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  1. Chemical structure and biochemical significance of lysolecithins from rat liver

    NARCIS (Netherlands)

    Bosch, H. van den; Deenen, L.L.M. van

    1965-01-01

    1. 1. Synthetic lecithins containing in 2-position a [14C]fatty acid constituent were found to be hydrolysed by rat-liver homogenates so as to form both 1-acyl-glycero-3-phosphorylcholine and 2-acyl-glycero-3-phosphorylcholine. 2. 2. A comparison of the fatty acid pattern of lysolecithin obtained

  2. Expression and significance of HIF-1α and VEGF in rats with diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    Hong-Tao Yan; Guan-Fang Su

    2014-01-01

    Objective:To investigate the expression of hypoxia inducible factor-1α(HIF-1α) and vascular endothelial growth factor(VEGF) in diabetic retinopathy(DR) rats and its effect on theDR occurrence and development.Methods:A total of120SD rats were randomly divided into trial group and control group with60 in each.STZi.p. was used in the trial group to establish theDM model, citrate buffer salt of same amount was usedi.p. to the control group.1,3 and6 months after injection, respective20 rats were sacrificed in each group to observe expression ofHIF-1α andVEGF in the rat retina tissue at different time points.Results:Expression ofHIF-1α andVEGF were negative in the control group; expression ofHIF-1α andVEGF protein in retinal tissue were weak after1 month ofDR mold formation.It showed progressive enhancement along with the progression in different organizations, differences between groups were significant (P<0.05).Conclusions:Expressions ofHIF-1α andVEGF were correlated with disease progression in early diabetic retinopathy.Retinal oxygen can induce over-expression ofHIF-1α andVEGF.It shows thatHIF-1α andVEGF play an important role in the pathogenesis ofDR.

  3. Microarray Analysis of the Developing Rat Mandible

    Institute of Scientific and Technical Information of China (English)

    Hideo KABURAGI; Naoyuki SUGANO; Maiko OSHIKAWA; Ryosuke KOSHI; Naoki SENDA; Kazuhiro KAWAMOTO; Koichi ITO

    2007-01-01

    To analyze the molecular events that occur in the developing mandible, we examined the expression of 8803 genes from samples taken at different time points during rat postnatal mandible development.Total RNA was extracted from the mandibles of 1-day-old, 1-week-old, and 2-week-old rats. Complementary RNA (cRNA) was synthesized from cDNA and biotinylated. Fragmented cRNA was hybridized to RGU34A GeneChip arrays. Among the 8803 genes tested, 4344 were detectable. We identified 148 genes with significantly increased expression, and 19 genes with significantly decreased expression. A comprehensive analysis appears to be an effective method of studying the complex process of development.

  4. The expression and significance of tyrosine hydroxylase in the brain tissue of Parkinsons disease rats

    OpenAIRE

    Chen, Yuan; Lian, Yajun; Ma, Yunqing; Wu, Chuanjie; Zheng, Yake; Xie, Nanchang

    2017-01-01

    The expression and significance of tyrosine hydroxylase (TH) in brain tissue of rats with Parkinson's disease (PD) were explored and analyzed. A total of 120 clean-grade and healthy adult Wistar rats weighing 180–240 g were randomly divided equally into four groups according to the random number table method. Rats were sacrificed before and after the model establishment for 3, 6 or 8 weeks. The number of revolutions in rats was observed and the relative expression of TH mRNA in brain tissue w...

  5. Cyclosporin A significantly improves preeclampsia signs and suppresses inflammation in a rat model.

    Science.gov (United States)

    Hu, Bihui; Yang, Jinying; Huang, Qian; Bao, Junjie; Brennecke, Shaun Patrick; Liu, Huishu

    2016-05-01

    Preeclampsia is associated with an increased inflammatory response. Immune suppression might be an effective treatment. The aim of this study was to examine whether Cyclosporin A (CsA), an immunosuppressant, improves clinical characteristics of preeclampsia and suppresses inflammation in a lipopolysaccharide (LPS) induced preeclampsia rat model. Pregnant rats were randomly divided into 4 groups: group 1 (PE) rats each received LPS via tail vein on gestational day (GD) 14; group 2 (PE+CsA5) rats were pretreated with LPS (1.0 μg/kg) on GD 14 and were then treated with CsA (5mg/kg, ip) on GDs 16, 17 and 18; group 3 (PE+CsA10) rats were pretreated with LPS (1.0 μg/kg) on GD 14 and were then treated with CsA (10mg/kg, ip) on GDs 16, 17 and 18; group 4 (pregnant control, PC) rats were treated with the vehicle (saline) used for groups 1, 2 and 3. Systolic blood pressure, urinary albumin, biometric parameters and the levels of serum cytokines were measured on day 20. CsA treatment significantly reduced LPS-induced systolic blood pressure and the mean 24-h urinary albumin excretion. Pro-inflammatory cytokines IL-6, IL-17, IFN-γ and TNF-α were increased in the LPS treatment group but were reduced in (LPS+CsA) group (Ppreeclampsia signs and attenuated inflammatory responses in the LPS induced preeclampsia rat model which suggests that immunosuppressant might be an alternative management option for preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Significance of glucagon for insulin secretion and hepatic glycogenolysis during exercise in rats

    DEFF Research Database (Denmark)

    Richter, Erik; Galbo, H; Holst, J J

    1981-01-01

    The significance of glucagon and of the sympatho-adrenal system for insulin secretion and hepatic glycogen depletion during exercise was studied. Male rats were either adrenodemedullated and chemically sympathectomized with 6-hydroxydopamine (SX) or sham-treated (C). During light ether anesthesia......, cardiac blood for glucose analysis and a biopsy of the liver were obtained, and either antigen-stripped glucagon antibodies (A) or control gamma globulins (N) in saline were injected through the cardiac cannula. Subsequently, the rats swam in tepid water (33-34 degree C) for 100 minutes with a tail weight...... attached (2% of body weight). Then cardiac blood was drawn for analysis of glucose, insulin and glucagon, and a sample of the liver was collected. In both CA and CN rats, the blood glucose concentration tended to increase (p less than 0.1) during exercise, whereas hepatic glycogen depletion and the plasma...

  7. Characteristics and significance of D-tagatose-induced liver enlargement in rats: An interpretative review.

    Science.gov (United States)

    Bär, A

    1999-04-01

    This review addresses the issue of asymptomatic liver enlargement in rats. It was necessitated by the observation of significantly increased liver weights in rats fed diets with 10 to 20% D-tagatose, a potential new bulk sweetener, for between 28 and 90 days. Increases of liver size without accompanying histopathological changes or impairment of organ function have been observed in rats in response to the ingestion of various xenobiotic compounds (including some food additives), changes of dietary composition (e.g. , high doses of fructose and sucrose), metabolic aberrations (e.g., diabetes), as well as normal pregnancy and lactation. The underlying mechanism(s) are not yet understood in detail but peroxisome proliferation, microsomal enzyme induction, increased storage of glycogen or lipids, and hyperfunction due to an excessive workload are well-established causes of hepatomegaly in rats. In D-tagatose- and fructose-fed rats, a treatment-related increase of hepatic glycogen storage was identified as a likely cause of the liver enlargement. Dietary levels of 5% and about 15-20% were determined as no-effect levels (NOEL) for D-tagatose- and fructose-induced liver enlargement, respectively. At doses above the NOEL, D-tagatose is about four times more efficient than fructose in inducing liver enlargement. On the other hand, the estimated intake of D-tagatose from its intended uses in food is about four times lower than the actual fructose intake. Consequently, a similar safety margin would apply for both sugars. Considering the similarity of the liver effects in rats of fructose, a safe food ingredient, and D-tagatose, the absence of histopathological changes in rats fed a diet with 20% D-tagatose for 90 days, and the absence of adverse long-term consequences of glycogen-induced liver enlargement in rats, it is concluded that the observed liver enlargement in D-tagatose-fed rats has no relevance for the assessment of human safety of this substance. Copyright 1999

  8. Developmental Toxicity Studies with Pregabalin in Rats: Significance of Alterations in Skull Bone Morphology.

    Science.gov (United States)

    Morse, Dennis C; Henck, Judith W; Bailey, Steven A

    2016-04-01

    Pregabalin was administered to pregnant Wistar rats during organogenesis to evaluate potential developmental toxicity. In an embryo-fetal development study, compared with controls, fetuses from pregabalin-treated rats exhibited increased incidence of jugal fused to maxilla (pregabalin 1250 and 2500 mg/kg) and fusion of the nasal sutures (pregabalin 2500 mg/kg). The alterations in skull development occurred in the presence of maternal toxicity (reduced body weight gain) and developmental toxicity (reduced fetal body weight and increased skeletal variations), and were initially classified as malformations. Subsequent investigative studies in pregnant rats treated with pregabalin during organogenesis confirmed the advanced jugal fused to maxilla, and fusion of the nasal sutures at cesarean section (gestation day/postmating day [PMD] 21) in pregabalin-treated groups. In a study designed to evaluate progression of skull development, advanced jugal fused to maxilla and fusion of the nasal sutures was observed on PMD 20-25 and PMD 21-23, respectively (birth occurs approximately on PMD 22). On postnatal day (PND) 21, complete jugal fused to maxilla was observed in the majority of control and 2500 mg/kg offspring. No treatment-related differences in the incidence of skull bone fusions occurred on PND 21, indicating no permanent adverse outcome. Based on the results of the investigative studies, and a review of historical data and scientific literature, the advanced skull bone fusions were reclassified as anatomic variations. Pregabalin was not teratogenic in rats under the conditions of these studies. © 2016 Wiley Periodicals, Inc.

  9. [Subcutaneous transplants of juvenile rat testicular tissues continue to develop and secret androgen in adult rats].

    Science.gov (United States)

    Yu, Zhou; Wang, Tong; Cui, Jiangbo; Song, Yajuan; Ma, Xianjie; Su, Yingjun; Peng, Pai

    2017-12-01

    Objective To explore the effects of subcutaneous microenvironment of adult rats on survival, development and androgen secretion of Leydig cells of transplanted juvenile rat testis. Methods Healthy adult SD rats were randomly divided into control group, sham group, castrated group and non-castrated group. Rats in the control group were kept intact, no testis was transplanted subcutaneously after adult recipients were castrated in the sham group; 5-7-day juvenile rat testes were transplanted subcutaneously in the castrated group, with one testis per side; Testes resected from juvenile rats were directly transplanted subcutaneously on both sides of the recipients in the non-castrated group. The grafts were obtained and weighed 4 weeks later. Then the histological features of the grafts were examined by HE staining; the expression and distribution of hydroxysteroid 17-beta dehydrogenase 1 (HSD-17β1) were investigated by immunohistochemistry; and the serum androgen level was determined by ELISA. Results The average mass of grafts obtained from the castrated group was significantly higher than that of the non-castrated group. Immunohistochemistry indicated that Leydig cells were visible in the tissues from both the castrated and non-castrated groups, but the number of HSD-17β1-posotive cells in the castrated group was larger than that in the non-castrated group. ELISA results showed that the serum androgen level was higher in the control group and non-castrated group than in the sham group and castrated group, and compared with the sham group, the serum androgen level in the castrated group was significantly higher. Conclusion The juvenile rat testis subcutaneously transplanted could further develop under the adult recipient rat skin, and the Leydig cells of grafts harbored the ability to produce and secret androgen.

  10. St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats

    International Nuclear Information System (INIS)

    Yang, Shih-Ying; Juang, Shin-Hun; Tsai, Shang-Yuan; Chao, Pei-Dawn Lee; Hou, Yu-Chi

    2012-01-01

    St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window. This study investigated the effect of SJW on MTX pharmacokinetics in rats. Rats were orally given MTX alone and coadministered with 300 and 150 mg/kg of SJW, and 25 mg/kg of diclofenac, respectively. Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method. The results showed that 300 mg/kg of SJW significantly increased the AUC 0−t and C max of MTX by 163% and 60%, respectively, and 150 mg/kg of SJW significantly increased the AUC 0−t of MTX by 55%. In addition, diclofenac enhanced the C max of MTX by 110%. The mortality of rats treated with SJW was higher than that of controls. In conclusion, coadministration of SJW significantly increased the systemic exposure and toxicity of MTX. The combined use of MTX with SJW would need to be with caution. -- Highlights: ► St. John's wort significantly increased the AUC 0−t and C max of methotrexate. ► Coadministration of St. John's wort increased the exposure and toxicity of methotrexate. ► The combined use of methotrexate with St. John's wort will need to be with caution.

  11. Postnatal development of plasma amino acids in hyperphagic rats.

    Science.gov (United States)

    Salvadó, M J; Segués, T; Arola, L

    1991-01-01

    The effect of feeding a highly palatable high-energy cafeteria diet on individual amino acid levels in plasma during postnatal development of the rat has been evaluated and compared to chow-fed controls. The cafeteria diet selected by the rats was hypercaloric and hyperlipidic, with practically the same amount of carbohydrate as the control diet, and slightly hyperproteic. In response to cafeteria feeding, significant decreases were observed in plasma serine and cysteine along the period studied. Significant changes with age during the growth period were shown by cafeteria-fed animals, which were not observed in control rats. Citrulline levels were lower on days 10 and 14 in cafeteria pups than in chow pups. Methionine was highest on day 30. Threonine was also higher at days 20 and 30, as was valine but with a nadir at day 10. Lysine showed maximal values on days 14 and 30.

  12. Development of Quantitative Framework for Event Significance Evaluation

    International Nuclear Information System (INIS)

    Lee, Durk Hun; Kim, Min Chull; Kim, Inn Seock

    2010-01-01

    There is an increasing trend in quantitative evaluation of the safety significance of operational events using Probabilistic Safety Assessment (PSA) technique. An integrated framework for evaluation of event significance has been developed by Korea Institute of Nuclear Safety (KINS), which consists of an assessment hierarchy and a number of matrices. The safety significance of various events, e.g., internal or external initiating events that occurred during at-power or shutdown conditions, can be quantitatively analyzed using this framework, and then, the events rated according to their significance. This paper briefly describes the basic concept of the integrated quantitative framework for evaluation of event significance, focusing on the assessment hierarchy

  13. Selective excretion of IgA in rat bronchial secretions: lack of significant contribution from plasma IgA

    International Nuclear Information System (INIS)

    Lemaitre-Coelho, I.; Yamakido, M.; Montgomery, P.C.; Langendries, A.E.; Vaerman, J.P.

    1982-01-01

    Concentrated rat bronchial washings (BW) were analyzed by gel-filtration and immunochemical methods. BW contained mainly albumin, transferrin and IgG. Free secretory component and secretory IgA were identified in BW; the BW-IgA had the same three sedimentation coefficients, i.e. +/- 11 S, 13 S, 15 S by sucrose density gradient ultracentrifugation, as rat milk and rat bile IgA; the three peaks were secretory IgA. Compared to serum, and relatively to albumin, BW were significantly enriched in IgA, although much less than rat bile. Purified polyclonal rat polymeric 125 I-IgA was injected intravenously into normal rats, and into rats with bile duct ligation or partial hepatectomy, which decrease the liver plasma-to-bile transfer of IgA. BW were then collected, one or four hours later, to assess the recovery of the 125 I-IgA in BW and to estimate the contribution of serum IgA to BW-IgA. Very little 125 I-IgA (less than 0.2%) was recovered in all BW. The specific activity, measured only in the rat with the highest recovery in BW, was 20 times lower in BW than in serum. The data demonstrate that rat serum IgA does not contribute significantly to IgA in BW

  14. Neonatal infection produces significant changes in immune function with no associated learning deficits in juvenile rats.

    Science.gov (United States)

    Osborne, Brittany F; Caulfield, Jasmine I; Solomotis, Samantha A; Schwarz, Jaclyn M

    2017-10-01

    The current experiments examined the impact of early-life immune activation and a subsequent mild immune challenge with lipopolysaccharide (LPS; 25µg/kg) on hippocampal-dependent learning, proinflammatory cytokine expression in the brain, and peripheral immune function in juvenile male and female rats at P24, an age when hippocampal-dependent learning and memory first emerges. Our results indicate that neonatal infection did not produce learning deficits in the hippocampal-dependent context pre-exposure facilitation effect paradigm in juvenile males and females, contrary to what has been observed in adults. Neonatal infection produced an increase in baseline IL-1β expression in the hippocampus (HP) and medial prefrontal cortex (mPFC) of juvenile rats. Furthermore, neonatally infected rats showed exaggerated IL-1β expression in the HP following LPS treatment as juveniles; and juvenile females, but not males, showed exaggerated IL-1β expression in the mPFC following LPS treatment. Neonatal infection attenuated the production of IL-6 expression following LPS treatment in both the brain and the spleen, and neonatal infection decreased the numbers of circulating white blood cells in juvenile males and females, an effect that was further exacerbated by subsequent LPS treatment. Together, our data indicate that the consequences of neonatal infection are detectable even early in juvenile development, though we found no concomitant hippocampal-dependent learning deficits at this young age. These findings underscore the need to consider age and associated on-going neurodevelopmental processes as important factors contributing to the emergence of cognitive and behavioral disorders linked to early-life immune activation. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1221-1236, 2017. © 2017 Wiley Periodicals, Inc.

  15. L-carnitine significantly decreased aging of rat adipose tissue-derived mesenchymal stem cells.

    Science.gov (United States)

    Mobarak, Halimeh; Fathi, Ezzatollah; Farahzadi, Raheleh; Zarghami, Nosratollah; Javanmardi, Sara

    2017-03-01

    Mesenchymal stem cells are undifferentiated cells that have the ability to divide continuously and tissue regeneration potential during the transplantation. Aging and loss of cell survival, is one of the main problems in cell therapy. Since the production of free radicals in the aging process is effective, the use of antioxidant compounds can help in scavenging free radicals and prevent the aging of cells. The aim of this study is evaluate the effects of L-carnitine (LC) on proliferation and aging of rat adipose tissue-derived mesenchymal stem cells (rADSC). rADSCs were isolated from inguinal region of 5 male Rattus rats. Oil red-O, alizarin red-S and toluidine blue staining were performed to evaluate the adipogenic, osteogenic and chondrogenic differentiation of rADSCs, respectively. Flow cytometric analysis was done for investigating the cell surface markers. The methyl thiazol tetrazolium (MTT) method was used to determine the cell proliferation of rADSCs following exposure to different concentrations of LC. rADSCs aging was evaluated by beta-galactosidase staining. The results showed significant proliferation of rADSCs 48 h after treatment with concentrations of 0.2 mM LC. In addition, in the presence of 0.2 mM LC, rADSCs appeared to be growing faster than control group and 0.2 mM LC supplementation could significantly decrease the population doubling time and aging of rADSCs. It seems that LC would be a good antioxidant to improve lifespan of rADSCs due to the decrease in aging.

  16. [The expression and significance of VIP and its receptor in the cochlea of different degrees of chronic alcoholism rats].

    Science.gov (United States)

    Feng, Jing; Liu, Haibing

    2015-07-01

    To determine whether chronic alcoholism alters the expression levels of Vasoactive intestinal polypeptide (VIP) and its receptor (VIPR1) in the cochlea of chronic alcoholism rats. We measured their expression levels in 30 SD rats, in which we created models of different degrees of chronic alcoholism. We investigated the presence of the mRNA of VIP in the cochlea of chronic alcoholism rats and controls by reverse transcription-polymerase chain reaction (RT-PCR) method. We investigated the presence of proteins of VIPR1 in poisoned rats and controls by western blot. We also evaluated the local distribution of VIP cells by immunohistochemistry. We found that the levels of VIP and VIPR1 were downregulated in the chronic alcoholism groups compared to the controls group. The differences in some expression levels were significant different between chronic alcoholism rats and control rats. Moreover, at different degrees of alcohol poisoning in rats, the contents of VIP and VIPR1 differed. Decreased levels of VIP and VIPR1 were detected in the deep chronic alcoholism group compared to the group with low-degree poisoning (P 0.05). These results suggest that VIP and VIPR1 play an important role in the auditory function in rats with chronic alcoholism. Chronic alcoholism may cause a peptide hormone secretion imbalance in the auditory system, eventually leading to hearing loss.

  17. Spaceflight Affects Postnatal Development of the Aortic Wall in Rats

    Directory of Open Access Journals (Sweden)

    Shin-ichiro Katsuda

    2014-01-01

    Full Text Available We investigated effect of microgravity environment during spaceflight on postnatal development of the rheological properties of the aorta in rats. The neonate rats were randomly divided at 7 days of age into the spaceflight, asynchronous ground control, and vivarium control groups (8 pups for one dam. The spaceflight group rats at 9 days of age were exposed to microgravity environment for 16 days. A longitudinal wall strip of the proximal descending thoracic aorta was subjected to stress-strain and stress-relaxation tests. Wall tensile force was significantly smaller in the spaceflight group than in the two control groups, whereas there were no significant differences in wall stress or incremental elastic modulus at each strain among the three groups. Wall thickness and number of smooth muscle fibers were significantly smaller in the spaceflight group than in the two control groups, but there were no significant differences in amounts of either the elastin or collagen fibers among the three groups. The decreased thickness was mainly caused by the decreased number of smooth muscle cells. Plastic deformation was observed only in the spaceflight group in the stress-strain test. A microgravity environment during spaceflight could affect postnatal development of the morphological and rheological properties of the aorta.

  18. Significance of Internet in Development of Graphic Communications

    OpenAIRE

    Tajana Koren

    2000-01-01

    It is impossible to think of development of graphic communications - even based on traditional principles - without knowledge and application of new technologies, which are enabling a new conception of graphic design. First of all, here is the significant role of Internet, as a means of communications, interactive source of information and a way of expression. New possibilities are urging a new creativity. Social aspects of new technologies should not be neglected. Only permanent education wi...

  19. MRI and morphological observation in C6 glioma model rats and significance

    International Nuclear Information System (INIS)

    Zhou Ying; Yuan Bo; Wang Hao; Lu Jin; Yuan Changji; Ma Yue; Tong Dan; Zhang Kun; Gao Feng; Wu Xiaogang

    2013-01-01

    Objective: To establish stable and reliable rat C6 glioma model, and to perform MRI dynamic observation and pathomorphological observation in model animal brain, and to provide experimental basis for pharmaceutical research on anti-glioma drugs. Methods: The C6 glioma cells were cultured and 20 μL cultural fluid containing 1×10 6 C6 cells was sterotactically implanted into the left caudate nuclei in 10 male Wistar rats, respectively. The changes in the behavior of the rats after implantation were observed and recorded. MRI dynamic scanning was performed in 10 rats 2, 3 and 4 weeks after implantation and the brain tissues were taken for general and pathological examination when the 10 rats were naturally dead. The survival period of tumor-bearing rats was calculated. Results: 2 weeks after implantation the rats showed decreased activities and food intake, fur lackluster, and conjunctival congestion and so on; 3 weeks later, some rats appeared nerve symptoms such as body twitch, body hemiplegy, body distortion, rotation and so on. All the 10 rats died in 8-30 d. The median survival period of the tumor-bearing rats was 18 d, the average survival period was (18.3±7.3) d. The pathological examination showed that the tumor cells were arranged irregularly closely and karyokinesis was easy to see; tumor vascular tissue proliferation and tumor invasive growth into surrounding normal tissues were found. The expression of glial fibrillary acidic protein (GFAP) was positive in the tumors. Conclusion: A stable animal model of intracranial glioma is successfully established by stereotactic implantation of C6 cells into the rat caudate nucleus. The results of MRI dynamic observation and pathohistological observation on the model animal brain tissue. Can provide experimental basis for selecting the appropriate time window to perform the pharmaceutical research on anti-glioma drugs. (authors)

  20. Significance and survival of Enterococci during the house fly development.

    Science.gov (United States)

    Ghosh, Anuradha; Akhtar, Mastura; Holderman, Chris; Zurek, Ludek

    2014-01-01

    House flies are among the most important nonbiting insect pests of medical and veterinary importance. Larvae develop in decaying organic substrates and their survival strictly depends on an active microbial community. House flies have been implicated in the ecology and transmission of enterococci, including multi-antibiotic-resistant and virulent strains of Enterococcus faecalis. In this study, eight American Type Culture Collection type strains of enterococci including Enterococcus avium, Enterococcus casseliflavus, Enterococcus durans, Enterococcus hirae, Enterococcus mundtii, Enterococcus gallinarum, Enterococcusfaecalis, and Enterococcusfaecium were evaluated for their significance in the development of house flies from eggs to adults in bacterial feeding assays. Furthermore, the bacterial colonization of the gut of teneral flies as well as the importance of several virulence traits of E. faecalis in larval mortality was assessed. Overall survival of house flies (egg to adult) was significantly higher when grown with typically nonpathogenic enterococcal species such as E. hirae (76.0% survival), E. durans (64.0%), and E. avium (64.0%) compared with that with clinically important species E. faecalis (24.0%) and E. faecium (36.0%). However, no significant differences in survival of house fly larvae were detected when grown with E. faecalis strains carrying various virulence traits, including isogenic mutants of the human clinical isolate E. faecalis V583 with in-frame deletions of gelatinase, serine protease, and capsular polysaccharide serotype C. Enterococci were commonly detected in fly puparia (range: 75-100%; concentration: 103-105 CFU/puparium);however, the prevalence of enterococci in teneral flies varied greatly: from 25.0 (E. casseliflavus) to 89.5% (E. hirae). In conclusion, depending on the species, enterococci variably support house fly larval development and colonize the gut of teneral adults. The human pathogenic species, E. faecalis and E. faecium

  1. Significance and impact of nuclear research in developing countries

    International Nuclear Information System (INIS)

    1987-01-01

    The main purpose of this conference was to gather representatives of universities, research institutes, governmental agencies and industry, as well as IAEA staff, to report on and to assess the significance and impact of nuclear science and technology in developing countries. Thirty-four papers from 17 countries were presented, which are included in the proceedings, as well as reports of three workshops on ''Basic and applied research'', on ''The IAEA's involvement in the implementation of national nuclear programmes'', and on ''Policy and management issues''. The presentation of these reports clearly reflects the fact that all the nuclear activities involved in the programmes of industrialized countries are in progress in developing countries, i.e. most of the aspects of applications in the field of nuclear power, research reactors, food and agriculture, industry and earth sciences, and life sciences. A separate abstract was prepared for each of these papers

  2. Prenatal prochloraz treatment significantly increases pregnancy length and reduces offspring weight but does not affect social-olfactory memory in rats

    DEFF Research Database (Denmark)

    Dmytriyeva, Oksana; Klementiev, Boris; Berezin, Vladimir

    2013-01-01

    Metabolites of the commonly used imidazole fungicide prochloraz are androgen receptor antagonists. They have been shown to block androgen-driven development and compromise reproductive function. We tested the effect of prochloraz on cognitive behavior following exposure to this fungicide during...... the perinatal period. Pregnant Wistar rats were administered a 200mg/kg dose of prochloraz on gestational day (GD) 7, GD11, and GD15. The social recognition test (SRT) was performed on 7-week-old male rat offspring. We found an increase in pregnancy length and a significantly reduced pup weight on PND15 and PND...

  3. High Autophagy in the Naked Mole Rat may Play a Significant Role in Maintaining Good Health

    Directory of Open Access Journals (Sweden)

    Shanmin Zhao

    2014-02-01

    Full Text Available Background/Aims: The maximum lifespan of the naked mole rat is over 28.3 years, which exceeds that of any other rodent species, suggesting that age-related changes in its body composition and functionality are either attenuated or delayed in this extraordinarily long-lived species. However, the mechanisms underlying the aging process in this species are poorly understood. In this study, we investigated whether long-lived naked mole rats display more autophagic activity than short-lived mice. Methods: Hepatic stellate cells isolated from naked mole rats were treated with 50 nM rapamycin or 20 mM 3-methyladenine (3-MA for 12 or 24 h. Expression of the autophagy marker proteins LC3-II and beclin 1 was measured with western blotting and immunohistochemistry. The induction of apoptosis was analyzed by flow cytometry. Results: Our results demonstrate that one-day-old naked mole rats have higher levels of autophagy than one-day-old short-lived C57BL/6 mice, and that both adult naked mole rats (eight months old and adult C57BL/6 mice (eight weeks old have high basal levels of autophagy, which may be an important mechanism inhibiting aging and reducing the risk of age-related diseases. Conclusion: Here, we report that autophagy facilitated the survival of hepatic stellate cells from the naked mole rat, and that treatment with 3-MA or rapamycin increased the ratio of apoptotic cells to normal hepatic stellate cells.

  4. Dietary inulin intake and age can significantly affect intestinal absorption of calcium and magnesium in rats: a stable isotope approach

    Science.gov (United States)

    Coudray, Charles; Rambeau, Mathieu; Feillet-Coudray, Christine; Tressol, Jean Claude; Demigne, Christian; Gueux, Elyett; Mazur, Andrzej; Rayssiguier, Yves

    2005-01-01

    Background previous studies have shown that non-digestible inulin-type fructan intake can increase intestinal mineral absorption in both humans and animals. However, this stimulatory effect on intestinal absorption may depend on experimental conditions such as duration of fermentable fiber intake, mineral diet levels and animals' physiological status, in particular their age. Objectives the aim of this study was to determine the effect of inulin intake on Ca and Mg absorption in rats at different age stages. Methods eighty male Wistar rats of four different ages (2, 5, 10 and 20 months) were randomized into either a control group or a group receiving 3.75% inulin in their diet for 4 days and then 7.5% inulin for three weeks. The animals were fed fresh food and water ad libitum for the duration of the experiment. Intestinal absorption of Ca and Mg was determined by fecal monitoring using stable isotopic tracers. Ca and Mg status was also assessed. Results absorption of Ca and Mg was significantly lower in the aged rats (10 and 20 mo) than in the young and adult rat groups. As expected, inulin intake increased Ca and Mg absorption in all four rat groups. However, inulin had a numerically greater effect on Ca absorption in aged rats than in younger rats whereas its effect on Mg absorption remained similar across all four rat age groups. Conclusion the extent of the stimulatory effect of inulin on absorption of Ca may differ according to animal ages. Further studies are required to explore this effect over longer inulin intake periods, and to confirm these results in humans. PMID:16253138

  5. Development of rat telencephalic neurons after prenatal x-irradiation

    International Nuclear Information System (INIS)

    Norton, S.

    1979-01-01

    Telencephalic neurons of rats, irradiated at day 15 of gestation with 125 R, develop synaptic connections on dendrites during maturation which appear to be normal spines in Golgi-stained light microscope preparations. At six weeks of postnatal age both control and irradiated rats have spiny dendritic processes on cortical pyramidal cells and caudate Golgi type II neurons. However, when the rats are 6 months old the irradiated rats have more neurons with beaded dendritic processes that lack spines or neurons and are likely to be degenerating neurons. The apparently normal development of the neurons followed by degeneration in the irradiated rat has a parallel in previous reports of the delayed hyperactivity which develops in rats irradiated on the fifteenth gestational day

  6. Pharmacological kynurenine 3-monooxygenase enzyme inhibition significantly reduces neuropathic pain in a rat model.

    Science.gov (United States)

    Rojewska, Ewelina; Piotrowska, Anna; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2016-03-01

    Recent studies have highlighted the involvement of the kynurenine pathway in the pathology of neurodegenerative diseases, but the role of this system in neuropathic pain requires further extensive research. Therefore, the aim of our study was to examine the role of kynurenine 3-monooxygenase (Kmo), an enzyme that is important in this pathway, in a rat model of neuropathy after chronic constriction injury (CCI) to the sciatic nerve. For the first time, we demonstrated that the injury-induced increase in the Kmo mRNA levels in the spinal cord and the dorsal root ganglia (DRG) was reduced by chronic administration of the microglial inhibitor minocycline and that this effect paralleled a decrease in the intensity of neuropathy. Further, minocycline administration alleviated the lipopolysaccharide (LPS)-induced upregulation of Kmo mRNA expression in microglial cell cultures. Moreover, we demonstrated that not only indirect inhibition of Kmo using minocycline but also direct inhibition using Kmo inhibitors (Ro61-6048 and JM6) decreased neuropathic pain intensity on the third and the seventh days after CCI. Chronic Ro61-6048 administration diminished the protein levels of IBA-1, IL-6, IL-1beta and NOS2 in the spinal cord and/or the DRG. Both Kmo inhibitors potentiated the analgesic properties of morphine. In summary, our data suggest that in neuropathic pain model, inhibiting Kmo function significantly reduces pain symptoms and enhances the effectiveness of morphine. The results of our studies show that the kynurenine pathway is an important mediator of neuropathic pain pathology and indicate that Kmo represents a novel pharmacological target for the treatment of neuropathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Relationship between blood-retinal barrier development and formation of selenite nuclear cataract in rat

    Directory of Open Access Journals (Sweden)

    Ping Lu

    2017-12-01

    Full Text Available AIM: To investigate the relationship between development of blood-retinal barrier and formation of selenite nuclear cataract in rat. METHODS: Activity of GPx, MDA level in lens and selenium content in the eyeballs of different ages rats were determined. Besides, lanthanum hydroxide \\〖La(OH3\\〗 tracer method was used to detect development status of blood-retina barrier at different ages. RESULTS: The result showed that the enzyme activity of GPx was highest in young rats before open eyes, but then decreased gradually with age. Distribution of La(OH3 in retinal pigment epithelial layer of 20-day-old rats was significantly less than 11-day-old rats. Injecting sodium selenite to 9-day-old rats, lanthanum hydroxide increased obviously and extended to the inner layers of the retina after 48h, and the retinal pigment epithelial layer was damaged seriously; while injecting sodium selenite to 18-day-old rats with the same dose, number of lanthanum hydroxide decreased significantly and did not extend to the inner layer after 48h.Before opening eyes, the content of MDA in the lens of rats was the highest, and decreased significantly after opening eyes. The Se group was 5 times as that of the control group. Besides, in these groups of rats, selenium content in the eyeballs and MDA level in the lens were in agreement with the change of La(OH3 distribution. CONCLUSION: These results indicated that antioxidant capacity in the eyelid unopened rats is not the main reason for selenite induced cataract formation. The real reason is that blood-retina barrier development is not mature in the eyelid unopened rats.

  8. HIV-1 transgenic rats develop T cell abnormalities

    International Nuclear Information System (INIS)

    Reid, William; Abdelwahab, Sayed; Sadowska, Mariola; Huso, David; Neal, Ashley; Ahearn, Aaron; Bryant, Joseph; Gallo, Robert C.; Lewis, George K.; Reitz, Marvin

    2004-01-01

    HIV-1 infection leads to impaired antigen-specific T cell proliferation, increased susceptibility of T cells to apoptosis, progressive impairment of T-helper 1 (Th1) responses, and altered maturation of HIV-1-specific memory cells. We have identified similar impairments in HIV-1 transgenic (Tg) rats. Tg rats developed an absolute reduction in CD4 + and CD8 + T cells able to produce IFN-γ following activation and an increased susceptibility of T cells to activation-induced apoptosis. CD4 + and CD8 + effector/memory (CD45RC - CD62L - ) pools were significantly smaller in Tg rats compared to non-Tg controls, although the converse was true for the naieve (CD45RC + CD62L + ) T cell pool. Our interpretation is that the HIV transgene causes defects in the development of T cell effector function and generation of specific effector/memory T cell subsets, and that activation-induced apoptosis may be an essential factor in this process

  9. Significant long-term, but not short-term, hippocampal-dependent memory impairment in adult rats exposed to alcohol in early postnatal life.

    Science.gov (United States)

    Goodfellow, Molly J; Lindquist, Derick H

    2014-09-01

    In rodents, ethanol exposure in early postnatal life is known to induce structural and functional impairments throughout the brain, including the hippocampus. Herein, rat pups were administered one of three ethanol doses over postnatal days (PD) 4-9, a period of brain development comparable to the third trimester of human pregnancy. As adults, control and ethanol rats were trained and tested in a variant of hippocampal-dependent one-trial context fear conditioning. In Experiment 1, subjects were placed into a novel context and presented with an immediate footshock (i.e., within ∼8 sec). When re-exposed to the same context 24 hr later low levels of conditioned freezing were observed. Context pre-exposure 24 hr prior to the immediate shock reversed the deficit in sham-intubated and unintubated control rats, enhancing freezing behavior during the context retention test. Even with context pre-exposure, however, significant dose-dependent reductions in contextual freezing were seen in ethanol rats. In Experiment 2, the interval between context pre-exposure and the immediate shock was shortened to 2 hr, in addition to the standard 24 hr. Ethanol rats trained with the 2 hr, but not 24 hr, interval displayed retention test freezing levels roughly equal to controls. Results suggest the ethanol rats can encode a short-term context memory and associate it with the aversive footshock 2 hr later. In the 24 hr ethanol rats the short-term context memory is poorly transferred or consolidated into long-term memory, we propose, impeding the memory's subsequent retrieval and association with shock. © 2014 Wiley Periodicals, Inc.

  10. Development of ELISA kit for rat albumin

    International Nuclear Information System (INIS)

    Yuan Zhigang; Han Shiquan; Liu Yibing; Xu Wenge; Jia Juanjuan

    2009-01-01

    The Anti-rat albumin serum was prepared by immunized the sheep with rat albumin. A ELISA method was established for rat albumin. The measurement range of the assay was 1-50 mg/L, sensitivity of the assay was 0.42 mg/L, recovery rate was 85.0%-106.0%. Intra-and inter-assay variation coefficients were <8.9% and <12.8% respectively. The correlation coefficients between measured and expected values were 0.999 after serial dilution of the urine samples with high concentrations of rat albumin. A good correlation was observed between the ELISA and RIA methods, and the kit for rat albumin might provide a convenience in exploitation of renal drugs and experimental injury of the kidney. (authors)

  11. The significance of Basotho philosophy of development as ...

    African Journals Online (AJOL)

    This article examines Basotho indigenous knowledge systems particularly in the way that they are embedded in proverbs, as containing a philosophy of their development. It seeks to analyse the pre-colonial Basotho's perspective with regard to the question of development as expressed in their arts and beliefs. There has ...

  12. Celecoxib does not significantly delay bone healing in a rat femoral osteotomy model: a bone histomorphometry study

    Directory of Open Access Journals (Sweden)

    Iwamoto J

    2011-12-01

    Full Text Available Jun Iwamoto1, Azusa Seki2, Yoshihiro Sato3, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Hamri Co, Ltd, Tokyo, Japan; 3Department of Neurology, Mitate Hospital, Fukuoka, JapanBackground and objective: The objective of the present study was to determine whether celecoxib, a cyclo-oxygenase-2 inhibitor, would delay bone healing in a rat femoral osteotomy model by examining bone histomorphometry parameters.Methods: Twenty-one 6-week-old female Sprague-Dawley rats underwent a unilateral osteotomy of the femoral diaphysis followed by intramedullary wire fixation; the rats were then divided into three groups: the vehicle administration group (control, n = 8, the vitamin K2 administration (menatetrenone 30 mg/kg orally, five times a week group (positive control, n = 5, and the celecoxib administration (4 mg/kg orally, five times a week group (n = 8. After 6 weeks of treatment, the wires were removed, and a bone histomorphometric analysis was performed on the bone tissue inside the callus. The lamellar area relative to the bone area was significantly higher and the total area and woven area relative to the bone area were significantly lower in the vitamin K2 group than in the vehicle group. However, none of the structural parameters, such as the callus and bone area relative to the total area, lamellar and woven areas relative to the bone area, or the formative and resorptive parameters such as osteoclast surface, number of osteoclasts, osteoblast surface, osteoid surface, eroded surface, and bone formation rate per bone surface differed significantly between the vehicle and celecoxib groups.Conclusion: The present study implies that celecoxib may not significantly delay bone healing in a rat femoral osteotomy model based on the results of a bone histomorphometric analysis.Keywords: femoral osteotomy, bone healing, callus, rat, celecoxib

  13. Development and functional significance of dorsal air bags in ...

    African Journals Online (AJOL)

    Histological examination of the air bags showed that they were integumentary structures composed of an outer epidermis and an inner dermis. The air bags were not connected to the respiratory system. The body temperature (Tb) of Monteiro's Hornbill nestlings increased significantly with increasing age. Comparisons of ...

  14. Significant prolongation of hamster liver transplant survival in Lewis rats by total-lymphoid irradiation, cyclosporine, and splenectomy

    International Nuclear Information System (INIS)

    Yamaguchi, Y.; Halperin, E.C.; Harland, R.C.; Wyble, C.; Bollinger, R.R.

    1990-01-01

    The effects of total lymphoid irradiation, cyclosporine and splenectomy alone and in combination have been studied in liver transplants from the LVG hamster to the LEW rat. Neither CsA alone, splenectomy alone, nor TLI alone prolonged graft survival. CsA/splenectomy and TLI/CsA produced significant prolongation of graft survival. TLI/CsA/splenectomy prolonged graft survival by over sixfold compared with controls. While CsA alone was ineffective in reducing lymphocytotoxic antidonor antibody, splenectomy alone or CsA/splenectomy did significantly suppress production of antibody. Only very low levels of antibody could be detected in animals treated with TLI/CsA/splenectomy. TLI/CsA/splenectomy has an immunosuppressive effect sufficient to significantly prolong liver graft survival in the LVG hamster to LEW rat combination and may represent a promising treatment protocol in experimental cross-species transplantation

  15. The Significance of Student Organizations to Leadership Development.

    Science.gov (United States)

    Rosch, David M; Collins, Jasmine D

    2017-09-01

    Student organizations have existed for almost as long as educational institutions have. This chapter examines the historical role of student organizations in developing leadership capacity in students, as well as their current roles on high school and collegiate campuses in creating transformational environments for student leadership learning and growth. © 2017 Wiley Periodicals, Inc., A Wiley Company.

  16. Some conditions for significant contribution from photovoltaics to sustainable development

    International Nuclear Information System (INIS)

    Coiante, D.

    1994-03-01

    In medium-long term perspective, the anthropogenic atmospheric pollution, due to fossil fuel burning, could be contained by massively using of renewable energy. Significant improvements are expected to arise from diffusion into use of large scale PV power systems. Considering the situation in Italy as a typical study case, a limit can be individuated, which makes that PV contribution to annual electric energy balance can reach a maximum of about 7%. Such a figure corresponds to about 2% in terms of contribution to total energy balance. Thus, the intermittent energy sources are destined, in Italy, to be confined to a role, just significant (7%) in the electric energy sector, but quite marginal (2%) with reference to expected environmental massive benefits. Apart from numerical results, this disappointing concept can be applied in general to all OCSE countries, wich globally produce the largest amount of world pollutant energy. Consequently, if photovoltaics wants to acquire a real environmental consistence, the limit of PV system diffusion has to be overcome. This can be attained by implementing the present grid-tied reference model for PV system diffusion by including an hydrogen production and storage system

  17. Environmental Enteropathy: Elusive but Significant Subclinical Abnormalities in Developing Countries

    Directory of Open Access Journals (Sweden)

    Koji Watanabe

    2016-08-01

    Full Text Available Environmental enteropathy/Environmental enteric dysfunction (EE/EED is a chronic disease of small intestine characterized by gut inflammation and barrier disruption, malabsorption and systemic inflammation in the absence of diarrhea. It is predominantly diseases of children in low income countries and is hypothesized to be caused by continuous exposure to fecally contaminated food, water and fomites. It had not been recognized as a priority health issue because it does not cause overt symptoms and was seen in apparently healthy individuals. However, there is a growing concern of EE/EED because of its impact on longitudinal public health issues, such as growth faltering, oral vaccine low efficacy and poor neurocognitive development. Recent works have provided important clues to unravel its complex pathogenesis, and suggest possible strategies for controlling EE/EED. However, effective diagnostic methods and interventions remain unsettled. Here, we review the existing literature, especially about its pathogenesis, and discuss a solution for children living in the developing world.

  18. The therapeutic relationship: historical development and contemporary significance.

    Science.gov (United States)

    O'Brien, A J

    2001-04-01

    The therapeutic relationship is a concept held by many to be fundamental to the identity of mental health nurses. While the therapeutic relationship was given formal expression in nursing theory in the middle of the last century, its origins can be traced to attendants' interpersonal practices in the asylum era. The dominance of medical understandings of mental distress, and the working-class status of asylum attendants, prevented the development of an account of mental health nursing based on attendants' relationships with asylum inmates. It was left to Peplau and other nursing theorists to describe mental health nursing as a therapeutic relationship in the 1940s and later. Some distinctive features of colonial life in New Zealand suggest that the ideal of the attendant as the embodiment of bourgeoisie values seems particularly unlikely to have been realized in the New Zealand context. However, New Zealand literature from the 20th century shows that the therapeutic relationship, as part of a general development of a therapeutic discourse, came to assume a central place in conceptualizations of mental health nursing. While the therapeutic relationship is not by itself a sufficient basis for professional continuity, it continues to play a fundamental role in mental health nurses' professional identity. The way in which the therapeutic relationship is articulated in the future will determine the meaning of the therapeutic relationship for future generations of mental health nurses.

  19. Extensive Gustatory Cortex Lesions Significantly Impair Taste Sensitivity to KCl and Quinine but Not to Sucrose in Rats.

    Directory of Open Access Journals (Sweden)

    Michelle B Bales

    Full Text Available Recently, we reported that large bilateral gustatory cortex (GC lesions significantly impair taste sensitivity to salts in rats. Here we extended the tastants examined to include sucrose and quinine in rats with ibotenic acid-induced lesions in GC (GCX and in sham-operated controls (SHAM. Presurgically, immediately after drinking NaCl, rats received a LiCl or saline injection (i.p., but postsurgical tests indicated a weak conditioned taste aversion (CTA even in controls. The rats were then trained and tested in gustometers to discriminate a tastant from water in a two-response operant taste detection task. Psychometric functions were derived for sucrose, KCl, and quinine. Our mapping system was used to determine placement, size, and symmetry of the lesions (~91% GC damage on average. For KCl, there was a significant rightward shift (ΔEC50 = 0.57 log10 units; p<0.001 in the GCX psychometric function relative to SHAM, replicating our prior work. There was also a significant lesion-induced impairment (ΔEC50 = 0.41 log10 units; p = 0.006 in quinine sensitivity. Surprisingly, taste sensitivity to sucrose was unaffected by the extensive lesions and was comparable between GCX and SHAM rats. The fact that such large bilateral GC lesions did not shift sucrose psychometric functions relative to SHAM, but did significantly compromise quinine and KCl sensitivity suggests that the neural circuits responsible for the detection of specific taste stimuli are partially dissociable. Lesion-induced impairments were observed in expression of a postsurgical CTA to a maltodextrin solution as assessed in a taste-oriented brief-access test, but were not reflected in a longer term 46-h two-bottle test. Thus, deficits observed in rats after extensive damage to the GC are also dependent on the test used to assess taste function. In conclusion, the degree to which the GC is necessary for the maintenance of normal taste detectability apparently depends on the chemical and

  20. Enhancement of Spatial Learning-Memory in Developing Rats via Mozart Music

    Institute of Scientific and Technical Information of China (English)

    Jian-Gao Yao; Yang Xia; Sheng-Jun Dai; Guang-Zhan Fang; Hua Guo; De-Zhong Yao

    2009-01-01

    This paper studies the effect of musical stimulations on the capability of the spatial learning-memory in developing rats by behavioral and electro-physiological techniques.Rats,which are exposed to Mozart's Sonata for Two Pianos in D Major,complete learning tasks of the Moriss water maze with significantly shorter latencies,and the power spectrum of alpha band of electrohippocampogram (EHG) significantly increase,compared with the control rats and rats exposed to the horror music.The results indicate that if given the stimulation of Mozart music in the developmental period of the auditory cortex,the capability of the spatial learning-memory can be significantly changed.The enhancement of alpha band of EHG may be related to the change of this function mainly.

  1. Martensite in steels: its significance, recent developments and trends

    International Nuclear Information System (INIS)

    Schulz-Beenken, A.S.

    1997-01-01

    Martensite is generally known as a hard but brittle microstructure. This is only true for high carbon plate martensite. Recently developed steels with a lath martensite microstructure offer an excellent toughness at yield strength of 1000 MPa yield strength. A transformation into lath martensite by glide as invariant shear mechanism is only possible at a carbon content below 0,03%. The source of both high strength and good toughness is the high dislocation density and the narrow lath width off less than 1 μm. By a thermomechanical treatment, that leads to a finer lath structure both strength and ductility can be improved to a yield strength of 1150 MPa and an elongation of 18%. As, unlike high carbon plate martensite, the hardness of lath martensite is not achieved by the distortion of the tetragonal cell by carbon atoms, the hardness of lath martensite remains stable up during an annealing treatment up to 600 C. This thermal stability of the lath martensit microstructure makes an additional increase of hardness by the precipitation of different types of intermetallic phases possible. The increase of the hardness from 300 HV to 600 HV by precipitation without volume changes and good cold deformability reveals many new application in manufacturing. In plate martensite too, comparatively high toughness values can be achieved, if carbon is replaced by nitrogen. The refining influence of nitrides on the austenite grain sizes and the precipitation of fine nitrides during the annealing process leads to impact values three times higher than those of comparable high carbon plate martensite. (orig.)

  2. Expression and location of α-fetoprotein during rat colon development

    Science.gov (United States)

    Liu, Xiao-Yan; Dong, Dan; Sun, Peng; Du, Jun; Gu, Luo; Ge, Ying-Bin

    2009-01-01

    AIM: To investigate the expression of α-fetoprotein (AFP), a cancer-associated fetal glycoprotein, and its involvement during rat colon development. METHODS: Colons from Sprague-Dawley rat fetuses, young and adult (8 wk old) animals were used in this study. Expression levels of AFP in colons of different development stage were detected by reverse-transcriptase PCR (RT-PCR) and Western blotting. To identify the cell location of AFP in the developing rat colons, double-immunofluorescent staining was performed using antibodies to specific cell markers and AFP, respectively. RESULTS: The highest levels of AFP mRNA were detected in colons of rats at embryonic day 18.5 (e18.5). Compared to e18.5 d, the AFP expression was significantly decreased during rat development [85% for e20.5, P colon from the embryo to the weaning stage by immunofluorescence and presents 72-kDa isoform in the developing rat colons by Western blotting. The dynamic expression of AFP in the various developmental stages of the colon indicates that AFP might be involved in many aspects of colon development. PMID:19360917

  3. Prenatal prochloraz treatment significantly increases pregnancy length and reduces offspring weight but does not affect social-olfactory memory in rats.

    Science.gov (United States)

    Dmytriyeva, Oksana; Klementiev, Boris; Berezin, Vladimir; Bock, Elisabeth

    2013-07-01

    Metabolites of the commonly used imidazole fungicide prochloraz are androgen receptor antagonists. They have been shown to block androgen-driven development and compromise reproductive function. We tested the effect of prochloraz on cognitive behavior following exposure to this fungicide during the perinatal period. Pregnant Wistar rats were administered a 200 mg/kg dose of prochloraz on gestational day (GD) 7, GD11, and GD15. The social recognition test (SRT) was performed on 7-week-old male rat offspring. We found an increase in pregnancy length and a significantly reduced pup weight on PND15 and PND40 but no effect of prenatal prochloraz exposure on social investigation or acquisition of social-olfactory memory. Copyright © 2012 Elsevier GmbH. All rights reserved.

  4. Rats

    Directory of Open Access Journals (Sweden)

    Alexey Kondrashov

    2012-01-01

    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  5. The effect of prenatal exposure to diazepam on aspects of postnatal development and behavior in rats.

    Science.gov (United States)

    Gai, N; Grimm, V E

    1982-01-01

    In the present study the effects of chronic treatment of pregnant rats with diazepam on the physical and behavioral development of their offspring were investigated. Rats that were diazepam-exposed prenatally were compared to age-matched controls in terms of the following: number of littermates; birth weight and weight gain until weaning: motor development and coordination; simple motor learning; open field activity; performance on learning tasks of varying complexity; retention of these tasks. Nulliparous Wistar rats were injected s.c. for 16 days of their pregnancy was either 2.5, 5, of 10 mg/kg diazepam or an equal volume of vehicle. Prenatal diazepam treatment did not alter litter size, birth weight, or the righting reflex, but seemed to retard early motor development transiently. Diazepam pups showed longer latencies and less rearing in the open field. There were no differences between animals exposed to drug and vehicle in simple motor learning or in acquiring a simple successive discrimination task. However, there were significant dose-dependent differences on a complex six-choice simultaneous discrimination learning task, the diazepam-exposed rats making more errors and taking more time to reach the goal. A significant difference was seen again between diazepam- and vehicle-exposed rats on the retention test 10 days later. The results indicate that diazepam administered to pregnant rats has long-range effects on the behavior of the offspring, some becoming manifest even in maturity.

  6. St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Shih-Ying [Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan (China); Juang, Shin-Hun [Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Tsai, Shang-Yuan; Chao, Pei-Dawn Lee [School of Pharmacy, China Medical University, Taichung, Taiwan (China); Hou, Yu-Chi, E-mail: hou5133@gmail.com [School of Pharmacy, China Medical University, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China)

    2012-08-15

    St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window. This study investigated the effect of SJW on MTX pharmacokinetics in rats. Rats were orally given MTX alone and coadministered with 300 and 150 mg/kg of SJW, and 25 mg/kg of diclofenac, respectively. Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method. The results showed that 300 mg/kg of SJW significantly increased the AUC{sub 0−t} and C{sub max} of MTX by 163% and 60%, respectively, and 150 mg/kg of SJW significantly increased the AUC{sub 0−t} of MTX by 55%. In addition, diclofenac enhanced the C{sub max} of MTX by 110%. The mortality of rats treated with SJW was higher than that of controls. In conclusion, coadministration of SJW significantly increased the systemic exposure and toxicity of MTX. The combined use of MTX with SJW would need to be with caution. -- Highlights: ► St. John's wort significantly increased the AUC{sub 0−t} and C{sub max} of methotrexate. ► Coadministration of St. John's wort increased the exposure and toxicity of methotrexate. ► The combined use of methotrexate with St. John's wort will need to be with caution.

  7. Maternal undernutrition significantly impacts ovarian follicle number and increases ovarian oxidative stress in adult rat offspring.

    Directory of Open Access Journals (Sweden)

    Angelica B Bernal

    Full Text Available BACKGROUND: We have shown recently that maternal undernutrition (UN advanced female pubertal onset in a manner that is dependent upon the timing of UN. The long-term consequence of this accelerated puberty on ovarian function is unknown. Recent findings suggest that oxidative stress may be one mechanism whereby early life events impact on later physiological functioning. Therefore, using an established rodent model of maternal UN at critical windows of development, we examined maternal UN-induced changes in offspring ovarian function and determined whether these changes were underpinned by ovarian oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: Our study is the first to show that maternal UN significantly reduced primordial and secondary follicle number in offspring in a manner that was dependent upon the timing of maternal UN. Specifically, a reduction in these early stage follicles was observed in offspring born to mothers undernourished throughout both pregnancy and lactation. Additionally, antral follicle number was reduced in offspring born to all mothers that were UN regardless of whether the period of UN was restricted to pregnancy or lactation or both. These reductions were associated with decreased mRNA levels of genes critical for follicle maturation and ovulation. Increased ovarian protein carbonyls were observed in offspring born to mothers UN during pregnancy and/or lactation and this was associated with peroxiredoxin 3 hyperoxidation and reduced mRNA levels; suggesting compromised antioxidant defence. This was not observed in offspring of mothers UN during lactation alone. CONCLUSIONS: We propose that maternal UN, particularly at a time-point that includes pregnancy, results in reduced offspring ovarian follicle numbers and mRNA levels of regulatory genes and may be mediated by increased ovarian oxidative stress coupled with a decreased ability to repair the resultant oxidative damage. Together these data are suggestive of

  8. Adverse effects on sexual development in rat offspring after low dose exposure to a mixture of endocrine disrupting pesticides

    DEFF Research Database (Denmark)

    Hass, Ulla; Boberg, Julie; Christiansen, Sofie

    2012-01-01

    The present study investigated whether a mixture of low doses of five environmentally relevant endocrine disrupting pesticides, epoxiconazole, mancozeb, prochloraz, tebuconazole and procymidone, would cause adverse developmental toxicity effects in rats. In rat dams, a significant increase...... and cumulative intake, because of the potentially serious impact of mixed exposure on development and reproduction in humans....

  9. Impact of environmental noise on growth and neuropsychological development of newborn rats.

    Science.gov (United States)

    Zheng, Yanyan; Meng, Meng; Zhao, Congmin; Liao, Wei; Zhang, Yuping; Wang, Liyan; Wen, Enyi

    2014-05-01

    We aimed to investigate the effects of environmental noise exposure on the growth and neuropsychological development in neonatal rats. Twenty-four postnatal 7-day-old Sprague-Dawley rats were randomly assigned into control, high-noise and reduced noise groups. The rats in the high-noise group were exposed to 90 dB white noise, and those in the control group were grown under standard condition, while those in the reduced noise group were exposed to standard condition with sound-absorbing cotton. Ten, 15, and 20 days post noise exposure, both the body weight and length of the rats in high-noise group were lower than those in the control and reduced noise groups, respectively. The secretion of growth hormone was significantly decreased in the rats exposed to high noise environment, compared to those exposed to standard condition and reduced noise. More interestingly, the swimming distance was apparently increased and the swimming speed was significantly decreased in high-noise group compared with those in control and reduced noise groups. Importantly, the mRNA and protein levels of SYP in the rats hippocampus were significantly decreased in high-noise group compare with those in control and reduced noise groups. Similarly, the positive expression of SYP in the CA1 region of hippocampus was also significantly decreased in the high noise group rats. In conclusion, our results demonstrated that high noise exposure could decrease the production of growth hormone and SYP in neonatal rats, which may retard the growth of weight and length and the capability of learning and memory. Copyright © 2014 Wiley Periodicals, Inc.

  10. Gluconeogenesis in rat placenta during foetal development

    International Nuclear Information System (INIS)

    Bagewadikar, R.S.; Sharma, C.; Nadkarni, G.B.

    1977-01-01

    Variations in glycogen levels in rat placenta have been correlated with gluconeogenesis in this tissue. Placental homogenate could synthesize substantial amounts of glucose from L-alanine-U- 14 C in early pregnancy. This has been substantiated by the observed enhancement in the activities of glucose 6-phosphatase, fructose 1, 6-diphosphatase and phosphoenolpyruvate carboxykinase. Gluconeogenic activity in placenta could proceed till the foetal liver was able to take over this function. The increase or decrease in placental glycogen is concomitant with glycogen synthetase, but not phosphorylase, activity. The reversible catalytic properties of placental aldolase also show subtle functional changes during and late phases of gestation. (author)

  11. Gluconeogenesis in rat placenta during foetal development

    Energy Technology Data Exchange (ETDEWEB)

    Bagewadikar, R S; Sharma, C; Nadkarni, G B [Bhabha Atomic Research Centre, Bombay (India). Biochemistry and Food Technology Div.

    1977-01-01

    Variations in glycogen levels in rat placenta have been correlated with gluconeogenesis in this tissue. Placental homogenate could synthesize substantial amounts of glucose from L-alanine-U-/sup 14/C in early pregnancy. This has been substantiated by the observed enhancement in the activities of glucose 6-phosphatase, fructose 1, 6-diphosphatase and phosphoenolpyruvate carboxykinase. Gluconeogenic activity in placenta could proceed till the foetal liver was able to take over this function. The increase or decrease in placental glycogen is concomitant with glycogen synthetase, but not phosphorylase, activity. The reversible catalytic properties of placental aldolase also show subtle functional changes during and late phases of gestation.

  12. Effects of enriched uranium on developing brain damage of neonatal rats

    International Nuclear Information System (INIS)

    Gu Guixiong; Zhu Shoupeng; Wang Liuyi; Yang Shuqin; Zhu Lingli

    2001-01-01

    The model of irradiation-induced brain damage in vivo was settled first of all. The micro-auto-radiographic tracing showed that when the rat's brain at postnatal day after lateral ventricle injection with enriched uranium 235 U the radionuclides were mainly accumulated in the nucleus. At the same time autoradiographic tracks appeared in the cytoplasm and interval between cells. The effects of cerebrum exposure to alpha irradiation by enriched uranium on somatic growth and neuro-behavior development of neonatal rats were examined by determination of multiple parameters. In the growth and development of the neonatal rat's cerebrum exposure to enriched uranium, the somatic growth such as body weight and brain weight increase was lower significantly. The data indicated that the neonatal wistar rats having cerebrum exposure to alpha irradiation by enriched uranium showed delayed growth and abnormal neuro-behavior. The changes of neuron specific enolase (NSE), interleukin-1 β (IL- β), superoxide dismutase (SOD), and endothelin (ET) in cerebellum, cerebral cortex, hippocampus, diencephalons of the rat brain after expose to alpha irradiation by enriched uranium were examined with radioimmunoassay. The results showed that SOD and ET can be elevated by the low dose irradiation of enriched uranium, and can be distinctly inhibited by the high dose. The data in view of biochemistry indicated firstly that alpha irradiation from enriched uranium on the developing brain damage of neonatal rats were of sensibility, fragility and compensation in nervous cells

  13. Effects of enriched uranium on developing brain damage of neonatal rats

    Energy Technology Data Exchange (ETDEWEB)

    Guixiong, Gu; Shoupeng, Zhu; Liuyi, Wang; Shuqin, Yang; Lingli, Zhu [Suzhou Medical College, Suzhou (China)

    2001-04-01

    The model of irradiation-induced brain damage in vivo was settled first of all. The micro-auto-radiographic tracing showed that when the rat's brain at postnatal day after lateral ventricle injection with enriched uranium {sup 235}U the radionuclides were mainly accumulated in the nucleus. At the same time autoradiographic tracks appeared in the cytoplasm and interval between cells. The effects of cerebrum exposure to alpha irradiation by enriched uranium on somatic growth and neuro-behavior development of neonatal rats were examined by determination of multiple parameters. In the growth and development of the neonatal rat's cerebrum exposure to enriched uranium, the somatic growth such as body weight and brain weight increase was lower significantly. The data indicated that the neonatal wistar rats having cerebrum exposure to alpha irradiation by enriched uranium showed delayed growth and abnormal neuro-behavior. The changes of neuron specific enolase (NSE), interleukin-1 {beta} (IL- {beta}), superoxide dismutase (SOD), and endothelin (ET) in cerebellum, cerebral cortex, hippocampus, diencephalons of the rat brain after expose to alpha irradiation by enriched uranium were examined with radioimmunoassay. The results showed that SOD and ET can be elevated by the low dose irradiation of enriched uranium, and can be distinctly inhibited by the high dose. The data in view of biochemistry indicated firstly that alpha irradiation from enriched uranium on the developing brain damage of neonatal rats were of sensibility, fragility and compensation in nervous cells.

  14. Autoradiography of 90Sr in developing rats

    International Nuclear Information System (INIS)

    Olsen, I.; Jonsen, J.

