorphic CYP2D6 and N-demethylation by several enzymes, CYP2C19, CYP2C9, and CYP3A4. The observed overall pharmacokinetic effect was most probably the result of decreased N-demethylation of venlafaxine by (1) reduced expression of CYP2C19 due to a genetic deficit and (2) inhibition of CYP2C9 by cotrimoxazole.

  6. Free methionine supplementation limits alcohol-induced liver damage in rats

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Bode, C.; Bode, J.C.

    1998-01-01

    Alcohol feeding to rats that were submitted to a jejunoileal bypass operation has been shown to result in liver damage being comparable with alcohol-induced liver disease in man. In the present study, a striking effect of free methionine consumption on histological liver injury, triglyceride accu...

  7. Shear-induced structural transformation and plasticity in ultraincompressible ReB2 limit its hardness

    Czech Academy of Sciences Publication Activity Database

    Zhang, R. F.; Legut, Dominik; Niewa, R.; Argon, A. S.; Veprek, S.

    2010-01-01

    Roč. 82, č. 10 (2010), 104104/1-104104/7 ISSN 1098-0121 Institutional research plan: CEZ:AV0Z20410507 Keywords : ReB2 * ab initio * ultrahard * shear-induced transformation Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 3.772, year: 2010

  8. Yi Qi Qing Re Gao-containing serum inhibits lipopolysaccharide-induced rat mesangial cell proliferation by suppressing the Wnt pathway and TGF-β1 expression.

    Science.gov (United States)

    Yang, Liping; Sun, Xueyan; Zhan, Yongli; Liu, Huijie; Wen, Yumin; Mao, Huimin; Dong, X I; Li, Ping

    2016-04-01

    The aim of the present study was to investigate the effect of Yi Qi Qing Re Gao-containing serum (YQ-S) on rat mesangial cell (MC) proliferation and to investigate the underlying mechanism. MCs were divided into the control, lipopolysaccharide (LPS)-stimulated, YQ-S and fosinopril-containing serum (For-S) groups, and cultured for 48 h. An MTT assay was used to evaluate the proliferation of MCs. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis were conducted to detect the expression levels of Wnt4, β-catenin and transforming growth factor (TGF)-β1 in MCs. The results indicated that YQ-S inhibited LPS-induced MC proliferation. The Wnt4 and TGF-β1 mRNA expression levels were reduced in the YQ-S group (P<0.01 or P<0.05). Furthermore, the Wnt4, β-catenin and TGF-β1 protein expression levels were suppressed in the YQ-S group (P<0.01 or P<0.05). Therefore, YQ-S appears to inhibit MC proliferation, and its mechanism may involve the inhibition of the Wnt signaling pathway and downregulation of TGF-β1 expression.

  9. Efficacy of vitamins a and or E as antioxidants against serum glucose, liver glycogen and lipid discrepancy induced by gamma radiation during the estrus cycle of rats

    International Nuclear Information System (INIS)

    Abou-Safi, H.M.; Hussein, A.H.; El-Sayed, N.M.

    1999-01-01

    This work is directed to study the role of vitamins A and E treatment solely. or in combination against gamma-radiation effects during pro-estrus stage stage on serum glucose, liver content of glycogen, total and lipid fractions (triglycerides, total cholesterol, HDL-and LDL- cholesterol) in serum measured during the estrus stage of the rat estrus cycle. Animals were divided into six groups: untreated control, injected with sesame oil as a vehicle for vitamins injection (i.p.) whole body gamma-irradiated (6 GY), injected with vitamin A Two hours before irradiation, irradiated then injected after one hour with vitamin E, and injected with vitamins A and E pre- and post irradiation. The results demonstrated that irradiation induced significant elevations in the levels of all the measured parameters except in HDL-cholesterol. BOth vitamins ameliorated the recorded elevations during the estrus stage. The combined treatment with vitamins A and E reflected a potent harmony between protective roles of these two antioxidants pre- and post irradiation respectively, that normalized the levels of the measured parameters. The authors suggest that vitamins A and E treatment could enhance and reinforce the natural endogenous defences (steroids, particulary E 2 ) in the body against gamma irradiation and/or other environmental pollutants causing lipid peroxidation, especially during the period of ovulation. Moreover, it is worthy to consider this treatment as a hypolipidemic agent for patients with obesity, atherosclerosis and coronary artery diseases

  10. Indagation of serum and salivary reactive oxygen metabolite and cortisol levels in chronic periodontitis and stress-induced chronic periodontitis patients

    Directory of Open Access Journals (Sweden)

    Uma Sudhakar

    2017-01-01

    Full Text Available Background: Periodontal disease is not a conventional bacterial infection but is an inflammatory disease initiated by immune response against a group of microorganisms in susceptible hosts. There are many intriguing researches that unfold the secrets of chronic periodontitis. The current researches in chronic periodontitis are directed toward an approach that respects the scientific relationship between the various risk factors, the genetic factors, and the progression of the disease. Aim: This study aims to evaluate the cortisol and reactive oxygen metabolites (ROM concentration in serum and to find out their association in periodontal health and disease. Materials and Methods: In this study, totally thirty patients have been taken and divided into two groups of chronic periodontitis (Group I and stress-induced chronic periodontitis (Group II and evaluated the correlation between the ROM and cortisol levels in them. This is the first study, where both the levels of ROM and cortisol are checked in the serum and saliva. The analysis is done to check the association between them. Statistical Analysis: The data were statistically analyzed using software program (SPSSV 16, Pearson correlation, and paired t-test. Results: Comparison of the mean ROM levels in Group I and Group II showed that mean ROM level in Group II is highly significant than Group I. Conclusion: Our study suggests that stress can have a role in the progression of periodontal disease by increasing the cortisol and ROM levels.

  11. Indagation of serum and salivary reactive oxygen metabolite and cortisol levels in chronic periodontitis and stress-induced chronic periodontitis patients.

    Science.gov (United States)

    Sudhakar, Uma; Thyagarajan, Ramakrishnan; Jeyapal, Bhagyameena; Jagadeesh, Sushuruthi; Jayakumar, Parvathee

    2017-01-01

    Periodontal disease is not a conventional bacterial infection but is an inflammatory disease initiated by immune response against a group of microorganisms in susceptible hosts. There are many intriguing researches that unfold the secrets of chronic periodontitis. The current researches in chronic periodontitis are directed toward an approach that respects the scientific relationship between the various risk factors, the genetic factors, and the progression of the disease. This study aims to evaluate the cortisol and reactive oxygen metabolites (ROM) concentration in serum and to find out their association in periodontal health and disease. In this study, totally thirty patients have been taken and divided into two groups of chronic periodontitis (Group I) and stress-induced chronic periodontitis (Group II) and evaluated the correlation between the ROM and cortisol levels in them. This is the first study, where both the levels of ROM and cortisol are checked in the serum and saliva. The analysis is done to check the association between them. The data were statistically analyzed using software program (SPSSV 16), Pearson correlation, and paired t -test. Comparison of the mean ROM levels in Group I and Group II showed that mean ROM level in Group II is highly significant than Group I. Our study suggests that stress can have a role in the progression of periodontal disease by increasing the cortisol and ROM levels.

  12. Conformational fluctuation dynamics of domain I of human serum albumin in the course of chemically and thermally induced unfolding using fluorescence correlation spectroscopy.

    Science.gov (United States)

    Yadav, Rajeev; Sengupta, Bhaswati; Sen, Pratik

    2014-05-22

    The present study elucidates the involvement of conformational fluctuation dynamics during chemically and thermally induced unfolding of human serum albumin (HSA) by fluorescence correlation spectroscopic (FCS) study, time-resolved fluorescence measurements, and circular dichroism (CD) spectroscopic methods. Two fluorescent probes, tetramethylrhodamine-5-maleimide (TMR) and N-(7-dimethylamino-4-methylcoumarin-3-yl) iodoacetamide (DACIA) were used to selectively label the domain I of HSA through the reaction with cys-34 for these studies. The guanidine hydrochloride (GnHCl) induced global structural change of HSA is monitored through its hydrodynamic radius (r(H)) and CD response, which is found to be two step in nature. In FCS experiment, along with the diffusion time component we have observed an exponential relaxation time component (τ(R)) that has been ascribed to the concerted chain dynamics of HSA. Unlike in the global structural change, we found that the τ(R) value changes in a different manner in the course of the unfolding. The dependence of τ(R) on the concentration of GnHCl was best fitted with a four state model, indicating the involvement of two intermediate states during the unfolding process, which were not observed through the CD response and r(H) data. The fluorescence lifetime measurement also supports our observation of intermediate states during the unfolding of HSA. However, no such intermediate states were observed during thermally induced unfolding of HSA.

  13. High-NaCl Diet Aggravates Cardiac Injury in Rats with Adenine-Induced Chronic Renal Failure and Increases Serum Troponin T Levels

    DEFF Research Database (Denmark)

    Kashioulis, Pavlos; Hammarsten, Ola; Marcussen, Niels

    2016-01-01

    AIMS: To examine the effects of 2 weeks of high-NaCl diet on left ventricular (LV) morphology and serum levels of cardiac troponin T (cTnT) in rats with adenine-induced chronic renal failure (ACRF). METHODS: Male Sprague-Dawley rats either received chow containing adenine or were pair......-fed an identical diet without adenine [controls (C)]. Approximately 10 weeks after the beginning of the study, the rats were randomized to either remain on a normal NaCl diet (NNa; 0.6%) or to be switched to high-NaCl chow (HNa; 4%) for 2 weeks, after which acute experiments were performed. RESULTS: Rats with ACRF...... showed statistically significant increases (p rats (p

  14. Lack of the serum- and glucocorticoid-inducible kinase SGK1 improves muscle force characteristics and attenuates fibrosis in dystrophic mdx mouse muscle

    DEFF Research Database (Denmark)

    Steinberger, Martin; Föller, Michael; Vogelgesang, Silke

    2015-01-01

    Duchenne muscular dystrophy (DMD) is a human genetic disease characterized by fibrosis and severe muscle weakness. Currently, there is no effective treatment available to prevent progressive fibrosis in skeletal muscles. The serum- and glucocorticoid-inducible kinase SGK1 regulates a variety...... of physiological functions and participates in fibrosis stimulation. Here, we investigated whether SGK1 influences structure, function and/or fibrosis of the muscles from the mdx mouse, an animal model for DMD. As expected, mdx muscles showed the typical pathological features of muscular dystrophy including fiber...... size variations, central nuclei of muscle fibers, fibrosis in the diaphragm, and force reduction by 30–50 %. Muscles from sgk1 -/- mice were histologically overall intact and specific force was only slightly reduced compared to wild-type muscles. Surprisingly, soleus and diaphragm muscles of mdx/sgk1...

  15. Chemotherapy-induced gastrointestinal toxicity is associated with changes in serum and urine metabolome and fecal microbiota in male Sprague-Dawley rats.

    Science.gov (United States)

    Forsgård, Richard A; Marrachelli, Vannina G; Korpela, Katri; Frias, Rafael; Collado, Maria Carmen; Korpela, Riitta; Monleon, Daniel; Spillmann, Thomas; Österlund, Pia

    2017-08-01

    Chemotherapy-induced gastrointestinal toxicity (CIGT) is a complex process that involves multiple pathophysiological mechanisms. We have previously shown that commonly used chemotherapeutics 5-fluorouracil, oxaliplatin, and irinotecan damage the intestinal mucosa and increase intestinal permeability to iohexol. We hypothesized that CIGT is associated with alterations in fecal microbiota and metabolome. Our aim was to characterize these changes and examine how they relate to the severity of CIGT. A total of 48 male Sprague-Dawley rats were injected intraperitoneally either with 5-fluorouracil (150 mg/kg), oxaliplatin (15 mg/kg), or irinotecan (200 mg/kg). Body weight change was measured daily after drug administration and the animals were euthanized after 72 h. Blood, urine, and fecal samples were collected at baseline and at the end of the experiment. The changes in the composition of fecal microbiota were analyzed with 16S rRNA gene sequencing. Metabolic changes in serum and urine metabolome were measured with 1 mm proton nuclear magnetic resonance ( 1 H-NMR). Irinotecan increased the relative abundance of Fusobacteria and Proteobacteria, while 5-FU and oxaliplatin caused only minor changes in the composition of fecal microbiota. All chemotherapeutics increased the levels of serum fatty acids and N(CH 3 ) 3 moieties and decreased the levels of Krebs cycle metabolites and free amino acids. Chemotherapeutic drugs, 5-fluorouracil, oxaliplatin, and irinotecan, induce several microbial and metabolic changes which may play a role in the pathophysiology of CIGT. The observed changes in intestinal permeability, fecal microbiota, and metabolome suggest the activation of inflammatory processes.

  16. The plastic work required to induce the limit pressure of a plain cylinder

    International Nuclear Information System (INIS)

    Lee, K.S.; Moreton, D.N.; Moffat, D.G.

    2005-01-01

    There has recently been a revival of interest in the definition of the limit and plastic loads of a structure, particularly piping components. Recent proposals have suggested definitions based upon plastic work. In order to normalise such quantities, the plastic work associated with the limit pressure of a plain cylinder may be required. Whilst no unique value for this quantity can be obtained through analysis, this article demonstrates that classical methods allow solutions to be obtained through an empirical route and through an analysis using several approximations. This latter analysis is shown to be adequate for the applications envisaged here

  17. [The relationship between ischemic preconditioning-induced infarction size limitation and duration of test myocardial ischemia].

    Science.gov (United States)

    Blokhin, I O; Galagudza, M M; Vlasov, T D; Nifontov, E M; Petrishchev, N N

    2008-07-01

    Traditionally infarction size reduction by ischemic preconditioning is estimated in duration of test ischemia. This approach limits the understanding of real antiischemic efficacy of ischemic preconditioning. Present study was performed in the in vivo rat model of regional myocardial ischemia-reperfusion and showed that protective effect afforded by ischemic preconditioning progressively decreased with prolongation of test ischemia. There were no statistically significant differences in infarction size between control and preconditioned animals when the duration of test ischemia was increased up to 1 hour. Preconditioning ensured maximal infarction-limiting effect in duration of test ischemia varying from 20 to 40 minutes.

  18. 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.

  19. Dysfunctional breathing and reaching one’s physiological limit as causes of exercise-induced dyspnoea

    Directory of Open Access Journals (Sweden)

    Julie Depiazzi

    2016-06-01

    This review provides an overview of the spectrum of conditions that can present as exercise-­induced breathlessness experienced by young subjects participating in sport and aims to promote understanding of the need for accurate assessment of an individual’s symptoms. We will highlight the high incidence of nonasthmatic causes, which simply require reassurance or simple interventions from respiratory physiotherapists or speech pathologists.

  20. Glycogen synthase kinase-3β ablation limits pancreatitis-induced acinar-to-ductal metaplasia.

    Science.gov (United States)

    Ding, Li; Liou, Geou-Yarh; Schmitt, Daniel M; Storz, Peter; Zhang, Jin-San; Billadeau, Daniel D

    2017-09-01

    Acinar-to-ductal metaplasia (ADM) is a reversible epithelial transdifferentiation process that occurs in the pancreas in response to acute inflammation. ADM can rapidly progress towards pre-malignant pancreatic intraepithelial neoplasia (PanIN) lesions in the presence of mutant KRas and ultimately pancreatic adenocarcinoma (PDAC). In the present work, we elucidate the role and related mechanism of glycogen synthase kinase-3beta (GSK-3β) in ADM development using in vitro 3D cultures and genetically engineered mouse models. We show that GSK-3β promotes TGF-α-induced ADM in 3D cultured primary acinar cells, whereas deletion of GSK-3β attenuates caerulein-induced ADM formation and PanIN progression in Kras G12D transgenic mice. Furthermore, we demonstrate that GSK-3β ablation influences ADM formation and PanIN progression by suppressing oncogenic KRas-driven cell proliferation. Mechanistically, we show that GSK-3β regulates proliferation by increasing the activation of S6 kinase. Taken together, these results indicate that GSK-3β participates in early pancreatitis-induced ADM and thus could be a target for the treatment of chronic pancreatitis and the prevention of PDAC progression. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  1. Hepatocyte growth factor limits autoimmune neuroinflammation via glucocorticoid-induced leucine zipper expression in dendritic cells.

    Science.gov (United States)

    Benkhoucha, Mahdia; Molnarfi, Nicolas; Dunand-Sauthier, Isabelle; Merkler, Doron; Schneiter, Gregory; Bruscoli, Stefano; Riccardi, Carlo; Tabata, Yasuhiko; Funakoshi, Hiroshi; Nakamura, Toshikazu; Reith, Walter; Santiago-Raber, Marie-Laure; Lalive, Patrice H

    2014-09-15

    Autoimmune neuroinflammation, including multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), a prototype for T cell-mediated autoimmunity, is believed to result from immune tolerance dysfunction leading to demyelination and substantial neurodegeneration. We previously showed that CNS-restricted expression of hepatocyte growth factor (HGF), a potent neuroprotective factor, reduced CNS inflammation and clinical deficits associated with EAE. In this study, we demonstrate that systemic HGF treatment ameliorates EAE through the development of tolerogenic dendritic cells (DCs) with high expression levels of glucocorticoid-induced leucine zipper (GILZ), a transcriptional repressor of gene expression and a key endogenous regulator of the inflammatory response. RNA interference-directed neutralization of GILZ expression by DCs suppressed the induction of tolerance caused by HGF. Finally, adoptive transfer of HGF-treated DCs from wild-type but not GILZ gene-deficient mice potently mediated functional recovery in recipient mice with established EAE through effective modulation of autoaggressive T cell responses. Altogether, these results show that by inducing GILZ in DCs, HGF reproduces the mechanism of immune regulation induced by potent immunomodulatory factors such as IL-10, TGF-β1, and glucocorticoids and therefore that HGF therapy may have potential in the treatment of autoimmune dysfunctions. Copyright © 2014 by The American Association of Immunologists, Inc.

  2. Serum sickness

    Science.gov (United States)

    ... the problem should be stopped. Avoid using that medicine or antiserum in the future. ... Call your provider if you received medicine or antiserum in the last 4 weeks and have symptoms of serum sickness.

  3. The serum concentration of tumor necrosis factor alpha is not an index of growth-hormone- or obesity-induced insulin resistance.

    Science.gov (United States)

    Pincelli, A I; Brunani, A; Scacchi, M; Dubini, A; Borsotti, R; Tibaldi, A; Pasqualinotto, L; Maestri, E; Cavagnini, F

    2001-01-01

    The tumor necrosis factor alpha (TNF-alpha) might play a central role in insulin resistance, a frequent correlate of obesity likely contributing to some obesity-associated complications. Adult growth hormone (GH) deficiency syndrome (GHDA) shares with obesity excessive fat mass, hyperlipidemia, increased cardiovascular risk, and insulin resistance. On the other hand, GH has been shown to induce transient deterioration of glucose metabolism and insulin resistance when administered in normal humans and in GHDA patients. No information is presently available on the relationship between serum TNF-alpha levels and insulin sensitivity in GHDA. We compared the serum TNF-alpha levels found in 10 GHDA patients before and after a 6-month recombinant human GH therapy (Genotropin), in an insulin resistance prone population of 16 obese (OB) patients and in 38 normal-weight healthy blood donors (controls). The insulin sensitivity was assessed by a euglycemic-hyperinsulinemic glucose clamp in all the GHDA patients and in 10 OB and in 6 control subjects. The serum TNF-alpha levels were not significantly different in OB patients (42.2 +/- 12.81 pg/ml), in GHDA patients at baseline (71.3 +/- 23.97 pg/ml), and in controls (55.3 +/- 14.28 pg/ml). A slight decrease of TNF-alpha values was noted in GHDA patients after 6 months of recombinant human GH treatment (44.5 +/- 20.19 pg/ml; NS vs. baseline). The insulin sensitivity (M) was significantly reduced in OB patients (2.4 +/- 0.30 mg/kg/min) as compared with control subjects (7.5 +/- 0.39 mg/kg/min) and in GHDA patients both at baseline (6.6 +/- 0.6 mg/kg/min) and after recombinant human GH therapy (5.6 +/- 0.7 mg/kg/min). The insulin sensitivity in the GHDA patients, similar to that of controls at baseline, worsened after recombinant human GH treatment (p < 0.05 vs. baseline; p = 0.05 vs. controls). Linear regression analysis showed no correlation between TNF-alpha and M values (see text) in all patient groups. These data indicate

  4. Serum Amyloid A Induces Toll-Like Receptor 2-Dependent Inflammatory Cytokine Expression and Atrophy in C2C12 Skeletal Muscle Myotubes.

    Science.gov (United States)

    Passey, Samantha L; Bozinovski, Steven; Vlahos, Ross; Anderson, Gary P; Hansen, Michelle J

    2016-01-01

    Skeletal muscle wasting is an important comorbidity of Chronic Obstructive Pulmonary Disease (COPD) and is strongly correlated with morbidity and mortality. Patients who experience frequent acute exacerbations of COPD (AECOPD) have more severe muscle wasting and reduced recovery of muscle mass and function after each exacerbation. Serum levels of the pro-inflammatory acute phase protein Serum Amyloid A (SAA) can rise more than 1000-fold in AECOPD and are predictively correlated with exacerbation severity. The direct effects of SAA on skeletal muscle are poorly understood. Here we have examined SAA effects on pro-inflammatory cachectic cytokine expression (IL-6 and TNFα) and atrophy in C2C12 myotubes. SAA increased IL-6 (31-fold) and TNFα (6.5-fold) mRNA levels compared to control untreated cells after 3h of SAA treatment, and increased secreted IL-6 protein at 24h. OxPAPC, a dual TLR2 and TLR4 inhibitor, reduced the response to SAA by approximately 84% compared to SAA alone, and the TLR2 neutralising antibody T2.5 abolished SAA-induced expression of IL-6, indicating that SAA signalling in C2C12 myotubes is primarily via TLR2. SAA also reduced myotube width by 10-13% and induced a 2.5-fold increase in the expression of the muscle atrophy gene Atrogin-1, suggesting direct effects of SAA on muscle wasting. Blocking of TLR2 inhibited the SAA-induced decrease in myotube width and Atrogin-1 gene expression, indicating that SAA induces atrophy through TLR2. These data demonstrate that SAA stimulates a robust pro-inflammatory response in skeletal muscle myotubes via the TLR2-dependent release of IL-6 and TNFα. Furthermore, the observed atrophy effects indicate that SAA could also be directly contributing to the wasting and poor recovery of muscle mass. Therapeutic strategies targeting this SAA-TLR2 axis may therefore ameliorate muscle wasting in AECOPD and a range of other inflammatory conditions associated with loss of muscle mass.

  5. Fe induced optical limiting properties of Zn1-xFexS nanospheres

    Science.gov (United States)

    Vineeshkumar, T. V.; Raj, D. Rithesh; Prasanth, S.; Unnikrishnan, N. V.; Mahadevan Pillai, V. P.; Sudarasanakumar, C.

    2018-02-01

    Zn1-xFexS (x = 0.00, 0.01, 0.03, 0.05) nanospheres were synthesized by polyethylene glycol assisted hydrothermal method. XRD studies revealed that samples of all concentrations exhibited cubic structure with crystallite grain size 7-9 nm. TEM and SEM show the formation of nanospheres by dense aggregation of smaller particles. Increasing Zn/Fe ratio tune the band gap from 3.4 to 3.2 eV and also quenches the green luminescence. FTIR spectra reveal the presence of capping agent, intensity variation and shifting of LO and TO phonon modes confirm the presence of Fe ions. Nonlinear optical properties were measured using open and closed aperture z-scan techniques, employing frequency doubled 532 nm pumping sources which indicated reverse saturable absorption (RSA) process. The nonlinear optical coefficients are obtained by two photon absorption (2PA). Composition dependent nonlinear optical coefficients ;β;, nonlinear refractive index, third order susceptibility and optical limiting threshold were estimated. The sample shows good nonlinear absorption and enhancement of optical limiting behavior with increasing Fe volume fraction. Contribution of RSA on optical nonlinearity of Zn1-xFexS nanospheres are also investigated using three different input energies. Zn1-xFexS with comparatively small limiting threshold value is a promising candidate for optical power limiting applications.

  6. Serum Creatinine: Not So Simple!

    Science.gov (United States)

    Delanaye, Pierre; Cavalier, Etienne; Pottel, Hans

    2017-01-01

    Measuring serum creatinine is cheap and commonly done in daily practice. However, interpretation of serum creatinine results is not always easy. In this review, we will briefly remind the physiological limitations of serum creatinine due notably to its tubular secretion and the influence of muscular mass or protein intake on its concentration. We mainly focus on the analytical limitations of serum creatinine, insisting on important concept such as reference intervals, standardization (and IDMS traceability), analytical interferences, analytical coefficient of variation (CV), biological CV and critical difference. Because the relationship between serum creatinine and glomerular filtration rate is hyperbolic, all these CVs will impact not only the precision of serum creatinine but still more the precision of different creatinine-based equations, especially in low or normal-low creatinine levels (or high or normal-high glomerular filtration rate range). © 2017 S. Karger AG, Basel.

  7. Plasma-induced evolution behavior of space-charge-limited current for multiple-needle cathodes

    International Nuclear Information System (INIS)

    Li Limin; Liu Lie; Zhang Jun; Wen Jianchun; Liu Yonggui; Wan Hong

    2009-01-01

    Properties of the plasma and beam flow produced by tufted carbon fiber cathodes in a diode powered by a ∼500 kV, ∼400 ns pulse are investigated. Under electric fields of 230-260 kV cm -1 , the electron current density was in the range 210-280 A cm -2 , and particularly at the diode gap of 20 mm, a maximum beam power density of about 120 MW cm -2 was obtained. It was found that space-charge-limited current exhibited an evolution behavior as the accelerating pulse proceeded. There exists a direct relation between the movement of plasma within the diode and the evolution of space-charge-limited current. Initially in the accelerating pulse, the application of strong electric fields caused the emission sites to explode, forming cathode flares or plasma spots, and in this stage the space-charge-limited current was approximately described by a multiple-needle cathode model. As the pulse proceeded, these plasma spots merged and expanded towards the anode, thus increasing the emission area and shortening the diode gap, and the corresponding space-charge-limited current followed a planar cathode model. Finally, the space-charge-limited current is developed from a unipolar flow into a bipolar flow as a result of the appearance of anode plasma. In spite of the nonuniform distribution of cathode plasma, the cross-sectional uniformity of the extracted electron beam is satisfactory. The plasma expansion within the diode is found to be a major factor in the diode perveance growth and instability. These results show that these types of cathodes can offer promising applications for high-power microwave tubes.

  8. Serum neopterin and soluble CD163 as markers of macrophage activation in paracetamol (acetaminophen)-induced human acute liver injury.

    Science.gov (United States)

    Craig, D G; Lee, P; Pryde, E A; Hayes, P C; Simpson, K J

    2013-12-01

    Macrophage activation is implicated in the pathogenesis of the systemic inflammatory response syndrome (SIRS) following paracetamol (acetaminophen) overdose (POD). Neopterin is synthesised from macrophages and reflects the intensity of monocyte/macrophage activation. Soluble CD163 (sCD163) is a marker of alternatively activated M2 macrophages. To examine neopterin and sCD163 levels in a cohort of acute liver injury patients. Consecutive patients (n = 41, (18 (43.9%) male) with acute liver injury were enrolled. Neopterin and sCD163 levels were measured by ELISA. A total of 24/33 (72.7%) POD patients developed hepatic encephalopathy (HE), and therefore acute liver failure. Both neopterin and sCD163 levels were significantly higher in PODs compared with chronic liver disease (neopterin P paracetamol overdose, and reflect the degree of macrophage activation in this condition. Serum neopterin in particular may have value as an early proxy marker of macrophage activation following paracetamol overdose. © 2013 John Wiley & Sons Ltd.

  9. Mechanical joining of materials with limited ductility: Analysis of process-induced defects

    Science.gov (United States)

    Jäckel, M.; Coppieters, S.; Hofmann, M.; Vandermeiren, N.; Landgrebe, D.; Debruyne, D.; Wallmersberger, T.; Faes, K.

    2017-10-01

    The paper shows experimental and numerical analyses of the clinching process of 6xxx series aluminum sheets in T6 condition and the self-pierce riveting process of an aluminum die casting. In the experimental investigations the damage behavior of the materials when using different tool parameters is analyzed. The focus of the numerical investigations is the damage prediction by a comparison of different damage criteria. Moreover, strength-and fatigue tests were carried out to investigate the influence of the joining process-induced damages on the strength properties of the joints.

  10. Resting egg production induced by food limitation in the calanoid copepod Acartia tonsa

    DEFF Research Database (Denmark)

    Drillet, Guillaume; Hansen, Benni W.; Kiørboe, Thomas

    2011-01-01

    Three populations of the copepod Acartia tonsa, two from the Baltic Sea and one from the U.S. East Coast, were compared for resting egg production at conditions of saturating and limiting food availability. All three populations produced eggs that hatched within 72 h when incubated at 17°C...... (subitaneous eggs), but the two Baltic populations in addition produced eggs that hatched at a much slower rate, in the course of a month (delayed hatching eggs [DHE]). Such eggs were not produced by the U.S. population. The fraction of DHE increased when food was limiting. Females from a Baltic population...... that were incubated individually all produced subitaneous eggs, but about half the females consistently also produced DHE. Cold storage that mimicked boreal winter conditions synchronized the hatching of DHE after extended storage, indicating that spring hatching of DHE might seed the water column...

  11. Dispersal limitation induces long-term biomass collapse in overhunted Amazonian forests.

    Science.gov (United States)

    Peres, Carlos A; Emilio, Thaise; Schietti, Juliana; Desmoulière, Sylvain J M; Levi, Taal

    2016-01-26

    Tropical forests are the global cornerstone of biological diversity, and store 55% of the forest carbon stock globally, yet sustained provisioning of these forest ecosystem services may be threatened by hunting-induced extinctions of plant-animal mutualisms that maintain long-term forest dynamics. Large-bodied Atelinae primates and tapirs in particular offer nonredundant seed-dispersal services for many large-seeded Neotropical tree species, which on average have higher wood density than smaller-seeded and wind-dispersed trees. We used field data and models to project the spatial impact of hunting on large primates by ∼ 1 million rural households throughout the Brazilian Amazon. We then used a unique baseline dataset on 2,345 1-ha tree plots arrayed across the Brazilian Amazon to model changes in aboveground forest biomass under different scenarios of hunting-induced large-bodied frugivore extirpation. We project that defaunation of the most harvest-sensitive species will lead to losses in aboveground biomass of between 2.5-5.8% on average, with some losses as high as 26.5-37.8%. These findings highlight an urgent need to manage the sustainability of game hunting in both protected and unprotected tropical forests, and place full biodiversity integrity, including populations of large frugivorous vertebrates, firmly in the agenda of reducing emissions from deforestation and forest degradation (REDD+) programs.

  12. Ethylene limits abscisic acid- or soil drying-induced stomatal closure in aged wheat leaves.

    Science.gov (United States)

    Chen, Lin; Dodd, Ian C; Davies, William J; Wilkinson, Sally

    2013-10-01

    The mechanism of age-induced decreased stomatal sensitivity to abscisic acid (ABA) and soil drying has been explored here. Older, fully expanded leaves partly lost their ability to close stomata in response to foliar ABA sprays, and soil drying which stimulated endogenous ABA production, while young fully expanded leaves closed their stomata more fully. However, ABA- or soil drying-induced stomatal closure of older leaves was partly restored by pretreating plants with 1-methylcyclopropene (1-MCP), which can antagonize ethylene receptors, or by inoculating soil around the roots with the rhizobacterium Variovorax paradoxus 5C-2, which contains 1-aminocyclopropane-1-carboxylic acid (ACC)-deaminase. ACC (the immediate biosynthetic precursor of ethylene) sprays revealed higher sensitivity of stomata to ethylene in older leaves than younger leaves, despite no differences in endogenous ACC concentrations or ethylene emission. Taken together, these results indicate that the relative insensitivity of stomatal closure to ABA and soil drying in older leaves is likely due to altered stomatal sensitivity to ethylene, rather than ethylene production. To our knowledge, this is the first study to mechanistically explain diminished stomatal responses to soil moisture deficit in older leaves, and the associated reduction in leaf water-use efficiency. © 2013 John Wiley & Sons Ltd.

  13. Vitamin D fails to prevent serum starvation- or staurosporine-induced apoptosis in human and rat osteosarcoma-derived cell lines

    International Nuclear Information System (INIS)

    Witasp, Erika; Gustafsson, Ann-Catrin; Cotgreave, Ian; Lind, Monica; Fadeel, Bengt

    2005-01-01

    Previous studies have suggested that 1,25(OH) 2 D 3 , the active form of vitamin D 3 , may increase the survival of bone-forming osteoblasts through an inhibition of apoptosis. On the other hand, vitamin D 3 has also been shown to trigger apoptosis in human cancer cells, including osteosarcoma-derived cell lines. In the present study, we show that 1,25(OH) 2 D 3 induces a time- and dose-dependent loss of cell viability in the rat osteosarcoma cell line, UMR-106, and the human osteosarcoma cell line, TE-85. We were unable, however, to detect nuclear condensation, phosphatidylserine externalization, or other typical signs of apoptosis in this model. Moreover, 1,25(OH) 2 D 3 failed to protect against apoptosis induced by serum starvation or incubation with the protein kinase inhibitor, staurosporine. These in vitro findings are thus at variance with several previous reports in the literature and suggest that induction of or protection against apoptosis of bone-derived cells may not be a primary function of vitamin D 3

  14. Role of urea in controlling radiation-induced changes in some amino acids level and protein end products in blood serum of rats

    International Nuclear Information System (INIS)

    El-Kashef, H.S.; Saada, H.N.

    1991-01-01

    In previous studies (Helen Saada, 1982), urea could successfully act as a good radio-protector. It helps the recovery from changes induced by gamma irradiation in soluble protein contents, and percentage of protein fractions as well as some enzymatic activity. In the present study, it has been found that urea acts also as adequate radioprotector against radiation induced changes in the level of free and tied amino acids, glucosamine,free ammonia and urea concentration in the blood serum of white rats. The radioprotective role of urea was very clear on the first day after irradiation as manifested by the levels of free amino acids and protein end products (urea and ammonia). While in the case of tied amino acids, the action of urea as a radioprotector could be noticed lately, on the third post-irradiation day. The recovery from radiation hazards depended not only on the time lapse after irradiation but also on the chemical structure of the molecule which presents or constitutes the biological matter.2 tab.,1 fig

  15. Edaravone protects against oxygen-glucose-serum deprivation/restoration-induced apoptosis in spinal cord astrocytes by inhibiting integrated stress response

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    Bin Dai

    2017-01-01

    Full Text Available We previously found that oxygen-glucose-serum deprivation/restoration (OGSD/R induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-like endoplasmic reticulum kinase (PERK, eukaryotic initiation factor 2-alpha (eIF2α and activating transcription factor 4 (ATF4. We hypothesized that edaravone, a low molecular weight, lipophilic free radical scavenger, would reduce OGSD/R-induced apoptosis of spinal cord astrocytes. To test this, we established primary cultures of rat astrocytes, and exposed them to 8 hours/6 hours of OGSD/R with or without edaravone (0.1, 1, 10, 100 μM treatment. We found that 100 μM of edaravone significantly suppressed astrocyte apoptosis and inhibited the release of reactive oxygen species. It also inhibited the activation of caspase-12 and caspase-3, and reduced the expression of homologous CCAAT/enhancer binding protein, phosphorylated (p-PERK, p-eIF2α, and ATF4. These results point to a new use of an established drug in the prevention of OGSD/R-mediated spinal cord astrocyte apoptosis via the integrated stress response.

