Micronuclei frequency in albino rats exposed to high natural radiation

International Nuclear Information System (INIS)

Aneesh, D.; Godwin Wesley, S.

2013-01-01

Genotoxicity and DNA damage endpoints are used to evaluate results in the context of cell survival. Genotoxicity in mammalian cells is monitored mostly by using cytokinesis-block micronucleus (CBMN) assay. The score of micronuclei (MN) in peripheral blood lymphocytes can be used as a biomarker and also as a bio-dosimeter of radiation exposure. In the present study the effect of natural radiation on albino rats has been investigated, to find out if there is any increase in MN frequency in peripheral blood lymphocytes. Animals at the age of 2-3 weeks were exposed to natural radiation, at the dose of 10.38 μGyh -1 for a period of 6 months. A parallel control set was also maintained (0.12 μGy h -1 '). Blood samples were collected from both test (exposed to natural radiation) and control rats. Lymphocyte culture was done following 'microculture techniques' for 72 h. Cytochalasin B, at a concentration of 6.0 μg/ml, was added to the lymphocyte cultures at 44 h to block cytokinesis. The frequency of MN was evaluated by scoring a total of 1000 binucleated (BN) cells from one slide. The frequency of MN among the rats exposed to natural radiation was found to be 1.83±0.05 per 1000 BN cells and in the control it was 1.82±0.07 per 1000 BN cells. No statistically significant difference in the MN frequencies of exposed and control groups (p>0.05) was seen. The lower MN frequency in natural radiation exposed rats could be an indication of adaptive response. (author)

The dual anti-inflammatory and antioxidant activities of natural honey promote cell proliferation and neural regeneration in a rat model of colitis.

Science.gov (United States)

Nooh, Hanaa Z; Nour-Eldien, Nermeen M

2016-07-01

A decreased antioxidant capacity and excessive inflammation are well-known features in the pathogenesis of ulcerative colitis (UC). Recent evidence has suggested a role of honey in reducing colitis-induced inflammatory and oxidative stress markers. In this study, we examined whether the anti-inflammatory and anti-oxidative properties of honey have a beneficial effect on the enteric innervation and cellular proliferation of UC in rat. The colitis was induced in rats by dextran sodium sulphate (DSS). The effect of natural honey on induced colitis was assessed by the following parameters in colonic samples: tissue injury, inflammatory infiltration, interleukin-1β and -6, superoxide dismutase and reduced glutathione. In addition, the expression of tumour necrosis factor-α, inducible NO synthase, caspase-3, CD34, Ki67, S100, c-kit, and neuron-specific enolase were examined by immunohistochemistry. Compared to the DSS-induced colitis group, the honey-treated group had significantly improved macroscopic and microscopic scores and exhibited the down-regulation of oxidative, inflammatory, and apoptotic markers. In addition, up-regulation of intrinsic muscular innervation and epithelial cellular proliferation markers was detected. These results provide new insight into the beneficial role of natural honey in the treatment of DSS-induced colitis via the inhibition of colonic motor dysfunction and the inflammatory-oxidative-apoptotic cascade. In addition, the role of honey in epithelial regeneration was clarified. Copyright © 2016 Elsevier GmbH. All rights reserved.

Biomechanics of cellular solids.

Science.gov (United States)

Gibson, Lorna J

2005-03-01

Materials with a cellular structure are widespread in nature and include wood, cork, plant parenchyma and trabecular bone. Natural cellular materials are often mechanically efficient: the honeycomb-like microstructure of wood, for instance, gives it an exceptionally high performance index for resisting bending and buckling. Here we review the mechanics of a wide range of natural cellular materials and examine their role in lightweight natural sandwich structures (e.g. iris leaves) and natural tubular structures (e.g. plant stems or animal quills). We also describe two examples of engineered biomaterials with a cellular structure, designed to replace or regenerate tissue in the body.

Effect of electromagnetic fields at 2.45 GHz on the levels of cellular stress proteins HSP-90 and 70 in the rat thyroid

International Nuclear Information System (INIS)

Misa Agustino, M. J.; Alvarez-Folgueras, M.; Jorge-Mora, M. T.; Jorge Barreiro, F. J.; Ares Pena, F. J.; Lleiro, J.; Lopez Martin, M. E.

2011-01-01

In this study we analyzed the cellular stress levels achieved by heat shock proteins (HSP) 90 and 70 in rat thyroid tissue after exposure to radio waves in TWG experimental system. Parallel measurements of body stress in animals by rectal temperature probes allow us to determine whether there is any interaction between temperature increases and cellular stress.

Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors

OpenAIRE

DiGiovanna, J.; Dominici, N.; Friedli, L.; Rigosa, J.; Duis, S.; Kreider, J.; Beauparlant, J.; van den Brand, R.; Schieppati, M.; Micera, S.; Courtine, G.

2016-01-01

Contrary to cats and primates, cortical contribution to hindlimb locomotor movements is not critical in rats. However, the importance of the motor cortex to regain locomotion after neurological disorders in rats suggests that cortical engagement in hindlimb motor control may depend on the behavioral context. To investigate this possibility, we recorded whole-body kinematics, muscle synergies, and hindlimb motor cortex modulation in freely moving rats performing a range of natural locomotor pr...

Cellular location of rat muscle ferritins and their preferential loss during cell isolation.

Science.gov (United States)

Linder, M C; Roboz, M; McKown, M J; Pardridge, W M; Zak, R

1984-04-10

Heart and other muscles of the rat contain two forms of ferritin separable in polyacrylamide gel electrophoresis. The cellular location of the fast- and slow-migrating ferritins was investigated using primary cultures of hindlimb skeletal muscle, and isolated myocardial cell populations. Muscle and non-muscle cells were isolated in good yield from hearts of adult rats pretreated with large doses of iron to increase their ferritin content. In virtually all cases, the isolated muscle cells contained traces only of the fast-migrating species and the non-muscle cells contained small amounts of the slow-migrating ferritin. During cell isolation, 90-100% of both ferritins was lost and could be recovered in the perfusates and solutions employed, while one third of the total tissue protein, and a larger percentage of creatine phosphokinase, was recovered in the isolated cells. Primary cultures of thigh muscle from adult rats which had differentiated into multi-nucleated myotubes, were incubated for 1-3 days with chelated iron. These cells contained substantial amounts of the electrophoretically fast migrating ferritin, with its characteristic larger Stokes' radius (determined by quantitative polyacrylamide gel electrophoresis). None of the slow-migrating ferritin species was detected, although hindlimb muscle from iron-treated rats contained both forms. It is concluded that the fast-migrating ferritin of muscle, which is much larger and more asymmetric than other ferritins, is confined to the muscle cell population, while the other form is predominantly or exclusively in the non-muscle cells. Both ferritins are lost preferentially over other proteins during procedures which injure muscle tissue.

Various irrigation fluids affect postoperative brain edema and cellular damage during experimental neurosurgery in rats.

Science.gov (United States)

Doi, Kazuhisa; Kawano, Takeshi; Morioka, Yujiro; Fujita, Yasutaka; Nishimura, Masuhiro

2006-12-01

This study was conducted to investigate how various irrigation fluids used during neurosurgical procedures affect the degree of postoperative brain edema and cellular damage during experimental neurosurgery in rats. The cerebral cortex was exposed and incised crosswise with a surgical knife under irrigation with an artificial CSF, lactated Ringer's solution, or normal saline. Four hours after injury, irrigation was stopped and brain tissue samples were obtained from injured and uninjured sites. Specific gravity, cerebrovascular permeability, and TTC staining of the samples were evaluated. Incision and irrigation of the brain were not performed on the control group. At the injured site, specific gravities of the samples in the normal saline group and the lactated Ringer's solution group were significantly lower than the specific gravity in the artificial CSF group. The EB concentration was significantly higher in the lactated Ringer's solution group and relatively high in the normal saline group as compared with the artificial CSF group. TTC staining did not differ significantly between the artificial CSF group and the control group. It was significantly lower in the lactated Ringer's solution group and the normal saline group than in the control group and the artificial CSF group. As compared with normal saline and lactated Ringer's solution, artificial CSF reduced postoperative brain edema, cerebrovascular permeability, and cellular damage in sites injured by experimental neurosurgery in rats.

Comparative genome and evolutionary analysis of naturally occurring Beilong virus in brown and black rats.

Science.gov (United States)

Woo, Patrick C Y; Wong, Annette Y P; Wong, Beatrice H L; Lam, Carol S F; Fan, Rachel Y Y; Lau, Susanna K P; Yuen, Kwok-Yung

2016-11-01

Recently, we reported the presence of Beilong virus in spleen and kidney samples of brown rats and black rats, suggesting that these rodents could be natural reservoirs of Beilong virus. In this study, four genomes of Beilong virus from brown rats and black rats were sequenced. Similar to the Beilong virus genome sequenced from kidney mesangial cell line culture, those of J-virus from house mouse and Tailam virus from Sikkim rats, these four genomes from naturally occurring Beilong virus also contain the eight genes (3'-N-P/V/C-M-F-SH-TM-G-L-5'). In these four genomes, the attachment glycoprotein encoded by the G gene consists of 1046 amino acids; but for the original Beilong virus genome sequenced from kidney mesangial cell line, the G CDS was predicted to be prematurely terminated at position 2205 (TGG→TAG), resulting in a 734-amino-acid truncated G protein. This phenomenon of a lack of nonsense mutation in naturally occurring Beilong viruses was confirmed by sequencing this region of 15 additional rodent samples. Phylogenetic analyses showed that the cell line and naturally occurring Beilong viruses were closely clustered, without separation into subgroups. In addition, these viruses were further clustered with J-virus and Tailam virus, with high bootstrap supports of >90%, forming a distinct group in Paramyxoviridae. Brown rats and black rats are natural reservoirs of Beilong virus. Our results also supports that the recently proposed genus, Jeilongvirus, should encompass Beilong virus, J-virus and Tailam virus as members. Copyright © 2016 Elsevier B.V. All rights reserved.

Association of cellular and molecular responses in the rat mammary gland to 17β-estradiol with susceptibility to mammary cancer

International Nuclear Information System (INIS)

Ding, Lina; Zhao, Yang; Warren, Christopher L; Sullivan, Ruth; Eliceiri, Kevin W; Shull, James D

2013-01-01

We are using ACI and BN rats, which differ markedly in their susceptibility to 17β-estradiol (E2)-induced mammary cancer, to identify genetic variants and environmental factors that determine mammary cancer susceptibility. The objective of this study was to characterize the cellular and molecular responses to E2 in the mammary glands of ACI and BN rats to identify qualitative and quantitative phenotypes that associate with and/or may confer differences in susceptibility to mammary cancer. Female ACI and BN rats were treated with E2 for 1, 3 or 12 weeks. Mammary gland morphology and histology were examined by whole mount and hematoxylin and eosin (H&E) staining. Cell proliferation and epithelial density were evaluated by quantitative immunohistochemistry. Apoptosis was evaluated by quantitative western blotting and flow cytometry. Mammary gland differentiation was examined by immunohistochemistry. Gene expression was evaluated by microarray, qRT-PCR and quantitative western blotting assays. Extracellular matrix (ECM) associated collagen was evaluated by Picrosirius Red staining and Second Harmonic Generation (SHG) microscopy. The luminal epithelium of ACI rats exhibited a rapid and sustained proliferative response to E2. By contrast, the proliferative response exhibited by the mammary epithelium of BN rats was restrained and transitory. Moreover, the epithelium of BN rats appeared to undergo differentiation in response to E2, as evidenced by production of milk proteins as well as luminal ectasia and associated changes in the ECM. Marked differences in expression of genes that encode proteins with well-defined roles in mammary gland development (Pgr, Wnt4, Tnfsf11, Prlr, Stat5a, Areg, Gata3), differentiation and milk production (Lcn2, Spp1), regulation of extracellular environment (Mmp7, Mmp9), and cell-cell or cell-ECM interactions (Cd44, Cd24, Cd52) were observed. We propose that these cellular and molecular phenotypes are heritable and may underlie, at least in

Cellular and humoral immunity after vaccination or natural mumps infection.

Science.gov (United States)

Terada, Kihei; Hagihara, Kimiko; Oishi, Tomohiro; Miyata, Ippei; Akaike, Hiroto; Ogita, Satoko; Ohno, Naoki; Ouchi, Kazunobu

2017-08-01

This study measured cell-mediated immunity (CMI) and serum antibody to clarify the basis of breakthrough after vaccination and reinfection after mumps. From a pool of 54 college students, 17 seronegative subjects and 14 subjects with intermediate level of antibodies against mumps were vaccinated with a monovalent mumps vaccine, and CMI was assessed using interferon-γ release assay. CMI positivity according to pre-existing antibody level, defined as titer  0.05), respectively. Vaccination or even natural mumps infection did not always induce both cellular and humoral immunity. © 2017 Japan Pediatric Society.

Depolarization-stimulated 42K+ efflux in rat aorta is calcium- and cellular volume-dependent

International Nuclear Information System (INIS)

Magliola, L.; Jones, A.W.

1987-01-01

The purpose of this study was to investigate the factors controlling membrane permeability to potassium of smooth muscle cells from rat aorta stimulated by depolarization. The increase 42 K+ efflux (change in the rate constant) induced by depolarization (application of high concentrations of potassium chloride) was inhibited significantly by the calcium antagonists diltiazem and nisoldipine. Parallel inhibitory effects on contraction were observed. Diltiazem also inhibited potassium-stimulated 36 Cl- efflux. The addition of 25-150 mM KCl to normal physiologic solution stimulated 42 K+ efflux in a concentration-dependent manner. Diltiazem suppressed potassium-stimulated 42 K+ efflux approximately 90% at 25 mM KCl and approximately 40% at 150 mM KCl. The ability of nisoldipine to inhibit 42 K+ efflux also diminished as the potassium chloride concentration was elevated. The component of efflux that was resistant to calcium antagonists probably resulted from a decrease in the electrochemical gradient for potassium. Cellular water did not change during potassium addition. Substitution of 80 and 150 mM KCl for sodium chloride produced cellular swelling and enhanced potassium-stimulated 42 K+ efflux compared with potassium chloride addition. The addition of sucrose to prevent cellular swelling reduced efflux response to potassium substitution toward that of potassium addition. A hypoosmolar physiologic solution produced an increase in the 42 K+ efflux and a contracture that were both prevented by the addition of sucrose. We concluded that the depolarization-mediated 42 K+ efflux has three components: one is calcium dependent; a second is dependent on cellular volume; and a third is resistant to inhibition by calcium antagonists

Arecoline augments cellular proliferation in the prostate gland of male Wistar rats

International Nuclear Information System (INIS)

Saha, Indraneel; Chatterjee, Aniruddha; Mondal, Anushree; Maiti, Bishwa Ranjan; Chatterji, Urmi

2011-01-01

Areca nut chewing is the fourth most popular habit in the world due to its effects as a mild stimulant, causing a feeling of euphoria and slightly heightened alertness. Areca nuts contain several alkaloids and tannins, of which arecoline is the most abundant and known to have several adverse effects in humans, specially an increased risk of oral cancer. On evaluating the effects of arecoline on the male endocrine physiology in Wistar rats, it was found that arecoline treatment led to an overall enlargement and increase in the wet weight of the prostate gland, and a two-fold increase in serum gonadotropin and testosterone levels. Since the prostate is a major target for testosterone, the consequences of arecoline consumption were studied specifically in the prostate gland. Arecoline treatment led to an increase in the number of rough endoplasmic reticulum and reduction of secretory vesicles, signifying a hyperactive state of the prostate. Increased expression of androgen receptors in response to arecoline allowed for enhanced effect of testosterone in the prostate of treated animals, which augmented cell proliferation, subsequently confirmed by an increase in the expression of Ki-67 protein. Cellular proliferation was also the outcome of concomitant over expression of the G 1 -to-S cell cycle regulatory proteins, cyclin D1 and CDK4, both at the transcriptional and translational levels. Taken together, the findings provide the first evidence that regular use of arecoline may lead to prostatic hyperplasia and hypertrophy, and eventually to disorders associated with prostate enlargement. - Highlights: → Effect of arecoline was investigated on the endocrine physiology of male Wistar rats. → Increase observed in prostate size, wet weight, serum testosterone and gonadotropins. → Arecoline increased RER, expression of androgen receptor and cellular proliferation. → Upregulation of cyclin D1 and CDK4 seen at transcriptional and translational levels. → It may cause

The Na{sup +}/K{sup +} -pump in rat peritoneal mast cells: Some aspects of regulatio of activity and cellular fusion

Energy Technology Data Exchange (ETDEWEB)

Knudsen, T. [Odense Univ., Dept. of Pharmacology, Inst. of Medical Biology, The Faculty of Health Scineces (Denmark)

1995-12-31

The mast cell contains potent mediators of inflammation which are released after IgE-directed and non-IgE-directed stimulation of the cell. This highly specialized cell is therefore ascribed a role in the pathogenesis of disease states in which the inflammatory response plays a role for the development of the clinical symptoms. Thus, besides being of interest in basic research, studies of the cellular processes leading to release of inflammatory mediators from the mast cell also also have important clinical implications. The aim of the present work has been to document the existence of the Na{sup +}/K{sup +}-pump in rat peritoneal mast cells, to investigate the regulation of the pump activity and to explore whether modulation of the pump activity interferes with the cellular stimulus/secretion coupling mechanism. The Na{sup +}/K{sup +}-pump activity following stimulation of the mast cell was also investigated. The pump activity was assessed as the ouabain-sensitive cellular potassium uptake with {sup 86}Rb{sup +} as a tracer for potassium. The histamine release from the mast cell following IgE-directed and non-IgE-directed stimulation of the cell was used as a parameter of cellular degranulation. Histamine was measured by spectrofluorometry. Besides describing aspects of the function and regulation of the Na{sup +}/K{sup +}-pump in the rat peritoneal mast cell, this thesis points to the potential role of sodium transport mechanisms in mast cell physiology. Pharmacological manipulations of such transport mechanisms might in the future add to the treatment of allergic diseases. (au) 253 refs.

Evidence for increased cellular uptake of glutamate and aspartate in the rat hippocampus during kainic acid seizures. A microdialysis study using the "indicator diffusion' method

DEFF Research Database (Denmark)

Bruhn, T; Christensen, Thomas; Diemer, Nils Henrik

1997-01-01

Using a newly developed technique, based on microdialysis, which allows cellular uptake of glutamate and aspartate to be studied in awake animals, we investigated uptake of glutamate and aspartate in the hippocampal formation of rats during limbic seizures induced by systemical administration of ....... The results indicate that during KA-induced seizures, uptake of glutamate and aspartate is increased, possibly aimed at maintaining the extracellular homeostasis of these two excitatory amino acids.......Using a newly developed technique, based on microdialysis, which allows cellular uptake of glutamate and aspartate to be studied in awake animals, we investigated uptake of glutamate and aspartate in the hippocampal formation of rats during limbic seizures induced by systemical administration...... of kainic acid (KA). With [14C]mannitol as an extracellular reference substance, the cellular extraction of the test substance [3H]D-aspartate was measured at different stages of seizure-activity. The results were compared to those obtained in a sham operated control group. During severe generalized clonic...

Localization of cellular retinol-binding protein and retinol-binding protein in cells comprising the blood-brain barrier of rat and human

International Nuclear Information System (INIS)

MacDonald, P.N.; Ong, D.E.; Bok, D.

1990-01-01

Brain is not generally recognized as an organ that requires vitamin A, perhaps because no obvious histologic lesions have been observed in severely vitamin A-deficient animals. However, brain tissue does contain cellular vitamin A-binding proteins and a nuclear receptor protein for retinoic acid. In the present study, immunohistochemical techniques were used to determine the cell-specific location of cellular retinol-binding protein in human and rat brain tissue. Cellular retinol-binding protein was localized specifically within the cuboidal epithelial cells of the choroid plexus, two primary sites of the mammalian blood-brain barrier. In addition, autoradiographic procedures demonstrated binding sites for serum retinol-binding protein in the choroidal epithelium. These observations suggest that a significant movement of retinol across the blood-brain barrier may occur

Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors.

Science.gov (United States)

DiGiovanna, Jack; Dominici, Nadia; Friedli, Lucia; Rigosa, Jacopo; Duis, Simone; Kreider, Julie; Beauparlant, Janine; van den Brand, Rubia; Schieppati, Marco; Micera, Silvestro; Courtine, Grégoire

2016-10-05

Contrary to cats and primates, cortical contribution to hindlimb locomotor movements is not critical in rats. However, the importance of the motor cortex to regain locomotion after neurological disorders in rats suggests that cortical engagement in hindlimb motor control may depend on the behavioral context. To investigate this possibility, we recorded whole-body kinematics, muscle synergies, and hindlimb motor cortex modulation in freely moving rats performing a range of natural locomotor procedures. We found that the activation of hindlimb motor cortex preceded gait initiation. During overground locomotion, the motor cortex exhibited consistent neuronal population responses that were synchronized with the spatiotemporal activation of hindlimb motoneurons. Behaviors requiring enhanced muscle activity or skilled paw placement correlated with substantial adjustment in neuronal population responses. In contrast, all rats exhibited a reduction of cortical activity during more automated behavior, such as stepping on a treadmill. Despite the facultative role of the motor cortex in the production of locomotion in rats, these results show that the encoding of hindlimb features in motor cortex dynamics is comparable in rats and cats. However, the extent of motor cortex modulations appears linked to the degree of volitional engagement and complexity of the task, reemphasizing the importance of goal-directed behaviors for motor control studies, rehabilitation, and neuroprosthetics. We mapped the neuronal population responses in the hindlimb motor cortex to hindlimb kinematics and hindlimb muscle synergies across a spectrum of natural locomotion behaviors. Robust task-specific neuronal population responses revealed that the rat motor cortex displays similar modulation as other mammals during locomotion. However, the reduced motor cortex activity during more automated behaviors suggests a relationship between the degree of engagement and task complexity. This relationship

Recombinant tumor necrosis factor alpha inhibits growth of methylcholanthrene-induced sarcoma and enhances natural killer activity of tumor-infiltrating lymphocytes in aging rats

International Nuclear Information System (INIS)

Ziolkowska, Maria; Nowak Joanna, J.; Janiak, Marek; Ryzewska, Alicja

1994-01-01

The effect of recombinant human tumor necrosis factors alpha (rHuTNF-α) on the growth of immunogenic, methylcholanthrene-induced sarcoma (MC-Sa) and natural killer (NK) cell activity of tumor-infiltrating lymphocytes (TIL) in adult and aging rats was investigated. In both groups of animals the growth of transplantable MC-Sa was markedly and similarly inhibited by multiple intratumoral (i.t.) injections of rHuTF-α. This effect was accompanied by stimulation of NK activity of tumor-infiltrating lymphocytes in adult as well as in aging rats. Studies ''in vitro'' demonstrated additionally that rHuTNF-α was a potent stimulator of NK but not of ADCC (antibody-dependent cellular cytotoxicity) activity of spleen lymphocytes from healthy animals. Our results indicate that the antitumor effect of TNF-α is comparable in adult and in aging rats bearing immunogenic MC-Sa. The inhibition of MC-Sa growth may be attributed not only to the TNF-α-induced necrosis of the neoplastic tissue but also to the ''in vivo'' stimulatory effect of this cytokine upon the NK-type function of lymphocytes infiltrating the tumor mass. (author). 31 refs, 5 figs, 2 tabs

Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats

International Nuclear Information System (INIS)

Rashid, Kahkashan; Sil, Parames C.

2015-01-01

The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus. - Highlights: • STZ induced cellular stress plays a vital role in pancreatic dysfunction. • Cellular stress causes inflammation, pancreatic islet cell death and diabetes. • Deregulation of Nrf-2

Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats

Energy Technology Data Exchange (ETDEWEB)

Rashid, Kahkashan; Sil, Parames C., E-mail: parames@jcbose.ac.in

2015-02-01

The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus. - Highlights: • STZ induced cellular stress plays a vital role in pancreatic dysfunction. • Cellular stress causes inflammation, pancreatic islet cell death and diabetes. • Deregulation of Nrf-2

3-bromopyruvate inhibits glycolysis, depletes cellular glutathione, and compromises the viability of cultured primary rat astrocytes.

Science.gov (United States)

Ehrke, Eric; Arend, Christian; Dringen, Ralf

2015-07-01

The pyruvate analogue 3-bromopyruvate (3-BP) is an electrophilic alkylator that is considered a promising anticancer drug because it has been shown to kill cancer cells efficiently while having little toxic effect on nontumor cells. To test for potential adverse effects of 3-BP on brain cells, we exposed cultured primary rat astrocytes to 3-BP and investigated the effects of this compound on cell viability, glucose metabolism, and glutathione (GSH) content. The presence of 3-BP severely compromised cell viability and slowed cellular glucose consumption and lactate production in a time- and concentration-dependent manner, with half-maximal effects observed at about 100 µM 3-BP after 4 hr of incubation. The cellular hexokinase activity was not affected in 3-BP-treated astrocytes, whereas within 30 min after application of 3-BP the activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was inhibited, and cellular GSH content was depleted in a concentration-dependent manner, with half-maximal effects observed at about 30 µM 3-BP. The depletion of cellular GSH after exposure to 100 µM 3-BP was not prevented by the presence of 10 mM of the monocarboxylates lactate or pyruvate, suggesting that 3-BP is not taken up into astrocytes predominantly by monocarboxylate transporters. The data suggest that inhibition of glycolysis by inactivation of GAPDH and GSH depletion contributes to the toxicity that was observed for 3-BP-treated cultured astrocytes. © 2014 Wiley Periodicals, Inc.

Neural Representations of Natural and Scrambled Movies Progressively Change from Rat Striate to Temporal Cortex

Science.gov (United States)

Vinken, Kasper; Van den Bergh, Gert; Vermaercke, Ben; Op de Beeck, Hans P.

2016-01-01

In recent years, the rodent has come forward as a candidate model for investigating higher level visual abilities such as object vision. This view has been backed up substantially by evidence from behavioral studies that show rats can be trained to express visual object recognition and categorization capabilities. However, almost no studies have investigated the functional properties of rodent extrastriate visual cortex using stimuli that target object vision, leaving a gap compared with the primate literature. Therefore, we recorded single-neuron responses along a proposed ventral pathway in rat visual cortex to investigate hallmarks of primate neural object representations such as preference for intact versus scrambled stimuli and category-selectivity. We presented natural movies containing a rat or no rat as well as their phase-scrambled versions. Population analyses showed increased dissociation in representations of natural versus scrambled stimuli along the targeted stream, but without a clear preference for natural stimuli. Along the measured cortical hierarchy the neural response seemed to be driven increasingly by features that are not V1-like and destroyed by phase-scrambling. However, there was no evidence for category selectivity for the rat versus nonrat distinction. Together, these findings provide insights about differences and commonalities between rodent and primate visual cortex. PMID:27146315

Induction of Cellular Metallothionein in Irradiated Rats Supplemented with Egyptian Propolis Extract

International Nuclear Information System (INIS)

Nada, A.SH.; Azab, KH.SH.

2005-01-01

Proplis, a resinous yellow to dark substance collected by worker honeybees has been extensively used in folk medicine for management of a wide spectrum of disorders. The current study was conducted to evaluate the role of Egyptian propolis extract in modification of metallothionen (MT) induction in rats exposed to whole body fractionated gamma irradiation (delivered as 1.5 Gy every day up to 7.5 Gy total dose) and the relevance of certain metals (Cu, Zn, Mg, Mn and Fe) for metallothionein induction. In addition, lipid peroxides (thiobarbituric acid reactive substance; TEARS) and reduced glutathione (GSH) concentrations were observed in different subjected tissues. Metal content of crude propolis and certain related natural forms (bee pollen and honey) were also identified. Propolis extract was supplemented daily to rats (10 ml/kg body wt/day) by stomach tube, 15 days before and during exposure to gamma radiation. Experimental investigations were carried out on the 1st and 10th days after the last irradiation fraction in liver, kidney, brain, heart, lung and spleen tissues. The results obtained reveal that the administration of propolis extract increased significantly the metallothionein (MT) concentration in all examined tissues as compared with control rats. Records on all subjected tissues imparted that propolis extract supplementation has significantly minimized the radiation-induced increases in the amount of TBARS, maintained GSH con centration within normal levels except for lung and spleen and increased MT levels comparing to irradiated rats. Furthermore, significant amelioration in the levels of trace metals was observed such as zinc and copper in liver, kidney and brain. It could be postulated that the prolonged administration of Egyptian propolis extract attenuates the lipid peroxidation process in different rat's tissues and that might attributed to its antioxidant potency partially expressed through MT induction, maintenance of GSH levels and the

Biphasic stimulation of cellular calcium concentration by 3,5,3'-triiodothyronine in rat thymocytes

International Nuclear Information System (INIS)

Segal, J.

1988-01-01

3,5,3'-Triiodothyronine (T 3 ) produced a rapid and transient increase in 45 Ca uptake and cytoplasmic free calcium concentration in rat thymocytes, which is the most rapid effect of T 3 in this system. This effect was manifested in cells suspended in medium containing 1 mM calcium. The T 3 effect on 45 Ca uptake was evident at 15-30 s, reached maximum at 30-60 s, and returned to control values at 5 min. The T 3 effect on cytoplasmic free calcium concentration was seen after 30 s, reached maximum at 7 min, and returned to control values after 24 min. In cells suspended in Ca 2+ -free medium, T 3 produced a similar rapid increase in 45 Ca uptake, which was sustained for at least 60 min, but T 3 failed to change cytoplasmic free calcium concentration. Alprenolol (10 μM) blocked the stimulatory effects of T 3 on these two functions in a similar fashion. From these results, the authors suggest that in rat thymocytes T 3 influences cellular calcium economy through a biphasic mechanism in which T 3 first increases calcium uptake which, in turn, if followed by a release of calcium from intracellular pool(s), resulting in a further increase in cytoplasmic free calcium concentration and the activation of Ca 2+ -regulated systems. Moreover, the present study provides further support for the postulate that in the rat thymocyte calcium serves as the first messenger for the plasma membrane-mediated stimulatory effects of T 3 on several metabolic functions

Cellular and Axonal Diversity in Molecular Layer Heterotopia of the Rat Cerebellar Vermis

Directory of Open Access Journals (Sweden)

Sarah E. Van Dine

2013-01-01

Full Text Available Molecular layer heterotopia of the cerebellar primary fissure are a characteristic of many rat strains and are hypothesized to result from defect of granule cells exiting the external granule cell layer during cerebellar development. However, the cellular and axonal constituents of these malformations remain poorly understood. In the present report, we use histochemistry and immunocytochemistry to identify neuronal, glial, and axonal classes in molecular layer heterotopia. In particular, we identify parvalbumin-expressing molecular layer interneurons in heterotopia as well as three glial cell types including Bergmann glia, Olig2-expressing oligodendrocytes, and Iba1-expressing microglia. In addition, we document the presence of myelinated, serotonergic, catecholaminergic, and cholinergic axons in heterotopia indicating possible spinal and brainstem afferent projections to heterotopic cells. These findings are relevant toward understanding the mechanisms of normal and abnormal cerebellar development.

Inbred Rats as a Model to Study Persistent Renal Leptospirosis and Associated Cellular Immune Responsiveness

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Jarlath E. Nally

2018-03-01

Full Text Available Pathogenic species of Leptospira cause leptospirosis, a bacterial zoonotic disease with a global distribution affecting over one million people annually. Rats are regarded as one of the most significant reservoir hosts of infection for human disease, and in the absence of clinical signs of infection, excrete large numbers of organisms in their urine. A unique biological equilibrium exists between pathogenic leptospires and reservoir hosts of infection, but surprisingly, little is known concerning the host's cellular immune response that facilitates persistent renal colonization. To address this deficiency, we established and applied an immunocompetent inbred rat model of persistent renal colonization; leptospires were detected in urine of experimentally infected rats by 3 weeks post-infection and remained positive until 8 weeks post-infection. However, there was little, if any, evidence of inflammation in colonized renal tubules. At 8 weeks post-infection, a robust antibody response was detected against lipopolysaccharide and protein outer membrane (OM components. Purified B and T cells derived from the spleen of infected and non-infected rats proliferated in response to stimulation with 0.5 μg of OM fractions of Leptospira, including CD4+ T cells, which comprised 40% of proliferating cells, compared to 25% in non-infected controls. However, analysis of gene expression did not determine which immunoregulatory pathways were activated. Lymphocytes purified from the lymph node draining the site of colonization, the renal lymph node, also showed an increase in percentage of proliferating B and T cells. However, in contrast to a phenotype of 40% CD4+ T cells in the spleen, the phenotype of proliferating T cells in the renal lymph node comprised 65% CD4+ T cells. These results confirm that the renal lymph node, the local lymphoid organ, is a dominant site containing Leptospira reactive CD4+ T cells and highlight the need to consider the local, vs

Histochemical detection of the in vivo produced cellular aldehydes by means of direct Schiff's reaction in CCl/sub 4/ intoxicated rat liver

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Taper, H.S.; Somer, M.P.; Lans, M.; Gerlache, J. de; Roberfroid, M.

1988-04-01

A histochemical technique for detection of the in vivo induced cellular aldehydes based on the direct Schiff's reaction is reported in this paper. CCl/sub 4/-intoxicated rat liver was used as an experimental model. Fresh and non-pretreated rat liver cryostat sections fixed in 10% formol calcium solution and washed in distilled water were exposed to Schiff's reagent. The sections were then immersed in two baths of sodium bisulphite solution, then in water, dehydrated in ethanol, cleared in xylene and mounted in a synthetic anhydrous mounting medium. As Schiff positive areas presented well circumscribed foci which increased with time following intoxication, semiquantitative planimetric measurements were feasible. The direct Schiff's reaction detects cellular aldehydes in a sensitive, rapid histologically and topographically estimable way. The appearance of these aldehydes precedes distinctly morphological alterations detectable by other histochemical of histological techniques. No positive results were obtained in control, non-intocicated rat livers. Inhibitons of this direct Schiff's was obtained in positive control rat liver sections preincubated in solutions of aldehyde blockers. Histochemical detection of aldehydes may give useful information on different aspects of tissue and organ intoxication such as their topography, appearance, evolution, extension, consequences and effects of treatment. The direct Schiff's reaction can be considered as a valuable tool in fundamental and applied reasearch dealing with various toxicological, environmental, pathological, cancer-related and therapeutic problems.

Antioxidant-Rich Fraction of Urtica dioica Mediated Rescue of Striatal Mito-Oxidative Damage in MPTP-Induced Behavioral, Cellular, and Neurochemical Alterations in Rats.

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Bisht, Rohit; Joshi, Bhuwan Chandra; Kalia, Ajudhiya Nath; Prakash, Atish

2017-09-01

Parkinson's disease (PD) having a complex and multi-factorial neuropathology includes mainly the degeneration of the dopaminergic nigrostriatal pathway, which is a cumulative effect of depleted endogenous antioxidant enzymes, increased oxidative DNA damage, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. The present study was designed to investigate the neuroprotective effect of a potent antioxidant from Urtica dioica in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism. MPTP was administered intranigrally for the induction of PD in male Wistar rats. Behavioral alterations were assessed in between the study period. Animals were sacrificed immediately after behavioral session, and different biochemical, cellular, and neurochemical parameters were measured. Intranigrally repeated administration of MPTP showed significant impairment of motor co-ordination and marked increase of mito-oxidative damage and neuroinflammation in rats. Intranigral MPTP significantly decreases the dopamine and its metabolites with impairment of dopaminergic cell density in rat brain. However, post-treatment with the potent antioxidant fraction of Urtica dioica Linn. (UD) (20, 40, 80 mg/kg) improved the motor function, mito-oxidative defense alteration significantly and dose dependently in MPTP-treated rats. In addition, the potent antioxidant fraction of UD attenuated the pro-inflammatory cytokines (TNF-α and IL-β) and restored the level of dopamine and its metabolites in MPTP-induced PD in rats. Moreover, minocycline (30 mg/kg) with lower dose of UD (20 mg/kg) had significantly potentiated the protective effect of minocycline as compared to its effect with other individual drug-treated groups. In conclusion, Urtica dioica protected the dopaminergic neurons probably by reducing mito-oxidative damage, neuroinflammation, and cellular alteration along with enhanced neurotrophic potential. The above results revealed that the antioxidant rich

Toxicity studies in rats fed nature cure bitters | Aniagu | African ...

African Journals Online (AJOL)

Graded doses of Nature Cure Bitters (NCB) were administered daily (100, 200 and 400 mg/kg p.o) to rats for 28 days and the effects on body weight, organ weight, clinical signs, gross pathology, haematology, histology and serum biochemical parameters were evaluated. The relative weights of the heart, liver and testes of ...

Radiation induced microvascular damage in the rat spinal cord: cellular and secretory factors

International Nuclear Information System (INIS)

Pfeffer, M. Raphael; Siegal, Tali; Meltzer, A; Shezen, E; Ovadia, Haim

1996-01-01

Purpose/Objective: To investigate the short and long-term effect of radiation on micro vessel permeability, endothelin and nitric oxide production, and cellular profile in the spinal cord of rats and to evaluate the influence of recombinant human manganese superoxide dismutase (r-hMnSOD) on these effects. Materials and Methods: The thoracolumbar spinal cord of Fischer rats was irradiated to a dose of 15 Gy. At various times afterwards the rats were killed and the spinal cord was excised. Endothelin and nitric oxide synthase (NOS) activity and microvascular permeability were assayed quantitatively. Astrocytes, microglia, vascular basal membrane and neuro filaments were immunohistochemically evaluated. Results: None of the rats developed signs of neurological dysfunction. Endothelin concentrations in the spinal cord were significantly reduced 18 hours after irradiation and continued to decrease until after 10 days (p=<0.007). After 56 days endothelin concentration returned to normal and then rose to markedly elevated levels at 120 and 180 days (p=<0.002). NOS activity was reduced soon after irradiation and remained very low throughout the period of observation despite the changes in endothelin. Vascular permeability was markedly increased after 18 hours and again after 120 and 180 days. Treatment with r-hMnSOD had no effect on normal vascular permeability but abolished the increase in vascular permeability seen after irradiation. Standard microscopic examination revealed no changes in the irradiated spinal cord. Immunohistochemical stains showed a progressive increase in the number of microglial cells per field after 120 and 180 days (p=<0.0003). An increase in astrocytic cells was seen after 180 days with an earlier short lasting peak after 14 days. No abnormalities were found in blood vessel configuration, density and diameter. Vascular basal membrane and neuro filaments were unchanged throughout the study. Conclusions: Following radiation to the spinal cord there

Quantum features of natural cellular automata

International Nuclear Information System (INIS)

Elze, Hans-Thomas

2016-01-01

Cellular automata can show well known features of quantum mechanics, such as a linear rule according to which they evolve and which resembles a discretized version of the Schrödinger equation. This includes corresponding conservation laws. The class of “natural” Hamiltonian cellular automata is based exclusively on integer-valued variables and couplings and their dynamics derives from an Action Principle. They can be mapped reversibly to continuum models by applying Sampling Theory. Thus, “deformed” quantum mechanical models with a finite discreteness scale l are obtained, which for l → 0 reproduce familiar continuum results. We have recently demonstrated that such automata can form “multipartite” systems consistently with the tensor product structures of nonrelativistic many-body quantum mechanics, while interacting and maintaining the linear evolution. Consequently, the Superposition Principle fully applies for such primitive discrete deterministic automata and their composites and can produce the essential quantum effects of interference and entanglement. (paper)

Effect of naturally mouldy wheat or fungi administration on metallothioneins level in brain tissues of rats.

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Vasatkova, Anna; Krizova, Sarka; Krystofova, Olga; Adam, Vojtech; Zeman, Ladislav; Beklova, Miroslava; Kizek, Rene

2009-01-01

The aim of this study is to determine level of metallothioneins (MTs) in brain tissues of rats administered by feed mixtures with different content of mouldy wheat or fungi. Selected male laboratory rats of Wistar albino at age of 28 days were used in our experiments. The rats were administered by feed mixtures with different content of vitamins, naturally mouldy wheat or fungi for 28 days. At the very end of the experiment, the animals were put to death and brains were sampled. MT level was determined by differential pulse voltammetry Brdicka reaction. We found that MTs' level in brain tissues from rats administered by standard feed mixtures was significantly higher compared to the level of MTs in rats supplemented by vitamins. Further we studied the effect of supplementation of naturally mouldy wheat on MTs level in rats. In mouldy wheat we detected the presence of following fungi species: Mucor spp., Absidia spp., Penicillium spp., Aspergillus spp. and Fusarium spp. Moreover we also identified and quantified following mycotoxins - deoxynivalenol, zearalenone, T2-toxin and aflatoxins. Level of MTs determined in rats treated with 33 or 66% of mouldy wheat was significantly lower compared to control ones. On the other hand rats treated with 100% of mouldy wheat had less MTs but not significantly. Supplementation of vitamins to rats fed by mouldy wheat had adverse effect on MTs level compared to rats with no other supplementation by vitamins. Moreover vitamins supplementation has no effect on MTs level in brain tissues of rats treated or non-treated with Ganoderma lucidum L. Both mycotoxins and vitamins have considerable effect on level of MTs in brain tissues. It can be assumed that the administered substances markedly influence redox metabolism, which could negatively influence numerous biochemical pathways including those closely related with MTs.

Behavioral, cellular and molecular maladaptations covary with exposure to pyridostigmine bromide in a rat model of gulf war illness pain.

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Cooper, B Y; Flunker, L D; Johnson, R D; Nutter, T J

2018-08-01

Many veterans of Operation Desert Storm (ODS) struggle with the chronic pain of Gulf War Illness (GWI). Exposure to insecticides and pyridostigmine bromide (PB) have been implicated in the etiology of this multisymptom disease. We examined the influence of 3 (DEET (N,N-diethyl-meta-toluamide), permethrin, chlorpyrifos) or 4 GW agents (DEET, permethrin, chlorpyrifos, pyridostigmine bromide (PB)) on the post-exposure ambulatory and resting behaviors of rats. In three independent studies, rats that were exposed to all 4 agents consistently developed both immediate and delayed ambulatory deficits that persisted at least 16 weeks after exposures had ceased. Rats exposed to a 3 agent protocol (PB excluded) did not develop any ambulatory deficits. Cellular and molecular studies on nociceptors harvested from 16WP (weeks post-exposure) rats indicated that vascular nociceptor Na v 1.9 mediated currents were chronically potentiated following the 4 agent protocol but not following the 3 agent protocol. Muscarinic linkages to muscle nociceptor TRPA1 were also potentiated in the 4 agent but not the 3 agent, PB excluded, protocol. Although K v 7 activity changes diverged from the behavioral data, a K v 7 opener, retigabine, transiently reversed ambulation deficits. We concluded that PB played a critical role in the development of pain-like signs in a GWI rat model and that shifts in Na v 1.9 and TRPA1 activity were critical to the expression of these pain behaviors. Copyright © 2018 Elsevier Inc. All rights reserved.

Arginine vasopressin increases cellular free calcium concentration and adenosine 3',5'-monophosphate production in rat renal papillary collecting tubule cells in culture

International Nuclear Information System (INIS)

Ishikawa, S.; Okada, K.; Saito, T.

1988-01-01

The role of calcium (Ca) in the cellular action of arginine vasopressin (AVP) was examined in rat renal papillary collecting tubule cells in culture. AVP increased both the cellular free Ca concentration ([Ca2+]i) using fura-2, and cAMP production in a dose-dependent manner. AVP-induced cellular Ca mobilization was totally blocked by the antagonist to the antidiuretic action of AVP, and somewhat weakened by the antagonist to the vascular action of AVP. 1-Deamino-8-D-AVP (dDAVP). an antidiuretic analog of AVP, also increased [Ca2+] significantly. Cellular Ca mobilization was not obtained with cAMP, forskolin (a diterpene activator of adenylate cyclase), or phorbol-12-myristate-13-acetate. The early phase of [Ca2+]i depended on the intracellular Ca pool, since an AVP-induced rise in [Ca2+]i was obtained in cells pretreated with Ca-free medium containing 1 mM EGTA, verapamil, or cobalt, which blocked cellular Ca uptake. Also, AVP increased 45 Ca2+ influx during the initial 10 min, which initiated the sustained phase of cellular Ca mobilization. However, cellular cAMP production induced by AVP during the 10-min observation period was diminished in the cells pretreated with Ca-free medium, verapamil, or cobalt, but was still significantly higher than the basal level. This was also diminished by a high Ca concentration in medium. These results indicate that 1) AVP concomitantly regulates cellular free Ca as well as its second messenger cAMP production; 2) AVP-induced elevation of cellular free Ca is dependent on both the cellular Ca pool and extracellular Ca; and 3) there is an optimal level of extracellular Ca to modulate the AVP action in renal papillary collecting tubule cells

Resistance to Reperfusion Injury Following Short Term Postischemic Administration of Natural Honey in Globally Ischemic Isolated Rat Heart

OpenAIRE

Haleh Vaez; Mehrban Samadzadeh; Fahimeh Zahednezhad; Moslem Najafi

2012-01-01

Purpose: Results of our previous study revealed that preischemic perfusion of honey before zero flow global ischemia had cardioprotective effects in rat. The present study investigated potential resistance to reperfusion injury following short term postischemic administration of natural honey in globally ischemic isolated rat heart. Methods: Male Wistar rats were divided into five groups (n=10-13). The rat hearts were isolated, mounted on a Langendorff apparatus, allowed to equilibra...

Antioxidant properties of Taraxacum officinale fruit extract are involved in the protective effect against cellular death induced by sodium nitroprusside in brain of rats.

Science.gov (United States)

Colle, Dirleise; Arantes, Letícia Priscilla; Rauber, Ricardo; de Mattos, Sérgio Edgar Campos; Rocha, João Batista Teixeira da; Nogueira, Cristina Wayne; Soares, Félix Alexandre Antunes

2012-07-01

Taraxacum officinale Weber (Asteraceae), known as dandelion, is used for medicinal purposes due to its choleretic, diuretic, antitumor, antioxidant, antiinflammatory, and hepatoprotective properties. We sought to investigate the protective activity of T. officinale fruit extract against sodium nitroprusside (SNP)-induced decreased cellular viability and increased lipid peroxidation in the cortex, hippocampus, and striatum of rats in vitro. To explain the mechanism of the extract's antioxidant activity, its putative scavenger activities against NO, DPPH·, OH·, and H(2)O(2) were determined. Slices of cortex, hippocampus, and striatum were treated with 50 μM SNP and T. officinale fruit ethanolic extract (1-20 µg/mL) to determine cellular viability by MTT reduction assay. Lipid peroxidation was measure in cortical, hippocampal and striatal slices incubates with SNP (5 µM) and T. officinale fruit extract (1-20 µg/mL). We also determined the scavenger activities of T. officinale fruit extract against NO·, DPPH·, OH·, and H(2)O(2), as well as its iron chelating capacity. The extract (1, 5, 10, and 20 μg/mL) protected against SNP-induced decreases in cellular viability and increases in lipid peroxidation in the cortex, hippocampus, and striatum of rats. The extract had scavenger activity against DPPH· and NO· at low concentrations and was able to protect against H(2)O(2) and Fe(2+)-induced deoxyribose oxidation. T. officinale fruit extract has antioxidant activity and protects brain slices against SNP-induced cellular death. Possible mechanisms of action include its scavenger activities against reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are attributed to the presence of phenolic compounds in the extract.

The preventive effect of vitamin C on the cellular and functional integrity of kidney cells in rats following repeated exposure to paraquat

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Benjamin Nnamdi Okolonkwo

2014-11-01

Full Text Available Paraquat (PQ is a bipyridylium herbicide that is applied around trees in orchards and between crop rows to control broad-leaved and grassy weeds. Its oxidation results in the formation of superoxides which causes damage to cellular components. In this study, we determined the antioxidant effect vitamin C has on the cellular integrity of kidney function in rats following repeated exposure to PQ. Ninety-six male rats, grouped twelve rats per subgroup (A, Avit.c, B, Bvit.c, C, Cvit.c, D and Dvit.c were intraperitoneally injected with different sublethal increasing doses (0, 0, 2, 2, 4, 4, 6 and 6 mg/kg body weight of PQ respectively on biweekly (14 days intervals over a period of three months (84 days. Subsequently, the subgrouped animals (Avit.c, Bvit.c, Cvit.c and Dvit.c were maintained orally with 1 g/L vitamin C, while the other subgrouped animals (A, B, C and D received drinking water with negligible vitamin content throughout the study period. At the end of each monthly (28 days treatment, four animals per subgroup were selected. Urine samples were collected from each of the selected rats, after which each of the animals were anaesthetized with gaseous isoflurane and 5 mL of blood samples were collected using cardiac puncture procedure. The animals were later decapitated and their kidneys harvested. The samples collected were analyzed for urine [specific gravity (SG, pH, protein and glucose], blood (urea, creatinine, total protein and glucose, and the histological studies on kidney slides. The dose and exposure- time dependent PQ toxicity resulted in the reduction in urinary pH, elevation in urinary SG, and the detectable presence of protein and glucose in urine. It also caused marked elevation in serum urea and creatinine levels with reduction in serum protein and glucose levels and alterations in the cellular integrity of the renal architecture, especially the glomeruli and tubular tissues. Treatments on the PQ insulted animals with vitamin

Cellular adverse actions of dibromoacetonitrile, a by-product in water bacterial control, at sublethal levels in rat thymocytes.

Science.gov (United States)

Kishida, Takumi; Akiyoshi, Kenji; Erdenedalai, Erdenebat; Enhetomuru, Anu; Imai, Shoji; Oyama, Yasuo

2018-09-01

The aim of this study was to investigate the effects of dibromoacetonitrile (DBAN), a by-product in water bacterial control, at sublethal concentrations on rat thymocytes, by using a cytometric technique with appropriate fluorescent dyes. By using this method, the possibility that DBAN induces cellular actions related to oxidative stress was assessed. DBAN reduced the content of cellular nonprotein thiols under Zn 2+ -free conditions. It elevated the intracellular level of Zn 2+ , being independent from external Zn 2+ . DBAN increased cell vulnerability to the cytotoxic action of hydrogen peroxide. These actions of DBAN were likely related to oxidative stress. DBAN is formed by the reaction of bromides and chlorinated oxidants during water disinfection. Hydrolysis of 2,2-dibromo-3-nitrilopropionamide, an antimicrobial used in hydraulic fracturing fluids for production of shale gas and oil, produces DBAN. Therefore, the concern regarding the levels of DBAN in industrial water systems is necessary to avoid the environmental risk to humans and wild mammals. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect Of GAMMA Irradiated Thyme As Natural Antioxidant On Hypercholesterolemia Senile Rats

International Nuclear Information System (INIS)

El-Shahat, A.N.; Hamza, R.G.

2011-01-01

Hypercholesterolemia, high cholesterol diet and oxidative stress increase serum total cholesterol and LDL-cholesterol levels resulting in increased risk for development of atherosclerosis. Thyme (as antioxidant) has been commonly used in foods mainly for the flavour and preservation and also as herbal medicinal products. Antioxidants play an important role in inhibiting and scavenging free radicals, thus, providing protection to humans against infectious and degenerative diseases. This study was carried out to determine the effect of using thyme as supplement on serum levels of lipids, glucose and lipid peroxidation in hypercholesterolemia senile rats. GC-MS analysis of essential oil showed that the number of identified compounds was 12, especially thymol and carvacrol (natural antioxidants). Senile male rats were fed on hypercholesterolemia diet (HCD) containing cholesterol (1% w/w) and sodium cholate (0.2% w/w). Twenty eight male rats were equally and randomly categorized into four groups. Rats of group (1) fed on balanced commercial diet, group (2) fed on high cholesterol diet for 8 weeks, groups (3) and (4) fed on high cholesterol diet supplemented with either raw or irradiated thyme (1% w/w) for 8 weeks. The results obtained revealed that rats fed on high cholesterol diet significantly showed increase in serum total lipids, TG, TC, LDL-C, VLDL-C as well as ratio risk, associated with remarkable decrease in HDL-C. A significant increase was observed in the level of lipid peroxidation (TBARS) associated with significant decrease in hepatic antioxidant enzymes (glutathion reductase; GSH and catalase; CAT) and total antioxidant capacity. Also, high cholesterol diet induced significant elevation in the level of glucose and liver enzymes (AST, ALT, ALP). The results obtained revealed that feeding rats on HCD containing either raw or irradiated thyme (1% w/w) induced significant improvement in the mentioned parameters. Also, the thyme suppressed lipid peroxidation

Formation of human hepatocyte-like cells with different cellular phenotypes by human umbilical cord blood-derived cells in the human-rat chimeras

International Nuclear Information System (INIS)

Sun, Yan; Xiao, Dong; Zhang, Ruo-Shuang; Cui, Guang-Hui; Wang, Xin-Hua; Chen, Xi-Gu

2007-01-01

We took advantage of the proliferative and permissive environment of the developing pre-immune fetus to develop a noninjury human-rat xenograft small animal model, in which the in utero transplantation of low-density mononuclear cells (MNCs) from human umbilical cord blood (hUCB) into fetal rats at 9-11 days of gestation led to the formation of human hepatocyte-like cells (hHLCs) with different cellular phenotypes, as revealed by positive immunostaining for human-specific alpha-fetoprotein (AFP), cytokeratin 19 (CK19), cytokeratin 8 (CK8), cytokeratin 18 (CK18), and albumin (Alb), and with some animals exhibiting levels as high as 10.7% of donor-derived human cells in the recipient liver. More interestingly, donor-derived human cells stained positively for CD34 and CD45 in the liver of 2-month-old rat. Human hepatic differentiation appeared to partially follow the process of hepatic ontogeny, as evidenced by the expression of AFP gene at an early stage and albumin gene at a later stage. Human hepatocytes generated in this model retained functional properties of normal hepatocytes. In this xenogeneic system, the engrafted donor-derived human cells persisted in the recipient liver for at least 6 months after birth. Taken together, these findings suggest that the donor-derived human cells with different cellular phenotypes are found in the recipient liver and hHLCs hold biological activity. This humanized small animal model, which offers an in vivo environment more closely resembling the situations in human, provides an invaluable approach for in vivo investigating human stem cell behaviors, and further in vivo examining fundamental mechanisms controlling human stem cell fates in the future

Natural cytolytic activity in mice with natural or induced cellular defects. I. Differential ability of in vitro interleukin-2 addition to augment natural cytolytic function

International Nuclear Information System (INIS)

Ades, E.W.; Hinson, A.; Butler, L.D.

1986-01-01

The ability of in vitro addition of recombinant interleukin 2 (rIL-2) to differentially enhance natural cytotoxicity was assessed using cells from mice with natural and induced cellular defects. In vivo treatment with most immunosuppressive or cytoreductive agents, anti-asialo-GM1 antibody, or gamma irradiation dramatically reduced in vitro cytotoxicity against natural killer (NK) sensitive targets by direct reduction in either percentage specific lysis or lytic units per spleen. In most cases, in vitro addition of rIL-2 (at concentrations causing augmented NK function in cells from naive Balb/C mice) enhanced cytotoxic activity of cells from treatment groups to a normal value but not within the rIL-2-enhanced range of nontreated animals. Additionally, cytotoxic activity of cells from animals treated with certain drugs or gamma irradiation could be augmented by rIL-2 when measured by percentage lysis but not lytic units per spleen. In vivo treatment with cyclosporin A did not affect natural cytotoxic activity and addition of rIL-2 augmented the NK activity in a similar fashion to the profile of naive cells. In experiments using cells from beige (C57Bl/6-bg) mice which have a natural defect in NK activity against YAC-1 targets, addition of rIL-2 (at concentrations causing augmented natural cytotoxic function in cells from C57Bl/6 mice) could not effectively enhance in vitro natural cytotoxic function

Natural cytolytic activity in mice with natural or induced cellular defects. I. Differential ability of in vitro interleukin-2 addition to augment natural cytolytic function

Energy Technology Data Exchange (ETDEWEB)

Ades, E.W.; Hinson, A.; Butler, L.D.

1986-08-01

The ability of in vitro addition of recombinant interleukin 2 (rIL-2) to differentially enhance natural cytotoxicity was assessed using cells from mice with natural and induced cellular defects. In vivo treatment with most immunosuppressive or cytoreductive agents, anti-asialo-GM1 antibody, or gamma irradiation dramatically reduced in vitro cytotoxicity against natural killer (NK) sensitive targets by direct reduction in either percentage specific lysis or lytic units per spleen. In most cases, in vitro addition of rIL-2 (at concentrations causing augmented NK function in cells from naive Balb/C mice) enhanced cytotoxic activity of cells from treatment groups to a normal value but not within the rIL-2-enhanced range of nontreated animals. Additionally, cytotoxic activity of cells from animals treated with certain drugs or gamma irradiation could be augmented by rIL-2 when measured by percentage lysis but not lytic units per spleen. In vivo treatment with cyclosporin A did not affect natural cytotoxic activity and addition of rIL-2 augmented the NK activity in a similar fashion to the profile of naive cells. In experiments using cells from beige (C57Bl/6-bg) mice which have a natural defect in NK activity against YAC-1 targets, addition of rIL-2 (at concentrations causing augmented natural cytotoxic function in cells from C57Bl/6 mice) could not effectively enhance in vitro natural cytotoxic function.

Comparative studies in the cellular immunostimulation by whole body irradiation

International Nuclear Information System (INIS)

Dietz, R.; Schwarze, G.

1992-01-01

The effect of the cellular immune response by total body irradiation was investigated. The transplant survival (skin grafts) was determined as immune parameter. Donors were colony bred Wistar rats and recipients were colony bred Sprague Dawley rats. The investigations were carried out with irradiated rats and with rats irradiated after thymectomy and/or adrenalectomy as well as with animals without irradiation. A single total-body irradiation (1 and 2 Gy) was administered. The skin graft survival in irradiated rats was significant shorter (radiogenic immunostimulation) than in unirradiated rats; there were no significant differences between the operated (thymectomy and/or adrenalectomy) and not operated animals. Including precedent examinations this radiogenic immunostimulation is caused by relativly selective inactivation of T-suppressor cells. (orig.) [de

Direct anti-atherosclerotic therapy; development of natural anti-atherosclerotic drugs preventing cellular cholesterol retention.

Science.gov (United States)

Orekhov, Alexander N

2013-01-01

The results of numerous clinical trials with statins and other drugs have demonstrated the principal possibility of the prevention and regression of atherosclerosis by pharmacotherapy. This review describes the use of cultured human arterial cells for the mass screening of anti-atherosclerotic substances, the investigation of the mechanisms responsible for their atherosclerosis-related effects, and the optimization of anti-atherosclerotic and anti-atherogenic drug and dietary therapies. Natural products can be considered promising drugs for anti-atherosclerotic therapy. Our basic studies have shown that cellular lipidosis is the principal event in the genesis of atherosclerotic lesions. Using cellular models and natural products, we have developed an approach to prevent lipid accumulation in arterial cells. Based on our knowledge of atherosclerosis, we developed drugs that possess direct anti-atherosclerotic activity. Two-year treatment with allicor (garlic powder) has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Inflaminat (calendula, elder, and violet), which possesses anti-cytokine activity, has been shown to cause the regression of carotid atherosclerosis following the treatment of asymptomatic men for one year. The phytoestrogen-rich drug karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid) prevents the development of carotid atherosclerosis in postmenopausal women. Thus, our basic findings were successfully translated into clinical practice. Because of this translation, a novel approach to antiatherosclerotic therapy was developed. Our clinical trial confirmed the efficacy of both the novel approach and the novel drugs.

Ultrastructural and cellular damage to rat lung with x-rays: a search for target cell in lung tissue

Energy Technology Data Exchange (ETDEWEB)

Furuta, I

1975-03-01

Radiation effects on the peripheral alveoli of conventional rats were examined by means of electron microscopy. The right hemithorax alone was exposed to various single doses of x rays. The initial cellular lesions selectively involved the cytoplasms of alveolar capillary endothelial (Ed) and type 1 epithelial (Ep 1) cells in a dose-dependent fashion, where the major alterations were multifocal vacuolations and swellings. These lesions became visible as early as 1 hr after 1000 R (the assumed mean lethal dose for Ed cells) and more. However, progenitor Ep 2 cells exhibited no obvious cytoplasmic lesions by the doses below 2000 R, indicating that Ep 2 cells are more resistant to x rays. With time following 1000 R, the capillary Ed blebbing abruptly developed in various forms from the sites presumably other than the Ed junctions. The Ed blebs and interstitial edema progressed until about 2 weeks without recovery, while some signs of cellular recovery were recognized in Ep 1 cells during this period. The observations after a long period of 6 months following 1000 R showed that the typical pulmonary fibrotic changes were initiated in the interstitium perhaps around unrepaired capillaries. Further, inflammatory reaction characterized by massive cellular infiltations was superimposed on developing pulmonary fibrosis. Considering the current knowledge about the cell sensitivity and renewal in stable tissues, the present results imply that capillary Ed cell is the primary target for the radiation lesion leading to the secondary pulmonary alterations.

Cellular localization of transforming growth factor-alpha mRNA in rat forebrain.

Science.gov (United States)

Seroogy, K B; Lundgren, K H; Lee, D C; Guthrie, K M; Gall, C M

1993-05-01

The cellular localization of transforming growth factor-alpha (TGF alpha) mRNA in juvenile and adult rat forebrain was examined using in situ hybridization with a 35S-labeled cRNA probe. TGF alpha cRNA-labeled neuronal perikarya were distributed across many forebrain regions including the olfactory bulb, caudate-putamen, nucleus accumbens, olfactory tubercle, ventral pallidum, amygdala, hippocampal stratum granulosum and CA3 stratum pyramidale, and piriform, entorhinal, and retrosplenial cortices. TGF alpha cRNA-hybridizing cells were also localized to several thalamic nuclei and to the suprachiasmatic, dorsomedial, and ventromedial nuclei of the hypothalamus. In addition, labeled cells were present in regions of white matter including the corpus callosum, anterior commissure, internal and external capsules, optic tract, and lateral olfactory tract. Thus, both neurons and glia appear to synthesize TGF alpha in normal brain. Hybridization densities were greater in neuronal fields at 2 weeks of age compared with the adult, suggesting a role for TGF alpha in the development of several forebrain systems. Our results demonstrating the prominent and wide-spread expression of TGF alpha mRNA in forebrain, combined with the extremely low abundance of epidermal growth factor mRNA in brain, support the argument that TGF alpha is the principal endogenous ligand for the epidermal growth factor receptor in normal brain.

The cellular distribution of extracellular superoxide dismutase in macrophages is altered by cellular activation but unaffected by the natural occurring R213G substitution

DEFF Research Database (Denmark)

Gottfredsen, Randi Heidemann; Goldstrohm, David; Hartney, John

2014-01-01

and associated with the cell surface via the extracellular matrix (ECM)-binding region. Upon cellular activation induced by lipopolysaccharide, EC-SOD is relocated and detected both in the cell culture medium and in lipid raft structures. Although the secreted material presented a significantly reduced ligand......-binding capacity, this could not be correlated to proteolytic removal of the ECM-binding region, because the integrity of the material recovered from the medium was comparable to that of the cell surface-associated protein. The naturally occurring R213G amino acid substitution located in the ECM-binding region...

Fish oil supplementation associated with decreased cellular degeneration and increased cellular proliferation 6 weeks after middle cerebral artery occlusion in the rat

Directory of Open Access Journals (Sweden)

Pascoe MC

2015-01-01

Full Text Available Michaela C Pascoe,1 David W Howells, 2David P Crewther,1 Leeanne M Carey,2,3 Sheila G Crewther4 1Brain Sciences Institute, Swinburne University, ²Florey Institute of Neuroscience and Mental Health, University of Melbourne, 3Department of Occupational Therapy, School of Allied Health La Trobe University, 4School of Psychological Science, La Trobe University, Melbourne, VIC, Australia Abstract: Anti-inflammatory long-chain omega-3 polyunsaturated fatty acids (n-3-LC-PUFAs are both neuroprotective and have antidepressive effects. However the influence of dietary supplemented n-3-LC-PUFAs on inflammation-related cell death and proliferation after middle cerebral artery occlusion (MCAo-induced stroke is unknown. We have previously demonstrated that anxiety-like and hyperactive locomotor behaviors are reduced in n-3-LC-PUFA-fed MCAo animals. Thus in the present study, male hooded Wistar rats were exposed to MCAo or sham surgeries and examined behaviorally 6 weeks later, prior to euthanasia and examination of lesion size, cell death and proliferation in the dentate gyrus, cornu ammonis region of the hippocampus of the ipsilesional hemispheres, and the thalamus of the ipsilesional and contralesional hemispheres. Markers of cell genesis and cell degeneration in the hippocampus or thalamus of the ipsilesional hemisphere did not differ between surgery and diet groups 6 weeks post MCAo. Dietary supplementation with n-3-LC-PUFA decreased cell degeneration and increased cell proliferation in the thalamic region of the contralesional hemisphere. MCAo–associated cell degeneration in the hippocampus and thalamus positively correlated with anxiety-like and hyperactive locomotor behaviors previously reported in these animals. These results suggest that anti-inflammatory n-3-LC-PUFA supplementation appears to have cellular protective effects after MCAo in the rat, which may affect behavioral outcomes. Keywords: apoptosis, polyunsaturated fatty acids

Increased Expression of Intercellular Adhesion Molecule-1, Vascular Cellular Adhesion Molecule-1 and Leukocyte Common Antigen in Diabetic Rat Retina

Institute of Scientific and Technical Information of China (English)

Ningyan Bai; Shibo Tang; Jing Ma; Yan Luo; Shaofeng Lin

2003-01-01

Purpose: To understand the expression and distribution of intercellular adhesion molecule- 1(ICAM- 1),vascular cellular adhesion molecule- 1 (VCAM- 1)and CD45 (Leukocyte Common Antigen) in the control nondiabetic and various courses of diabetic rats retina. To explore the role of adhesion molecules (Ams) and the adhesion of leukocytes to vascular endothelial cells via Ams in diabetic retinopathy(DR).Methods: Sixty healthy adult male Wistar rats were randomly divided into diabetic groups(induced by Streptozotocin, STZ) and normal control groups. Rats in these two groups were further randomly divided into 3, 7, 14, 30, 90 and 180 days-group,including 5 rats respectively. The immunohistochemical studies of ICAM-1, VCAM-1 and CD45 were carried out in the retinal digest preparations or retinal paraffin sections, and the results were analyzed qualitatively, semi-quantitatively.Results: No positive reaction of VCAM-1 was found, and weak reactions of ICAM-1,CD45 were found in nondiabetic rats retina. The difference of 6 control groups had no statistical significance(P ＞ 0.05). The increased ICAM-1 and CD45 staining pattern were detectable 3 days after diabetes induction, and a few VCAM-1 positive cells were observed in the retinal blood capillaries. The difference of diabetes and control is significant( P ＜ 0.05).Following the course, the expressions of ICAM-1, VCAM-1 and CD45 were increasingly enhanced, reaching a peak at the 14th day.Conclusion: Increased expression of ICAM-1, VCAM-1 and leukocytes adhering and stacking in retinal capillaries are the very early events in DR. Coherence of expression and distribution of the three further accounts for it is the key point for the onset of DR that Ams mediates leukocytes adhesion and endothelial cell injury.

Malignant monoblasts can function as effector cells in natural killer cell and antibody-dependent cellular cytotoxicity assays

DEFF Research Database (Denmark)

Hokland, P; Hokland, M; Ellegaard, J

1981-01-01

This is the first report describing natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) of malignant monoblasts. Pure acute monoblastic leukemia was diagnosed in bone marrow aspirations from two patients by use of conventional cytochemical methods as well as multiple immunolog...... no modulation was seen in ADCC. These findings are discussed in the light of our present knowledge of lymphoid NK cells. Udgivelsesdato: 1981-May...

Zero Flow Global Ischemia-Induced Injuries in Rat Heart Are Attenuated by Natural Honey

OpenAIRE

Najafi, Moslem; Zahednezhad, Fahimeh; Samadzadeh, Mehrban; Vaez, Haleh

2012-01-01

Purpose: In the present study, effects of preischemic administration of natural honey on cardiac arrhythmias and myocardial infarction size during zero flow global ischemia were investigated in isolated rat heart. Methods: The isolated hearts were subjected to 30 min zero flow global ischemia followed by 120 min reperfusion then perfused by a modified drug free Krebs-Henseleit solution throughout the experiment (control) or the solution containing 0.25, 0.5, 1 and 2% of natural honey...

Electromagnetic cellular interactions.

Science.gov (United States)

Cifra, Michal; Fields, Jeremy Z; Farhadi, Ashkan

2011-05-01

Chemical and electrical interaction within and between cells is well established. Just the opposite is true about cellular interactions via other physical fields. The most probable candidate for an other form of cellular interaction is the electromagnetic field. We review theories and experiments on how cells can generate and detect electromagnetic fields generally, and if the cell-generated electromagnetic field can mediate cellular interactions. We do not limit here ourselves to specialized electro-excitable cells. Rather we describe physical processes that are of a more general nature and probably present in almost every type of living cell. The spectral range included is broad; from kHz to the visible part of the electromagnetic spectrum. We show that there is a rather large number of theories on how cells can generate and detect electromagnetic fields and discuss experimental evidence on electromagnetic cellular interactions in the modern scientific literature. Although small, it is continuously accumulating. Copyright © 2010 Elsevier Ltd. All rights reserved.

1024-Pixel CMOS Multimodality Joint Cellular Sensor/Stimulator Array for Real-Time Holistic Cellular Characterization and Cell-Based Drug Screening.

Science.gov (United States)

Park, Jong Seok; Aziz, Moez Karim; Li, Sensen; Chi, Taiyun; Grijalva, Sandra Ivonne; Sung, Jung Hoon; Cho, Hee Cheol; Wang, Hua

2018-02-01

This paper presents a fully integrated CMOS multimodality joint sensor/stimulator array with 1024 pixels for real-time holistic cellular characterization and drug screening. The proposed system consists of four pixel groups and four parallel signal-conditioning blocks. Every pixel group contains 16 × 16 pixels, and each pixel includes one gold-plated electrode, four photodiodes, and in-pixel circuits, within a pixel footprint. Each pixel supports real-time extracellular potential recording, optical detection, charge-balanced biphasic current stimulation, and cellular impedance measurement for the same cellular sample. The proposed system is fabricated in a standard 130-nm CMOS process. Rat cardiomyocytes are successfully cultured on-chip. Measured high-resolution optical opacity images, extracellular potential recordings, biphasic current stimulations, and cellular impedance images demonstrate the unique advantages of the system for holistic cell characterization and drug screening. Furthermore, this paper demonstrates the use of optical detection on the on-chip cultured cardiomyocytes to real-time track their cyclic beating pattern and beating rate.