    1979-01-01

    The distribution patterns of 90 Sr in five littermate, 8-day-old Wistar rats were studied by whole body autoradiography. Rats were killed 15 min, 1, 4, 24, and 72 h after a single intraperitoneal injection of the isotope. Immediately after administration, 90 Sr was distributed throughout most of the soft tissues of the body. The soft tissue deposits had practically disappeared after 4 h. In the hard tissues of the body 90 Sr accumulated up to 24-72 h. Fifteen minutes after injection the uptake of 90 Sr in the enamel of the teeth was highest in the occlusal and incisal regions. 90 Sr gradually accumulated throughout the enamel and after 72 h its distribution in this layer was fairly uniform. Immediately after injection a narrow zone of radioactivity appeared in the dentin near the pulp. This zone broadened with time towards the dentinoenamel junction and included the intire dentin layer 72 h after injection. Initially, the uptake of 90 Sr was higher in the dentin than in the enamel, particularly in the cervical areas of the crown. This difference became less apparent with time. There was good correlation between the uptake in the teeth and bones, supporting the use of teeth as indicators of the 90 Sr body burden. (author)

  15. T-2 mycotoxin treatment of newborn rat pups does not significantly affect nervous system functions in adulthood.

    Science.gov (United States)

    Varró, Petra; Béldi, Melinda; Kovács, Melinda; Világi, Ildikó

    2018-03-01

    T-2 toxin is primarily produced by Fusarium sp. abundant under temperate climatic conditions. Its main harmful effect is the inhibition of protein synthesis. Causing oxidative stress, it also promotes lipid peroxidation and changes plasma membrane phospholipid composition; this may lead to nervous system alterations. The aim of the present study was to examine whether a single dose of T-2 toxin administered at newborn age has any long-lasting effects on nervous system functions. Rat pups were treated on the first postnatal day with a single intraperitoneal dose of T-2 toxin (0.2 mg/bwkg). Body weight of treated pups was lower during the second and third week of life, compared to littermates; later, weight gain was recovered. At young adulthood, behavior was tested in the open field, and no difference was observed between treated and control rats. Field potential recordings from somatosensory cortex and hippocampus slices did not reveal any significant difference in neuronal network functions. In case of neocortical field EPSP, the shape was slightly different in treated pups. Long-term synaptic plasticity was also comparable in both groups. Seizure susceptibility of the slices was not different, either. In conclusion, T-2 toxin did not significantly affect basic nervous system functions at this dose.

  16. Spontaneous motor activity during the development and maintenance of diet-induced obesity in the rat.

    Science.gov (United States)

    Levin, B E

    1991-09-01

    More than 80% of most daily spontaneous activities (assessed in an Omnitech activity monitor) occurred during the last hour of light and 12 h of the dark phase in 8 chow-fed male Sprague-Dawley rats. Thirty additional rats were, therefore, monitored over this 13-h period to assess the relationship of activity to the development and maintenance of diet-induced obesity (DIO) on a diet high in energy, fat and sucrose (CM diet). Nine of 20 rats became obese after 3 months on the CM diet, with 71% greater weight gain than 10 chow-fed controls. Eleven of 20 rats were diet resistant (DR), gaining the same amount of weight as chow-fed rats. Neither initial activity levels nor initial body weights on chow (Period I) differed significantly across retrospectively identified groups. After 3 months on CM diet or chow (Period II), as well as after an additional 3 months after CM diet-fed rats returned to chow (Period III), there were significant inverse correlations (r = -.606 to -.370) between body weight at the time of testing and various measures of movement in the horizontal plane. There was no relationship to dietary content nor consistent correlations of body weight or diet group to vertical movements, an indirect measure of ingestive behavior. Patterns of time spent in the vertical position were significantly different for DIO vs. DR rats in Period III, however. Thus, differences in food intake and metabolic efficiency, rather than differences in nocturnal activity, are probably responsible for the greater weight gain in DIO-prone rats placed on CM diet.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. [Effect of leptin on long-term spatial memory of rats with white matter damage in developing brain].

    Science.gov (United States)

    Feng, Er-Cui; Jiang, Li

    2017-12-01

    To investigate the neuroprotective effect of leptin by observing its effect on spatial memory of rats with white matter damage in developing brain. A total of 80 neonatal rats were randomly divided into 3 groups: sham-operation (n=27), model (n=27) and leptin intervention (n=27). The rats in the model and leptin intervention groups were used to prepare a model of white matter damage in developing brain, and the rats in the leptin intervention group were given leptin (100 μg/kg) diluted with normal saline immediately after modelling for 4 consecutive days. The survival rate of the rats was observed and the change in body weight was monitored. When the rats reached the age of 21 days, the Morris water maze test was used to evaluate spatial memory. There was no significant difference in the survival rate of rats between the three groups (P>0.05). Within 10 days after birth, the leptin intervention group had similar body weight as the sham-operation group and significantly lower body weight than the model group (P0.05). The results of place navigation showed that from the second day of experiment, there was a significant difference in the latency period between the three groups (Pmemory impairment of rats with white matter damage in developing brain. It thus exerts a neuroprotective effect, and is worthy of further research.

  18. Development of cholecystokinin binding sites in rat upper gastrointestinal tract

    International Nuclear Information System (INIS)

    Robinson, P.H.; Moran, T.H.; Goldrich, M.; McHugh, P.R.

    1987-01-01

    Autoradiography using 125 I-labeled Bolton Hunter-CCK-33 was used to study the distribution of cholecystokinin binding sites at different stages of development in the rat upper gastrointestinal tract. Cholecystokinin (CCK) binding was present in the distal stomach, esophagus, and gastroduodenal junction in the rat fetus of gestational age of 17 days. In the 20-day fetus, specific binding was found in the gastric mucosa, antral circular muscle, and pyloric sphincter. Mucosal binding declined during postnatal development and had disappeared by day 15. Antral binding declined sharply between day 10 and day 15 and disappeared by day 50. Pyloric muscle binding was present in fetal stomach and persisted in the adult. Pancreatic CCK binding was not observed before day 10. These results suggest that CCK may have a role in the control of gastric emptying and ingestive behavior in the neonatal rat

  19. Development of cholecystokinin binding sites in rat upper gastrointestinal tract

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, P.H.; Moran, T.H.; Goldrich, M.; McHugh, P.R.

    1987-04-01

    Autoradiography using /sup 125/I-labeled Bolton Hunter-CCK-33 was used to study the distribution of cholecystokinin binding sites at different stages of development in the rat upper gastrointestinal tract. Cholecystokinin (CCK) binding was present in the distal stomach, esophagus, and gastroduodenal junction in the rat fetus of gestational age of 17 days. In the 20-day fetus, specific binding was found in the gastric mucosa, antral circular muscle, and pyloric sphincter. Mucosal binding declined during postnatal development and had disappeared by day 15. Antral binding declined sharply between day 10 and day 15 and disappeared by day 50. Pyloric muscle binding was present in fetal stomach and persisted in the adult. Pancreatic CCK binding was not observed before day 10. These results suggest that CCK may have a role in the control of gastric emptying and ingestive behavior in the neonatal rat.

  20. A New Rat Model of Epileptic Spasms Based on Methylazoxymethanol-Induced Malformations of Cortical Development

    Directory of Open Access Journals (Sweden)

    Eun-Hee Kim

    2017-06-01

    Full Text Available Malformations of cortical development (MCDs can cause medically intractable epilepsies and cognitive disabilities in children. We developed a new model of MCD-associated epileptic spasms by treating rats prenatally with methylazoxymethanol acetate (MAM to induce cortical malformations and postnatally with N-methyl-d-aspartate (NMDA to induce spasms. To produce cortical malformations to infant rats, two dosages of MAM (15 mg/kg, intraperitoneally were injected to pregnant rats at gestational day 15. In prenatally MAM-exposed rats and the controls, spasms were triggered by single (6 mg/kg on postnatal day 12 (P12 or 10 mg/kg on P13 or 15 mg/kg on P15 or multiple doses (P12, P13, and P15 of NMDA. In prenatally MAM-exposed rats with single NMDA-provoked spasms at P15, we obtain the intracranial electroencephalography and examine the pretreatment response to adrenocorticotropic hormone (ACTH or vigabatrin. Rat pups prenatally exposed to MAM exhibited a significantly greater number of spasms in response to single and multiple postnatal NMDA doses than vehicle-exposed controls. Vigabatrin treatment prior to a single NMDA dose on P15 significantly suppressed spasms in MAM group rats (p < 0.05, while ACTH did not. The MAM group also showed significantly higher fast oscillation (25–100 Hz power during NMDA-induced spasms than controls (p = 0.047. This new model of MCD-based epileptic spasms with corresponding features of human spasms will be valuable for future research of the developmental epilepsy.

  1. Significance of the expression of matrix metalloproteinase-9 (MMP-9) in brain tissue of rat models of experimental intracerebral haemorrhage (ICH)

    International Nuclear Information System (INIS)

    Wu Jiami; Liu Shengda

    2005-01-01

    Objective: To study the relationship between the brain tissue expression of MMP-9 and brain water content in rat models of experimental ICH. Methods: Rat models of ICH were prepared with intracerebral (caudate nuclei) injection of autologous noncoagulated blood (50 μl). Animals were sacrificed at 6h, 12h, 24h, 48h, 72h, 120h, lw, 2w and the MMP-9 expressions at the periphery of intracerebral hematoma were examined with immunohisto chemistry. The brain water content was also determined at the same time. Control models were prepared with intracerebral sham injection of normal saline. Results: (1) In the ICH models, the number of MMP-9 positive capillaries at the periphery of hematoma began to rise at 6h (vs that of sham group, P < 0.01 ) with peak at 48h, then gradually dropped. At lwk, the number was still significantly higher than that in the sham group (P <0.01 ). However, there were no expression at 2wk. (2) The brain water content in the ICH group was significantly increased at 12h (vs sham group, P < 0.05) with peak at 72h. At lwk, the brain water content was still significantly higher in the ICH group (P <0.01 ) but at 2wk, the brain water content was about the same in both groups. (3) Animals injected with different amounts of blood (30 μl, 50 μl, 100 μl) showed increased expression of MMP-9 along with the increase of dose (P<0.01). (4) The MMP-9 expression was positively correlated with the brain water content (r=0.8291, P<0.05). Conclusion: In the rat models, MMP-9 expression was activated after ICH. The increase paralleled that of the amount of haemorrhage and brain water content. It was postulated that MMP-9 enhanced development of brain edema through degrading of the blood brain barrier component substances. (authors)

  2. Quantitative analysis of development and aging of genital corpuscles in glans penis of the rat.

    Science.gov (United States)

    Shiino, Mizuho; Hoshi, Hideo; Kawashima, Tomokazu; Ishikawa, Youichi; Takayanagi, Masaaki; Murakami, Kunio; Kishi, Kiyoshi; Sato, Fumi

    2015-02-01

    The aim of the present postnatal developmental study was to determine densities of unique genital corpuscles (GCs) in glans penis of developing and aged rats. GCs were identified as corpuscular endings consisting of highly branched and coiled axons with many varicosities, which were immunoreactive for protein gene product 9.5. In addition, GCs were immunoreactive for calcitonin gene-related peptide and substance P, but not for vasoactive intestinal polypeptide and neuropeptide Y. GCs were not found in the glans penis of 1 week old rats. Densities of GCs were low at 3 weeks, significantly increased at 5 and 10 weeks, reached the peak of density at 40 weeks, and tended to decrease at 70 and 100 weeks. Sizes of GCs were small in 3 weeks old rats, increased at 5 and 10 weeks, reached the peak-size at 40 weeks and reduced in size at 70 and 100 weeks. Considering sexual maturation of the rat, the results reveal that GCs of the rat begins to develop postnatal and reaches to the peak of their development after puberty and continues to exist until old age, in contrast to prenatal and early postnatal development of other sensory receptors of glabrous skin. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Prenatal development toxicity study of zinc oxide nanoparticles in rats

    Directory of Open Access Journals (Sweden)

    Hong JS

    2014-12-01

    Full Text Available Jeong-Sup Hong,1,2 Myeong-Kyu Park,1 Min-Seok Kim,1 Jeong-Hyeon Lim,1 Gil-Jong Park,1 Eun-Ho Maeng,1 Jae-Ho Shin,3 Meyoung-Kon Kim,4 Jayoung Jeong,5 Jin-A Park,2 Jong-Choon Kim,6 Ho-Chul Shin2 1Health Care Research Laboratory, Korea Testing and Research Institute, Gimpo, South Korea; 2College of Veterinary Medicine, Konkuk University, Seoul, South Korea; 3Department of Biomedical Laboratory Science, Eulji University, Seongnam-si, South Korea; 4Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, South Korea; 5Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungcheongbuk-do, South Korea; 6College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea Abstract: This study investigated the potential adverse effects of zinc oxide nanoparticles ([ZnOSM20(+ NPs] zinc oxide nanoparticles, positively charged, 20 nm on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague-Dawley rats. ZnOSM20(+ NPs were administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All dams were subjected to a cesarean section on gestational day 20, and all of the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight after administration of 400 mg/kg/day NPs; reduced food consumption after administration of 200 and 400 mg/kg/day NPs; and decreased liver weight and increased adrenal glands weight after administration of 400 mg/kg/day NPs. However, no treatment-related difference in: number of corpora lutea; number of implantation sites; implantation rate (%; resorption; dead fetuses; litter size; fetal deaths and placental weights; and sex ratio were observed between the groups. On the other hand, significant decreases between treatment groups and controls were seen for fetal weights after

  4. Asthma pregnancy alters postnatal development of chromaffin cells in the rat adrenal medulla.

    Directory of Open Access Journals (Sweden)

    Xiu-Ming Wu

    Full Text Available Adrenal neuroendocrine plays an important role in asthma. The activity of the sympathoadrenal system could be altered by early life events. The effects of maternal asthma during pregnancy on the adrenal medulla of offspring remain unknown.This study aims to explore the influence of maternal asthma during pregnancy on the development and function of adrenal medulla in offspring from postnatal day 3 (P3 to postnatal day 60 (P60. Asthmatic pregnant rats (AP, nerve growth factor (NGF-treated pregnant rats (NP and NGF antibody-treated pregnant rats (ANP were sensitized and challenged with ovalbumin (OVA; NP and ANP were treated with NGF and NGF antibody respectively. Offspring rats from the maternal group were divided into four groups: offspring from control pregnant rats (OCP, offspring from AP (OAP, offspring from NP (ONP, and offspring from ANP (OANP. The expressions of phenylethanolamine N-methyltransferase (PNMT protein in adrenal medulla were analyzed. The concentrations of epinephrine (EPI, corticosterone and NGF in serum were measured. Adrenal medulla chromaffin cells (AMCC were prone to differentiate into sympathetic nerve cells in OAP and ONP. Both EPI and PNMT were decreased in OAP from P3 to P14, and then reached normal level gradually from P30 to P60, which were lower from birth to adulthood in ONP. Corticosterone concentration increased significantly in OAP and ONP.Asthma pregnancy may promote AMCC to differentiate into sympathetic neurons in offspring rats and inhibit the synthesis of EPI, resulting in dysfunction of bronchial relaxation.

  5. Tartrazine and the developing nervous system of rats.

    Science.gov (United States)

    Sobotka, T J; Brodie, R E; Spaid, S L

    1977-05-01

    Rat dams were exposed to the artificial food color tartrazine (FD&C Yellow no. 5) at dietary levels of 0, 1, and 2% during gestation and lactation. The experimental offspring were continued on the same diets for approximately 3 months after weaning. No adverse physical or behavioral effects were noted in the dams. Fetal development and postnatal viability of the offspring were also normal. The only effect on postnatal development of the central nervous system (CNS) was a small transient change in neuromotor clinging ability of female offspring. The limited effect of tartrazine on the CNS was further evidenced by the facts that (1) the neurobehavioral profiles of the experimental weanlings revealed no significant abnormalities, and (2) morphochemical analysis of brain tissue, as well as brain weights, revealed no abnormalities. Tartrazine did appear to exert more general signs of toxicity in the offspring--namely, depressed body weight, an apparent reduction in thymus weight, and a slight elevation of red blood cells and hemoglobin.

  6. Acute hypothalamic suppression significantly affects trabecular bone but not cortical bone following recovery and ovariectomy surgery in a rat model

    Directory of Open Access Journals (Sweden)

    Vanessa R. Yingling

    2016-01-01

    Full Text Available Background. Osteoporosis is “a pediatric disease with geriatric consequences.” Bone morphology and tissue quality co-adapt during ontogeny for sufficient bone stiffness. Altered bone morphology from hypothalamic amenorrhea, a risk factor for low bone mass in women, may affect bone strength later in life. Our purpose was to determine if altered morphology following hypothalamic suppression during development affects cortical bone strength and trabecular bone volume (BV/TV at maturity.Methods. Female rats (25 days old were assigned to a control (C group (n = 45 that received saline injections (.2 cc or an experimental group (GnRH-a (n = 45 that received gonadotropin releasing hormone antagonist injections (.24 mg per dose for 25 days. Fifteen animals from each group were sacrificed immediately after the injection protocol at Day 50 (C, GnRH-a. The remaining animals recovered for 135 days and a subset of each group was sacrificed at Day 185 ((C-R (n = 15 and (G-R (n = 15. The remaining animals had an ovariectomy surgery (OVX at 185 days of age and were sacrificed 40 days later (C-OVX (n = 15 and (G-OVX (n = 15. After sacrifice femurs were mechanically tested and scanned using micro CT. Serum C-terminal telopeptides (CTX and insulin-like growth factor 1 (IGF-1 were measured. Two-way ANOVA (2 groups (GnRH-a and Control X 3 time points (Injection Protocol, Recovery, post-OVX was computed.Results. GnRH-a injections suppressed uterine weights (72% and increased CTX levels by 59%. Bone stiffness was greater in the GnRH-a groups compared to C. Ash content and cortical bone area were similar between groups at all time points. Polar moment of inertia, a measure of bone architecture, was 15% larger in the GnRH-a group and remained larger than C (19% following recovery. Both the polar moment of inertia and cortical area increased linearly with the increases in body weight. Following the injection protocol, trabecular BV/TV was 31% lower in the Gn

  7. Development of the rat larynx: a histological study.

    Science.gov (United States)

    Alli, Opeyemi; Berzofsky, Craig; Sharma, Sansar; Pitman, Michael J

    2013-12-01

    To evaluate and describe the cartilaginous and muscular development of the rat larynx. Histologic evaluation. The larynges of Sprague Dawley rats of embryonic day (E) 13, 15, 17, 19, 21, postnatal day 0, 14, and adult of 250 gm were collected. Four larynges of each age were harvested, cut into 15-μm serial sections, stained with hematoxylin and eosin, and evaluated under light microscopy. Representative digital images were recorded and evaluated at the preglottic (supraglottic in humans), glottic, and postglottic (subglottic in humans) levels. Brachial arches were observed at E13. At E17, immature structures of the larynx, including skeletal muscle, cartilage, and the lumen were identifiable. Chondrification and muscle formation were clearly seen by E19. The muscular and cartilagenous components of the larynx were well established by E21. During the span between birth and adult maturation, the size of the larynx increased from a height of 1.10 mm to 2.90 mm, and from a width of 1.80 mm to 5.40 mm, and from a length of 1.38 mm to 4.77 mm in the stained section. Although developed at E21, the laryngeal structures continued to grow by approximately 30%. Rat laryngeal development parallels that in mice and humans. In the rat, at E17 immature structures of the larynx are identifiable, they are well developed at birth and grow by approximately 30% into adulthood. Understanding the chronology and morphology of the embryogenesis of the rat laryngeal musculature is essential and will allow for further evaluation of the embryologic innervation of these muscles. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  8. Development of antibodies against the rat brain somatostatin receptor.

    Science.gov (United States)

    Theveniau, M; Rens-Domiano, S; Law, S F; Rougon, G; Reisine, T

    1992-05-15

    Somatostatin (SRIF) is a neurotransmitter in the brain involved in the regulation of motor activity and cognition. It induces its physiological actions by interacting with receptors. We have developed antibodies against the receptor to investigate its structural properties. Rabbit polyclonal antibodies were generated against the rat brain SRIF receptor. These antibodies (F4) were able to immunoprecipitate solubilized SRIF receptors from rat brain and the cell line AtT-20. The specificity of the interaction of these antibodies with SRIF receptors was further demonstrated by immunoblotting. F4 detected SRIF receptors of 60 kDa from rat brain and adrenal cortex and the cell lines AtT-20, GH3, and NG-108, which express high densities of SRIF receptors. They did not detect immunoreactive material from rat liver or COS-1, HEPG, or CRL cells, which do not express functional SRIF receptors. In rat brain, 60-kDa immunoreactivity was detected by F4 in the hippocampus, cerebral cortex, and striatum, which have high densities of SRIF receptors. However, F4 did not interact with proteins from cerebellum and brain stem, which express few SRIF receptors. Immunoreactive material cannot be detected in rat pancreas or pituitary, which have been reported to express a 90-kDa SRIF receptor subtype. The selective detection of 60-kDa SRIF receptors by F4 indicates that the 60- and 90-kDa SRIF receptor subtypes are immunologically distinct. The availability of antibodies that selectively detect native and denatured brain SRIF receptors provides us with a feasible approach to clone the brain SRIF receptor gene(s).

  9. Phenomenon of hormesis on γ-irradiated developing rat pups

    International Nuclear Information System (INIS)

    Ruda, V.P.; Kuzin, A.M.

    1991-01-01

    Development of rat pups was shown to accelerate body mass up 121% of control) afetr γ-irradiation on day 21 of the postnatal development (2.88 cGy, dose-rate of 0.12 cGy/h). Higher cumulative doses (14.4 and 144 cGy) did not influence the body mass growth, and inhibition was only caused by doses exceeding 150 cGy

  10. Development of a Rat Model of Hypothermia

    National Research Council Canada - National Science Library

    DuBose, David A; Morehouse, David H; Rufolo, Dennis; Blaha, Michael; Leon, Lisa R

    2005-01-01

    Hypothermia can significantly impact the outcome of military missions, since it is a seasonal and geographic pervasive physiological phenomenon that reduces not only soldier performance, but may lead to their death...

  11. Significance of ACTH4-10 in the control of hippocampal corticosterone receptor capacity of hypophysectomized rats

    NARCIS (Netherlands)

    Veldhuis, H D; De Kloet, E R

    1982-01-01

    The effect of hypophysectomy on the number of corticosterone receptor sites was investigated in three rat brain regions and was compared with the effect of long-term adrenalectomy. Subsequently, the effect on receptor capacity was measured after the hypophysectomized rats had received as

  12. Lack of toxic effect of technical azadirachtin during postnatal development of rats.

    Science.gov (United States)

    Srivastava, M K; Raizada, R B

    2007-03-01

    Azadirachtin, a biopesticide has been evaluated for its possible toxic effects during postnatal development of rats over two generations. Rats were fed 100, 500 and 1000ppm technical azadirachtin through diet which is equivalent to 5, 25 and 50mg/kg body weight of rats. Technical azadirachtin has not produced any adverse effects on reproductive function and data were comparable to control animals over two generations. There were no toxicological effect in parent rats as evidenced by clinical signs of toxicity, enzymatic parameters like AST, ALT, ALP, S. bilirubin, S. cholesterol, total protein and histopathology of liver, brain, kidney and testes/ovary. The litters of F(1B) and F(2B) generations were devoid of any morphological, visceral and teratological changes. The percent cumulative loss and growth index of pups were also comparable to respective controls in successive growth period of 0, 4, 7, 14 and 21 days in two generations. There were no major malformations in fetuses while some insignificant minor skeletal variations like missing 5th sternebrae and bipartite thoracic centre found were not compound or dose related. No significant pathomorphological changes were observed in liver, kidney, brain and gonads of F(2B) pups. In conclusion rats fed technical azadirachtin showed no evidence of cumulative effects on postnatal development and reproductive performance over two generations. Absence of any major adverse reproductive effects in adults as well as in 21 days old pups of F(2B) generation suggest the safe use of technical azadirachtin as a biopesticide.

  13. Development of T Lymphocytes in the Nasal-associated Lymphoid Tissue (NALT from Growing Wistar Rats

    Directory of Open Access Journals (Sweden)

    Gustavo A. Sosa

    2004-01-01

    Full Text Available The aim of the present report was to study the development of several T-lymphocyte subsets in the nasal-associated lymphoid tissue (NALT of growing Wistar rats. CD5+ and CD4+ lymphocytes gradually increased with age. A predominance of CD8α+ over CD4+ T cells was found from 7 to 45 days but from 45 to 60 days of age T helper cells outnumbered the cytotoxic subpopulation. The majority of CD8+ T lymphocytes expressed the heterodimeric isoform. The most relevant findings by immunohistochemistry are: (1 the predominance of TCRγδ+ and CD8α+ cells at 7 days postpartum over all the other T-cell subpopulations; and (2 that TCRγβ+ outnumbered TCRαβ+ T cells from 7 to 45 days postpartum whereas αβ T cells predominated in 45- and 60-day-old rats. Besides, cytometric studies have shown that the percentages of TCRγ+, CD8+, as well as the population coexpressing both phenotypes (TCRγδ+CD8α+, were significantly higher in rats at 7 days postpartum when compared to 60 day-old rats. In the present study, the finding of a high number of γδ+ and CD8+ T cells early in NALT development may indicate the importance of these subpopulations in the protection of the nasal mucosa in suckling and weaning Wistar rats.

  14. Effects of iron supplementation on growth, gut microbiota, metabolomics and cognitive development of rat pups.

    Directory of Open Access Journals (Sweden)

    Erica E Alexeev

    Full Text Available Iron deficiency is common during infancy and therefore iron supplementation is recommended. Recent reports suggest that iron supplementation in already iron replete infants may adversely affect growth, cognitive development, and morbidity.Normal and growth restricted rat pups were given iron daily (30 or 150 μg/d from birth to postnatal day (PD 20, and followed to PD56. At PD20, hematology, tissue iron, and the hepatic metabolome were measured. The plasma metabolome and colonic microbial ecology were assessed at PD20 and PD56. T-maze (PD35 and passive avoidance (PD40 tests were used to evaluate cognitive development.Iron supplementation increased iron status in a dose-dependent manner in both groups, but no significant effect of iron on growth was observed. Passive avoidance was significantly lower only in normal rats given high iron compared with controls. In plasma and liver of normal and growth-restricted rats, excess iron increased 3-hydroxybutyrate and decreased several amino acids, urea and myo-inositol. While a profound difference in gut microbiota of normal and growth-restricted rats was observed, with iron supplementation differences in the abundance of strict anaerobes were observed.Excess iron adversely affects cognitive development, which may be a consequence of altered metabolism and/or shifts in gut microbiota.

  15. Development of the adrenal axis in the neonatal rat

    Energy Technology Data Exchange (ETDEWEB)

    Guillet, Ronnie [Univ. of Rochester, NY (United States)

    1977-01-01

    Plasma corticosterone and ACTH concentrations were determined in neonatal rats 1, 7, 14, and 21 days old, under a variety of experimental conditions, to obtain more information on the postnatal development of the rat hypothalamo-adrenal (HHA) axis. The results indicate that: (1) there is a diminution followed by an increase in responsiveness of the adrenal gland, but the pituitary response to direct hormonal stimulation is unchanged during the first three postnatal weeks; (2) continued stimulation of the adrenal by ACTH or of the central nervous system (CNS) or hypothalamus by corticosterone is necessary during early postnatal development to allow normal maturation of the HHA axis; and (3) feedback inhibition is operative by birth, at least to a moderate degree. Taken together, the studies suggest that both the adrenal and pituitary glands are potentially functional at birth, but that the hypothalamic and CNS mediators of the stress response are not mature until at least the second or third postnatal week. (ERB)

  16. Passive stiffness of rat skeletal muscle undernourished during fetal development

    Directory of Open Access Journals (Sweden)

    Ana Elisa Toscano

    2010-01-01

    Full Text Available OBJECTIVES: The aim of the study was to investigate the effect of fetal undernutrition on the passive mechanical properties of skeletal muscle of weaned and young adult rats. INTRODUCTION: A poor nutrition supply during fetal development affects physiological functions of the fetus. From a mechanical point of view, skeletal muscle can be also characterized by its resistance to passive stretch. METHODS: Male Wistar rats were divided into two groups according to their mother's diet during pregnancy: a control group (mothers fed a 17% protein diet and an isocaloric low-protein group (mothers fed a 7.8% protein diet. At birth, all mothers received a standardized meal ad libitum. At the age of 25 and 90 days, the soleus muscle and extensor digitorum longus (EDL muscles were removed in order to test the passive mechanical properties. A first mechanical test consisted of an incremental stepwise extension test using fast velocity stretching (500 mm/s enabling us to measure, for each extension stepwise, the dynamic stress (σd and the steady stress (σs. A second test consisted of a slow velocity stretch in order to calculate normalized stiffness and tangent modulus from the stress-strain relationship. RESULTS: The results for the mechanical properties showed an important increase in passive stiffness in both the soleus and EDL muscles in weaned rat. In contrast, no modification was observed in young adult rats. CONCLUSIONS: The increase in passive stiffness in skeletal muscle of weaned rat submitted to intrauterine undernutrition it is most likely due to changes in muscle passive stiffness.

  17. HMGB1 promotes the development of pulmonary arterial hypertension in rats.

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    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.

  18. Rats with steroid-induced polycystic ovaries develop hypertension and increased sympathetic nervous system activity

    Directory of Open Access Journals (Sweden)

    Ploj Karolina

    2005-09-01

    Full Text Available Abstract Background Polycystic ovary syndrome (PCOS is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, abdominal obesity, hyperandrogenism, hypertension, and insulin resistance. Methods Our objectives in this study were (1 to estimate sympathetic-adrenal medullary (SAM activity by measuring mean systolic blood pressure (MSAP in rats with estradiol valerate (EV-induced PCO; (2 to estimate alpha1a and alpha2a adrenoceptor expression in a brain area thought to mediate central effects on MSAP regulation and in the adrenal medulla; (3 to assess hypothalamic-pituitary-adrenal (HPA axis regulation by measuring adrenocorticotropic hormone (ACTH and corticosterone (CORT levels in response to novel-environment stress; and (4 to measure abdominal obesity, sex steroids, and insulin sensitivity. Results The PCO rats had significantly higher MSAP than controls, higher levels of alpha1a adrenoceptor mRNA in the hypothalamic paraventricular nucleus (PVN, and lower levels of alpha2a adrenoceptor mRNA in the PVN and adrenal medulla. After exposure to stress, PCO rats had higher ACTH and CORT levels. Plasma testosterone concentrations were lower in PCO rats, and no differences in insulin sensitivity or in the weight of intraabdominal fat depots were found. Conclusion Thus, rats with EV-induced PCO develop hypertension and increased sympathetic and HPA-axis activity without reduced insulin sensitivity, obesity, or hyperandrogenism. These findings may have implications for mechanisms underlying hypertension in PCOS.

  19. Disturbed sensorimotor and electrophysiological patterns in lead intoxicated rats during development are restored by curcumin I.

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    Hind Benammi

    Full Text Available Lead poisoning is one of the most significant health problem of environmental origin. It is known to cause different damages in the central and peripheral nervous system which could be represented by several neurophysiological and behavioral symptoms. In this study we firstly investigated the effect of lead prenatal exposure in rats to (3g/L, from neonatal to young age, on the motor/sensory performances, excitability of the spinal cord and gaits during development. Then we evaluated neuroprotective effects of curcumin I (Cur I against lead neurotoxicity, by means of grasping and cliff avoidance tests to reveal the impairment of the sensorimotor functions in neonatal rats exposed prenatally to lead. In addition, extracellular recordings of motor output in spinal cord revealed an hyper-excitability of spinal networks in lead treated rats. The frequency of induced fictive locomotion was also increased in treated rats. At the young age, rats exhibited an impaired locomotor gait. All those abnormalities were attenuated by Cur I treatment at a dose of 16g/kg. Based on our finding, Cur I has shown features of a potent chemical compound able to restore the neuronal and the relative locomotor behaviors disturbances induced by lead intoxication. Therefore, this chemical can be recommended as a new therapeutic trial against lead induced neurotoxicity.

  20. Chronic intermittent hyperoxia alters the development of the hypoxic ventilatory response in neonatal rats.

    Science.gov (United States)

    Logan, Sarah; Tobin, Kristina E; Fallon, Sarah C; Deng, Kevin S; McDonough, Amy B; Bavis, Ryan W

    2016-01-01

    Chronic exposure to sustained hyperoxia alters the development of the respiratory control system, but the respiratory effects of chronic intermittent hyperoxia have rarely been investigated. We exposed newborn rats to short, repeated bouts of 30% O2 or 60% O2 (5 bouts h(-1)) for 4-15 days and then assessed their hypoxic ventilatory response (HVR; 10 min at 12% O2) by plethysmography. The HVR tended to be enhanced by intermittent hyperoxia at P4 (early phase of the HVR), but it was significantly reduced at P14-15 (primarily late phase of the HVR) compared to age-matched controls; the HVR recovered when individuals were returned to room air and re-studied as adults. To investigate the role of carotid body function in this plasticity, single-unit carotid chemoafferent activity was recorded in vitro. Intermittent hyperoxia tended to decrease spontaneous action potential frequency under normoxic conditions but, contrary to expectations, hypoxic responses were only reduced at P4 (not at P14) and only in rats exposed to higher O2 levels (i.e., intermittent 60% O2). Rats exposed to intermittent hyperoxia had smaller carotid bodies, and this morphological change may contribute to the blunted HVR. In contrast to rats exposed to intermittent hyperoxia beginning at birth, two weeks of intermittent 60% O2 had no effect on the HVR or carotid body size of rats exposed beginning at P28; therefore, intermittent hyperoxia-induced respiratory plasticity appears to be unique to development. Although both intermittent and sustained hyperoxia alter carotid body development and the HVR of rats, the specific effects and time course of this plasticity differs. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Fibronectin distribution during the development of fetal rat skin

    DEFF Research Database (Denmark)

    Gibson, W T; Couchman, J R; Weaver, A C

    1983-01-01

    Fibronectin distribution during fetal rat skin development has been studied immunocytochemically at the light and electron microscope level from 16 days of gestation to birth. The dermal-epidermal junction, the dermis, and connective tissue around developing muscle were shown by light microscopy......, and there was also staining associated with the underlying fine collagen fibrils. These observations are further evidence for the proposed role of fibronectin as a mediator of the cell-matrix interactions which are of importance for tissue development and maintenance....

  2. Effects of hyper- and hypothyroidism on the development and proliferation of testicular cells in prepubertal rats.

    Science.gov (United States)

    Fadlalla, Mohamed Babo; Wei, Quanwei; Fedail, Jaafar Sulieman; Mehfooz, Asif; Mao, Dagan; Shi, Fangxiong

    2017-12-01

    Thyroid hormones are important in the development and regulation of testes. This study was conducted to determine the effects of hyper- and hypothyroidism on testicular development in prepubertal rats aged 20-70 days. Weaning male rats (20 days old) until day 70 age were randomly divided into four groups: control, hyperthyroid (hyper-T), hypothyroid (hypo-T) and hypothyroid treated with thyroxine (T4) (hypo-T+T4). The results indicated that thyroid hormones caused a significant effect in body and testis weights, and food and water consumption. In addition there were changes in serum concentrations of tri-iodothyronine, T4, thyroid stimulating hormone (TSH) and testosterone. Histomorphology showed a significant decrease in seminiferous tubule diameter in hyper-T compared to the other groups. Leydig cell numbers showed a significant elevation in hyper-T but not in hypo-T groups. Immunostaining indicated that TSH receptor (TSHR), thyroid hormone receptors α/β (TRαβ) and proliferating cell nuclear antigen (PCNA) have the roles in testicular development. Our findings suggest that hyper- and hypo-thyroidism regulate testicular cell proliferation and spermatogenesis in prepubertal rats, indicating that expression of TSHR, TRαβ and PCNA may be regulated by thyroid hormones that are involved in testicular development; and that the administration of T4 to the hypo-T+T4 group leads to an improvement in the testicular condition. © 2017 Japanese Society of Animal Science.

  3. Studies on the postnatal development of the rat liver plasma membrane following maternal ethanol ingestion

    Energy Technology Data Exchange (ETDEWEB)

    Rovinski, B

    1984-01-01

    Studies on the developing rat liver and on the structure and function of the postnatal rat liver plasma membrane were carried out following maternal consumption of alcohol during pregnancy and lactation. A developmental study of alcohol dehydrogenase (ADH) indicated that both the activity and certain kinetic properties of the enzyme from the progeny of alcohol-fed and pair-fed mothers were similar. Fatty liver, however, developed in the alcoholic progeny only after ADH appeared on a day 19 of gestation. Further studies on structural and functional changes were then undertaken on the postnatal development of the rat liver plasma membrane. Radioligand binding studies performed using the hapatic alpha{sub 1}-adrenergic receptor as a plasma membrane probe demonstrated a significant decrease in receptor density in the alcoholic progeny, but no changes in binding affinity. Finally, the fatty acid composition of constituent phospholipids and the cholesterol content of rat liver plasma membranes were determined. All these observations suggest that membrane alterations in the newborn may be partially responsible for the deleterious action(s) of maternal alcoholism at the molecular level.

  4. Development of neuropeptide Y-mediated heart innervation in rats.

    Science.gov (United States)

    Masliukov, Petr M; Moiseev, Konstantin; Emanuilov, Andrey I; Anikina, Tatyana A; Zverev, Alexey A; Nozdrachev, Alexandr D

    2016-02-01

    Neuropeptide Y (NPY) plays a trophic role in the nervous and vascular systems and in cardiac hypertrophy. However, there is no report concerning the expression of NPY and its receptors in the heart during postnatal development. In the current study, immunohistochemistry and Western blot analysis was used to label NPY, and Y1R, Y2R, and Y5R receptors in the heart tissue and intramural cardiac ganglia from rats of different ages (newborn, 10 days old, 20 days old, 30 days old, 60 days old, 1 year old, and 2 years old).The obtained data suggest age-dependent changes of NPY-mediated heart innervation. The density of NPY-immunoreactive (IR) fibers was the least in newborn animals and increased in the first 20 days of life. In the atria of newborn and 10-day-old rats, NPY-IR fibers were more abundant compared with the ventricles. The vast majority of NPY-IR fibers also contained tyrosine hydroxylase, a key enzyme in catecholamine synthesis.The expression of Y1R increased between 10 and 20 days of life. Faint Y2R immunoreactivity was observed in the atria and ventricles of 20-day-old and older rats. In contrast, the highest level of the expression of Y5R was found in newborn pups comparing with more adult rats. All intramural ganglionic neurons were also Y1R-IR and Y5R-IR and Y2R-negative in all studied animals.Thus, the increasing of density of NPY-containing nerve fibers accompanies changes in relation of different subtypes of NPY receptors in the heart during development.

  5. Unilateral nasal obstruction affects motor representation development within the face primary motor cortex in growing rats.

    Science.gov (United States)

    Abe, Yasunori; Kato, Chiho; Uchima Koecklin, Karin Harumi; Okihara, Hidemasa; Ishida, Takayoshi; Fujita, Koichi; Yabushita, Tadachika; Kokai, Satoshi; Ono, Takashi

    2017-06-01

    Postnatal growth is influenced by genetic and environmental factors. Nasal obstruction during growth alters the electromyographic activity of orofacial muscles. The facial primary motor area represents muscles of the tongue and jaw, which are essential in regulating orofacial motor functions, including chewing and jaw opening. This study aimed to evaluate the effect of chronic unilateral nasal obstruction during growth on the motor representations within the face primary motor cortex (M1). Seventy-two 6-day-old male Wistar rats were randomly divided into control ( n = 36) and experimental ( n = 36) groups. Rats in the experimental group underwent unilateral nasal obstruction after cauterization of the external nostril at 8 days of age. Intracortical microstimulation (ICMS) mapping was performed when the rats were 5, 7, 9, and 11 wk old in control and experimental groups ( n = 9 per group per time point). Repeated-measures multivariate ANOVA was used for intergroup and intragroup statistical comparisons. In the control and experimental groups, the total number of positive ICMS sites for the genioglossus and anterior digastric muscles was significantly higher at 5, 7, and 9 wk, but there was no significant difference between 9 and 11 wk of age. Moreover, the total number of positive ICMS sites was significantly smaller in the experimental group than in the control at each age. It is possible that nasal obstruction induced the initial changes in orofacial motor behavior in response to the altered respiratory pattern, which eventually contributed to face-M1 neuroplasticity. NEW & NOTEWORTHY Unilateral nasal obstruction in rats during growth periods induced changes in arterial oxygen saturation (SpO 2 ) and altered development of the motor representation within the face primary cortex. Unilateral nasal obstruction occurring during growth periods may greatly affect not only respiratory function but also craniofacial function in rats. Nasal obstruction should be treated

  6. Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

    Science.gov (United States)

    Pong, Alice C; Jugé, Lauriane; Bilston, Lynne E; Cheng, Shaokoon

    2017-01-01

    Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

  7. Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats

    International Nuclear Information System (INIS)

    Singh, Bhupendra; Mense, Sarah M.; Bhat, Nimee K.; Putty, Sandeep; Guthiel, William A.; Remotti, Fabrizio; Bhat, Hari K.

    2010-01-01

    Phytoestrogens are plant compounds that structurally mimic the endogenous estrogen 17β-estradiol (E 2 ). Despite intense investigation, the net effect of phytoestrogen exposure on the breast remains unclear. The objective of the current study was to examine the effects of quercetin on E 2 -induced breast cancer in vivo. Female ACI rats were given quercetin (2.5 g/kg food) for 8 months. Animals were monitored weekly for palpable tumors, and at the end of the experiment, rats were euthanized, breast tumor and different tissues excised so that they could be examined for histopathologic changes, estrogen metabolic activity and oxidant stress. Quercetin alone did not induce mammary tumors in female ACI rats. However, in rats implanted with E 2 pellets, co-exposure to quercetin did not protect rats from E 2 -induced breast tumor development with 100% of the animals developing breast tumors within 8 months of treatment. No changes in serum quercetin levels were observed in quercetin and quercetin + E 2 -treated groups at the end of the experiment. Tumor latency was significantly decreased among rats from the quercetin + E 2 group relative to those in the E 2 group. Catechol-O-methyltransferase (COMT) activity was significantly downregulated in quercetin-exposed mammary tissue. Analysis of 8-isoprostane F 2α (8-iso-PGF 2α ) levels as a marker of oxidant stress showed that quercetin did not decrease E 2 -induced oxidant stress. These results indicate that quercetin (2.5 g/kg food) does not confer protection against breast cancer, does not inhibit E 2 -induced oxidant stress and may exacerbate breast carcinogenesis in E 2 -treated ACI rats. Inhibition of COMT activity by quercetin may expose breast cells chronically to E 2 and catechol estrogens. This would permit longer exposure times to the carcinogenic metabolites of E 2 and chronic exposure to oxidant stress as a result of metabolic redox cycling to estrogen metabolites, and thus quercetin may exacerbate E 2 -induced

  8. Olanzapine-induced weight gain: lessons learned from developing rat models

    OpenAIRE

    van der Zwaal, E.M.

    2011-01-01

    Olanzapine is an effective and commonly prescribed antipsychotic drug, used for the treatment of schizophrenia and bipolar disorder. Unfortunately significant weight gain is a common side effect. In order to effectively address this side effect, it is crucial to gain insight into the underlying mechanisms. Therefore, this thesis describes the development of a number of rat models that were designed to determine the effects of olanzapine on different aspects of energy balance. In both short- a...

  9. Increased expression of heat shock protein 105 in rat uterus of early pregnancy and its significance in embryo implantation

    Directory of Open Access Journals (Sweden)

    Hu Zhao-Yuan

    2009-03-01

    Full Text Available Abstract Background Heat shock proteins (Hsps are a set of highly conserved proteins, Hsp105, has been suggested to play a role in reproduction. Methods Spatio-temporal expression of Hsp105 in rat uterus during peri-implantation period was examined by immunohistochemistry and Western blot, pseudopregnant uterus was used as control. Injection of antisense oligodeoxynucleotides to Hsp105 into pregnant rat uteri was carried out to look at effect of Hsp105 on embryo implantation. Results Expression of Hsp105 was mainly in the luminal epithelium on day 1 of pregnancy, and reached a peak level on day 5, whereas in stroma cells, adjacent to the implanting embryo, the strongest expression of Hsp105 was observed on day 6. The immunostaining profile in the uterus was consistent with that obtained by Western blot in the early pregnancy. In contrast, no obvious peak level of Hsp105 was observed in the uterus of pseudopregnant rat on day 5 or day 6. Furthermore, injection of antisense oligodeoxynucleotides to Hsp105 into the rat uterine horn on day 3 of pregnancy obviously suppressed the protein expression as expected and reduced number of the implanted embryos as compared with the control. Conclusion Temporal and spatial changes in Hsp105 expression in pregnant rat uterus may play a physiological role in regulating embryo implantation.

  10. Effects of chronic treatment with valproate and oxcarbazepine on testicular development in rats.

    Science.gov (United States)

    Cansu, Ali; Ekinci, Ozgür; Serdaroglu, Ayse; Gürgen, Seren Gulsen; Ekinci, Ozalp; Erdogan, Deniz; Coskun, Zafer Kutay; Tunc, Lutfi

    2011-04-01

    The aim of this study was to examine the potential effects of valproate (VPA) and oxcarbazepine (OXC) on testicular development in rats. Forty-two Wistar rats were randomly divided into three groups of 14 rats each. Each group received the following via gavage over 90 days: group 1, tap water (control group); group 2, VPA (300mg/kg/day); group 3, OXC (100mg/kg/day). After sacrifice, body, testicular and epididymidis weights were measured. Testes were sampled, fixed and processed, and quantitative morphometric analysis of Sertoli cells, spermatocytes and spermatids was performed in stages II, V and XII by histopathological examination. Immunohistochemical staining was performed to transform growth factor beta 1 (TGF-β1) and p53, and the apoptotic index was assessed using the TUNEL method. Testis and relative testis weights were significantly lower in the VPA group compared to the control group (p0.05). Apoptotic cell counts and p53 immunoreaction were significantly high and TGF-β1 expression was significantly lower in the VPA group compared to that of the control group (p0.05). Our results show that VPA treatment from prepuberty to adulthood significantly negatively affects spermatogenesis, not only by reducing testicular weight, but also by increasing apoptotic death and p53 and decreasing TGF-β1 activation. OXC has a minimal side effect on testicular development. Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  11. Gross hepatic changes in developing albino rats exposed to valproic acid

    International Nuclear Information System (INIS)

    Khan, M.; Khattak, S.T.; Elahi, M.

    2011-01-01

    Background: Valproid Acid (VPA) is a broad spectrum antiepileptic drug. Its use during pregnancy has been associated with congenital anomalies and hepatotoxicity. This study was designed to assess the effects of VPA on the gross structure of liver in developing albino rats exposed to the drug during various trimesters of pregnancy. Methods: In this experimental study 40 pregnant rats were divided into 4 equal groups A, B, C and D. Group A received VPA in a dose of 500 mg/Kg/day intraperitonealy (I/P) on days 3, 4 and 5 of gestation. Group B received the drug in a dose of 500 mg/Kg/day I/P on days 8, 9 and 10 of gestation. Group C received VPA in a dose of 500 mg/Kg/day I/P on days 16, 17 and 18 of gestation. Group D received no treatment and was kept as a control group. On day 21, the rats were euthanised by cervical dislocation. The liver of the foetuses were dissected out for the assessment of their gross structure. Results: Foetal liver of the experimental groups showed significant decrease in weight as well as relative tissue weight index (RTWI) as compared to the control group, although the gross appearance of the foetal liver was normal in all the groups. Conclusion: The use of VPA during various trimesters of pregnancy produces hepatotoxicity in the developing rats. So, the use of this drug during pregnancy should be carefully decided. (author)

  12. Enhanced inhibitory effects of TBT chloride on the development of F1 rats.

    Science.gov (United States)

    Asakawa, H; Tsunoda, M; Kaido, T; Hosokawa, M; Sugaya, C; Inoue, Y; Kudo, Y; Satoh, T; Katagiri, H; Akita, H; Saji, M; Wakasa, M; Negishi, T; Tashiro, T; Aizawa, Y

    2010-05-01

    Neurotoxicity is one of the major effects of tributyltin (TBT). The effects on the next generation of F(1) rats exposed to TBT via the placenta and their dams' milk may be stronger than those on adults. Pregnant Wister rats were exposed to TBT at 0 and 125 ppm in their food. Half of the female F(1) rats in both groups were exposed to TBT at 125 ppm in their food from 9 to 15 weeks of age. Female F(1) rats were divided into the following groups: the control-control (CC) group, with no exposure; the TBT-control (TC) group, exposed to TBT via the placenta and their dams' milk; the control-TBT (CT) group, exposed to TBT via their food from 9 to 15 weeks of age; and the TBT-TBT (TT) group, exposed to TBT via the placenta, their dams' milk, and their food (n = 10/group). After administration, an open-field test and prepulse inhibition (PPI) test were performed at 15 weeks of age. The mean body weights of the TC and TT groups were significantly lower than that of the CC group from 9 to 15 weeks of age. The mean relative thymus weight of the TC and TT groups was significantly lower than that of the CC group. In the open-field test, a marked decrease in the total locomotion distance was observed in the TT group. The mean values in the TT and TC groups were significantly lower than that in the CC group. For the locomotion distance between 15 and 20 min, the mean values in the CT, TC, and TT groups were significantly lower than that in the CC group. The mean locomotor distance between 25 and 30 min in the TT group was significantly lower than that in the CC and TC groups. The mean values of instances of wall rearing in the TC, CT, and TT groups were significantly lower than that in the CC group. The mean value of face washing or body washing in the TT group was significantly lower than that in the CT group. There were no significant differences in indexes of the PPI test. Exposure to TBT via the placenta and their dams' milk inhibited the development of F(1) rats, which

  13. Development of mechanical hypersensitivity in rats during heroin and ethanol dependence: alleviation by CRF₁ receptor antagonism.

    Science.gov (United States)

    Edwards, Scott; Vendruscolo, Leandro F; Schlosburg, Joel E; Misra, Kaushik K; Wee, Sunmee; Park, Paula E; Schulteis, Gery; Koob, George F

    2012-02-01

    Animal models of drug dependence have described both reductions in brain reward processes and potentiation of stress-like (or anti-reward) mechanisms, including a recruitment of corticotropin-releasing factor (CRF) signaling. Accordingly, chronic exposure to opiates often leads to the development of mechanical hypersensitivity. We measured paw withdrawal thresholds (PWTs) in male Wistar rats allowed limited (short access group: ShA) or extended (long access group: LgA) access to heroin or cocaine self-administration, or in rats made dependent on ethanol via ethanol vapor exposure (ethanol-dependent group). In heroin self-administering animals, after transition to LgA conditions, thresholds were reduced to around 50% of levels observed at baseline, and were also significantly lower than thresholds measured in animals remaining on the ShA schedule. In contrast, thresholds in animals self-administering cocaine under either ShA (1 h) or LgA (6 h) conditions were unaltered. Similar to heroin LgA rats, ethanol-dependent rats also developed mechanical hypersensitivity after eight weeks of ethanol vapor exposure compared to non-dependent animals. Systemic administration of the CRF1R antagonist MPZP significantly alleviated the hypersensitivity observed in rats dependent on heroin or ethanol. The emergence of mechanical hypersensitivity with heroin and ethanol dependence may thus represent one critical drug-associated negative emotional state driving dependence on these substances. These results also suggest a recruitment of CRF-regulated nociceptive pathways associated with escalation of intake and dependence. A greater understanding of relationships between chronic drug exposure and pain-related states may provide insight into mechanisms underlying the transition to drug addiction, as well as reveal new treatment opportunities. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Effect of lead acetate on neurobehavioral development of rats

    Directory of Open Access Journals (Sweden)

    Mello C.F.

    1998-01-01

    Full Text Available We investigated the effects of lead exposure during the pre- and postnatal period on the neurobehavioral development of female Wistar rats (70-75 days of age, 120-150 g using a protocol of lead intoxication that does not affect weight gain. Wistar rats were submitted to lead acetate intoxication by giving their dams 1.0 mM lead acetate. Control dams received deionized water. Growth and neuromotor development were assessed by monitoring daily the following parameters in 20 litters: body weight, ear unfolding, incisor eruption, eye opening, righting, palmar grasp, negative geotaxis, cliff avoidance and startle reflex. Spontaneous alternation was assessed on postnatal day 17 using a T maze. The animals' ability to equilibrate on a beaker rim was measured on postnatal day 19. Lead intoxication was confirmed by measuring renal, hepatic and cerebral lead concentration in dams and litters. Lead treatment hastened the day of appearance of the following parameters: eye opening (control: 13.5 ± 0.6, N = 88; lead: 12.9 ± 0.6, N = 72; P<0.05, startle reflex (control: 13.0 ± 0.8, N = 88; lead: 12.0 ± 0.7, N = 72; P<0.05 and negative geotaxis. On the other hand, spontaneous alternation performance was hindered in lead-exposed animals (control: 37.6 ± 19.7; lead: 57.5 ± 28.3% of alternating animals; P<0.05. These results suggest that lead exposure without concomitant undernutrition alters rat development, affecting specific subsets of motor skills.

  15. MiR-200a is involved in rat epididymal development by targeting β-catenin mRNA

    Institute of Scientific and Technical Information of China (English)

    Xiaojiang Wu; Botao Zhao; Wei Li; Yue Chen; Ruqiang Liang; Lin Li; Youxin Jin; Kangcheng Ruan

    2012-01-01

    The expression of 350 microRNAs (miRNAs) in epididymis of rat from postnatal development to adult (from postnatal days 7-70) was profiled with home-made miRNA microarray.Among them,48 miRNAs changed significantly, in which the expression of miR-200a increased obviously with time,in a good agreement with that obtained from northern blot analysis.The real-time quantitative-polymerase chain reaction result indicated that temporal expression of rat β-catenin was exactly inversed to that of miR-200a during rat epididymal development,implying that miR-200a might also target β-catenin mRNA in rat epididymis as reported by Saydam et al.in humans.The bioinformatic analysis indicated that 3' untranslated region of rat β-catenin mRNA did contain a putative binding site for miR-200a.Meanwhile,it was found that the sequence of this binding site was different from that of human β-catenin mRNA with a deletion of two adjacent nucleotides (U and C).But the results of luciferase targeting assay in HEK 293T cells and the overexpression of miR-200a in rat NRK cells demonstrated that miR-200a did target rat β-catenin mRNA and cause the suppression of its expression.All these results show that miR-200a should be involved in rat epididymal development by targeting β-catenin mRNA of rat and suppressing its expression.

  16. Wistar-Kyoto Female Rats Are More Susceptible to Develop Sugar Binging: A Comparison with Wistar Rats

    Directory of Open Access Journals (Sweden)

    Helena Papacostas-Quintanilla

    2017-05-01

    Full Text Available The hedonic component of the feeding behavior involves the mesolimbic reward system and resembles addictions. Nowadays, the excessive consumption of sucrose is considered addictive. The Wistar-Kyoto (WKY rat strain is prone to develop anxiety and addiction-like behavior; nevertheless, a lack of information regarding their vulnerability to develop sugar binging-like behavior (SBLB and how it affects the reward system persist. Therefore, the first aim of the present study was to compare the different predisposition of two rat strains, Wistar (W and WKY to develop the SBLB in female and male rats. Also, we studied if the SBLB-inducing protocol produces changes in anxiety-like behavior using the plus-maze test (PMT and, analyzed serotonin (5-HT and noradrenaline (NA concentrations in brain areas related to anxiety and ingestive behavior (brain stem, hypothalamus, nucleus accumbens, and amygdala. Finally, we evaluated whether fluoxetine, a drug that has been effective in reducing the binge-eating frequency, body weight, and severity of binge eating disorder, could also block this behavior. Briefly, WKY and W female rats were exposed to 30% sucrose solution (2 h, 3 days/week for 4 weeks, and fed up ad libitum. PMT was performed between the last two test periods. Immediately after the last test where sucrose access was available, rats were decapitated and brain areas extracted for high-performance liquid chromatography analysis. The results showed that both W and WKY female and male rats developed the SBLB. WKY rats consumed more calories and ingested a bigger amount of sucrose solution than their W counterpart. This behavior was reversed by using fluoxetine, rats exposed to the SBLB-inducing protocol presented a rebound effect during the washout period. On female rats, the SBLB-inducing protocol induced changes in NA concentrations on WKY, but not on W rats. No changes were found in 5-HT levels. Finally, animals that developed SBLB showed increased

  17. Outer brain barriers in rat and human development

    DEFF Research Database (Denmark)

    Brøchner, Christian B; Holst, Camilla Bjørnbak; Møllgård, Kjeld

    2015-01-01

    Complex barriers at the brain's surface, particularly in development, are poorly defined. In the adult, arachnoid blood-cerebrospinal fluid (CSF) barrier separates the fenestrated dural vessels from the CSF by means of a cell layer joined by tight junctions. Outer CSF-brain barrier provides...... diffusion restriction between brain and subarachnoid CSF through an initial radial glial end feet layer covered with a pial surface layer. To further characterize these interfaces we examined embryonic rat brains from E10 to P0 and forebrains from human embryos and fetuses (6-21st weeks post...

  18. Developing a Speaker Identification System for the DARPA RATS Project

    DEFF Research Database (Denmark)

    Plchot, O; Matsoukas, S; Matejka, P

    2013-01-01

    This paper describes the speaker identification (SID) system developed by the Patrol team for the first phase of the DARPA RATS (Robust Automatic Transcription of Speech) program, which seeks to advance state of the art detection capabilities on audio from highly degraded communication channels. ...... such as CFCCs out-perform MFCC front-ends on noisy audio, and (c) fusion of multiple systems provides 24% relative improvement in EER compared to the single best system when using a novel SVM-based fusion algorithm that uses side information such as gender, language, and channel id....

  19. Curative effects of sodium fusidate on the development of dinitrobenzenesulfonic acid-induced colitis in rats

    DEFF Research Database (Denmark)

    Di Marco, Roberto; Mangano, Katia; Quattrocchi, Cinzia

    2003-01-01

    Fusidic acid and sodium fusidate (fusidin) are antibiotics with low toxicity and powerful immunomodulatory activities in vitro and in vivo. In this study we have evaluated the effect of fusidin on the development of dinitrobenzenesulfonic acid (DNB)-induced colitis in rats that serves....... These entailed a significant reduction in body weight loss, smaller increase in colon weights, milder macroscopic damage, and lower histological scores. In addition, when sacrificed at the end of the study, fusidin-treated rats had significantly lower blood levels of tumor necrosis factor alpha and interferon......-gamma compared with untreated controls. The present findings concur with the beneficial actions of fusidin in a pilot study conducted in patients with Crohn's disease and warrant controlled studies in humans with IBD....

  20. Olfactory granule cell development in normal and hyperthyroid rats.

    Science.gov (United States)

    Brunjes, P C; Schwark, H D; Greenough, W T

    1982-10-01

    Dendritic development was examined in olfactory bulbs of both normal 7-, 14-, 21- and 60-day-old rats and littermates treated on postnatal days 1-4 with 1 microgram/g body weight of L-thyroxine sodium. Tissue was processed via the Golgi-Cox technique and subjected to quantitative analyses of mitral and internal layer granule cell development. These populations of granule cells were selected because their pattern of late proliferation suggested potentially greater susceptibility to postnatal hormonal alterations. Although neonatal hyperthyroidism induces widespread acceleration of maturation, including precocious chemosensitivity, granule cell development was unaffected relative to littermate controls. Both normal and hyperthyroid groups exhibited an inverted U-shaped pattern of cellular development, with rapid dendritic dendritic growth and expansion occurring during the earliest ages tested, but with loss of processes and dendritic field size occurring after day 21.

  1. High doses of garlic extract significantly attenuated the ratio of serum LDL to HDL level in rat-fed with hypercholesterolemia diet.

    Science.gov (United States)

    Ebrahimi, Tahereh; Behdad, Behnoosh; Abbasi, Maryam Agha; Rabati, Rahman Ghaffarzadegan; Fayyaz, Amir Farshid; Behnod, Vahid; Asgari, Ali

    2015-06-20

    Hypercholesterolemia is associated with an increased risk of heart disease. In this study, we investigated the antihyperlipidemic effects of garlic (Allium sativum L.) in rat models of hypercholesterolemic. Wistar male rats were randomly divided into 4 diet groups with garlic supplementation. Male Wistar rats were fed by standard pellet diet (group I), standard diet supplemented with 4% garlic (group II), lipogenic diet (containing sunflower oil, cholesterol and ethanol) equivalent to 200 mg raw garlic/kg body weight (raw) (group III) and lipogenic diet equivalent to 400 mg raw garlic/kg body weight (raw) (group IV). Rats fed 400 g/kg garlic extract(GE), had a significantly lower concentration of serum low-density lipoprotein cholesterol (LDL-C) cholesterol and elevated HDL -C cholesterol at day 28 (P garlic supplementation (P garlic in reducing lateral side effects of hyperlipidemia. Our data demonstrate that GE has protective effects on HDL in rats with high LDL intake. Therefore, it could be used to remedy hypercholesterolemia with help reduce risk of coronary heart disease The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1834155749171141.

  2. In utero exposure to chloroquine alters sexual development in the male fetal rat

    International Nuclear Information System (INIS)

    Clewell, Rebecca A.; Pluta, Linda; Thomas, Russell S.; Andersen, Melvin E.

    2009-01-01

    Chloroquine (CQ), a drug that has been used extensively for the prevention and treatment of malaria, is currently considered safe for use during pregnancy. However, CQ has been shown to disrupt steroid homeostasis in adult rats and similar compounds, such as quinacrine, inhibit steroid production in the Leydig cell in vitro. To explore the effect of in utero CQ exposure on fetal male sexual development, pregnant Sprague-Dawley rats were given a daily dose of either water or chloroquine diphosphate from GD 16-18 by oral gavage. Chloroquine was administered as 200 mg/kg CQ base on GD 16, followed by two maintenance doses of 100 mg/kg CQ base on GD 16 and 18. Three days of CQ treatment resulted in reduced maternal and fetal weight on GD 19 and increased necrosis and steatosis in the maternal liver. Fetal livers also displayed mild lipid accumulation. Maternal serum progesterone was increased after CQ administration. Fetal testes testosterone, however, was significantly decreased. Examination of the fetal testes revealed significant alterations in vascularization and seminiferous tubule development after short-term CQ treatment. Anogenital distance was not altered. Microarray and RT-PCR showed down-regulation of several genes associated with cholesterol transport and steroid synthesis in the fetal testes. This study indicates that CQ inhibits testosterone synthesis and normal testis development in the rat fetus at human relevant doses.