  16. Linking carbon and water limitations to drought-induced mortality of Pinus flexilis seedlings

    Science.gov (United States)

    Reinhardt, Keith; Germino, Matthew J.; Kueppers, Lara M.; Domec, Jean-Christophe; Mitton, Jeffry

    2015-01-01

    Survival of tree seedlings at high elevations has been shown to be limited by thermal constraints on carbon balance, but it is unknown if carbon relations also limit seedling survival at lower elevations, where water relations may be more important. We measured and modeled carbon fluxes and water relations in first-year Pinus flexilis seedlings in garden plots just beyond the warm edge of their natural range, and compared these with dry-mass gain and survival across two summers. We hypothesized that mortality in these seedlings would be associated with declines in water relations, more so than with carbon-balance limitations. Rather than gradual declines in survivorship across growing seasons, we observed sharp, large-scale mortality episodes that occurred once volumetric soil-moisture content dropped below 10%. By this point, seedling water potentials had decreased below −5 MPa, seedling hydraulic conductivity had decreased by 90% and seedling hydraulic resistance had increased by >900%. Additionally, non-structural carbohydrates accumulated in aboveground tissues at the end of both summers, suggesting impairments in phloem-transport from needles to roots. This resulted in low carbohydrate concentrations in roots, which likely impaired root growth and water uptake at the time of critically low soil moisture. While photosynthesis and respiration on a leaf area basis remained high until critical hydraulic thresholds were exceeded, modeled seedling gross primary productivity declined steadily throughout the summers. At the time of mortality, modeled productivity was insufficient to support seedling biomass-gain rates, metabolism and secondary costs. Thus the large-scale mortality events that we observed near the end of each summer were most directly linked with acute, episodic declines in plant hydraulic function that were linked with important changes in whole-seedling carbon relations.

  17. Localization of atomic excitation beyond the diffraction limit using electromagnetically induced transparency

    Science.gov (United States)

    Miles, J. A.; Das, Diptaranjan; Simmons, Z. J.; Yavuz, D. D.

    2015-09-01

    We experimentally demonstrate the localization of excitation between hyperfine ground states of 87Rb atoms to as small as λ /13 -wide spatial regions. We use ultracold atoms trapped in a dipole trap and utilize electromagnetically induced transparency (EIT) for the atomic excitation. The localization is achieved by combining a spatially varying coupling laser (standing wave) with the intensity dependence of EIT. The excitation is fast (150 ns laser pulses) and the dark-state fidelity can be made higher than 94% throughout the standing wave. Because the width of the localized regions is much smaller than the wavelength of the driving light, traditional optical imaging techniques cannot resolve the localized features. Therefore, to measure the excitation profile, we use an autocorrelation-like method where we perform two EIT sequences separated by a time delay, during which we move the standing wave.

  18. Loss-induced limits to phase measurement precision with maximally entangled states

    International Nuclear Information System (INIS)

    Rubin, Mark A.; Kaushik, Sumanth

    2007-01-01

    The presence of loss limits the precision of an approach to phase measurement using maximally entangled states, also referred to as NOON states. A calculation using a simple beam-splitter model of loss shows that, for all nonzero values L of the loss, phase measurement precision degrades with increasing number N of entangled photons for N sufficiently large. For L above a critical value of approximately 0.785, phase measurement precision degrades with increasing N for all values of N. For L near zero, phase measurement precision improves with increasing N down to a limiting precision of approximately 1.018L radians, attained at N approximately equal to 2.218/L, and degrades as N increases beyond this value. Phase measurement precision with multiple measurements and a fixed total number of photons N T is also examined. For L above a critical value of approximately 0.586, the ratio of phase measurement precision attainable with NOON states to that attainable by conventional methods using unentangled coherent states degrades with increasing N, the number of entangled photons employed in a single measurement, for all values of N. For L near zero this ratio is optimized by using approximately N=1.279/L entangled photons in each measurement, yielding a precision of approximately 1.340√(L/N T ) radians

  19. Serum-Induced Differentiation of Glioblastoma Neurospheres Leads to Enhanced Migration/Invasion Capacity That Is Associated with Increased MMP9.

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    Justin V Joseph

    Full Text Available Glioblastoma (GBM is a highly infiltrative brain tumor in which cells with properties of stem cells, called glioblastoma stem cells (GSCs, have been identified. In general, the dominant view is that GSCs are responsible for the initiation, progression, invasion and recurrence of this tumor. In this study, we addressed the question whether the differentiation status of GBM cells is associated with their invasive capacity. For this, several primary GBM cell lines were used, cultured either as neurospheres known to enrich for GSCs or in medium supplemented with 10% FCS that promotes differentiation. The differentiation state of the cells was confirmed by determining the expression of stem cell and differentiation markers. The migration/invasion potential of these cells was tested using in vitro assays and intracranial mouse models. Interestingly, we found that serum-induced differentiation enhanced the invasive potential of GBM cells, which was associated with enhanced MMP9 expression. Chemical inhibition of MMP9 significantly reduced the invasive potential of differentiated cells in vitro. Furthermore, the serum-differentiated cells could revert back to an undifferentiated/stem cell state that were able to form neurospheres, although with a reduced efficiency as compared to non-differentiated counterparts. We propose a model in which activation of the differentiation program in GBM cells enhances their infiltrative potential and that depending on microenvironmental cues a significant portion of these cells are able to revert back to an undifferentiated state with enhanced tumorigenic potential. Thus, effective therapy should target both GSCs and differentiated offspring and targeting of differentiation-associated pathways may offer therapeutic opportunities to reduce invasive growth of GBM.

  20. Inducible nitric oxide synthase in heart tissue and nitric oxide in serum of Trypanosoma cruzi-infected rhesus monkeys: association with heart injury.

    Directory of Open Access Journals (Sweden)

    Cristiano Marcelo Espinola Carvalho

    Full Text Available BACKGROUND: The factors contributing to chronic Chagas' heart disease remain unknown. High nitric oxide (NO levels have been shown to be associated with cardiomyopathy severity in patients. Further, NO produced via inducible nitric oxide synthase (iNOS/NOS2 is proposed to play a role in Trypanosoma cruzi control. However, the participation of iNOS/NOS2 and NO in T. cruzi control and heart injury has been questioned. Here, using chronically infected rhesus monkeys and iNOS/NOS2-deficient (Nos2(-/- mice we explored the participation of iNOS/NOS2-derived NO in heart injury in T. cruzi infection. METHODOLOGY: Rhesus monkeys and C57BL/6 and Nos2(-/- mice were infected with the Colombian T. cruzi strain. Parasite DNA was detected by polymerase chain reaction, T. cruzi antigens and iNOS/NOS2(+ cells were immunohistochemically detected in heart sections and NO levels in serum were determined by Griess reagent. Heart injury was assessed by electrocardiogram (ECG, echocardiogram (ECHO, creatine kinase heart isoenzyme (CK-MB activity levels in serum and connexin 43 (Cx43 expression in the cardiac tissue. RESULTS: Chronically infected monkeys presented conduction abnormalities, cardiac inflammation and fibrosis, which resembled the spectrum of human chronic chagasic cardiomyopathy (CCC. Importantly, chronic myocarditis was associated with parasite persistence. Moreover, Cx43 loss and increased CK-MB activity levels were primarily correlated with iNOS/NOS2(+ cells infiltrating the cardiac tissue and NO levels in serum. Studies in Nos2(-/- mice reinforced that the iNOS/NOS2-NO pathway plays a pivotal role in T. cruzi-elicited cardiomyocyte injury and in conduction abnormalities that were associated with Cx43 loss in the cardiac tissue. CONCLUSION: T. cruzi-infected rhesus monkeys reproduce features of CCC. Moreover, our data support that in T. cruzi infection persistent parasite-triggered iNOS/NOS2 in the cardiac tissue and NO overproduction might contribute

  1. The effects of aqueous extract of stevia plant (Stevia rebaudiana on serum concentration of vaspin and Angiopoietin-like Protein-3 in streptozotocin induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Samad Akbarzadeh

    2015-05-01

    Full Text Available Background: Considering the importance of the prevalence of diabetes which involves approximately 6% of the world's adult population, the need for low-calorie natural sweetener is felt more than ever. Recent studies have shown that hormones such as vaspin and Angiopoietin-like Protein3 (ANGPTL3 are associated with diabetes. The purpose of this study is to evaluate the effect of Stevia (Stevia rebaudiana plant (as a low calorie sugar on serum concentration of vaspin and ANGPTL3 in diabetic rats. Materials and Methods: In this case-control study, forty male wistar rats weighing 180-250 g were divided into 5 equal groups: control, diabetic control and doses of 250, 500 and 750 mg/kg/BW/day of Stevia extract treatment. Diabetes was induced by intravenous injection of Streptozotocin (60 mg/kg. After 5 days, the rats with glucose above 300 mg/dl were considered as diabetic. The Stevia treatment groups received 250, 500 and 750 mg of Stevia extract for thirty days. At the end of experiment, blood samples were obtained measurement of vaspin, ANGPTL3, triglycerides, cholesterol, HDL, glucose, insulin and ALP. Histological study of the pancreas and liver biopsy were also performed. The results of the treatment and control groups were analyzed by SPSS software and P<0.05 was considered statistically significant. Results: The level of alkaline phosphatase, insulin resistance index, glucose and triglyceride were decreased significantly in the groups 250 and 500 compared with the diabetic control group(p≤0.05. However, insulin levels, HOMA.B, vaspin, ANGPTL3 and weight of the rats in all treatment groups were not significantly different from the control diabetic group. There were no histological changes in pancreatic and liver tissue following Stevia treatment. Conclusion: Administration of Stevia extract via reduction in serum glucose, triglyceride and insulin resistance can be effective in lowering the blood sugar and lipid, also lowering concentrations

  2. Corticosteroid-induced asthma: a manifestation of limited hyperinfection syndrome due to Strongyloides stercoralis.

    Science.gov (United States)

    Sen, P; Gil, C; Estrellas, B; Middleton, J R

    1995-09-01

    Inadequate therapeutic response to parenteral corticosteroids in patients with acute bronchial asthma is infrequent. We report four patients whose bronchial asthma symptoms worsened after treatment with parenteral corticosteroids. All had larvae of Strongyloides stercoralis in the stool. The new attack or the exacerbation of asthma appeared to be precipitated by systemic corticosteroid administration. The paradoxic therapeutic response of asthma to glucocorticoides was the major pulmonary manifestation of Strongyloides superinfection; there was no evidence of other organ involvement. Individuals with new onset of bronchial asthma or worsening of asthmatic episodes concurrent with the use of systemic corticosteroids should have thorough investigation for possible superinfection due to Strongyloides stercoralis. This is particularly important for patients who have resided in areas where intestinal helminthic infections are endemic. Discontinuance of steroid therapy or reduction in dosage of parenteral steroids appears necessary. Treatment with thiabendazole appears to be effective in patients with limited hyperinfection syndrome.

  3. Design limits for HT9 cladding using stress-induced aging data

    International Nuclear Information System (INIS)

    Fox, G.L.

    1986-04-01

    Stress-temperature design guidelines are developed for the ferritic/martensitic cladding material HT9. High temperature operation for HT9 may cause microstructural changes/aging which softens the structure and causes increased creep rates. Higher creep strains means cladding breech becomes more probable before the end of the expected pin lifetime. Tertiary creep is considered an indication of microstructural changes and is to be avoided in fuel pin operation. The creep rate correlation, which includes tertiary creep, is examined for information on stress-temperature relationships which promote aging. This approach leads to design limits for HT9 which are compared with expected hot channel conditions for fuel pins in the Core Demonstration Experiment (CDE) planned for FFTF. The results show aging should not be significant for CDE

  4. Update in the understanding of altitude-induced limitations to performance in team-sport athletes.

    Science.gov (United States)

    Billaut, François; Aughey, Robert J

    2013-12-01

    The internationalism of field-based team sports (TS) such as football and rugby requires teams to compete in tournaments held at low to moderate altitude (∼1200-2500 m). In TS, acceleration, speed and aerobic endurance are physical characteristics associated with ball possession and, ultimately, scoring. While these qualities are affected by the development of neuromuscular fatigue at sea level, arterial hypoxaemia induced by exposure to altitude may further hinder the capacity to perform consecutive accelerations (CAC) or sprint endurance and thereby change the outcome of a match. The higher the altitude, the more severe the hypoxaemia, and thus, the larger the expected decline in aerobic endurance, CAC and match running performance. Therefore, it is critical for athletes and coaches to understand how arterial hypoxaemia affects aerobic endurance and CAC and the magnitude of decline they may face at altitude for optimal preparation and increased chances of success. This mini review summarises the effects of acute altitude/hypoxia exposure on aerobic endurance, CAC and activity profiles of TS athletes performing in the laboratory and during matches at natural altitude, and analyses the latest findings about the consequences of arterial hypoxaemia on the relationship between peripheral perturbations, neural adjustments and performance during repeated sprints or CAC. Finally, we briefly discuss how altitude training can potentially help athletes prepare for competition at altitude.

  5. The development of fieldable laser-induced breakdown spectrometer: No limits on the horizon

    International Nuclear Information System (INIS)

    Fortes, F.J.; Laserna, J.J.

    2010-01-01

    In this review, new trends in the development of fieldable instrumentation based on laser-induced breakdown spectroscopy (LIBS) and its recent applications is presented. Depending on the LIBS configuration we will distinguish between portable, remote and stand-off instruments. Moreover, the development of portable systems gives greater flexibility and also increases the range of LIBS applications. In general, portable instruments are employed in close-contact applications like immovable artworks, contaminated soils and environmental diagnostic, while remote and stand-off instruments are normally used in analytical applications at distances where access to the sample is difficult or hazardous. Although remote and stand-off instruments are both used for chemical analysis at distances, the instrumental configurations are completely different. In remote analysis, an optical fiber is employed to deliver the laser energy a certain distance. This approach has been usually restricted to industrial applications, bulk analysis in water, geological measurements and chemical analysis on nuclear stations. In the case of stand-off applications, the laser beam and the returning plasma light are transmitted in an open-path configuration. In this article we also discuss the instrumental requirements in the design of remote and stand-off instruments.

  6. Serum metabonomics study of the hepatoprotective effect of Corydalis saxicola Bunting on carbon tetrachloride-induced acute hepatotoxicity in rats by (1)H NMR analysis.

    Science.gov (United States)

    Liang, Yong-Hong; Tang, Chao-Ling; Lu, Shi-Yin; Cheng, Bang; Wu, Fang; Chen, Zhao-Ni; Song, Fangming; Ruan, Jun-Xiang; Zhang, Hong-Ye; Song, Hui; Zheng, Hua; Su, Zhi-Heng

    2016-09-10

    Corydalis saxicola Bunting (CS), a traditional Chinese folk medicine, has been effectively used for treating liver disease in Zhuang nationality in South China. However, the exact hepatoprotective mechanism of CS was still looking forward to further elucidation by far. In present work, metabonomic study of biochemical changes in the serum of carbon tetrachloride (CCl4)-induced acute liver injury rats after CS treatment were performed using proton nuclear magnetic resonance ((1)H-NMR) analysis. Metabolic profiling by means of principal components analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) indicated that the metabolic perturbation caused by CCl4 was reduced by CS treatment. A total of 9 metabolites including isoleucine (1), lactate (2), alanine (3), glutamine (4), acetone (5), succinate (6), phosphocholine (7), d-glucose (8) and glycerol (9) were considered as potential biomarkers involved in the development of CCl4-induced acute liver injury. According to pathway analysis by metabolites identified and correlation network construction by Pearson's correlation coefficency matrix, alanine, aspartate and glutamate metabolism and glycerolipid metabolism were recognized as the most influenced metabolic pathways associated with CCl4 injury. As a result, notably, deviations of metabolites 1, 3, 4, 7 and 9 in the process of CCl4-induced acute liver injury were improved by CS treatment, which suggested that CS mediated synergistically abnormalities of the metabolic pathways, composed of alanine, aspartate and glutamate metabolism and glycerolipid metabolism. In this study, it was the first report to investigate the hepatoprotective effect of the CS based on metabonomics strategy, which may be a potentially powerful tool to interpret the action mechanism of traditional Chinese folk medicines. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis.

    Science.gov (United States)

    Tekieh, E; Zaringhalam, Jalal; Manaheji, H; Maghsoudi, N; Alani, B; Zardooz, H

    2011-01-01

    Interleukin (IL)-6 is known to cause pro- and anti-inflammatory effects during different stages of inflammation. Recent therapeutic investigations have focused on treatment of various inflammatory disorders with anti-cytokine substances. As a result, the aim of this study was to further elucidate the influence of IL-6 in hyperalgesia and edema during different stages of Complete Freund's Adjuvant (CFA)-induced arthritis (AA) in male Wistar rats. AA was induced by a single subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 was administered either daily or weekly during the 21 days of study. Spinal mu opioid receptor (mOR) expression was detected by Western blotting. Daily and weekly treatment with an anti-IL-6 antibody significantly decreased paw edema in the AA group compared to the AA control group. Additionally, daily and weekly anti-IL-6 administration significantly reduced hyperalgesia on day 7 in the AA group compared to the AA control group; however, there were significant increases in hyperalgesia in the antibody-treated group on days 14 and 21 compared to the AA control group. IL-6 antibody-induced increases in hyperalgesia on the 14 th and 21 st days after CFA injection correlated with a time-dependent, significant reduction in spinal mOR expression during anti-IL-6 treatment. Our study confirmed the important time-dependent relationship between serum IL-6 levels and hyperalgesia during AA. These results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment.

  8. Superior serum half life of albumin tagged TNF ligands

    International Nuclear Information System (INIS)

    Mueller, Nicole; Schneider, Britta; Pfizenmaier, Klaus; Wajant, Harald

    2010-01-01

    Due to their immune stimulating and apoptosis inducing properties, ligands of the TNF family attract increasing interest as therapeutic proteins. A general limitation of in vivo applications of recombinant soluble TNF ligands is their notoriously rapid clearance from circulation. To improve the serum half life of the TNF family members TNF, TWEAK and TRAIL, we genetically fused soluble variants of these molecules to human serum albumin (HSA). The serum albumin-TNF ligand fusion proteins were found to be of similar bioactivity as the corresponding HSA-less counterparts. Upon intravenous injection (i.v.), serum half life of HSA-TNF ligand fusion proteins, as determined by ELISA, was around 15 h as compared to approximately 1 h for all of the recombinant control TNF ligands without HSA domain. Moreover, serum samples collected 6 or 24 h after i.v. injection still contained high TNF ligand bioactivity, demonstrating that there is only limited degradation/inactivation of circulating HSA-TNF ligand fusion proteins in vivo. In a xenotransplantation model, significantly less of the HSA-TRAIL fusion protein compared to the respective control TRAIL protein was required to achieve inhibition of tumor growth indicating that the increased half life of HSA-TNF ligand fusion proteins translates into better therapeutic action in vivo. In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands.

  9. Enhancement of laser-induced breakdown spectroscopy (LIBS) Detection limit using a low-pressure and short-pulse laser-induced plasma process.

    Science.gov (United States)

    Wang, Zhen Zhen; Deguchi, Yoshihiro; Kuwahara, Masakazu; Yan, Jun Jie; Liu, Ji Ping

    2013-11-01

    Laser-induced breakdown spectroscopy (LIBS) technology is an appealing technique compared with many other types of elemental analysis because of the fast response, high sensitivity, real-time, and noncontact features. One of the challenging targets of LIBS is the enhancement of the detection limit. In this study, the detection limit of gas-phase LIBS analysis has been improved by controlling the pressure and laser pulse width. In order to verify this method, low-pressure gas plasma was induced using nanosecond and picosecond lasers. The method was applied to the detection of Hg. The emission intensity ratio of the Hg atom to NO (IHg/INO) was analyzed to evaluate the LIBS detection limit because the NO emission (interference signal) was formed during the plasma generation and cooling process of N2 and O2 in the air. It was demonstrated that the enhancement of IHg/INO arose by decreasing the pressure to a few kilopascals, and the IHg/INO of the picosecond breakdown was always much higher than that of the nanosecond breakdown at low buffer gas pressure. Enhancement of IHg/INO increased more than 10 times at 700 Pa using picosecond laser with 35 ps pulse width. The detection limit was enhanced to 0.03 ppm (parts per million). We also saw that the spectra from the center and edge parts of plasma showed different features. Comparing the central spectra with the edge spectra, IHg/INO of the edge spectra was higher than that of the central spectra using the picosecond laser breakdown process.

  10. First upper limits on the radar cross section of cosmic-ray induced extensive air showers

    Science.gov (United States)

    Abbasi, R. U.; Abe, M.; Abou Bakr Othman, M.; Abu-Zayyad, T.; Allen, M.; Anderson, R.; Azuma, R.; Barcikowski, E.; Belz, J. W.; Bergman, D. R.; Besson, D.; Blake, S. A.; Byrne, M.; Cady, R.; Chae, M. J.; Cheon, B. G.; Chiba, J.; Chikawa, M.; Cho, W. R.; Farhang-Boroujeny, B.; Fujii, T.; Fukushima, M.; Gillman, W. H.; Goto, T.; Hanlon, W.; Hanson, J. C.; Hayashi, Y.; Hayashida, N.; Hibino, K.; Honda, K.; Ikeda, D.; Inoue, N.; Ishii, T.; Ishimori, R.; Ito, H.; Ivanov, D.; Jayanthmurthy, C.; Jui, C. C. H.; Kadota, K.; Kakimoto, F.; Kalashev, O.; Kasahara, K.; Kawai, H.; Kawakami, S.; Kawana, S.; Kawata, K.; Kido, E.; Kim, H. B.; Kim, J. H.; Kim, J. H.; Kitamura, S.; Kitamura, Y.; Kunwar, S.; Kuzmin, V.; Kwon, Y. J.; Lan, J.; Lim, S. I.; Lundquist, J. P.; Machida, K.; Martens, K.; Matsuda, T.; Matsuyama, T.; Matthews, J. N.; Minamino, M.; Mukai, K.; Myers, I.; Nagasawa, K.; Nagataki, S.; Nakamura, T.; Nonaka, T.; Nozato, A.; Ogio, S.; Ogura, J.; Ohnishi, M.; Ohoka, H.; Oki, K.; Okuda, T.; Ono, M.; Oshima, A.; Ozawa, S.; Park, I. H.; Prohira, S.; Pshirkov, M. S.; Rezazadeh-Reyhani, A.; Rodriguez, D. C.; Rubtsov, G.; Ryu, D.; Sagawa, H.; Sakurai, N.; Sampson, A. L.; Scott, L. M.; Schurig, D.; Shah, P. D.; Shibata, F.; Shibata, T.; Shimodaira, H.; Shin, B. K.; Smith, J. D.; Sokolsky, P.; Springer, R. W.; Stokes, B. T.; Stratton, S. R.; Stroman, T. A.; Suzawa, T.; Takai, H.; Takamura, M.; Takeda, M.; Takeishi, R.; Taketa, A.; Takita, M.; Tameda, Y.; Tanaka, H.; Tanaka, K.; Tanaka, M.; Thomas, S. B.; Thomson, G. B.; Tinyakov, P.; Tkachev, I.; Tokuno, H.; Tomida, T.; Troitsky, S.; Tsunesada, Y.; Tsutsumi, K.; Uchihori, Y.; Udo, S.; Urban, F.; Vasiloff, G.; Venkatesh, S.; Wong, T.; Yamane, R.; Yamaoka, H.; Yamazaki, K.; Yang, J.; Yashiro, K.; Yoneda, Y.; Yoshida, S.; Yoshii, H.; Zollinger, R.; Zundel, Z.

    2017-01-01

    TARA (Telescope Array Radar) is a cosmic ray radar detection experiment colocated with Telescope Array, the conventional surface scintillation detector (SD) and fluorescence telescope detector (FD) near Delta, Utah, U.S.A. The TARA detector combines a 40 kW, 54.1 MHz VHF transmitter and high-gain transmitting antenna which broadcasts the radar carrier over the SD array and within the FD field of view, towards a 250 MS/s DAQ receiver. TARA has been collecting data since 2013 with the primary goal of observing the radar signatures of extensive air showers (EAS). Simulations indicate that echoes are expected to be short in duration (∼ 10 μs) and exhibit rapidly changing frequency, with rates on the order 1 MHz/μs. The EAS radar cross-section (RCS) is currently unknown although it is the subject of over 70 years of speculation. A novel signal search technique is described in which the expected radar echo of a particular air shower is used as a matched filter template and compared to waveforms obtained by triggering the radar DAQ using the Telescope Array fluorescence detector. No evidence for the scattering of radio frequency radiation by EAS is obtained to date. We report the first quantitative RCS upper limits using EAS that triggered the Telescope Array Fluorescence Detector. The transmitter is under the direct control of experimenters, and in a radio-quiet area isolated from other radio frequency (RF) sources. The power and radiation pattern are known at all times. Forward power up to 40 kW and gain exceeding 20 dB maximize energy density in the radar field. Continuous wave (CW) transmission gives 100% duty cycle, as opposed to pulsed radar. TARA utilizes a high sample rate DAQ (250 MS/s). TARA is colocated with a large state-of-the-art conventional CR observatory, allowing the radar data stream to be sampled at the arrival times of known cosmic ray events. Each of these attributes of the TARA detector has been discussed in detail in the literature [8]. A map

  11. Hepatopulmonary syndrome induced by common bile duct ligation in a rabbit model: correlation between pulmonary vascular dilatation on thin-section CT and angiography and serum nitrite concentration or endothelial nitric oxide synthase (eNOS)1 expression

    International Nuclear Information System (INIS)

    Lee, Ki Nam; Yoon, Seong Kuk; Lee, Jin Wha; Kim, Ki Nam; Park, Byung Ho; Kwak, Jong Young; Jeong, Jin Sook; Kim, Young Hoon

    2004-01-01

    To investigate the correlation between radiologic vascular dilatation and serum nitrite concentration and eNOS expression in the endothelial cell and pneumocyte in a rabbit model of hepatopulmonary syndrome induced by common bile duct ligation (CBDL). Thin-section CT scans of the lung and pulmonary angiography were obtained 3 weeks after CBDL (n=6), or a sham operation (n=4), and intrapulmonary vasodilatation was assessed. The diameter and tortuosity of peripheral vessels in the right lower lobe by thin-section CT and angiography at the same level of the right lower lobe in all subjects were correlated to serum nitrite concentration and eNOS (endothelial nitric oxide synthase) expression as determined by immunostaining. The diameters of pulmonary vessels on thin-section CT were well correlated with nitrite concentrations in serum (r=0.92, ρ < 0.001). Dilated pulmonary vessels were significantly correlated with an increased eNOS expression (r=0.94, ρ < 0.0001), and the severity of pulmonary vessel tortuosity was found to be well correlated with serum nitrite concentration (r=0.90, ρ < 0.001). The peripheral pulmonary vasculature in hepatopulmonary syndrome induced by CBLD was dilated on thin-section CT and on angiographs. Our findings suggest that peripheral pulmonary vascular dilatations are correlated with serum nitrite concentrations and pulmonary eNOS expression

  12. Clinical significance of determination of changes of plasma Hcy and serum folic acid and vitamin B{sub 12} levels in patients with pregnancy induced hypertension complicated with nephr opathy

    Energy Technology Data Exchange (ETDEWEB)

    Dongxia, Zhou; Xiaoli, Pan; Fangwen, Xie; Jifeng, Fan [Shuyang County People' s Hospital, Jiangsu, Shuyang (China)

    2007-10-15

    Objective: To investigate the clinical significance of changes of plasma homocysteine (Hcy), serum folic acid and vitamin B{sub 12} levels in patients with pregnancy induced hypertension (PIH) complicated with nephropathy. Methods: Plasma Hcy levels was measured with immuno chemistry and serum folic acid and vitamin B{sub 12} levels were detected with RIA in 32 pregnant women with PIH complicated with nephrophy and 70 pregnant women with PIH but without nephrophy and 35 pregnant women without PIH (as controls). Results; The plasma Hcy levels in patients with PIH were significantly higher than those without (i.e. controls) (P<0.01), while the serum folic acid, vitaminB{sub 12} levels decreased markedly (P<0.01). Among the pregnant women with PIH, plasma Hcy levels were significantly higher and serum folic acid, B{sub 12} levels were significantly lower in the patients complicated with nepropathy than those in patients without nephropathy (P<0.01). conclusion: Determination of plasma Hcy and serum folic acid and vitaminB{sub 12} levels is clinically useful in the management in patients with pregnancy induced hypertension complicated with nephropthy. (authors)

  13. Induced critical current density limit of Ag sheathed Bi-2223 tape conductor

    International Nuclear Information System (INIS)

    Ogiwara, H.; Satou, M.; Yamada, Y.; Kitamura, T.; Hasegawa, T.

    1994-01-01

    The authors have already reported the best critical current density of 66,000 A/cm 2 with an Ag sheathed Bi-2223 tape conductor. The Brick-wall model is for explaining the current transport mechanism of this conductor. The model has its roots in the fact that the Bi-2223 tape core is a complicated stack of crystals which have a mica-flake structure. The orientation of the crystals which have a mica-flake structure. The orientation of the crystals seriously affects the current transport capability. Moreover, the contacts between the stacking crystals are very important. The transport current flows dividing into many branch paths. Under high magnetic field, the different paths experienced different electromagnetic forces. Differences between the electromagnetic forces on the different crystals can affect the contacts so as to increase resistivity and decrease overall critical current density of the tape. This effect can foretell the limit of the critical current density obtainable with these kinds of conductors

  14. Power harvesting by electromagnetic coupling from wind-induced limit cycle oscillations

    Science.gov (United States)

    Boccalero, G.; Olivieri, S.; Mazzino, A.; Boragno, C.

    2017-09-01

    Recent developments of low-power microprocessors open to new applications such as wireless sensor networks (WSN) with the consequent problem of autonomous powering. For this purpose, a possible strategy is represented by energy harvesting from wind or other flows exploiting fluid-structure interactions. In this work, we present an updated picture of a flutter-based device characterized by fully passive dynamics and a simple constructive layout, where limit cycle oscillations are undergone by an elastically bounded wing. In this case, the conversion from mechanical to electrical energy is performed by means of an electromagnetic coupling between a pair of coils and magnets. A centimetric-size prototype is shown to harvest energy from low wind velocities (between 2 and 4 m s-1), reaching a power peak of 14 mW, representing a valuable amount for applications related to WSN. A mathematical description of the nonlinear dynamics is then provided by a quasi-steady phenomenological model, revealing satisfactory agreement with the experimental framework within a certain parametric range and representing a useful tool for future optimizations.

  15. Effect of Drought on Herbivore-Induced Plant Gene Expression: Population Comparison for Range Limit Inferences

    Directory of Open Access Journals (Sweden)

    Gunbharpur Singh Gill

    2016-03-01

    Full Text Available Low elevation “trailing edge” range margin populations typically face increases in both abiotic and biotic stressors that may contribute to range limit development. We hypothesize that selection may act on ABA and JA signaling pathways for more stable expression needed for range expansion, but that antagonistic crosstalk prevents their simultaneous co-option. To test this hypothesis, we compared high and low elevation populations of Boechera stricta that have diverged with respect to constitutive levels of glucosinolate defenses and root:shoot ratios; neither population has high levels of both traits. If constraints imposed by antagonistic signaling underlie this divergence, one would predict that high constitutive levels of traits would coincide with lower plasticity. To test this prediction, we compared the genetically diverged populations in a double challenge drought-herbivory growth chamber experiment. Although a glucosinolate defense response to the generalist insect herbivore Spodoptera exigua was attenuated under drought conditions, the plastic defense response did not differ significantly between populations. Similarly, although several potential drought tolerance traits were measured, only stomatal aperture behavior, as measured by carbon isotope ratios, was less plastic as predicted in the high elevation population. However, RNAseq results on a small subset of plants indicated differential expression of relevant genes between populations as predicted. We suggest that the ambiguity in our results stems from a weaker link between the pathways and the functional traits compared to transcripts.

  16. Degradation and aggregation of delta sleep-inducing peptide (DSIP) and two analogs in plasma and serum

    International Nuclear Information System (INIS)

    Graf, M.V.; Saegesser, B.; Schoenenberger, G.A.

    1987-01-01

    The biostability of DSIP (delta sleep-inducing peptide) and two analogs in blood was investigated in order to determine if rates of inactivation contribute to variable effects in vivo. Incubation of DSIP in human or rat blood led to release of products having retention times on a gel filtration column equivalent to Trp. Formation of products was dependent on temperature, time, and species. Incubation of 125 I-N-Tyr-DSIP and 125 I-N-Tyr-P-DSIP, a phosphorylated analog, revealed slower degradation and, in contrast to DSIP, produced complex formation. An excess of unlabeled material did not displace the radioactivity supporting the assumption of non-specific binding/aggregation. It was concluded that the rapid disappearance of injected DSIP in blood was due to degradation, whereas complex formation together with slower degradation resulted in longer persistence of apparently intact analogs. Whether this could explain the sometimes stronger and more consistent effects of DSIP-analogs remains to be examined

  17. Metabolite profiling uncovers plasmid-induced cobalt limitation under methylotrophic growth conditions.

    Directory of Open Access Journals (Sweden)

    Patrick Kiefer

    2009-11-01

    Full Text Available The introduction and maintenance of plasmids in cells is often associated with a reduction of growth rate. The reason for this growth reduction is unclear in many cases.We observed a surprisingly large reduction in growth rate of about 50% of Methylobacterium extorquens AM1 during methylotrophic growth in the presence of a plasmid, pCM80 expressing the tetA gene, relative to the wild-type. A less pronounced growth delay during growth under non-methylotrophic growth conditions was observed; this suggested an inhibition of one-carbon metabolism rather than a general growth inhibition or metabolic burden. Metabolome analyses revealed an increase in pool sizes of ethylmalonyl-CoA and methylmalonyl-CoA of more than 6- and 35-fold, respectively, relative to wild type, suggesting a strongly reduced conversion of these central intermediates, which are essential for glyoxylate regeneration in this model methylotroph. Similar results were found for M. extorquens AM1 pCM160 which confers kanamycin resistance. These intermediates of the ethylmalonyl-CoA pathway have in common their conversion by coenzyme B(12-dependent mutases, which have cobalt as a central ligand. The one-carbon metabolism-related growth delay was restored by providing higher cobalt concentrations, by heterologous expression of isocitrate lyase as an alternative path for glyoxylate regeneration, or by identification and overproduction of proteins involved in cobalt import.This study demonstrates that the introduction of the plasmids leads to an apparent inhibition of the cobalt-dependent enzymes of the ethylmalonyl-CoA pathway. Possible explanations are presented and point to a limited cobalt concentration in the cell as a consequence of the antibiotic stress.