Special Issue: Redox Active Natural Products and Their Interaction with Cellular Signalling Pathways

Directory of Open Access Journals (Sweden)

Claus Jacob

2014-11-01

Full Text Available During the last decade, research into natural products has experienced a certain renaissance. The urgent need for more and more effective antibiotics in medicine, the demand for ecologically friendly plant protectants in agriculture, “natural” cosmetics and the issue of a sustainable and healthy nutrition in an ageing society have fuelled research into Nature’s treasure chest of “green gold”. Here, redox active secondary metabolites from plants, fungi, bacteria and other (micro-organisms often have been at the forefront of the most interesting developments. These agents provide powerful means to interfere with many, probably most cellular signaling pathways in humans, animals and lower organisms, and therefore can be used to protect, i.e., in form of antioxidants, and to frighten off or even kill, i.e., in form of repellants, antibiotics, fungicides and selective, often catalytic “sensor/effector” anticancer agents. Interestingly, whilst natural product research dates back many decades, in some cases even centuries, and compounds such as allicin and various flavonoids have been investigated thoroughly in the past, it has only recently become possible to investigate their precise interactions and mode(s of action inside living cells. Here, fluorescent staining and labelling on the one side, and appropriate detection, either qualitatively under the microscope or quantitatively in flow cytometers and plate readers, on the other, enable researchers to obtain the various pieces of information necessary to construct a fairly complete puzzle of how such compounds act and interact in living cells. Complemented by the more traditional activity assays and Western Blots, and increasingly joined by techniques such as proteomics, chemogenetic screening and mRNA profiling, these cell based bioanalytical techniques form a powerful platform for “intracellular diagnostics”. In the case of redox active compounds, especially of Reactive Sulfur

Isolation of Trichophyton mentogrophytes var mentogrophytes from naturally infected laboratory albino rats: experimental infection and treatment in rabbits

Directory of Open Access Journals (Sweden)

N. A. Issa

2009-01-01

Full Text Available The present study demonstrated for the first time the occurrence of dermatophytosis in naturally infected rats and from asymptomatic and from breeding boxes of white rats kept in animal housing of college of Veterinary Medicine, University of Dohuk, Iraq. The prevalence rate of infection was (28%, clinically infected rats characterized by appearance of scaly ovoid type lesions with crusty edge and patch of hair loss mostly seen on the back, neck and face of the infected rats, itching was reported in some rats. Only one species of the trichophyton, T. mentogrophytes var mentogrophytes was isolated with growth rate (85.71% of samples collected from clinically infected rats, and (28.57% from asymptomatic and from breeding cages, the growth was observed within the 21 days at 25ºC on Sabouraud's Dextrose Agar. Lacto phenol cotton blue staining slides of T. mentogrophytes var mentogrophytes revealed both microconidia and macroconidia. Microconidia found in numerous numbers often in dense cluster which were hyaline, smooth walled and predominantly spherical to sub spherical in shape, varying numbers of chlamydoconidia. Spiral hyphae and smooth, thin walled clavate shaped multicelled macroconidia were also present. The study also dealt with experimental infection in rabbits with T. mentogrophytes var mentogrophytes and treated by two drugs, natural herbal preparation of acidic pomegranate (Punica granatum fruit and synthetic nystatine ointment. The complete recovery of lesions was recorded after 14 days and 21 days of topical application of a pomegranate and nystatine ointment for 5 successive days respectively.

Iron Oxide Nanoparticles Stimulates Extra-Cellular Matrix Production in Cellular Spheroids

Directory of Open Access Journals (Sweden)

Megan Casco

2017-01-01

Full Text Available Nanotechnologies have been integrated into drug delivery, and non-invasive imaging applications, into nanostructured scaffolds for the manipulation of cells. The objective of this work was to determine how the physico-chemical properties of magnetic nanoparticles (MNPs and their spatial distribution into cellular spheroids stimulated cells to produce an extracellular matrix (ECM. The MNP concentration (0.03 mg/mL, 0.1 mg/mL and 0.3 mg/mL, type (magnetoferritin, shape (nanorod—85 nm × 425 nm and incorporation method were studied to determine each of their effects on the specific stimulation of four ECM proteins (collagen I, collagen IV, elastin and fibronectin in primary rat aortic smooth muscle cell. Results demonstrated that as MNP concentration increased there was up to a 6.32-fold increase in collagen production over no MNP samples. Semi-quantitative Immunohistochemistry (IHC results demonstrated that MNP type had the greatest influence on elastin production with a 56.28% positive area stain compared to controls and MNP shape favored elastin stimulation with a 50.19% positive area stain. Finally, there are no adverse effects of MNPs on cellular contractile ability. This study provides insight on the stimulation of ECM production in cells and tissues, which is important because it plays a critical role in regulating cellular functions.

Influence of extra-cellular and intra-cellular acting thiol oxidants on the 45calcium uptake by the islets of Langerhans of the rat

International Nuclear Information System (INIS)

Haegele, R.G.

1981-01-01

The glucose-stimulated calcium uptake by the islets of Langerhans is dependent on the intra-cellular GSH/GSSG ratios. The inhibition of calcium uptake is not the consequence of a direct oxidation of membrane-fixed thiol groups. In contrast, direct oxidation of extra cellular thiols leads to an increase in calcium uptake when intra-cellular oxidation is simultaneously prevented. Since this effect only occurs at high intra-cellular GSH/GSSG ratios it can be assumed that the redox state of extra-cellular thiols is dependent on the redox state of the intra-cellular GSH/GSSG ratios. These findings support the theory that the oxidation of extra-cellular thiols by thiol oxidants leads to an increase in calcium uptake and that the extent of uptake is higher, the more the redox state of the extra-cellular thiols tends towards the reduced state prior to oxidation. (orig./MG) [de

Na+ -K+ pump activity in rat peritoneal mast cells: inhibition by extracellular calcium

DEFF Research Database (Denmark)

Knudsen, Torben; Johansen, Torben

1989-01-01

1. Pure populations of rat peritoneal mast cells were used to study cellular potassium uptake. The radioactive potassium analogue, 86rubidium, was used as a tracer for potassium for measurements of the activity of the cellular potassium uptake process. 2. The ouabain-sensitive and the ouabain......-resistant potassium (86rubidium) uptake of mast cells incubated in the presence of calcium, 1 mmol l-1, were very low, 52 and 147 pmol per 10(6) cells min-1. 3. Calcium-deprivation of the cells uncovered a large capacity ouabain-sensitive potassium (86rubidium) uptake mechanism. The activity of the uptake mechanism...... was decreased by reintroduction of calcium into the cell suspension, and it was dependent on cellular energy metabolism, temperature and pH. 4. The potassium (86rubidium) uptake of mast cells incubated in a calcium-free medium occurs through an active and ouabain-sensitive mechanism that has the nature...

Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts.

Science.gov (United States)

Waly, Mostafa I; Al-Rawahi, Amani S; Al Riyami, Marwa; Al-Kindi, Mohamed A; Al-Issaei, Halima K; Farooq, Sardar A; Al-Alawi, Ahmed; Rahman, Mohammad S

2014-02-18

Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats; the cytotoxicity of AOM is considered to mediate oxidative stress. This study investigated the chemopreventive effect of three natural extracts [pomegranate peel extract (PomPE), papaya peel extract (PapPE) and seaweed extract (SE)] against AOM-induced oxidative stress and carcinogenesis in rat colon. Eighty Sprague-Dawley rats (aged 4 weeks) were randomly divided into 8 groups (10 rats/group). Control group was fed a basal diet; AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of PomPE, PapPE or SE, in the presence or absence of AOM injection. All animals were continuously fed ad-libitum until aged 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, genotoxicity (induced micronuclei (MN) cells enumeration), and glutathione and lipid peroxidation. Our results showed that AOM-induced ACF development and pathological changes in the colonic mucosal tissues, increased bone marrow MN cells and oxidative stress (glutathione depletion, lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with PomPE, PapPE or SE significantly ameliorated the cytotoxic effects of AOM. The results of this study provide in-vivo evidence that PomPE, PapPE and SE reduced the AOM-induced colon cancer in rats, through their potent anti-oxidant activities.

On Elementary and Algebraic Cellular Automata

Science.gov (United States)

Gulak, Yuriy

In this paper we study elementary cellular automata from an algebraic viewpoint. The goal is to relate the emergent complex behavior observed in such systems with the properties of corresponding algebraic structures. We introduce algebraic cellular automata as a natural generalization of elementary ones and discuss their applications as generic models of complex systems.

Inhibition by natural dietary substances of gastrointestinal absorption of starch and sucrose in rats and pigs: 1. Acute studies.

Science.gov (United States)

Preuss, Harry G; Echard, Bobby; Bagchi, Debasis; Stohs, Sidney

2007-08-06

Rapid gastrointestinal absorption of refined carbohydrates (CHO) is linked to perturbed glucose-insulin metabolism that is, in turn, associated with many chronic health disorders. We assessed the ability of various natural substances, commonly referred to as "CHO blockers," to influence starch and sucrose absorption in vivo in ninety-six rats and two pigs. These natural enzyme inhibitors of amylase/sucrase reportedly lessen breakdown of starches and sucrose in the gastrointestinal tract, limiting their absorption. To estimate absorption, groups of nine SD rats were gavaged with water or water plus rice starch and/or sucrose; and circulating glucose was measured at timed intervals thereafter. For each variation in the protocol a total of at least nine different rats were studied with an equal number of internal controls on three different occasions. The pigs rapidly drank CHO and inhibitors in their drinking water. In rats, glucose elevations above baseline over four hours following rice starch challenge as estimated by area-under-curve (AUC) were 40%, 27%, and 85% of their internal control after ingesting bean extract, hibiscus extract, and l-arabinose respectively in addition to the rice starch. The former two were significantly different from control. L-Arabinose virtually eliminated the rising circulating glucose levels after sucrose challenge, whereas hibiscus and bean extracts were associated with lesser decreases than l-arabinose that were still significantly lower than control. The glucose elevations above baseline over four hours in rats receiving sucrose (AUC) were 51%, 43% and 2% of control for bean extract, hibiscus extract, and L-arabinose, respectively. Evidence for dose-response of bean and hibiscus extracts is reported. Giving the natural substances minus CHO challenge caused no significant changes in circulating glucose concentrations, indicating no major effects on overall metabolism. A formula combining these natural products significantly

Co(III)EDTA as extra-cellular marker in μPIXE-analysis of rat cardiomyocytes

International Nuclear Information System (INIS)

Quaedackers, J.A.; Queens, R.M.G.J.; Mutsaers, P.H.A.; Voigt, M.J.A. de; Vusse, G.J. van der

1998-01-01

In previous studies no clear difference was found between the intra- and extra-cellular compartment in nuclear microprobe elemental distribution maps of freeze-dried cryo sections of heart tissue. Probably due to artefacts during the preparation of these samples, the intra-cellular and the extra-cellular content of elements are mixed up. In this article a method, using NaCo(III)EDTA as an extra-cellular marker, was applied to deconvolute the total ion content in an extra- and intra-cellular contribution. This method was both applied to normoxic heart tissue and low-flow ischemic heart tissue. Intra-cellular ion concentrations calculated from the corrected ion contents of the normoxic tissue agrees well with literature values. Moreover a clear elevation of the intra-cellular sodium and chlorine concentration was found in low-flow ischemic tissue. (orig.)

Effect Of Using Black Cumin (Nigella Sativa) As Natural Antioxidant On Hyperlipidaemia And Antioxidant Activities In Senile Rats

International Nuclear Information System (INIS)

HAMZA, R.G.; MAHMOUD, K.A.

2009-01-01

The black cumin (Nigella sativa) is one of the important herbal plants that used widely in most of human diseases and food preservation. Chemical composition of irradiated black cumin (10 kGy); moisture, ash, crude protein, crude lipid, total carbohydrate and crude fiber, were evaluated. The GC for analysis of fatty acids showed that the number of identified fatty acids was 9; the important one was linoleic (natural antioxidant). GC/MS used for analysis of essential oil showed that the number of identified compounds was 16; the important ones were thymoquinone, eugenol and linalool (natural antioxidants). Also, this study was performed to examine the efficacy of the black cumin to ameliorate the induced hyperlipidemia in senile rats. Twenty eight male rats were equally and randomly categorized into four groups. High fat diet (20g fat / 100g diet) was daily administered to rats for 6 weeks. Other animals where fed daily on either raw or irradiated black cumin diet (1% w/w) for 6 weeks. The results revealed that high fat diet fed to rats significantly induced an increase in serum phospholipids, TG, TC, LDL-C, atherogenic index and lipid peroxides (MDA). Significant decrease was observed in HDL-C, blood antioxidant enzymes activity (superoxide dismutase and catalase) and concentration of reduced glutathione (GSH). The results obtained revealed that feeding rats on diet containing either raw or irradiated black cumin (1% w/w) induced significant improvement in the above mentioned parameters. There was non- significant difference between non-irradiated and irradiated black cumin. Moreover, supplementation of black cumin in diet of rats can offer protection against free radicals generated through oxidative stress as a consequence of hyperlipidemic food.

Effect Of Using Black Cumin (Nigella Sativa) As Natural Antioxidant On Hyperlipidaemia And Antioxidant Activities In Senile Rats

Energy Technology Data Exchange (ETDEWEB)

HAMZA, R G; MAHMOUD, K A [Food Irradiation Research Dept., National Centre for Radiation Research and Technology, Atomic Energy Authority, Cairo (Egypt)

2009-07-01

The black cumin (Nigella sativa) is one of the important herbal plants that used widely in most of human diseases and food preservation. Chemical composition of irradiated black cumin (10 kGy); moisture, ash, crude protein, crude lipid, total carbohydrate and crude fiber, were evaluated. The GC for analysis of fatty acids showed that the number of identified fatty acids was 9; the important one was linoleic (natural antioxidant). GC/MS used for analysis of essential oil showed that the number of identified compounds was 16; the important ones were thymoquinone, eugenol and linalool (natural antioxidants). Also, this study was performed to examine the efficacy of the black cumin to ameliorate the induced hyperlipidemia in senile rats. Twenty eight male rats were equally and randomly categorized into four groups. High fat diet (20g fat / 100g diet) was daily administered to rats for 6 weeks. Other animals where fed daily on either raw or irradiated black cumin diet (1% w/w) for 6 weeks. The results revealed that high fat diet fed to rats significantly induced an increase in serum phospholipids, TG, TC, LDL-C, atherogenic index and lipid peroxides (MDA). Significant decrease was observed in HDL-C, blood antioxidant enzymes activity (superoxide dismutase and catalase) and concentration of reduced glutathione (GSH). The results obtained revealed that feeding rats on diet containing either raw or irradiated black cumin (1% w/w) induced significant improvement in the above mentioned parameters. There was non- significant difference between non-irradiated and irradiated black cumin. Moreover, supplementation of black cumin in diet of rats can offer protection against free radicals generated through oxidative stress as a consequence of hyperlipidemic food.

Evaluation of the radioprotective and curative role of a natural antioxidant against cellular ultrastructural hazards induced in rats by gamma radiation exposure

International Nuclear Information System (INIS)

Abdel-Azeem, M.G.

2005-01-01

This study was designed to investigate the effects of Nigella sativa known as black seed in the amelioration of the histological disorders that occur in different tissues of albino rats exposed to 8 Gy whole body gamma irradiation, delivered as a single dose. Nigella sativa oil was administered daily to rats at a dose of 30 mg / 100 g body weight by gavage, 10 days before irradiation and to another group 10 days after irradiation. Experimental investigations performed one day after radiation for the first group and ten days after radiation for the second group showed that Nigella sativa treatment exerted a radioprotective and curative role on the fine structure of the renal tissue detected as swelling and cristalysis of mitochondria, fragmentation and dilatation damage in the rough endoplasmic reticulum which exhibited in various degrees such as active lysosomes, irregular nuclear membrane, clumped marginal chromatin, pyknotic nucleus with abnormal brush border, absence of infolding and irregularity of basement membrane. Moreover, the radiated hepatic cells showed dilation and thickness in membrane of blood sinasoid as well as lysis of cytoplasmic matrix. Treatment of rats with Nigella sativa during 10 consecutive days either before or after exposure to 8 Gy single dose led to partial improvement of hepatic and kidney cells.The results of the current study indicated that Nigella sativa oil exerted an important protective and curative role against radiation-induced damage in the ultrastructure configuration of kidney and liver cells

Multi-scale modeling with cellular automata: The complex automata approach

NARCIS (Netherlands)

Hoekstra, A.G.; Falcone, J.-L.; Caiazzo, A.; Chopard, B.

2008-01-01

Cellular Automata are commonly used to describe complex natural phenomena. In many cases it is required to capture the multi-scale nature of these phenomena. A single Cellular Automata model may not be able to efficiently simulate a wide range of spatial and temporal scales. It is our goal to

Systemic molecular and cellular changes induced in rats upon inhalation of JP-8 petroleum fuel vapor.

Science.gov (United States)

Hanas, Jay S; Bruce Briggs, G; Lerner, Megan R; Lightfoot, Stan A; Larabee, Jason L; Karsies, Todd J; Epstein, Robert B; Hanas, Rushie J; Brackett, Daniel J; Hocker, James R

2010-05-01

Limited information is available regarding systemic changes in mammals associated with exposures to petroleum/hydrocarbon fuels. In this study, systemic toxicity of JP-8 jet fuel was observed in a rat inhalation model at different JP-8 fuel vapor concentrations (250, 500, or 1000 mg/m(3), for 91 days). Gel electrophoresis and mass spectrometry sequencing identified the alpha-2 microglobulin protein to be elevated in rat kidney in a JP-8 dose-dependent manner. Western blot analysis of kidney and lung tissue extracts revealed JP-8 dependent elevation of inducible heat shock protein 70 (HSP70). Tissue changes were observed histologically (hematoxylin and eosin staining) in liver, kidney, lung, bone marrow, and heart, and more prevalently at medium or high JP-8 vapor phase exposures (500-1000 mg/m(3)) than at low vapor phase exposure (250 mg/m(3)) or non-JP-8 controls. JP-8 fuel-induced liver alterations included dilated sinusoids, cytoplasmic clumping, and fat cell deposition. Changes to the kidneys included reduced numbers of nuclei, and cytoplasmic dumping in the lumen of proximal convoluted tubules. JP-8 dependent lung alterations were edema and dilated alveolar capillaries, which allowed clumping of red blood cells (RBCs). Changes in the bone marrow in response to JP-8 included reduction of fat cells and fat globules, and cellular proliferation (RBCs, white blood cells-WBCs, and megakaryocytes). Heart tissue from JP-8 exposed animals contained increased numbers of inflammatory and fibroblast cells, as well as myofibril scarring. cDNA array analysis of heart tissue revealed a JP-8 dependent increase in atrial natriuretic peptide precursor mRNA and a decrease in voltage-gated potassium (K+) ion channel mRNA.

Zero Flow Global Ischemia-Induced Injuries in Rat Heart Are Attenuated by Natural Honey

Science.gov (United States)

Najafi, Moslem; Zahednezhad, Fahimeh; Samadzadeh, Mehrban; Vaez, Haleh

2012-01-01

Purpose: In the present study, effects of preischemic administration of natural honey on cardiac arrhythmias and myocardial infarction size during zero flow global ischemia were investigated in isolated rat heart. Methods: The isolated hearts were subjected to 30 min zero flow global ischemia followed by 120 min reperfusion then perfused by a modified drug free Krebs-Henseleit solution throughout the experiment (control) or the solution containing 0.25, 0.5, 1 and 2% of natural honey for 15 min before induction of global ischemia (treated groups), respectively. Cardiac arrhythmias were determined based on the Lambeth conventions and the infarct size was measured by computerized planimetry. Results: Myocardial infarction size was 55.8±7.8% in the control group, while preischemic perfusion of honey (0.25, 0.5, 1 and 2%) reduced it to 39.3±11, 30.6±5.5 (Phoney concentrations and infarction size reduction was observed (R2=0.9948). In addition, total number of ventricular ectopic beats were significantly decreased by all used concentrations of honey (PHoney (0.25, 0.5 and 1 %) also lowered incidence of irreversible ventricular fibrillation (Phoney treated groups. Conclusion: Preischemic administration of natural honey before zero flow global ischemia can protect isolated rat heart against ischemia/reperfusion injuries as reduction of infarction size and arrhythmias. Maybe, antioxidant and free radical scavenging activities of honey, reduction of necrotized tissue and providing energy sources may involve in these cardioprotective effects of honey. PMID:24312788

Natural Detoxification Capacity to Inactivate Nerve Agents Sarin and VX in the Rat Blood

Directory of Open Access Journals (Sweden)

Jiří Bajgar

2016-03-01

Full Text Available Background: The method of continual determination of the rat blood cholinesterase activity was developed to study the changes of the blood cholinesterases following different intervetions. Aims: The aim of this study is registration of cholinesterase activity in the rat blood and its changes to demonstrate detoxification capacity of rats to inactivate sarin or VX in vivo. Methods: The groups of female rats were premedicated (ketamine and xylazine and cannulated to a. femoralis. Continual blood sampling (0.02 ml/min and monitoring of the circulating blood cholinesterase activity were performed. Normal activity was monitored 1–2 min and then the nerve agent was administered i.m. (2× LD50. Using different time intervals of the leg compression and relaxation following the agent injection, cholinesterase activity was monitored and according to the inhibition obtained, detoxification capacity was assessed. Results: Administration of sarin to the leg, then 1 and 5 min compression and 20 min later relaxation showed that further inhibition in the blood was not observed. On the other hand, VX was able to inhibit blood cholinesterases after this intervention. Conclusions: The results demonstrated that sarin can be naturally detoxified on the contrary to VX. Described method can be used as model for other studies dealing with changes of cholinesterases in the blood following different factors.

The rat acute-phase protein {alpha}{sub 2}-macroglobulin plays a central role in amifostine-mediated radioprotection

Energy Technology Data Exchange (ETDEWEB)

Mirjana, Mihailovic; Goran, Poznanovic; Nevena, Grdovic; Melita, Vidakovic; Svetlana, Dinic; Ilijana, Grigorov; Desanka, Bogojevic, E-mail: mista@ibiss.bg.ac.r [Department of Molecular Biology, Institute for Biological Research ' Sinisa Stankovic' , University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade (Serbia)

2010-09-15

Previously we reported that elevated circulating concentrations of the acute-phase (AP) protein {alpha}{sub 2}-macroglobulin ({alpha}{sub 2}M), either as typically occurring in pregnant female rats or after administration to male rats, provides radioprotection, displayed as 100% survival of experimental animals exposed to total-body irradiation with 6.7 Gy (LD{sub 50/30}) x-rays, that is as effective as that afforded by the synthetic radioprotector amifostine. The finding that amifostine administration induces a 45-fold increase in {alpha}{sub 2}M in the circulation led us to hypothesise that {alpha}{sub 2}M assumes an essential role in both natural and amifostine-mediated radioprotection in the rat. In the present work we examined the activation of cytoprotective mechanisms in rat hepatocytes after the exogenous administration of {alpha}{sub 2}M and amifostine. Our results showed that the IL6/JAK/STAT3 hepatoprotective signal pathway, described in a variety of liver-injury models, upregulated the {alpha}{sub 2}M gene in amifostine-pretreated animals. In both {alpha}{sub 2}M- and amifostine-pretreated rats we observed the activation of the Akt signalling pathways that mediate cellular survival. At the cellular level this was reflected as a significant reduction of irradiation-induced DNA damage that allowed for the rapid and complete restoration of liver mass and ultimately at the level of the whole organism the complete restoration of body weight. We conclude that the selective upregulation of {alpha}{sub 2}M plays a central role in amifostine-provided radioprotection.

Role of cellular adhesions in tissue dynamics spectroscopy

Science.gov (United States)

Merrill, Daniel A.; An, Ran; Turek, John; Nolte, David

2014-02-01

Cellular adhesions play a critical role in cell behavior, and modified expression of cellular adhesion compounds has been linked to various cancers. We tested the role of cellular adhesions in drug response by studying three cellular culture models: three-dimensional tumor spheroids with well-developed cellular adhesions and extracellular matrix (ECM), dense three-dimensional cell pellets with moderate numbers of adhesions, and dilute three-dimensional cell suspensions in agarose having few adhesions. Our technique for measuring the drug response for the spheroids and cell pellets was biodynamic imaging (BDI), and for the suspensions was quasi-elastic light scattering (QELS). We tested several cytoskeletal chemotherapeutic drugs (nocodazole, cytochalasin-D, paclitaxel, and colchicine) on three cancer cell lines chosen from human colorectal adenocarcinoma (HT-29), human pancreatic carcinoma (MIA PaCa-2), and rat osteosarcoma (UMR-106) to exhibit differences in adhesion strength. Comparing tumor spheroid behavior to that of cell suspensions showed shifts in the spectral motion of the cancer tissues that match predictions based on different degrees of cell-cell contacts. The HT-29 cell line, which has the strongest adhesions in the spheroid model, exhibits anomalous behavior in some cases. These results highlight the importance of using three-dimensional tissue models in drug screening with cellular adhesions being a contributory factor in phenotypic differences between the drug responses of tissue and cells.

Cellular responses to modified Plasmodium falciparum MSP119 antigens in individuals previously exposed to natural malaria infection

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Awobode Henrietta O

2009-11-01

Full Text Available Abstract Background MSP1 processing-inhibitory antibodies bind to epitopes on the 19 kDa C-terminal region of the Plasmodium falciparum merozoite surface protein 1 (MSP119, inhibiting erythrocyte invasion. Blocking antibodies also bind to this antigen but prevent inhibitory antibodies binding, allowing invasion to proceed. Recombinant MSP119 had been modified previously to allow inhibitory but not blocking antibodies to continue to bind. Immunization with these modified proteins, therefore, has the potential to induce more effective protective antibodies. However, it was unclear whether the modification of MSP119 would affect critical T-cell responses to epitopes in this antigen. Methods The cellular responses to wild-type MSP119 and a panel of modified MSP119 antigens were measured using an in-vitro assay for two groups of individuals: the first were malaria-naïve and the second had been naturally exposed to Plasmodium falciparum infection. The cellular responses to the modified proteins were examined using cells from malaria-exposed infants and adults. Results Interestingly, stimulation indices (SI for responses induced by some of the modified proteins were at least two-fold higher than those elicited by the wild-type MSP119. A protein with four amino acid substitutions (Glu27→Tyr, Leu31→Arg, Tyr34→Ser and Glu43→Leu had the highest stimulation index (SI up to 360 and induced large responses in 64% of the samples that had significant cellular responses to the modified proteins. Conclusion This study suggests that specific MSP119 variants that have been engineered to improve their antigenicity for inhibitory antibodies, retain T-cell epitopes and the ability to induce cellular responses. These proteins are candidates for the development of MSP1-based malaria vaccines.

A sub-chronic toxicity evaluation of a natural astaxanthin-rich carotenoid extract of Paracoccus carotinifaciens in rats

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Toyohisa Katsumata

2014-01-01

Full Text Available Astaxanthin is believed to be beneficial to human health because it possesses strong antioxidant properties. A natural astaxanthin-rich carotenoid extract (ARE was produced by a well-controlled fermentation of a natural bacteria Paracoccus carotinifaciens, followed by the extraction and enrichment of the final product comprising mixture of carotenoids that is predominantly astaxanthin. The aim of this study was to evaluate the sub-chronic toxicity of the ARE using 6 week old Sprague-Dawley SPF rats [Crl:CD(SD]. The test article was suspended in olive oil and administered daily to the rats by oral gavage for 13 weeks at doses of 0 (olive oil, 250, 500 or 1000 mg/kg/day. Each group consisted of 10 animals of each sex. No deaths occurred and no treatment-related changes were observed in the detailed clinical observations, manipulative tests, grip strength, motor activity, body weights, food consumption, ophthalmology, urinalysis, hematology, blood chemistry, organ weight, necropsy or histopathology. Dark-red feces were observed throughout the administration period in all treated groups due to excretion of the colored test article. Based on these results, it was concluded that the no observed adverse effect level (NOAEL for ARE was at least 1000 mg/kg/day for male and female rats, respectively.

The New Cellular Immunology

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Claman, Henry N.

1973-01-01

Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

Evaluation of cellular viability by quantitative autoradiographic study of myocardial uptake of a fatty acid analogue in isoproterenol-induced focal rat heart necrosis

International Nuclear Information System (INIS)

Humbert, T.; Luu-Duc, C.; Comet, M.; Demenge, P.

1991-01-01

Previous studies led us to hypothesize that a fatty acid analogue, 15-p-iodophenyl-β-methyl pentadecanoic acid (IMPPA or BMIPP), which is taken up but not quickly metabolized by heart cells, would be a more suitable tracer of cellular viability that 201 Tl. Biodistribution studies of 1- 14 C-IMPPA in conscious, freely moving rats showed that the concentration ratio of radioactivity in the heart with respect to the blood was about 8 for at least 60 min after intravenous administration, permitting its use as a putative tracer in these conscious, freely moving rats. Thereafter, the myocardial uptake of 14 C-IMPPA was studied in isoproterenol-treated rats (daily treatment for 10 days in order to induce cardiac hypertrophy and necrotic foci) with respect to control ones. Comparison of myocardial localizations by quantitative autoradiography of the uptake of 201 Tl and 14 C-IMPPA with that of triphenyltetrazolium chloride (TTC) staining enabled comparative evaluation of nutritional blood flow, localization and uptake of 14 C-IMPPA and necrotic foci size. Distributions of 14 C-IMPPA and 201 Tl in control rats' hearts were homogenous, like TTC staining. In infarcted hearts, areas of decreased 14 C-IMPPA uptake were nearly the same (100%±5%) as those unstained by TTC. These areas were larger than those showing a decrease in thallium uptake (about 70%±5% of the total scar size). Therefore, IMPPA seems to be a more accurate and sensitive indicator of necrosis localization compared with thallium. It may be a useful agent for assessment of myocardial viability by single photon emission tomography (SPET) imaging. (orig.)

Naturally occurring genetic variability in expression of Gsta4 is associated with differential survival of axotomized rat motoneurons

DEFF Research Database (Denmark)

Mikael, Ström; Al Nimer, Faiez; Lindblom, Rickard

2012-01-01

A large number of molecular pathways have been implicated in the degeneration of axotomized motoneurons. We previously have demonstrated substantial differences in the survival rate of axotomized motoneurons across different rat strains. Identification of genetic differences underlying such natur...

Cellular structures in a system of interacting particles

International Nuclear Information System (INIS)

Lev, B.I.

2009-01-01

The general description of the formation of a cellular structure in the system of interacting particles is proposed. The analytical results for possible cellular structures in the usual colloidal systems, systems of particles immersed in a liquid crystal, and gravitational systems have been presented. It is shown that the formation of a cellular structure in all systems of interacting particles at different temperatures and concentrations of particles has the same physical nature

Cellular localization of kinin B1 receptor in the spinal cord of streptozotocin-diabetic rats with a fluorescent [Nα-Bodipy]-des-Arg9-bradykinin

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Gaudreau Pierrette

2009-03-01

Full Text Available Abstract Background The kinin B1 receptor (B1R is upregulated by pro-inflammatory cytokines, bacterial endotoxins and hyperglycaemia-induced oxidative stress. In animal models of diabetes, it contributes to pain polyneuropathy. This study aims at defining the cellular localization of B1R in thoracic spinal cord of type 1 diabetic rats by confocal microscopy with the use of a fluorescent agonist, [Nα-Bodipy]-des-Arg9-BK (BdABK and selective antibodies. Methods Diabetes was induced by streptozotocin (STZ; 65 mg/kg, i.p.. Four days post-STZ treatment, B1R expression was confirmed by quantitative real-time PCR and autoradiography. The B1R selectivity of BdABK was determined by assessing its ability to displace B1R [125I]-HPP-desArg10-Hoe140 and B2R [125I]-HPP-Hoe 140 radioligands. The in vivo activity of BdABK was also evaluated on thermal hyperalgesia. Results B1R was increased by 18-fold (mRNA and 2.7-fold (binding sites in the thoracic spinal cord of STZ-treated rats when compared to control. BdABK failed to displace the B2R radioligand but displaced the B1R radioligand (IC50 = 5.3 nM. In comparison, IC50 values of B1R selective antagonist R-715 and B1R agonist des-Arg9-BK were 4.3 nM and 19 nM, respectively. Intraperitoneal BdABK and des-Arg9-BK elicited dose-dependent thermal hyperalgesia in STZ-treated rats but not in control rats. The B1R fluorescent agonist was co-localized with immunomarkers of microglia, astrocytes and sensory C fibers in the spinal cord of STZ-treated rats. Conclusion The induction and up-regulation of B1R in glial and sensory cells of the spinal cord in STZ-diabetic rats reinforce the idea that kinin B1R is an important target for drug development in pain processes.

Multi-cellular natural killer (NK) cell clusters enhance NK cell activation through localizing IL-2 within the cluster

Science.gov (United States)

Kim, Miju; Kim, Tae-Jin; Kim, Hye Mi; Doh, Junsang; Lee, Kyung-Mi

2017-01-01

Multi-cellular cluster formation of natural killer (NK) cells occurs during in vivo priming and potentiates their activation to IL-2. However, the precise mechanism underlying this synergy within NK cell clusters remains unclear. We employed lymphocyte-laden microwell technologies to modulate contact-mediated multi-cellular interactions among activating NK cells and to quantitatively assess the molecular events occurring in multi-cellular clusters of NK cells. NK cells in social microwells, which allow cell-to-cell contact, exhibited significantly higher levels of IL-2 receptor (IL-2R) signaling compared with those in lonesome microwells, which prevent intercellular contact. Further, CD25, an IL-2R α chain, and lytic granules of NK cells in social microwells were polarized toward MTOC. Live cell imaging of lytic granules revealed their dynamic and prolonged polarization toward neighboring NK cells without degranulation. These results suggest that IL-2 bound on CD25 of one NK cells triggered IL-2 signaling of neighboring NK cells. These results were further corroborated by findings that CD25-KO NK cells exhibited lower proliferation than WT NK cells, and when mixed with WT NK cells, underwent significantly higher level of proliferation. These data highlights the existence of IL-2 trans-presentation between NK cells in the local microenvironment where the availability of IL-2 is limited.

Population Structure of Rat-Derived Pneumocystis carinii in Danish Wild Rats

DEFF Research Database (Denmark)

Palmer, Robert J.; Settnes, Osvald P.; Lodal, Jens

2000-01-01

The rat model of Pneumocystis carinii pneumonia is frequently used to study human P. carinii infection, but there are many differences between the rat and human infections. We studied naturally acquired P. carinii in wild rats to examine the relevance of the rat model for human infection. P. cari...

Cellular and biochemical actions of adrenal glucocorticoid hormones on rat thymic lymphocytes.

OpenAIRE

Young, D A; Voris, B P; Nicholson, M L

1981-01-01

The molecular, biochemical, and cellular effects of adrenal glucocorticoid hormones on thymic lymphocytes are reviewed, with emphasis on their relationship to the growth suppressive and lethal actions that occur in lymphoid tissues when glucocorticoids are administered to the whole animal. The data support the hypothesis that the hormonal inhibition of growth and development is a consequence of its ability to suppress cellular energy production, causing the cells to behave as though they were...

Reduction of acute rejection by bone marrow mesenchymal stem cells during rat small bowel transplantation.

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Yang Yang

Full Text Available Bone marrow mesenchymal stem cells (BMMSCs have shown immunosuppressive activity in transplantation. This study was designed to determine whether BMMSCs could improve outcomes of small bowel transplantation in rats.Heterotopic small bowel transplantation was performed from Brown Norway to Lewis rats, followed by infusion of BMMSCs through the superficial dorsal veins of the penis. Controls included rats infused with normal saline (allogeneic control, isogeneically transplanted rats (BN-BN and nontransplanted animals. The animals were sacrificed after 1, 5, 7 or 10 days. Small bowel histology and apoptosis, cytokine concentrations in serum and intestinal grafts, and numbers of T regulatory (Treg cells were assessed at each time point.Acute cellular rejection occurred soon after transplantation and became aggravated over time in the allogeneic control rats, with increase in apoptosis, inflammatory response, and T helper (Th1/Th2 and Th17/Treg-related cytokines. BMMSCs significantly attenuated acute cellular rejection, reduced apoptosis and suppressed the concentrations of interleukin (IL-2, IL-6, IL-17, IL-23, tumor necrosis factor (TNF-α, and interferon (IFN-γ while upregulating IL-10 and transforming growth factor (TGF-β expression and increasing Treg levels.BMMSCs improve the outcomes of allogeneic small bowel transplantation by attenuating the inflammatory response and acute cellular rejection. Treatment with BMMSCs may overcome acute cellular rejection in small bowel transplantation.

Radiation-induced PKC signaling system in cultured rat hepatocytes

International Nuclear Information System (INIS)

Nakajima, Tetsuo; Yukawa, Osami

1998-01-01

Radiation effects on living organisms are mainly caused through reactive oxygen species (ROS) on living cells. It is known that ROS damages various membranes and the bio membranes play an important role in cellular signal transduction pathways. The effects of radiation on cellular signal transduction pathways in cultured rat hepatocytes have been studied

1,4-Naphthoquinones: From Oxidative Damage to Cellular and Inter-Cellular Signaling

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Lars-Oliver Klotz

2014-09-01

Full Text Available Naphthoquinones may cause oxidative stress in exposed cells and, therefore, affect redox signaling. Here, contributions of redox cycling and alkylating properties of quinones (both natural and synthetic, such as plumbagin, juglone, lawsone, menadione, methoxy-naphthoquinones, and others to cellular and inter-cellular signaling processes are discussed: (i naphthoquinone-induced Nrf2-dependent modulation of gene expression and its potentially beneficial outcome; (ii the modulation of receptor tyrosine kinases, such as the epidermal growth factor receptor by naphthoquinones, resulting in altered gap junctional intercellular communication. Generation of reactive oxygen species and modulation of redox signaling are properties of naphthoquinones that render them interesting leads for the development of novel compounds of potential use in various therapeutic settings.

Evidence for a Na+-Ca2+ exchanger in rat pancreatic ducts

DEFF Research Database (Denmark)

Hug, M; Pahl, C; Novak, I

1996-01-01

Only recently has it been recognized that intracellular Ca2+ is an important cellular mediator in pancreatic ducts. The aim of the present study was to characterize the Ca2+ efflux pathway in ducts freshly prepared from rat pancreas. Lowering of extracellular Na+ concentration resulted in a signi......Only recently has it been recognized that intracellular Ca2+ is an important cellular mediator in pancreatic ducts. The aim of the present study was to characterize the Ca2+ efflux pathway in ducts freshly prepared from rat pancreas. Lowering of extracellular Na+ concentration resulted...

Induced Chronic Prostatitis in Rats

African Journals Online (AJOL)

Similarly, compared with reference group (176.1 ± 12.1 pg/ml), IL-1β level of prostate tissues of high-dose PCS ..... Fig 1: Effect of PCS extract on the histomorphology of prostate tissues in rats. ... involved with cellular recruitment, fever, acute.

Surface Dynamic Process Simulation with the Use of Cellular Automata

International Nuclear Information System (INIS)

Adamska-Szatko, M.; Bala, J.

2010-01-01

Cellular automata are known for many applications, especially for physical and biological simulations. Universal cellular automata can be used for modelling complex natural phenomena. The paper presents simulation of surface dynamic process. Simulation uses 2-dimensional cellular automata algorithm. Modelling and visualisation were created by in-house developed software with standard OpenGL graphic library. (authors)

A study of the biological effects of rare earth elements at cellular level using nuclear techniques

International Nuclear Information System (INIS)

Feng Zhihui; Wang Xi; Zhang Sunxi; An Lizhi; Zhang Jingxia; Yao Huiying

2001-01-01

Objective: To investigate the biological effects and the effecting mechanisms of rare earth elements La, Gd and Ce on cultured rat cells. Methods: The biological effects of La 3+ on cultured rat cells and the subcellular distribution of La and Gd and Ce, and the inflow of 45 Ca 2+ into the cells and total cellular calcium were measured by isotopic tracing, Proton Induced X Ray Emission Analysis (PIXE) and the techniques of biochemistry and cellular biology. Results: La 3+ at the concentration of 10- 10( or 10 -9 ) - 10 -6 mol/L significantly increased quantity of incorporation of 3 H-TdR into DNA, total cellular protein and the activity of succinic dehydrogenase of mitochondria. The cell cycle analysis showed that the proportions of cells in S phase were accordingly increased acted by La 3+ at above range of concentration. But these values were significantly decreased when concentration of La 3+ raised to 10 -4 - 10 -3 mol/L. It was further discovered that La, Gd and Ce distributed mostly in the nuclei, and then in membranes. Gd and Ce also promoted the inflow of 45 Ca 2+ into the cells and increased the total calcium content in cells. Conclusions: 1) La 3+ at a wide concentration range of 10 -10 ( or 10 -9 ) - 10 -6 mol/L promotes proliferation of cultured rat cells, but at even higher concentration (10 -4 - 10 -3 mol/L) shows cellular toxicity, and there is a striking dose-effect relationship. 2) La, Gd and Ce can enter the cells and mainly distribute in the nuclei. 3) Gd and Ce can promote the inflow of extracellular Ca 2+ into the cells and increase total cellular calcium

Cellular Automata Ideas in Digital Circuits and Switching Theory.

Science.gov (United States)

Siwak, Pawel P.

1985-01-01

Presents two examples which illustrate the usefulness of ideas from cellular automata. First, Lee's algorithm is recalled and its cellular nature shown. Then a problem from digraphs, which has arisen from analyzing predecessing configurations in the famous Conway's "game of life," is considered. (Author/JN)

Propofol ameliorates doxorubicin-induced oxidative stress and cellular apoptosis in rat cardiomyocytes

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Lai, H.C. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Yeh, Y.C. [Graduate Institute of Natural Healing Sciences, Nanhua University, Chiayi, Taiwan (China); Wang, L.C. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Ting, C.T.; Lee, W.L. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Lee, H.W. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wang, K.Y. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine, Chung-Shan Medical University, Taichung, Taiwan (China); Wu, A. [College of Biological Science, University of California, Davis (United States); Su, C.S. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Liu, T.J., E-mail: trliu@vghtc.gov.tw [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan (China)

2011-12-15

Background: Propofol is an anesthetic with pluripotent cytoprotective properties against various extrinsic insults. This study was designed to examine whether this agent could also ameliorate the infamous toxicity of doxorubicin, a widely-used chemotherapeutic agent against a variety of cancer diseases, on myocardial cells. Methods: Cultured neonatal rat cardiomyocytes were administrated with vehicle, doxorubicin (1 {mu}M), propofol (1 {mu}M), or propofol plus doxorubicin (given 1 h post propofol). After 24 h, cells were harvested and specific analyses regarding oxidative/nitrative stress and cellular apoptosis were conducted. Results: Trypan blue exclusion and MTT assays disclosed that viability of cardiomyocytes was significantly reduced by doxorubicin. Contents of reactive oxygen and nitrogen species were increased and antioxidant enzymes SOD1, SOD2, and GPx were decreased in these doxorubicin-treated cells. Mitochondrial dehydrogenase activity and membrane potential were also depressed, along with activation of key effectors downstream of mitochondrion-dependent apoptotic signaling. Besides, abundance of p53 was elevated and cleavage of PKC-{delta} was induced in these myocardial cells. In contrast, all of the above oxidative, nitrative and pro-apoptotic events could be suppressed by propofol pretreatment. Conclusions: Propofol could extensively counteract oxidative/nitrative and multiple apoptotic effects of doxorubicin in the heart; hence, this anesthetic may serve as an adjuvant agent to assuage the untoward cardiac effects of doxorubicin in clinical application. -- Highlights: Black-Right-Pointing-Pointer We evaluate how propofol prevents doxorubicin-induced toxicity in cardiomyocytes. Black-Right-Pointing-Pointer Propofol reduces doxorubicin-imposed nitrative and oxidative stress. Black-Right-Pointing-Pointer Propofol suppresses mitochondrion-, p53- and PKC-related apoptotic signaling. Black-Right-Pointing-Pointer Propofol ameliorates apoptosis and

Cellular Biochemistry and Cytogenetics in a Rat Lung Tumor Model

Science.gov (United States)

1984-10-01

lung tumor system the specific aims are: 1. To conduct studies of the effect of 3-methylchlanthrene (MCA) on DNA synthesis and cell proliferation in...alkylation of nucleic acids of the rat by N-methyl-N- nitrosourea , dimethylnitrosamine, dimethylsulfate, and methylmethanesulfonate. Biochem. J. 110:39-47

Effect of electromagnetic fields at 2.45 GHz on the levels of cellular stress proteins HSP-90 and 70 in the rat thyroid; Efecto de los campos electromagneticos a 2,45 GHz sobre los niveles de proteinas de estres celular HSP-90 y 70 en el toroides de rata

Energy Technology Data Exchange (ETDEWEB)

Misa Agustino, M. J.; Alvarez-Folgueras, M.; Jorge-Mora, M. T.; Jorge Barreiro, F. J.; Ares Pena, F. J.; Lleiro, J.; Lopez Martin, M. E.

2011-07-01

In this study we analyzed the cellular stress levels achieved by heat shock proteins (HSP) 90 and 70 in rat thyroid tissue after exposure to radio waves in TWG experimental system. Parallel measurements of body stress in animals by rectal temperature probes allow us to determine whether there is any interaction between temperature increases and cellular stress.

The vasopressin deficient Brattleboro rats: A natural knockout model used in the search for CNS effects of vasopressin

NARCIS (Netherlands)

Bohus, B; de Wied, David; Urban, I.J.A.; Burbach, J.P.H.; De Wied, D.

1999-01-01

Behavioral neuroscience is using mon and more gene knockout techniques to produce animals with a specific deletion. These studies have their precedent in nature. A mutation may result in a limited genetic defect, as seen in the vasopressin (VP) deficiency in the Brattleboro rat. The mutation is in a

Histological and histochemical studies on liver of rat subjected to synergistic effect of natural and synthetic food colorants and/or gamma irradiation

International Nuclear Information System (INIS)

Soliman, O.; Hafez, M. N.; Abd El Maguid, A.

2007-01-01

The present work has been carried out to detect some histological and histochemical changes in the liver of albino rats after oral administration of a mixture of the synthetic food colorants tartrazine and brilliant blue and/ or gamma-irradiation (5 Gy). The possible ameliorative effect of the natural food colorant beta-carotene (30 mg/ kg body wt) orally administered with the synthetic food colorants tartrazine and brilliant blue and irradiation was evaluated. Rats were divided into five groups: 1- Control group. 2- Group received a food colorant mixture of tartrazine and brilliant blue (100 mg/ kg body wt). 3- Group received gamma-irradiation at 5 Gy. 4-Animals received the food colorant mixture for 2 weeks and were irradiated. 5- Animals received beta-carotene (30 mg/ kg body wt) with the food colorant mixture for 2 weeks and were then irradiated (5 Gy). Administration of tartrazine and brilliant blue caused histopathological and histochemical changes in the liver of rat manifested by haemorrhage, vacuolar degeneration of hepatocytes, dilatation of blood sinusoids, scattered necrotic areas and a decrease in the mucopolysaccharides content. The radiation caused infiltration of inflammatory cells in the portal area, necrosis with pyknosis and karyolysis of nuclei and a decrease in the mucopolysaccharide content of hepatic cells 1 and 3 days post-irradiation. The present work also showed that the natural food colorant beta-carotene reduced the toxicity of the synthetic food colorants tartrazine and brilliant blue and gamma-irradiation when the natural pigment was given together with the synthetic dyes used as food additives. In conclusion, synthetic food colours and/ or radiation induced histopathological and histochemical disturbances in rats. On the other hand, administration of the natural food colorant beta-carotene had a significant protective role against the damaging effects induced by these synthetic colours mixture

Elastomeric Cellular Structure Enhanced by Compressible Liquid Filler

Science.gov (United States)

Sun, Yueting; Xu, Xiaoqing; Xu, Chengliang; Qiao, Yu; Li, Yibing

2016-05-01

Elastomeric cellular structures provide a promising solution for energy absorption. Their flexible and resilient nature is particularly relevant to protection of human bodies. Herein we develop an elastomeric cellular structure filled with nanoporous material functionalized (NMF) liquid. Due to the nanoscale infiltration in NMF liquid and its interaction with cell walls, the cellular structure has a much enhanced mechanical performance, in terms of loading capacity and energy absorption density. Moreover, it is validated that the structure is highly compressible and self-restoring. Its hyper-viscoelastic characteristics are elucidated.

Retinal S-opsin dominance in Ansell's mole-rats (Fukomys anselli) is a consequence of naturally low serum thyroxine.

Science.gov (United States)

Henning, Yoshiyuki; Mladěnková, Nella; Burda, Hynek; Szafranski, Karol; Begall, Sabine

2018-03-12

Mammals usually possess a majority of medium-wavelength sensitive (M-) and a minority of short-wavelength sensitive (S-) opsins in the retina, enabling dichromatic vision. Unexpectedly, subterranean rodents from the genus Fukomys exhibit an S-opsin majority, which is exceptional among mammals, albeit with no apparent adaptive value. Because thyroid hormones (THs) are pivotal for M-opsin expression and metabolic rate regulation, we have, for the first time, manipulated TH levels in the Ansell's mole-rat (Fukomys anselli) using osmotic pumps. In Ansell's mole-rats, the TH thyroxine (T4) is naturally low, likely as an adaptation to the harsh subterranean ecological conditions by keeping resting metabolic rate (RMR) low. We measured gene expression levels in the eye, RMR, and body mass (BM) in TH-treated animals. T4 treatment increased both, S- and M-opsin expression, albeit M-opsin expression at a higher degree. However, this plasticity was only given in animals up to approximately 2.5 years. Mass-specific RMR was not affected following T4 treatment, although BM decreased. Furthermore, the T4 inactivation rate is naturally higher in F. anselli compared to laboratory rodents. This is the first experimental evidence that the S-opsin majority in Ansell's mole-rats is a side effect of low T4, which is downregulated to keep RMR low.

Comparative studies in the cellular immunostimulation by whole body irradiation. Vergleichende Untersuchungen ueber die zellulaere Immunstimulation durch Ganzkoerperbestrahlung

Energy Technology Data Exchange (ETDEWEB)

Dietz, R.; Schwarze, G. (Service de Radiologie, Centre Hospitalier de Luxembourg (Luxembourg) Medizinische Universitaetsklinik I, Homburg/Saar (Germany))

1992-04-01

The effect of the cellular immune response by total body irradiation was investigated. The transplant survival (skin grafts) was determined as immune parameter. Donors were colony bred Wistar rats and recipients were colony bred Sprague Dawley rats. The investigations were carried out with irradiated rats and with rats irradiated after thymectomy and/or adrenalectomy as well as with animals without irradiation. A single total-body irradiation (1 and 2 Gy) was administered. The skin graft survival in irradiated rats was significant shorter (radiogenic immunostimulation) than in unirradiated rats; there were no significant differences between the operated (thymectomy and/or adrenalectomy) and not operated animals. Including precedent examinations this radiogenic immunostimulation is caused by relativly selective inactivation of T-suppressor cells. (orig.).

hematological and biochemical studies on the effect of some natural antioxidants pre-injection in irradiated rats

International Nuclear Information System (INIS)

Ashour, S.E.S.

2011-01-01

The present work was carried out in order to evaluate the biological activities of some natural antioxidants such as ziziphus and olive leaves extract as radioprotective agents on male albino rats treated with gamma irradiation. The results showed that the ethanolic extract of ziziphus and olive leaves have high content of phenolic and flavonoid compound. GC-MS showed that ethanolic extracts of ziziphus and olive leaves contains some important phenolic compounds include (Catechin, Chlorogenic,Zizyphine F, Luteolin and Succinylsulfathiazol), (Caffeic acid, Quercetin, Rutin, Diosmetine, Luteolin-7-glucoside and Oleuropein) respectively. γ-irradiation caused a significant decrease in body weight after 2 weeks as compared with control group. Administration of ethanolic extracts of olive and ziziphus leaves to normal rats exhibited a decrease in body weight after 2 weeks as compared with control group.The determination of different biological parameters showed a significant high level of ALT, AST, ALP, creatinine and urea in rat serum treated with gamma radiation. A significant depression in Hb, RBCs, HCT, MCV, WBC and PLT in rats after exposure to gamma radiation was noticed. The ethanolic extracts of ziziphus leaves and olive leaves application have been found to regulate the hematological parameters with narrow range around the normal level. A depressive effect of radiation was noticed on total protein, and albumin. Ethanolic extracts of olive and ziziphus leaves enhanced the accumulation of protein fraction.

Resistance to Reperfusion Injury Following Short Term Postischemic Administration of Natural Honey in Globally Ischemic Isolated Rat Heart

Directory of Open Access Journals (Sweden)

Haleh Vaez

2012-08-01

Full Text Available Purpose: Results of our previous study revealed that preischemic perfusion of honey before zero flow global ischemia had cardioprotective effects in rat. The present study investigated potential resistance to reperfusion injury following short term postischemic administration of natural honey in globally ischemic isolated rat heart. Methods: Male Wistar rats were divided into five groups (n=10-13. The rat hearts were isolated, mounted on a Langendorff apparatus, allowed to equilibrate for 30 min then subjected to 30 min global ischemia. In the control group, the hearts were reperfused with drug free normal Krebs-Henseleit (K/H solution before ischemia and during 120 min reperfusion. In the treatment groups, reperfusion was initiated with K/H solution containing different concentration of honey (0.25, 0.5, 1 and 2% for 15 min and was resumed until the end of 120 min with normal K/H solution. Results: In the control group, VEBs number was 784±199, while in honey concentration of 0.25, 0.5, 1 and 2%, it decreased to 83±23 (P<0.001, 138±48 (P<0.01, 142±37 (P<0.001 and 157±40 (P<0.01, respectively. Number and duration of VT and time spent in reversible VF were also reduced by honey. In the control group, the infarct size was 54.1±7.8%, however; honey (0.25, 0.5, 1 and 2% markedly lowered the value to 12.4±2.4, 12.7±3.3, 11.3±2.6 and 7.9±1.7 (P<0.001, respectively. Conclusion: Postischemic administration of natural honey in global ischemia showed protective effects against ischemia/reperfusion (I/R injuries in isolated rat heart. Antioxidant and radical scavenging activity, lipoperoxidation inhibition, reduction of necrotized tissue, presence of rich energy sources, various type of vitamins, minerals and enzymes and formation of NO-contain metabolites may probably involve in those cardioprotective effects.

Light Weight Biomorphous Cellular Ceramics from Cellulose Templates

Science.gov (United States)

Singh, Mrityunjay; Yee, Bo-Moon; Gray, Hugh R. (Technical Monitor)

2003-01-01

Bimorphous ceramics are a new class of materials that can be fabricated from the cellulose templates derived from natural biopolymers. These biopolymers are abundantly available in nature and are produced by the photosynthesis process. The wood cellulose derived carbon templates have three- dimensional interconnectivity. A wide variety of non-oxide and oxide based ceramics have been fabricated by template conversion using infiltration and reaction-based processes. The cellular anatomy of the cellulose templates plays a key role in determining the processing parameters (pyrolysis, infiltration conditions, etc.) and resulting ceramic materials. The processing approach, microstructure, and mechanical properties of the biomorphous cellular ceramics (silicon carbide and oxide based) have been discussed.

Synergetic effect of topological cue and periodic mechanical tension-stress on osteogenic differentiation of rat bone mesenchymal stem cells.

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Liu, Yao; Yang, Guang; Ji, Huanzhong; Xiang, Tao; Luo, En; Zhou, Shaobing

2017-06-01

Mesenchymal stem cells (MSCs) are able to self-renew and differentiate into tissues of mesenchymal origin, making them to be significant for cell-based therapies, such as metabolic bone diseases and bone repair. Regulating the differentiation of MSCs is significant for bone regeneration. Electrospun fibers mimicking natural extracellular matrix (ECM), is an effective artificial ECM to regulate the behaviors and fates of MSCs. The aligned electrospun fibers can modulate polar cell pattern of bone mesenchymal stem cells, which leads to more obvious osteogenic differentiation. Apart from the topographic effect of electrospun fibers, mechanical cues can also intervene the cell behaviors. In this study, the osteogenic differentiation of rat bone mesenchymal stem cells was evaluated, which were cultured on aligned/random electrospun fiber mats materials under mechanical tension intervention. Scanning electron microscope and immune-fluorescent staining were used to directly observe the polarity changing of cellular morphology and cytoskeleton. The results proved that aligned electrospun fibers could be more conducive to promote osteogenic differentiation of rat bone mesenchymal stem cells and this promotion of osteogenic differentiation was enhanced by tension intervention. These results were correlated to the quantitative real-time PCR assay. In general, culturing rat bone mesenchymal stem cells on electrospun fibers under the intervention of mechanical tension is an effective way to mimic a more real cellular microenvironment. Copyright © 2017 Elsevier B.V. All rights reserved.

Zero Flow Global Ischemia-Induced Injuries in Rat Heart Are Attenuated by Natural Honey

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Moslem Najafi

2012-06-01

Full Text Available Purpose: In the present study, effects of preischemic administration of natural honey on cardiac arrhythmias and myocardial infarction size during zero flow global ischemia were investigated in isolated rat heart. Methods:The isolated hearts were subjected to 30 min zero flow global ischemia followed by 120 min reperfusion then perfused by a modified drug free Krebs-Henseleit solution throughout the experiment (control or the solution containing 0.25, 0.5, 1 and 2% of natural honey for 15 min before induction of global ischemia (treated groups, respectively. Cardiac arrhythmias were determined based on the Lambeth conventions and the infarct size was measured by computerized planimetry. Results: Myocardial infarction size was 55.8±7.8% in the control group, while preischemic perfusion of honey (0.25, 0.5, 1 and 2% reduced it to 39.3±11, 30.6±5.5 (P<0.01, 17.9±5.6 (P<0.001 and 8.7±1.1% (P<0.001, respectively. A direct linear correlation between honey concentrations and infarction size reduction was observed (R2=0.9948. In addition, total number of ventricular ectopic beats were significantly decreased by all used concentrations of honey (P<0.05 during reperfusion time. Honey (0.25, 0.5 and 1 % also lowered incidence of irreversible ventricular fibrillation (P<0.05. Moreover, number and duration of ventricular tachycardia were reduced in all honey treated groups. Conclusion: Preischemic administration of natural honey before zero flow global ischemia can protect isolated rat heart against ischemia/reperfusion injuries as reduction of infarction size and arrhythmias. Maybe, antioxidant and free radical scavenging activities of honey, reduction of necrotized tissue and providing energy sources may involve in these cardioprotective effects of honey.

A Preliminary Trypanocidal Study of Natural and Synthetic ...

African Journals Online (AJOL)

Eighty healthy Wistar albino rats were used to investigate the trypanocidal effect of natural and synthetic supplements of zinc and magnesium in combination with diminazene aceturate in Trypanosoma congolense-inoculated rats. The rats were randomly divided into eight groups in study '1' (involving the natural ...

Evaluating the Toxicity of the Analgesic Glutaminase Inhibitor 6-Diazo-5-Oxo-L-Norleucine in vitro and on Rat Dermal Skin Fibroblasts

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Crosby, Heith A; Ihnat, Michael; Miller, Kenneth E

2018-01-01

6-diazo-5-oxo-l-norleucine (DON) is a glutamine antagonist produced naturally by Streptomyces. It inhibits several glutamine-dependent enzyme pathways. Of particular note is its inhibitory effect on the mitochondrial enzyme, glutaminase (GLS), the primary producer of neuronal glutamate. Glutamate is an excitatory neurotransmitter released by primary sensory peripheral nerve terminals and spinal synaptic terminals during pain signaling. Previous work using the tail incision and inflammatory models of pain has demonstrated that a single application of the glutaminase inhibitor, DON, into a surgical incision or the paw of arthritic animals results in pain relief. Even though this compound shows promise as a therapeutic agent, limited data exist regarding its dermal toxicity. As a first approach, we evaluated the effect of several concentrations of DON, on the viability, mitochondrial oxidative capacity and proliferation of rat skin fibroblasts, and then examined the effect of DON after incubation with human liver microsomes on proliferation. Finally, we evaluated DON treated rat skin (tail and hind paw) for cellular necrosis, inflammation and mitotic bodies. No significant effects (p > 0.05) of DON were noted on apoptosis, necrosis, and mitochondrial activity in experiments with cultured rat skin fibroblasts. Flow cytometry revealed the absence of apoptosis in cells treated at the IC50 of 232.5 μM. Enhanced toxicity post-exposure to human microsomes was not observed when compared to DON alone. The H&E staining of the rat skin revealed no obvious pathology in the DON treatment group (10 mM). DON has no/minimal cellular toxicity in vitro on dermal fibroblasts at concentrations that effectively provide analgesia. The local application of concentrations greater than the in vitro IC50 for DON revealed no in vivo skin toxicity. These data provide results indicating zero-to-minimal cellular toxicity with DON and support the further investigation of DON as an analgesic. PMID

Adolescent cannabinoid exposure effects on natural reward seeking and learning in rats.

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Schoch, H; Huerta, M Y; Ruiz, C M; Farrell, M R; Jung, K M; Huang, J J; Campbell, R R; Piomelli, D; Mahler, S V

2018-01-01

Adolescence is characterized by endocannabinoid (ECB)-dependent refinement of neural circuits underlying emotion, learning, and motivation. As a result, adolescent cannabinoid receptor stimulation (ACRS) with phytocannabinoids or synthetic agonists like "Spice" cause robust and persistent changes in both behavior and circuit architecture in rodents, including in reward-related regions like medial prefrontal cortex and nucleus accumbens (NAc). Here, we examine persistent effects of ACRS with the cannabinoid receptor 1/2 specific agonist WIN55-212,2 (WIN; 1.2 mg/kg/day, postnatal day (PD) 30-43), on natural reward-seeking behaviors and ECB system function in adult male Long Evans rats (PD 60+). WIN ACRS increased palatable food intake, and altered attribution of incentive salience to food cues in a sign-/goal-tracking paradigm. ACRS also blunted hunger-induced sucrose intake, and resulted in increased anandamide and oleoylethanolamide levels in NAc after acute food restriction not seen in controls. ACRS did not affect food neophobia or locomotor response to a novel environment, but did increase preference for exploring a novel environment. These results demonstrate that ACRS causes long-term increases in natural reward-seeking behaviors and ECB system function that persist into adulthood, potentially increasing liability to excessive natural reward seeking later in life.

Aged blood factors decrease cellular responses associated with delayed gingival wound repair.

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María Paz Saldías

Full Text Available Aging is a gradual biological process characterized by a decrease in cell and organism functions. Gingival wound healing is one of the impaired processes found in old rats. Here, we studied the in vivo wound healing process using a gingival repair rat model and an in vitro model using human gingival fibroblast for cellular responses associated to wound healing. To do that, we evaluated cell proliferation of both epithelial and connective tissue cells in gingival wounds and found decreased of Ki67 nuclear staining in old rats when compared to their young counterparts. We next evaluated cellular responses of primary gingival fibroblast obtained from young subjects in the presence human blood serum of individuals of different ages. Eighteen to sixty five years old masculine donors were classified into 3 groups: "young" from 18 to 22 years old, "middle-aged" from 30 to 48 years old and "aged" over 50 years old. Cell proliferation, measured through immunofluorescence for Ki67 and flow cytometry for DNA content, was decreased when middle-aged and aged serum was added to gingival fibroblast compared to young serum. Myofibroblastic differentiation, measured through alpha-smooth muscle actin (α-SMA, was stimulated with young but not middle-aged or aged serum both the protein levels and incorporation of α-SMA into actin stress fibers. High levels of PDGF, VEGF, IL-6R were detected in blood serum from young subjects when compared to middle-aged and aged donors. In addition, the pro-inflammatory cytokines MCP-1 and TNF were increased in the serum of aged donors. In old rat wound there is an increased of staining for TNF compared to young wound. Moreover, healthy gingiva (non injury shows less staining compared to a wound site, suggesting a role in wound healing. Moreover, serum from middle-aged and aged donors was able to stimulate cellular senescence in young cells as determined by the expression of senescence associated beta-galactosidase and histone H2

Effects of diethylene glycol butyl ether and butoxyethoxyacetic acid on rat and human erythrocytes.

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Udden, M M

2005-03-28

The toxicity of diethylene glycol butyl ether (DGBE), and its principal metabolite, butoxyethoxyacetic acid (BEAA), were assessed in vitro for rat and human red blood cells. Rat erythrocytes showed evidence of mild hemolysis when exposed to BEAA at concentrations of 5 or 10 mM for 4 h. BEAA treated rat red blood cells also showed evidence of sub-hemolytic damage: increased spherocytosis, a shift in distribution of cell size to larger cells, a significant increase in mean cellular volume, and a decrease in cellular deformability. However, DGBE had no effect on rat red blood cell morphology, cell size, hemolysis or deformability. There was no hemolysis when human red blood cells were exposed to DGBE or BEAA at the same concentrations. No changes in mean cellular volume, distribution of cell size, or morphologic appearance of human red blood cells were observed. No evidence for decreased deformability of human red blood cells exposed to DGBE or BEAA was found. In conclusion, BEAA has weak hemolytic activity and sub-hemolytic effects in vitro on rat erythrocytes, which is consistent with the finding of mild hemolysis when the parent compound DGBE is administered to rats by gavage. The absence of hemolysis or sub-hemolytic damage when human red blood cells were exposed to BEAA or DGBE in vitro indicates that it is unlikely that hemolysis will occur as a result of human exposure to DGBE.

Algorithm for cellular reprogramming.

Science.gov (United States)

Ronquist, Scott; Patterson, Geoff; Muir, Lindsey A; Lindsly, Stephen; Chen, Haiming; Brown, Markus; Wicha, Max S; Bloch, Anthony; Brockett, Roger; Rajapakse, Indika

2017-11-07

The day we understand the time evolution of subcellular events at a level of detail comparable to physical systems governed by Newton's laws of motion seems far away. Even so, quantitative approaches to cellular dynamics add to our understanding of cell biology. With data-guided frameworks we can develop better predictions about, and methods for, control over specific biological processes and system-wide cell behavior. Here we describe an approach for optimizing the use of transcription factors (TFs) in cellular reprogramming, based on a device commonly used in optimal control. We construct an approximate model for the natural evolution of a cell-cycle-synchronized population of human fibroblasts, based on data obtained by sampling the expression of 22,083 genes at several time points during the cell cycle. To arrive at a model of moderate complexity, we cluster gene expression based on division of the genome into topologically associating domains (TADs) and then model the dynamics of TAD expression levels. Based on this dynamical model and additional data, such as known TF binding sites and activity, we develop a methodology for identifying the top TF candidates for a specific cellular reprogramming task. Our data-guided methodology identifies a number of TFs previously validated for reprogramming and/or natural differentiation and predicts some potentially useful combinations of TFs. Our findings highlight the immense potential of dynamical models, mathematics, and data-guided methodologies for improving strategies for control over biological processes. Copyright © 2017 the Author(s). Published by PNAS.

Biofabrication and testing of a fully cellular nerve graft

International Nuclear Information System (INIS)

Owens, Christopher M; Marga, Francoise; Forgacs, Gabor; Heesch, Cheryl M

2013-01-01

Rupture of a nerve is a debilitating injury with devastating consequences for the individual's quality of life. The gold standard of repair is the use of an autologous graft to bridge the severed nerve ends. Such repair however involves risks due to secondary surgery at the donor site and may result in morbidity and infection. Thus the clinical approach to repair often involves non-cellular solutions, grafts composed of synthetic or natural materials. Here we report on a novel approach to biofabricate fully biological grafts composed exclusively of cells and cell secreted material. To reproducibly and reliably build such grafts of composite geometry we use bioprinting. We test our grafts in a rat sciatic nerve injury model for both motor and sensory function. In particular we compare the regenerative capacity of the biofabricated grafts with that of autologous grafts and grafts made of hollow collagen tubes by measuring the compound action potential (for motor function) and the change in mean arterial blood pressure as consequence of electrically eliciting the somatic pressor reflex. Our results provide evidence that bioprinting is a promising approach to nerve graft fabrication and as a consequence to nerve regeneration. (paper)

Phenotypic characterization of neurotensin messenger RNA-expressing cells in the neuroleptic-treated rat striatum: a detailed cellular co-expression study

Energy Technology Data Exchange (ETDEWEB)

Emson, P C; Westmore, K; Augood, S J [MRC Molecular Neuroscience Group, The Department of Neurobiology, The Babraham Institute, Babraham, Cambridge (United Kingdom)

1996-12-11

The chemical phenotype of proneurotensin messenger RNA-expressing cells was determined in the acute haloperidol-treated rat striatum using a combination of [{sup 35}S]-labelled and alkaline phosphatase-labelled oligonucleotides. Cellular sites of proneurotensin messenger RNA expression were visualized simultaneously on tissue sections processed to reveal cellular sites of preproenkephalin A messenger RNA or the dopamine and adenylate cyclase phosphoprotein-32, messenger RNA. The cellular co-expression of preproenkepahlin A and preprotachykinin messenger RNA was also examined within forebrain structures. Cellular sites of preproenkephalin A and dopamine and adenylate cyclase phosphoprotein-32 messenger RNAs were visualized using alkaline phosphatase-labelled oligonucleotides whilst sites of preprotachykinin and proneurotensin messenger RNA expression were detected using [{sup 35}S]-labelled oligos. Cellular sites of enkephalin and dopamine and adenylate cyclase phosphoprotein-32 gene expression were identified microscopically by the concentration of purple alkaline phosphatase reaction product within the cell cytoplasm, whereas sites of substance P and proneurotensin gene expression were identified by the dense clustering of silver grains overlying cells.An intense hybridization signal was detected for all three neuropeptide messenger RNAs in the striatum, the nucleus accumbens and septum. Dopamine and adenylate cyclase phosphoprotein-32 messenger RNA was detected within the neostriatum but not within the septum. In all forebrain regions examined, with the exception of the islands of Cajella, the cellular expression of enkephalin messenger RNA and substance P messenger RNA was discordant; the two neuropeptide messenger RNAs were detected essentially in different cells, although in the striatum and nucleus accumbens occasional isolated cells were detected which contained both hybridization signals; dense clusters of silver grains overlay alkaline phosphatase

Phenotypic characterization of neurotensin messenger RNA-expressing cells in the neuroleptic-treated rat striatum: a detailed cellular co-expression study

International Nuclear Information System (INIS)

Emson, P.C.; Westmore, K.; Augood, S.J.