  3. Pancreatic morphogenesis and extracellular matrix organization during rat development.

    Science.gov (United States)

    Hisaoka, M; Haratake, J; Hashimoto, H

    1993-07-01

    We investigated the rat pancreatic morphology at various developmental stages ranging from 12 days of gestation to the neonatal stage, with special emphasis on alterations in extracellular matrix organization in vivo. The rat pancreatic development in utero could be divided into four representative stages as follows: (1) initial epithelial buds (12 days of gestation), (2) elongated and branching epithelium (13-14 days), (3) tubular structure (15-16 days), and (4) acinar structure (17 days or more). Ultrastructurally, the fetal and neonatal pancreata were almost constantly encompassed by continuous basal lamina, except for the earliest stage, in which minute disruptions of basal lamina were observed. Through the disruption, the direct epithelial-mesenchymal contact was formed between an endocrine cell and an adjacent mesenchymal cell, which implied epithelial-mesenchymal interactions in processes of endocrine cell differentiation. Collagen fibrils were frequently accumulated at the cleft (branchpoint) of the branching epithelium during the second and third stages mentioned above. Immunohistochemically, fibronectin and collagen type-I were localized particularly beside the neck (narrow part) or cleft of the pancreatic epithelium at these stages, although continuous linear localization of these matrices was noted around the initial pancreatic bud. This was in contrast to invariable linear localization of laminin and collagen type-IV at the epithelial/mesenchymal interface throughout the pancreatic development. Diffuse fibrillar localization of fibronectin and collagen type-I in the mesenchyme was pronounced at the later stages and after birth. Collagen type-III was only focally detectable around the pancreatic epithelium from the second stage, and its distinct localization was noted in the interlobular connective tissue after birth. Thus, chronological changes in extracellular matrix organization seemed to be closely related to morphogenetic processes of the rat

  4. Optimization of reagent concentration for radioiodination of rat C-peptide II in development of radioimmunoassay procedure for rats

    Directory of Open Access Journals (Sweden)

    B R Manupriya

    2018-01-01

    Full Text Available Rat C-peptide is a polypeptide molecule made up of 31 amino acids and secreted from pancreas into circulation in two isoforms I and II. Quantification of rat C-peptide II in rat serum is important as it is directly related to the diagnosis of carbohydrate metabolism abnormalities, pancreatic performance analysis, monitoring of hypoglycemia, and diabetes-related illness in rat model. The aim of the present work is to develop a tracer by chloramine-T method for radioimmunoassay (RIA procedure and to determine the optimum amount of chloramine-T required for the preparation of stable radioiodinated product with a specific activity of around 24.97 MBq/μg, corresponding to 1 125I atom per molecule of the peptide. Tyrosylated rat C-peptide II was selected for the radioiodination procedure as rat C-peptide II does not contain either tyrosine or histidine which is mandatory for the incorporation of 125I atom to the rat C-peptide II. Tyrosylated rat C-peptide II was subjected to radioiodination by chloramine-T method with different concentrations of chloramine-T and sodium metabisulfite (MBS to obtain a stable radiolabeled compound. Optimized reaction conditions relating to the concentration of chloramine-T (10 μg and MBS (20 μg yielded a stable 125I-rat C-peptide II with specific activity of 21.01 MBq/μg corresponding to 0.84 125I atoms per molecule of the peptide. Preparation of high integrity tracer of rat C-peptide II was achieved by combining one molecule of oxidant (chloramine-T and two molecule of reductant (MBS.

  5. Resistant starch but not enzymatic treated waxy maize delays development of diabetes in Zucker Diabetic Fatty rats

    DEFF Research Database (Denmark)

    Hedemann, Mette Skou; Hermansen, Kjeld; Pedersen, Sven

    2017-01-01

    excretion during week 8 in rats fed the GLU and EMS diets than that of rats fed S and RS showed that they were diabetic. Urinary nontargeted metabolomics revealed that the diabetic state of rats fed S, GLU, and EMS diets influenced microbial metabolism, as well as amino acid, lipid, and vitamin metabolism......Background: The incidence of type 2 diabetes (T2D) is increasing worldwide, and nutritional management of circulating glucose may be a strategic tool in the prevention of T2D. Objective: We studied whether enzymatically modified waxy maize with an increased degree of branching delayed the onset...... glucose concentrations in feed-deprived rats, none of the groups developed diabetes. However, in week 9, plasma glucose after feed deprivation was significantly lower in rats fed the S and RS diets (13.5 mmol/L) than in rats fed the GLU and EMS diets (17.0–18.9 mmol/L), and rats fed RS had lower HbA1c (4...

  6. The effect of food hardness on the development of dental caries in alloxan-induced diabetic rats.

    Science.gov (United States)

    Nakahara, Yutaka; Sano, Tomoya; Kodama, Yasushi; Ozaki, Kiyokazu; Matsuura, Tetsuro

    2013-01-01

    We have previously shown that dental caries may be produced in diabetic rodent models fed with noncariogenic standard diets; however, many studies usually add large amounts of sugar to the diet to induce dental caries. Moreover, the physical properties of cariogenic diets have been reported as an important factor in the formation of caries. The aim of this study was to clarify the effect of the hardness of non-cariogenic diets on the development of dental caries in diabetic rodents. Seven-week-old female F344 rats were divided into 4 groups: intact rats fed with a standard pelletized or powdered diet and alloxan-induced diabetic rats fed with a standard pelletized or powdered diet. All of the rats were sacrificed at 52 weeks of age for morphological examinations on their dental tissue. Dental caries had developed and extended to all the molars in the diabetic rats that were fed with both the pelletized and powdered diets. Moreover, the lesion was significantly enhanced in the powdered diet group compared to that in the pelletized diet group. In conclusion, food hardness is an important factor influencing the development of dental caries in diabetic rats.

  7. The Effect of Food Hardness on the Development of Dental Caries in Alloxan-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Yutaka Nakahara

    2013-01-01

    Full Text Available We have previously shown that dental caries may be produced in diabetic rodent models fed with noncariogenic standard diets; however, many studies usually add large amounts of sugar to the diet to induce dental caries. Moreover, the physical properties of cariogenic diets have been reported as an important factor in the formation of caries. The aim of this study was to clarify the effect of the hardness of non-cariogenic diets on the development of dental caries in diabetic rodents. Seven-week-old female F344 rats were divided into 4 groups: intact rats fed with a standard pelletized or powdered diet and alloxan-induced diabetic rats fed with a standard pelletized or powdered diet. All of the rats were sacrificed at 52 weeks of age for morphological examinations on their dental tissue. Dental caries had developed and extended to all the molars in the diabetic rats that were fed with both the pelletized and powdered diets. Moreover, the lesion was significantly enhanced in the powdered diet group compared to that in the pelletized diet group. In conclusion, food hardness is an important factor influencing the development of dental caries in diabetic rats.

  8. Long-Term Effects of Chronic Oral Ritalin Administration on Cognitive and Neural Development in Adolescent Wistar Kyoto Rats

    Directory of Open Access Journals (Sweden)

    Jennifer L. Cornish

    2012-09-01

    Full Text Available The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD often results in chronic treatment with psychostimulants such as methylphenidate (MPH, Ritalin®. With increases in misdiagnosis of ADHD, children may be inappropriately exposed to chronic psychostimulant treatment during development. The aim of this study was to assess the effect of chronic Ritalin treatment on cognitive and neural development in misdiagnosed “normal” (Wistar Kyoto, WKY rats and in Spontaneously Hypertensive Rats (SHR, a model of ADHD. Adolescent male animals were treated for four weeks with oral Ritalin® (2 × 2 mg/kg/day or distilled water (dH2O. The effect of chronic treatment on delayed reinforcement tasks (DRT and tyrosine hydroxylase immunoreactivity (TH-ir in the prefrontal cortex was assessed. Two weeks following chronic treatment, WKY rats previously exposed to MPH chose the delayed reinforcer significantly less than the dH2O treated controls in both the DRT and extinction task. MPH treatment did not significantly alter cognitive performance in the SHR. TH-ir in the infralimbic cortex was significantly altered by age and behavioural experience in WKY and SHR, however this effect was not evident in WKY rats treated with MPH. These results suggest that chronic treatment with MPH throughout adolescence in “normal” WKY rats increased impulsive choice and altered catecholamine development when compared to vehicle controls.

  9. Exposure to urban PM1 in rats: development of bronchial inflammation and airway hyperresponsiveness.

    Science.gov (United States)

    Filep, Ágnes; Fodor, Gergely H; Kun-Szabó, Fruzsina; Tiszlavicz, László; Rázga, Zsolt; Bozsó, Gábor; Bozóki, Zoltán; Szabó, Gábor; Peták, Ferenc

    2016-03-10

    Several epidemiological and laboratory studies have evidenced the fact that atmospheric particulate matter (PM) increases the risk of respiratory morbidity. It is well known that the smallest fraction of PM (PM1 - particulate matter having a diameter below 1 μm) penetrates the deepest into the airways. The ratio of the different size fractions in PM is highly variable, but in industrial areas PM1 can be significant. Despite these facts, the health effects of PM1 have been poorly investigated and air quality standards are based on PM10 and PM2.5 (PM having diameters below 10 μm and 2.5 μm, respectively) concentrations. Therefore, this study aimed at determining whether exposure to ambient PM1 at a near alert threshold level for PM10 has respiratory consequences in rats. Rats were either exposed for 6 weeks to 100 μg/m(3) (alert threshold level for PM10 in Hungary) urban submicron aerosol, or were kept in room air. End-expiratory lung volume, airway resistance (Raw) and respiratory tissue mechanics were measured. Respiratory mechanics were measured under baseline conditions and following intravenous methacholine challenges to characterize the development of airway hyperresponsiveness (AH). Bronchoalveolar lavage fluid (BALF) was analyzed and lung histology was performed. No significant differences were detected in lung volume and mechanical parameters at baseline. However, the exposed rats exhibited significantly greater MCh-induced responses in Raw, demonstrating the progression of AH. The associated bronchial inflammation was evidenced by the accumulation of inflammatory cells in BALF and by lung histology. Our findings suggest that exposure to concentrated ambient PM1 (mass concentration at the threshold level for PM10) leads to the development of mild respiratory symptoms in healthy adult rats, which may suggest a need for the reconsideration of threshold limits for airborne PM1.

  10. Prenatal PCBs disrupt early neuroendocrine development of the rat hypothalamus

    International Nuclear Information System (INIS)

    Dickerson, Sarah M.; Cunningham, Stephanie L.; Gore, Andrea C.

    2011-01-01

    Neonatal exposure to endocrine disrupting chemicals (EDCs) such as polychlorinated biphenyls (PCBs) can interfere with hormone-sensitive developmental processes, including brain sexual differentiation. We hypothesized that disruption of these processes by gestational PCB exposure would be detectable as early as the day after birth (postnatal day (P) 1) through alterations in hypothalamic gene and protein expression. Pregnant Sprague-Dawley rats were injected twice, once each on gestational days 16 and 18, with one of the following: DMSO vehicle; the industrial PCB mixture Aroclor 1221 (A1221); a reconstituted mixture of the three most prevalent congeners found in humans, PCB138, PCB153, and PCB180; or estradiol benzoate (EB). On P1, litter composition, anogenital distance (AGD), and body weight were assessed. Pups were euthanized for immunohistochemistry of estrogen receptor α (ERα) or TUNEL labeling of apoptotic cells or quantitative PCR of 48 selected genes in the preoptic area (POA). We found that treatment with EB or A1221 had a sex-specific effect on developmental apoptosis in the neonatal anteroventral periventricular nucleus (AVPV), a sexually dimorphic hypothalamic region involved in the regulation of reproductive neuroendocrine function. In this region, exposed females had increased numbers of apoptotic nuclei, whereas there was no effect of treatment in males. For ERα, EB treatment increased immunoreactive cell numbers and density in the medial preoptic nucleus (MPN) of both males and females, while A1221 and the PCB mixture had no effect. PCR analysis of gene expression in the POA identified nine genes that were significantly altered by prenatal EDC exposure, in a manner that varied by sex and treatment. These genes included brain-derived neurotrophic factor, GABA B receptors-1 and -2, IGF-1, kisspeptin receptor, NMDA receptor subunits NR2b and NR2c, prodynorphin, and TGFα. Collectively, these results suggest that the disrupted sexual differentiation

  11. Maternal deprivation decelerates postnatal morphological lung development of F344 rats.

    Science.gov (United States)

    Hupa, Katharina Luise; Schmiedl, Andreas; Pabst, Reinhard; Von Hörsten, Stephan; Stephan, Michael

    2014-02-01

    Intensive medical care at premature born infants is often associated with separation of neonates from their mothers. Here, early artificial prolonged separation of rat pups from their dams (Maternal Deprivation, MD) was used to study potential impact on morphological lung maturation. Furthermore, we investigated the influence of an endogenous deficiency of the neuropeptide-cleaving dipeptidyl peptidase IV (DPP4), since the effects of MD are known to be partly mediated via neuropeptidergic effects, hypothesizing that MD will lead to a retardation of postnatal lung development, DPP4-dependendly. We used wild type and CD26/DPP4 deficient rats. For MD, the dam was placed each day into a separate cage for 2 h, while the pups remained in the nest on their own. Morphological lung maturation and cell proliferation at the postnatal days 7, 10, 14, and 21 were determined morphometrically. Maternally deprived wild types showed a retarded postnatal lung development compared with untreated controls in both substrains. During alveolarization, an increased thickness of alveolar septa and a decreased surface of septa about 50% were found. At the end of the morphological lung maturation, the surface of the alveolar septa was decreased at about 25% and the septal thickness remained increased about 20%. The proliferation rate was also decreased about 50% on day 14. However, the MD induced effects were less pronounced in DPP4-deficient rats, due to a significant deceleration already induced by DPP4-deficiency. Thus, MD as a model for postnatal stress experience influences remarkably postnatal development of rats, which is significantly modulated by the DPP4-system. Copyright © 2013 Wiley Periodicals, Inc.

  12. [The effects of strontium in drinking water on growth and development of rat bone].

    Science.gov (United States)

    Xu, F; Zhang, X; Liu, J; Fan, M

    1997-05-01

    Effects of strontium at a high level in drinking water on growth and development of rat bone were studied. The results showed that Sr2+ concentration from 5 to 500 mg/L in drinking water could increase the contents of strontium in blood serum, urine, femur, mixilla and tooth in Wistar rats exposed to Sr2+ for 12 weeks with an obvious dose-response relationship. In addition, strontium at over 50 mg/L could decrease the contents of calcium in bone, increase the contents of calcium in tooth and bone density, and decrease the levels of calcium in blood serum except female rats at the 12th week. Effects of Sr2+ on body weight, body length, AKP activity of serum, calcium content of urine and breaking load of bended femur for rats were not found. However, there are differences in the effects of strontium on growth and development of bone between male and female rats. At the 12th week the content of calcium in blood serum decreased in male rats but increased in female rats in exposed groups. At the 4th and 8th weeks, urine Hop/Cr in male rats increased but it remained normal level in female rats. Sr2+ increased the bone density of mixilla in male rats but it did not increase that of femur in female rats. It is suggested that such changes may be a result of the differences in endocritic regulation and metabolic process between two sexes.

  13. Abnormal expression of ephrin-A5 affects brain development of congenital hypothyroidism rats.

    Science.gov (United States)

    Suo, Guihai; Shen, Feifei; Sun, Baolan; Song, Honghua; Xu, Meiyu; Wu, Youjia

    2018-05-14

    EphA5 and its ligand ephrin-A5 interaction can trigger synaptogenesis during early hippocampus development. We have previously reported that abnormal EphA5 expression can result in synaptogenesis disorder in congenital hypothyroidism (CH) rats. To better understand its precise molecular mechanism, we further analyzed the characteristics of ephrin-A5 expression in the hippocampus of CH rats. Our study revealed that ephrin-A5 expression was downregulated by thyroid hormone deficiency in the developing hippocampus and hippocampal neurons in rats. Thyroxine treatment for hypothyroid hippocampus and triiodothyronine treatment for hypothyroid hippocampal neurons significantly improved ephrin-A5 expression but could not restore its expression to control levels. Hypothyroid hippocampal neurons in-vitro showed synaptogenesis disorder characterized by a reduction in the number and length of neurites. Furthermore, the synaptogenesis-associated molecular expressions of NMDAR-1 (NR1), PSD95 and CaMKII were all downregulated correspondingly. These results suggest that ephrin-A5 expression may be decreased in CH, and abnormal activation of ephrin-A5/EphA5 signaling affects synaptogenesis during brain development. Such findings provide an important basis for exploring the pathogenesis of CH genetically.

  14. Identity Development of Literacy Teachers of Adolescents with Significant Cognitive Disabilities

    Science.gov (United States)

    Roberts, Carly A.

    2013-01-01

    This study employs the theory of identity development and figured worlds to investigate how historical and current education context, preservice and inservice teacher preparation, and school and classroom context influence the development of the literacy teaching identity of teachers of adolescents with significant cognitive disabilities. A…

  15. In vivo and in vitro study of /sub 90/Sr in developing rat molar enamel

    International Nuclear Information System (INIS)

    White, B.A.; Deaton, T.G.; Bawden, J.W.

    1980-01-01

    The uptake patterns of /sub 90/Sr in developing rat molar enamel were studied in vivo and in vitro. Autoradiographic methods were used that preclude loss or translocation of tracers associated with water-soluble compounds in the sections. In eight-day-old rats injected with the tracer, /sub 90/Sr uptake in the enamel was significantly less than for dentin and bone, particularly at early sacrifice times. The uptake pattern of 90Sr was somewhat different from that previously observed for /sub 45/Ca. The in vitro experiments indicated that the viable intact enamel organ limits uptake of /sub 90/Sr by enamel in both the secretory and maturation phases of enamel formation

  16. Morphological and Histopathological Changes in Orofacial Structures of Experimentally Developed Acromegaly-Like Rats: An Overview

    Directory of Open Access Journals (Sweden)

    Masahiro Iikubo

    2012-01-01

    Full Text Available Tongue enlargement and mandibular prognathism are clinically recognized in almost all patients with acromegaly. An acromegaly-like rat model recently developed by exogenous administration of insulin-like growth factor I (IGF-I was used to investigate morphological and histopathological changes in orofacial structures and to clarify whether these changes were reversible. Exogenous administration of IGF-I evoked specific enlargement of the tongue with identifiable histopathological changes (increased muscle bundle width, increased space between muscle bundles, and increased epithelial thickness, elongation of the mandibular alveolar bone and ascending ramus, and lateral expansion of the mandibular dental arch. Regarding histopathological changes in the mandibular condyle, the cartilaginous layer width, bone matrix ratio, and number of osteoblasts were all significantly greater in this rat model. After normalization of the circulating IGF-I level, tongue enlargement and histopathological changes in the tongue and mandibular condyle were reversible, whereas morphological skeletal changes in the mandible remained.

  17. Critical androgen-sensitive periods of rat penis and clitoris development

    OpenAIRE

    Welsh, M.; Macleod, D. J.; Walker, M.; Smith, L. B.; Sharpe, R. M.

    2010-01-01

    Androgen control of penis development/growth is unclear. In rats, androgen action in a foetal 'masculinisation programming window' (MPW; e15.5-e18.5)' predetermines penile length and hypospadias occurrence. This has implications for humans (e.g. micropenis). Our studies aimed to establish in rats when androgen action/administration affects development/growth of the penis and if deficits in MPW androgen action were rescuable postnatally. Thus, pregnant rats were treated with flutamide during t...

  18. Interaction of renal failure and dyslipidaemia in the development of calcific aortic valve disease in rats.

    Science.gov (United States)

    Gillis, Kris; Roosens, Bram; Bala, Gezim; Remory, Isabel; Hernot, Sophie; Delvenne, Philippe; Mestrez, Fabienne; Droogmans, Steven; Cosyns, Bernard

    2017-10-01

    Calcific aortic valve disease (CAVD) is currently the most common heart valve disease worldwide and is known to be an active process. Both renal failure and dyslipidaemia are considered to be promoting factors for the development of valvular calcifications. The aim of this study is to prospectively evaluate the respective contribution and interaction of renal failure and dyslipidaemia on CAVD in a rat model, using echocardiography and compared with histology. Sixty-eight male Wistar rats were prospectively divided in eight groups, each fed a different diet to induce renal failure alone and combined with hyperlipidaemia or hypercholesterolemia. CAVD was detected and quantified by calibrated integrated backscatter of ultrasound (cIB) and compared with the histological calcium score. The study follow-up was 20 weeks. At the end of the study, the cIB value and the calcium score of the aortic valve were significantly increased in the group with isolated renal failure but not with dyslipidaemia. The combination of renal failure with high cholesterol or high-fat diet did not significantly increase calcifications further. Renal failure alone does induce aortic valve calcifications in a rat model of CAVD, whereas dyslipidaemia alone does not. The combination of renal failure with dyslipidaemia does not increase calcification further. These findings suggest that a combination of atherosclerotic and calcifying factors is not required to induce aortic valve calcifications in this model.

  19. Effects of the phytoestrogen genistein on the development of the reproductive system of Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    Siti Rosmani Md Zin

    2013-01-01

    Full Text Available OBJECTIVES: Genistein is known to influence reproductive system development through its binding affinity for estrogen receptors. The present study aimed to further explore the effect of Genistein on the development of the reproductive system of experimental rats. METHODS: Eighteen post-weaning female Sprague Dawley rats were divided into the following groups: (i a control group that received vehicle (distilled water and Tween 80; (ii a group treated with 10 mg/kg body weight (BW of Genistein (Gen 10; and (iii a group treated with a higher dose of Genistein (Gen 100. The rats were treated daily for three weeks from postnatal day 22 (P22 to P42. After the animals were sacrificed, blood samples were collected, and the uteri and ovaries were harvested and subjected to light microscopy and immunohistochemical study. RESULTS: A reduction of the mean weekly BW gain and organ weights (uteri and ovaries were observed in the Gen 10 group compared to the control group; these findings were reversed in the Gen 100 group. Follicle stimulating hormone and estrogen levels were increased in the Gen 10 group and reduced in the Gen 100 group. Luteinizing hormone was reduced in both groups of Genistein-treated animals, and there was a significant difference between the Gen 10 and control groups (p<0.05. These findings were consistent with increased atretic follicular count, a decreased number of corpus luteum and down-regulation of estrogen receptors-a in the uterine tissues of the Genistein-treated animals compared to the control animals. CONCLUSION: Post-weaning exposure to Genistein could affect the development of the reproductive system of ovarian-intact experimental rats because of its action on the hypothalamic-pituitary-gonadal axis by regulating hormones and estrogen receptors.

  20. Oral Morphine Consumption Reduces Lens Development in Rat Embryos

    Directory of Open Access Journals (Sweden)

    Hossein Bahadoran

    2012-07-01

    Full Text Available Objective: Consumption of morphine, during pregnancy, in addition to inducing defects in the mother’s nervous system function, caused defects or delays in the formation and evolution of embryonic visual system. In the present study, changes in lens development was assessed in embryos exposed in utero to morphine. Material and Methods: Female Wistar rats (250-300 g were mated with male rats and pregnancy was determined by sperm observation in vaginal smear. This day was considered as embryonic day zero (E0. The females were then divided randomly into the experimental and the control groups. The control group received tap water and the experimental group received morphine (0.05 mg/ml in their water. On embryonic day 13 ( E13, blood samples were collected from the retro-orbital sinus of all animals for plasma corticosterone detection. On embryonic day 17(E17, the animals were killed by an overdose of chloroform and the embryos were taken out surgically. The embryos were fixed in 10% formalin for 30 days. At this time, the head of the embryos were removed for tissue processing and Hematoxylin- Eosin (H&E staining. The samples were evaluated using light microscope and MOTIC software. Results: Our data indicated that plasma corticosterone level was dramatically increased and the lens was thinner in the experimental group. (Although the proliferation of lens cells increased in the experiment group but that lens had delay in removing the proliferated and elongation cells with abnormal density in the lateral part of the lens in compare with control group. I have no idea what the authors are stating here. Moreover, the opening of the eyelids was delayed in the off springs of the mothers who received morphine. Conclusions: This study showed that morphine consumption during pregnancy leads to defects in fetal visual system development, particularly in the lens, and eyelids.

  1. Rapid development of Leydig cell tumors in a Wistar rat substrain

    NARCIS (Netherlands)

    Teerds, K. J.; de rooij, D. G.; de Jong, F. H.; Rommerts, F. F.

    1991-01-01

    In 78% of the Wistar rats (substrain U) studied, spontaneous Leydig cell tumors developed between the ages of 12 and 30 months. The first signs of tumor development, in the form of nodules of Leydig cells, were already apparent in 1-month-old U-rats. These nodules of Leydig cells were found in all

  2. On the Characteristics and the Development Significance of Hangzhou Lotus Culture

    Directory of Open Access Journals (Sweden)

    Shi Hongbin

    2015-01-01

    Full Text Available Lotus is the symbol of honesty, goodness, beauty and purity in the eyes of the Chinese people. The development of tourism in Hangzhou is inseparable from the lotus culture connotation. This paper analyzes the necessity to enhance the lotus culture in the city of Hangzhou, and discusses the Hangzhou Lotus Culture and its regional characteristics. The article indicates the further significance of the development of lotus culture tourism resources in Hangzhou.

  3. Physical and behavioral development in rats after late prenatal exposure to diazepam.

    Science.gov (United States)

    Lall, S B; Sahoo, R N

    1990-01-01

    The effect of late prenatal exposure to diazepam (DZP) on physical and behavioral development of rat pups was investigated. Prenatal exposure to DZP (20 mg/kg, sc, in last week of pregnancy) did not alter litter size and no gross malformations were noted at birth. Body weight at birth and subsequent weight gain was significantly less in these animals. The development of reflexes and neuromuscular maturation was normal. Open field locomotor activity and rearing scores were significantly decreased. Test of social play in juvenile rats revealed normal pattern of sexual dimorphism with increased masculinized behavior. Acquisition and retention of passive avoidance task was not affected by DZP exposure, however, retention of brightness discrimination task was significantly decreased. The hypnotic effect of a challenge dose of DZP and convulsive effect of pentylene tetrazole remained unaltered. Open field activity test in adult animals revealed increased ambulation. Probe dose of amphetamine in these animals caused paradoxical decrease in activity. It is concluded that exposure to high dose of DZP during late prenatal period may not manifest in physical or neuromuscular impairment during early development period, except for weight loss, however, it may have long term effects on behavior becoming manifest in adolescence and at maturity.

  4. Nitric oxide and thyroid hormone receptor alpha 1 contribute to ovarian follicular development in immature hyper- and hypo-thyroid rats.

    Science.gov (United States)

    Zheng, Kaizhi; Sulieman, Fedail Jaafar; Li, Junrong; Wei, Quanwei; Xu, Mulin; Shi, Fangxiong

    2015-03-01

    Thyroid dysfunction can cause ovarian cycle and ovulatory disturbances, however, the molecular link(s) between these two disorders remains largely unknown. In the current study, we examined the roles of nitric oxide synthase (NOS) and thyroid hormone receptor alpha 1 (TRα1) in these disorders using immature hyper-thyroid (hyper-T) and hypo-thyroid (hypo-T) rats. In comparison to controls, hyper-T rats had higher serum concentrations of triiodothyronine (T3) and thyroxine (T4), whereas hypo-T rats had lower serum T3 and T4. Serum estradiol (E2) level was decreased in both hyper-T and hypo-T animals and serum E2 in hyper-T rats were lower than in hypo-T rats. We found that neuronal NOS (nNOS) and TRα1 were present in oocytes, granulosa cells and theca cells of all examined rat groups. Ovarian nitric oxide (NO) content and the constitutive NOS (cNOS) activity in hyper-T rats were significantly decreased compared with control or hypo-T rats. Moreover, the number of large antral follicles was reduced in hyper-T rats, and number of primordial follicles was decreased in hypo-T rats compared with control rats. In conclusion, we observed an association between thyroid hormone and NO signaling pathways during the process of ovarian follicular development in immature rats. In hyperthyroidism, thyroid hormones induced an estrogen deficiency that inhibited the function of nNOS, resulting in the inhibition of NO synthesis and suppressed development of large antral follicles, while in hypothyroidism only development of primordial follicles was inhibited. Copyright © 2014 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  5. Glucose intolerance develops prior to increased adiposity and accelerated cessation of estrous cyclicity in female growth-restricted rats

    Science.gov (United States)

    Intapad, Suttira; Dasinger, John Henry; Brown, Andrew D.; Fahling, Joel M.; Esters, Joyee; Alexander, Barbara T.

    2015-01-01

    Background The incidence of metabolic disease increases in early menopause. Low birth weight influences the age at menopause. Thus, this study tested the hypothesis that intrauterine growth restriction programs early reproductive aging and impaired glucose homeostasis in female rats. Methods Estrous cyclicity, body composition, and glucose homeostasis were determined in female control and growth-restricted rats at 6 and 12 months of age; sex steroids at 12 months. Results Glucose intolerance was present at 6 months of age prior to cessation of estrous cyclicity and increased adiposity in female growth-restricted rats. However, female growth-restricted rats exhibited persistent estrus and a significant increase in adiposity, fasting glucose and testosterone at 12 months of age (Pgrowth-restricted rats (Pgrowth programmed glucose intolerance that developed prior to early estrous acyclicity; yet, fasting glucose levels were elevated in conjunction with increased adiposity, accelerated cessation of estrous cyclicity and a shift towards testosterone excess at 12 months of age in female growth-restricted rats. PMID:26854801

  6. The development and significance of vesicular-arbuscular mycorrhizas as influenced by agricultural practices

    NARCIS (Netherlands)

    Ruissen, M.A.

    1982-01-01

    The development and significance of vesicular- arbuscular mycorrhizas (VAM) in wheat and potatoes have been studied in relation to various farming systems and agricultural practices. The effects of farming systems on VAM have been observed on three neighbouring experimental farms in the vicinity of

  7. Processes underlying the nutritional programming of embryonic development by iron deficiency in the rat.

    Directory of Open Access Journals (Sweden)

    Angelina Swali

    Full Text Available Poor iron status is a global health issue, affecting two thirds of the world population to some degree. It is a particular problem among pregnant women, in both developed and developing countries. Feeding pregnant rats a diet deficient in iron is associated with both hypertension and reduced nephron endowment in adult male offspring. However, the mechanistic pathway leading from iron deficiency to fetal kidney development remains elusive. This study aimed to establish the underlying processes associated with iron deficiency by assessing gene and protein expression changes in the rat embryo, focussing on the responses occurring at the time of the nutritional insult. Analysis of microarray data showed that iron deficiency in utero resulted in the significant up-regulation of 979 genes and down-regulation of 1545 genes in male rat embryos (d13. Affected processes associated with these genes included the initiation of mitosis, BAD-mediated apoptosis, the assembly of RNA polymerase II preinitiation complexes and WNT signalling. Proteomic analyses highlighted 7 proteins demonstrating significant up-regulation with iron deficiency and the down-regulation of 11 proteins. The main functions of these key proteins included cell proliferation, protein transport and folding, cytoskeletal remodelling and the proteasome complex. In line with our recent work, which identified the perturbation of the proteasome complex as a generalised response to in utero malnutrition, we propose that iron deficiency alone leads to a more specific failure in correct protein folding and transport. Such an imbalance in this delicate quality-control system can lead to cellular dysfunction and apoptosis. Therefore these findings offer an insight into the underlying mechanisms associated with the development of the embryo during conditions of poor iron status, and its health in adult life.

  8. Development of an accident sequence precursor methodology and its application to significant accident precursors

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Seung Hyun; Park, Sung Hyun; Jae, Moo Sung [Dept. of of Nuclear Engineering, Hanyang University, Seoul (Korea, Republic of)

    2017-03-15

    The systematic management of plant risk is crucial for enhancing the safety of nuclear power plants and for designing new nuclear power plants. Accident sequence precursor (ASP) analysis may be able to provide risk significance of operational experience by using probabilistic risk assessment to evaluate an operational event quantitatively in terms of its impact on core damage. In this study, an ASP methodology for two operation mode, full power and low power/shutdown operation, has been developed and applied to significant accident precursors that may occur during the operation of nuclear power plants. Two operational events, loss of feedwater and steam generator tube rupture, are identified as ASPs. Therefore, the ASP methodology developed in this study may contribute to identifying plant risk significance as well as to enhancing the safety of nuclear power plants by applying this methodology systematically.

  9. Study on developing brain damage of neonatal rats induced by enriched uranium

    International Nuclear Information System (INIS)

    Gu Guixiong; Zhu Shoupeng; Yang Shuqin

    2000-01-01

    Objective: The injurious effects of enriched uranium 235 U on developing brain of neonatal Wistar pure bred rats were studied. Methods: The model of irradiation induced brain damage in vivo was settled. The effects of cerebrum exposure by 235 U on somatic growth and neuro-behavior development of neonatal rats were examined by thirteen index determination of multiple parameters. The dynamic retention of autoradiographic tracks of 235 U in cells of developing brain was observed. The changes of NSE, IL-1β, SOD, and ET in cerebral cortex, hippocampus, diencephalon, cerebellum after expose to 235 U were examined with radioimmunoassay. Results: The somatic growth such as increase of body weight and brain weight was lower significantly. The retardation of development was found such as eye opening, sensuous function as auditory startle, movement and coordination function and activity as swimming, physiological reflexes as negative geotaxis, surface righting, grasping reflex suspension and the tendency behavior. The data showed delayed growth and abnormal neuro-behavior. The micro-autoradiographic tracing showed that the tracks of 235 U were mainly accumulated in the nucleus of developing brain. At the same time only few tracks appeared in the cytoplasm and interval between cells. Experimental study showed that when the dose of 235 U irradiation was increased, the level of NSE was decreased and the IL-1β was increased. However, the results indicated that SOD and ET can be elevated by the low dose irradiation of 235 U, and can be inhibited by the high dose. Conclusion: The behavior of internal irradiation from 235 U on the developing brain damage of neonatal rats were of sensibility and compensation in nervous cells

  10. The development of radioimmunoassay kit for rat albumin

    International Nuclear Information System (INIS)

    Yuan Zhigang; Han Shiquan; Liu Yibing; Xu Wenge

    2006-01-01

    The Anti-rat albumin serum is prepared by immunized the sheep with rat albumin. A radioimmunoassay method is established for rat albumin. The measurement range of the assay is 1-50 mg/L, sensitivity of the assay is 0.12 mg/L, recovery rate is 97.8%- 108.4%. Intra- and inter-assay variation coefficients are <4.0% and <8.2% respectively. The correlation coefficients between measured and expected values are more than 0.990 after serial dilution of the urine samples with high concentrations of rat albumin. The kit for rat albumin might provide a convenience in exploitation of renal drugs and experimental in- jury of the kidney. (authors)

  11. A neurorobotic platform for locomotor prosthetic development in rats and mice

    Science.gov (United States)

    von Zitzewitz, Joachim; Asboth, Leonie; Fumeaux, Nicolas; Hasse, Alexander; Baud, Laetitia; Vallery, Heike; Courtine, Grégoire

    2016-04-01

    Objectives. We aimed to develop a robotic interface capable of providing finely-tuned, multidirectional trunk assistance adjusted in real-time during unconstrained locomotion in rats and mice. Approach. We interfaced a large-scale robotic structure actuated in four degrees of freedom to exchangeable attachment modules exhibiting selective compliance along distinct directions. This combination allowed high-precision force and torque control in multiple directions over a large workspace. We next designed a neurorobotic platform wherein real-time kinematics and physiological signals directly adjust robotic actuation and prosthetic actions. We tested the performance of this platform in both rats and mice with spinal cord injury. Main Results. Kinematic analyses showed that the robotic interface did not impede locomotor movements of lightweight mice that walked freely along paths with changing directions and height profiles. Personalized trunk assistance instantly enabled coordinated locomotion in mice and rats with severe hindlimb motor deficits. Closed-loop control of robotic actuation based on ongoing movement features enabled real-time control of electromyographic activity in anti-gravity muscles during locomotion. Significance. This neurorobotic platform will support the study of the mechanisms underlying the therapeutic effects of locomotor prosthetics and rehabilitation using high-resolution genetic tools in rodent models.

  12. Epidermal growth factor and lung development in the offspring of the diabetic rat

    DEFF Research Database (Denmark)

    Thulesen, J; Poulsen, Steen Seier; Nexø, Ebba

    2000-01-01

    Fetuses of diabetic mothers who were exposed to excessive glucose show delayed maturation. Under these conditions, altered growth factor expression or signaling may have important regulatory influences. We examined the role of epidermal growth factor (EGF) in lung development and maternal diabetes...... in the rat. In order to evaluate the possible role of glucose for the expression of EGF and the growth of lung tissue, we performed in vitro studies with organotypic cultures of fetal alveolar cells obtained from control rats. Compared to pups of normal rats, the newborn rats of untreated diabetic rats had...... and was associated with a reduced intensity of surfactant protein A-IR. The only difference observed between pups of treated diabetic rats and controls was a decrease in the lung weight:body weight ratio. In organotypic cultures, the presence of 13 mmol/L glucose in the cell media increased immunoreactive staining...

  13. Development of obesity in Zucker obese (fafa) rat in absence of hyperphagia.

    Science.gov (United States)

    Cleary, M P; Vasselli, J R; Greenwood, M R

    1980-03-01

    The free-feeding, genetically obese rat is hyperphagic, hyperinsulinemic, and hypertriglyceridemic and has increased fat cell size and number compared to its lean littermate. These experiments demonstrate that, when fafa rats are prevented from expressing hyperphagia throughout life, the complete obese "syndrome" still develops. Furthermore, life-long food restriction does not prevent increased lipoprotein lipase in the fafa rat. The data support the concept that a peripheral metabolic adaptation, probably in lipid metabolism, results in preferential shunting of dietary substrate in the restricted obese rats to adipose tissue with concomitant decreases in other tissues.

  14. Effects of perinatal asphyxia on the neurobehavioral and retinal development of newborn rats.

    Science.gov (United States)

    Kiss, Peter; Szogyi, Donat; Reglodi, Dora; Horvath, Gabor; Farkas, Jozsef; Lubics, Andrea; Tamas, Andrea; Atlasz, Tamas; Szabadfi, Krisztina; Babai, Norbert; Gabriel, Robert; Koppan, Miklos

    2009-02-19

    Perinatal asphyxia during delivery produces long-term deficits and represents a major problem in both neonatal and pediatric care. Several morphological, biochemical and behavioral changes have been described in rats exposed to perinatal asphyxia. The aim of the present study was to evaluate how perinatal asphyxia affects the complex early neurobehavioral development and retinal structure of newborn rats. Asphyxia was induced in ready-to-deliver mothers by removing the pups by cesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily during the first 3 weeks, and motor coordination tests were performed on postnatal weeks 3-5. After completion of the testing procedure, retinas were removed for histological analysis. We found that in spite of the fast catch-up-growth of asphyctic pups, nearly all examined reflexes were delayed by 1-4 days: negative geotaxis, sensory reflexes, righting reflexes, development of fore- and hindlimb grasp and placing, gait and auditory startle reflexes. Time to perform negative geotaxis, surface righting and gait reflexes was significantly longer during the first few weeks in asphyctic pups. Among the motor coordination tests, a markedly weaker performance was observed in the grid walking and footfault test and in the walk initiation test. Retinal structure showed severe degeneration in the layer of the photoreceptor and bipolar cell bodies. In summary, our present study provided a detailed description of reflex and motor development following perinatal asphyxia, showing that asphyxia led to a marked delay in neurobehavioral development and a severe retinal degeneration.

  15. Effects of genistein in the maternal diet on reproductive development and spatial learning in male rats.

    Science.gov (United States)

    Ball, Evan R; Caniglia, Mary Kay; Wilcox, Jenna L; Overton, Karla A; Burr, Marra J; Wolfe, Brady D; Sanders, Brian J; Wisniewski, Amy B; Wrenn, Craige C

    2010-03-01

    Endocrine disruptors, chemicals that disturb the actions of endogenous hormones, have been implicated in birth defects associated with hormone-dependent development. Phytoestrogens are a class of endocrine disruptors found in plants. In the current study we examined the effects of exposure at various perinatal time periods to genistein, a soy phytoestrogen, on reproductive development and learning in male rats. Dams were fed genistein-containing (5 mg/kg feed) food during both gestation and lactation, during gestation only, during lactation only, or during neither period. Measures of reproductive development and body mass were taken in the male offspring during postnatal development, and learning and memory performance was assessed in adulthood. Genistein exposure via the maternal diet decreased body mass in the male offspring of dams fed genistein during both gestation and lactation, during lactation only, but not during gestation only. Genistein decreased anogenital distance when exposure was during both gestation and lactation, but there was no effect when exposure was limited to one of these time periods. Similarly, spatial learning in the Morris water maze was impaired in male rats exposed to genistein during both gestation and lactation, but not in rats exposed during only one of these time periods. There was no effect of genistein on cued or contextual fear conditioning. In summary, the data indicate that exposure to genistein through the maternal diet significantly impacts growth in male offspring if exposure is during lactation. The effects of genistein on reproductive development and spatial learning required exposure throughout the pre- and postnatal periods. Copyright 2009 Elsevier Inc. All rights reserved.

  16. Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

    DEFF Research Database (Denmark)

    Mortensen, B T; Jensen, P O; Helledie, N

    1998-01-01

    The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats....

  17. Effects of prenatal exposure to xylene on postnatal development and behavior in rats

    DEFF Research Database (Denmark)

    Hass, Ulla; Lund, S. P.; Simonsen, L.

    1995-01-01

    The effects of prenatal exposure to the organic solvent xylene (dimethylbenzene, GAS-no 1330-20-7) on postnatal development and behavior in rats were studied. Pregnant rats (Mol:WIST) were exposed to 500 ppm technical xylene 6 h per day on gestation days 7-20. The dose level was selected so as no...

  18. Development and significance of a fetal electrocardiogram recorded by signal-averaged high-amplification electrocardiography.

    Science.gov (United States)

    Hayashi, Risa; Nakai, Kenji; Fukushima, Akimune; Itoh, Manabu; Sugiyama, Toru

    2009-03-01

    Although ultrasonic diagnostic imaging and fetal heart monitors have undergone great technological improvements, the development and use of fetal electrocardiograms to evaluate fetal arrhythmias and autonomic nervous activity have not been fully established. We verified the clinical significance of the novel signal-averaged vector-projected high amplification ECG (SAVP-ECG) method in fetuses from 48 gravidas at 32-41 weeks of gestation and in 34 neonates. SAVP-ECGs from fetuses and newborns were recorded using a modified XYZ-leads system. Once noise and maternal QRS waves were removed, the P, QRS, and T wave intervals were measured from the signal-averaged fetal ECGs. We also compared fetal and neonatal heart rates (HRs), coefficients of variation of heart rate variability (CV) as a parasympathetic nervous activity, and the ratio of low to high frequency (LF/HF ratio) as a sympathetic nervous activity. The rate of detection of a fetal ECG by SAVP-ECG was 72.9%, and the fetal and neonatal QRS and QTc intervals were not significantly different. The neonatal CVs and LF/HF ratios were significantly increased compared with those in the fetus. In conclusion, we have developed a fetal ECG recording method using the SAVP-ECG system, which we used to evaluate autonomic nervous system development.

  19. Involvement of hypothalamic cyclooxygenase-2, interleukin-1β and melanocortin in the development of docetaxel-induced anorexia in rats.

    Science.gov (United States)

    Yamamoto, Kouichi; Asano, Keiko; Ito, Yui; Matsukawa, Naoki; Kim, Seikou; Yamatodani, Atsushi

    2012-12-16

    Docetaxel, a taxane derivative, is frequently used for the treatment of advanced breast cancer, non-small cell lung cancer, and metastatic prostate cancer. Clinical reports demonstrated that docetaxel-based chemotherapy often induces anorexia, but the etiology is not completely understood. To elucidate possible mechanisms, we investigated the involvement of central interleukin (IL)-1β, cyclooxygenase (COX)-2, and pro-opiomelanocortin (POMC) in the development of docetaxel-induced anorexia in rats. Rats received docetaxel (10mg/kg, i.p.) with or without pretreatment with selective COX-2 inhibitors, NS-398 (10 and 30 mg/kg, i.g.) or celecoxib (10 and 30 mg/kg, i.g.), and a non-selective COX inhibitor, indomethacin (10mg/kg, i.g.), then food intake was monitored for 24h after administration. We also examined expression of IL-1β, COX-2, and POMC mRNA in hypothalamus of docetaxel-treated rats and the effect of a COX-2 inhibitor on docetaxel-induced POMC mRNA expression. Food consumption in rats was significantly decreased 24h after administration of docetaxel and anorexia was partially reversed by all COX inhibitors. Administration of docetaxel increased IL-1β, COX-2, and POMC mRNA expression in the hypothalamus of rats. The time required to increase these gene expressions was comparable to the latency period of docetaxel-induced anorexia in rats. In addition, pretreatment with COX-2 inhibitors suppressed docetaxel-induced expression of POMC mRNA. These results suggest that IL-1β and COX-2 mRNA expression and subsequent activation of POMC in the hypothalamus may contribute to the development of docetaxel-induced anorexia in rats. Copyright © 2012. Published by Elsevier Ireland Ltd.

  20. The effect of exposure of rats during prenatal period to radiation spreading from mobile phones on renal development.

    Science.gov (United States)

    Bedir, Recep; Tumkaya, Levent; Şehitoğlu, İbrahim; Kalkan, Yıldıray; Yilmaz, Adnan; Şahin, Osman Zikrullah

    2015-03-01

    The aim of this study was to investigate the effects of exposure to a 900-MHz electromagnetic field (EMF) produced by mobile phones on the renal development of prenatal rats. Histopathological changes and apoptosis in the kidneys, together with levels of urea, creatinine and electrolyte in serum were determined. A total of 14 Sprague-Dawley rats were studied. Pregnant rats were divided into two equal groups: a control group and an EMF-exposed group. The study group was exposed to 900-MHz of EMF during the first 20 days of pregnancy, while the control group was unexposed to EMF. Sections obtained from paraffin blocks were stained for caspase-3 by immunohistochemistry, hematoxylin-eosin and Masson's trichrome. Mild congestion and tubular defects, and dilatation of Bowman's capsule were observed in the kidney tissues of rats in the exposed group. Apoptosis was evaluated using anti-caspase-3; stronger positive staining was observed in the renal tubular cells in the study group than those of the control group. Although there was a significant difference between the study and control groups in terms of K+ level (p0.05). Our study shows that the electromagnetic waves propagated from mobile phones have harmful effects on the renal development of prenatal rats.

  1. Review on the Significance of Local Plan for Coastal Reclamation Development: The Case of Malacca, Malaysia

    Directory of Open Access Journals (Sweden)

    Ishak Nor Syafa’ah

    2016-01-01

    Full Text Available A Development Plan acts as a planning and controlling instrument that helps to guide in decision making of current and future development. Therefore, in the Malaysian Town and Country Planning Act 1976 (Act 172, the provision of development plan from each level of the planning administration is stated in the Act under Section 6B till Section 16B. In examining the significance of one of the many development plans in Malaysia, i.e. the local plan, this paper therefore, focuses on the provision of a local plan by the Local Planning Authority (LPA of the said area. This paper, thus, aims to evaluate the Central Malacca Local Plan since Malacca is currently experiencing rapid growth in development along the coastal area. The primary data was obtained from interviews with the related planning authorities via face-to-face method. While, secondary data was gathered from related legal documents, policies and guidelines, as well as the existing development plan for the purpose of an in-depth data. Findings revealed incapability of the existing local plan to assist the development control in deciding the planning permission for reclaimed area. The existing local plan shows no zoning for coastal reclamation area because of the rapid growing development and time consuming procedure to amend the local plan according to the Act 172. In addition, the Act 172 and the process in amending the local plan should be more flexible and able to address the current issue efficiently. Finally, the paper concludes with a suggestion for further exploration in order to achieve an operative development process and functioning practice of the local plan.

  2. Development of pulmonary oxygen toxicity in rats after hyperoxic exposure

    Directory of Open Access Journals (Sweden)

    Siermontowski Piotr

    2014-06-01

    Full Text Available The aim of the study was to examine the effects of hyperbaric oxygen on lung aeration on an animal experimental model and compare the obtained results with the anticipated scope of damage to pulmonary parenchyma in humans under the same exposure conditions. The research was carried out on Black Hood rats that were kept in a hyperbaric chamber designed for animals in an atmosphere of pure oxygen and at overpressures of 0.15, 0.2, 0.3, 0.4, and 0.5 MPa for 1, 2 or 4 h. After sacrificing the animals, histopathological specimens were obtained encompassing cross-sections of entire lungs, which were subjected to qualitative and quantitative examination with the use of the 121-point Haug grid. A statistically significant decrease in pulmonary parenchyma was observed as a result of an increasing oxygen partial pressure as well as with prolonged exposure time. The intensification of changes observed was much higher than expected on the basis of calculations performed with the use of tables.

  3. Effects of Preweaning Polysensorial Enrichment upon Development of the Parietal Cortical Plate of Undernourished Rats: A Stereological Study

    OpenAIRE

    González, Héctor; Adaro, Luis; Hernández, Alejandro; Fernández, Víctor

    2014-01-01

    This investigation was undertaken in order to quantify the effects of early polysensorial enrichment on the development of cortical pyramids, located in the parietal cortex of rats simultaneously submitted to protein-energy undernutrition. A short period of stimulation during suckling significantly decreases the cellular density in the cortical plate (phylogenetic-ontogenetic evolutionary index). Results suggest that the cerebral cortex develops according to a sophisticated neuronal network, ...

  4. A simple LC-MS/MS method for quantitative analysis of underivatized neurotransmitters in rats urine: assay development, validation and application in the CUMS rat model.

    Science.gov (United States)

    Zhai, Xue-jia; Chen, Fen; Zhu, Chao-ran; Lu, Yong-ning

    2015-11-01

    Many amino acid neurotransmitters in urine are associated with chronic stress as well as major depressive disorders. To better understand depression, an analytical LC-MS/MS method for the simultaneous determination of 11 underivatized neurotransmitters (4-aminohippurate, 5-HIAA, glutamate, glutamine, hippurate, pimelate, proline, tryptophan, tyramine, tyrosine and valine) in a single analytical run was developed. The advantage of this method is the simple preparation in that there is no need to deconjugate the urine samples. The quantification range was 25-12,800 ng mL(-1) with >85.8% recovery for all analytes. The nocturnal urine concentrations of the 11 neurotransmitters in chronic unpredictable mild stress (CUMS) model rats and control group (n = 12) were analyzed. A series of significant changes in urinary excretion of neurotransmitters could be detected: the urinary glutamate, glutamine, hippurate and tyramine concentrations were significantly lower in the CUMS group. In addition, the urinary concentrations of tryptophan as well as tyrosine were significantly higher in chronically stressed rats. This method allows the assessment of the neurotransmitters associated with CUMS in rat urine in a single analytical run, making it suitable for implementation as a routine technique in depression research. Copyright © 2015 John Wiley & Sons, Ltd.

  5. Reduced connectivity and inter-hemispheric symmetry of the sensory system in a rat model of vulnerability to developing depression.

    Science.gov (United States)

    Ben-Shimol, E; Gass, N; Vollmayr, B; Sartorius, A; Goelman, G

    2015-12-03

    Defining the markers corresponding to a high risk of developing depression in humans would have major clinical significance; however, few studies have been conducted since they are not only complex but also require homogeneous groups. This study compared congenital learned helpless (cLH) rats, selectively bred for high stress sensitivity and learned helplessness (LH) behavior, to congenital non-learned helpless (cNLH) rats that were bred for resistance to uncontrollable stress. Naïve cLH rats show some depression-like behavior but full LH behavior need additional stress, making this model ideal for studying vulnerability to depression. Resting-state functional connectivity obtained from seed correlation analysis was calculated for multiple regions that were selected by anatomy AND by a data-driven approach, independently. Significance was determined by t-statistic AND by permutation analysis, independently. A significant reduction in functional connectivity was observed by both analyses in the cLH rats in the sensory, motor, cingulate, infralimbic, accumbens and the raphe nucleus. These reductions corresponded primarily to reduced inter-hemispheric connectivity. The main reduction however was in the sensory system. It is argued that reduced connectivity and inter-hemispheric connectivity of the sensory system reflects an internal convergence state which may precede other depressive symptomatology and therefore could be used as markers for vulnerability to the development of depression. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Dual odontogenic origins develop at the early stage of rat maxillary incisor development.

    Science.gov (United States)

    Kriangkrai, Rungarun; Iseki, Sachiko; Eto, Kazuhiro; Chareonvit, Suconta

    2006-03-01

    Developmental process of rat maxillary incisor has been studied through histological analysis and investigation of tooth-related gene expression patterns at initial tooth development. The tooth-related genes studied here are fibroblast growth factor-8 (Fgf-8), pituitary homeobox gene-2 (Pitx-2), sonic hedgehog (Shh), muscle segment homeobox-1 (Msx-1), paired box-9 (Pax-9) and bone morphogenetic protein-4 (Bmp-4). The genes are expressed in oral epithelium and/or ectomesenchyme at the stage of epithelial thickening to the early bud stage of tooth development. Both the histological observation and tooth-related gene expression patterns during early stage of maxillary incisor development demonstrate that dual odontogenic origins aligned medio-laterally in the medial nasal process develop, subsequently only single functional maxillary incisor dental placode forms. The cascade of tooth-related gene expression patterns in rat maxillary incisor studied here is quite similar to those of the previous studies in mouse mandibular molar, even though the origins of oral epithelium and ectomesenchyme involved in development of maxillary incisor and mandibular molar are different. Thus, we conclude that maxillary incisor and mandibular molar share a similar signaling control of Fgf-8, Pitx-2, Shh, Msx-1, Pax-9 and Bmp-4 genes at the stage of oral epithelial thickening to the early bud stage of tooth development.

  7. Exposure of pregnant rats to uranium and restraint stress: Effects on postnatal development and behavior of the offspring

    International Nuclear Information System (INIS)

    Sanchez, Domenec J.; Belles, Montserrat; Albina, Maria L.; Gomez, Mercedes; Linares, Victoria; Domingo, Jose L.

    2006-01-01

    The effects on postnatal development and behavior were assessed in the offspring of female rats concurrently exposed to uranium (U) and restraint stress. Adult female rats were administered uranyl acetate dihydrate (UAD) in the drinking water at doses of 0, 40 and 80 mg/(kg day) for 4 weeks before mating with untreated males, as well as during pregnancy and lactation. One-half of female rats in each group were concurrently subjected to restraint (2 h/day). On gestation day 14, one-half of restrained and unrestrained rats were sacrificed in order to evaluate maternal toxicity and gestational parameters. Pups were evaluated for physical development, neuromotor maturation, and behavior. Uranium concentrations were also determined in various tissues of dams and fetuses. In all uranium-treated groups, the highest concentrations of this element were found in kidney and bone, being considerably higher than those in brain. Uranium levels in tissues of dam or fetuses were not significantly affected by restraint. No significant interactions between uranium and restraint could be observed in maternal toxicity. Moreover, no relevant effects of uranium, maternal restraint, or their combination were noted on developmental landmarks in the offspring. In the passive avoidance test, at 40 and 80 mg UAD/(kg day) restraint significantly modified passive avoidance acquisition (T1) and retention time (T2) 24 h later. However, no significant differences were observed on the Morris water maze test. The results of the present study indicate that, in general terms, exposure of female rats to UAD before mating with untreated males, as well as during gestation and lactation, did not cause relevant dose-related adverse effects on postnatal development and behavior of the offspring. The influence of stress was very limited

  8. Transplacental and early life exposure to inorganic arsenic affected development and behavior in offspring rats

    Energy Technology Data Exchange (ETDEWEB)

    Xi, Shuhua; Jin, Yaping; Sun, Guifan [China Medical University, Department of Environmental and Occupational Health, College of Public Health, Shenyang, Liaoning (China); Sun, Wenjuan; Wang, Fengzhi [Shenyang Medical College, Department of Preventive Medicine, Shenyang, Liaoning (China)

    2009-06-15

    To evaluate the developmental neurotoxicity of arsenic in offspring rats by transplacental and early life exposure to sodium arsenite in drinking water, the pregnant rats or lactating dams, and weaned pups were given free access to drinking water, which contained arsenic at concentrations of 0, 10, 50, 100 mg/L from GD 6 until PND 42. A battery of physical and behavioral tests was applied to evaluate the functional outcome of pups. Pups in arsenic exposed groups weighed less than controls throughout lactation and weaning. Body weight of 10, 50 and 100 mg/L arsenic exposed groups decreased significantly on PND 42, 16 and 12, respectively. Physical development (pinna unfolding, fur appearance, incisor eruption, or eye opening) in pups displayed no significant differences between control and arsenic treated groups. The number of incidences within the 100 mg/L arsenic treated group, in tail hung, auditory startle and visual placing showed significant decrease compared to the control group (p<0.05). In square water maze test, the trained numbers to finish the trials successfully in 50 and 100 mg/L arsenic exposed groups increased remarkably compared to control group, and there was a dose-related increase (p<0.01) observed. Taken together, these data show that exposure of inorganic arsenite to pregnant dams and offspring pups at levels up to 100 mg/L in drinking water may affect their learning and memory functions and neuromotor reflex. (orig.)

  9. Developing the RIAM method (rapid impact assessment matrix) in the context of impact significance assessment

    International Nuclear Information System (INIS)

    Ijaes, Asko; Kuitunen, Markku T.; Jalava, Kimmo

    2010-01-01

    In this paper the applicability of the RIAM method (rapid impact assessment matrix) is evaluated in the context of impact significance assessment. The methodological issues considered in the study are: 1) to test the possibilities of enlarging the scoring system used in the method, and 2) to compare the significance classifications of RIAM and unaided decision-making to estimate the consistency between these methods. The data used consisted of projects for which funding had been applied for via the European Union's Regional Development Trust in the area of Central Finland. Cases were evaluated with respect to their environmental, social and economic impacts using an assessment panel. The results showed the scoring framework used in RIAM could be modified according to the problem situation at hand, which enhances its application potential. However the changes made in criteria B did not significantly affect the final ratings of the method, which indicates the high importance of criteria A1 (importance) and A2 (magnitude) to the overall results. The significance classes obtained by the two methods diverged notably. In general the ratings given by RIAM tended to be smaller compared to intuitive judgement implying that the RIAM method may be somewhat conservative in character.

  10. Poly(lactic-co-glycolide) polymer constructs cross-linked with human BMP-6 and VEGF protein significantly enhance rat mandible defect repair.

    Science.gov (United States)

    Das, Anusuya; Fishero, Brian A; Christophel, J Jared; Li, Ching-Ju; Kohli, Nikita; Lin, Yong; Dighe, Abhijit S; Cui, Quanjun

    2016-04-01

    We have previously shown that the combined delivery of mesenchymal stem cells (MSCs), vascular endothelial growth factor (VEGF) and bone morphogenetic protein 6 (BMP-6) induces significantly more bone formation than that induced by the delivery of any single factor or a combination of any two factors. We now determine whether the exogenous addition of VEGF and BMP-6 is sufficient for bone healing when MSCs are not provided. Poly(lactic-co-glycolic acid) (PLAGA) microsphere-based three-dimensional scaffolds (P) were fabricated by thermal sintering of PLAGA microspheres. The scaffolds were chemically cross-linked with 200 ng recombinant human VEGF (P(VEGF)) or BMP-6 (P(BMP-6)) or both (P(VEGF+BMP-6)) by the EDC-NHS-MES method. Release of the proteins from the scaffolds was detected for 21 days in vitro which confirmed their comparable potential to supply the proteins in vivo. The scaffolds were delivered to a critical-sized mandibular defect created in 32 Sprague Dawley rats. Significant bone regeneration was observed only in rats with P(VEGF+BMP-6) scaffolds at weeks 2, 8 and 12 as revealed by micro-computer tomography. Vascular ingrowth was higher in the P(VEGF+BMP-6) group as seen by microfil imaging than in other groups. Trichrome staining revealed that a soft callus formed in P(VEGF), P(BMP-6) and P(VEGF+BMP-6) but not in P. MSCs isolated from rat femurs displayed expression of the bone-specific marker osteocalcin when cultured with P(VEGF), P(BMP-6), or P(VEGF+BMP-6) but not with P. Robust mineralization and increased alkaline phosphatase gene expression were seen in rat MSCs when cultured on P(VEGF+BMP-6) but not on P, P(VEGF), or P(BMP-6). Thus, unlike the delivery of VEGF or BMP-6 alone, the combined delivery of VEGF and BMP-6 to the bone defect significantly enhanced bone repair through the enhancement of angiogenesis and the differentiation of endogenously recruited MSCs into the bone repair site.

  11. The Significance of Protein Components in Heterogeneous Eggs for Embrionic Development and Larvas Persistence of Cyprinidae

    Directory of Open Access Journals (Sweden)

    Zalepukhin Valeriy Vladimirovich

    2014-12-01

    Full Text Available Endogenous heterogeneity of females and their eggs is one of the most important factors of annual generation’s formation in nature-spawn and incubative centers. Its assessment is significant for comprehending the notion of biochemical changes in proximate prespawn period. Between the shares of egg’s biochemical composition of Cyprinidae species only protein and b-lipoproteids levels are incovering constant and authentic correlations with embrionic development and larval survival in the conditions of artificial reproduction. The promotion of protein’s level to 20 – 24 % (in wet weigth in percolating eggs positively affects the fertilization and larvae vitality. This trend is fair for the domesticated and nature-spawn fish. The same significance is important for the b-lipoproteids level in ovular eggs of grass carp (Ctenopharyngodon idella Val.. The optimal concentration is 100-200 mg % in wet weight.

  12. Effects of thioperamide on seizure development and memory impairment induced by pentylenetetrazole-kindling epilepsy in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Li-san; CHEN Jie-fang; CHEN Guan-feng; HU Xing-yue; DING Mei-ping

    2013-01-01

    Background Histamine H3 receptor antagonists have been considered as potential drugs to treat central nervous system diseases.However,whether these drugs can inhibit epileptogenesis remains unclear.This study aimed to investigate the effects of thioperamide,a selective and potent histamine H3 receptor antagonist,on the seizure development and memory impairment induced by pentylenetetrazole (PTZ)-kindling epilepsy in rats.Methods Chemical kindling was elicited by repeated intraperitoneal (ip) injections of a subconvulsant dose of PTZ (35 mg/kg) once every 48 hours for 12 times,and seizure activity of kindling was recorded for 30 minutes.Control rats were ip injected with saline instead of PTZ.Morris water maze was used to evaluate the spatial memory.Phosphorylated cyclic adenosine monophosphate response element binding protein (p-CREB) was tested by Western blotting in hippocampus.Results Intracerebroventricular (icv) injections with thioperamide (10 μg,20 μg) 30 minutes before every PTZ injections,significantly prolonged the onset of PTZ-kindling and inhibited the seizure stages.PTZ-kindling seizures led to the impairment of spatial memory in rats,and thioperamide ameliorated the impairment of spatial learning and memory.Compared to non-kindling rats,there was a significant decrease in p-CREB level in hippocampus of the PTZ-kindling rats,which was reversed by thioperamide.Conclusions Thioperamide plays a protective role in seizure development and cognitive impairment of PTZ-induced kindling in rats.The protection of thioperamide in cognitive impairment is possibly associated with the enhancement of CREB-dependent transcription.