  18. Effects of tissue-preparation-induced callose synthesis on estimates of plasmodesma size exclusion limits.

    Science.gov (United States)

    Radford, J E; White, R G

    2001-01-01

    Plasmodesmata are often characterised by their size exclusion limit (SEL), which is the molecular weight of the largest dye, introduced by microinjection, that will move from cell to cell. In this study, we investigated whether commonly used techniques for isolation and manipulation of tissues, and microinjection of fluorescent dyes, affected the SEL, and whether any such effects could be ameliorated by inhibiting callose deposition. We examined young root epidermal cells of Arabidopsis thaliana and staminal hair cells of Tradescantia virginiana, two tissues often used in experiments on symplastic transport. Transport in root tips dissected from the main plant body and in stamen hairs removed from the base of the stamen filament was compared with transport in undissected roots and stamen hairs attached to the base of the filament, respectively. Tissues were microinjected with fluorescent dyes (457 Da to > 3 kDa) with or without prior incubation in the callose deposition inhibitors 2-deoxy-D-glucose or aniline blue fluorochrome. In both tissues, dissection reduced the SEL, which was largely prevented by prior incubation in 2-deoxy-D-glucose but not by incubation in aniline blue fluorochrome. Thus, standard methods for tissue preparation can cause sufficient callose deposition to reduce cell-to-cell transport, and this needs to be considered in studies employing microinjection. Introduction of the dyes by pressure injection rather than iontophoresis decreased the SEL in A. thaliana but increased it in T. virginiana, showing that these two injection techniques do not necessarily give identical results and that plasmodesmata in different tissues may respond differently to similar experimental procedures.

  19. Serum levels at moment of breeding of triiodothyronine (T3), thyroxine (T4), and progesterone in Saanen goats females during normal and induced heat and testosterone in 12 Saanen goats males

    International Nuclear Information System (INIS)

    Prestes, Nereu C.; Vulcano, Luiz C.; Mamprim, Maria J.; Oba, Eunice

    1996-01-01

    The aim of this experiment was to measure the level of triiodothyronine(T 3 ), thyroxine(T 4 ) and progesterone in the serum of females Saanen goats. The progesterone levels were: 0.59 and 0.79 ng/μl considering breeding during normal and induced heat respectively. The T 3 values were: 192.8 and 251.32 ng/dl while T 4 values were: 36.38 and 31.68 ng/dl in the same condition above. The average testosterone level at the moment of breeding in the serum of 12 males was 1.38 pg/ml. (author)

  20. Assessment of drug-induced arrhythmic risk using limit cycle and autocorrelation analysis of human iPSC-cardiomyocyte contractility

    Energy Technology Data Exchange (ETDEWEB)

    Kirby, R. Jason [Sanford Burnham Prebys Medical Discovery Institute, Conrad Prebys Center for Chemical Genomics, 6400 Sanger Rd, Orlando, FL 32827 (United States); Qi, Feng [Sanford Burnham Prebys Medical Discovery Institute, Applied Bioinformatics Facility, 6400 Sanger Rd, Orlando, FL 32827 (United States); Phatak, Sharangdhar; Smith, Layton H. [Sanford Burnham Prebys Medical Discovery Institute, Conrad Prebys Center for Chemical Genomics, 6400 Sanger Rd, Orlando, FL 32827 (United States); Malany, Siobhan, E-mail: smalany@sbpdiscovery.org [Sanford Burnham Prebys Medical Discovery Institute, Conrad Prebys Center for Chemical Genomics, 6400 Sanger Rd, Orlando, FL 32827 (United States)

    2016-08-15

    Cardiac safety assays incorporating label-free detection of human stem-cell derived cardiomyocyte contractility provide human relevance and medium throughput screening to assess compound-induced cardiotoxicity. In an effort to provide quantitative analysis of the large kinetic datasets resulting from these real-time studies, we applied bioinformatic approaches based on nonlinear dynamical system analysis, including limit cycle analysis and autocorrelation function, to systematically assess beat irregularity. The algorithms were integrated into a software program to seamlessly generate results for 96-well impedance-based data. Our approach was validated by analyzing dose- and time-dependent changes in beat patterns induced by known proarrhythmic compounds and screening a cardiotoxicity library to rank order compounds based on their proarrhythmic potential. We demonstrate a strong correlation for dose-dependent beat irregularity monitored by electrical impedance and quantified by autocorrelation analysis to traditional manual patch clamp potency values for hERG blockers. In addition, our platform identifies non-hERG blockers known to cause clinical arrhythmia. Our method provides a novel suite of medium-throughput quantitative tools for assessing compound effects on cardiac contractility and predicting compounds with potential proarrhythmia and may be applied to in vitro paradigms for pre-clinical cardiac safety evaluation. - Highlights: • Impedance-based monitoring of human iPSC-derived cardiomyocyte contractility • Limit cycle analysis of impedance data identifies aberrant oscillation patterns. • Nonlinear autocorrelation function quantifies beat irregularity. • Identification of hERG and non-hERG inhibitors with known risk of arrhythmia • Automated software processes limit cycle and autocorrelation analyses of 96w data.

  1. Assessment of drug-induced arrhythmic risk using limit cycle and autocorrelation analysis of human iPSC-cardiomyocyte contractility

    International Nuclear Information System (INIS)

    Kirby, R. Jason; Qi, Feng; Phatak, Sharangdhar; Smith, Layton H.; Malany, Siobhan

    2016-01-01

    Cardiac safety assays incorporating label-free detection of human stem-cell derived cardiomyocyte contractility provide human relevance and medium throughput screening to assess compound-induced cardiotoxicity. In an effort to provide quantitative analysis of the large kinetic datasets resulting from these real-time studies, we applied bioinformatic approaches based on nonlinear dynamical system analysis, including limit cycle analysis and autocorrelation function, to systematically assess beat irregularity. The algorithms were integrated into a software program to seamlessly generate results for 96-well impedance-based data. Our approach was validated by analyzing dose- and time-dependent changes in beat patterns induced by known proarrhythmic compounds and screening a cardiotoxicity library to rank order compounds based on their proarrhythmic potential. We demonstrate a strong correlation for dose-dependent beat irregularity monitored by electrical impedance and quantified by autocorrelation analysis to traditional manual patch clamp potency values for hERG blockers. In addition, our platform identifies non-hERG blockers known to cause clinical arrhythmia. Our method provides a novel suite of medium-throughput quantitative tools for assessing compound effects on cardiac contractility and predicting compounds with potential proarrhythmia and may be applied to in vitro paradigms for pre-clinical cardiac safety evaluation. - Highlights: • Impedance-based monitoring of human iPSC-derived cardiomyocyte contractility • Limit cycle analysis of impedance data identifies aberrant oscillation patterns. • Nonlinear autocorrelation function quantifies beat irregularity. • Identification of hERG and non-hERG inhibitors with known risk of arrhythmia • Automated software processes limit cycle and autocorrelation analyses of 96w data

  2. Acute serum amyloid A induces migration, angiogenesis, and inflammation in synovial cells in vitro and in a human rheumatoid arthritis/SCID mouse chimera model.

    LENUS (Irish Health Repository)

    Connolly, Mary

    2010-06-01

    Serum amyloid A (A-SAA), an acute-phase protein with cytokine-like properties, is expressed at sites of inflammation. This study investigated the effects of A-SAA on chemokine-regulated migration and angiogenesis using rheumatoid arthritis (RA) cells and whole-tissue explants in vitro, ex vivo, and in vivo. A-SAA levels were measured by real-time PCR and ELISA. IL-8 and MCP-1 expression was examined in RA synovial fibroblasts, human microvascular endothelial cells, and RA synovial explants by ELISA. Neutrophil transendothelial cell migration, cell adhesion, invasion, and migration were examined using transwell leukocyte\\/monocyte migration assays, invasion assays, and adhesion assays with or without anti-MCP-1\\/anti-IL-8. NF-kappaB was examined using a specific inhibitor and Western blotting. An RA synovial\\/SCID mouse chimera model was used to examine the effects of A-SAA on cell migration, proliferation, and angiogenesis in vivo. High expression of A-SAA was demonstrated in RA patients (p < 0.05). A-SAA induced chemokine expression in a time- and dose-dependent manner (p < 0.05). Blockade with anti-scavenger receptor class B member 1 and lipoxin A4 (A-SAA receptors) significantly reduced chemokine expression in RA synovial tissue explants (p < 0.05). A-SAA induced cell invasion, neutrophil-transendothelial cell migration, monocyte migration, and adhesion (all p < 0.05), effects that were blocked by anti-IL-8 or anti-MCP-1. A-SAA-induced chemokine expression was mediated through NF-kappaB in RA explants (p < 0.05). Finally, in the RA synovial\\/SCID mouse chimera model, we demonstrated for the first time in vivo that A-SAA directly induces monocyte migration from the murine circulation into RA synovial grafts, synovial cell proliferation, and angiogenesis (p < 0.05). A-SAA promotes cell migrational mechanisms and angiogenesis critical to RA pathogenesis.

  3. Interval training-induced alleviation of rigidity and hypertonia in patients with Parkinson's disease is accompanied by increased basal serum brain-derived neurotrophic factor.

    Science.gov (United States)

    Marusiak, Jarosław; Żeligowska, Ewa; Mencel, Joanna; Kisiel-Sajewicz, Katarzyna; Majerczak, Joanna; Zoladz, Jerzy A; Jaskólski, Artur; Jaskólska, Anna

    2015-04-01

    To examine the effects of cycloergometric interval training on parkinsonian rigidity, relaxed biceps brachii muscle tone in affected upper extremities, and serum level of brain-derived neurotrophic factor. Case series, repeated-measures design, pilot study. Eleven patients with mild-to-moderate Parkinson's disease (Hoehn & Yahr scale 2.3 ± 0.72), recruited from a neurological clinic, underwent cycle training and were tested along with non-trained, healthy control subjects (n = 11) in a motor control laboratory. Patients underwent 8 weeks of interval training (3 × 1-h sessions weekly, consisting of a 10-min warm-up, 40 min of interval exercise, and 10-min cool-down) on a stationary cycloergometer. Parkinsonian rigidity (Unified Parkinson's Disease-Rating-Scale) in the upper extremity, resting biceps brachii muscle tone (myometric stiffness and frequency), and brain-derived neurotrophic factor level were measured 1-3 days before interval training cycle started and 6-10 days after the last training session. Training resulted in a decrease in rigidity (p = 0.048) and biceps brachii myometric muscle stiffness (p = 0.030) and frequency (p = 0.006), and an increase in the level of brain-derived neurotrophic factor (p = 0.035) relative to pre-training values. The increase in brain-derived neurotrophic factor level correlated with improvements in parkinsonian rigidity (p = 0.025), biceps brachii myometric stiffness (p = 0.001) and frequency (p = 0.002). Training-induced alleviation of parkinsonian rigidity and muscle tone decrease may be associated with neuroplastic changes caused by a training-induced increase in the level of brain-derived neurotrophic factor.

  4. Specific estrogen-induced cell proliferation of cultured Syrian hamster renal proximal tubular cells in serum-free chemically defined media

    International Nuclear Information System (INIS)

    Oberley, T.D.; Lauchner, L.J.; Pugh, T.D.; Gonzalez, A.; Goldfarb, S.; Li, S.A.; Li, J.J.

    1989-01-01

    It has long been recognized that the renal proximal tubular epithelium of the hamster is a bona fide estrogen target tissue. The effect of estrogens on the growth of proximal tubule cell explants and dissociated single cells derived from these explant outgrowths has been studied in culture. Renal tubular cells were grown on a PF-HR-9 basement membrane under serum-free chemically defined culture conditions. At 7-14 days in culture, cell number was enhanced 3-fold in the presence of either 17β-estradiol or diethylstilbestrol. A similar 3-fold increase in cell number was also seen at 1 nM 17β-estradiol in subcultured dissociated single tubular cells derived from hamster renal tubular explant outgrowths at 21 days in culture. Concomitant exposure of tamoxifen at 3-fold molar excess in culture completely abolished the increase in cell number seen with 17β-estradiol. The proliferation effect of estrogens on proximal tubular cell growth appears to be species specific since 17β-estradiol did not alter the growth of either rat or guinea pig proximal tubules in culture. In addition, at 7-10 days in culture in the presence of 17β-estradiol, [ 3 H]thymidine labeling of hamster tubular cells was enhanced 3-fold. These results clearly indicate that estrogens can directly induce primary epithelial cell proliferation at physiologic concentrations and provide strong additional evidence for an important hormonal role in the neoplastic transformation of the hamster kidney

  5. Rapid dimerization of quercetin through an oxidative mechanism in the presence of serum albumin decreases its ability to induce cytotoxicity in MDA-MB-231 cells

    International Nuclear Information System (INIS)

    Pham, Anh; Bortolazzo, Anthony; White, J. Brandon

    2012-01-01

    Highlights: ► Quercetin cannot be detected intracellularly despite killing MDA-MB-231 cells. ► Quercetin forms a heterodimer through oxidation in media with serum. ► The quercetin heterodimer does not kill MDA-MB-231 cells. ► Ascorbic acid stabilizes quercetin increasing cell death in quercetin treated cells. ► Quercetin, and not a modified form, is responsible for apoptosis and cell death. -- Abstract: Quercetin is a member of the flavonoid family and has been previously shown to have a variety of anti-cancer activities. We and others have reported anti-proliferation, cell cycle arrest, and induction of apoptosis of cancer cells after treatment with quercetin. Quercetin has also been shown to undergo oxidation. However, it is unclear if quercetin or one of its oxidized forms is responsible for cell death. Here we report that quercetin rapidly oxidized in cell culture media to form a dimer. The quercetin dimer is identical to a dimer that is naturally produced by onions. The quercetin dimer and quercetin-3-O-glucopyranoside are unable to cross the cell membrane and do not kill MDA-MB-231 cells. Finally, supplementing the media with ascorbic acid increases quercetin’s ability to induce cell death probably by reduction oxidative dimerization. Our results suggest that an unmodified quercetin is the compound that elicits cell death.

  6. Rapid dimerization of quercetin through an oxidative mechanism in the presence of serum albumin decreases its ability to induce cytotoxicity in MDA-MB-231 cells

    Energy Technology Data Exchange (ETDEWEB)

    Pham, Anh; Bortolazzo, Anthony [Department of Biological Sciences, San Jose State University, San Jose, CA 95192-0100 (United States); White, J. Brandon, E-mail: Brandon.White@sjsu.edu [Department of Biological Sciences, San Jose State University, San Jose, CA 95192-0100 (United States)

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer Quercetin cannot be detected intracellularly despite killing MDA-MB-231 cells. Black-Right-Pointing-Pointer Quercetin forms a heterodimer through oxidation in media with serum. Black-Right-Pointing-Pointer The quercetin heterodimer does not kill MDA-MB-231 cells. Black-Right-Pointing-Pointer Ascorbic acid stabilizes quercetin increasing cell death in quercetin treated cells. Black-Right-Pointing-Pointer Quercetin, and not a modified form, is responsible for apoptosis and cell death. -- Abstract: Quercetin is a member of the flavonoid family and has been previously shown to have a variety of anti-cancer activities. We and others have reported anti-proliferation, cell cycle arrest, and induction of apoptosis of cancer cells after treatment with quercetin. Quercetin has also been shown to undergo oxidation. However, it is unclear if quercetin or one of its oxidized forms is responsible for cell death. Here we report that quercetin rapidly oxidized in cell culture media to form a dimer. The quercetin dimer is identical to a dimer that is naturally produced by onions. The quercetin dimer and quercetin-3-O-glucopyranoside are unable to cross the cell membrane and do not kill MDA-MB-231 cells. Finally, supplementing the media with ascorbic acid increases quercetin's ability to induce cell death probably by reduction oxidative dimerization. Our results suggest that an unmodified quercetin is the compound that elicits cell death.

  7. [Effects of interleukin-18 and hypoxia-inducible factor-1α in serum and gingival tissues of rat model with periodontitis exposed to chronic intermittent hypoxia].

    Science.gov (United States)

    Wang, Bin; Wang, Xiaoqin

    2015-08-01

    This study evaluates the expression of interleukin-18 (IL-18) and hypoxia-inducible factor (HIF)-lα in rat periodontitis model exposed to normoxia and chronic intermittent hypoxia (CIH) environments. The possible correlation between periodontitis and obstructive sleep apnea-hypopnea syndrome (OSAHS) was also investigated. Methods: Thirty-two Sprague-Dawley (SD) rats were randomly assigned into four groups: normoxia control, normoxia periodontitis, hypoxia control, and hypoxia periodontitis groups. The periodontitis models were established by ligating the bilateral maxillary second molars and employing high-carbohydrate diets. Rats in hypoxia control and hypoxia periodontitis groups were exposed to CIH treatment mimicking a moderately severe OSAHS condition. All animals were sacrificed after eight weeks, and the clinical periodontal indexes were detected. The levels of IL-18 and HIF-1α in serum and gingival tissues were determined using enzyme-linked immunosorbent assay (ELISA). The correlation between attachment loss (AL) and the levels of IL-18 and HIF-lα in hypoxia periodontitis group was evaluated. The levels of IL-18 and HIF-lα in hypoxia periodontitis group were significantly higher than that in normoxia periodontitis and hypoxia control groups (Pperiodontal tissues, which is correlated with IL-18 and HIF-lα levels.

  8. A butter diet induces higher levels of n-3 PUFA and of n-3/n-6 PUFA ratio in rat serum and hearts than a safflower oil diet.

    Science.gov (United States)

    Hirai, K; Ozeki, Y; Nakano, T; Takezoe, R; Nakanishi, M; Asano, Y; Higuchi, H

    2001-01-01

    The effects of a 47-week diet of butter or safflower oil as fat in combination with casein or soy protein as protein were observed for the serum concentrations of lipids and fatty acid compositions in rat serum and heart. Serum total cholesterol (Chol) did not differ among the four experimental diet groups. In the butter groups, significantly higher low-density lipoprotein (LDL)-Chol and lower high-density lipoprotein (HDL)-Chol were observed than in the safflower oil groups (psafflower oil groups (psafflower oil groups, the butter groups showed higher n-3 polyunsaturated fatty acids (PUFA) contents and lower n-6 PUFA contents in serum and the hearts (psafflower oil groups of under 0.01 in serum and 0.02 and 0.03 in the hearts (safflower oil-casein diet and safflower oil-soy protein diet, respectively) (psafflower oil diet in rat serum and hearts over a long feeding period.

  9. Limited transplantation of antigen-expressing hematopoietic stem cells induces long-lasting cytotoxic T cell responses.

    Directory of Open Access Journals (Sweden)

    Warren L Denning

    2011-02-01

    Full Text Available Harnessing the ability of cytotoxic T lymphocytes (CTLs to recognize and eradicate tumor or pathogen-infected cells is a critical goal of modern immune-based therapies. Although multiple immunization strategies efficiently induce high levels of antigen-specific CTLs, the initial increase is typically followed by a rapid contraction phase resulting in a sharp decline in the frequency of functional CTLs. We describe a novel approach to immunotherapy based on a transplantation of low numbers of antigen-expressing hematopoietic stem cells (HSCs following nonmyeloablative or partially myeloablative conditioning. Continuous antigen presentation by a limited number of differentiated transgenic hematopoietic cells results in an induction and prolonged maintenance of fully functional effector T cell responses in a mouse model. Recipient animals display high levels of antigen-specific CTLs four months following transplantation in contrast to dendritic cell-immunized animals in which the response typically declines at 4-6 weeks post-immunization. Majority of HSC-induced antigen-specific CD8+ T cells display central memory phenotype, efficiently kill target cells in vivo, and protect recipients against tumor growth in a preventive setting. Furthermore, we confirm previously published observation that high level engraftment of antigen-expressing HSCs following myeloablative conditioning results in tolerance and an absence of specific cytotoxic activity in vivo. In conclusion, the data presented here supports potential application of immunization by limited transplantation of antigen-expressing HSCs for the prevention and treatment of cancer and therapeutic immunization of chronic infectious diseases such as HIV-1/AIDS.

  10. Lithium limits trimethyltin-induced cytotoxicity and proinflammatory response in microglia without affecting the concurrent autophagy impairment.

    Science.gov (United States)

    Fabrizi, Cinzia; Pompili, Elena; Somma, Francesca; De Vito, Stefania; Ciraci, Viviana; Artico, Marco; Lenzi, Paola; Fornai, Francesco; Fumagalli, Lorenzo

    2017-02-01

    Trimethyltin (TMT) is a highly toxic molecule present as an environmental contaminant causing neurodegeneration particularly of the limbic system both in humans and in rodents. We recently described the occurrence of impairment in the late stages of autophagy in TMT-intoxicated astrocytes. Here we show that similarly to astrocytes also in microglia, TMT induces the precocious block of autophagy indicated by the accumulation of the autophagosome marker, microtubule associated protein light chain 3. Consistent with autophagy impairment we observe in TMT-treated microglia the accumulation of p62/SQSTM1, a protein specifically degraded through this pathway. Lithium has been proved effective in limiting neurodegenerations and, in particular, in ameliorating symptoms of TMT intoxication in rodents. In our in vitro model, lithium displays a pro-survival and anti-inflammatory action reducing both cell death and the proinflammatory response of TMT-treated microglia. In particular, lithium exerts these activities without reducing TMT-induced accumulation of light chain 3 protein. In fact, the autophagic block imposed by TMT is unaffected by lithium administration. These results are of interest as defects in the execution of autophagy are frequently observed in neurodegenerative diseases and lithium is considered a promising therapeutic agent for these pathologies. Thus, it is relevant that this cation can still maintain its pro-survival and anti-inflammatory role in conditions of autophagy block. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  11. Fragile X Mental Retardation Protein Is Required to Maintain Visual Conditioning-Induced Behavioral Plasticity by Limiting Local Protein Synthesis.

    Science.gov (United States)

    Liu, Han-Hsuan; Cline, Hollis T

    2016-07-06

    Fragile X mental retardation protein (FMRP) is thought to regulate neuronal plasticity by limiting dendritic protein synthesis, but direct demonstration of a requirement for FMRP control of local protein synthesis during behavioral plasticity is lacking. Here we tested whether FMRP knockdown in Xenopus optic tectum affects local protein synthesis in vivo and whether FMRP knockdown affects protein synthesis-dependent visual avoidance behavioral plasticity. We tagged newly synthesized proteins by incorporation of the noncanonical amino acid azidohomoalanine and visualized them with fluorescent noncanonical amino acid tagging (FUNCAT). Visual conditioning and FMRP knockdown produce similar increases in FUNCAT in tectal neuropil. Induction of visual conditioning-dependent behavioral plasticity occurs normally in FMRP knockdown animals, but plasticity degrades over 24 h. These results indicate that FMRP affects visual conditioning-induced local protein synthesis and is required to maintain the visual conditioning-induced behavioral plasticity. Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. Exaggerated dendritic protein synthesis resulting from loss of fragile X mental retardation protein (FMRP) is thought to underlie cognitive deficits in FXS, but no direct evidence has demonstrated that FMRP-regulated dendritic protein synthesis affects behavioral plasticity in intact animals. Xenopus tadpoles exhibit a visual avoidance behavior that improves with visual conditioning in a protein synthesis-dependent manner. We showed that FMRP knockdown and visual conditioning dramatically increase protein synthesis in neuronal processes. Furthermore, induction of visual conditioning-dependent behavioral plasticity occurs normally after FMRP knockdown, but performance rapidly deteriorated in the absence of FMRP. These studies show that FMRP negatively regulates local protein synthesis and is required to maintain visual conditioning-induced

  12. Protective effects of Mangifera indica L extract (Vimang), and its major component mangiferin, on iron-induced oxidative damage to rat serum and liver.

    Science.gov (United States)

    Pardo-Andreu, Gilberto L; Barrios, Mariela Forrellat; Curti, Carlos; Hernández, Ivones; Merino, Nelson; Lemus, Yeny; Martínez, Ioanna; Riaño, Annia; Delgado, René

    2008-01-01

    In vivo preventive effects of a Mangifera indica L extract (Vimang) or its major component mangiferin on iron overload injury have been studied in rats given respectively, 50, 100, 250 mg kg(-1) body weight of Vimang, or 40 mg kg(-1) body weight of mangiferin, for 7 days prior to, and for 7 days following the administration of toxic amounts of iron-dextran. Both Vimang or mangiferin treatment prevented iron overload in serum as well as liver oxidative stress, decreased serum and liver lipid peroxidation, serum GPx activity, and increased serum and liver GSH, serum SOD and the animals overall antioxidant condition. Serum iron concentration was decreased although at higher doses, Vimang tended to increase it; percent tranferrin saturation, liver weight/body mass ratios, liver iron content was decreased. Treatment increased serum iron-binding capacity and decreased serum levels of aspartate-amine transferase (ASAT) and alanine-amine transferase (ALAT), as well as the number of abnormal Kupffer cells in iron-loaded livers. It is suggested that besides acting as antioxidants, Vimang extract or its mangiferin component decrease liver iron by increasing its excretion. Complementing earlier in vitro results from our group, it appears possible to support the hypothesis that Vimang and mangiferin present therapeutically useful effects in iron overload related diseases.

  13. Bacillus coagulans GBI-30, 6086 limits the recurrence of Clostridium difficile-Induced colitis following vancomycin withdrawal in mice

    Science.gov (United States)

    2012-01-01

    Background Recently, we found that the probiotic strain Bacillus coagulans GBI-30, 6086 (GanedenBC30) improved indices of Clostridium difficile (C. difficile)-induced colitis in mice (Fitzpatrick et al., Gut Pathogens, 2011). Our goal was to determine if BC30 could also prevent the recurrence of C. difficile-induced colitis in mice, following initial treatment with vancomycin. During study days 0 through 5, mice were treated with antibiotics. On day 6, the C. difficile strain VPI 10463 was given by oro-gastric gavage at ≈ 5x104 CFU to induce colitis. Mice were treated on study days 6 to 10 with vancomycin (50 mg/kg) (vanco) or vehicle (saline) by gavage. On days 10 to16, mice were dosed by gavage with saline vehicle or BC30 (2 x 109 CFU per day). Mice were monitored for mortality, weight loss and diarrhea. On study days 14, 16 and 17, stools and colons were collected for analyzing other parameters of colitis. Results The mean stool consistency score in Vehicle/C.difficile/Vanco mice increased from 0.4 (day 10) to a range of 1.1 to 1.4 (days 14 to 17), indicating the recurrence of colitis. On days 13 through 17, the stool consistency scores for the vancomycin/BC30 mice were significantly lower (p< 0.05) than for the vancomycin/vehicle cohort of animals. On day 17, 88.9% of mice treated with BC30 had normal stools, while this value was 0% with vehicle treatment (p value = 0.0004). Colonic myeloperoxidase (Units/2 cm colon) was significantly (p < 0.05) reduced from 4.3 ± 0.7 (Vehicle/C.difficile/Vanco) to 2.6 ± 0.2 (BC30/C. Difficle/Vanco). The colonic histology score and Keratinocyte derived-chemokine level in the colon were also lower in BC30 treated mice. Summary In BC30-treated mice, there was evidence of better stool consistency, as well as improved biochemical and histological indices of colitis, following initial treatment of animals with vancomycin. Conclusion BC30 limited the recurrence of CD-induced colitis following vancomycin withdrawal in mice. PMID

  14. Bacillus coagulans GBI-30, 6086 limits the recurrence of Clostridium difficile-Induced colitis following vancomycin withdrawal in mice.

    Science.gov (United States)

    Fitzpatrick, Leo R; Small, Jeffrey S; Greene, Wallace H; Karpa, Kelly D; Farmer, Sean; Keller, David

    2012-10-22

    Recently, we found that the probiotic strain Bacillus coagulans GBI-30, 6086 (GanedenBC30) improved indices of Clostridium difficile (C. difficile)-induced colitis in mice (Fitzpatrick et al., Gut Pathogens, 2011). Our goal was to determine if BC30 could also prevent the recurrence of C. difficile-induced colitis in mice, following initial treatment with vancomycin. During study days 0 through 5, mice were treated with antibiotics. On day 6, the C. difficile strain VPI 10463 was given by oro-gastric gavage at ≈ 5x104 CFU to induce colitis. Mice were treated on study days 6 to 10 with vancomycin (50 mg/kg) (vanco) or vehicle (saline) by gavage. On days 10 to16, mice were dosed by gavage with saline vehicle or BC30 (2 x 109 CFU per day). Mice were monitored for mortality, weight loss and diarrhea. On study days 14, 16 and 17, stools and colons were collected for analyzing other parameters of colitis. The mean stool consistency score in Vehicle/C.difficile/Vanco mice increased from 0.4 (day 10) to a range of 1.1 to 1.4 (days 14 to 17), indicating the recurrence of colitis. On days 13 through 17, the stool consistency scores for the vancomycin/BC30 mice were significantly lower (p< 0.05) than for the vancomycin/vehicle cohort of animals. On day 17, 88.9% of mice treated with BC30 had normal stools, while this value was 0% with vehicle treatment (p value = 0.0004). Colonic myeloperoxidase (Units/2 cm colon) was significantly (p < 0.05) reduced from 4.3 ± 0.7 (Vehicle/C.difficile/Vanco) to 2.6 ± 0.2 (BC30/C. Difficle/Vanco). The colonic histology score and Keratinocyte derived-chemokine level in the colon were also lower in BC30 treated mice. In BC30-treated mice, there was evidence of better stool consistency, as well as improved biochemical and histological indices of colitis, following initial treatment of animals with vancomycin. BC30 limited the recurrence of CD-induced colitis following vancomycin withdrawal in mice.

  15. Increased serum erythropoietin activity in rats following intrarenal injection of nickel subsulfide

    International Nuclear Information System (INIS)

    Hopfer, S.M.; Sunderman, F.W. Jr.; Fredrickson, T.N.; Morse, E.E.

    1979-01-01

    To investigate the pathopysiologic mechanisms of nickel-induced erythocytosis, serum erythropoietin activities were measured in (a) pooled serum from rats at 2 wk after intrarenal injection of αNi 3 S 2 (5 mg/rat), and (b) pooled serum from control rats at 2 wk after intrarenal injection of sterile NaCl vehicle (0.4 ml/rat). A sensitive erythropoietin bioassay was employed, which entailed repetitive administration of test serums to post-hypoxic polycythemic mice in divided doses (12 s.c. injections of 0.5 ml of serum at 6 h intervals for 3 da; total dose = 6 ml of serum/mouse). The erythropoietin detection limit was approx. = 20 I.U./liter of serum. In mice which received pooled serum from αNi 3 S 2 -treated rats, erythrocyte 59 Fe-uptake averaged 28% (S.D. +- 5) (vs 3.7 +- 1.1% in control rats; P 3 S 2 -treated rats averaged 130 I.U./liter (S.D. +- 18) (vs 27 +- 6 I.U./liter in control rats; P 3 S 2 is mediated by increased serum erythropoietin activity

  16. Serum level of expressed in renal carcinoma (ERC)/ mesothelin in rats with mesothelial proliferative lesions induced by multi-wall carbon nanotube (MWCNT).

    Science.gov (United States)

    Sakamoto, Yoshimitsu; Dai, Nakae; Hagiwara, Yoshiaki; Satoh, Kanako; Ohashi, Norio; Fukamachi, Katsumi; Tsuda, Hiroyuki; Hirose, Akihiko; Nishimura, Tetsuji; Hino, Okio; Ogata, Akio

    2010-04-01

    Expressed in renal carcinoma (ERC)/mesothelin is a good biomarker for human mesothelioma and has been investigated for its mechanistic rationale during the mesothelioma development. Studies are thus ongoing in our laboratories to assess expression of ERC/mesothelin in sera and normal/proliferative/neoplastic mesothelial tissues of animals untreated or given potentially mesothelioma-inducible xenobiotics, by an enzyme-linked immunosorbent assay (ELISA) for N- and C-(terminal fragments of) ERC/mesothelin and immunohistochemistry for C-ERC/mesothelin. In the present paper, we intend to communicate our preliminary data, because this is the first report to show how and from what stage the ERC/mesothelin expression changes during the chemical induction of mesothelial proliferative/neoplatic lesions. Serum N-ERC/mesothelin levels were 51.4 +/- 5.6 ng/ml in control male Fischer 344 rats, increased to 83.6 +/- 11.2 ng/ml in rats given a single intrascrotal administration of 1 mg/kg body weight of multi-wall carbon nanotube (MWCNT) and bearing mesothelial hyperplasia 52 weeks thereafter, and further elevated to 180 +/- 77 ng/ml in rats similarly treated and becoming moribund 40 weeks thereafter, or killed as scheduled at the end of week 52, bearing mesothelioma. While C-ERC/mesothelin was expressed in normal and hyperplastic mesothelia, the protein was detected only in epithelioid mesothelioma cells at the most superficial layer. It is thus suggested that ERC/mesothelin can be used as a biomarker of mesothelial proliferative lesions also in animals, and that the increase of levels may start from the early stage and be enhanced by the progression of the mesothelioma development.

  17. The Prognostic Significance of The Serum Tumor Necrosis Factor (TNF-Related Apoptosis-Inducing Ligand (TRAIL in Childhood Acute Leukemias

    Directory of Open Access Journals (Sweden)

    Zeliha Haytoglu

    2015-12-01

    Results: The comparison of the average values of the TRAIL levels in acute leukemia patients and control group have shown that patients with leukemia have low serum TRAIL levels (p=0.002. In patients with high-risk-grade (HRG of ALL compared with control group have shown low serum TRAIL levels in HRG of ALL (p=0.008. In patients with common acute lymphoblastic leukemia antigen(CALLA(- B ALL compared with control group have shown low serum TRAIL levels in CALLA(- B ALL (p=0.004. Children with acute leukemias (ALL, AML who died during treatment compared with survived group have shown low levels of serum TRAIL in expired patients (p=0.004. Conclusion: As a result, serum TRAIL might play a role in leukomegenesis. The low levels of serum TRAIL detected in our patients may be associated with leukomogenezis and impaired TRAIL-mediated apoptosis. To suggest soluble TRAIL's role in acute leukemias detection of TRAIL-mediated apoptosis is needed. The low serum TRAIL may be used as a sign of bad prognosis. For more comphrensive results prospective studies with greaater number of patients are needed. [Cukurova Med J 2015; 40(4.000: 774-781

  18. H2O2 treatment or serum deprivation induces autophagy and apoptosis in naked mole-rat skin fibroblasts by inhibiting the PI3K/Akt signaling pathway.