1996-01-01

The chemical phenotype of proneurotensin messenger RNA-expressing cells was determined in the acute haloperidol-treated rat striatum using a combination of [ 35 S]-labelled and alkaline phosphatase-labelled oligonucleotides. Cellular sites of proneurotensin messenger RNA expression were visualized simultaneously on tissue sections processed to reveal cellular sites of preproenkephalin A messenger RNA or the dopamine and adenylate cyclase phosphoprotein-32, messenger RNA. The cellular co-expression of preproenkepahlin A and preprotachykinin messenger RNA was also examined within forebrain structures. Cellular sites of preproenkephalin A and dopamine and adenylate cyclase phosphoprotein-32 messenger RNAs were visualized using alkaline phosphatase-labelled oligonucleotides whilst sites of preprotachykinin and proneurotensin messenger RNA expression were detected using [ 35 S]-labelled oligos. Cellular sites of enkephalin and dopamine and adenylate cyclase phosphoprotein-32 gene expression were identified microscopically by the concentration of purple alkaline phosphatase reaction product within the cell cytoplasm, whereas sites of substance P and proneurotensin gene expression were identified by the dense clustering of silver grains overlying cells.An intense hybridization signal was detected for all three neuropeptide messenger RNAs in the striatum, the nucleus accumbens and septum. Dopamine and adenylate cyclase phosphoprotein-32 messenger RNA was detected within the neostriatum but not within the septum. In all forebrain regions examined, with the exception of the islands of Cajella, the cellular expression of enkephalin messenger RNA and substance P messenger RNA was discordant; the two neuropeptide messenger RNAs were detected essentially in different cells, although in the striatum and nucleus accumbens occasional isolated cells were detected which contained both hybridization signals; dense clusters of silver grains overlay alkaline phosphatase-positive cells

Coordination of early cellular reactions during activation of bone resorption in the rat mandible periosteum: An immunohistochemical study

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Bassam Hassan

2017-10-01

Full Text Available The activation step of bone remodeling remains poorly characterized. Activation comprises determination of the site to be remodeled, osteoclast precursor recruitment, their migration to the site of remodeling, and differentiation. These actions involve different compartments and cell types. The aim of this study was to investigate events and cell types involved during activation. We used a bone remodeling model in rats where extractions of the upper jaw molars initiate remodeling of the antagonist lower jaw (mandible cortex along the periosteum. In this model osteoclastic resorption peaks 4 days after extractions. We previously reported that mast cell activation in the periosteum fibrous compartment is an early event of activation, associated with recruitment of circulating monocyte osteoclast precursors. By using immunohistochemistry, we observed 9 hours after induction a spatially oriented expression of InterCellular Adhesion Molecule-1 in the vessels that was inhibited by antagonists of histamine receptors 1 and 2. It was followed at 12 hours by the recruitment of ED1+ monocytes. In parallel, at 9 hours, Vascular Cellular Adhesion Molecule-1+ fibroblast-like cells scattered in the fibrous compartment of the periosteum between the vessels and the osteogenic compartment increased; these cells may be implicated in osteoclast precursor migration. Receptor Activator of NF KappaB Ligand+ cells increased at 12 hours in the osteogenic compartment and reached a peak at 18 hours. At 24 hours the numbers of osteogenic cells and subjacent osteocytes expressing semaphorin 3a, a repulsive for osteoclast precursors, decreased before returning to baseline at 48 hours. These data show that during activation the two periosteum compartments and several cell types are coordinated to recruit and guide osteoclast precursors towards the bone surface. Keywords: Biological sciences, Cell biology, Physiology, Dentistry

Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism.

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Pierce, Janet D; Gupte, Raeesa; Thimmesch, Amanda; Shen, Qiuhua; Hiebert, John B; Brooks, William M; Clancy, Richard L; Diaz, Francisco J; Harris, Janna L

2018-06-01

Following traumatic brain injury (TBI), there is significant secondary damage to cerebral tissue from increased free radicals and impaired mitochondrial function. This imbalance between reactive oxygen species (ROS) production and the effectiveness of cellular antioxidant defenses is termed oxidative stress. Often there are insufficient antioxidants to scavenge ROS, leading to alterations in cerebral structure and function. Attenuating oxidative stress following a TBI by administering an antioxidant may decrease secondary brain injury, and currently many drugs and supplements are being investigated. We explored an over-the-counter supplement called ubiquinol (reduced form of coenzyme Q10), a potent antioxidant naturally produced in brain mitochondria. We administered intra-arterial ubiquinol to rats to determine if it would reduce mitochondrial damage, apoptosis, and severity of a contusive TBI. Adult male F344 rats were randomly assigned to one of three groups: (1) Saline-TBI, (2) ubiquinol 30 minutes before TBI (UB-PreTBI), or (3) ubiquinol 30 minutes after TBI (UB-PostTBI). We found when ubiquinol was administered before or after TBI, rats had an acute reduction in brain mitochondrial damage, apoptosis, and two serum biomarkers of TBI severity, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1). However, in vivo neurometabolic assessment with proton magnetic resonance spectroscopy did not show attenuated injury-induced changes. These findings are the first to show that ubiquinol preserves mitochondria and reduces cellular injury severity after TBI, and support further study of ubiquinol as a promising adjunct therapy for TBI. © 2018 Wiley Periodicals, Inc.

Functional neurokinin and NMDA receptor activity in an animal naturally lacking substance P: the naked mole-rat.

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Antje Brand

Full Text Available Naked mole-rats are extremely unusual among mammals in that their cutaneous C-fibers lack the neuropeptide Substance P (SP. In other mammals, SP plays an important role in nociception: it is released from C-fibers onto spinal neurons where it facilitates NMDA receptor activity and causes sensitization that can last for minutes, hours or days. In the present study, we tested the effects of intrathecal application of: 1 SP, 2 an SP antagonist (GR-82334, and 3 an NMDA antagonist (APV on heat-evoked foot withdrawal. In the naked mole-rat, at a high enough concentration, application of SP caused a large, immediate, and long-lasting sensitization of foot withdrawal latency that was transiently reversed by application of either antagonist. However, neither SP nor NMDA antagonists had an effect when administered alone to naïve animals. In contrast, both antagonists induced an increase in basal withdrawal latency in mice. These results indicate that spinal neurons in naked mole-rats have functional SP and NMDA receptors, but that these receptors do not participate in heat-evoked foot withdrawal unless SP is experimentally introduced. We propose that the natural lack of SP in naked mole-rat C-fibers may have resulted during adaptation to living in a chronically high carbon dioxide, high ammonia environment that, in other mammals, would stimulate C-fibers and evoke nocifensive behavior.

Functional neurokinin and NMDA receptor activity in an animal naturally lacking substance P: the naked mole-rat.

Science.gov (United States)

Brand, Antje; Smith, Ewan St J; Lewin, Gary R; Park, Thomas J

2010-12-21

Naked mole-rats are extremely unusual among mammals in that their cutaneous C-fibers lack the neuropeptide Substance P (SP). In other mammals, SP plays an important role in nociception: it is released from C-fibers onto spinal neurons where it facilitates NMDA receptor activity and causes sensitization that can last for minutes, hours or days. In the present study, we tested the effects of intrathecal application of: 1) SP, 2) an SP antagonist (GR-82334), and 3) an NMDA antagonist (APV) on heat-evoked foot withdrawal. In the naked mole-rat, at a high enough concentration, application of SP caused a large, immediate, and long-lasting sensitization of foot withdrawal latency that was transiently reversed by application of either antagonist. However, neither SP nor NMDA antagonists had an effect when administered alone to naïve animals. In contrast, both antagonists induced an increase in basal withdrawal latency in mice. These results indicate that spinal neurons in naked mole-rats have functional SP and NMDA receptors, but that these receptors do not participate in heat-evoked foot withdrawal unless SP is experimentally introduced. We propose that the natural lack of SP in naked mole-rat C-fibers may have resulted during adaptation to living in a chronically high carbon dioxide, high ammonia environment that, in other mammals, would stimulate C-fibers and evoke nocifensive behavior.

Involvement of growth factors and their receptors in radon-induced rat lung tumors

International Nuclear Information System (INIS)

Leung, F.C.; Dagle, G.E.; Cross, F.T.

1992-01-01

In this paper we examine the role of growth factors (GF) and their receptors (GFR) in radon-induced rat lung tumors. Inhalation exposure of radon and its daughters induced lung tumors in rats, but the molecule/cellular mechanisms are not known. Recent evidence suggests that GF/GFR play a critical role in the growth and development of lung cancer in humans and animals. We have developed immunocytochemical methods for identifying sites of production and action of GF/GFR at the cellular level; for example, the avidin-biotin horseradish peroxidase technique. In radon-induced rat epidermoid carcinomas, epidermal growth factor (EGF), EGF-receptors (EGF-R), transforming growth factor alpha (TGF-α), and bombesin were found to be abnormally expressed. These abnormal expressions, mainly associated with epidermoid carcinomas of the lung, were not found in any other lung tumor types. Our data suggest that EGF, EGF-R, TGF-α, and bombesin are involved in radon oncogenesis in rat lungs, especially in epidermoid carcinomas, possibly through the autocrine/paracrine pathway

Voluntary Ingestion of Natural Cocoa Extenuated Hepatic Damage in Rats with Experimentally Induced Chronic Alcoholic Toxicity

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Godwin Sokpor

2012-05-01

Full Text Available Background: Chronic ethanol ingestion causes hepatic damage imputable to an increasedoxidative stress engendered by alcoholic toxicity. Polyphenols in cocoa have antioxidant properties, and natural cocoa powder (NCP contains the highest levels of total antioxidant capacity when compared to all other kinds of edible cocoa products. This study tested the hypothesis that dietary supplementation with NCP mitigates hepatic injury resulting from chronic ethanol consumption. Three groups of eight randomized Sprague-Dawley rats were fed standardrat food and treated daily for 12 weeks as follows: (i the Ethanol-water group was given unrestricted access to 40% (v/v ethanol for 12 hours (at night followed by water for the remaining 12 hours (daytime, (ii the Ethanol-cocoa group had similarly unrestricted access to 40% ethanol for 12 hours followed by 2% (w/v NCP for 12 hours, and (iii the control group was not given alcohol and had unrestricted access to only water which was synchronously replenished every 12 hours as it was for the ethanol treated animals.Results: Qualitative structural liver damage evidenced by hepatocyte cytoplasmic fatty accumulation, nuclear alterations, and disruption of general liver micro-architecture, was severe in the ethanol-water group when compared with the ethanol-cocoa group of rats. Design-based stereologic assessment yielded a significantly greater volume (Tukey’s HSD, p = 0.0005 ofundamaged hepatocytes (9.61 ml, SD 2.18 ml in the ethanol-cocoa group as opposed to theethanol-water group of rats (2.34 ml, SD 1.21 ml. Control rats had 10.34 ml (SD 1.47 ml of undamaged hepatocytes, and that was not significantly greater (Tukey’s HSD, p=0.659 than the value for the ethanol-cocoa group of rats. Relative to controls, therefore, histomorphometryFunctional Foods in Health and Disease 2012, 2(5:166- 187 showed 93% hepatocyte preservation from alcoholic injury in rats that voluntarily imbibed NCP suspension compared with 23% in

Aging contributes to inflammation in upper extremity tendons and declines in forelimb agility in a rat model of upper extremity overuse.

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David M Kietrys

Full Text Available We sought to determine if tendon inflammatory and histopathological responses increase in aged rats compared to young rats performing a voluntary upper extremity repetitive task, and if these changes are associated with motor declines. Ninety-six female Sprague-Dawley rats were used in the rat model of upper extremity overuse: 67 aged and 29 young adult rats. After a training period of 4 weeks, task rats performed a voluntary high repetition low force (HRLF handle-pulling task for 2 hrs/day, 3 days/wk for up to 12 weeks. Upper extremity motor function was assessed, as were inflammatory and histomorphological changes in flexor digitorum and supraspinatus tendons. The percentage of successful reaches improved in young adult HRLF rats, but not in aged HRLF rats. Forelimb agility decreased transiently in young adult HRLF rats, but persistently in aged HRLF rats. HRLF task performance for 12 weeks lead to increased IL-1beta and IL-6 in flexor digitorum tendons of aged HRLF rats, compared to aged normal control (NC as well as young adult HRLF rats. In contrast, TNF-alpha increased more in flexor digitorum tendons of young adult 12-week HRLF rats than in aged HRLF rats. Vascularity and collagen fibril organization were not affected by task performance in flexor digitorum tendons of either age group, although cellularity increased in both. By week 12 of HRLF task performance, vascularity and cellularity increased in the supraspinatus tendons of only aged rats. The increased cellularity was due to increased macrophages and connective tissue growth factor (CTGF-immunoreactive fibroblasts in the peritendon. In conclusion, aged rat tendons were overall more affected by the HRLF task than young adult tendons, particularly supraspinatus tendons. Greater inflammatory changes in aged HRLF rat tendons were observed, increases associated temporally with decreased forelimb agility and lack of improvement in task success.

Brain plasticity of rats exposed to prenatal immobilization stress

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Badalyan B. Yu.

2011-10-01

Full Text Available Aim. This histochemical and immunohistochemical study was aimed at examining the brain cellular structures of newborn rats exposed to prenatal immobilization (IMO stress. Methods. Histochemical method on detection of Ca2+-dependent acid phosphatase activity and ABC immunohistochemical technique. Results. Cell structures with radial astrocytes marker GFAP, neuroepithelial stem cell marker gene nestin, stem-cells marker and the hypothalamic neuroprotective proline-rich polypeptide PRP-1 (Galarmin, a natural cytokine of a common precursor to neurophysin vasopressin associated glycoprotein have been revealed in several brain regions. Conclusions. Our findings indicate the process of generation of new neurons in response to IMO and PRP-1 involvement in this recovery mechanism, as PRP-1-Ir was detected in the above mentioned cell structures, as well as in the neurons and nerve fibers.

Inhibition of HMGB1 Translocation by Green Tea Extract in Rats Exposed to Environmental Tobacco Smoke

OpenAIRE

Sirintip Chaichalotornkul; Wisuda Suvitayavat; Vanida Sangalangkarn; Yuko Nawa; Kiyoshi Kikuchi; Koichi Kawahara; Tawee Saiwichai; Somphong Narkpinit; Pratap Singhasivanon; Ikuro Maruyama; Salunya Tancharoen

2012-01-01

Environmental tobacco smoke (ETS) exposure is linked to carcinogenic, oxidative and inflammatory cellular reactions. Green tea polyphenol reportedly plays a role in the prevention of inflammation-related diseases. To evaluate the effects of green tea extract (GTE) on cellular location of High Mobility Group Box-1 (HMGB1) protein, we studied the lung tissue in rats exposed to cigarette smoke (CS). Rats were divided into three groups; CS, CSG, and C, which were groups of CS-treated only, CS-tre...

Cellular glutathione prevents cytolethality of monomethylarsonic acid

International Nuclear Information System (INIS)

Sakurai, Teruaki; Kojima, Chikara; Ochiai, Masayuki; Ohta, Takami; Sakurai, Masumi H.; Waalkes, Michael P.; Fujiwara, Kitao

2004-01-01

Inorganic arsenicals are clearly toxicants and carcinogens in humans. In mammals, including humans, inorganic arsenic often undergoes methylation, forming compounds such as monomethylarsonic acid (MMAs V ) and dimethylarsinic acid (DMAs V ). However, much less information is available on the in vitro toxic potential or mechanisms of these methylated arsenicals, especially MMAs V . We studied the molecular mechanisms of in vitro cytolethality of MMAs V using a rat liver epithelial cell line (TRL 1215). MMAs V was not cytotoxic in TRL 1215 cells even at concentrations exceeding 10 mM, but it became weakly cytotoxic and induced both necrotic and apoptotic cell death when cellular reduced glutathione (GSH) was depleted with the glutathione synthase inhibitor, L-buthionine-[S,R]-sulfoximine (BSO), or the glutathione reductase inhibitor, carmustine. Similar results were observed in the other mammalian cells, such as human skin TIG-112 cells, chimpanzee skin CRT-1609 cells, and mouse metallothionein (MT) positive and MT negative embryonic cells. Ethacrynic acid (EA), an inhibitor of glutathione S-transferase (GST) that catalyses GSH-substrate conjugation, also enhanced the cytolethality of MMAs V , but aminooxyacetic acid (AOAA), an inhibitor of β-lyase that catalyses the final breakdown of GSH-substrate conjugates, had no effect. Both the cellular GSH levels and the cellular GST activity were increased by the exposure to MMAs V in TRL 1215 cells. On the other hand, the addition of exogenous extracellular GSH enhanced the cytolethality of MMAs V , although cellular GSH levels actually prevented the cytolethality of combined MMAs V and exogenous GSH. These findings indicate that human arsenic metabolite MMAs V is not a highly toxic compound in mammalian cells, and the level of cellular GSH is critical to its eventual toxic effects

Biodistribution study of 153Sm-EDTMP produced by irradiation of natural and enriched Samarium, in rats

International Nuclear Information System (INIS)

Meftahi, M.; Bahrami Samani, A.; Babaei, M. H.; Shamsaei Zafarghandi, M.; Ghannadi Maragheh, M.

2010-01-01

''1 53 Sm-EDTMP is one of the well known radiopharmaceuticals for pain palliation of bone metastases. Despite that, it is used just in a few countries. It is due to some reasons like being costly enriched samarium that usually used as target for irradiation and short half-life of 153 Sm. In this investigation, certain amounts of radiopharmaceuticals prepared by irradiation of enriched and natural samarium were injected to some normal rats. Then, the rodents were sacrificed and some of their organs were removed. All of the mentioned stages were performed in order to consider the possibility of exploiting natural samarium instead of enriched samarium by study of biodistribution of both radiopharmaceuticals in various organs especially in bone as the target tissue. At the end, the acceptable results were obtained using natural samarium in comparison with the enriched samarium from the point of view of the biodistribution studies.

Cocoa-enriched diet enhances antioxidant enzyme activity and modulates lymphocyte composition in thymus from young rats.

Science.gov (United States)

Ramiro-Puig, Emma; Urpí-Sardà, Mireia; Pérez-Cano, Francisco J; Franch, Angels; Castellote, Cristina; Andrés-Lacueva, Cristina; Izquierdo-Pulido, Maria; Castell, Margarida

2007-08-08

Cocoa is a rich source of flavonoids, mainly (-)-epicatechin, (+)-catechin, and procyanidins. This article reports the effect of continuous cocoa intake on antioxidant capacity in plasma and tissues, including lymphoid organs and liver, from young rats. Weaned Wistar rats received natural cocoa (4% or 10% food intake) for three weeks, corresponding to their infancy. Flavonoid absorption was confirmed through the quantification of epicatechin metabolites in urine. Total antioxidant capacity (TAC) and the activity of antioxidant enzymes, superoxide dismutase (SOD) and catalase, were examined. Cocoa intake enhanced TAC in all tissues especially in thymus. Moreover, thymus SOD and catalase activities were also dose-dependently increased by cocoa. It was also analyzed whether the enhanced antioxidant system in thymus could influence its cellular composition. An increase in the percentage of thymocytes in advanced development stage was found. In summary, cocoa diet enhances thymus antioxidant defenses and influences thymocyte differentiation.

Nigella sativa oil Ameliorates ionizing Radiation induced cellular injury in Male Albino Rats

International Nuclear Information System (INIS)

Mohamed, E.T.; El-Kady, A.A.

2013-01-01

Nigella sativa (NS), commonly known as black seed, is a plant spices in which thymoquinone is the main active ingredient isolated from the black seeds. The seeds of Nigella sativa are used in herbal medicine all over the world for the treatment and prevention of a number of diseases. The aim of this study was focused on investigating the possible protective effect of NS against gamma radiation induced nephrotoxicity and inflammatory changes in male albino rats. Twenty four albino rats were divided into four equal groups as follows: control group, irradiated group (animals subjected to whole body gamma irradiation at a dose of 6 Gy), treated group (rats treated with 0.2 ml/kg, i.p., NS oil for 4 weeks), and treated irradiated group (animals treated with 0.2 mL/kg, i.p., NS oil for 4 weeks then exposed to whole body gamma irradiation at a dose of 6 Gy). The obtained results revealed that the administration of Nigella sativa oil to irradiated rats significantly ameliorated the changes induced in kidney antioxidant system; catalase and glutathione peroxidase activities as well as reduced glutathione concentration. Also, NS oil restored the kidney function indices (urea and creatinine) near normal level when compared with their equivalent values in irradiated rats. In addition, the changes in serum tumor necrosis factor alpha (TNF-α), Interleukin-1β (IL-1β) and Interleukin-6 (IL-6) activities were markedly improved compared to the corresponding values of irradiated group. The histopathological results showed distinctive pattern of ischemic renal injury in irradiated group, while in treated- irradiated group the renal tissues showed relatively well-preserved architecture with or without focal degeneration. In conclusion, NS acts in the kidney as a potent scavenger of free radicals to prevent or ameliorates the toxic effects of gamma irradiation as shown in the biochemical and histopathological study and also NS oil might provide substantial protection against

Comparative gastroprotective effects of natural honey, nigella sativa and cimetidine against acetylsalicylic acid Induced gastric ulcer in albino rats

International Nuclear Information System (INIS)

Bukhari, M.H.; Khalil, J.; Zahid, M.; Ansari, N.

2011-01-01

Natural honey (NH) and Nigella sativa (NS) seeds have been in use as a natural remedy for over thousands of years in various parts of the world. The aim of this study was to assess the protective effects of NS (Nigella sativa) and NH (natural honey) on acetylsalicylic acid induced gastric ulcer in an experimental model with comparison to Cimetidine (CD). The study was conducted on 100 male albino rats, divided into 5 groups, with 20 animals in each group. Group A was used as a control and treated with Gum Tragacanth (GT). Eighty animals of the other groups were given acetylsalicylic acid (0.2 gm/kg body weight for 3 days) to produce ulcers by gavage. Two animals from each group were sacrificed for the detection of gastric ulcers. The remaining 72 animals were equally divided in four groups (B, C, D and E). The rats in group B, C and D were given NS, NH, and CD respectively while those in E were kept as such. No gastric lesions were seen in control group A while all the animals in group E revealed gastric ulcers. The animals of group B, C and D showed healing effects in 15/18 (83%), 14/18 (78%) and 17/18 (94%) animals grossly; 13/18 (72%), 14/18 (78%) and 16/18 (89%) rats showed recovery on microscopic examination respectively. The healing effects were almost the same in all three groups therefore, the statistical difference was not significant among them (p =0.40 and 0.65) while significant from group E (p=0.0000075, 0.0000016 and 0.0000012 respectively). NS and NH are equally effective in healing of gastric ulcer similar to cimetidine. Further broad spectrum studies as well as clinical trials should be conducted before the use of these products as routine medicines. (author)

Moringa oleifera-based diet protects against nickel-induced hepatotoxicity in rats

Science.gov (United States)

Stephen Adeyemi, Oluyomi; Sokolayemji Aroge, Cincin; Adewumi Akanji, Musbau

2017-01-01

Multiple health-promoting effects have been attributed to the consumption of Moringa oleifera leaves, as part of diet without adequate scientific credence. This study evaluated the effect of M. oleifera-based diets on nickel (Ni) - induced hepatotoxicity in rats. Male rats assigned into six groups were given oral administration of 20 mg/kg body weight nickel sulfate in normal saline and either fed normal diet orM. oleifera-based diets for 21 days. All animals were sacrificed under anesthesia 24 hours after the last treatment. Ni exposure elevated the rat plasma activities of alanine transaminase, aspartate transaminase and alkaline phosphatase significantly. Ni exposure also raised the levels of triglyceride, total cholesterol and low-density lipoprotein cholesterol while depleting the high-density lipoprotein cholesterol concentration. Further, Ni exposure raised rat plasma malondialdehyde but depleted reduced glutathione concentrations. The histopathological presentations revealed inflammation and cellular degeneration caused by Ni exposure. We show evidence thatM. oleifera-based diets protected against Ni-induced hepatotoxicity by improving the rat liver function indices, lipid profile as well as restoring cellular architecture and integrity. Study lends credence to the health-promoting value ofM. oleifera as well as underscores its potential to attenuate hepatic injury. PMID:28808207

Cellular strategies to cope with protein aggregation

NARCIS (Netherlands)

Scior, Annika; Juenemann, Katrin; Kirstein, Janine

2016-01-01

Nature has evolved several mechanisms to detoxify intracellular protein aggregates that arise upon proteotoxic challenges. These include the controlled deposition of misfolded proteins at distinct cellular sites, the protein disaggregation and refolding by molecular chaperones and/or degradation of

Ebselen alters cellular oxidative status and induces endoplasmic reticulum stress in rat hippocampal astrocytes.

Science.gov (United States)

Santofimia-Castaño, Patricia; Izquierdo-Alvarez, Alicia; de la Casa-Resino, Irene; Martinez-Ruiz, Antonio; Perez-Lopez, Marcos; Portilla, Juan C; Salido, Gines M; Gonzalez, Antonio

2016-05-16

Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is an organoselenium radical scavenger compound, which has strong antioxidant and anti-inflammatory effects. Because of its properties, it may be protective against injury to the nervous tissue. However, evidence suggests that its glutathione peroxidase activity could underlie certain deleterious actions on cell physiology. In this study we have analyzed the effect of ebselen on rat hippocampal astrocytes in culture. Cellular oxidative status, cytosolic free-Ca(2+) concentration ([Ca(2+)]c), setting of endoplasmic reticulum stress and phosphorylation of glial fibrillary acidic protein and major mitogen-activated protein kinases were analyzed. Our results show that ebselen induced a concentration-dependent increase in the generation of reactive oxygen species in the mitochondria. We observed a concentration-dependent increase in global cysteine oxidation and in the level of malondialdehyde in the presence of ebselen. We also detected increases in catalase, glutathione S-transferase and glutathione reductase activity. Ebselen also evoked a concentration-dependent increase in [Ca(2+)]c. Moreover, we observed a concentration-dependent increase in the phosphorylation of the unfolded protein response markers, eukaryotic translation initiation factor 2α and X-box binding protein 1. Finally, ebselen also induced an increase in the phosphorylation of glial fibrillary acidic protein, SAPK/JNK, p38 MAPK and p44/42 MAPK. Our results provide strong evidence that implicate endoplasmic reticulum stress and activation of crucial mitogen-activated protein kinases in an oxidative damage of cells in the presence of ebselen. The compound thus might exert deleterious actions on astrocyte physiology that could compromise their function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Creatine supplementation reduces sleep need and homeostatic sleep pressure in rats.

Science.gov (United States)

Dworak, Markus; Kim, Tae; Mccarley, Robert W; Basheer, Radhika

2017-06-01

Sleep has been postulated to promote brain energy restoration. It is as yet unknown if increasing the energy availability within the brain reduces sleep need. The guanidine amino acid creatine (Cr) is a well-known energy booster in cellular energy homeostasis. Oral Cr-monohydrate supplementation (CS) increases exercise performance and has been shown to have substantial effects on cognitive performance, neuroprotection and circadian rhythms. The effect of CS on cellular high-energy molecules and sleep-wake behaviour is unclear. Here, we examined the sleep-wake behaviour and brain energy metabolism before and after 4-week-long oral administration of CS in the rat. CS decreased total sleep time and non-rapid eye movement (NREM) sleep significantly during the light (inactive) but not during the dark (active) period. NREM sleep and NREM delta activity were decreased significantly in CS rats after 6 h of sleep deprivation. Biochemical analysis of brain energy metabolites showed a tendency to increase in phosphocreatine after CS, while cellular adenosine triphosphate (ATP) level decreased. Microdialysis analysis showed that the sleep deprivation-induced increase in extracellular adenosine was attenuated after CS. These results suggest that CS reduces sleep need and homeostatic sleep pressure in rats, thereby indicating its potential in the treatment of sleep-related disorders. © 2017 European Sleep Research Society.

Propolis attenuates oxidative injury in brain and lung of nitric oxide synthase inhibited rats

Directory of Open Access Journals (Sweden)

Zeliha Selamoglu-Talas

2015-10-01

Full Text Available Background: The blocking of nitric oxide synthase (NOS activity may reason vasoconstriction with formation of reactive oxygen species. Propolis has biological and pharmacological properties, such as antioxidant. The aim of this study was to examine the antioxidant effects of propolis which natural product on biochemical parameters in brain and lung tissues of acute nitric oxide synthase inhibited rats by Nω-nitro-L-arginine methyl ester (L-NAME.Methods: Rats have been received L-NAME (40 mg/kg, intraperitoneally, NOS inhibitor for 15 days to produce hypertension and propolis (200mg/kg, by gavage the lastest 5 of 15 days.Results: There  were  the  increase  (P<0.001  in  the  malondialdehyde  levels  in  the  L-NAME treatment groups when compared to control rats, but the decrease (P<0.001 in the catalase activities in both brain and lung tissues. There were statistically changes (P<0.001 in these parameters of L-NAME+propolis treated rats as compared with L-NAME-treated group.Conclusion: The application of L-NAME to the Wistar rats resulted in well developed oxidative stress. Also, propolis may influence endothelial NO production. Identification of such compounds and characterisation of their cellular actions may increase our knowledge of the regulation of endothelial NO production and could provide valuable clues for the prevention or treatment of hypertensive diseases and oxidative stress.

UVB-induced decreased resistance to Trichinella spiralis in the rat is related to impaired cellular immunity

International Nuclear Information System (INIS)

Goettsch, W.; Garssen, J.; Loveren, H. van; Gruijl, F.R. de

1996-01-01

Our laboratory has demonstrated in preliminary experiments that UVB exposure using the Kromayer lamp can induce increased numbers of Trichinella spiralis larvae in carcasses of infected Wistar rats, without affecting specific antibody titers to this parasite. In this study, orally T.spiralis-infected Wistar rats were exposed to subery-thermal doses of UVB radiation using FS40 lamps during different time periods before or after infection. A significant increase in the number of T. spiralis larvae was found in the carcasses of rats that were UVB irradiated daily for 7 consecutive days in the second week after infection. Additionally, increased numbers of larvae were also detected histologically in the tongue of rats that were exposed the first and the second week after infection. Lymphocyte stimulation assays using mesenteral lymph node cells indicated that UVB exposure also impaired the specific lymphocyte response to T. spiralis. Moreover, DTH responses to T. spiralis were severely impaired in rats that were UVB irradiated daily for 7 consecutive days in the second week after infection. Thus, these data combined with the data of the Kromayer study indicate that exposure of rats to FS40 irradiation following oral infection with T. spiralis leads to increased numbers of larvae in systemic sites and impaired T-cell immunity to the parasite. (Author)

Psychological stress, cocaine and natural reward each induce endoplasmic reticulum stress genes in rat brain.

Science.gov (United States)

Pavlovsky, A A; Boehning, D; Li, D; Zhang, Y; Fan, X; Green, T A

2013-08-29

Our prior research has shown that the transcription of endoplasmic reticulum (ER) stress transcription factors activating transcription factor 3 (ATF3) and ATF4 are induced by amphetamine and restraint stress in rat striatum. However, presently the full extent of ER stress responses to psychological stress or cocaine, and which of the three ER stress pathways is activated is unknown. The current study examines transcriptional responses of key ER stress target genes subsequent to psychological stress or cocaine. Rats were subjected to acute or repeated restraint stress or cocaine treatment and mRNA was isolated from dorsal striatum, medial prefrontal cortex and nucleus accumbens brain tissue. ER stress gene mRNA expression was measured using quantitative polymerase chain reaction (PCR) and RNA sequencing. Restraint stress and cocaine-induced transcription of the classic ER stress-induced genes (BIP, CHOP, ATF3 and GADD34) and of two other ER stress components x-box binding protein 1 (XBP1) and ATF6. In addition, rats living in an enriched environment (large group cage with novel toys changed daily) exhibited rapid induction of GADD34 and ATF3 after 30 min of exploring novel toys, suggesting these genes are also involved in normal non-pathological signaling. However, environmental enrichment, a paradigm that produces protective addiction and depression phenotypes in rats, attenuated the rapid induction of ATF3 and GADD34 after restraint stress. These experiments provide a sensitive measure of ER stress and, more importantly, these results offer good evidence of the activation of ER stress mechanisms from psychological stress, cocaine and natural reward. Thus, ER stress genes may be targets for novel therapeutic targets for depression and addiction. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Thallium kinetics in rat cardiac transplant rejection

International Nuclear Information System (INIS)

Barak, J.H.; LaRaia, P.J.; Boucher, C.A.; Fallon, J.T.; Buckley, M.J.

1988-01-01

Cardiac transplant rejection is a very complex process involving both cellular and vascular injury. Recently, thallium imaging has been used to assess acute transplant rejection. It has been suggested that changes in thallium kinetics might be a sensitive indicator of transplant rejection. Accordingly, thallium kinetics were assessed in vivo in acute untreated rat heterotopic (cervical) transplant rejection. Male Lewis rats weighing 225-250 g received heterotopic heart transplants from syngeneic Lewis rats (group A; n = 13), or allogeneic Brown Norway rats (group B; n = 11). Rats were imaged serially on the 2nd and the 7th postoperative days. Serial cardiac thallium content was determined utilizing data collected every 150 sec for 2 hr. The data were fit to a monoexponential curve and the decay rate constant (/sec) derived. By day 7 all group B hearts had histological evidence of severe acute rejection, and demonstrated decreased global contraction. Group A hearts showed normal histology and contractility. However, thallium uptakes and washout of the two groups were the same. Peak thallium uptake of group B was +/- 3758 1166 counts compared with 3553 +/- 950 counts in the control group A (P = 0.6395); The 2-hr percentage of washout was 12.1 +/- 1.04 compared with 12.1 +/- 9.3 (P = 1.0000); and the decay constant was -0.00002065 +/- 0.00001799 compared with -0.00002202 +/- 0.00001508 (P = 0.8409). These data indicate that in vivo global thallium kinetics are preserved during mild-to-severe acute transplant rejection. These findings suggest that the complex cellular and extracellular processes of acute rejection limit the usefulness of thallium kinetics in the detection of acute transplant rejection

Complex Automata: Multi-scale Modeling with Coupled Cellular Automata

NARCIS (Netherlands)

Hoekstra, A.G.; Caiazzo, A.; Lorenz, E.; Falcone, J.-L.; Chopard, B.; Hoekstra, A.G.; Kroc, J.; Sloot, P.M.A.

2010-01-01

Cellular Automata (CA) are generally acknowledged to be a powerful way to describe and model natural phenomena [1-3]. There are even tempting claims that nature itself is one big (quantum) information processing system, e.g. [4], and that CA may actually be nature’s way to do this processing [5-7].

Study of the radioprotective efficiency of combined administration of natural antioxidants and a sulfhydryl compound in feverish irradiated rats

International Nuclear Information System (INIS)

Radwan, R.R.

2008-01-01

In the present experiments, a study of the radioprotective effects of natural antioxidants, rutin alone, vitamine E alone or each of them combined with synthetic radioprotector, cysteine have been investigated in irradiated and feverish irradiated rats. Furthermore, the oxidative stress bio markers and certain liver function tests of the irradiated and the feverish whole body irradiated rats were examined. Two main sets of animals were used: The 1st set was constructed in order to study the effect of irradiation, while the second set was used to study the effect of irradiation on feverish rats. The effect of irradiation was evaluated by exposing the whole body of rats to gamma radiation at acute single dose level of 6.5 Gy. Rutin was orally daily administered for two weeks before irradiation in a dose of 1.064 mmol/kg , vitamine E was injected intraperitoneally daily for seven days before irradiation in a dose of 50 mg/100 g. While, cysteine was intraperitoneally administered only 30 min. before irradiation in a dose of 30 mg/kg. In order to determine the antipyretic effect of the drugs, body temperature of each animal was measured before induction of hyperthermia as well as 18 hours following yeast injection. Rats were treated with the tested drugs before induction of fever then exposed to whole body gamma radiation at acute single dose level of 6.5 Gy and body temperature of each animal was measured 3 days after irradiation

Study of the radioprotective efficiency of combined administration of natural antioxidants and a sulfhydryl compound in feverish irradiated rats

Energy Technology Data Exchange (ETDEWEB)

Radwan, R R [Pharmacist in National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo (Egypt)

2008-07-01

In the present experiments, a study of the radioprotective effects of natural antioxidants, rutin alone, vitamine E alone or each of them combined with synthetic radioprotector, cysteine have been investigated in irradiated and feverish irradiated rats. Furthermore, the oxidative stress bio markers and certain liver function tests of the irradiated and the feverish whole body irradiated rats were examined. Two main sets of animals were used: The 1st set was constructed in order to study the effect of irradiation, while the second set was used to study the effect of irradiation on feverish rats. The effect of irradiation was evaluated by exposing the whole body of rats to gamma radiation at acute single dose level of 6.5 Gy. Rutin was orally daily administered for two weeks before irradiation in a dose of 1.064 mmol/kg , vitamine E was injected intraperitoneally daily for seven days before irradiation in a dose of 50 mg/100 g. While, cysteine was intraperitoneally administered only 30 min. before irradiation in a dose of 30 mg/kg. In order to determine the antipyretic effect of the drugs, body temperature of each animal was measured before induction of hyperthermia as well as 18 hours following yeast injection. Rats were treated with the tested drugs before induction of fever then exposed to whole body gamma radiation at acute single dose level of 6.5 Gy and body temperature of each animal was measured 3 days after irradiation.

Partial synchronization of spermatogenesis in the immature Djungarian hamster, but not in the immature Wistar rat

NARCIS (Netherlands)

van Haaster, L. H.; de rooij, D. G.

1994-01-01

The frequencies of the cellular associations of the seminiferous epithelium were determined at various ages after birth in immature Djungarian hamsters and Wistar rats. The frequencies of the cellular associations present in immature animals were then compared with the frequencies of the

Effect of certain natural antioxidants in protecting against damage caused by gamma radiation in ischemic rat intestine

International Nuclear Information System (INIS)

Hassan, T.A.A.

2009-01-01

Oxidative stress plays an important role in various clinical pathologies one of which is ischemia/reperfusion (I/R)- induced injury. Intestinal I/R enhances production of reactive oxygen species (ROS), inflammatory mediators and induces apoptosis. In other hand. the intestinal tract shows a high sensitivity to ionizing radiation due to a rapid cell turnover and is often implicated in radiation sickness the radiation damage may either be a consequence of a direct effect resulting in disruption of critical molecule (such as an enzyme or DNA) or an indirect effect through ionization of water molecules and formation of ROS. consequently, supplementation of antioxidants may be a beneficial approach to protect against cellular damages associated with oxidative stress. the current study was aimed to evaluate the possible protective effects of vitamin E (100 mg/kg p.o.), tomato extract (67 mg/kg. p.o.) and turmeric (100 mg/kg, p.o) against ileal injury induced in rats by total occlusion of the superior mesenteric artery for 30 min followed by reperfusion for another 30 min. Furthermore, this protective effect of the mentioned drugs was extended into injury that could happened in ileal tissues of rats exposed to (6 Gy) gamma radiation followed by intestinal I/R. Drugs were administered one daily for 14 consecutive days prior to the ischemic insult. Damage induced by I/R was manifested by depletion of ileal content of reduced glutathion (GSH) as well as Lactate dehydrogenas (LDH) activity, associated with elevation of ileal contents of thiobarbituric acid reactive substances (TBARS), nitrite, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Intestinal ischemic insults were exacerbated by radiation injury on comparing different untreated controls; except the ileal content of GSH which has elevated due to the preconditioning effect of irradiation. Vitamin E provided a significant protection against the decrease in LDH activity as well as the increase in TBARS

Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure

OpenAIRE

Tang, Suk Peng; Kuttulebbai Nainamohamed Salam, Sirajudeen; Jaafar, Hasnan; Gan, Siew Hua; Muzaimi, Mustapha; Sulaiman, Siti Amrah

2017-01-01

Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2?mL/kg/day), Tualang honey (1.0?g/kg/day), or ubiquinol (0.2?g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were i...

Effect of various chemicals on the metabolism of benzo(a)pyrene by cultured rat colon

DEFF Research Database (Denmark)

Autrup, Herman; Harris, Curtis C.; Fugaro, Steven

1977-01-01

The effect of various co- and anti-carcinogens of colon carcinogenesis on the metabolism of benzo(a)pyrene (BP) in cultured rat colon is reported. Rat colon enzymatically converted BP into metabolites which bind to cellular macromolecules i.e., DNA and protein. Activity of aryl hydrocarbon...

Uptake and degradation of natural surfactant by isolated rat granular pneumocytes

International Nuclear Information System (INIS)

Fisher, A.B.; Chander, A.; Reicherter, J.

1987-01-01

It has been previously shown that isolated granular pneumocytes internalize and degrade dipalmitoylphosphatidylcholine (DPPC) in synthetic lipid vesicles and reutilize degradation products for phosphatidylcholine (PC) synthesis. In this study, the authors evaluated the uptake and degradation of radiolabeled natural surfactant (NS) isolated from lung lavage after perfusing isolated rat lungs with [ 3 H]choline. Uptake of NS by isolated granular pneumocytes was increased approximately fourfold compared with synthetic liposomes, suggesting that physical form or a component (e.g., a protein) of NS plays a role in phospholipid uptake by these cells. Uptake was significantly decreased by metabolic inhibitors, indicating an energy requirement for this process. After 2-h incubation, the pattern of radioactivity in cells compared with NS showed a significant decrease in PC and DSPC and increase in free choline, choline phosphate, and CDP-choline. This pattern of metabolism indicates degradation of PC and metabolic reutilization of products. These studies support the hypothesis that alveolar phospholipids are accumulated and reutilized by granular pneumocytes for surfactant synthesis

Design and implementation of a novel mechanical testing system for cellular solids.

Science.gov (United States)

Nazarian, Ara; Stauber, Martin; Müller, Ralph

2005-05-01

Cellular solids constitute an important class of engineering materials encompassing both man-made and natural constructs. Materials such as wood, cork, coral, and cancellous bone are examples of cellular solids. The structural analysis of cellular solid failure has been limited to 2D sections to illustrate global fracture patterns. Due to the inherent destructiveness of 2D methods, dynamic assessment of fracture progression has not been possible. Image-guided failure assessment (IGFA), a noninvasive technique to analyze 3D progressive bone failure, has been developed utilizing stepwise microcompression in combination with time-lapsed microcomputed tomographic imaging (microCT). This method allows for the assessment of fracture progression in the plastic region, where much of the structural deformation/energy absorption is encountered in a cellular solid. Therefore, the goal of this project was to design and fabricate a novel micromechanical testing system to validate the effectiveness of the stepwise IGFA technique compared to classical continuous mechanical testing, using a variety of engineered and natural cellular solids. In our analysis, we found stepwise compression to be a valid approach for IGFA with high precision and accuracy comparable to classical continuous testing. Therefore, this approach complements the conventional mechanical testing methods by providing visual insight into the failure propagation mechanisms of cellular solids. (c) 2005 Wiley Periodicals, Inc.

Flaw tolerance vs. performance: A tradeoff in metallic glass cellular structures

International Nuclear Information System (INIS)

Chen, Wen; Liu, Ze; Robinson, Hannah Mae; Schroers, Jan

2014-01-01

Stochastic cellular structures are prevalent in nature and engineering materials alike. They are difficult to manipulate and study systematically and almost always contain imperfections. To design and characterize various degrees of imperfections in perfect periodic, stochastic and natural cellular structures, we fabricate a broad range of metallic glass cellular structures from perfectly periodic to highly stochastic by using a novel artificial microstructure approach based on thermoplastic replication of metallic glasses. For these cellular structures, precisely controlled imperfections are implemented and their effects on the mechanical response are evaluated. It is found that the mechanical performance of the periodic structures is generally superior to that of the stochastic structures. However, the stochastic structures experience a much higher tolerance to flaws than the periodic structure, especially in the plastic regime. The different flaw tolerance is explained by the stress distribution within the various structures, which leads to an overall 'strain-hardening' behavior of the stochastic structure compared to a 'strain-softening' behavior in the periodic structure. Our findings reveal how structure, 'strain-hardening' and flaw tolerance are microscopically related in structural materials

Long-term organ culture of adult rat colon

DEFF Research Database (Denmark)

Shamsuddin, A.K.M.; Barrett, L.A.; Autrup, Herman

1978-01-01

. The effect of in vivo carcinogen pretreatment was also studied. The explant culture from control untreated animals showed good epithelial differentiation with crypts until 6 weeks. In contrast, the explants from animals pretreated with 4 weekly doses of azoxymethane consistently showed epithelial......Colon explants from adult rats were maintained in culture for over 3 months in our laboratories with good epithelial preservation and cellular differentiation. The light and transmission electron microscopic features of rat colon mucosa during the culture period are described. In all the explants...

Proteomic analysis of cellular response induced by boron neutron capture reaction in human squamous cell carcinoma SAS cells

International Nuclear Information System (INIS)

Sato, Akira; Itoh, Tasuku; Imamichi, Shoji; Kikuhara, Sota; Fujimori, Hiroaki; Hirai, Takahisa; Saito, Soichiro; Sakurai, Yoshinori; Tanaka, Hiroki; Nakamura, Hiroyuki; Suzuki, Minoru

2015-01-01

To understand the mechanism of cell death induced by boron neutron capture reaction (BNCR), we performed proteome analyses of human squamous tumor SAS cells after BNCR. Cells were irradiated with thermal neutron beam at KUR after incubation under boronophenylalanine (BPA)(+) and BPA(−) conditions. BNCR mainly induced typical apoptosis in SAS cells 24 h post-irradiation. Proteomic analysis in SAS cells suggested that proteins functioning in endoplasmic reticulum, DNA repair, and RNA processing showed dynamic changes at early phase after BNCR and could be involved in the regulation of cellular response to BNCR. We found that the BNCR induces fragments of endoplasmic reticulum-localized lymphoid-restricted protein (LRMP). The fragmentation of LRMP was also observed in the rat tumor graft model 20 hours after BNCT treatment carried out at the National Nuclear Center of the Republic of Kazakhstan. These data suggest that dynamic changes of LRMP could be involved during cellular response to BNCR. - Highlights: • BNCR in human squamous carcinoma cells caused typical apoptotic features. • BNCR induced fragments of LRMP, in human squamous carcinoma and rat tumor model. • The fragmentation of LRMP could be involved in cellular response to BNCR.

Cellular mechanisms underlying the laxative effect of flavonol naringenin on rat constipation model.

Directory of Open Access Journals (Sweden)

Zi-Huan Yang

Full Text Available BACKGROUND & AIMS: Symptoms of constipation are extremely common, especially in the elderly. The present study aim to identify an efficacious treatment strategy for constipation by evaluating the secretion-promoting and laxative effect of a herbal compound, naringenin, on intestinal epithelial anion secretion and a rat constipation model, respectively. METHODS/PRINCIPAL FINDINGS: In isolated rat colonic crypts, mucosal addition of naringenin (100 microM elicited a concentration-dependent and sustained increase in the short-circuit current (I(SC, which could be inhibited in Cl- free solution or by bumetanide and DPC (diphenylamine-2-carboxylic acid, but not by DIDS (4, 4'- diisothiocyanatostilbene-2, 2'-disulfonic acid. Naringenin could increase intracellular cAMP content and PKA activity, consisted with that MDL-12330A (N-(Cis-2-phenyl-cyclopentyl azacyclotridecan-2-imine-hydrochloride pretreatment reduced the naringenin-induced I(SC. In addition, significant inhibition of the naringenin-induced I(SC by quinidine indicated that basolateral K+ channels were involved in maintaining this cAMP-dependent Cl- secretion. Naringenin-evoked whole cell current which exhibited a linear I-V relationship and time-and voltage- independent characteristics was inhibited by DPC, indicating that the cAMP activated Cl- conductance most likely CFTR (cystic fibrosis transmembrane conductance regulator was involved. In rat constipation model, administration of naringenin restored the level of fecal output, water content and mucus secretion compared to loperamide-administrated group. CONCLUSIONS: Taken together, our data suggest that naringenin could stimulate Cl- secretion in colonic epithelium via a signaling pathway involving cAMP and PKA, hence provide an osmotic force for subsequent colonic fluid secretion by which the laxative effect observed in the rat constipation model. Naringenin appears to be a novel alternative treatment strategy for constipation.

Resistance to Reperfusion Injury Following Short Term Postischemic Administration of Natural Honey in Globally Ischemic Isolated Rat Heart

Science.gov (United States)

Vaez, Haleh; Samadzadeh, Mehrban; Zahednezhad, Fahimeh; Najafi, Moslem

2012-01-01

Purpose: Results of our previous study revealed that preischemic perfusion of honey before zero flow global ischemia had cardioprotective effects in rat. The present study investigated potential resistance to reperfusion injury following short term postischemic administration of natural honey in globally ischemic isolated rat heart. Methods: Male Wistar rats were divided into five groups (n=10-13). The rat hearts were isolated, mounted on a Langendorff apparatus, allowed to equilibrate for 30 min then subjected to 30 min global ischemia. In the control group, the hearts were reperfused with drug free normal Krebs-Henseleit (K/H) solution before ischemia and during 120 min reperfusion. In the treatment groups, reperfusion was initiated with K/H solution containing different concentration of honey (0.25, 0.5, 1 and 2%) for 15 min and was resumed until the end of 120 min with normal K/H solution. Results: In the control group, VEBs number was 784±199, while in honey concentration of 0.25, 0.5, 1 and 2%, it decreased to 83±23 (Phoney. In the control group, the infarct size was 54.1±7.8%, however; honey (0.25, 0.5, 1 and 2%) markedly lowered the value to 12.4±2.4, 12.7±3.3, 11.3±2.6 and 7.9±1.7 (Phoney in global ischemia showed protective effects against ischemia/reperfusion (I/R) injuries in isolated rat heart. Antioxidant and radical scavenging activity, lipoperoxidation inhibition, reduction of necrotized tissue, presence of rich energy sources, various type of vitamins, minerals and enzymes and formation of NO-contain metabolites may probably involve in those cardioprotective effects. PMID:24312792

Engagement of the Rat Hindlimb Motor Cortex across Natural Locomotor Behaviors

NARCIS (Netherlands)

DiGiovanna, J.; Dominici, N.; Friedli, L.; Rigosa, J.; Duis, S.; Kreider, J.; Beauparlant, J.; van den Brand, R.; Schieppati, M.; Micera, S.; Courtine, G.

2016-01-01

Contrary to cats and primates, cortical contribution to hindlimb locomotor movements is not critical in rats. However, the importance of the motor cortex to regain locomotion after neurological disorders in rats suggests that cortical engagement in hindlimb motor control may depend on the behavioral

Reversible uranyl fluoride nephrotoxicity in the Long Evans rat

International Nuclear Information System (INIS)

Diamond, G.L.; Morrow, P.E.; Panner, B.J.; Gelein, R.M.; Baggs, R.B.

1989-01-01

Severity and duration of renal injury produced by low levels of uranyl fluoride (UO2F2) were examined in the rat. Rats received multiple ip injections of UO2F2 (cumulative dose: 0.66 or 1.32 mg U/kg body wt). Renal injury was characterized histologically by cellular and tubular necrosis of pars recta of proximal tubule (S2 and S3), with less severe cellular injury to thick ascending limb of loop of Henle and collecting tubule. Injury was evident when renal uranium levels were between 0.7 and 1.4 micrograms U/g wet kidney and was most severe when renal uranium burden was between 3.4 and 5.6 micrograms U/g. Repair of injury was rapid, with complete restoration within 35 days after exposure. Associated with injury were abnormalities in renal function, including impaired tubular reabsorption, proteinuria, and enzymuria, which appeared temporally related, to variable degrees, to progression of renal injury. Thus, reversible renal injury occurs in the rat at levels of uranium in kidney below the present Nuclear Regulatory Commission standard of 3 micrograms U/g kidney for renal injury in humans

Cellular-based sea level gauge

Digital Repository Service at National Institute of Oceanography (India)

Desai, R.G.P.; Joseph, A.

treaties with greater transparency. Among the various communication technologies used for real-time transmission of sea-level data are the wired telephone connection, VHF/UHF transceivers, satellite transmit terminals and cellular connectivity. Wired... telephone connections are severely susceptible to loss of connectivity during natural disasters such as storm surges, primarily because of telephone line breakage. Communication via VHF/UHF transceivers is limited by line-of-sight distance between...

Diabetes increases susceptibility of primary cultures of rat proximal tubular cells to chemically induced injury

International Nuclear Information System (INIS)

Zhong Qing; Terlecky, Stanley R.; Lash, Lawrence H.

2009-01-01

Diabetic nephropathy is characterized by increased oxidative stress and mitochondrial dysfunction. In the present study, we prepared primary cultures of proximal tubular (PT) cells from diabetic rats 30 days after an ip injection of streptozotocin and compared their susceptibility to oxidants (tert-butyl hydroperoxide, methyl vinyl ketone) and a mitochondrial toxicant (antimycin A) with that of PT cells isolated from age-matched control rats, to test the hypothesis that PT cells from diabetic rats exhibit more cellular and mitochondrial injury than those from control rats when exposed to these toxicants. PT cells from diabetic rats exhibited higher basal levels of reactive oxygen species (ROS) and higher mitochondrial membrane potential, demonstrating that the PT cells maintain the diabetic phenotype in primary culture. Incubation with either the oxidants or mitochondrial toxicant resulted in greater necrotic and apoptotic cell death, greater evidence of morphological damage, greater increases in ROS, and greater decreases in mitochondrial membrane potential in PT cells from diabetic rats than in those from control rats. Pretreatment with either the antioxidant N-acetyl-L-cysteine or a catalase mimetic provided equivalent protection of PT cells from both diabetic and control rats. Despite the greater susceptibility to oxidative and mitochondrial injury, both cytoplasmic and mitochondrial glutathione concentrations were markedly higher in PT cells from diabetic rats, suggesting an upregulation of antioxidant processes in diabetic kidney. These results support the hypothesis that primary cultures of PT cells from diabetic rats are a valid model in which to study renal cellular function in the diabetic state.

All-trans retinoic acid protects against arsenic-induced uterine toxicity in female Sprague–Dawley rats

International Nuclear Information System (INIS)

Chatterjee, A.; Chatterji, U.

2011-01-01

Background and purpose: Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agent for reversing reproductive disorders. Experimental approach: Rats exposed to arsenic for 28 days were allowed to either recover naturally or were treated simultaneously with ATRA for 28 days or treatment continued up to 56 days. Hematoxylin–eosin double staining was used to evaluate changes in the uterine histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression of the estrogen receptor (ERα), an estrogen responsive gene vascular endothelial growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was assessed by RT-PCR, immunohistochemistry and western blot analysis. Key results: ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and gonadotropin levels in a dose- and time-dependent manner, along with recovery of luminal epithelial cells and endometrial glands. Concomitant up regulation of ERα, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days. Conclusions and implications: Collectively, the results reveal that ATRA reverses arsenic-induced disruption of the circulating levels of gonadotropins and estradiol, and degeneration of luminal epithelial cells and endometrial glands of the rat uterus, indicating resumption of their functional status. Since structural and functional maintenance of the pubertal uterus is under the influence of estradiol, ATRA consequently up regulated the estrogen receptor and resumed cellular proliferation, possibly by an antioxidant therapeutic approach against arsenic toxicity. Highlights: ► Arsenic disrupts the uterine histology and

All-trans retinoic acid protects against arsenic-induced uterine toxicity in female Sprague-Dawley rats

Energy Technology Data Exchange (ETDEWEB)

Chatterjee, A.; Chatterji, U., E-mail: urmichatterji@gmail.com

2011-12-15

Background and purpose: Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agent for reversing reproductive disorders. Experimental approach: Rats exposed to arsenic for 28 days were allowed to either recover naturally or were treated simultaneously with ATRA for 28 days or treatment continued up to 56 days. Hematoxylin-eosin double staining was used to evaluate changes in the uterine histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression of the estrogen receptor (ER{alpha}), an estrogen responsive gene vascular endothelial growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was assessed by RT-PCR, immunohistochemistry and western blot analysis. Key results: ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and gonadotropin levels in a dose- and time-dependent manner, along with recovery of luminal epithelial cells and endometrial glands. Concomitant up regulation of ER{alpha}, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days. Conclusions and implications: Collectively, the results reveal that ATRA reverses arsenic-induced disruption of the circulating levels of gonadotropins and estradiol, and degeneration of luminal epithelial cells and endometrial glands of the rat uterus, indicating resumption of their functional status. Since structural and functional maintenance of the pubertal uterus is under the influence of estradiol, ATRA consequently up regulated the estrogen receptor and resumed cellular proliferation, possibly by an antioxidant therapeutic approach against arsenic toxicity. Highlights: Black-Right-Pointing-Pointer Arsenic

Overview of cellular automaton models for corrosion

International Nuclear Information System (INIS)

Perez-Brokate, Cristian Felipe; De Lamare, Jacques; Dung di Caprio; Feron, Damien; Chausse, Annie

2014-01-01

A review of corrosion process modeling using cellular automata methods is presented. This relatively new and growing approach takes into account the stochastic nature of the phenomena and uses physico-chemical rules to make predictions at a mesoscopic scale. Milestone models are analyzed and perspectives are established. (authors)

Uptake rate of cationic mitochondrial inhibitor MKT-077 determines cellular oxygen consumption change in carcinoma cells.

Directory of Open Access Journals (Sweden)

John L Chunta

Full Text Available OBJECTIVE: Since tumor radiation response is oxygen-dependent, radiosensitivity can be enhanced by increasing tumor oxygenation. Theoretically, inhibiting cellular oxygen consumption is the most efficient way to increase oxygen levels. The cationic, rhodacyanine dye-analog MKT-077 inhibits mitochondrial respiration and could be an effective metabolic inhibitor. However, the relationship between cellular MKT-077 uptake and metabolic inhibition is unknown. We hypothesized that rat and human mammary carcinoma cells would take up MKT-077, causing a decrease in oxygen metabolism related to drug uptake. METHODS: R3230Ac rat breast adenocarcinoma cells were exposed to MKT-077. Cellular MKT-077 concentration was quantified using spectroscopy, and oxygen consumption was measured using polarographic electrodes. MKT-077 uptake kinetics were modeled by accounting for uptake due to both the concentration and potential gradients across the plasma and mitochondrial membranes. These kinetic parameters were used to model the relationship between MKT-077 uptake and metabolic inhibition. MKT-077-induced changes in oxygen consumption were also characterized in MDA-MB231 human breast carcinoma cells. RESULTS: Cells took up MKT-077 with a time constant of ∼1 hr, and modeling showed that over 90% of intracellular MKT-077 was bound or sequestered, likely by the mitochondria. The uptake resulted in a rapid decrease in oxygen consumption, with a time constant of ∼30 minutes. Surprisingly the change in oxygen consumption was proportional to uptake rate, not cellular concentration. MKT-077 proved a potent metabolic inhibitor, with dose-dependent decreases of 45-73% (p = 0.003. CONCLUSIONS: MKT-077 caused an uptake rate-dependent decrease in cellular metabolism, suggesting potential efficacy for increasing tumor oxygen levels and radiosensitivity in vivo.

Cellular consequences of sleep deprivation in the brain.

Science.gov (United States)

Cirelli, Chiara

2006-10-01

Several recent studies have used transcriptomics approaches to characterize the molecular correlates of sleep, waking, and sleep deprivation. This analysis may help in understanding the benefits that sleep brings to the brain at the cellular level. The studies are still limited in number and focus on a few brain regions, but some consistent findings are emerging. Sleep, spontaneous wakefulness, short-term, and long-term sleep deprivation are each associated with the upregulation of hundreds of genes in the cerebral cortex and other brain areas. In fruit flies as well as in mammals, three categories of genes are consistently upregulated during waking and short-term sleep deprivation relative to sleep. They include genes involved in energy metabolism, synaptic potentiation, and the response to cellular stress. In the rat cerebral cortex, transcriptional changes associated with prolonged sleep loss differ significantly from those observed during short-term sleep deprivation. However, it is too early to draw firm conclusions relative to the molecular consequences of sleep deprivation, and more extensive studies using DNA and protein arrays are needed in different species and in different brain regions.

Bioinspired Cellular Structures: Additive Manufacturing and Mechanical Properties

Science.gov (United States)

Stampfl, J.; Pettermann, H. E.; Liska, R.

Biological materials (e.g., wood, trabecular bone, marine skeletons) rely heavily on the use of cellular architecture, which provides several advantages. (1) The resulting structures can bear the variety of "real life" load spectra using a minimum of a given bulk material, featuring engineering lightweight design principles. (2) The inside of the structures is accessible to body fluids which deliver the required nutrients. (3) Furthermore, cellular architectures can grow organically by adding or removing individual struts or by changing the shape of the constituting elements. All these facts make the use of cellular architectures a reasonable choice for nature. Using additive manufacturing technologies (AMT), it is now possible to fabricate such structures for applications in engineering and biomedicine. In this chapter, we present methods that allow the 3D computational analysis of the mechanical properties of cellular structures with open porosity. Various different cellular architectures including disorder are studied. In order to quantify the influence of architecture, the apparent density is always kept constant. Furthermore, it is shown that how new advanced photopolymers can be used to tailor the mechanical and functional properties of the fabricated structures.

Cellular and tissue expression of DAPIT, a phylogenetically conserved peptide

Directory of Open Access Journals (Sweden)

H. Kontro

2012-05-01

Full Text Available DAPIT (Diabetes Associated Protein in Insulin-sensitive Tissues is a small, phylogenetically conserved, 58 amino acid peptide that was previously shown to be down-regulated at mRNA level in insulin-sensitive tissues of type 1 diabetes rats. In this study we characterize a custom made antibody against DAPIT and confirm the mitochondrial presence of DAPIT on cellular level. We also show that DAPIT is localized in lysosomes of HUVEC and HEK 293T cells. In addition, we describe the histological expression of DAPIT in several tissues of rat and man and show that it is highly expressed especially in cells with high aerobic metabolism and epithelial cells related to active transport of nutrients and ions. We propose that DAPIT, in addition to indicated subunit of mitochondrial F-ATPase, is also a subunit of lysosomal V-ATPase suggesting that it is a common component in different proton pumps.

DIFFERENTIAL BINDING OF HUMAN INTERLEUKIN-1 (IL-1) RECEPTOR ANTAGONIST TO NATURAL AND RECOMBINANT SOLUBLE AND CELLULAR IL-1 TYPE-I RECEPTORS

DEFF Research Database (Denmark)

Svenson, Morten; Nedergaard, Susanne; Heegaard, Peter M. H.

1995-01-01

antagonist (IL-1ra). Recombinant soluble human IL-1RI expressed in COS cells (sIL-1RI) consists of the extracellular part of the receptor and binds all three known IL-1 species but preferentially to IL-1ra. We further characterized the sizes and binding of IL-1raBF and sIL-1RI to IL-1ra by polyacrylamide gel...... electrophoresis in the presence of sodium dodecylsulfate, ligand binding interference analyses, N-glycosidase treatment, concanavalin A affinity chromatography, and with the use of monoclonal antibodies (mAb) to human recombinant IL-1ra. We also evaluated the binding of IL-1ra to cellular IL-1RI on MRC5...... binding of both molecules to IL-1ra. Both factors blocked binding of IL-1ra to cellular IL-1RI, as did mAb to IL-1ra, but the sites on IL-1ra which bound to the mAb, and to IL-1raBF and sIL-1RI, differed. We conclude that there are important differences between the natural and recombinant forms of soluble...

Study on the effect of hypoxia on apoptosis of cultured newly born rat cardiac myocytes

International Nuclear Information System (INIS)

Su Weidong; Li Huiqiang; Yao Zhi

2005-01-01

Objective: To investigate the possible hypoxia-mediated cellular apoptosis after ischemic cardiac injury via a model of cultured newly born rat cardiac myocytes. Methods: Cardiac myocytes cultures from newly born rats (1-3d) were examined for apoptosis with HE stain and flow cytometry after cultured 96h and again examined after exposure to hypoxic environment for 16h. Results: Apoptotic changes were evident in the hypoxic culture cells. The HE stain revealed cellular shrinkage, nuclear chromosomal condensation with cytoplasmic eosinophilia. Also, distinct apoptosis peak was observed in the flow cytometry. Conclusion: This experiment proved that hypoxic model of cardiac myocyte culture showed definite apoptosis of the cells. (authors)

Introduction of transplantation tolerance after total lymphoid irradiation: cellular mechanisms

International Nuclear Information System (INIS)

Strober, S.; King, D.P.; Gottlieb, M.; Hoppe, R.T.; Kaplan, H.S.

1981-01-01

High-dose fractionated total lymphoid irradiation (TLI) is a safe, routine regimen used to treat patients with lymphoid malignancies. Although few side effects are associated with the regimen, a profound suppression of cell-mediated immunity is observed for several years after therapy, as judged by both in vivo and in vitro assays. A profound immunosuppression has also been observed in mice and rats given TLI. Recently, we have achieved similar results using TLI in nonmatched bone marrow transplantation in outbred dogs. The experimental work in animals and underlying cellular mechanisms are reviewed here

Cellular distribution and function of ion channels involved in transport processes in rat tracheal epithelium.

Science.gov (United States)

Hahn, Anne; Faulhaber, Johannes; Srisawang, Lalita; Stortz, Andreas; Salomon, Johanna J; Mall, Marcus A; Frings, Stephan; Möhrlen, Frank

2017-06-01

Transport of water and electrolytes in airway epithelia involves chloride-selective ion channels, which are controlled either by cytosolic Ca 2+ or by cAMP The contributions of the two pathways to chloride transport differ among vertebrate species. Because rats are becoming more important as animal model for cystic fibrosis, we have examined how Ca 2+ - dependent and cAMP- dependent Cl - secretion is organized in the rat tracheal epithelium. We examined the expression of the Ca 2+ -gated Cl - channel anoctamin 1 (ANO1), the cystic fibrosis transmembrane conductance regulator (CFTR) Cl - channel, the epithelial Na + channel ENaC, and the water channel aquaporin 5 (AQP5) in rat tracheal epithelium. The contribution of ANO1 channels to nucleotide-stimulated Cl - secretion was determined using the channel blocker Ani9 in short-circuit current recordings obtained from primary cultures of rat tracheal epithelial cells in Ussing chambers. We found that ANO1, CFTR and AQP5 proteins were expressed in nonciliated cells of the tracheal epithelium, whereas ENaC was expressed in ciliated cells. Among nonciliated cells, ANO1 occurred together with CFTR and Muc5b and, in addition, in a different cell type without CFTR and Muc5b. Bioelectrical studies with the ANO1-blocker Ani9 indicated that ANO1 mediated the secretory response to the nucleotide uridine-5'-triphosphate. Our data demonstrate that, in rat tracheal epithelium, Cl - secretion and Na + absorption are routed through different cell types, and that ANO1 channels form the molecular basis of Ca 2+ -dependent Cl - secretion in this tissue. These characteristic features of Cl - -dependent secretion reveal similarities and distinct differences to secretory processes in human airways. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Simulation of root forms using cellular automata model

International Nuclear Information System (INIS)

Winarno, Nanang; Prima, Eka Cahya; Afifah, Ratih Mega Ayu

2016-01-01

This research aims to produce a simulation program for root forms using cellular automata model. Stephen Wolfram in his book entitled “A New Kind of Science” discusses the formation rules based on the statistical analysis. In accordance with Stephen Wolfram’s investigation, the research will develop a basic idea of computer program using Delphi 7 programming language. To best of our knowledge, there is no previous research developing a simulation describing root forms using the cellular automata model compared to the natural root form with the presence of stone addition as the disturbance. The result shows that (1) the simulation used four rules comparing results of the program towards the natural photographs and each rule had shown different root forms; (2) the stone disturbances prevent the root growth and the multiplication of root forms had been successfully modeled. Therefore, this research had added some stones, which have size of 120 cells placed randomly in the soil. Like in nature, stones cannot be penetrated by plant roots. The result showed that it is very likely to further develop the program of simulating root forms by 50 variations

Simulation of root forms using cellular automata model

Energy Technology Data Exchange (ETDEWEB)

Winarno, Nanang, E-mail: nanang-winarno@upi.edu; Prima, Eka Cahya [International Program on Science Education, Universitas Pendidikan Indonesia, Jl. Dr. Setiabudi no 229, Bandung40154 (Indonesia); Afifah, Ratih Mega Ayu [Department of Physics Education, Post Graduate School, Universitas Pendidikan Indonesia, Jl. Dr. Setiabudi no 229, Bandung40154 (Indonesia)

2016-02-08

This research aims to produce a simulation program for root forms using cellular automata model. Stephen Wolfram in his book entitled “A New Kind of Science” discusses the formation rules based on the statistical analysis. In accordance with Stephen Wolfram’s investigation, the research will develop a basic idea of computer program using Delphi 7 programming language. To best of our knowledge, there is no previous research developing a simulation describing root forms using the cellular automata model compared to the natural root form with the presence of stone addition as the disturbance. The result shows that (1) the simulation used four rules comparing results of the program towards the natural photographs and each rule had shown different root forms; (2) the stone disturbances prevent the root growth and the multiplication of root forms had been successfully modeled. Therefore, this research had added some stones, which have size of 120 cells placed randomly in the soil. Like in nature, stones cannot be penetrated by plant roots. The result showed that it is very likely to further develop the program of simulating root forms by 50 variations.

Lempel-Ziv complexity analysis of one dimensional cellular automata.

Science.gov (United States)

Estevez-Rams, E; Lora-Serrano, R; Nunes, C A J; Aragón-Fernández, B

2015-12-01

Lempel-Ziv complexity measure has been used to estimate the entropy density of a string. It is defined as the number of factors in a production factorization of a string. In this contribution, we show that its use can be extended, by using the normalized information distance, to study the spatiotemporal evolution of random initial configurations under cellular automata rules. In particular, the transfer information from time consecutive configurations is studied, as well as the sensitivity to perturbed initial conditions. The behavior of the cellular automata rules can be grouped in different classes, but no single grouping captures the whole nature of the involved rules. The analysis carried out is particularly appropriate for studying the computational processing capabilities of cellular automata rules.

IGF-I enhances cellular senescence via the reactive oxygen species-p53 pathway

Energy Technology Data Exchange (ETDEWEB)

Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Takahashi, Yutaka, E-mail: takahash@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)

2012-08-24

Highlights: Black-Right-Pointing-Pointer Cellular senescence plays an important role in tumorigenesis and aging process. Black-Right-Pointing-Pointer We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. Black-Right-Pointing-Pointer IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. Black-Right-Pointing-Pointer These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated {beta}-galactosidase (SA-{beta}-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, {gamma}H2AX, the increased levels of p53 and p21 proteins, and activated SA-{beta}-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-{beta}-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.

IGF-I enhances cellular senescence via the reactive oxygen species–p53 pathway

International Nuclear Information System (INIS)

Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro; Takahashi, Yutaka

2012-01-01

Highlights: ► Cellular senescence plays an important role in tumorigenesis and aging process. ► We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. ► IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. ► These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated β-galactosidase (SA-β-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, γH2AX, the increased levels of p53 and p21 proteins, and activated SA-β-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-β-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.

Noninvasive Evaluation of Cellular Proliferative Activity in Brain Neurogenic Regions in Rats under Depression and Treatment by Enhanced [18F]FLT-PET Imaging.