  13. Development of Safety Significance Evaluation Program for Accidents and Events in NPPs

    International Nuclear Information System (INIS)

    Yang, Hui Chang; Hong, Seok Jin; Cho, Nam Chul; Chung, Dae Wook; Lee, Chang Joo

    2010-01-01

    To evaluate the significance in terms of safety for the accidents and events occurred in nuclear power plants using probabilistic safety assessment techniques can provide useful insights to the regulator. Based on the quantified risk information of accident or event occurred, regulators can decide which regulatory areas should be focused than the others. To support these regulatory analysis activities, KINS-ASP program was developed. KINS-ASP program can supports the risk increase due to the occurred accidents or events by providing the graphic interfaces and linked quantification engines for the PSA experts and non- PSA acquainted regulators both

  14. Significance of bacteria in oviposition and larval development of the sand fly Lutzomyia longipalpis

    Science.gov (United States)

    2012-01-01

    Background Microbial ecology of phlebotomine sand flies is not well understood although bacteria likely play an important role in the sand fly biology and vector capacity for Leishmania parasites. In this study, we assessed the significance of the microbial community of rabbit feces in oviposition and larval development of Lutzomyia longipalpis as well as bacterial colonization of the gut of freshly emerged flies. Methods Sterile (by autoclaving) and non-sterile (control) rabbit feces were used in the two-choice assay to determine their oviposition attractiveness to sand fly females. Bacteria were identified by amplification and sequencing of the 16S rRNA gene with universal eubacterial primers. Sterile, control (non-sterile), and sterilized and inoculated rabbit feces were used to assess the significance of bacteria in L. longipalpis development. Newly emerged adult flies were surface-sterilized and screened for the bacterial population size and diversity by the culturing approach. The digestive tract of L4 sterile and control larvae was incubated with Phalloidin to visualize muscle tissues and DAPI to visualize nuclei. Results Two-choice behavioural assays revealed a great preference of L. longipalpis to lay eggs on rabbit feces with an active complex bacterial community (control) (85.8 % of eggs) in comparison to that of sterile (autoclaved) rabbit feces (14.2 %). Bioassays demonstrated that L. longipalpis larvae can develop in sterile rabbit feces although development time to adult stage was greatly extended (47 days) and survival of larvae was significantly lower (77.8 %) compared to that of larvae developing in the control rabbit feces (32 days and 91.7 %). Larval survival on sterilized rabbit feces inoculated with the individual bacterial isolates originating from this substrate varied greatly depending on a bacterial strain. Rhizobium radiobacter supported larval development to adult stage into the greatest extent (39 days, 88.0 %) in

  15. Development of an Experimental Model of Diabetes Co-Existing with Metabolic Syndrome in Rats

    Directory of Open Access Journals (Sweden)

    Rajesh Kumar Suman

    2016-01-01

    Full Text Available Background. The incidence of metabolic syndrome co-existing with diabetes mellitus is on the rise globally. Objective. The present study was designed to develop a unique animal model that will mimic the pathological features seen in individuals with diabetes and metabolic syndrome, suitable for pharmacological screening of drugs. Materials and Methods. A combination of High-Fat Diet (HFD and low dose of streptozotocin (STZ at 30, 35, and 40 mg/kg was used to induce metabolic syndrome in the setting of diabetes mellitus in Wistar rats. Results. The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for the study to induce diabetes mellitus. Various components of metabolic syndrome such as dyslipidemia (increased triglyceride, total cholesterol, LDL cholesterol, and decreased HDL cholesterol, diabetes mellitus (blood glucose, HbA1c, serum insulin, and C-peptide, and hypertension {systolic blood pressure} were mimicked in the developed model of metabolic syndrome co-existing with diabetes mellitus. In addition to significant cardiac injury, atherogenic index, inflammation (hs-CRP, decline in hepatic and renal function were observed in the HF-DC group when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis, and inflammation in heart, pancreas, liver, and kidney of HF-DC group as compared to NC. Conclusion. The present study has developed a unique rodent model of metabolic syndrome, with diabetes as an essential component.

  16. Development of an Experimental Model of Diabetes Co-Existing with Metabolic Syndrome in Rats.

    Science.gov (United States)

    Suman, Rajesh Kumar; Ray Mohanty, Ipseeta; Borde, Manjusha K; Maheshwari, Ujwala; Deshmukh, Y A

    2016-01-01

    Background. The incidence of metabolic syndrome co-existing with diabetes mellitus is on the rise globally. Objective. The present study was designed to develop a unique animal model that will mimic the pathological features seen in individuals with diabetes and metabolic syndrome, suitable for pharmacological screening of drugs. Materials and Methods. A combination of High-Fat Diet (HFD) and low dose of streptozotocin (STZ) at 30, 35, and 40 mg/kg was used to induce metabolic syndrome in the setting of diabetes mellitus in Wistar rats. Results. The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for the study to induce diabetes mellitus. Various components of metabolic syndrome such as dyslipidemia {(increased triglyceride, total cholesterol, LDL cholesterol, and decreased HDL cholesterol)}, diabetes mellitus (blood glucose, HbA1c, serum insulin, and C-peptide), and hypertension {systolic blood pressure} were mimicked in the developed model of metabolic syndrome co-existing with diabetes mellitus. In addition to significant cardiac injury, atherogenic index, inflammation (hs-CRP), decline in hepatic and renal function were observed in the HF-DC group when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis, and inflammation in heart, pancreas, liver, and kidney of HF-DC group as compared to NC. Conclusion. The present study has developed a unique rodent model of metabolic syndrome, with diabetes as an essential component.

  17. THE SIGNIFICANCE OF CUMULATIVE WATER BALANCE IN THE DEVELOPMENT OF EARLY COMPLICATIONS AFTER MAJOR ABDOMINAL SURGERY.

    Science.gov (United States)

    Musaeva, T S; Karipidi, M K; Zabolotskikh, I B

    2016-11-01

    a comprehensive assessment of the water balance on the basis of daily, cumulative balance and 10% of the body weight gain and their role in the development of early complications after major abdominal surgery. A retrospective study of the perioperative period in 150 patients who underwent major abdomi- nal surgery was performed. The physical condition of the patients corresponded to ASA 3 class. The average age was 46 (38-62) years. The following stages ofresearch: an analysis of daily balance and cumulative balance in complicated and uncomplicated group and their role in the development of complications; the timing of development ofcomplications and possible relationship with fluid overload and the development of complications; changes in the level of albumin within 10 days of the postoperative period. The analysis of complications didn't show significant differences between complicated and uncomplicated groups according to the water balance during the surgery and by the end of the first day. When constructing the area under the ROC curve (A UROC) low resolution ofthe balance in intraoperative period and the first day and the balance on the second day to predict complications was shown. Significant diferences according to the cumulative balance was observed from the third day of the postoperative period Also with the third day of the postoperative period there is a good resolution for prediction ofpostoperative complications according to the cumulative balance with the cut-offpoint > of 50,7 ml/kg. the excessive infusion therapy is a predictor of adverse outcome in patients after major abdominal surgery. Therefore, after 3 days of postoperative period it is important to maintain mechanisms for the excretion of excess fluid or limitations of infusion therapy.

  18. Teaching Strategies for Significant Development of Reading of Learners Understanding in Primary Education

    Directory of Open Access Journals (Sweden)

    María Edixa Araujo Riveros

    2017-02-01

    Full Text Available This article aims to propose a manual significant for the development of reading comprehension in students of Educational Unit The Batatal located in the parish Marcelino Briceño, municipality Baralt, Zulia state teaching strategies. To do this, it is based theoretically on the contributions of authors like Campos (2011 Camilloni (2012, Castedo (2011, Ortiz (2012, among others. Methodologically, it developed following the modality of feasible project, which was applied to a population of 24 teachers from the selected institution. survey the survey with a structured according Likert scale questionnaire type instrument, and twenty-four items was used as a technique. The validity was obtained through expert judgment, the reliability of =, 9216 was calculated using Cronbach's alpha coefficient. The results led to the conclusion that teachers had weaknesses related to the implementation of teaching strategies that will enable the development of reading comprehension in students by providing input for the design of the proposed manual. It is recommended to use different strategies for different levels of reading comprehension in accordance with the development achieved by their students.

  19. The challenges of ESRD care in developing economies: sub-Saharan African opportunities for significant improvement.

    Science.gov (United States)

    Bamgboye, Ebun Ladipo

    Chronic kidney disease (CKD) is a significant cause of morbidity and mortality in sub-Saharan Africa. This, along with other noncommunicable diseases like hypertension, diabetes, and heart diseases, poses a double burden on a region that is still struggling to cope with the scourge of communicable diseases like malaria, tuberculosis, HIV, and more recently Ebola. Causes of CKD in the region are predominantly glomerulonephritis and hypertension, although type 2 diabetes is also becoming a significant cause as is the retroviral disease. Patients are generally younger than in the developed world, and there is a significant male preponderance. Most patients are managed by hemodialysis, with peritoneal dialysis and kidney transplantation being available in only few countries in the region. Government funding and support for dialysis is often unavailable, and when available, often with restrictions. There is a dearth of trained manpower to treat the disease, and many countries have a limited number of units, which are often ill-equipped to deal adequately with the number of patients who require end-stage renal disease (ESRD) care in the region. Although there has been a significant improvement when compared with the situation, even as recently as 10 years ago, there is also the potential for further improvement, which would significantly improve the outcomes in patients with ESRD in the region. The information in this review was obtained from a combination of renal registry reports (published and unpublished), published articles, responses to a questionnaire sent to nephrologists prior to the World Congress of Nephrology (WCN) in Cape Town, and from nephrologists attending the WCN in Cape Town (March 13 - 17, 2015).

  20. β-lipotropin is the major opioid-like peptide of human pituitary and rat pars distalis: lack of significant β-endorphin

    International Nuclear Information System (INIS)

    Liotta, A.S.; Suda, T.; Krieger, D.T.

    1978-01-01

    β-Lipotropin is the predominant opioid peptide of the human pituitary and rat pars distalis and is present in concentrations essentially equimolar with corticotropin. When freshly obtained nonfrozen rat anterior pituitaries were homogenized with 0.2 M HCl, approximately 98% of the immunoreactivity detected utilizing an antiserum that crossreacts equally with β-lipotropin and β-endorphin coeluted with 125 I-labeled human β-lipotropin upon molecular sieve chromatography. The remainder of the activity eluted with synthetic human β-endorphin. Similar results were obtained for human pituitary. HCl homogenization of thawed tissue or homogenization of fresh tissue with acetic acid yielded substantially greater concentrations of β-endorphin and decreased concentrations of β-lipotropin. In human subjects, acute anterior pituitary stimulation using either insulin-induced hypoglycemia or vasopressin administration was associated with increased plasma β-lipotropin and corticotropin levels. At the time of peak concentrations, no significant levels of β-endorphin were detectable. These data indicate the lack of significant amounts of β-endorphin in human pituitary. Additionally, there appears to be no specific intrapituitary conversion of β-lipotropin to β-endorphin

  1. Clinical significance of changes of serum IL-6 and TNF-α levels in rat models of hypoxic-ischemia brain injury

    International Nuclear Information System (INIS)

    Niu Tingxian; Shi Zhiyong; Luo Jianjun

    2009-01-01

    Objective: To explore the clinical significance of changes of serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels in rat models of hypoxic-ischemia (HI) brain injury. Methods: Seventy five rat HI brain injury nodels were prepared with bilateral occlusion of common carotid artery for 24rs followed 2hrs later by hypoxia (breathing 8% oxygen) for 2hrs. One fifth of the animals were sacrificed at 4h, 8h, 12h, 24h and 48h later respectively, the serum and brain homogenate concentrations of IL-6 and TNF-α were determined with RIA and brain tissues were pathologically examined. Results: The concentrations of IL-6 and TNF-α were dynamically changed within 48h in serum and brain homogenate. Peak values occurred at 24h with serum and at 12h with brain homogenate. Meanwhile, levels of both cytokines were significantly higher in the models than those in controls (P<0.01 or P<0.05). Conclusion: The concentrations of IL-6 and TNF-α were dynamically(sham operation only, 15 animals) changed and might be regarded as the clinical markers of degree of HI brain injury. (authors)

  2. Measure of significance of holotropic breathwork in the development of self-awareness

    DEFF Research Database (Denmark)

    Miller, Tanja; Nielsen, Laila

    2015-01-01

    OBJECTIVES: To investigate whether Holotropic Breathwork™ (HB; Grof Transpersonal Training, Mill Valley, CA) has any significance in the development of self-awareness. DESIGN: A quasi-experiment design and multiple case studies. A single case design was replicated. The statistical design was a re......OBJECTIVES: To investigate whether Holotropic Breathwork™ (HB; Grof Transpersonal Training, Mill Valley, CA) has any significance in the development of self-awareness. DESIGN: A quasi-experiment design and multiple case studies. A single case design was replicated. The statistical design...... MEASURES: The novices (n = 9) underwent positive temperament changes and the experienced participants (n = 11) underwent positive changes in character. Overall, positive self-awareness changes were indicated; the participants' (n = 20) scores for persistence temperament, interpersonal problems, overly.......864; pre-during-test p = 0.0215, pre-post-test p = 0.021, pre-post-test d = 0.5). Pre-test hostility mean (50.50 ± 10.395) decreased at post-test (47.20 ± 9.001; p = 0.0185; d = 0.3). The Inventory of Interpersonal Problems total pre-test mean (59.05 ± 17.139) was decreased at post-test (54.8 ± 12.408; p...

  3. Changes in brain development of rat fetus exposed to 137Cs γ rays in different pregnant periods of the female rats

    International Nuclear Information System (INIS)

    Guo Yuefeng; Wang Mingming

    2004-01-01

    Pregnant rats in 11d and 16d of their pregnancy were given one-off whole body exposure by 137 Cs γ rays to 0.2, 0.4, 0.9 and 2.0 Gy, respectively. Changes were observed in conditioned drinking response and cerebrum hippocampi cone cell number of the baby rats exposed to the γ rays in different periods of their embryo development. As a result, that pregnant rats exposed to 137 Cs γ rays in different pregnant periods may induce significant decrease in cerebrum hippocampi cone cell number and achieving rate of conditioned drinking response of the babies. The dose-response relationship can be described by Y=a-b log 10 D. The achieving rate of conditioned drinking response were significantly correlated to cerebrum hippocampi cone cell number in the babies, and the achieving rate of conditioned drinking response of the babies exposed at pregnant 11d was lower than others exposed at pregnant 16d

  4. Effect of agmatine on the development of morphine dependence in rats: potential role of cAMP system

    Science.gov (United States)

    Aricioglu, Feyza; Means, Andrea; Regunathan, Soundar

    2010-01-01

    Agmatine is an endogenous amine derived from arginine that potentiates morphine analgesia and blocks symptoms of naloxone-precipitated morphine withdrawal in rats. In this study, we sought to determine whether treatment with agmatine during the development of morphine dependence inhibits the withdrawal symptoms and that the effect is mediated by cAMP system. Exposure of rats to morphine for 7 days resulted in marked naloxone-induced withdrawal symptoms and agmatine treatment along with morphine significantly decreasing the withdrawal symptoms. The levels of cAMP were markedly increased in morphine-treated rat brain slices when incubated with naloxone and this increase was significantly reduced in rats treated with morphine and agmatine. The induction of tyrosine hydroxylase after morphine exposure was also reduced in locus coeruleus when agmatine was administered along with morphine. We conclude that agmatine reduces the development of dependence to morphine and that this effect is probably mediated by the inhibition of cAMP signaling pathway during chronic morphine exposure. PMID:15541421

  5. The effect of x-irradiation on the implantation and development of the white rat fetus

    International Nuclear Information System (INIS)

    Danius, J.; Bahauddin, R.

    1976-01-01

    X-ray whole body irradiation (200R, exposure dose) was performed on young virgin females of about 4 months old. The female rats, divided into three groups, were treated as follows: Female rats as control (unirradiated = 1Kt): female rats irradiated before mating (RSbK), and female rats irradiated after mating (RSsK). The average number of surviving foetuses at 20 days gestational stage of 1Kt was compared with that of RSbK, and no significant difference was found (P<=0.05) while the difference between the average number of RSsK foetuses compared with that of 1Kt and RSbK was highly significant (P<0.01). A decrease in the average number of surviving foetuses was found in RSsK, although the analysis of variance of all groups, revealed no significant difference (P<=0.05) in the average number of implantations and weight of the foetuses. (author)

  6. De rijping van het cerebellum; a study of the postnatal development of the rat cerebellum.

    NARCIS (Netherlands)

    Ebels, E.J.

    1969-01-01

    Chapter I: INTRODUCTION In this investigation the development of the rat cerebellum from 0 -30 days after birth is studied morphologically, by means of enzymchistochemistry and electronmicroscopy. Enzymchistochemistry and electronmicroscopy were chosen because changes in enzyme content or enzyme

  7. Chronic administration of ethanol leaf extract of Moringa oleifera Lam. (Moringaceae) may compromise glycaemic efficacy of Sitagliptin with no significant effect in retinopathy in a diabetic rat model.

    Science.gov (United States)

    Olurishe, Comfort; Kwanashie, Helen; Zezi, Abdulkadiri; Danjuma, Nuhu; Mohammed, Bisalla

    2016-12-24

    Moringa oleifera Lam. (Moringaceae) has gained awareness for its antidiabetic effect, and is used as alternative therapy or concurrently with orthodox medicines such as sitagliptin in diabetes mellitus. This is without ascertaining the possibility of drug-herb interactions, which could either lead to enhanced antidiabetic efficacy, increased toxicity, or compromised glycaemic control with negative consequence in diabetic retinopathy. To investigate the effect, of sitagliptin (50mg/kg), Moringa oleifera (300mg/kg) leaf extract, and a combination of both on glycaemic control parameters, lenticular opacity and changes in retinal microvasculature in alloxan (150mg/kg i.p) induced diabetic rat model. Seven groups of eight rats per group were used, with groups I, II and VII as normal (NC), diabetic (DC) and post-prandial controls (PPC). Groups III to VI were diabetic rats on sitagliptin (III), M. oleifera (IV), sitagliptin and M. oleifera (SM) (V), for 42 days with 2 weeks delayed treatment in a post-prandial hyperglycaemic group (PPSM) (VI). Glycaemic control parameters, insulin levels, body weights, and effects of retinal microvasculature on lenticular opacity/morphology were investigated. A significant decrease in fasting blood glucose (FBG) levels was displayed in SM group from day 14(60%) (p<0.01) to day 28 (38%) (p<0.01) of treatment, compared to day 1. Thereafter, a steady increase of up to 57% on day 42 compared to day 28 was observed. A significant decrease in random blood glucose (RBG) levels, were demonstrated on day 42 (24%) (p<0.001), compared to day 1. No significant difference was seen in mean serum levels of insulin across groups. No significant changes in body weights. Evidence of mild lenticular opacity was observed, with no significant effect in pathologic lesions in the retina. The chronic co-administration of sitagliptin and M. oleifera showed a progressive decrease in anti-hyperglycaemic effect of sitagliptin, and although it delayed the onset of

  8. Significance of United Nations Conference on Environment and Development (UNCED). Chikyu summit no igi

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, T [Ministry of Construction, Tokyo (Japan)

    1992-10-01

    On the significance of UNCED, the background, the results of the conference and the reflection to the construction administration were described. The causes of global environmental problems such as the global warming, the ozone layer destruction and the decrease of forests can mainly be classified into 3. These are the problem of socio-economic activities of advanced countries such as mass production, mass consumption and mass dumping, the problem originating from the poverty in developing countries and the problem originating from the interests between advanced countries and developing countries. The main results in the UNCED were as follows: the signature to the two conventions as to the climate change and the biological diversity, the statement as to the principle for forests, the Rio Declaration which should be said to be the world constitution concerning the environment and development, and the adoption of the Agenda 21 of the draft which summarized the policies and measures. The Agenda 21 includes the fund, the technology transfer and the organization problems. In order to reflect these problems to the construction administration, it is necessary to promote the energy policy, the establishment of efficient traffic system, the effective land utilization, the appropriate management of river spaces, the urban policy and the recycling of resources.

  9. Significant progress towards development of the low-level radioactive waste disposal facility in Illinois

    International Nuclear Information System (INIS)

    Klebe, M.; Henry, T.L.; Corpstein, P.

    1996-01-01

    Development of disposal sites for low-level radioactive waste is a complicated legal, regulatory and public sector process. Development of the low-level radioactive waste disposal facility to support generators in Illinois and Kentucky is well under way. Significant progress has been made to re-engineer the siting development process capitalizing on prior lessons learned and a recommitment from Illinois state leadership assuring the future success of the program. Comparisons of why this new process will succeed are the major focus of this paper. Specific changes in approach from the previous process including changes in the Illinois Management Act (Management Act), creation of the Illinois Low-Level Radioactive Waste Siting Task Group (Task Group), new roles for the Illinois State Geologic Survey and Illinois State Water Survey (Scientific Surveys) and the Illinois Department of Nuclear Safety (IDNS), a new contractor reliance approach and increased confidence on the open-quote science close-quote are the major contrasts between the previous process and the new process currently underway

  10. Development of rat visual system after prenatal X-irradiation

    International Nuclear Information System (INIS)

    Brueckner, G.; Biesold, D.; Mares, V.

    1980-01-01

    Rats pregnant for 16 or 19 days (ED 16 or 19) were irradiated with 1 Gy and killed after 24 hrs or at age 24 or 180 days. The primary influence of X-rays consists in a lethal lesion of cells located in the periventricular zone as well as some of the more differentiated cells in the brain parenchyma. After irradiation on ED 16, the acute damage was greater in the cerebral cortex and the superior colliculus (SC) than in the lateral geniculate nucleus (LGN). Irradiation on ED 19 damaged mainly the cortical part of the visual system. In adult animals the acute radiation damage results in a deficit in packing density and the total number of neurons. Animals irradiated on ED 16 revealed more pronounced changes in deep layers of the cortex (L VI) than in the superficial layers. The deficit was smaller in the SC, and in the LGN an increase in the packing density of nerve cells was found. In animals irradiated on ED 19, the deficit in neurons density occurred mainly in more superficial layers of the cortex, with a maximum deficit in layer IV. From comparison of acute and final changes it may be concluded that the damage of preneuroblastic cell populations is compensated during later embryonic development, while the damage induced in populations already at early neuroblast stage is irreversible and leads to a permanent deficit. Glia cell population is altered in a similar way as the number of neurons in regions poor in myelin, while in regions rich in myelin the number of glia cells seems to depend on changes in the number of efferent and afferent nerve fibres. (author)

  11. Sex difference in mecp2 expression during a critical period of rat brain development.

    Science.gov (United States)

    Kurian, Joseph R; Forbes-Lorman, Robin M; Auger, Anthony P

    2007-09-01

    Pervasive developmental disorder is a classification covering five related conditions including the neurodevelopmental disorder Rett syndrome (RTT) and autism. Of these five conditions, only RTT has a known genetic cause with mutations in Methyl-CpG-binding protein 2 (MeCP2), a global repressor of gene expression, responsible for the majority of RTT cases. However, recent evidence indicates that reduced MeCP2 expression or activity is also found in autism and other disorders with overlapping phenotypes. Considering the sex difference in autism diagnosis, with males diagnosed four times more often than females, we questioned if a sex difference existed in the expression of MeCP2, in particular within the amygdala, a region that develops atypically in autism. We found that male rats express significantly less mecp2 mRNA and protein than females within the amygdala, as well as the ventromedial hypothalamus (VMH), but not within the preoptic area (POA) on post-natal day 1 (PN1). At PN10 these differences were gone; however, on this day males had more mecp2 mRNA than females within the POA. The transient sex difference of mecp2 expression during the steroid-sensitive period of brain development suggests that mecp2 may participate in normal sexual differentiation of the rat brain. Considering the strong link between MeCP2 and neurodevelopmental disorders, the lower levels of mecp2 expression in males may also underlie a biological risk for mecp2-related neural disorders.

  12. ALLOPURINOL DOES NOT DECREASE BLOOD PRESSURE OR PREVENT THE DEVELOPMENT OF HYPERTENSION IN THE DOCA-SALT RAT MODEL

    Science.gov (United States)

    Szasz, Theodora; Linder, A. Elizabeth; Davis, Robert P.; Burnett, Robert; Fink, Gregory D.; Watts, Stephanie W.

    2010-01-01

    Reactive oxygen species (ROS) play an important role in the pathogenesis of hypertension, disease in which ROS levels and markers of oxidative stress are increased. Xanthine oxidase (XO) is a ROS-producing enzyme the activity of which may increase during hypertension. Studies on XO inhibition effects on BP have yielded controversial results. We hypothesized that XO inhibition would decrease BP or attenuate the development of DOCA-salt hypertension. We administered the XO inhibitor, allopurinol (50 mg/kg/day, orally) or its vehicle to rats during the established or development stages of DOCA-salt hypertension. We validated XO inhibition by HPLC measurements of XO metabolites in urine, serum and tissues demonstrating decrease in products, increase in substrates and detection of the active metabolite of allopurinol, oxypurinol. We monitored BP continuously via radiotelemetry and performed gross evaluations of target organs of hypertension. Allopurinol treatment did not impact the course of DOCA-salt hypertension, regardless of the timing of administration. Aside from a significant decrease in pulse pressure in allopurinol-treated rats, no positive differences were observed between the allopurinol and the vehicle-treated rats. We conclude that XO does not play an important role in the development or maintenance of hypertension in the rat DOCA-salt hypertension model. PMID:20881613

  13. Allopurinol does not decrease blood pressure or prevent the development of hypertension in the deoxycorticosterone acetate-salt rat model.

    Science.gov (United States)

    Szasz, Theodora; Linder, A Elizabeth; Davis, Robert P; Burnett, Robert; Fink, Gregory D; Watts, Stephanie W

    2010-12-01

    Reactive oxygen species play an important role in the pathogenesis of hypertension, disease in which reactive oxygen species levels and markers of oxidative stress are increased. Xanthine oxidase (XO) is a reactive oxygen species-producing enzyme the activity of which may increase during hypertension. Studies on XO inhibition effects on blood pressure have yielded controversial results. We hypothesized that XO inhibition would decrease blood pressure or attenuate the development of deoxycorticosterone acetate (DOCA)-salt hypertension. We administered the XO inhibitor, allopurinol (50 mg/kg per day, orally) or its vehicle to rats during the established or development stages of DOCA-salt hypertension. We validated XO inhibition by high-performance liquid chromatography measurements of XO metabolites in urine, serum, and tissues demonstrating a decrease in products, increase in substrates, and detection of the active metabolite of allopurinol, oxypurinol. We monitored blood pressure continuously through radiotelemetry and performed gross evaluations of target organs of hypertension. Allopurinol treatment did not impact the course of DOCA-salt hypertension regardless of the timing of administration. Aside from a significant decrease in pulse pressure in allopurinol-treated rats, no positive differences were observed between the allopurinol and the vehicle-treated rats. We conclude that XO does not play an important role in the development or maintenance of hypertension in the rat DOCA-salt hypertension model.

  14. Relationship of adipocyte size to hyperphagia in developing male obese Zucker rats.

    Science.gov (United States)

    Vasselli, J R; Fiene, J A; Maggio, C A

    1992-01-01

    In growing male obese Zucker rats, hyperphagia reaches a maximum or "breakpoint" and declines at an earlier age with high fat than with chow-type diets. A serial adipose tissue biopsy technique was used to correlate changes of retroperitoneal adipocyte size and feeding behavior in 5- to 7-wk-old male lean and obese rats fed laboratory chow or a 35% fat diet until 30 wk of age. Although chow-fed groups had significantly greater cumulative intake, fat-fed groups had significantly greater body weight gain, retroperitoneal depot weight, and adipocyte number. Mean adipocyte size increased continuously in chow-fed groups but decreased over weeks 20-30 in fat-fed groups, reflecting increased adipocyte number. In fat-fed obese rats, hyperphagia reached a breakpoint at 11 wk and disappeared by 13 wk. In chow-fed obese rats, hyperphagia reached a breakpoint at 15-16 wk and disappeared by 19 wk. Biopsy samples revealed that adipocyte size of fat-fed obese rats was already close to maximal at 10 wk (1.12 micrograms lipid), while that of chow-fed obese rats only approached maximal at 20 wk (0.81 microgram lipid). At these time points, lipoprotein lipase activity paralleled adipocyte size. These data indicate that the duration of the growing obese rat's hyperphagia coincides with adipocyte filling and suggest the existence of feeding stimulatory and inhibitory signals from adipose tissue.

  15. Altered placental development in undernourished rats: role of maternal glucocorticoids

    Directory of Open Access Journals (Sweden)

    Chen Chun-Hung

    2011-08-01

    Full Text Available Abstract Maternal undernutrition (MUN during pregnancy may lead to fetal intrauterine growth restriction (IUGR, which itself predisposes to adult risk of obesity, hypertension, and diabetes. IUGR may stem from insufficient maternal nutrient supply or reduced placental nutrient transfer. In addition, a critical role for maternal stress-induced glucocorticoids (GCs has been suggested to contribute to both IUGR and the ensuing risk of adult metabolic syndrome. While GC-induced fetal organ defects have been examined, there have been few studies on placental responses to MUN-induced maternal stress. Therefore, we hypothesize that 50% MUN associates with increased maternal GC levels and decreased placental HSD11B. This in turn leads to decreased placental and fetal growth, hence the need to investigate nutrient transporters. We measured maternal serum levels of corticosterone, and the placental basal and labyrinth zone expression of glucocorticoid receptor (NR3C1, 11-hydroxysteroid dehydrogenase B 1 (HSD11B-1 predominantly activates cortisone to cortisol and 11-dehydrocorticosterone (11-DHC to corticosterone, although can sometimes drive the opposing (inactivating reaction, and HSD11B-2 (only inactivates and converts corticosterone to 11-DHC in rodents in control and MUN rats at embryonic day 20 (E20. Moreover, we evaluated the expression of nutrient transporters for glucose (SLC2A1, SLC2A3 and amino acids (SLC38A1, 2, and 4. Our results show that MUN dams displayed significantly increased plasma corticosterone levels compared to control dams. Further, a reduction in fetal and placental weights was observed in both the mid-horn and proximal-horn positions. Notably, the placental labyrinth zone, the site of feto-maternal exchange, showed decreased expression of HSD11B1-2 in both horns, and increased HSD11B-1 in proximal-horn placentas, but no change in NR3C1. The reduced placental GCs catabolic capacity was accompanied by downregulation of SLC2A3, SLC

  16. Corruption Significantly Increases the Capital Cost of Power Plants in Developing Contexts

    Directory of Open Access Journals (Sweden)

    Kumar Biswajit Debnath

    2018-03-01

    Full Text Available Emerging economies with rapidly growing population and energy demand, own some of the most expensive power plants in the world. We hypothesized that corruption has a relationship with the capital cost of power plants in developing countries such as Bangladesh. For this study, we analyzed the capital cost of 61 operational and planned power plants in Bangladesh. Initial comparison study revealed that the mean capital cost of a power plant in Bangladesh is twice than that of the global average. Then, the statistical analysis revealed a significant correlation between corruption and the cost of power plants, indicating that higher corruption leads to greater capital cost. The high up-front cost can be a significant burden on the economy, at present and in the future, as most are financed through international loans with extended repayment terms. There is, therefore, an urgent need for the review of the procurement and due diligence process of establishing power plants, and for the implementation of a more transparent system to mitigate adverse effects of corruption on megaprojects.

  17. The development and significance of the DOE Safeguards and Security standards and criteria

    International Nuclear Information System (INIS)

    Toman, J.

    1987-01-01

    In October 1985, the DOE Assistant Secretary for Defense Programs created a task force to develop inspection standards and criteria for Safeguards and Security. These standards and criteria (S/C) would provide the DOE Inspection and Evaluation (I and E) teams with the guidance needed to assess the security posture of DOE's nuclear and other important facilities. The Lawrence Livermore National Laboratory was designated the lead management organization for the structuring, administration, and execution of the overall task force effort and appointed the Executive Secretary. The Office of Security Evaluations (OSE) became the responsible DOE organization, and its Director assumed the role of Chairman of the Task Force Executive Committee. At its peak, the Task Force consisted of approximately 200 people who were considered to be experts in eight major topical areas. The composition of the experts was almost evenly divided between DOE and contractor employees. The collective wisdom of these experts was used in a consensus process to develop the S/C that are now published in draft form. These S/C have been used in more than ten inspections since May 1986 with much success. This paper discusses the process used to achieve the desired end result and the significance of the Task Force's accomplishments

  18. [Significance of early diagnosis of posterior urethral valves in fetus for further development - own experience].

    Science.gov (United States)

    Krzemień, Grażyna; Szmigielska, Agnieszka; Wawer, Zofia; Roszkowska-Blaim, Maria

    2013-01-01

    The incidence of posterior urethral valves is estimated to be from 3:1000 to 8:1000 and this is one of the most common causes of obstruction of urinary tract in boys. About 13-17% of children with posterior urethral valves develop end stage renal failure. We present a  6-month-old boy with late diagnosis of posterior urtehral valves. Antenatal ultrasound investigation of the urinary tract was normal. A small degree of oligohydramnios was found during delivery. At the age of six months the boy was admitted to hospital because of urinary tract infection, hypertension (130/90 mmHg) and acute kidney injury (urea - 46 mg/dL, creatinine - 1.1 mg/dL, GFR - 35.5 mL/min/1.73 m2 ). Bilateral hydronephrosis and megaureters, low-capacity bladder with hypertrophied wall were seen on ultrasound examination. Voiding cystourethrograhy revealed vesicoureteral refluxes (III/V), hypertrophy of the bladder wall with numerous diverticula and dilated posterior urethra. During urethroscopy urethral valves were resected. Increased intravesical pressure (leak point up to 305 cm H2 O) was found on urodynamic test. Renal scintigraphy (99mTc-EC) revealed decreased intake of isotope in the left kidney (5%), and the right kidney intake was 95% ERPF. The patient was qualified for left-sided nephrectomy, which was postponed because of high leak point and high risk of worsening of vesicoureteral reflux to right kidney after nephrectomy. Anticholinergic and α-blocker treatment was started. At the age of 11 months left-side nephrectomy was performed because of recurrent urinary tract infections. After 3.5-year follow-up blood pressure, physical development, kidney function tests, and urinalysis are normal. Additionally to this investigation the significance of early diagnosis including prenatal (PUV) for further development as well as further therapeutic procedure is discussed.

  19. The reversible P2Y12 antagonist ACT-246475 causes significantly less blood loss than ticagrelor at equivalent antithrombotic efficacy in rat.

    Science.gov (United States)

    Rey, Markus; Kramberg, Markus; Hess, Patrick; Morrison, Keith; Ernst, Roland; Haag, Franck; Weber, Edgar; Clozel, Martine; Baumann, Martine; Caroff, Eva; Hubler, Francis; Riederer, Markus A; Steiner, Beat

    2017-10-01

    The P2Y 12 receptor is a validated target for prevention of major adverse cardiovascular events in patients with acute coronary syndrome. The aim of this study was to compare two direct-acting, reversible P2Y 12 antagonists, ACT-246475 and ticagrelor, in a rat thrombosis model by simultaneous quantification of their antithrombotic efficacy and surgery-induced blood loss. Blood flow velocity was assessed in the carotid artery after FeCl 3 -induced thrombus formation using a Doppler flow probe. At the same time, blood loss after surgical wounding of the spleen was quantified. Continuous infusions of ACT-246475 and ticagrelor prevented the injury-induced reduction of blood flow in a dose-dependent manner. High doses of both antagonists normalized blood flow and completely abolished thrombus formation as confirmed by histology. Intermediate doses restored baseline blood flow to ≥65%. However, ACT-246475 caused significantly less increase of blood loss than ticagrelor; the difference in blood loss was 2.6-fold (P ACT-246475 and ticagrelor on vascular tone. At concentrations needed to achieve maximal antithrombotic efficacy, ticagrelor compared with ACT-246475 significantly increased carotid blood flow velocity in vivo (P = 0.003), induced vasorelaxation of precontracted rat femoral arteries, and inhibited contraction of femoral artery induced by electrical field stimulation or by phenylephrine. Overall, ACT-246475 showed a significantly wider therapeutic window than ticagrelor. The absence of vasodilatory effects due to high selectivity of ACT-246475 for P2Y 12 provides potential arguments for the observed safety advantage of ACT-246475 over ticagrelor. © 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

  20. The Development and Significance of Standards for Smoking-Machine Methodology

    Directory of Open Access Journals (Sweden)

    Baker R

    2014-12-01

    Full Text Available Bialous and Yach have recently published an article in Tobacco Control in which they claim that all smoking-machine standards stem from a method developed unilaterally by the tobacco industry within the Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA. Using a few highly selective quotations from internal tobacco company memos, they allege, inter alia, that the tobacco industry has changed the method to suit its own needs, that because humans do not smoke like machines the standards are of little value, and that the tobacco industry has unjustifiably made health claims about low “tar” cigarettes. The objectives of this paper are to review the development of smoking-machine methodology and standards, involvement of relative parties, outline the significance of the results and explore the validity of Bialous and Yach's claims. The large volume of published scientific information on the subject together with other information in the public domain has been consulted. When this information is taken into account it becomes obvious that the very narrow and restricted literature base of Bialous and Yach's analysis has resulted in them, perhaps inadvertedly, making factual errors, drawing wrong conclusions and writing inaccurate statements on many aspects of the subject. The first smoking-machine standard was specified by the Federal Trade Commission (FTC, a federal government agency in the USA, in 1966. The CORESTA Recommended Method, similar in many aspects to that of the FTC, was developed in the late 1960s and published in 1969. Small differences in the butt lengths, smoke collection and analytical procedures in methods used in various countries including Germany, Canada and the UK, developed later, resulted in about a 10% difference in smoke “tar” yields. These differences in methodology were harmonised in a common International Organisation for Standardisation (ISO Standard Method in 1991, after a considerable amount

  1. Music exposure improves spatial cognition by enhancing the BDNF level of dorsal hippocampal subregions in the developing rats.

    Science.gov (United States)

    Xing, Yingshou; Chen, Wenxi; Wang, Yanran; Jing, Wei; Gao, Shan; Guo, Daqing; Xia, Yang; Yao, Dezhong

    2016-03-01

    Previous research has shown that dorsal hippocampus plays an important role in spatial memory process. Music exposure can enhance brain-derived neurotrophic factor (BDNF) expression level in dorsal hippocampus (DH) and thus enhance spatial cognition ability. But whether music experience may affect different subregions of DH in the same degree remains unclear. Here, we studied the effects of exposure to Mozart K.448 on learning behavior in developing rats using the classical Morris water maze task. The results showed that early music exposure could enhance significantly learning performance of the rats in the water maze test. Meanwhile, the BDNF/TrkB level of dorsal hippocampus CA3 (dCA3) and dentate gyrus (dDG) was significantly enhanced in rats exposed to Mozart music as compared to those without music exposure. In contrast, the BDNF/TrkB level of dorsal hippocampus CA1 (dCA1) was not affected. The results suggest that the spatial memory improvement by music exposure in rats may be associated with the enhanced BDNF/TrkB level of dCA3 and dDG. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Development and validation of the activity significance personal evaluation (ASPEn) scale.

    Science.gov (United States)

    Mallinson, Trudy; Schepens Niemiec, Stacey L; Carlson, Mike; Leland, Natalie; Vigen, Cheryl; Blanchard, Jeanine; Clark, Florence

    2014-12-01

    Engagement in desired occupations can promote health and wellbeing in older adults. Assessments of engagement often measure frequency, amount or importance of specific activities. This study aimed to develop a scale to measure older adults' evaluation of the extent to which their everyday activities are contributing to their health and wellness. Eighteen items, each scored with a seven-point rating scale, were initially developed by content experts, covering perceptions of how daily activities contribute to physical and mental health, as well as satisfaction and activity participation in the last six months. Rasch analysis methods were used to refine the scale using the pencil and paper responses of 460 community-living older adults. Initial Rasch analysis indicated three unlabelled rating scale categories were seldom used, reducing measurement precision. Five items were conceptually different by misfit statistics and principal component analysis. Subsequently, those items were removed and the number of rating scale steps reduced to 4. The remaining 13-item, 4-step scale, termed the Activity Significance Personal Evaluation (ASPEn), formed a unidimensional hierarchy with good fit statistics and targeting. Person separation reliability (2.7) and internal consistency (.91) indicated the tool is appropriate for individual person measurement. Relative validity indicated equivalence between Rasch measures and total raw scores. ASPEn is a brief, easily administered assessment of older adults' perception of the contribution of everyday activities to personal health and wellness. ASPEn may facilitate occupational therapy practice by enabling clinicians to assess change in meaning of an older adult's activity over time. © 2014 Occupational Therapy Australia.

  3. Effects of clothianidin exposure on sperm quality, testicular apoptosis and fatty acid composition in developing male rats.

    Science.gov (United States)

    Bal, Ramazan; Türk, Gaffari; Yılmaz, Ökkeş; Etem, Ebru; Kuloğlu, Tuncay; Baydaş, Gıyasettin; Naziroğlu, Mustafa

    2012-06-01

    Clothianidin (CTD) is one of the latest members of the synthetic organic insecticides, the neonicotinoids. In the present study, it was aimed to investigate if daily oral administration of CTD at low doses for 90 days has any deleterious effects on reproductive functions of developing male rats. Animals were randomly divided into four groups of six rats each, assigned as control rats, or rats treated with 2 (CTD-2), 8 (CTD-8) or 32 (CTD-32) mg CTD/kg body weight by oral gavage. The significant decreases of the absolute weights of right cauda epididymis and seminal vesicles, and body weight were detected in the animals exposed to CTD administration at 32 mg/kgBW/day. Epididymal sperm concentration decreased significantly in CTD-32 group and the abnormal sperm rates increased in CTD-8 and CTD-32 groups when compared to control group. The testosterone level was significantly decreased in CTD-32 group when compared to control group. The administration of all CTD doses resulted in a significant decrease in the level of GSH. The number of TUNEL-positive cells significantly increased in the germinal epithelium of testis of rats exposed to CTD at 32 mg/kgBW/day. In groups CTD-8 and CTD-32, only docosapentaenoic, arachidonic, palmitic and palmitoleic acids were significantly elevated when compared to control. The ratios of 20:4/18:2 and 18:1n-9/18:0 were decreased when rats exposed to CTD. Sperm DNA fragmentation was observed in CTD-32 group, but not CTD-2 and CTD-8. It is concluded that low doses of CTD exposure during critical stages of sexual maturation had moderate detrimental effects on reproductive organ system and more severe effects are likely to be observed at higher dose levels. In addition, the reproductive system may be more sensitive to exposure of CTD even earlier in development (prenatal and early postnatal), and therefore it could be expected that more severe effects could also be observed at the NOAEL dose levels, if dosing had occurred in utero or early

  4. Weight-related stigma is a significant psychosocial stressor in developing countries: Evidence from Guatemala.

    Science.gov (United States)

    Hackman, Joseph; Maupin, Jonathan; Brewis, Alexandra A

    2016-07-01

    Weight-related stigma is established as a major psychosocial stressor and correlate of depression among people living with obesity in high-income countries. Anti-fat beliefs are rapidly globalizing. The goal of the study is to (1) examine how weight-related stigma, enacted as teasing, is evident among women from a lower-income country and (2) test if such weight-related stigma contributes to depressive symptoms. Modeling data for 12,074 reproductive-age women collected in the 2008-2009 Guatemala National Maternal-Infant Health Survey, we demonstrate that weight-related teasing is (1) experienced by those both underweight and overweight, and (2) a significant psychosocial stressor. Effects are comparable to other factors known to influence women's depressive risk in lower-income countries, such as living in poverty, experiencing food insecurity, or suffering sexual/domestic violence. That women's failure to meet local body norms-whether they are overweight or underweight-serves as such a strong source of psychological distress is particularly concerning in settings like Guatemala where high levels of over- and under-nutrition intersect at the household and community level. Current obesity-centric models of weight-related stigma, developed from studies in high-income countries, fail to recognize that being underweight may create similar forms of psychosocial distress in low-income countries. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Development and Significance of the E-surveillance System for Contact Allergies in Slovenia.

    Science.gov (United States)

    Dugonik, Aleksandra; Kalač Pandurovič, Maja; Vok, Marko; Dugonik, Bogdan

    2017-07-01

    This paper describes the development and significance of online systems for the collection and analysis of medical data (patch test results) with a web application. Modern digital tools greatly aid in collecting, combining, and preserving the data in a way that is friendly, undemanding and time-efficient for the dermatologist. Creating a central database for the results of patch testing provides a better picture of contact sensitivity and characteristics of allergic contact dermatitis in Slovenia. An electronic database and connected network was started in Slovenia in 2010. Data from skin allergy units since 2000 has also been included retrospectively. At present (Oct 2016), the database contains the data of 19,772 patch tests performed by seven skin allergy units. Creating a central database of the results of patch testing provides a larger and therefore more credible collection of data. Immediate integration and data processing enable a current overview of contact sensitivity for each participating center as well as at the national level. Data can be easily transferred to other databases or edited with other software tools. This on-line register has worked flawlessly for more than five years. We have contributed data to the European Surveillance System on Contact Allergies (ESSCA) network database since 2012, which, along with the Deutsche Kontaktallergie-Gruppe system of collecting patch test data for German-speaking countries, represents the only multicenter surveillance system of patch test results in Europe.

  6. Decreased prothrombotic effects of pegylated recombinant human megakaryocyte growth and development factor in thrombocytopenic state in a rat thrombosis model.

    Science.gov (United States)

    Nishiyama, U; Kuwaki, T; Akahori, H; Kato, T; Ikeda, Y; Miyazaki, H

    2005-02-01

    Previous in vitro studies demonstrated that thrombopoietin (TPO) acts on platelets to activate a variety of intracellular signaling pathways and to enhance platelet sensitivity to multiple agonists. Little is known, however, about whether TPO exerts prothrombotic effects in vivo. The aim of this study was to examine the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a pegylated N-terminal domain of human TPO, in a rat model of venous thrombosis. A microthrombus was photochemically induced on the vessel wall of a mesenteric venule, but the vessel was not occluded by it. A single intravenous injection of PEG-rHuMGDF (3 microg kg(-1)) after the thrombus generation into normal rats enhanced the thrombus size, resulting in transient thrombotic occlusion in the majority of rats. Stimulatory effects on thrombus growth were also observed following administration of glycosylated recombinant human full-length TPO (6 microg kg(-1)). In rats rendered thrombocytopenic by total body irradiation, however, PEG-rHuMGDF, even at 300 microg kg(-1), did not induce a significant increase in thrombus size or thrombotic occlusion. Platelets from thrombocytopenic rats had decreased surface levels of c-Mpl and decreased sensitivity to PEG-rHuMGDF in an in vitro aggregation response. Thus, decreased prothrombotic effects of PEG-rHuMGDF in thrombocytopenic rats might be the result not only of low platelet counts but also of decreased platelet reactivity to PEG-rHuMGDF. These results indicate that PEG-rHuMGDF has little effect on venous thrombus formation in thrombocytopenic states associated with high endogenous TPO levels.

  7. Embryo-fetal development toxicity of honokiol microemulsion intravenously administered to pregnant rats.

    Science.gov (United States)

    Zhang, Qianqian; Ye, Xiangfeng; Wang, Lingzhi; Peng, Bangjie; Zhang, Yingxue; Bao, Jie; Li, Wanfang; Wei, Jinfeng; Wang, Aiping; Jin, Hongtao; Chen, Shizhong

    2016-02-01

    The aim of this study was to evaluate the embryo-fetal development toxicity of honokiol microemulsion. The drug was intravenously injected to pregnant SD rats at dose levels of 0, 200, 600 and 2000 μg/kg/day from day 6-15 of gestation. All the pregnant animals were observed for body weights and any abnormal changes and subjected to caesarean-section on gestation day (GD) 20; all fetuses obtained from caesarean-section were assessed by external inspection, visceral and skeletal examinations. No treatment-related external alterations as well as visceral and skeletal malformations were observed in honokiol microemulsion groups. There was no significant difference in the body weight gain of the pregnant rats, average number of corpora lutea, and the gravid uterus weight in the honokiol microemulsion groups compared with the vehicle control group. However, at a dose level of 2000 μg/kg/day, there was embryo-fetal developmental toxicity observed, including a decrease in the body length and tail length of fetuses. In conclusion, the no-observed-adverse-effect level (NOAEL) of honokiol microemulsion is 600 μg/kg/day, 75 times above the therapeutic dosage and it has embryo-fetal toxicity at a dose level of 2000 μg/kg/day, which is approximately 250 times above the therapeutic dosage. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Changes in calcium uptake rate by rat cardiac mitochondria during postnatal development.

    Science.gov (United States)

    Bassani, R A; Fagian, M M; Bassani, J W; Vercesi, A E

    1998-10-01

    Ca2+ uptake, transmembrane electrical potential (Deltapsim) and oxygen consumption were measured in isolated ventricular mitochondria of rats from 3 days to 5 months of age. Estimated values of ruthenium red-sensitive, succinate-supported maximal rate of Ca2+ uptake (Vmax, expressed as nmol Ca2+/min/mg protein) were higher in neonates and gradually fell during postnatal development (from 435+/-24 at 3-6 days, to 156+/-10 in adults,Palpha-ketoglutarate as substrates) and state 3ADP (alpha-ketoglutarate-supported) respiration rates, as well as Deltapsim values (approximately-150 mV). Respiration-independent Deltapsim and Ca2+ uptake, supported by valinomycin-induced K+ efflux were also investigated at these ages. A transient Deltapsim (approximately -30 mV) was evoked by valinomycin in both neonatal and adult mitochondria. Respiration-independent Ca2+ uptake was also transient, but its initial rate was significantly higher in neonates than in adults (49. 4+/-10.0v 28.0+/-5.7 mmol Ca2+/min/mg protein,P<0.01). These results indicate that Ca2+ uptake capacity of rat cardiac mitochondria is remarkably high just after birth and declines over the first weeks of postnatal life, without change in apparent affinity of the transporter. Increased mitochondrial Ca2+ uptake rate in neonates appears to be related to the uniporter itself, rather than to modification of the driving force of the transport. Copyright 1998 Academic Press

  9. ANTXR2 Knock-Out Does Not Result in the Development of Hypertension in Rats.

    Science.gov (United States)

    Liu, Xiaoyan; Yuan, Wen; Li, Jing; Yang, Lei; Cai, Jun

    2017-02-01

    Our recent genetic study as well as robust evidences reported by previous genome-wide association studies (GWASs) have indicated that the single nucleotide polymorphism rs16998073, located near gene anthrax toxin receptor 2 (ANTXR2), was significantly associated with hypertension in Asians and Europeans. The aim of the present study was to determine whether ANTXR2 is the causal gene of hypertension at the 4q21 locus using an ANTXR2 knock-out model. Relative expression of ANTXR2 in Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) were determined by real-time quantitative polymerase chain reaction and western blot analysis. ANTXR2 knock-out rats were created using CRISPR/Cas9-mediated genome editing and blood pressure values were measured in ANTXR2 -/- and wild type (WT) rats by tail-cuff method and carotid arterial catheterization method. Neither the mRNA nor protein levels of ANTXR2 were significantly different between tissues from SHRs and WKYs. To create ANTXR2 -/- rats, 67 base pairs were deleted in exon 1 of ANTXR2 using CRISPR/Cas9-mediated genome editing. ANTXR2 protein decreased significantly in aortas of ANTXR2 -/- rats, suggesting sufficient efficiency of ANTXR2 knock-out in this model. However, ANTXR2 -/- rats exhibited nearly the same blood pressure as WT rats at baseline conditions as well as during Angiotensin II (400ng/kg/min) infusion or high-salt diet treatment. These findings suggest that ANTXR2 might not be associated with hypertension and thus further functional analysis is warranted to identify the causal gene at this locus. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Tissue-specific splicing pattern of fibronectin messenger RNA precursor during development and aging in rat

    OpenAIRE

    1991-01-01

    Fibronectin isoforms are generated by the alternative splicing of a primary transcript derived from a single gene. In rat at least three regions of the molecule are involved: EIIIA, EIIIB, and V. This study investigated the splicing patterns of these regions during development and aging, by means of ribonuclease protection analysis. Between fetal and adult rat, the extent of inclusion of the EIIIA and/or EIIIB region in fibronectin mRNA varied according to the type of tissue analyzed; but the...

  11. Diagnostical significance of dimethylarginine in the development of hepatorenal syndrome in patients with alcoholic liver cirrhosis

    Directory of Open Access Journals (Sweden)

    Ničković Vanja

    2012-01-01

    Full Text Available Background/Aim. Chronic consumption of alcohol during a longer period of time leads to the development of cirrhosis with the reduction in metabolic liver function and disorders in arginine metabolism. Hepatorenal syndrome (HRS is the most severe complication of alcoholic liver cirrhosis. The aim of the study was to analyze disorders in arginine metabolism by monitoring concentrations of asymmetric dimethylarginine (ADMA and symmetric dimethylarginine (SDMA in patients with liver cirrhosis and HRS. Methods. The study included three groups of subjects: a group of patients with cirrhosis and HRS (24 patients, a group of patients with cirrhosis without HRS (18 patients and a control group composed of 42 healthy voluntary blood donors. Concentrations of ADMA, SDMA and L-arginine in plasma were measured in all groups using the high pressure liquid chromatography (HPLC method. Results. The concentration of SDMA was significantly higher in the patients with HRS compared to the patients without HRS and it was also higher than the values obtained from the healthy participants (1.76 ± 0.3 μmol/L; 1.01 ± 0.32 and 0.520 ± 0.18 μmol/L, respectively; p < 0.01. The concentrations of ADMA were higher in the cirrhotic patients with HRS than in those without this serious complication of cirrhosis. The concentration of ADMA in all the examined cirrhotic patients was higher than those obtained from healthy volunteers (1.35 ± 0.27 μmol/L, 1.05 ± 0.35 μmol/L and 0.76 ± 0.21 μmol/L, respectively. In the patients with terminal alcoholic liver cirrhosis, the concentrations of ADMA and SDMA correlated with the progress of cirrhosis as well as with the development of cirrhosis complications. In the patients with HRS there was a positive correlation between creatinine and SDMA in plasma (r2 = 0.0756, p < 0.001 which was not found between creatinine and ADMA. Conclusion. The obtained results demonstrate that the increase in SDMA concentration is proportionate to

  12. Protective effect of pyruvate against ethanol-induced apoptotic neurodegeneration in the developing rat brain.

    Science.gov (United States)

    Ullah, Najeeb; Naseer, Muhammad Imran; Ullah, Ikram; Lee, Hae Young; Koh, Phil Ok; Kim, Myeong Ok

    2011-12-01

    Exposure to alcohol during the early stages of brain development can lead to neurological disorders in the CNS. Apoptotic neurodegeneration due to ethanol exposure is a main feature of alcoholism. Exposure of developing animals to alcohol (during the growth spurt period in particular) elicits apoptotic neuronal death and causes fetal alcohol effects (FAE) or fetal alcohol syndrome (FAS). A single episode of ethanol intoxication (at 5 g/kg) in a seven-day-old developing rat can activate the apoptotic cascade, leading to widespread neuronal death in the brain. In the present study, we investigated the potential protective effect of pyruvate against ethanol-induced neuroapoptosis. After 4h, a single dose of ethanol induced upregulation of Bax, release of mitochondrial cytochrome-c into the cytosol, activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP-1), all of which promote apoptosis. These effects were all reversed by co-treatment with pyruvate at a well-tolerated dosage (1000 mg/kg). Histopathology performed at 24 and 48 h with Fluoro-Jade-B and cresyl violet stains showed that pyruvate significantly reduced the number of dead cells in the cerebral cortex, hippocampus and thalamus. Immunohistochemical analysis at 24h confirmed that ethanol-induced cell death is both apoptotic and inhibited by pyruvate. These findings suggest that pyruvate treatment attenuates ethanol-induced neuronal cell loss in the developing rat brain and holds promise as a safe therapeutic and neuroprotective agent in the treatment of neurodegenerative disorders in newborns and infants. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Leptin administration affects growth and skeletal development in a rat intrauterine growth restriction model: preliminary study.

    Science.gov (United States)

    Bar-El Dadon, Shimrit; Shahar, Ron; Katalan, Vered; Monsonego-Ornan, Efrat; Reifen, Ram

    2011-09-01

    Skeletal abnormalities are one of the hallmarks of growth delay during gestation. The aim of this study was to determine changes induced by leptin in skeletal growth and development in a rat model of intrauterine growth retardation (IUGR) and to elucidate the possible underlying mechanisms. Intrauterine growth retardation was induced prepartum and the effects of leptin to mothers prenatally or to offspring postnatally were studied. Radii were harvested and tested mechanically and structurally. Tibias were evaluated for growth-plate morphometry. On day 40 postpartum, total bone length and mineral density and tibial growth-plate width and numbers of cells within its zones of offspring treated with leptin were significantly greater than in the control group. Postnatal leptin administration in an IUGR model improves the structural properties and elongation rate of bone. These findings could pave the way to preventing some phenotypic presentations of IUGR. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Effect of noise on the development of induced sclerotic processes in the rat aorta.

    Science.gov (United States)

    Antov, G; Ivanovich, E; Kazakova, B; Goranova, L

    1985-01-01

    The authors studied the effect of 95 and 85 dB noise on the aortic wall of white rats fed for a period of 6 weeks an atherogenic diet (cholesterol + cholic acid + vitamin D2). Noise alone did not cause significant changes in the metabolism and structure of the aorta. The atherogenic diet alone caused segmental enlargement of the intercellular substance, disorganization of tissue elements, and destruction of smooth-muscle cells with marked activation of anaerobic processes, an increase in collagen content and a decrease in globular proteins and elastin. Simultaneous action of noise and of the atherogenic diet produced more pronounced biochemical and morphological alterations in the aortic wall than the diet alone. Noise not only contributes to the development of sclerotic processes but causes also complicated lesions of the aortic wall.

  15. Expression of Oct-4 is significantly associated with the development and prognosis of colorectal cancer

    Science.gov (United States)

    ZHOU, HUAN; HU, YU; WANG, WEIPENG; MAO, YONG; ZHU, JINGJIE; ZHOU, BIN; SUN, JING; ZHANG, XUEGUANG

    2015-01-01

    Octamer-binding transcription factor 4 (Oct-4), is an essential transcription factor, which is required for pluripotency and self-renewal in embryonic stem cells and germ cells. It is also involved in maintaining cancer stem-like properties in certain types of tumor, and is an important biomarker for cancer stem cells. The present study investigated whether Oct-4 expression was associated with colorectal cancer (CRC). In order to achieve this, primary CRC tissues, matched non-tumor tissues and benign polyp tissues, representing different stages of carcinogenesis, were obtained, and Oct-4 expression was analyzed using reverse transcription-quantitative polymerase chain reaction, flow cytometry analysis and immunohistochemistry. Furthermore, the medical records of patients with CRC were reviewed, and clinicopathological analysis was performed in order to assess the association between Oct-4 expression and certain clinicopathological parameters. It was shown that the transcription and translation of Oct-4 increased in a stepwise manner, from non-tumor to benign polyp tissues, and from benign polyps to CRC tissues. Oct-4 expression in CRC was significantly correlated with histological grade (P=0.007), lymph node metastasis (P=0.027), distant metastasis (P=0.017) and TNM stage (P=0.041). Kaplan-Meier survival curve analysis demonstrated that Oct-4+ cases had a shorter median survival time (37.0 months) compared with Oct-4− cases (76.0 months; P=0.001). These results indicated that aberrant expression of Oct-4 may be involved in the development of CRC. Thus, Oct-4 may be a biomarker for the prediction, diagnosis or assessment of prognosis in CRC, in addition to a potential target for the treatment of this disease. PMID:26622555

  16. The socio-economic significance of the Turkish coastal environment for sustainable development.

    Science.gov (United States)

    Kuleli, Tuncay

    2015-05-01

    The objective of this study was to estimate the contribution from the coastal resources in the coastal region to the national economy for sustainable development. There was no separate data base for the coastal zone so that the contribution from the coastal resources in the coastal region to the national economy was not evaluated. In estimating the significance of Turkish coastal cities, indirect methods and the geographical information system were used. In conclusion, it was found that 61.09% of the total national gross domestic product and 50.75% of the national agricultural, 90.98% of the national fisheries, 68.19% of the national tourism and 71.82% of the national industrial gross domestic product came from the coastal zone. It was determined that while coastal cities of Turkey had 28.23% of the national surface area, the coastal district had 12.96%; in other words, 21.5 million (28.04%) of the national population lived in 101.5 thousand km(2) (12.96%) of the national surface area. Approximately 44% of the national gross domestic product comes from the top ten coastal cities. According to the contribution ratio to the national economy of each coastal city, these low-lying coastal cities have about $16 billion risk value. An analysis showed that the coastal zone is very important for the national economy of Turkey and also the pressure on the coastal zone is very high. At a time of increasing pressures on coastal resources of Turkey, the decision-makers need the most up-to-date information on the full range of values these resources provide in order to make decisions that best reflect the public interest.

  17. Effects of protein-deficient nutrition during rat pregnancy and development on developmental hindlimb crossing due to methylmercury intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Chakrabarti, S.K.; Bai, Chengjiang [Montreal Univ., Quebec (Canada). Dept. de Medecine du Travail et Hygiene du Milieu

    2000-07-01

    Pregnant rats were fed either a control (20% protein) or low (3.5%) protein diet during gestation and lactation. The pups were separated from their mothers on postnatal day 21, and were given the same dient as their corresponding mothers. The groups of pups from each diet group were treated on either postnatal day 21 or postnatal day 60 with 7.5 mg methylmercury chloride (MeHgCl) per kg b.w. once daily by gavage for 10 consecutive days, and the development of ataxia (hind-limb corossing) was monitored. The offspring from mothers on the protein-deficient diet were found to be more sensitive to MeHg-induced ataxia than those on the protein-sufficient diet. The former accumulated more mercury in different brain regions than the latter. The rates of protein synthesis in different brain regions of the offspring fed the protein-deficient diet were significantly reduced compared with the rates in those fed the protein-sufficient diet. However, MeHg treatment did not significantly modify the rates of such protein synthesis further in protein-deficient rats. Thus, a significantly much higher inhibition of the intrinsic rates of protein synthesis in different brain regions due to severe protein deficiency, as observed in this study, may be partly responsible for the increased susceptibility of developing rats fed a protein-deficient diet to MeHg-induced ataxia, or hindlimb crossing, although other factor(s) might also be involved. (orig.)