    Science.gov (United States)

    Zhao, Shanmin; Li, Li; Wang, Shiyong; Yu, Chenlin; Xiao, Bang; Lin, Lifang; Cong, Wei; Cheng, Jishuai; Yang, Wenjing; Sun, Wei; Cui, Shufang

    2016-12-20

    Naked mole-rats (NMR; Heterocephalus glaber) display extreme longevity and resistance to cancer. Here, we examined whether autophagy contributes to the longevity of NMRs by assessing the effects of the PI3K/Akt pathway inhibitor LY294002 and the autophagy inhibitor chloroquine (CQ) on autophagy and apoptosis in NMR skin fibroblasts. Serum starvation, H2O2 treatment, and LY294002 treatment all increased the LC3-II/LC3-I ratio and numbers of double-membraned autophagosomes and autophagic vacuoles, and decreased levels of p70S6K, p-AktSer473, and p-AktThr308. By contrast, CQ treatment decreased p70S6K, AktSer473, and AktThr308 levels. The Bax/Bcl-2 ratio increased after 12 h of exposure to LY294002 or CQ. These data show that inhibiting the Akt pathway promotes autophagy and apoptosis in NMR skin fibroblasts. Furthermore, LY294002 or CQ treatment decreased caspase-3, p53, and HIF1-α levels, suggesting that serum starvation or H2O2 treatment increase autophagy and apoptosis in NMR skin fibroblasts by inhibiting the PI3K/Akt pathway. CQ-induced inhibition of late autophagy stages also prevented Akt activation and induced apoptosis. Finally, the HIF-1α and p53 pathways were involved in serum starvation- or H2O2-induced autophagy in NMR skin fibroblasts.

  19. Chronic Inhibition of PDE5 Limits Pro-Inflammatory Monocyte-Macrophage Polarization in Streptozotocin-Induced Diabetic Mice.

    Science.gov (United States)

    Venneri, Mary Anna; Giannetta, Elisa; Panio, Giuseppe; De Gaetano, Rita; Gianfrilli, Daniele; Pofi, Riccardo; Masciarelli, Silvia; Fazi, Francesco; Pellegrini, Manuela; Lenzi, Andrea; Naro, Fabio; Isidori, Andrea M

    2015-01-01

    Diabetes mellitus is characterized by changes in endothelial cells that alter monocyte recruitment, increase classic (M1-type) tissue macrophage infiltration and lead to self-sustained inflammation. Our and other groups recently showed that chronic inhibition of phosphodiesterase-5 (PDE5i) affects circulating cytokine levels in patients with diabetes; whether PDE5i also affects circulating monocytes and tissue inflammatory cell infiltration remains to be established. Using murine streptozotocin (STZ)-induced diabetes and in human vitro cell-cell adhesion models we show that chronic hyperglycemia induces changes in myeloid and endothelial cells that alter monocyte recruitment and lead to self-sustained inflammation. Continuous PDE5i with sildenafil (SILD) expanded tissue anti-inflammatory TIE2-expressing monocytes (TEMs), which are known to limit inflammation and promote tissue repair. Specifically, SILD: 1) normalizes the frequency of circulating pro-inflammatory monocytes triggered by hyperglycemia (53.7 ± 7.9% of CD11b+Gr-1+ cells in STZ vs. 30.4 ± 8.3% in STZ+SILD and 27.1 ± 1.6% in CTRL, PTEMs (30.9 ± 3.6% in STZ+SILD vs. 6.9 ± 2.7% in STZ, P TEMs are defective in chronic hyperglycemia and that SILD normalizes their levels by facilitating the shift from classic (M1-like) to alternative (M2-like)/TEM macrophage polarization. Restoration of tissue TEMs with PDE5i could represent an additional pharmacological tool to prevent end-organ diabetic complications.

  20. Small-angle X-ray scattering studies on the X-ray induced aggregation of ribonnuclease, lactate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase and serum albumin. A comparison with malate synthase

    International Nuclear Information System (INIS)

    Zipper, P.; Gatterer, H.G.; Schutz, J.; Durchschlag, H.

    1980-01-01

    The X-ray induced aggregation of ribonuclease, lactate dehydrogenase (LDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and serum albumin in aqueous solution was monitored in situ by means of small-angle X-ray scattering. Measurements carried out with ribonuclease, LDH and serum albumin in the absence of dithiothreitol (DTT) and with GAPDH in the presence of 0.2mM DTT established the following series for the rates of aggregation of the proteins under these conditions: ribonuclease >LDH> >GAPDH> serum albumin. Within six hours from the beginning of irradiation (i.e. about the time required for the exposure of one complete scattering curve under the conditions of our experiments) the following increases of R tilde resulted: ribonuclease 9%, LDH 7%, GAPDH 4%, serum albumin <1%. Changes of R tilde exceeding 1% are, of course, too high to be tolerated in conventional scattering experiments. Measurements carried out with LDH and GAPDH in the presence of 2mM DTT established a strong protective effect of DTT against the X-ray induced aggregation of these enzymes. The initial increase of R tilde upon irradiation of LDH and GAPDH in the presence of 2mM DTT was found to be even lower than the increase of R tilde observed when serum albumin was irradiated in the absence of DTT. However, the observed decrease of anti x of LDH and GAPDH at the early stages of irradiation suggested the occurrence of fragmentation of the enzymes as another consequence of radiation damage. This finding is discussed in context with the results from previous scattering experiments and electrophoretic studies on malate synthase. (author)

  1. Interleukin 37 limits monosodium urate crystal-induced innate immune responses in human and murine models of gout.

    Science.gov (United States)

    Liu, Lei; Xue, Yu; Zhu, Yingfeng; Xuan, Dandan; Yang, Xue; Liang, Minrui; Wang, Juan; Zhu, Xiaoxia; Zhang, Jiong; Zou, Hejian

    2016-11-18

    Interleukin (IL)-37 has emerged as a fundamental inhibitor of innate immunity. Acute gout is a self-limiting inflammatory response to monosodium urate (MSU) crystals. In the current study, we assessed the preventive and therapeutic effect of recombinant human IL-37 (rhIL-37) in human and murine gout models. We investigated the expression of IL-37 in patients with active and inactive gouty arthritis and assessed the effect of rhIL-37 in human and murine gout models: a human monocyte cell line (THP-1) and human synovial cells (containing macrophage-like and fibroblast-like synoviocytes) exposed to MSU crystals, a peritoneal murine model of gout and a murine gouty arthritis model. After inhibition of Mer receptor tyrosine kinase (Mertk), levels of IL-1β, IL-8 and chemokine (C-C motif) ligand 2 (CCL-2) were detected by ELISA and expression of mammalian homologs of the drosophila Mad gene 3 (Smad), suppressor of cytokine signaling 3 (SOCS3), NACHT-LRR-PYD-containing protein 3 (NLRP3), and IL-8R of THP-1 were assessed by qPCR and western blot to explore the molecular mechanisms. Our studies strongly indicated that rhIL-37 played a potent immunosuppressive role in the pathogenesis of experimental gout models both in vitro and in vivo, by downregulating proinflammatory cytokines and chemokines, markedly reducing neutrophil and monocyte recruitment, and mitigating pathological joint inflammation. In our studies, rhIL-37 suppressed MSU-induced innate immune responses by enhancing expression of Smad3 and IL-1R8 to trigger multiple intracellular switches to block inflammation, including inhibition of NLRP3 and activation of SOCS3. Mertk signaling participated in rhIL-37 inhibitory pathways in gout models. By inhibition of Mertk, the anti-inflammatory effect of rhIL-37 was partly abrogated, and IL-1R8, Smad3 and S​OCS3 expression were suppressed, whereas NLRP3 expression was reactivated. Our studies reveal that IL-37 limits runaway inflammation initiated by MSU crystal-induced

  2. The current state of serum biomarkers of hepatotoxicity.

    Science.gov (United States)

    Ozer, Josef; Ratner, Marcia; Shaw, Martin; Bailey, Wendy; Schomaker, Shelli

    2008-03-20

    The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTalpha) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in

  3. The current state of serum biomarkers of hepatotoxicity

    International Nuclear Information System (INIS)

    Ozer, Josef; Ratner, Marcia; Shaw, Martin; Bailey, Wendy; Schomaker, Shelli

    2008-01-01

    The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTα) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in early

  4. Chronic Inhibition of PDE5 Limits Pro-Inflammatory Monocyte-Macrophage Polarization in Streptozotocin-Induced Diabetic Mice.

    Directory of Open Access Journals (Sweden)

    Mary Anna Venneri

    Full Text Available Diabetes mellitus is characterized by changes in endothelial cells that alter monocyte recruitment, increase classic (M1-type tissue macrophage infiltration and lead to self-sustained inflammation. Our and other groups recently showed that chronic inhibition of phosphodiesterase-5 (PDE5i affects circulating cytokine levels in patients with diabetes; whether PDE5i also affects circulating monocytes and tissue inflammatory cell infiltration remains to be established. Using murine streptozotocin (STZ-induced diabetes and in human vitro cell-cell adhesion models we show that chronic hyperglycemia induces changes in myeloid and endothelial cells that alter monocyte recruitment and lead to self-sustained inflammation. Continuous PDE5i with sildenafil (SILD expanded tissue anti-inflammatory TIE2-expressing monocytes (TEMs, which are known to limit inflammation and promote tissue repair. Specifically, SILD: 1 normalizes the frequency of circulating pro-inflammatory monocytes triggered by hyperglycemia (53.7 ± 7.9% of CD11b+Gr-1+ cells in STZ vs. 30.4 ± 8.3% in STZ+SILD and 27.1 ± 1.6% in CTRL, P<0.01; 2 prevents STZ-induced tissue inflammatory infiltration (4-fold increase in F4/80+ macrophages in diabetic vs. control mice by increasing renal and heart anti-inflammatory TEMs (30.9 ± 3.6% in STZ+SILD vs. 6.9 ± 2.7% in STZ, P <0.01, and 11.6 ± 2.9% in CTRL mice; 3 reduces vascular inflammatory proteins (iNOS, COX2, VCAM-1 promoting tissue protection; 4 lowers monocyte adhesion to human endothelial cells in vitro through the TIE2 receptor. All these changes occurred independently from changes of glycemic status. In summary, we demonstrate that circulating renal and cardiac TEMs are defective in chronic hyperglycemia and that SILD normalizes their levels by facilitating the shift from classic (M1-like to alternative (M2-like/TEM macrophage polarization. Restoration of tissue TEMs with PDE5i could represent an additional pharmacological tool to prevent

  5. Serum ferritin

    International Nuclear Information System (INIS)

    Rochna Viola, E.M.; Diaz de Domingo, N.B.; Lazarowski, A.

    1981-01-01

    Serum ferritin (SF) concentration as determined by the immunoradiometric method allows the direct measurement of a fraction of the body ferritin pool. In normal subjects, SF is an excellent index of body iron stores. In certain conditions associated with increased ferritin synthesis (such as liver disease, inflammation, malignancy, chronic disorders, ineffective erythropoiesis, or during ferrotherapy), SF may not accurately reflect body iron stores. In hyposideremic anemias SF concentration permits to differentiate those due to iron deficiency from those due to chronic disorders. With a good assay quality, subnormal SF levels are incontrovertible in the diagnosis of iron deficiency. SF determination has been investigated as possible tumor marker. When performed in combination with the alpha-fetoprotein assay, SF enhances the specificity of serodiagnosis of hepatoma. SF results must be interpreted bearing in mind the possible participation of circumstances that i) modify the body iron stores and ii) lead to increased ferritin synthesis. (author) [es

  6. Accuracy of point-of-care serum creatinine devices for detecting patients at risk of contrast-induced nephropathy: a critical overview.

    Science.gov (United States)

    Martínez Lomakin, Felipe; Tobar, Catalina

    2014-12-01

    Contrast-induced nephropathy (CIN) is a common event in hospitals, with reported incidences ranging from 1 to 30%. Patients with underlying kidney disease have an increased risk of developing CIN. Point-of-care (POC) creatinine devices are handheld devices capable of providing quantitative data on a patient's kidney function that could be useful in stratifying preventive measures. This overview aims to synthesize the current evidence on diagnostic accuracy and clinical utility of POC creatinine devices in detecting patients at risk of CIN. Five databases were searched for diagnostic accuracy studies or clinical trials that evaluated the usefulness of POC devices in detecting patients at risk of CIN. Selected articles were critically appraised to assess their individual risk of bias by the use of standard criteria; 13 studies were found that addressed the diagnostic accuracy or clinical utility of POC creatinine devices. Most studies incurred a moderate to high risk of bias. Overall concordance between POC devices and reference standards (clinical laboratory procedures) was found to be moderate, with 95% limits of agreement often lying between -35.4 and +35.4 µmol/L (-0.4 and +0.4 mg/dL). Concordance was shown to decrease with worsening kidney function. Data on the clinical utility of these devices were limited, but a significant reduction in time to diagnosis was reported in two studies. Overall, POC creatinine devices showed a moderate concordance with standard clinical laboratory creatinine measurements. Several biases could have induced optimism in these estimations. Results obtained from these devices may be unreliable in cases of severe kidney failure. Randomized trials are needed to address the clinical utility of these devices.

  7. Quench limits

    International Nuclear Information System (INIS)

    Sapinski, M.

    2012-01-01

    With thirteen beam induced quenches and numerous Machine Development tests, the current knowledge of LHC magnets quench limits still contains a lot of unknowns. Various approaches to determine the quench limits are reviewed and results of the tests are presented. Attempt to reconstruct a coherent picture emerging from these results is taken. The available methods of computation of the quench levels are presented together with dedicated particle shower simulations which are necessary to understand the tests. The future experiments, needed to reach better understanding of quench limits as well as limits for the machine operation are investigated. The possible strategies to set BLM (Beam Loss Monitor) thresholds are discussed. (author)

  8. Influence of percutaneous stimulation of hepatic region with mid-frequency pulse current on the activity of serum GSH-PX, SOD, T-AOC and the content of malondialdehyde in exercise-induced fatigued soldiers

    Directory of Open Access Journals (Sweden)

    Peng-yi DAI

    2014-03-01

    Full Text Available Objective  To explore the influence of percutaneous stimulation of the hepatic region with mid-frequency pulsed current on the serum activity of glutathione peroxidase (GSH-PX, superoxide dismutase (SOD and total antioxidant capacity and content of malondialdehyde (MDA in exercise-induced fatigued soldiers. Methods  Sixty healthy male recruits without training history were randomly divided into control group and stimulation group (n=30. Subjects in both groups received intensive training for 5 weeks (trained from Monday to Saturday, and rest on Sunday to establish an exercise-induced fatigue model. The recruits in stimulation group received rehabilitation therapy of percutaneous stimulation of the hepatic region with mid-frequency pulse current (frequency was 1024Hz, dynamic cycle 1s, stimulation time 20min, output intensity ≤80mA after the training immediately. In every Sunday morning of the 1st, 3rd and 5th week, venous blood samples were obtained from recruits of both groups for determination of the serum activity of GSH-PX, SOD and T-AOC and content of MDA. Results  In both groups, the serum activity of GSH-PX and T-AOC on 5th weekend was lower than that of 1st and 3rd weekends, and the serum activity of GSH-PX and T-AOC on 3rd weekend was lower than that of 1st weekend (P0.05; the serum MDA content on 5th weekend was higher than that of 3rd and 1st weekends, and the content on 3rd weekend was higher than that of 1st weekend (P<0.01. The activity of GSH-PX, SOD and T-AOC increased and the MDA content decreased on 1st, 3rd and 5th weekends in stimulation group when compared with control group (P<0.05, P<0.01. Conclusions  The percutaneous stimulation of the hepatic region by mid-frequency pulsed current in exercise-induced fatigued soldiers may improve the activity of antioxidant enzymes in the liver, enhance the function of antioxidant system, promote free radical scavenging, delay the occurrence of and promote the recovery from

  9. A novel functional site of extracellular matrix metalloproteinase inducer (EMMPRIN) that limits the migration of human uterine cervical carcinoma cells.

    Science.gov (United States)

    Sato, Takashi; Watanabe, Mami; Hashimoto, Kei; Ota, Tomoko; Akimoto, Noriko; Imada, Keisuke; Nomizu, Motoyoshi; Ito, Akira

    2012-01-01

    EMMPRIN (extracellular matrix metalloproteinase inducer)/CD147, a membrane-bound glycoprotein with two extracellular loop domains (termed loops I and II), progresses tumor invasion and metastasis by increasing the production of matrix metalloproteinase (MMP) in peritumoral stoma cells. EMMPRIN has also been associated with the control of migration activity in some tumor cells, but little is known about how EMMPRIN regulates tumor cell migration. In the present study, EMMPRIN siRNA suppressed the gene expression and production of EMMPRIN in human uterine cervical carcinoma SKG-II cells. An in vitro scratch wound assay showed enhancement of migration of EMMPRIN-knockdown SKG-II cells. In addition, the SKG-II cell migration was augmented by adding an E. coli-expressed human EMMPRIN mutant with two extracellular loop domains (eEMP-I/II), which bound to the cell surface of SKG-II cells. However, eEMP-I/II suppressed the native EMMPRIN-mediated augmentation of proMMP-1/procollagenase-1 production in a co-culture of the SKG-II cells and human uterine cervical fibroblasts, indicating that the augmentation of SKG-II cell migration resulted from the interference of native EMMPRIN functions by eEMP-I/II on the cell surface. Furthermore, a systematic peptide screening method using nine synthetic EMMPRIN peptides coding the loop I and II domains (termed EM1-9) revealed that EM9 (170HIENLNMEADPGQYR184) facilitated SKG-II cell migration. Moreover, SKG-II cell migration was enhanced by administration of an antibody against EM9, but not EM1 which is a crucial site for the MMP inducible activity of EMMPRIN. Therefore, these results provide novel evidence that EMMPRIN on the cell surface limits the cell migration of human uterine cervical carcinoma cells through 170HIENLNMEADPGQYR184 in the loop II domain. Finally, these results should provide an increased understanding of the functions of EMMPRIN in malignant cervical carcinoma cells, and could contribute to the development of

  10. Circulating angiostatin serum level in patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Zofia Gerlicz-Kowalczuk

    2017-12-01

    Full Text Available Introduction : Systemic sclerosis (SSc is achronic connective tissue disease characterized by microangiopathy with inadequate angiogenesis. Angiostatin (AS is a potent antiangiogenic factor specifically inhibiting proliferation and inducing apoptosis of vascular endothelial cells. Aim : To evaluate the level of angiostatin in the serum of patients with SSc. Material and methods : Serum levels of AS were measured in 20 SSc patients and 12 healthy controls. Results : A statistically significant difference in the serum levels of AS in SSc patients was observed compared to the control group (636.51 vs. 869.20 ng/ml; p = 0.012. Significant correlations between limited and disseminated SSc (lSSc/dSSc were not found, however, a difference between lSSc and the control group was demonstrated (620.00 vs. 869.20 ng/ml; p = 0.011. The serum level of AS was not associated positively with organ changes caused by SSc. However, a statistically significant lower serum level of AS was observed in patients with SSc and no esophageal (p = 0.008 or pulmonary changes (p = 0.007 compared to the control group. Conclusions : Our results reveal significant differences in AS level in SSc patients compared to the healthy controls, and suggest that a low level of AS may occur as a result of impaired angiogenesis.

  11. Leaping lizards landing on leaves: escape-induced jumps in the rainforest canopy challenge the adhesive limits of geckos.

    Science.gov (United States)

    Higham, Timothy E; Russell, Anthony P; Niklas, Karl J

    2017-06-01

    The remarkable adhesive capabilities of geckos have garnered attention from scientists and the public for centuries. Geckos are known to have an adhesive load-bearing capacity far in excess (by 100-fold or more) of that required to support their body mass or accommodate the loading imparted during maximal locomotor acceleration. Few studies, however, have investigated the ecological contexts in which geckos use their adhesive system and how this may influence its properties. Here we develop a modelling framework to assess whether their prodigious adhesive capacity ever comes under selective challenge. Our investigation is based upon observations of escape-induced aerial descents of canopy-dwelling arboreal geckos that are rapidly arrested by clinging to leaf surfaces in mid-fall. We integrate ecological observations, adhesive force measurements, and body size and shape measurements of museum specimens to conduct simulations. Using predicted bending mechanics of petioles and leaf midribs, we find that the drag coefficient of the gecko, the size of the gecko and the size of the leaf determine impact forces. Regardless of the landing surface, safety factors for geckos range from a maximum of just over 10 to a minimum of well under one, which would be the point at which the adhesive system fails. In contrast to previous research that intimates that gecko frictional adhesive capacity is excessive relative to body mass, we demonstrate that realistic conditions in nature may result in frictional capacity being pushed to its limit. The rapid arrest of the lizard from its falling velocity likely results in the maximal loading to which the adhesive system is exposed during normal activities. We suggest that such activities might be primary determinants in driving their high frictional adhesive capacity. © 2017 The Author(s).

  12. Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications

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    Adekunle Ebenezer Omole

    2018-05-01

    Full Text Available The discovery of induced pluripotent stem cells (iPSCs by Shinya Yamanaka in 2006 was heralded as a major breakthrough of the decade in stem cell research. The ability to reprogram human somatic cells to a pluripotent embryonic stem cell-like state through the ectopic expression of a combination of embryonic transcription factors was greeted with great excitement by scientists and bioethicists. The reprogramming technology offers the opportunity to generate patient-specific stem cells for modeling human diseases, drug development and screening, and individualized regenerative cell therapy. However, fundamental questions have been raised regarding the molecular mechanism of iPSCs generation, a process still poorly understood by scientists. The efficiency of reprogramming of iPSCs remains low due to the effect of various barriers to reprogramming. There is also the risk of chromosomal instability and oncogenic transformation associated with the use of viral vectors, such as retrovirus and lentivirus, which deliver the reprogramming transcription factors by integration in the host cell genome. These challenges can hinder the therapeutic prospects and promise of iPSCs and their clinical applications. Consequently, extensive studies have been done to elucidate the molecular mechanism of reprogramming and novel strategies have been identified which help to improve the efficiency of reprogramming methods and overcome the safety concerns linked with iPSC generation. Distinct barriers and enhancers of reprogramming have been elucidated, and non-integrating reprogramming methods have been reported. Here, we summarize the progress and the recent advances that have been made over the last 10 years in the iPSC field, with emphasis on the molecular mechanism of reprogramming, strategies to improve the efficiency of reprogramming, characteristics and limitations of iPSCs, and the progress made in the applications of iPSCs in the field of disease modelling

  13. Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications.

    Science.gov (United States)

    Omole, Adekunle Ebenezer; Fakoya, Adegbenro Omotuyi John

    2018-01-01

    The discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka in 2006 was heralded as a major breakthrough of the decade in stem cell research. The ability to reprogram human somatic cells to a pluripotent embryonic stem cell-like state through the ectopic expression of a combination of embryonic transcription factors was greeted with great excitement by scientists and bioethicists. The reprogramming technology offers the opportunity to generate patient-specific stem cells for modeling human diseases, drug development and screening, and individualized regenerative cell therapy. However, fundamental questions have been raised regarding the molecular mechanism of iPSCs generation, a process still poorly understood by scientists. The efficiency of reprogramming of iPSCs remains low due to the effect of various barriers to reprogramming. There is also the risk of chromosomal instability and oncogenic transformation associated with the use of viral vectors, such as retrovirus and lentivirus, which deliver the reprogramming transcription factors by integration in the host cell genome. These challenges can hinder the therapeutic prospects and promise of iPSCs and their clinical applications. Consequently, extensive studies have been done to elucidate the molecular mechanism of reprogramming and novel strategies have been identified which help to improve the efficiency of reprogramming methods and overcome the safety concerns linked with iPSC generation. Distinct barriers and enhancers of reprogramming have been elucidated, and non-integrating reprogramming methods have been reported. Here, we summarize the progress and the recent advances that have been made over the last 10 years in the iPSC field, with emphasis on the molecular mechanism of reprogramming, strategies to improve the efficiency of reprogramming, characteristics and limitations of iPSCs, and the progress made in the applications of iPSCs in the field of disease modelling, drug discovery and

  14. Nitrogen limitation and slow drying induce desiccation tolerance in conjugating green algae (Zygnematophyceae, Streptophyta from polar habitats.

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    Martina Pichrtová

    Full Text Available Filamentous Zygnematophyceae are typical components of algal mats in the polar hydro-terrestrial environment. Under field conditions, they form senescent vegetative cells, designated as pre-akinetes, which are tolerant to desiccation and osmotic stress.Pre-akinete formation and desiccation tolerance was investigated experimentally under monitored laboratory conditions in four strains of Arctic and Antarctic isolates with vegetative Zygnema sp. morphology. Phylogenetic analyses of rbcL sequences revealed one Arctic strain as genus Zygnemopsis, phylogenetically distant from the closely related Zygnema strains. Algae were cultivated in liquid or on solidified medium (9 weeks, supplemented with or lacking nitrogen. Nitrogen-free cultures (liquid as well as solidified consisted of well-developed pre-akinetes after this period. Desiccation experiments were performed at three different drying rates (rapid: 10% relative humidity, slow: 86% rh and very slow; viability, effective quantum yield of PS II, visual and ultrastructural changes were monitored. Recovery and viability of pre-akinetes were clearly dependent on the drying rate: slower desiccation led to higher levels of survival. Pre-akinetes survived rapid drying after acclimation by very slow desiccation.The formation of pre-akinetes in polar Zygnema spp. and Zygnemopsis sp. is induced by nitrogen limitation. Pre-akinetes, modified vegetative cells, rather than specialized stages of the life cycle, can be hardened by mild desiccation stress to survive rapid drying. Naturally hardened pre-akinetes play a key role in stress tolerance and dispersal under the extreme conditions of polar regions, where sexual reproduction and production of dormant stages is largely suppressed.

  15. Quantitative measurement of a candidate serum biomarker peptide derived from α2-HS-glycoprotein, and a preliminary trial of multidimensional peptide analysis in females with pregnancy-induced hypertension.

    Science.gov (United States)

    Hamamura, Kensuke; Yanagida, Mitsuaki; Ishikawa, Hitoshi; Banzai, Michio; Yoshitake, Hiroshi; Nonaka, Daisuke; Tanaka, Kenji; Sakuraba, Mayumi; Miyakuni, Yasuka; Takamori, Kenji; Nojima, Michio; Yoshida, Koyo; Fujiwara, Hiroshi; Takeda, Satoru; Araki, Yoshihiko

    2018-03-01

    Purpose We previously attempted to develop quantitative enzyme-linked immunosorbent assay (ELISA) systems for the PDA039/044/071 peptides, potential serum disease biomarkers (DBMs) of pregnancy-induced hypertension (PIH), primarily identified by a peptidomic approach (BLOTCHIP®-mass spectrometry (MS)). However, our methodology did not extend to PDA071 (cysteinyl α2-HS-glycoprotein 341-367 ), due to difficulty to produce a specific antibody against the peptide. The aim of the present study was to establish an alternative PDA071 quantitation system using liquid chromatography-multiple reaction monitoring (LC-MRM)/MS, to explore the potential utility of PDA071 as a DBM for PIH. Methods We tested heat/acid denaturation methods in efforts to purify serum PDA071 and developed an LC-MRM/MS method allowing for specific quantitation thereof. We measured serum PDA071 concentrations, and these results were validated including by three-dimensional (3D) plotting against PDA039 (kininogen-1 439-456 )/044 (kininogen-1 438-456 ) concentrations, followed by discriminant analysis. Results PDA071 was successfully extracted from serum using a heat denaturation method. Optimum conditions for quantitation via LC-MRM/MS were developed; the assayed serum PDA071 correlated well with the BLOTCHIP® assay values. Although the PDA071 alone did not significantly differ between patients and controls, 3D plotting of PDA039/044/071 peptide concentrations and construction of a Jackknife classification matrix were satisfactory in terms of PIH diagnostic precision. Conclusions Combination analysis using both PDA071 and PDA039/044 concentrations allowed PIH diagnostic accuracy to be attained, and our method will be valuable in future pathophysiological studies of hypertensive disorders of pregnancy.

  16. The Effect of Methanolic Extract of Otostegia persica on Serum Glucose Level and Renal Function Indicators in Streptozotocin Induced Diabetic Rats

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    Mahdiye Hedayati

    2012-05-01

    Full Text Available Background: Regarding the antioxidant property of Otostegia persica extract and the role of antioxidants in Diabetes mellitus treatment, in this study the effect of extract on serum glucose level and renal function indicators was determined in diabetic male rats. Materials and Methods: Diabetes mellitus (type I was inducted in male rats using intraperitoneal injection of streptozotocin (STZ (65 mg/kg. To determine blood glucose, urea, and creatinine serum levels; fasting blood samples were collected twice (before STZ injection and 5 days later. The rats with their serum glucose level exceeding 250 mg/dl were considered diabetic and divided into 10 groups separately received Otostegia persica alcoholic extract (100, 200, and 300 mg/kg/day doses, glibenclamide with 600 µg/kg dose and 0.5 ml distilled water for 3 and 6 days using gavage. After 3 and 6 days, blood samples were collected again and glucose, urea, and creatinine serum levels were assessed using spectrophotometry technique by respective kits.Results: Treating diabetic rats by Otostegia persica extract (100, 200, and 300 mg/kg/day doses for 6 days results in a significant decrease of glucose and creatinine, yet an increase of serum urea with 200 mg/kg dose. Also, administration of the extract for 3 days (300 mg/kg reduced glucose, and (in various doses urea and creatinine serum levels. Conclusion: Otostegia persica extract has hypoglycemic effect and administering it in diabetes mellitus not only had no undesirable renal side effects, but also improved renal function to some extent.

  17. Major histocompatibility complex class I-related chain A/B (MICA/B) expression in tumor tissue and serum of pancreatic cancer: Role of uric acid accumulation in gemcitabine-induced MICA/B expression

    International Nuclear Information System (INIS)

    Xu, Xiulong; Rao, Geetha S; Groh, Veronika; Spies, Thomas; Gattuso, Paolo; Kaufman, Howard L; Plate, Janet; Prinz, Richard A

    2011-01-01

    Major histocompatibility complex class I-related chain A and B (MICA/B) are two stress-inducible ligands that bind the immunoreceptor NKG2D and play an important role in mediating the cyotoxicity of NK and T cells. In this study, we sought to study MICA/B expression in pancreatic cancer and to determine whether and how genotoxic drugs such as gemcitabine can affect MICA/B expression and natural killer cytotoxity. Seven pancreatic cancer cell lines were analyzed for MICA/B expression by flow cytometry and for their sensitivity to NK-92 cell killing by a 51 Cr release assay. MICA/B expression in tumor tissues and sera of pancreatic cancer was analyzed by immunohistochemical staining (IHC) and ELISA, respectively. Two MICA/B-positive cell lines were sensitive to the cytotoxic activity of NK-92 cells. Other two MICA/B-positive cell lines and three MICA/B-negative cell lines were resistant to NK-92 cell killing. MICA/B expression was positive in 17 of 25 (68%) pancreatic ductal adenocarcinomas but not in normal pancreatic ductal epithelial cells. Serum MICA/B levels were significantly elevated in patients with pancreatic adenocarcinomas but did not correlate with the stage of pancreatic cancer and patient survival. Gemcitabine therapy led to increased serum MICA levels in 6 of 10 patients with detectable serum MICA. Allopurinol, an inhibitor of xanthine oxidoreductase that converts xanthine to uric acid, blocked uric acid production, MICA/B expression, and sensitivity to NK-92 cell killing toward a PANC-1 cancer cell line exposed to radiation and two genotoxic drugs, gemcitabine and 5-fluorouracil. The levels of MICA/B expression in serum and tissue of pancreatic cancer are elevated. DNA damage-induced MICA/B expression is mediated through increased uric acid production

  18. Major histocompatibility complex class I-related chain A/B (MICA/B expression in tumor tissue and serum of pancreatic cancer: Role of uric acid accumulation in gemcitabine-induced MICA/B expression

    Directory of Open Access Journals (Sweden)

    Kaufman Howard L

    2011-05-01

    Full Text Available Abstract Background Major histocompatibility complex class I-related chain A and B (MICA/B are two stress-inducible ligands that bind the immunoreceptor NKG2D and play an important role in mediating the cyotoxicity of NK and T cells. In this study, we sought to study MICA/B expression in pancreatic cancer and to determine whether and how genotoxic drugs such as gemcitabine can affect MICA/B expression and natural killer cytotoxity. Methods Seven pancreatic cancer cell lines were analyzed for MICA/B expression by flow cytometry and for their sensitivity to NK-92 cell killing by a 51Cr release assay. MICA/B expression in tumor tissues and sera of pancreatic cancer was analyzed by immunohistochemical staining (IHC and ELISA, respectively. Results Two MICA/B-positive cell lines were sensitive to the cytotoxic activity of NK-92 cells. Other two MICA/B-positive cell lines and three MICA/B-negative cell lines were resistant to NK-92 cell killing. MICA/B expression was positive in 17 of 25 (68% pancreatic ductal adenocarcinomas but not in normal pancreatic ductal epithelial cells. Serum MICA/B levels were significantly elevated in patients with pancreatic adenocarcinomas but did not correlate with the stage of pancreatic cancer and patient survival. Gemcitabine therapy led to increased serum MICA levels in 6 of 10 patients with detectable serum MICA. Allopurinol, an inhibitor of xanthine oxidoreductase that converts xanthine to uric acid, blocked uric acid production, MICA/B expression, and sensitivity to NK-92 cell killing toward a PANC-1 cancer cell line exposed to radiation and two genotoxic drugs, gemcitabine and 5-fluorouracil. Conclusions The levels of MICA/B expression in serum and tissue of pancreatic cancer are elevated. DNA damage-induced MICA/B expression is mediated through increased uric acid production.

  19. Lithium ameliorates sleep deprivation-induced mania-like behavior, hypothalamic-pituitary-adrenal (HPA) axis alterations, oxidative stress and elevations of cytokine concentrations in the brain and serum of mice.

    Science.gov (United States)

    Valvassori, Samira S; Resende, Wilson R; Dal-Pont, Gustavo; Sangaletti-Pereira, Heron; Gava, Fernanda F; Peterle, Bruna R; Carvalho, André F; Varela, Roger B; Dal-Pizzol, Felipe; Quevedo, João

    2017-06-01

    The goal of the present study was to investigate the effects of lithium administration on behavior, oxidative stress parameters and cytokine levels in the periphery and brain of mice subjected to an animal model of mania induced by paradoxical sleep deprivation (PSD). Male C57 mice were treated with saline or lithium for 7 days. The sleep deprivation protocol started on the 5th day during for the last 36 hours of the treatment period. Immediately after the sleep deprivation protocol, animals locomotor activity was evaluated and serum and brain samples was extracted to evaluation of corticosterone and adrenocorticotropic hormone circulating levels, oxidative stress parameters and citokynes levels. The results showed that PSD induced hyperactivity in mice, which is considered a mania-like behavior. PSD increased lipid peroxidation and oxidative damage to DNA, as well as causing alterations to antioxidant enzymes in the frontal cortex, hippocampus and serum of mice. In addition, PSD increased the levels of cytokines in the brains of mice. Treatment with lithium prevented the mania-like behavior, oxidative damage and cytokine alterations induced by PSD. Improving our understanding of oxidative damage in biomolecules, antioxidant mechanisms and the inflammatory system - alterations presented in the animal models of mania - is important in helping us to improve our knowledge concerning the pathophysiology of BD, and the mechanisms of action employed by mood stabilizers. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. ResDE Two-Component Regulatory System Mediates Oxygen Limitation-Induced Biofilm Formation by Bacillus amyloliquefaciens SQR9.