Science.gov (United States)

Tamura, Yasuhisa; Takahashi, Kayo; Takata, Kumi; Eguchi, Asami; Yamato, Masanori; Kume, Satoshi; Nakano, Masayuki; Watanabe, Yasuyoshi; Kataoka, Yosky

2016-08-03

Neural stem cells in two neurogenic regions, the subventricular zone and the subgranular zone (SGZ) of the hippocampal dentate gyrus, can divide and produce new neurons throughout life. Hippocampal neurogenesis is related to emotions, including depression/anxiety, and the therapeutic effects of antidepressants, as well as learning and memory. The establishment of in vivo imaging for proliferative activity of neural stem cells in the SGZ might be used to diagnose depression and to monitor the therapeutic efficacy of antidepressants. Positron emission tomography (PET) imaging with 3'-deoxy-3'-[(18)F]fluoro-l-thymidine ([(18)F]FLT) has been studied to allow visualization of proliferative activity in two neurogenic regions of adult mammals; however, the PET imaging has not been widely used because of lower accumulation of [(18)F]FLT, which does not allow quantitative assessment of the decline in cellular proliferative activity in the SGZ under the condition of depression. We report the establishment of an enhanced PET imaging method with [(18)F]FLT combined with probenecid, an inhibitor of drug transporters at the blood-brain barrier, which can allow the quantitative visualization of neurogenic activity in rats. Enhanced PET imaging allowed us to evaluate reduced cell proliferation in the SGZ of rats with corticosterone-induced depression, and further the recovery of proliferative activity in rats under treatment with antidepressants. This enhanced [(18)F]FLT-PET imaging technique with probenecid can be used to assess the dynamic alteration of neurogenic activity in the adult mammalian brain and may also provide a means for objective diagnosis of depression and monitoring of the therapeutic effect of antidepressant treatment. Adult hippocampal neurogenesis may play a role in major depression and antidepressant therapy. Establishment of in vivo imaging for hippocampal neurogenic activity may be useful to diagnose depression and monitor the therapeutic efficacy of

Trimethyltin (TMT) neurotoxicity in organotypic rat hippocampal slice cultures

DEFF Research Database (Denmark)

Noraberg, J; Gramsbergen, J B; Fonnum, F

1998-01-01

) propidium iodide (PI) uptake, (b) lactate dehydrogenase (LDH) efflux into the culture medium, (c) cellular cobalt uptake as an index of calcium influx, (d) ordinary Nissl cell staining, and (e) immunohistochemical staining for microtubule-associated protein 2 (MAP-2). Cellular degeneration as assessed...... to in vivo cell stain observations of rats acutely exposed to TMT. The mean PI uptake of the cultures and the LDH efflux into the medium were highly correlated. The combined results obtained by the different markers indicate that the hippocampal slice culture method is a feasible model for further studies...

effect of electromagnetic fields from cellular phone base stations on some physiological and biophysical properties of rats

International Nuclear Information System (INIS)

Mahmoud, A.H.

2006-01-01

the hazards of exposure to EMFs are observed on different tissues, the mechanistic by which EMFs can produce such effect still need to be delineated. the present study aims to monitor the possibility of modulation in the different physiological and biophysical properties of the organs after exposure to microwave produced from mobile phone base station at frequency of 900 MHz. one hundred and ten pregnant rats were exposed for periods of 5 and 12 week's at distances of 8,15 and 25 meter from the station antenna (0.01,0.05 and 0.036 MW/cm 2 ) the groups exposed for 5 weeks classified into two halves, one half was used for direct effect studies and the other was used for delayed effects studies (45 days post irradiation). haematological investigations demonstrated non significant changes in (RBC's), (Hb),(PCV) and (MCV)of exposed and delayed rats for 5,12 weeks. the young's of exposed rats show non considerable increase in RBC's, Hb and PCV. significant increases were observed in serum total protein , albumin and globulin levels in 5 and 12 weeks exposed rats and more significant increase in delayed rats

Assessment of selenium bioavailability from naturally produced high-selenium soy foods in selenium-deficient rats.

Science.gov (United States)

Yan, Lin; Reeves, Philip G; Johnson, LuAnn K

2010-10-01

We assessed the bioavailability of selenium (Se) from a protein isolate and tofu (bean curd) prepared from naturally produced high-Se soybeans. The Se concentrations of the soybeans, the protein isolate and tofu were 5.2±0.2, 11.4±0.1 and 7.4±0.1mg/kg, respectively. Male weanling Sprague-Dawley rats were depleted of Se by feeding them a 30% Torula yeast-based diet (4.1μg Se/kg) for 56 days, and then they were replenished with Se for an additional 50 days by feeding them the same diet containing 14, 24 or 30 μg Se/kg from the protein isolate or 13, 23 or 31 μg Se/kg from tofu, respectively. l-Selenomethionine (SeMet) was used as a reference. Selenium bioavailability was determined on the basis of the restoration of Se-dependent enzyme activities and tissue Se concentrations in Se-depleted rats, comparing those responses for the protein isolate and tofu to those for SeMet by using a slope-ratio method. Dietary supplementation with the protein isolate or tofu resulted in linear or log-linear, dose-dependent increases in glutathione peroxidase activities in blood and liver and in thioredoxin reductase activity in liver. Furthermore, supplementation with the protein isolate or tofu resulted in linear or log-linear, dose-dependent increases in the Se concentrations of plasma, liver, muscle and kidneys. These results indicated an overall bioavailability of approximately 101% for Se from the protein isolate and 94% from tofu, relative to SeMet. We conclude that Se from naturally produced high-Se soybeans is highly bioavailable in this model and that high-Se soybeans may be a good dietary source of Se. Published by Elsevier GmbH.

Comparison of Mucosal, Subcutaneous and Intraperitoneal Routes of Rat Leptospira Infection

Science.gov (United States)

Zilber, Anne-Laure; Belli, Patrick; Grezel, Delphine; Artois, Marc; Kodjo, Angeli; Djelouadji, Zoheira

2016-01-01

Leptospirosis is a zoonosis found worldwide that is caused by a spirochete. The main reservoirs of Leptospira, which presents an asymptomatic infection, are wild rodents, including the brown rat (Rattus norvegicus). Experimental studies of the mechanisms of its renal colonization in rats have previously used an intraperitoneal inoculation route. However, knowledge of rat-rat transmission requires the use of a natural route of inoculation, such as a mucosal or subcutaneous route. We investigated for the first time the effects of subcutaneous and mucosal inoculation routes compared to the reference intraperitoneal route during Leptospira infection in adult rats. Infection characteristics were studied using Leptospira renal isolation, serology, and molecular and histological analyses. Leptospira infection was asymptomatic using each inoculation route, and caused similar antibody production regardless of renal colonization. The observed renal colonization rates were 8 out of 8 rats, 5 out of 8 rats and 1 out of 8 rats for the intraperitoneal, mucosal and subcutaneous inoculation routes, respectively. Thus, among the natural infection routes studied, mucosal inoculation was more efficient for renal colonization associated with urinary excretion than the subcutaneous route and induced a slower-progressing infection than the intraperitoneal route. These results can facilitate understanding of the infection modalities in rats, unlike the epidemiological studies conducted in wild rats. Future studies of other natural inoculation routes in rat models will increase our knowledge of rat-rat disease transmission and allow the investigation of infection kinetics. PMID:27031867

In vitro chemical and cellular tests applied to uranium trioxide with different hydration states

International Nuclear Information System (INIS)

Ansoborlo, E.; Chalabreysse, J.; Henge-Napoli, M.H.; Pujol, E.

1992-01-01

A simple and rapid in vitro chemical solubility test applicable to industrial uranium trioxide (UO 3 ) was developed together with two in vitro cellular tests using rat alveolar macrophages maintained either in gas phase or in alginate beads at 37 degrees C. Industrial UO 3 was characterized by particle size, X-ray, and IR spectra, and chemical transformation (e.g., aging and hydration of the dust) was also studied. Solvents used for the in vitro chemical solubility study included carbonates, citrates, phosphates, water, Eagle's basal medium, and Gamble's solution (simulated lung fluid), alone, with oxygen, or with superoxide ions. Results, expressed in terms of the half-time of dissolution, according to International Commission on Radiological Protection (ICRP) classification (D,W,Y), varied for different hydration states of UO 3 , showing a lower solubility of hydrated UO 3 in solvents compared to basic UO 3 or UO 3 heated at 450 degrees C. Two in vitro cellular tests on cultured rat alveolar macrophages (cells maintained in gas phase and cells immobilized in alginate beads) were used on the same UO 3 samples and generally showed a lower solution transfer rate in the presence of macrophages than in the culture medium alone. The results of in vitro chemical and cellular tests were compared, with four main conclusions; a good reproducibility of the three tests in Eagle's basal medium of the effect of hydration state on solubility, the classification of UO 3 in terms of ICRP solubility criteria, and the ability of macrophoges to decrease uranium solubility in medium. 16 refs., 3 figs., 4 tabs

Dependence of anaphylactic histamine release from rat mast cells on cellular energy metabolism

DEFF Research Database (Denmark)

Johansen, Torben

1981-01-01

The relation between anaphylactic histamine release and the adenosine triphosphate (ATP) content of the mast cells was studied. The cells were incubated with glycolytic (2-deoxyglucose) and respiratory inhibitors (antimycin A and oligomycin) in order to decrease the ATP content of the cells prior...... to initiation of the release process by the antigen-antibody reaction. The secretory capacity of mast cells was less related to the cellular level of ATP at the time of activation of the release process by the antigen-antibody reaction than to the rate of cellular energy supply. Furthermore, mast cells were...... pretreated with 2-deoxyglucose. The release of histamine from these cells was reduced when respiratory inhibitors were added to the cell suspension 5 to 20 sec after exposure of the cells to antigen. This may indicate that the secretory process requires energy, and it seems necessary that energy should...

Evaluation of humoral and cellular immune responses to a DNA vaccine encoding chicken type II collagen for rheumatoid arthritis in normal rats.

Science.gov (United States)

Xiao, Zhao; Juan, Long; Song, Yun; Zhijian, Zhang; Jing, Jin; Kun, Yu; Yuna, Hao; Dongfa, Dai; Lili, Ding; Liuxin, Tan; Fei, Liang; Nan, Liu; Fang, Yuan; Yuying, Sun; Yongzhi, Xi

2015-01-01

A major challenge in the development of effective therapies for rheumatoid arthritis (RA) is finding a method for the specific inhibition of the inflammatory disease processes without the induction of generalized immunosuppression. Of note, the development of therapeutic DNA vaccines and boosters that may restore immunological tolerance remains a high priority. pcDNA-CCOL2A1 is a therapeutic DNA vaccine encoding chicken type II collagen(CCII). This vaccine was developed by our laboratory and has been shown to exhibit efficacy comparable to that of the current "gold standard" treatment, methotrexate (MTX). Here, we used enzyme-linked immunosorbent assays with anti-CII IgG antibodies, quantified the expression levels of Th1, Th2, and Th3 cytokines, and performed flow cytometric analyses of different T-cell subsets, including Th1, Th2, Th17, Tc, Ts, Treg, and CD4(+)CD29(+)T cells to systemically evaluate humoral and cellular immune responses to pcDNA-CCOL2A1 vaccine in normal rats. Similar to our observations at maximum dosage of 3 mg/kg, vaccination of normal rats with 300 μg/kg pcDNA-CCOL2A1 vaccine did not induce the production of anti-CII IgG. Furthermore, no significant changes were observed in the expression levels of pro-inflammatory cytokines interleukin (IL)-1α, IL-5, IL-6, IL-12(IL-23p40), monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, regulated on activation in normal T-cell expressed and secreted (RANTES), receptor activator for nuclear factor-κB ligand (RANKL), and granulocyte colony-stimulating factor (G-CSF) or anti-inflammatory cytokines IL-4 and IL-10 in vaccinated normal rats relative to that in controls(P > 0.05). However, transforming growth factor (TGF)-β levels were significantly increased on days 10 and 14, while interferon (IFN)-γ and tumor necrosis factor (TNF)-α levels were significantly decreased on days 28 and 35 after vaccination(P 0.05), with the exception of Treg cells, which were significantly

A Naturally Transmitted Epitheliotropic Polyomavirus Pathogenic in Immunodeficient Rats: Characterization, Transmission, and Preliminary Epidemiologic Studies.

Science.gov (United States)

Besch-Williford, Cynthia; Pesavento, Patricia; Hamilton, Shari; Bauer, Beth; Kapusinszky, Beatrix; Phan, Tung; Delwart, Eric; Livingston, Robert; Cushing, Susan; Watanabe, Rie; Levin, Stephen; Berger, Diana; Myles, Matthew

2017-07-01

We report the identification, pathogenesis, and transmission of a novel polyomavirus in severe combined immunodeficient F344 rats with null Prkdc and interleukin 2 receptor gamma genes. Infected rats experienced weight loss, decreased fecundity, and mortality. Large basophilic intranuclear inclusions were observed in epithelium of the respiratory tract, salivary and lacrimal glands, uterus, and prostate gland. Unbiased viral metagenomic sequencing of lesioned tissues identified a novel polyomavirus, provisionally named Rattus norvegicus polyomavirus 2 (RatPyV2), which clustered with Washington University (WU) polyomavirus in the Wuki clade of the Betapolyomavirus genus. In situ hybridization analyses and quantitative polymerase chain reaction (PCR) results demonstrated viral nucleic acids in epithelium of respiratory, glandular, and reproductive tissues. Polyomaviral disease was reproduced in Foxn1 rnu nude rats cohoused with infected rats or experimentally inoculated with virus. After development of RatPyV2-specific diagnostic assays, a survey of immune-competent rats from North American research institutions revealed detection of RatPyV2 in 7 of 1,000 fecal samples by PCR and anti-RatPyV2 antibodies in 480 of 1,500 serum samples. These findings suggest widespread infection in laboratory rat populations, which may have profound implications for established models of respiratory injury. Additionally, RatPyV2 infection studies may provide an important system to investigate the pathogenesis of WU polyomavirus diseases of man.

Cellular Scale Anisotropic Topography Guides Schwann Cell Motility

Science.gov (United States)

Mitchel, Jennifer A.; Hoffman-Kim, Diane

2011-01-01

Directed migration of Schwann cells (SC) is critical for development and repair of the peripheral nervous system. Understanding aspects of motility specific to SC, along with SC response to engineered biomaterials, may inform strategies to enhance nerve regeneration. Rat SC were cultured on laminin-coated microgrooved poly(dimethyl siloxane) platforms that were flat or presented repeating cellular scale anisotropic topographical cues, 30 or 60 µm in width, and observed with timelapse microscopy. SC motion was directed parallel to the long axis of the topography on both the groove floor and the plateau, with accompanying differences in velocity and directional persistence in comparison to SC motion on flat substrates. In addition, feature dimension affected SC morphology, alignment, and directional persistence. Plateaus and groove floors presented distinct cues which promoted differential motility and variable interaction with the topographical features. SC on the plateau surfaces tended to have persistent interactions with the edge topography, while SC on the groove floors tended to have infrequent contact with the corners and walls. Our observations suggest the capacity of SC to be guided without continuous contact with a topographical cue. SC exhibited a range of distinct motile morphologies, characterized by their symmetry and number of extensions. Across all conditions, SC with a single extension traveled significantly faster than cells with more or no extensions. We conclude that SC motility is complex, where persistent motion requires cellular asymmetry, and that anisotropic topography with cellular scale features can direct SC motility. PMID:21949703

Antioxidant potential properties of mushroom extract (Agaricus bisporus) against aluminum-induced neurotoxicity in rat brain.

Science.gov (United States)

Waly, Mostafa I; Guizani, Nejib

2014-09-01

Aluminum (Al) is an environmental toxin that induces oxidative stress in neuronal cells. Mushroom cultivar extract (MCE) acted as a potent antioxidant agent and protects against cellular oxidative stress in human cultured neuronal cells. This study aimed to investigate the neuroprotective effect of MCE against Al-induced neurotoxicity in rat brain. Forty Sprague-Dawley rats were divided into 4 groups (10 rats per group), control group, MCE-fed group, Al-administered group and MCE/Al-treated group. Animals were continuously fed ad-libitum their specific diets for 4 weeks. At the end of the experiment, all rats were sacrificed and the brain tissues were homogenized and examined for biochemical measurements of neurocellular oxidative stress indices [glutathione (GSH), Total Antioxidant Capacity (TAC), antioxidant enzymes and oxidized dichlorofluorescein (DCF)]. Al-administration caused inhibition of antioxidant enzymes and a significant decrease in GSH and TAC levels, meanwhile it positively increased cellular oxidized DCF level, as well as Al concentration in brain tissues. Feeding animals with MCE had completely offset the Al-induced oxidative stress and significantly restrict the Al accumulation in brain tissues of Al-administered rats. The results obtained suggest that MCE acted as a potent dietary antioxidant and protects against Al-mediated neurotoxicity, by abrogating neuronal oxidative stress.

Evaluation of Effect of a New Natural Radioprotectors in Nano Particles Form From Zinc Coumarate and Zinc Caffeiate on Rats Exposed to Gamma Rays

International Nuclear Information System (INIS)

El -Metwaly, M.A.A.

2012-01-01

Natural Radioprotectors as para -coumaric acids and caffeic acids are natural compounds in nano form zinc coumarate nano particles (Zn Coum.NPs) and zinc caffeiate nano particles (Zn Caf.NPs) have been shown to confer various biological effects, anticancer, enhance immune system and antioxidant properties. The present study was undertaken to evaluate the radio protective and possess ability of Zn Coum.NPs and Zn Caf.NPs against whole body -irradiation with a dose of 3 Gy, 4 times, every week up to 12 Gy. Zn Coum.NPs and Zn Caf.NPs were given to rats by intraperitoneal injection at a concentration of 5 mg/kg and 15 mg/kg body weight respectively, for 7 successive days, post irradiation for (Zn Coum.NPs + Zn Caf.NPs) and [(Zn Coum.NPs + Zn Caf.NPs) + Irradiated] groups and for 30 successive days for (Zn Coum.NPs + Zn Caf.NPs), [(Zn Coum.NPs + Zn Caf.NPs) + Irradiated] and [Irradiated + (Zn Coum.NPs + Zn Caf.NPs)] groups. The results indicated that gamma- irradiated group caused a significant decrease of body weight, antioxidants levels and (ThCD 4 and TcCD 8 ), and disorder in morphological, hematological, lipid profile and cell cycle as well as liver and kidney dysfunction, and increased in lipid peroxidation, nitric oxide, free radicals and DNA fragment, and histological changes in the hepatic tissues as vacuoles degeneration and necrosis of a great number of hepatocytes together with several hemorrhage and interstitial oedema. Whilst, the treatment with Zn Coum.NPs + Zn Caf.NPs pre or post-exposure to gamma-ray protected cellular system from harmful effects of gamma-radiation. The results clearly indicated that Zn Coum.NPs and Zn Caf.NPs possess protective effect to protect bimolecules from radiation induced damage and ability to scavenge free radicals might be playing an important role in its radio protective manifestation especially in cancer treatment with radiotherapy

Perturbations of dynamics of homogeneous two-dimensional cellular automata

Energy Technology Data Exchange (ETDEWEB)

Makowiec, D [Gdansk Univ. (Poland)

1993-04-01

The probabilistic approach provides a useful tool for understanding the nature of dynamics of cellular automata. It allows not only clarification of different results of the evolution but also gives explanation to the physical meaning of the rules. (author). 11 refs, 4 figs.

HISTOLOGICAL STUDIES OF THE EFFECTS OF MONOSODIUM GLUTAMATE ON THE INFERIOR COLLICULUS OF ADULT WISTAR RATS.

Directory of Open Access Journals (Sweden)

A.O. Eweka.

2008-01-01

Full Text Available Histological effects of Monosodium glutamate (MSG commonly used as food additive on the inferior colliculus (IC of adult Wistar rats were carefully studied. The rats of both sexes (n=24, average weight of 185g were randomly assigned into two treatments (n=16 and control (n=8 groups. The rats in the treatment groups received 3g and 6g of MSG thoroughly mixed with their feeds for fourteen days, while the control rats received equal amounts of feeds without MSG added. The rats were fed with growers' mash purchased from Edo Feeds and Flour Mill Ltd, Ewu, Edo State and were given water liberally. The rats were sacrificed on day fifteen of the experiment. The inferior colliculus was carefully dissected out and quickly fixed in 10% formal saline for routine histological study after H&E method.The histological findings after H&E methods indicated that the treated sections of the inferior colliculus showed some cellular degenerative changes, cellular hypertrophy, and autophagic vacuoles with some intercellular vacuolations appearing in the stroma, and some degree of neuronal hypertrophy when compared to the control sections.These findings indicate that MSG consumption may have a deleterious effect on the neurons of the inferior colliculus (IC. MSG may probably have adverse effects on the auditory sensibilities by its deleterious effects on the nerve cells of the IC of adult Wistar rats. It is recommended that further studies aimed at corroborating these observations be carried out.

HISTOLOGICAL EFFECTS OF CHRONIC CONSUMPTION OF NUTMEG ON THE LATERAL GENICULATE BODY OF ADULT WISTAR RATS.

Directory of Open Access Journals (Sweden)

J.O. Adjene

2010-01-01

Full Text Available The effects of chronic consumption of nutmeg commonly used as a spice in various dishes, as components of teas and soft drinks or mixed in milk and alcohol on the lateral geniculate body of adult wistar rats was studied.The rats of both sexes, with average weight of 200g were randomly assigned into treatment and control groups. The rats in the treatment group (n=8 received 2g of nutmeg thoroughly mixed with the feeds on a daily basis for thirty-two days. The control group (n=8 received equal amount of feeds daily without nutmeg added for thirty-two days. The growers mash feeds was obtained from Edo Feeds and Flour Mill Limited, Ewu, Edo State, Nigeria and the rats were given water liberally. The rats were sacrificed on the thirty-three day of the experiment. The lateral geniculate body was carefully dissected out and quickly fixed in 10% formal saline for histological study.The findings indicate that rats in the treated group showed some cellular degenerative changes like sparse cellular population, pyknotic nuclei with some microcystic changes, edema and vacuolations in the stroma of the treated lateral geniculate body as compared to that of the control group.Chronic consumption of nutmeg may therefore have an adverse effect on the visual sensibilities by affecting the microanatomy of the lateral geniculate body of adult wistar rats. It is recommended for further studies aimed at corroborating these observations.

Quantitative changes in the cellularity of the rat subependymal plate after X-irradiation

Energy Technology Data Exchange (ETDEWEB)

Hubbard, B; Hopewell, J W [Oxford Univ. (UK). Churchill Hospital Research Institute

1980-07-01

The brains of young adult rats were irradiated with a single dose of 8 Gy (800 rad) of 250 kVp X-rays. Within 2 weeks of treatment the cell population of the subependymal plate was reduced by 30%. During this period the cell cycle time remained unchanged but the labelling index was reduced. The cell population subsequently returned to normal after 39-52 weeks. Damage and subsequent recovery of the plate was due mainly to changes in the number of cells with small dark nuclei. Cells with small and large light nuclei were little affected. A model for the production and differentiation of cells in the subependymal region is proposed on the basis of age-related changes in the total number and proportions of the various cell types in the subependymal plate of normal rats. This is discussed both in terms of the radiation response of cells in the plate and the manifestation of delayed white matter necrosis after higher doses.

Resveratrol and Red Wine Function as Antioxidants in the Nervous System without Cellular Proliferative Effects during Experimental Diabetes

Science.gov (United States)

Venturini, Carina Duarte; Merlo, Suélen; Souto, André Arigony; Fernandes, Marilda da Cruz; Gomez, Rosane; Rhoden, Claudia Ramos

2010-01-01

Chronic hyperglycemia increases oxidative stress status and has been associated with neurological complications in diabetic individuals. This study compared the antioxidant properties of red wine or resveratrol in different brain areas of diabetic and non-diabetic rats, and investigated the effect of them on hippocampal cell proliferation in hippocampal dentate gyrus of diabetic rats. Streptozotocin-induced diabetic and control rats were treated with red wine (4 mL/kg), resveratrol (20 mg/kg) or saline, by oral gavage, for 21 days. Lipid peroxidation (TBARS), catalase and superoxide dismutase were measured to evaluate the oxidative stress and the BrdU-positive cells were assessed to measure changes in cellular proliferation. In diabetic animals, resveratrol showed antioxidant property in the hippocampus and in the striatum, while red wine had an antioxidant effect only in the hippocampus. Neither red wine nor resveratrol reversed the lower hippocampal cell proliferation in diabetic rats. Daily doses of red wine or resveratrol have an antioxidant effect in rats depending on the brain area and the glycemic status. PMID:21307644

Resveratrol and Red Wine Function as Antioxidants in the Nervous System without Cellular Proliferative Effects during Experimental Diabetes

Directory of Open Access Journals (Sweden)

Carina Duarte Venturini

2010-01-01

Full Text Available Chronic hyperglycemia increases oxidative stress status and has been associated with neurological complications in diabetic individuals. This study compared the antioxidant properties of red wine or resveratrol in different brain areas of diabetic and non-diabetic rats, and investigated the effect of them on hippocampal cell proliferation in hippocampal dentate gyrus of diabetic rats. Streptozotocin-induced diabetic and control rats were treated with red wine (4 mL/kg, resveratrol (20 mg/kg or saline, by oral gavage, for 21 days. Lipid peroxidation (TBARS, catalase and superoxide dismutase were measured to evaluate the oxidative stress and the BrdU-positive cells were assessed to measure changes in cellular proliferation. In diabetic animals, resveratrol showed antioxidant property in the hippocampus and in the striatum, while red wine had an antioxidant effect only in the hippocampus. Neither red wine nor resveratrol reversed the lower hippocampal cell proliferation in diabetic rats. Daily doses of red wine or resveratrol have an antioxidant effect in rats depending on the brain area and the glycemic status.

Natural history of extensive diaphragmatic injury on the right side: experimental study in rats

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Jorge Henrique Rivaben

2014-08-01

Full Text Available OBJECTIVE: To evaluate the natural healing of the rat diaphragm that suffered an extensive right penetrating injury.METHODS: Animals were submitted to an extensive penetrating injury in right diaphragm. The sample consisted of 40 animals. The variables studied were initial weight, weight 21 days after surgery; healing of the diaphragm, non-healing of the diaphragm, and herniated abdominal contents into the chest.RESULTS: Ten animals were used as controls for weight and 30 animals were operated. Two animals died during the experiment, so 28 animals formed the operated group; healing of the diaphragm occurred in 15 animals (54%, 11 other animals showed diaphragmatic hernia (39% and in two we observed only diaphragmatic injury without hernia (7%. Among the herniated organs, the liver was found in 100% of animals, followed by the omentum in 77%, small bowel in 62%, colon in 46%, stomach in 31% and spleen in 15%. The control group and the diaphragmatic healing subgroup showed increased weight since the beginning of the study and the 21 days after surgery (p <0.001. The unhealed group showed no change in weight (p = 0.228.CONCLUSION: there is a predominance of spontaneous healing in the right diaphragm; animals in which there was no healing of the diaphragm did not gain weight, and the liver was the organ present in 100% the diaphragmatic surface in all rats with healed diaphragm or not.

[Variability of hemodynamic parameters and resistance to stress damage in rats of different strains].

Science.gov (United States)

Belkina, L M; Popkova, E V; Lakomkin, V L; Kirillina, T N; Zhukova, A G; Sazontova, T G; Usacheva, M A; Kapel'ko, V I

2006-02-01

Total power of heart rate variability and baroreflex sensitivity were significantly smaller in the August rats than in the Wistar rats, but adrenal and plasma catecholamine contents were considerably higher in the former ones. 1 hour after stress (30 min in cold water), plasma catecholamine was increased 2-fold in Wistar rats, while in August rats the adrenaline concentration increased only by 58% and the were no changes in noradrenaline content. At the same time, activation of catecholamine metabolism in the adrenal glands was similar in both groups. The oxidative stress induced by hydrogen peroxide depressed the contractile function of isolated heart in the August rats to a smaller extent as compared to Wistar rats, control ones and after the cold-water stress. This effect correlated with more pronounced stability ofantioxidant enzymes in the August rats. It seems that the greater resistance to stress damage in the August rats is mediated by enhanced power of defense mechanisms both at systemic and cellular levels.

Cellular Immunity State of Protein-deficient Rats with the Toxic Liver Injury

Directory of Open Access Journals (Sweden)

O.N. Voloshchuk

2017-05-01

Full Text Available Studies on the role of immunity mechanisms in the emergence and maintenance of inflammatory and destructive processes in the liver under toxic hepatitis and nutrient deficiency are topical. The aim of research – to study the quantitative content and functional activity of leukocytes under the conditions of acetaminophen-induced hepatitis on the background of nutritional protein deficiency. The most pronounced changes in cell-mediated immunity are observed in protein-deficient animals with toxic hepatitis. The pronounced defects of both specific and non-specific cellular immunity were manifested by the leukocytosis, increase number of segmented neutrophils in blood serum against decrease their phagocytic index and phagocytic number, reduction of total lymphocyte number, and simultaneously lowering of T- and B-lymphocytes was established under the conditions of acetaminophen-induced hepatotoxicity on the background of protein deficiency. Installed changes indicate the defective formation of functional immunity state which can manifest by decrease the body’s ability to carry out the reaction of cellular and humoral immunity. Research results may be used for the rationale of therapeutic approaches to the elimination and correction of the consequences of immunological status disturbances under the conditions of acetaminophen-induced hepatitis, aggravated by the alimentary protein deprivation.

Treatment of Partial Thickness Burns with a Novel Extracellular Matrix in Rats (Rattus norvegicus)

Science.gov (United States)

2016-12-20

partial thickness burn was produced using a brass scale weight. Groups of 10 rats were randomly assigned to the various treatments . Jackets made from...Objectives: The objective this study was to examine the cellular and immune responses to various extracellular matrices (ECM) in a rat burn model...significant difference between treatments in terms of mean wound area (p = 0.77). Histologic examination revealed that all of the grafts were infected, with

Motivational responses to natural and drug rewards in rats with neonatal ventral hippocampal lesions: an animal model of dual diagnosis schizophrenia.

Science.gov (United States)

Chambers, R Andrew; Self, David W

2002-12-01

The high prevalence of substance use disorders in schizophrenia relative to the general population and other psychiatric diagnoses could result from developmental neuropathology in hippocampal and cortical structures that underlie schizophrenia. In this study, we tested the effects of neonatal ventral hippocampal lesions on instrumental behavior reinforced by sucrose pellets and intravenous cocaine injections. Lesioned rats acquired sucrose self-administration faster than sham-lesioned rats, but rates of extinction were not altered. Lesioned rats also responded at higher rates during acquisition of cocaine self-administration, and tended to acquire self-administration faster. Higher response rates reflected perseveration of responding during the post-injection "time-out" periods, and a greater incidence of binge-like cocaine intake, which persisted even after cocaine self-administration stabilized. In contrast to sucrose, extinction from cocaine self-administration was prolonged in lesioned rats, and reinstatement of cocaine seeking induced by cocaine priming increased compared with shams. These results suggest that neonatal ventral hippocampal lesions facilitate instrumental learning for both natural and drug rewards, and reduce inhibitory control over cocaine taking while promoting cocaine seeking and relapse after withdrawal. The findings are discussed in terms of possible developmental or direct effects of the lesions, and both positive reinforcement (substance use vulnerability as a primary disease symptom) and negative reinforcement (self-medication) theories of substance use comorbidity in schizophrenia.

Redox modulation of cellular stress response and lipoxin A4 expression by Hericium Erinaceus in rat brain: relevance to Alzheimer's disease pathogenesis.

Science.gov (United States)

Trovato, A; Siracusa, R; Di Paola, R; Scuto, M; Ontario, M L; Bua, Ornella; Di Mauro, Paola; Toscano, M A; Petralia, C C T; Maiolino, L; Serra, A; Cuzzocrea, S; Calabrese, Vittorio

2016-01-01

There has been a recent upsurge of interest in complementary medicine, especially dietary supplements and foods functional in delaying the onset of age-associated neurodegenerative diseases. Mushrooms have long been used in traditional medicine for thousands of years, being now increasingly recognized as antitumor, antioxidant, antiviral, antibacterial and hepatoprotective agent also capable to stimulate host immune responses. Here we provide evidence of neuroprotective action of Hericium Herinaceus when administered orally to rat. Expression of Lipoxin A4 (LXA4) was measured in different brain regions after oral administration of a biomass Hericium preparation, given for 3 month. LXA4 up-regulation was associated with an increased content of redox sensitive proteins involved in cellular stress response, such as Hsp72, Heme oxygenase -1 and Thioredoxin. In the brain of rats receiving Hericium, maximum induction of LXA4 was observed in cortex, and hippocampus followed by substantia Nigra, striatum and cerebellum. Increasing evidence supports the notion that oxidative stress-driven neuroinflammation is a fundamental cause in neurodegenerative diseases. As prominent intracellular redox system involved in neuroprotection, the vitagene system is emerging as a neurohormetic potential target for novel cytoprotective interventions. Vitagenes encode for cytoprotective heat shock proteins 70, heme oxygenase-1, thioredoxin and Lipoxin A4. Emerging interest is now focussing on molecules capable of activating the vitagene system as novel therapeutic target to minimize deleterious consequences associated with free radical-induced cell damage, such as in neurodegeneration. LXA4 is an emerging endogenous eicosanoid able to promote resolution of inflammation, acting as an endogenous "braking signal" in the inflammatory process. In addition, Hsp system is emerging as key pathway for modulation to prevent neuronal dysfunction, caused by protein misfolding. Conceivably, activation of

Biomimetic approaches to modulate cellular adhesion in biomaterials: A review.

Science.gov (United States)

Rahmany, Maria B; Van Dyke, Mark

2013-03-01

Natural extracellular matrix (ECM) proteins possess critical biological characteristics that provide a platform for cellular adhesion and activation of highly regulated signaling pathways. However, ECM-based biomaterials can have several limitations, including poor mechanical properties and risk of immunogenicity. Synthetic biomaterials alleviate the risks associated with natural biomaterials but often lack the robust biological activity necessary to direct cell function beyond initial adhesion. A thorough understanding of receptor-mediated cellular adhesion to the ECM and subsequent signaling activation has facilitated development of techniques that functionalize inert biomaterials to provide a biologically active surface. Here we review a range of approaches used to modify biomaterial surfaces for optimal receptor-mediated cell interactions, as well as provide insights into specific mechanisms of downstream signaling activation. In addition to a brief overview of integrin receptor-mediated cell function, so-called "biomimetic" techniques reviewed here include (i) surface modification of biomaterials with bioadhesive ECM macromolecules or specific binding motifs, (ii) nanoscale patterning of the materials and (iii) the use of "natural-like" biomaterials. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The naked mole-rat exhibits an unusual cardiac myofilament protein profile providing new insights into heart function of this naturally subterranean rodent.

Science.gov (United States)

Grimes, Kelly M; Barefield, David Y; Kumar, Mohit; McNamara, James W; Weintraub, Susan T; de Tombe, Pieter P; Sadayappan, Sakthivel; Buffenstein, Rochelle

2017-12-01

The long-lived, hypoxic-tolerant naked mole-rat well-maintains cardiac function over its three-decade-long lifespan and exhibits many cardiac features atypical of similar-sized laboratory rodents. For example, they exhibit low heart rates and resting cardiac contractility, yet have a large cardiac reserve. These traits are considered ecophysiological adaptations to their dank subterranean atmosphere of low oxygen and high carbon dioxide levels and may also contribute to negligible declines in cardiac function during aging. We asked if naked mole-rats had a different myofilament protein signature to that of similar-sized mice that commonly show both high heart rates and high basal cardiac contractility. Adult mouse ventricles predominantly expressed α-myosin heavy chain (97.9 ± 0.4%). In contrast, and more in keeping with humans, β myosin heavy chain was the dominant isoform (79.0 ± 2.0%) in naked mole-rat ventricles. Naked mole-rat ventricles diverged from those of both humans and mice, as they expressed both cardiac and slow skeletal isoforms of troponin I. This myofilament protein profile is more commonly observed in mice in utero and during cardiomyopathies. There were no species differences in phosphorylation of cardiac myosin binding protein-C or troponin I. Phosphorylation of both ventricular myosin light chain 2 and cardiac troponin T in naked mole-rats was approximately half that observed in mice. Myofilament function was also compared between the two species using permeabilized cardiomyocytes. Together, these data suggest a cardiac myofilament protein signature that may contribute to the naked mole-rat's suite of adaptations to its natural subterranean habitat.

Analysis of cellular and extracellular DNA in fingerprints

Energy Technology Data Exchange (ETDEWEB)

Button, Julie M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2014-09-09

It has been previously shown that DNA can be recovered from latent fingerprints left on various surfaces [R. A. H. van Oorschot and M. K. Jones, Nature 387, 767 (1997)]. However, the source of the DNA, extracellular versus cellular origin, is difficult to determine. If the DNA is cellular, it is believed to belong to skin cells while extracellular DNA is believed to originate from body fluids such as sweat [D. J. Daly et. al, Forensic Sci. Int. Genet. 6, 41-46 (2012); V. V. Vlassov et. al, BioEssays 29, 654-667 (2007)]. The origin of the DNA in fingerprints has implications for processing and interpretation of forensic evidence. The determination of the origin of DNA in fingerprints is further complicated by the fact that the DNA in fingerprints tends to be at a very low quantity [R. A. H. van Oorschot and M. K. Jones, Nature 387, 767 (1997)]. This study examined fingerprints from five volunteers left on sterilized glass slides and plastic pens. Three fingerprints were left on each glass slide (thumb, index, and middle fingers) while the pens were held as if one was writing with them. The DNA was collected from the objects using the wet swabbing technique (TE buffer). Following collection, the cellular and extracellular components of each sample were separated using centrifugation and an acoustofluidics system. Centrifugation is still the primary separation technique utilized in forensics laboratories, while acoustic focusing uses sound waves to focus large particles (cells) into low pressure nodes, separating them from the rest of the sample matrix. After separation, all samples were quantified using real-time quantitative PCR (qPCR). The overall trend is that there is more DNA in the extracellular fractions than cellular fractions for both centrifugation and acoustofluidic processing. Additionally, more DNA was generally collected from the pen samples than the samples left on glass slides.

Cellular mechanism underlying formaldehyde-stimulated Cl- secretion in rat airway epithelium.

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Yu-Li Luo

Full Text Available BACKGROUND: Recent studies suggest that formaldehyde (FA could be synthesized endogeneously and transient receptor potential (TRP channel might be the sensor of FA. However, the physiological significance is still unclear. METHODOLOGY/PRINCIPAL FINDINGS: The present study investigated the FA induced epithelial Cl(- secretion by activation of TRPV-1 channel located in the nerve ending fiber. Exogenously applied FA induced an increase of I(SC in intact rat trachea tissue but not in the primary cultured epithelial cells. Western blot and immunofluorescence analysis identified TRPV-1 expression in rat tracheal nerve ending. Capsazepine (CAZ, a TRPV-1 specific antagonist significantly blocked the I(SC induced by FA. The TRPV-1 agonist capsaicin (Cap induced an increase of I(SC, which was similar to the I(SC induced by FA. L-703606, an NK-1 specific inhibitor and propranolol, an adrenalin β receptor inhibitor significantly abolished the I(SC induced by FA or Cap. In the ion substitute analysis, FA could not induce I(SC in the absence of extracelluar Cl(-. The I(SC induced by FA could be blocked by the non-specific Cl(- channel inhibitor DPC and the CFTR specific inhibitor CFTR(i-172, but not by the Ca(2+-activated Cl(- channel inhibitor DIDS. Furthermore, both forskolin, an agonist of adenylate cyclase (AC and MDL-12330A, an antagonist of AC could block FA-induced I(SC. CONCLUSION: Our results suggest that FA-induced epithelial I(SC response is mediated by nerve, involving the activation of TRPV-1 and release of adrenalin as well as substance P.

Experimental approaches to identify cellular G-quadruplex structures and functions.

Science.gov (United States)

Di Antonio, Marco; Rodriguez, Raphaël; Balasubramanian, Shankar

2012-05-01

Guanine-rich nucleic acids can fold into non-canonical DNA secondary structures called G-quadruplexes. The formation of these structures can interfere with the biology that is crucial to sustain cellular homeostases and metabolism via mechanisms that include transcription, translation, splicing, telomere maintenance and DNA recombination. Thus, due to their implication in several biological processes and possible role promoting genomic instability, G-quadruplex forming sequences have emerged as potential therapeutic targets. There has been a growing interest in the development of synthetic molecules and biomolecules for sensing G-quadruplex structures in cellular DNA. In this review, we summarise and discuss recent methods developed for cellular imaging of G-quadruplexes, and the application of experimental genomic approaches to detect G-quadruplexes throughout genomic DNA. In particular, we will discuss the use of engineered small molecules and natural proteins to enable pull-down, ChIP-Seq, ChIP-chip and fluorescence imaging of G-quadruplex structures in cellular DNA. Copyright © 2012 Elsevier Inc. All rights reserved.

Cellular automata codebooks applied to compact image compression

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Radu DOGARU

2006-12-01

Full Text Available Emergent computation in semi-totalistic cellular automata (CA is used to generate a set of basis (or codebook. Such codebooks are convenient for simple and circuit efficient compression schemes based on binary vector quantization, applied to the bitplanes of any monochrome or color image. Encryption is also naturally included using these codebooks. Natural images would require less than 0.5 bits per pixel (bpp while the quality of the reconstructed images is comparable with traditional compression schemes. The proposed scheme is attractive for low power, sensor integrated applications.

Impaired exercise performance and skeletal muscle mitochondrial function in rats with secondary carnitine deficiency

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Jamal BOUITBIR

2016-08-01

Full Text Available Purpose: The effects of carnitine depletion upon exercise performance and skeletal muscle mitochondrial function remain largely unexplored. We therefore investigated the effect of N-trimethyl-hydrazine-3-propionate (THP, a carnitine analogue inhibiting carnitine biosynthesis and renal carnitine reabsorption, on physical performance and skeletal muscle mitochondrial function in rats.Methods: Male Sprague Dawley rats were treated daily with water (control rats; n=12 or with 20 mg/100 g body weight THP (n=12 via oral gavage for 3 weeks. Following treatment, half of the animals of each group performed an exercise test until exhaustion.Results: Distance covered and exercise performance were lower in THP-treated compared to control rats. In the oxidative soleus muscle, carnitine depletion caused atrophy (-24% and impaired function of complex II and IV of the mitochondrial electron transport chain. The free radical leak (ROS production relative to oxygen consumption was increased and the cellular glutathione pool decreased. Moreover, mRNA expression of markers of mitochondrial biogenesis and mitochondrial DNA were decreased in THP-treated compared to control rats. In comparison, in the glycolytic gastrocnemius muscle, carnitine depletion was associated with impaired function of complex IV and increased free radical leak, whilst muscle weight and cellular glutathione pool were maintained. Markers of mitochondrial proliferation and mitochondrial DNA were unaffected.Conclusions: Carnitine deficiency is associated with impaired exercise capacity in rats treated with THP. THP-induced carnitine deficiency is associated with impaired function of the electron transport chain in oxidative and glycolytic muscle as well as with atrophy and decreased mitochondrial DNA in oxidative muscle.

Molecular and cytogenetic characterization of radon-induced lung tumors in the rat

International Nuclear Information System (INIS)

Dano, Laurent

2000-01-01

Radon is a natural radioactive gas. This radioelement, which is an α-particle emitter, is omnipresent in the environment. Inhalation of atmospheric radon is the major exposure route in man of natural radioactivity which results in respiratory tract contamination. An increased lung cancer risk associated with radon inhalation has been shown both in humans and animals by epidemiological and experimental studies, respectively. In rats, characterization of dose-effect relationships has led to the construction of statistical models that may help theoretically in the prediction of human health involvements of both occupational and domestic chronic exposure to radon. However, little is known about the cellular and molecular mechanisms of radon-induced lung carcinogenesis. In the laboratory, a model of lung cancers induced in rats after radon inhalation is available. This model represents a good tool to identify and characterize the genetic events contributing to the development of radon-induced lung tumors. Carrying out a global approach based on the combined use of classical and molecular cytogenetic methods, the analysis of 17 neoplasms allowed the identification of chromosomal regions frequently altered in these tumors. Numerous similarities have been found between our results and the cytogenetic data for human lung cancers, suggesting common underlying genetic molecular mechanisms for lung cancer development in both species. Moreover, our study has allowed to point to tumor suppressor genes and proto-oncogenes potentially involved in radon-induced lung carcinogenesis. Thus, our results may aid further molecular studies aimed either at confirming the role of these candidate genes or at demonstrating the involvement of yet to be identified genes. (author) [fr

Molecular characterization of radon-induced rat lung tumors

International Nuclear Information System (INIS)

Guillet Bastide, K.

2008-11-01

The radon gas is a well known lung carcinogenic factor in human at high doses but the cancer risk at low doses is not established. Indeed, epidemiological studies at low doses are difficult to conduct because of the human exposure to other lung carcinogenic factors. These data underlined the necessity to conduct experiments on lung tumors developed on animal model. The aim of this work was to characterize rat lung tumors by working on a series of radon-induced tumors that included adenocarcinomas (A.C.), squamous cell carcinomas (S.C.C.) and adeno-squamous carcinomas (A.S.C.), that are mixed tumors with both A.C. and S.C.C. cellular components. A C.G.H. analysis of the three types of tumors allowed us to define chromosomal recurrent unbalances and to target candidate genes potentially implicated in lung carcinogenesis, as p16Ink4a, p19Arf, Rb1, K-Ras or c-Myc. A more precise analysis of the p16Ink4a/Cdk4/Rb1 and p19Arf/Mdm2/Tp53 pathways was performed and indicated that the Rb1 pathway was frequently inactivated through an absence of p16 Ink4a protein expression, indicating that it has a major role in rat lung carcinogenesis. Finally, a comparative transcriptomic analysis of the three types of tumors allowed us to show for the first time that the complex tumors A.S.C. have a transcriptomic profile in accordance with their mixed nature but that they also display their own expression profiles specificities. This work allowed us to find molecular characteristics common to murine and human lung tumors, indicating that the model of lung tumors in rat is pertinent to search for radiation-induced lung tumors specificities and to help for a better molecular identification of this type of tumors in human. (author)

Designing beauty the art of cellular automata

CERN Document Server

Martínez, Genaro

2016-01-01

This fascinating, colourful book offers in-depth insights and first-hand working experiences in the production of art works, using simple computational models with rich morphological behaviour, at the edge of mathematics, computer science, physics and biology. It organically combines ground breaking scientific discoveries in the theory of computation and complex systems with artistic representations of the research results. In this appealing book mathematicians, computer scientists, physicists, and engineers brought together marvelous and esoteric patterns generated by cellular automata, which are arrays of simple machines with complex behavior. Configurations produced by cellular automata uncover mechanics of dynamic patterns formation, their propagation and interaction in natural systems: heart pacemaker, bacterial membrane proteins, chemical rectors, water permeation in soil, compressed gas, cell division, population dynamics, reaction-diffusion media and self-organisation. The book inspires artists to tak...

Irradiated diets and its effect on testes and adrenal gland of rats

International Nuclear Information System (INIS)

Kushwaha, A.K.S.; Hasan, S.S.

1988-01-01

The present investigation was undertaken to study the feeding effects of irradiated normal diet (consisting of equal parts of gram and wheat) and irradiated low protein diet (consisting one part of normal diet and three parts of wheat) on male rats for various periods starting from weaning time. Rats maintained on irradiated low protein diets showed decrease in the activity of androgen sensitive enzymes i.e., alkaline and acid phosphatase while an increase in the cholesterol content of the testes compared with irradiated normal controls. Diminution in androgen sensitive enzymes and accumulation of cholesterol in the rat testes suggest non-conversion of cholesterol into steriod hormones after feeding of irradiated low protein. Besides, rats fed on irradiated low protein diet showed increased cellular activity in the adrenal cortex and medulla as compared to rats fed on the irradiated normal diet. (author). 12 refs., 4 tabs

Resveratrol prevents alveolar bone loss in an experimental rat model of periodontitis.

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Bhattarai, Govinda; Poudel, Sher Bahadur; Kook, Sung-Ho; Lee, Jeong-Chae

2016-01-01

Resveratrol is an antioxidant and anti-inflammatory polyphenol. Periodontitis is induced by oral pathogens, where a systemic inflammatory response accompanied by oxidative stress is the major event initiating disease. We investigated how resveratrol modulates cellular responses and the mechanisms related to this modulation in lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (hGFs). We also explored whether resveratrol protects rats against alveolar bone loss in an experimental periodontitis model. Periodontitis was induced around the first upper molar of the rats by applying ligature infused with LPS. Stimulating hGFs with 5μg/ml LPS augmented the expression of cyclooxygenase-2, matrix metalloproteinase (MMP)-2, MMP-9, and Toll-like receptor-4. LPS treatment also stimulated the production of reactive oxygen species (ROS) and the phosphorylation of several protein kinases in the cells. However, the expression of heme oxygenase-1 (HO-1) and nuclear factor-E2 related factor 2 (Nrf2) was inhibited by the addition of LPS. Resveratrol treatment almost completely inhibited all of these changes in LPS-stimulated cells. Specifically, resveratrol alone augmented HO-1 induction via Nrf2-mediated signaling. Histological and micro-CT analyses revealed that administration of resveratrol (5mg/kg body weight) improved ligature/LPS-mediated alveolar bone loss in rats. Resveratrol also attenuated the production of inflammation-related proteins, the formation of osteoclasts, and the production of circulating ROS in periodontitis rats. Furthermore, resveratrol suppressed LPS-mediated decreases in HO-1 and Nrf2 levels in the inflamed periodontal tissues. Collectively, our findings suggest that resveratrol protects rats from periodontitic tissue damage by inhibiting inflammatory responses and by stimulating antioxidant defense systems. The aims of this study were to investigate how resveratrol modulates cellular responses and the mechanisms related to this modulation in

Label-Free Analysis of Cellular Lipid Droplet Formation by Non-Linear Microscopy

Science.gov (United States)

Schie, Iwan W.

Cellular lipid droplets (LD) are cellular organelles that can be found in every cell type. Recent research indicates that cellular LD are involved in a large number of cellular metabolic functions, such as lipid metabolism, protection from lipotoxicity, protein storage and degradation, and many more. LD formation is frequently associated with adverse health effects, i.e. alcoholic and non-alcoholic fatty liver disease, diabetes type-2, as well as many cardiovascular disorders. Despite their wide presence, LDs are the least studied and most poorly understood cellular organelles. Typically, LDs are investigated using fluorescence-based techniques that require staining with exogenous fluorophores. Other techniques, e.g. biochemical assays, require the destruction of cells that prohibit the analysis of living cells. Therefore, in my thesis research I developed a novel compound fast-scanning nonlinear optical microscope equipped with the ability to also acquire Raman spectra at specific image locations. This system allows us to image label-free cellular LD formation in living cells and analyze the composition of single cellular LDs. Images can be acquired at near video-rate (˜16 frames/s). Furthermore, the system has the ability to acquire very large images of tissue of up to 7.5x15 cm2 total area by stitching together scans with dimensions of 1x1 mm2 in less than 1 minute. The system also enables the user to acquire Raman spectra from points of interest in the multiphoton images and provides chemically-specific data from sample volumes as small as 1 femtoliter. In my thesis I used this setup to determine the effects of VLDL lipolysis products on primary rat hepatocytes. By analyzing the Raman spectra and comparing the peak ratios for saturated and unsaturated fatty acid it was determined that the small cellular LD are highly saturated, while large cellular LDs contain mostly unsaturated lipids. Furthermore, I established a method to determine the specific contribution

Cellular Kinetics of Perivascular MSC Precursors

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William C. W. Chen

2013-01-01

Full Text Available Mesenchymal stem/stromal cells (MSCs and MSC-like multipotent stem/progenitor cells have been widely investigated for regenerative medicine and deemed promising in clinical applications. In order to further improve MSC-based stem cell therapeutics, it is important to understand the cellular kinetics and functional roles of MSCs in the dynamic regenerative processes. However, due to the heterogeneous nature of typical MSC cultures, their native identity and anatomical localization in the body have remained unclear, making it difficult to decipher the existence of distinct cell subsets within the MSC entity. Recent studies have shown that several blood-vessel-derived precursor cell populations, purified by flow cytometry from multiple human organs, give rise to bona fide MSCs, suggesting that the vasculature serves as a systemic reservoir of MSC-like stem/progenitor cells. Using individually purified MSC-like precursor cell subsets, we and other researchers have been able to investigate the differential phenotypes and regenerative capacities of these contributing cellular constituents in the MSC pool. In this review, we will discuss the identification and characterization of perivascular MSC precursors, including pericytes and adventitial cells, and focus on their cellular kinetics: cell adhesion, migration, engraftment, homing, and intercellular cross-talk during tissue repair and regeneration.

The cytoskeleton of digitonin-treated rat hepatocytes.

OpenAIRE

Fiskum, G; Craig, S W; Decker, G L; Lehninger, A L

1980-01-01

Treatment of isolated rat hepatocptes with low concentrations of digitonin increases the permeability of the plsma membrane to cytosolic proteins without causing release of organelles such as mitochondria into the surrounding medium. Electron microscopy showed that treatment of the cells with increasing concentations of digitonin results in a progressive loss in the continuity of the plasma membrane, while most other aspects of cellular morphology remain normal. Depletion of background staini...

Hierarchical cellular designs for load-bearing biocomposite beams and plates

International Nuclear Information System (INIS)

Burgueno, Rigoberto; Quagliata, Mario J.; Mohanty, Amar K.; Mehta, Geeta; Drzal, Lawrence T.; Misra, Manjusri

2005-01-01

Scrutiny into the composition of natural, or biological materials convincingly reveals that high material and structural efficiency can be attained, even with moderate-quality constituents, by hierarchical topologies, i.e., successively organized material levels or layers. The present study demonstrates that biologically inspired hierarchical designs can help improve the moderate properties of natural fiber polymer composites or biocomposites and allow them to compete with conventional materials for load-bearing applications. An overview of the mechanics concepts that allow hierarchical designs to achieve higher performance is presented, followed by observation and results from flexural tests on periodic and hierarchical cellular beams and plates made from industrial hemp fibers and unsaturated polyester resin biocomposites. The experimental data is shown to agree well with performance indices predicted by mechanics models. A procedure for the multi-scale integrated material/structural analysis of hierarchical cellular biocomposite components is presented and its advantages and limitations are discussed

Alterations of polyunsaturated fatty acid metabolism in ovarian tissues of polycystic ovary syndrome rats.

Science.gov (United States)

Huang, Rong; Xue, Xinli; Li, Shengxian; Wang, Yuying; Sun, Yun; Liu, Wei; Yin, Huiyong; Tao, Tao

2018-03-30

The metabolism of polyunsaturated fatty acids (PUFAs) remains poorly characterized in ovarian tissues of patients with polycystic ovary syndrome (PCOS). This study aimed to explore alterations in the levels of PUFAs and their metabolites in serum and ovarian tissues in a PCOS rat model treated with a high-fat diet and andronate. Levels of PUFAs and their metabolites were measured using gas/liquid chromatography-mass spectrometry after the establishment of a PCOS rat model. Only 3 kinds of PUFAs [linoleic acid, arachidonic acid (AA) and docosahexaenoic acid] were detected in both the circulation and ovarian tissues of the rats, and their concentrations were lower in ovarian tissues than in serum. Moreover, significant differences in the ovarian levels of AA were observed between control, high-fat diet-fed and PCOS rats. The levels of prostaglandins, AA metabolites via the cyclooxygenase (COX) pathway, in ovarian tissues of the PCOS group were significantly increased compared to those in the controls. Further studies on the mechanism underlying this phenomenon showed a correlation between decreased expression of phosphorylated cytosolic phospholipase A2 (p-cPLA2) and increased mRNA and protein expression of COX2, potentially leading to a deeper understanding of altered AA and prostaglandin levels in ovarian tissues of PCOS rats. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

The renoprotective activity of hesperetin in cisplatin induced nephrotoxicity in rats: Molecular and biochemical evidence.

Science.gov (United States)

Kumar, Mukesh; Dahiya, Vicky; Kasala, Eshvendar Reddy; Bodduluru, Lakshmi Narendra; Lahkar, Mangala

2017-05-01

Nephrotoxicity remain a major life-threatening complication in cancer patients on cisplatin chemotherapy. In this study, we investigated the protective effect and possible cellular mechanism of the hesperetin, a naturally-occurring bioflavonoid against cisplatin-induced renal injury in rats. Hesperetin was administered at a dose of 50mg/kg and 100mg/kg orally for 10days and cisplatin (7.5mg/kg, ip) was administered on the 5th day of experiment. Cisplatin induced nephrotoxicity was evidenced by alteration in the level of markers such as blood urea nitrogen, creatinine, serum albumin and severe histopathological changes in kidney. Cisplatin administration also resulted in significant increase in the tissue oxidative stress and inflammatory cytokines. The level of antioxidants enzymes were decreased significantly in the cisplatin administered rats. Hesperetin treatment (50mg/kg and 100mg/kg) normalized the renal function by attenuation of the cisplatin-induced oxidative stress, lipid peroxidation, and inflammatory cytokines and histopathological alterations. On the basis of these experimental findings our present study postulate that co-administration of hesperetin with cisplatin chemotherapy may be promising preventive approach to limit the major mortal side effect of cisplatin. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Selenium bioavailability from naturally produced high-selenium peas and oats in selenium-deficient rats.

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Yan, Lin; Johnson, LuAnn K

2011-06-08

This study determined the bioavailability of selenium (Se) from yellow peas and oats harvested from the high-Se soil of South Dakota, United States. The Se concentrations were 13.5 ± 0.2 and 2.5 ± 0.1 mg/kg (dry weight) for peas and oats, respectively. Male weanling Sprague-Dawley rats were depleted of Se by feeding them a 30% Torula yeast-based diet (4.1 μg Se/kg) for 56 days, and then they were replenished with Se for an additional 50 days by feeding them the same diet supplemented with 20, 30, or 40 μg Se/kg from peas or oats, respectively. Selenium bioavailability was determined on the basis of the restoration of Se-dependent enzyme activities and tissue Se concentrations in Se-depleted rats, comparing those responses for yellow peas and oats to those for l-selenomethionine (SeMet; used as a reference) by using a slope-ratio method. Dietary supplementation with peas or oats resulted in linear or log-linear, dose-dependent increases in glutathione peroxidase activities in blood and liver and in thioredoxin reductase activity in liver. Supplementation with peas or oats resulted in linear or log-linear, dose-dependent increases in Se concentrations of plasma, liver, gastrocnemius muscle, and kidneys. The overall bioavailability was approximately 88% for Se from yellow peas and 92% from oats, compared to SeMet. It was concluded that Se from naturally produced high-Se yellow peas or oats is highly bioavailable in this model and that these high-Se foods may be a good dietary source of Se.

Humoral and cellular immune responses in gluten-treated suckling or hand-fed rats

Czech Academy of Sciences Publication Activity Database

Kozáková, Hana; Štěpánková, Renata; Tučková, Ludmila; Šinkora, Marek; Jelínková, L.; Tlaskalová, Helena

2000-01-01

Roč. 49, - (2000), s. 665-672 ISSN 0862-8408 R&D Projects: GA ČR GA306/99/1383; GA ČR GA303/00/1370; GA AV ČR IAA7020808; GA MZd IZ4150 Institutional research plan: CEZ:AV0Z5020903 Keywords : model of coeliac disease * rats * proliferation Subject RIV: EC - Immunology Impact factor: 1.366, year: 2000

In Utero Hepatocellular Transplantation in Rats

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Emma Muñoz-Sáez

2013-01-01

Full Text Available This work represents a step forward in the experimental design of an in utero hepatocellular transplantation model in rats. We focused on the enrichment optimization of isolated fetal hepatocytes suspension, arranging the surgery methodology of in utero transplantation, monitoring the biodistribution of the transplanted hepatocytes, and assessing the success of the transplants. Rat fetuses have been transplanted at the 17th embryonic day (ED17 with fetal hepatocytes isolated from rats at the end of pregnancy (ED21. We assessed possible differences between lymphocyte population, CD4 positive, CD8 positive, double-positive T-cells, and anti-inflammatory cytokines interleukins 4 and 10 (IL4 and IL10 as well. Cellular viability reached the rates of 90–95%. Transplanted groups had a limited success. Transplanted hepatocytes were not able to pass through the hematoplacental barrier. The hepatocytes injected were primarily located in the liver. There was an upward trend in the whole amount of T CD4 and T CD8 cells. There was an increased IL4 in the transplanted groups observed in the pregnant rats. The possibility to induce tolerance in fetuses with a hepatocyte transplant in utero could be a key point to avoid the immunosuppression treatments which must be undergone by transplanted patients.

Incidence and nature of tumors induced in Sprague-Dawley rats by gamma-irradiation

International Nuclear Information System (INIS)

Gross, L.; Dreyfuss, Y.; Faraggiana, T.

1988-01-01

In our previous studies carried out on inbred rats of the Sprague-Dawley strain, the tumor incidence was increased following irradiation (150 rads, 5 times, at weekly intervals), from 22 to 93% in females and from 5 to 59% in males. Experiments here reported suggest that 2 consecutive total-body gamma-irradiations of 150 rads each are sufficient to induce in rats the development of tumors, some malignant; 18 of 19 females (94.7%) developed tumors at an average age of 11.4 mo, and seven of the 14 males in this group (50%) developed tumors at an average age of 10.4 mo. In the second group, which received 3 consecutive gamma-irradiations, 20 of 23 females (86.9%) and 5 of 13 males (38.4%) developed tumors at average ages of 9.1 and 7.5 mo, respectively. In the third group, among rats which received 4 consecutive gamma-irradiations, 17 of 19 females (89.4%) and 4 of 12 males (33.3%) developed tumors at average ages of 9.4 and 10.5 mo, respectively. The etiology of tumors either developing spontaneously or induced by irradiation in rats remains to be clarified. Our attempts to detect virus particles by electron microscopy in such tumors or lymphomas have not been successful. As a working hypothesis, we are tempted to theorize that tumors or lymphomas developing spontaneously or induced by gamma irradiation in rats are caused by latent viral agents which are integrated into the cell genome and are cell associated, i.e., not separable from the rat tumor cells by conventional methods thus far used

Platinum nanozymes recover cellular ROS homeostasis in an oxidative stress-mediated disease model

Science.gov (United States)

Moglianetti, Mauro; de Luca, Elisa; Pedone, Deborah; Marotta, Roberto; Catelani, Tiziano; Sartori, Barbara; Amenitsch, Heinz; Retta, Saverio Francesco; Pompa, Pier Paolo

2016-02-01

In recent years, the use of nanomaterials as biomimetic enzymes has attracted great interest. In this work, we show the potential of biocompatible platinum nanoparticles (Pt NPs) as antioxidant nanozymes, which combine abundant cellular internalization and efficient scavenging activity of cellular reactive oxygen species (ROS), thus simultaneously integrating the functions of nanocarriers and antioxidant drugs. Careful toxicity assessment and intracellular tracking of Pt NPs proved their cytocompatibility and high cellular uptake, with compartmentalization within the endo/lysosomal vesicles. We have demonstrated that Pt NPs possess strong and broad antioxidant properties, acting as superoxide dismutase, catalase, and peroxidase enzymes, with similar or even superior performance than natural enzymes, along with higher adaptability to the changes in environmental conditions. We then exploited their potent activity as radical scavenging materials in a cellular model of an oxidative stress-related disorder, namely human Cerebral Cavernous Malformation (CCM) disease, which is associated with a significant increase in intracellular ROS levels. Noteworthily, we found that Pt nanozymes can efficiently reduce ROS levels, completely restoring the cellular physiological homeostasis.In recent years, the use of nanomaterials as biomimetic enzymes has attracted great interest. In this work, we show the potential of biocompatible platinum nanoparticles (Pt NPs) as antioxidant nanozymes, which combine abundant cellular internalization and efficient scavenging activity of cellular reactive oxygen species (ROS), thus simultaneously integrating the functions of nanocarriers and antioxidant drugs. Careful toxicity assessment and intracellular tracking of Pt NPs proved their cytocompatibility and high cellular uptake, with compartmentalization within the endo/lysosomal vesicles. We have demonstrated that Pt NPs possess strong and broad antioxidant properties, acting as superoxide

Antifungal activity of redox-active benzaldehydes that target cellular antioxidation

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Mahoney Noreen

2011-05-01

Full Text Available Abstract Background Disruption of cellular antioxidation systems should be an effective method for control of fungal pathogens. Such disruption can be achieved with redox-active compounds. Natural phenolic compounds can serve as potent redox cyclers that inhibit microbial growth through destabilization of cellular redox homeostasis and/or antioxidation systems. The aim of this study was to identify benzaldehydes that disrupt the fungal antioxidation system. These compounds could then function as chemosensitizing agents in concert with conventional drugs or fungicides to improve antifungal efficacy. Methods Benzaldehydes were tested as natural antifungal agents against strains of Aspergillus fumigatus, A. flavus, A. terreus and Penicillium expansum, fungi that are causative agents of human invasive aspergillosis and/or are mycotoxigenic. The yeast Saccharomyces cerevisiae was also used as a model system for identifying gene targets of benzaldehydes. The efficacy of screened compounds as effective chemosensitizers or as antifungal agents in formulations was tested with methods outlined by the Clinical Laboratory Standards Institute (CLSI. Results Several benzaldehydes are identified having potent antifungal activity. Structure-activity analysis reveals that antifungal activity increases by the presence of an ortho-hydroxyl group in the aromatic ring. Use of deletion mutants in the oxidative stress-response pathway of S. cerevisiae (sod1Δ, sod2Δ, glr1Δ and two mitogen-activated protein kinase (MAPK mutants of A. fumigatus (sakAΔ, mpkCΔ, indicates antifungal activity of the benzaldehydes is through disruption of cellular antioxidation. Certain benzaldehydes, in combination with phenylpyrroles, overcome tolerance of A. fumigatus MAPK mutants to this agent and/or increase sensitivity of fungal pathogens to mitochondrial respiration inhibitory agents. Synergistic chemosensitization greatly lowers minimum inhibitory (MIC or fungicidal (MFC

Localizing by autoradiography at -195 deg radioactive areas in rats exposed to a high flux of thermal neutrons, importance of phosphorus 32 in consecutive internal irradiation

International Nuclear Information System (INIS)

Chanteur, J.; Pellerin, P.

1961-01-01

Rats weighing 25 g were exposed for 5 mn to a flux of 6.10 12 thermal neutrons/cm 2 /s. Anatomical autoradiography at -195 deg. C has enabled the radioactive organs to be easily localised, to follow in course of time the decrease of radioactivity, and from it to deduce the probable nature of the numerous emitters in question. In particular, the phosphorus 32 has thus appeared to be one of those responsible for internal irradiation, general, on the one hand, by activating cellular phosphorus, local, on the other, by activating bony phosphates. Owing to this, an accidental irradiation by neutrons might have consequences that are both somatic (elective irradiation of the bone marrow) and genetic (activation of nucleic acids). The gamma spectrometry has confirmed the nature of certain other emitters. (author) [fr

Expression of calmodulin mRNA in rat olfactory neuroepithelium.

Science.gov (United States)

Biffo, S; Goren, T; Khew-Goodall, Y S; Miara, J; Margolis, F L

1991-04-01

A calmodulin (CaM) cDNA was isolated by differential hybridization screening of a lambda gt10 library prepared from rat olfactory mucosa. This cDNA fragment, containing most of the open reading frame of the rat CaMI gene, was subcloned and used to characterize steady-state expression of CaM mRNA in rat olfactory neuroepithelium and bulb. Within the bulb mitral cells are the primary neuronal population expressing CaM mRNA. The major CaM mRNA expressed in the olfactory mucosa is 1.7 kb with smaller contributions from mRNAs of 4.0 and 1.4 kb. CaM mRNA was primarily associated with the olfactory neurons and, despite the cellular complexity of the tissue and the known involvement of CaM in diverse cellular processes, was only minimally evident in sustentacular cells, gland cells or respiratory epithelium. Following bulbectomy CaM mRNA declines in the olfactory neuroepithelium as does olfactory marker protein (OMP) mRNA. In contrast to the latter, CaM mRNA makes a partial recovery by one month after surgery. These results, coupled with those from in situ hybridization, indicate that CaM mRNA is expressed in both mature and immature olfactory neurons. The program regulating CaM gene expression in olfactory neurons is distinct from those controlling expression of B50/GAP43 in immature, or OMP in mature, neurons respectively.

Plant Natural Product Formononetin Protects Rat Cardiomyocyte H9c2 Cells against Oxygen Glucose Deprivation and Reoxygenation via Inhibiting ROS Formation and Promoting GSK-3β Phosphorylation

Directory of Open Access Journals (Sweden)

Yuanyuan Cheng

2016-01-01

Full Text Available The opening of mitochondrial permeability transition pore (mPTP is a major cause of cell death in ischemia reperfusion injury. Based on our pilot experiments, plant natural product formononetin enhanced the survival of rat cardiomyocyte H9c2 cells during oxygen glucose deprivation (OGD and reoxygenation. For mechanistic studies, we focused on two major cellular factors, namely, reactive oxygen species (ROS and glycogen synthase kinase 3β (GSK-3β, in the regulation of mPTP opening. We found that formononetin suppressed the formation of ROS and superoxide in a concentration-dependent manner. Formononetin also rescued OGD/reoxygenation-induced loss of mitochondrial membrane integrity. Further studies suggested that formononetin induced Akt activation and GSK-3β (Ser9 phosphorylation, thereby reducing GSK-3β activity towards mPTP opening. PI3K and PKC inhibitors abolished the effects of formononetin on mPTP opening and GSK-3β phosphorylation. Immunoprecipitation experiments further revealed that formononetin increased the binding of phosphor-GSK-3β to adenine nucleotide translocase (ANT while it disrupted the complex of ANT with cyclophilin D. Moreover, immunofluorescence revealed that phospho-GSK-3β (Ser9 was mainly deposited in the space between mitochondria and cell nucleus. Collectively, these results indicated that formononetin protected cardiomyocytes from OGD/reoxygenation injury via inhibiting ROS formation and promoting GSK-3β phosphorylation.

Neuromodulation of hypoglossal motoneurons: cellular and developmental mechanisms.

Science.gov (United States)

Bayliss, D A; Viana, F; Talley, E M; Berger, A J

1997-11-01

Hypoglossal motoneurons (HMs) in the caudal brainstem have a respiratory-related activity pattern and contribute to control of upper airway resistance. In this review, we focus primarily on signalling mechanisms utilized by neurotransmitters to enhance HM excitability. In particular, we consider: (1) the membrane depolarization induced by a number of different putative transmitters [thyrotropin-releasing hormone (TRH), serotonin (5-HT), norepinephrine (NE)]; and (2) the inhibition of a calcium-dependent spike after hyperpolarization (AHP) by 5-HT and its effect on firing behavior. Potential functional consequences on HM behavior of these different neurotransmitter effects is discussed. In addition, we describe postnatal changes in transmitter effects and suggest potential cellular mechanisms to explain those developmental changes. Most of the data discussed are derived from in vitro electrophysiological recordings performed in preparations from neonatal and adult rats.