  18. Perinatal and chronic hypothyroidism impair behavioural development in male and female rats.

    NARCIS (Netherlands)

    Wijk, van N.; Rijntjes, E.; Heijning, van de B.J.

    2008-01-01

    Perinatal and chronic hypothyroidism impair behavioural development in male and female rats. EXP PHYSIOL 00(0) 000-000, 0000. - A lack of thyroid hormone, i.e. hypothyroidism, during early development results in multiple morphological and functional alterations in the developing brain. In the

  19. Insulin and vanadium protect against osteoarthritis development secondary to diabetes mellitus in rats.

    Science.gov (United States)

    El Karib, Abbas O; Al-Ani, Bahjat; Al-Hashem, Fahaid; Dallak, Mohammad; Bin-Jaliah, Ismaeel; El-Gamal, Basiouny; Bashir, Salah O; Eid, Refaat A; Haidara, Mohamed A

    2016-07-01

    Diabetic complications such as cardiovascular disease and osteoarthritis (OA) are among the common public health problems. The effect of insulin on OA secondary to diabetes has not been investigated before in animal models. Therefore, we sought to determine whether insulin and the insulin-mimicking agent, vanadium can protect from developing OA in diabetic rats. Type 1 diabetes mellitus (T1DM) was induced in Sprague-Dawley rats and treated with insulin and/or vanadium. Tissues harvested from the articular cartilage of the knee joint were examined by scanning electron microscopy, and blood samples were assayed for oxidative stress and inflammatory biomarkers. Eight weeks following the induction of diabetes, a profound damage to the knee joint compared to the control non-diabetic group was observed. Treatment of diabetic rats with insulin and/or vanadium differentially protected from diabetes-induced cartilage damage and deteriorated fibrils of collagen fibers. The relative biological potencies were insulin + vanadium > insulin > vanadium. Furthermore, there was about 2- to 5-fold increase in TNF-α (from 31.02 ± 1.92 to 60.5 ± 1.18 pg/ml, p 1) and IL-6 (from 64.67 ± 8.16 to 338.0 ± 38.9 pg/ml, p 1) cytokines and free radicals measured as TBARS (from 3.21 ± 0.37 to 11.48 ± 1.5 µM, p 1) in the diabetic group, which was significantly reduced with insulin and or vanadium. Meanwhile, SOD decreased (from 17.79 ± 8.9 to 8.250.29, p 1) and was increased with insulin and vanadium. The relative potencies of the treating agents on inflammatory and oxidative stress biomarkers were insulin + vanadium > insulin > vanadium. The present study demonstrates that co-administration of insulin and vanadium to T1DM rats protect against diabetes-induced OA possibly by lowering biomarkers of inflammation and oxidative stress.

  20. Sexual dimorphism in development of kidney damage in aging Fischer-344 rats.

    Science.gov (United States)

    Sasser, Jennifer M; Akinsiku, Oladele; Moningka, Natasha C; Jerzewski, Katie; Baylis, Chris; LeBlanc, Amanda J; Kang, Lori S; Sindler, Amy L; Muller-Delp, Judy M

    2012-08-01

    Aging kidneys exhibit slowly developing injury and women are usually protected compared with men, in association with maintained renal nitric oxide. Our purpose was to test 2 hypotheses: (1) that aging intact Fischer-344 (F344) female rats exhibit less glomerular damage than similarly aged males, and (2) that loss of female ovarian hormones would lead to greater structural injury and dysregulation of the nitric oxide synthase (NOS) system in aging F344 rat kidneys. We compared renal injury in F344 rats in intact, ovariectomized, and ovariectomized with estrogen replaced young (6 month) and old (24 month) female rats with young and old intact male rats and measured renal protein abundance of NOS isoforms and oxidative stress. There was no difference in age-dependent glomerular damage between young or old intact male and female F344 rats, and neither ovariectomy nor estrogen replacement affected renal injury; however, tubulointerstitial injury was greater in old males than in old females. These data suggest that ovarian hormones do not influence these aspects of kidney aging in F344 rats and that the greater tubulointerstitial injury is caused by male sex. Old males had greater kidney cortex NOS3 abundance than females, and NOS1 abundance (alpha and beta isoforms) was increased in old males compared with both young males and old females. NOS abundance was preserved with age in intact females, ovariectomy did not reduce NOS1 or NOS3 protein abundance, and estrogen replacement did not uniformly elevate NOS proteins, suggesting that estrogens are not primary regulators of renal NOS abundance in this strain. Nicotinamide adenine dinucleotide phosphate oxidase-dependent superoxide production and nitrotyrosine immunoreactivity were increased in aging male rat kidneys compared with females, which could compromise renal nitric oxide production and/or bioavailability. The kidney damage expressed in aging F344 rats is fairly mild and is not related to loss of renal cortex NOS3

  1. Influence of omega-3 fatty acids from the flaxseed (Linum usitatissimum) on the brain development of newborn rats.

    Science.gov (United States)

    Lenzi Almeida, K C; Teles Boaventura, G; Guzmán Silva, M A

    2011-01-01

    The importance of essential fatty acids, in particular the omega-3 family, in the central nervous system development of newborns is well documented. The flaxseed (Linum usitatissimum) is considered one of the best vegetable sources of omega-3 fatty acids. The influence of omega-3 fatty acids from flaxseed on the brain development of newborn rats was evaluated. Pups of the F1 generation were obtained from 18 female Wistar rats divided in 3 groups (n=6), FG: fed with diet based on Flaxseed added with casein, CG: Casein, and MCG: Modified Casein supplemented with fibers and soybean oil. Newborn pups were weighted and submitted to euthanasia; brains were collected for evaluation of weight and lipid profile through gaseous chromatography. Significant increase in brain weight (39%) and relative brain weight (37%) was verified in pups from mothers fed with flaxseed diet. The omega-3 (n-3) fatty acids from the flaxseed were found in abundance in the diet made with this oleaginous and also significant increase in docosahexaenoic acid (DHA) (38%), as well as in total of omega-3 (n-3) fatty acids (62%). Maternal diet of flaxseed during pregnancy influences the incorporation of omega-3 fatty acid in the composition of brain tissue, assuring a good development of this organ in newborn rats.

  2. Leukemia inhibitory factor in rat fetal lung development: expression and functional studies.

    Directory of Open Access Journals (Sweden)

    Cristina Nogueira-Silva

    Full Text Available BACKGROUND: Leukemia inhibitory factor (LIF and interleukin-6 (IL-6 are members of the family of the glycoprotein 130 (gp130-type cytokines. These cytokines share gp130 as a common signal transducer, which explains why they show some functional redundancy. Recently, it was demonstrated that IL-6 promotes fetal lung branching. Additionally, LIF has been implicated in developmental processes of some branching organs. Thus, in this study LIF expression pattern and its effects on fetal rat lung morphogenesis were assessed. METHODOLOGY/PRINCIPAL FINDINGS: LIF and its subunit receptor LIFRα expression levels were evaluated by immunohistochemistry and western blot in fetal rat lungs of different gestational ages, ranging from 13.5 to 21.5 days post-conception. Throughout all gestational ages studied, LIF was constitutively expressed in pulmonary epithelium, whereas LIFRα was first mainly expressed in the mesenchyme, but after pseudoglandular stage it was also observed in epithelial cells. These results point to a LIF epithelium-mesenchyme cross-talk, which is known to be important for lung branching process. Regarding functional studies, fetal lung explants were cultured with increasing doses of LIF or LIF neutralizing antibodies during 4 days. MAPK, AKT, and STAT3 phosphorylation in the treated lung explants was analyzed. LIF supplementation significantly inhibited lung growth in spite of an increase in p44/42 phosphorylation. On the other hand, LIF inhibition significantly stimulated lung growth via p38 and Akt pathways. CONCLUSIONS/SIGNIFICANCE: The present study describes that LIF and its subunit receptor LIFRα are constitutively expressed during fetal lung development and that they have an inhibitory physiological role on fetal lung branching.

  3. Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    Oluwafemi O. Oguntibeju

    2016-01-01

    Full Text Available Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ- induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg aqueous solution was administered (daily orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC, ferric reducing antioxidant power (FRAP, catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue.

  4. Infertility diagnosis has a significant impact on the transcriptome of developing blastocysts.

    Science.gov (United States)

    McCallie, Blair R; Parks, Jason C; Griffin, Darren K; Schoolcraft, William B; Katz-Jaffe, Mandy G

    2017-08-01

    Is the human blastocyst transcriptome associated with infertility diagnosis, specifically: polycystic ovaries (PCO), male factor (MF) and unexplained (UE)? The global blastocyst transcriptome was significantly altered in association with a PCO, MF and UE infertility diagnosis. Infertility diagnosis has an impact on the probability for a successful outcome following an IVF cycle. Limited information is known regarding the relationship between a specific infertility diagnosis and blastocyst transcription during preimplantation development. Blastocysts created during infertility treatment from patients with specific infertility diagnoses (PCO, MF and UE) were analyzed for global transcriptome compared to fertile donor oocyte blastocysts (control). Surplus cryopreserved blastocysts were donated with patient consent and institutional review board approval. Female patients were infertility diagnosis: PCO (n = 50), MF (n = 50), UE (n = 50) and fertile donor oocyte controls (n = 50). Pooled blastocysts were lysed for RNA isolation followed by microarray analysis using the SurePrint G3 Human Gene Expression Microarray. Validation was performed on significant genes of interest using real-time quantitative PCR (RT-qPCR). Transcription alterations were observed for all infertility etiologies compared to controls, resulting in differentially expressed genes: PCO = 869, MF = 348 and UE = 473 (P 2-fold). Functional annotation of biological and molecular processes revealed both similarities, as well as differences, across the infertility groups. All infertility etiologies displayed transcriptome alterations in signal transducer activity, receptor binding, reproduction, cell adhesion and response to stimulus. Blastocysts from PCO patients were also enriched for apoptotic genes while MF blastocysts displayed enrichment for genes involved in cancer processes. Blastocysts from couples with unexplained infertility displayed transcription alterations related to various disease states

  5. Free radical activity during development of insulin-dependent diabetes mellitus in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Pitkaenen, O.M.; Akerblom, H.K.; Sariola, H.; Andersson, S.M. (Univ. of Helsinki (Finland)); Martin, J.M. (Hospital for Sick Children, Toronto, Ontario (Canada)); Hallman, M. (Univ. of California, Irvine (United States))

    1991-01-01

    Free radical-induced lipid peroxidation was quantified by measuring expired pentane from diabetic prone BB Wistar rats of 45-90 d of age. Insulin-dependent diabetes mellitus was manifest at the age of 71 {plus minus} 8 d. Expired pentane increased from 2.1 {plus minus} 0.7 to 5.0 {plus minus}3.0 pmol/100g/min (p <0.01) at manifestation of the disease and remained high throughout the test period. In healthy age-matched control rats it persisted low. In rats made diabetic with streptozotocin, expired pentane remained low. The changes in expired pentane suggest that the development of endogenous insulin-dependent diabetes mellitus in BB rats is associated with increased free radical activity. This is not due to hyperglycemia or ketosis per se, and reflects a fundamental difference in the free radical activity between the spontaneously diabetic BB rats and the disease produced by streptozotocin. Development of spontaneous insulin-dependent diabetes in BB rats is associated with increased free radical activity that persists after the manifestation of the disease.

  6. Postnatal development of rats exposed to fluoxetine or venlafaxine during the third week of pregnancy

    Directory of Open Access Journals (Sweden)

    V.A. da-Silva

    1999-01-01

    Full Text Available The aim of the present study was to compare the toxic effects of fluoxetine (F (8 and 16 mg/kg and venlafaxine (V (40 and 80 mg/kg administered during the third week of pregnancy on early development of rats. Both antidepressants were administered by gavage on pregnancy days 15 to 20 to groups of 10 to 12 animals each. Duration of gestation, food and water consumption, number of live pups and birth weight were recorded. Litters were culled to six pups at birth (day 1 and followed for growth until weaning (day 25. On day 60, a male and a female from each litter were injected with the 5-HT1 agonist, 5-methoxy-N,N-dimethyltryptamine (6 mg/kg, ip and the serotonergic syndrome was graded. Fluoxetine but not venlafaxine reduced the duration of pregnancy when compared to the control (C group (F = 21.1 days and C = 21.6 days, mean, P<0.02; maximum = 22 days and minimum = 21 days in both groups. The highest doses of both fluoxetine, 16 mg/kg (F16, and venlafaxine, 80 mg/kg (V80, reduced the food intake of pregnant rats, resulting in different rates of body weight gain during treatment (from pregnancy day 15 to day 20: F16 = 29.0 g, V80 = 28.7 g vs C = 39.5 g (median. Birth weight was influenced by treatment and sex (P<0.05; two-way ANOVA. Both doses of fluoxetine or venlafaxine reduced the body weight of litters; however, the body weight of litters from treated dams was equal to the weight of control litters by the time of weaning. At weaning there was no significant difference in weight between sexes. There was no difference among groups in number of live pups at birth, stillbirths, mortality during the lactation period or in the manifestation of serotonergic syndrome in adult rats. The occurrence of low birth weight among pups born to dams which did not show reduced food ingestion or reduction of body weight gain during treatment with lower doses of fluoxetine or venlafaxine suggests that these drugs may have a deleterious effect on prenatal

  7. High-fructose diet during periadolescent development increases depressive-like behavior and remodels the hypothalamic transcriptome in male rats

    Science.gov (United States)

    Harrell, Constance S.; Burgado, Jillybeth; Kelly, Sean D.; Johnson, Zachary P.; Neigh, Gretchen N.

    2015-01-01

    Fructose consumption, which promotes insulin resistance, hypertension, and dyslipidemia, has increased by over 25% since the 1970s. In addition to metabolic dysregulation, fructose ingestion stimulates the hypothalamic-pituitary-adrenal (HPA) axis leading to elevations in glucocorticoids. Adolescents are the greatest consumers of fructose, and adolescence is a critical period for maturation of the HPA axis. Repeated consumption of high levels of fructose during adolescence has the potential to promote long-term dysregulation of the stress response. Therefore, we determined the extent to which consumption of a diet high in fructose affected behavior, serum corticosterone, and hypothalamic gene expression using a whole-transcriptomics approach. In addition, we examined the potential of a high-fructose diet to interact with exposure to chronic adolescent stress. Male Wistar rats fed the periadolescent high-fructose diet showed increased anxiety-like behavior in the elevated plus maze and depressive-like behavior in the forced swim test in adulthood, irrespective of stress history. Periadolescent fructose-fed rats also exhibited elevated basal corticosterone concentrations relative to their chow-fed peers. These behavioral and hormonal responses to the high-fructose diet did not occur in rats fed fructose during adulthood only. Finally, rats fed the high-fructose diet throughout development underwent marked hypothalamic transcript expression remodeling, with 966 genes (5.6%) significantly altered and a pronounced enrichment of significantly altered transcripts in several pathways relating to regulation of the HPA axis. Collectively, the data presented herein indicate that diet, specifically one high in fructose, has the potential to alter behavior, HPA axis function, and the hypothalamic transcriptome in male rats. PMID:26356038

  8. Early ovarian follicular development in prepubertal Wistar rats acutely exposed to androgens.

    Science.gov (United States)

    Paixão, L; Velez, L M; Santos, B R; Tusset, C; Lecke, S B; Motta, A B; Spritzer, P M

    2016-08-01

    Androgens may directly modulate early ovarian follicular development in preantral stages and androgen excess before puberty may disrupt this physiological process. Therefore, the aim of this study was to investigate the dynamics of follicular morphology and circulating androgen and estradiol levels in prepubertal Wistar rats acutely exposed to androgens. Prepubertal female Wistar rats were distributed into three groups: control, equine chorionic gonadotropin (eCG) intervention and eCG plus dehydroepiandrosterone (DHEA) intervention (eCG+DHEA). Serum DHEA, testosterone and estradiol levels were determined, and ovarian morphology and morphometry were assessed. The eCG+DHEA group presented increased serum estradiol and testosterone levels as compared with the control group (P<0.01), and higher serum DHEA concentration v. the eCG-only and control groups (P<0.01). In addition, the eCG+DHEA group had a higher number of, and larger-sized, primary and secondary follicles as compared with the control group (P<0.05). The eCG group presented intermediate values for number and size of primary and secondary follicles, without significant differences as compared with the other two groups. The number of antral follicles was higher in the eCG+DHEA and eCG groups v. controls (P<0.05). The number of primordial, atretic and cystic follicles were similar in all groups. In conclusion, the present experimental model using an acute eCG+DHEA intervention was useful to investigate events involved in initial follicular development under hyperandrogenic conditions, and could provide a reliable tool to study defective follicular development with possible deleterious reproductive consequences later in life.

  9. The modulatory effect of estradiol benzoate on superoxide dismutase activity in the developing rat brain

    Directory of Open Access Journals (Sweden)

    Pejic S.

    2003-01-01

    Full Text Available The sensitivity of copper,zinc (CuZn- and manganese (Mn-superoxide dismutase (SOD to exogenous estradiol benzoate (EB was investigated in Wistar rats during postnatal brain development. Enzyme activities were measured in samples prepared from brains of rats of both sexes and various ages between 0 and 75 days, treated sc with 0.5 µg EB/100 g body weight in 0.1 ml olive oil/100 g body weight, 48 and 24 h before sacrifice. In females, EB treatment stimulated MnSOD activity on days 0 (66.1%, 8 (72.7% and 15 (81.7%. In males, the stimulatory effect of EB on MnSOD activity on day 0 (113.6% disappeared on day 8 and on days 15 and 45 it became inhibitory (40.3 and 30.5%, respectively. EB had no effect on the other age groups. The stimulatory effect of EB on CuZnSOD activity in newborn females (51.8% changed to an inhibitory effect on day 8 (38.4% and disappeared by day 45 when inhibition was detected again (48.7%. In males, the inhibitory effect on this enzyme was observed on days 0 (45.0% and 15 (28.9%, and then disappeared until day 60 when a stimulatory effect was observed (38.4%. EB treatment had no effect on the other age groups. The sensitivity of MnSOD to estradiol differed significantly between sexes during the neonatal and prepubertal period, whereas it followed a similar pattern thereafter. The sensitivity of CuZnSOD to estradiol differed significantly between sexes during most of the study period. Regression analysis showed that the sensitivity of MnSOD to this estrogen tended to decrease similarly in both sexes, whereas the sensitivity of CuZnSOD showed a significantly different opposite tendency in female and male rats. These are the first reports indicating hormonal modulation of antioxidant enzyme activities related to the developmental process.

  10. Significance of energy for the standard of living, the economic development and the environment

    International Nuclear Information System (INIS)

    Haefele, W.

    1977-01-01

    In this contribution, after introductory remarks on the present global energy supply situation, the main reasons for the constantly rising energy demand are discussed (development of developing countries, growth in the world population, and growth in the industrial countries), and possibilities are presented to meet this demand by means of new energy sources (nuclear, solar, wind, tidal energy, etc.). (RW) [de

  11. Colonic insufflation with carbon monoxide gas inhibits the development of intestinal inflammation in rats

    Directory of Open Access Journals (Sweden)

    Takagi Tomohisa

    2012-09-01

    Full Text Available Abstract Background The pathogenesis of inflammatory bowel disease (IBD is complex, and an effective therapeutic strategy has yet to be established. Recently, carbon monoxide (CO has been reported to be capable of reducing inflammation by multiple mechanisms. In this study, we evaluated the role of colonic CO insufflation in acute colitis induced by trinitrobenzene sulfonic acid (TNBS in rats. Methods Acute colitis was induced with TNBS in male Wistar rats. Following TNBS administration, the animals were treated daily with 200 ppm of intrarectal CO gas. The distal colon was removed to evaluate various parameters of inflammation, including thiobarbituric acid (TBA-reactive substances, tissue-associated myeloperoxidase (MPO activity, and the expression of cytokine-induced neutrophil chemoattractant (CINC-1 in colonic mucosa 7 days after TNBS administration. Results The administration of TNBS induced ulceration with surrounding edematous swelling in the colon. In rats treated with CO gas, the colonic ulcer area was smaller than that of air-treated rats 7 days after TNBS administration. The wet colon weight was significantly increased in the TNBS-induced colitis group, which was markedly abrogated by colonic insufflation with CO gas. The increase of MPO activity, TBA-reactive substances, and CINC-1 expression in colonic mucosa were also significantly inhibited by colonic insufflation with CO gas. Conclusions Colonic insufflation with CO gas significantly ameliorated TNBS-induced colitis in rats. Clinical application of CO gas to improve colonic inflammatory conditions such as IBD might be useful.

  12. Significance and Role of Small and Middle Entreprises in Economic Development

    Directory of Open Access Journals (Sweden)

    Bandur Miodrag

    2016-06-01

    Full Text Available Small and middle enterprises (SME are becoming more and more the subject of interest in developed countries in which small and middle companies represent a factor of development. The developed countries of the word put SME into focus of their economic strategies and programs and- by concrete macro-economic measures- the aimed politics to SME has a direct impact to reduction on business costs and improvement of liquidation (thus, competitive position of SME, through tax bonds. However, BiH still does not develop tax politics and praxis of many developed countries, which causes a lack of attention and improvement of the sector of SME. This is what many research in BiH confirmed. The changes in social-economic system based on the market commerce create suitable conditions for development of various activities which should be profitable and keep up with the development, with continuous adaptation to constant changes on market, which gives the advantage to SME or, so called, small business. Such companies most often represent the collision of ownership, management and risk, so the knowledge and skill needed for successful management include a very wide range.

  13. Reproductive Toxicity of Zishen Yutai Pill in Rats: The Fertility and Early Embryonic Development Study (Segment I

    Directory of Open Access Journals (Sweden)

    Li Zhou

    2016-01-01

    Full Text Available Purpose. This study was aimed to investigate the reproductive toxicity of Zishen Yutai Pill (ZYP on fertility and early embryonic development in rats. Methods. SD rats were randomly divided into 5 groups: vehicle control group (distilled water, i.g., positive control group (80 mg/kg of cyclophosphamide, i.p., and three ZYP-treated groups (3, 6, and 12 g/kg/d, i.e., 12x, 24x, and 48x clinical doses, i.g.. The high dose was set as the maximum gavage dosage. Results. Cyclophosphamide showed diverse hazards, such as decreased weight of male reproductive organs and sperm density (P<0.05. However, there were no obvious effects of ZYP on physical signs, animal behavior, and survival rate, as well as on weight and food intake during the premating and gestation periods. Importantly, there were no significant adverse effects of ZYP on indexes of copulation, fecundity and fertility indexes, weights and coefficients of male reproductive organs, epididymal sperm number and motility, estrous cycle, preimplantation loss rate, and implantation rate. Besides, the numbers of live and resorbed fetuses per litter were not significantly altered. Conclusions. ZYP had no reproductive toxicities on fertility and early embryonic development in rats at 48x equivalent clinical doses.

  14. Gypenosides attenuate the development of L-DOPA-induced dyskinesia in 6-hydroxydopamine-lesioned rat model of Parkinson's disease.

    Science.gov (United States)

    Shin, Keon Sung; Zhao, Ting Ting; Park, Keun Hong; Park, Hyun Jin; Hwang, Bang Yeon; Lee, Chong Kil; Lee, Myung Koo

    2015-04-21

    Gypenosides (GPS) and ethanol extract of Gynostemma pentaphyllum (GP-EX) show anxiolytic effects on affective disorders in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of Parkinson's disease (PD). Long-term administration of L-3,4-dihydroxyphenylalanine (L-DOPA) leads to the development of severe motor side effects such as L-DOPA-induced-dyskinesia (LID) in PD. The present study investigated the effects of GPS and GP-EX on LID in a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD. Daily administration of L-DOPA (25 mg/kg) in the 6-OHDA-lesioned rat model of PD for 22 days induced expression of LID, which was determined by the body and locomotive AIMs scores and contralateral rotational behaviors. However, co-treatments of GPS (25 and 50 mg/kg) or GP-EX (50 mg/kg) with L-DOPA significantly attenuated the development of LID without compromising the anti-parkinsonian effects of L-DOPA. In addition, the increases in ∆FosB expression and ERK1/2 phosphorylation in 6-OHDA-lesioned rats induced by L-DOPA administration were significantly reduced by co-treatment with GPS (25 and 50 mg/kg) or GP-EX (50 mg/kg). These results suggest that GPS (25 and 50 mg/kg) and GP-EX (50 mg/kg) effectively attenuate the development of LID by modulating the biomarker activities of ∆FosB expression and ERK1/2 phosphorylation in the 6-OHDA-lesioned rat model of PD. GPS and GP-EX will be useful adjuvant therapeutics for LID in PD.

  15. Significance of investigating allelopathic interactions of marine organisms in the discovery and development of cytotoxic compounds

    Digital Repository Service at National Institute of Oceanography (India)

    Singh, A.; Thakur, N.L.

    like (1) growth interactions (e.g. overgrowth by corals) [27], (2) aggressive behaviour (e.g., induced development of sweeper tentacles by bryozoans [28], (3) feeding interactions (e.g., extracoelenteric digestion via mesenteries filaments...

  16. Diet composition determines course of hyperphagia in developing Zucker obese rats.

    Science.gov (United States)

    Vasselli, J R; Maggio, C A

    1990-12-01

    Previous observations from this laboratory indicate that, during growth, the hyperphagia of the male genetically obese Zucker rat reaches a peak or "breakpoint" and then declines. To examine the effect of dietary macronutrient content on the course of hyperphagia, groups of male lean and obese rats were maintained from 5-28 weeks of age on powdered chow, or isocaloric diets (3.6 kcal/g) containing 72% of calories as corn oil, dextrose, or soy isolate protein (n = 5 lean and obese rats/diet). On chow, hyperphagia was maintained at a level of 7-8 g above lean control intake until a "breakpoint" was reached at 17 weeks, and obese intake declined to lean control level. On the fat diet, hyperphagia was increased to 10 g/day when a breakpoint was reached at 8 weeks. On the dextrose and protein diets, hyperphagia at a level of 3-4 g/day reached breakpoints at weeks 18 and 16, respectively. On all diets, the intakes of obese rats were precisely equal to the intakes of lean control rats by weeks 19-20. These data show that the magnitude and duration of hyperphagia in the developing obese rat are influenced by diet composition. Previously, we have proposed that the obese rat's hyperphagia arises from rapid adipocyte filling. Since high-fat diets facilitate adipocyte enlargement, the early "breakpoint" of hyperphagia seen with the high-fat diet may indicate that this feeding stimulation decreases as the fat cells of the obese rat approach maximal size.

  17. Expression of nitric oxide synthase during the development of RCS rat retinas.

    Science.gov (United States)

    Sharma, R K; Warfvinge, K; Ehinger, B

    2001-01-01

    Nitric oxide (NO) has been reported to be both neurodestructive and neuroprotective in the central nervous system and could possibly play an important role in neurodegenerative disorders. On the assumption that NO synthesis may influence degenerative processes in the retina, we have examined the development and distribution of nitric-oxide-synthase(NOS)-immunoreactive cells in developing Royal College of Surgeons (RCS) rat retinas, which is an animal model for retinal degeneration. An antibody against constitutive neuronal NOS was used for immunocytochemistry on RCS rat retinas from postnatal (PN) days 3, 7, 10, 14, 35, 70 and 281 and compared with that in the normal rats of PN days 3, 7, 10, 14, 54 and adults. Immunoreactive cells were not seen in PN 3 retinas but were distinctly seen in the PN 7 retina along with a plexus in the inner plexiform layer. In both groups (normal and RCS rats) a distinct sublayering of the plexus in the inner plexiform layer could be seen at PN 10, which became more distinct at PN 14. The immunoreactive cells were detected also in the oldest retina examined, which was PN 281 in the case of RCS rats. In both groups, certain amacrine cells, certain bipolar cells and certain horizontal cells were found to be immunoreactive. In conclusion, the developmental timetable of the NOS immunoreactivity was identical in the normal and the RCS rat retinas. The NOS-immunoreactive cells persisted in the RCS retinas even when the retina had degenerated extensively. Abnormalities with the inducible isoforms of NOS cannot be ruled out from this study. We conclude that the chronological and qualitative development of the constitutive neuronal NOS immunoreactivity is normal in RCS rat retinas. Copyright 2001 S. Karger AG, Basel

  18. Development of a melatonin RIA and observation on the plasma melatonin contents in rat models of chronic hyperirritable-depression

    International Nuclear Information System (INIS)

    Rong Yang; Sun Acheng; Ma Cong; Zhao Zhong; Gui Yuning; Li Jianjun; Wang Guangkai; Guo Xiazhen

    2005-01-01

    Objective: To establish a new melatonin assay and to investigate the changes of plasma melatonin content in rat models of chronic hyperirritable-depression. Methods: Quality melatonin antiserum was obtained from immunization of Newzealand white rabbit with melatonin immunogen derived from conjugation of melatonin to bovine thyroglobulin using formaldehyde. Radioiodinated melatonin was used as tracer and a melatonin assay was developed through non-equilibrium competition. Twenty rat models of chronic hyperirritable-depression were prepared with multiple randomly-combined stimuli as previously reported. Plasma and pineal body tissue contents of melatonin in the models were examined in midsummer (n=10) and mid-winter (n=10) with the newly developed melatonin RIA. Contents of melatonin were also determined in 20 control rats. Results: The antiserum possessed very low cross-reaction rate with several melatonin analogous tested (0.09%-2.3%). At the titer of 1:1800, the maximal combination rate was 41%. The affinity constant was 1.7 x 10 9 L/M. The specific radioactivity of the tracer 125 I-melatonin was 55 μCi/μg, with radio-chemical purity of 93% and the tracer was stable at 4 degree C for 65 days. The assay was of high sensitivity (lower detection limit 5pg/ml), intra-CV, 6.5 %; inter-CV, 11%. The plasma and pineal body tissue contents of melatonin in the rat models were consistently significantly lower than those in control rats both during summer and winter, while the contents of melatonin during winter were always significantly higher than those during summer in both groups of animals. Conclusion: The newly developed assay was of good specificity and sensitivity with stable agents (65 days). The experimental results demonstrated definite correlationship between the depression disorder and melatonin contents in the rat models, however, the disorder was not seasonally affective. The seasonal variation of the melatonin contents in the animals was due to different

  19. Prognostic factors in advanced breast cancer: Race and receptor status are significant after development of metastasis.

    Science.gov (United States)

    Ren, Zhiyong; Li, Yufeng; Shen, Tiansheng; Hameed, Omar; Siegal, Gene P; Wei, Shi

    2016-01-01

    Prognostic factors are well established in early-stage breast cancer (BC), but less well-defined in advanced disease. We analyzed 323 BC patients who had distant relapse during follow-up from 1997 to 2010 to determine the significant clinicopathologic factors predicting survival outcomes. By univariate analysis, race, tumor grade, estrogen and progesterone receptors (ER/PR) and HER2 status were significantly associated with overall survival (OS) and post-metastasis survival (PMS). Applying a Cox regression model revealed that all these factors remained significant for PMS, while race, tumor grade and HER2 were independent factors for OS. Tumor grade was the only significant factor for metastasis-free survival by univariate and multivariate analyses. Our findings demonstrated that being Caucasian, hormonal receptor positive (HR+) and HER2 positive (HER2+) were all associated with a decreased hazard of death and that patients with HR+/HER2+ tumors had superior outcomes to those with HR+/HER2- disease. Further, PR status held a prognostic value over ER, thus reflecting the biologic mechanism of the importance of the functional ER pathway and the heterogeneity in the response to endocrine therapy. These observations indicate that the patients' genetic makeup and the intrinsic nature of the tumor principally govern BC progression and prognosticate the long-term outcomes in advanced disease. Copyright © 2015 Elsevier GmbH. All rights reserved.

  20. Early polymorphonuclear leukocyte accumulation correlates with the development of posttraumatic cerebral edema in rats

    International Nuclear Information System (INIS)

    Schoettle, R.J.; Kochanek, P.M.; Magargee, M.J.; Uhl, M.W.; Nemoto, E.M.

    1990-01-01

    To evaluate the role of polymorphonuclear leukocytes (PMNs) in the development of posttraumatic cerebral edema, we quantitatively assessed the time course and magnitude of PMN accumulation and its relationship to cerebral edema formation after cerebral trauma in 78 rats. 111 In-labeled PMN accumulation was measured in 26 rats in the first 8 h after right hemispheric percussive cerebral trauma or a sham control condition. 51 Cr-labeled erythrocyte accumulation was measured simultaneously in 22 rats to assess the contribution of expansion of blood volume to early posttraumatic PMN accumulation. Edema formation [right-left (R-L) hemispheric difference in percent brain water], R-L hemispheric labeled-PMN accumulation, and blood volume index-adjusted PMN accumulation were measured between 0-2 h and 4-8 h posttrauma. PMN accumulation was elevated markedly in the first 2 h posttrauma compared with values in sham controls (13.45 +/- 2.53 vs -0.03 +/- 0.31, p less than 0.01) but not when adjusted for blood volume index (BVI), suggesting that PMN accumulation in the first 2 h posttrauma was due to expansion of blood volume. Between 4 and 8 h posttrauma, however, both total (2.56 +/- 0.82 vs -0.29 +/- 0.52) and BVI-adjusted (8.78 +/- 3.97 vs -0.48 +/- 0.79) PMN accumulation were elevated (p less than 0.05) compared with sham. Brain edema and total PMN accumulation were significantly correlated at both 2 h and 8 h posttrauma (r2 = 0.77, p less than 0.001, and r2 = 0.69, p less than 0.002, respectively), but a significant correlation between edema and BVI-adjusted PMN accumulation was observed only at 8 h posttrauma (r2 = 0.96, p less than 0.001). These data show that PMN accumulation after traumatic brain injury occurs with an initial phase explained by an increase in blood volume in the first 2 h posttrauma followed by a subsequent acute inflammatory phase

  1. Significant Problems in Geothermal Development in California, Final Report on Four Workshops, December 1978 - March 1979

    Energy Technology Data Exchange (ETDEWEB)

    None

    1979-07-15

    From November 1978 through March 1979 the California Geothermal Resources Board held four workshops on the following aspects of geothermal development in California: County Planning for Geothermal Development; Federal Leasing and Environmental Review Procedures; Transmission Corridor Planning; and Direct Heat Utilization. One of the objectives of the workshops was to increase the number of people aware of geothermal resources and their uses. This report is divided into two parts. Part 1 provides summaries of all the key information discussed in the workshops. For those people who were not able to attend, this part of the report provides you with a capsule version of the workshop sessions. Part 2 focuses on the key issues raised at the workshops which need to be acted upon to expedite geothermal resource development that is acceptable to local government and environmentally prudent. For the purpose of continuity, similar Geothermal Resources Task Force recommendations are identified.

  2. Anesthesia-related neurotoxicity and the developing animal brain is not a significant problem in children

    DEFF Research Database (Denmark)

    Hansen, Tom G

    2015-01-01

    development with functional deficits in learning and behavior later in life. Initial studies were mainly performed in immature rodent pups, but more recent studies have included nonhumans primates (rhesus monkeys). Given the number of neonates, infants, and young children anesthetized annually worldwide......A multitude of animal studies have shown that virtually all general anesthetics used in clinical practice possibly during a vulnerable period of brain development (i.e., brain growth spurt, peak of synaptogenesis) may lead to neurodegeneration (particularly apoptosis) and abnormal synaptic...... the anesthetics. Currently, there is no need to change current anesthetic clinical practice or to postpone or cancel truly urgent surgeries in young children....

  3. 3. Impact of altered gravity on CNS development and behavior in male and female rats

    Science.gov (United States)

    Sajdel-Sulkowska, E. M.; Nguon, K.; Ladd, B.; Sulkowski, V. A.; Sulkowski, Z. L.; Baxter, M. G.

    The present study examined the effect of altered gravity on CNS development. Specifically, we compared neurodevelopment, behavior, cerebellar structure and protein expression in rat neonates exposed perinatally to hypergravity. Pregnant Sprague-Dawley rats were exposed to 1.5G-1.75G hypergravity on a 24-ft centrifuge starting on gestational day (G) 10, through giving birth on G22/G23, and nursing their offspring through postnatal day (P) 21. Cerebellar mass on P6 was decreased in 1.75G-exposed male pups by 27.5 percent; in 1.75G-exposed female pups it was decreased by 22.5 percent. The observed cerebellar changes were associated with alterations in neurodevelopment and motor behavior. Exposure to hypergravity impaired performance on the following neurocognitive tests: (1) righting time on P3 was more than doubled in 1.75G-exposed rats and the effect appeared more pronounced in female pups, (2) startle response on P10 was delayed in both male and female HG pups; HG pups were one-fifth as likely to respond to a clapping noise as SC pups, and (3) performance on a rotorod on P21 was decreased in HG pups; the duration of the stay on rotorod recorded for HG pups of both sexes was one tenth of the SC pups. Furthermore, Western blot analysis of selected cerebellar proteins suggested gender-specific changes in glial and neuronal proteins. On P6, GFAP expression was decreased by 59.2 percent in HG males, while no significant decrease was observed in female cerebella. Synaptophysin expression was decreased in HG male neonates by 29.9 percent and in HG female neonates by 20.7 percent as compared to its expression in SC cerebella. The results of this experiment suggest that perinatal exposure to hypergravity affects cerebellar development and behavior differently in male and female neonates. If one accepts that hypergravity is a good paradigm to study the effect of microgravity on the CNS, and since males and females were shown to respond differently to hypergravity, it can be

  4. Development and testing of an assessment instrument for the formative peer review of significant event analyses.

    Science.gov (United States)

    McKay, J; Murphy, D J; Bowie, P; Schmuck, M-L; Lough, M; Eva, K W

    2007-04-01

    To establish the content validity and specific aspects of reliability for an assessment instrument designed to provide formative feedback to general practitioners (GPs) on the quality of their written analysis of a significant event. Content validity was quantified by application of a content validity index. Reliability testing involved a nested design, with 5 cells, each containing 4 assessors, rating 20 unique significant event analysis (SEA) reports (10 each from experienced GPs and GPs in training) using the assessment instrument. The variance attributable to each identified variable in the study was established by analysis of variance. Generalisability theory was then used to investigate the instrument's ability to discriminate among SEA reports. Content validity was demonstrated with at least 8 of 10 experts endorsing all 10 items of the assessment instrument. The overall G coefficient for the instrument was moderate to good (G>0.70), indicating that the instrument can provide consistent information on the standard achieved by the SEA report. There was moderate inter-rater reliability (G>0.60) when four raters were used to judge the quality of the SEA. This study provides the first steps towards validating an instrument that can provide educational feedback to GPs on their analysis of significant events. The key area identified to improve instrument reliability is variation among peer assessors in their assessment of SEA reports. Further validity and reliability testing should be carried out to provide GPs, their appraisers and contractual bodies with a validated feedback instrument on this aspect of the general practice quality agenda.

  5. Significance of mineralogy in the development of flowsheets for processing uranium ores

    International Nuclear Information System (INIS)

    1980-01-01

    This report has been prepared from material developed at and subsequent to a consultants' meeting held in Vienna in January 1978. The main purpose of the meeting was to prepare a document in the form of a guide for planning and developing treatment flowsheets for uranium ore processing. It was apparent that ore mineralogy, analysed, described and interpreted in ways most meaningful to the metallurgist, is the most essential information required for forming the basis of such planning. This topic, here termed metallurgical mineralogy, is therefore a major theme of this publication. In preparing the report the Agency has borne in mind the important need to impart the experience and knowledge gained in the more developed countries to those who are in the early stages of exploiting their uranium resources. The contents may be criticized as lacking, in some respects, the requisite depth and detail of treatment. The Agency and the consultants are conscious of the need to expand the information in a number of ways. However, the report is presented in its present form in the belief that, as the first attempt to correlate, on a world-wide basis, ore type with processing, it will be considered as a useful basis for future development of these themes

  6. Development of the PCAD Model to Assess Biological Significance of Acoustic Disturbance

    Science.gov (United States)

    2015-09-30

    Simmons, L. Thomas, P. Tyack, and J. Harwood. 2014. Using short-term measures of behaviour to estimate long-term fitness of southern elephant seals...2013. Testing Decision Rules for Categorizing Species’ Extinction Risk to Help Develop Quantitative Listing Criteria for the US Endangered Species

  7. Dynamic metabolome profiling reveals significant metabolic changes during grain development of bread wheat (Triticum aestivum L.).

    Science.gov (United States)

    Zhen, Shoumin; Dong, Kun; Deng, Xiong; Zhou, Jiaxing; Xu, Xuexin; Han, Caixia; Zhang, Wenying; Xu, Yanhao; Wang, Zhimin; Yan, Yueming

    2016-08-01

    Metabolites in wheat grains greatly influence nutritional values. Wheat provides proteins, minerals, B-group vitamins and dietary fiber to humans. These metabolites are important to human health. However, the metabolome of the grain during the development of bread wheat has not been studied so far. In this work the first dynamic metabolome of the developing grain of the elite Chinese bread wheat cultivar Zhongmai 175 was analyzed, using non-targeted gas chromatography/mass spectrometry (GC/MS) for metabolite profiling. In total, 74 metabolites were identified over the grain developmental stages. Metabolite-metabolite correlation analysis revealed that the metabolism of amino acids, carbohydrates, organic acids, amines and lipids was interrelated. An integrated metabolic map revealed a distinct regulatory profile. The results provide information that can be used by metabolic engineers and molecular breeders to improve wheat grain quality. The present metabolome approach identified dynamic changes in metabolite levels, and correlations among such levels, in developing seeds. The comprehensive metabolic map may be useful when breeding programs seek to improve grain quality. The work highlights the utility of GC/MS-based metabolomics, in conjunction with univariate and multivariate data analysis, when it is sought to understand metabolic changes in developing seeds. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  8. Safety analysis of final disposal of nuclear waste - significance, development and challenges

    International Nuclear Information System (INIS)

    Andersson, Kjell; Norrby, Soeren; Simic, Eva; Wene, Clas-Otto

    2007-05-01

    The report starts with a review of the role and development of safety assessments from the middle of the 70's up until today. Then follows a section on how the assessment is performed today. The demands from the licensing authorities is then described. The report ends with a chapter on conclusions and reflections

  9. Significance of monitoring of the phytoradiobiological researches for development of agrarian radiology in Georgia

    International Nuclear Information System (INIS)

    Gogebashvili, M.E.; Ivanishvili, N.I.

    2012-01-01

    Full text : Monitoring of development of concrete scientific discipline-multifactorial process and at studying of its efficiency is necessary selection of adequate ways of the analysis. Especially it is important under conditions cardinal changes of schemes of management of a science, level of financing and serious redistribution of personnel structure. It has occurred last years in many Post-Soviet countries. Thus, the question of the control and regulation of development of scientific directions to become rather actual. It is known, that selection of adequate criteria of the estimation is necessary for monitoring of a condition of various scientific directions. It is natural, if we consider a science as reception innovation process knowledge it is necessary to track distribution and growth of number of thematic scientific publications. For the task in view decision namely to carry out monitoring of development of radio plant biology in Georgia within the limits of an agrarian science the known method of an estimation of scientific publications on Key Word has been used. It demands creation of new mechanisms of management by development of a science with the assistance of regulating academic and state structures

  10. Significant involvement of agricultural holdings in rural tourism development in Serbia

    Directory of Open Access Journals (Sweden)

    Gajić Tamara

    2017-01-01

    Full Text Available There are a large number of farms in Serbia, which survived with a little capital and labor, and today one of the perspectives they see in the integration with the rural tourism. Tourism development is an incentive for the introduction of improvements in agricultural production, processing and supply of food, as well as the introduction of modern standards that are difficult to apply on small farms because of the high costs of their implementation. Rural tourism in Serbia is not at a satisfactory level of development, although there are all preconditions for its intensive development. Due to unfavorable political and economic position of Serbia, rural tourism has not encountered the support of its favorable development among its competitors. The authors have tried to point out a study for the attitude of the hosts as a service providers on the current status and problems faced in providing services in rural tourism. Investigated in 15 municipalities in Vojvodina (Northern Serbia, Southwestern Serbia and Southeastern Serbia, and in a total of 46 owners of small farms. Using the tests methods questionnaires and processing in SPSS, version 19.0, and analysis of the data, authors led to the confirmation of certain hypotheses of which started in the investigation.

  11. Separation Anxiety in Parents of Adolescents: Theoretical Significance and Scale Development.

    Science.gov (United States)

    Hock, Ellen; Eberly, Mary; Bartle-Haring, Suzanne; Ellwanger, Pamela; Widaman, Keith F.

    2001-01-01

    Developed and validated Parents of Adolescents Separation Anxiety Scale with parents of sixth, eighth, tenth, and twelfth graders, and college freshmen and seniors. Factor analyses supported two subscales: Anxiety about Adolescent Distancing (AAD) and Comfort with Secure Base Role (CSBR); both showed distinctive change patterns with child age.…

  12. Professional Training of Social Workers: Development of Professionally Significant Qualities in the Future Social Workers

    Science.gov (United States)

    Minzhanov, Nurlan A.; Ertysbaeva, Gaukhar N.; Abdakimova, Madina K.; Ishanov, Pirmagambet Z.

    2016-01-01

    Today, the traditional approach to professional training is obsolete. This problem has determined the need to create new didactic forms related to the organization of training in the modern education system. The purpose of this study was to analyze possible development of professionally important qualities and abilities in the future social care…

  13. Development and comparison of a minimally-invasive model of autologous clot pulmonary embolism in Sprague-Dawley and Copenhagen rats

    Directory of Open Access Journals (Sweden)

    Sanapareddy Nina

    2010-02-01

    Full Text Available Abstract Background Experimental models of pulmonary embolism (PE that produce pulmonary hypertension (PH employ many different methods of inducing acute pulmonary occlusion. Many of these models induce PE with intravenous injection of exogenous impervious objects that may not completely reproduce the physiological properties of autologous thromboembolism. Current literature lacks a simple, well-described rat model of autlogous PE. Objective: Test if moderate-severity autologous PE in Sprague-Dawley (SD and Copenhagen (Cop rats can produce persistent PH. Methods blood was withdrawn from the jugular vein, treated with thrombin-Ca++ and re-injected following pretreatment with tranexamic acid. Hemodynamic values, clot weights and biochemical measurements were performed at 1 and 5 days. Results Infusion of clot significantly increased the right ventricular peak systolic pressure to 45-55 mm Hg, followed by normalization within 24 hours in SD rats, and within 5 days in COP rats. Clot lysis was 95% (24 hours and 97% (5 days in SD rats and was significantly lower in COP rats (70%, 24 hours; 87% 5 days. Plasma D-dimer was elevated in surgical sham animals and was further increased 8 hours after pulmonary embolism. Neither strain showed a significant increase in bronchoalveolar chemotactic activity, myeloperoxidase activity, leukocyte infiltration, or chemokine accumulation, indicating that there was no significant pulmonary inflammation. Conclusions Both SD and COP rats exhibited near complete fibrinolysis of autologous clot PE within 5 days. Neither strain developed persistent PH. Experimental models of PE designed to induce sustained PH and a robust inflammatory response appear to require significant, persistent pulmonary vascular occlusion.

  14. Repetitive long-term hyperbaric oxygen treatment (HBOT administered after experimental traumatic brain injury in rats induces significant remyelination and a recovery of sensorimotor function.

    Directory of Open Access Journals (Sweden)

    Klaus Kraitsy

    Full Text Available Cells in the central nervous system rely almost exclusively on aerobic metabolism. Oxygen deprivation, such as injury-associated ischemia, results in detrimental apoptotic and necrotic cell loss. There is evidence that repetitive hyperbaric oxygen therapy (HBOT improves outcomes in traumatic brain-injured patients. However, there are no experimental studies investigating the mechanism of repetitive long-term HBOT treatment-associated protective effects. We have therefore analysed the effect of long-term repetitive HBOT treatment on brain trauma-associated cerebral modulations using the lateral fluid percussion model for rats. Trauma-associated neurological impairment regressed significantly in the group of HBO-treated animals within three weeks post trauma. Evaluation of somatosensory-evoked potentials indicated a possible remyelination of neurons in the injured hemisphere following HBOT. This presumption was confirmed by a pronounced increase in myelin basic protein isoforms, PLP expression as well as an increase in myelin following three weeks of repetitive HBO treatment. Our results indicate that protective long-term HBOT effects following brain injury is mediated by a pronounced remyelination in the ipsilateral injured cortex as substantiated by the associated recovery of sensorimotor function.

  15. [Significance of re-evaluation and development of Chinese herbal drugs].

    Science.gov (United States)

    Gao, Yue; Ma, Zengchun; Zhang, Boli

    2012-01-01

    The research of new herbal drugs involves in new herbal drugs development and renew the old drugs. It is necessary to research new herbal drugs based on the theory of traditional Chinese medicine (TCM). The current development of famous TCM focuses on the manufacture process, quality control standards, material basis and clinical research. But system management of security evaluation is deficient, the relevant system for the safety assessment TCM has not been established. The causes of security problems, security risks, target organ of toxicity, weak link of safety evaluation, and ideas of safety evaluation are discussed in this paper. The toxicology research of chinese herbal drugs is necessary based on standard of good laboratory practices (GLP), the characteristic of Chinese herbal drugs is necessary to be fully integrated into safety evaluation. The safety of new drug research is necessary to be integrated throughout the entire process. Famous Chinese medicine safety research must be paid more attention in the future.

  16. Development of the National Transplant Program Has Significantly Decreased but Not Ended Transplant Tourism in Montenegro.

    Science.gov (United States)

    Ratkovic, M; Basic Jukic, N; Kastelan, Z; Radunovic, D; Kavaric, P; Brezak, J; Topalovic Grkovic, M; Hudolin, T; Prelevic, V

    2018-06-01

    Organ transplantation has prolonged and improved the lives of many patients around the world. However, a widespread shortage of donors remains the main factor that has led to organ trafficking and transplant tourism. To stop transplant tourism and to provide optimal treatment for its citizens with end-stage renal disease, Montenegro started performing renal transplantations in September 2012. Thirty-five transplantations have been performed since that time, 34 from living donors and only 1 from a deceased donor. This practice has significantly decreased but not ended transplant tourism in Montenegro. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. THE SIGNIFICANCE OF BREASTFEEDING FOR THE INFANT GROWTH AND DEVELOPMENT: A REVIEW

    Directory of Open Access Journals (Sweden)

    N. I. Ursova

    2015-01-01

    Full Text Available Based on the literature, the review shows the real value of breast milk as the most optimal type of postnatal feeding of infants. We describe biological mechanisms that are supposed to mediate  the influence of breastfeeding on maturation of  immune response, regulation of intestinal functions, trophic effect on small and large intestinal  mucosa, its microflora and somatic growth of an  infant. In infancy, the protective properties of  breast milk against intestinal infections are largely related to its prebiotic effect. According to the  results of the studies on the structure of the milk  fat mycella envelope, their protein not only participate in bacterial adhesion, but also exert substantial anti-microbial activity due to presence of  antimicrobial components. We discuss the role  of protective nutrients, such as zinc, iron, iodine,  selenium and vitamin A and review the results of studies performed in various countries and aimed at evaluation of an association between the type of feeding of an infant in the 1  year of life and the risk of development of somatic abnormalities. A strong influence of micronutrient deficiencies in the pregnant and breastfeeding woman on delay of in utero development has been shown, as well as its contribution to formation of congenital ab- st normalities of any organ or system, connective  tissue dysplasia, initiation and development of alimentary-related conditions in infants.

  18. Effects of experimental suppression of active (REM) sleep during early development upon adult brain and behavior in the rat.

    Science.gov (United States)

    Mirmiran, M; Scholtens, J; van de Poll, N E; Uylings, H B; van der Gugten, J; Boer, G J

    1983-04-01

    In order to test the hypothesis that active sleep (AS) is important for the normal development of the central nervous system, 3 different deprivation methods were applied to male Wistar rat pups during the first month of life. Daily injection of clomipramine from 8 to 21 days of age reduced the high level of AS to less than the adult value throughout most of the experimental period. Administration of clonidine from 8 to 21 days of life induced an almost total suppression of AS. Instrumental deprivation, using the 'pendulum' method, led to a significant (but less severe) AS reduction during 2-4 weeks of postnatal age. Open-field behavior testing in adulthood revealed a higher than normal level of ambulation in all 3 experimental groups. Masculine sexual responses were deficient, due to a low level of both mounts and ejaculations, in both clomipramine- and clonidine-treated animals. Neither passive avoidance learning nor dark preference tests revealed any differences between the experimental and control rats. Sleep observations showed that there was an abnormally high incidence of large myoclonic jerks during AS in both clomipramine- and clonidine-treated rats. Subsequent measurement of regional brain weights showed a significant reduction in the cerebral cortex and medulla oblongata, as compared with the respective control groups, in both the clomipramine- and the clonidine-treated rats. In addition, DNA and protein determination in the affected brain areas showed a proportional reduction in the cortex and in the medulla. These results demonstrate that interference with normal functioning either of AS per se or of specific monoaminergic transmitter systems during early development can produce long-lasting behavioral as well as brain morphological and biochemical abnormalities in later life.

  19. Development of rat female genital cortex and control of female puberty by sexual touch.

    Directory of Open Access Journals (Sweden)

    Constanze Lenschow

    2017-09-01

    Full Text Available Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch.

  20. Development of rat female genital cortex and control of female puberty by sexual touch.

    Science.gov (United States)

    Lenschow, Constanze; Sigl-Glöckner, Johanna; Brecht, Michael

    2017-09-01

    Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory) male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch.

  1. Influence of fat/carbohydrate ratio on progression of fatty liver disease and on development of osteopenia in male rats fed alcohol via total enteral nutrition (TEN)

    Science.gov (United States)

    Alcohol abuse is associated with the development of fatty liver disease and also with significant bone loss in both genders. In this study, we examined ethanol (EtOH)-induced pathology in response to diets with differing fat/carbohydrate ratios. Male Sprague-Dawley rats were fed intragastrically wit...

  2. A Review of New and Developing Technology to Significantly Improve Mars Sample-Return Missions

    Science.gov (United States)

    Carsey, F.; Brophy, J.; Gilmore, M.; Rodgers, D.; Wilcox, B.

    2000-07-01

    A JPL development activity was initiated in FY 1999 for the purpose of examining and evaluating technologies that could materially improve future (i.e., beyond the 2005 launch) Mars sample return missions. The scope of the technology review was comprehensive and end-to-end; the goal was to improve mass, cost, risk, and scientific return. A specific objective was to assess approaches to sample return with only one Earth launch. While the objective of the study was specifically for sample-return, in-situ missions can also benefit from using many of the technologies examined.

  3. Expression of glucocorticoid receptor and glucose transporter-1 during placental development in the diabetic rat

    Directory of Open Access Journals (Sweden)

    Ramazan Demir

    2011-07-01

    Full Text Available In various tissues, glucocorticoids (GCs are known to downregulate glucose transport systems; however, their effects on glucose transporters (GLUTs in the placenta of a diabetic rat are unknown. Glucocorticoid hormone action within the cell is regulated by the glucocorticoid receptor (GR. Thus, this study was designed to investigate the relationship between GR and glucose transporter expression in the placenta of the diabetic rat. Our immunohistochemical results indicated that GR and glucose transporter protein 1 (GLUT 1 are expressed ubiquitously in the trophoblast and endothelial cells of the labyrinthine zone, where maternal fetal transport takes place in the rat placenta. Expression of GR in the junctional zone of the rat placenta was detected in giant cells, and in some spongiotrophoblast cells, but not in the glycogen cells. GLUT 1 was present, especially in glycogen cells during early pregnancy, and in the spongiotrophoblast cells of the junctional zone during late pregnancy. Amounts of GR and GLUT 1 protein were increased towards the end of gestation both in the control and the diabetic placenta. However, at days 17 and 19 of gestation, only the placental GR protein was significantly increased in the streptozotocin-induced diabetic rats compared to control rats. Diabetes led to a significant decrease in placental weight at gestation day 15. In contrast, at gestational days 17 and 21, the weights of the diabetic placenta were significantly increased as compared with the controls. Moreover, diabetes induced fetus intrauterine growth retardation at gestational days 13, 17 and 21. In conclusion, the localization pattern of GR and GLUT 1 proteins in the same cell types led us to believe that there might be a relationship between GR and GLUT 1 expressions at the cellular level. GLUT 1 does not play a pivotal role in diabetic pregnancies. However, placental growth abnormalities during diabetic pregnancy may be related to the amount of GR

  4. Effects of in utero and lactational exposure to triphenyltin chloride on pregnancy outcome and postnatal development in rat offspring.

    Science.gov (United States)

    Grote, Konstanze; Hobler, Carolin; Andrade, Anderson J M; Grande, Simone Wichert; Gericke, Christine; Talsness, Chris E; Appel, Klaus E; Chahoud, Ibrahim

    2007-09-05

    The organotin compound (OTC) triphenyltin (TPT) is used extensively as a herbicide, pesticide and fungicide in agriculture as well as, together with tributyltin (TBT), in marine antifouling paints. We studied the effects of in utero exposure to 2 or 6 mg triphenyltinchloride (TPTCl)/kgb.w. on pregnancy outcome and postnatal development in rat offspring. Gravid Wistar rats were treated per gavage from gestational day 6 until the end of lactation. In the 6 mg TPTCl dose group gestational mortality in dams as well as an increased incidence of anticipated and delayed parturition was observed. Furthermore, treatment resulted in a significant increase in perinatal mortality, a decrease in lactational body weight gain as well as in delayed physical maturation of offspring. Similarily, exposure to 2mg TPTCl/kgb.w. resulted in a significant increase in perinatal mortality and in delayed eye opening. Lactational body weight gain and other landmarks of physical maturation were unaffected in the low dose group. We conclude, that in utero exposure to TPTCl at the described dose levels severely affected pregnancy outcome and perinatal survival of offspring. These results were unexpected, as in two earlier studies with pubertal rats TPTCl at the same dose levels no signs of general toxicity were observed.

  5. Comparative Immunohistochemical Analysis of Ochratoxin A Tumourigenesis in Rats and Urinary Tract Carcinoma in Humans; Mechanistic Significance of p-S6 Ribosomal Protein Expression

    Directory of Open Access Journals (Sweden)

    Sarah Pinder

    2012-09-01

    Full Text Available Ochratoxin A (OTA is considered to be a possible human urinary tract carcinogen, based largely on a rat model, but no molecular genetic changes in the rat carcinomas have yet been defined. The phosphorylated-S6 ribosomal protein is a marker indicating activity of the mammalian target of rapamycin, which is a serine/threonine kinase with a key role in protein biosynthesis, cell proliferation, transcription, cellular metabolism and apoptosis, while being functionally deregulated in cancer. To assess p-S6 expression we performed immunohistochemistry on formalin-fixed and paraffin-embedded tumours and normal tissues. Marked intensity of p-S6 expression was observed in highly proliferative regions of rat renal carcinomas and a rare angiosarcoma, all of which were attributed to prolonged exposure to dietary OTA. Only very small OTA-generated renal adenomas were negative for p-S6. Examples of rat subcutaneous fibrosarcoma and testicular seminoma, as well as of normal renal tissue, showed no or very weak positive staining. In contrast to the animal model, human renal cell carcinoma, upper urinary tract transitional cell carcinoma from cases of Balkan endemic nephropathy, and a human angiosarcoma were negative for p-S6. The combined findings are reminiscent of constitutive changes in the rat tuberous sclerosis gene complex in the Eker strain correlated with renal neoplasms, Therefore rat renal carcinogenesis caused by OTA does not obviously mimic human urinary tract tumourigenesis.

  6. [The development of molecular human genetics and its significance for perspectives of modern medicine].

    Science.gov (United States)

    Coutelle, C; Speer, A; Grade, K; Rosenthal, A; Hunger, H D

    1989-01-01

    The introduction of molecular human genetics has become a paradigma for the application of genetic engineering in medicine. The main principles of this technology are the isolation of molecular probes, their application in hybridization reactions, specific gene-amplification by the polymerase chain reaction, and DNA sequencing reactions. These methods are used for the analysis of monogenic diseases by linkage studies and the elucidation of the molecular defect causing these conditions, respectively. They are also the basis for genomic diagnosis of monogenic diseases, introduced into the health care system of the GDR by a national project on Duchenne/Becker muscular dystrophy, Cystic Fibrosis and Phenylketonuria. The rapid development of basic research on the molecular analysis of the human genome and genomic diagnosis indicates, that human molecular genetics is becoming a decisive basic discipline of modern medicine.

  7. Brand as a significant element of the regional development strategy at the example of Devin

    Directory of Open Access Journals (Sweden)

    Goranova Penka

    2015-01-01

    Full Text Available The idea of (regional branding is an important issue in modern business environment. Theoretical studies in this area are few, compared to research papers that have been dedicated to traditional brands and branding. A practical research on brand as an important element of regional development strategy can thus provide a series of useful information that marketers can use in their marketing strategies and in branding process in particular. The aim of this article is an assessment of regional branding, at the example of Devin. The article consists of two main parts. The first part focuses on defining regional branding and discussing why regional branding is important. The second part analyses the brand Devin and shows how a regional brand can evolve from a concept to reality.

  8. The head problem. The organizational significance of segmentation in head development.

    Science.gov (United States)

    Horder, Tim J; Presley, Robert; Slípka, Jaroslav

    2010-01-01

    This review argues for the segmental basis of chordate head organization which, like somite-based segmental organization in the trunk, takes its origin from early mesodermal development. The review builds on, and brings up to date, Goodrich's well-known scheme of head organization. It surveys recent data in support of this scheme and shows how evidence and arguments supposedly in conflict with it can be accommodated. Many of the arguments revolve around matters of methodology; the limitations of older LM, SEM (on which the concept of "somitomeres" is based) and recent molecular evidence (which has sometimes been seen as allocating the central role in head organization to the CNS and the neural crest) are highlighted and shown to explain a number of claims contrary to Goodrich's. We provide (in Part 2) a new, comparative survey of the best available evidence most directly relevant to the Goodrich Bauplan, with a special emphasis on stem chordates. The postotic region has commonly been seen as segmentally organized: the critical issues concern the preotic region. There are many reasons why Goodrich's three preotic segments may become specialized during evolution and why the underlying initial segmental organization may be overridden in later stages during embryonic development; we refer to a number of these. We conclude that the preotic segmental Bauplan is remarkably conserved and most explicitly demonstrated among stem forms, but we also suggest that the concept of the prechordal plate requires careful reexamination. Central to our overall analysis is the importance of the epigenetic nature of embryogenesis; its implications are made clear. Finally we speculate on evolutionary implications for the origin of the head and its specialized features. The review is intended to serve as a resource giving access to references to a wealth of now neglected, older data on anamniote embryology.