    Science.gov (United States)

    Zhou, Xuan; Zhang, Nan; Xia, Liming; Li, Qing; Shao, Jiahui; Shen, Qirong; Zhang, Ruifu

    2018-04-15

    Efficient biofilm formation and root colonization capabilities facilitate the ability of beneficial plant rhizobacteria to promote plant growth and antagonize soilborne pathogens. Biofilm formation by plant-beneficial Bacillus strains is triggered by environmental cues, including oxygen deficiency, but the pathways that sense these environmental signals and regulate biofilm formation have not been thoroughly elucidated. In this study, we showed that the ResDE two-component regulatory system in the plant growth-promoting rhizobacterium Bacillus amyloliquefaciens strain SQR9 senses the oxygen deficiency signal and regulates biofilm formation. ResE is activated by sensing the oxygen limitation-induced reduction of the NAD + /NADH pool through its PAS domain, stimulating its kinase activity, and resulting in the transfer of a phosphoryl group to ResD. The phosphorylated ResD directly binds to the promoter regions of the qoxABCD and ctaCDEF operons to improve the biosynthesis of terminal oxidases, which can interact with KinB to activate biofilm formation. These results not only revealed the novel regulatory function of the ResDE two-component system but also contributed to the understanding of the complicated regulatory network governing Bacillus biofilm formation. This research may help to enhance the root colonization and the plant-beneficial efficiency of SQR9 and other Bacillus rhizobacteria used in agriculture. IMPORTANCE Bacillus spp. are widely used as bioinoculants for plant growth promotion and disease suppression. The exertion of their plant-beneficial functions is largely dependent on their root colonization, which is closely related to their biofilm formation capabilities. On the other hand, Bacillus is the model bacterium for biofilm study, and the process and molecular network of biofilm formation are well characterized (B. Mielich-Süss and D. Lopez, Environ Microbiol 17:555-565, 2015, https://doi.org/10.1111/1462-2920.12527; L. S. Cairns, L. Hobley, and

  1. Use of cystatin C and serum creatinine for the diagnosis of contrast-induced nephropathy in patients undergoing contrast-enhanced computed tomography at an oncology centre.

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    Joao Italo Fortalesa Melo

    Full Text Available Our aim was to assess renal function using as laboratory measurements serum creatinine and cystatin C concentrations before and after administration of low-osmolarity (nonionic iodinated contrast medium in patients with cancer undergoing computed tomography (CT.This prospective study included 400 oncologic outpatients. Serum creatinine and cystatin C concentrations were measured before and 72 h after contrast administration. Glomerular filtration rates (GFRs were estimated using serum creatinine-based [Modification of Diet in Renal Disease (MDRD and Cockroft-Gault and cystatin C based (Larsson equations. Exploratory data analysis was performed. The nonparametric Wilcoxon test was used to compare pre and post contrast of test results and estimated clearance. The confidence interval used in the analysis was 95%.Compared with the pre-contrast values, the mean serum creatinine concentration was significantly higher and average GFRs estimated using MDRD and Cockcroft-Gault equations were significantly lower after the administration of contrast (p <0.001. It was also observed a significant increase after contrast in the concentration of Cystatin C (p = 0.015. In addition, a decrease in GFR estimated using the average Larsson (p = 0.021 was observed between time points. However, none of the patients presented clinically significant nephropathy.Assessment using serum creatinine and cystatin C concentrations showed changes in renal function among patients with cancer undergoing contrast-enhanced CT examination in this study. No significant renal damage related to the use of low-osmolarity iodinated contrast medium of the type and dosage employed in this study was observed. This contrast medium is thus safe for use in patients with cancer.

  2. Reduced insulin-like growth factor-I serum levels in formerly obese women subjected to laparoscopic-adjustable gastric banding or diet-induced long-term caloric restriction.

    Science.gov (United States)

    Mitterberger, Maria C; Mattesich, Monika; Klaver, Elise; Piza-Katzer, Hildegunde; Zwerschke, Werner

    2011-11-01

    Life-span extension in laboratory rodents induced by long-term caloric restriction correlates with decreased serum insulin-like growth factor-I (IGF-I) levels. Reduced activity of the growth hormone/IGF-I signaling system slows aging and increases longevity in mutant mouse models. In the present study, we show that long-term caloric restriction achieved by two different interventions for 4 years, either laparoscopic-adjustable gastric banding or reducing diet, leads to reduced IGF-I serum levels in formerly obese women relative to normal-weight women eating ad libitum. Moreover, we present evidence that the long-term caloric restriction interventions reduce fasting growth hormone serum levels. The present study indicates that the activity of the growth hormone/IGF-I axis is reduced in long-term calorically restricted formerly obese humans. Furthermore, our findings suggest that the duration and severity of the caloric restriction intervention are important for the outcome on the growth hormone/IGF-I axis in humans.

  3. Oxidation-induced phase transformations and lifetime limits of chromia-forming nickel-base alloy 625

    Energy Technology Data Exchange (ETDEWEB)

    Chyrkin, Anton

    2011-12-05

    in literature as uphill-diffusion phenomenon. Also the M{sub 6}C carbide is found to dissolve in the subsurface zone during high-temperature oxidation of alloy 625 although chromium is only a minor constituent in this (Ni{sub 3}Mo{sub 3})C base carbide The thermodynamic calculations revealed the carbide dissolution to find its cause in the increasing carbon activity with decreasing chromium content which forced carbon to diffuse back from the subscale zone towards the bulk alloy resulting in carbide dissolution beneath the chromia scale. SPE is experimentally found to be substantially less pronounced in thin foils than in thick specimens of alloy 625. It could be shown that this effect is related to the smaller reservoirs of the scale-forming element chromium as well as that of the δ-Ni{sub 3}Nb phase stabilizing element niobium in the thin specimens. As the thinner specimens (thickness in the range of 0.1 mm) become more rapidly depleted in chromium resulting in flatter chromium depletion profiles, a smaller driving force for uphill-diffusion of Nb towards the scale/alloy interface leads to a substantially less pronounced δ-phase enrichment/depletion than in specimens of a few mm thickness. Decreasing specimen thickness suppresses the enrichment/depletion process of the δ-Ni{sub 3}Nb phase and results in complete dissolution of the M{sub 6}C carbide after longer exposure times. SPE is not observed during oxidation of extremely thin-walled specimens, e.g. extremely thin foils or metal foam particles fabricated from alloy 625. During high-temperature oxidation of metal foams consisting of e.g. 20-60 µm diameter particles, the δ-Ni{sub 3}Nb phase enrichment at the scale/alloy interface does not occur and can thus be virtually ignored when modelling the oxidation-induced lifetime limits of alloy 625 metal foams. The lifetime prediction based on the finite-difference calculation of the chromium depletion at the metal/oxide interface of a spherical metal foam

  4. Bacillus coagulans GBI-30, 6086 limits the recurrence of Clostridium difficile-Induced colitis following vancomycin withdrawal in mice

    OpenAIRE

    Fitzpatrick, Leo R; Small, Jeffrey S; Greene, Wallace H; Karpa, Kelly D; Farmer, Sean; Keller, David

    2012-01-01

    Abstract Background Recently, we found that the probiotic strain Bacillus coagulans GBI-30, 6086 (GanedenBC30) improved indices of Clostridium difficile (C. difficile)-induced colitis in mice (Fitzpatrick et al., Gut Pathogens, 2011). Our goal was to determine if BC30 could also prevent the recurrence of C. difficile-induced colitis in mice, following initial treatment with vancomycin. During study days 0 through 5, mice were treated with antibiotics. On day 6, the C. difficile strain VPI 104...

  5. Effects of Parsley (Petroselinum crispum) and its Flavonol Constituents, Kaempferol and Quercetin, on Serum Uric Acid Levels, Biomarkers of Oxidative Stress and Liver Xanthine Oxidoreductase Aactivity inOxonate-Induced Hyperuricemic Rats.

    Science.gov (United States)

    Haidari, Fatemeh; Keshavarz, Seid Ali; Mohammad Shahi, Majid; Mahboob, Soltan-Ali; Rashidi, Mohammad-Reza

    2011-01-01

    Increased serum uric acid is known to be a major risk related to the development of several oxidative stress diseases. The aim of this study was to investigate the effect of parsley, quercetin and kaempferol on serum uric acid levels, liver xanthine oxidoreductase activity and two non-invasive biomarkers of oxidative stress (total antioxidant capacity and malondialdehyde concentration) in normal and oxonate-induced hyperuricemic rats. A total of 60 male Wistar rats were randomly divided into ten equal groups; including 5 normal groups (vehicle, parsley, quercetin, kaempferol and allopurinol) and 5 hyperuricemic groups (vehicle, parsley, quercetin, kaempferol and allopurinol). Parsley (5 g/Kg), quercetin (5 mg/Kg), kaempferol (5 mg/Kg) and allopurinol (5 mg/Kg) were administrated to the corresponding groups by oral gavage once a day for 2 weeks. The results showed that parsley and its flavonol did not cause any significant reduction in the serum uric acid levels in normal rats, but significantly reduced the serum uric acid levels of hyperuricemic rats in a time-dependent manner. All treatments significantly inhibited liver xanthine oxidoreductase activity. Parsley, kaempferol and quercetin treatment led also to a significant increase in total antioxidant capacity and decrease in malondialdehyde concentration in hyperuricemic rats. Although the hypouricemic effect of allopurinol was much higher than that of parsley and its flavonol constituents, it could not significantly change oxidative stress biomarkers. These features of parsley and its flavonols make them as a possible alternative for allopurinol, or at least in combination therapy to minimize the side effects of allopurinol to treat hyperuricemia and oxidative stress diseases.

  6. Exercise-induced serum enzyme elevations confounding the evaluation of investigational drug toxicity. Report of two cases in a vaccine trial.

    Science.gov (United States)

    Johnson, Casey; Monath, Thomas P; Kanesa-Thasan, Niranjan; Mathis, Danell; Miller, Chuck; Shapiro, Seth; Nichols, Richard; McCarthy, Karen; Deary, Alison; Bedford, Philip

    2005-01-01

    Two subjects developed marked elevations in creatine kinase and other serum enzymes associated with mild myalgia during a randomized, double-blind, controlled Phase 1 clinical trial of an investigational live, attenuated vaccine against West Nile virus (ChimeriVax-WN02). One subject had received ChimeriVax-WN02 while the other subject was enrolled in an active control group and received licensed yellow fever 17D vaccine (YF-VAX). Subsequently, the clinical trial was interrupted, and an investigation was begun to evaluate the enzyme abnormalities. As daily serum samples were collected for determination of quantitative viremia, it was possible to define the enzyme elevations with precision and to relate these elevations to physical activity of the subjects, symptoms, and virological and serological measurements. Evaluation of both subjects clearly showed that skeletal muscle injury, and not cardiac or hepatic dysfunction, was responsible for the biochemical abnormalities. This investigation also implicated strenuous exercise as the cause of the apparent muscle injury rather than the study vaccines. As a result of this experience, subjects engaged in future early-stage trials of these live, attenuated viral vaccines will be advised not to engage in contact sports or new or enhanced exercise regimens for which they are not trained or conditioned. The inclusion of placebo control arm (in lieu of or addition to an active vaccine control) will also be useful in differentiating causally related serum enzyme elevations.

  7. Evaluation of maternal serum hypoxia inducible factor-1α, progranulin and syndecan-1 levels in pregnancies with early- and late-onset preeclampsia.

    Science.gov (United States)

    Alici Davutoğlu, Ebru; Akkaya Firat, Asuman; Ozel, Ayşegül; Yılmaz, Nevin; Uzun, Isil; Temel Yuksel, Ilkbal; Madazlı, Riza

    2018-08-01

    To determine the serum levels of HIF-1 α, progranulin, and syndecan-1 in preeclampsia (PE) and normal pregnancy, and to compare whether these markers demonstrate any difference between early-onset PE (EO-PE) and late-onset PE (LO-PE). This cross-sectional study was conducted on 27 women with EO-PE, 27 women with LO-PE, and 26 healthy normotensive pregnant controls matched for gestational age. Maternal levels of serum HIF-1 α, progranulin, and syndecan-1 were measured with the use of an enzyme-linked immunosorbent assay kit. Statistical analysis revealed significant differences between the control and the PE groups in progranulin (p progranulin levels were significantly higher in LO-PE compared with the other two groups (EO-PE versus LO-PE and LO-PE versus controls p = .000). Control group presented significantly higher syndecan-1 levels, than EO and LO-PE (p progranulin levels (r = .439, p= .000). Serum progranulin may have potential to be used as a biomarker for the differentiation of EO-PE and LO-PE. The co-operative action between HIF-1 α and progranulin might play a key role in the pathogenesis of LO-PE. The predominant feature of LO-PE seems to be an inflammatory process, whereas in EO-PE placentation problem seems to be the main pathology.

  8. Immune responses induced in rabbits after oral administration of bovine serum albumin in combination with different adjuvants (herb extracts, aluminium hydroxide and platinum nanoparticles

    Directory of Open Access Journals (Sweden)

    G. Bižanov

    2016-12-01

    Full Text Available The aim of the current study was to evaluate the immunostimulatory activity of 10 different herbal extracts from Vitex agnus-castus, Vinca major, Aloe arborescens and the polyherbal product containing extracts from Sambucus nigra, Primula versis, Pinus alba, Gentiana lutea, Cetraria islandica, Eucaliptus globulus, Citrus limon and aluminium hydroxide, as well as platinum nanoparticles. Rabbits were immunized three times orally with bovine serum albumin (BSA in combination with the components mentioned above. BSA-specific IgA antibodies in saliva and IgG antibodies in serum were examined by ELISA. It was found that the rabbits immunized with BSA in combination with either platinum nanoparticles or aluminium hydroxide had higher titres of BSA-specific IgA antibodies in their saliva at day 56 of observation. Likewise, rabbits treated with BSA and Vinca major or Aloe arborescens extracts showed higher levels of BSA-specific IgG antibodies in the serum at the end of observation. These results suggest that some plant extracts, aluminium hydroxide and platinum nanoparticles components could be used as oral adjuvants or as immunomodulators for rabbits.

  9. Polymerized soluble venom--human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Patterson, R.; Suszko, I.M.; Grammer, L.C.

    1985-03-01

    Extensive previous studies have demonstrated that attempts to produce polymers of Hymenoptera venoms for human immunotherapy resulted in insoluble precipitates that could be injected with safety but with very limited immunogenicity in allergic patients. We now report soluble polymers prepared by conjugating bee venom with human serum albumin with glutaraldehyde. The bee venom-albumin polymer (BVAP) preparation was fractionated on Sephacryl S-300 to have a molecular weight range higher than catalase. /sup 125/I-labeled bee venom phospholipase A was almost completely incorporated into BVAP. Rabbit antibody responses to bee venom and bee venom phospholipase A were induced by BVAP. Human antisera against bee venom were absorbed by BVAP. No new antigenic determinants on BVAP were present as evidenced by absorption of antisera against BVAP by bee venom and albumin. BVAP has potential immunotherapeutic value in patients with anaphylactic sensitivity to bee venom.

  10. Polymerized soluble venom--human serum albumin

    International Nuclear Information System (INIS)

    Patterson, R.; Suszko, I.M.; Grammer, L.C.

    1985-01-01

    Extensive previous studies have demonstrated that attempts to produce polymers of Hymenoptera venoms for human immunotherapy resulted in insoluble precipitates that could be injected with safety but with very limited immunogenicity in allergic patients. We now report soluble polymers prepared by conjugating bee venom with human serum albumin with glutaraldehyde. The bee venom-albumin polymer (BVAP) preparation was fractionated on Sephacryl S-300 to have a molecular weight range higher than catalase. 125 I-labeled bee venom phospholipase A was almost completely incorporated into BVAP. Rabbit antibody responses to bee venom and bee venom phospholipase A were induced by BVAP. Human antisera against bee venom were absorbed by BVAP. No new antigenic determinants on BVAP were present as evidenced by absorption of antisera against BVAP by bee venom and albumin. BVAP has potential immunotherapeutic value in patients with anaphylactic sensitivity to bee venom

  11. The Effect of Cloud Ear Fungus (Auricularia polytricha on Serum Total Cholesterol, LDL And HDL Levels on Wistar Rats Induced by Reused Cooking Oil

    Directory of Open Access Journals (Sweden)

    Budinastiti Ratih

    2018-01-01

    Full Text Available The usage of reused cooking oil affects the increase of serum total cholesterol (TC and LDL, also the decrease of serum HDL. This condition escalates the risk of atherosclerosis, which could lead to the incidence of cardiovascular disease. Cloud ear fungus is a natural antioxidant that contains polysaccharides, flavonoids, niacin, and vitamin C, which can improve the lipid profiles. Objective of this research is to analyze the impact of water from boiled cloud ear fungus on total cholesterol, LDL, and HDL level of Wistar rats that have been given reused cooking oil. This study is a true experimental research with post test only control group design, using 12 weeks-aged male Wistar rats (n = 24 that were randomly divided into 4 groups. K1 as the negative control, K2 was given reused cooking oil and standard diet, K3 was given water from boiled cloud ear fungus and standard diet, and K4 was given reused cooking oil, water from boiled cloud ear fungus and standard diet. Serum total cholesterol, LDL, and HDL levels were measured by the CHOD-PAP method after 28 days treatment. The study showed that TC mean value of K1 (80.2217 ± 3.61 mg / dL, K2 (195.8483 ± 5.47 mg / dL, K3 (75.5800 ± 4.02 mg / dL, and K4 (110.8683 ± 5.82 mg / dL; p = 0.000. LDL mean value of K1 (29.9200 ± 1.53 mg / dL, K2 (78.4167 ± 1.77 mg / dL, K3 (24.3167 ± 1.77 mg / dL, and K4 (40, 1617 ± 2.84 mg / dL; p = 0.000. HDL mean value of K1 (65.8950 ± 1.99 mg / dL, K2 (24.3233 ± 1.44 mg / dL, K3 (73.2300 ± 1.92 mg / dL, and K4 (54, 9550 ± 2.04 mg / dL; p= 0.000. Conclusion: Water from boiled cloud ear fungus decreases the serum total cholesterol and LDL, 06006 increases serum HDL levels of Wistar rats that has been given reused cooking oil.

  12. The Effect of Cloud Ear Fungus (Auricularia polytricha) on Serum Total Cholesterol, LDL And HDL Levels on Wistar Rats Induced by Reused Cooking Oil

    Science.gov (United States)

    Budinastiti, Ratih; Sunoko, Henna Rya; Widiastiti, Nyoman Suci

    2018-02-01

    The usage of reused cooking oil affects the increase of serum total cholesterol (TC) and LDL, also the decrease of serum HDL. This condition escalates the risk of atherosclerosis, which could lead to the incidence of cardiovascular disease. Cloud ear fungus is a natural antioxidant that contains polysaccharides, flavonoids, niacin, and vitamin C, which can improve the lipid profiles. Objective of this research is to analyze the impact of water from boiled cloud ear fungus on total cholesterol, LDL, and HDL level of Wistar rats that have been given reused cooking oil. This study is a true experimental research with post test only control group design, using 12 weeks-aged male Wistar rats (n = 24) that were randomly divided into 4 groups. K1 as the negative control, K2 was given reused cooking oil and standard diet, K3 was given water from boiled cloud ear fungus and standard diet, and K4 was given reused cooking oil, water from boiled cloud ear fungus and standard diet. Serum total cholesterol, LDL, and HDL levels were measured by the CHOD-PAP method after 28 days treatment. The study showed that TC mean value of K1 (80.2217 ± 3.61 mg / dL), K2 (195.8483 ± 5.47 mg / dL), K3 (75.5800 ± 4.02 mg / dL), and K4 (110.8683 ± 5.82 mg / dL); p = 0.000. LDL mean value of K1 (29.9200 ± 1.53 mg / dL), K2 (78.4167 ± 1.77 mg / dL), K3 (24.3167 ± 1.77 mg / dL), and K4 (40, 1617 ± 2.84 mg / dL); p = 0.000. HDL mean value of K1 (65.8950 ± 1.99 mg / dL), K2 (24.3233 ± 1.44 mg / dL), K3 (73.2300 ± 1.92 mg / dL), and K4 (54, 9550 ± 2.04 mg / dL); p= 0.000. Conclusion: Water from boiled cloud ear fungus decreases the serum total cholesterol and LDL, 06006 increases serum HDL levels of Wistar rats that has been given reused cooking oil.

  13. Interferon gamma-inducible protein 16 (IFI16 and anti-IFI16 antibodies in primary Sjögren’s syndrome: findings in serum and minor salivary glands

    Directory of Open Access Journals (Sweden)

    A. Alunno

    2016-02-01

    Full Text Available The interferon (IFN signature, namely the overexpression of IFN-inducible genes is a crucial aspect in the pathogenesis of primary Sjögren’s syndrome (pSS. The IFN-inducible IFI16 protein, normally expressed in cell nuclei, may be overexpressed, mislocalized in the cytoplasm and secreted in the extracellular milieu in several autoimmune disorders including pSS. This leads to tolerance breaking to this self-protein and development of anti-IFI16 antibodies. The aim of this study was to identify pathogenic and clinical significance of IFI16 and anti-IFI16 autoantibodies in pSS. IFI16 and anti-IFI16 were assessed in the serum of 30 pSS patients and one-hundred healthy donors (HD by ELISA. IFI16 was also evaluated in 5 minor salivary glands (MSGs of pSS patients and 5 MSGs of non-pSS patients with sicca symptoms by immunohistochemistry. Normal MSGs do not constitutively express IFI16. Conversely, in pSS-MSGs a marked expression and cytoplasmic mislocalization of IFI16 by epithelial cells was observed with infiltrations in lymphocytes and peri/ intra-lesional endothelium. pSS patients display higher serum levels of both IFI16 and anti-IFI16 autoantibodies compared to HD. Our data suggest that IFI16 protein may be involved in the initiation and perpetuation of glandular inflammation occurring in pSS.

  14. Real-time monitoring of airborne beryllium, at OSHA limit levels, by time-resolved laser-induced breakdown spectroscopy

    International Nuclear Information System (INIS)

    Radziemski, L.J.; Loree, T.R.; Cremers, D.A.

    1982-01-01

    Real-time detection of beryllium particulate is being investigated by the new technique of laser-induced breakdown spectroscopy. For beryllium detection we monitor the 313.1-nm feature of once ionized beryllium (Be II). Numerous publications describe the technique, our beryllium results, and other applications. Here we summarize the important points and describe our experiments with beryllium

  15. Biological constraints limit the use of rapamycin-inducible FKBP12-Inp54p for depleting PIP2 in dorsal root ganglia neurons.

    Science.gov (United States)

    Coutinho-Budd, Jaeda C; Snider, Samuel B; Fitzpatrick, Brendan J; Rittiner, Joseph E; Zylka, Mark J

    2013-09-08

    Rapamycin-induced translocation systems can be used to manipulate biological processes with precise temporal control. These systems are based on rapamycin-induced dimerization of FK506 Binding Protein 12 (FKBP12) with the FKBP Rapamycin Binding (FRB) domain of mammalian target of rapamycin (mTOR). Here, we sought to adapt a rapamycin-inducible phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phosphatase (Inp54p) system to deplete PIP2 in nociceptive dorsal root ganglia (DRG) neurons. We genetically targeted membrane-tethered CFP-FRBPLF (a destabilized FRB mutant) to the ubiquitously expressed Rosa26 locus, generating a Rosa26-FRBPLF knockin mouse. In a second knockin mouse line, we targeted Venus-FKBP12-Inp54p to the Calcitonin gene-related peptide-alpha (CGRPα) locus. We hypothesized that after intercrossing these mice, rapamycin treatment would induce translocation of Venus-FKBP12-Inp54p to the plasma membrane in CGRP+ DRG neurons. In control experiments with cell lines, rapamycin induced translocation of Venus-FKBP12-Inp54p to the plasma membrane, and subsequent depletion of PIP2, as measured with a PIP2 biosensor. However, rapamycin did not induce translocation of Venus-FKBP12-Inp54p to the plasma membrane in FRBPLF-expressing DRG neurons (in vitro or in vivo). Moreover, rapamycin treatment did not alter PIP2-dependent thermosensation in vivo. Instead, rapamycin treatment stabilized FRBPLF in cultured DRG neurons, suggesting that rapamycin promoted dimerization of FRBPLF with endogenous FKBP12. Taken together, our data indicate that these knockin mice cannot be used to inducibly deplete PIP2 in DRG neurons. Moreover, our data suggest that high levels of endogenous FKBP12 could compete for binding to FRBPLF, hence limiting the use of rapamycin-inducible systems to cells with low levels of endogenous FKBP12.

  16. The Effect of Hydroalcoholic Extract of Glycyrrhizaglabra L. (licorice Root on Serum Level of Glucose, Triglyceride and Cholesterol in Polycystic Ovary Syndrome Induced by Letrozole in Rats

    Directory of Open Access Journals (Sweden)

    F Barazesh

    2016-05-01

    Full Text Available Background & aim: Polycystic ovary syndrome (PCOS is the most common endocrine disorder which effects 15.6 %  of women in Iran. Licorice (Glycyrrhizaglabra L. has phytoestrogenic and anti-diabetic effects. The aim of this study was to investigate the effects of hydro-alcoholic Licorice root extract on blood sugar, triglycerides and cholesterol in the rats with PCOS. Methods: In the present experimental study, 50 female puber Sprague dawley (180±20 gr rats with regular sexual cycle were entered in the study.  Studied groups included: first, the Normal group, receiving carrier (normal saline (2 ml/kg daily orally for 21 days. Then, the letrozole group which received letrozole (1 mg/kg dissolved in normal saline (2 ml/kg for 21 days and then normal saline (2 ml/kg daily orally for 30 days. The last groups, Treatment groups 1 and 2, which received letrozole (1 mg/kg dissolved in normal saline (2 ml/kg for 21 days then hydroalcoholic extract of Licorice root (200 and 400 mg/kg dissolved in normal saline (2 ml/kg daily, orally for 30 days respectively. To conclude, blood samples were collected from the heart and also the serum level of blood sugar, triglyceride and cholesterol was measured. The data were analyzed using one-way ANOVA (p< 0.05. Results: The mean serum level of blood sugar increased in the Letrozole group compared to the normal group and decreased in the treatment groups compared to Letrozole group (p< 0.05. No statistically significant differences were seen in mean of serum level of triglyceride and cholesterol between all groups. Conclusion: The licoricecan extract improved the adverse side-effects caused by diabetese in polycystic ovary syndrome However, its effect on dyslipidemia in patients requiring further investigations.

  17. Modification of Death rate and Disturbances induced in the Levels of serum total Lipids and free fatty acids of irradiated rats by ascorbic acid and serotonin

    International Nuclear Information System (INIS)

    Mahdy, A.M.; Saada, H.N.; Osama, Z.S.

    1999-01-01

    Intraperitoneal injection of normal rats with ascorbic acid (10 mg/100 g body weight ) or serotonin (2 mg/100 g body weight) had no harmful effect on the life span. Moreover, the levels of serum total lipids and free fatty acids did not show any significant changes at 3, 7, 10 and 14 days after injection. Administration of ascorbic acid or serotonin to rats at the pre mentioned doses, 15 minutes, before gamma irradiation at 7.5 Gy (single dose ) improved the survival time of rats and the hyperlipemic state recorded after radiation exposure

  18. The Suppression of Adjuvant-induced Inflammation and the Inhibition of the Serum and Tissue IL-17, TNF-α and IL-1β levels by Thymol and Carvacrol

    Directory of Open Access Journals (Sweden)

    Nasser Gholijani

    2017-06-01

    Full Text Available Background and Aim: Thymol and carvacrol are two important components of thyme that have multiple medicinal uses. This study investigates the in vivo effects of these natural products on adjuvant-induced inflammation and secretion of interleukin (IL-17 and key inflammatory cytokines in rats. Materials and Methods: We injected complete Freund’s adjuvant (CFA into the hind paws of rats in order to induce inflammation. Each of the CFA-treated rat groups received gavages of thymol, carvacrol, or vehicle (CFA-only group. Rats’ paws and ankle edema were measured and then we were able to determine an inflammatory score based on the results. After 72 h of inflammation induction, sera were collected and subsequently inflamed tissue extracts were prepared for cytokine assay by ELISA. Results: Both components significantly decreased paw edema in rats (p<0.01. Thymol decreased ankle edema to 61.6% of edema in CFA-only rats (p<0.001. We observed a decreased inflammatory score in the thymol and carvacrol-treated rats. The evaluation of the tissue and serum inflammatory cytokine levels showed that both components decreased tumor necrosis factor (TNF-α levels (p<0.05. Thymol and carvacrol reduced interleukin (IL-1β serum and tissue levels, respectively. These components reduced tissue levels of IL-17 from 148.4±13.4pg/ml in CFA-only rats to 90.1±18.9pg/ml (thymol and 82.3±9.2pg/ml (carvacrol. Both components decreased serum IL-17 levels in rats (p<0.05. In comparison, the anti-inflammatory drug, indomethacin, reduced the inflammatory score and decreased tissue TNF-α and IL-1β levels but did not affect IL-17 production. Conclusion: Carvacrol and thymol could relieve inflammation symptoms possibly by downregulating serum and tissue IL-17 expression in addition to key pro-inflammatory cytokines, TNFα and IL-1β.

  19. Serum Removal from Culture Induces Growth Arrest, Ploidy Alteration, Decrease in Infectivity and Differential Expression of Crucial Genes in Leishmania infantum Promastigotes.

    Directory of Open Access Journals (Sweden)

    Pedro J Alcolea

    Full Text Available Leishmania infantum is one of the species responsible for visceral leishmaniasis. This species is distributed basically in the Mediterranean basin. A recent outbreak in humans has been reported in Spain. Axenic cultures are performed for most procedures with Leishmania spp. promastigotes. This model is stable and reproducible and mimics the conditions of the gut of the sand fly host, which is the natural environment of promastigote development. Culture media are undefined because they contain mammalian serum, which is a rich source of complex lipids and proteins. Serum deprivation slows down the growth kinetics and therefore, yield in biomass. In fact, we have confirmed that the growth rate decreases, as well as infectivity. Ploidy is also affected. Regarding the transcriptome, a high-throughput approach has revealed a low differential expression rate but important differentially regulated genes. The most remarkable profiles are: up-regulation of the GINS Psf3, the fatty acyl-CoA synthase (FAS1, the glyoxylase I (GLO1, the hydrophilic surface protein B (HASPB, the methylmalonyl-CoA epimerase (MMCE and an amastin gene; and down-regulation of the gPEPCK and the arginase. Implications for metabolic adaptations, differentiation and infectivity are discussed herein.

  20. Serum Removal from Culture Induces Growth Arrest, Ploidy Alteration, Decrease in Infectivity and Differential Expression of Crucial Genes in Leishmania infantum Promastigotes.

    Science.gov (United States)

    Alcolea, Pedro J; Alonso, Ana; Moreno-Izquierdo, Miguel A; Degayón, María A; Moreno, Inmaculada; Larraga, Vicente

    2016-01-01

    Leishmania infantum is one of the species responsible for visceral leishmaniasis. This species is distributed basically in the Mediterranean basin. A recent outbreak in humans has been reported in Spain. Axenic cultures are performed for most procedures with Leishmania spp. promastigotes. This model is stable and reproducible and mimics the conditions of the gut of the sand fly host, which is the natural environment of promastigote development. Culture media are undefined because they contain mammalian serum, which is a rich source of complex lipids and proteins. Serum deprivation slows down the growth kinetics and therefore, yield in biomass. In fact, we have confirmed that the growth rate decreases, as well as infectivity. Ploidy is also affected. Regarding the transcriptome, a high-throughput approach has revealed a low differential expression rate but important differentially regulated genes. The most remarkable profiles are: up-regulation of the GINS Psf3, the fatty acyl-CoA synthase (FAS1), the glyoxylase I (GLO1), the hydrophilic surface protein B (HASPB), the methylmalonyl-CoA epimerase (MMCE) and an amastin gene; and down-regulation of the gPEPCK and the arginase. Implications for metabolic adaptations, differentiation and infectivity are discussed herein.

  1. Limitations of Using IL-17A and IFN-γ-Induced Protein 10 to Detect Bovine Tuberculosis

    Science.gov (United States)

    Xin, Ting; Gao, Xintao; Yang, Hongjun; Li, Pingjun; Liang, Qianqian; Hou, Shaohua; Sui, Xiukun; Guo, Xiaoyu; Yuan, Weifeng; Zhu, Hongfei; Ding, Jiabo; Jia, Hong

    2018-01-01

    Bovine tuberculosis (bTB) is primarily caused by infection with Mycobacterium bovis, which belongs to the Mycobacterium tuberculosis complex. The airborne route is considered the most common for transmission of M. bovis, and more than 15% of cattle with bTB shed the Mycobacterium, which can be detect by nested PCR to amplify mycobacterial mpb70 from a nasal swab from a cow. To screen for cytokines fostering early and accurate detection of bTB, peripheral blood mononuclear cells were isolated from naturally M. bovis-infected, experimentally M. bovis 68002-infected, and uninfected cattle, then these cells were stimulated by PPD-B, CFP-10-ESAT-6 (CE), or phosphate-buffered saline (PBS) for 6 h. The levels of interferon gamma (IFN-γ), IFN-γ-induced protein 10 (IP-10), IL-6, IL-12, IL-17A, and tumor necrosis factor alpha mRNA were measured using real-time PCR. To explore the cytokines associated with different periods of M. bovis infection, cattle were divided into three groups: PCR-positive, PCR-negative, and uninfected using the tuberculin skin test, CFP-10/ESAT-6/TB10.4 protein cocktail-based skin test, IFN-γ release assay (IGRA), CFP-10/ESAT-6 (CE)-based IGRA, and nested PCR. The expression of IP-10, IL-17A, and IFN-γ proteins induced by PPD-B, CE, or PBS was detected by ELISA. The results showed that levels of PPD-B-stimulated IL-17A and IP-10 (mRNA and protein), and CE-induced IP-10 (mRNA and protein) were significantly higher in cattle naturally or experimentally infected with M. bovis than in those that were uninfected. The levels of PPD-B- or CE-induced IL-17A and IP-10 (protein) could be used to differentiate M. bovis-infected calves from uninfected ones for 6 to 30 weeks post-infection, whereas PPD-B- and CE-induced IP-10 and IL-17A mRNA expression could be used to differentiate M. bovis-infected calves from uninfected ones between 6 and 58 weeks post-infection. However, CE-induced IL-17A (protein) was not a reliable indicator of M. bovis infection

  2. Human serum activates CIDEB-mediated lipid droplet enlargement in hepatoma cells

    International Nuclear Information System (INIS)

    Singaravelu, Ragunath; Lyn, Rodney K.; Srinivasan, Prashanth; Delcorde, Julie; Steenbergen, Rineke H.; Tyrrell, D. Lorne; Pezacki, John P.