Phorate-induced oxidative stress, DNA damage and transcriptional activation of p53 and caspase genes in male Wistar rats

Energy Technology Data Exchange (ETDEWEB)

Saquib, Quaiser [Department of Zoology, College of Science, King Saud University, Riyadh (Saudi Arabia); Attia, Sabry M. [Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh (Saudi Arabia); Siddiqui, Maqsood A. [Department of Zoology, College of Science, King Saud University, Riyadh (Saudi Arabia); Aboul-Soud, Mourad A.M. [Department of Zoology, College of Science, King Saud University, Riyadh (Saudi Arabia); Biochemistry Department, Faculty of Agriculture, Cairo University, 12613 Giza (Egypt); Al-Khedhairy, Abdulaziz A. [Department of Zoology, College of Science, King Saud University, Riyadh (Saudi Arabia); Giesy, John P. [Department of Zoology, College of Science, King Saud University, Riyadh (Saudi Arabia); Department of Biomedical and Veterinary Biosciences and Toxicology Centre, University of Saskatchewan, Saskatoon, Canada S7N 5B3 (Canada); Zoology Department and Center for Integrative Toxicology, Michigan State University, East Lansing 48824 (United States); Musarrat, Javed, E-mail: musarratj1@yahoo.com [Department of Zoology, College of Science, King Saud University, Riyadh (Saudi Arabia); Department of Microbiology, Faculty of Agricultural Sciences, AMU, Aligarh (India)

2012-02-15

Male Wistar rats exposed to a systemic organophosphorus insecticide, phorate [O,O-diethyl S-[(ethylthio) methyl] phosphorothioate] at varying oral doses of 0.046, 0.092 or 0.184 mg phorate/kg bw for 14 days, exhibited substantial oxidative stress, cellular DNA damage and activation of apoptosis-related p53, caspase 3 and 9 genes. The histopathological changes including the pyknotic nuclei, inflammatory leukocyte infiltrations, renal necrosis, and cardiac myofiber degeneration were observed in the liver, kidney and heart tissues. Biochemical analysis of catalase and glutathione revealed significantly lesser activities of antioxidative enzymes and lipid peroxidation in tissues of phorate exposed rats. Furthermore, generation of intracellular reactive oxygen species and reduced mitochondrial membrane potential in bone marrow cells confirmed phorate-induced oxidative stress. Significant DNA damage was measured through comet assay in terms of the Olive tail moment in bone marrow cells of treated animals as compared to control. Cell cycle analysis also demonstrated the G{sub 2}/M arrest and appearance of a distinctive SubG{sub 1} peak, which signified induction of apoptosis. Up-regulation of tumor suppressor p53 and caspase 3 and 9 genes, determined by quantitative real-time PCR and enzyme-linked immunosorbent assay, elucidated the activation of intrinsic apoptotic pathways in response to cellular stress. Overall, the results suggest that phorate induces genetic alterations and cellular toxicity, which can adversely affect the normal cellular functioning in rats. -- Highlights: ► This is the first report on molecular toxicity of phorate in an in vivo test system. ► Phorate induces biochemical and histological changes in liver, kidney and heart. ► Rats treated with phorate exhibited DNA damage in bone marrow cells. ► Phorate induces apoptosis, oxidative stress and alters mitochondrial fluorescence. ► Phorate induces transcriptional changes and enhanced

Phorate-induced oxidative stress, DNA damage and transcriptional activation of p53 and caspase genes in male Wistar rats

International Nuclear Information System (INIS)

Saquib, Quaiser; Attia, Sabry M.; Siddiqui, Maqsood A.; Aboul-Soud, Mourad A.M.; Al-Khedhairy, Abdulaziz A.; Giesy, John P.; Musarrat, Javed

2012-01-01

Male Wistar rats exposed to a systemic organophosphorus insecticide, phorate [O,O-diethyl S-[(ethylthio) methyl] phosphorothioate] at varying oral doses of 0.046, 0.092 or 0.184 mg phorate/kg bw for 14 days, exhibited substantial oxidative stress, cellular DNA damage and activation of apoptosis-related p53, caspase 3 and 9 genes. The histopathological changes including the pyknotic nuclei, inflammatory leukocyte infiltrations, renal necrosis, and cardiac myofiber degeneration were observed in the liver, kidney and heart tissues. Biochemical analysis of catalase and glutathione revealed significantly lesser activities of antioxidative enzymes and lipid peroxidation in tissues of phorate exposed rats. Furthermore, generation of intracellular reactive oxygen species and reduced mitochondrial membrane potential in bone marrow cells confirmed phorate-induced oxidative stress. Significant DNA damage was measured through comet assay in terms of the Olive tail moment in bone marrow cells of treated animals as compared to control. Cell cycle analysis also demonstrated the G 2 /M arrest and appearance of a distinctive SubG 1 peak, which signified induction of apoptosis. Up-regulation of tumor suppressor p53 and caspase 3 and 9 genes, determined by quantitative real-time PCR and enzyme-linked immunosorbent assay, elucidated the activation of intrinsic apoptotic pathways in response to cellular stress. Overall, the results suggest that phorate induces genetic alterations and cellular toxicity, which can adversely affect the normal cellular functioning in rats. -- Highlights: ► This is the first report on molecular toxicity of phorate in an in vivo test system. ► Phorate induces biochemical and histological changes in liver, kidney and heart. ► Rats treated with phorate exhibited DNA damage in bone marrow cells. ► Phorate induces apoptosis, oxidative stress and alters mitochondrial fluorescence. ► Phorate induces transcriptional changes and enhanced activities of

Neonatal maternal separation up-regulates protein signalling for cell survival in rat hypothalamus.

Science.gov (United States)

Irles, Claudine; Nava-Kopp, Alicia T; Morán, Julio; Zhang, Limei

2014-05-01

We have previously reported that in response to early life stress, such as maternal hyperthyroidism and maternal separation (MS), the rat hypothalamic vasopressinergic system becomes up-regulated, showing enlarged nuclear volume and cell number, with stress hyperresponsivity and high anxiety during adulthood. The detailed signaling pathways involving cell death/survival, modified by adverse experiences in this developmental window remains unknown. Here, we report the effects of MS on cellular density and time-dependent fluctuations of the expression of pro- and anti-apoptotic factors during the development of the hypothalamus. Neonatal male rats were exposed to 3 h-daily MS from postnatal days 2 to 15 (PND 2-15). Cellular density was assessed in the hypothalamus at PND 21 using methylene blue staining, and neuronal nuclear specific protein and glial fibrillary acidic protein immunostaining at PND 36. Expression of factors related to apoptosis and cell survival in the hypothalamus was examined at PND 1, 3, 6, 9, 12, 15, 20 and 43 by Western blot. Rats subjected to MS exhibited greater cell-density and increased neuronal density in all hypothalamic regions assessed. The time course of protein expression in the postnatal brain showed: (1) decreased expression of active caspase 3; (2) increased Bcl-2/Bax ratio; (3) increased activation of ERK1/2, Akt and inactivation of Bad; PND 15 and PND 20 were the most prominent time-points. These data indicate that MS can induce hypothalamic structural reorganization by promoting survival, suppressing cell death pathways, increasing cellular density which may alter the contribution of these modified regions to homeostasis.

Inhibition of HMGB1 Translocation by Green Tea Extract in Rats Exposed to Environmental Tobacco Smoke

Directory of Open Access Journals (Sweden)

Sirintip Chaichalotornkul

2012-01-01

Full Text Available Environmental tobacco smoke (ETS exposure is linked to carcinogenic, oxidative and inflammatory cellular reactions. Green tea polyphenol reportedly plays a role in the prevention of inflammation-related diseases. To evaluate the effects of green tea extract (GTE on cellular location of High Mobility Group Box-1 (HMGB1 protein, we studied the lung tissue in rats exposed to cigarette smoke (CS. Rats were divided into three groups; CS, CSG, and C, which were groups of CS-treated only, CS-treated with GTE dietary supplement, and the control, respectively. Our findings by immunocytochemistry showed that abundant HMGB1 translocated from the nucleus to the cytoplasm in the lung tissues of rats that were exposed to CS, whereas HMGB1 was localized to the nuclei of CSG and C group. For in vitro studies, cotinine stimulated the secretion of HMGB1 in a dose and time dependent manner and the HMGB1 level was suppressed by GTE in murine macrophage cell lines. Our results could suggest that GTE supplementation which could suppress HMGB1 may offer a beneficial effect against diseases.

The cellular and Genomic response of rat dopaminergic neurons (N27) to coated nanosilver

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This study examined if nanosilver (nanoAg) of different sizes and coatings were differentially toxic to oxidative stress-sensitive neurons. N27 rat dopaminergic neurons were exposed (0.5-5ppm) to a set of nanoAg of different sizes (10nm, 75nm) and coatings (PVP, citrate) and thei...

The Natural History of Pneumonic Tularemia in Female Fischer 344 Rats after Inhalational Exposure to Aerosolized Francisella tularensis Subspecies tularensis Strain SCHU S4.

Science.gov (United States)

Hutt, Julie A; Lovchik, Julie A; Dekonenko, Alexander; Hahn, Andrew C; Wu, Terry H

2017-02-01

The inbred Fischer 344 rat is being evaluated for testing novel vaccines and therapeutics against pneumonic tularemia. Although primary pneumonic tularemia in humans typically occurs by inhalation of aerosolized bacteria, the rat model has relied on intratracheal inoculation of organisms because of safety and equipment issues. We now report the natural history of pneumonic tularemia in female Fischer 344 rats after nose-only inhalational exposure to lethal doses of aerosolized Francisella tularensis subspecies tularensis, strain SCHU S4. Our results are consistent with initial uptake of aerosolized SCHU S4 from the nasal cavity, lungs, and possibly the gastrointestinal tract. Bacteremia with hematogenous dissemination was first detected 2 days after exposure. Shortly thereafter, the infected rats exhibited fever, tachypnea, and hypertension that persisted for 24 to 36 hours and then rapidly decreased as animals succumbed to infection between days 5 and 8 after exposure. Tachycardia was observed briefly, but only after the core body temperature and blood pressure began to decrease as the animals were near death. Initial neutrophilic and histiocytic inflammation in affected tissues became progressively more fibrinous and necrotizing over time. At death, as many as 10 10 colony-forming units were found in the lungs, spleen, and liver. Death was attributed to sepsis and disseminated intravascular coagulation. Overall, the pathogenesis of pneumonic tularemia in the female F344 rat model appears to replicate the disease in humans. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Andrographis paniculata leaf extract prevents thioacetamide-induced liver cirrhosis in rats.

Directory of Open Access Journals (Sweden)

Daleya Abdulaziz Bardi

Full Text Available This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given intraperitoneal injections of vehicle 10% Tween-20, 5 mL/kg (normal control or 200 mg/kg TAA thioacetamide (to induce liver cirrhosis three times per week. Three additional groups were treated with thioacetamide plus daily oral silymarin (50 mg/kg or ELAP (250 or 500 mg/kg. Liver injury was assessed using biochemical tests, macroscopic and microscopic tissue analysis, histopathology, and immunohistochemistry. In addition, HepG2 and WRL-68 cells were treated in vitro with ELAP fractions to test cytotoxicity. Rats treated with ELAP exhibited significantly lower liver/body weight ratios and smoother, more normal liver surfaces compared with the cirrhosis group. Histopathology using Hematoxylin and Eosin along with Masson's Trichrome stain showed minimal disruption of hepatic cellular structure, minor fibrotic septa, a low degree of lymphocyte infiltration, and minimal collagen deposition after ELAP treatment. Immunohistochemistry indicated that ELAP induced down regulation of proliferating cell nuclear antigen. Also, hepatic antioxidant enzymes and oxidative stress parameters in ELAP-treated rats were comparable to silymarin-treated rats. ELAP administration reduced levels of altered serum liver biomarkers. ELAP fractions were non-cytotoxic to WRL-68 cells, but possessed anti-proliferative activity on HepG2 cells, which was confirmed by a significant elevation of lactate dehydrogenase, reactive oxygen species, cell membrane permeability, cytochrome c, and caspase-8,-9, and, -3/7 activity in HepG2 cells. A reduction of mitochondrial membrane potential was also detected in ELAP-treated HepG2 cells. The hepatoprotective effect of 500 mg/kg of ELAP is proposed

Andrographis paniculata leaf extract prevents thioacetamide-induced liver cirrhosis in rats.

Science.gov (United States)

Abdulaziz Bardi, Daleya; Halabi, Mohammed Farouq; Hassandarvish, Pouya; Rouhollahi, Elham; Paydar, Mohammadjavad; Moghadamtousi, Soheil Zorofchian; Al-Wajeeh, Nahla Saeed; Ablat, Abdulwali; Abdullah, Nor Azizan; Abdulla, Mahmood Ameen

2014-01-01

This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP) on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given intraperitoneal injections of vehicle 10% Tween-20, 5 mL/kg (normal control) or 200 mg/kg TAA thioacetamide (to induce liver cirrhosis) three times per week. Three additional groups were treated with thioacetamide plus daily oral silymarin (50 mg/kg) or ELAP (250 or 500 mg/kg). Liver injury was assessed using biochemical tests, macroscopic and microscopic tissue analysis, histopathology, and immunohistochemistry. In addition, HepG2 and WRL-68 cells were treated in vitro with ELAP fractions to test cytotoxicity. Rats treated with ELAP exhibited significantly lower liver/body weight ratios and smoother, more normal liver surfaces compared with the cirrhosis group. Histopathology using Hematoxylin and Eosin along with Masson's Trichrome stain showed minimal disruption of hepatic cellular structure, minor fibrotic septa, a low degree of lymphocyte infiltration, and minimal collagen deposition after ELAP treatment. Immunohistochemistry indicated that ELAP induced down regulation of proliferating cell nuclear antigen. Also, hepatic antioxidant enzymes and oxidative stress parameters in ELAP-treated rats were comparable to silymarin-treated rats. ELAP administration reduced levels of altered serum liver biomarkers. ELAP fractions were non-cytotoxic to WRL-68 cells, but possessed anti-proliferative activity on HepG2 cells, which was confirmed by a significant elevation of lactate dehydrogenase, reactive oxygen species, cell membrane permeability, cytochrome c, and caspase-8,-9, and, -3/7 activity in HepG2 cells. A reduction of mitochondrial membrane potential was also detected in ELAP-treated HepG2 cells. The hepatoprotective effect of 500 mg/kg of ELAP is proposed to result from

Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model.

Science.gov (United States)

Zeng, Lingling; Yang, Yang; Hu, Yujuan; Sun, Yu; Du, Zhengde; Xie, Zhen; Zhou, Tao; Kong, Weijia

2014-01-01

Age-related dysfunction of the central auditory system, also known as central presbycusis, can affect speech perception and sound localization. Understanding the pathogenesis of central presbycusis will help to develop novel approaches to prevent or treat this disease. In this study, the mechanisms of central presbycusis were investigated using a mimetic aging rat model induced by chronic injection of D-galactose (D-Gal). We showed that malondialdehyde (MDA) levels were increased and manganese superoxide dismutase (SOD2) activity was reduced in the auditory cortex in natural aging and D-Gal-induced mimetic aging rats. Furthermore, mitochondrial DNA (mtDNA) 4834 bp deletion, abnormal ultrastructure and cell apoptosis in the auditory cortex were also found in natural aging and D-Gal mimetic aging rats. Sirt3, a mitochondrial NAD+-dependent deacetylase, has been shown to play a crucial role in controlling cellular reactive oxygen species (ROS) homeostasis. However, the role of Sirt3 in the pathogenesis of age-related central auditory cortex deterioration is still unclear. Here, we showed that decreased Sirt3 expression might be associated with increased SOD2 acetylation, which negatively regulates SOD2 activity. Oxidative stress accumulation was likely the result of low SOD2 activity and a decline in ROS clearance. Our findings indicate that Sirt3 might play an essential role, via the mediation of SOD2, in central presbycusis and that manipulation of Sirt3 expression might provide a new approach to combat aging and oxidative stress-related diseases.

Mitochondrial ribosomal protein S18-2 evokes chromosomal instability and transforms primary rat skin fibroblasts

KAUST Repository

Kashuba, Elena; Carbone, Ennio; Di Fabrizio, Enzo M.; Tirinato, Luca; Petruchek, Maria; Drummond, Catherine; Kovalevska, Larysa; Gurrapu, Sreeharsha; Mushtaq, Muhammad; Darekar, Suhas D.

2015-01-01

We have shown earlier that overexpression of the human mitochondrial ribosomal protein MRPS18-2 (S18-2) led to immortalization of primary rat embryonic fibroblasts. The derived cells expressed the embryonic stem cell markers, and cellular pathways

Cellular antioxidant effects of atorvastatin in vitro and in vivo.

Science.gov (United States)

Wassmann, Sven; Laufs, Ulrich; Müller, Kirsten; Konkol, Christian; Ahlbory, Katja; Bäumer, Anselm T; Linz, Wolfgang; Böhm, Michael; Nickenig, Georg

2002-02-01

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may exert direct effects on vascular cells and beneficially influence endothelial dysfunction. Because reactive oxygen species (ROS) may lead to vascular damage and dysfunction, we investigated the effect of atorvastatin on ROS production and the underlying mechanisms in vitro and in vivo. Cultured rat aortic vascular smooth muscle cells were incubated with 10 micromol/L atorvastatin. Angiotensin II-induced and epidermal growth factor-induced ROS production were significantly reduced by atorvastatin (dichlorofluorescein fluorescence laser microscopy). Atorvastatin downregulated mRNA expression of the NAD(P)H oxidase subunit nox1, whereas p22phox mRNA expression was not significantly altered (reverse transcription-polymerase chain reaction, Northern analysis). Membrane translocation of rac1 GTPase, which is required for the activation of NAD(P)H oxidase, was inhibited by atorvastatin (Western blot). mRNA expression of superoxide dismutase isoforms and glutathione peroxidase was not modified by atorvastatin, whereas catalase expression was upregulated at mRNA and protein levels, resulting in an increased enzymatic activity. Effects of atorvastatin on ROS production and nox1, rac1, and catalase expression were inhibited by L-mevalonate but not by 25-hydroxycholesterol. In addition, spontaneously hypertensive rats were treated with atorvastatin for 30 days. ROS production in aortic segments was significantly reduced in statin-treated rats (lucigenin chemiluminescence). Treatment with atorvastatin reduced vascular mRNA expression of p22phox and nox1 and increased aortic catalase expression. mRNA expression of superoxide dismutases, glutathione peroxidase, and NAD(P)H oxidase subunits gp91phox, p40phox, p47phox, and p67phox remained unchanged. Translocation of rac1 from the cytosol to the cell membrane was also reduced in vivo. Thus, atorvastatin exerts cellular antioxidant effects in cultured rat

A truncated conical beam model for analysis of the vibration of rat whiskers.

Science.gov (United States)

Yan, Wenyi; Kan, Qianhua; Kergrene, Kenan; Kang, Guozheng; Feng, Xi-Qiao; Rajan, Ramesh

2013-08-09

A truncated conical beam model is developed to study the vibration behaviour of a rat whisker. Translational and rotational springs are introduced to better represent the constraint conditions at the base of the whiskers in a living rat. Dimensional analysis shows that the natural frequency of a truncated conical beam with generic spring constraints at its ends is inversely proportional to the square root of the mass density. Under all the combinations of the classical free, pinned, sliding or fixed boundary conditions of a truncated conical beam, it is proved that the natural frequency can be expressed as f = α(rb/L(2))E/ρ and the frequency coefficient α only depends on the ratio of the radii at the two ends of the beam. The natural frequencies of a representative rat whisker are predicted for two typical situations: freely whisking in air and the tip touching an object. Our numerical results show that there exists a window where the natural frequencies of a rat whisker are very sensitive to the change of the rotational constraint at the base. This finding is also confirmed by the numerical results of 18 whiskers with their data available from literature. It can be concluded that the natural frequencies of a rat whisker can be adjusted within a wide range through manipulating the constraints of the follicle on the rat base by a behaving animal. Copyright © 2013 Elsevier Ltd. All rights reserved.

Measurements of natural levels of 14C in human's and rat's tissues by accelerator mass spectrometry in Korea

International Nuclear Information System (INIS)

Cho, S.Y.; Khu, H.J.; Kang, J.H.; Yoon, M.Y.; Kim, J.C.

2005-01-01

Accelerator mass spectrometry (AMS) is the most sensitive, safe and precise analytical method for quantifying long-lived isotope in biomedical research with animals as well as human beings. In Korea, AMS Laboratory has been operating successfully for years measuring especially archaeological samples for 14 C dating. In this year, a biological sample pretreatment facility was setup to work on biomedical applications. As a preliminary study, we have measured the natural background levels of 14 C in tissues and blood of humans and rats have been measured. The results were agreed with the other reported levels and gave stable and reproducible results within 1-2%. (author)

MUSCARINIC ACETYLCHOLINE RECEPTOR-EXPRESSION IN ASTROCYTES IN THE CORTEX OF YOUNG AND AGED RATS

NARCIS (Netherlands)

VANDERZEE, EA; DEJONG, GI; STROSBERG, AD; LUITEN, PGM

The present report describes the cellular and subcellular distribution pattern of immunoreactivity to M35, a monoclonal antibody raised against purified muscarinic acetylcholine receptor protein, in astrocytes in the cerebral cortex of young and aged rats. Most M35-positive astrocytes were localized

Distribution of Inositol 1,4,5-Trisphosphate Receptors in Rat Osteoclasts

International Nuclear Information System (INIS)

Morikawa, Kazumasa; Goto, Tetsuya; Tanimura, Akihiko; Kobayashi, Shigeru; Maki, Kenshi

2008-01-01

Inositol 1,4,5-trisphosphate (IP 3 ) receptors (IP 3 Rs) are Ca 2+ channels that localize to intracellular Ca 2+ stores such as the endoplasmic reticulum (ER). Recently, IP 3 Rs were found to participate in the formation of the cytoskeleton and cellular adhesions. In this study, we examined the cellular localization of type I, II, and III IP 3 Rs to assess their role in cellular adhesion in rat osteoclasts. Rat bone marrow cells were cultured in α-MEM with 10% fetal bovine serum, M-CSF, RANKL, and 1,25(OH) 2 D 3 for 1 week to promote osteoclast formation. Type I, II, and III IP 3 R expression in the osteoclasts was then examined by RT-PCR. Double-staining was performed using antibodies against type I, II, and III IP 3 Rs and DiOC 6 , an ER marker, or TRITC-phalloidin, an actin filament marker. Expression of all three IP 3 Rs was detected in the newly formed osteoclasts; however, the localization of the type I and II IP 3 Rs was predominantly close to nuclear, and possibly colocalized with the ER, while the type III IP 3 Rs were localized to the ER and podosomes, actin-rich adhesion structures in osteoclasts. These findings suggest that type III IP 3 Rs are associated with osteoclast adhesion

Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally.

Science.gov (United States)

Barrett, Catherine E; Hennessey, Thomas M; Gordon, Katelyn M; Ryan, Steve J; McNair, Morgan L; Ressler, Kerry J; Rainnie, Donald G

2017-01-01

The amygdala controls socioemotional behavior and has consistently been implicated in the etiology of autism spectrum disorder (ASD). Precocious amygdala development is commonly reported in ASD youth with the degree of overgrowth positively correlated to the severity of ASD symptoms. Prenatal exposure to VPA leads to an ASD phenotype in both humans and rats and has become a commonly used tool to model the complexity of ASD symptoms in the laboratory. Here, we examined abnormalities in gene expression in the amygdala and socioemotional behavior across development in the valproic acid (VPA) rat model of ASD. Rat dams received oral gavage of VPA (500 mg/kg) or saline daily between E11 and 13. Socioemotional behavior was tracked across development in both sexes. RNA sequencing and proteomics were performed on amygdala samples from male rats across development. Effects of VPA on time spent in social proximity and anxiety-like behavior were sex dependent, with social abnormalities presenting in males and heightened anxiety in females. Across time VPA stunted developmental and immune, but enhanced cellular death and disorder, pathways in the amygdala relative to saline controls. At postnatal day 10, gene pathways involved in nervous system and cellular development displayed predicted activations in prenatally exposed VPA amygdala samples. By juvenile age, however, transcriptomic and proteomic pathways displayed reductions in cellular growth and neural development. Alterations in immune pathways, calcium signaling, Rho GTPases, and protein kinase A signaling were also observed. As behavioral, developmental, and genomic alterations are similar to those reported in ASD, these results lend support to prenatal exposure to VPA as a useful tool for understanding how developmental insults to molecular pathways in the amygdala give rise to ASD-related syndromes.

Cellular basis for accumulation of 111In-labeled leukocytes and platelets in rejecting cardiac allografts: concise communication

International Nuclear Information System (INIS)

Wang, T.S.; Oluwole, S.; Fawwaz, R.A.; Wolff, M.; Kuromoto, N.; Satake, K.; Hardy, M.A.; Alderson, P.O.

1982-01-01

Biodistribution and imaging studies in rats showed that 111 In-labeled leukocytes and platelets accumulate progressively with time after transplantation in cardiac allografts undergoing rejection, but do not accumulate in normal syngeneic heart grafts. Maximum heart allograft-to-blood ratios of 9:1 were obtained, and allograft-to-native heart ratios of 17:1. Microscopic studies of the rejecting cardiac allografts showed that histologic findings paralleled the cellular changes predicted by the radionuclide studies. Intravenously administered 67 Ga citrate and /sup 99m/Tc sulfur colloid failed to show significant accumulation in rejecting grafts. The findings suggest that cellular rejection, rather than nonspecific inflammatory changes, is the primary basis for accumulation of 111 In leukocytes and platelets in rejecting cardiac allografts

Cellular basis for accumulation of In-111-labeled leukocytes and platelets in rejecting cardiac allografts: concise communication

International Nuclear Information System (INIS)

Wang, T.S.T.; Oluwole, S.; Fawwaz, R.A.; Wolff, M.; Kuromoto, N.; Satake, K.; Hardy, M.A.; Alderson, P.O.

1982-01-01

Biodistribution and imaging studies in rats showed that In-111-labeled leukocytes and platelets accumulate progressively with time after transplantation in cardiac allografts undergoing rejection, but do not accumulate in normal syngeneic heart grafts. Maximum heart allograft-to-blood ratios of 9:1 were obtained, and allograft-to-native heart ratios of 17:1. Microscopic studies of the rejecting cardiac allografts showed that histologic findings paralleled the cellular changes predicted by the radionuclide studies. Intravenously administered Ga-67 citrate and Tc-99m sulfur colloid failed to show significant accumulation in rejecting grafts. The findings suggest that cellular rejection, rather than nonspecific inflammatory changes, is the primary basis for accumulation of In-111 leukocytes and platelets in rejecting cardiac allografts

Intractable problems in reversible cellular automata

International Nuclear Information System (INIS)

Vatan, F.

1988-01-01

The billiard ball model, a classical mechanical system in which all parameters are real variables, can perform all digital computations. An eight-state, 11-neighbor reversible cellular automaton (an entirely discrete system in which all parameters are integer variables) can simulate this model. One of the natural problems for this system is to determine the shape of a container so that they initial specific distribution of gas molecules eventually leads to a predetermined distribution. This problem if PSPACE-complete. Related intractable and decidable problems are discussed as well

Cellular gravity

NARCIS (Netherlands)

F.C. Gruau; J.T. Tromp (John)

1999-01-01

textabstractWe consider the problem of establishing gravity in cellular automata. In particular, when cellular automata states can be partitioned into empty, particle, and wall types, with the latter enclosing rectangular areas, we desire rules that will make the particles fall down and pile up on

High-strength cellular ceramic composites with 3D microarchitecture.

Science.gov (United States)

Bauer, Jens; Hengsbach, Stefan; Tesari, Iwiza; Schwaiger, Ruth; Kraft, Oliver

2014-02-18

To enhance the strength-to-weight ratio of a material, one may try to either improve the strength or lower the density, or both. The lightest solid materials have a density in the range of 1,000 kg/m(3); only cellular materials, such as technical foams, can reach considerably lower values. However, compared with corresponding bulk materials, their specific strength generally is significantly lower. Cellular topologies may be divided into bending- and stretching-dominated ones. Technical foams are structured randomly and behave in a bending-dominated way, which is less weight efficient, with respect to strength, than stretching-dominated behavior, such as in regular braced frameworks. Cancellous bone and other natural cellular solids have an optimized architecture. Their basic material is structured hierarchically and consists of nanometer-size elements, providing a benefit from size effects in the material strength. Designing cellular materials with a specific microarchitecture would allow one to exploit the structural advantages of stretching-dominated constructions as well as size-dependent strengthening effects. In this paper, we demonstrate that such materials may be fabricated. Applying 3D laser lithography, we produced and characterized micro-truss and -shell structures made from alumina-polymer composite. Size-dependent strengthening of alumina shells has been observed, particularly when applied with a characteristic thickness below 100 nm. The presented artificial cellular materials reach compressive strengths up to 280 MPa with densities well below 1,000 kg/m(3).

HDACi: cellular effects, opportunities for restorative dentistry.

LENUS (Irish Health Repository)

Duncan, H F

2011-12-01

Acetylation of histone and non-histone proteins alters gene expression and induces a host of cellular effects. The acetylation process is homeostatically balanced by two groups of cellular enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). HAT activity relaxes the structure of the human chromatin, rendering it transcriptionally active, thereby increasing gene expression. In contrast, HDAC activity leads to gene silencing. The enzymatic balance can be \\'tipped\\' by histone deacetylase inhibitors (HDACi), leading to an accumulation of acetylated proteins, which subsequently modify cellular processes including stem cell differentiation, cell cycle, apoptosis, gene expression, and angiogenesis. There is a variety of natural and synthetic HDACi available, and their pleiotropic effects have contributed to diverse clinical applications, not only in cancer but also in non-cancer areas, such as chronic inflammatory disease, bone engineering, and neurodegenerative disease. Indeed, it appears that HDACi-modulated effects may differ between \\'normal\\' and transformed cells, particularly with regard to reactive oxygen species accumulation, apoptosis, proliferation, and cell cycle arrest. The potential beneficial effects of HDACi for health, resulting from their ability to regulate global gene expression by epigenetic modification of DNA-associated proteins, also offer potential for application within restorative dentistry, where they may promote dental tissue regeneration following pulpal damage.

Activation of human natural killer cells by the soluble form of cellular prion protein

International Nuclear Information System (INIS)

Seong, Yeon-Jae; Sung, Pil Soo; Jang, Young-Soon; Choi, Young Joon; Park, Bum-Chan; Park, Su-Hyung; Park, Young Woo; Shin, Eui-Cheol

2015-01-01

Cellular prion protein (PrP C ) is widely expressed in various cell types, including cells of the immune system. However, the specific roles of PrP C in the immune system have not been clearly elucidated. In the present study, we investigated the effects of a soluble form of recombinant PrP C protein on human natural killer (NK) cells. Recombinant soluble PrP C protein was generated by fusion of human PrP C with the Fc portion of human IgG 1 (PrP C -Fc). PrP C -Fc binds to the surface of human NK cells, particularly to CD56 dim NK cells. PrP C -Fc induced the production of cytokines and chemokines and the degranulation of granzyme B from NK cells. In addition, PrP C -Fc facilitated the IL-15-induced proliferation of NK cells. PrP C -Fc induced phosphorylation of ERK-1/2 and JNK in NK cells, and inhibitors of the ERK or the JNK pathways abrogated PrP C -Fc-induced cytokine production in NK cells. In conclusion, the soluble form of recombinant PrP C -Fc protein activates human NK cells via the ERK and JNK signaling pathways. - Highlights: • Recombinant soluble PrP C (PrP C -Fc) was generated by fusion of human PrP C with IgG1 Fc portion. • PrP C -Fc protein induces the production of cytokines and degranulation from human NK cells. • PrP C -Fc protein enhances the IL-15-induced proliferation of human NK cells. • PrP C -Fc protein activates human NK cells via the ERK and JNK signaling pathways

Sphingosine-1-phosphate stimulates rat primary chondrocyte proliferation

International Nuclear Information System (INIS)

Kim, Mi-Kyoung; Lee, Ha Young; Kwak, Jong-Young; Park, Joo-In; Yun, Jeanho; Bae, Yoe-Sik

2006-01-01

Rat primary chondrocytes express the sphingosine-1-phosphate (S1P) receptor, S1P 2 , S1P 3 , S1P 4 , but not S1P 1 . When chondrocytes were stimulated with S1P or phytosphingosine-1-phosphate (PhS1P, an S1P 1 - and S1P 4 -selective agonist), phospholipase C-mediated cytosolic calcium increase was dramatically induced. S1P and PhS1P also stimulated two kinds of mitogen-activated protein kinases, extracellular signal-regulated kinase (ERK) and p38 kinase in chondrocytes. In terms of the two phospholipids-mediated functional modulation of chondrocytes, S1P and PhS1P stimulated cellular proliferation. The two phospholipids-induced chondrocyte proliferations were almost completely blocked by PD98059 but not by SB203580, suggesting that ERK but not p38 kinase is essentially required for the proliferation. Pertussis toxin almost completely inhibited the two phospholipids-induced cellular proliferation and ERK activation, indicating the crucial role of G i protein. This study demonstrates the physiological role of two important phospholipids (S1P and PhS1P) on the modulation of rat primary chondrocyte proliferation, and the crucial role played by ERK in the process

Cellular registration without behavioral recall of olfactory sensory input under general anesthesia.

Science.gov (United States)

Samuelsson, Andrew R; Brandon, Nicole R; Tang, Pei; Xu, Yan

2014-04-01

Previous studies suggest that sensory information is "received" but not "perceived" under general anesthesia. Whether and to what extent the brain continues to process sensory inputs in a drug-induced unconscious state remain unclear. One hundred seven rats were randomly assigned to 12 different anesthesia and odor exposure paradigms. The immunoreactivities of the immediate early gene products c-Fos and Egr1 as neural activity markers were combined with behavioral tests to assess the integrity and relationship of cellular and behavioral responsiveness to olfactory stimuli under a surgical plane of ketamine-xylazine general anesthesia. The olfactory sensory processing centers could distinguish the presence or absence of experimental odorants even when animals were fully anesthetized. In the anesthetized state, the c-Fos immunoreactivity in the higher olfactory cortices revealed a difference between novel and familiar odorants similar to that seen in the awake state, suggesting that the anesthetized brain functions beyond simply receiving external stimulation. Reexposing animals to odorants previously experienced only under anesthesia resulted in c-Fos immunoreactivity, which was similar to that elicited by familiar odorants, indicating that previous registration had occurred in the anesthetized brain. Despite the "cellular memory," however, odor discrimination and forced-choice odor-recognition tests showed absence of behavioral recall of the registered sensations, except for a longer latency in odor recognition tests. Histologically distinguishable registration of sensory processing continues to occur at the cellular level under ketamine-xylazine general anesthesia despite the absence of behavioral recognition, consistent with the notion that general anesthesia causes disintegration of information processing without completely blocking cellular communications.

Visualization of cholinoceptive neurons in the rat neocortex : colocalization of muscarinic and nicotinic acetylcholine receptors

NARCIS (Netherlands)

Zee, E.A. van der; Streefland, C.; Strosberg, A.D.; Schröder, H.; Luiten, P.G.M.

The present investigation analyzes the cellular distribution of muscarinic and nicotinic acetylcholine receptors in rat neocortex, by use of monoclonal antibodies raised against purified receptor proteins. The degree of colocalization of both types of receptors was determined by way of

Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

Science.gov (United States)

Kolosova, Nataliya G; Vitovtov, Anton O; Muraleva, Natalia A; Akulov, Andrey E; Stefanova, Natalia A; Blagosklonny, Mikhail V

2013-06-01

Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

Parallel Genetic Algorithms for calibrating Cellular Automata models: Application to lava flows

International Nuclear Information System (INIS)

D'Ambrosio, D.; Spataro, W.; Di Gregorio, S.; Calabria Univ., Cosenza; Crisci, G.M.; Rongo, R.; Calabria Univ., Cosenza

2005-01-01

Cellular Automata are highly nonlinear dynamical systems which are suitable far simulating natural phenomena whose behaviour may be specified in terms of local interactions. The Cellular Automata model SCIARA, developed far the simulation of lava flows, demonstrated to be able to reproduce the behaviour of Etnean events. However, in order to apply the model far the prediction of future scenarios, a thorough calibrating phase is required. This work presents the application of Genetic Algorithms, general-purpose search algorithms inspired to natural selection and genetics, far the parameters optimisation of the model SCIARA. Difficulties due to the elevated computational time suggested the adoption a Master-Slave Parallel Genetic Algorithm far the calibration of the model with respect to the 2001 Mt. Etna eruption. Results demonstrated the usefulness of the approach, both in terms of computing time and quality of performed simulations

Redox Status and Neuro Inflammation Indexes in Cerebellum and Motor Cortex of Wistar Rats Supplemented with Natural Sources of Omega-3 Fatty Acids and Astaxanthin: Fish Oil, Krill Oil, and Algal Biomass.

Science.gov (United States)

Polotow, Tatiana G; Poppe, Sandra C; Vardaris, Cristina V; Ganini, Douglas; Guariroba, Maísa; Mattei, Rita; Hatanaka, Elaine; Martins, Maria F; Bondan, Eduardo F; Barros, Marcelo P

2015-09-28

Health authorities worldwide have consistently recommended the regular consumption of marine fishes and seafood to preserve memory, sustain cognitive functions, and prevent neurodegenerative processes in humans. Shrimp, crabs, lobster, and salmon are of particular interest in the human diet due to their substantial provision of omega-3 fatty acids (n-3/PUFAs) and the antioxidant carotenoid astaxanthin (ASTA). However, the optimal ratio between these nutraceuticals in natural sources is apparently the key factor for maximum protection against most neuro-motor disorders. Therefore, we aimed here to investigate the effects of a long-term supplementation with (n-3)/PUFAs-rich fish oil, ASTA-rich algal biomass, the combination of them, or krill oil (a natural combination of both nutrients) on baseline redox balance and neuro-inflammation indexes in cerebellum and motor cortex of Wistar rats. Significant changes in redox metabolism were only observed upon ASTA supplementation, which reinforce its antioxidant properties with a putative mitochondrial-centered action in rat brain. Krill oil imposed mild astrocyte activation in motor cortex of Wistar rats, although no redox or inflammatory index was concomitantly altered. In summary, there is no experimental evidence that krill oil, fish oil, oralgal biomass (minor variation), drastically change the baseline oxidative conditions or the neuro-inflammatory scenario in neuromotor-associated rat brain regions.

Fenitrothion action at the endocannabinoid system leading to spermatotoxicity in Wistar rats

International Nuclear Information System (INIS)

Ito, Yuki; Tomizawa, Motohiro; Suzuki, Himiko; Okamura, Ai; Ohtani, Katsumi; Nunome, Mari; Noro, Yuki; Wang, Dong; Nakajima, Tamie; Kamijima, Michihiro

2014-01-01

Organophosphate (OP) compounds as anticholinesterase agents may secondarily act on diverse serine hydrolase targets, revealing unfavorable physiological effects including male reproductive toxicity. The present investigation proposes that fenitrothion (FNT, a major OP compound) acts on the endocannabinoid signaling system in male reproductive organs, thereby leading to spermatotoxicity (sperm deformity, underdevelopment, and reduced motility) in rats. FNT oxon (bioactive metabolite of FNT) preferentially inhibited the fatty acid amide hydrolase (FAAH), an endocannabinoid anandamide (AEA) hydrolase, in the rat cellular membrane preparation from the testis in vitro. Subsequently, male Wistar rats were treated orally with 5 or 10 mg/kg FNT for 9 weeks and the subchronic exposure unambiguously deteriorated sperm motility and morphology. The activity-based protein profiling analysis with a phosphonofluoridate fluorescent probe revealed that FAAH was selectively inhibited among the FNT-treated cellular membrane proteome in testis. Intriguingly, testicular AEA (endogenous substrate of FAAH) levels were elevated along with the FAAH inhibition caused by the subchronic exposure. More importantly, linear regression analyses for the FNT-elicited spermatotoxicity reveal a good correlation between the testicular FAAH activity and morphological indices or sperm motility. Accordingly, the present study proposes that the FNT-elicited spermatotoxicity appears to be related to inhibition of FAAH leading to overstimulation of the endocannabinoid signaling system, which plays crucial roles in spermatogenesis and sperm motility acquirement. - Highlights: • Subchronic exposure to fenitrothion induces spermatotoxicity in rats. • The fatty acid amide hydrolase is a potential target for the spermatotoxicity. • Overstimulation of the endocannabinoid signal possibly leads to the spermatotoxicity

Fenitrothion action at the endocannabinoid system leading to spermatotoxicity in Wistar rats

Energy Technology Data Exchange (ETDEWEB)

Ito, Yuki, E-mail: yukey@med.nagoya-cu.ac.jp [Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601 (Japan); Tomizawa, Motohiro [Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601 (Japan); Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo 156-8502 (Japan); Suzuki, Himiko [Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601 (Japan); Okamura, Ai [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Ohtani, Katsumi [National Institute of Occupational Safety and Health, Kanagawa 214-8585 (Japan); Nunome, Mari; Noro, Yuki [Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601 (Japan); Wang, Dong; Nakajima, Tamie [Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya 466-8550 (Japan); Kamijima, Michihiro, E-mail: kamijima@med.nagoya-cu.ac.jp [Department of Occupational and Environmental Health, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601 (Japan)

2014-09-15

Organophosphate (OP) compounds as anticholinesterase agents may secondarily act on diverse serine hydrolase targets, revealing unfavorable physiological effects including male reproductive toxicity. The present investigation proposes that fenitrothion (FNT, a major OP compound) acts on the endocannabinoid signaling system in male reproductive organs, thereby leading to spermatotoxicity (sperm deformity, underdevelopment, and reduced motility) in rats. FNT oxon (bioactive metabolite of FNT) preferentially inhibited the fatty acid amide hydrolase (FAAH), an endocannabinoid anandamide (AEA) hydrolase, in the rat cellular membrane preparation from the testis in vitro. Subsequently, male Wistar rats were treated orally with 5 or 10 mg/kg FNT for 9 weeks and the subchronic exposure unambiguously deteriorated sperm motility and morphology. The activity-based protein profiling analysis with a phosphonofluoridate fluorescent probe revealed that FAAH was selectively inhibited among the FNT-treated cellular membrane proteome in testis. Intriguingly, testicular AEA (endogenous substrate of FAAH) levels were elevated along with the FAAH inhibition caused by the subchronic exposure. More importantly, linear regression analyses for the FNT-elicited spermatotoxicity reveal a good correlation between the testicular FAAH activity and morphological indices or sperm motility. Accordingly, the present study proposes that the FNT-elicited spermatotoxicity appears to be related to inhibition of FAAH leading to overstimulation of the endocannabinoid signaling system, which plays crucial roles in spermatogenesis and sperm motility acquirement. - Highlights: • Subchronic exposure to fenitrothion induces spermatotoxicity in rats. • The fatty acid amide hydrolase is a potential target for the spermatotoxicity. • Overstimulation of the endocannabinoid signal possibly leads to the spermatotoxicity.

Acute Ethanol Gavage Attenuates Hemorrhage/Resuscitation-Induced Hepatic Oxidative Stress in Rats

Directory of Open Access Journals (Sweden)

B. Relja

2012-01-01

Full Text Available Acute ethanol intoxication increases the production of reactive oxygen species (ROS. Hemorrhagic shock with subsequent resuscitation (H/R also induces ROS resulting in cellular and hepatic damage in vivo. We examined the role of acute ethanol intoxication upon oxidative stress and subsequent hepatic cell death after H/R. 14 h before H/R, rats were gavaged with single dose of ethanol or saline (5 g/kg, EtOH and ctrl; H/R_EtOH or H/R_ctrl, resp.. Then, rats were hemorrhaged to a mean arterial blood pressure of 30±2 mmHg for 60 min and resuscitated. Two control groups underwent surgical procedures without H/R (sham_ctrl and sham_EtOH, resp.. Liver tissues were harvested at 2, 24, and 72 h after resuscitation. EtOH-gavage induced histological picture of acute fatty liver. Hepatic oxidative (4-hydroxynonenal, 4-HNE and nitrosative (3-nitrotyrosine, 3-NT stress were significantly reduced in EtOH-gavaged rats compared to controls after H/R. Proapoptotic caspase-8 and Bax expressions were markedly diminished in EtOH-gavaged animals compared with controls 2 h after resuscitation. EtOH-gavage increased antiapoptotic Bcl-2 gene expression compared with controls 2 h after resuscitation. iNOS protein expression increased following H/R but was attenuated in EtOH-gavaged animals after H/R. Taken together, the data suggest that acute EtOH-gavage may attenuate H/R-induced oxidative stress thereby reducing cellular injury in rat liver.

Control of alanine metabolism in rat liver by transport processes or cellular metabolism.

OpenAIRE

Fafournoux, P; Rémésy, C; Demigné, C

1983-01-01

1. Factors governing hepatic utilization of alanine were studied in vivo and in vitro in rats adapted to increasing dietary protein. 2. Hepatic alanine utilization was enhanced 5-fold with a 90%-casein diet, compared with a 13%-casein diet. The increased uptake resulted from enhanced fractional extraction in the presence of high concentrations of alanine in the portal vein. 3. The increase in alanine metabolism on high-protein diets was associated with an increase in alanine aminotransferase ...

The prospective protective effect of selenium nanoparticles against chromium-induced oxidative and cellular damage in rat thyroid

Directory of Open Access Journals (Sweden)

Hassanin KMA

2013-05-01

Full Text Available Kamel MA Hassanin,1 Samraa H Abd El-Kawi,2 Khalid S Hashem1 1Department of Biochemistry, Faculty of Veterinary Medicine, 2Department of Histology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt Background: Nanotechnology has enabled researchers to synthesize nanosize particles that possess increased surface areas. Compared to conventional microparticles, it has resulted in increased interactions with biological targets. Objective: The objective of this study was to determine the protective ability of selenium nanoparticles against hexavalent chromium-induced thyrotoxicity. Design: Twenty male rats were used in the study, and arbitrarily assigned to four groups. Group 1 was the control group, and was given phosphate-buffered saline. Group 2 was the chromium-treated group and was given K2Cr2O7 60 µg/kg body weight intraperitoneally as a single dose on the third day of administration. Group 3 was the nano-selenium-treated group and was given selenium nanoparticles (size 3–20 nm 0.5 mg/kg body weight intraperitoneally daily for 5 consecutive days. Group 4 was the nano-selenium chromium-treated group, which received selenium nanoparticles for 5 days and a single dose of K2Cr2O7 on the third day of administration. Materials and methods: Blood samples were collected from rats for measuring thyroid hormones (free triiodothyronine [T3] and free thyroxine [T4] and oxidative and antioxidant parameters (malondialdehyde [MDA], reduced glutathione [GSH], catalase, and superoxide dismutase [SOD]. Upon dissection, thyroid glands were taken for histopathological examination by using paraffin preparations stained with hematoxylin and eosin (H&E and Masson’s trichrome. Immunohistochemical staining was performed for detecting cellular proliferation using Ki67 antibodies. Results: The present study shows that K2Cr2O7 has a toxic effect on the thyroid gland as a result of inducing a marked oxidative damage and release of reactive oxygen species

Research on garlic capsule and selenium-vitamin A, vitamin B, vitamin C applied in therapy of acute hepatocellular damage in a rat model

Directory of Open Access Journals (Sweden)

Jacob Kehinde Akintunde

2015-10-01

Conclusions: Collectively, the results suggest that therapeutic dose of lisinopril elicits toxicity in male rats through induction of oxidative damage and depletion of cellular adenosine triphosphate. The reversal effects of GAR and SACE during lisinopril treatment suggest that these antioxidants may find clinical application in cellular damage involving ROS and adenosine triphosphate.

Gene expression changes induced by the tumorigenic pyrrolizidine alkaloid riddelliine in liver of Big Blue rats

Science.gov (United States)

Mei, Nan; Guo, Lei; Liu, Ruqing; Fuscoe, James C; Chen, Tao

2007-01-01

Background Pyrrolizidine alkaloids (PAs) are probably the most common plant constituents that poison livestock, wildlife, and humans worldwide. Riddelliine is isolated from plants grown in the western United States and is a prototype of genotoxic PAs. Riddelliine was used to investigate the genotoxic effects of PAs via analysis of gene expression in the target tissue of rats in this study. Previously we observed that the mutant frequency in the liver of rats gavaged with riddelliine was 3-fold higher than that in the control group. Molecular analysis of the mutants indicated that there was a statistically significant difference between the mutational spectra from riddelliine-treated and control rats. Results Riddelliine-induced gene expression profiles in livers of Big Blue transgenic rats were determined. The female rats were gavaged with riddelliine at a dose of 1 mg/kg body weight 5 days a week for 12 weeks. Rat whole genome microarray was used to perform genome-wide gene expression studies. When a cutoff value of a two-fold change and a P-value less than 0.01 were used as gene selection criteria, 919 genes were identified as differentially expressed in riddelliine-treated rats compared to the control animals. By analysis with the Ingenuity Pathway Analysis Network, we found that these significantly changed genes were mainly involved in cancer, cell death, tissue development, cellular movement, tissue morphology, cell-to-cell signaling and interaction, and cellular growth and proliferation. We further analyzed the genes involved in metabolism, injury of endothelial cells, liver abnormalities, and cancer development in detail. Conclusion The alterations in gene expression were directly related to the pathological outcomes reported previously. These results provided further insight into the mechanisms involved in toxicity and carcinogenesis after exposure to riddelliine, and permitted us to investigate the interaction of gene products inside the signaling networks

Adenovirus type 5 induces progression of quiescent rat cells into S phase without polyamine accumulation.

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Cheetham, B F; Shaw, D C; Bellett, A J

1982-01-01

Adenovirus type 5 induces cellular DNA synthesis and thymidine kinase in quiescent rat cells but does not induce ornithine decarboxylase. We now show that unlike serum, adenovirus type 5 fails to induce S-adenosylmethionine decarboxylase or polyamine accumulation. The inhibition by methylglyoxal bis(guanylhydrazone) of the induction of thymidine kinase by adenovirus type 5 is probably unrelated to its effects on polyamine biosynthesis. Thus, induction of cellular thymidine kinase and DNA replication by adenovirus type 5 is uncoupled from polyamine accumulation. PMID:7177112

Toxicity of hydroxyurea in rats and dogs.

Science.gov (United States)

Morton, Daniel; Reed, Lori; Huang, Wenhu; Marcek, John M; Austin-LaFrance, Robert; Northcott, Carrie A; Schelling, Scott H; Enerson, Bradley E; Tomlinson, Lindsay

2015-06-01

The toxicity of hydroxyurea, a treatment for specific neoplasms, sickle-cell disease, polycythemia, and thrombocytosis that kills cells in mitosis, was assessed in repeat-dose, oral gavage studies in rats and dogs and a cardiovascular study in telemetered dogs. Hydroxyurea produced hematopoietic, lymphoid, cardiovascular, and gastrointestinal toxicity with steep dose response curves. In rats dosed for 10 days, 50 mg/kg/day was tolerated; 500 mg/kg/day produced decreased body weight gain; decreased circulating leukocytes, erythrocytes, and platelets; decreased cellularity of thymus, lymph nodes, and bone marrow; and epithelial degeneration and/or dysplasia of the stomach and small intestine; 1,500 mg/kg/day resulted in deaths on day 5. In dogs, a single dose at ≥ 250 mg/kg caused prostration leading to unscheduled euthanasia. Dogs administered 50 mg/kg/day for 1 month had decreased circulating leukocytes, erythrocytes, and platelets; increased bone marrow cellularity with decreased maturing granulocytes; increased creatinine kinase activity; and increased iron pigment in bone marrow and hepatic sinusoidal cells. In telemetered dogs, doses ≥ 15 mg/kg decreased systolic blood pressure (BP); 50 mg/kg increased diastolic BP, heart rate, and change in blood pressure over time (+dP/dt), and decreased QT and PR intervals and maximum left ventricular systolic and end diastolic pressures with measures returning to control levels within 24 hr. © 2014 by The Author(s).

Cytoplasmic binding and disposition kinetics of diclofenac in the isolated perfused rat liver

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Weiss, Michael; Kuhlmann, Olaf; Hung, Daniel Y; Roberts, Michael S

2000-01-01

The binding kinetics of diclofenac to hepatocellular structures were evaluated in the perfused rat liver using the multiple indicator dilution technique and a stochastic model of organ transit time density.The single-pass, in situ rat liver preparation was perfused with buffer solution (containing 2% albumin) at 30 ml min−1. Diclofenac and [14C]-sucrose (extracellular reference) were injected simultaneously as a bolus dose into the portal vein (six experiments in three rats). An analogous series of experiments was performed with [14C]-diclofenac and [3H]-sucrose.The diclofenac outflow data were analysed using three models of intracellular distribution kinetics, assuming (1) instantaneous distribution and binding (well-mixed model), (2) ‘slow' binding at specific intracellular sites after instantaneous distribution throughout the cytosol (slow binding model), and (3) ‘slowing' of cytoplasmic diffusion due to instantaneous binding (slow diffusion model).The slow binding model provided the best description of the data. The rate constants for cellular influx and sequestration were 0.126±0.026 and 0.013±0.009 s−1, respectively. The estimated ratio of cellular initial distribution volume to extracellular volume of 2.82 indicates an almost instantaneous distribution in the cellular water space, while the corresponding ratio of 5.54 estimated for the apparent tissue distribution volume suggests a relatively high hepatocellular binding. The non-instantaneous intracellular equilibration process was characterized by time constants of the binding and unbinding process of 53.8 and 49.5 s, respectively. The single-pass availability of diclofenac was 86%. The results obtained with [14C]-diclofenac and [3H]-sucrose were not statistically different. PMID:10903973

Olive Oil effectively mitigates ovariectomy-induced osteoporosis in rats

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Saleh Hanan A

2011-02-01

Full Text Available Abstract Background Osteoporosis, a reduction in bone mineral density, represents the most common metabolic bone disease. Postmenopausal women are particularly susceptible to osteoporosis when their production of estrogen declines. For these women, fracture is a leading cause of morbidity and mortality. This study was conducted to evaluate the protective effects of olive oil supplementation against osteoporosis in ovariectomized (OVX rats. Methods We studied adult female Wistar rats aged 12-14 months, divided into three groups: sham-operated control (SHAM, ovariectomized (OVX, and ovariectomized rats supplemented with extravirgin olive oil (Olive-OVX orally for 12 weeks; 4 weeks before ovariectomy and 8 weeks after. At the end of the experiment, blood samples were collected. Plasma levels of calcium, phosphorus, alkaline phosphatase (ALP, malondialdehyde (MDA, and nitrates were assayed. Specimens from both the tibia and the liver were processed for light microscopic examination. Histomorphometric analysis of the tibia was also performed. Results The OVX-rats showed a significant decrease in plasma calcium levels, and a significant increase in plasma ALP, MDA, and nitrates levels. These changes were attenuated by olive oil supplementation in the Olive-OVX rats. Light microscopic examination of the tibia of the OVX rats revealed a significant decrease in the cortical bone thickness (CBT and the trabecular bone thickness (TBT. In addition, there was a significant increase in the osteoclast number denoting bone resorption. In the Olive-OVX rats these parameters were markedly improved as compared to the OVX group. Examination of the liver specimens revealed mononuclear cellular infiltration in the portal areas in the OVX-rats which was not detected in the Olive-OVX rats. Conclusions Olive oil effectively mitigated ovariectomy-induced osteoporosis in rats, and is a promising candidate for the treatment of postmenopausal osteoporosis.

Serrapeptase and nattokinase intervention for relieving Alzheimer's disease pathophysiology in rat model.

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Fadl, N N; Ahmed, H H; Booles, H F; Sayed, A H

2013-07-01

Serrapeptase (SP) and nattokinase (NK) are proteolytic enzymes belonging to serine proteases. In this study, we hypothesized that SP and NK could modulate certain factors that are associated with Alzheimer's disease (AD) pathophysiology in the experimental model. Oral administration of aluminium chloride (AlCl3) in a dose of 17 mg/kg body weight (bw) daily for 45 days induced AD-like pathology in male rats with a significant increase in brain acetylcholinesterase (AchE) activity, transforming growth factor β (TGF-β), Fas and interleukin-6 (IL-6) levels. Meanwhile, AlCl3 supplementation produced significant decrease in brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) when compared with control values. Also, AlCl3 administration caused significant decline in the expression levels of disintegrin and metalloproteinase domain 9 (ADAM9) and a disintegrin and metalloproteinase domain 10 (ADAM10) genes in the brain. Histological investigation of brain tissue of rat model of AD showed neuronal degeneration in the hippocampus and focal hyalinosis with cellular as well as a cellular amyloid plaques formation. Oral administration of SP or NK in a rat model of AD daily for 45 days resulted in a significant decrease in brain AchE activity, TGF-β, Fas and IL-6 levels. Also, the treatment with these enzymes produced significant increase in BDNF and IGF-1 levels when compared with the untreated AD-induced rats. Moreover, both SP and NK could markedly increase the expression levels of ADAM9 and ADAM10 genes in the brain tissue of the treated rats. These findings were well confirmed by the histological examination of the brain tissue of the treated rats. The present results support our hypothesis that the oral administration of proteolytitc enzymes, SP and/or NK, would have an effective role in modulating certain factors characterizing AD. Thus, these enzymes may have a therapeutic application in the treatment of AD.

A comparative cellular and molecular biology of longevity database.

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Stuart, Jeffrey A; Liang, Ping; Luo, Xuemei; Page, Melissa M; Gallagher, Emily J; Christoff, Casey A; Robb, Ellen L

2013-10-01

Discovering key cellular and molecular traits that promote longevity is a major goal of aging and longevity research. One experimental strategy is to determine which traits have been selected during the evolution of longevity in naturally long-lived animal species. This comparative approach has been applied to lifespan research for nearly four decades, yielding hundreds of datasets describing aspects of cell and molecular biology hypothesized to relate to animal longevity. Here, we introduce a Comparative Cellular and Molecular Biology of Longevity Database, available at ( http://genomics.brocku.ca/ccmbl/ ), as a compendium of comparative cell and molecular data presented in the context of longevity. This open access database will facilitate the meta-analysis of amalgamated datasets using standardized maximum lifespan (MLSP) data (from AnAge). The first edition contains over 800 data records describing experimental measurements of cellular stress resistance, reactive oxygen species metabolism, membrane composition, protein homeostasis, and genome homeostasis as they relate to vertebrate species MLSP. The purpose of this review is to introduce the database and briefly demonstrate its use in the meta-analysis of combined datasets.

Social stress engages opioid regulation of locus coeruleus norepinephrine neurons and induces a state of cellular and physical opiate dependence.

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Chaijale, Nayla N; Curtis, Andre L; Wood, Susan K; Zhang, Xiao-Yan; Bhatnagar, Seema; Reyes, Beverly As; Van Bockstaele, Elisabeth J; Valentino, Rita J

2013-09-01

Stress is implicated in diverse psychiatric disorders including substance abuse. The locus coeruleus-norepinephrine (LC-NE) system is a major stress response system that is also a point of intersection between stress neuromediators and endogenous opioids and so may be a site at which stress can influence drug-taking behaviors. As social stress is a common stressor for humans, this study characterized the enduring impact of repeated social stress on LC neuronal activity. Rats were exposed to five daily consecutive sessions of social stress using the resident-intruder model or control manipulation. LC discharge rate recorded 2 days after the last manipulation was decreased in stressed rats compared with controls. By 10 days after the last manipulation, LC rates were comparable between groups. Systemic administration of the opiate antagonist, naloxone, robustly increased LC discharge rate in a manner suggestive of opiate withdrawal, selectively in stressed rats when administered 2 or 10 days after the last manipulation. This was accompanied by behavioral signs of mild opiate withdrawal. Western blot and electron microscopic studies indicated that repeated social stress decreased corticotropin-releasing factor type 1 receptor and increased μ-opioid receptor levels in the LC. Together, the results suggest that repeated social stress engages endogenous opioid modulation of LC activity and induces signs of cellular and physical opiate dependence that endure after the stress. These cellular effects may predispose individuals with a history of repeated social stress to substance abuse behaviors.

Inbred rats as a model to study persistent renal colonization and associated cellular immune responsiveness

Science.gov (United States)

Pathogenic species of Leptospira cause leptospirosis, a bacterial zoonotic disease with a global distribution affecting over one million people annually. Rats are regarded as one of the most significant reservoir hosts of infection for human disease, and in the absence of clinical signs of infection...

Rat brain sagittal organotypic slice cultures as an ex vivo dopamine cell loss system.

Science.gov (United States)

McCaughey-Chapman, Amy; Connor, Bronwen

2017-02-01

Organotypic brain slice cultures are a useful tool to study neurological function as they provide a more complex, 3-dimensional system than standard 2-dimensional in vitro cell cultures. Building on a previously developed mouse brain slice culture protocol, we have developed a rat sagittal brain slice culture system as an ex vivo model of dopamine cell loss. We show that rat brain organotypic slice cultures remain viable for up to 6 weeks in culture. Using Fluoro-Gold axonal tracing, we demonstrate that the slice 3-dimensional cytoarchitecture is maintained over a 4 week culturing period, with particular focus on the nigrostriatal pathway. Treatment of the cultures with 6-hydroxydopamine and desipramine induces a progressive loss of Fluoro-Gold-positive nigral cells with a sustained loss of tyrosine hydroxylase-positive nigral cells. This recapitulates the pattern of dopaminergic degeneration observed in the rat partial 6-hydroxydopamine lesion model and, most importantly, the progressive pathology of Parkinson's disease. Our slice culture platform provides an advance over other systems, as we demonstrate for the first time 3-dimensional cytoarchitecture maintenance of rat nigrostriatal sagittal slices for up to 6 weeks. Our ex vivo organotypic slice culture system provides a long term cellular platform to model Parkinson's disease, allowing for the elucidation of mechanisms involved in dopaminergic neuron degeneration and the capability to study cellular integration and plasticity ex vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

Mitochondrial ribosomal protein S18-2 evokes chromosomal instability and transforms primary rat skin fibroblasts

KAUST Repository

Kashuba, Elena

2015-05-12

We have shown earlier that overexpression of the human mitochondrial ribosomal protein MRPS18-2 (S18-2) led to immortalization of primary rat embryonic fibroblasts. The derived cells expressed the embryonic stem cell markers, and cellular pathways that control cell proliferation, oxidative phosphorylation, cellular respiration, and other redox reactions were activated in the immortalized cells. Here we report that, upon overexpression of S18-2 protein, primary rat skin fibroblasts underwent cell transformation. Cells passed more than 300 population doublings, and two out of three tested clones gave rise to tumors in experimental animals. Transformed cells showed anchorage-independent growth and loss of contact inhibition; they expressed epithelial markers, such as E-cadherin and β-catenin. Transformed cells showed increased telomerase activity, disturbance of the cell cycle, and chromosomal instability. Taken together, our data suggest that S18-2 is a newly identified oncoprotein that may be involved in cancerogenesis.

Cuttlebone-like V2O5 Nanofibre Scaffolds - Advances in Structuring Cellular Solids

Science.gov (United States)

Knöller, Andrea; Runčevski, Tomče; Dinnebier, Robert E.; Bill, Joachim; Burghard, Zaklina

2017-02-01

The synthesis of ceramic materials combining high porosity and permeability with good mechanical stability is challenging, as optimising the latter requires compromises regarding the first two properties. Nonetheless, significant progress can be made in this direction by taking advantage of the structural design principles evolved by nature. Natural cellular solids achieve good mechanical stability via a defined hierarchical organisation of the building blocks they are composed of. Here, we report the first synthetic, ceramic-based scaffold whose architecture closely mimics that of cuttlebone -a structural biomaterial whose porosity exceeds that of most other natural cellular solids, whilst preserving an excellent mechanical strength. The nanostructured, single-component scaffold, obtained by ice-templated assembly of V2O5 nanofibres, features a highly sophisticated and elaborate architecture of equally spaced lamellas, which are regularly connected by pillars as lamella support. It displays an unprecedented porosity of 99.8 %, complemented by an enhanced mechanical stability. This novel bioinspired, functional material not only displays mechanical characteristics similar to natural cuttlebone, but the multifunctionality of the V2O5 nanofibres also renders possible applications, including catalysts, sensors and electrodes for energy storage.

Cellular MR Imaging

Directory of Open Access Journals (Sweden)

Michel Modo

2005-07-01

Full Text Available Cellular MR imaging is a young field that aims to visualize targeted cells in living organisms. In order to provide a different signal intensity of the targeted cell, they are either labeled with MR contrast agents in vivo or prelabeled in vitro. Either (ultrasmall superparamagnetic iron oxide [(USPIO] particles or (polymeric paramagnetic chelates can be used for this purpose. For in vivo cellular labeling, Gd3+- and Mn2+- chelates have mainly been used for targeted hepatobiliary imaging, and (USPIO-based cellular imaging has been focused on imaging of macrophage activity. Several of these magneto-pharmaceuticals have been FDA-approved or are in late-phase clinical trials. As for prelabeling of cells in vitro, a challenge has been to induce a sufficient uptake of contrast agents into nonphagocytic cells, without affecting normal cellular function. It appears that this issue has now largely been resolved, leading to an active research on monitoring the cellular biodistribution in vivo following transplantation or transfusion of these cells, including cell migration and trafficking. New applications of cellular MR imaging will be directed, for instance, towards our understanding of hematopoietic (immune cell trafficking and of novel guided (stem cell-based therapies aimed to be translated to the clinic in the future.

PERIPHERAL LIPOPOLYSACCHARIDE STIMULATION INDUCES INTERLEUKIN-1-BETA MESSENGER-RNA IN RAT-BRAIN MICROGLIAL CELLS

NARCIS (Netherlands)

BUTTINI, M; BODDEKE, H

The inflammatory cytokine interleukin-1 acts as an endogenous pyrogen in organisms affected by infectious diseases and has been shown to influence the activity of the central nervous system. Using in situ hybridization histochemistry, we have examined the cellular source of interleukin-1 beta in rat

[Crabtree effect caused by ketoses in isolated rat hepatocytes].

Science.gov (United States)

Martínez, P; Carrascosa, J M; Núñez de Castro, I

1982-01-01

Oxygen uptake and glycolytic activity were studied in hepatocytes isolated from fed rats. The addition of fructose or tagatose resulted in a 38% and 31% inhibition of cellular respiration respectively. The addition of 10 mM D-glyceraldehyde caused a slight Crabtree effect. Glucose, L-sorbose, or glycerol failed to modify oxygen consumption. Only incubation in the presence of fructose showed a high aerobic glycolysis measured by lactate production.

Cellular and extracellular dehydration, and angiotensin as stimuli to drinking in the common iguana Iguana iguana.

Science.gov (United States)

Fitzsimons, J T; Kaufman, S

1977-01-01

1. After water deprivation, the iguana promptly drank slightly more than enough water to restore the body fluids to isotonicity even under conditions of hypervolaemia. 2. In response to systemic injections of hypertonic solutions of NaCl and sucrose, the iguana drank and retained enough water to dilute the injected load to isotonicity irrespective of whether water was offered immediately or after 3 hr, and irrespective of whether the solute was administered I.V. or I.P. 3. Hypertonic solutions to glucose, urea, sorbitol and KCl caused little drinking. 4. The long latencies to drinking after hypertonic loads, which were not dependent on the nature of the solute, the route of administration or the dosage, were shown not to be a result of slow distribution of the solute throughout the body fluids. 5. Clearance of injected solutes via renal and extra-renal (nasal salt gland) routes was negligible during the 6 hr experimental period. 6. Measurements of plasma [Na], haematocrit, osmotic pressure and inulin space showed that the iguana drank, in response to cellular dehydration, enough water to restore the intracellular fluid volume to normal. 7. We conclude that, in response to substances which dehydrate cells, the iguana regulates its body osmolality precisely and efficiently provided it is able to do so by drinking. In this respect the responses of the iguana are similar to those of the nephrectomized rat since, in the short term, both rely exclusively on drinking to restore cellular water to normal. 8. The iguana also drinks in response to extracellular dehydration produced by hyperoncotic peritoneal dialysis, and in response to I.P. angiotensin II. PMID:850202

Programmable cellular arrays. Faults testing and correcting in cellular arrays

International Nuclear Information System (INIS)

Cercel, L.

1978-03-01

A review of some recent researches about programmable cellular arrays in computing and digital processing of information systems is presented, and includes both combinational and sequential arrays, with full arbitrary behaviour, or which can realize better implementations of specialized blocks as: arithmetic units, counters, comparators, control systems, memory blocks, etc. Also, the paper presents applications of cellular arrays in microprogramming, in implementing of a specialized computer for matrix operations, in modeling of universal computing systems. The last section deals with problems of fault testing and correcting in cellular arrays. (author)

Effects of thyroxine and dexamethasone on rat submandibular glands

International Nuclear Information System (INIS)

Sagulin, G.B.; Roomans, G.M.

1989-01-01

Glucocorticoids and thyroxine are known to have a marked effect on the flow rate and protein composition of rat parotid saliva in hormonally intact animals. In the present study, the effects of a one-week treatment of male rats with dexamethasone and thyroxine were studied by electron microscopy and x-ray micro-analysis, and by measurement of the flow rate and determination of the chemical composition of pilocarpine-induced submandibular saliva. Thyroxine had the most extensive effects on the submandibular gland. The acinar cells were enlarged and filled with mucus; the cellular calcium concentration was significantly increased. The flow rate of the submandibular saliva was significantly reduced compared with that in saline-injected control animals. Thyroxine caused an increase in the concentrations of protein, total calcium, and potassium in the saliva. Dexamethasone had no significant effects on gland ultrastructure or on the elemental composition of the acinar cells; flow rate was not affected, but the concentrations of protein, calcium, and potassium were significantly increased. The effects of dexamethasone and thyroxine on the flow rate and protein composition of pilocarpine-induced rat submandibular saliva differ from those reported earlier for rat parotid saliva after simultaneous stimulation with pilocarpine and isoproterenol

Rat testicular impairment induced by electromagnetic radiation from a conventional cellular telephone and the protective effects of the antioxidants vitamins C and E.

Science.gov (United States)

Al-Damegh, Mona Abdullah

2012-07-01

The aim of this study was to investigate the possible effects of electromagnetic radiation from conventional cellular phone use on the oxidant and antioxidant status in rat blood and testicular tissue and determine the possible protective role of vitamins C and E in preventing the detrimental effects of electromagnetic radiation on the testes. The treatment groups were exposed to an electromagnetic field, electromagnetic field plus vitamin C (40 mg/kg/day) or electromagnetic field plus vitamin E (2.7 mg/kg/day). All groups were exposed to the same electromagnetic frequency for 15, 30, and 60 min daily for two weeks. There was a significant increase in the diameter of the seminiferous tubules with a disorganized seminiferous tubule sperm cycle interruption in the electromagnetism-exposed group. The serum and testicular tissue conjugated diene, lipid hydroperoxide, and catalase activities increased 3-fold, whereas the total serum and testicular tissue glutathione and glutathione peroxidase levels decreased 3-5 fold in the electromagnetism-exposed animals. Our results indicate that the adverse effect of the generated electromagnetic frequency had a negative impact on testicular architecture and enzymatic activity. This finding also indicated the possible role of vitamins C and E in mitigating the oxidative stress imposed on the testes and restoring normality to the testes.