  9. Coping with perceived racism: a significant factor in the development of obesity in African American women?

    Science.gov (United States)

    Mwendwa, Denee T; Gholson, Georica; Sims, Regina C; Levy, Shellie-Anne; Ali, Mana; Harrell, C Jules; Callender, Clive O; Campbell, Alfonso L

    2011-07-01

    African American women have the highest rates of obesity in the United States. The prevalence of obesity in this group calls for the identification of psychosocial factors that increase risk. Psychological stress has been associated with obesity in women; however, there is scant literature that has explored the impact of racism on body mass index (BMI) in African American women. The current study aimed to determine whether emotional responses and behavioral coping responses to perceived racism were associated with BMI in African American women. A sample of 110 African American women participated in a community-based study. Height and weight measurements were taken to calculate BMI and participants completed the Perceived Racism Scale and the Perceived Stress Scale. Hierarchical regression analyses demonstrated a significant relationship between BMI and behavioral coping responses to perceived racism. Findings for emotional responses to perceived racism and appraisal of one's daily life as stressful were nonsignificant. Mean comparisons of BMI groups showed that obese African American women used more behavioral coping responses to perceived racism as compared to normal-weight and overweight women in the sample. Findings suggest that behavioral coping responses better explained increased risk for obesity in African American women. A biobehavioral pathway may explain this finding with a stress-response process that includes cortisol reactivity. Maladaptive behavioral coping responses may also provide insight into obesity risk. Future research is needed to determine which behavioral coping responses place African American women at greater risk for obesity.

  10. Regulation of glutamate dehydrogenase expression in the developing rat liver: control at different levels in the prenatal period

    NARCIS (Netherlands)

    Das, A. T.; Salvadó, J.; Boon, L.; Biharie, G.; Moorman, A. F.; Lamers, W. H.

    1996-01-01

    To study the regulation of the expression of glutamate dehydrogenase (Glu-DH) in rat liver during development, the Glu-DH mRNA concentration in the liver of rats ranging in age from 14 days prenatal development to 3 months after birth was determined. This concentration increased up to two days

  11. Disrupted social development enhances the motivation for cocaine in rats

    NARCIS (Netherlands)

    Baarendse, P.J.J.; Limpens, J.H.W.; Vanderschuren, L.J.M.J.|info:eu-repo/dai/nl/126514917

    2014-01-01

    for behavioural development. In particular, social play behaviour during post-weaning development is thought to facilitate the attainment of social, emotional and cognitive capacities. Conversely, social insults during development can cause longlasting behavioural impairments and increase the

  12. Progressive degradation of alloy 690 and the development of a significant improvement in alloy 800CR

    International Nuclear Information System (INIS)

    Staehle, Roger W.; Arioka, Koji; Tapping, Robert

    2015-01-01

    The present most widely used alloys for tubing in steam generators and structural materials in water cooled reactors are Alloy 690 and Alloy 800. However, both alloys, while improved over Alloy 600 may not meet the needs of longer range applications in the range of 80-100 years. Alloy 690 sustains damage resulting from the formation of cavities at grain boundaries which eventually cover about 50% of the area of the grain boundaries with the remainder covering being covered with carbides. The cavities seem to nucleate on the carbides leaving the grain boundaries a structure of cavities and carbides. Such a structure will lead the Alloy 690 to fail completely. Normal Alloy 800 does not produce such cavities and probably retains a large amount of its corrosion resistance but does sustain progressive SCC at low rate. A new alloy, 800CR, has been developed in a collaboration among Arioka, Tapping, and Staehle. This alloy is based on a Cr composition of 23.5-27% with the remainder retaining the previous Alloy 800 composition. 800CR sustains a crack velocity about 100 times less than Alloy 690 and a negligible rate of initiation. The 800CR, alloy is now seeking a patent. (authors)

  13. Autoantibodies in renal diseases – clinical significance and recent developments in serological detection

    Directory of Open Access Journals (Sweden)

    Gianna eKirsztajn

    2015-05-01

    Full Text Available Autoimmune dysfunctions are the bête noire in a range of debilitating nephropathies. Autoimmune-mediated damage to the kidneys can be triggered by autoantibodies directed against specific proteins or renal structures, for example the phospholipase A2 receptor or the glomerular basement membrane, resulting in glomerular diseases such as primary membranous nephropathy or Goodpasture’s disease. Moreover, secondary damage to the kidney can be part of the wide-reaching effects of systemic autoimmune diseases such as vasculitis or systemic lupus erythematosus (SLE – the latter counts lupus nephritis among its most severe manifestations. Systemic autoimmune diseases are characterized by non-organ-specific autoantibodies, directed for example against neutrophil cytoplasmic antigens in systemic vasculitis and against double-stranded DNA and nucleosomes in SLE.A large variety of innovative and highly specific and sensitive autoantibody tests have been developed in the last years that are available to identify autoimmune kidney diseases at an early stage. Thus, serological in vitro diagnostics allow for appropriate interventional therapy in order to prevent disease progression often resulting in need of dialysis and transplantation.

  14. Methodological development for selection of significant predictors explaining fatal road accidents.

    Science.gov (United States)

    Dadashova, Bahar; Arenas-Ramírez, Blanca; Mira-McWilliams, José; Aparicio-Izquierdo, Francisco

    2016-05-01

    Identification of the most relevant factors for explaining road accident occurrence is an important issue in road safety research, particularly for future decision-making processes in transport policy. However model selection for this particular purpose is still an ongoing research. In this paper we propose a methodological development for model selection which addresses both explanatory variable and adequate model selection issues. A variable selection procedure, TIM (two-input model) method is carried out by combining neural network design and statistical approaches. The error structure of the fitted model is assumed to follow an autoregressive process. All models are estimated using Markov Chain Monte Carlo method where the model parameters are assigned non-informative prior distributions. The final model is built using the results of the variable selection. For the application of the proposed methodology the number of fatal accidents in Spain during 2000-2011 was used. This indicator has experienced the maximum reduction internationally during the indicated years thus making it an interesting time series from a road safety policy perspective. Hence the identification of the variables that have affected this reduction is of particular interest for future decision making. The results of the variable selection process show that the selected variables are main subjects of road safety policy measures. Published by Elsevier Ltd.

  15. The functional significance of cortical reorganization and the parallel development of CI therapy

    Directory of Open Access Journals (Sweden)

    Edward eTaub

    2014-06-01

    Full Text Available For the 19th and the better part of the 20th centuries two correlative beliefs were strongly held by almost all neuroscientists and practitioners in the field of neurorehabilitation. The first was that after maturity the adult CNS was hardwired and fixed, and second that in the chronic phase after CNS injury no substantial recovery of function could take place no matter what intervention was employed. However, in the last part of the 20th century evidence began to accumulate that neither belief was correct. First, in the 1960s and 1970s, in research with primates given a surgical abolition of somatic sensation from a single forelimb, which rendered the extremity useless, it was found that behavioral techniques could convert the limb into an extremity that could be used extensively. Beginning in the late 1980s, the techniques employed with deafferented monkeys were translated into a rehabilitation treatment, termed Constraint Induced Movement therapy or CI therapy, for substantially improving the motor deficit of the upper and lower extremities in the chronic phase after stroke. CI therapy has been applied successfully to other types of damage to the CNS such as traumatic brain injury, cerebral palsy, multiple sclerosis, and spinal cord injury, and it has also been used to improve function in focal hand dystonia and for aphasia after stroke. As this work was proceeding, it was being shown during the 1980s and 1990s that sustained modulation of afferent input could alter the structure of the CNS and that this topographic reorganization could have relevance to the function of the individual. The alteration in these once fundamental beliefs has given rise to important recent developments in neuroscience and neurorehabilitation and holds promise for further increasing our understanding of CNS function and extending the boundaries of what is possible in neurorehabilitation.

  16. Mixtures of environmentally relevant endocrine disrupting chemicals affect mammary gland development in female and male rats

    DEFF Research Database (Denmark)

    Mandrup, Karen Riiber; Johansson, Hanna Katarina Lilith; Boberg, Julie

    2015-01-01

    Estrogenic chemicals are able to alter mammary gland development in female rodents, but little is known on the effects of anti-androgens and mixtures of endocrine disrupting chemicals (EDCs) with dissimilar modes of action. Pregnant rat dams were exposed during gestation and lactation to mixtures...

  17. Effects of prenatal exposure to toluene on postnatal development and behavior in rats

    DEFF Research Database (Denmark)

    Hougaard, K. S.; Hass, Ulla; Lund, S. P.

    1999-01-01

    Development and neurobehavioral effects of prenatal exposure to toluene (CAS 108-88-3) were studied after exposing pregnant rats (Mol:WIST) to 1800 ppm of the solvent for 6 h daily on days 7-20 of gestation. Body weights of exposed offspring were lower until day 10 after parturition. Neurobehavio...

  18. Selenium prevents tumor development in a rat model for chemical carcinogenesis

    DEFF Research Database (Denmark)

    Bjorkhem-Bergman, L.; Torndal, U. B.; Eken, S.

    2005-01-01

    Previous studies in animals and humans have shown that selenium compounds can prevent cancer development. In this work we studied the tumor preventive effect of selenium supplementation, administrated as selenite, in the initiation, promotion and progression phases in a synchronized rat model for...

  19. Cortical interhemispheric responses to rhythmic stimulation are influenced by status epilepticus in developing rats

    Czech Academy of Sciences Publication Activity Database

    Tsenov, Grygoriy; Mareš, Pavel

    2005-01-01

    Roč. 46, č. S6 (2005), s. 209-210 ISSN 0013-9580. [International Epilepsy Congress /26./. 28.08.2005-01.09.2005, Paris] Institutional research plan: CEZ:AV0Z50110509 Keywords : status epilepticus * interhemispheric responses * developing rats Subject RIV: ED - Physiology

  20. Influence of age and immunization on development of gingivitis in rats

    DEFF Research Database (Denmark)

    Lekic, P; Klausen, B; Friis-Hasché, E

    1989-01-01

    To study the effect of age and antigenic priming on the development of gingivitis, 33 healthy rats were placed in contact with Streptococcus mutans, Actinomyces viscosus, Fusobacterium nucleatum, and Bacteroides gingivalis. On days 0, 3, 7, and 14 after inoculation, the gingival condition...

  1. Postnatal development and behaviour of Wistar rats after prenatal toluene exposure

    Energy Technology Data Exchange (ETDEWEB)

    Thiel, R. [Fachbereich Humanmedizin, Universitaetsklinikum Benjamin Franklin, Inst. fuer Toxikologie und Embryopharmakologie, Freie Univ. Berlin (Germany); Chahoud, I. [Fachbereich Humanmedizin, Universitaetsklinikum Benjamin Franklin, Inst. fuer Toxikologie und Embryopharmakologie, Freie Univ. Berlin (Germany)

    1997-02-01

    Pregnant Wistar rats were treated with different concentrations of toluene by inhalation (300, 600, 1000 and 1200 ppm) from day 9 to day 21 of pregnancy for 6 h a day in a whole-body inhalation chamber (controls inhaled fresh air only). From day 22, rats were kept single-caged and were allowed to deliver. Besides a detailed evaluation of the physical development of the offspring we performed the following tests: forelimb-grasp reflex, righting reflex, cliff-drop aversion reflex, maintainance of balance on a rotating rod, measurement of locomotor activity and learning ability in a discrimination learning test. A toluene exposure of 1200 ppm resulted in a reduced body weight of rat dams and offspring and a higher mortality until weaning. The physical development (incisor eruption, eye opening and vaginal opening) was retarded in this group. There were no clear-cut and concentration-dependent differences in the development of reflexes, rota rod performance and locomotor activity between the offspring of animals exposed to toluene and the controls. Likewise, no effects were found on learning ability in the operant conditioning task. Compared to the controls there were no differences in mating, fertility and pregnancy indexes in the F{sub 1}-generation. The tests performed have provided no evidence that toluene exposures {<=} 1200 ppm induce adverse effects on the behaviour of rat offspring exposed during late embryonic and fetal development. (orig.). With 8 figs., 7 tabs.

  2. Effects of metabotropic glutamate receptor 5 antagonist MPEP on learning in developing rats

    Czech Academy of Sciences Publication Activity Database

    Mikulecká, Anna; Mareš, Pavel

    2007-01-01

    Roč. 18, Suppl. 1 (2007), S48-S48 ISSN 0955-8810. [Biennial Meeting of the European Behavioural Pharmacology Society /12./. 31.08.2007-03.09.2007, Tübingen] Institutional research plan: CEZ:AV0Z50110509 Keywords : MPEP * developing rats * behavioral parameters Subject RIV: ED - Physiology

  3. Oxidative Stress in the Developing Rat Brain due to Production of Reactive Oxygen and Nitrogen Species

    Czech Academy of Sciences Publication Activity Database

    Wilhelm, Jiří; Vytášek, Richard; Uhlík, Jiří; Vajner, Luděk

    2016-01-01

    Roč. 2016, č. 2016 (2016), č. článku 5057610. ISSN 1942-0900 R&D Projects: GA ČR(CZ) GAP303/11/0298 Institutional support: RVO:67985823 Keywords : oxidative stress * developing rat brain * lipid peroxidation Subject RIV: ED - Physiology Impact factor: 4.593, year: 2016

  4. IPRODIONE DELAYS MALE RAT PUBERTAL DEVELOPMENT, REDUCING SERUM TESTOSTERONE AND EX VIVO TESTOSTERONE PRODUCTION

    Science.gov (United States)

    Iprodione (IPRO) is a dichlorophenyl dicarboximide fungicide similar to the androgen receptor (AR) antagonist vinclozolin. The current studies were designed to determine if IPRO would delay male rat pubertal development like vinclozolin and to identify the mechanism(s) of action...

  5. Extinction, Reacquisition, and Rapid Forgetting of Eyeblink Conditioning in Developing Rats

    Science.gov (United States)

    Brown, Kevin L.; Freeman, John H.

    2014-01-01

    Eyeblink conditioning is a well-established model for studying the developmental neurobiology of associative learning and memory. However, age differences in extinction and subsequent reacquisition have yet to be studied using this model. The present study examined extinction and reacquisition of eyeblink conditioning in developing rats. In…

  6. The significance of soils and soil science towards realization of the United Nations Sustainable Development Goals

    Science.gov (United States)

    Keesstra, Saskia D.; Bouma, Johan; Wallinga, Jakob; Tittonell, Pablo; Smith, Pete; Cerdà, Artemi; Montanarella, Luca; Quinton, John N.; Pachepsky, Yakov; van der Putten, Wim H.; Bardgett, Richard D.; Moolenaar, Simon; Mol, Gerben; Jansen, Boris; Fresco, Louise O.

    2016-04-01

    In this forum paper we discuss how soil scientists can help to reach the recently adopted UN Sustainable Development Goals (SDGs) in the most effective manner. Soil science, as a land-related discipline, has important links to several of the SDGs, which are demonstrated through the functions of soils and the ecosystem services that are linked to those functions (see graphical abstract in the Supplement). We explore and discuss how soil scientists can rise to the challenge both internally, in terms of our procedures and practices, and externally, in terms of our relations with colleague scientists in other disciplines, diverse groups of stakeholders and the policy arena. To meet these goals we recommend the following steps to be taken by the soil science community as a whole: (i) embrace the UN SDGs, as they provide a platform that allows soil science to demonstrate its relevance for realizing a sustainable society by 2030; (ii) show the specific value of soil science: research should explicitly show how using modern soil information can improve the results of inter- and transdisciplinary studies on SDGs related to food security, water scarcity, climate change, biodiversity loss and health threats; (iii) take leadership in overarching system analysis of ecosystems, as soils and soil scientists have an integrated nature and this places soil scientists in a unique position; (iii) raise awareness of soil organic matter as a key attribute of soils to illustrate its importance for soil functions and ecosystem services; (iv) improve the transfer of knowledge through knowledge brokers with a soil background; (v) start at the basis: educational programmes are needed at all levels, starting in primary schools, and emphasizing practical, down-to-earth examples; (vi) facilitate communication with the policy arena by framing research in terms that resonate with politicians in terms of the policy cycle or by considering drivers, pressures and responses affecting impacts of land

  7. Myenteric denervation differentially reduces enteroendocrine serotonin cell population in rats during postnatal development.

    Science.gov (United States)

    Hernandes, Luzmarina; Fernandes, Marilda da Cruz; Pereira, Lucieni Cristina Marques da Silva; Freitas, Priscila de; Gama, Patrícia; Alvares, Eliana Parisi

    2006-05-01

    The enteric nervous and enteroendocrine systems regulate different processes in the small intestine. Ablation of myenteric plexus with benzalkonium chloride (BAC) stimulates epithelial cell proliferation, whereas endocrine serotonin cells may inhibit the process. To evaluate the connection between the systems and the influence of myenteric plexus on serotoninergic cells in rats during postnatal development, the ileal plexus was partially removed with BAC. Rats were treated at 13 or 21 days and sacrificed after 15 days. The cell bodies of myenteric neurons were stained by beta NADH-diaphorase to detect the extension of denervation. The number of enteroendocrine cells in the ileum was estimated in crypts and villi in paraffin sections immunostained for serotonin. The number of neurons was reduced by 27.6 and 45% in rats treated on the 13th and 21st days, respectively. We tried to establish a correlation of denervation and the serotonin population according to the age of treatment. We observed a reduction of immunolabelled cells in the crypts of rats treated at 13 days, whereas this effect was seen in the villi of rats denervated at 21 days. These results suggest that the enteric nervous system might control the enteroendocrine cell population and this complex mechanism could be correlated to changes in cell proliferation.

  8. Development of mPMab-1, a Mouse-Rat Chimeric Antibody Against Mouse Podoplanin.

    Science.gov (United States)

    Yamada, Shinji; Kaneko, Mika K; Nakamura, Takuro; Ichii, Osamu; Konnai, Satoru; Kato, Yukinari

    2017-04-01

    Podoplanin (PDPN), the ligand of C-type lectin-like receptor-2, is used as a lymphatic endothelial marker. We previously established clone PMab-1 of rat IgG 2a as a specific monoclonal antibody (mAb) against mouse PDPN. PMab-1 is also very sensitive in immunohistochemical analysis; however, rat mAbs seem to be unfavorable for pathologists because anti-mouse IgG and anti-rabbit IgG are usually used as secondary antibodies in commercially available kits for immunohistochemical analysis. In this study, we develop a mouse-rat chimeric antibody, mPMab-1 of mouse IgG 2a , which was derived from rat PMab-1 mAb. Immunohistochemical analysis shows that mPMab-1 detects podocytes of the kidney, lymphatic endothelial cells of the colon, and type I alveolar cells of the lung. Importantly, mPMab-1 is more sensitive than PMab-1. This conversion strategy from rat mAb to mouse mAb could be applicable to other mAbs.

  9. Abnormal peripubertal development of the rat mammary gland following exposure in utero and during lactation to a mixture of genistein and the food contaminant vinclozolin.

    Science.gov (United States)

    El Sheikh Saad, H; Meduri, G; Phrakonkham, P; Bergès, R; Vacher, S; Djallali, M; Auger, J; Canivenc-Lavier, M C; Perrot-Applanat, M

    2011-07-01

    The impact of early exposure to endocrine disruptor mixtures on mammary gland development is poorly known. Here, we identify the effects of a conception to weaning exposure of rats to the phytoestrogen genistein (G) and/or the antiandrogen vinclozolin (V) at 1mg/kg-d, alone or in association. Using several approaches, we found that G- and GV-exposed rats displayed significantly greater epithelial branching and proliferation, wider terminal end buds than controls at PND35, as well as ductal hyperplasia and periductal fibrosis. Focal branching defects were present in V-exposed rats. An increased ER and AR expression was observed in G- and GV- as compared to V-exposed rats at PND35. Surprisingly, a significant number of GV- and to a lesser extent, V-exposed animals displayed abnormal hyperplasic alveolar structures at PND50. Thus, gestational and lactational exposure to low doses of genistein plus vinclozolin may seriously affect peripubertal development of the rat mammary gland. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Effects of combined exposure to anti-androgens on development and sexual dimorphic behaviour in rats

    DEFF Research Database (Denmark)

    Christiansen, Sofie

    Summary Background: Androgens are key regulators of male sexual differentiation during the in utero and early postnatal development. Exposure to endocrine disrupting chemicals (EDCs) that counteract androgen action at some stage in these periods can permanently demasculinise male foetuses and lead......?  Is sexually dimorphic behaviour in rats affected at lower dose levels of anti-androgens and thereby a more sensitive endpoint than morphological effects on the male external reproductive organs? The thesis is based on the results of in vivo studies where mated female Wistar rats were exposed to anti......-androgens either alone or in mixtures during pregnancy and lactation. The endpoints examined for anti-androgenic effects in the offspring were: Anogenital distance (AGD), nipple retention (NR), and external (morphological) malformations in pups and sexually mature male rats. Furthermore, the effects of the anti...

  11. Detection of expressional changes induced by intrauterine growth restriction in the developing rat pancreas.

    Science.gov (United States)

    Zhang, Lin; Chen, Wei; Dai, Yuee; Zhu, Ziyang; Liu, Qianqi

    2016-07-01

    Intrauterine growth retardation (IUGR) is a disorder that can result in permanent changes in the physiology and metabolism of the newborn, which increased the risk of disease in adulthood. Evidence supports IUGR as a risk factor for the development of diabetes mellitus, which could reflect changes in pancreas developmental pathways. We sought to characterize the IUGR-induced alterations of the complex pathways of pancreas development in a rat model of IUGR. We analyzed the pancreases of Sprague Dawley rats after inducing IUGR by feeding a maternal low calorie diet from gestational day 1 until term. IUGR altered the pancreatic structure, islet areas, and islet quantities and resulted in abnormal morphological changes during pancreatic development, as determined by HE staining and light microscopy. We identified multiple differentially expressed genes in the pancreas by RT-PCR. The genes of the insulin/FoxO1/Pdx1/MafA signaling pathway were first expressed at embryonic day 14 (E14). The expressions of insulin and MafA increased as the fetus grew while the expressions of FoxO1 and Pdx1 decreased. Compared with the control rats, the expressions of FoxO1, Pdx1, and MafA were lower in the IUGR rats, whereas insulin levels showed no change. Microarray profiling, in combination with quantitative real-time PCR, uncovered a subset of microRNAs that changed in their degree of expression throughout pancreatic development. In conclusion, our data support the hypothesis that IUGR influences the development of the rat pancreas. We also identified new pathways that appear to be programmed by IUGR. © 2016 by the Society for Experimental Biology and Medicine.

  12. Effect of maternal excessive sodium intake on postnatal brain development in rat offspring.

    Science.gov (United States)

    Shin, Jung-a; Ahn, Young-mo; Lee, Hye-ah; Park, Hyesook; Kim, Young-ju; Lee, Hwa-young

    2015-04-01

    Postnatal brain development is affected by the in utero environment. Modern people usually have a high sodium intake. The aim of this study was to investigate the effect of sodium hyperingestion during pregnancy on the postnatal brain development of rat offspring. The sodium-overloaded rats received 1.8% NaCl in their drinking water for 7 days during the last week of gestation. Their body weight, urine, and blood levels of sodium and other parameters were measured. Some rats were sacrificed at pregnancy day 22 and the weight and length of the placenta and foetus were measured. The cerebral cortex and hippocampus were obtained from their offspring at postnatal day 1 and at postnatal weeks 1, 2, 4, and 8. Western blot analyses were conducted with brain tissue lysates. The sodium-overloaded animals had decreased weight gain in the last week of gestation as well as decreased food intake, increased water intake, urine volume, urine sodium, and serum sodium. There were no differences in placental weight and length. The foetuses of sodium-overloaded rats showed decreased body weight and size, and this difference was maintained postnatally for 2 weeks. In the cerebral cortex and hippocampus of the offspring, the protein levels of myelin basic protein, calmodulin/calcium-dependent protein kinase II, and brain-derived neurotrophic factor were decreased or aberrantly expressed. The present data suggest that increased sodium intake during pregnancy affects the brain development of the offspring.

  13. Chronic Oral Capsaicin Exposure During Development Leads to Adult Rats with Reduced Taste Bud Volumes.

    Science.gov (United States)

    Omelian, Jacquelyn M; Samson, Kaeli K; Sollars, Suzanne I

    2016-09-01

    Cross-sensory interaction between gustatory and trigeminal nerves occurs in the anterior tongue. Surgical manipulations have demonstrated that the strength of this relationship varies across development. Capsaicin is a neurotoxin that affects fibers of the somatosensory lingual nerve surrounding taste buds, but not fibers of the gustatory chorda tympani nerve which synapse with taste receptor cells. Since capsaicin is commonly consumed by many species, including humans, experimental use of this neurotoxin provides a naturalistic perturbation of the lingual trigeminal system. Neonatal or adults rats consumed oral capsaicin for 40 days and we examined the cross-sensory effect on the morphology of taste buds across development. Rats received moderate doses of oral capsaicin, with chronic treatments occurring either before or after taste system maturation. Tongue morphology was examined either 2 or 50 days after treatment cessation. Edema, which has been previously suggested as a cause of changes in capsaicin-related gustatory function, was also assessed. Reductions in taste bud volume occurred 50 days, but not 2 days post-treatment for rats treated as neonates. Adult rats at either time post-treatment were unaffected. Edema was not found to occur with the 5 ppm concentration of capsaicin we used. Results further elucidate the cooperative relationship between these discrete sensory systems and highlight the developmentally mediated aspect of this interaction. Chronic exposure to even moderate levels of noxious stimuli during development has the ability to impact the orosensory environment, and these changes may not be evident until long after exposure has ceased.

  14. Oxcarbazepine causes neurocyte apoptosis and developing brain damage by triggering Bax/Bcl-2 signaling pathway mediated caspase 3 activation in neonatal rats.

    Science.gov (United States)

    Song, Y; Zhong, M; Cai, F-C

    2018-01-01

    Anti-epileptic drugs (AEDs) are the main methods for treatment of neonatal seizures; however, a few AEDs may cause developing brain damage of neonate. This study aims to investigate effects of oxcarbazepine (OXC) on developing brain damage of neonatal rats. Both of neonatal and adult rats were divided into 6 groups, including Control, OXC 187.5 mg/kg, OXC 281.25 mg/kg, OXC 375 mg/kg group, LEV and PHT group. Body weight and brain weight were evaluated. Hematoxylin and eosin (HE) and Nissl staining were used to observe neurocyte morphology and Nissl bodies, respectively. Apoptosis was examined using TUNEL assay, and caspase 8 activity was evaluated using spectrophotometer method. Cytochrome C-release was evaluated using flow cytometry. Western blot was used to examine Bax and Bcl-2 expression. OXC 375 mg/kg treatment significantly decreased brain weight compared to Control group in neonatal rats (P5 rats) (pOxcarbazepine at a concentration of 281.25 mg/kg or more causes neurocyte apoptosis and developing brain damage by triggering Bax/Bcl-2 signaling pathway mediated caspase 3 activation in neonatal rats.

  15. Altered ERK1/2 Signaling in the Brain of Learned Helpless Rats: Relevance in Vulnerability to Developing Stress-Induced Depression

    Directory of Open Access Journals (Sweden)

    Yogesh Dwivedi

    2016-01-01

    Full Text Available Extracellular signal-regulated kinase 1/2- (ERK1/2- mediated cellular signaling plays a major role in synaptic and structural plasticity. Although ERK1/2 signaling has been shown to be involved in stress and depression, whether vulnerability to develop depression is associated with abnormalities in ERK1/2 signaling is not clearly known. The present study examined ERK1/2 signaling in frontal cortex and hippocampus of rats that showed vulnerability (learned helplessness, (LH or resiliency (non-learned helplessness, (non-LH to developing stress-induced depression. In frontal cortex and hippocampus of LH rats, we found that mRNA and protein expressions of ERK1 and ERK2 were significantly reduced, which was associated with their reduced activation and phosphorylation in cytosolic and nuclear fractions, where ERK1 and ERK2 target their substrates. In addition, ERK1/2-mediated catalytic activities and phosphorylation of downstream substrates RSK1 (cytosolic and nuclear and MSK1 (nuclear were also lower in the frontal cortex and hippocampus of LH rats without any change in their mRNA or protein expression. None of these changes were evident in non-LH rats. Our study indicates that ERK1/2 signaling is differentially regulated in LH and non-LH rats and suggests that abnormalities in ERK1/2 signaling may be crucial in the vulnerability to developing depression.

  16. Glucagon-like peptide-1 acutely affects renal blood flow and urinary flow rate in spontaneously hypertensive rats despite significantly reduced renal expression of GLP-1 receptors

    DEFF Research Database (Denmark)

    Ronn, Jonas; Jensen, Elisa P; Wewer Albrechtsen, Nicolai J

    2017-01-01

    to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP-1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP-1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect......Glucagon-like peptide-1 (GLP-1) is an incretin hormone increasing postprandial insulin release. GLP-1 also induces diuresis and natriuresis in humans and rodents. The GLP-1 receptor is extensively expressed in the renal vascular tree in normotensive rats where acute GLP-1 treatment leads...... in the kidney from SHR. However, acute intrarenal infusion of GLP-1 increased MAP, RBF, dieresis, and natriuresis without affecting heart rate in both rat strains. These results suggest that the acute renal effects of GLP-1 in SHR are caused either by extrarenal GLP-1 receptors activating other mechanisms (e...

  17. Effect of zinc oxide nanoparticles on dams and embryo–fetal development in rats

    Directory of Open Access Journals (Sweden)

    Hong J

    2014-12-01

    Full Text Available Jeong-Sup Hong,1,2 Myeong-Kyu Park,1 Min-Seok Kim,1 Jeong-Hyeon Lim,1 Gil-Jong Park,1 Eun-Ho Maeng,1 Jae-Ho Shin,3 Yu-Ri Kim,4 Meyoung-Kon Kim,4 Jong-Kwon Lee,5 Jin-A Park,2 Jong-Choon Kim,6 Ho-Chul Shin2 1Health Care Research Laboratory, Korea Testing and Research Institute, Gimpo, 2College of Veterinary Medicine, Konkuk University, Seoul, 3Department of Biomedical Laboratory Science, Eulji University, Seongnam-si, 4Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, 5Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungcheongbuk-do, 6College of Veterinary Medicine, Chonnam National University, Gwangju, Korea Abstract: This study investigated the potential adverse effects of zinc oxide nanoparticles (ZnOSM20[-] NPs; negatively charged, 20 nm on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague Dawley rats. ZnOSM20(- NPs were administered to pregnant rats by gavage at 0 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day. All dams were subjected to caesarean section on gestational day 20, and all the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight at 400 mg/kg/day and decreased liver weight, and increased adrenal glands weight at 200 mg/kg/day and 400 mg/kg/day. However, no treatment-related difference in the number of corpora lutea, the number of implantation sites, the implantation rate (%, resorption, dead fetuses, litter size, fetal deaths, fetal and placental weights, and sex ratio were observed between the groups. Morphological examinations of the fetuses demonstrated no significant difference in the incidences of abnormalities between the groups. No significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed

  18. Influence of gastric pH modifiers on development of intestinal metaplasia induced by X-irradiation in rats

    International Nuclear Information System (INIS)

    Watanabe, Hiromitsu; Okamoto, Taro; Fudaba, Yasuhiro; Ogundigie, P.S.; Ito, Akihiro

    1993-01-01

    The influence of gastric pH on intestinal metaplasia was examined in male Crj:CD(SD) rats. At the age of 5 weeks, animals were irradiated with two 10 Gy doses of X-rays to the gastric region at a 3-day interval (total 20 Gy), and 6 months after irradiation, received either secretin or histamine in silicon tubes for 2 months or had their bilateral submandibular salivary glands removed. The incidences of intestinal metaplasia in the fundus of animals after administration of secretin or histamine, or removal of the salivary glands were reduced, along with the pH values, as compared with values for rats given X-rays alone. In both the pyloric and the fundic gland mucosae, the numbers of alkaline phosphatase (ALP)-positive foci and type B metaplasias (intestinal crypts without Paneth cells) were also significantly decreased (P<0.01). In a second experiment, started six months after irradiation, rats were kept on 1% sodium chloride (NaCl) diet for 6 months. Subsequent removal of salivary glands along with histamine treatment brought about a marked drop in pH and in numbers of ALP-positive foci after three and five days. The present results thus indicated that development and maintenance of intestinal metaplasia can be influenced by a decrease of pH value. (author)

  19. Repercussions of mild diabetes on pregnancy in Wistar rats and on the fetal development

    Directory of Open Access Journals (Sweden)

    Saito Felipe H

    2010-04-01

    Full Text Available Abstract Background Experimental models are necessary to elucidate diabetes pathophysiological mechanisms not yet understood in humans. Objective: To evaluate the repercussions of the mild diabetes, considering two methodologies, on the pregnancy of Wistar rats and on the development of their offspring. Methods In the 1st induction, female offspring were distributed into two experimental groups: Group streptozotocin (STZ, n = 67: received the β-cytotoxic agent (100 mg STZ/kg body weight - sc on the 1st day of the life; and Non-diabetic Group (ND, n = 14: received the vehicle in a similar time period. In the adult life, the animals were mated. After a positive diagnosis of pregnancy (0, female rats from group STZ presenting with lower glycemia than 120 mg/dL received more 20 mg STZ/kg (ip at day 7 of pregnancy (2nd induction. The female rats with glycemia higher than 120 mg/dL were discarded because they reproduced results already found in the literature. In the mornings of days 0, 7, 14 and 21 of the pregnancy glycemia was determined. At day 21 of pregnancy (at term, the female rats were anesthetized and killed for maternal reproductive performance and fetal development analysis. The data were analyzed using Student-Newman-Keuls, Chi-square and Zero-inflated Poisson (ZIP Tests (p Results STZ rats presented increased rates of pre (STZ = 22.0%; ND = 5.1% and post-implantation losses (STZ = 26.1%; ND = 5.7%, reduced rates of fetuses with appropriate weight for gestational age (STZ = 66%; ND = 93% and reduced degree of development (ossification sites. Conclusion Mild diabetes led a negative impact on maternal reproductive performance and caused intrauterine growth restriction and impaired fetal development.

  20. Motor System Development Depends on Experience: A Microgravity Study of Rats

    Science.gov (United States)

    Walton, Kerry D.; Llinas, Rodolfo R.; Kalb, Robert; Hillman, Dean; DeFelipe, Javier; Garcia-Segura, Luis Miguel

    2003-01-01

    Animals move about their environment by sensing their surroundings and making adjustments according to need. All animals take the force of gravity into account when the brain and spinal cord undertake the planning and execution of movements. To what extent must animals learn to factor in the force of gravity when making neural calculations about movement? Are animals born knowing how to respond to gravity, or must the young nervous system learn to enter gravity into the equation? To study this issue, young rats were reared in two different gravitational environments (the one-G of Earth and the microgravity of low Earth orbit) that necessitated two different types of motor operations (movements) for optimal behavior. We inquired whether those portions of the young nervous system involved in movement, the motor system, can adapt to different gravitational levels and, if so, the cellular basis for this phenomenon. We studied two groups of rats that had been raised for 16 days in microgravity (eight or 14 days old at launch) and compared their walking and righting (ability to go from upside down to upright) and brain structure to those of control rats that developed on Earth. Flight rats were easily distinguished from the age-matched ground control rats in terms of both motor function and central nervous system structure. Mature surface righting predominated in control rats on the day of landing (R+O), while immature righting predominated in the flight rats on landing day and 30 days after landing. Some of these changes appear to be permanent. Several conclusions can be drawn from these studies: (1) Many aspects of motor behavior are preprogrammed into the young nervous system. In addition, several aspects of motor behavior are acquired as a function of the interaction of the developing organism and the rearing environment; (2) Widespread neuroanatomical differences between one-G- and microgravity-reared rats indicate that there is a structural basis for the adaptation

  1. The effectiveness of the anti-CD11d treatment is reduced in rat models of spinal cord injury that produce significant levels of intraspinal hemorrhage.

    Science.gov (United States)

    Geremia, N M; Hryciw, T; Bao, F; Streijger, F; Okon, E; Lee, J H T; Weaver, L C; Dekaban, G A; Kwon, B K; Brown, A

    2017-09-01

    We have previously reported that administration of a CD11d monoclonal antibody (mAb) improves recovery in a clip-compression model of SCI. In this model the CD11d mAb reduces the infiltration of activated leukocytes into the injured spinal cord (as indicated by reduced intraspinal MPO). However not all anti-inflammatory strategies have reported beneficial results, suggesting that success of the CD11d mAb treatment may depend on the type or severity of the injury. We therefore tested the CD11d mAb treatment in a rat hemi-contusion model of cervical SCI. In contrast to its effects in the clip-compression model, the CD11d mAb treatment did not improve forelimb function nor did it significantly reduce MPO levels in the hemi-contused cord. To determine if the disparate results using the CD11d mAb were due to the biomechanical nature of the cord injury (compression SCI versus contusion SCI) or to the spinal level of the injury (12th thoracic level versus cervical) we further evaluated the CD11d mAb treatment after a T12 contusion SCI. In contrast to the T12 clip compression SCI, the CD11d mAb treatment did not improve locomotor recovery or significantly reduce MPO levels after T12 contusion SCI. Lesion analyses revealed increased levels of hemorrhage after contusion SCI compared to clip-compression SCI. SCI that is accompanied by increased intraspinal hemorrhage would be predicted to be refractory to the CD11d mAb therapy as this approach targets leukocyte diapedesis through the intact vasculature. These results suggest that the disparate results of the anti-CD11d treatment in contusion and clip-compression models of SCI are due to the different pathophysiological mechanisms that dominate these two types of spinal cord injuries. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  2. Changes in expression of Class 3 Semaphorins and their receptors during development of the rat retina and superior colliculus.

    Science.gov (United States)

    Sharma, Anil; LeVaillant, Chrisna J; Plant, Giles W; Harvey, Alan R

    2014-07-26

    Members of the Semaphorin 3 family (Sema3s) influence the development of the central nervous system, and some are implicated in regulating aspects of visual system development. However, we lack information about the timing of expression of the Sema3s with respect to different developmental epochs in the mammalian visual system. In this time-course study in the rat, we document for the first time changes in the expression of RNAs for the majority of Class 3 Semaphorins (Sema3s) and their receptor components during the development of the rat retina and superior colliculus (SC). During retinal development, transcript levels changed for all of the Sema3s examined, as well as Nrp2, Plxna2, Plxna3, and Plxna4a. In the SC there were also changes in transcript levels for all Sema3s tested, as well as Nrp1, Nrp2, Plxna1, Plxna2, Plxna3, and Plxna4a. These changes correlate with well-established epochs, and our data suggest that the Sema3s could influence retinal ganglion cell (RGC) apoptosis, patterning and connectivity in the maturing retina and SC, and perhaps guidance of RGC and cortical axons in the SC. Functionally we found that SEMA3A, SEMA3C, SEMA3E, and SEMA3F proteins collapsed purified postnatal day 1 RGC growth cones in vitro. Significantly this is a developmental stage when RGCs are growing into and within the SC and are exposed to Sema3 ligands. These new data describing the overall temporal regulation of Sema3 expression in the rat retina and SC provide a platform for further work characterising the functional impact of these proteins on the development and maturation of mammalian visual pathways.

  3. Evaluation of Neonatal Streptozotocin Induced Diabetic Rat Model for the Development of Cataract

    Directory of Open Access Journals (Sweden)

    Madhoosudan A. Patil

    2014-01-01

    Full Text Available Type 2 diabetes (T2D generally follows prediabetes (PD conditions such as impaired fasting glucose (IFG and/or impaired glucose tolerance (IGT. Although studies reported an association of IGT or IFG with cataract, the experimental basis for PD associated cataract is not known. Hence, we evaluated neonatal streptozotocin (nSTZ induced rat model to study PD associated cataractogenesis by injecting STZ to two-day old rats. While majority (70% of nSTZ injected pups developed IGT (nSTZ-PD by two months but not cataract even after seven months, remaining (30% nSTZ rats developed hyperglycemia (nSTZ-D by two months and mature cataract by seven months. Lens biochemical analysis indicated increased oxidative stress as indicated by increased SOD activity, lipid peroxidation, and protein carbonyl levels in nSTZ-D cataractous lens. There was also increased polyol pathway as assessed by aldose reductase activity and sorbitol levels. Though nSTZ-PD animals have not shown any signs of lenticular opacity, insolubilization of proteins along with enhanced polyol pathway was observed in the lens. Further there was increased oxidative stress in lens of IGT animals. These results suggest that oxidative stress along with increased polyol pathway might play a role in IGT-associated lens abnormalities. In conclusion, nSTZ-PD rat model could aid to investigate IGT-associated lens abnormalities.

  4. Effect of Marine Collagen Peptides on Physiological and Neurobehavioral Development of Male Rats with Perinatal Asphyxia

    Directory of Open Access Journals (Sweden)

    Linlin Xu

    2015-06-01

    Full Text Available Asphyxia during delivery produces long-term deficits in brain development. We investigated the neuroprotective effects of marine collagen peptides (MCPs, isolated from Chum Salmon skin by enzymatic hydrolysis, on male rats with perinatal asphyxia (PA. PA was performed by immersing rat fetuses with uterine horns removed from ready-to-deliver rats into a water bath for 15 min. Caesarean-delivered pups were used as controls. PA rats were intragastrically administered with 0.33 g/kg, 1.0 g/kg and 3.0 g/kg body weight MCPs from postnatal day 0 (PND 0 till the age of 90-days. Behavioral tests were carried out at PND21, PND 28 and PND 90. The results indicated that MCPs facilitated early body weight gain of the PA pups, however had little effects on early physiological development. Behavioral tests revealed that MCPs facilitated long-term learning and memory of the pups with PA through reducing oxidative damage and acetylcholinesterase (AChE activity in the brain, and increasing hippocampus phosphorylated cAMP-response element binding protein (p-CREB and brain derived neurotrophic factor (BDNF expression.

  5. GENE EXPRESSION PROFILES IN THE DEVELOPING RAT CEREBELLUM AND HIPPOCAMPUS

    Science.gov (United States)

    Development of the nervous system is a complex program, involving coordinated growth of axons and their targets. In rodents, rapid brain growth occurs during early postnatal development. At this time, several fundamental processes, such as dendritic and axonal outgrowth and the e...

  6. Development and adaptation to resection of infant rat gut

    NARCIS (Netherlands)

    J.E. de Vries

    1982-01-01

    textabstractInfants with malrotation of the gut easily develop midgut volvuluse If this volvulus is not treated immediately, ischemic necrosis of the small bowel may develop rapidly. The treatment of these children requires extensive small bowel resection. Infrequently, children are born with

  7. Effects of Maternal Lead Acetate Exposure during Lactation on Postnatal Development of Testis in Offspring Wistar Rats

    Directory of Open Access Journals (Sweden)

    Mehran Dorostghoal

    2011-03-01

    Full Text Available Objective(sDuring recent years, there has been an increasing interest in contribution of environmental pollutants as heavy metals to human male infertility. Present study was aimed to investigate the effects of maternal lead acetate exposure during lactation on postnatal development of testis in offspring rats.Materials and MethodsA total of 60 female rats randomly divided into four equal groups; control and three treatment groups received 20, 100 and 300 mg/kg/day lead acetate via drinking water from day 2 to day 21 of lactation. At 7, 14, 21, 28, 60, 90 and 120 days after birth, the testis weight and volume of offspring were measured and their epididymal semen analyzed. Following tissue processing, 5 μm sections were stained with haematoxylin-eosin and evaluated with quantitative techniques. Testicular parameters in different groups were compared by one-way ANOVA.ResultsTestis weight and volume of offspring decreased significantly in a dose-related manner in moderate (P< 0.05 and high (P< 0.01 doses groups. Dose-dependent significant reductions were seen in seminiferous tubules diameter and germinal epithelium height during neonatal, prepubertal and postpubertal periods in moderate (P< 0.05 and high (P< 0.01 doses groups until 90 and 120 days after birth, respectively. Significant decreases were observed in mean sperm density of offspring at puberty in moderate and high doses groups until 90 and 120 days after birth, respectively. Testosterone levels decreased significantly in a dose-related manner at puberty in moderate and high doses groups. ConclusionPresent study showed maternal lead acetate exposure during lactation caused dose-related and long-term alterations of testicular parameters in offspring rats.

  8. The Effect of Maternal Thyroid Disorders (Hypothyroidism and Hyperthyroidism During Pregnancy and Lactation on Skin Development in Wistar Rat Newborns

    Directory of Open Access Journals (Sweden)

    Maryam Amerion

    2013-05-01

    Full Text Available   Objective(s: Previous studies have shown that thyroid hormones are necessary for normal development of many organs and because of the importance of skin as the largest and the most important organ in human body protection in spite of external environment, the study of thyroid hormones effects on skin development is considerable. In this survey we have tried to study the effects of maternal hypothyroidism on skin development in fetus during pregnancy and lactation by immunohistochemistry technique.   Materials and Methods: Rats were divided into 4 groups, hypothyroids, hyperthyroids, hypothyroids are treated with levothyroxin and a control group. The rat mothers were exposed to PTU with 50 mg/lit dosage and levothyroxin with 1 mg/lit dosage and PTU and levothyroxin simultaneously and with the same dosage respectively in hypothyroid, hyperthyroid and treated hypothyroids with levothyroxin groups. After 14 days, blood sample was taken from mothers, and if thyroid hormones level had change well, mating was allowed. After pregnancy and delivery, 1th day dorsal skin (as the sample for pregnancy assay and 10th day skin (as for lactation assay was used for immunohystochemical and morphometric studies. Results: In this study it was observed that maternal hypothyroidism during pregnancy and lactation causes significant increase in laminin expression, in most areas of skin, and maternal hyperthyroidism during pregnancy and lactation causes significant decrease in laminin expression. Also significant decrease was observed in hair follicles number and epidermis thickness in hypothyroidism groups. Conclusion: This study showed maternal hypothyroidism causes significant decrease in epidermis thickness and hair follicles number and it causes less hair in fetus. Also maternal hypothyroidism causes large changes in laminin expression in different parts of skin. At the same time,maternal hyperthyroidism causes opposite results. In fact, thyroid hormones

  9. The importance of dietary control in the development of a peanut allergy model in Brown Norway rats

    NARCIS (Netherlands)

    Jonge, J.D. de; Knippels, L.M.J.; Ezendam, J.; Odink, J.; Penninks, A.H.; Loveren, H. van

    2007-01-01

    This report describes the further development of a peanut allergy model in Brown Norway (BN) rats and in particular the importance of allergen-free breeding of the laboratory animals for the allergen to be used. For this purpose BN rats were bred for 3 generations on soy- and peanut-free feed since

  10. Cytomegalovirus-enhanced development of transplant arteriosclerosis in the rat; effect of timing of infection and recipient responsiveness

    NARCIS (Netherlands)

    Hillebrands, JL; van Dam, JG; Onuta, G; Klatter, FA; Grauls, G; Bruggeman, CA; Rozing, J

    Cytomegalovirus (CMV) is put forward as a risk factor for transplant arteriosclerosis (TA). In this article, we studied CMV-enhanced development of TA in rats in different donor/recipient combinations in relation to the timing of infection. Recipient rats transplanted with an aortic allograft (BN to

  11. Effect of hypothyroidism on ovarian follicular development, granulosa cell proliferation and peripheral hormone levels in the prepubertal rat

    NARCIS (Netherlands)

    Dijkstra, G.; de rooij, D. G.; de Jong, F. H.; van den Hurk, R.

    1996-01-01

    The aim of this study was to examine the effects of prepubertal hypothyroidism on ovarian development in rats. Therefore, from birth up to day 40 postpartum, rats were given 6-propyl-2-thiouracil (PTU) via the drinking water of mothers and pups. At ages ranging from 12 to 40 days, ovarian weights

  12. Glucagon-like peptide-1 acutely affects renal blood flow and urinary flow rate in spontaneously hypertensive rats despite significantly reduced renal expression of GLP-1 receptors.

    Science.gov (United States)

    Ronn, Jonas; Jensen, Elisa P; Wewer Albrechtsen, Nicolai J; Holst, Jens Juul; Sorensen, Charlotte M

    2017-12-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone increasing postprandial insulin release. GLP-1 also induces diuresis and natriuresis in humans and rodents. The GLP-1 receptor is extensively expressed in the renal vascular tree in normotensive rats where acute GLP-1 treatment leads to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP-1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP-1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect of acute intrarenal infusion of GLP-1. We hypothesized that GLP-1 would increase diuresis and natriuresis and reduce MAP in SHR. Immunohistochemical staining and in situ hybridization for the GLP-1 receptor were used to localize GLP-1 receptors in the kidney. Sevoflurane-anesthetized normotensive Sprague-Dawley rats and SHR received a 20 min intrarenal infusion of GLP-1 and changes in MAP, RBF, heart rate, dieresis, and natriuresis were measured. The vasodilatory effect of GLP-1 was assessed in isolated interlobar arteries from normo- and hypertensive rats. We found no expression of GLP-1 receptors in the kidney from SHR. However, acute intrarenal infusion of GLP-1 increased MAP, RBF, dieresis, and natriuresis without affecting heart rate in both rat strains. These results suggest that the acute renal effects of GLP-1 in SHR are caused either by extrarenal GLP-1 receptors activating other mechanisms (e.g., insulin) to induce the renal changes observed or possibly by an alternative renal GLP-1 receptor. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  13. Modified High-Sucrose Diet-Induced Abdominally Obese and Normal-Weight Rats Developed High Plasma Free Fatty Acid and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Li Cao

    2012-01-01

    Full Text Available Introduction. Metabolically obese but normal-weight (MONW individuals have metabolic features of overt obesity, and abdominal adiposity is common in them. Animal models of MONW individuals are lacking. We aimed to develop an abdominally obese and normal-weight (AONW rat model. Methods and Results. Young male Sprague-Dawley rats were fed chow or a modified high-sucrose (HS diet for 20 weeks. The HS diet induced increased visceral adipose tissue without increased body weight, reduced glucose disposal rates, and increased hepatic glucose output during the hyperinsulinemic-euglycemic clamp, increased plasma glucose during the intraperitoneal glucose tolerance test, and increased plasma free fatty acids. Hepatic lipidosis and hepatocyte mitochondria swelling were found in HS rats through light microscopy and transmission electron microscopy; similar impairments were not observed in muscle. RT-PCR showed that mRNA expression of uncoupling protein 3 and peroxisome proliferator-activated receptor-gamma coactivator 1α increased in muscle of HS rats, while expression of mitochondrial transcription factor A, glucose transporter type 4, and insulin receptor substrate-1 did not change significantly. Conclusion. AONW rats developed metabolic disorders seen in MONW individuals. Steatosis, mitochondrial morphologic changes, and insulin resistance were more serious in liver than in muscle. Genes involved in fatty acid metabolism and mitochondrial function changed in less impaired muscle.

  14. Modified high-sucrose diet-induced abdominally obese and normal-weight rats developed high plasma free fatty acid and insulin resistance.

    Science.gov (United States)

    Cao, Li; Liu, Xuehui; Cao, Hongyi; Lv, Qingguo; Tong, Nanwei

    2012-01-01

    Metabolically obese but normal-weight (MONW) individuals have metabolic features of overt obesity, and abdominal adiposity is common in them. Animal models of MONW individuals are lacking. We aimed to develop an abdominally obese and normal-weight (AONW) rat model. Young male Sprague-Dawley rats were fed chow or a modified high-sucrose (HS) diet for 20 weeks. The HS diet induced increased visceral adipose tissue without increased body weight, reduced glucose disposal rates, and increased hepatic glucose output during the hyperinsulinemic-euglycemic clamp, increased plasma glucose during the intraperitoneal glucose tolerance test, and increased plasma free fatty acids. Hepatic lipidosis and hepatocyte mitochondria swelling were found in HS rats through light microscopy and transmission electron microscopy; similar impairments were not observed in muscle. RT-PCR showed that mRNA expression of uncoupling protein 3 and peroxisome proliferator-activated receptor-gamma coactivator 1α increased in muscle of HS rats, while expression of mitochondrial transcription factor A, glucose transporter type 4, and insulin receptor substrate-1 did not change significantly. AONW rats developed metabolic disorders seen in MONW individuals. Steatosis, mitochondrial morphologic changes, and insulin resistance were more serious in liver than in muscle. Genes involved in fatty acid metabolism and mitochondrial function changed in less impaired muscle.

  15. Effects of heavy ions on the development of male gonads in fetal rats

    International Nuclear Information System (INIS)

    Wang, Bing; Murakami, Masahiro; Eguchi-Kasai, Kiyomi; Shang, Yi; Tanaka, Kaoru; Hayata, Isamu

    2004-01-01

    Effects of exposure to accelerated heavy ion beam on the development of rats in late organogenesis were studied both in utero and in vitro, with a special focus to the response of male gonads. Either rat fetuses in utero or the cultured fetal testes in vitro were irradiated with carbon or Ne ion beams at a dose range from 0.1 Gy to 2.5 Gy. In addition to the linear energy transfer (LET) value of 13 keV/μm of carbon ion beams and of 30 keV/m of Ne ion beams for the in utero irradiation, the LET values at 40, 60, and 80 keV/μm of carbon ion beams were also applied for the in vitro investigation. In the mean time, effects from X-irradiations estimated under the same biological endpoints were studied comparatively for the relative biological effectiveness (RBE) estimation of the accelerated heavy ion irradiations. Although the statistical analysis of results was not finished, certain tendencies were found as follows: For the in utero studies, pups from dams received the accelerated heavy ion irradiations showed higher incidences of prenatal death and preweaning mortality, markedly delayed accomplishment in their physiological markers and reflexes and gain in body weight compared to that exposed to X-irradiations at the same doses. Significantly reduced ratios of main organ weight to body weight including brain, heart, thymus, lung, liver, kidney and testis were also observed in the pups from dams received the accelerated heavy ion irradiations compared to that exposed to X-irradiations at the same doses at postnatal ages of 1, 2 and three months. In addition, testes obtained at these postnatal ages are being studied on testicular development including conditions of the seminiferous tubules, the numbers of germ cells and Sertoli cells. For the in vitro experiments, pathological analysis of apoptosis occurrence in the cultured testes after X-irradiation or exposure to accelerated heavy ion beam is also now under investigation. From the third year, we would like to

  16. The role of mitochondrial DNA large deletion for the development of presbycusis in Fischer 344 rats.

    Science.gov (United States)

    Yin, Shankai; Yu, Zhiping; Sockalingam, Ravi; Bance, Manohar; Sun, Genlou; Wang, Jian

    2007-09-01

    Age-related hearing loss, or presbycusis, has been associated with large-scale mitochondrial DNA (mtDNA) deletion in previous studies. However, the role of this mtDNA damage in presbycusis is still not clear because the deletion in inner ears has not been measured quantitatively and analyzed in parallel with the time course of presbycusis. In the present study, the deletion was quantified using quantitative real-time PCR (qRT-PCR) in male Fischer 344 rats of different ages. It was found that the deletion increased quickly during young adulthood and reached over 60% at 6 months of age. However, a significant hearing loss was not seen until after 12 months of age. The results suggest that the existence of the deletion per se does not necessarily imply cochlear damage, but rather a critical level of the accumulated deletion seems to precede the hearing loss. The long delay may indicate the involvement of mechanisms other than mtDNA deletion in the development of presbycusis.

  17. Lead reduces tension development and the myosin ATPase activity of the rat right ventricular myocardium

    Directory of Open Access Journals (Sweden)

    D.V. Vassallo

    2008-09-01

    Full Text Available Lead (Pb2+ poisoning causes hypertension, but little is known regarding its acute effects on cardiac contractility. To evaluate these effects, force was measured in right ventricular strips that were contracting isometrically in 45 male Wistar rats (250-300 g before and after the addition of increasing concentrations of lead acetate (3, 7, 10, 30, 70, 100, and 300 µM to the bath. Changes in rate of stimulation (0.1-1.5 Hz, relative potentiation after pauses of 15, 30, and 60 s, effect of Ca2+ concentration (0.62, 1.25, and 2.5 mM, and the effect of isoproterenol (20 ng/mL were determined before and after the addition of 100 µM Pb2+. Effects on contractile proteins were evaluated after caffeine treatment using tetanic stimulation (10 Hz and measuring the activity of the myosin ATPase. Pb2+ produced concentration-dependent force reduction, significant at concentrations greater than 30 µM. The force developed in response to increasing rates of stimulation became smaller at 0.5 and 0.8 Hz. Relative potentiation increased after 100 µM Pb2+ treatment. Extracellular Ca2+ increment and isoproterenol administration increased force development but after 100 µM Pb2+ treatment the force was significantly reduced suggesting an effect of the metal on the sarcolemmal Ca2+ influx. Concentration of 100 µM Pb2+ also reduced the peak and plateau force of tetanic contractions and reduced the activity of the myosin ATPase. Results showed that acute Pb2+ administration, although not affecting the sarcoplasmic reticulum activity, produces a concentration-dependent negative inotropic effect and reduces myosin ATPase activity. Results suggest that acute lead administration reduced myocardial contractility by reducing sarcolemmal calcium influx and the myosin ATPase activity. These results also suggest that lead exposure is hazardous and has toxicological consequences affecting cardiac muscle.

  18. Expression patterns and role of PTEN in rat peripheral nerve development and injury.

    Science.gov (United States)

    Chen, Hui; Xiang, Jianping; Wu, Junxia; He, Bo; Lin, Tao; Zhu, Qingtang; Liu, Xiaolin; Zheng, Canbin

    2018-05-29

    Studies have suggested that phosphatase and tensin homolog (PTEN) plays an important role in neuroprotection and neuronal regeneration. To better understand the potential role of PTEN with respect to peripheral nerve development and injury, we investigated the expression pattern of PTEN at different stages of rat peripheral nerve development and injury and subsequently assessed the effect of pharmacological inhibition of PTEN using bpV(pic) on axonal regeneration in a rat sciatic nerve crush injury model. During the early stages of development, PTEN exhibits low expression in neuronal cell bodies and axons. From embryonic day (E) 18.5 and postnatal day (P)5 to adult, PTEN protein becomes more detectable, with high expression in the dorsal root ganglia (DRG) and axons. PTEN expression is inhibited in peripheral nerves, preceding myelination during neuronal development and remyelination after acute nerve injury. Low PTEN expression after nerve injury promotes Akt/mammalian target of rapamycin (mTOR) signaling pathway activity. In vivo pharmacological inhibition of PTEN using bpV(pic) promoted axonal regrowth, increased the number of myelinated nerve fibers, improved locomotive recovery and enhanced the amplitude response and nerve conduction velocity following stimulation in a rat sciatic nerve crush injury model. Thus, we suggest that PTEN may play potential roles in peripheral nerve development and regeneration and that inhibition of PTEN expression is beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Effects of Prenatal Irradiation with an Accelerated Heavy-Ion Beam on Postnatal Development in Rats

    Science.gov (United States)

    Wang, B.; Murakami, M.; Eguchi-Kasai, K.; Nojima, K.; Shang, Y.; Tanaka, K.; Fujita, K.; Coffigny, H.; Hayata, I.

    Effects on postnatal neurophysiological development in offspring were studied following exposure of pregnant Wistar rats to accelerated neon-ion beams with a LET value of about 30 keV mu m at a dose range from 0 1 Gy to 2 0Gy on the 15th day of gestation The age at which four physiologic markers appeared and five reflexes were acquired was examined prior to weaning Gain in body weight was monitored until the offspring were 3 months old Male offspring were evaluated as young adults using two behavioral tests The effects of X-rays at 200 kVp measured for the same biological end points were studied for comparison Our previous study on carbon-ion beams with a LET value of about 13 keV mu m was also cited to elucidate a possible LET-related effect For most of the endpoints at early age significant alteration was even observed in offspring prenatally received 0 1 Gy of accelerated neon ions while neither X rays nor carbon-ions under the same dose resulted in such a significant alteration compared to that from the sham-irradiated dams All offspring whose mothers received 2 0 Gy died prior to weaning Offspring from dams irradiated with accelerated neon ions generally showed higher incidences of prenatal death and preweaning mortality markedly delayed accomplishment in their physiological markers and reflexes and gain in body weight compared to those exposed to X-rays or carbon ions at doses of 0 1 to 1 5 Gy Significantly reduced ratios of main organ weight to body weight at postnatal ages of 30 60 and 90 days were also observed

  20. Maternal Style Selectively Shapes Amygdalar Development and Social Behavior in Rats Genetically Prone to High Anxiety.

    Science.gov (United States)

    Cohen, Joshua L; Glover, Matthew E; Pugh, Phyllis C; Fant, Andrew D; Simmons, Rebecca K; Akil, Huda; Kerman, Ilan A; Clinton, Sarah M

    2015-01-01

    The early-life environment critically influences neurodevelopment and later psychological health. To elucidate neural and environmental elements that shape emotional behavior, we developed a rat model of individual differences in temperament and environmental reactivity. We selectively bred rats for high versus low behavioral response to novelty and found that high-reactive (bred high-responder, bHR) rats displayed greater risk-taking, impulsivity and aggression relative to low-reactive (bred low-responder, bLR) rats, which showed high levels of anxiety/depression-like behavior and certain stress vulnerability. The bHR/bLR traits are heritable, but prior work revealed bHR/bLR maternal style differences, with bLR dams showing more maternal attention than bHRs. The present study implemented a cross-fostering paradigm to examine the contribution of maternal behavior to the brain development and emotional behavior of bLR offspring. bLR offspring were reared by biological bLR mothers or fostered to a bLR or bHR mother and then evaluated to determine the effects on the following: (1) developmental gene expression in the hippocampus and amygdala and (2) adult anxiety/depression-like behavior. Genome-wide expression profiling showed that cross-fostering bLR rats to bHR mothers shifted developmental gene expression in the amygdala (but not hippocampus), reduced adult anxiety and enhanced social interaction. Our findings illustrate how an early-life manipulation such as cross-fostering changes the brain's developmental trajectory and ultimately impacts adult behavior. Moreover, while earlier studies highlighted hippocampal differences contributing to the bHR/bLR phenotypes, our results point to a role of the amygdala as well. Future work will pursue genetic and cellular mechanisms within the amygdala that contribute to bHR/bLR behavior either at baseline or following environmental manipulations. © 2015 S. Karger AG, Basel.

  1. Development of telmisartan in the therapy of spinal cord injury: pre-clinical study in rats

    Directory of Open Access Journals (Sweden)

    Lin CM

    2015-08-01

    Full Text Available Chien-Min Lin,1,* Jo-Ting Tsai,2,* Chen Kuei Chang,1 Juei-Tang Cheng,3 Jia-Wei Lin11Department of Neurosurgery, 2Department of Radiation Oncology, Shuang Ho Hospital-Taipei Medical University, 3Institute of Medical Science, College of Health Science, Chang Jung Christian University, Tainan City, Taiwan*These authors contributed equally to this workBackground: Decrease of peroxisome proliferator-activated receptors-δ (PPARδ expression has been observed after spinal cord injury (SCI. Increase of PPARδ may improve the damage in SCI. Telmisartan, the antihypertensive agent, has been mentioned to increase the expression of PPARδ. Thus, we are going to screen the effectiveness of telmisartan in SCI for the development of it in clinical application.Methods: In the present study, we used compressive SCI in rats. Telmisartan was then used to evaluate the influence in rats after SCI. Change in PPARδ expression was identified by Western blots. Also, behavioral tests were performed to check the recovery of damage.Results: Recovery of damage from SCI was observed in telmisartan-treated rats. Additionally, this action of telmisartan was inhibited by GSK0660 at the dose sufficient to block PPARδ. However, metformin at the dose enough to activate adenosine monophosphate-activated protein kinase failed to produce similar action as telmisartan. Thus, mediation of adenosine monophosphate-activated protein kinase in this action of telmisartan can be rule out. Moreover, telmisartan reversed the expressions of PPARδ in rats with SCI.Conclusion: The obtained data suggest that telmisartan can improve the damage of SCI in rats through an increase in PPARδ expression. Thus, telmisartan is useful to be developed as an agent in the therapy of SCI.Keywords: PPARδ, AMPK, spinal cord injury, angiotensin receptor blocker, metformin

  2. The effect of a hyperdynamic environment on the development of the rat retina

    Science.gov (United States)

    Murakami, D. M.; Fuller, C. A.