    2013-01-01

    Highlights: •Human serum induced differentiation of hepatoma cells increases cellular lipid droplet (LD) size. •The observed increase in LD size correlates with increased PGC-1α and CIDEB expression. •Induction of CIDEB expression correlates with rescue of VLDL secretion and loss of ADRP. •siRNA knockdown of CIDEB impairs the human serum mediated increase in LD size. •This system represents a cost-efficient model to study CIDEB’s role in lipid biology. -- Abstract: Human hepatocytes constitutively express the lipid droplet (LD) associated protein cell death-inducing DFFA-like effector B (CIDEB). CIDEB mediates LD fusion, as well as very-low-density lipoprotein (VLDL) maturation. However, there are limited cell culture models readily available to study CIDEB’s role in these biological processes, as hepatoma cell lines express negligible levels of CIDEB. Recent work has highlighted the ability of human serum to differentiate hepatoma cells. Herein, we demonstrate that culturing Huh7.5 cells in media supplemented with human serum activates CIDEB expression. This activation occurs through the induced expression of PGC-1α, a positive transcriptional regulator of CIDEB. Coherent anti-Stokes Raman scattering (CARS) microscopy revealed a correlation between CIDEB levels and LD size in human serum treated Huh7.5 cells. Human serum treatment also resulted in a rapid decrease in the levels of adipose differentiation-related protein (ADRP). Furthermore, individual overexpression of CIDEB was sufficient to down-regulate ADRP protein levels. siRNA knockdown of CIDEB revealed that the human serum mediated increase in LD size was CIDEB-dependent. Overall, our work highlights CIDEB’s role in LD fusion, and presents a new model system to study the PGC-1α/CIDEB pathway’s role in LD dynamics and the VLDL pathway

  3. Human serum activates CIDEB-mediated lipid droplet enlargement in hepatoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Singaravelu, Ragunath [Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Lyn, Rodney K. [Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Srinivasan, Prashanth [National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Delcorde, Julie [Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Steenbergen, Rineke H.; Tyrrell, D. Lorne [Department of Medical Microbiology and Immunology, University of Alberta (Canada); Li Ka Shing Institute of Virology, Katz Centre for Pharmacy and Health Research, Edmonton, Alberta T6G 2S2 (Canada); Pezacki, John P., E-mail: John.Pezacki@nrc-cnrc.gc.ca [Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada)

    2013-11-15

    Highlights: •Human serum induced differentiation of hepatoma cells increases cellular lipid droplet (LD) size. •The observed increase in LD size correlates with increased PGC-1α and CIDEB expression. •Induction of CIDEB expression correlates with rescue of VLDL secretion and loss of ADRP. •siRNA knockdown of CIDEB impairs the human serum mediated increase in LD size. •This system represents a cost-efficient model to study CIDEB’s role in lipid biology. -- Abstract: Human hepatocytes constitutively express the lipid droplet (LD) associated protein cell death-inducing DFFA-like effector B (CIDEB). CIDEB mediates LD fusion, as well as very-low-density lipoprotein (VLDL) maturation. However, there are limited cell culture models readily available to study CIDEB’s role in these biological processes, as hepatoma cell lines express negligible levels of CIDEB. Recent work has highlighted the ability of human serum to differentiate hepatoma cells. Herein, we demonstrate that culturing Huh7.5 cells in media supplemented with human serum activates CIDEB expression. This activation occurs through the induced expression of PGC-1α, a positive transcriptional regulator of CIDEB. Coherent anti-Stokes Raman scattering (CARS) microscopy revealed a correlation between CIDEB levels and LD size in human serum treated Huh7.5 cells. Human serum treatment also resulted in a rapid decrease in the levels of adipose differentiation-related protein (ADRP). Furthermore, individual overexpression of CIDEB was sufficient to down-regulate ADRP protein levels. siRNA knockdown of CIDEB revealed that the human serum mediated increase in LD size was CIDEB-dependent. Overall, our work highlights CIDEB’s role in LD fusion, and presents a new model system to study the PGC-1α/CIDEB pathway’s role in LD dynamics and the VLDL pathway.

  4. Protein electrophoresis - serum

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003540.htm Protein electrophoresis - serum To use the sharing features on ... JavaScript. This lab test measures the types of protein in the fluid (serum) part of a blood ...

  5. Inhibition of the αvβ6 integrin leads to limited alteration of TGF-α-induced pulmonary fibrosis

    Science.gov (United States)

    Madala, Satish K.; Korfhagen, Thomas R.; Schmidt, Stephanie; Davidson, Cynthia; Edukulla, Ramakrishna; Ikegami, Machiko; Violette, Shelia M.; Weinreb, Paul H.; Sheppard, Dean

    2014-01-01

    A number of growth factors and signaling pathways regulate matrix deposition and fibroblast proliferation in the lung. The epidermal growth factor receptor (EGFR) family of receptors and the transforming growth factor-β (TGF-β) family are active in diverse biological processes and are central mediators in the initiation and maintenance of fibrosis in many diseases. Transforming growth factor-α (TGF-α) is a ligand for the EGFR, and doxycycline (Dox)-inducible transgenic mice conditionally expressing TGF-α specifically in the lung epithelium develop progressive fibrosis accompanied with cachexia, changes in lung mechanics, and marked pleural thickening. Although recent studies demonstrate that EGFR activation modulates the fibroproliferative effects involved in the pathogenesis of TGF-β induced pulmonary fibrosis, in converse, the direct role of EGFR induction of the TGF-β pathway in the lung is unknown. The αvβ6 integrin is an important in vivo activator of TGF-β activation in the lung. Immunohistochemical analysis of αvβ6 protein expression and bronchoalveolar analysis of TGF-β pathway signaling indicates activation of the αvβ6/TGF-β pathway only at later time points after lung fibrosis was already established in the TGF-α model. To determine the contribution of the αvβ6/TGF-β pathway on the progression of established fibrotic disease, TGF-α transgenic mice were administered Dox for 4 wk, which leads to extensive fibrosis; these mice were then treated with a function-blocking anti-αvβ6 antibody with continued administration of Dox for an additional 4 wk. Compared with TGF-α transgenic mice treated with control antibody, αvβ6 inhibition significantly attenuated pleural thickening and altered the decline in lung mechanics. To test the effects of genetic loss of the β6 integrin, TGF-α transgenic mice were mated with β6-null mice and the degree of fibrosis was compared in adult mice following 8 wk of Dox administration. Genetic ablation of

  6. Characterization of the up-down asymmetry of density fluctuations induced by a lower modular limiter in Tore Supra

    International Nuclear Information System (INIS)

    Fenzi, C.; Devynck, P.; Garbet, X.; Antar, G.; Capes, H.; Laviron, C.; Truc, A.; Gervais, F.; Hennequin, P.; Quemeneur, A.

    1999-01-01

    In magnetic fusion devices, the effect of plasma facing components on plasma turbulence is a key issue for several reasons. Firstly, the edge turbulence controls the power deposition on plasma facing components. Secondly, the possible influence of the edge parameters on the core fluctuations is a central question, since the core turbulent transport is responsible for the confinement degradation. It is in practice difficult to determine whether the plasma core influences the edge, or the opposite. We show here that spatial edge asymmetries of density fluctuations, and particularly up-down asymmetries, provide a powerful tool to investigate this problem. In TORE SUPRA, previous scaling analyses with various plasma parameters have emphasized that a very clear effect on the asymmetry level appears when the plasma leans on the lower modular limiter located close to the measurement chord. We present here recent measurement results concerning that specific case. They tend to show that the limiter configuration has some effect on the core turbulence. (authors)

  7. The Effects of Hydro-alcoholic Extract of Raspberry Fruit on Ovarian follicles and serum parameters in Poly Cystic Ovary Syndrome-Induced Rat

    Directory of Open Access Journals (Sweden)

    mohamad Nabiuni

    2015-02-01

    Full Text Available Background & aim: Polycystic Ovary Syndrome is an endocrine disorder leading to lack of ovulation and has inflammatory aspects. Raspberry extract, with possession of bioactive compounds such as Anthocyanins and polyphenols, have anti-inflammatory properties. In this study, the anti-inflammatory effects of raspberry extract on the development process of ovarian follicles and hormones level of pituitary, ovarian, and liver in rats suffering from PCOS were examined. Methods: In the present experimental study, 120 adult Wistar rats were divided into three groups of control, PCOS, and treated with raspberry. The induction of syndrome was done by 2mg Estradiol valerate. After a period of 60 days, 100, 150 and 200 mg/kg BW raspberry extract was injected intraperitoneally. Control group received no injection. Ten days after the last injection, all groups were anesthetized by chloroform and the serum and ovary of all groups were collected in order to investigate the histological and serologic changes. Data obtained were analyzed by using one-way ANOVA. Results: Raspberry-treated group showed a significant decrease in the hormones rate of testosterone, estradiol, LH, and CRP compared with PCOS (p<0.05, whereas a significant increase was observed in the serum level of Progesterone and FSH (p<0.05. A significant increase was observed in the number of corpus luteum and granulosa layer thickness in the raspberry-treated group compared with PCOS (p<0.05. Conclusion: The results demonstrated that the antioxidant and anti-inflammatory effects of raspberry extract was effective on regulating the hormones, CRPand improving of cysts which led to the initiation of ovulation.

  8. One-night sleep deprivation induces changes in the DNA methylation and serum activity indices of stearoyl-CoA desaturase in young healthy men.

    Science.gov (United States)

    Skuladottir, Gudrun Valgerdur; Nilsson, Emil Karl; Mwinyi, Jessica; Schiöth, Helgi Birgir

    2016-08-26

    Sleep deprivation has been associated with obesity among adults, and accumulating data suggests that stearoyl-CoA desaturase 1 (SCD1) expression has a relevant impact on fatty acid (FA) composition of lipid pools and obesity. The aim of this study was to investigate the effect of one-night total sleep deprivation (TSD) on DNA methylation in the 5'-prime region of SCD1, and whether detected changes in DNA methylation are associated with SCD activity indices (product to precursor FA ratios; 16:1n-7/16:0 and 18:1n-9/18:0) derived from serum phospholipids (PL). Sixteen young, normal-weight, healthy men completed two study sessions, one with one-night TSD and one with one-night normal sleep (NS). Sleep quality and length was assessed by polysomnography, and consisted of electroencephalography, electrooculography, and electromyography. Fasting whole blood samples were collected on the subsequent morning for analysis of DNA methylation and FAs in serum PL. Linear regression analyses were performed to assess the association between changes in DNA methylation and SCD activity indices. Three CpG sites close to the transcription start site (TSS) of SCD1 (cg00954566, cg24503796, cg14089512) were significantly differentially methylated in dependency of sleep duration (-log10 P-value > 1.3). Both SCD-16 and SCD-18 activity indices were significantly elevated (P DNA methylation changes of the three mentioned probes in the 5' region of SCD1. Our results suggest a relevant link between TSD, hepatic SCD1 expression and de-novo fatty acid synthesis via epigenetically driven regulatory mechanisms.

  9. Age-associated and deslorelin-induced declines in serum anti-Müllerian hormone concentrations in female cheetahs, Acinonyx jubatus.

    Science.gov (United States)

    Place, Ned J; Crosier, Adrienne E; Comizzoli, Pierre; Nagashima, Jennifer B; Haefele, Holly; Schmidt-Küntzel, Anne; Marker, Laurie L

    2017-09-01

    Anti-Müllerian hormone (AMH) is widely used in human medicine to non-invasively estimate the size of the ovarian follicle reserve and to predict the ovarian response to gonadotropin stimulation in the context of assisted reproductive technologies (e.g., IVF). These applications of AMH testing have recently expanded to non-human mammals, with production animals, such as cows, goats and sheep being the primary focus of AMH research. However, few investigations have involved exotic species, and in particular carnivores. In this study, we measured AMH concentrations (0.078-3.078ng/mL) in archived serum samples that had been collected from 36 adult female cheetahs across their reproductive lifespan (2-15years of age). Similar to other mammals, AMH concentration in cheetahs declined with age, and its variability among females of the same age was considerable. The rates at which AMH declined over time in individual cheetahs were also highly variable. Five cheetahs had been contracepted with the long-acting GnRH agonist deslorelin for 6-18months prior to sample collection, and their AMH concentrations were relatively low compared to untreated females. In this first study of AMH in an exotic carnivore, the findings demonstrate that the age-associated decline in AMH is highly variable and that deslorelin appears to suppress AMH concentration in serum. Owing to the increased use of assisted reproductive technologies in ex situ populations of threatened and endangered species, such as cheetahs, the present study's findings will need to be taken into consideration if AMH is to be used successfully to optimize breeding management decisions in exotic species. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. The preliminary observation of the changes of β-actin,coagulant and inflammatory factors in mice serum induced by γ rays irradiation

    International Nuclear Information System (INIS)

    Zhang Qingzhi; Wang Jia; Cheng Ying; Li Mingjuan; Min Rui

    2010-01-01

    In order to learn the effect of β-actin in acute radiation injury, the changeable pattern with time of plasma β-actin, PT, APTT, FIB and IL-8 in mice spleen tissue exposed to 6 Gy γ-rays radiation was investigated.Blood and spleen were collected at immediate, 1, 2, 3, 4, 7 and 14 d after irradiation, respectively. The contents of blood β-actin were detected by magnetic bead separation enzyme-linked immunosorbent. An STAGO blood coagulation instrument was used to determine PT, APTT and FIB. DNA expression of IL-8 was detected by real time-PCR analyzer. The results show that the level of β-actin in serum of irradiated mice is higher than that of normal control group at all different post-irradiation time points although the change of β-actin in serum of irradiated mice with time schedule shows a pattern which increases within 1d and declines beyond 1d. The trend of the changes in plasma PT, APTT, FIB and in spleen IL-8 and time pattern of these changes are similar to that in plasma β-actin in irradiated mice. The difference in values and the time phase between plasma β-actin and other indexes is the reaching time of peak values and the declining levels of the values. These results are valuable for studying the role of β-actin in acute radiation sickness pathology process and can be used to explore new factors influencing and regulating pathology process. (authors)

  11. Global Energy Development and Climate-Induced Water Scarcity—Physical Limits, Sectoral Constraints, and Policy Imperatives

    Directory of Open Access Journals (Sweden)

    Christopher A. Scott

    2015-08-01

    Full Text Available The current accelerated growth in demand for energy globally is confronted by water-resource limitations and hydrologic variability linked to climate change. The global spatial and temporal trends in water requirements for energy development and policy alternatives to address these constraints are poorly understood. This article analyzes national-level energy demand trends from U.S. Energy Information Administration data in relation to newly available assessments of water consumption and life-cycle impacts of thermoelectric generation and biofuel production, and freshwater availability and sectoral allocations from the U.N. Food and Agriculture Organization and the World Bank. Emerging, energy-related water scarcity flashpoints include the world’s largest, most diversified economies (Brazil, India, China, and USA among others, while physical water scarcity continues to pose limits to energy development in the Middle East and small-island states. Findings include the following: (a technological obstacles to alleviate water scarcity driven by energy demand are surmountable; (b resource conservation is inevitable, driven by financial limitations and efficiency gains; and (c institutional arrangements play a pivotal role in the virtuous water-energy-climate cycle. We conclude by making reference to coupled energy-water policy alternatives including water-conserving energy portfolios, intersectoral water transfers, virtual water for energy, hydropower tradeoffs, and use of impaired waters for energy development.

  12. On the formation of limit cycle of the friction-induced stick-slip vibration in oilwell drillstring

    Directory of Open Access Journals (Sweden)

    Xiaohua Zhu

    2015-03-01

    Full Text Available In this paper, the stick-slip vibration in oilwell drillstring is studied. The drilling system is modelled as a lumped-parameter torsional pendulum and the interaction between the drill bit and the rock is treated as Coulomb friction. Equation of motion of the drill bit is established and the dynamic responses of the drill bit are obtained. A drilling system with the drillstring length 3000 m is analysed, in which the system parameters are selected by reference to the actual drilling situation. After the slip vibrations in the initial stage, final state of the drill bit is a stable stick-slip vibration of which the limit cycle is a closed loop. In order to find the stability of the limit cycle corresponds to the periodically stick-slip vibration, different initial conditions for the drill bit are studied. Results show that the drill bit will lead to a periodic motion and the phase trajectories ultimately converge to the same limit cycle corresponds to stable stick-slip vibration.

  13. Serum iron test

    Science.gov (United States)

    Fe+2; Ferric ion; Fe++; Ferrous ion; Iron - serum; Anemia - serum iron; Hemochromatosis - serum iron ... A blood sample is needed. Iron levels are highest in the morning. Your health care provider will likely have you do this test in the morning.

  14. Role of dystroglycan in limiting contraction-induced injury to the sarcomeric cytoskeleton of mature skeletal muscle.

    Science.gov (United States)

    Rader, Erik P; Turk, Rolf; Willer, Tobias; Beltrán, Daniel; Inamori, Kei-Ichiro; Peterson, Taylor A; Engle, Jeffrey; Prouty, Sally; Matsumura, Kiichiro; Saito, Fumiaki; Anderson, Mary E; Campbell, Kevin P

    2016-09-27

    Dystroglycan (DG) is a highly expressed extracellular matrix receptor that is linked to the cytoskeleton in skeletal muscle. DG is critical for the function of skeletal muscle, and muscle with primary defects in the expression and/or function of DG throughout development has many pathological features and a severe muscular dystrophy phenotype. In addition, reduction in DG at the sarcolemma is a common feature in muscle biopsies from patients with various types of muscular dystrophy. However, the consequence of disrupting DG in mature muscle is not known. Here, we investigated muscles of transgenic mice several months after genetic knockdown of DG at maturity. In our study, an increase in susceptibility to contraction-induced injury was the first pathological feature observed after the levels of DG at the sarcolemma were reduced. The contraction-induced injury was not accompanied by increased necrosis, excitation-contraction uncoupling, or fragility of the sarcolemma. Rather, disruption of the sarcomeric cytoskeleton was evident as reduced passive tension and decreased titin immunostaining. These results reveal a role for DG in maintaining the stability of the sarcomeric cytoskeleton during contraction and provide mechanistic insight into the cause of the reduction in strength that occurs in muscular dystrophy after lengthening contractions.

  15. Laser-induced Ni(Pt) germanosilicide formation through a self-limiting melting phenomenon on Si1-xGex/Si heterostructure

    International Nuclear Information System (INIS)

    Setiawan, Y.; Lee, P. S.; Pey, K. L.; Wang, X. C.; Lim, G. C.; Tan, B. L.

    2007-01-01

    Laser-induced Ni(Pt) germanosilicide formation on Si 1-x Ge x /Si substrate has resulted in the formation of smooth Ni(Pt) germanosilicide/Si interface with minimum interface roughness which is preferred as a contact material. A confined (self-limiting) melting phenomenon occurred during the laser-induced silicidation process at laser fluence of 0.4 J cm -2 (just at the melting threshold of the sample). This phenomenon is caused by significant differences in material properties of Si 1-x Ge x alloy and Si substrates. Formation of highly textured [Ni 1-v (Pt) v ](Si 1-y Ge y ) phase was detected in the sample after 20-pulsed laser thermal annealing at 0.4 J cm -2 . The formation mechanism of the Ni(Pt) monogermanosilicide is discussed

  16. Vitrectomy with internal limiting membrane peeling versus inverted internal limiting membrane flap technique for macular hole-induced retinal detachment: a systematic review of literature and meta-analysis.

    Science.gov (United States)

    Yuan, Jing; Zhang, Ling-Lin; Lu, Yu-Jie; Han, Meng-Yao; Yu, Ai-Hua; Cai, Xiao-Jun

    2017-11-28

    To evaluate the effects on vitrectomy with internal limiting membrane (ILM) peeling versus vitrectomy with inverted internal limiting membrane flap technique for macular hole-induced retinal detachment (MHRD). Pubmed, Cochrane Library, and Embase were systematically searched for studies that compared ILM peeling with inverted ILM flap technique for macular hole-induced retinal detachment. The primary outcomes are the rate of retinal reattachment and the rate of macular hole closure 6 months later after initial surgery, the secondary outcome is the postoperative best-corrected visual acuity (BCVA) 6 months later after initial surgery. Four studies that included 98 eyes were selected. All the included studies were retrospective comparative studies. The preoperative best-corrected visual acuity was equal between ILM peeling and inverted ILM flap technique groups. It was indicated that the rate of retinal reattachment (odds ratio (OR) = 0.14, 95% confidence interval (CI):0.03 to 0.69; P = 0.02) and macular hole closure (OR = 0.06, 95% CI:0.02 to 0.19; P peeling. However, there was no statistically significant difference in postoperative best-corrected visual acuity (mean difference (MD) 0.18 logarithm of the minimum angle of resolution; 95% CI -0.06 to 0.43 ; P = 0.14) between the two surgery groups. Compared with ILM peeling, vitrectomy with inverted ILM flap technique resulted significantly higher of the rate of retinal reattachment and macular hole closure, but seemed does not improve postoperative best-corrected visual acuity.

  17. Evaluation of changes in serum chemistry in association with feed withdrawal or high dose oral gavage with Dextran Sodium Sulfate (DSS) induced gut leakage in broiler chickens

    Science.gov (United States)

    Dextran sodium sulfate (DSS) has been shown to be effective at inducing enteric inflammation in broiler chickens, resulting in increased leakage of orally administered fluorescein isothiocyanate dextran to circulation. In a previous study, two doses of DSS (0.45g/dose) administered as oral gavage re...

  18. Improvement in limit of detection in particle induced X-ray emission by means of rise time and pulse shape discrimination

    Energy Technology Data Exchange (ETDEWEB)

    Papp, Tibor E-mail: tibpapp@netscape.nettibpapp@yahoo.ca; Lakatos, Tamas; Nejedly, Zdenek; Campbell, John L

    2002-04-01

    A digital signal processor, based upon high-rate sampling of the preamplifier output, and equipped with rise time and pulse shape discrimination, has been tested in three situations. This processor provided significant improvement of particle induced X-ray emission and X-ray fluorescence detection limits over the state of the art analog processors, depending on the energy and intensity distribution of the X-ray spectra. Additionally it had a superior performance when measurements were performed in an environment of large electronic noise and in large nuclear background environment. It has also improved the reduction of several artifacts in X-ray spectra.

  19. Interleukin-12 induces a Th1-like response to Burkholderia mallei and limited protection in BALB/c mice.

    Science.gov (United States)

    Amemiya, Kei; Meyers, Jennifer L; Trevino, Sylvia R; Chanh, Tran C; Norris, Sarah L; Waag, David M

    2006-02-27

    We evaluated the effect of interleukin (IL)-12 on the immune response to Burkholderia mallei in BALB/c mice. Mice were vaccinated with non-viable B. mallei cells with or without IL-12. There was a seven- to nine-fold increase in IgG2a levels, and a significant increase in the proliferative response and interferon (IFN)-gamma production by splenocytes from mice that received B. mallei and IL-12. We saw an increase in survivors in the groups of mice that received B. mallei and IL-12 when challenged, compared to mice that received only B. mallei or IL-12. The results suggest that IL-12 can enhance the Th1-like immune response to B. mallei and mediate limited protection from a lethal challenge.

  20. Effects of glucose, lactate and basic FGF as limiting factors on the expansion of human induced pluripotent stem cells.

    Science.gov (United States)

    Horiguchi, Ikki; Urabe, Yusuke; Kimura, Keiichi; Sakai, Yasuyuki

    2018-01-01

    Pluripotent stem cells (PSCs) are one of the promising cell sources for tissue engineering and drug screening. However, mass production of induced pluripotent stem cells (iPSCs) is still developing. Especially, a huge amount of culture medium usage causes expensive cost in the mass production process. In this report, we reduced culture medium usage by extending interval of changing culture medium. In parallel, we also increased glucose concentration and supplied heparan sulfate to avoid depletion of glucose and bFGF, respectively. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses showed that reducing medium change frequency increased differentiation marker expressions but high glucose concentration downregulated these expressions. In contrast, heparan sulfate did not prevent differentiation marker expressions. According to analyses of growth rate, cell growth with extended medium change interval was decreased in later stage of log growth phase despite the existence of high glucose concentration and heparan sulfate. This result and culturing iPSCs with lactate showed that the accumulation of excreted lactate decreased the growth rate regardless of pH control. Conclusively, these experiments show that adding glucose and removing lactate are important to expand iPSCs with reduced culture medium usage. This knowledge should be useful to design economical iPSC mass production and differentiation system. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  1. Increasing sensitivity of arc-induced long-period gratings—pushing the fabrication technique toward its limits

    International Nuclear Information System (INIS)

    Smietana, M; Bock, W J; Mikulic, P; Chen, J

    2011-01-01

    This paper presents an investigation of the sensing properties of long-period gratings (LPGs) written with the electric-arc technique in commonly used standard germanium-doped Corning SMF28 and boron co-doped Fibercore PS1250/1500 fibers. In order to increase the sensitivity of the LPGs, we studied and established for each fiber the writing parameters allowing for the coupling of the highest possible order of cladding modes at a resonance wavelength around λ = 1550 nm. The sensitivity of the LPGs to refractive index, to temperature and to hydrostatic pressure was investigated. The experimental results were supported by extensive numerical simulations. Thanks to the well-established and precisely controlled arc-writing process, we were able to reduce the minimum period of the gratings down to 345 and 221 µm, respectively, for LPGs based on the SMF28 and PS1250/1500 fibers. To the best of our knowledge, these are the shortest periods ever achieved for these fibers using the arc-manufacturing technique. The pressure sensitivities of 13 and 220 pm bar −1 are the highest ever measured for LPGs written in the SMF28 and PS1250/1500 fibers, respectively. Moreover, a reduction in the diameters of the SMF28 fiber induced by the arc was found, which significantly affected the distribution of resonances generated by the coupled cladding modes

  2. Spectroscopic analyses on sonocatalytic damage to bovine serum albumin (BSA) induced by ZnO/hydroxylapatite (ZnO/HA) composite under ultrasonic irradiation

    Science.gov (United States)

    Wang, Zhiqiu; Li, Ying; Wang, Jun; Zou, Mingming; Gao, Jingqun; Kong, Yumei; Li, Kai; Han, Guangxi

    ZnO/hydroxylapatite (ZnO/HA) composite with HA molar content of 6.0% was prepared by the method of precipitation and heat-treated at 500 °C for 40 min and was characterized by powder X-ray diffraction (XRD). The sonocatalytic activities of ZnO/HA composite was carried out through the damage of bovine serum albumin (BSA) in aqueous solution. Furthermore, the effects of several factors on the damage of BSA molecules were evaluated by means of UV-vis and fluorescence spectra. Experimental results indicated that the damage degree of BSA aggravated with the increase of ultrasonic irradiation time, irradiation power and ZnO/HA addition amount, but weakened with the increase of solution acidity and ionic strength. In addition, the damage site to BSA was also studied by synchronous fluorescence technology and the damage site was mainly at tryptophan (Trp) residue. This paper provides a valuable reference for driving sonocatalytic method to treat tumor in clinic application.

  3. Serum Starvation-Induced Voltage-Gated Potassium Channel Kv7.5 Expression and Its Regulation by Sp1 in Canine Osteosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Bo Hyung Lee

    2014-01-01

    Full Text Available The KCNQ gene family, whose members encode Kv7 channels, belongs to the voltage-gated potassium (Kv channel group. The roles of this gene family have been widely investigated in nerve and muscle cells. In the present study, we investigated several characteristics of Kv7.5, which is strongly expressed in the canine osteosarcoma cell line, CCL-183. Serum starvation upregulated Kv7.5 expression, and the Kv7 channel opener, flupirtine, attenuated cell proliferation by arresting cells in the G0/G1 phase. We also showed that Kv7.5 knockdown helps CCL-183 cells to proliferate. In an effort to find an endogenous regulator of Kv7.5, we used mithramycin A to reduce the level of the transcription factor Sp1, and it strongly inhibited the induction of Kv7.5 in CCL-183 cells. These results suggest that the activation of Kv7.5 by flupirtine may exert an anti-proliferative effect in canine osteosarcoma. Therefore, Kv7.5 is a possible molecular target for canine osteosarcoma therapy.

  4. Extensive but not Limited Repeated Trials in Passive Avoidance Task Induce Stress-like Symptoms and Affect Memory Function in Rats.

    Science.gov (United States)

    Tabassum, Saiqa; Haider, Saida

    2018-02-10

    Stressful and emotionally arousing experiences are remembered, and previous reports show that repeated exposure to stressful condition enhances emotional learning. However, the usefulness of the repeated exposure depends on the intensity and duration. Although repeated training as a strategy to improve memory performance is receiving increased attention from researchers, repeated training may induce stressful effects that have not yet been considered. The present study investigated whether exposure to repetitive learning trials with limited or extensive durations in a passive avoidance task (PAT) would be beneficial or harmful to emotional memory performance in rats. Rats were exposed to repetitive learning trials for two different durations in the limited exposure (exposure to four repetitive trials) and extensive exposure groups (exposure to 16 repetitive trials) in a single day to compare the impact of both conditions on rat emotional memory performance. Alterations in corticosterone content and associated oxidative and neurochemical systems were assessed to explore the underlying mechanism responsible for changes in emotional memory. Following extensive exposure, a negative impact on emotional memory was observed compared with the limited exposure group. A lack of any further improvement in memory function following extensive training exposure was supported by increased corticosterone levels, decreased 5-hydroxytryptamine (5-HT) levels and abnormal oxidative stress levels, which may induce negative effects on memory consolidation. It is suggested that limited exposure to repetitive learning trials is more useful for studying improvement in emotional memory, whereas extensive exposure may produce chronic stress-like condition that can be detrimental and responsible for compromised memory performance. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Dual action of high estradiol doses on MNU-induced prostate neoplasms in a rodent model with high serum testosterone: Protective effect and emergence of unstable epithelial microenvironment.

    Science.gov (United States)

    Gonçalves, Bianca F; de Campos, Silvana G P; Góes, Rejane M; Scarano, Wellerson R; Taboga, Sebastião R; Vilamaior, Patricia S L

    2017-06-01

    Estrogens are critical players in prostate growth and disease. Estrogen therapy has been the standard treatment for advanced prostate cancer for several decades; however, it has currently been replaced by alternative anti-androgenic therapies. Additionally, studies of its action on prostate biology, resulting from an association between carcinogens and estrogen, at different stages of life are scarce or inconclusive about its protective and beneficial role on induced-carcinogenesis. Thus, the aim of this study was to determine whether estradiol exerts a protective and/or stimulatory role on N-methyl-N-nitrosurea-induced prostate neoplasms. We adopted a rodent model that has been used to study induced-prostate carcinogenesis: the Mongolian gerbil. We investigated the occurrence of neoplasms, karyometric patterns, androgen and estrogen receptors, basal cells, and global methylation status in ventral and dorsolateral prostate tissues. Histopathological analysis showed that estrogen was able to slow tumor growth in both lobes after prolonged treatment. However, a true neoplastic regression was observed only in the dorsolateral prostate. In addition to the protective effects against neoplastic progression, estrogen treatment resulted in an epithelium that exhibited features distinctive from a normal prostate, including increased androgen-insensitive basal cells, high androgens and estrogen receptor positivity, and changes in DNA methylation patterns. Estrogen was able to slow tumor growth, but the epithelium exhibited features distinct from a normal prostatic epithelium, and this unstable microenvironment could trigger lesion recurrence over time. © 2017 Wiley Periodicals, Inc.

  6. Effects of serum immunoglobulins from patients with complex regional pain syndrome (CRPS) on depolarisation-induced calcium transients in isolated dorsal root ganglion (DRG) neurons.

    Science.gov (United States)

    Reilly, Joanne M; Dharmalingam, Backialakshmi; Marsh, Stephen J; Thompson, Victoria; Goebel, Andreas; Brown, David A

    2016-03-01

    Complex regional pain syndrome (CRPS) is thought to have an auto-immune component. One such target recently proposed from the effects of auto-immune IgGs on Ca(2+) transients in cardiac myocytes and cell lines is the α1-adrenoceptor. We have tested whether such IgGs exerted comparable effects on nociceptive sensory neurons isolated from rat dorsal root ganglia. Depolarisation-induced [Ca(2+)]i transients were generated by applying 30 mM KCl for 2 min and monitored by Fura-2 fluorescence imaging. No IgGs tested (including 3 from CRPS patients) had any significant effect on these [Ca(2+)]i transients. However, IgG from one CRPS patient consistently and significantly reduced the K(+)-induced response of cells that had been pre-incubated for 24h with a mixture of inflammatory mediators (1 μM histamine, 5-hydroxytryptamine, bradykinin and PGE2). Since this pre-incubation also appeared to induce a comparable inhibitory response to the α1-agonist phenylephrine, this is compatible with the α1-adrenoceptor as a target for CRPS auto-immunity. A mechanism whereby this might enhance pain is suggested. Copyright © 2015. Published by Elsevier Inc.

  7. Effect of exogenous leptin on serum levels of lipids, glucose, renal and hepatic variables in both genders of obese and streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Parichehr Hayatdavoudi

    2015-11-01

    Full Text Available Objective(s: Leptin exerts various effects on appetite and body weight. Disruption of the obesitygene is precedent to fatness. Insulin or glucose elevates leptin, but streptozotocin reduces it. However, controversial data exist for the effects of leptin on diabetes and leptin level in each gender. Leptin can damage the kidney function but little evidence exists for its hepatic effects. The aim of this study was to investigate the probable sex-dependent differences in blood sugar levels, lipid profile, and renal and hepatic biochemical factors in the obesity and streptozotocin-induced diabetic rats after leptin administration. Materials and Methods: Wistar rats of both sexes were randomly divided into two groups, namely obese and diabetic rats. Each group was further divided into male and female subgroups. Extra fat and carbohydrate was added to the diet to induce obesity. Furthermore, streptozotocin (55 mg/kg, IP was injected to induce diabetes. The treatment groups received leptin (0.1 mg/kg SC for 10 days, and then, blood samples were taken from the orbital sinus for laboratory evaluations. Results: Leptin resulted in a significant weight loss in both sexes (P

  8. EGF Prevents the Neuroendocrine Differentiation of LNCaP Cells Induced By Serum Deprivation: The Modulator Role of P13K/Akt

    Directory of Open Access Journals (Sweden)

    Rosa M. Martín-Orozco

    2007-08-01

    Full Text Available The primary focus of this investigation was to study the relationship between neuroendocrine (NE differentiation, epidermal growth factor (EGF because both have been implicated in the progression of prostate cancer. For this purpose, we used gefitinib, trastuzumab, which are inhibitors of EGF receptor (EGFR, ErbB2, respectively. EGF prevents NE differentiation induced by androgen depletion. This effect is prevented by gefitinib, which blocks the activation of EGFR, ErbB2, stimulation of mitogen-activated protein kinase (MAPK, cell proliferation induced by EGF. Conversely, trastuzumab does not inhibit the effect of EGF on EGFR phosphorylation, MAPK activity, cell proliferation, NE differentiation, although it reduces ErbB2 levels specifically, suggesting that ErbB2 is not necessary to inhibit NE differentiation. Prevention of NE differentiation by EGF is mediated by a MAPK-dependent mechanism, requires constitutive Akt activation. The abrogation of the PI3K/Akt pathway changes the role of EGF from inhibitor to inductor of NE differentiation. We show that EGFR tyrosine kinase, MAPK, PI3K inhibitors inhibit the cell proliferation stimulated by EGF but induce the acquisition of NE phenotype. Altogether, the present data should be borne in mind when designing new clinical schedules for the treatment of prostate cancer, including the use of ErbB receptors, associated signaling pathway inhibitors.