Activation of human natural killer cells by the soluble form of cellular prion protein

Energy Technology Data Exchange (ETDEWEB)

Seong, Yeon-Jae [Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of); Hafis Clinic, Seoul (Korea, Republic of); Sung, Pil Soo; Jang, Young-Soon; Choi, Young Joon [Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of); Park, Bum-Chan [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Park, Su-Hyung [Laboratory of Translational Immunology and Vaccinology, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of); Park, Young Woo [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Shin, Eui-Cheol, E-mail: ecshin@kaist.ac.kr [Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of)

2015-08-21

Cellular prion protein (PrP{sup C}) is widely expressed in various cell types, including cells of the immune system. However, the specific roles of PrP{sup C} in the immune system have not been clearly elucidated. In the present study, we investigated the effects of a soluble form of recombinant PrP{sup C} protein on human natural killer (NK) cells. Recombinant soluble PrP{sup C} protein was generated by fusion of human PrP{sup C} with the Fc portion of human IgG{sub 1} (PrP{sup C}-Fc). PrP{sup C}-Fc binds to the surface of human NK cells, particularly to CD56{sup dim} NK cells. PrP{sup C}-Fc induced the production of cytokines and chemokines and the degranulation of granzyme B from NK cells. In addition, PrP{sup C}-Fc facilitated the IL-15-induced proliferation of NK cells. PrP{sup C}-Fc induced phosphorylation of ERK-1/2 and JNK in NK cells, and inhibitors of the ERK or the JNK pathways abrogated PrP{sup C}-Fc-induced cytokine production in NK cells. In conclusion, the soluble form of recombinant PrP{sup C}-Fc protein activates human NK cells via the ERK and JNK signaling pathways. - Highlights: • Recombinant soluble PrP{sup C} (PrP{sup C}-Fc) was generated by fusion of human PrP{sup C} with IgG1 Fc portion. • PrP{sup C}-Fc protein induces the production of cytokines and degranulation from human NK cells. • PrP{sup C}-Fc protein enhances the IL-15-induced proliferation of human NK cells. • PrP{sup C}-Fc protein activates human NK cells via the ERK and JNK signaling pathways.

Effect of Nigella sativa Linn oil on tramadol-induced hepato- and nephrotoxicity in adult male albino rats

Directory of Open Access Journals (Sweden)

A. Elkhateeb

2015-01-01

Full Text Available The present study was carried out to evaluate the role of Nigella sativa Linn (NsL oil against subacute tramadol-induced hepatotoxicity, nephrotoxicity as well as oxidative stress in adult male albino rats. Sixty adult male albino rats were divided into four groups. Group I: control group; 30 rats equally subdivided into: Ia; −ve control group, Ib; +ve control group received saline, Ic; +ve control group received corn oil. Group II: 10 rats received NsL oil; 1 mg/kg in 1 ml corn oil/day, group III: 10 rats received tramadol; 30 mg/kg/day, group IV: 10 rats received tramadol + NsL oil in the previous doses. Treatments were given by gavage for 30 days. Then rats were sacrificed and specimens from the livers and kidneys were taken for biochemical and histopathological study. Biochemical data showed elevated liver enzymes; alanine transaminase (ALT, aspartate transaminase (AST, gamma glutamyltransferase (GGT, bilirubin as well as urea and creatinine in tramadol group. A significant increase in hepatic and renal malondialdehyde (MDA and a decrease in glutathione peroxidase (GPx levels were also noticed. Histological analysis of the liver showed vacuolated hepatocyte cytoplasm indicating hydropic degeneration with binucleated cells, apoptotic nuclei, congested central veins, cellular infiltration and hemorrhage. Kidney sections revealed atrophied glomeruli with collapsed tufts and wide Bowman's space, degenerated tubules, hemorrhage and mononuclear cellular infiltration. There was also an increase in area % of collagen fibers in both organs. Concomitant use of NsL oil with tramadol induced partial improvement in the hepato- and nephrotoxic effects. In conclusion, this study suggested that concomitant use of NsL oil with tramadol proved to be capable of ameliorating tramadol-induced hepato- and nephrotoxicity which might be due to its antioxidant potential.

Monocyte Activation in Immunopathology: Cellular Test for Development of Diagnostics and Therapy

Directory of Open Access Journals (Sweden)

Ekaterina A. Ivanova

2016-01-01

Full Text Available Several highly prevalent human diseases are associated with immunopathology. Alterations in the immune system are found in such life-threatening disorders as cancer and atherosclerosis. Monocyte activation followed by macrophage polarization is an important step in normal immune response to pathogens and other relevant stimuli. Depending on the nature of the activation signal, macrophages can acquire pro- or anti-inflammatory phenotypes that are characterized by the expression of distinct patterns of secreted cytokines and surface antigens. This process is disturbed in immunopathologies resulting in abnormal monocyte activation and/or bias of macrophage polarization towards one or the other phenotype. Such alterations could be used as important diagnostic markers and also as possible targets for the development of immunomodulating therapy. Recently developed cellular tests are designed to analyze the phenotype and activity of living cells circulating in patient’s bloodstream. Monocyte/macrophage activation test is a successful example of cellular test relevant for atherosclerosis and oncopathology. This test demonstrated changes in macrophage activation in subclinical atherosclerosis and breast cancer and could also be used for screening a panel of natural agents with immunomodulatory activity. Further development of cellular tests will allow broadening the scope of their clinical implication. Such tests may become useful tools for drug research and therapy optimization.

Susceptibility to radiation-induced mammary carcinoma in genetically resistant Copenhagen rats

International Nuclear Information System (INIS)

Kamiya, Kenji; Nitta, Yumiko; Gould, M.N.

2000-01-01

The objective of this experiment was to compare the cellular basis of mammary cancer induction by a chemical carcinogen with induction by ionizing radiation in three strains of rats (inbred that have different genetic susceptibilities: COP rats, F344 rats, and WF rats). Rats were given a single intraperitoneal injection of 50 mg MNU/kg body weight as a mammary-tumor-inducing chemical carcinogen and were irradiated with a 3.0 Gy dose of 60 Co gamma rays at a dose rate of 26.58±1.19 cGy/min. The rats were inspected weekly, and they were killed and necropsied whenever palpable tumors were detected or they became moribund. The histopathological and immunohistochemical characteristics of the mammary tumors were investigated. A transplantation experiment using selected primary mammary tumors that developed in COP rats exposed to gamma rays was also performed to investigate the transplantability of mammary tumors induced by ionizing radiation. The sensitivity of the WF and F344 rats and the resistance of the COP rats to mammary carcinoma induction by the chemical carcinogen MNU was confirmed. In contrast to the chemical carcinogens, no difference in susceptibility to radiation induction of mammary carcinomas was detected among the three strains of rats, and immunohistochemical examination indicated that the radiation-induced carcinomas consisted of more highly differentiated cells than the MNU-induced cancers. The results of the experiment appear to support the hypothesis that differentiated mammary gland tissue is more resistant to chemical carcinogens than to cancer induction by radiation. The authors conclude that radiation-induced cancers in rats may develop via different pathways or from different cell populations than chemically induced cancers. (K.H.)

Susceptibility to radiation-induced mammary carcinoma in genetically resistant Copenhagen rats

Energy Technology Data Exchange (ETDEWEB)

Kamiya, Kenji; Nitta, Yumiko [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine; Gould, M.N.

2000-07-01

The objective of this experiment was to compare the cellular basis of mammary cancer induction by a chemical carcinogen with induction by ionizing radiation in three strains of rats (inbred that have different genetic susceptibilities: COP rats, F344 rats, and WF rats). Rats were given a single intraperitoneal injection of 50 mg MNU/kg body weight as a mammary-tumor-inducing chemical carcinogen and were irradiated with a 3.0 Gy dose of {sup 60} Co gamma rays at a dose rate of 26.58{+-}1.19 cGy/min. The rats were inspected weekly, and they were killed and necropsied whenever palpable tumors were detected or they became moribund. The histopathological and immunohistochemical characteristics of the mammary tumors were investigated. A transplantation experiment using selected primary mammary tumors that developed in COP rats exposed to gamma rays was also performed to investigate the transplantability of mammary tumors induced by ionizing radiation. The sensitivity of the WF and F344 rats and the resistance of the COP rats to mammary carcinoma induction by the chemical carcinogen MNU was confirmed. In contrast to the chemical carcinogens, no difference in susceptibility to radiation induction of mammary carcinomas was detected among the three strains of rats, and immunohistochemical examination indicated that the radiation-induced carcinomas consisted of more highly differentiated cells than the MNU-induced cancers. The results of the experiment appear to support the hypothesis that differentiated mammary gland tissue is more resistant to chemical carcinogens than to cancer induction by radiation. The authors conclude that radiation-induced cancers in rats may develop via different pathways or from different cell populations than chemically induced cancers. (K.H.)

Chronic aspiration of gastric and duodenal contents and their effects on inflammatory cytokine production in respiratory system of rats.

OpenAIRE

Mitra Samareh Fekri; Hamid Reza Poursalehi; Hamid Najafipour; Beydolah Shahouzahi; Nasrin Bazargan Harandi

2014-01-01

Gastroesophageal reflux disease (GERD) is defined with clinical symptoms of heart burning and regurgitation. It may be associated with external esophageal symptoms such as chronic cough, asthma, laryngitis, chronic lung disease, sinusitis and pulmonary fibrosis. In the present study, rats with chronic aspiration of gastroduodenal contents were studied for cellular phenotypes and cytokine concentrations in bronchoalveolar lavage and lung tissue. Thirty-six male Albino N-MRI rats were randomly ...

Chronic administration of thiamine pyrophosphate decreases age-related histological atrophic testicular changes and improves sexual behavior in male Wistar rats.

Science.gov (United States)

Hernández-Montiel, H L; Vásquez López, C M; González-Loyola, J G; Vega-Anaya, G C; Villagrán-Herrera, M E; Gallegos-Corona, M A; Saldaña, C; Ramos Gómez, M; García Horshman, P; García Solís, P; Solís-S, J C; Robles-Osorio, M L; Ávila Morales, J; Varela-Echavarría, A; Paredes Guerrero, R

2014-06-01

Aging is a multifactorial universal process and constitutes the most important risk factor for chronic-degenerative diseases. Although it is a natural process, pathological aging arises when these changes occur quickly and the body is not able to adapt. This is often associated with the generation of reactive oxygen species (ROS), inflammation, and a decrease in the endogenous antioxidant systems, constituting a physiopathological state commonly found in chronic-degenerative diseases. At the testicular level, aging is associated with tissue atrophy, decreased steroidogenesis and spermatogenesis, and sexual behavior disorders. This situation, in addition to the elevated generation of ROS in the testicular steroidogenesis, provides a critical cellular environment causing oxidative damage at diverse cellular levels. To assess the effects of a reduction in the levels of ROS, thiamine pyrophosphate (TPP) was chronically administered in senile Wistar rats. TPP causes an activation of intermediate metabolism routes, enhancing cellular respiration and decreasing the generation of ROS. Our results show an overall decrease of atrophic histological changes linked to aging, with higher levels of serum testosterone, sexual activity, and an increase in the levels of endogenous antioxidant enzymes in TPP-treated animals. These results suggest that TPP chronic administration decreases the progression of age-related atrophic changes by improving the intermediate metabolism, and by increasing the levels of antioxidant enzymes.

Effects of long-term administration of aspartame on biochemical indices, lipid profile and redox status of cellular system of male rats.

Science.gov (United States)

Adaramoye, Oluwatosin A; Akanni, Olubukola O

2016-01-01

Aspartame (N-L-α-aspartyl-L-phenylalanine-1-methyl ester) (ASP) is a synthetic sweetener used in foods and its safety remains controversial. The study was designed to investigate the effects of long-term administration of aspartame on redox status, lipid profile and biochemical indices in tissues of male Wistar rats. Rats were assigned into four groups and given distilled water (control), aspartame at doses of 15 mg/kg (ASP 1), 35 mg/kg (ASP 2) and 70 mg/kg (ASP 3) daily by oral gavage for consecutive 9 weeks. Administration of ASP 2 and ASP 3 significantly increased the weight of liver and brain, and relative weight of liver of rats. Lipid peroxidation products significantly increased in the kidney, liver and brain of rats at all doses of ASP with concomitant depletion of antioxidant parameters, viz. glutathione-s-transferase, glutathione peroxidase, superoxide dismutase, catalase and reduced glutathione. Furthermore, ASP 2 and ASP 3 significantly increased the levels of gamma glutamyl transferase by 70% and 85%; alanine aminotransferase by 66% and 117%; aspartate aminotransferase by 21% and 48%; urea by 72% and 58% and conjugated bilirubin by 63% and 64%, respectively. Also, ASP 2 and ASP 3 significantly increased the levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol in the rats. Histological findings showed that ASP 2 and ASP 3 caused cyto-architectural changes such as degeneration, monocytes infiltration and necrotic lesions in brain, kidney and liver of rats. Aspartame may induce redox and lipid imbalance in rats via mechanism that involves oxidative stress and depletion of glutathione-dependent system.

Histopathological Study of Cyclosporine Pulmonary Toxicity in Rats

Directory of Open Access Journals (Sweden)

Said Said Elshama

2016-01-01

Full Text Available Cyclosporine is considered one of the common worldwide immunosuppressive drugs that are used for allograft rejection prevention. However, articles that address adverse effects of cyclosporine use on the vital organs such as lung are still few. This study aims to investigate pulmonary toxic effect of cyclosporine in rats by assessment of pulmonary histopathological changes using light and electron microscope examination. Sixty male adult albino rats were divided into three groups; each group consists of twenty rats. The first received physiological saline while the second and third groups received 25 and 40 mg/kg/day of cyclosporine, respectively, by gastric gavage for forty-five days. Cyclosporine reduced the lung and body weight with shrinkage or pyknotic nucleus of pneumocyte type II, degeneration of alveoli and interalveolar septum beside microvilli on the alveolar surface, emphysema, inflammatory cellular infiltration, pulmonary blood vessels congestion, and increase of fibrous tissues in the interstitial tissues and around alveoli with negative Periodic Acid-Schiff staining. Prolonged use of cyclosporine induced pulmonary ultrastructural and histopathological changes with the lung and body weight reduction depending on its dose.

47 CFR 22.970 - Unacceptable interference to part 90 non-cellular 800 MHz licensees from cellular radiotelephone...

Science.gov (United States)

2010-10-01

...-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. 22.970 Section... MOBILE SERVICES Cellular Radiotelephone Service § 22.970 Unacceptable interference to part 90 non-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. (a) Definition...

Injectable Polyurethane Composite Scaffolds Delay Wound Contraction and Support Cellular Infiltration and Remodeling in Rat Excisional Wounds

Science.gov (United States)

Adolph, Elizabeth J.; Hafeman, Andrea E.; Davidson, Jeffrey M.; Nanney, Lillian B.; Guelcher, Scott A.

2011-01-01

Injectable scaffolds present compelling opportunities for wound repair and regeneration due to their ability to fill irregularly shaped defects and deliver biologics such as growth factors. In this study, we investigated the properties of injectable polyurethane biocomposite scaffolds and their application in cutaneous wound repair using a rat excisional model. The scaffolds have a minimal reaction exotherm and clinically relevant working and setting times. Moreover, the biocomposites have mechanical and thermal properties consistent with rubbery elastomers. In the rat excisional wound model, injection of settable biocomposite scaffolds stented the wounds at early time points, resulting in a regenerative rather than a scarring phenotype at later time points. Measurements of wound width and thickness revealed that the treated wounds were less contracted at day 7 compared to blank wounds. Analysis of cell proliferation and apoptosis showed that the scaffolds were biocompatible and supported tissue ingrowth. Myofibroblast formation and collagen fiber organization provided evidence that the scaffolds have a positive effect on extracellular matrix remodeling by disrupting the formation of an aligned matrix under elevated tension. In summary, we have developed an injectable biodegradable polyurethane biocomposite scaffold that enhances cutaneous wound healing in a rat model. PMID:22105887

Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling

Energy Technology Data Exchange (ETDEWEB)

Lovelace, Erica S.; Wagoner, Jessica; MacDonald, James; Bammler, Theo; Bruckner, Jacob; Brownell, Jessica; Beyer, Richard; Zink, Erika M.; Kim, Young-Mo; Kyle, Jennifer E.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Metz, Thomas O.; Farin, Federico; Oberlies, Nicholas H.; Polyak, Steve

2015-08-28

Silymarin (SM), a natural product, is touted as a liver protectant and preventer of both chronic inflammation and diseases. To define how SM elicits these effects at a systems level, we performed transcriptional profiling, metabolomics, and signaling studies in human liver and T cell lines. Multiple pathways associated with cellular stress and metabolism were modulated by SM treatment within 0.5 to four hours: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4). Metabolomics analyses revealed suppression of glycolytic, TCA cycle, and amino acid metabolism by SM treatment. Antiinflammatory effects arose with prolonged (i.e. 24 hours) SM exposure, with suppression of multiple proinflammatory mRNAs and nuclear factor kappa B (NF-κB) and forkhead box O (FOXO) signaling. Studies with murine knock out cells revealed that SM inhibition of both mTOR and NF-κB was partially AMPK dependent, while SM inhibition of the mTOR pathway in part required DDIT4. Thus, SM activates stress and repair responses that culminate in an anti-inflammatory phenotype. Other natural products induced similar stress responses, which correlated with their ability to suppress inflammation. Therefore, natural products like SM may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation.

Caffeine and Aspirin Protecting Albino Rats A gainst Biochemical and Histological Disorders Induced by Whole Body Gamma Irradiation

International Nuclear Information System (INIS)

Abd El-Rahman, N.A.; Sherif, N.H.

2015-01-01

Caffeine is an alkaloid (purine derivative) that contains flavonoids, where as aspirin, natural component of mammalian tissue ( acetylsalicylic acid) is one of the most commonly used non steroidal anti - inflammatory , and it is a necessary factor in the utilization of long - chain fatty acids to produce energy. Furthermore, it has been shown to protect cells from per oxidative stress. Th e objective of the present study is to evaluate the efficacy of caffeine (1,3,7 - trimethyl xanthine) 80 mg/kg b.wt. a nd aspirin ( acetylsalicylic acid) in the amelioration of the physiological and histological changes in stomach and intestine of rats exposed to gamma irradiation . Male albino rats were divided into 8 groups. 1 - Control group: rats not subject to any treatment, 2 - Caffeine group: rats received caffeine ( 80 ml/Kg body weight )via intraperitoneal injection for 21 days, 3 - Aspirin group: rats received aspirin (150 mg / kg body) via intraperitoneal injection for 21 days , 4 - Caffeine + Aspirin group: rats received caffeine a nd aspirin treatment, 5 - Radiation groups: rats were whole body gamma irradiated at 8 Gy , 6 - Caffeine + Radiation group: rats received caffeine for 21 days before whole body gamma irradiation at 8 Gy, 7 - Aspirin + Radiation group: rats received aspirin during 21 days before w hole body gamma irradiation , 8 - Caffeine + Aspirin + Radiation group: rats received caffeine parallel to aspirin for 21 days before whole body gamma irradiation. Animals were sacrificed 24 hrs post irradiation. The results demonstrated that rats exposed to whole body gamma irradiation showed a significant increase in alanine amino transferase (AL ) , aspartate amino transferase ( AST), and alkaline phosphatase (ALP) activities, and a significant decrease in total protein indicating liver injury. A significant increase in urea, creatinine, Na + ,and K + were recorded indicating kidney damage. Alteration of liver and kidney functions was accompanied by a significant

Heterogeneous cellular networks

CERN Document Server

Hu, Rose Qingyang

2013-01-01

A timely publication providing coverage of radio resource management, mobility management and standardization in heterogeneous cellular networks The topic of heterogeneous cellular networks has gained momentum in industry and the research community, attracting the attention of standardization bodies such as 3GPP LTE and IEEE 802.16j, whose objectives are looking into increasing the capacity and coverage of the cellular networks. This book focuses on recent progresses,  covering the related topics including scenarios of heterogeneous network deployment, interference management i

Immune responses to implanted human collagen graft in rats

International Nuclear Information System (INIS)

Quteish, D.; Dolby, A.E.

1991-01-01

Immunity to collagen implants may be mediated by cellular and humoral immune responses. To examine the possibility of such immunological reactivity and crossreactivity to collagen, 39 Sprague-Dawley rats (female, 10 weeks old, approximately 250 g wt) were implanted subcutaneously at thigh sites with crosslinked, freeze-dried human placental type I collagen grafts (4x4x2 mm) which had been irradiated (520 Gray) or left untreated. Blood was obtained by intracardiac sampling prior to implantation or from normal rats, and at various times afterwards when the animals were sacrificed. The sera from these animals were examined for circulating antibodies to human, bovine and rat tail (type I) collagens by enzyme-linked immunosorbent assay (ELISA). Also, the lymphoblastogenic responses of spleen lymphocytes from the irradiated collagen-implanted animals were assessed in culture by measuring thymidine uptake with autologous and normal rat sera in the presence of human bovine type I collagens. Implantation of the irradiated and non-irradiated collagen graft in rats led to a significant increase in the level of circulating antibodies to human collagen. Also antibody to bovine and rat tail collagens was detectable in the animals implanted with irradiated collagen grafts but at a lower level than the human collagen. There was a raised lymphoblastogenic response to both human and bovine collagens. The antibody level and lymphoblastogenesis to the tested collagens gradually decreased towards the end of the post-implantation period. (author)

Redox Status and Neuro Inflammation Indexes in Cerebellum and Motor Cortex of Wistar Rats Supplemented with Natural Sources of Omega-3 Fatty Acids and Astaxanthin: Fish Oil, Krill Oil, and Algal Biomass

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Tatiana G. Polotow

2015-09-01

Full Text Available Health authorities worldwide have consistently recommended the regular consumption of marine fishes and seafood to preserve memory, sustain cognitive functions, and prevent neurodegenerative processes in humans. Shrimp, crabs, lobster, and salmon are of particular interest in the human diet due to their substantial provision of omega-3 fatty acids (n-3/PUFAs and the antioxidant carotenoid astaxanthin (ASTA. However, the optimal ratio between these nutraceuticals in natural sources is apparently the key factor for maximum protection against most neuro-motor disorders. Therefore, we aimed here to investigate the effects of a long-term supplementation with (n-3/PUFAs-rich fish oil, ASTA-rich algal biomass, the combination of them, or krill oil (a natural combination of both nutrients on baseline redox balance and neuro-inflammation indexes in cerebellum and motor cortex of Wistar rats. Significant changes in redox metabolism were only observed upon ASTA supplementation, which reinforce its antioxidant properties with a putative mitochondrial-centered action in rat brain. Krill oil imposed mild astrocyte activation in motor cortex of Wistar rats, although no redox or inflammatory index was concomitantly altered. In summary, there is no experimental evidence that krill oil, fish oil, oralgal biomass (minor variation, drastically change the baseline oxidative conditions or the neuro-inflammatory scenario in neuromotor-associated rat brain regions.

Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model.

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Lingling Zeng

Full Text Available Age-related dysfunction of the central auditory system, also known as central presbycusis, can affect speech perception and sound localization. Understanding the pathogenesis of central presbycusis will help to develop novel approaches to prevent or treat this disease. In this study, the mechanisms of central presbycusis were investigated using a mimetic aging rat model induced by chronic injection of D-galactose (D-Gal. We showed that malondialdehyde (MDA levels were increased and manganese superoxide dismutase (SOD2 activity was reduced in the auditory cortex in natural aging and D-Gal-induced mimetic aging rats. Furthermore, mitochondrial DNA (mtDNA 4834 bp deletion, abnormal ultrastructure and cell apoptosis in the auditory cortex were also found in natural aging and D-Gal mimetic aging rats. Sirt3, a mitochondrial NAD+-dependent deacetylase, has been shown to play a crucial role in controlling cellular reactive oxygen species (ROS homeostasis. However, the role of Sirt3 in the pathogenesis of age-related central auditory cortex deterioration is still unclear. Here, we showed that decreased Sirt3 expression might be associated with increased SOD2 acetylation, which negatively regulates SOD2 activity. Oxidative stress accumulation was likely the result of low SOD2 activity and a decline in ROS clearance. Our findings indicate that Sirt3 might play an essential role, via the mediation of SOD2, in central presbycusis and that manipulation of Sirt3 expression might provide a new approach to combat aging and oxidative stress-related diseases.

Effects of high-altitude exercise training on contractile function of rat skinned cardiomyocyte.

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Cazorla, O; Aït Mou, Y; Goret, L; Vassort, G; Dauzat, M; Lacampagne, A; Tanguy, S; Obert, P

2006-09-01

Previous studies have questioned whether there is an improved cardiac function after high-altitude training. Accordingly, the present study was designed specifically to test whether this apparent blunted response of the whole heart to training can be accounted for by altered mechanical properties at the cellular level. Adult rats were trained for 5 weeks under normoxic (N, NT for sedentary and trained animals, respectively) or hypobaric hypoxic (H, HT) conditions. Cardiac morphology and function were evaluated by echocardiography. Calcium Ca2+ sensitivity of the contractile machinery was estimated in skinned cardiomyocytes isolated from the left ventricular (LV) sub-epicardium (Epi) and sub-endocardium (Endo) at short and long sarcomere lengths (SL). Cardiac remodelling was harmonious (increase in wall thickness with chamber dilatation) in NT rats and disharmonious (hypertrophy without chamber dilatation) in HT rats. Contrary to NT rats, HT rats did not exhibit enhancement in global cardiac performance evaluated by echocardiography. Stretch- dependent Ca2+ sensitization of the myofilaments (cellular index of the Frank-Starling mechanism) increased from Epi to Endo in N rats. Training in normoxic conditions further increased this stretch-dependent Ca2+ sensitization. Chronic hypoxia did not significantly affect myofibrilar Ca2+ sensitivity. In contrast, high-altitude training decreased Ca2+ sensitivity of the myofilaments at both SL, mostly in Endo cells, resulting in a loss of the transmural gradient of the stretch-dependent Ca2+ sensitization. Expression of myosin heavy chain isoforms was affected both by training and chronic hypoxia but did not correlate with mechanical data. Training at sea level increased the transmural gradient of stretch-dependent Ca2+ sensitization of the myofilaments, accounting for an improved Frank-Starling mechanism. High-altitude training depressed myofilament response to Ca2+, especially in the Endo layer. This led to a reduction in

Effects of acrolein on the production of corticosterone in male rats.

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Yeh, Yung-Hsing; Chou, Jou-Chun; Weng, Ting-Chun; Lieu, Fu-Kong; Lin, Jou-Yu; Yeh, Chii-Chang; Hu, Sindy; Wang, Paulus S; Idova, Galina; Wang, Shyi-Wu

2016-07-01

Acrolein, an α, β-unsaturated aldehyde, exists in a wide range of sources. Acrolein can be not only generated from all types of smoke but also produced endogenously from the metabolism by lipid peroxidation. The cellular influence of acrolein is due to its electrophilic character via binding to and depleting cellular nucleophiles. Although the toxicity of acrolein has been extensively studied, there is relatively little information about its impact on hormone release. This study aimed at the effect of acrolein on hypothalamic-pituitary-adrenal (H-P-A) axis. In an in vivo study, male rats were administrated with acrolein for 1 or 3days. The plasma corticosterone in response to a single injection of adrenocorticotropic hormone (ACTH) increased slowly in acrolein-pretreated rats than in control rats. Further investigating the steroidogenic pathway, the protein expressions of steroidogenic acute regulatory protein (StAR) and the upper receptor-melanocortin 2 receptor (MC2R) were attenuated in acrolein-treated groups. Another experiment using trilostane showed less activity of P450scc in zona fasciculata-reticularis (ZFR) cells in acrolein-treated groups. In addition to the suppressed ability of corticosterone production in ZFR cells, acrolein even had extended influence at higher concentrations. The lower ACTH was observed in the plasma from acrolein-pretreated rats. In an in vitro study, ZFR cells were incubated with acrolein and the results showed that corticosterone concentrations in media were decreased in a dose-dependent manner. Acrolein also desensitized the response of the ZFR cells to ACTH. These results suggested that acrolein decreased the releasing ability of corticosterone via an inhibition on the response of ZFR cells to ACTH and the reduction of protein expressions of StAR and MC2R as well as the activity of P450scc in rat ZFR cells. The present evidences showed that the H-P-A axis was affected by the administration of acrolein. Copyright © 2016

Immune cell distribution and immunoglobulin levels change following sciatic nerve injury in a rat model

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Wei Yuan

2016-07-01

Full Text Available Objective(s: To investigate the systemic and local immune status of two surgical rat models of sciatic nerve injury, a crushed sciatic nerve, and a sciatic nerve transection Materials and Methods:Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups: sham-operation (control group, sciatic nerve crush, and sciatic nerve transaction. Sciatic nerve surgery was performed. The percentage of CD4+ cells and the CD4+/CD8+ratio were determined by flow cytometry. Serum IgM and IgG levels were analyzed by ELISA. T-cells (CD3 and macrophages (CD68 in sciatic nerve tissue sections were identified through immunohistochemistry. Results: Compared to sham-operated controls, in rats that underwent nerve injury, the percentage of CD4+ cells and the CD4+/CD8+ ratio in the peripheral blood were significantly  decreased 7 days after surgery, serum IgM levels were increased 14 days after surgery, and serum IgG levels were increased 21 days after surgery. There were a large number of CD3+ cells and a small number of CD68+ cells in sciatic nerve tissue sections 21 days after surgery, indicating T-cell and macrophage activation and infiltration. Local IgG deposition was also detected at the nerve injury site 21 days after surgery. Conclusion: Rat humoral and cellular immune status changed following sciatic nerve injury, particularly with regard to the cellular immune response at the nerve injury site.

47 CFR 22.909 - Cellular markets.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular markets...

Spatiotemporal Stochastic Modeling of IoT Enabled Cellular Networks: Scalability and Stability Analysis

KAUST Repository

Gharbieh, Mohammad; Elsawy, Hesham; Bader, Ahmed; Alouini, Mohamed-Slim

2017-01-01

The Internet of Things (IoT) is large-scale by nature, which is manifested by the massive number of connected devices as well as their vast spatial existence. Cellular networks, which provide ubiquitous, reliable, and efficient wireless access, will play fundamental rule in delivering the first-mile access for the data tsunami to be generated by the IoT. However, cellular networks may have scalability problems to provide uplink connectivity to massive numbers of connected things. To characterize the scalability of cellular uplink in the context of IoT networks, this paper develops a traffic-aware spatiotemporal mathematical model for IoT devices supported by cellular uplink connectivity. The developed model is based on stochastic geometry and queueing theory to account for the traffic requirement per IoT device, the different transmission strategies, and the mutual interference between the IoT devices. To this end, the developed model is utilized to characterize the extent to which cellular networks can accommodate IoT traffic as well as to assess and compare three different transmission strategies that incorporate a combination of transmission persistency, backoff, and power-ramping. The analysis and the results clearly illustrate the scalability problem imposed by IoT on cellular network and offer insights into effective scenarios for each transmission strategy.

Spatiotemporal Stochastic Modeling of IoT Enabled Cellular Networks: Scalability and Stability Analysis

KAUST Repository

Gharbieh, Mohammad

2017-05-02

The Internet of Things (IoT) is large-scale by nature, which is manifested by the massive number of connected devices as well as their vast spatial existence. Cellular networks, which provide ubiquitous, reliable, and efficient wireless access, will play fundamental rule in delivering the first-mile access for the data tsunami to be generated by the IoT. However, cellular networks may have scalability problems to provide uplink connectivity to massive numbers of connected things. To characterize the scalability of cellular uplink in the context of IoT networks, this paper develops a traffic-aware spatiotemporal mathematical model for IoT devices supported by cellular uplink connectivity. The developed model is based on stochastic geometry and queueing theory to account for the traffic requirement per IoT device, the different transmission strategies, and the mutual interference between the IoT devices. To this end, the developed model is utilized to characterize the extent to which cellular networks can accommodate IoT traffic as well as to assess and compare three different transmission strategies that incorporate a combination of transmission persistency, backoff, and power-ramping. The analysis and the results clearly illustrate the scalability problem imposed by IoT on cellular network and offer insights into effective scenarios for each transmission strategy.

Early metabolic responses to lithium/pilocarpine-induced status epilepticus in rat brain.

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Imran, Imran; Hillert, Markus H; Klein, Jochen

2015-12-01

The lithium-pilocarpine model of status epilepticus is a well-known animal model of temporal lobe epilepsy. We combined this model with in vivo microdialysis to investigate energy metabolites and acute cellular membrane damage during seizure development. Rats were implanted with dialysis probes and pretreated with lithium chloride (127 mg/kg i.p.). Twenty-four hours later, they received pilocarpine (30 mg/kg s.c.) which initiated seizures within 30 min. In the dialysate from rat hippocampus, we observed a transient increase in glucose and a prominent, five-fold increase in lactate during seizures. Lactate release was because of neuronal activation as it was strongly reduced by infusion of tetrodotoxin, administration of atropine or when seizures were terminated by diazepam or ketamine. In ex vivo assays, mitochondrial function as measured by respirometry was not affected by 90 min of seizures. Extracellular levels of choline, however, increased two-fold and glycerol levels 10-fold, which indicate cellular phospholipid breakdown during seizures. Within 60 min of pilocarpine administration, hydroxylation of salicylate increased two-fold and formation of isoprostanes 20-fold, revealing significant oxidative stress in hippocampal tissue. Increases in lactate, glycerol and isoprostanes were abrogated, and increases in choline were completely prevented, when hippocampal probes were perfused with calcium-free solution. Similarly, administration of pregabalin (100 mg/kg i.p.), a calcium channel ligand, 15 min prior to pilocarpine strongly attenuated parameters of membrane damage and oxidative stress. We conclude that seizure development in a rat model of status epilepticus is accompanied by increases in extracellular lactate, choline and glycerol, and by oxidative stress, while mitochondrial function remains intact for at least 90 min. Membrane damage depends on calcium influx and can be prevented by treatment with pregabalin. Status epilepticus (SE) was induced in rats by

Proteomic Analysis of Lysine Acetylation Sites in Rat Tissues Reveals Organ Specificity and Subcellular Patterns

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Alicia Lundby

2012-08-01

Full Text Available Lysine acetylation is a major posttranslational modification involved in a broad array of physiological functions. Here, we provide an organ-wide map of lysine acetylation sites from 16 rat tissues analyzed by high-resolution tandem mass spectrometry. We quantify 15,474 modification sites on 4,541 proteins and provide the data set as a web-based database. We demonstrate that lysine acetylation displays site-specific sequence motifs that diverge between cellular compartments, with a significant fraction of nuclear sites conforming to the consensus motifs G-AcK and AcK-P. Our data set reveals that the subcellular acetylation distribution is tissue-type dependent and that acetylation targets tissue-specific pathways involved in fundamental physiological processes. We compare lysine acetylation patterns for rat as well as human skeletal muscle biopsies and demonstrate its general involvement in muscle contraction. Furthermore, we illustrate that acetylation of fructose-bisphosphate aldolase and glycerol-3-phosphate dehydrogenase serves as a cellular mechanism to switch off enzymatic activity.

Topiramate as a neuroprotective agent in a rat model of spinal cord injury

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Firat Narin

2017-01-01

Full Text Available Topiramate (TPM is a widely used antiepileptic and antimigraine agent which has been shown to exert neuroprotective effects in various experimental traumatic brain injury and stroke models. However, its utility in spinal cord injury has not been studied extensively. Thus, we evaluated effects of TPM on secondary cellular injury mechanisms in an experimental rat model of traumatic spinal cord injury (SCI. After rat models of thoracic contusive SCI were established by free weight-drop method, TPM (40 mg/kg was given at 12-hour intervals for four times orally. Post TPM treatment, malondialdehyde and protein carbonyl levels were significantly reduced and reduced glutathione levels were increased, while immunoreactivity for endothelial nitric oxide synthase, inducible nitric oxide synthase, and apoptotic peptidase activating factor 1 was diminished in SCI rats. In addition, TPM treatment improved the functional recovery of SCI rats. This study suggests that administration of TPM exerts neuroprotective effects on SCI.

Xanthine Oxidase Inhibitor, Allopurinol, Prevented Oxidative Stress, Fibrosis, and Myocardial Damage in Isoproterenol Induced Aged Rats.

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Sagor, Md Abu Taher; Tabassum, Nabila; Potol, Md Abdullah; Alam, Md Ashraful

2015-01-01

We evaluated the preventive effect of allopurinol on isoproterenol (ISO) induced myocardial infarction in aged rats. Twelve- to fourteen-month-old male Long Evans rats were divided into three groups: control, ISO, and ISO + allopurinol. At the end of the study, all rats were sacrificed for blood and organ sample collection to evaluate biochemical parameters and oxidative stress markers analyses. Histopathological examinations were also conducted to assess inflammatory cell infiltration and fibrosis in heart and kidneys. Our investigation revealed that the levels of oxidative stress markers were significantly increased while the level of cellular antioxidants, catalase activity, and glutathione concentration in ISO induced rats decreased. Treatment with allopurinol to ISO induced rats prevented the elevated activities of AST, ALT, and ALP enzymes, and the levels of lipid peroxidation products and increased reduced glutathione concentration. ISO induced rats also showed massive inflammatory cells infiltration and fibrosis in heart and kidneys. Furthermore, allopurinol treatment prevented the inflammatory cells infiltration and fibrosis in ISO induced rats. In conclusion, the results of our study suggest that allopurinol treatment is capable of protecting heart of ISO induced myocardial infarction in rats probably by preventing oxidative stress, inflammation, and fibrosis.

Selective lymphoid irradiation: III. Prolongation of cardiac xenografts and allografts in presensitized rats

International Nuclear Information System (INIS)

Hardy, M.A.; Oluwole, S.; Fawwaz, R.; Satake, K.; Nowygrod, R.; Reemtsma, K.

1982-01-01

Selective lymphoid irradiation (SLI) with palladium-109-hematoporphyrin (Pd-H) combined with antilymphocyte globulin (ALG) induces either donor-specific permanent rat heart allograft acceptance or significant allograft prolongation depending on the degree of donor-recipient matching. The purpose of this study was to determine if SLI combined with ALG can affect ACI heart allograft survival in Lewis recipients presensitized to ACI, and of hamster heart xenografts of Lewis rats. SLI combined with ALG delays allograft and xenograft rejection in the presence of induced or preformed antidonor antibodies, and converts primarily a humoral rejection into a cellular rejection by mechanisms as yet uncertain. Such peritransplant treatment had significant effect on the levels of antidonor complement-dependent cytotoxic antibody titers but did not correlate directly with graft survival. Histological analysis of rejected hearts in all groups demonstrated primarily a humoral hyperacute rejection in control animals and in recipients treated with ALG alone, while peritransplant treatment with Pd-H and ALG resulted not only in prolonged graft survival but histologically, primarily a cellular rejection of the graft

Pan-neuronal calcium imaging with cellular resolution in freely swimming zebrafish.

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Kim, Dal Hyung; Kim, Jungsoo; Marques, João C; Grama, Abhinav; Hildebrand, David G C; Gu, Wenchao; Li, Jennifer M; Robson, Drew N

2017-11-01

Calcium imaging with cellular resolution typically requires an animal to be tethered under a microscope, which substantially restricts the range of behaviors that can be studied. To expand the behavioral repertoire amenable to imaging, we have developed a tracking microscope that enables whole-brain calcium imaging with cellular resolution in freely swimming larval zebrafish. This microscope uses infrared imaging to track a target animal in a behavior arena. On the basis of the predicted trajectory of the animal, we applied optimal control theory to a motorized stage system to cancel brain motion in three dimensions. We combined this motion-cancellation system with differential illumination focal filtering, a variant of HiLo microscopy, which enabled us to image the brain of a freely swimming larval zebrafish for more than an hour. This work expands the repertoire of natural behaviors that can be studied with cellular-resolution calcium imaging to potentially include spatial navigation, social behavior, feeding and reward.

[Electroacupuncture Intervention Enhances Splenic Natural Killer Cell Activity via Inhibiting Phosphorylation of ERK 5 in the Hypothalamus of Surgically Traumatized Rats].

Science.gov (United States)

Chen, Yan; Li, Jing; Zhu, Ke-ying; Xiao, Sheng; Wang, Yan-qing; Wu, Gen-cheng; Wang, Jun

2015-06-01

To observe the effect of electroacupuncture (EA) on cytotoxic activity of splenic natural killer (NK) cells after surgical trauma via extracellular signal-regulated kinase (ERK) 5 pathway in the rats' hypothalamus, so as to explore its mechanism underlying improving immune disorders after surgery. Sprague-Dawley rats were randomly divided into the following 6 groups: control, trauma model, EA, sham EA, 4 nmol-BIX 02188 (an inhibitor for ERK 5 catalytic activity) and 20 nmol-BIX 02188 (n = 6 rats per group). The surgical trauma model was established by making a longitudinal incision (6 cm in length) along the median line of the back to expose the spinal column and another longitudinal incision along the abdominal median line. EA (2 Hz/15 Hz, 1 - 2 mA) was applied to bilateral "Zusanli" (ST 36) for 30 min immediately after surgery. For rats of the BIX groups, intra-lateral ventricular microinjection of BIX 02188 (10 µL, 4 nmol or 20 nmol, or saline for control rats) was conducted 30 min before the surgery. The expression level and protein of phosphorylated ERK 5 (p-ERK 5) and corticotropin-releasing factor (CRF) protein were measured by immunohistochemistry and Western blot, respectively. The cytotoxicity of splenic NK cells and the expression of splenic Perforin and Granzyme-B genes were measured by lactate dehydrogenase (LDH) release assay and real-time PCR, respectively. In comparison with the control group, hypothalamic p-ERK 5 immunoactivity, p-ERK 5 protein and CRF protein expression levels were significantly up-regulated in the model group (Psplenic NK cell cytotoxicity and Perforin mRNA and Granzyme-B mRNA expression levels were notably down-regulated in the model group (P 0. 05) except the increased p-ERK 5 protein in the 4 nmol-BIX 02188 group. In addition, the down-regulated NK cell activity, Perforin mRNA and Granzyme-B mRNA expression levels were significantly reversed in the EA and 20 nmol-BIX 02188 groups (Psplenic NK cytotoxicity and Perforin and

Effect of aflatoxin-B1 doses simulating natural food contamination reproductive steroid hormones in rats

International Nuclear Information System (INIS)

Gamal, M.H.; EL-Banna, I.M.

2002-01-01

Aflatoxin B1 (AFB1) is the most toxic metabolite synthesized by aspergillus flavus. The mycotoxins was found to be endemic contaminant in underdeveloped countries and in egypt was documented as a pollutant of a wide variety of products for human and animal nutrition. Carcinogenic and mutagenic effects of AFB1 has been investigated extensively, while very scare information is available about other possible endocrine effects of the toxin which might precedes carcinogenic effects. This study was performed to investigate the effects of in vivo administration of AFB1 via intraperitoneal injection (I.P) in adult male rats to show its effects on rat reproductive function and to illucidate the effects of acute, chronic and sub toxic (endimomemitic) AFB1 doses on male rat steroid function. Intraperitoneal injection (I.P) of AFB 1 doses in adult male rats revealed that AFB1 caused significant decrease in serum testosterone and cortisol (early), while a significant increase was observed in progesterone (P 4 ) and Estrodial (E 2 ) (late)

Correlation between LH secretion in castrated rats with cellular proliferation and synthesis of DNA in the anterior pituitary gland.

Science.gov (United States)

Romano, M I; Machiavelli, G A; Pérez, R L; Carricarte, V; Burdman, J A

1984-07-01

The relationship between the release of LH and the synthesis of DNA was studied in the anterior pituitary gland of castrated rats. Cell types were characterized immunocytochemically. Castration significantly (P less than 0.01) increased the concentration of LH in serum (1326%) and the incorporation of [3H]thymidine into pituitary DNA (72%). This was accompanied by an increment in the activity of the enzyme DNA polymerase-alpha (58%) and in the number of mitoses (from 2 +/- 0.1/mm2 in intact rats to 21 +/- 0.8/mm2 15 days after castration). Only 20% of the mitoses found in the pituitary gland of castrated rats were positively stained with the antiserum against the beta-subunit of LH. The other 80% did not stain either with LH antiserum or with antisera against the other pituitary hormones. There was a significant (P less than 0.01) increase in the number of LH cells in castrated rats (48%). All the changes produced in the anterior pituitary gland after castration were prevented by the administration of dihydrotestosterone. The results demonstrate that a stimulation of LH release is followed by an increase of DNA synthesis and cell proliferation of gonadotrophs in the anterior pituitary gland.

Exposure to Rats and Rat-Associated Leptospira and Bartonella Species Among People Who Use Drugs in an Impoverished, Inner-City Neighborhood of Vancouver, Canada.

Science.gov (United States)

McVea, David A; Himsworth, Chelsea G; Patrick, David M; Lindsay, L Robbin; Kosoy, Michael; Kerr, Thomas

2018-02-01

Rat infestations are common, particularly in impoverished, inner-city neighborhoods. However, there has been little research into the nature and consequences of rat exposure in these neighborhoods, particularly in Canada. In this study, we sought to characterize exposure to rats and rat-associated Leptospira interrogans and Bartonella tribocorum, as well as risk factors associated with exposure, in residents (n = 202) of the Downtown Eastside (DTES) neighborhood of Vancouver, Canada. There was no evidence of exposure to rat-associated L. interrogans but 6/202 (3.0%) of participants were exposed to B. tribocorum, which is known to be circulating among DTES rats. We also found that frequent and close rat exposure was common among DTES residents, and that this exposure was particularly associated with injection drug use and outdoor income-generating activities (e.g., drug dealing). These risk factors may be good targets for interventions geared toward effectively reducing rat exposure.

Ouabain binding to cultured vascular smooth muscle cells of the spontaneously hypertensive rat

International Nuclear Information System (INIS)

Hopp, L.; Khalil, F.; Tamura, H.; Kino, M.; Searle, B.M.; Tokushige, A.; Aviv, A.

1986-01-01

The binding of ouabain and K + to the Na + pump were analyzed in serially passed cultured vascular smooth muscle cells (VSMCs) originating from spontaneously hypertensive (SH) Wistar-Kyoto (WKY), and American Wistar (W) rats. The techniques have utilized analyses of displacement of [ 3 H]ouabain by both unlabeled ouabain and K + from specific binding sites on the VSMCs. The authors have found that 1) each of the VSMC preparations from the three rat strains appeared to demonstrate one population of specific ouabain receptors (Na + pumps); 2) the number of Na + pump units of both the SH and WKY rats was significantly lower than the number of Na + pump units of W rat VSMCs; 3) the equilibrium dissociation constant values (μM) for ouabain in VSMCs of SH and WKY rats were similar but were significantly higher than that of VSMCs derived from W rats; and 4) among the VSMCs originating from the three rat strains, the apparent equilibrium dissociation constant value for K + (mM) was the lowest in those of the SH rat compared with VSMCs of the WKY rat and W rat. Previous studies have demonstrated increased passive Na + and K + transport rate constants of SH rat VSMCs compared with either W or WKY rat cells. These findings suggest the possibility of higher permeabilities of the SH cells. They propose that the combined effect of a low number of Na + pump units with higher permeabilities to Na + and K + predisposes VSMCs of the SH rat to disturbances in their cellular ionic regulation. These genetic defects, if they occur in vivo, may lead to an increase in the vascular tone

Multiscale evaluation of cellular adhesion alteration and cytoskeleton remodeling by magnetic bead twisting.

Science.gov (United States)

Isabey, Daniel; Pelle, Gabriel; André Dias, Sofia; Bottier, Mathieu; Nguyen, Ngoc-Minh; Filoche, Marcel; Louis, Bruno

2016-08-01

Cellular adhesion forces depend on local biological conditions meaning that adhesion characterization must be performed while preserving cellular integrity. We presently postulate that magnetic bead twisting provides an appropriate stress, i.e., basically a clamp, for assessment in living cells of both cellular adhesion and mechanical properties of the cytoskeleton. A global dissociation rate obeying a Bell-type model was used to determine the natural dissociation rate ([Formula: see text]) and a reference stress ([Formula: see text]). These adhesion parameters were determined in parallel to the mechanical properties for a variety of biological conditions in which either adhesion or cytoskeleton was selectively weakened or strengthened by changing successively ligand concentration, actin polymerization level (by treating with cytochalasin D), level of exerted stress (by increasing magnetic torque), and cell environment (by using rigid and soft 3D matrices). On the whole, this multiscale evaluation of the cellular and molecular responses to a controlled stress reveals an evolution which is consistent with stochastic multiple bond theories and with literature results obtained with other molecular techniques. Present results confirm the validity of the proposed bead-twisting approach for its capability to probe cellular and molecular responses in a variety of biological conditions.

Biochemical Studies on Camel Milk as a Radioprotector in Irradiated Rats

International Nuclear Information System (INIS)

Ali, S.E.

2008-01-01

This work, was conducted to evaluate the possible capability of camel milk, as a radioprotector in irradiated (4.0 Gy) rats. Two examinations were performed after two and four weeks post irradiation. γ-irradiation caused significant disorders in hematological, physiological parameters and liver cellular aspects. Drinking of camel milk induced no adverse effect on the tested parameters. Moreover, it minimized and ameliorated the radiation disorders

Leucine-rich repeat kinase 2 (LRRK2-deficient rats exhibit renal tubule injury and perturbations in metabolic and immunological homeostasis.

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Daniel Ness

Full Text Available Genetic evidence links mutations in the LRRK2 gene with an increased risk of Parkinson's disease, for which no neuroprotective or neurorestorative therapies currently exist. While the role of LRRK2 in normal cellular function has yet to be fully described, evidence suggests involvement with immune and kidney functions. A comparative study of LRRK2-deficient and wild type rats investigated the influence that this gene has on the phenotype of these rats. Significant weight gain in the LRRK2 null rats was observed and was accompanied by significant increases in insulin and insulin-like growth factors. Additionally, LRRK2-deficient rats displayed kidney morphological and histopathological alterations in the renal tubule epithelial cells of all animals assessed. These perturbations in renal morphology were accompanied by significant decreases of lipocalin-2, in both the urine and plasma of knockout animals. Significant alterations in the cellular composition of the spleen between LRRK2 knockout and wild type animals were identified by immunophenotyping and were associated with subtle differences in response to dual infection with rat-adapted influenza virus (RAIV and Streptococcus pneumoniae. Ontological pathway analysis of LRRK2 across metabolic and kidney processes and pathological categories suggested that the thioredoxin network may play a role in perturbing these organ systems. The phenotype of the LRRK2 null rat is suggestive of a complex biology influencing metabolism, immune function and kidney homeostasis. These data need to be extended to better understand the role of the kinase domain or other biological functions of the gene to better inform the development of pharmacological inhibitors.

Chrysin treatment improves diabetes and its complications in liver, brain, and pancreas in streptozotocin-induced diabetic rats.

Science.gov (United States)

Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Samini, Fariborz; Farkhondeh, Tahereh

2016-04-01

Chrysin (CH) is a natural flavonoid with pharmacological influences. The purpose of the current study was the assessment of possible protective effects of CH against oxidative damage in the serum, liver, brain, and pancreas of streptozotocin (STZ)- induced diabetic rats. In the present study, the rats were divided into the following groups of 8 animals each: control, untreated diabetic, 3 CH (20, 40, 80 mg/kg/day)-treated diabetic groups. To find out the modulations of cellular antioxidant defense systems, malondialdehyde (MDA) level and antioxidant enzymes including glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities were determined in the serum, liver, brain, and pancreas. STZ caused an elevation of glucose, MDA, TG, TC, LDL-C and with reduction of HDL-C, total protein, SOD, CAT, and GST in the serum, liver, brain, and pancreas (p < 0.01). The findings showed that the significant elevation in the glucose, MDA, TG, TC, LDL-C and reduction of HDL-C, total protein, SOD, CAT, and GST were ameliorated in the CH-treated diabetic groups versus to the untreated groups, in a dose dependent manner (p < 0.05). The current study offers that CH may be recovered diabetes and its complications by modification of oxidative stress.

Cellular Reflectarray Antenna

Science.gov (United States)

Romanofsky, Robert R.

2010-01-01

The cellular reflectarray antenna is intended to replace conventional parabolic reflectors that must be physically aligned with a particular satellite in geostationary orbit. These arrays are designed for specified geographical locations, defined by latitude and longitude, each called a "cell." A particular cell occupies nominally 1,500 square miles (3,885 sq. km), but this varies according to latitude and longitude. The cellular reflectarray antenna designed for a particular cell is simply positioned to align with magnetic North, and the antenna surface is level (parallel to the ground). A given cellular reflectarray antenna will not operate in any other cell.

Different cellular responses evoked by natural and stoichiometric synthetic chrysotile asbestos

International Nuclear Information System (INIS)

Gazzano, Elena; Foresti, Elisabetta; Lesci, Isidoro Giorgio; Tomatis, Maura; Riganti, Chiara; Fubini, Bice; Roveri, Norberto; Ghigo, Dario

2005-01-01

The carcinogenic potency of asbestos, including chrysotile, is well established. Several physico-chemical features of the fibers appear implied, such as fibrous habit, size, crystallinity, morphology, and surface active metal ions, where free radical generation may take place. In contrast to other asbestos forms, iron is not a stoichiometric component of chrysotile, but is only present together with other extraneous ions as a magnesium- and silicon-replacing contaminant. To determine the role played by contaminating ions and morphological features of the fibers, a stoichiometric chrysotile with constant structure and morphology was synthesized in hydrothermal conditions. Free radical generation and the effects of these fibers on human lung epithelial A549 cells have been compared to that elicited by a well known toxic natural chrysotile (UICC A, from Rhodesia). After a 24-h incubation, the natural, but not the synthetic, form exerted a cytotoxic effect, detected as leakage of lactate dehydrogenase. Homolytic rupture of a C-H bond and lipoperoxidation in A549 cells took place in the presence of the natural, but not of the synthetic, chrysotile. Antioxidant systems were also affected differently. The pentose phosphate pathway and its regulatory enzyme glucose 6-phosphate dehydrogenase were markedly inhibited only by the natural specimen, which also caused a depletion of intracellular reduced glutathione in A549 cells. These results suggest that metal ions, fiber size and state of the surface play a crucial role in the oxidative stress caused by chrysotile asbestos. Stoichiometric synthetic fibers may thus be proposed as a reference standard (negative control) for toxicological studies

Brain Insulin Administration Triggers Distinct Cognitive and Neurotrophic Responses in Young and Aged Rats.

Science.gov (United States)

Haas, Clarissa B; Kalinine, Eduardo; Zimmer, Eduardo R; Hansel, Gisele; Brochier, Andressa W; Oses, Jean P; Portela, Luis V; Muller, Alexandre P

2016-11-01

Aging is a major risk factor for cognitive deficits and neurodegenerative disorders, and impaired brain insulin receptor (IR) signaling is mechanistically linked to these abnormalities. The main goal of this study was to investigate whether brain insulin infusions improve spatial memory in aged and young rats. Aged (24 months) and young (4 months) male Wistar rats were intracerebroventricularly injected with insulin (20 mU) or vehicle for five consecutive days. The animals were then assessed for spatial memory using a Morris water maze. Insulin increased memory performance in young rats, but not in aged rats. Thus, we searched for cellular and molecular mechanisms that might account for this distinct memory response. In contrast with our expectation, insulin treatment increased the proliferative activity in aged rats, but not in young rats, implying that neurogenesis-related effects do not explain the lack of insulin effects on memory in aged rats. Furthermore, the expression levels of the IR and downstream signaling proteins such as GSK3-β, mTOR, and presynaptic protein synaptophysin were increased in aged rats in response to insulin. Interestingly, insulin treatment increased the expression of the brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) receptors in the hippocampus of young rats, but not of aged rats. Our data therefore indicate that aged rats can have normal IR downstream protein expression but failed to mount a BDNF response after challenge in a spatial memory test. In contrast, young rats showed insulin-mediated TrkB/BDNF response, which paralleled with improved memory performance.

Histopathological changes by the use of soft reline materials: a rat model study.

Science.gov (United States)

Bail, Michele; Meister, Lissandra Matos Brol; Campagnoli, Eduardo Bauml; Jorge, Janaina Habib; Ban, Manuella de Cassia Iglesias; Sanchez-Ayala, Alfonso; Campanha, Nara Hellen

2014-01-01

To assess the histopathological changes of rat palatal mucosa exposed to soft reline materials. Forty-five adult female Wistar rats with controlled living conditions and fed ad libitum were employed. Palatal appliances of heat-polymerized acrylic resin Lucitone 550 were manufactured and worn by forty animals during 14 days. Five animals did not use the appliances (G1) and were used to control the appliance influence. One experimental group (n = 10) used the appliances without any relining material (G2) to control the material effect. Three experimental groups (n = 10) received the following soft reline materials below appliances: Dentusoft (G3), Dentuflex (G4), and Trusoft (G5). Appliances from half of each experimental group(n = 5) was immersed in water bath at 55°C for 10 min before use. Animals were slaughtered and the palates were fixed in 10% buffered formalin. Hematoxylin and eosin stained sections of 5 µm were analyzed by computerized planimetry. Cellular compartment, keratin and total epithelial thickness, and basement membrane length were measured to histopathological description.Analysis of variance and Tukey post-hoc test were used to data examination(α = 0.05). For heat-treatment groups, G4 showed less elongated ridges at the basal layer interface (p = 0.037) than G2. When comparing the conditions with and without heat-treatment, only G2 showed a significant decrease in the cellular compartment, keratin layer and total epithelium thickness (p<0.05). The post-polymerization for Lucitone 550 was an effective method to reduce the changes in the rat palatal mucosa. The soft reline materials tested did not cause significant histopathological changes in the rat palatal mucosa.

Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney.

Science.gov (United States)

Cano-Europa, Edgar; Blas-Valdivia, Vanessa; Franco-Colin, Margarita; Gallardo-Casas, Carlos Angel; Ortiz-Butrón, Rocio

2011-01-01

It is known that a hypothyroidism-induced hypometabolic state protects against oxidative damage caused by toxins. However, some workers demonstrated that antithyroid drug-induced hypothyroidism can cause cellular damage. Our objective was to determine if methimazole (an antithyroid drug) or hypothyroidism causes cellular damage in the liver, kidney, lung, spleen and heart. Twenty-five male Wistar rats were divided into 5 groups: euthyroid, false thyroidectomy, thyroidectomy-induced hypothyroidism, methimazole-induced hypothyroidism (60 mg/kg), and treatment with methimazole (60 mg/kg) and a T₄ injection (20 μg/kg/d sc). At the end of the treatments (4 weeks for the pharmacological groups and 8 weeks for the surgical groups), the animals were anesthetized with sodium pentobarbital and they were transcardially perfused with 10% formaldehyde. The spleen, heart, liver, lung and kidney were removed and were processed for embedding in paraffin wax. Coronal sections were stained with hematoxylin-eosin. At the end of treatment, animals with both the methimazole- and thyroidectomy-induced hypothyroidism had a significant reduction of serum concentration of thyroid hormones. Only methimazole-induced hypothyroidism causes cellular damage in the kidney, lung, liver, heart, kidney and spleen. In addition, animals treated with methimazole and T₄ showed cellular damage in the lung, spleen and renal medulla with lesser damage in the liver, renal cortex and heart. The thyroidectomy only altered the lung structure. The alterations were prevented by T₄ completely in the heart and partially in the kidney cortex. These results indicate that tissue damage found in hypothyroidism is caused by methimazole. Copyright © 2009 Elsevier GmbH. All rights reserved.

Linearizable cellular automata

International Nuclear Information System (INIS)

Nobe, Atsushi; Yura, Fumitaka

2007-01-01

The initial value problem for a class of reversible elementary cellular automata with periodic boundaries is reduced to an initial-boundary value problem for a class of linear systems on a finite commutative ring Z 2 . Moreover, a family of such linearizable cellular automata is given

Effect of some natural products on the level of thyroid related hormones in rats

International Nuclear Information System (INIS)

Sheikh Idris, A. S. A.

2011-03-01

This study was designed based on the basis of interesting information derived from traditional medicine about the uses of three plants i.e (moringa Oleifera, citrus aurantifolia and coriandrum sativum). These plants are used in Sudanese folkloric medicine to treat many diseases such as thyroid, cancer, diabetics and inflammations. This study was designed to evaluate biological activity of these previously mentioned plants and investigate the effect of different concentrations of their extracts on the level of thyroid hormones of male and females swiss wistar rats. Further studies were performed to investigate the potentiality of moringa as a useful agent for the regulation of hyperthyroidism. The three plant sample were collected purchased from different locations in Sudan and identified and authenticated by Mr. Yahia Suleiman technical herbarium at medicinal and Aromatic Plant Research Institute (MAPRA) at National Center of Research, Khartoum, Sudan. A voucher specimen was deposited at herbarium of MAPRI. The plants under investigation were successively extracted at room temperature with petroleum ether, ethy 1 acetate and ethanol using shaker apparatus. Fifty seven adult swiss wister rats of 3-4 months of age, weighing 70-150g were used in this research study. Animals were divided into groups has received dose of extract, equivalent to 200 mg/kg/day for 10 days. In the pilot studies, 30 rats were divided into nine groups to estimate the effect of the extracts (moringa oleifera, citrus aurantifolia and coriandrum) on T3 and T4 and TSH hormones level in the normal and treated rats. The extracts of coriandrum sativum seeds was the most active as it has reduced the level of thyroid hormones than the other extract by decreasing T3 and T4 hormones while TSH level undetectable values this could be due to the absence of the TSH level in rats serum or could be attributed to the method used since the method is specific for human samples not rats. Consequently the 80

Effect of some natural products on the level of thyroid related hormones in rats

Energy Technology Data Exchange (ETDEWEB)

Sheikh Idris, A. S. A. [Sudan Academy of Sciences, Atomic Energy Council, Khartoum (Sudan)

2011-03-15

This study was designed based on the basis of interesting information derived from traditional medicine about the uses of three plants i.e (moringa Oleifera, citrus aurantifolia and coriandrum sativum). These plants are used in Sudanese folkloric medicine to treat many diseases such as thyroid, cancer, diabetics and inflammations. This study was designed to evaluate biological activity of these previously mentioned plants and investigate the effect of different concentrations of their extracts on the level of thyroid hormones of male and females swiss wistar rats. Further studies were performed to investigate the potentiality of moringa as a useful agent for the regulation of hyperthyroidism. The three plant sample were collected purchased from different locations in Sudan and identified and authenticated by Mr. Yahia Suleiman technical herbarium at medicinal and Aromatic Plant Research Institute (MAPRA) at National Center of Research, Khartoum, Sudan. A voucher specimen was deposited at herbarium of MAPRI. The plants under investigation were successively extracted at room temperature with petroleum ether, ethy 1 acetate and ethanol using shaker apparatus. Fifty seven adult swiss wister rats of 3-4 months of age, weighing 70-150g were used in this research study. Animals were divided into groups has received dose of extract, equivalent to 200 mg/kg/day for 10 days. In the pilot studies, 30 rats were divided into nine groups to estimate the effect of the extracts (moringa oleifera, citrus aurantifolia and coriandrum) on T3 and T4 and TSH hormones level in the normal and treated rats. The extracts of coriandrum sativum seeds was the most active as it has reduced the level of thyroid hormones than the other extract by decreasing T3 and T4 hormones while TSH level undetectable values this could be due to the absence of the TSH level in rats serum or could be attributed to the method used since the method is specific for human samples not rats. Consequently the 80

The similia principle: results obtained in a cellular model system.

Science.gov (United States)

Wiegant, Fred; Van Wijk, Roeland

2010-01-01

This paper describes the results of a research program focused on the beneficial effect of low dose stress conditions that were applied according to the similia principle to cells previously disturbed by more severe stress conditions. In first instance, we discuss criteria for research on the similia principle at the cellular level. Then, the homologous ('isopathic') approach is reviewed, in which the initial (high dose) stress used to disturb cellular physiology and the subsequent (low dose) stress are identical. Beneficial effects of low dose stress are described in terms of increased cellular survival capacity and at the molecular level as an increase in the synthesis of heat shock proteins (hsps). Both phenomena reflect a stimulation of the endogenous cellular self-recovery capacity. Low dose stress conditions applied in a homologous approach stimulate the synthesis of hsps and enhance survival in comparison with stressed cells that were incubated in the absence of low dose stress conditions. Thirdly, the specificity of the low dose stress condition is described where the initial (high dose) stress is different in nature from the subsequently applied (low dose) stress; the heterologous or 'heteropathic' approach. The results support the similia principle at the cellular level and add to understanding of how low dose stress conditions influence the regulatory processes underlying self-recovery. In addition, the phenomenon of 'symptom aggravation' which is also observed at the cellular level, is discussed in the context of self-recovery. Finally, the difference in efficiency between the homologous and the heterologous approach is discussed; a perspective is indicated for further research; and the relationship between studies on the similia principle and the recently introduced concept of 'postconditioning hormesis' is emphasized. Copyright 2009 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

Effects of amphetamine administration on neurogenesis in adult rats

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Tomasz Stępień

2017-12-01

Full Text Available In our study expression of phospho-(Ser-10-histone H3 (pH3S10, a marker for the early stage of neurogenesis, and cellular early response genes were investigated using c-Fos protein as an example of a transcription factor in the neurogenic process in rats. Neurogenesis in the adult brain is regulated by endo- and exogenous factors, which influence the proliferation potential of progenitor cells and accelerate the dendritic development of newborn neurons. D-amphetamine, a psychoactive substance, is one of the exogenous factors able to influence the process of neurogenesis. The rats were injected with D-amphetamine at a dose of 1.5 mg/kg/body weight (b.w. under one administration scheme. Analysis of the pH3S10 and c-Fos expression levels in the group of D-amphetamine administered rats provided evidence of enhanced expression of these proteins in the regions of neurogenesis occurrence in rats. However, conclusions concerning stimulant effects of amphetamine on neurogenesis should be formulated with great caution, taking into account amphetamine dosage and the administration scheme. It should also be remembered that doses of psychoactive substances used in animal models can be lethal to humans.

Localizing by autoradiography at -195 deg radioactive areas in rats exposed to a high flux of thermal neutrons, importance of phosphorus 32 in consecutive internal irradiation; Localisation par autoradiographie a -195 deg des zones radioactives chez le rat expose a un haut flux de neutrons thermiques, importance du phosphore 32 dans l'irradiation interne consecutive

Energy Technology Data Exchange (ETDEWEB)

Chanteur, J; Pellerin, P [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

1961-07-01

Rats weighing 25 g were exposed for 5 mn to a flux of 6.10{sup 12} thermal neutrons/cm{sup 2}/s. Anatomical autoradiography at -195 deg. C has enabled the radioactive organs to be easily localised, to follow in course of time the decrease of radioactivity, and from it to deduce the probable nature of the numerous emitters in question. In particular, the phosphorus 32 has thus appeared to be one of those responsible for internal irradiation, general, on the one hand, by activating cellular phosphorus, local, on the other, by activating bony phosphates. Owing to this, an accidental irradiation by neutrons might have consequences that are both somatic (elective irradiation of the bone marrow) and genetic (activation of nucleic acids). The gamma spectrometry has confirmed the nature of certain other emitters. (author) [French] Des rats de 25 g ont ete exposes pendant 5 mn a un flux de 6.10{sup 12} neutrons thermiques/cm{sup 2}/s. L'autoradiographie anatomique a -195 deg. C a permis de localiser facilement les organes radioactifs, de suivre dans le temps la decroissance de la radioactivite, et d'en deduire la nature probable des nombreux emetteurs en cause. En particulier, le phosphore 32 est ainsi apparu comme l'un des responsables de l'irradiation interne, d'une part generale par activation du phosphore cellulaire, d'autre part locale par activation des phosphates osseux. Une irradiations accidentelle par neutrons aurait, de ce fait, des consequences a la fois somatiques (irradiation elective de la moelle osseuse) et genetiques (activation des acides nucleiques). La spectrometrie gamma a confirme la nature de certains autres emetteurs. (auteur)

A new rapid kindling variant for induction of cortical epileptogenesis in freely moving rats

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Juan Carlos Morales

2014-07-01

Full Text Available Kindling, one of the most used models of experimental epilepsy is based on daily electrical stimulation in several brain structures. Unlike the classic or slow kindling protocols (SK, the rapid kindling types (RK described until now require continuous stimulation at suprathreshold intensities applied directly to the same brain structure used for subsequent electrophysiological and inmunohistochemical studies, usually the hippocampus. However, the cellular changes observed in these rapid protocols, such as astrogliosis and neuronal loss, could be due to experimental manipulation more than to epileptogenesis-related alterations. Here, we developed a new RK protocol in order to generate an improved model of temporal lobe epilepsy (TLE which allows gradual progression of the epilepsy as well as obtaining an epileptic hippocampus, thus avoiding direct surgical manipulation and electric stimulation over this structure. This new protocol consists of basolateral amygdala (BLA stimulation with 10 trains of biphasic pulses (10s;50Hz per day with 20 minutes-intervals, during 3 consecutive days, using a subconvulsive and subthreshold intensity, which guarantees tissue integrity. The progression of epileptic activity was evaluated in freely moving rats through EEG recordings from cortex and amygdala, accompanied with synchronized video recordings. Moreover, we assessed the effectiveness of RK protocol and the establishment of epilepsy by evaluating cellular alterations of hippocampal slices from kindled rats. RK protocol induced convulsive states similar to SK protocols but in 3 days, with persistently lowered threshold to seizure induction and epileptogenic-dependent cellular changes in amygdala projection areas. We concluded that this novel RK protocol introduces a new variant of the chronic epileptogenesis models in freely moving rats, which is faster, highly reproducible and causes minimum cell damage with respect to that observed in other experimental

Simulation Based Optimization of Complex Monolithic Composite Structures Using Cellular Core Technology

Science.gov (United States)

Hickmott, Curtis W.