    1985-01-01

    The effects of a 2 G field on the retinal development of the layers in the rat and central visual system nuclei are investigated. The thickness of the retinal layers, ganglion cells, and brains of male and female Wistar rats suspended from an 18 foot diameter centrifuge creating a 2 G field are evaluated and compared with a control group. A decrease in the thickness of the outer nuclear layer (ONL) of 37.1 percent, of 58.5 percent in the inner nuclear layer (INL), and of 28.8 percent in the inner plexiform layer (IPL), and a reduction in body weight are observed in the 2-G rats. The data reveal that the ganglion cells and visual system nuclei activity correspond well with the control data; however, the medial terminal nucleus (MTN) activity is inhibited in the 2-G rats. It is concluded that the differences in ONL and IPL are attributed to body weight reduction, but the INL and MTN are affected by the 2-G conditions.

  3. Dietary-Induced Chronic Hypothyroidism Negatively Affects Rat Follicular Development and Ovulation Rate and Is Associated with Oxidative Stress.

    Science.gov (United States)

    Meng, Li; Rijntjes, Eddy; Swarts, Hans; Bunschoten, Annelies; van der Stelt, Inge; Keijer, Jaap; Teerds, Katja

    2016-04-01

    The long-term effects of chronic hypothyroidism on ovarian follicular development in adulthood are not well known. Using a rat model of chronic diet-induced hypothyroidism initiated in the fetal period, we investigated the effects of prolonged reduced plasma thyroid hormone concentrations on the ovarian follicular reserve and ovulation rate in prepubertal (12-day-old) and adult (64-day-old and 120-day-old) rats. Besides, antioxidant gene expression, mitochondrial density and the occurrence of oxidative stress were analyzed. Our results show that continuous hypothyroidism results in lower preantral and antral follicle numbers in adulthood, accompanied by a higher percentage of atretic follicles, when compared to euthyroid age-matched controls. Not surprisingly, ovulation rate was lower in the hypothyroid rats. At the age of 120 days, the mRNA and protein content of superoxide dismutase 1 (SOD1) were significantly increased while catalase (CAT) mRNA and protein content was significantly decreased, suggesting a disturbed antioxidant defense capacity of ovarian cells in the hypothyroid animals. This was supported by a significant reduction in the expression of peroxiredoxin 3 ( ITALIC! Prdx3), thioredoxin reductase 1 ( ITALIC! Txnrd1), and uncoupling protein 2 ( ITALIC! Ucp2) and a downward trend in glutathione peroxidase 3 ( ITALIC! Gpx3) and glutathione S-transferase mu 2 ( ITALIC! Gstm2) expression. These changes in gene expression were likely responsible for the increased immunostaining of the oxidative stress marker 4-hydroxynonenal. Together these results suggest that chronic hypothyroidism initiated in the fetal/neonatal period results in a decreased ovulation rate associated with a disturbance of the antioxidant defense system in the ovary. © 2016 by the Society for the Study of Reproduction, Inc.

  4. A quantitative magnetic resonance histology atlas of postnatal rat brain development with regional estimates of growth and variability.

    Science.gov (United States)

    Calabrese, Evan; Badea, Alexandra; Watson, Charles; Johnson, G Allan

    2013-05-01

    There has been growing interest in the role of postnatal brain development in the etiology of several neurologic diseases. The rat has long been recognized as a powerful model system for studying neuropathology and the safety of pharmacologic treatments. However, the complex spatiotemporal changes that occur during rat neurodevelopment remain to be elucidated. This work establishes the first magnetic resonance histology (MRH) atlas of the developing rat brain, with an emphasis on quantitation. The atlas comprises five specimens at each of nine time points, imaged with eight distinct MR contrasts and segmented into 26 developmentally defined brain regions. The atlas was used to establish a timeline of morphometric changes and variability throughout neurodevelopment and represents a quantitative database of rat neurodevelopment for characterizing rat models of human neurologic disease. Published by Elsevier Inc.

  5. In vivo blockade of acetylcholinesterase increases intraovarian acetylcholine and enhances follicular development and fertility in the rat.

    Science.gov (United States)

    Urra, Javier; Blohberger, Jan; Tiszavari, Michelle; Mayerhofer, Artur; Lara, Hernan E

    2016-07-21

    Growth and differentiation of ovarian follicles are regulated by systemic and local factors, which may include acetylcholine (ACh). Granulosa cells (GCs) of growing follicles and luteal cells produce ACh and in cultured GCs it exerts trophic actions via muscarinic receptors. However, such actions were not studied in vivo. After having established that rat ovarian GCs and luteal cells express the ACh-metabolizing enzyme ACh esterase (AChE), we examined the consequences of local application of an AChE inhibitor, huperzine A (HupA), by osmotic minipump delivery into the ovarian bursa of hemiovariectomized rats. Saline was used in the control group. Local delivery of HupA for 4 weeks increased ovarian ACh content. Estrus cyclicity was not changed indicating a locally restricted range of HupA action. The number of primordial and primary follicles was unaffected, but small secondary follicles significantly increased in the HupA group. Furthermore, a significant increase in the number of corpora lutea suggested increased ovulatory events. In support, as shown upon mating, HupA-treated females had significantly increased implantation sites and more pups. Thus the data are in support of a trophic role of ACh in follicular development and ovulation and point to an important role of ACh in female fertility.

  6. Postdependent state in rats as a model for medication development in alcoholism.

    Science.gov (United States)

    Meinhardt, Marcus W; Sommer, Wolfgang H

    2015-01-01

    Rational development of novel therapeutic strategies for alcoholism requires understanding of its underlying neurobiology and pathophysiology. Obtaining this knowledge largely relies on animal studies. Thus, choosing the appropriate animal model is one of the most critical steps in pre-clinical medication development. Among the range of animal models that have been used to investigate excessive alcohol consumption in rodents, the postdependent model stands out. It was specifically developed to test the role of negative affect as a key driving force in a perpetuating addiction cycle for alcoholism. Here, we will describe our approach to make rats dependent via chronic intermittent exposure to alcohol, discuss the validity of this model, and compare it with other commonly used animal models of alcoholism. We will summarize evidence that postdependent rats fulfill several criteria of a 'Diagnostic and Statistical Manual of Mental Disorders IV/V-like' diagnostic system. Importantly, these animals show long-lasting excessive consumption of and increased motivation for alcohol, and evidence for loss of control over alcohol intake. Our conclusion that postdependent rats are an excellent model for medication development for alcoholism is underscored by a summary of more than two dozen pharmacological tests aimed at reversing these abnormal alcohol responses. We will end with open questions on the use of this model. In the tradition of the Sanchis-Segura and Spanagel review, we provide comic strips that illustrate the postdependent procedure and relevant phenotypes in this review. © 2014 Society for the Study of Addiction.

  7. Maternal creatine supplementation affects the morpho-functional development of hippocampal neurons in rat offspring.

    Science.gov (United States)

    Sartini, S; Lattanzi, D; Ambrogini, P; Di Palma, M; Galati, C; Savelli, D; Polidori, E; Calcabrini, C; Rocchi, M B L; Sestili, P; Cuppini, R

    2016-01-15

    Creatine supplementation has been shown to protect neurons from oxidative damage due to its antioxidant and ergogenic functions. These features have led to the hypothesis of creatine supplementation use during pregnancy as prophylactic treatment to prevent CNS damage, such as hypoxic-ischemic encephalopathy. Unfortunately, very little is known on the effects of creatine supplementation during neuron differentiation, while in vitro studies revealed an influence on neuron excitability, leaving the possibility of creatine supplementation during the CNS development an open question. Using a multiple approach, we studied the hippocampal neuron morphological and functional development in neonatal rats born by dams supplemented with 1% creatine in drinking water during pregnancy. CA1 pyramidal neurons of supplemented newborn rats showed enhanced dendritic tree development, increased LTP maintenance, larger evoked-synaptic responses, and higher intrinsic excitability in comparison to controls. Moreover, a faster repolarizing phase of action potential with the appearance of a hyperpolarization were recorded in neurons of the creatine-treated group. Consistently, CA1 neurons of creatine exposed pups exhibited a higher maximum firing frequency than controls. In summary, we found that creatine supplementation during pregnancy positively affects morphological and electrophysiological development of CA1 neurons in offspring rats, increasing neuronal excitability. Altogether, these findings emphasize the need to evaluate the benefits and the safety of maternal intake of creatine in humans. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Locomotion and physical development in rats treated with ionizing radiation in utero

    International Nuclear Information System (INIS)

    Zaman, M.S.; Hupp, E.W.; Lancaster, F.E.

    1993-01-01

    Effects of ionizing radiation on the emergence of locomotor skill, and physical development were studied in laboratory rats (Fisher F-344 inbred strain). Rats were treated with 3 different doses of radiation (150 rad, 15 rad, and 6.8 rad) delivered on the 20th day of prenatal life. Results indicated that relatively moderate (15 rad) to high (150 rad) doses of radiation had effects on certain locomotion and physical development parameters. Exposure to 150 rad delayed pivoting, cliff-avoidance, upper jaw tooth eruption, and decreased body weights. Other parameters, such as negative geotaxis, eye opening, and lower jaw tooth eruption were marginally delayed in the 150 rad treated animals. Exposure to 15 rad delayed pivoting and cliff-avoidance

  9. Citric acid inhibits development of cataracts, proteinuria and ketosis in streptozotocin (type1) diabetic rats

    Science.gov (United States)

    Nagai, Ryoji; Nagai, Mime; Shimasaki, Satoko; Baynes, John W.; Fujiwara, Yukio

    2010-01-01

    Although many fruits such as lemon and orange contain citric acid, little is known about beneficial effects of citric acid on health. Here we measured the effect of citric acid on the pathogenesis of diabetic complications in streptozotocin-induced diabetic rats. Although oral administration of citric acid to diabetic rats did not affect blood glucose concentration, it delayed the development of cataracts, inhibited accumulation of advanced glycation end products (AGEs) such as Nε-(carboxyethyl)lysine (CEL) and Nε-(carboxymethyl)lysine (CML) in lens proteins, and protected against albuminuria and ketosis . We also show that incubation of protein with acetol, a metabolite formed from acetone by acetone monooxygenase, generate CEL, suggesting that inhibition of ketosis by citric acid may lead to the decrease in CEL in lens proteins. These results demonstrate that the oral administration of citric acid ameliorates ketosis and protects against the development of diabetic complications in an animal model of type 1 diabetes. PMID:20117096

  10. Early postnatal development of rat brain is accompanied by generation of lipofuscin-like pigments

    Czech Academy of Sciences Publication Activity Database

    Wilhelm, J.; Ivica, J.; Kagan, Dmytro; Svoboda, Petr

    2011-01-01

    Roč. 347, 1-2 (2011), s. 157-162 ISSN 0300-8177 R&D Projects: GA MŠk(CZ) LC554; GA AV ČR(CZ) IAA500110606 Institutional research plan: CEZ:AV0Z50110509 Keywords : brain * early development * lipofuscin-like pigments * fluorescence * rat Subject RIV: CE - Biochemistry Impact factor: 2.057, year: 2011

  11. Anticonvulsant action of two antagonists of NMDA receptors in developing rats

    Czech Academy of Sciences Publication Activity Database

    Mareš, Pavel; Lojková, Denisa; Mikulecká, Anna

    2006-01-01

    Roč. 47, č. S4 (2006), s. 314-314 ISSN 0013-9580. [Annual Meeting of the American Epilepsy Society and Canadian League against Epilepsy. 01.12.2006-05.12.2006, San Diego, CA] R&D Projects: GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : memantine * ifenprodil * developing rats Subject RIV: ED - Physiology

  12. Development of the acoustic startle response in rats and its change after early acoustic trauma

    Czech Academy of Sciences Publication Activity Database

    Rybalko, Natalia; Chumak, Tetyana; Bureš, Zbyněk; Popelář, Jiří; Šuta, Daniel; Syka, Josef

    2015-01-01

    Roč. 286, jul 1 (2015), s. 212-221 ISSN 0166-4328 R&D Projects: GA ČR(CZ) GAP303/12/1347; GA ČR(CZ) GBP304/12/G069; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378041 Keywords : auditory system * rat * acoustic startle reflex * development * critical period * noise exposure Subject RIV: FH - Neurology Impact factor: 3.002, year: 2015

  13. Generation of hydrogen peroxide in the developing rat heart: the role of elastin metabolism

    Czech Academy of Sciences Publication Activity Database

    Wilhelm, J.; Ošťádalová, Ivana; Vytášek, R.; Vajner, L.

    2011-01-01

    Roč. 358, 1-2 (2011), s. 215-220 ISSN 0300-8177 R&D Projects: GA MŠk(CZ) 1M0510 Grant - others:GA ČR(CZ) GAP303/11/0298 Program:GA Institutional research plan: CEZ:AV0Z50110509 Keywords : rat heart * ontogenetic development * hydrogen peroxide * elastin * fluorescence Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.057, year: 2011

  14. Periodization of the early postnatal development in the rat with particular attention to the weaning period

    Czech Academy of Sciences Publication Activity Database

    Ošťádalová, Ivana; Babický, A.

    2012-01-01

    Roč. 61, Suppl.1 (2012), S1-S7 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510; GA ČR(CZ) GAP303/12/1162 Institutional research plan: CEZ:AV0Z50110509 Keywords : rat * ontogenic development * presuckling period * suckling period * weaning period Subject RIV: ED - Physiology Impact factor: 1.531, year: 2012

  15. Development of a bio-magnetic measurement system and sensor configuration analysis for rats

    Science.gov (United States)

    Kim, Ji-Eun; Kim, In-Seon; Kim, Kiwoong; Lim, Sanghyun; Kwon, Hyukchan; Kang, Chan Seok; Ahn, San; Yu, Kwon Kyu; Lee, Yong-Ho

    2017-04-01

    Magnetoencephalography (MEG) based on superconducting quantum interference devices enables the measurement of very weak magnetic fields (10-1000 fT) generated from the human or animal brain. In this article, we introduce a small MEG system that we developed specifically for use with rats. Our system has the following characteristics: (1) variable distance between the pick-up coil and outer Dewar bottom (˜5 mm), (2) small pick-up coil (4 mm) for high spatial resolution, (3) good field sensitivity (45 ˜ 80 fT /cm/√{Hz} ) , (4) the sensor interval satisfies the Nyquist spatial sampling theorem, and (5) small source localization error for the region to be investigated. To reduce source localization error, it is necessary to establish an optimal sensor layout. To this end, we simulated confidence volumes at each point on a grid on the surface of a virtual rat head. In this simulation, we used locally fitted spheres as model rat heads. This enabled us to consider more realistic volume currents. We constrained the model such that the dipoles could have only four possible orientations: the x- and y-axes from the original coordinates, and two tangentially layered dipoles (local x- and y-axes) in the locally fitted spheres. We considered the confidence volumes according to the sensor layout and dipole orientation and positions. We then conducted a preliminary test with a 4-channel MEG system prior to manufacturing the multi-channel system. Using the 4-channel MEG system, we measured rat magnetocardiograms. We obtained well defined P-, QRS-, and T-waves in rats with a maximum value of 15 pT/cm. Finally, we measured auditory evoked fields and steady state auditory evoked fields with maximum values 400 fT/cm and 250 fT/cm, respectively.

  16. Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus

    Science.gov (United States)

    Jugé, Lauriane; Pong, Alice C.; Bongers, Andre; Sinkus, Ralph; Bilston, Lynne E.; Cheng, Shaokoon

    2016-01-01

    Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P hydrocephalus development. PMID:26848844

  17. Low-dose effects of bisphenol A on early sexual development in male and female rats

    DEFF Research Database (Denmark)

    Christiansen, Sofie; Petersen, Marta Axelstad; Boberg, Julie

    2014-01-01

    the influence of BPA on early sexual development in male and female rats at dose levels covering both regulatory no observed adverse effect levels (NOAELs) (5 and 50 mg/kg bw per day) as well as doses in the microgram per kilogram dose range (0.025 and 0.25 mg/kg bw per day). Time-mated Wistar rats (n=22) were...... in both sexes indicates effects on prenatal sexual development and provides new evidence of low-dose adverse effects of BPA in rats in the microgram per kilogram dose range. The NOAEL in this study is clearly below 5 mg/kg for BPA, which is used as the basis for establishment of the current tolerable......Bisphenol A (BPA) is widely detected in human urine and blood. BPA has been reported to impair many endpoints for reproductive and neurological development; however, it is controversial whether BPA has effects in the microgram per kilogram dose range. The aim of the current study was to examine...

  18. Genetic Regulation of Development of Thymic Lymphomas Induced by N‐Propyl‐N‐nitrosourea in the Rat

    Science.gov (United States)

    Fukami, Hiroko; Nishimura, Mayumi; Matsuyama, Mutsushi

    1995-01-01

    To clarify the linkage between Hbb and Tls‐1 (thymic lymphoma susceptible‐1) loci and to investigate other loci concerned in thymic lymphomagenesis, the BUF/Mna rat, which is highly sensitive to the lymphomagenic activity of N‐propyl‐N‐nitrosourea (PNU), the WKY/NCrj rat, reported to be resistant, and their cross offspring were subjected to genetic analysis. F1 hybrid and backcross generations were raised from the 2 strains, and 6 genetic markers including Hbb were analyzed in individuals of the backcross generation. However, no linkage between Hbb and Tls‐1 loci could be demonstrated since WKY rats also developed a high incidence of thymic lymphomas in response to PNU. Nevertheless, thymic lymphomas developed more rapidly and reached a larger size in the BUF rats. F1 rats expressed a rather rapid and large tumor growth phenotype, while the [(WKY × BUF) × WKY] backcross generation consisted of rats with either rapidly growing or slowly growing tumors. It was thus concluded that rapid development of thymic lymphomas is determined by a gene, provisionally designated Tls‐3. Analysis of the relationship between 6 genetic markers and development of thymic lymphoma in the backcross generation demonstrated that the Tls‐3 locus is loosely linked to the Gc locus, suggesting a possible location on rat chromosome 14. Tls‐3 may not be identical with Tls‐1 and other genes known to be relevant to thymic tumors, but its relationship with Tls‐2 remains obscure. PMID:7559080

  19. Adult and embryonic GAD transcripts are spatiotemporally regulated during postnatal development in the rat brain.

    Directory of Open Access Journals (Sweden)

    Anke Popp

    Full Text Available BACKGROUND: GABA (gamma-aminobutyric acid, the main inhibitory neurotransmitter in the brain, is synthesized by glutamic acid decarboxylase (GAD. GAD exists in two adult isoforms, GAD65 and GAD67. During embryonic brain development at least two additional transcripts exist, I-80 and I-86, which are distinguished by insertions of 80 or 86 bp into GAD67 mRNA, respectively. Though it was described that embryonic GAD67 transcripts are not detectable during adulthood there are evidences suggesting re-expression under certain pathological conditions in the adult brain. In the present study we systematically analyzed for the first time the spatiotemporal distribution of different GADs with emphasis on embryonic GAD67 mRNAs in the postnatal brain using highly sensitive methods. METHODOLOGY/PRINCIPAL FINDINGS: QPCR was used to precisely investigate the postnatal expression level of GAD related mRNAs in cortex, hippocampus, cerebellum, and olfactory bulb of rats from P1 throughout adulthood. Within the first three postnatal weeks the expression of both GAD65 and GAD67 mRNAs reached adult levels in hippocampus, cortex, and cerebellum. The olfactory bulb showed by far the highest expression of GAD65 as well as GAD67 transcripts. Embryonic GAD67 splice variants were still detectable at birth. They continuously declined to barely detectable levels during postnatal development in all investigated regions with exception of a comparatively high expression in the olfactory bulb. Radioactive in situ hybridizations confirmed the occurrence of embryonic GAD67 transcripts in the olfactory bulb and furthermore detected their localization mainly in the subventricular zone and the rostral migratory stream. CONCLUSIONS/SIGNIFICANCE: Embryonic GAD67 transcripts can hardly be detected in the adult brain, except for specific regions associated with neurogenesis and high synaptic plasticity. Therefore a functional role in processes like proliferation, migration or

  20. Effects of oral, subchronic cadmium administration on fertility prenatal and postnatal progeny development in rats

    Energy Technology Data Exchange (ETDEWEB)

    Baranski, B.; Stetkiewicz, I.; Sitarek, K.; Szymczak, W.

    1983-12-01

    Cadmium chloride was administered by gavage to female rats 5 days a week for 5 weeks, then during mating and gestation periods at doses of 0.04, 0.4, and 4 mg Cd/kg/day. Treatment with cadmium neither affected the survival and fertility of females, nor produced overt fetotoxic effects. Fetal cadmium concentration was not related to the level of exposure. Litter size, body weight gain and viability of offspring during 2 months after parturition were similar in all groups. The exploratory locomotor activity of 2-month-old males and females born to rats given 0.4 and 4 mg Cd/kg/day was significantly reduced. The progeny of cadmium-treated females showed decreased performance in the rotarod test. In general, the degree of behavioral impairment was dose-related.

  1. Segmental neuropathic pain does not develop in male rats with complete spinal transections.

    Science.gov (United States)

    Hubscher, Charles H; Kaddumi, Ezidin G; Johnson, Richard D

    2008-10-01

    In a previous study using male rats, a correlation was found between the development of "at-level" allodynia in T6-7 dermatomes following severe T8 spinal contusion injury and the sparing of some myelinated axons within the core of the lesion epicenter. To further test our hypothesis that this sparing is important for the expression of allodynia and the supraspinal plasticity that ensues, an injury that severs all axons (i.e., a complete spinal cord transection) was made in 15 male rats. Behavioral assessments were done at level throughout the 30-day recovery period followed by terminal electrophysiological recordings (urethane anesthesia) from single medullary reticular formation (MRF) neurons receiving convergent nociceptive inputs from receptive fields above, at, and below the lesion level. None of the rats developed signs of at-level allodynia (versus 18 of 26 male rats following severe contusion). However, the terminal recording (206 MRF neurons) data resembled those obtained previously post-contusion. That is, there was evidence of neuronal hyper-excitability (relative to previous data from intact controls) to high- and low-threshold mechanical stimulation for "at-level" (dorsal trunk) and "above-level" (eyelids and face) cutaneous territories. These results, when combined with prior data on intact controls and severe/moderate contusions, indicate that (1) an anatomically incomplete injury (some lesion epicenter axonal sparing) following severe contusion is likely important for the development of allodynia and (2) the neuronal hyper-excitability at the level of the medulla is likely involved in nociceptive processes that are not directly related to the conscious expression of pain-like avoidance behaviors that are being used as evidence of allodynia.

  2. Impaired brain development in the rat following prenatal exposure to methylazoxymethanol acetate at gestational day 17 and neurotrophin distribution

    NARCIS (Netherlands)

    Fiore, M; Grace, AA; Korf, J; Stampachiacchiere, B; Aloe, L

    2004-01-01

    Several neuropsychiatric disorders, including schizophrenia, are the consequence of a disrupted development of the CNS. Accordingly, intrauterine exposure to toxins may increase the risk for psychopathology. We investigated whether prenatal exposure of rats to the neurotoxin methylaxoxymethanol

  3. Effect of in vivo heart irradiation on the development of antioxidant defenses and cardiac functions in the rat

    International Nuclear Information System (INIS)

    Benderitter, M.; Assem, M.; Maupoil, V.

    1995-01-01

    During radiotherapy of thoracic tumors, the heart is often included in the primary treatment volume, and chronic impairment of myocardial function occurs. The cellular biomolecules are altered directly by radiation or damaged indirectly by free radical production. The purpose of this investigation was to evaluate the biochemical and functional response of the rat heart to a single high dose of radiation. The effect of 20 Gy local X irradiation was determined in the heart of Wistar rats under general anesthesia. Mechanical performances were measured in vitro using an isolated perfused working heart model, and cardiac antioxidant defenses were also evaluated. Hearts were studied at 1 and 4 months after irradiation. This single dose of radiation induced a marked drop in the mechanical activity of the rat heart: aortic output was significantly reduced (18% less than control values) at 1 month postirradiation and remained depressed for the rest of the experimental period (21% less than control 4 months after treatment). This suggests the development of myocardial failure after irradiation. The decline of functional parameters was associated with changes in antioxidant defenses. The decrease in cardiac levels of vitamin E (-30%) was associated with an increase in the levels of Mn-SOD and glustathione peroxidase (+45.5% and +32%, respectively, at 4 months postirradiation). However, cardiac vitamin C and catalase levels remained constant. Since these antioxidant defenses were activated relatively long after irradiation, it is suggested that this was probable due to the production of free radical species associated with the development of inflammation. 49 refs., 8 figs., 1 tab

  4. Involvement of high mobility group box 1 in the development and maintenance of chemotherapy-induced peripheral neuropathy in rats

    International Nuclear Information System (INIS)

    Nishida, Takeshi; Tsubota, Maho; Kawaishi, Yudai; Yamanishi, Hiroki; Kamitani, Natsuki; Sekiguchi, Fumiko; Ishikura, Hiroyasu; Liu, Keyue; Nishibori, Masahiro; Kawabata, Atsufumi

    2016-01-01

    Given that high mobility group box 1 (HMGB1), a nuclear protein, once released to the extracellular space, promotes nociception, we asked if inactivation of HMGB1 prevents or reverses chemotherapy-induced painful neuropathy in rats and also examined possible involvement of Toll-like receptor 4 (TLR4) and the receptor for advanced glycation endproduct (RAGE), known as targets for HMGB1. Painful neuropathy was produced by repeated i.p. administration of paclitaxel or vincristine in rats. Nociceptive threshold was determined by the paw pressure method and/or von Frey test in the hindpaw. Tissue protein levels were determined by immunoblotting. Repeated i.p. administration of the anti-HMGB1-neutralizing antibody or recombinant human soluble thrombomodulin (rhsTM), known to inactivate HMGB1, prevented the development of hyperalgesia and/or allodynia induced by paclitaxel or vincristine in rats. A single i.p. or intraplantar (i.pl.) administration of the antibody or rhsTM reversed the chemotherapy-induced neuropathy. A single i.pl. administration of a TLR4 antagonist or low molecular weight heparin, known to inhibit RAGE, attenuated the hyperalgesia caused by i.pl. HMGB1 and also the chemotherapy-induced painful neuropathy. Paclitaxel or vincristine treatment significantly decreased protein levels of HMGB1 in the dorsal root ganglia, but not sciatic nerves. HMGB1 thus participates in both development and maintenance of chemotherapy-induced painful neuropathy, in part through RAGE and TLR4. HMGB1 inactivation is considered useful to prevent and treat the chemotherapy-induced painful neuropathy.

  5. DEVELOPMENT OF CRITERIA FOR EVALUATION OF THE FORMATION OF PROFESSIONALLY SIGNIFICANT LEADERSHIP QUALITIES AMONG STUDENTS OF PEDAGOGICAL COLLEGE

    Directory of Open Access Journals (Sweden)

    N. V. Kubarkova

    2016-01-01

    Full Text Available The aim of the article is to give a theoretical justification of the criteria, indicators and measuring instruments for diagnostics of professionally significant leadership qualities of a teacher.Methods. Research material is presented from positions of the system and activity approaches. The first one allowed to develop the structure of professionally significant leadership qualities of a teacher, which includes twelve individual abilities and traits. The second one, abilities and individual features, their manifestation and development are considered from the standpoint of systemogenesis of professional activity. From these positions defined criteria basis for the diagnosis of professionally significant leadership qualities of a teacher. Methods of content analysis and content-logical intersections are used while defining the concept of «professionally significant leadership qualities of a teacher» and elaboration of its component composition. The method of concept analysis is used to determine criteria and indicators for diagnostics of professionally significant leadership qualities of a teacher.Results. The criteria and indicators, diagnostic tools for the detection of the formation of professionally significant leadership qualities of students of pedagogical college; the characteristic of used methods are given. Scientific novelty. The article provides a definition of the concept «professionally significant qualities of leadership of the teacher» is defined by the author; essence of such qualities is revealed.Practical significance. Described in this article approaches to definition of criteria and indicators may be of interest to researchers, graduate students, undergraduates. Listed diagnostic tools can be used in the performance appraisal of teachers for evaluating their leadership qualities.

  6. Wfs1- deficient rats develop primary symptoms of Wolfram syndrome: insulin-dependent diabetes, optic nerve atrophy and medullary degeneration.

    Science.gov (United States)

    Plaas, Mario; Seppa, Kadri; Reimets, Riin; Jagomäe, Toomas; Toots, Maarja; Koppel, Tuuliki; Vallisoo, Tuuli; Nigul, Mait; Heinla, Indrek; Meier, Riho; Kaasik, Allen; Piirsoo, Andres; Hickey, Miriam A; Terasmaa, Anton; Vasar, Eero

    2017-08-31

    Wolfram syndrome (WS) is a rare autosomal-recessive disorder that is caused by mutations in the WFS1 gene and is characterized by juvenile-onset diabetes, optic atrophy, hearing loss and a number of other complications. Here, we describe the creation and phenotype of Wfs1 mutant rats, in which exon 5 of the Wfs1 gene is deleted, resulting in a loss of 27 amino acids from the WFS1 protein sequence. These Wfs1-ex5-KO232 rats show progressive glucose intolerance, which culminates in the development of diabetes mellitus, glycosuria, hyperglycaemia and severe body weight loss by 12 months of age. Beta cell mass is reduced in older mutant rats, which is accompanied by decreased glucose-stimulated insulin secretion from 3 months of age. Medullary volume is decreased in older Wfs1-ex5-KO232 rats, with the largest decreases at the level of the inferior olive. Finally, older Wfs1-ex5-KO232 rats show retinal gliosis and optic nerve atrophy at 15 months of age. Electron microscopy revealed axonal degeneration and disorganization of the myelin in the optic nerves of older Wfs1-ex5-KO232 rats. The phenotype of Wfs1-ex5-KO232 rats indicates that they have the core symptoms of WS. Therefore, we present a novel rat model of WS.

  7. The effects of low dose ionizing radiation on the development of rat cerebral cortex, (2)

    International Nuclear Information System (INIS)

    Matsushita, Koji

    1993-01-01

    In order to study the molecular mechanisms of neuronal migration on developing rat cerebral cortex, we need a tissue culture system in which neuronal migration can be observed. We prepared a tissue culture system of embryonic rat cerebral cortex starting on embryonic day 16 and cultivating it for 48 hours. The autoradiographic study in this system revealed not only the migration of 3 H-thymidine labeled neurons but also neuronal migration delays from low doses of ionizing radiation of more than 10 cGy. In addition, on immunohistochemical study, cell-cell adhesion molecule N-CAM staining was remarkably decreased in the matrix cell layer. In the tissue culture system where monoclonal anti-N-CAM antibodies were added, neuronal migration delay comparable to that of 20 cGy radiation was found. In conclusion, it was speculated that neuronal migration delay might be caused by disturbed N-CAM synthesis in matrix cells after low dose ionizing radiation. (author)

  8. Peripheral Nerve Injury in Developing Rats Reorganizes Representation Pattern in Motor Cortex

    Science.gov (United States)

    Donoghue, John P.; Sanes, Jerome N.

    1987-02-01

    We investigated the effect of neonatal nerve lesions on cerebral motor cortex organization by comparing the cortical motor representation of normal adult rats with adult rats that had one forelimb removed on the day of birth. Mapping of cerebral neocortex with electrical stimulation revealed an altered relationship between the motor cortex and the remaining muscles. Whereas distal forelimb movements are normally elicited at the lowest threshold in the motor cortex forelimb area, the same stimuli activated shoulder and trunk muscles in experimental animals. In addition, an expanded cortical representation of intact body parts was present and there was an absence of a distinct portion of motor cortex. These data demonstrate that representation patterns in motor cortex can be altered by peripheral nerve injury during development.

  9. Development and application of a methodology for the analysis of significant human related event trends in nuclear power plants

    International Nuclear Information System (INIS)

    Cho, H.Y.

    1981-01-01

    A methodology is developed to identify and flag significant trends related to the safety and availability of U.S. commercial nuclear power plants. The development is intended to aid in reducing likelihood of human errors. To assure that the methodology can be easily adapted to various types of classification schemes of operation data, a data bank classified by the Transient Analysis Classification and Evaluation (TRACE) scheme is selected for the methodology. The significance criteria for human-initiated events affecting the systems and for events caused by human deficiencies were developed. Clustering analysis was used to verify the learning trend in multidimensional histograms. A computer code is developed based on the K-Means algorithm and applied to find the learning period in which error rates are monotonously decreasing with plant age. The Freeman-Tukey (F-T) deviates are used to select generic problems identified by a large positive value (here approximately over 2.0) for the deviate. The identified generic problems are: decision errors which are highly associated with reactor startup operations in the learning period of PWR plants (PWRs), response errors which are highly associated with Secondary Non-Nuclear Systems (SNS) in PWRs, and significant errors affecting systems and which are caused by response action are highly associated with startup reactor mode in BWRS

  10. Androgen-mediated development of irradiation-induced thyroid tumors in rats: dependence on animal age during interval of androgen replacement in castrated males

    International Nuclear Information System (INIS)

    Hofmann, C.; Oslapas, R.; Nayyar, R.; Paloyan, E.

    1986-01-01

    When male Long-Evans rats at age 8 weeks were radiation treated (40 microCi Na131I), thyroid follicular adenomas and carcinomas were observed at age 24 months with a high incidence of 94%. Castration of males prior to irradiation significantly reduced this tumor incidence to 60%. When testosterone (T) was replaced in castrated, irradiated male rats, differentially increased incidences of thyroid tumors occurred. Immediate (age 2-6 mo) or early (age 6-12 mo) T replacement at approximate physiologic levels led to thyroid follicular tumor incidences of 100 and 82%, respectively, whereas intermediate (12-18 mo) or late (18-24 mo) T treatment led to only 70 and 73% incidences, respectively. Continuous T replacement (2-24 mo) in castrated irradiated male rats raised thyroid tumor incidence to 100%. Since elevated thyroid-stimulating hormone (TSH) is a reported requisite for development of radiation-associated thyroid tumors, the effects of T on serum TSH levels were examined. Mean serum TSH values in all irradiated animal groups were significantly elevated above age-matched nonirradiated animals at 6, 12, 18, and 24 months. Serum TSH levels were higher in continuous T-replaced irradiated castrates than in intact, irradiated males, whereas such intact male TSH levels were greater than those for irradiated castrates without T treatment. Interval T replacement in castrated male rats was associated with increased serum TSH levels during the treatment interval and with lowered TSH levels after discontinuation of T treatment, particularly in irradiated rats. However, when irradiated, castrated males received late T replacement (age 18-24 mo), there was no elevation of TSH at the end of the treatment interval. An indirect effect of T via early stimulation of TSH may be partly responsible for the high incidence of irradiation-induced thyroid tumors in rats

  11. Comparison of single, fractionated and hyperfractionated irradiation on the development of normal tissue damage in rat lung

    International Nuclear Information System (INIS)

    Giri, P.G.S.; Kimler, B.F.; Giri, U.P.; Cox, G.G.; Reddy, E.K.

    1985-01-01

    The effect of fractionated thoracic irradiation on the development of normal tissue damage in rats was compared to that produced by single doses. Animals received a single dose of 15 Gy, 30 Gy in 10 daily fractions of 3 Gy each (fractionation), or 30 Gy in 30 fractions of 1 Gy each 3 times a day (hyperfractionation). The treatments produced minimal lethality since a total of only 6 animals died between days 273 and 475 after the initiation of treatment, with no difference in survival observed between the control and any of the 3 treated groups. Despite the lack of lethality, evidence of lung damage was obtained by histological examination. Animals that had received either single doses or fractionated doses had more of the pulmonary parenchyma involved than did animals that had received hyperfractionated doses. The authors conclude that, in the rat lung model, a total radiation dose of 30 Gy fractionated over 14 days produces no more lethality nor damage to lung tissue than does 15 Gy delivered as a single dose. However, long-term effects as evidenced by deposits of collagen and development of fibrosis are significantly reduced by hyperfractionation when compared to single doses and daily fractionation

  12. Benford's law first significant digit and distribution distances for testing the reliability of financial reports in developing countries

    Science.gov (United States)

    Shi, Jing; Ausloos, Marcel; Zhu, Tingting

    2018-02-01

    We discuss a common suspicion about reported financial data, in 10 industrial sectors of the 6 so called "main developing countries" over the time interval [2000-2014]. These data are examined through Benford's law first significant digit and through distribution distances tests. It is shown that several visually anomalous data have to be a priori removed. Thereafter, the distributions much better follow the first digit significant law, indicating the usefulness of a Benford's law test from the research starting line. The same holds true for distance tests. A few outliers are pointed out.

  13. Development of Eimeria nieschulzi (Coccidia, Apicomplexa Gamonts and Oocysts in Primary Fetal Rat Cells

    Directory of Open Access Journals (Sweden)

    Hong Chen

    2013-01-01

    Full Text Available The in vitro production of gametocytes and oocysts of the apicomplexan parasite genus Eimeria is still a challenge in coccidiosis research. Until today, an in vitro development of gametocytes or oocysts had only been shown in some Eimeria species. For several mammalian Eimeria species, partial developments could be achieved in different cell types, but a development up to gametocytes or oocysts is still lacking. This study compares several permanent cell lines with primary fetal cells of the black rat (Rattus norvegicus concerning the qualitative in vitro development of the rat parasite Eimeria nieschulzi. With the help of transgenic parasites, the developmental progress was documented. The selected Eimeria nieschulzi strain constitutively expresses the yellow fluorescent protein and a macrogamont specific upregulated red tandem dimer tomato. In the majority of all investigated host cells the development stopped at the second merozoite stage. In a mixed culture of cells derived from inner fetal organs the development of schizont generations I-IV, macrogamonts, and oocysts were observed in crypt-like organoid structures. Microgamonts and microgametes could not be observed and oocysts did not sporulate under air supply. By immunohistology, we could confirm that wild-type E. nieschulzi stages can be found in the crypts of the small intestine. The results of this study may be helpful for characterization of native host cells and for development of an in vitro cultivation system for Eimeria species.

  14. Intrauterine Growth Restriction Alters the Postnatal Development of the Rat Cerebellum.

    Science.gov (United States)

    McDougall, Annie R A; Wiradjaja, Vanny; Azhan, Aminath; Li, Anqi; Hale, Nadia; Wlodek, Mary E; Hooper, Stuart B; Wallace, Megan J; Tolcos, Mary

    2017-01-01

    Intrauterine growth restriction (IUGR) is a major cause of antenatal brain injury. We aimed to characterize cerebellar deficits following IUGR and to investigate the potential underlying cellular and molecular mechanisms. At embryonic day 18, pregnant rats underwent either sham surgery (controls; n = 23) or bilateral uterine vessel ligation to restrict blood flow to fetuses (IUGR; n = 20). Offspring were collected at postnatal day 2 (P2), P7, and P35. Body weights were reduced at P2, P7, and P35 in IUGR offspring (p < 0.05) compared with controls. At P7, the width of the external granule layer (EGL) was 30% greater in IUGR than control rats (p < 0.05); there was no difference in the width of the proliferative zone or in the density of Ki67-positive cells in the EGL. Bergmann glia were disorganized at P7 and P35 in IUGR pups, and by P35, there was a 10% decrease in Bergmann glial fiber density (p < 0.05) compared with controls. At P7, trophoblast antigen-2 (Trop2) mRNA and protein levels in the cerebellum were decreased by 88 and 40%, respectively, and astrotactin 1 mRNA levels were increased by 20% in the IUGR rats (p < 0.05) compared with controls; there was no difference in ASTN1 protein. The expressions of other factors known to regulate cerebellar development (astrotactin 2, brain-derived neurotrophic factor, erb-b2 receptor tyrosine kinase 4, neuregulin 1, sonic hedgehog and somatostatin) were not different between IUGR and control rats at P7 or P35. These data suggest that damage to the migratory scaffold (Bergmann glial fibers) and alterations in the genes that influence migration (Trop2 and Astn1) may underlie the deficits in postnatal cerebellar development following IUGR. © 2017 S. Karger AG, Basel.

  15. Activation of retinal stem cells in the proliferating marginal region of RCS rats during development of retinitis pigmentosa.

    Science.gov (United States)

    Jian, Qian; Xu, Haiwei; Xie, Hanping; Tian, Chunyu; Zhao, Tongtao; Yin, ZhengQin

    2009-11-06

    Retinal stem cells (RSCs) have been demonstrated at the proliferating marginal regions from the pars plana of ciliary body to the ciliary marginal zone (CMZ) in adult lower vertebrates and mammals. Investigations in the lower vertebrates have provided some evidence that RSCs can proliferate following retinal damage; however, the evidence that this occurs in mammals is not clear. In this study, we explored RSCs proliferation potential of adult mammalian in proliferating marginal regions of Royal College of Surgeons (RCS) rats, an animal model for retinitis pigmentosa (RP). The proliferation was evaluated using BrdU labeling, and Chx-10 as markers to discern progenitor cell of CMZ in Long-Evan's and RCS rats at different postnatal day (PND) after eye opening. We found that few Chx-10 and BrdU labeled cells in the proliferating marginal regions of Long-Evan's rats, which significantly increased in RCS rats at PND30 and PND60. Consistent with this, Chx-10/Vimentin double staining cells in the center retina of RCS rats increased significantly at PND30 after eye opening. In addition, mRNA expression of Shh, Ptch1 and Smo was up-regulated in RCS rats at PND60 compared to age-matched Long-Evan's rats, which revealed Shh/ptc pathway involving in the activation of RSCs. These results suggest that RSCs in the mammalian retinal proliferating marginal regions has the potential to regenerate following degeneration.

  16. From Forest Landscape to Agricultural Landscape in the Developing Tropical Country of Malaysia: Pattern, Process, and Their Significance on Policy

    Science.gov (United States)

    Abdullah, Saiful Arif; Hezri, Adnan A.

    2008-11-01

    Agricultural expansion and deforestation are spatial processes of land transformation that impact on landscape pattern. In peninsular Malaysia, the conversion of forested areas into two major cash crops—rubber and oil palm plantations—has been identified as driving significant environmental change. To date, there has been insufficient literature studying the link between changes in landscape patterns and land-related development policies. Therefore, this paper examines: (i) the links between development policies and changes in land use/land cover and landscape pattern and (ii) the significance and implications of these links for future development policies. The objective is to generate insights on the changing process of land use/land cover and landscape pattern as a functional response to development policies and their consequences for environmental conditions. Over the last century, the development of cash crops has changed the country from one dominated by natural landscapes to one dominated by agricultural landscapes. But the last decade of the century saw urbanization beginning to impact significantly. This process aligned with the establishment of various development policies, from land development for agriculture between the mid 1950s and the 1970s to an emphasis on manufacturing from the 1980s onward. Based on a case study in Selangor, peninsular Malaysia, a model of landscape pattern change is presented. It contains three stages according to the relative importance of rubber (first stage: 1900-1950s), oil palm (second stage: 1960s-1970s), and urban (third stage: 1980s-1990s) development that influenced landscape fragmentation and heterogeneity. The environmental consequences of this change have been depicted through loss of biodiversity, geohazard incidences, and the spread of vector-borne diseases. The spatial ecological information can be useful to development policy formulation, allowing diagnosis of the country’s “health” and sustainability

  17. Significant changes in the amounts of neurotransmitter and related substances in rat brain induced by subacute exposure to low levels of toluene and xylene

    Energy Technology Data Exchange (ETDEWEB)

    Honma, T.; Sudo, A.; Miyagawa, M.; Sato, M.; Hasegawa, H.

    1983-01-01

    Rats were exposed to toluene and xylene at 200-800 ppm for 30 days. After exposure, changes in the dopamine, norepinephrine, serotonin, acetylcholine (ACh), cyclic AMP, cyclic GMP, GABA, glutamic acid, glutamine, aspartic acid, taurine, glycine and alanine content of different areas of the brain were investigated. ACh in the striatum and whole brain were reduced dose-dependently by toluene and xylene. The reduction at 800 ppm of the solvents was in the range of 10 to 20% of the ACh content of the control rats. Toluene and xylene caused different changes in monoamine content other than ACh, but the changes were not dose-dependent. Among the seven free amino acids that are the main amino acid components of the brain, the glutamine content was increased by toluene and xylene at 800 ppm. Decrease in ACh and increase in glutamine in the brain appear to be phenomena common to many kinds of organic solvents including toluene and xylene after acute and subacute exposure.

  18. Altered feeding patterns in rats exposed to a palatable cafeteria diet: increased snacking and its implications for development of obesity.

    Directory of Open Access Journals (Sweden)

    Sarah I Martire

    Full Text Available BACKGROUND: Rats prefer energy-rich foods over chow and eat them to excess. The pattern of eating elicited by this diet is unknown. We used the behavioral satiety sequence to classify an eating bout as a meal or snack and compared the eating patterns of rats fed an energy rich cafeteria diet or chow. METHODS: Eight week old male Sprague Dawley rats were exposed to lab chow or an energy-rich cafeteria diet (plus chow for 16 weeks. After 5, 10 and 15 weeks, home-cage overnight feeding behavior was recorded. Eating followed by grooming then resting or sleeping was classified as a meal; whereas eating not followed by the full sequence was classified as a snack. Numbers of meals and snacks, their duration, and waiting times between feeding bouts were compared between the two conditions. RESULTS: Cafeteria-fed rats ate more protein, fat and carbohydrate, consistently ingesting double the energy of chow-fed rats, and were significantly heavier by week 4. Cafeteria-fed rats tended to take multiple snacks between meals and ate fewer meals than chow-fed rats. They also ate more snacks at 5 weeks, were less effective at compensating for snacking by reducing meals, and the number of snacks in the majority of the cafeteria-fed rats was positively related to terminal body weights. CONCLUSIONS: Exposure to a palatable diet had long-term effects on feeding patterns. Rats became overweight because they initially ate more frequently and ultimately ate more of foods with higher energy density. The early increased snacking in young cafeteria-fed rats may represent the establishment of eating habits that promote weight gain.

  19. The development of the glucocorticoid receptor system in the rat limbic brain. 2

    International Nuclear Information System (INIS)

    Meaney, M.J.; Sapolsky, R.M.; McEwen, B.S.

    1985-01-01

    The authors report the results of an autoradiographic analysis of the postnatal development of the hippocampal glucocorticoid receptor system in the rat brain. Quantitative analysis of the autoradiograms revealed a varied pattern of gradual development towards adult receptor concentrations during the second week of life. Receptor concentrations in the dentate gyrus increased dramatically between Days 9 and 15, while the changes during this period in the pyramidal layers of Ammon's horn seemed to reflect both structural changes in these regions as well as increases in receptor concentrations. (orig.)

  20. Effect of tritium (tritium water) on prenatal and postnatal development of rats

    International Nuclear Information System (INIS)

    Bajrakova, A.; Baev, I.; Yagova, A.

    1983-01-01

    Female rats were injected intraperitoneally on the first day after their fecundation with 3,7 kBq/g b.w. tritium water - activity which under these conditions does not increase prenatal death rate. The postnatal development of the born alive was traced in respect to the lethality rate and growth rate (mean bodily weight in dynamics up to the 60-th day p.p.) and compared with that of the offsprings from the control group. It was shown that the used activity tritium water during the initial stages of embryonic development does not result in deviations from the norm. (authors)

  1. Minocycline attenuates the development of diabetic neuropathy by inhibiting spinal cord Notch signaling in rat.

    Science.gov (United States)

    Yang, Cheng; Gao, Jie; Wu, Banglin; Yan, Nuo; Li, Hui; Ren, Yiqing; Kan, Yufei; Liang, Jiamin; Jiao, Yang; Yu, Yonghao

    2017-10-01

    We studied the effects of minocycline (an inhibitor of microglial activation) on the expression and activity of Notch-1 receptor, and explored the therapeutic efficacy of minocycline combined with Notch inhibitor DAPT in the treatment of diabetic neuropathic pain (DNP). Diabetic rat model was established by intraperitoneal injection (ip) of Streptozotocin (STZ). Expression and activity of Notch-1 and expression of macrophage/microglia marker Iba-1 were detected by WB. Diabetes induction significantly attenuated sciatic nerve conduction velocity, and dramatically augmented the expression and the activity of Notch-1 in the lumbar enlargement of the spinal cord. Minocycline treatment, however, accelerated the decreased conduction velocity of sciatic nerve and suppressed Notch-1expression and activity in diabetic rats. Similar to DAPT treatment, minocycline administration also prolonged thermal withdrawal latency (TWL) and increase mechanical withdrawal threshold (MWT) in diabetic rats in response to heat or mechanical stimulation via inhibition the expression and the activity of Notch-1 in spinal cord. Combination of DAPT and minocycline further inhibited Notch-1 receptor signaling and reduce neuropathic pain exhibited as improved TWL and MWT. Our study revealed a novel mechanism of Notch-1 receptor inhibition in spinal cord induced by minocycline administration, and suggested that the combination of minocycline and DAPT has the potential to treat DNP. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Neurobehavioral, reflexological and physical development of Wistar rat offspring exposed to ayahuasca during pregnancy and lactation

    Directory of Open Access Journals (Sweden)

    Carolina Dizioli Rodrigues de Oliveira

    2011-09-01

    Full Text Available Ayahuasca is a hallucinogenic beverage prepared by the decoction of plants native to the Amazon Basin region. The beverage has been used throughout the world by members of some syncretic religious movements. Despite the recent legalization of ayahuasca in Brazil for religious purposes, there is little pre-clinical and clinical information attesting to its safety, particularly in relation to the use during pregnancy. The aim of the current work was to determine the effects of perinatal exposure to ayahuasca (from the 6th day of pregnancy to the 10th day of lactation on physical, reflexology and neurobehavioral parameters of the Wistar rat offspring. The offspring showed no statistically significant changes in the physical and reflexology parameters evaluated. However, in adult rats, perinatally exposed to ayahuasca, an increase in frequency of entries in open arms in elevated plus-maze test, a decrease in total time of interaction in social interaction test, a decrease in time of latency for the animal to start swimming and a decrease of the minimum convulsant dose induced by pentylenetetrazol were observed. In conclusion, our results showed that the use of ayahuasca by mothers during pregnancy and lactation reduced the general anxiety and social motivation of the rat offspring. Besides, it promoted a higher sensitivity for initiation and spread of seizure activity.

  3. Neurobehavioral, reflexological and physical development of Wistar rat offspring exposed to ayahuasca during pregnancy and lactation

    Directory of Open Access Journals (Sweden)

    Carolina Dizioli Rodrigues de Oliveira

    2011-12-01

    Full Text Available Ayahuasca is a hallucinogenic beverage prepared by the decoction of plants native to the Amazon Basin region. The beverage has been used throughout the world by members of some syncretic religious movements. Despite the recent legalization of ayahuasca in Brazil for religious purposes, there is little pre-clinical and clinical information attesting to its safety, particularly in relation to the use during pregnancy. The aim of the current work was to determine the effects of perinatal exposure to ayahuasca (from the 6th day of pregnancy to the 10th day of lactation on physical, reflexology and neurobehavioral parameters of the Wistar rat offspring. The offspring showed no statistically significant changes in the physical and reflexology parameters evaluated. However, in adult rats, perinatally exposed to ayahuasca, an increase in frequency of entries in open arms in elevated plus-maze test, a decrease in total time of interaction in social interaction test, a decrease in time of latency for the animal to start swimming and a decrease of the minimum convulsant dose induced by pentylenetetrazol were observed. In conclusion, our results showed that the use of ayahuasca by mothers during pregnancy and lactation reduced the general anxiety and social motivation of the rat offspring. Besides, it promoted a higher sensitivity for initiation and spread of seizure activity.

  4. Intraarterial Microdosing, a Novel Drug Development Approach, Proof-of-Concept PET Study in Rats

    Science.gov (United States)

    Burt, Tal; Rouse, Douglas C.; Lee, Kihak; Wu, Huali; Layton, Anita T.; Hawk, Thomas C.; Weitzel, Douglas H.; Chin, Bennett B.; Cohen-Wolkowiez, Michael; Chow, Shein-Chung; Noveck, Robert J.

    2016-01-01

    Intraarterial microdosing (IAM) is a novel drug development approach combining intraarterial drug delivery and microdosing. We aimed to demonstrate that IAM leads to target exposure similar to that of systemic full-dose administration but with minimal systemic exposure. IAM could enable the safe, inexpensive, and early study of novel drugs at the first-in-human stage and the study of established drugs in vulnerable populations. Methods Insulin was administered intraarterially (ipsilateral femoral artery) or systemically to 8 CD IGS rats just before blood sampling or 60-min 18F-FDG uptake PET imaging of ipsilateral and contralateral leg muscles (lateral gastrocnemius) and systemic muscles (spinotrapezius). The 18F-FDG uptake slope analysis was used to compare the interventions. Plasma levels of insulin and glucose were compared using area under the curve calculated by the linear trapezoidal method. A physiologically based computational pharmacokinetics/pharmacodynamics model was constructed to simulate the relationship between the administered dose and response over time. Results 18F-FDG slope analysis found no difference between IAM and systemic full-dose slopes (0.0066 and 0.0061, respectively; 95% confidence interval [CI], −0.024 to 0.029; P = 0.7895), but IAM slope was statistically significantly greater than systemic microdose (0.0018; 95% CI, −0.045 to −0.007; P = 0.0147) and sham intervention (−0.0015; 95% CI, 0.023–0.058; P = 0.0052). The pharmacokinetics/pharmacodynamics data were used to identify model parameters that describe membrane insulin binding and glucose–insulin dynamics. Conclusion Target exposure after IAM was similar to systemic full dose administration but with minimal systemic effects. The computational pharmacokinetics/pharmacodynamics model can be generalized to predict whole-body response. Findings should be validated in larger, controlled studies in animals and humans using a range of targets and classes of drugs. PMID

  5. Early life vincristine exposure evokes mechanical pain hypersensitivity in the developing rat.

    Science.gov (United States)

    Schappacher, Katie A; Styczynski, Lauren; Baccei, Mark L

    2017-09-01

    Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, acute lymphoblastic leukemia. Although clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part because of the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, this study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat. Low doses of VNC (15 or 30 μg/kg) failed to alter nociceptive withdrawal reflexes at any age examined compared with vehicle-injected littermate controls. Meanwhile, high dose VNC (60 μg/kg) evoked mechanical hypersensitivity in both sexes beginning at P26 that persisted until adulthood and included both static and dynamic mechanical allodynia. Hind paw withdrawal latencies to noxious heat and cold were unaffected by high doses of VNC, suggesting a selective effect of neonatal VNC on mechanical pain sensitivity. Gross and fine motor function appeared normal after VNC treatment, although a small decrease in weight gain was observed. The VNC regimen also produced a significant decrease in intraepidermal nerve fiber density in the hind paw skin by P33. Overall, the present results demonstrate that high-dose administration of VNC during the early postnatal period selectively evokes a mechanical hypersensitivity that is slow to emerge during adolescence, providing further evidence that aberrant sensory input during early life can have prolonged consequences for pain processing.

  6. Metabolic adjustments with the development, treatment, and recurrence of obesity in obesity-prone rats.

    Science.gov (United States)

    MacLean, Paul S; Higgins, Janine A; Johnson, Ginger C; Fleming-Elder, Brooke K; Peters, John C; Hill, James O

    2004-08-01

    Obesity is reaching epidemic proportions and predisposes afflicted individuals to several comorbidities. For these individuals, losing weight has proven to be an easier feat than maintaining a reduced weight. In obesity-prone rats, we examined if there is a metabolic propensity to regain weight after a period of significant weight loss. Twenty-four-hour energy expenditure (EE), sleeping metabolic rate (SMR), and nonprotein respiratory quotient (NPRQ) were obtained by indirect calorimetry with urinary nitrogen analysis and normalized to fat mass (FM) and fat-free mass (FFM) acquired by dual-energy X-ray absorptiometry. Obesity-prone rats were examined after free access to a high-fat diet for 16 wk to establish the obese state. They were again examined after 2 wk of calorie restriction, which reduced body weight (14%) and FM (32%). Rats were again examined after a further 8 wk of intake-regulated weight maintenance or ad libitum feeding that led to weight regain. Metabolic data were compared with preobese and age-matched controls. Weight loss suppressed EE and SMR beyond what was expected for the change in metabolic mass. This elevated metabolic efficiency persisted throughout weight maintenance but resolved after 8 wk of regain. Adjusted NPRQ values were elevated in weight-maintained and weight-regaining rats, suggesting a preference for carbohydrate utilization. These data support the concept that weight reduction in obesity is accompanied by metabolic adjustments beyond the drive to consume calories that predispose to weight regain, and some aspects of this adjustment persist with prolonged weight maintenance and during weight regain.

  7. Effects of maternal separation on the neurobehavioral development of newborn Wistar rats.

    Science.gov (United States)

    Farkas, Jozsef; Reglodi, Dora; Gaszner, Balazs; Szogyi, Donat; Horvath, Gabor; Lubics, Andrea; Tamas, Andrea; Frank, Falko; Besirevic, Dario; Kiss, Peter

    2009-05-29

    Animal models of neonatal stress, like maternal separation, may provide important correlation with human stress-related disorders. Early maternal deprivation has been shown to cause several short- and long-term neurochemical and behavioral deficits. Little is known about the early neurobehavioral development after postnatal stress. The aim of the present study was to investigate the development of reflexes and motor coordination in male and female pups subjected to maternal deprivation. Pups were removed from their mothers from postnatal day 1-14, for 3h daily. Somatic development (weight gain, eye opening, ear unfolding, incisor eruption) and reflex development was tested during the first 3 weeks. The appearance of the following reflexes was investigated: crossed extensor, grasping, placing, gait, righting and sensory reflexes, and negative geotaxis. Timely performance of negative geotaxis, righting and gait were also tested daily during the first 3 weeks. Motor coordination and open-field tests were performed on postnatal weeks 3-5 (rotarod, elevated grid-walk, footfault, rope suspension, inclined board and walk initiation tests). The results revealed that a 3-h-long daily maternal separation did not lead to a marked delay or enhancement in reflex development and motor coordination. A subtle enhancement was observed in the appearance of hindlimb grasp and gait reflexes, and a better performance in footfault test in male rats suffering from maternal deprivation. In contrast, female maternally deprived (MD) rats displayed a slight delay in forelimb grasp and air righting reflex appearance, and surface righting performance. Open-field activity was not changed in maternally deprived rats. In summary, our present observations indicate that maternal deprivation does not induce drastic changes in early neurodevelopment, therefore, further research is needed to determine the onset of behavioral alterations in subject with maternal deprivation history. Gender differences

  8. Vitamin D-dependent rat renal calcium-binding protein: development of a radioimmunoassay, tissue distribution, and immunologic identification

    International Nuclear Information System (INIS)

    Sonnenberg, J.; Pansini, A.R.; Christakos, S.

    1984-01-01

    A sensitive double antibody RIA has been developed for the 28,000 mol wt rat renal vitamin D-dependent calcium-binding protein. Using this assay, concentrations of calcium-binding protein (CaBP) as low as 30 ng can be measured. The assay is precise (intraassay variability, 5.0%) and reproductible (interassay variability, 8.2%). Measurements of renal CaBP by RIA showed a good correlation with measurements of CaBP by the chelex resin assay and by polyacrylamide gel analysis by densitometric tracing using a purified CaBP marker. The concentration of CaBP in the vitamin D-replete rat kidney is 7.3 +/- 1.0 (mean +/- SEM) micrograms/mg protein. In vitamin D-deficient rats the level of renal CaBP is 2.6 +/- 0.3 micrograms/mg protein. Tissue distribution of immunoreactive rat renal CaBP showed the highest concentration of CaBP in the rat cerebellum (38.3 +/- 5.1 micrograms/mg protein). Lower concentrations of immunoreactive CaBP were detected in several other rat tissues. No immunoreactive CaBP was detected in rat or human serum. In necropsy human kidney and cerebellum, high levels of immunoreactive CaBP were also detected (1.5 +/- 0.1 and 27.3 +/- 2.1 micrograms/mg protein, respectively). When extracts of rat kidney and brain and human cerebellum and kidney were assayed at several dilutions, immunodisplacement curves parallel to that of pure renal CaBP were observed, indicating immunochemical similarity. Fractionation of extracts of rat cerebellum, human kidney, and human cerebellum on Sephadex G-100 revealed immunoreactivity and calcium-binding activity in the 28,000 mol wt region similar to rat kidney

  9. Life-table studies revealed significant effects of deforestation on the development and survivorship of Anopheles minimus larvae.

    Science.gov (United States)

    Wang, Xiaoming; Zhou, Guofa; Zhong, Daibin; Wang, Xiaoling; Wang, Ying; Yang, Zhaoqing; Cui, Liwang; Yan, Guiyun

    2016-06-06

    Many developing countries are experiencing rapid ecological changes such as deforestation and shifting agricultural practices. These environmental changes may have an important consequence on malaria due to their impact on vector survival and reproduction. Despite intensive deforestation and malaria transmission in the China-Myanmar border area, the impact of deforestation on malaria vectors in the border area is unknown. We conducted life table studies on Anopheles minimus larvae to determine the pupation rate and development time in microcosms under deforested, banana plantation, and forested environments. The pupation rate of An. minimus was 3.8 % in the forested environment. It was significantly increased to 12.5 % in banana plantations and to 52.5 % in the deforested area. Deforestation reduced larval-to-pupal development time by 1.9-3.3 days. Food supplementation to aquatic habitats in forested environments and banana plantations significantly increased larval survival rate to a similar level as in the deforested environment. Deforestation enhanced the survival and development of An. minimus larvae, a major malaria vector in the China-Myanmar border area. Experimental determination of the life table parameters on mosquito larvae under a variety of environmental conditions is valuable to model malaria transmission dynamics and impact by climate and environmental changes.