  9. PERK pathway is involved in oxygen-glucose-serum deprivation-induced NF-kB activation via ROS generation in spinal cord astrocytes.

    Science.gov (United States)

    Liu, Jinbo; Du, Lijian

    2015-11-13

    Mitochondrial dysfunction is a direct target of hypoxic/ischemic stress in astrocytes, which results in the increased production of reactive oxygen species (ROS). Previous reports showed that ROS can activate NF-kB in spinal cord astrocytes, which occurs as a secondary injury during the pathological process of spinal cord injury (SCI). Protein kinase RNA (PKR)-like ER kinase (PERK) plays an important role in mitochondrial dysfunction. To elucidate the specific role of PERK in hypoxic/ischemic-induced NF-kB activation in spinal astrocytes, we utilized an in vitro oxygen-glucose deprivation (OGD) model, which showed an enhanced formation of ROS and NF-kB activation. Knockdown of PERK resulted in reduced activation of PERK and ROS generation in astrocytes under OGD conditions. Notably, the knockdown of PERK also induced NF-kB activation in astrocytes. These data suggest that PERK is required for the hypoxic/ischemic-induced-dependent regulation of ROS and that it is involved in NF-kB activation in the astrocytes. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Effects of estrogen supplementation on PCB 126-induced effects on vertebral bone, vitamin D and thyroxin levels in serum of rats

    Energy Technology Data Exchange (ETDEWEB)

    P. Monica Lind [Karolinska Inst., Inst. of Environmental Medicine, Stockholm (Sweden); Nyberg, I.; Oerberg, J. [Uppsala Univ., Dept. of Environmental Toxicology (Sweden)

    2004-09-15

    Own and others experimental studies in rat have demonstrated that high affinity Aryl hydrocarbon Receptor (AhR) ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the dioxin-like PCB congener, 3,3',4,4',5-pentachlorobiphenyl (PCB126), impair normal bone metabolism and result in increased bone fragility. No experimental study have, up to now, investigated effects of POCs on vertebra in bone-toxicological studies. Recently a Swedish epidemiological study showed that Swedish east-coast fishermen's wives have a significantly increased incidence for hospitalized vertebral fractures when compared with west-coast fishermen's wives7. The results give some indirect support for the notion that a high dietary intake of POCs through fatty fish might be a risk factor for vertebral fractures. The levels of POCs are much higher in the fish from the Baltic Sea compared with fish from the sea on the Swedish West coast. Vertebral bone consists to a larger extent than e.g. the long bones of trabecular bone which compared with cortical bone has a much higher metabolism and a more rapid bone turnover. It is therefore more likely to find more obvious effects of endocrine disruption in trabecular bone than in cortical bone. As an extension of our previous work, the goals of this study are therefore to (1) investigate interactive effects between PCB126 exposure, estrogen depletion (OVX) and estrogen supplementation (2) investigate the effects of PCB126 exposure of the trabecular rich vertebral bone (3) analyse serum levels 25OH- vitamin D and thyroxin as these are both important for bone tissue homeostasis and as biomarkers for organochlorines exposure.

  11. Exposure of Human CD8+ T Cells to Type-2 Cytokines Impairs Division and Differentiation and Induces Limited Polarization

    Directory of Open Access Journals (Sweden)

    Annette Fox

    2018-05-01

    Full Text Available Effector CD8+ T cells generally produce type-1 cytokines and mediators of the perforin/granzyme cytolytic pathway, yet type-2-polarized CD8+ cells (Tc2 are detected in type-2 (T2 cytokine-driven diseases such as asthma. It is unclear whether T2 cytokine exposure during activation is sufficient to polarize human CD8+ T cells. To address this question, a protocol was developed for high-efficiency activation of human CD8+ T cells in which purified single cells or populations were stimulated with plate-bound anti-CD3 and anti-CD11a mAb for up to 8 days in T2 polarizing or neutral conditions, before functional analysis. Activation of CD8+ naïve T cells (TN in T2 compared with neutral conditions decreased the size of single-cell clones, although early division kinetics were equivalent, indicating an effect on overall division number. Activation of TN in T2 conditions followed by brief anti-CD3 mAb restimulation favored expression of T2 cytokines, GATA3 and Eomes, and lowered expression of type-1 cytokines, Prf1, Gzmb, T-BET, and Prdm1. However, IL-4 was only weakly expressed, and PMA and ionomycin restimulation favored IFN-γ over IL-4 expression. Activation of TN in T2 compared with neutral conditions prevented downregulation of costimulatory (CD27, CD28 and lymph-node homing receptors (CCR7 and CD95 acquisition, which typically occur during differentiation into effector phenotypes. CD3 was rapidly and substantially induced after activation in neutral, but not T2 conditions, potentially contributing to greater division and differentiation in neutral conditions. CD8+ central memory T cells (TCM were less able to enter division upon reactivation in T2 compared with neutral conditions, and were more refractory to modulating IFN-γ and IL-4 production than CD8+ TN. In summary, while activation of TN in T2 conditions can generate T2 cytokine-biased cells, IL-4 expression is weak, T2 bias is lost upon strong restimulation, differentiation, and division

  12. Effects of non-fatiguing respiratory muscle loading induced by expiratory flow limitation during strenuous incremental cycle exercise on metabolic stress and circulating natural killer cells.

    Science.gov (United States)

    Rolland-Debord, Camille; Morelot-Panzini, Capucine; Similowski, Thomas; Duranti, Roberto; Laveneziana, Pierantonio

    2017-12-01

    Exercise induces release of cytokines and increase of circulating natural killers (NK) lymphocyte during strong activation of respiratory muscles. We hypothesised that non-fatiguing respiratory muscle loading during exercise causes an increase in NK cells and in metabolic stress indices. Heart rate (HR), ventilation (VE), oesophageal pressure (Pes), oxygen consumption (VO 2 ), dyspnoea and leg effort were measured in eight healthy humans (five men and three women, average age of 31 ± 4 years and body weight of 68 ± 10 kg), performing an incremental exercise testing on a cycle ergometer under control condition and expiratory flow limitation (FL) achieved by putting a Starling resistor. Blood samples were obtained at baseline, at peak of exercise and at iso-workload corresponding to that reached at the peak of FL exercise during control exercise. Diaphragmatic fatigue was evaluated by measuring the tension time index of the diaphragm. Respiratory muscle overloading caused an earlier interruption of exercise. Diaphragmatic fatigue did not occur in the two conditions. At peak of flow-limited exercise compared to iso-workload, HR, peak inspiratory and expiratory Pes, NK cells and norepinephrine were significantly higher. The number of NK cells was significantly related to ΔPes (i.e. difference between the most and the less negative Pes) and plasmatic catecholamines. Loading of respiratory muscles is able to cause an increase of NK cells provided that activation of respiratory muscles is intense enough to induce a significant metabolic stress.

  13. Spinal fusion limits upper body range of motion during gait without inducing compensatory mechanisms in adolescent idiopathic scoliosis patients.

    Science.gov (United States)

    Holewijn, R M; Kingma, I; de Kleuver, M; Schimmel, J J P; Keijsers, N L W

    2017-09-01

    Previous studies show a limited alteration of gait at normal walking speed after spinal fusion surgery for adolescent idiopathic scoliosis (AIS), despite the presumed essential role of spinal mobility during gait. This study analyses how spinal fusion affects gait at more challenging walking speeds. More specifically, we investigated whether thoracic-pelvic rotations are reduced to a larger extent at higher gait speeds and whether compensatory mechanisms above and below the stiffened spine are present. 18 AIS patients underwent gait analysis at increasing walking speeds (0.45 to 2.22m/s) before and after spinal fusion. The range of motion (ROM) of the upper (thorax, thoracic-pelvic and pelvis) and lower body (hip, knee and ankle) was determined in all three planes. Spatiotemporal parameters of interest were stride length and cadence. Spinal fusion diminished transverse plane thoracic-pelvic ROM and this difference was more explicit at higher walking speeds. Transversal pelvis ROM was also decreased but this effect was not affected by speed. Lower body ROM, step length and cadence remained unaffected. Despite the reduction of upper body ROM after spine surgery during high speed gait, no altered spatiotemporal parameters or increased compensatory ROM above or below the fusion (i.e. in the shoulder girdle or lower extremities) was identified. Thus, it remains unclear how patients can cope so well with such major surgery. Future studies should focus on analyzing the kinematics of individual spinal levels above and below the fusion during gait to investigate possible compensatory mechanisms within the spine. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Limited growth recovery after drought-induced forest dieback in very defoliated trees of two pine species

    Directory of Open Access Journals (Sweden)

    Guillermo eGuada

    2016-04-01

    Full Text Available Mediterranean pine forests display high resilience after extreme climatic events such as severe droughts. However, recent dry spells causing growth decline and triggering forest dieback challenge the capacity of some forests to recover following major disturbances. To describe how resilient the responses of forests to drought can be, we quantified growth dynamics in plantations of two pine species (Scots pine, black pine located in south-eastern Spain and showing drought-triggered dieback. Radial growth was characterized at inter- (tree-ring width and intra-annual (xylogenesis scales in three defoliation levels. It was assumed that the higher defoliation the more negative the impact of drought on tree growth. Tree-ring width chronologies were built and xylogenesis was characterized three years after the last severe drought occurred. Annual growth data and the number of tracheids produced in different stages of xylem formation were related to climate data at several time scales. Drought negatively impacted growth of the most defoliated trees in both pine species. In Scots pine, xylem formation started earlier in the non-defoliated than in the most defoliated trees. Defoliated trees presented the shortest duration of the radial-enlargement phase in both species. On average the most defoliated trees formed 60% of the number of mature tracheids formed by the non-defoliated trees in both species. Since radial enlargement is the xylogenesis phase most tightly related to final growth, this explains why the most defoliated trees grew the least due to their altered xylogenesis phases. Our findings indicate a very limited resilience capacity of drought-defoliated Scots and black pines. Moreover, droughts produce legacy effects on xylogenesis of highly defoliated trees which could not recover previous growth rates and are thus more prone to die.

  15. Vitrectomy with internal limiting membrane peeling vs no peeling for Macular Hole-induced Retinal Detachment (MHRD): a meta-analysis.

    Science.gov (United States)

    Su, Jing; Liu, Xinquan; Zheng, Lijun; Cui, Hongping

    2015-06-20

    we conducted our meta-analysis of published studies to assess existing evidence about the efficacy and safety of vitrectomy with ILM peeling vs. that of vitrectomy with no ILM peeling for Macular hole-induced retinal detachment. Databases, including Pubmed, Cochrane Library, Ovid, Web of Science, Wanfang and CNKI, were searched to identify studies comparing outcomes following vitrectomy with ILM peeling and that with no ILM peeling for macular hole-induced retinal detachment. The meta-analysis was performed by RevMan 5.1. Six comparative studies comprising 180 eyes were identified. It was indicated that the rate of retinal reattachment (Odds ratio (OR) = 3.03, 95 % Confidence interval (CI):1.35 to 6.78; P = 0.007) and macular hole closure (OR = 6.74, 95 % CI:3.26 to 13.93; P peeling than that in the group of vitrectomy with no ILM peeling. However, the improved BCVA (Weighted mean difference (WMD) = 0.14, 95 % CI: -0.20 to 0.47; P = 0.42) and the rate of postoperative complications were similar between the two groups. Vitrectomy with internal limiting membrane peeling is an efficient and safe procedure for macular hole-induced retinal detachment.

  16. Acacia nilotica leave extract and glyburide: comparison of fasting flood glucose, serum insulin, b-thromboglubulin levels and platelet aggregation in treptozotocin induced diabetic rats

    International Nuclear Information System (INIS)

    Asad, M.; Munir, T.A.; Afzal, N.

    2011-01-01

    Objectives: To evaluate the hypoglycaemic and anti-platelet aggregation effect of aqueous methanol extract of Acacia Nilotica (AN) leaves compared with glyburide on streptozotocin induced diabetic rats. Methods: Diabetes mellitus was induced in 90 out of 120 albino rats by administering 50 mg/kg body weight (b.w) streptozotocin and was confirmed by measuring fasting blood glucose level >200 mg/dL on fourth post-induction day. The rats were equally divided into 4 groups, A (normal control), B (diabetic control), C (diabetic rats treated with AN extract) and group D (diabetic rats treated with glyburide). The rats of group C and D were given 300 mg/kg b.w AN extract and 900 mu gm/kg b.w glyburide respectively for 3 weeks. Blood glucose was measured by gluco meter, platelet aggregation by Dia-Med method and insulin and b-thrombo globulin by ELISA technique. Results: A significant increase (p<0.05) in fasting blood glucose, b-thrombo globulin and platelet aggregation and a significant decrease (p<0.05) in insulin levels was observed in streptozotocin induced diabetic rats than the normal controls. The rats treated with AN extract and glyburide showed a significant decrease (p<0.05) in fasting blood glucose and increase (p<0.05) in insulin levels than the diabetic control rats. However, the levels in both the treatment groups remained significantly different than the normal controls. A significant decrease (p<0.05) in b-thrombo globulin levels was seen in diabetic rats treated with glyburide than the diabetic control rats and diabetic rats treated with AN extract. Conclusions: AN leaves extract result into hypoglycaemic and anti-platelet aggregation activity in diabetic rats as that of glyburide. (author)

  17. Laparoscopic limited Heller myotomy without anti-reflux procedure does not induce significant long-term gastroesophageal reflux.

    Science.gov (United States)

    Zurita Macías Valadez, L C; Pescarus, R; Hsieh, T; Wasserman, L; Apriasz, I; Hong, D; Gmora, S; Cadeddu, M; Anvari, M

    2015-06-01

    Laparoscopic Heller myotomy with partial fundoplication is the gold standard treatment for achalasia. Laparoscopic limited Heller myotomy (LLHM) with no anti-reflux procedure is another possible option. A review of prospectively collected data was performed on patients who underwent LLHM from January 1998 to December 2012. Evaluation included gastroscopy, esophageal manometry, 24-h pH-metry, and the Short Form(36) Health Survey(SF-36) questionnaire at baseline and 6 months, as well as the global symptom score at baseline, 6 months, and 5 years post-surgery. Comparison between outcomes was performed with a paired t student's test. 126 patients underwent LLHM. Of these, 60 patients had complete pre and post-operative motility studies. 57 % were female, patient mean age was 45.7 years, with a mean follow-up of 10.53 months. Mean operative time was 56.1 min, and the average length of stay was 1.7 days. At 6 months, a significant decrease in the lower esophageal sphincter resting pressure (29.1 vs. 7.1 mmHg; p < 0.001) and nadir (16.4 vs. 4.3 mmHg; p < 0.001) was observed. Normal esophageal acid exposure (total pH < 4 %) was observed in 68.3 % patients. Nevertheless, of the remaining 31.7 % with abnormal pH-metry, only 21.6 % were clinically symptomatic and all were properly controlled with medical treatment without requiring anti-reflux surgery. Significant improvement in all pre-operative symptoms was observed at 6 months and maintained over 5 years. Dysphagia score was reduced from 9.8 pre-operatively to 2.6 at 5 years (p < 0.001), heartburn score from 3.82 to 2 (p < 0.01), and regurgitation score from 7.5 to 0.8 (p < 0.001). Only one patient (0.8 %) presented with recurrent dysphagia requiring reoperation. LLHM without anti-reflux procedure is an effective long-term treatment for achalasia and does not cause symptomatic GERD in three quarters of patients. The remaining patients are well controlled on anti-reflux medications. It is believed that similar clinical

  18. 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.

  19. Transforming Growth Factor β-1 (TGF-β1) Is a Serum Biomarker of Radiation Induced Fibrosis in Patients Treated With Intracavitary Accelerated Partial Breast Irradiation: Preliminary Results of a Prospective Study

    Energy Technology Data Exchange (ETDEWEB)

    Boothe, Dustin L. [Weill Cornell Medical College of Cornell University, New York, New York (United States); Coplowitz, Shana [Department of Radiation Oncology, Stich Radiation Center, Weill Cornell Medical College of Cornell University, New York, New York (United States); Greenwood, Eleni [Weill Cornell Medical College of Cornell University, New York, New York (United States); Barney, Christian L. [Department of Radiation Oncology, Ohio State University, Columbus, Ohio (United States); Christos, Paul J. [Division of Biostatistics and Epidemiology, Department of Public Health, Weill Cornell Medical College of Cornell University, New York, New York (United States); Parashar, Bhupesh; Nori, Dattatreyudu; Chao, K. S. Clifford [Department of Radiation Oncology, Stich Radiation Center, Weill Cornell Medical College of Cornell University, New York, New York (United States); Wernicke, A. Gabriella, E-mail: gaw9008@med.cornell.edu [Department of Radiation Oncology, Stich Radiation Center, Weill Cornell Medical College of Cornell University, New York, New York (United States)

    2013-12-01

    Purpose: To examine a relationship between serum transforming growth factor β -1 (TGF-β1) values and radiation-induced fibrosis (RIF). Methods and Materials: We conducted a prospective analysis of the development of RIF in 39 women with American Joint Committee on Cancer stage 0-I breast cancer treated with lumpectomy and accelerated partial breast irradiation via intracavitary brachytherapy (IBAPBI). An enzyme-linked immunoassay (Quantikine, R and D, Minneapolis, MN) was used to measure serum TGF-β1 before surgery, before IBAPBI, and during IBAPBI. Blood samples for TGF-β1 were also collected from 15 healthy, nontreated women (controls). The previously validated tissue compliance meter (TCM) was used to objectively assess RIF. Results: The median time to follow-up for 39 patients was 44 months (range, 5-59 months). RIF was graded by the TCM scale as 0, 1, 2, and 3 in 5 of 20 patients (25%), 6 of 20 patients (30%), 5 of 20 patients (25%), and 4 of 20 patients (20%), respectively. The mean serum TGF-β1 values were significantly higher in patients before surgery than in disease-free controls, as follows: all cancer patients (30,201 ± 5889 pg/mL, P=.02); patients with any type of RIF (32,273 ± 5016 pg/mL, P<.0001); and women with moderate to severe RIF (34,462 ± 4713 pg/mL, P<0.0001). Patients with moderate to severe RIF had significantly elevated TGF-β1 levels when compared with those with none to mild RIF before surgery (P=.0014) during IBAPBI (P≤0001), and the elevation persisted at 6 months (P≤.001), 12 months (P≤.001), 18 months (P≤.001), and 24 months (P=.12). A receiver operating characteristic (ROC) curve of TGF-β1 values predicting moderate to severe RIF was generated with an area under the curve (AUC){sub ROC} of 0.867 (95% confidence interval 0.700-1.000). The TGF-β1 threshold cutoff was determined to be 31,000 pg/mL, with associated sensitivity and specificity of 77.8% and 90.0%, respectively. Conclusions: TGF-β1 levels correlate with

  20. The effect of realistic forces in finite epitaxial islands: Equilibrium structure, stability limits and substrate-induced dissociation of migrating clusters

    Science.gov (United States)

    Milchev, Andrey; Markov, Ivan

    1985-06-01

    The behaviour of finite epitaxial islands in the periodic field of the substrate is theoretically investigated. The harmonic interactions, traditionally adopted in the model of Frank and Van der Merwe, are replaced by Toda and Morse potentials and sets of difference recursion equations, governing the equilibrium properties of the system, are derived and solved numerically. It is shown that allowing for anharmonicity in the interactions in the deposit reveals several qualiatively new effects, such as: (1) The existence of substrate-induced rupture of anharmonic clusters which migrate on the substrate. It is predicted that such dissociation should be enhanced, if (a) the energy barrier for surface diffusion is increased, (b) the natural incompatibility between substrate and deposit is decreased, and (c) the size of the clusters grows. (2) A split in the misfit stability limits for pseudomorphism and for spontaneous generation of misfit dislocations with respect to the sign of the misfit. The limits corresponding to negative misfit rapidly increase while the positive misfit limits decrease (in absolute terms) with growing degree of anharmonicity. (3) A marked asymmetry in the magnitude of various properties of the clusters, such as adhesion to the substrate, activation energy for surface diffusion, mean strain, dislocation lengths, etc., with respect to the sign of the mismatch between surface and deposit.

  1. Serum, liver, and lung levels of the major extracellular matrix components at the early stage of BCG-induced granulomatosis depending on the infection route.

    Science.gov (United States)

    Kim, L B; Shkurupy, V A; Putyatina, A N

    2015-01-01

    Experiments on the model of mouse BCG-induced granulomatous showed that the content of glycosaminoglycans and proteoglycans in the extracellular matrix of the liver and lungs are changed at the early stages of inflammation (days 3 and 30 postinfection) before cell destruction in the organs begins. This is related to degradation of extracellular matrix structures. Their high content in the blood and interstitium probably contributes to the formation of granulomas, fibroblast proliferation and organ fibrosis. These processes depend on the infection route that determines different conditions for generalization of the inflammation process. Intravenous method of vaccine injection is preferable to use when designing the experiments simulating tuberculosis granulomatosis, especially for the analysis of its early stages.

  2. Super-quenched Molecular Probe Based on Aggregation-Induced Emission and Photoinduced Electron Transfer Mechanisms for Formaldehyde Detection in Human Serum.

    Science.gov (United States)

    Yang, Haitao; Wang, Fujia; Zheng, Jilin; Lin, Hao; Liu, Bin; Tang, Yi-Da; Zhang, Chong-Jing

    2018-06-04

    Energy transfer between fluorescent dyes and quenchers is widely used in the design of light-up probes. Although dual quenchers are more effective in offering lower background signals and higher turn-on ratios than one quencher, such probes are less explored in practice as they require both quenchers to be within the proximity of the fluorescent core. In this contribution, we utilized intramolecular motion and photoinduced electron transfer (PET) as quenching mechanisms to build super-quenched light-up probes based on fluorogens with aggregation-induced emission. The optimized light-up probe possesses negligible background and is able to detect not only free formaldehyde (FA) but also polymeric FA, with an unprecedented turn-on ratio of >4900. We envision that this novel dual quenching strategy will help to develop various light-up probes for analyte sensing. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Spectroscopic investigation of the effect of salt on binding of tartrazine with two homologous serum albumins: quantification by use of the Debye-Hückel limiting law and observation of enthalpy-entropy compensation.

    Science.gov (United States)

    Bolel, Priyanka; Datta, Shubhashis; Mahapatra, Niharendu; Halder, Mintu

    2012-08-30

    Formation of ion pair between charged molecule and protein can lead to interesting biochemical phenomena. We report the evolution of thermodynamics of the binding of tartrazine, a negatively charged azo colorant, and serum albumins with salt. The dye binds predominantly electrostatically in low buffer strengths; however, on increasing salt concentration, affinity decreases considerably. The calculated thermodynamic parameters in high salt indicate manifestation of nonelectrostatic interactions, namely, van der Waals force and hydrogen bonding. Site-marker competitive binding studies and docking simulations indicate that the dye binds with HSA in the warfarin site and with BSA at the interface of warfarin and ibuprofen binding sites. The docked poses indicate nearby amino acid positive side chains, which are possibly responsible for electrostatic interaction. Using the Debye-Hückel interionic attraction theory for binding equilibria, it is shown that, for electrostatic binding the calculated free energy change increases linearly with square root of ionic strength. Also UV-vis, fluorescence, CD data indicate a decrease of interaction with salt concentration. This study quantitatively relates how ionic strength modulates the strength of the protein-ligand electrostatic interaction. The binding enthalpy and entropy have been found to compensate one another. The enthalpy-entropy compensation (EEC), general property of weak intermolecular interactions, has been discussed.

  4. Limiting the Magnitude of Potential Injection-Induced Seismicity Associated With Waste-Water Disposal, Hydraulic Fracturing and CO2 Sequestration

    Science.gov (United States)

    Zoback, Mark

    2017-04-01

    In this talk, I will address the likelihood for fault slip to occur in response to fluid injection and the likely magnitude of potentially induced earthquakes. First, I will review a methodology that applies Quantitative Risk Assessment to calculate the probability of a fault exceeding Mohr-Coulomb slip criteria. The methodology utilizes information about the local state of stress, fault strike and dip and the estimated pore pressure perturbation to predict the probability of the fault slip as a function of time. Uncertainties in the input parameters are utilized to assess the probability of slip on known faults due to the predictable pore pressure perturbations. Application to known faults in Oklahoma has been presented by Walsh and Zoback (Geology, 2016). This has been updated with application to the previously unknown faults associated with M >5 earthquakes in the state. Second, I will discuss two geologic factors that limit the magnitudes of earthquakes (either natural or induced) in sedimentary sequences. Fundamentally, the layered nature of sedimentary rocks means that seismogenic fault slip will be limited by i) the velocity strengthening frictional properties of clay- and carbonate-rich rock sequences (Kohli and Zoback, JGR, 2013; in prep) and ii) viscoplastic stress relaxation in rocks with similar composition (Sone and Zoback, Geophysics, 2013a, b; IJRM, 2014; Rassouli and Zoback, in prep). In the former case, if fault slip is triggered in these types of rocks, it would likely be aseismic due the velocity strengthening behavior of faults. In the latter case, the stress relaxation could result in rupture termination in viscoplastic formations. In both cases, the stratified nature of sedimentary rock sequences could limit the magnitude of potentially induced earthquakes. Moreover, even when injection into sedimentary rocks initiates fault slip, earthquakes large enough to cause damage will usually require slip on faults sufficiently large that they extend

  5. Zinc in human serum

    International Nuclear Information System (INIS)

    Kiilerich, S.

    1987-01-01

    The zinc ion is essential for the living organism. Many pathological conditions have been described as a consequence of zinc deficiency. As zinc constitutes less than 0.01 per cent of the body weight, it conventionally belongs to the group of trace elements. The method of atomic absorption spectrophotometry is used to measure the concentration of zinc in serum and urine from healthy persons. The assumptions of the method is discussed. The importance of proteinbinding, diet and the diurnal variation of serum zinc concentration is presented. Serum versus plasma zinc concentration is discussed. Reference serum zinc values from 104 normal subjects are given. Zinc in serum is almost entirely bound to proteins. A preliminary model for the estimation of the distribution of zinc between serum albumin and α 2 -macroglobulin is set up. This estimate has been examined by an ultracentrufugation method. The binding of zinc to a α 2 -macroglobulin in normal persons is appoximately 7 per cent, in patients with cirrhosis of the liver of alcoholic origin approximately 6 per cent, in patients with insulin dependent diabetes mellitus approximately 5 per cent, and in patients with chronic renal failure approximately 2 per cent. It is concluded, therefore, that for clinical purposes it is sufficient to use the concentration of total serum zinc corrected for the concentration of serum albumin. (author)

  6. Value of serum tenascin-C in patients with acute myocardial infarction

    African Journals Online (AJOL)

    Rania Gaber

    2015-10-09

    Oct 9, 2015 ... Aliquots of serum were delivered into Eppendorf tubes. Serum samples have been .... Tenascin-C induced by aldosterone-mediated inflammation. J · Cardiovasc .... nosis estimation and targeted therapy. Cell Adh Migr 2015 ...

  7. Effect of consumption of red wine, spirits, and beer on serum homocysteine.

    Science.gov (United States)

    van der Gaag, M S; Ubbink, J B; Sillanaukee, P; Nikkari, S; Hendriks, H F

    2000-04-29

    Serum homocysteine increases after moderate consumption of red wine and spirits, not after moderate consumption of beer. Vitamin B6 in beer seems to prevent the alcohol-induced rise in serum homocysteine.

  8. Serum growth hormone-binding protein in obesity: effect of a short-term, very low calorie diet and diet-induced weight loss

    DEFF Research Database (Denmark)

    Rasmussen, M H; Ho, K K; Kjems, L

    1996-01-01

    +/-SEM)] before and after an average weight loss of 30.3 +/- 4.6 kg and in 18 age- and sex matched normal subjects (BMI, 23.0 +/- 0.4 kg/m2) and studied the effects of a very low calorie diet over 4 days in 5 normal subjects and a subgroup of obese subjects before (n = 6) and after (n = 5) weight loss...... was positively correlated to insulin as well as proinsulin levels (r = 0.60; P diet-induced massive weight loss, GHBP levels were restored to normal in obese subjects (BMI, 27.8 +/- 1.4 kg/m2). Multiple stepwise regression analysis revealed that changes...... days of a very low calorie diet, although mean insulin levels fell significantly in the normal subgroup as well as in the obese subgroup studied after weight loss. In summary, GHBP levels are elevated in obesity, are restored to normal by massive weight loss, and are unaffected by short term...

  9. Diet-induced obesity, exogenous leptin-, and MADB106 tumor cell challenge affect tissue leukocyte distribution and serum levels of cytokines in F344 rats.

    Science.gov (United States)

    Behrendt, Patrick; Buchenauer, Tobias; Horn, Rüdiger; Brabant, Georg; Jacobs, Roland; Bode, Felix; Stephan, Michael; Nave, Heike

    2010-08-01

    The adipocyte-derived catabolic protein leptin alters cell-mediated immunity and cytokine crosstalk. This may provide new insights into the altered immune response, seen in obese individuals. Therefore, we determined the tissue distribution of immune cells in diet-induced obese (dio) and normal weight F344 rats challenged with MADB106 tumor cells or leptin. Immune cell distribution in blood (by FACS analysis) and tissues (NK cells in spleen and liver, immunohistologically) as well as pro-inflammatory cytokines (IL-6, TNF-α; by flow cytometry) were investigated in 28 normal weight and 28 dio rats (n = 4-6/group). Pro-inflammatory cytokines were increased 3-fold for IL-6 and 7-fold for TNF-α in obese animals. Higher numbers of blood monocytes and NK cells were found in obese as compared to normal weight animals. In dio rats challenged with leptin and MADB106 tumor cells, monocyte numbers were decreased as compared to the obese control animals. Immunohistochemistry revealed an altered NK cell distribution in a compartment-, treatment-, and bodyweight-specific manner. In conclusion, our data reveal a distinct distribution pattern of monocytes and NK cells in dio rats as compared to normal weight littermates and an additional modulatory effect of a leptin- and MADB106 tumor cell challenge.

  10. Combined Efficacy of Gallic Acid and MiADMSA with Limited Beneficial Effects Over MiADMSA Against Arsenic-induced Oxidative Stress in Mouse.

    Science.gov (United States)

    Pachauri, Vidhu; Flora, Sjs

    2015-01-01

    Gallic acid is an organic acid known for its antioxidant and anticancer properties. The present study is focused on evaluating the role of gallic acid in providing better therapeutic outcomes against arsenic-induced toxicity. Animals pre-exposed to arsenic were treated with monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), a new chelating drug, alone and in combination with gallic acid, consecutively for 10 days. The study suggests that (1) gallic acid in presence of MiADMSA is only moderately beneficial against arsenic, (2) monotherapy with gallic acid is more effective than in combination with MiADMSA after arsenic exposure in reducing oxidative injury, and (3) MiADMSA monotherapy as reported previously provides significant therapeutic efficacy against arsenic. Thus, based on the present results, we conclude that gallic acid is effective against arsenic-induced oxidative stress but provides limited additional beneficial effects when administered in combination with MiADMSA. We still recommend that lower doses of gallic acid be evaluated both individually and in combination with MiADMSA, as it might not exhibit the shortcomings we observed with higher doses in this study.

  11. Stress-inducible expression of At DREB1A in transgenic peanut (Arachis hypogaea L.) increases transpiration efficiency under water-limiting conditions.

    Science.gov (United States)

    Bhatnagar-Mathur, Pooja; Devi, M Jyostna; Reddy, D Srinivas; Lavanya, M; Vadez, Vincent; Serraj, R; Yamaguchi-Shinozaki, K; Sharma, Kiran K

    2007-12-01

    Water deficit is the major abiotic constraint affecting crop productivity in peanut (Arachis hypogaea L.). Water use efficiency under drought conditions is thought to be one of the most promising traits to improve and stabilize crop yields under intermittent water deficit. A transcription factor DREB1A from Arabidopsis thaliana, driven by the stress inducible promoter from the rd29A gene, was introduced in a drought-sensitive peanut cultivar JL 24 through Agrobacterium tumefaciens-mediated gene transfer. The stress inducible expression of DREB1A in these transgenic plants did not result in growth retardation or visible phenotypic alterations. T3 progeny of fourteen transgenic events were exposed to progressive soil drying in pot culture. The soil moisture threshold where their transpiration rate begins to decline relative to control well-watered (WW) plants and the number of days needed to deplete the soil water was used to rank the genotypes using the average linkage cluster analysis. Five diverse events were selected from the different clusters and further tested. All the selected transgenic events were able to maintain a transpiration rate equivalent to the WW control in soils dry enough to reduce transpiration rate in wild type JL 24. All transgenic events except one achieved higher transpiration efficiency (TE) under WW conditions and this appeared to be explained by a lower stomatal conductance. Under water limiting conditions, one of the selected transgenic events showed 40% higher TE than the untransformed control.

  12. Mast cell chymase degrades the alarmins heat shock protein 70, biglycan, HMGB1, and interleukin-33 (IL-33) and limits danger-induced inflammation.