Cellular core tooling is a new technology which has the capability to manufacture complex integrated monolithic composite structures. This novel tooling method utilizes thermoplastic cellular cores as inner tooling. The semi-rigid nature of the cellular cores makes them convenient for lay-up, and under autoclave temperature and pressure they soften and expand providing uniform compaction on all surfaces including internal features such as ribs and spar tubes. This process has the capability of developing fully optimized aerospace structures by reducing or eliminating assembly using fasteners or bonded joints. The technology is studied in the context of evaluating its capabilities, advantages, and limitations in developing high quality structures. The complex nature of these parts has led to development of a model using the Finite Element Analysis (FEA) software Abaqus and the plug-in COMPRO Common Component Architecture (CCA) provided by Convergent Manufacturing Technologies. This model utilizes a "virtual autoclave" technique to simulate temperature profiles, resin flow paths, and ultimately deformation from residual stress. A model has been developed simulating the temperature profile during curing of composite parts made with the cellular core technology. While modeling of composites has been performed in the past, this project will look to take this existing knowledge and apply it to this new manufacturing method capable of building more complex parts and develop a model designed specifically for building large, complex components with a high degree of accuracy. The model development has been carried out in conjunction with experimental validation. A double box beam structure was chosen for analysis to determine the effects of the technology on internal ribs and joints. Double box beams were manufactured and sectioned into T-joints for characterization. Mechanical behavior of T-joints was performed using the T-joint pull-off test and compared to traditional

Rat testicular impairment induced by electromagnetic radiation from a conventional cellular telephone and the protective effects of the antioxidants vitamins C and E

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Mona Abdullah Al-Damegh

2012-07-01

Full Text Available OBJECTIVE: The aim of this study was to investigate the possible effects of electromagnetic radiation from conventional cellular phone use on the oxidant and antioxidant status in rat blood and testicular tissue and determine the possible protective role of vitamins C and E in preventing the detrimental effects of electromagnetic radiation on the testes. MATERIALS AND METHODS: The treatment groups were exposed to an electromagnetic field, electromagnetic field plus vitamin C (40 mg/kg/day or electromagnetic field plus vitamin E (2.7 mg/kg/day. All groups were exposed to the same electromagnetic frequency for 15, 30, and 60 min daily for two weeks. RESULTS: There was a significant increase in the diameter of the seminiferous tubules with a disorganized seminiferous tubule sperm cycle interruption in the electromagnetism-exposed group. The serum and testicular tissue conjugated diene, lipid hydroperoxide, and catalase activities increased 3-fold, whereas the total serum and testicular tissue glutathione and glutathione peroxidase levels decreased 3-5 fold in the electromagnetism-exposed animals. CONCLUSION: Our results indicate that the adverse effect of the generated electromagnetic frequency had a negative impact on testicular architecture and enzymatic activity. This finding also indicated the possible role of vitamins C and E in mitigating the oxidative stress imposed on the testes and restoring normality to the testes.

Parameters and characteristics governing cellular internalization and trans-barrier trafficking of nanostructures

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Murugan K

2015-03-01

Full Text Available Karmani Murugan, Yahya E Choonara, Pradeep Kumar, Divya Bijukumar, Lisa C du Toit, Viness Pillay Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Abstract: Cellular internalization and trans-barrier transport of nanoparticles can be manipulated on the basis of the physicochemical and mechanical characteristics of nanoparticles. Research has shown that these factors significantly influence the uptake of nanoparticles. Dictating these characteristics allows for the control of the rate and extent of cellular uptake, as well as delivering the drug-loaded nanosystem intra-cellularly, which is imperative for drugs that require a specific cellular level to exert their effects. Additionally, physicochemical characteristics of the nanoparticles should be optimal for the nanosystem to bypass the natural restricting phenomena of the body and act therapeutically at the targeted site. The factors at the focal point of emerging smart nanomedicines include nanoparticle size, surface charge, shape, hydrophobicity, surface chemistry, and even protein and ligand conjugates. Hence, this review discusses the mechanism of internalization of nanoparticles and ideal nanoparticle characteristics that allow them to evade the biological barriers in order to achieve optimal cellular uptake in different organ systems. Identifying these parameters assists with the progression of nanomedicine as an outstanding vector of pharmaceuticals. Keywords: nanoparticles, transport mechanisms, cellular uptake, size, shape, charge

IN UTERO EXPOSURE TO THE FUNGICIDE PROCYMIDONE AND DIBUTYL PHTHALATE PRODUCE DOSE ADDITIVE DISRUPTIONS OF MALE RAT SEXUAL DIFFERENTIATION

Science.gov (United States)

Procymidone (PRO) and dibutyl phthalate (DBP) alter male rat sexual differentiation by disrupting the androgen-signaling pathway via distinctly different cellular mechanisms of toxicity. DBP inhibits fetal Leydig cell androgen production whereas PRO binds AR and blocks androgen a...

Platelet-rich plasma in bone repair of irradiated tibiae of Wistar rats

International Nuclear Information System (INIS)

Gumieiro, Emne Hammoud; Abrahao, Marcio; Jahn, Ricardo Schmitutz; Segretto, Helena; Alves, Maria Tereza de Seixas; Nannmark, Ulf; Granstroem, Goesta; Dib, Luciano Lauria

2010-01-01

Purpose: to evaluate the influence of PRP addition on bone repair of circular defects created in irradiated tibiae of rats by histometric analysis. Methods: sixty male Wistar rats had the right tibiae irradiated with 30 Gy. After 30 days monocortical defects were created and platelet-rich plasma as applied in 30 rats. In the control group defects were created but not filled. The animals were sacrificed after 4, 7, 14, 21, 56 and 84 days and the tibiae removed for histological processing. Results: there was a tendency in the PRP group to increased bone neoformation from 14-days to 84-days; in the control group increased bone neoformation was not seen after 21 days or later. Conclusion: the addition of platelet-rich plasma had a beneficial effect in the initial cellular regeneration period and enhanced bone formation in later periods when compared to control. (author)

RADIOPROTECTIVE EFFECT OF LYCOPENE IN GAMMA IRRADIATED ALBINO RATS

International Nuclear Information System (INIS)

MOHAMED, M.I.; ALI, S.E.; HAGGAG, A.M.

2007-01-01

The present study was designed to explore the radioprotective potential of lycopene in gamma irradiated male rats. Four groups, each of sixteen rats, were assigned as follows: the first was untreated (control group), the second fed on chow diet mixed with 300 mg lycopene/kg diet (lycopene group), the third exposed to 6.5 Gy gamma radiation (irradiated group) and the fourth fed on chow mixed with 300 mg lycopene/kg and exposed to 6.5 Gy gamma radiation (irradiated and treated group). Animals exposed to ionizing radiation experienced decline in their body weights, increased ALT and AST enzymes and decreased serum albumin level. The study also showed decline in hemoglobin, total white blood cells count and blood platelets count. Bone marrow examination revealed profound hypoplasis and reduction of the cellular elements. Histological examination of liver, spleen, testis and intestine showed disruption of normal architecture of these organs. Irradiated and treated animals maintained a more or less steady body weight, and improved serum ALT, AST and albumin in comparison with those irradiated. The results also showed increased hemoglobin, total white blood cells, platelets count and partial improvement of bone marrow cellularity. Lycopene was also capable of partial preservation of normal architecture of liver, spleen, intestine and testis in gamma irradiated group.In conclusion, lycopene seems to be a useful radioprotector probably because of its potent antioxidant property

Structure and Electromagnetic Properties of Cellular Glassy Carbon Monoliths with Controlled Cell Size

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Andrzej Szczurek

2018-05-01

Full Text Available Electromagnetic shielding is a topic of high importance for which lightweight materials are highly sought. Porous carbon materials can meet this goal, but their structure needs to be controlled as much as possible. In this work, cellular carbon monoliths of well-defined porosity and cell size were prepared by a template method, using sacrificial paraffin spheres as the porogen and resorcinol-formaldehyde (RF resin as the carbon precursor. Physicochemical studies were carried out for investigating the conversion of RF resin into carbon, and the final cellular monoliths were investigated in terms of elemental composition, total porosity, surface area, micropore volumes, and micro/macropore size distributions. Electrical and electromagnetic (EM properties were investigated in the static regime and in the Ka-band, respectively. Due to the phenolic nature of the resin, the resultant carbon was glasslike, and the special preparation protocol that was used led to cellular materials whose cell size increased with density. The materials were shown to be relevant for EM shielding, and the relationships between those properties and the density/cell size of those cellular monoliths were elucidated.

Acute and Conditioned Blood Pressure Changes in Relation to Social and Psychosocial Stimuli in Rats

NARCIS (Netherlands)

Fokkema, Dirk S.; Koolhaas, Jaap M.

1985-01-01

The naturally occurring tendency to compete with other rats for territorial space has been used to study individual behavior characteristics and blood pressure reactivity to social stimuli in adult male TMD-S3 rats. The competitive characteristics of the individual rats are consistent in two

The JCR:LA-cp rat: a novel rodent model of cystic medial necrosis.

Science.gov (United States)

Pung, Yuh Fen; Chilian, William M; Bennett, Martin R; Figg, Nichola; Kamarulzaman, Mohd Hamzah

2017-03-01

Although there are multiple rodent models of the metabolic syndrome, very few develop vascular complications. In contrast, the JCR:LA-cp rat develops both metabolic syndrome and early atherosclerosis in predisposed areas. However, the pathology of the normal vessel wall has not been described. We examined JCR:LA control (+/+) or cp/cp rats fed normal chow diet for 6 or 18 mo. JCR:LA-cp rats developed multiple features of advanced cystic medial necrosis including "cysts," increased collagen formation and proteoglycan deposition around cysts, apoptosis of vascular smooth muscle cells, and spotty medial calcification. These appearances began within 6 mo and were extensive by 18 mo. JCR:LA-cp rats had reduced medial cellularity, increased medial thickness, and vessel hypoxia that was most marked in the adventitia. In conclusion, the normal chow-fed JCR:LA-cp rat represents a novel rodent model of cystic medial necrosis, associated with multiple metabolic abnormalities, vascular smooth muscle cell apoptosis, and vessel hypoxia. NEW & NOTEWORTHY Triggers for cystic medial necrosis (CMN) have been difficult to study due to lack of animal models to recapitulate the pathologies seen in humans. Our study is the first description of CMN in the rat. Thus the JCR:LA-cp rat represents a useful model to investigate the underlying molecular changes leading to the development of CMN. Copyright © 2017 the American Physiological Society.

Modeling integrated cellular machinery using hybrid Petri-Boolean networks.

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Natalie Berestovsky

Full Text Available The behavior and phenotypic changes of cells are governed by a cellular circuitry that represents a set of biochemical reactions. Based on biological functions, this circuitry is divided into three types of networks, each encoding for a major biological process: signal transduction, transcription regulation, and metabolism. This division has generally enabled taming computational complexity dealing with the entire system, allowed for using modeling techniques that are specific to each of the components, and achieved separation of the different time scales at which reactions in each of the three networks occur. Nonetheless, with this division comes loss of information and power needed to elucidate certain cellular phenomena. Within the cell, these three types of networks work in tandem, and each produces signals and/or substances that are used by the others to process information and operate normally. Therefore, computational techniques for modeling integrated cellular machinery are needed. In this work, we propose an integrated hybrid model (IHM that combines Petri nets and Boolean networks to model integrated cellular networks. Coupled with a stochastic simulation mechanism, the model simulates the dynamics of the integrated network, and can be perturbed to generate testable hypotheses. Our model is qualitative and is mostly built upon knowledge from the literature and requires fine-tuning of very few parameters. We validated our model on two systems: the transcriptional regulation of glucose metabolism in human cells, and cellular osmoregulation in S. cerevisiae. The model produced results that are in very good agreement with experimental data, and produces valid hypotheses. The abstract nature of our model and the ease of its construction makes it a very good candidate for modeling integrated networks from qualitative data. The results it produces can guide the practitioner to zoom into components and interconnections and investigate them

Histopathological Features of Ornithodoros lahorensis Bite on Rat

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M Tavassoli

2007-08-01

Full Text Available Background: Besides of transmitting several diseases to animals, and tick paralysis, Ornithodoros lahorensis induce skin lesions. This experiment was done to determine histopathological features of adult O. lahorensis bite on rat.Methods: In this investigation adult male rats were infested with O. lahorensis ticks. Animals were divided into two groups and euthanized two days and two weeks after infestation. The skin samples were fixed in 10% buffer formal saline and processed and sections were stained with hematoxylin & eosin.Results: The lesions reflected the clinical and gross findings, with hyperemia, edema and vacuolation in the early stages, cellular infiltrations, principally lymphocyte accompanied vascular changes. Newly formed fibrous tissue with large number of hyperemic capillaries and active inflammatory process in which lymphocytes and eosinophils were the predominant cells, were seen after two weeks. Foci of necrosis in the epithelium with remnant of infiltration of polymorphonucular cells with sever hemorrhages were also evident. Vascular changes included prevascular infiltration of lymphocyte and fibrinoied ne­crosis on the vessel walls.Conclusion: This study well documented the different pathological changes of skin of rats with O. lahorensis.

Major depressive disorder mediates accelerated aging in rats subjected to chronic mild stress.

Science.gov (United States)

Xie, Xiaoxian; Chen, Yangyang; Ma, Lingyan; Shen, Qichen; Huang, Liangfeng; Zhao, Binggong; Wu, Tao; Fu, Zhengwei

2017-06-30

Major depressive disorder (MDD) has a complex etiology and is characterized by a change in mood and psychophysiological state. MDD has been shown to mediate accelerated biological aging in patients, although the underlying mechanism is not well understood. In the present study, we used a chronic mild stress (CMS) paradigm to induce anhedonia, one of the main symptoms of MDD. CMS induced depression-like symptoms in rats, including reduced sucrose preference and increased immobility time in the forced swim test. Moreover, stressed rats travelled a shorter total distance, had fewer grid line crossings, and spent less time in the outer zone in the open field test than controls. CMS altered the levels of 5-hydroxytryptophan, dopamine, and corticosterone in the serum and hippocampus (P<0.05); these rats also exhibited impaired liver function, decreased telomerase activity, and telomere shortening, which was associated with increased oxidative damage along with decreased superoxide dismutase and glutathione reductase activities. Mitochondria in CMS-treated rats showed ultrastructural damage as well as reduced DNA content and integrity. These findings provide physiological and cellular evidence that the MDD can mediate accelerated aging in rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Protective effects of Tribulus terrestris L extract against acute kidney injury induced by reperfusion injury in rats.

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Najafi, Houshang; Firouzifar, Mohammad Reza; Shafaat, Omid; Changizi Ashtiyani, Saeed; Hosseini, Nasser

2014-07-01

This study aimed to investigate the protective effect of aerial parts of the Tribulus terrestris L extract on acute kidney injury (AKI) induced by ischemia for 30 minutes and reperfusion for 24 hours in rats. Ten male Sprague-Dawley rats in the AKI and 10 in the Tribulus terrestris groups received the extract solvent and extract of the plant (11 mg/kg), respectively, for 13 days (oral administration). On day 14, ischemia for 30 minutes and reperfusion for 24 hours were induced on the rats. In the last 6 hours of the reperfusion period (24 hours), urine samples were collected in metabolic cages. At the end of this period, blood samples were also taken to determine plasma urea nitrogen, creatinine, and electrolyte concentrations. The kidney tissues were collected for measuring the level of oxidative stress and histological studies. They were compared with the sham operation group and a control group with normal diet and no operation. In the Tribulus terrestris group, the increase in plasma creatinine and urea nitrogen concentrations was significantly less following reperfusion, and their values reached the same level as that in the sham group. Creatinine clearance and urine osmolarity in the Tribulus terrestris group was higher in comparison with the AKI group, whereas sodium absolute excretion, fractional excretion of potassium, oxidative stress, and cellular damages were less. Oral administration of Tribulus terrestris extract for 2 weeks can decrease kidney functional disturbance, oxidative stress, and cellular damages following reperfusion injury in rats.

Cellular content and biosynthesis of polyamines during rooster spermatogenesis.

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Oliva, R; Vidal, S; Mezquita, C

1982-01-01

The natural polyamines spermine and spermidine, and the diamine putrescine, were extracted from rooster testis cells separated by sedimentation at unit gravity, and from vas-deferens spermatozoa. The ratios spermine/DNA and spermidine/DNA were kept relatively constant throughout spermatogenesis, whereas the ratio putrescine/DNA rose in elongated spermatids. The cellular content of spermine, spermidine and putrescine decreased markedly in mature spermatozoa. Two rate-limiting enzymes in the biosynthetic pathway of polyamines, ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase, showed their highest activities at the end of spermiogenesis and were not detectable in vas-deferens spermatozoa. A marked reduction in cell volume during spermiogenesis without a parallel decrease in the cellular content of polyamines suggests the possibility that the marked changes in chromatin composition and structure occurring in rooster late spermatids could take place in an ambience of high polyamine concentration. Images PLATE 1 PMID:7159401

Integrated transcriptomic and proteomic evaluation of gentamicin nephrotoxicity in rats

International Nuclear Information System (INIS)

Com, Emmanuelle; Boitier, Eric; Marchandeau, Jean-Pierre; Brandenburg, Arnd; Schroeder, Susanne; Hoffmann, Dana; Mally, Angela; Gautier, Jean-Charles

2012-01-01

Gentamicin is an aminoglycoside antibiotic, which induces renal tubular necrosis in rats. In the context of the European InnoMed PredTox project, transcriptomic and proteomic studies were performed to provide new insights into the molecular mechanisms of gentamicin-induced nephrotoxicity. Male Wistar rats were treated with 25 and 75 mg/kg/day subcutaneously for 1, 3 and 14 days. Histopathology observations showed mild tubular degeneration/necrosis and regeneration and moderate mononuclear cell infiltrate after long-term treatment. Transcriptomic data indicated a strong treatment-related gene expression modulation in kidney and blood cells at the high dose after 14 days of treatment, with the regulation of 463 and 3241 genes, respectively. Of note, the induction of NF-kappa B pathway via the p38 MAPK cascade in the kidney, together with the activation of T-cell receptor signaling in blood cells were suggestive of inflammatory processes in relation with the recruitment of mononuclear cells in the kidney. Proteomic results showed a regulation of 163 proteins in kidney at the high dose after 14 days of treatment. These protein modulations were suggestive of a mitochondrial dysfunction with impairment of cellular energy production, induction of oxidative stress, an effect on protein biosynthesis and on cellular assembly and organization. Proteomic results also provided clues for potential nephrotoxicity biomarkers such as AGAT and PRBP4 which were strongly modulated in the kidney. Transcriptomic and proteomic data turned out to be complementary and their integration gave a more comprehensive insight into the putative mode of nephrotoxicity of gentamicin which was in accordance with histopathological findings. -- Highlights: ► Gentamicin induces renal tubular necrosis in rats. ► The mechanisms of gentamicin nephrotoxicity remain still elusive. ► Transcriptomic and proteomic analyses were performed to study this toxicity in rats. ► Transcriptomic and proteomic

Basal and insulin-stimulated skeletal muscle sugar transport in endotoxic and bacteremic rats

International Nuclear Information System (INIS)

Westfall, M.V.; Sayeed, M.M.

1988-01-01

Membrane glucose transport with and without insulin was studied in soleus muscle from 5-h endotoxic rats (40 mg/kg Salmonella enteritidis lipopolysaccharide), and in soleus and epitrochlearis muscles from 12-h bacteremic (Escherichia coli, 4 X 10(10) CFU/kg) rats. Glucose transport was measured in muscles by evaluating the fractional efflux of 14 C-labeled 3-O-methylglucose ( 14 C-3-MG) after loading muscles with 14 C-3-MG. Basal 3-MG transport was elevated in soleus muscles from endotoxic as well as in soleus and epitrochlearis muscles from bacteremic rats compared with time-matched controls. Low insulin concentrations stimulated 14 C-3-MG transport more in bacteremic and endotoxic rat muscles than in controls. However, sugar transport in the presence of high insulin dose was attenuated in soleus and epitrochlearis muscles from bacteremic rats and soleus muscles from endotoxic rats compared with controls. Analysis of the dose-response relationship with ALLFIT revealed that the maximal transport response to insulin was significantly decreased in both models of septic shock. Sensitivity to insulin (EC50) was increased in endotoxic rat muscles, and a somewhat similar tendency was observed in bacteremic rat soleus muscles. Neural and humoral influences and/or changes in cellular metabolic energy may contribute to the increase in basal transport. Shifts in insulin-mediated transport may be due to alterations in insulin-receptor-effector coupling and/or the number of available glucose transporters

Hemodynamic Effect of Laser Therapy in Spontaneously Hypertensive Rats

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Tomimura, Suely, E-mail: suelytomimura@uol.com.br [Programa de Pós-Graduação em Biofotônica em Ciências da Saúde da Universidade Nove de Julho (UNINOVE) (Brazil); Silva, Bianca Passos Assumpção [Programa de Graduação e Pós-Graduação em Medicina da UNINOVE (Brazil); Sanches, Iris Callado [Laboratório de Fisiologia Translacional da UNINOVE (Brazil); Canal, Marina [Programa de Graduação e Pós-Graduação em Medicina da UNINOVE (Brazil); Consolim-Colombo, Fernanda [Programa de Graduação e Pós-Graduação em Medicina da UNINOVE (Brazil); Unidade de Hipertensão e Central Médica de Laser do Instituto do Coração - Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (InCor/HC-FMUSP), São Paulo, SP (Brazil); Conti, Felipe Fernandes; Angelis, Katia De [Laboratório de Fisiologia Translacional da UNINOVE (Brazil); Chavantes, Maria Cristina [Programa de Pós-Graduação em Biofotônica em Ciências da Saúde da Universidade Nove de Julho (UNINOVE) (Brazil); Programa de Graduação e Pós-Graduação em Medicina da UNINOVE (Brazil); Unidade de Hipertensão e Central Médica de Laser do Instituto do Coração - Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (InCor/HC-FMUSP), São Paulo, SP (Brazil)

2014-08-15

Systemic arterial hypertension (SAH) is considered to be the greatest risk factor for the development of neuro-cardiovascular pathologies, thus constituting a severe Public Health issue in the world. The Low-Level Laser Therapy (LLLT), or laser therapy, activates components of the cellular structure, therefore converting luminous energy into photochemical energy and leading to biophysical and biochemical reactions in the mitochondrial respiratory chain. The LLLT promotes cellular and tissue photobiomodulation by means of changes in metabolism, leading to molecular, cellular and systemic changes. The objective of this study was to analyze the action of low-level laser in the hemodynamic modulation of spontaneously hypertensive rats, in the long term. Animals (n = 16) were randomly divided into the Laser Group (n = 8), which received three weekly LLLT irradiations for seven weeks, and into the Sham Group (n = 8), which received three weekly simulations of laser for seven weeks, accounting for 21 applications in each group. After seven weeks, animals were cannulated by the implantation of a catheter in the left carotid artery. On the following day, the systemic arterial pressure was recorded. The Laser Group showed reduced levels of mean blood pressure, with statistically significant reduction (169 ± 4 mmHg* vs. 182 ± 4 mmHg from the Sham Group) and reduced levels of diastolic pressure (143 ± 4 mmHg* vs. 157 ± 3 mmHg from the Sham Group), revealing a 13 and 14 mmHg decrease, respectively. Besides, there was a concomitant important decline in heart rate (312 ± 14 bpm vs. 361 ± 13 bpm from the Sham Group). Therefore, laser therapy was able to produce hemodynamic changes, thus reducing pressure levels in spontaneously hypertensive rats.

Hemodynamic Effect of Laser Therapy in Spontaneously Hypertensive Rats

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Suely Tomimura

2014-08-01

Full Text Available Systemic arterial hypertension (SAH is considered to be the greatest risk factor for the development of neuro-cardiovascular pathologies, thus constituting a severe Public Health issue in the world. The Low-Level Laser Therapy (LLLT, or laser therapy, activates components of the cellular structure, therefore converting luminous energy into photochemical energy and leading to biophysical and biochemical reactions in the mitochondrial respiratory chain. The LLLT promotes cellular and tissue photobiomodulation by means of changes in metabolism, leading to molecular, cellular and systemic changes. The objective of this study was to analyze the action of low-level laser in the hemodynamic modulation of spontaneously hypertensive rats, in the long term. Animals (n = 16 were randomly divided into the Laser Group (n = 8, which received three weekly LLLT irradiations for seven weeks, and into the Sham Group (n = 8, which received three weekly simulations of laser for seven weeks, accounting for 21 applications in each group. After seven weeks, animals were cannulated by the implantation of a catheter in the left carotid artery. On the following day, the systemic arterial pressure was recorded. The Laser Group showed reduced levels of mean blood pressure, with statistically significant reduction (169 ± 4 mmHg* vs. 182 ± 4 mmHg from the Sham Group and reduced levels of diastolic pressure (143 ± 4 mmHg* vs. 157 ± 3 mmHg from the Sham Group, revealing a 13 and 14 mmHg decrease, respectively. Besides, there was a concomitant important decline in heart rate (312 ± 14 bpm vs. 361 ± 13 bpm from the Sham Group. Therefore, laser therapy was able to produce hemodynamic changes, thus reducing pressure levels in spontaneously hypertensive rats.

Eicosapentenoic Acid Attenuates Allograft Rejection in an HLA-B27/EGFP Transgenic Rat Cardiac Transplantation Model.

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Liu, Zhong; Hatayama, Naoyuki; Xie, Lin; Kato, Ken; Zhu, Ping; Ochiya, Takahiro; Nagahara, Yukitoshi; Hu, Xiang; Li, Xiao-Kang

2012-01-01

The development of an animal model bearing definite antigens is important to facilitate the evaluation and modulation of specific allo-antigen responses after transplantation. In the present study, heterotopic cardiac transplantation was performed from F344/EGFPTg and F344/HLA-B27Tg rats to F344 rats. The F344 recipients accepted the F344/EGFPTg transplants, whereas they rejected the cardiac tissue from the F344/HLA-B27Tg rats by 39.4 ± 6.5 days, due to high production of anti-HLA-B27 IgM- and IgG-specific antibodies. In addition, immunization of F344 rats with skin grafts from F344/HLA-B27Tg rats resulted in robust production of anti- HLA-B27 IgM and IgG antibodies and accelerated the rejection of a secondary cardiac allograft (7.4 ± 1.9 days). Of interest, the F344 recipients rejected cardiac grafts from double transgenic F344/HLA-B27&EGFPTg rats within 9.0 ± 3.2 days, and this was associated with a significant increase in the infiltration of lymphocytes by day 7, suggesting a role for cellular immune rejection. Eicosapentenoic acid (EPA), one of the ω-3 polyunsaturated fatty acids in fish oil, could attenuate the production of anti-HLA IgG antibodies and B-cell proliferation, significantly prolonging double transgenic F344HLA-B27&EGFPTg to F344 rat cardiac allograft survival (36.1 ± 13.6 days). Moreover, the mRNA expression in the grafts was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), revealing an increase in the expression of the HO-1, IL-10, TGF-β, IDO, and Foxp3 genes in the EPA-treated group. Hence, our data indicate that HLA-B27 and/or GFP transgenic proteins are useful for establishing a unique animal transplantation model to clarify the mechanism underlying the allogeneic cellular and humoral immune response, in which the transplant antigens are specifically presented. Furthermore, we also demonstrated that EPA was effective in the treatment of rat cardiac allograft rejection and may allow the development of

Proteomic analysis of 3-MCPD and 3-MCPD dipalmitate toxicity in rat testis.

Science.gov (United States)

Sawada, Stefanie; Oberemm, Axel; Buhrke, Thorsten; Meckert, Christine; Rozycki, Christel; Braeuning, Albert; Lampen, Alfonso

2015-09-01

Thermal treatment of foodstuff containing fats and salt promotes the formation of 3-chloropropane-1,2-diol (3-MCPD) and its fatty acid esters. 3-MCPD-exposed rats develop testicular lesions and Leydig cell tumors. 3-MCPD and 3-MCPD ester toxicity is thought to be caused by 3-MCPD and its metabolites, since 3-MCPD esters are hydrolyzed in the gut. Inhibition of glycolysis is one of the few known molecular mechanisms of 3-MCPD toxicity. To obtain deeper insight into this process, a comparative proteomic approach was chosen, based on a 28-days repeated-dose feeding study with male Wistar rats. Animals received equimolar doses of 3-MCPD or 3-MCPD dipalmitate. A lower dose of 3-MCPD dipalmitate was also administered. Absence of histopathological changes supported an analysis of early cellular disturbance. Testes were analyzed by two-dimensional gel electrophoresis followed by mass-spectrometric protein identification. Data provide a comprehensive overview of proteomic changes induced by 3-MCPD and 3-MCPD dipalmitate in rat testis in an early phase of organ impairment. Results are compatible with known 3-MCPD effects on reproductive function, substantially extend our knowledge about cellular responses to 3-MCPD and support the hypothesis that toxicity of 3-MCPD and 3-MCPD esters is mediated via common effectors. DJ-1 was identified as a candidate marker for 3-MCPD exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aerobic exercise training rescues cardiac protein quality control and blunts endoplasmic reticulum stress in heart failure rats.

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Bozi, Luiz H M; Jannig, Paulo R; Rolim, Natale; Voltarelli, Vanessa A; Dourado, Paulo M M; Wisløff, Ulrik; Brum, Patricia C

2016-11-01

Cardiac endoplasmic reticulum (ER) stress through accumulation of misfolded proteins plays a pivotal role in cardiovascular diseases. In an attempt to reestablish ER homoeostasis, the unfolded protein response (UPR) is activated. However, if ER stress persists, sustained UPR activation leads to apoptosis. There is no available therapy for ER stress relief. Considering that aerobic exercise training (AET) attenuates oxidative stress, mitochondrial dysfunction and calcium imbalance, it may be a potential strategy to reestablish cardiac ER homoeostasis. We test the hypothesis that AET would attenuate impaired cardiac ER stress after myocardial infarction (MI). Wistar rats underwent to either MI or sham surgeries. Four weeks later, rats underwent to 8 weeks of moderate-intensity AET. Myocardial infarction rats displayed cardiac dysfunction and lung oedema, suggesting heart failure. Cardiac dysfunction in MI rats was paralleled by increased protein levels of UPR markers (GRP78, DERLIN-1 and CHOP), accumulation of misfolded and polyubiquitinated proteins, and reduced chymotrypsin-like proteasome activity. These results suggest an impaired cardiac protein quality control. Aerobic exercise training improved exercise capacity and cardiac function of MI animals. Interestingly, AET blunted MI-induced ER stress by reducing protein levels of UPR markers, and accumulation of both misfolded and polyubiquinated proteins, which was associated with restored proteasome activity. Taken together, our study provide evidence for AET attenuation of ER stress through the reestablishment of cardiac protein quality control, which contributes to better cardiac function in post-MI heart failure rats. These results reinforce the importance of AET as primary non-pharmacological therapy to cardiovascular disease. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Synchrony of plant cellular circadian clocks with heterogeneous properties under light/dark cycles.

Science.gov (United States)

Okada, Masaaki; Muranaka, Tomoaki; Ito, Shogo; Oyama, Tokitaka

2017-03-22

Individual cells in a plant can work independently as circadian clocks, and their properties are the basis of various circadian phenomena. The behaviour of individual cellular clocks in Lemna gibba was orderly under 24-h light/dark cycles despite their heterogeneous free-running periods (FRPs). Here, we reveal the entrainment habits of heterogeneous cellular clocks using non-24-h light/dark cycles (T-cycles). The cellular rhythms of AtCCA1::LUC under T = 16 h cycles showed heterogeneous entrainment that was associated with their heterogeneous FRPs. Under T = 12 h cycles, most cells showed rhythms having ~24-h periods. This suggested that the lower limit of entrainment to the light/dark cycles of heterogeneous cellular circadian clocks is set to a period longer than 12 h, which enables them to be synchronous under ~24-h daily cycles without being perturbed by short light/dark cycles. The entrainment habits of individual cellular clocks are likely to be the basis of the circadian behaviour of plant under the natural day-night cycle with noisy environmental fluctuations. We further suggest that modifications of EARLY FLOWERING3 (ELF3) in individual cells deviate the entrainability to shorter T-cycles possibly by altering both the FRPs and light responsiveness.

Cellular Particle Dynamics simulation of biomechanical relaxation processes of multi-cellular systems

Science.gov (United States)

McCune, Matthew; Kosztin, Ioan

2013-03-01

Cellular Particle Dynamics (CPD) is a theoretical-computational-experimental framework for describing and predicting the time evolution of biomechanical relaxation processes of multi-cellular systems, such as fusion, sorting and compression. In CPD, cells are modeled as an ensemble of cellular particles (CPs) that interact via short range contact interactions, characterized by an attractive (adhesive interaction) and a repulsive (excluded volume interaction) component. The time evolution of the spatial conformation of the multicellular system is determined by following the trajectories of all CPs through numerical integration of their equations of motion. Here we present CPD simulation results for the fusion of both spherical and cylindrical multi-cellular aggregates. First, we calibrate the relevant CPD model parameters for a given cell type by comparing the CPD simulation results for the fusion of two spherical aggregates to the corresponding experimental results. Next, CPD simulations are used to predict the time evolution of the fusion of cylindrical aggregates. The latter is relevant for the formation of tubular multi-cellular structures (i.e., primitive blood vessels) created by the novel bioprinting technology. Work supported by NSF [PHY-0957914]. Computer time provided by the University of Missouri Bioinformatics Consortium.

Stably Expressed Genes Involved in Basic Cellular Functions.

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Kejian Wang

Full Text Available Stably Expressed Genes (SEGs whose expression varies within a narrow range may be involved in core cellular processes necessary for basic functions. To identify such genes, we re-analyzed existing RNA-Seq gene expression profiles across 11 organs at 4 developmental stages (from immature to old age in both sexes of F344 rats (n = 4/group; 320 samples. Expression changes (calculated as the maximum expression / minimum expression for each gene of >19000 genes across organs, ages, and sexes ranged from 2.35 to >109-fold, with a median of 165-fold. The expression of 278 SEGs was found to vary ≤4-fold and these genes were significantly involved in protein catabolism (proteasome and ubiquitination, RNA transport, protein processing, and the spliceosome. Such stability of expression was further validated in human samples where the expression variability of the homologous human SEGs was significantly lower than that of other genes in the human genome. It was also found that the homologous human SEGs were generally less subject to non-synonymous mutation than other genes, as would be expected of stably expressed genes. We also found that knockout of SEG homologs in mouse models was more likely to cause complete preweaning lethality than non-SEG homologs, corroborating the fundamental roles played by SEGs in biological development. Such stably expressed genes and pathways across life-stages suggest that tight control of these processes is important in basic cellular functions and that perturbation by endogenous (e.g., genetics or exogenous agents (e.g., drugs, environmental factors may cause serious adverse effects.

Concomitant apoptosis and regeneration of liver cells as a mechanism of liver-tumor promotion by β-naphthoflavone involving TNFα-signaling due to oxidative cellular stress in rats

International Nuclear Information System (INIS)

Kuwata, Kazunori; Shibutani, Makoto; Hayashi, Hitomi; Shimamoto, Keisuke; Hayashi, Shim-Mo; Suzuki, Kazuhiko; Mitsumori, Kunitoshi

2011-01-01

β-Naphthoflavone (BNF) is a strong inducer of cytochrome P450 1A enzymes, and exerts liver tumor-promoting activity through enhancement of oxidative stress responses in rats. This study investigated the role of the tissue environment surrounding hepatocellular preneoplastic lesions in the early tumor-promotion stage by BNF, using enzymatically modified isoquercitrin (EMIQ) as an anti-oxidative chemopreventive agent. Male F344 rats were fed a diet containing BNF (0.5%) for 6 weeks, with or without EMIQ (0.2%) in the drinking water, 2 weeks after initiation with N-diethylnitrosamine, and were subjected to two-thirds partial hepatectomy 1 week after starting BNF-promotion. BNF-treatment increased concentrations of liver thiobarbituric acid-reactive substances, single liver cells expressing glutathione S-transferase placental form or heme oxygenase (HO)-1, and concomitant apoptosis and proliferation of liver cells. Transcript upregulation of anti-oxidative enzymes (Aldh1a1 and Nqo1), cell cycle-related molecules (Cdc20 and Cdkn2b) and inflammation-related molecules including proinflammatory cytokines (Ccl2, Col1a1, Il6, Nos2 and Serpine1) was also evident. Furthermore, BNF increased HO-1-expressing Kupffer cells and liver cells expressing tumor necrosis factor receptor 1 (TNFR1) and the TNFR1-associated death domain. Most of these BNF-induced fluctuations disappeared or were suppressed by EMIQ in conjunction with suppression of tumor-promotion. Tnf transcript levels with BNF were also suppressed by EMIQ. These results suggest that BNF-induced oxidative stress causes single liver cell toxicity, allowing subsequent concomitant apoptosis and regeneration involving inflammatory responses including TNFα-signaling, contributing to tumor promotion. Kupffer cells may act to protect against inflammatory stimuli induced as a result of oxidative cellular stress by BNF, causing proinflammatory cytokine level fluctuations.

Toxicological and biochemical investigations in rats administered “kaun” (trona a natural food additive used in Nigeria

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K.E. Imafidon

2016-12-01

Full Text Available Trona, a geological mineral, is often used as a natural food additive in many parts of Nigeria. This work was done to evaluate trona for metal content, acute toxicity and biochemical effects on vital organs such as the liver and the kidney. Consequently, graded doses of 10, 100, 1000, 1500 and 5000 mg trona per kg body weight were administered to determine their effects on body weight changes, relative organ weight, acute toxicity, liver and renal function indices and oxidative status of rats. Elemental analyses revealed the presence of high levels of sodium and iron, the presence of heavy metals such as cadmium, zinc and lead were also detected. There were losses in weights only at the 5000 mg/kg dose levels; relative liver and kidney weights were not affected. Acute toxicity tests recorded no mortality and no visible sign of toxicity. There were significant increases in ALT, AST and ALP activities at all dose levels except at the 10 mg/kg dose level. Liver MDA levels were significantly increased while catalase and SOD activities were significantly reduced in all the test rats compared with control. Kidney MDA levels were only affected at dose levels 5000 mg/kg; kidney SOD and catalase activities were not significantly affected. Creatinine, sodium and potassium levels were also not affected. These results show that trona may elicit toxic effects on the liver on prolonged administration, however no toxic effect was observed on the kidney within the duration of this study.

Topology optimization of adaptive fluid-actuated cellular structures with arbitrary polygonal motor cells

International Nuclear Information System (INIS)

Lv, Jun; Tang, Liang; Li, Wenbo; Liu, Lei; Zhang, Hongwu

2016-01-01

This paper mainly focuses on the fast and efficient design method for plant bioinspired fluidic cellular materials and structures composed of polygonal motor cells. Here we developed a novel structural optimization method with arbitrary polygonal coarse-grid elements based on multiscale finite element frameworks. The fluidic cellular structures are meshed with irregular polygonal coarse-grid elements according to their natural size and the shape of the imbedded motor cells. The multiscale base functions of solid displacement and hydraulic pressure are then constructed to bring the small-scale information of the irregular motor cells to the large-scale simulations on the polygonal coarse-grid elements. On this basis, a new topology optimization method based on the resulting polygonal coarse-grid elements is proposed to determine the optimal distributions or number of motor cells in the smart cellular structures. Three types of optimization problems are solved according to the usages of the fluidic cellular structures. Firstly, the proposed optimization method is utilized to minimize the system compliance of the load-bearing fluidic cellular structures. Second, the method is further extended to design biomimetic compliant actuators of the fluidic cellular materials due to the fact that non-uniform volume expansions of fluid in the cells can induce elastic action. Third, the optimization problem focuses on the weight minimization of the cellular structure under the constraints for the compliance of the whole system. Several representative examples are investigated to validate the effectiveness of the proposed polygon-based topology optimization method of the smart materials. (paper)

The influence of dietary Cu and diabetes on tissue 67Cu retention kinetics in rats

International Nuclear Information System (INIS)

Uriu-Hare, J.Y.; Rucker, R.B.; Keen, C.L.

1991-01-01

Compared to controls, diabetes results in higher plasma, liver and kidney Cu concentrations. Since alterations in Cu metabolism may be associated with diabetic pathology, the authors investigated how Cu metabolism is affected by diabetes and dietary Cu intake. Nondiabetic and STZ diabetic rats were fed Cu suppl. or Cu def. diets for 5 wks. Rats were intubated with 28 μCi 67 Cu and killed after 8, 16, 24, 32, 64, or 128 h. There were marked effects of both diet and diabetes on 67 Cu metabolism. Independent of diabetes, deficient rats had a higher % of retained 67 Cu, in liver, plasma, RBC, muscle, spleen, brain, lung, uterus, and intestine than adequate Cu rats. Independent of dietary Cu, diabetic rats had a lower % of retained 67 Cu in liver, plasma, RBC, muscle, spleen, lung, bone, pancreas, skin, uterus and heart than controls. Differential effects were noted for kidney; adequate Cu diabetic rats had a higher % of retained 67 Cu than all other groups. Marked effects of both diet and diabetes were evident when tissue Cu turnover was examined. Compared to Cu suppl. rats, Cu def. rats had a slower turnover of 67 Cu, in liver, plasma, intestine, pancreas, eye, brain, muscle, spleen, lung and heart. Diabetic rats had a slower turnover of 67 Cu than nondiabetic rats in liver, plasma, intestine, pancreas, eye, kidney, RBC and uterus. The data imply that a focus on Cu metabolism with regard to cellular Cu trafficking and pathology may be warranted

3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration

Science.gov (United States)

Hu, Yu; Wu, Yao; Gou, Zhiyuan; Tao, Jie; Zhang, Jiumeng; Liu, Qianqi; Kang, Tianyi; Jiang, Shu; Huang, Siqing; He, Jiankang; Chen, Shaochen; Du, Yanan; Gou, Maling

2016-08-01

Tissue engineered conduits have great promise for bridging peripheral nerve defects by providing physical guiding and biological cues. A flexible method for integrating support cells into a conduit with desired architectures is wanted. Here, a 3D-printing technology is adopted to prepare a bio-conduit with designer structures for peripheral nerve regeneration. This bio-conduit is consisted of a cryopolymerized gelatin methacryloyl (cryoGelMA) gel cellularized with adipose-derived stem cells (ASCs). By modeling using 3D-printed “lock and key” moulds, the cryoGelMA gel is structured into conduits with different geometries, such as the designed multichannel or bifurcating and the personalized structures. The cryoGelMA conduit is degradable and could be completely degraded in 2-4 months in vivo. The cryoGelMA scaffold supports the attachment, proliferation and survival of the seeded ASCs, and up-regulates the expression of their neurotrophic factors mRNA in vitro. After implanted in a rat model, the bio-conduit is capable of supporting the re-innervation across a 10 mm sciatic nerve gap, with results close to that of the autografts in terms of functional and histological assessments. The study describes an indirect 3D-printing technology for fabricating cellularized designer conduits for peripheral nerve regeneration, and could lead to the development of future nerve bio-conduits for clinical use.

In-vivo studies of mechanisms of haematologic oncogenesis after exposure to ionizing radiation utilizing a model of rats deficient in Potassium 53

International Nuclear Information System (INIS)

Casado, J.A.; Bauluz, C.; Vidania, R. de; Real, A.

1997-01-01

The development of an appropriate radiation protection system is based on the knowledge of health effects of moderate and low radiation. The knowledge of these effects at present is insufficient for determining with exactness the health risks of the said exposure. Epidemiological studies have serious limitations which stand in the way of addressing these problems. Through studies with new experimental models, interesting information can be obtained in this respect and in particular on the oncogenic mechanism of radiation. In this study, rats deficient in Phosphorus 53 have been used to study the impact of haematological cancer after irradiation. For the purpose of characterizing populations potentially implicated in carcinogenic development, cellular morphological analyses and expression of surface markers have been carried out and the content of DNA in haematopoietic cells has been looked into. Rats with Phosphorus 53 develop fundamentally altered lymphomas after irradiation. Leukaemias were also observed, even though the number of rats examined was low. The proposed methodology demonstrates great potential through the study of cellular changes and associated molecules in radiation induced carcinogenic development

Synergistic effect of aluminum and ionizing radiation upon ultrastructure, oxidative stress and apoptotic alterations in Paneth cells of rat intestine.

Science.gov (United States)

Eltahawy, N A; Elsonbaty, S M; Abunour, S; Zahran, W E

2017-03-01

Environmental and occupational exposure to aluminum along with ionizing radiation results in serious health problems. This study was planned to investigate the impact of oxidative stress provoked by exposure to ionizing radiation with aluminum administration upon cellular ultra structure and apoptotic changes in Paneth cells of rat small intestine . Animals received daily aluminum chloride by gastric gavage at a dose 0.5 mg/Kg BW for 4 weeks. Whole body gamma irradiation was applied at a dose 2 Gy/week up to 8 Gy. Ileum malondialdehyde, advanced oxidative protein products, protein carbonyl and tumor necrosis factor-alpha were assessed as biomarkers of lipid peroxidation, protein oxidation and inflammation respectively along with superoxide dismutase, catalase, and glutathione peroxidase activities as enzymatic antioxidants. Moreover, analyses of cell cycle division and apoptotic changes were evaluated by flow cytometry. Intestinal cellular ultra structure was investigated using transmission electron microscope.Oxidative and inflammatory stresses assessment in the ileum of rats revealed that aluminum and ionizing radiation exposures exhibited a significant effect upon the increase in oxidative stress biomarkers along with the inflammatory marker tumor necrosis factor-α accompanied by a significant decreases in the antioxidant enzyme activities. Flow cytometric analyses showed significant alterations in the percentage of cells during cell cycle division phases along with significant increase in apoptotic cells. Ultra structurally, intestinal cellular alterations with marked injury in Paneth cells at the sites of bacterial translocation in the crypt of lumens were recorded. The results of this study have clearly showed that aluminum and ionizing radiation exposures induced apoptosis with oxidative and inflammatory disturbance in the Paneth cells of rat intestine, which appeared to play a major role in the pathogenesis of cellular damage. Furthermore, the

Dopaminergic enhancement of cellular adhesion in bone marrow derived mesenchymal stem cells (MSCs).

Science.gov (United States)

Chen, Si; Bai, Bing; Lee, Dong Joon; Diachina, Shannon; Li, Yina; Wong, Sing Wai; Wang, Zhengyan; Tseng, Henry C; Ko, Ching-Chang

2017-08-01

Dopamine (DA) is a well-known neurotransmitter and critical element in the mussel adhesive protein that has gained increasing attention for its role in cellular growth enhancement in biomaterials, including cellular adhesion improvement. As the mechanism underlying this remains unclear, the objective of this study was to explore the effects of DA on the adhesion properties of bone marrow derived rat mesenchymal stem cells (rMSCs) using an hydroxyapatite gelatin nanocomposite biomaterial and to test whether the effects are mediated through various endogenously expressed DA receptors. Primary rMSCs were pretreated with D1-like antagonist, D2-like antagonist, or a combination of these antagonists followed by treatment with 50 μM DA and cellular adhesion quantification at 0.5, 1, 2 and 4 hours post DA addition. DA was found to increase rMSC adhesion and spreading at the 0.5 hour time-point and the dopaminergic effect on cell adhesion was partially blocked by DA antagonists. In addition, the D1-like and D2-like antagonists appeared to have a similar effect on rMSCs. Immunofluorescent staining indicated that the rMSC spreading area was significantly increased in the DA treated group versus the control group. Treatment of the D1-like DA antagonists with DA revealed that the actin filaments of rMSCs could not connect the membrane with the nucleus. In summary, DA was found to enhance early rMSC adhesion partially via DA receptor activation.

Effect of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity.

Science.gov (United States)

Topdag, M; Iseri, M; Gelenli, E; Yardimoglu, M; Yazir, Y; Ulubil, S A; Topdag, D O; Ustundag, E

2012-11-01

This study aimed to contribute to the literature on the prevention and treatment of ototoxicity due to various drugs and chemicals. This study compared the histological effects of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity, in 36 rats. Dexamethasone and memantine had significant effects on the stria vascularis, organ of Corti and spiral ganglion (p piracetam decreased the apoptosis rate, this effect was not statistically significant (p > 0.05). Dexamethasone and memantine were found superior to piracetam in reducing apoptosis due to cisplatin ototoxicity. Further studies of this subject are needed, incorporating electron microscopy and auditory brainstem response testing.

Aging and the Disposition and Toxicity of Mercury in Rats

Science.gov (United States)

Bridges, Christy C.; Joshee, Lucy; Zalups, Rudolfs K.

2014-01-01

Progressive loss of functioning nephrons, secondary to age-related glomerular disease, can impair the ability of the kidneys to effectively clear metabolic wastes and toxicants from blood. Additionally, as renal mass is diminished, cellular hypertrophy occurs in functional nephrons that remain. We hypothesize that these nephrons are exposed to greater levels of nephrotoxicants, such as inorganic mercury (Hg2+), and thus are at an increased risk of becoming intoxicated by these compounds. The purpose of the present study was to characterize the effects of aging on the disposition and renal toxicity of Hg2+ in young adult and aged Wistar rats. Paired groups of animals were injected (i.v.) with either a 0.5 μmol • kg−1 non-nephrotoxic or a 2.5 μmol • kg−1 nephrotoxic dose of mercuric chloride (HgCl2). Plasma creatinine and renal biomarkers of proximal tubular injury were greater in both groups of aged rats than in the corresponding groups of young adult rats. Histologically, evidence of glomerular sclerosis, tubular atrophy, interstitial inflammation and fibrosis were significant features of kidneys from aged animals. In addition, proximal tubular necrosis, especially along the straight segments in the inner cortex and outer stripe of the outer medulla was a prominent feature in the renal sections from both aged and young rats treated with the nephrotoxic dose of HgCl2. Our findings indicate 1) that overall renal function is significantly impaired in aged rats, resulting in chronic renal insufficiency and 2) the disposition of HgCl2 in aging rats is significantly altered compared to that of young rats. PMID:24548775

Aging and the disposition and toxicity of mercury in rats.

Science.gov (United States)

Bridges, Christy C; Joshee, Lucy; Zalups, Rudolfs K

2014-05-01

Progressive loss of functioning nephrons, secondary to age-related glomerular disease, can impair the ability of the kidneys to effectively clear metabolic wastes and toxicants from blood. Additionally, as renal mass is diminished, cellular hypertrophy occurs in functional nephrons that remain. We hypothesize that these nephrons are exposed to greater levels of nephrotoxicants, such as inorganic mercury (Hg(2+)), and thus are at an increased risk of becoming intoxicated by these compounds. The purpose of the present study was to characterize the effects of aging on the disposition and renal toxicity of Hg(2+) in young adult and aged Wistar rats. Paired groups of animals were injected (i.v.) with either a 0.5μmol·kg(-1) non-nephrotoxic or a 2.5μmol·kg(-1) nephrotoxic dose of mercuric chloride (HgCl2). Plasma creatinine and renal biomarkers of proximal tubular injury were greater in both groups of aged rats than in the corresponding groups of young adult rats. Histologically, evidence of glomerular sclerosis, tubular atrophy, interstitial inflammation and fibrosis were significant features of kidneys from aged animals. In addition, proximal tubular necrosis, especially along the straight segments in the inner cortex and outer stripe of the outer medulla was a prominent feature in the renal sections from both aged and young rats treated with the nephrotoxic dose of HgCl2. Our findings indicate 1) that overall renal function is significantly impaired in aged rats, resulting in chronic renal insufficiency and 2) the disposition of HgCl2 in aging rats is significantly altered compared to that of young rats. Copyright © 2014 Elsevier Inc. All rights reserved.

Dynamic behavior of cellular materials and cellular structures: Experiments and modeling

Science.gov (United States)

Gao, Ziyang

Cellular solids, including cellular materials and cellular structures (CMS), have attracted people's great interests because of their low densities and novel physical, mechanical, thermal, electrical and acoustic properties. They offer potential for lightweight structures, energy absorption, thermal management, etc. Therefore, the studies of cellular solids have become one of the hottest research fields nowadays. From energy absorption point of view, any plastically deformed structures can be divided into two types (called type I and type II), and the basic cells of the CMS may take the configurations of these two types of structures. Accordingly, separated discussions are presented in this thesis. First, a modified 1-D model is proposed and numerically solved for a typical type II structure. Good agreement is achieved with the previous experimental data, hence is used to simulate the dynamic behavior of a type II chain. Resulted from different load speeds, interesting collapse modes are observed, and the parameters which govern the cell's post-collapse behavior are identified through a comprehensive non-dimensional analysis on general cellular chains. Secondly, the MHS specimens are chosen as an example of type I foam materials because of their good uniformity of the cell geometry. An extensive experimental study was carried out, where more attention was paid to their responses to dynamic loadings. Great enhancement of the stress-strain curve was observed in dynamic cases, and the energy absorption capacity is found to be several times higher than that of the commercial metal foams. Based on the experimental study, finite elemental simulations and theoretical modeling are also conducted, achieving good agreements and demonstrating the validities of those models. It is believed that the experimental, numerical and analytical results obtained in the present study will certainly deepen the understanding of the unsolved fundamental issues on the mechanical behavior of

Tributyltin chloride induces renal dysfunction by inflammation and oxidative stress in female rats.

Science.gov (United States)

Coutinho, João V S; Freitas-Lima, Leandro C; Freitas, Frederico F C T; Freitas, Flávia P S; Podratz, Priscila L; Magnago, Rafaella P L; Porto, Marcella L; Meyrelles, Silvana S; Vasquez, Elisardo C; Brandão, Poliane A A; Carneiro, Maria T W D; Paiva-Melo, Francisca D; Miranda-Alves, Leandro; Silva, Ian V; Gava, Agata L; Graceli, Jones B

2016-10-17

Tributyltin chloride (TBT) is an organometallic pollutant that is used as a biocide in antifouling paints. TBT induces several toxic and endocrine-disrupting effects. However, studies evaluating the effects of TBT on renal function are rare. This study demonstrates that TBT exposure is responsible for improper renal function as well as the development of abnormal morphophysiology in mammalian kidneys. Female rats were treated with TBT, and their renal morphophysiology was assessed. Morphophysiological abnormalities such as decreased glomerular filtration rate and increased proteinuria levels were observed in TBT rats. In addition, increases in inflammation, collagen deposition and α-smooth muscle actin (α-SMA) protein expression were observed in TBT kidneys. A disrupted cellular redox balance and apoptosis in kidney tissue were also observed in TBT rats. TBT rats demonstrated reduced serum estrogen levels and estrogen receptor-α (ERα) protein expression in renal cortex. Together, these data provide in vivo evidence that TBT is toxic to normal renal function and that these effects may be associated with renal histopathology complications, such as inflammation and fibrosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Analysis of disease-associated objects at the Rat Genome Database

Science.gov (United States)

Wang, Shur-Jen; Laulederkind, Stanley J. F.; Hayman, G. T.; Smith, Jennifer R.; Petri, Victoria; Lowry, Timothy F.; Nigam, Rajni; Dwinell, Melinda R.; Worthey, Elizabeth A.; Munzenmaier, Diane H.; Shimoyama, Mary; Jacob, Howard J.

2013-01-01

The Rat Genome Database (RGD) is the premier resource for genetic, genomic and phenotype data for the laboratory rat, Rattus norvegicus. In addition to organizing biological data from rats, the RGD team focuses on manual curation of gene–disease associations for rat, human and mouse. In this work, we have analyzed disease-associated strains, quantitative trait loci (QTL) and genes from rats. These disease objects form the basis for seven disease portals. Among disease portals, the cardiovascular disease and obesity/metabolic syndrome portals have the highest number of rat strains and QTL. These two portals share 398 rat QTL, and these shared QTL are highly concentrated on rat chromosomes 1 and 2. For disease-associated genes, we performed gene ontology (GO) enrichment analysis across portals using RatMine enrichment widgets. Fifteen GO terms, five from each GO aspect, were selected to profile enrichment patterns of each portal. Of the selected biological process (BP) terms, ‘regulation of programmed cell death’ was the top enriched term across all disease portals except in the obesity/metabolic syndrome portal where ‘lipid metabolic process’ was the most enriched term. ‘Cytosol’ and ‘nucleus’ were common cellular component (CC) annotations for disease genes, but only the cancer portal genes were highly enriched with ‘nucleus’ annotations. Similar enrichment patterns were observed in a parallel analysis using the DAVID functional annotation tool. The relationship between the preselected 15 GO terms and disease terms was examined reciprocally by retrieving rat genes annotated with these preselected terms. The individual GO term–annotated gene list showed enrichment in physiologically related diseases. For example, the ‘regulation of blood pressure’ genes were enriched with cardiovascular disease annotations, and the ‘lipid metabolic process’ genes with obesity annotations. Furthermore, we were able to enhance enrichment of neurological

Simultaneous development of antibody-dependent cellular cytotoxicity (ADCC) and natural killer (NK) activity in irradiated mice reconstituted with bone marrow cells

International Nuclear Information System (INIS)

Sihvola, M.; Hurme, M.

1987-01-01

Spleen cells from irradiated, bone marrow-reconstituted mice were tested for their ability to mediate antibody-dependent cellular cytotoxicity against P815 target (ADCC-P815), ADCC against sheep red blood cells (ADCC-SRBC), and natural killer (NK) activity judged as YAC-1 lysis at different times after bone marrow reconstitution. Donor-derived ADCC-P815 effectors were found to appear in the spleens 10-12 days after bone marrow reconstitution simultaneously with the appearance of donor-derived NK cells. NK cells recently derived from bone marrow are known to express the Thy-1 antigen; the phenotype of the ''early'' ADCC-P815 effectors was found to be the same as that of NK cells, i.e., Thy-1+, asialo-GM1+. These data suggest that ADCC-P815 effector cells belong to the NK cell population. ADCC-SRBC, in contrast to ADCC-P815 and NK activity, was already high on Day 7 after bone marrow reconstitution. However, it was mediated partly by recipient-derived effectors. ADCC-SRBC effectors were characterized to be different from ADCC-P815 effectors

Gender-Dimorphic Regulation of Skeletal Muscle Proteins in Streptozotocin-Induced Diabetic Rats

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Minji Choi

2013-03-01

Full Text Available Background: Despite the fact that sexual differences increase diabetic risk and contribute to the need for gender-specific care, there remain contradictory results as to whether or not sexual dimorphism increases susceptibility to the development of type 1 diabetes mellitus. Methods: To examine gender-dimorphic regulation of skeletal muscle proteins between healthy control and STZ-induced diabetic rats of both genders, we performed differential proteome analysis using two-dimensional electrophoresis combined with mass spectrometry. Results: Animal experiments revealed that STZ treatment rendered female rats more susceptible to induction of diabetes than their male littermates with significantly lower plasma insulin levels due to hormonal regulation. Proteomic analysis of skeletal muscle identified a total of 21 proteins showing gender-dimorphic differential expression patterns between healthy controls and diabetic rats. Most interestingly, gender-specific proteome comparison showed that male and female rats displayed differential regulation of proteins involved in muscle contraction, carbohydrate, and lipid metabolism, as well as oxidative phosphorylation and cellular stress. Conclusion: The current proteomic study revealed that impaired protein regulation was more prominent in the muscle tissue of female diabetic rats, which were more susceptible to STZ-induced diabetes. We expect that the present proteomic data can provide valuable information for evidence-based gender-specific treatment of diabetes.

Molecular, cellular, and tissue engineering

CERN Document Server

Bronzino, Joseph D

2015-01-01

Known as the bible of biomedical engineering, The Biomedical Engineering Handbook, Fourth Edition, sets the standard against which all other references of this nature are measured. As such, it has served as a major resource for both skilled professionals and novices to biomedical engineering. Molecular, Cellular, and Tissue Engineering, the fourth volume of the handbook, presents material from respected scientists with diverse backgrounds in molecular biology, transport phenomena, physiological modeling, tissue engineering, stem cells, drug delivery systems, artificial organs, and personalized medicine. More than three dozen specific topics are examined, including DNA vaccines, biomimetic systems, cardiovascular dynamics, biomaterial scaffolds, cell mechanobiology, synthetic biomaterials, pluripotent stem cells, hematopoietic stem cells, mesenchymal stem cells, nanobiomaterials for tissue engineering, biomedical imaging of engineered tissues, gene therapy, noninvasive targeted protein and peptide drug deliver...

Blunted neuronal calcium response to hypoxia in naked mole-rat hippocampus.

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Bethany L Peterson

Full Text Available Naked mole-rats are highly social and strictly subterranean rodents that live in large communal colonies in sealed and chronically oxygen-depleted burrows. Brain slices from naked mole-rats show extreme tolerance to hypoxia compared to slices from other mammals, as indicated by maintenance of synaptic transmission under more hypoxic conditions and three fold longer latency to anoxic depolarization. A key factor in determining whether or not the cellular response to hypoxia is reversible or leads to cell death may be the elevation of intracellular calcium concentration. In the present study, we used fluorescent imaging techniques to measure relative intracellular calcium changes in CA1 pyramidal cells of hippocampal slices during hypoxia. We found that calcium accumulation during hypoxia was significantly and substantially attenuated in slices from naked mole-rats compared to slices from laboratory mice. This was the case for both neonatal (postnatal day 6 and older (postnatal day 20 age groups. Furthermore, while both species demonstrated more calcium accumulation at older ages, the older naked mole-rats showed a smaller calcium accumulation response than even the younger mice. A blunted intracellular calcium response to hypoxia may contribute to the extreme hypoxia tolerance of naked mole-rat neurons. The results are discussed in terms of a general hypothesis that a very prolonged or arrested developmental process may allow adult naked mole-rat brain to retain the hypoxia tolerance normally only seen in neonatal mammals.

Blunted neuronal calcium response to hypoxia in naked mole-rat hippocampus.

Science.gov (United States)

Peterson, Bethany L; Larson, John; Buffenstein, Rochelle; Park, Thomas J; Fall, Christopher P

2012-01-01

Naked mole-rats are highly social and strictly subterranean rodents that live in large communal colonies in sealed and chronically oxygen-depleted burrows. Brain slices from naked mole-rats show extreme tolerance to hypoxia compared to slices from other mammals, as indicated by maintenance of synaptic transmission under more hypoxic conditions and three fold longer latency to anoxic depolarization. A key factor in determining whether or not the cellular response to hypoxia is reversible or leads to cell death may be the elevation of intracellular calcium concentration. In the present study, we used fluorescent imaging techniques to measure relative intracellular calcium changes in CA1 pyramidal cells of hippocampal slices during hypoxia. We found that calcium accumulation during hypoxia was significantly and substantially attenuated in slices from naked mole-rats compared to slices from laboratory mice. This was the case for both neonatal (postnatal day 6) and older (postnatal day 20) age groups. Furthermore, while both species demonstrated more calcium accumulation at older ages, the older naked mole-rats showed a smaller calcium accumulation response than even the younger mice. A blunted intracellular calcium response to hypoxia may contribute to the extreme hypoxia tolerance of naked mole-rat neurons. The results are discussed in terms of a general hypothesis that a very prolonged or arrested developmental process may allow adult naked mole-rat brain to retain the hypoxia tolerance normally only seen in neonatal mammals.

Enhancing repair of radiation-induced strand breaks in cellular DNA as a radiotherapeutic potential

International Nuclear Information System (INIS)

Nair, C.K.K.

2014-01-01

Protection of mammalian organisms including man from deleterious effects of ionizing radiation is of paramount importance and development of effective approaches to combat radiation damages using non-toxic radioprotectors is of considerable interest for defence, nuclear industries, radiation accidents, space travels, etc., besides the protection of normal tissues during radiotherapy of tumours. Many synthetic as well as natural compounds have been investigated in the recent past for their efficacy to protect the biological systems from radiation induced damages. They include sulfhydryl compounds, antioxidants, plant extracts, immune-modulators, and other agents. However, the inherent toxicity of many of the synthetic agents at the effective radio-protective concentration warranted further search for safer and more effective radio-protectors. In this context, therapeutic radioprotectors which are effective on post irradiation administration are of special relevance. One of the property that can be applied while screening for such radiation protective therapeutics is their ability to enhance repair of radiation-induced lesions in cellular DNA in terms of cellular repair index based on the parameters of the DNA following comet assay. Post irradiation administration of some natural and synthetic agents have shown their potential to enhance repair of radiation-induced strand breaks in cellular DNA in mice. These include phytoceuticals such as gallic acid, sesamol etc., extracts of medicinal plants such as Andrographis panniculata, and a few synthetic compounds such as tocopherol-mono-glucoside. The talk will give an overview of the work on DNA repair enhancement by a few natural and synthetic agents. (author)

Statistical mechanics of cellular automata

International Nuclear Information System (INIS)

Wolfram, S.

1983-01-01

Cellular automata are used as simple mathematical models to investigate self-organization in statistical mechanics. A detailed analysis is given of ''elementary'' cellular automata consisting of a sequence of sites with values 0 or 1 on a line, with each site evolving deterministically in discrete time steps according to p definite rules involving the values of its nearest neighbors. With simple initial configurations, the cellular automata either tend to homogeneous states, or generate self-similar patterns with fractal dimensions approx. =1.59 or approx. =1.69. With ''random'' initial configurations, the irreversible character of the cellular automaton evolution leads to several self-organization phenomena. Statistical properties of the structures generated are found to lie in two universality classes, independent of the details of the initial state or the cellular automaton rules. More complicated cellular automata are briefly considered, and connections with dynamical systems theory and the formal theory of computation are discussed

Preparation of Well-Dispersed Chitosan/Alginate Hollow Multilayered Microcapsules for Enhanced Cellular Internalization

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Carla Ribeiro

2018-03-01

Full Text Available Hollow multilayered capsules have shown massive potential for being used in the biomedical and biotechnology fields, in applications such as cellular internalization, intracellular trafficking, drug delivery, or tissue engineering. In particular, hollow microcapsules, developed by resorting to porous calcium carbonate sacrificial templates, natural-origin building blocks and the prominent Layer-by-Layer (LbL technology, have attracted increasing attention owing to their key features. However, these microcapsules revealed a great tendency to aggregate, which represents a major hurdle when aiming for cellular internalization and intracellular therapeutics delivery. Herein, we report the preparation of well-dispersed polysaccharide-based hollow multilayered microcapsules by combining the LbL technique with an optimized purification process. Cationic chitosan (CHT and anionic alginate (ALG were chosen as the marine origin polysaccharides due to their biocompatibility and structural similarity to the extracellular matrices of living tissues. Moreover, the inexpensive and highly versatile LbL technology was used to fabricate core-shell microparticles and hollow multilayered microcapsules, with precise control over their composition and physicochemical properties, by repeating the alternate deposition of both materials. The microcapsules’ synthesis procedure was optimized to extensively reduce their natural aggregation tendency, as shown by the morphological analysis monitored by advanced microscopy techniques. The well-dispersed microcapsules showed an enhanced uptake by fibroblasts, opening new perspectives for cellular internalization.

Nucleus accumbens neuronal maturation differences in young rats bred for low versus high voluntary running behaviour

Science.gov (United States)

Roberts, Michael D; Toedebusch, Ryan G; Wells, Kevin D; Company, Joseph M; Brown, Jacob D; Cruthirds, Clayton L; Heese, Alexander J; Zhu, Conan; Rottinghaus, George E; Childs, Thomas E; Booth, Frank W

2014-01-01

We compared the nucleus accumbens (NAc) transcriptomes of generation 8 (G8), 34-day-old rats selectively bred for low (LVR) versus high voluntary running (HVR) behaviours in rats that never ran (LVRnon-run and HVRnon-run), as well as in rats after 6 days of voluntary wheel running (LVRrun and HVRrun). In addition, the NAc transcriptome of wild-type Wistar rats was compared. The purpose of this transcriptomics approach was to generate testable hypotheses as to possible NAc features that may be contributing to running motivation differences between lines. Ingenuity Pathway Analysis and Gene Ontology analyses suggested that ‘cell cycle’-related transcripts and the running-induced plasticity of dopamine-related transcripts were lower in LVR versus HVR rats. From these data, a hypothesis was generated that LVR rats might have less NAc neuron maturation than HVR rats. Follow-up immunohistochemistry in G9–10 LVRnon-run rats suggested that the LVR line inherently possessed fewer mature medium spiny (Darpp-32-positive) neurons (P running wheel access in our G9–10 LVRs uniquely increased their Darpp-32-positive and Dcx-positive neuron densities. In summary, NAc cellularity differences and/or the lack of running-induced plasticity in dopamine signalling-related transcripts may contribute to low voluntary running motivation in LVR rats. PMID:24665095

Neural networks and cellular automata in experimental high energy physics

Energy Technology Data Exchange (ETDEWEB)

Denby, B

1988-06-01

Within the past few years, two novel computing techniques, cellular automata and neural networks, have shown considerable promise in the solution of problems of a very high degree of complexity, such as turbulent fluid flow, image processing, and pattern recognition. Many of the problems faced in experimental high energy physics are also of this nature. Track reconstruction in wire chambers and cluster finding in cellular calorimeters, for instance, involve pattern recognition and high combinatorial complexity since many combinations of hits or cells must be considered in order to arrive at the final tracks or clusters. Here we examine in what way connective network methods can be applied to some of the problems of experimental high energy physics. It is found that such problems as track and cluster finding adapt naturally to these approaches. When large scale hard-wired connective networks become available, it will be possible to realize solutions to such problems in a fraction of the time required by traditional methods. For certain types of problems, faster solutions are already possible using model networks implemented on vector or other massively parallel machines. It should also be possible, using existing technology, to build simplified networks that will allow detailed reconstructed event information to be used in fast trigger decisions.

Neural networks and cellular automata in experimental high energy physics

International Nuclear Information System (INIS)

Denby, B.

1987-11-01

Within the past few years, two novel computing techniques, cellular automata and neural networks, have shown considerable promise in the solution of problems of a very high degree of complexity, such as turbulent fluid flow, image processing, and pattern recognition. Many of the problems faced in experimental high energy physics are also of this nature. Track reconstruction in wire chambers and cluster finding in cellular calorimeters, for instance, involve pattern recognition and high combinatorial complexity since many combinations of hits or cells must be considered in order to arrive at the final tracks or clusters. Here we examine in what way connective network methods can be applied to some of the problems of experimental high physics. It is found that such problems as track and cluster finding adapt naturally to these approaches. When large scale hardwired connective networks become available, it will be possible to realize solutions to such problems in a fraction of the time required by traditional methods. For certain types of problems, faster solutions are already possible using model networks implemented on vector or other massively parallel machines. It should also be possible, using existing technology, to build simplified networks that will allow detailed reconstructed event information to be used in fast trigger decisions

Neural networks and cellular automata in experimental high energy physics

International Nuclear Information System (INIS)

Denby, B.

1988-01-01

Within the past few years, two novel computing techniques, cellular automata and neural networks, have shown considerable promise in the solution of problems of a very high degree of complexity, such as turbulent fluid flow, image processing, and pattern recognition. Many of the problems faced in experimental high energy physics are also of this nature. Track reconstruction in wire chambers and cluster finding in cellular calorimeters, for instance, involve pattern recognition and high combinatorial complexity since many combinations of hits or cells must be considered in order to arrive at the final tracks or clusters. Here we examine in what way connective network methods can be applied to some of the problems of experimental high energy physics. It is found that such problems as track and cluster finding adapt naturally to these approaches. When large scale hard-wired connective networks become available, it will be possible to realize solutions to such problems in a fraction of the time required by traditional methods. For certain types of problems, faster solutions are already possible using model networks implemented on vector or other massively parallel machines. It should also be possible, using existing technology, to build simplified networks that will allow detailed reconstructed event information to be used in fast trigger decisions. (orig.)

Role of certain plant natural products or gamma radiation in the control of mutagenic activity of some heterocyclic amines

International Nuclear Information System (INIS)

Abu Ghadeer, A.R.M.; El-Sedeek, A.B.A.; Salem, A.M.; Abu Zaid, M.M.