    Science.gov (United States)

    Roy, Ananya; Ganesh, Goutham; Sippola, Helena; Bolin, Sara; Sawesi, Osama; Dagälv, Anders; Schlenner, Susan M; Feyerabend, Thorsten; Rodewald, Hans-Reimer; Kjellén, Lena; Hellman, Lars; Åbrink, Magnus

    2014-01-03

    During infection and tissue damage, virulence factors and alarmins are pro-inflammatory and induce activation of various immune cells including macrophages and mast cells (MCs). Activated MCs instantly release preformed inflammatory mediators, including several proteases. The chymase mouse mast cell protease (MCPT)-4 is thought to be pro-inflammatory, whereas human chymase also degrades pro-inflammatory cytokines, suggesting that chymase instead limits inflammation. Here we explored the contribution of MCPT4 and human chymase to the control of danger-induced inflammation. We found that protein extracts from wild type (WT), carboxypeptidase A3-, and MCPT6-deficient mice and MCs and recombinant human chymase efficiently degrade the Trichinella spiralis virulence factor heat shock protein 70 (Hsp70) as well as endogenous Hsp70. MC-(W(sash))-, serglycin-, NDST2-, and MCPT4-deficient extracts lacked this capacity, indicating that chymase is responsible for the degradation. Chymase, but not MC tryptase, also degraded other alarmins, i.e. biglycan, HMGB1, and IL-33, a degradation that was efficiently blocked by the chymase inhibitor chymostatin. IL-7, IL-22, GM-CSF, and CCL2 were resistant to chymase degradation. MCPT4-deficient conditions ex vivo and in vivo showed no reduction in added Hsp70 and only minor reduction of IL-33. Peritoneal challenge with Hsp70 resulted in increased neutrophil recruitment and TNF-α levels in the MCPT4-deficient mice, whereas IL-6 and CCL2 levels were similar to the levels found in WT mice. The rapid and MC chymase-specific degradation of virulence factors and alarmins may depend on the presence of accessible extended recognition cleavage sites in target substrates and suggests a protective and regulatory role of MC chymase during danger-induced inflammation.

  13. Mast Cell Chymase Degrades the Alarmins Heat Shock Protein 70, Biglycan, HMGB1, and Interleukin-33 (IL-33) and Limits Danger-induced Inflammation*

    Science.gov (United States)

    Roy, Ananya; Ganesh, Goutham; Sippola, Helena; Bolin, Sara; Sawesi, Osama; Dagälv, Anders; Schlenner, Susan M.; Feyerabend, Thorsten; Rodewald, Hans-Reimer; Kjellén, Lena; Hellman, Lars; Åbrink, Magnus

    2014-01-01

    During infection and tissue damage, virulence factors and alarmins are pro-inflammatory and induce activation of various immune cells including macrophages and mast cells (MCs). Activated MCs instantly release preformed inflammatory mediators, including several proteases. The chymase mouse mast cell protease (MCPT)-4 is thought to be pro-inflammatory, whereas human chymase also degrades pro-inflammatory cytokines, suggesting that chymase instead limits inflammation. Here we explored the contribution of MCPT4 and human chymase to the control of danger-induced inflammation. We found that protein extracts from wild type (WT), carboxypeptidase A3-, and MCPT6-deficient mice and MCs and recombinant human chymase efficiently degrade the Trichinella spiralis virulence factor heat shock protein 70 (Hsp70) as well as endogenous Hsp70. MC-(Wsash)-, serglycin-, NDST2-, and MCPT4-deficient extracts lacked this capacity, indicating that chymase is responsible for the degradation. Chymase, but not MC tryptase, also degraded other alarmins, i.e. biglycan, HMGB1, and IL-33, a degradation that was efficiently blocked by the chymase inhibitor chymostatin. IL-7, IL-22, GM-CSF, and CCL2 were resistant to chymase degradation. MCPT4-deficient conditions ex vivo and in vivo showed no reduction in added Hsp70 and only minor reduction of IL-33. Peritoneal challenge with Hsp70 resulted in increased neutrophil recruitment and TNF-α levels in the MCPT4-deficient mice, whereas IL-6 and CCL2 levels were similar to the levels found in WT mice. The rapid and MC chymase-specific degradation of virulence factors and alarmins may depend on the presence of accessible extended recognition cleavage sites in target substrates and suggests a protective and regulatory role of MC chymase during danger-induced inflammation. PMID:24257755

  14. [Effect of twirling-reinforcing-reducing needling manipulations on contents of serum acetylcholine and arterial NOS and cGMP in stress-induced hypertension rats].

    Science.gov (United States)

    Liu, Wei; Zhu, Ling-Qun; Chen, Si-Si; Lu, Shu-Chao; Tang, Jie; Liu, Qing-Guo

    2015-04-01

    To observe the effect of twirling-reinforcing or reducing needling manipulations on plasma acetylcholine (Ach) content and expression of nitric oxide synthetase (NOS) and cyclic guanosine monophosphate (cGMP) in thoracic artery tissue in stress-induced hypertension rats. A total of 60 male rats were randomly divided into blank control, model, acupuncture (no-needle-manipulation) , twirling-reinforcing needling and twirling-reducing needling groups (n = 12 in each group). The stress hypertension model was established by giving the animals with noise and electric shock stimulation (paw), twice a day for 15 days. Acupuncture stimulation was applied to bilateral "Taichong" (LR 3) for 1 min, followed by retaining the needles for 20 min. The treatment was conducted once daily for 7 days. Systolic blood pressure of the rat's tail was detected with non-invasive method and plasma Ach, and NOS and cGMP contents in the thoracic artery tissue were measured using ELISA method. Compared with the control group, the systolic blood pressure was significantly higher in the model group after 15 days' stress stimulation (P arterial NOS and cGMP were markedly down-regulated (P arterial cGMP content was found in the no-needle-manipulation group (P > 0.05). The effect of the twirling-reducing needling was superior to that of no-needle-manipulation and twirling-reinforcing needling in lowering blood pressure and raising plasma Ach content (P hypertensive effect in stress hypertension rats, which may be associated with its effects in raising blood Ach, and arterial NOS and cGMP levels.

  15. Serum trace elements as nutritional markers in a case with acute aortic dissection

    International Nuclear Information System (INIS)

    Miura, Y.; Suwabe, A.; Tawara, M.; Endo, R.; Ikeda, K.; Sera, K.

    2008-01-01

    Serum trace elements were analyzed by particle induced X-ray emission (PIXE) method in a patient with acute aortic dissection during the supportive process by a Nutrition support team (NST). The patient was a 53-year old male who suffered from acute aortic dissection on March 1, 2007. He received emergent Bentall operation and bow pars total displacement. Since he suffered from diarrhea as a result of hypoalbuminemia and bowel dysfunction, enteral nutrition was not sufficient to maintain adequate intake. Therefore, we also used parenteral nutrition until the 97th disease day. Afterwards, the patient managed only with enteral nutrition. We measured serum trace elements during these periods. Serum trace elements such as Fe, Zn and Se were preserved within normal ranges. On the other hand, Cu gradually decreased until the 54th disease day (44 μg/l) and stayed in the lower levels around the detection limit until the 109th disease day. Thereafter, Cu slightly increased and reached 117 μg/l on the 131st disease day (reference range of serum Cu in adult males: 700-1,300 μg/l). It was suggested that the serum levels of these trace elements might reflect the nutritional stages of the patient and could be useful as clinical markers for nutritional therapies. (author)

  16. Trypanosoma cruzi: Serum levels of nitric oxide and expression of inducible nitric oxide synthase in myocardium and spleen of dogs in the acute stage of infection with metacyclic or blood trypomastigotes.

    Science.gov (United States)

    Vieira, Paula Melo de Abreu; Francisco, Amanda Fortes; de Souza, Sheler Martins; Malaquias, Luiz Cosme Cotta; Reis, Alexandre Barbosa; Giunchetti, Rodolfo Cordeiro; Veloso, Vanja Maria; de Lana, Marta; Tafuri, Washington Luiz; Carneiro, Cláudia Martins

    2009-01-01

    The participation of nitric oxide (NO) in the control of blood parasitemia and parasitism during the acute phase of infection in dogs inoculated with blood trypomastigotes (BT) or metacyclic trypomastigotes (MT group) of Berenice-78 Trypanosoma cruzi strain has been evaluated. Animals of the MT group (n=4) presented increased levels of serum NO throughout the infection when compared with the BT (n=4) or control (n=4) groups, and a delay in parasitemia peak compared with the BT group. In spleen fragments, tissue parasitism was not observed but the MT group presented larger areas associated with inducible NO synthase (iNOS) in relation to BT and control groups. Heart fragments of MT-infected animals exhibited comparatively low tissue parasitism and high iNOS expression, while animals of the BT group presented high inflammatory infiltrate, high tissue parasitism and low iNOS expression. These results indicate that the source of inoculum can interfere with the development of the acute phase of Chagas disease, and may also trigger a distinct parasite-host interaction during this phase.

  17. Nutrient-induced stimulation of protein synthesis in mouse skeletal muscle is limited by the mTORC1 repressor REDD1.

    Science.gov (United States)

    Gordon, Bradley S; Williamson, David L; Lang, Charles H; Jefferson, Leonard S; Kimball, Scot R

    2015-04-01

    In skeletal muscle, the nutrient-induced stimulation of protein synthesis requires signaling through the mechanistic target of rapamycin complex 1 (mTORC1). Expression of the repressor of mTORC1 signaling, regulated in development and DNA damage 1 (REDD1), is elevated in muscle during various atrophic conditions and diminished under hypertrophic conditions. The question arises as to what extent REDD1 limits the nutrient-induced stimulation of protein synthesis. The objective was to examine the role of REDD1 in limiting the response of muscle protein synthesis and mTORC1 signaling to a nutrient stimulus. Wild type REDD1 gene (REDD1(+/+)) and disruption in the REDD1 gene (REDD1(-/-)) mice were feed deprived for 16 h and randomized to remain feed deprived or refed for 15 or 60 min. The tibialis anterior was then removed for analysis of protein synthesis and mTORC1 signaling. In feed-deprived mice, protein synthesis and mTORC1 signaling were significantly lower in REDD1(+/+) than in REDD1(-/-) mice. Thirty minutes after the start of refeeding, protein synthesis in REDD1(+/+) mice was stimulated by 28%, reaching a value similar to that observed in feed-deprived REDD1(-/-) mice, and was accompanied by increased phosphorylation of mTOR (Ser2448), p70S6K1 (Thr389), and 4E-BP1 (Ser65) by 81%, 167%, and 207%, respectively. In refed REDD1(-/-) mice, phosphorylation of mTOR (Ser2448), p70S6K1 (Thr389), and 4E-BP1 (Ser65) were significantly augmented above the values observed in refed REDD1(+/+) mice by 258%, 405%, and 401%, respectively, although protein synthesis was not coordinately increased. Seventy-five minutes after refeeding, REDD1 expression in REDD1(+/+) mice was reduced (∼15% of feed-deprived REDD1(+/+) values), and protein synthesis and mTORC1 signaling were not different between refed REDD1(+/+) mice and REDD1(-/-) mice. The results show that REDD1 expression limits protein synthesis in mouse skeletal muscle by inhibiting mTORC1 signaling during periods of feed

  18. Serum Antibody Biomarkers for ASD

    Science.gov (United States)

    2015-10-01

    typically developing control. US, unaffected sibling control. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a...typically developing (TD) children (e.g., Warren et al., 1990; Singh, 2009). The goal of this study is to identify a serum antibody biomarker for ASD using...50% less IgG1 antibody in ASD boys vs . TD boys (p=0.0096). The level of ASD1 binding to the AM group was the same as to the ASD boys. These data

  19. Hepatitis C Virus Sensing by Human Trophoblasts Induces Innate Immune Responses and Recruitment of Maternal NK Cells: Potential Implications for Limiting Vertical Transmission.

    Science.gov (United States)

    Giugliano, Silvia; Petroff, Margaret G; Warren, Bryce D; Jasti, Susmita; Linscheid, Caitlin; Ward, Ashley; Kramer, Anita; Dobrinskikh, Evgenia; Sheiko, Melissa A; Gale, Michael; Golden-Mason, Lucy; Winn, Virginia D; Rosen, Hugo R

    2015-10-15

    Hepatitis C virus (HCV) is the world's most common blood-borne viral infection for which there is no vaccine. The rates of vertical transmission range between 3 and 6% with odds 90% higher in the presence of HIV coinfection. Prevention of vertical transmission is not possible because of lack of an approved therapy for use in pregnancy or an effective vaccine. Recently, HCV has been identified as an independent risk factor for preterm delivery, perinatal mortality, and other complications. In this study, we characterized the immune responses that contribute to the control of viral infection at the maternal-fetal interface (MFI) in the early gestational stages. In this study, we show that primary human trophoblast cells and an extravillous trophoblast cell line (HTR8), from first and second trimester of pregnancy, express receptors relevant for HCV binding/entry and are permissive for HCV uptake. We found that HCV-RNA sensing by human trophoblast cells induces robust upregulation of type I/III IFNs and secretion of multiple chemokines that elicit recruitment and activation of decidual NK cells. Furthermore, we observed that HCV-RNA transfection induces a proapoptotic response within HTR8 that could affect the morphology of the placenta. To our knowledge, for the first time, we demonstrate that HCV-RNA sensing by human trophoblast cells elicits a strong antiviral response that alters the recruitment and activation of innate immune cells at the MFI. This work provides a paradigm shift in our understanding of HCV-specific immunity at the MFI as well as novel insights into mechanisms that limit vertical transmission but may paradoxically lead to virus-related pregnancy complications. Copyright © 2015 by The American Association of Immunologists, Inc.

  20. Limitaciones técnicas de los métodos para cuantificar tiroglobulina sérica y su repercusión clínica Technical limitations of methods to quantify the serum thyroglobulin and its clinical repercussion

    Directory of Open Access Journals (Sweden)

    Julio César Rodríguez González

    2010-04-01

    -isotopic reagents, a lower sample volume, shorter incubation times, as well as a better sensitivity and feasibility of automation. It is essential that clinicians know and understand the technical limitations inherent of serum thyroglobulin assessment and its repercussion on its clinical usefulness to an effective and efficient use of this test during the postoperative follow-up of patients presenting thyroid differential cancer.

  1. Reactions of nitroxide radicals in aqueous solutions exposed to non-thermal plasma: limitations of spin trapping of the plasma induced species

    Science.gov (United States)

    Gorbanev, Yury; Stehling, Nicola; O'Connell, Deborah; Chechik, Victor

    2016-10-01

    Low temperature (‘cold’) atmospheric pressure plasmas have gained much attention in recent years due to their biomedical effects achieved through the interactions of plasma-induced species with the biological substrate. Monitoring of the radical species in an aqueous biological milieu is usually performed via electron paramagnetic resonance (EPR) spectroscopy using various nitrone spin traps, which form persistent radical adducts with the short-lived radicals. However, the stability of these nitroxide radical adducts in the plasma-specific environment is not well known. In this work, chemical transformations of nitroxide radicals in aqueous solutions using a model nitroxide 4-oxo-TEMPO were studied using EPR and LC-MS. The kinetics of the nitroxide decay when the solution was exposed to plasma were assessed, and the reactive pathways proposed. The use of different scavengers enabled identification of the types of reactive species which cause the decay, indicating the predominant nitroxide group reduction in oxygen-free plasmas. The 2H adduct of the PBN spin trap (PBN-D) was shown to decay similarly to the model molecule 4-oxo-TEMPO. The decay of the spin adducts in plasma-treated solutions must be considered to avoid rendering the spin trapping results unreliable. In particular, the selectivity of the decay indicated the limitations of the PTIO/PTI nitroxide system in the detection of nitric oxide.

  2. antioxidants, cadmium-induced toxicity, serum biochemical

    African Journals Online (AJOL)

    Daniel Owu

    Nigerian Journal of Physiological Sciences 24 (2): 177 -185 ©Physiological Society of Nigeria, 2009. Available ... time-dependent destruction of the histology of the liver, kidney and testes. ... shown to inhibit the activities of various pancreatic proteases (Hideaki ..... endocrine organs hence damage to the tissue will result in ...

  3. Qian Yang Yu Yin Granule-containing serum inhibits angiotensin II-induced proliferation, reactive oxygen species production, and inflammation in human mesangial cells via an NADPH oxidase 4-dependent pathway.

    Science.gov (United States)

    Ding, Kang; Wang, Yan; Jiang, Weimin; Zhang, Yu; Yin, Hongping; Fang, Zhuyuan

    2015-03-25

    Qian Yang Yu Yin Granule (QYYYG), a traditional Chinese herbal medicine, has been indicated for renal damage in hypertension for decades in China, but little remains known regarding its underlying molecular mechanism. Therefore, we performed the current study in order to investigate the underlying molecular mechanism of QYYYG in the treatment of hypertensive renal damage. We hypothesize that QYYYG relieves hypertensive renal injury through an angiotensin II (Ang II)-nicotinamide adenine dinucleotide phosphate (NAPDH)-oxidase (NOX)-reactive oxygen species (ROS) pathway. In this study, we investigated the effects of QYYYG-containing serum (QYGS) in human mesangial cells (HMCs) against Ang II-induced cell proliferation, ROS production, and inflammation through the seropharmacological method. We found that QYGS could inhibit cell proliferation in Ang II-treated HMCs. In addition, QYGS considerably suppressed production of ROS, decreased mRNA and protein expression of NAPDH-oxidase 4 (NOX4), p22 (phox) , and activated Ras-related C3 botulinum toxin substrate 1 (GTP-Rac1); as well as counteracted the up-regulation of inflammatory markers including tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) p65, and interleukin 6 (IL-6). These effects were further confirmed in HMCs transfected with specific small interfering RNA (siRNA) targeting NOX4. Taken together, these results suggest that a NOX4-dependent pathway plays an important role in regulating the inhibitory effect of QYGS. Our findings provide new insights into the molecular mechanisms of QYYYG and their role in the treatment of hypertensive nephropathy.

  4. [The National Serum Bank].

    Science.gov (United States)

    Magos-López, C; Sánchez-Villarreal, F; Gutiérrez, G; Tapia-Conyer, R

    1992-01-01

    A National Serum Bank was established to store sera obtained during the National Seroepidemiological Survey performed in Mexico in 1987. More than 70,000 serum samples were obtained from subjects of either sex 1-99 years of age in each of the 32 states of the country. The current collection of sera includes 28,704 male samples and 40,629 female samples. This paper describes the procedures for handling serum samples, including reception registry, storage and distribution to several laboratories for detection of measles, rubella, poliomyelitis, AIDS, diphtheria, pertussis, tetanus, brucella, salmonella, amoeba, toxoplasma, American trypanosomiasis and cysticercus. Determinations of total cholesterol were also made in order to describe its distribution and to identify the prevalence of hypercholesterolemia.

  5. A diet high in fat and sugar reverses anxiety-like behaviour induced by limited nesting in male rats: Impacts on hippocampal markers.

    Science.gov (United States)

    Maniam, Jayanthi; Antoniadis, Christopher P; Le, Vivian; Morris, Margaret J

    2016-06-01

    Stress exposure during early development is known to produce long-term mental health deficits. Stress promotes poor lifestyle choices such as poor diet. Early life adversity and diets high in fat and sugar (HFHS) are known to affect anxiety and memory. However additive effects of HFHS and stress during early development are less explored. Here, we examined whether early life stress (ELS) simulated by limited nesting (LN) induces anxiety-like behaviour and cognitive deficits that are modulated by HFHS diet. We examined key hippocampal markers involved in anxiety and cognition, testing the hypothesis that post-weaning HFHS following ELS would ameliorate anxiety-like behaviour but worsen memory and associated hippocampal changes. Sprague-Dawley rats were exposed to LN, postnatal days 2-9, and at weaning, male siblings were given unlimited access to chow or HFHS resulting in (Con-Chow, Con-HFHS, LN-Chow, LN-HFHS, n=11-15/group). Anxiety-like behaviour was assessed by Elevated Plus Maze (EPM) at 10 weeks and spatial and object recognition tested at 11 weeks of age. Rats were culled at 13 weeks. Hippocampal mRNA expression was measured using TaqMan(®) Array Micro Fluidic cards (Life Technologies). As expected HFHS diet increased body weight; LN and control rats had similar weights at 13 weeks, energy intake was also similar across groups. LN-Chow rats showed increased anxiety-like behaviour relative to control rats, but this was reversed by HFHS diet. Spatial and object recognition memory were unaltered by LN exposure or consumption of HFHS diet. Hippocampal glucocorticoid receptor (GR) protein was not affected by LN exposure in chow rats, but was increased by 45% in HFHS rats relative to controls. Hippocampal genes involved in plasticity and mood regulation, GSKα and GSKβ were affected, with reductions in GSKβ under both diet conditions, and reduced GSKα only in LN-HFHS versus Con-HFHS. Interestingly, HFHS diet and LN exposure independently reduced expression of

  6. HYPOLIPEMIC THERAPY AND LOW SERUM CHOLESTEROL CONCENTRATION

    Directory of Open Access Journals (Sweden)

    Vladmila Bojanic

    2004-01-01

    Full Text Available Low concentration of plasma lipoproteins (hypolipoproteinemia presents decreasing concentrations of all or particular lipids components. Classification of hypolipoproteinemia (hypoLP divides them into: primary (hereditary and secondary. Primary hipoLP are rare diseases and their main characteristic is disorder of apolipoproteins synthesis, which leads to low serum cholesterol concentration. Secondary hipoLP are presented in many diseases. They have diagnostic, prognostic significance and present good therapeutic marker. However, modern therapeutic approaches for aggressive lipid lowering pointed out many questions about physiological limits for cholesterol lowering. These approaches, also, open many questions about consequences of low serum concentration of total cholesterol and triglicerides.

  7. Radioimmunoassay of haloperidol in human serum: correlation of serum haloperidol with serum prolactin

    International Nuclear Information System (INIS)

    Poland, R.E.; Rubin, R.T.

    1981-01-01

    A radioimmunoassay (RIA) for measurement of serum haloperidol is described. Compared to gaschromatography (GC), RIA vaues average 40% higher. However, a simple organic extraction of serum yields statistically equivalent RIA and GC haloperidol determinations. For both men and women combined, there was a positive correlation between dose (mg/kg/day) and steady-state serum haloperidol level (r = +0.86) and between steady-state serum haloperidol and serum prolactin (PRL) concentration

  8. Scope and Limits of an anamnestic questionnaire in a control-induced low-endemicity helminthiasis setting in south-central Côte d'Ivoire.

    Science.gov (United States)

    Fürst, Thomas; Ouattara, Mamadou; Silué, Kigbafori D; N'Goran, Dje N; Adiossan, Lukas G; Bogoch, Isaac I; N'Guessan, Yao; Koné, Siaka; Utzinger, Jürg; N'Goran, Eliézer K

    2014-01-01

    Schistosomiasis and soil-transmitted helminthiasis are two high-burden neglected tropical diseases. In highly endemic areas, control efforts emphasize preventive chemotherapy. However, as morbidity, infection, and transmission begin to decrease, more targeted treatment is likely to become more cost-effective, provided that comparatively cheap diagnostic methods with reasonable accuracy are available. Adults were administered an anamnestic questionnaire in mid-2010 during a cross-sectional epidemiological survey in the Taabo health demographic surveillance system in south-central Côte d'Ivoire. Questions pertaining to risk factors and signs and symptoms for schistosomiasis and soil-transmitted helminthiasis were included. The individuals' helminth infection status and their belonging to three different anthelmintic treatment groups were compared with the questionnaire results (i) to inform the local health authorities about the epidemiological and clinical footprint of locally prevailing helminthiases, and (ii) to explore the scope and limits of an anamnestic questionnaire as monitoring tool, which eventually could help guiding the control of neglected tropical diseases in control-induced low-endemicity settings. Our study sample consisted of 195 adults (101 males, 94 females). We found prevalences of hookworm, Trichuris trichiura, Schistosoma haematobium, and Schistosoma mansoni of 39.0%, 2.7%, 2.1%, and 2.1%, respectively. No Ascaris lumbricoides infection was found. Helminth infection intensities were generally very low. Seven, 74 and 79 participants belonged to three different treatment groups. Multivariable logistic regression models revealed statistically significant (p<0.05) associations between some risk factors, signs, and symptoms, and the different helminth infections and treatment groups. However, the risk factors, signs, and symptoms showed weak diagnostic properties. The generally low prevalence and intensity of helminth infection in this part of

  9. Serum YKL-40

    DEFF Research Database (Denmark)

    Mylin, Anne K; Abildgaard, Niels; Johansen, Julia S

    2015-01-01

    to clinical progression, i.e. skeletal-related events (SREs), in 230 newly diagnosed patients with multiple myeloma receiving intravenous bisphosphonates. Serum concentrations of YKL-40 and biochemical bone markers (CTX-MMP, CTX-I, PINP) were measured at diagnosis. Patients were evaluated every third month...

  10. 79 - 81_Wali - Serum

    African Journals Online (AJOL)

    DR. AMINU

    2013-06-01

    Jun 1, 2013 ... SERUM ANTIOXIDANT VITAMINS LEVELS IN CHILDREN WITH SICKLE. CELL ANAEMIA IN ... play a role in the development of sickle cell anaemic complications. In the current study, ... vaso-occlusive episodes, acute chest syndrome and impaired ... frequency of sickling crises accompanied by tissue or.

  11. Serum immunoreactive calcitonin concentration in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Dugard, J; Kew, M C; Da Fonseca, M; Levin, J [University of the Witwatersrand, Johannesburg (South Africa)

    1982-08-21

    Having found raised serum calcitonin concentrations in 94% of patients with hepatocellular carcinoma when using a dextran-coated-charcoal radio-immunoassay, we have now repeated the study, using a double-antibody radio-immunoassay, in 102 further patients with hepatocellular carcinoma and 35 matched controls. Serum immunoreactive calcitonin concentrations (iCT) in the controls ranged from 10 to 310 pg/ml (mean 154,6 pg/ml). Values in the tumour patients ranged from 10 to 1,650 pg/ml (mean 302,6 pg/ml). The mean figures were significantly higher in the tumour patients (P smaller than 0,001), 35.5% of them having values above 310 pg/ml. In 65 of the patients serum iCT concentrations were also determined by dextran-coated-charcoal radio-immunoassay. Values ranged from 10 to 10780 pg/ml (mean 2,179 pg/ml). If 1,000 pg/ml is taken as the upper limit of normal, 69% of the patients had raised iCT concentrations. There was a good correlation (r=0,67; P smaller than 0,001) between serum iCT values measured with both methods in 50 patients. If measured by the double-antibody radio-immunoassay method, the serum calcitonin value is not useful as a marker for hepatocellular carcinoma.

  12. Serum immunoreactive calcitonin concentration in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Dugard, J.; Kew, M.C.; Da Fonseca, M.; Levin, J.

    1982-01-01

    Having found raised serum calcitonin concentrations is 94% of patients with hepatocellular carcinoma when using a dextran-coated-charcoal radio-immunoassay, we have now repeated the study, using a double-antibody radio-immunoassay, in 102 further patients with hepatocellular carcinoma and 35 matched controls. Serum immunoreactive calcitonin concentrations (iCT) in the controls ranged from 10 to 310 pg/ml (mean 154,6 pg/ml). Values in the tumour patients ranged from 10 to 1 650 pg/ml (mean 302,6 pg/ml). The mean figures were significantly higher in the tumour patients (P smaller than 0,001), 35,5% of them having values above 310 pg/ml. In 65 of the patients serum iCT concentrations were also determined by dextran-coated-charcoal radio-immunoassay. Values ranged from 10 to 10780 pg/ml (mean 2 179 pg/ml). If 1 000 pg/ml is taken as the upper limit of normal, 69% of the patients had raised iCT concentrations. There was a good correlation (r=0,67; P smaller than 0,001) between serum iCT values measured with both methods in 50 patients. If measured by the double-antibody radio-immunoassay method, the serum calcitonin value is not useful as a marker for hepatocellular carcinoma

  13. Hydroxylamine-induced oxidation of ferrous carbonylated truncated hemoglobins from Mycobacterium tuberculosis and Campylobacter jejuni is limited by carbon monoxide dissociation.

    Science.gov (United States)

    Ascenzi, Paolo; Ciaccio, Chiara; Gasperi, Tecla; Pesce, Alessandra; Caporaso, Lucia; Coletta, Massimo

    2017-08-01

    Hydroxylamine (HA) is an oxidant of ferrous globins and its action has been reported to be inhibited by CO, even though this mechanism has not been clarified. Here, kinetics of the HA-mediated oxidation of ferrous carbonylated Mycobacterium tuberculosis truncated hemoglobin N and O (Mt-trHbN(II)-CO and Mt-trHbO(II)-CO, respectively) and Campylobacter jejuni truncated hemoglobin P (Cj-trHbP(II)-CO), at pH 7.2 and 20.0 °C, are reported. Mixing Mt-trHbN(II)-CO, Mt-trHbO(II)-CO, and Cj-trHbP(II)-CO solution with the HA solution brings about absorption spectral changes reflecting the disappearance of the ferrous carbonylated derivatives with the concomitant formation of the ferric species. HA oxidizes irreversibly Mt-trHbN(II)-CO, Mt-trHbO(II)-CO, and Cj-trHbP(II)-CO with the 1:2 stoichiometry. The dissociation of CO turns out to be the rate-limiting step for the oxidation of Mt-trHbN(II)-CO, Mt-trHbO(II)-CO, and Cj-trHbP(II)-CO by HA. Values of the second-order rate constant for HA-mediated oxidation of Mt-trHbN(II)-CO, Mt-trHbO(II)-CO, and Cj-trHbP(II)-CO range between 8.8 × 10 4 and 8.6 × 10 7 M -1 s -1 , reflecting different structural features of the heme distal pocket. This study (1) demonstrates that the inhibitory effect of CO is linked to the dissociation of this ligand, giving a functional basis to previous studies, (2) represents the first comparative investigation of the oxidation of ferrous carbonylated bacterial 2/2 globins belonging to the N, O, and P groups by HA, (3) casts light on the correlation between kinetics of HA-mediated oxidation and carbonylation of globins, and (4) focuses on structural determinants modulating the HA-induced oxidation process.

  14. Scope and Limits of an anamnestic questionnaire in a control-induced low-endemicity helminthiasis setting in south-central Côte d'Ivoire.

    Directory of Open Access Journals (Sweden)

    Thomas Fürst

    Full Text Available BACKGROUND: Schistosomiasis and soil-transmitted helminthiasis are two high-burden neglected tropical diseases. In highly endemic areas, control efforts emphasize preventive chemotherapy. However, as morbidity, infection, and transmission begin to decrease, more targeted treatment is likely to become more cost-effective, provided that comparatively cheap diagnostic methods with reasonable accuracy are available. METHODOLOGY: Adults were administered an anamnestic questionnaire in mid-2010 during a cross-sectional epidemiological survey in the Taabo health demographic surveillance system in south-central Côte d'Ivoire. Questions pertaining to risk factors and signs and symptoms for schistosomiasis and soil-transmitted helminthiasis were included. The individuals' helminth infection status and their belonging to three different anthelmintic treatment groups were compared with the questionnaire results (i to inform the local health authorities about the epidemiological and clinical footprint of locally prevailing helminthiases, and (ii to explore the scope and limits of an anamnestic questionnaire as monitoring tool, which eventually could help guiding the control of neglected tropical diseases in control-induced low-endemicity settings. PRINCIPAL FINDINGS: Our study sample consisted of 195 adults (101 males, 94 females. We found prevalences of hookworm, Trichuris trichiura, Schistosoma haematobium, and Schistosoma mansoni of 39.0%, 2.7%, 2.1%, and 2.1%, respectively. No Ascaris lumbricoides infection was found. Helminth infection intensities were generally very low. Seven, 74 and 79 participants belonged to three different treatment groups. Multivariable logistic regression models revealed statistically significant (p<0.05 associations between some risk factors, signs, and symptoms, and the different helminth infections and treatment groups. However, the risk factors, signs, and symptoms showed weak diagnostic properties. CONCLUSIONS

  15. Scope and Limits of an Anamnestic Questionnaire in a Control-Induced Low-Endemicity Helminthiasis Setting in South-Central Côte d’Ivoire

    Science.gov (United States)

    Fürst, Thomas; Ouattara, Mamadou; Silué, Kigbafori D.; N’Goran, Dje N.; Adiossan, Lukas G.; Bogoch, Isaac I.; N’Guessan, Yao; Koné, Siaka; Utzinger, Jürg; N’Goran, Eliézer K.

    2013-01-01

    Background Schistosomiasis and soil-transmitted helminthiasis are two high-burden neglected tropical diseases. In highly endemic areas, control efforts emphasize preventive chemotherapy. However, as morbidity, infection, and transmission begin to decrease, more targeted treatment is likely to become more cost-effective, provided that comparatively cheap diagnostic methods with reasonable accuracy are available. Methodology Adults were administered an anamnestic questionnaire in mid-2010 during a cross-sectional epidemiological survey in the Taabo health demographic surveillance system in south-central Côte d’Ivoire. Questions pertaining to risk factors and signs and symptoms for schistosomiasis and soil-transmitted helminthiasis were included. The individuals’ helminth infection status and their belonging to three different anthelmintic treatment groups were compared with the questionnaire results (i) to inform the local health authorities about the epidemiological and clinical footprint of locally prevailing helminthiases, and (ii) to explore the scope and limits of an anamnestic questionnaire as monitoring tool, which eventually could help guiding the control of neglected tropical diseases in control-induced low-endemicity settings. Principal Findings Our study sample consisted of 195 adults (101 males, 94 females). We found prevalences of hookworm, Trichuris trichiura, Schistosoma haematobium, and Schistosoma mansoni of 39.0%, 2.7%, 2.1%, and 2.1%, respectively. No Ascaris lumbricoides infection was found. Helminth infection intensities were generally very low. Seven, 74 and 79 participants belonged to three different treatment groups. Multivariable logistic regression models revealed statistically significant (p<0.05) associations between some risk factors, signs, and symptoms, and the different helminth infections and treatment groups. However, the risk factors, signs, and symptoms showed weak diagnostic properties. Conclusions/Significance The generally

  16. Current limiters

    Energy Technology Data Exchange (ETDEWEB)

    Loescher, D.H. [Sandia National Labs., Albuquerque, NM (United States). Systems Surety Assessment Dept.; Noren, K. [Univ. of Idaho, Moscow, ID (United States). Dept. of Electrical Engineering

    1996-09-01

    The current that flows between the electrical test equipment and the nuclear explosive must be limited to safe levels during electrical tests conducted on nuclear explosives at the DOE Pantex facility. The safest way to limit the current is to use batteries that can provide only acceptably low current into a short circuit; unfortunately this is not always possible. When it is not possible, current limiters, along with other design features, are used to limit the current. Three types of current limiters, the fuse blower, the resistor limiter, and the MOSFET-pass-transistor limiters, are used extensively in Pantex test equipment. Detailed failure mode and effects analyses were conducted on these limiters. Two other types of limiters were also analyzed. It was found that there is no best type of limiter that should be used in all applications. The fuse blower has advantages when many circuits must be monitored, a low insertion voltage drop is important, and size and weight must be kept low. However, this limiter has many failure modes that can lead to the loss of over current protection. The resistor limiter is simple and inexpensive, but is normally usable only on circuits for which the nominal current is less than a few tens of milliamperes. The MOSFET limiter can be used on high current circuits, but it has a number of single point failure modes that can lead to a loss of protective action. Because bad component placement or poor wire routing can defeat any limiter, placement and routing must be designed carefully and documented thoroughly.

  17. The Human Seru