1999-01-01

The present study was designed to use ames test to evaluate the antimutagenic effect of some natural products on the lever microsomes extracted from rats and incubated with some chemical mutagens (heterocyclic compounds). Male swiss albino rats (120-140 g) were used as the source of liver microsomes. Three natural products (Nigella extract, garlic powder and sesame oil) were used to evaluate their antimutagenic activities on six heterocyclic amines. All the tested natural products exhibited their antimutagenic activities when added to the investigated heterocyclic compounds and the most effective product was nigella sativa. another group of rats was exposed to gamma-radiation (6.5 Gy) for testing the validity of ames test in quantitating mutagenicity using liver microsomes of irradiated rats. Liver microsomes from irradiated rats showed to lose ability for metabolic activation needed for heterocyclic amines to exert their mutagenic effect on salmonella typhimurium

Wireless Cellular Mobile Communications

OpenAIRE

Zalud, V.

2002-01-01

In this article is briefly reviewed the history of wireless cellular mobile communications, examined the progress in current second generation (2G) cellular standards and discussed their migration to the third generation (3G). The European 2G cellular standard GSM and its evolution phases GPRS and EDGE are described somewhat in detail. The third generation standard UMTS taking up on GSM/GPRS core network and equipped with a new advanced access network on the basis of code division multiple ac...

Osteochondral lesions in developing rats intoxicated with thallium twenty four hours after birth.

Science.gov (United States)

Barroso-Moguel, R; Villeda-Hernández, J; Méndez-Armenta, M; Ríos, C; Galván-Arzate, S

1992-01-01

An i.p. injection of a solution of thallium acetate in deionized water at a dose of 32 mg/kg, in 24-h-old rats, produces morphological and biochemical alterations in both cartilaginous and osseous tissues. From the beginning, there are alterations in the cartilaginous cell as well as in chrondrine, osteoblasts, osseous tissue and bone marrow. Rats were sacrificed at 24, 48, and 72 h and also at 7 days. Two animals survived for 50 days. One showed total irreversible alopecia while the other one had partial alopecia with discrete recovery. Both showed a low weight and a size of 8 cm. Microscopically, degenerative changes were produced consisting of alteration and death of many cartilaginous cells, uneven metachromasia and the chondrine and decrease of the growth cartilage, scanty bone trabeculae with few osteoblasts. The bone marrow showed few myeloblasts and megakaryocytes. Progressive cellular damage throughout the 50 days of survival represents a response of the thallium ionic accumulation and recycling in cellular mitochondria of all the body's cells. This appeared in our study as irreversible and progressive osteochondral alterations with atrophy of the skin and its adnexa, hyalinization of elastic and collagenous fibers with intense interstitial edema.

Antioxidant Properties and Cardioprotective Mechanism of Malaysian Propolis in Rats

Science.gov (United States)

Ahmed, Romana; Hossen, Md. Sakib; Ahmmed, Istiyak; Rumpa, Nur-E-Noushin; Sulaiman, Siti Amrah

2017-01-01

Propolis contains high concentrations of polyphenols, flavonoids, tannins, ascorbic acid, and reducing sugars and proteins. Malaysian Propolis (MP) has been reported to exhibit high 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and ferric reducing antioxidant power (FRAP) values. Herein, we report the antioxidant properties and cardioprotective properties of MP in isoproterenol- (ISO-) induced myocardial infarction in rats. Male Wistar rats (n = 32) were pretreated orally with an ethanol extract of MP (100 mg/kg/day) for 30 consecutive days. Subcutaneous injection of ISO (85 mg/kg in saline) for two consecutive days caused a significant increase in serum cardiac marker enzymes and cardiac troponin I levels and altered serum lipid profiles. In addition significantly increased lipid peroxides and decreased activities of cellular antioxidant defense enzymes were observed in the myocardium. However, pretreatment of ischemic rats with MP ameliorated the biochemical parameters, indicating the protective effect of MP against ISO-induced ischemia in rats. Histopathological findings obtained for the myocardium further confirmed the biochemical findings. It is concluded that MP exhibits cardioprotective activity against ISO-induced oxidative stress through its direct cytotoxic radical-scavenging activities. It is also plausible that MP contributed to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation. PMID:28261310

Antioxidant Properties and Cardioprotective Mechanism of Malaysian Propolis in Rats

Directory of Open Access Journals (Sweden)

Romana Ahmed

2017-01-01

Full Text Available Propolis contains high concentrations of polyphenols, flavonoids, tannins, ascorbic acid, and reducing sugars and proteins. Malaysian Propolis (MP has been reported to exhibit high 1,1-diphenyl-2-picrylhydrazyl (DPPH radical-scavenging activity and ferric reducing antioxidant power (FRAP values. Herein, we report the antioxidant properties and cardioprotective properties of MP in isoproterenol- (ISO- induced myocardial infarction in rats. Male Wistar rats (n=32 were pretreated orally with an ethanol extract of MP (100 mg/kg/day for 30 consecutive days. Subcutaneous injection of ISO (85 mg/kg in saline for two consecutive days caused a significant increase in serum cardiac marker enzymes and cardiac troponin I levels and altered serum lipid profiles. In addition significantly increased lipid peroxides and decreased activities of cellular antioxidant defense enzymes were observed in the myocardium. However, pretreatment of ischemic rats with MP ameliorated the biochemical parameters, indicating the protective effect of MP against ISO-induced ischemia in rats. Histopathological findings obtained for the myocardium further confirmed the biochemical findings. It is concluded that MP exhibits cardioprotective activity against ISO-induced oxidative stress through its direct cytotoxic radical-scavenging activities. It is also plausible that MP contributed to endogenous antioxidant enzyme activity via inhibition of lipid peroxidation.

MSAT and cellular hybrid networking

Science.gov (United States)

Baranowsky, Patrick W., II

Westinghouse Electric Corporation is developing both the Communications Ground Segment and the Series 1000 Mobile Phone for American Mobile Satellite Corporation's (AMSC's) Mobile Satellite (MSAT) system. The success of the voice services portion of this system depends, to some extent, upon the interoperability of the cellular network and the satellite communication circuit switched communication channels. This paper will describe the set of user-selectable cellular interoperable modes (cellular first/satellite second, etc.) provided by the Mobile Phone and described how they are implemented with the ground segment. Topics including roaming registration and cellular-to-satellite 'seamless' call handoff will be discussed, along with the relevant Interim Standard IS-41 Revision B Cellular Radiotelecommunications Intersystem Operations and IOS-553 Mobile Station - Land Station Compatibility Specification.

Furan induced ovarian damage in non-diabetic and diabetic rats and cellular protective role of lycopene.

Science.gov (United States)

Uçar, Semra; Pandir, Dilek

2017-11-01

In our work, furan, lycopene, and furan + lycopene treatments were applied to non-diabetic and diabetic female rats via gavage. Ovarian tissue alterations with histopathology, immunohistochemistry, malondialdehyde levels, oxidative stress parameters such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and harmful effect on ovarian tissue DNA were evaluated in all groups for 28 days. Furan caused the changes histological, ovarian cell's DNA structure, malondialdehyde levels, antioxidant enzymes activities as in a statistically significant manner in each group. Useful effect of lycopene was determined both in non-diabetic and diabetic treatment groups against furan according to the used experimental parameters. Although some histopathological alterations were seen in diabetic and non-diabetic/diabetic plus furan-treated group's ovarians, lycopene restored these variations near to normal levels in furan + lycopene treated groups for in 28 days. Additionally, the results of our immunohistochemical analysis and alterations of the oxidative stress parameters results also supported these findings. Our result confirms that lycopene has protective effect and significantly altered diabetes and furan-induced toxicity in the rat ovarian tissue.

Protective role of selenium and vitamins A, C and E against gamma irradiation-induced oxidative stress in diabetic rats

International Nuclear Information System (INIS)

Nagiub, N.I.; Abd El-maguid, A.; Saad, T.M.M.

2006-01-01

natural antioxidant mixture) might play to a certain extent an effective role on cellular damage induced by free radicals and it could also play an important role in maintaining the integrity of biological membranes and restoring the original histological pattern of the eye after radiation injury

Marine bioactive compounds: stereospecific anti-inflammatory activity of natural and synthetic cordiachromene A.

Science.gov (United States)

Benslimane, A F; Pouchus, Y F; Verbist, J F; Petit, J Y; Khettab, E N; Welin, L; Brion, J D

1992-01-01

A new synthesis is proposed for cordiachromene A (CCA), a bioactive component of the ascidian Aplidium antillense Gravier, using a method producing a racemic mixture. The anti-inflammatory activities of a natural extract and a chemically synthetic form of CCA were assessed in vivo by carrageenan-induced rat-paw edema. The activity of synthetic CCA was confirmed by a test on kaolin-induced granuloma in the rat. Strong activities were measured for both CCA, but comparison of results of the first test suggests that only the natural optically active isomer has an anti-inflammatory effect. CCA is similar to indomethacin in its effect on carrageenan-induced rat-paw edema and ten times as active as phenylbutazone.

The Progressive BSSG Rat Model of Parkinson's: Recapitulating Multiple Key Features of the Human Disease.

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Jackalina M Van Kampen

Full Text Available The development of effective neuroprotective therapies for Parkinson's disease (PD has been severely hindered by the notable lack of an appropriate animal model for preclinical screening. Indeed, most models currently available are either acute in nature or fail to recapitulate all characteristic features of the disease. Here, we present a novel progressive model of PD, with behavioural and cellular features that closely approximate those observed in patients. Chronic exposure to dietary phytosterol glucosides has been found to be neurotoxic. When fed to rats, β-sitosterol β-d-glucoside (BSSG triggers the progressive development of parkinsonism, with clinical signs and histopathology beginning to appear following cessation of exposure to the neurotoxic insult and continuing to develop over several months. Here, we characterize the progressive nature of this model, its non-motor features, the anatomical spread of synucleinopathy, and response to levodopa administration. In Sprague Dawley rats, chronic BSSG feeding for 4 months triggered the progressive development of a parkinsonian phenotype and pathological events that evolved slowly over time, with neuronal loss beginning only after toxin exposure was terminated. At approximately 3 months following initiation of BSSG exposure, animals displayed the early emergence of an olfactory deficit, in the absence of significant dopaminergic nigral cell loss or locomotor deficits. Locomotor deficits developed gradually over time, initially appearing as locomotor asymmetry and developing into akinesia/bradykinesia, which was reversed by levodopa treatment. Late-stage cognitive impairment was observed in the form of spatial working memory deficits, as assessed by the radial arm maze. In addition to the progressive loss of TH+ cells in the substantia nigra, the appearance of proteinase K-resistant intracellular α-synuclein aggregates was also observed to develop progressively, appearing first in the

Cerebellar abnormalities following hypoxia alone compared to hypoxic-ischemic forebrain injury in the developing rat brain

NARCIS (Netherlands)

Biran, V.; Heine, V.M.; Verney, C.; Sheldon, R.A.; Spadafora, R.; Vexler, Z.S.; Rowitch, D.H.; Ferriero, D.M.

2011-01-01

Two-day-old (P2) rat pups were subjected to either a global hypoxia or to electrocoagulation of the right carotid artery followed by 2.5. h hypoxia. Cellular and regional injury in the cerebellum (CB) was studied at 1, 2 and 19. days using immunohistology. Following hypoxia and hypoxia-ischemia, all

Winding through the WNT pathway during cellular development and demise.

Science.gov (United States)

Li, F; Chong, Z Z; Maiese, K

2006-01-01

In slightly over a period of twenty years, our comprehension of the cellular and molecular mechanisms that govern the Wnt signaling pathway continue to unfold. The Wnt proteins were initially implicated in viral carcinogenesis experiments associated with mammary tumors, but since this period investigations focusing on the Wnt pathways and their transmembrane receptors termed Frizzled have been advanced to demonstrate the critical nature of Wnt for the development of a variety of cell populations as well as the potential of the Wnt pathway to avert apoptotic injury. In particular, Wnt signaling plays a significant role in both the cardiovascular and nervous systems during embryonic cell patterning, proliferation, differentiation, and orientation. Furthermore, modulation of Wnt signaling under specific cellular influences can either promote or prevent the early and late stages of apoptotic cellular injury in neurons, endothelial cells, vascular smooth muscle cells, and cardiomyocytes. A number of downstream signal transduction pathways can mediate the biological response of the Wnt proteins that include Dishevelled, beta-catenin, intracellular calcium, protein kinase C, Akt, and glycogen synthase kinase-3beta. Interestingly, these cellular cascades of the Wnt-Frizzled pathways can participate in several neurodegenerative, vascular, and cardiac disorders and may be closely integrated with the function of trophic factors. Identification of the critical elements that modulate the Wnt-Frizzled signaling pathway should continue to unlock the potential of Wnt pathway for the development of new therapeutic options against neurodegenerative and vascular diseases.

Top-down cellular pyramids

Energy Technology Data Exchange (ETDEWEB)

Wu, A Y; Rosenfeld, A

1983-10-01

A cellular pyramid is an exponentially tapering stack of arrays of processors (cells), where each cell is connected to its neighbors (siblings) on its own level, to a parent on the level above, and to its children on the level below. It is shown that in some situations, if information flows top-down only, from fathers to sons, then a cellular pyramid may be no faster than a one-level cellular array; but it may be possible to use simpler cells in the pyramid case. 23 references.

Cellular decomposition in vikalloys

International Nuclear Information System (INIS)

Belyatskaya, I.S.; Vintajkin, E.Z.; Georgieva, I.Ya.; Golikov, V.A.; Udovenko, V.A.

1981-01-01

Austenite decomposition in Fe-Co-V and Fe-Co-V-Ni alloys at 475-600 deg C is investigated. The cellular decomposition in ternary alloys results in the formation of bcc (ordered) and fcc structures, and in quaternary alloys - bcc (ordered) and 12R structures. The cellular 12R structure results from the emergence of stacking faults in the fcc lattice with irregular spacing in four layers. The cellular decomposition results in a high-dispersion structure and magnetic properties approaching the level of well-known vikalloys [ru

Cellular packing, mechanical stress and the evolution of multicellularity

Science.gov (United States)

Jacobeen, Shane; Pentz, Jennifer T.; Graba, Elyes C.; Brandys, Colin G.; Ratcliff, William C.; Yunker, Peter J.

2018-03-01

The evolution of multicellularity set the stage for sustained increases in organismal complexity1-5. However, a fundamental aspect of this transition remains largely unknown: how do simple clusters of cells evolve increased size when confronted by forces capable of breaking intracellular bonds? Here we show that multicellular snowflake yeast clusters6-8 fracture due to crowding-induced mechanical stress. Over seven weeks ( 291 generations) of daily selection for large size, snowflake clusters evolve to increase their radius 1.7-fold by reducing the accumulation of internal stress. During this period, cells within the clusters evolve to be more elongated, concomitant with a decrease in the cellular volume fraction of the clusters. The associated increase in free space reduces the internal stress caused by cellular growth, thus delaying fracture and increasing cluster size. This work demonstrates how readily natural selection finds simple, physical solutions to spatial constraints that limit the evolution of group size—a fundamental step in the evolution of multicellularity.

The effects of sildenafil ciltrate on the lateral geniculate body of adult Wistar rats (Rattus norvegicus- A histological study

Directory of Open Access Journals (Sweden)

Andrew Osayame Eweka

2010-07-01

Full Text Available The histological effect of oral administration of sildenafil citrate (Viagra, commonly used as an aphrodisiac and for the treatment of erectile dysfunction on one of the visual relay centres namely the lateral geniculate body (LGB of adult Wistar rat was carefully studied. The rats of both sexes (n=24, average weight of 202g were randomly assigned into three treatment (n=18 and control (n=6 groups. The rats in the treatment groups ‘A’, ‘B’ and ‘C’ received respectively, 0.25mg/kg, 0.70mg/kg and 1.43mg/kg body weight of sildenafil citrate base dissolved in distilled water daily for 30 days, through orogastric feeding tube, while that of the control group D, received equal volume of distilled water daily during the period of the experiment. The rats were fed with growers’ mash obtained from Edo Feeds and Flour Mill Ltd, Ewu, Edo State, Nigeria and were given water liberally. The rats were sacrificed on day thirty-one of the experiment. The lateral geniculate body (LGB was carefully dissected out and quickly fixed in 10% formal saline for histological studies. The histological findings after H&E method indicated that the treated section of the lateral geniculate body (LGB showed some varying degree of reduced cellular population based on its sparse distribution, degenerative changes, cellular hypertrophy, and intercellular vacuolations appearing in the stroma. Varying dosage and long administration of sildenafil citrate may have some deleterious effects on the neurons of the intracranial visual relay centre and this may probably have some adverse effects on visual sensibilities by its deleterious effects on the cells of the lateral geniculate body (LGB of adult Wistar rats. It is therefore recommended that further studies aimed at corroborating these observations be carried out.

Point process models for localization and interdependence of punctate cellular structures.

Science.gov (United States)

Li, Ying; Majarian, Timothy D; Naik, Armaghan W; Johnson, Gregory R; Murphy, Robert F

2016-07-01

Accurate representations of cellular organization for multiple eukaryotic cell types are required for creating predictive models of dynamic cellular function. To this end, we have previously developed the CellOrganizer platform, an open source system for generative modeling of cellular components from microscopy images. CellOrganizer models capture the inherent heterogeneity in the spatial distribution, size, and quantity of different components among a cell population. Furthermore, CellOrganizer can generate quantitatively realistic synthetic images that reflect the underlying cell population. A current focus of the project is to model the complex, interdependent nature of organelle localization. We built upon previous work on developing multiple non-parametric models of organelles or structures that show punctate patterns. The previous models described the relationships between the subcellular localization of puncta and the positions of cell and nuclear membranes and microtubules. We extend these models to consider the relationship to the endoplasmic reticulum (ER), and to consider the relationship between the positions of different puncta of the same type. Our results do not suggest that the punctate patterns we examined are dependent on ER position or inter- and intra-class proximity. With these results, we built classifiers to update previous assignments of proteins to one of 11 patterns in three distinct cell lines. Our generative models demonstrate the ability to construct statistically accurate representations of puncta localization from simple cellular markers in distinct cell types, capturing the complex phenomena of cellular structure interaction with little human input. This protocol represents a novel approach to vesicular protein annotation, a field that is often neglected in high-throughput microscopy. These results suggest that spatial point process models provide useful insight with respect to the spatial dependence between cellular structures. �

Effect of Dietary Vitamin C on Orthodontic Tooth Movement in Rats

Directory of Open Access Journals (Sweden)

Amirfarhang Miresmaeili

2015-11-01

Full Text Available Objectives: Bone remodeling occurs during orthodontic treatment; this process enables tooth movement. Many factors can affect bone remodeling at the cellular level, such as nutritional supplements that can affect tooth movement. The present study was designed to evaluate the effect of dietary vitamin C on orthodontic tooth movement in rats. Materials and Methods: This study was carried out on 36 six-week male Wistar rats with a mean weight of 225+32 g, which were randomly allocated to two equal groups. Rats in the case group received 1wt% vitamin C in their daily water. Opening springs were placed on the incisor teeth of both case and control groups. After 17 days, rats were sacrificed; the distance between the mesio-incisal angles of these teeth was measured with a digital caliper. Histological sections were made containing incisor teeth and alveolar bone and stained by hematoxylin-eosin. The number of resorption lacunae was evaluated using light microscopy.Results: Our findings showed that the amount of tooth movement in the vitamin C group was significantly higher than that in the control group (P<0.001. The osteoclast counts were significantly higher in vitamin C group (P=0.036.Conclusion: Oral vitamin C can increase orthodontic tooth movement in rats with more osteoclast lacunae around root in the pressure area. 

Oxidative Stress Parameters and Erythrocyte Membrane Adenosine Triphosphatase Activities in Streptozotocin-induced Diabetic Rats Administered Aqueous Preparation of Kalanchoe Pinnata Leaves.

Science.gov (United States)

Menon, Nikhil; Sparks, Jean; Omoruyi, Felix O

2016-01-01

Diabetes mellitus is a chronic metabolic disease that according to the World Health Organization affects more than 382 million people. The rise in diabetes mellitus coupled with the lack of an effective treatment has led many to investigate medicinal plants to identify a viable alternative. To evaluate red blood cell (RBC) membrane adenosine triphosphatase (ATPase) activities and antioxidant levels in streptozotocin-induced diabetic rats administered aqueous preparation of Kalanchoe pinnata leaves. Diabetes mellitus was induced in rats by a single administration of streptozotocin (60 mg/kg). Diabetic rats were then treated with aqueous K. pinnata preparation (three mature leaves ~ 9.96 g/70 kg body weight or about 0.14 g/kg body weight/day) for 30 days. Serum glucose, RBC membrane ATPase activities, and antioxidant levels were determined. We noted weight loss and reduced food consumption in the treated diabetic group. Serum glucose levels were reduced in the treated diabetic group compared to the other groups. Superoxide dismutase activity and glutathione levels were not significantly elevated in the treated group compared to the diabetic group. However, serum catalase activity was significantly (P < 0.05) increased in the treated diabetic group compared to the other groups. Serum thiobarbituric acid reactive substances were not significantly altered among the groups. There was a significant (P < 0.05) increase in Mg(2+) ATPase activity and a nonsignificant increase in Na(+)/K(+) ATPase activity in the RBC membrane of the treated diabetic group compared to the diabetic group. The consumption of aqueous preparation of K. pinnata may accrue benefits in the management of diabetes by lowering oxidative stress often associated with the disease and improving the availability of cellular magnesium through an increase in the magnesium ATPase pump in the RBC membrane for increased cellular metabolism of glucose through the glycolytic pathway. We noted weight loss and

Lavandula angustifolia Extract Improves the Result of Human Umbilical Mesenchymal Wharton's Jelly Stem Cell Transplantation after Contusive Spinal Cord Injury in Wistar Rats

Science.gov (United States)

Yaghoobi, Kayvan; Kaka, Gholamreza; Mansouri, Korosh; Davoodi, Shaghayegh; Sadraie, Seyed Homayoon; Hosseini, Seyed Ruhollah

2016-01-01

Introduction. The primary trauma of spinal cord injury (SCI) results in severe damage to nervous functions. At the cellular level, SCI causes astrogliosis. Human umbilical mesenchymal stem cells (HUMSCs), isolated from Wharton's jelly of the umbilical cord, can be easily obtained. Previously, we showed that the neuroprotective effects of Lavandula angustifolia can lead to improvement in a contusive SCI model in rats. Objective. The aim of this study was to investigate the effect of L. angustifolia (Lav) on HUMSC transplantation after acute SCI. Materials and Methods. Sixty adult female rats were randomly divided into eight groups. Every week after SCI onset, all animals were evaluated for behavior outcomes. H&E staining was performed to examine the lesions after injury. GFAP expression was assessed for astrogliosis. Somatosensory evoked potential (SEP) testing was performed to detect the recovery of neural conduction. Results. Behavioral tests showed that the HUMSC group improved in comparison with the SCI group, but HUMSC + Lav 400 was very effective, resulting in a significant increase in locomotion activity. Sensory tests and histomorphological and immunohistochemistry analyses verified the potentiation effects of Lav extract on HUMSC treatment. Conclusion. Transplantation of HUMSCs is beneficial for SCI in rats, and Lav extract can potentiate the functional and cellular recovery with HUMSC treatment in rats after SCI. PMID:27057171

RatMap--rat genome tools and data.

Science.gov (United States)

Petersen, Greta; Johnson, Per; Andersson, Lars; Klinga-Levan, Karin; Gómez-Fabre, Pedro M; Ståhl, Fredrik

2005-01-01

The rat genome database RatMap (http://ratmap.org or http://ratmap.gen.gu.se) has been one of the main resources for rat genome information since 1994. The database is maintained by CMB-Genetics at Goteborg University in Sweden and provides information on rat genes, polymorphic rat DNA-markers and rat quantitative trait loci (QTLs), all curated at RatMap. The database is under the supervision of the Rat Gene and Nomenclature Committee (RGNC); thus much attention is paid to rat gene nomenclature. RatMap presents information on rat idiograms, karyotypes and provides a unified presentation of the rat genome sequence and integrated rat linkage maps. A set of tools is also available to facilitate the identification and characterization of rat QTLs, as well as the estimation of exon/intron number and sizes in individual rat genes. Furthermore, comparative gene maps of rat in regard to mouse and human are provided.

RatMap—rat genome tools and data

Science.gov (United States)

Petersen, Greta; Johnson, Per; Andersson, Lars; Klinga-Levan, Karin; Gómez-Fabre, Pedro M.; Ståhl, Fredrik

2005-01-01

The rat genome database RatMap (http://ratmap.org or http://ratmap.gen.gu.se) has been one of the main resources for rat genome information since 1994. The database is maintained by CMB–Genetics at Göteborg University in Sweden and provides information on rat genes, polymorphic rat DNA-markers and rat quantitative trait loci (QTLs), all curated at RatMap. The database is under the supervision of the Rat Gene and Nomenclature Committee (RGNC); thus much attention is paid to rat gene nomenclature. RatMap presents information on rat idiograms, karyotypes and provides a unified presentation of the rat genome sequence and integrated rat linkage maps. A set of tools is also available to facilitate the identification and characterization of rat QTLs, as well as the estimation of exon/intron number and sizes in individual rat genes. Furthermore, comparative gene maps of rat in regard to mouse and human are provided. PMID:15608244

Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus

Science.gov (United States)

Title (20 words): Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus. Introduction (120 words): Polybrominated diphenyl ethers (PBDE5) possess neurotoxic effects similar to those of PCBs. The cellular a...

Receptor-mediated uptake of low density lipoprotein stimulates bile acid synthesis by cultured rat hepatocytes

International Nuclear Information System (INIS)

Junker, L.H.; Davis, R.A.

1989-01-01

The cellular mechanisms responsible for the lipoprotein-mediated stimulation of bile acid synthesis in cultured rat hepatocytes were investigated. Adding 280 micrograms/ml of cholesterol in the form of human or rat low density lipoprotein (LDL) to the culture medium increased bile acid synthesis by 1.8- and 1.6-fold, respectively. As a result of the uptake of LDL, the synthesis of [14C]cholesterol from [2-14C]acetate was decreased and cellular cholesteryl ester mass was increased. Further studies demonstrated that rat apoE-free LDL and apoE-rich high density lipoprotein (HDL) both stimulated bile acid synthesis 1.5-fold, as well as inhibited the formation of [14C]cholesterol from [2-14C]acetate. Reductive methylation of LDL blocked the inhibition of cholesterol synthesis, as well as the stimulation of bile acid synthesis, suggesting that these processes require receptor-mediated uptake. To identify the receptors responsible, competitive binding studies using 125I-labeled apoE-free LDL and 125I-labeled apoE-rich HDL were performed. Both apoE-free LDL and apoE-rich HDL displayed an equal ability to compete for binding of the other, suggesting that a receptor or a group of receptors that recognizes both apolipoproteins is involved. Additional studies show that hepatocytes from cholestyramine-treated rats displayed 2.2- and 3.4-fold increases in the binding of apoE-free LDL and apoE-rich HDL, respectively. These data show for the first time that receptor-mediated uptake of LDL by the liver is intimately linked to processes activating bile acid synthesis

Effect of ionizing radiation on rat parotid gland

Energy Technology Data Exchange (ETDEWEB)

Boraks, George; Tampelini, Flavio Silva; Pereira, Kleber Fernando; Chopard, Renato Paulo [University of Sao Paulo (USP), SP (Brazil). Inst. of Biomedical Sciences. Dept. of Anatomy]. E-mail: rchopard@usp.br

2008-01-15

A common side effect of radiotherapy used in the treatment of oral cancer is the occurrence of structural and physiological alterations of the salivary glands due to exposure to ionizing radiation, as demonstrated by conditions such as decreased salivary flow. The present study evaluated ultrastructural alterations in the parotid glands of rats receiving a fractionated dose (1,500-cGy) of radiation emitted by a Cesium-137 source and rats that were not subjected to ionizing radiation. After sacrifice, the parotid glands were removed and examined by transmission electron microscopy. Damage such as cytoplasmic vacuolisation, dilatation of the endoplasmic reticulum and destruction of mitochondria, as well as damage to the cellular membrane of acinar cells, were observed. These findings lead to the conclusion that ionizing radiation promotes alterations in the glandular parenchyma, and that these alterations are directly related to the dose level of absorbed radiation. Certain phenomena that appear in the cytoplasm and nuclear material indicate that ionizing radiation causes acinar cell death (apoptosis). (author)

Rat Lungworm Expands into North America

Centers for Disease Control (CDC) Podcasts

2016-01-21

Emily York, integrated pest management specialist at the Sam Noble Museum of Natural History, discusses the rat lungworm expansion in North America.  Created: 1/21/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 1/21/2016.

Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure.

Science.gov (United States)

Tang, Suk Peng; Kuttulebbai Nainamohamed Salam, Sirajudeen; Jaafar, Hasnan; Gan, Siew Hua; Muzaimi, Mustapha; Sulaiman, Siti Amrah

2017-01-01

Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day), Tualang honey (1.0 g/kg/day), or ubiquinol (0.2 g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week) or PQ (10 mg/kg/week) once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ ( p honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung.

Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure

Science.gov (United States)

Sulaiman, Siti Amrah

2017-01-01

Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day), Tualang honey (1.0 g/kg/day), or ubiquinol (0.2 g/kg/day) throughout the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week) or PQ (10 mg/kg/week) once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ (p honey ameliorated the toxic effects observed in the midbrain and lungs. The beneficial effects of Tualang honey were comparable to those of ubiquinol, which was used as a positive control. These findings suggest that treatment with Tualang honey may protect against PQ-induced toxicity in the rat midbrain and lung. PMID:28127418

Effects of intraperitoneal and intranasal application of Lentinan on cellular response in rats.

Science.gov (United States)

Markova, Nadya; Kussovski, Vesselin; Radoucheva, Tatyana; Dilova, Krasimira; Georgieva, Neli

2002-11-01

Lentinan (Ajinomoto, Japan) was administrated intraperitoneally (i.p.) and intranasally (i.n.) at different doses (1, 5 and 10 mg/kg) to rats. Effectiveness of Lentinan treatment was evaluated by comparative testing of cell activation (establishing the number, glycolytic and acid phosphatase activity, H2O2 production and killing ability against Salmonella enteritidis and Staphylococcus aureus) at two different compartments--peritoneal and broncho-alveolar cavities. The results indicated that Lentinan induced high-grade activation of peritoneal cells (PCs) and especially of broncho-alveolar cells (BACs) with markedly enhanced effector function (killing ability against S. aureus). Generally, Lentinan, known usually with its parenteral routes of application, can be successful to stimulate the host cell response in the respiratory tract by intranasal route of administration.

The thorny path linking cellular senescence to organismalaging

Energy Technology Data Exchange (ETDEWEB)

Patil, Christopher K.; Mian, Saira; Campisi, Judith

2005-08-09

Half a century is fast approaching since Hayflick and colleagues formally described the limited ability of normal human cells to proliferate in culture (Hayflick and Moorhead, 1961). This finding--that normal somatic cells, in contrast to cancer cells, cannot divide indefinitely--challenged the prevailing idea that cells from mortal multicellular organisms were intrinsically ''immortal'' (Carrell, 1912). It also spawned two hypotheses, essential elements of which persist today. The first held that the restricted proliferation of normal cells, now termed cellular senescence, suppresses cancer (Hayflick, 1965; Sager, 1991; Campisi, 2001). The second hypothesis, as explained in the article by Lorenzini et al., suggested that the limited proliferation of cells in culture recapitulated aspects of organismal aging (Hayflick, 1965; Martin, 1993). How well have these hypotheses weathered the ensuing decades? Before answering this question, we first consider current insights into the causes and consequences of cellular senescence. Like Lorenzini et al., we limit our discussion to mammals. We also focus on fibroblasts, the cell type studied by Lorenzini et al., but consider other types as well. We suggest that replicative capacity in culture is not a straightforward assessment, and that it correlates poorly with both longevity and body mass. We speculate this is due to the malleable and variable nature of replicative capacity, which renders it an indirect metric of qualitative and quantitative differences among cells to undergo senescence, a response that directly alters cellular phenotype and might indirectly alter tissue structure and function.

Effect of hypertensive rat plasma on ion transport of cultured vascular smooth muscle

International Nuclear Information System (INIS)

Magargal, W.W.; Overbeck, H.W.

1986-01-01

We layered fresh, unprocessed plasma from healthy rats with early (less than or equal to 7 days) or benign, chronic (greater than 3 wk) one-kidney, one-clip hypertension and from paired one-kidney normotensive control rats over confluent primary-cultured rat aortic smooth muscle cells. Plasma from all rats increased cellular ouabain-sensitive 86 Rb + uptake and sodium content and decreased ouabain-insensitive 86 Rb + uptake compared with uptakes and content in the presence of balanced salt solution (P less than 0.01). Cells incubated in the presence of plasma from rats with early (P less than 0.02) or chronic hypertension (P less than 0.01) had significantly reduced ouabain-sensitive 86 Rb + uptake when compared with cells incubated in normotensive plasma, but their intracellular Na+ contents were not lower. We no longer detected this uptake difference when chronic hypertensives drank 0.9% NaCl instead of water. Plasma from hypertensive rats also altered ouabain-insensitive 86 Rb + uptake by the cultured cells. These findings of this new, reproducible, and specific assay system support the hypothesis that plasma factors inhibit the membrane sodium-potassium pump in vascular smooth muscle cells in this form of hypertension. The abnormality occurs in both early and chronic stages, but may not be related to sodium intake. The data also provide evidence for plasma factors in hypertension altering membrane K+ permeability

Curcumin protects against tartrazine-mediated oxidative stress and hepatotoxicity in male rats.

Science.gov (United States)

El-Desoky, G E; Abdel-Ghaffar, A; Al-Othman, Z A; Habila, M A; Al-Sheikh, Y A; Ghneim, H K; Giesy, J P; Aboul-Soud, M A M

2017-02-01

Synthetic dyes have been reported to exert detrimental effects on the health of humans. This study evaluated the effects of a diet containing tartrazine (Tz) on rats which included: i) biochemical parameters including hepatic enzymes, kidney functions and profiles of lipids; ii) markers of oxidative stress in cells by measuring concentrations of malondialdehyde (MDA) and glutathione (GSH); iii) activities of selected, key hepatic antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx); iv) pathologies of liver. Also, protective effects of three doses of curcumin (CUR), a natural food coloring agent, on these parameters in rats that had been co-exposed to Tz. Fifty Wistar male albino rats were randomly divided into five groups: Group I, control, where rats were fed a normal diet; Group II, rats were fed normal diets containing 7.5 mg Tz/kg diet, dry mass (dm); In Groups III, IV and V, rats were fed diets containing Tz plus 1.0, 2.0 or 4.0 g CUR/kg diet, dm, respectively. Whole blood was collected after 90 d of exposure, homogenates of liver were prepared and the above analyses were conducted. Exposure to Tz in the diet caused statistically significant (peffects on functions of liver and kidney and the profile of relative concentrations of lipids. CUR significantly (peffects on enzymatic and non-enzymatic antioxidant and indicators of oxidative stress about rats fed Tz (Group II) to values in control rats. However, co-administration of 1.0 g CUR with Tz (Group III) exhibited a negligible effect on those parameters. The results of this study suggest benefits of the use of CUR, as a promising natural food additive to counteract oxidative stress caused by dietary exposure to the synthetic dye Tz due to potent protective antioxidant activity. Blending some natural food additives, such as CUR with diets containing synthetic dyes, could moderate potential effects of these artificial dyes. Decreasing or removing toxins in

Nature cures nature: Hypericum perforatum attenuates physical withdrawal signs in opium dependent rats.

Science.gov (United States)

Khan, Munasib; Subhan, Fazal; Khan, Arif-Ullah; Abbas, Muzaffar; Ali, Gowhar; Rauf, Khalid; Gilani, Anwarul Hassan

2014-05-01

Hypericum perforatum Linn. (Hypericaceae) (St. John's wort) attenuates opium withdrawal signs. To explore the therapeutic potential of Hypericum perforatum in the management of opium-induced withdrawal syndrome. The effect of the Hypericum perforatum hydro-ethanol extract was investigated for potential to reverse naloxone (0.25 mg/kg)-induced opium withdrawal physical signs. Rats received opium extract (80-650 mg/kg) twice daily for 8 days along with Hypericum perforatum (20 mg/kg, orally) twice daily in chronic treatment and the same single dose 1 h before induction of withdrawal syndrome in the acute treated group. Hypericum perforatum reduced stereotype jumps and wet dog shake number in the chronic treatment compared to the saline control group (F(2, 24) = 3.968, p opium withdrawal syndrome possibly through direct or indirect interaction with opioid receptors. Further study is needed to clarify its mechanism.

Cellular automata and integrodifferential equation models for cell renewal in mosaic tissues

Science.gov (United States)

Bloomfield, J. M.; Sherratt, J. A.; Painter, K. J.; Landini, G.

2010-01-01

Mosaic tissues are composed of two or more genetically distinct cell types. They occur naturally, and are also a useful experimental method for exploring tissue growth and maintenance. By marking the different cell types, one can study the patterns formed by proliferation, renewal and migration. Here, we present mathematical modelling suggesting that small changes in the type of interaction that cells have with their local cellular environment can lead to very different outcomes for the composition of mosaics. In cell renewal, proliferation of each cell type may depend linearly or nonlinearly on the local proportion of cells of that type, and these two possibilities produce very different patterns. We study two variations of a cellular automaton model based on simple rules for renewal. We then propose an integrodifferential equation model, and again consider two different forms of cellular interaction. The results of the continuous and cellular automata models are qualitatively the same, and we observe that changes in local environment interaction affect the dynamics for both. Furthermore, we demonstrate that the models reproduce some of the patterns seen in actual mosaic tissues. In particular, our results suggest that the differing patterns seen in organ parenchymas may be driven purely by the process of cell replacement under different interaction scenarios. PMID:20375040

Enhanced systemic exposure of saquinavir via the concomitant use of curcumin-loaded solid dispersion in rats.

Science.gov (United States)

Kim, Su-A; Kim, Sung-Whan; Choi, Hoo-Kyun; Han, Hyo-Kyung

2013-08-16

The present study aimed to evaluate the effect of curcumin-loaded solid dispersion on the pharmacokinetics of saquinavir in rats. Solid dispersion (SD) formulation was prepared with Solutol® HS15 to improve the solubility and bioavailability of curcumin. Subsequently, its inhibition effect on P-gp mediated cellular efflux was examined by using NCI/ADR-RES cells overexpressing P-gp. Compared to the untreated curcumin, SD formulation enhanced the cellular uptake of rhodamine-123, a P-gp substrate by approximately 3 folds in NCI/ADR-RES cells. The oral and intravenous pharmacokinetics of saquinavir were also determined in rats with/without curcumin in the different formulations. Compared to the control given saquinavir alone, curcumin-loaded solid dispersion significantly (p<0.05) increased the oral exposure of saquinavir in rats, while it did not affect the intravenous pharmacokinetics of saquinavir. The AUC and Cmax of oral saquinavir increased by 3.8- and 2.7-folds, respectively in the presence of curcumin-loaded solid dispersion. In contrast, the untreated curcumin did not affect the oral pharmacokinetics of saquinavir. These results suggest that SD formulation of curcumin should be effective to improve the in vivo effectiveness of curcumin as an absorption enhancer, leading to the improved oral exposure of saquinavir. Copyright © 2013 Elsevier B.V. All rights reserved.

Behavioral and cellular consequences of high-electrode count Utah Arrays chronically implanted in rat sciatic nerve

Science.gov (United States)

Wark, H. A. C.; Mathews, K. S.; Normann, R. A.; Fernandez, E.

2014-08-01

Objective. Before peripheral nerve electrodes can be used for the restoration of sensory and motor functions in patients with neurological disorders, the behavioral and histological consequences of these devices must be investigated. These indices of biocompatibility can be defined in terms of desired functional outcomes; for example, a device may be considered for use as a therapeutic intervention if the implanted subject retains functional neurons post-implantation even in the presence of a foreign body response. The consequences of an indwelling device may remain localized to cellular responses at the device-tissue interface, such as fibrotic encapsulation of the device, or they may affect the animal more globally, such as impacting behavioral or sensorimotor functions. The objective of this study was to investigate the overall consequences of implantation of high-electrode count intrafascicular peripheral nerve arrays, High Density Utah Slanted Electrode Arrays (HD-USEAs; 25 electrodes mm-2). Approach. HD-USEAs were implanted in rat sciatic nerves for one and two month periods. We monitored wheel running, noxious sensory paw withdrawal reflexes, footprints, nerve morphology and macrophage presence at the tissue-device interface. In addition, we used a novel approach to contain the arrays in actively behaving animals that consisted of an organic nerve wrap. A total of 500 electrodes were implanted across all ten animals. Main results. The results demonstrated that chronic implantation (⩽8 weeks) of HD-USEAs into peripheral nerves can evoke behavioral deficits that recover over time. Morphology of the nerve distal to the implantation site showed variable signs of nerve fiber degeneration and regeneration. Cytology adjacent to the device-tissue interface also showed a variable response, with some electrodes having many macrophages surrounding the electrodes, while other electrodes had few or no macrophages present. This variability was also seen along the length

On the holistic approach in cellular and cancer biology: nonlinearity, complexity, and quasi-determinism of the dynamic cellular network.

Science.gov (United States)

Waliszewski, P; Molski, M; Konarski, J

1998-06-01

A keystone of the molecular reductionist approach to cellular biology is a specific deductive strategy relating genotype to phenotype-two distinct categories. This relationship is based on the assumption that the intermediary cellular network of actively transcribed genes and their regulatory elements is deterministic (i.e., a link between expression of a gene and a phenotypic trait can always be identified, and evolution of the network in time is predetermined). However, experimental data suggest that the relationship between genotype and phenotype is nonbijective (i.e., a gene can contribute to the emergence of more than just one phenotypic trait or a phenotypic trait can be determined by expression of several genes). This implies nonlinearity (i.e., lack of the proportional relationship between input and the outcome), complexity (i.e. emergence of the hierarchical network of multiple cross-interacting elements that is sensitive to initial conditions, possesses multiple equilibria, organizes spontaneously into different morphological patterns, and is controlled in dispersed rather than centralized manner), and quasi-determinism (i.e., coexistence of deterministic and nondeterministic events) of the network. Nonlinearity within the space of the cellular molecular events underlies the existence of a fractal structure within a number of metabolic processes, and patterns of tissue growth, which is measured experimentally as a fractal dimension. Because of its complexity, the same phenotype can be associated with a number of alternative sequences of cellular events. Moreover, the primary cause initiating phenotypic evolution of cells such as malignant transformation can be favored probabilistically, but not identified unequivocally. Thermodynamic fluctuations of energy rather than gene mutations, the material traits of the fluctuations alter both the molecular and informational structure of the network. Then, the interplay between deterministic chaos, complexity, self

The role of serotoninergic neurons in rats agressive behaviour.

Science.gov (United States)

Czlonkowski, A; Kostowski, W; Markowska, L; Markiewicz, L; Wiśniewska, I

1975-10-01

Lesions of the dorsal and medial raphe nuclei that caused a marked decrease of the 5-HT level in the forebrain induced in groupped rats intraspecies aggressiveness but failed to increase mouse-killing behaviour. In rats isolated for 3 weeks lesions of the raphe nuclei did not change behaviour of "killers" and natural "non-killers". The role of 5-HT in mechanism of the aggressive behaviour is discussed.

Toxicity evaluation of chlorinated organic compounds using immortalized rat hepatocytes; Fushika rat kansaibo wo mochiita yuki enso kagobutsu no dokusei hyoka no kokoromi

Energy Technology Data Exchange (ETDEWEB)

Sone, H; Nakajima, M; Yonemoto, J [National Institute for Environmental Studies, Tsukuba (Japan)

1997-11-10

Chlorinated organic compounds has high priority for toxicity screening among environmental hazardous chemicals. In the present study, we used immortalized rat hepatocytes as a liver model in vitro to evaluate the toxicity of nine chlorinated organic compounds. Toxicity of nine chlorinated organic compounds were evaluated to cellular viability of immortalized rat hapatocytes. The potency of the toxicity based on 50% inhibitory concentration (IC50) value was in the following order: triclocalban>triclosan>3,4-dichloroaniline>2,5-diclorophenol> 2,5-dichloroanisole>p-dichlorobenzene> p-chloroaniline>o-dichlorobenzene=tris (2-chloroethyl) phosphate. The rank order of cytotoxic potency of nine chemicals was compared with toxicity information using animals. The rank order of cytotoxic potency did not relative to the order referenced mean lethal dose (LD50) as an index of acute toxicity of rats or mice. However, the rank order of cytotoxic potency relatively correlated non-observed adverse effect level (NOAEL) under the exposure duration adjusted for chronic toxicity in vivo. These data suggests that the origin of testing cell had better to make match target organ of toxic chemicals for extrapolation from data of bioassay in vitro to in vivo. 16 refs., 2 figs., 3 tabs.

Genetic variation in the cellular response of Daphnia magna (Crustacea: Cladocera) to its bacterial parasite.

Science.gov (United States)

Auld, Stuart K J R; Scholefield, Jennifer A; Little, Tom J

2010-11-07

Linking measures of immune function with infection, and ultimately, host and parasite fitness is a major goal in the field of ecological immunology. In this study, we tested for the presence and timing of a cellular immune response in the crustacean Daphnia magna following exposure to its sterilizing endoparasite Pasteuria ramosa. We found that D. magna possesses two cell types circulating in the haemolymph: a spherical one, which we call a granulocyte and an irregular-shaped amoeboid cell first described by Metchnikoff over 125 years ago. Daphnia magna mounts a strong cellular response (of the amoeboid cells) just a few hours after parasite exposure. We further tested for, and found, considerable genetic variation for the magnitude of this cellular response. These data fostered a heuristic model of resistance in this naturally coevolving host-parasite interaction. Specifically, the strongest cellular responses were found in the most susceptible hosts, indicating resistance is not always borne from a response that destroys invading parasites, but rather stems from mechanisms that prevent their initial entry. Thus, D. magna may have a two-stage defence--a genetically determined barrier to parasite establishment and a cellular response once establishment has begun.

Progress of research on activation function of NK cell exposed to low dose radiation in adoptive cellular immunotherapy

International Nuclear Information System (INIS)

Pan Xiaosong; Shi Yujia; Yao Yimin; Xu Hong; Liu Fenju

2009-01-01

Natural killer cells is an important immunological factor in killing malignant cells. Low dose radiation can enhance proliferation and biological activity of NK cell. The involvement of P38MAPK signal pathway and endogenous glutathione induced by LDR may be the probable mechanism. Natural killer cell, especially adherent natural killer cell, is the preferential choice for adoptive cellular immunotherapy, which has a remarkable foreground in malignancy therapy.(authors)

Mechanisms of Enhanced Phrenic Long-Term Facilitation in SOD1G93A Rats

Science.gov (United States)

Satriotomo, Irawan; Grebe, Ashley M.

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease, causing muscle paralysis and death from respiratory failure. Effective means to preserve/restore ventilation are necessary to increase the quality and duration of life in ALS patients. At disease end-stage in a rat ALS model (SOD1G93A), acute intermittent hypoxia (AIH) restores phrenic nerve activity to normal levels via enhanced phrenic long-term facilitation (pLTF). Mechanisms enhancing pLTF in end-stage SOD1G93A rats are not known. Moderate AIH-induced pLTF is normally elicited via cellular mechanisms that require the following: Gq-protein-coupled 5-HT2 receptor activation, new BDNF synthesis, and MEK/ERK signaling (the Q pathway). In contrast, severe AIH elicits pLTF via a distinct mechanism that requires the following: Gs-protein-coupled adenosine 2A receptor activation, new TrkB synthesis, and PI3K/Akt signaling (the S pathway). In end-stage male SOD1G93A rats and wild-type littermates, we investigated relative Q versus S pathway contributions to enhanced pLTF via intrathecal (C4) delivery of small interfering RNAs targeting BDNF or TrkB mRNA, and MEK/ERK (U0126) or PI3 kinase/Akt (PI828) inhibitors. In anesthetized, paralyzed and ventilated rats, moderate AIH-induced pLTF was abolished by siBDNF and UO126, but not siTrkB or PI828, demonstrating that enhanced pLTF occurs via the Q pathway. Although phrenic motor neuron numbers were decreased in end-stage SOD1G93A rats (∼30% survival; p phrenic motor neurons (p phrenic motor plasticity results from amplification of normal cellular mechanisms versus addition/substitution of alternative mechanisms. Greater understanding of mechanisms underlying phrenic motor plasticity in ALS may guide development of new therapies to preserve and/or restore breathing in ALS patients. PMID:28500219

Mechanisms of Enhanced Phrenic Long-Term Facilitation in SOD1G93A Rats.

Science.gov (United States)

Nichols, Nicole L; Satriotomo, Irawan; Allen, Latoya L; Grebe, Ashley M; Mitchell, Gordon S

2017-06-14

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease, causing muscle paralysis and death from respiratory failure. Effective means to preserve/restore ventilation are necessary to increase the quality and duration of life in ALS patients. At disease end-stage in a rat ALS model ( SOD1 G93A ), acute intermittent hypoxia (AIH) restores phrenic nerve activity to normal levels via enhanced phrenic long-term facilitation (pLTF). Mechanisms enhancing pLTF in end-stage SOD1 G93A rats are not known. Moderate AIH-induced pLTF is normally elicited via cellular mechanisms that require the following: G q -protein-coupled 5-HT 2 receptor activation, new BDNF synthesis, and MEK/ERK signaling (the Q pathway). In contrast, severe AIH elicits pLTF via a distinct mechanism that requires the following: G s -protein-coupled adenosine 2A receptor activation, new TrkB synthesis, and PI3K/Akt signaling (the S pathway). In end-stage male S OD1 G93A rats and wild-type littermates, we investigated relative Q versus S pathway contributions to enhanced pLTF via intrathecal (C4) delivery of small interfering RNAs targeting BDNF or TrkB mRNA, and MEK/ERK (U0126) or PI3 kinase/Akt (PI828) inhibitors. In anesthetized, paralyzed and ventilated rats, moderate AIH-induced pLTF was abolished by siBDNF and UO126, but not siTrkB or PI828, demonstrating that enhanced pLTF occurs via the Q pathway. Although phrenic motor neuron numbers were decreased in end-stage SOD1 G93A rats (∼30% survival; p phrenic motor neurons ( p phrenic motor plasticity results from amplification of normal cellular mechanisms versus addition/substitution of alternative mechanisms. Greater understanding of mechanisms underlying phrenic motor plasticity in ALS may guide development of new therapies to preserve and/or restore breathing in ALS patients. Copyright © 2017 the authors 0270-6474/17/375834-12$15.00/0.

α-fetoprotein involvement during glucocorticoid-induced precocious maturation in rat colon.

Science.gov (United States)

Chen, Min; Sun, Peng; Liu, Xiao-Yan; Dong, Dan; Du, Jun; Gu, Luo; Ge, Ying-Bin

2011-06-28

To investigate the role of α-fetoprotein (AFP), a cancer-associated fetal glycoprotein, in glucocorticoid-induced precocious maturation in rat colon. Colons from suckling Sprague-Dawley rats were used in this study. Corticosterone acetate at a dose of 100 μg/g body weight was given to normal pups on days 7, 9 and 11 after birth to induce hypercorticoidism. Control animals were injected with identical volumes of normal saline. Some rats receiving corticosterone 7 d after birth were also treated with mifepristone (RU38486), a glucocorticoid cytoplasm receptor antagonist to investigate the effects of glucocorticoids (GCs). The morphological changes of the crypt depth and villous height of the villous zone in colon were observed as indices of colon maturation. Expression levels of AFP in colons were detected by reverse transcriptase polymerase chain reaction and Western blotting. To identify the cellular localization of AFP in developing rat colons, double-immunofluorescent staining was performed using antibodies to specific mesenchymal cell marker and AFP. Corticosterone increased the crypt depth and villous height in the colon of 8- and 10-d-old rats with hypercorticoidism compared with that in the control animals (120% in 8-d-old rats and 118% in 10-d-old rats in villous height, P = 0.021; 145% in 8-d-old rats and 124% in 10-d-old rats in crypt depth, P = 0.017). These increases were accompanied by an increase of AFP expression in both mRNA and protein (2.5-folds in 8-d-old and 2.5-folds in 10-d-old rats higher than in control animals, P = 0.035; 1.8-folds in 8-d-old and 1.3-folds in 10-d-old rats higher than in control animals, P = 0.023). Increased crypt depth and villous height and increased expression of AFP in the colon of rats with hypercorticoidism were blocked by mifepristone. Both had positive staining for AFP or vimentin, and overlapped in mesenchymal cells at each tested colon. GCs promote the development of rat colon. AFP appears to be involved, in

Recombinant IgG1 Fc hexamers block cytotoxicity and pathological changes in experimental in vitro and rat models of neuromyelitis optica.

Science.gov (United States)

Tradtrantip, Lukmanee; Felix, Christian M; Spirig, Rolf; Morelli, Adriana Baz; Verkman, A S

2018-05-01

Intravenous human immunoglobulin G (IVIG) may have therapeutic benefit in neuromyelitis optica spectrum disorders (herein called NMO), in part because of the anti-inflammatory properties of the IgG Fc region. Here, we evaluated recombinant Fc hexamers consisting of the IgM μ-tailpiece fused with the Fc region of human IgG1. In vitro, the Fc hexamers prevented cytotoxicity in aquaporin-4 (AQP4) expressing cells and in rat spinal cord slice cultures exposed to NMO anti-AQP4 autoantibody (AQP4-IgG) and complement, with >500-fold greater potency than IVIG or monomeric Fc fragments. Fc hexamers at low concentration also prevented antibody-dependent cellular cytotoxicity produced by AQP4-IgG and natural killer cells. Serum from rats administered a single intravenous dose of Fc hexamers at 50 mg/kg taken at 8 h did not produce complement-dependent cytotoxicity when added to AQP4-IgG-treated AQP4-expressing cell cultures. In an experimental rat model of NMO produced by intracerebral injection of AQP4-IgG, Fc hexamers at 50 mg/kg administered before and at 12 h after AQP4-IgG fully prevented astrocyte injury, complement activation, inflammation and demyelination. These results support the potential therapeutic utility of recombinant IgG1 Fc hexamers in AQP4-IgG seropositive NMO. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cellular automata analysis and applications

CERN Document Server

Hadeler, Karl-Peter

2017-01-01

This book focuses on a coherent representation of the main approaches to analyze the dynamics of cellular automata. Cellular automata are an inevitable tool in mathematical modeling. In contrast to classical modeling approaches as partial differential equations, cellular automata are straightforward to simulate but hard to analyze. In this book we present a review of approaches and theories that allow the reader to understand the behavior of cellular automata beyond simulations. The first part consists of an introduction of cellular automata on Cayley graphs, and their characterization via the fundamental Cutis-Hedlund-Lyndon theorems in the context of different topological concepts (Cantor, Besicovitch and Weyl topology). The second part focuses on classification results: What classification follows from topological concepts (Hurley classification), Lyapunov stability (Gilman classification), and the theory of formal languages and grammars (Kůrka classification). These classifications suggest to cluster cel...

Control of fibronectin synthesis by rat granulosa cells in culture

International Nuclear Information System (INIS)

Skinner, M.K.; Dorrington, J.H.

1984-01-01

The secreted and cellular [ 35 S]methionine-radiolabeled proteins of cultured rat granulosa cells were separated by electrophoresis on sodium dodecylsulfate (SDS) polyacrylamide gradient slab gels. From 24 to 72 h of culture FSH increased the intensity of labeling of most of the secreted proteins. A 220,000-dalton protein, however, increased in intensity only in control cultures and became the major secreted protein after 72 h, comprising 20% of the total radiolabeled proteins. This protein was identified as fibronectin by immunoprecipitation. There was no increase in the secreted or cellular fibronectin in FSH- or testosterone- and insulin-treated cultures. These studies indicate that a component of extracellular matrix is a major secretory product of unstimulated immature granulosa cells. As hormones induce the differentiated functions of granulosa cells in culture, the secretion of fibronectin is inhibited

Effect of 60Co-irradiation on normal and low protein diet fed rat brain

International Nuclear Information System (INIS)

Hasan, S.S.; Habibullah, M.

1980-01-01

The effect of whole-body irradiation (Co-60) on the brain tissue in Holtzmann strain adult male rats was studied. Two doses of irradiation (450 R,950 R) were tried on animals which were fed on normal as well as low protein diets over a period of 10 generations. In the normal rats, 450 R initially caused a lowered total protein. DNA and RNA content in the brain. After 7 days a tendency towards normalcy was observed. In the 950 R irradiated normal rats the diminution of protein content appeared irreversible. In malnourished 450 R irradiated rats, the protein content rose less steeply over the 7 days of observation. A higher dose of 950 R enhanced this effect on protein and also lowered the DNA content on day 5. The RNA content in the 950 R group with malnutrition showed a marked increase towards or beyond control perhaps as an expression of uncoupled feedback control. The paper gives evidence that protein deficiency may interfere with cellular regeneration in irradiated brain. (orig.) [de

Serum-thyroxine levels in microwave-exposed rats

International Nuclear Information System (INIS)

Lu, S.T.; Lebda, N.; Michaelson, S.M.; Pettit, S.

1985-01-01

The nature of the response of the thyroid gland in animals exposed to microwave irradiation is controversial. Animal experimentation has contributed to the controversy because both increased and decreased thyroid functions have been reported. The thyroxine concentration in rats as representative of thyroid function in animals exposed to 2.45-GHz, 120-Hz amplitude-modulated microwaves has been studied. These studies covered a long time span; rats from two commercial sources (BS and CR) were used and subjected to different numbers of exposures, and therefore these data were evaluated for their stability. Two factors could influence in the result significantly, i.e., source of animal and number of sham exposures. Rats used in the 2-hr exposures were from two different commercial sources; rats from CR had a higher (but normal) thyroxine concentration than did rats from BS. Therefore the data of these animals were separated by commercial source for reevaluation. Instead of increased thyroxine concentration in rats exposed at 25, 30, and 40 mW/cm 2 , changes were not noted in any microwave-exposed rats. The influence of sham exposure revealed that appropriate concurrent control and specification of animal source are needed in longitudinal studies. Furthermore, statistical procedures used can greatly influence the conclusions. Thus the specificity of changes in thyroxine concentration in rats exposed to microwaves because of its sporadic occurrence and because of inconsistencies among experiments was doubted

Chronic Voluntary Ethanol Consumption Induces Favorable Ceramide Profiles in Selectively Bred Alcohol-Preferring (P Rats.

Directory of Open Access Journals (Sweden)

Jessica Godfrey

Full Text Available Heavy alcohol consumption has detrimental neurologic effects, inducing widespread neuronal loss in both fetuses and adults. One proposed mechanism of ethanol-induced cell loss with sufficient exposure is an elevation in concentrations of bioactive lipids that mediate apoptosis, including the membrane sphingolipid metabolites ceramide and sphingosine. While these naturally-occurring lipids serve as important modulators of normal neuronal development, elevated levels resulting from various extracellular insults have been implicated in pathological apoptosis of neurons and oligodendrocytes in several neuroinflammatory and neurodegenerative disorders. Prior work has shown that acute administration of ethanol to developing mice increases levels of ceramide in multiple brain regions, hypothesized to be a mediator of fetal alcohol-induced neuronal loss. Elevated ceramide levels have also been implicated in ethanol-mediated neurodegeneration in adult animals and humans. Here, we determined the effect of chronic voluntary ethanol consumption on lipid profiles in brain and peripheral tissues from adult alcohol-preferring (P rats to further examine alterations in lipid composition as a potential contributor to ethanol-induced cellular damage. P rats were exposed for 13 weeks to a 20% ethanol intermittent-access drinking paradigm (45 ethanol sessions total or were given access only to water (control. Following the final session, tissues were collected for subsequent chromatographic analysis of lipid content and enzymatic gene expression. Contrary to expectations, ethanol-exposed rats displayed substantial reductions in concentrations of ceramides in forebrain and heart relative to non-exposed controls, and modest but significant decreases in liver cholesterol. qRT-PCR analysis showed a reduction in the expression of sphingolipid delta(4-desaturase (Degs2, an enzyme involved in de novo ceramide synthesis. These findings indicate that ethanol intake levels

Ca2+ uptake and cellular integrity in rat EDL muscle exposed to electrostimulation, electroporation, or A23187

DEFF Research Database (Denmark)

Gissel, Hanne; Clausen, Torben

2003-01-01

We tested the hypothesis that increased Ca2+ uptake in rat extensor digitorum longus (EDL) muscle elicits cell membrane damage as assessed from release of the intracellular enzyme lactate dehydrogenase (LDH). This was done by using 1) electrostimulation, 2) electroporation, and 3) the Ca2+ ionoph...

Particles and Patterns in Cellular Automata

International Nuclear Information System (INIS)

Jen, E.; Das, R.; Beasley, C.E.

1999-01-01

This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). Our objective has been to develop tools for studying particle interactions in a class of dynamical systems characterized by discreteness, determinism, local interaction, and an inherently parallel form of evolution. These systems can be described by cellular automata (CA) and the behavior we studied has improved our understanding of the nature of patterns generated by CAs, their ability to perform global computations, and their relationship to continuous dynamical systems. We have also developed a rule-table mathematics that enables one to custom-design CA rule tables to generate patterns of specified types, or to perform specified computational tasks

Induction of passive Heymann nephritis in complement component 6-deficient PVG rats.

Science.gov (United States)

Spicer, S Timothy; Tran, Giang T; Killingsworth, Murray C; Carter, Nicole; Power, David A; Paizis, Kathy; Boyd, Rochelle; Hodgkinson, Suzanne J; Hall, Bruce M

2007-07-01

Passive Heymann nephritis (PHN), a model of human membranous nephritis, is induced in susceptible rat strains by injection of heterologous antisera to rat renal tubular Ag extract. PHN is currently considered the archetypal complement-dependent form of nephritis, with the proteinuria resulting from sublytic glomerular epithelial cell injury induced by the complement membrane attack complex (MAC) of C5b-9. This study examined whether C6 and MAC are essential to the development of proteinuria in PHN by comparing the effect of injection of anti-Fx1A antisera into PVG rats deficient in C6 (PVG/C6(-)) and normal PVG rats (PVG/c). PVG/c and PVG/C6(-) rats developed similar levels of proteinuria at 3, 7, 14, and 28 days following injection of antisera. Isolated whole glomeruli showed similar deposition of rat Ig and C3 staining in PVG/c and PVG/C6(-) rats. C9 deposition was abundant in PVG/c but was not detected in PVG/C6(-) glomeruli, indicating C5b-9/MAC had not formed in PVG/C6(-) rats. There was also no difference in the glomerular cellular infiltrate of T cells and macrophages nor the size of glomerular basement membrane deposits measured on electron micrographs. To examine whether T cells effect injury, rats were depleted of CD8+ T cells which did not affect proteinuria in the early heterologous phase but prevented the increase in proteinuria associated with the later autologous phase. These studies showed proteinuria in PHN occurs without MAC and that other mechanisms, such as immune complex size, early complement components, CD4+ and CD8+ T cells, disrupt glomerular integrity and lead to proteinuria.

HMGB1 promotes the development of pulmonary arterial hypertension in rats.

Directory of Open Access Journals (Sweden)

Yukari Sadamura-Takenaka

Full Text Available Pulmonary arterial hypertension (PAH is characterized by increased pulmonary vascular resistance leading to right ventricular failure and death. Recent studies have suggested that chronic inflammatory processes are involved in the pathogenesis of PAH. However, the molecular and cellular mechanisms driving inflammation have not been fully elucidated.To elucidate the roles of high mobility group box 1 protein (HMGB1, a ubiquitous DNA-binding protein with extracellular pro-inflammatory activity, in a rat model of PAH.Male Sprague-Dawley rats were administered monocrotaline (MCT. Concentrations of HMGB1 in bronchoalveolar lavage fluid (BALF and serum, and localization of HMGB1 in the lung were examined over time. The protective effects of anti-HMGB1 neutralizing antibody against MCT-induced PAH were tested.HMGB1 levels in BALF were elevated 1 week after MCT injection, and this elevation preceded increases of other pro-inflammatory cytokines, such as TNF-α, and the development of PAH. In contrast, serum HMGB1 levels were elevated 4 weeks after MCT injection, at which time the rats began to die. Immunohistochemical analyses indicated that HMGB1 was translocated to the extranuclear space in periarterial infiltrating cells, alveolar macrophages, and bronchial epithelial cells of MCT-injected rats. Anti-HMGB1 neutralizing antibody protected rats against MCT-induced lung inflammation, thickening of the pulmonary artery wall, and elevation of right ventricular systolic pressure, and significantly improved the survival of the MCT-induced PAH rats.Our results identify extracellular HMGB1 as a promoting factor for MCT-induced PAH. The blockade of HMGB1 activity improved survival of MCT-induced PAH rats, and thus might be a promising therapy for the treatment of PAH.

Expression of inducible nitric oxide synthase in endotoxemic rat hepatocytes is dependent on the cellular glutathione status

NARCIS (Netherlands)

Vos, TA; van Goor, H; Tuyt, L; de Jager-Krikken, A; Leuvenink, R; Kuipers, F; Jansen, PLM; Moshage, H

The inducible nitric oxide synthase (iNOS) promoter contains nuclear factor kappa B (NF-kappa B) binding sites. NF-kappa B activation is determined, in part, by the intracellular redox status, The aim of this study was to determine the importance of the cellular glutathione status in relation to

Liposomal inhibition of acrolein-induced injury in rat cultured urothelial cells.

Science.gov (United States)

Nirmal, J; Wolf-Johnston, A S; Chancellor, M B; Tyagi, P; Anthony, M; Kaufman, J; Birder, L A

2014-10-01

To study the protection offered by empty liposomes (LPs) alone against acrolein-induced changes in urothelial cell viability and explored uptake of LPs by primary (rat) urothelial cells. Acrolein was used as a means to induce cellular damage and reduce urothelial cellular viability. The effect of acrolein or liposomal treatment on cellular proliferation was studied using 5-bromo-2'-deoxy-uridine assay. Cytokine release was measured after urothelial cells were exposed to acrolein. Temperature-dependent uptake study was carried out for fluorescent-labeled LPs using confocal microscopy. Liposome pretreatment protected against acrolein-induced decrease in urothelial cell proliferation. LPs also significantly affected the acrolein-induced cytokine (interferon-gamma) release offering protection to the urothelial cells against acrolein damage. We also observed a temperature-dependent urothelial uptake of fluorescent-labeled LPs occurred at 37 °C (but not at 4 °C). Empty LPs alone provide a therapeutic efficacy against acrolein-induced changes in urothelial cell viability and may be a promising local therapy for bladder diseases. Hence, our preliminary evidence provides support for liposome-therapy for urothelial protection and possible repair.

Bistable switches control memory and plasticity in cellular differentiation

Science.gov (United States)

Wang, Lei; Walker, Brandon L.; Iannaccone, Stephen; Bhatt, Devang; Kennedy, Patrick J.; Tse, William T.

2009-01-01

Development of stem and progenitor cells into specialized tissues in multicellular organisms involves a series of cell fate decisions. Cellular differentiation in higher organisms is generally considered irreversible, and the idea of developmental plasticity in postnatal tissues is controversial. Here, we show that inhibition of mitogen-activated protein kinase (MAPK) in a human bone marrow stromal cell-derived myogenic subclone suppresses their myogenic ability and converts them into satellite cell-like precursors that respond to osteogenic stimulation. Clonal analysis of the induced osteogenic response reveals ultrasensitivity and an “all-or-none” behavior, hallmarks of a bistable switch mechanism with stochastic noise. The response demonstrates cellular memory, which is contingent on the accumulation of an intracellular factor and can be erased by factor dilution through cell divisions or inhibition of protein synthesis. The effect of MAPK inhibition also exhibits memory and appears to be controlled by another bistable switch further upstream that determines cell fate. Once the memory associated with osteogenic differentiation is erased, the cells regain their myogenic ability. These results support a model of cell fate decision in which a network of bistable switches controls inducible production of lineage-specific differentiation factors. A competitive balance between these factors determines cell fate. Our work underscores the dynamic nature of cellular differentiation and explains mechanistically the dual properties of stability and plasticity associated with the process. PMID:19366677

Quantum Biology at the Cellular Level - elements of the research program

OpenAIRE

Bordonaro, Michael; Ogryzko, Vasily

2013-01-01

Quantum Biology is emerging as a new field at the intersection between fundamental physics and biology, promising novel insights into the nature and origin of biological order. We discuss several elements of QBCL (Quantum Biology at Cellular Level), a research program designed to extend the reach of quantum concepts to higher than molecular levels of biological organization. Key words. decoherence, macroscopic superpositions, basis-dependence, formal superposition, non-classical correlations,...

Selective survival of β1-adenergic receptors in rat cerebellum following neonatal X-irradiation

International Nuclear Information System (INIS)

Minneman, K.P.; Pittman, R.N.; Wolfe, B.B.; Molinoff, P.B.

1981-01-01

To investigate the cellular localization of β 1 - and β 2 -adrenergic receptors, the effects of intermittent neonatal X-irradiation focused on the cerebellum were determined on the densities of the two subtypes of β-adrenergic receptor. This treatment destroys the late-maturing cerebellar interneurons including the granule, basket and stellate cells. The total number of β 2 -adrenergic receptors per cerebellum was reduced by 81-83% in 6- and 12-week-old X-irradiated rats. However, the number of β 1 -adrenergic receptors per cerebellum in 6- and 12-week-old X-irradiated rats was not significantly different from that in control animals. The results suggest that β 2 receptors in the rat cerebellum are primarily associated with the small interneurons destroyed by neonatal X-irradiation. The β 1 receptors may be located on a cell population which is unaffected by this treatment, possibly on cerebellar Purkinje cells. (Auth.)

Monoamines and sexual function in rats bred for increased catatonic reactivity.

Science.gov (United States)

Klochkov, D V; Alekhina, T A; Kuznetsova, E G; Barykina, N N

2009-07-01

Body weight, ovary and uterus weight, the nature of estral cycles, and hypothalamus dopamine and noradrenaline levels and plasma testosterone levels were studied in female GC rats, bred for increased catatonic reactivity, at different stages of the estral cycle (estrus, proestrus). The outbred Wistar strain served as controls. On the background of decreased body weight, GC females showed impairments to the morphological cyclical changes in the ovaries and uterus, with a reduction in ovary weight in diestrus (p rats showed higher levels of these monoamines in estrus and lower levels in diestrus. Plasma testosterone levels in female GC rats were higher in diestrus than in estrus and in Wistar rats.

Melatonin synthesis: Acetylserotonin O-methyltransferase (ASMT) is strongly expressed in a subpopulation of pinealocytes in the male rat pineal gland

DEFF Research Database (Denmark)

Rath, Martin Fredensborg; Coon, Steven L.; Amaral, Fernanda G.

2016-01-01

The rat pineal gland has been extensively used in studies of melatonin synthesis. However, the cellular localization of melatonin synthesis in this species has not been investigated. Here we focus on the localization of melatonin synthesis using immunohistochemical methods to detect the last enzy...