  10. Chronic consumption of trans fat can facilitate the development of hyperactive behavior in rats.

    Science.gov (United States)

    Pase, C S; Roversi, Kr; Trevizol, F; Kuhn, F T; Dias, V T; Roversi, K; Vey, L T; Antoniazzi, C T; Barcelos, R C S; Bürger, M E

    2015-02-01

    In recent decades, the increased consumption of processed foods, which are rich in hydrogenated vegetable fat (HVF), has led to a decreased consumption of fish and oilseed, rich in omega-3 fatty acids. This eating habit provides an increased intake of trans fatty acids (TFA), which may be related to neuropsychiatric conditions, including inattention and hyperactivity. In this study, we evaluated the potential connection between prolonged trans fat consumption and development of hyperactivity-like symptoms in rats using different behavioral paradigms. Trans fat intake for 10 months (Experiment 1), as well as during pregnancy and lactation across two sequential generations of rats, (Experiment 4) induced active coping in the forced swimming task (FST). In addition, HVF supplementation was associated with increased locomotion before and after amphetamine (AMPH) administration (Experiment 2). Similarly, HVF supplementation during pregnancy and lactation were associated with increased locomotion in both young and adult rats (Experiment 3). Furthermore, trans fat intake across two sequential generations increased locomotor and exploratory activities following stressors (Experiment 4). From these results, we suggest that chronic consumption of trans fat is able to enhance impulsiveness and reactivity to novelty, facilitating hyperactive behaviors. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Mobile phone radiation during pubertal development has no effect on testicular histology in rats.

    Science.gov (United States)

    Tumkaya, Levent; Kalkan, Yildiray; Bas, Orhan; Yilmaz, Adnan

    2016-02-01

    Mobile phones are extensively used throughout the world. There is a growing concern about the possible public health hazards posed by electromagnetic radiation emitted from mobile phones. Potential health risk applies particularly to the most intensive mobile phone users-typically, young people. The aim of this study was to investigate the effects of mobile phone exposure to the testes, by assessing the histopathological and biochemical changes in the testicular germ cells of rats during pubertal development. A total of 12 male Sprague Dawley rats were used. The study group (n = 6) was exposed to a mobile phone for 1 h a day for 45 days, while the control group (n = 6) remained unexposed. The testes were processed with routine paraffin histology and sectioned. They were stained with hematoxylin-eosin, caspase 3, and Ki-67 and then photographed. No changes were observed between the groups (p > 0.05). The interstitial connective tissue and cells of the exposed group were of normal morphology. No abnormalities in the histological appearance of the seminiferous tubules, including the spermatogenic cycle stage, were observed. Our study demonstrated that mobile phones with a low specific absorption rate have no harmful effects on pubertal rat testicles. © The Author(s) 2013.

  12. Intracerebroventricular kainic acid administration to neonatal rats alters interneuron development in the hippocampus.

    Science.gov (United States)

    Dong, Hongxin; Csernansky, Cynthia A; Chu, Yunxiang; Csernansky, John G

    2003-10-10

    The effects of neonatal exposure to excitotoxins on the development of interneurons have not been well characterized, but may be relevant to the pathogenesis of neuropsychiatric disorders. In this study, the excitotoxin, kainic acid (KA) was administered to rats at postnatal day 7 (P7) by intracerebroventricular (i.c.v.) infusion. At P14, P25, P40 and P60, Nissl staining and immunohistochemical studies with the interneuron markers, glutamic acid decarboxylase (GAD-67), calbindin-D28k (CB) and parvalbumin (PV) were performed in the hippocampus. In control animals, the total number of interneurons, as well as the number of interneurons stained with GAD-67, CB and PV, was nearly constant from P14 through P60. In KA-treated rats, Nissl staining, GAD-67 staining, and CB staining revealed a progressive decline in the overall number of interneurons in the CA1 and CA3 subfields from P14 to P60. In contrast, PV staining in KA-treated rats showed initial decreases in the number of interneurons in the CA1 and CA3 subfields at P14 followed by increases that approached control levels by P60. These results suggest that, in general, early exposure to the excitotoxin KA decreases the number of hippocampal interneurons, but has a more variable effect on the specific population of interneurons labeled by PV. The functional impact of these changes may be relevant to the pathogenesis of neuropsychiatric disorders, such as schizophrenia.

  13. Herba Artemisiae Capillaris Extract Prevents the Development of Streptozotocin-Induced Diabetic Nephropathy of Rat

    Directory of Open Access Journals (Sweden)

    Jianan Geng

    2018-01-01

    Full Text Available Diabetic nephropathy (DN is a major cause of end-stage renal disease throughout the world; until now there is no specific drug available. In this work, we use herba artemisiae capillaris extract (HACE to alleviate renal fibrosis characterized by the excessive accumulation of extracellular matrix (ECM in rats, aiming to investigate the protective effect of the HACE on DN. We found that the intragastric treatment of high-dose HACE could reverse the effect of streptozotocin not only to decrease the level of blood glucose and blood lipid in different degree but also further to improve renal functions. It is worth mentioning that the effect of HACE treatment was comparable to the positive drug benazepril. Moreover, we found that HACE treatment could on one hand inhibit oxidative stress in DN rats through regulating enzymatic activity for scavenging reactive oxygen species and on the other hand increase the ECM degradation through regulating the activity of metalloproteinase-2 (MMP-2 and the expression of tissue transglutaminase (tTG, which explained why HACE treatment inhibited ECM accumulation. On the basis of above experimental results, we conclude that HACE prevents DN development in a streptozotocin-induced DN rat model, and HACE is a promising candidate to cure DN in clinic.

  14. Developing high-frequency ultrasound tomography for testicular tumor imaging in rats: An in vitro study

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chih-Chung, E-mail: cchuang@mail.ncku.edu.tw [Department of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan (China); Chen, Wei-Tsen [Department of Electrical Engineering, Fu Jen Catholic University, New Taipei City 24205, Taiwan (China)

    2014-01-15

    Purpose: This paper describes a feasibility study for developing a 35-MHz high-frequency ultrasound computed-tomography (HFUCT) system for imaging rat testicles. Methods: The performances of two kinds of HFUCT-attenuation and sound-speed UCT-based on transmission and pulse-echo modes were investigated in this study. Experiments were carried out using phantoms and actual rat testiclesin vitro. HFUCT images were reconstructed using a filtered backprojection algorithm. Results: The phantom experimental results indicated that all types of HFUCT can determine the dimensions of a plastic cylinder with a diameter of 500μm. Compared to sound-speed HFUCT, attenuation HFUCT exhibited a better performance in recognizing a tiny sclerosed region in a gelatin phantom. Therefore, the in vitro testicular experiments were performed using attenuation HFUCT based on transmission and pulse-echo modes. The experimentally measured attenuation coefficient and sound speed for healthy rat testicles were 2.92 ± 0.25 dB/mm and 1537 ± 25 m/s, respectively. Conclusions: A homogeneous texture was evident for healthy testicles using both modes. An artificial sclerosed tumor could also be clearly observed using two- and three-dimensional attenuation HFUCT in both modes. However, an object artifact was apparent in pulse-echo mode because of ultrasound beam refraction. All of the obtained experimental results indicate the potential of using HFUCT as a novel tool for monitoring the preclinical responses of testicular tumors in small animals.

  15. Developing high-frequency ultrasound tomography for testicular tumor imaging in rats: An in vitro study

    International Nuclear Information System (INIS)

    Huang, Chih-Chung; Chen, Wei-Tsen

    2014-01-01

    Purpose: This paper describes a feasibility study for developing a 35-MHz high-frequency ultrasound computed-tomography (HFUCT) system for imaging rat testicles. Methods: The performances of two kinds of HFUCT-attenuation and sound-speed UCT-based on transmission and pulse-echo modes were investigated in this study. Experiments were carried out using phantoms and actual rat testiclesin vitro. HFUCT images were reconstructed using a filtered backprojection algorithm. Results: The phantom experimental results indicated that all types of HFUCT can determine the dimensions of a plastic cylinder with a diameter of 500μm. Compared to sound-speed HFUCT, attenuation HFUCT exhibited a better performance in recognizing a tiny sclerosed region in a gelatin phantom. Therefore, the in vitro testicular experiments were performed using attenuation HFUCT based on transmission and pulse-echo modes. The experimentally measured attenuation coefficient and sound speed for healthy rat testicles were 2.92 ± 0.25 dB/mm and 1537 ± 25 m/s, respectively. Conclusions: A homogeneous texture was evident for healthy testicles using both modes. An artificial sclerosed tumor could also be clearly observed using two- and three-dimensional attenuation HFUCT in both modes. However, an object artifact was apparent in pulse-echo mode because of ultrasound beam refraction. All of the obtained experimental results indicate the potential of using HFUCT as a novel tool for monitoring the preclinical responses of testicular tumors in small animals

  16. An Evaluation of Significance of Herbal Acupuncture on Treating Limb Impediment Among the Children with Development Disabilities

    Directory of Open Access Journals (Sweden)

    Huh Young-Jin

    2004-02-01

    Full Text Available Objectives : This study was conducted to establish a standard and classify suitability in the treatment of limb impediment among the children with development disabilities using bee venom and eight principles herbal acupuncture. Methods : 10 patients with pediatric development disabilities with limb impediment as the main symptoms were chosen in this study. Bee venom herbal acupuncture and eight principles herbal acupuncture treatments were rendered and evaluated responses as well as pursuing most proper treatment methods. Results : 1. Bee venom herbal acupuncture showed a significant effects when used as supplement treatment technique for the children with partial movement, but insignificant for the children whom were unable to move. 2. Bee venom was effective for severe limb impediment and limb asthenia, whileas eight principles herbal acupuncture effective for mild limb impediment and spasticity. 3. Bee venom herbal acupuncture used in conjunction with eight principles herbal acupuncture for treating limb impediment among the children with development disabilities showed general improvement by intensifying muscular strength.

  17. Quantification of 5-hydroxytryptamine1A receptors in the cerebellum of normal and x-irradiated rats during postnatal development

    International Nuclear Information System (INIS)

    Matthiessen, L.; Daval, G.; Bailly, Y.; Gozlan, H.; Hamon, M.; Verge, D.

    1992-01-01

    5-Hydroxytryptamine 1A receptors were studied in rats during the first postnatal month in the normal cerebellum and in the granule cell-deprived cerebellum produced by X-irradiation at postnatal day 5. Quantitative autoradiographic studies on sagittal sections of cerebellar vermis, using [ 125 1]BH-8-MeO-N-PAT as radioligand or specific anti-receptor antibodies, revealed that 5-hydroxytryptamine 1A receptors existed in the molecular/Purkinje cell layer but at variable density from one lobule to another. Thus, in both normal and X-irradiated rats, the posterior lobules were more heavily labelled than the anterior ones, and the density of 5-hydroxytryptamine 1A sites decreased progressively in all the cerebellar folia down to hardly detectable levels at postnatal day 21. However, the intensity of labelling remained higher at postnatal day 8 and postnatal day 12 in X-irradiated rats than in age-paired controls. Measurements of [ 3 H]8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] specific binding to membranes from whole cerebellum confirmed that the density of 5-hydroxytryptamine 1A sites per mg membrane protein (B max ) was higher in X-irradiated animals than in age-paired controls. However, on a ''per cerebellum'' basis, no significant difference could be detected between the total number of 5-hydroxytryptamine 1A sites, which progressively increased in both control and X-irradiated animals during the first postnatal month. These results therefore show that 5-hydroxytryptamine 1A receptors are not located on developing granule cells. (author)

  18. Increased risk of cataract development in WNIN-obese rats due to accumulation of intralenticular sorbitol.

    Science.gov (United States)

    Reddy, Paduru Yadagiri; Giridharan, Nappan Veettil; Balakrishna, Nagalla; Validandi, Vakdevi; Pullakhandam, Raghu; Reddy, Geereddy Bhanuprakash

    2013-05-01

    Epidemiological studies have reported an association between obesity and increased incidence of ocular complications including cataract, yet the underlying biochemical and molecular mechanisms remained unclear. Previously we had demonstrated accumulation of sorbitol in the lens of obese rats (WNIN/Ob) and more so in a related strain with impaired glucose tolerance (WNIN/GR-Ob). However, only a few (15-20%) WNIN/Ob and WNIN/GR-Ob rats develop cataracts spontaneously with age. To gain further insights, we investigated the susceptibility of eye lens proteins of these obese rat strains to heat- and UV-induced aggregation in vitro, lens opacification upon glucose-mediated sorbitol accumulation ex vivo, and onset and progression of cataract was followed by galactose feeding and streptozotocin (STZ) injection. The results indicated increased susceptibility toward heat- or UV-induced aggregation of lens proteins in obese animals compared to their littermate lean controls. Further, in organ culture studies glucose-induced sorbitol accumulation was found to be higher and thus the lens opacification was faster in obese animals compared to their lean littermates. Also, the onset and progression of galactose- or STZ-induced cataractogenesis was faster in obese animals compared to lean control. These results together with our previous observations suggest that obesity status could lead to hyperaccumulation of sorbitol in eye lens, predisposing them to cataract, primarily by increasing their susceptibility to environmental and/or physiological factors. Further, intralenticular sorbitol accumulation beyond a threshold level could lead to cataract in WNIN/Ob and WNIN/GR-Ob rats. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

  19. NADPH-diaphorase expression in the Meibomian glands of rat palpebra in postnatal development

    Directory of Open Access Journals (Sweden)

    D. Kluchova

    2010-11-01

    Full Text Available In the current study, we aimed at investigating the presence of nitric oxide synthase (NOS positive nerve fibers in rat meibomian glands (MGs at various stages of development. There is good evidence to suggest that nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d is a surrogate for neuronal nitric oxide synthase (NOS. Sections of the central, upper eyelids of Wistar rats were processed histochemically for NADPH-d to investigate the presence and distribution of NOS-positive nerve fibers at the following time points: day 1 and weeks 1, 2 and 3 post partum, and in adult controls. At day 1, MG acini were lightly stained and located at a distance from the mucosal border. Vessels were accompanied by intensely stained NADPH-d positive nerve fibers. At the week 1 time point, both the vessels and the NADPH-d positive fibers were still present, but less numerous. MGs were now closer to the mucosa, so that the submucosa was thinner. The acini were mostly pale but occasionally darker. At week 3, there were fewer blood vessels in both the submucosa and within the septa. Darker acini were more common than lightly stained acini. NADPH-d positive dots were observed in the vicinity of the MGs. At the week 3 time point, MGs were adjacent to the mucosal border and stained more intensely than at earlier times; almost all acini were stained. The microscopic appearances were almost identical with those of adult palpebra. Submucosal and septal blood vessels and NADPH-d positive nerve fibers were less numerous. NADPH-d histochemical staining confirmed differences in the density of stained nerve fibers at different developmental stages. The greatest density of NADPH-d -positive nerve fibers occurred in 1-day-old rats whereas they were less numerous in adult rat eyelids. Nerves innervating MGs utilize nitric oxide (NO as a neurotransmitter mostly in early developmental stages and this need thereafter decreases and stabilizes at 3 weeks postnatally.

  20. Similarity between the effects of carbon-ion irradiation and X-irradiation on the development of rat brain

    International Nuclear Information System (INIS)

    Inouye, Minoru; Hayasaka, Shizu; Murata, Yoshiharu; Takahashi, Sentaro; Kubota, Yoshihisa

    2000-01-01

    The effects of carbon-ion irradiation and X-irradiation on the development of rat brain were compared. Twenty pregnant rats were injected with bromodeoxyuridine (BrdU) at 9 pm on day 18 pregnancy and divided into five groups. Three hours after injection (day 19.0) one group was exposed to 290 MeV/u carbon-ion radiation by a single dose of 1.5 Gy. Other groups were exposed to X-radiation by 1.5, 2.0 or 2.5 Gy, or sham-treated, respectively. Fetuses were removed from one dam in each group 8 h after exposure and examined histologically. Extensive cell death was observed in the brain mantle from the irradiated groups. The cell death after 1.5 Gy carbon-ion irradiation was remarkably more extensive than that after 1.5 Gy X-irradiation, but comparable to that after 2.0 Gy or 2.5 Gy X-irradiation. The remaining rats were allowed to give birth and the offspring were sacrificed at 6 weeks of age. All of the irradiated offspring manifested microcephaly. The size of the brain mantle exposed to 1.5 Gy carbon-ion radiation was significantly smaller than that exposed to 1.5 Gy X-radiation and larger than that exposed to 2.5 Gy X-radiation. A histological examination of the cerebral cortex revealed that cortical layers II-IV were malformed. The defect by 1.5 Gy carbon-ion irradiation was more severe than that by the same dose of X-irradiation. Although the BrdU-incorporated neurons were greatly reduced in number in all irradiated groups, these cells reached the superficial area of the cortex. These findings indicated that the effects of both carbon-ion irradiation and X-irradiation on the development of rat brain are similar in character, and the effect of 1.5 Gy carbon-ion irradiation compares to that of 2.0-2.5 Gy X-irradiation. (author)

  1. The potential of cell sheet technique on the development of hepatocellular carcinoma in rat models.

    Directory of Open Access Journals (Sweden)

    Alaa T Alshareeda

    Full Text Available Hepatocellular carcinoma (HCC is considered the 3rd leading cause of death by cancer worldwide with the majority of patients were diagnosed in the late stages. Currently, there is no effective therapy. The selection of an animal model that mimics human cancer is essential for the identification of prognostic/predictive markers, candidate genes underlying cancer induction and the examination of factors that may influence the response of cancers to therapeutic agents and regimens. In this study, we developed a HCC nude rat models using cell sheet and examined the effect of human stromal cells (SCs on the development of the HCC model and on different liver parameters such as albumin and urea.Transplanted cell sheet for HCC rat models was fabricated using thermo-responsive culture dishes. The effect of human umbilical cord mesenchymal stromal cells (UC-MSCs and human bone marrow mesenchymal stromal cells (BM-MSCs on the developed tumour was tested. Furthermore, development of tumour and detection of the liver parameter was studied. Additionally, angiogenesis assay was performed using Matrigel.HepG2 cells requires five days to form a complete cell sheet while HepG2 co-cultured with UC-MSCs or BM-MSCs took only three days. The tumour developed within 4 weeks after transplantation of the HCC sheet on the liver of nude rats. Both UC-MSCs and BM-MSCs improved the secretion of liver parameters by increasing the secretion of albumin and urea. Comparatively, the UC-MSCs were more effective than BM-MSCs, but unlike BM-MSCs, UC-MSCs prevented liver tumour formation and the tube formation of HCC.Since this is a novel study to induce liver tumour in rats using hepatocellular carcinoma sheet and stromal cells, the data obtained suggest that cell sheet is a fast and easy technique to develop HCC models as well as UC-MSCs have therapeutic potential for liver diseases. Additionally, the data procured indicates that stromal cells enhanced the fabrication of HepG2

  2. Iron supplement prevents lead-induced disruption of the blood-brain barrier during rat development

    International Nuclear Information System (INIS)

    Wang Qiang; Luo Wenjing; Zheng Wei; Liu Yiping; Xu Hui; Zheng Gang; Dai Zhongming; Zhang Wenbin; Chen Yaoming; Chen Jingyuan

    2007-01-01

    Children are known to be venerable to lead (Pb) toxicity. The blood-brain barrier (BBB) in immature brain is particularly vulnerable to Pb insults. This study was designed to test the hypothesis that Pb exposure damaged the integrity of the BBB in young animals and iron (Fe) supplement may prevent against Pb-induced BBB disruption. Male weanling Sprague-Dawley rats were divided into four groups. Three groups of rats were exposed to Pb in drinking water containing 342 μg Pb/mL as Pb acetate, among which two groups were concurrently administered by oral gavage once every other day with 7 mg Fe/kg and 14 mg Fe/kg as FeSO 4 solution as the low and high Fe treatment group, respectively, for 6 weeks. The control group received sodium acetate in drinking water. Pb exposure significantly increased Pb concentrations in blood by 6.6-folds (p < 0.05) and brain tissues by 1.5-2.0-folds (p < 0.05) as compared to controls. Under the electron microscope, Pb exposure in young animals caused an extensive extravascular staining of lanthanum nitrate in brain parenchyma, suggesting a leakage of cerebral vasculature. Western blot showed that Pb treatment led to 29-68% reduction (p < 0.05) in the expression of occludin as compared to the controls. Fe supplement among Pb-exposed rats maintained the normal ultra-structure of the BBB and restored the expression of occludin to normal levels. Moreover, the low dose Fe supplement significantly reduced Pb levels in blood and brain tissues. These data suggest that Pb exposure disrupts the structure of the BBB in young animals. The increased BBB permeability may facilitate the accumulation of Pb. Fe supplement appears to protect the integrity of the BBB against Pb insults, a beneficial effect that may have significant clinical implications

  3. The Role of Endothelin System in Renal Structure and Function during the Postnatal Development of the Rat Kidney.

    Science.gov (United States)

    Albertoni Borghese, María F; Ortiz, María C; Balonga, Sabrina; Moreira Szokalo, Rocío; Majowicz, Mónica P

    2016-01-01

    Renal development in rodents, unlike in humans, continues during early postnatal period. We aimed to evaluate whether the pharmacological inhibition of Endothelin system during this period affects renal development, both at structural and functional level in male and female rats. Newborn rats were treated orally from postnatal day 1 to 20 with vehicle or bosentan (Actelion, 20 mg/kg/day), a dual endothelin receptor antagonist (ERA). The animals were divided in 4 groups: control males, control females, ERA males and ERA females. At day 21, we evaluated renal function, determined the glomerular number by a maceration method and by morphometric analysis and evaluated possible structural renal alterations by three methods: 〈alpha〉-Smooth muscle actin (α-SMA) immunohistochemistry, Masson's trichrome and Sirius red staining. The pharmacological inhibition of Endothelin system with a dual ERA during the early postnatal period of the rat did not leads to renal damage in the kidneys of male and female rats. However, ERA administration decreased the number of glomeruli, the juxtamedullary filtration surface area and the glomerular filtration rate and increased the proteinuria. These effects could predispose to hypertension or renal diseases in the adulthood. On the other hand, these effects were more pronounced in male rats, suggesting that there are sex differences that could be greater later in life. These results provide evidence that Endothelin has an important role in rat renal postnatal development. However these results do not imply that the same could happen in humans, since human renal development is complete at birth.

  4. Critical androgen-sensitive periods of rat penis and clitoris development.

    Science.gov (United States)

    Welsh, Michelle; MacLeod, David J; Walker, Marion; Smith, Lee B; Sharpe, Richard M

    2010-02-01

    Androgen control of penis development/growth is unclear. In rats, androgen action in a foetal 'masculinisation programming window' (MPW; e15.5-e18.5)' predetermines penile length and hypospadias occurrence. This has implications for humans (e.g. micropenis). Our studies aimed to establish in rats when androgen action/administration affects development/growth of the penis and if deficits in MPW androgen action were rescuable postnatally. Thus, pregnant rats were treated with flutamide during the MPW +/- postnatal testosterone propionate (TP) treatment. To assess penile growth responsiveness, rats were treated with TP in various time windows (late foetal, neonatal through early puberty, puberty onset, or combinations thereof). Phallus length, weight, and morphology, hypospadias and anogenital distance (AGD) were measured in mid-puberty (d25) or adulthood (d90) in males and females, plus serum testosterone in adult males. MPW flutamide exposure reduced adult penile length and induced hypospadias dose-dependently; this was not rescued by postnatal TP treatment. In normal rats, foetal (e14.5-e21.5) TP exposure did not affect male penis size but increased female clitoral size. In males, TP exposure from postnatal d1-24 or at puberty (d15-24), increased penile length at d25, but not ultimately in adulthood. Foetal + postnatal TP (e14-postnatal d24) increased penile size at d25 but reduced it at d90 (due to reduced endogenous testosterone). In females, this treatment caused the biggest increase in adult clitoral size but, unlike in males, phallus size was unaffected by TP during puberty (d15-24). Postnatal TP treatment advanced penile histology at d25 to more resemble adult histology. AGD strongly correlated with final penis length. It is concluded that adult penile size depends critically on androgen action during the MPW but subsequent growth depends on later androgen exposure. Foetal and/or postnatal TP exposure does not increase adult penile size above its

  5. {sup 26}Al incorporation into the brain of rat fetuses through the placental barrier and subsequent metabolism in postnatal development

    Energy Technology Data Exchange (ETDEWEB)

    Yumoto, Sakae, E-mail: yumoto-s@viola.ocn.ne.j [Yumoto Institute of Neurology, Kawadacho 6-11, Shinjuku-ku, Tokyo 162-0054 (Japan); Nagai, Hisao [College of Humanities and Sciences, Nihon University, Tokyo (Japan); Kakimi, Shigeo [Faculty of Medicine, Nihon University, Tokyo (Japan); Matsuzaki, Hiroyuki [School of Engineering, The University of Tokyo, Tokyo (Japan)

    2010-04-15

    Aluminium (Al) inhibits prenatal and postnatal development of the brain. We used {sup 26}Al as a tracer, and measured {sup 26}Al incorporation into rat fetuses through the placental barrier by accelerator mass spectrometry (AMS). From day 15 to day 18 of gestation, {sup 26}AlCl{sub 3} was subcutaneously injected into pregnant rats. Considerable amounts of {sup 26}Al were measured in the tissues of newborn rats immediately after birth. The amounts of {sup 26}Al in the liver and kidneys decreased rapidly during postnatal development. However, approximately 15% of {sup 26}Al incorporated into the brain of fetuses remained in the brain of adult rats 730 days after birth.

  6. What the laboratory rat has taught us about social play behavior: role in behavioral development and neural mechanisms.

    Science.gov (United States)

    Vanderschuren, Louk J M J; Trezza, Viviana

    2014-01-01

    Social play behavior is the most vigorous and characteristic form of social interaction displayed by developing mammals. The laboratory rat is an ideal species to study this behavior, since it shows ample social play that can be easily recognized and quantified. In this chapter, we will first briefly describe the structure of social play behavior in rats. Next, we will discuss studies that used social isolation rearing during the period in life when social play is most abundant to investigate the developmental functions of social play behavior in rats, focusing on the consequences of play deprivation on social, cognitive, emotional, and sensorimotor development. Last, we will discuss the neural substrates of social play behavior in rats, with emphasis on the limbic corticostriatal circuits that underlie emotions and their influence on behavior.

  7. The significance of renewable energy use for economic output and environmental protection: evidence from the Next 11 developing economies.

    Science.gov (United States)

    Paramati, Sudharshan Reddy; Sinha, Avik; Dogan, Eyup

    2017-05-01

    Increasing economic activities in developing economies raise demand for energy mainly sourced from conventional sources. The consumption of more conventional energy will have a significant negative impact on the environment. Therefore, attention of policy makers has recently shifted towards the promotion of renewable energy generation and uses across economic activities to ensure low carbon economy. Given the recent scenario, in this paper, we aim to examine the role of renewable energy consumption on the economic output and CO 2 emissions of the next fastest developing economies of the world. The study employs several robust panel econometric models by using annual data from 1990 to 2012. Empirical findings confirm the significant long-run association among the variables. Similarly, results show that renewable energy consumption positively contributes to economic output and has an adverse effect on CO 2 emissions. Given our findings, we suggest policy makers of those economies to initiate further effective policies to promote more renewable energy generation and uses across economic activities to ensure sustainable economic development.

  8. The effects of female sex steroids on the development of autoimmune thyroiditis in thymectomized and irradiated rats

    International Nuclear Information System (INIS)

    Ahmed, S.A.; Young, P.R.; Penhale, W.J.

    1983-01-01

    Female PVG/c strain rats are more susceptible to induction of autoimmune thyroiditis initiated by thymectomy and irradiation (Tx-X) than similarly treated males. Pre-pubertal ovariectomy further augmented susceptibility. Administration of oestrogen or progesterone to groups of 4 weeks old ovariectomized Tx-X animals over a period of 15 weeks significantly altered induction of this condition. Oestrogen administered repeatedly at dose levels of 1 μg and 10 μg/100 g body weight resulted in partial suppression of thyroiditis with a corresponding change in the incidence of antibodies to thyroglobulin. Oestrogen administered by a single implantation had a suppressive effect on the development of autoimmunity in ovariectomized Tx-X females. Oestrogen given by either of these procedures also reduced the incidence of thyroiditis and autoantibody induction in orchidectomized male Tx-X rats. In contrast, repeated administration of progesterone at a dose of 250 mg and 1,500 μg/100 g body weight appeared to augment levels of autoimmunity. It is concluded that the differential susceptibility to the induction of autoimmunity by thymectomy and irradiation is the direct consequence of sex hormonal influences. The higher incidence of the disease in the female would appear to be determined by the balance between the activity of oestrogen and progesterone which would further appear to have antagonistic influences in this particular situation. (UK)

  9. Dose-rate effects for mammary tumor development in female Sprague-Dawley rats exposed to X and γ radiation

    International Nuclear Information System (INIS)

    Johnson, J.R.; Gragtmans, N.J.; Myers, D.K.; Jones, A.R.

    1989-01-01

    Mammary tumour development was followed in two experiments involving a total of 2229 female Sprague-Dawley rats exposed to various doses of X or γ rays at different dose rates. The data for another 462 rats exposed to tritiated water in one of these experiments were also analyzed. The incidence of adenocarcinomas and fibroadenomas at a given time after exposure increased linearly in proportion to total radiation dose for most groups. However, no significant increase in adenocarcinomas was observed with chronic γ exposures up to 1.1 Gy, and the increase in fibroadenomas observed with chronic gamma exposures at a dose rate of 0.0076 Gy h -1 up to an accumulated dose of 3.3 Gy was small compared to that observed after acute exposures. The incidence of all mammary tumors increased almost linearly with the log of dose rate in the range 0.0076 to 26.3 Gy h -1 for 3 Gy total dose of gamma rays. The effects of X rays appeared to be less influenced by dose rate than were the effects of γ rays. (author)

  10. A Comparative Analysis of Perinatal Development of Barrel Cortex in Rat, Mouse and Guinea Pig Using Acetylcholinesterase Histochemistry

    OpenAIRE

    ŞENDEMİR, Erdoğan

    2014-01-01

    The role of acetylcholinesterase (AChE) in the developing neocortex was reexamined by comparing its expression in rats, mice and guinea pigs, following the protocol for acetylcholinesterase histochemistry (described in Sendemir et al., 1996) in order to determine the suitability of the breeding colony at UludaÛ University for use as an animal model. A total of 103 pups as well as two adult animals of each species were used. In the rat pups, acetylcholinesterase-rich patches were d...

  11. Effects of prenatal irradiation with accelerated heavy-ion beams on postnatal development in rats: III. Testicular development and breeding activity

    Science.gov (United States)

    Wang, B.; Murakami, M.; Eguchi-Kasai, K.; Nojima, K.; Shang, Y.; Tanaka, K.; Watanabe, K.; Fujita, K.; Moreno, S. G.; Coffigny, H.; Hayata, I.

    With a significant increase in human activities dealing with space missions, potential teratogenic effects on the mammalian reproductive system from prenatal exposure to space radiation have become a hot topic that needs to be addressed. However, even for the ground experiments, such effects from exposure to high LET ionizing radiation are not as well studied as those for low LET ionizing radiations such as X-rays. Using the Heavy-Ion Medical Accelerator in Chiba (HIMAC) and Wistar rats, effects on gonads in prenatal male fetuses, on postnatal testicular development and on breeding activity of male offspring were studied following exposure of the pregnant animals to either accelerated carbon-ion beams with a LET value of about 13 keV/μm or neon-ion beams with a LET value of about 30 keV/μm at a dose range from 0.1 to 2.0 Gy on gestation day 15. The effects of X-rays at 200 kVp estimated for the same biological end points were studied for comparison. A significantly dose-dependent increase of apoptosis in gonocytes appeared 6 h after irradiations with a dose of 0.5 Gy or more. Measured delayed testis descent and malformed testicular seminiferous tubules were observed to be significantly different from the control animals at a dose of 0.5 Gy. These effects are observed to be dose- and LET-dependent. Markedly reduced testicular weight and testicular weight to body weight ratio were scored at postnatal day 30 even in the offspring that were prenatally irradiated with neon-ions at a dose of 0.1 Gy. A dose of 0.5 Gy from neon-ion beams induced a marked decrease in breeding activity in the prenatally irradiated male rats, while for the carbon-ion beams or X-rays, the significantly reduced breeding activity was observed only when the prenatal dose was at 1.0 Gy or more. These findings indicated that prenatal irradiations with heavy-ion beams on gestation day 15 generally induced markedly detrimental effects on prenatal gonads, postnatal testicular development and male

  12. Patterns of x-radiation-induced Schwann cell development in spinal cords of immature rats

    International Nuclear Information System (INIS)

    Gilmore, S.A.; Heard, J.K.; Leiting, J.E.

    1983-01-01

    Schwann cells, Schwann cell myelin, and connective tissue components develop in the spinal cord of the immature rat following exposure to x-rays. For the purposes of this paper, these intraspinal peripheral nervous tissue constituents are referred to as IPNT. A series of investigations are in progress to elucidate factors related to the development of IPNT, and the present study is a light microscopic evaluation of the relationship between the amount of radiation administered (1,000-3,000R) to the lumbosacral spinal cord in 3-day-old rats and the incidence and distribution of IPNT at intervals up to 60 days postirradiation (P-I). The results showed that IPNT was present in only 33% of the rats exposed to 1,000R, whereas its presence was observed in 86% or more of those in the 2,000-, 2,500-, and 3,000R groups. The distribution of IPNT was quite limited in the 1,000R group, where it was restricted to the spinal cord-dorsal root junction and was found in only a few sections within the irradiated area. The distribution was more widespread with increasing amounts of radiation, and IPNT occupied substantial portions of the dorsal funiculi and extended into the dorsal gray matter in the 3,000R group. In all aR mals developing IPNT in the groups receiving 2,000R or more, the IPNT was present in essentially all sections from the irradiated area. Further studies will compare in detail spinal cords exposed to 1,000R in which IPNT is an infrequent, limited occurrence with those exposed to higher doses where IPNT occurs in a more widespread fashion in essentially all animals

  13. Paternal stress prior to conception alters DNA methylation and behaviour of developing rat offspring.

    Science.gov (United States)

    Mychasiuk, R; Harker, A; Ilnytskyy, S; Gibb, R

    2013-06-25

    Although there has been an abundance of research focused on offspring outcomes associated with maternal experiences, there has been limited examination of the relationship between paternal experiences and offspring brain development. As spermatogenesis is a continuous process, experiences that have the ability to alter epigenetic regulation in fathers may actually change developmental trajectories of offspring. The purpose of this study was to examine the effects of paternal stress prior to conception on behaviour and the epigenome of both male and female developing rat offspring. Male Long-Evans rats were stressed for 27 consecutive days and then mated with control female rats. Early behaviour was tested in offspring using the negative geotaxis task and the open field. At P21 offspring were sacrificed and global DNA methylation levels in the hippocampus and frontal cortex were analysed. Paternal stress prior to conception altered behaviour of all offspring on the negative geotaxis task, delaying acquisition of the task. In addition, male offspring demonstrated a reduction in stress reactivity in the open field paradigm spending more time than expected in the centre of the open field. Paternal stress also altered DNA methylation patterns in offspring at P21, global methylation was reduced in the frontal cortex of female offspring, but increased in the hippocampus of both male and female offspring. The results from this study clearly demonstrate that paternal stress during spermatogenesis can influence offspring behaviour and DNA methylation patterns, and these affects occur in a sex-dependent manner. Development takes place in the centre of a complex interaction between maternal, paternal, and environmental influences, which combine to produce the various phenotypes and individual differences that we perceive. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. [Significance and necessity of developing quality of life questionnaire for cancer patients adapting to traditional Chinese medicine].

    Science.gov (United States)

    You, Jie

    2006-09-01

    The clinical evaluation system for therapeutic effects of tumor, which focuses on survival period and tumor response rate, has been proved not very proper for evaluating the therapeutic effects of traditional Chinese medicine (TCM). Quality of life (QOL) has been introduced into the effective evaluation system of TCM and integrative medicine because of its similarity in concept and extension with TCM at theory basis, syndrome differentiation-treatment, and evaluation of therapeutic effects. But there are no QOL questionnaires which can evaluate the therapeutic effects of TCM and integrative medicine precisely. This article discussed the necessity and significance of developing QOL questionnaire special for TCM.

  15. Bone matrix calcification during embryonic and postembryonic rat calvarial development assessed by SEM-EDX spectroscopy, XRD, and FTIR spectroscopy.

    Science.gov (United States)

    Henmi, Akiko; Okata, Hiroshi; Anada, Takahisa; Yoshinari, Mariko; Mikami, Yasuto; Suzuki, Osamu; Sasano, Yasuyuki

    2016-01-01

    Bone mineral is constituted of biological hydroxyapatite crystals. In developing bone, the mineral crystal matures and the Ca/P ratio increases. However, how an increase in the Ca/P ratio is involved in maturation of the crystal is not known. The relationships among organic components and mineral changes are also unclear. The study was designed to investigate the process of calcification during rat calvarial bone development. Calcification was evaluated by analyzing the atomic distribution and concentration of Ca, P, and C with scanning electron microscopy (SEM)-energy-dispersive X-ray (EDX) spectroscopy and changes in the crystal structure with X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Histological analysis showed that rat calvarial bone formation started around embryonic day 16. The areas of Ca and P expanded, matching the region of the developing bone matrix, whereas the area of C became localized around bone. X-ray diffraction and FTIR analysis showed that the amorphous-like structure of the minerals at embryonic day 16 gradually transformed into poorly crystalline hydroxyapatite, whereas the proportion of mineral to protein increased until postnatal week 6. FTIR analysis also showed that crystallization of hydroxyapatite started around embryonic day 20, by which time SEM-EDX spectroscopy showed that the Ca/P ratio had increased and the C/Ca and C/P ratios had decreased significantly. The study suggests that the Ca/P molar ratio increases and the proportion of organic components such as proteins of the bone matrix decreases during the early stage of calcification, whereas crystal maturation continues throughout embryonic and postembryonic bone development.

  16. Early-in-life dietary zinc deficiency and supplementation and mammary tumor development in adulthood female rats.

    Science.gov (United States)

    da Silva, Flávia R M; Grassi, Tony F; Zapaterini, Joyce R; Bidinotto, Lucas T; Barbisan, Luis F

    2017-06-01

    Zinc deficiency during pregnancy and postnatal life can adversely increase risk of developing human diseases at adulthood. The present study was designed to evaluate whether dietary zinc deficiency or supplementation during the pregnancy, lactation and juvenile stages interferes in the development of mammary tumors induced by 7,12-dimethylbenzanthracene (DMBA) in female Sprague-Dawley (SD) rats. Pregnant female SD rats were allocated into three groups: zinc-adequate diet (ZnA - 35-mg/kg chow), zinc-deficient diet (ZnD - 3-mg/kg chow) or zinc-supplemented diet (ZnS - 180-mg/kg chow) during gestational day 10 (GD 10) until the litters' weaning. Female offspring received the same diets as their dams until postnatal day (PND) 51. At PND 51, the animals received a single dose of DMBA (50 mg/kg, ig) and zinc-adequate diets. At PND 180, female were euthanized, and tumor samples were processed for histological evaluation and gene expression microarray analysis. The ZnD induced a significant reduction in female offspring body weight evolution and in mammary gland development. At late in life, the ZnD or ZnS did not alter the latency, incidence, multiplicity, volume or histological types of mammary tumors in relation to the ZnA group. However, the total tumor number in ZnS group was higher than in ZnA group, accompanied by distinct expression of 4 genes up- and 15 genes down-regulated. The present findings indicate that early-in-life dietary zinc supplementation, differently to zinc deficiency, has a potential to modify the susceptibility to the development of mammary tumors induced by DMBA. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Low-dose effects of bisphenol A on mammary gland development in rats

    DEFF Research Database (Denmark)

    Egebjerg, Karen Mandrup; Boberg, Julie; Isling, Louise Krag

    2016-01-01

    was to perform a study robust enough to contribute to the risk assessment of BPA and to elucidate possible biphasic dose–response relationships. We investigated mammary gland effects in the offspring at 22, 100, and 400 days of age. Male offspring showed increased mammary outgrowth on pup day (PD) 22 at 0.025 mg...... intraductal hyperplasia in female rats could be associated with an increased risk for developing hyperplastic lesions, which are parallels to early signs of breast neoplasia in women. Collectively, current knowledge on effects of BPA on mammary gland at low doses indicates that highly exposed humans may...

  18. [The dinitrosyl-iron complexes with cysteine block the development of experimental endometriosis in rats].

    Science.gov (United States)

    Burgova, E N; Tkachev, N A; Vanin, A F

    2012-01-01

    It has been shown that the administration of 0,5 ml of 5 mM aqueous solution of dinitrosyl-iron complexes (DNIC) with cysteine alleviated the development of experimental endometriosis in rats induced by surgical way: the size of endometriomes decreased 1.85 times when the DNIC was added every day during 10 days. The effect was suggested to be due to cytotoxic action of NO molecules and nitrosonium ions (NO+) released from rapidly decomposed DNIC in animal organism on endometriome tissues.

  19. Glial and neuronal connexin expression patterns in the rat spinal cord during development and following injury

    DEFF Research Database (Denmark)

    Lee, I. Hui; Lindqvist, Eva; Kiehn, Ole

    2005-01-01

    Spinal cord injury induces a complex cascade of degenerative and remodeling events evolving over time. The possible roles of changed intercellular communication via gap junctions after spinal cord injury (SCI) have remained relatively unexplored. We investigated the temporospatial expression...... patterns of gap junctional genes and proteins, connexin 43 (Cx43), Cx36, and Cx32, by in situ hybridization and immunohistochemistry in the rat neonatal, adult normal, and adult injured spinal cord. Cx36 was strongly expressed in immature neurons, and levels declined markedly during development, whereas Cx...

  20. Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences

    DEFF Research Database (Denmark)

    Dean, Afshan; van den Driesche, Sander; Wang, Yili

    2016-01-01

    Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development...... smaller ovaries and reduced follicle numbers during puberty/adulthood; as similar changes were found for F2 offspring of analgesic-exposed F1 fathers or mothers, we interpret this as potentially indicating an analgesic-induced change to GC in F1. Assuming our results are translatable to humans, they raise...

  1. Development of a UPLC-MS/MS Method for Simultaneous Determination of Six Flavonoids in Rat Plasma after Administration of Maydis stigma Extract and Its Application to a Comparative Pharmacokinetic Study in Normal and Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Bin-Bin Wei

    2017-07-01

    Full Text Available Maydis stigma is an important medicine herb used in many parts of the world for treatment of diabetes mellitus, which main bioactive ingredients are flavonoids. This paper describes for the first time a study on the comparative pharmacokinetics of six active flavonoid ingredients of Maydis stigma in normal and diabetic rats orally administrated with the decoction. Therefore, an efficient and sensitive ultra high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS method for the simultaneous determination of six anti-diabetic ingredients (cynaroside, quercetin, luteolin, isorhamnetin, rutin and formononetin of Maydis stigma in rat plasma has been developed and validated in plasma samples, which showed good linearity over a wide concentration range (r2 > 0.99, and gave a lower limit of quantification of 1.0 ng·mL−1 for the analytes. The intra- and interday assay variability was less than 15% for all analytes. The mean extraction recoveries and matrix effect of analytes and IS from rats plasma were all more than 85.0%. The stability results showed the measured concentration for six analytes at three QC levels deviated within 15.0%. The results indicated that significant differences in the pharmacokinetic parameters of the analytes were observed between the two groups of animals, whereby the absorptions of these analytes in the diabetic group were all significantly higher than those in the normal group, which provides an experimental basis for the role of Maydis stigma in anti-diabetic treatment.

  2. Comparative radioprotective studies of chlorpromazine and cysteamine on rat bone development; Effect on serum and bone proteins

    Energy Technology Data Exchange (ETDEWEB)

    Abdeen, A M; Ibrahim, H A; Badawy, M; Elkholy, W M.E.

    1986-01-01

    Experiments were planned to study the radioprotective effect of chlorpromazine (CPZ) and Cysteamine (Cys), when injected separately or combined before irradiation, on some factors affecting the development of rat bone. The results obtained can be summarized as follows: (1) The body weight decreased due to gamma-irradiation. (2) The mortality rate increased after irradiation, but diminished by single or double chemical injection before irradiation. (3) The serum total protein; albumin, globulin contents and A/G ratio were significantly increased, 6 hrs. After irradiation, then declined afterwards. (4) Histochemically, a decrease in bone protein content was demonstrates after irradiation. The above irradiation effects were suppressed by injection of the radioprotective substances. Their effect seems to be cumulative. 4 fig.,3 tab.

  3. Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development

    International Nuclear Information System (INIS)

    Sinha, Rohit Anthony; Pathak, Amrita; Mohan, Vishwa; Babu, Satish; Pal, Amit; Khare, Drirh; Godbole, Madan M.

    2010-01-01

    Hypothyroidism during early mammalian brain development is associated with decreased expression of various mitochondrial encoded genes along with evidence for mitochondrial dysfunction. However, in-spite of the similarities between neurological disorders caused by perinatal hypothyroidism and those caused by various genetic mitochondrial defects we still do not know as to how thyroid hormone (TH) regulates mitochondrial transcription during development and whether this regulation by TH is nuclear mediated or through mitochondrial TH receptors? We here in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1α, NRF-1α and Tfam. Also, we for the first time demonstrate a mitochondrial localization of thyroid hormone receptor (mTR) isoform in developing brain capable of binding a TH response element (DR2) present in D-loop region of mitochondrial DNA. These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development.

  4. Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development

    Energy Technology Data Exchange (ETDEWEB)

    Sinha, Rohit Anthony; Pathak, Amrita; Mohan, Vishwa; Babu, Satish; Pal, Amit; Khare, Drirh [Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014 (India); Godbole, Madan M., E-mail: madangodbole@yahoo.co.in [Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014 (India)

    2010-07-02

    Hypothyroidism during early mammalian brain development is associated with decreased expression of various mitochondrial encoded genes along with evidence for mitochondrial dysfunction. However, in-spite of the similarities between neurological disorders caused by perinatal hypothyroidism and those caused by various genetic mitochondrial defects we still do not know as to how thyroid hormone (TH) regulates mitochondrial transcription during development and whether this regulation by TH is nuclear mediated or through mitochondrial TH receptors? We here in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1{alpha}, NRF-1{alpha} and Tfam. Also, we for the first time demonstrate a mitochondrial localization of thyroid hormone receptor (mTR) isoform in developing brain capable of binding a TH response element (DR2) present in D-loop region of mitochondrial DNA. These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development.

  5. Expression and clinical significance of the HIF-1a/ET-2 signaling pathway during the development and treatment of polycystic ovary syndrome.

    Science.gov (United States)

    Wang, Fan; Zhang, Zhenghong; Wang, Zhaokai; Xiao, Kaizhuan; Wang, Qing; Su, Jingqian; Wang, Zhengchao

    2015-04-01

    Polycystic ovary syndrome (PCOS) is a major health problem in reproductive-aged women worldwide, but the precise pathogenesis of PCOS remains unclear. Our previous study revealed that hypoxia-inducible factor (HIF)-1a mediated endothelin (ET)-2 signaling plays an important role in ovulation in rats. Therefore, the present study used a PCOS rat model to test the hypotheses that HIF-1a signaling is expressed and inhibited in ovaries during PCOS formation and that the HIF-1a/ET-2 signaling pathway is a target of dimethyldiguanide (DMBG) in the clinical treatment of PCOS. First, the development of a PCOS model and the effect of DMBG treatment were examined through ovarian histology and serum hormone levels, which were consistent with previous reports. Second, HIF-1a and ET-2 expression were detected by immunohistochemistry and western blot. The results showed decreased HIF-1a/ET-2 expression in the ovaries of PCOS rats, whereas DMBG treatment reversed the protein decreases and improved the PCOS symptoms. Third, to understand the molecular mechanism, HIF-1a/ET-2 mRNA expression was also examined. Interestingly, HIF-1a mRNA increased in the ovaries of PCOS rats, while ET-2 mRNA decreased, indicating that HIF-1a protein degradation may be involved in POCS development and treatment. Finally, HIF prolyl hydroxylase (PHD) activity was examined to further clarify the contribution of HIF-1a signaling to the development and treatment of PCOS. The results suggested that the inhibition of HIF-1a/ET-2 signaling may be caused by increased PHD activity in PCOS. DMBG-treated PCOS may further activate HIF-1a signaling at least partly through inhibiting PHD activity. Taken together, these results indicate that HIF-1a signaling is inhibited in a PCOS rat model through increasing PHD activity. DMBG treatment improved PCOS by rescuing this pathway, suggesting that HIF-1a signaling plays an important role in the development and treatment of PCOS. This HIF-1a-mediated ET-2 signaling pathway

  6. Physiological properties of afferents to the rat cerebellum during normal development and after postnatal x irradiation

    International Nuclear Information System (INIS)

    Puro, D.G.

    1975-01-01

    The consequences of an altered cerebellar cortical development on afferent transmission and terminal organization were analyzed in adult rats which had received x irradiation to the cerebellum postnatally. Rats, anesthetized with 0.5 percent halothane, were studied in various ages from day 3 to adult. The ascending mossy and climbing fiber systems were activated by electrical stimulation of the limbs with needle electrodes. Stimulation of the motor cortex activated the descending climbing fiber pathways. Extracellular responses from cerebellar Purkinje cells were observed on an oscilloscope as poststimulus time histograms were constructed ''on-line''. Conclusions and assertions include: (1) Synaptogenesis between incoming afferent fibers and target neurons takes place early in cerebellar cortical development. (2) Mossy fiber transmission is mature before the bulk of cerebellar synaptogenesis occurs. (3) The ascending and descending components of the climbing fiber system mature, with respect to latency, in synchrony. (4) The terminal synaptic organization has little effect on the development of transmission characteristics in these afferent systems. (5) One possible mechanism by which an adult neural structure can have an abnormal synaptic organization is to maintain immature synaptic relationships due to the neonatal loss of interneurons

  7. Promoting Effects of Milk on the Development of 7,12-dimethylbenz(a)anthracene (DMBA)-induced Mammary Tumors in Rats

    International Nuclear Information System (INIS)

    Ma, De-Fu; Katoh, Ryohei; Zhou, Hong; Wang, Pei-Yu

    2007-01-01

    To assess the effect of milk on the development of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors, 48 female Sprague-Dawley rats treated with DMBA were divided into 3 groups and given 1 of 3 test solutions for 20 weeks as their drinking liquid: milk, estrone sulfate solution or tap water. The milk group showed a significantly great incidence (75%) in tumor development compared with the water group (38%) and was comparable to the estrone sulfate group (69%). Mean tumor number per rat in the milk group was significantly higher than that in the water group (p=0.009). We classified the mammary tumors into three histological types: intraductal papilloma, fibroadenoma, and adenocarcinoma. Although the percent of intraductal papilloma and fibroadenoma was almost same among the three groups, malignant tumor was found only in the milk and estrone sulfate groups. In conclusion, our results indicate that milk as well as estrone sulfate promotes the development of DMBA-induced mammary tumors in rat and could be associated with the occurrence of adenocarcinoma

  8. Relative accretion of /sup 99m/Tc-polyphosphate by forming and resorbing bone systems in rats: its significance in the pathologic basis of bone scanning

    International Nuclear Information System (INIS)

    Garcia, D.A.; Tow, D.E.; Kapur, K.K.; Wells, H.

    1976-01-01

    The relative roles of osteogenesis and osteolysis in the production of positive radionuclide images of skeletal lesions were investigated. The uptake of /sup 99m/Tc-polyphosphate (Tc-PP) by each process was measured in an animal model that permitted bone formation and resorption to be studied independently. Ten rats received intramuscular implants of bone-forming demineralized matrix (DM) and resorbing devitalized bone (DV). Radiographs and Tc-PP scintiscans were made each week thereafter. At 6 to 10 weeks, the implants and normal bone samples were removed, counted for /sup 99m/Tc, and examined histologically. The uptake of Tc-PP by DM implants was first detected on images made 3 weeks after implantation, and by DV implants, 1 to 2 weeks later. Serial radiography showed progressive calcification of DM and resorption of DV implants. Microscopic examinations of undecalcified sections, stained with a modified Goldner preparation, revealed vital-bone formation in the DM implants and osteoclastic resorption in the DV. Activity counts per gram of DM and DV implants were, respectively, 200 percent and 90 percent that of normal bone. Since only the bone-forming system (DM) accumulated Tc-PP at greater than normal concentrations, this study indicates that positive bone images of osteolytic lesions solely reflect compensatory osteogenic responses

  9. Immunologic differentiation of two high-affinity neurotensin receptor isoforms in the developing rat brain.

    Science.gov (United States)

    Boudin, H; Lazaroff, B; Bachelet, C M; Pélaprat, D; Rostène, W; Beaudet, A

    2000-09-11

    Earlier studies have demonstrated overexpression of NT1 neurotensin receptors in rat brain during the first 2 weeks of life. To gain insight into this phenomenon, we investigated the identity and distribution of NT1 receptor proteins in the brain of 10-day-old rats by using two different NT1 antibodies: one (Abi3) directed against the third intracellular loop and the other (Abi4) against the C-terminus of the receptor. Immunoblot experiments that used Abi3 revealed the presence of two differentially glycosylated forms of the NT1 receptor in developing rat brain: one migrating at 54 and the other at 52 kDa. Whereas the 54-kDa form was expressed from birth to adulthood, the 52-kDa form was detected only at 10 and 15 days postnatal. Only the 52-kDa isoform was recognized by Abi4. By immunohistochemistry, both forms of the receptor were found to be predominantly expressed in cerebral cortex and dorsal hippocampus, in keeping with earlier radioligand binding and in situ hybridization data. However, whereas Abi4 immunoreactivity was mainly concentrated within nerve cell bodies and extensively colocalized with the Golgi marker alpha-mannosidase II, Abi3 immunoreactivity was predominantly located along neuronal processes. These results suggest that the transitorily expressed 52-kDa protein corresponds to an immature, incompletely glycosylated and largely intracellular form of the NT1 receptor and that the 54-kDa protein corresponds to a mature, fully glycosylated, and largely membrane-associated form. They also indicate that antibodies directed against different sequences of G-protein-coupled receptors may yield isoform-specific immunohistochemical labeling patterns in mammalian brain. Finally, the selective expression of the short form of the NT1 receptor early in development suggests that it may play a specific role in the establishment of neuronal circuitry. Copyright 2000 Wiley-Liss, Inc.

  10. Development of a hyperpolarized 129Xe system on 3T for the rat lungs

    International Nuclear Information System (INIS)

    Sato, Hiroshi; Enmi, Jun-ichiro; Hayashi, Takuya

    2004-01-01

    MRI (magnetic resonance imaging) with 129 Xe has gained much attention as a diagnostic methodology because of its affinity for lipids and possible polarization. The quantitative estimation of net detectability and stability of hyperpolarized 129 Xe in the dissolved phase in vivo is valuable to the development of clinical applications. The goal of this study was to develop a stable hyperpolarized 129 Xe experimental 3T system to statistically analyze the dissolved-phase 129 Xe signal in the rat lungs. The polarization of 129 Xe with buffer gases at the optical pumping cell was measured under adiabatic fast passage against the temperature of an oven and laser absorption at the cell. The gases were insuffiated into the lungs of Sprague-Dawley rats (n=15, 400-550 g) through an endotracheal tube under spontaneous respiration. Frequency-selective spectroscopy was performed for the gas phase and dissolved phase. We analyzed the 129 Xe signal in the dissolved phase to measure the chemical shift, T 2 * , delay and its ratio in a rat lungs on 3T. The polarizer was able to produce polarized gas (1.1±0.47%, 120 cm 3 ) hundreds of times with the laser absorption ratio (25%) kept constant at the cell. The optimal buffer gas ratio of 25-50% rendered the maximum signal in the dissolved phase. Two dominant peaks of 211.8±0.9 and 201.1±0.6 ppm were observed with a delay of 0.4±0.9 and 0.9±1.0 s from the gas phase spectra. The ratios of their average signal to that of the gas phase were 5.6±5.2% and 4.4±4.7%, respectively. The T 2 * of the air space in the lungs was 2.5±0.5 ms, which was 3.8 times shorter than that in a syringe. We developed a hyperpolarized 129 Xe experimental system using a 3T MRI scanner that yields sufficient volume and polarization and quantitatively analyzed the dissolved-phase 129 Xe signal in the rat lungs. (author)

  11. Electroacupuncture Delays Hypertension Development through Enhancing NO/NOS Activity in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Hye Suk Hwang

    2011-01-01

    Full Text Available Using spontaneously hypertensive rats (SHR, this study investigated whether electroacupuncture (EA could reduce early stage hypertension by examining nitric oxide (NO levels in plasma and nitric oxide synthase (NOS levels in the mesenteric resistance artery. EA was applied to the acupuncture point Governor Vessel 20 (GV20 or to a non-acupuncture point in the tail twice weekly for 3 weeks under anesthesia. In conscious SHR and normotensive Wistar Kyoto (WKY rats, blood pressure was determined the day after EA treatment by the tail-cuff method. We measured plasma NO concentration, and evaluated endothelial NO syntheses (eNOS and neuronal NOS (nNOS protein expression in the mesenteric artery. Systolic blood pressure (SBP and diastolic blood pressure (DBP were lower after 3 weeks of GV20 treatment than EA at non-acupuncture point and no treatment control in SHR. nNOS expression by EA was significantly different between both WKY and no treatment SHR control, and EA at GV20 in SHR. eNOS expression was significantly high in EA at GV 20 compared with no treatment control. In conclusion, EA could attenuate the blood pressure elevation of SHR, along with enhancing NO/NOS activity in the mesenteric artery in SHR.

  12. Development of Lecithin Nanoemulsion Based Organogels for Permeation Enhancement of Metoprolol through Rat Skin

    Directory of Open Access Journals (Sweden)

    J. Varshosaz

    2013-01-01

    Full Text Available Background. Drugs with low oral bioavailability due to the first pass metabolism are good candidates for transdermal delivery. Objectives. The aim of this work was preparation of transdermal nanoemulsion of metoprolol which has high first pass metabolism. Methods. Three commercially available types of lecithin (200, 100p, and 170, three short chain alcohol (n-butanol, isopropyl alcohol, and n-propanol, and isopropyl myristate (IPM were used as surfactant, cosurfactant, and oil phase, respectively. The aqueous phase was composed of metoprolol tartrate. Nanoemulsions with different surfactant/cosurfactant weight ratio, various amounts of drug, and different types of alcohol were prepared, and their phase diagrams were studied. Drug release, permeability, and diffusion coefficient of the drug were studied using hairless rat skin. Results. A significant increase in drug solution rate was observed with increasing the metoprolol content in the nanoemulsions, while it decreased when lecithin concentration increased from 40% to 60%. Increasing the water content resulted in a significant increase in metoprolol release. N-butanol enhanced the drug flux from nanoemulsions more than n-propanol and isopropyl alcohol. The o/w nanoemulsions of metoprolol showed high flux and permeability through the skin. Conclusion. Both w/o and o/w nanoemulsions of metoprolol could enhance permeation and diffusion of metoprolol through rat skin.

  13. Postnatal development of resistance to short-term high-dose toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in TCDD-resistant and -semiresistant rats

    International Nuclear Information System (INIS)

    Simanainen, Ulla; Tuomisto, Jouni T.; Pohjanvirta, Raimo; Syrjaelae, Paula; Tuomisto, Jouko; Viluksela, Matti

    2004-01-01

    Despite great interspecies differences in adult 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) sensitivity, the toxic potency of TCDD is similar across species in fetal mortality. Han/Wistar (Kuopio; H/W) rats are exceptionally resistant to acute toxicity of TCDD, but show sensitivity to embryotoxicity and teratogenicity. The resistance of adult H/W rats to acute TCDD toxicity is based on a point mutation in the transactivation domain of the aryl hydrocarbon receptor (AHR) and to an unknown gene ''B''. This study investigated the time course of postnatal development of resistance to TCDD and the significance of genotypic variation in resistance development. H/W, line A (a new line with the H/W-type mutated AHR), and line B rats (a line with normal AHR but moderately resistant because of gene ''B'') were exposed to a single dose of TCDD 2-56 days after birth. H/W and line A rats received 1000 μg/kg; male and female B rats received 200 and 100 μg/kg, respectively. Survival was monitored for 42 days. Interestingly, although TCDD ceased growth and weight gain in all TCDD groups, the younger dosed animals did not seem to reach the body weight of the older dosed animals even in 100 days. The survival results after 42 days showed that line A rats are fairly resistant to TCDD immediately after birth, and their full TCDD resistance develops during the first week of life. The moderate resistance of line B rats develops approximately at the time of weaning. This difference in the time course of resistance development suggests that there are basic differences in pathways mediating resistance in lines A and B rats

  14. Embryonic skeleton development and neonatal learning and memory ability of rats anesthetized with pentobarbital sodium: Differences of administration occasion and time

    Institute of Scientific and Technical Information of China (English)

    Changling Peng; Yuhua Zhu; Ankang Hu; Xiaorong Zhu

    2006-01-01

    through electric mare method. Determine their study ability according to their correct rate of 90% or above of arrival at the safe area in 20 s. After they finally learned to arrive at the safe area correctly, test them once more in 24 hours and record the correct rate of 15 times.MAIN OUTCOME MEASURES: The rate of malformation in fetus and ability of learning and memory in one-month rats.RESULTS: A total of 80 female rats were anesthetized in this experiment. Totally 490 immature rats were tested with maze testing machine and 196 fetuses were stained with alizarin red S to observe the development of their skeleton. However, one of the 80 female rats was led to death because of overdose. ① Malformation experiment: Learning ability of second anesthesia group was evidently different from the control group while the other two groups were not in the electric mare method. The fetal skeleton malformation rate of three experimental groups was 87.0%, 60.9% and 17.9%, respectively, while it was 5.6% in the control group. ②Electric mare method: Times of rats which arrived at the safe regions were respectively 49.0±31.0, 68.0±35.0,47.0±31.0 and 44.0±21.0 in early anesthesia group, second anesthesia group, late anesthesia group and control group; and then, there was significant difference between the second anesthesia group and the control group (P < 0.05). Exact rates of memory of rats were respectively (64.36±14.35)%, (62.15±18.33)%, (54.19±12.28)% and (68.24±15.91)% in early anesthesia group, second anesthesia group, late anesthesia group and control group; and then, there were no significant differences as compared with the control group (P> 0.05).CONCLUSION: The influence of anesthesia with pentobarbital sodium is obvious in fetal skeleton development and learning and memory ability.

  15. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies.

    Science.gov (United States)

    Korde, Neha; Kristinsson, Sigurdur Y; Landgren, Ola

    2011-05-26

    Monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic plasma cell dyscrasias, with a propensity to progress to symptomatic MM. In recent years there have been improvements in risk stratification models (involving molecular markers) of both disorders, which have led to better understanding of the biology and probability of progression of MGUS and SMM. In the context of numerous molecular events and heterogeneous risk of progression, developing individualized risk profiles for patients with MGUS and SMM represents an ongoing challenge that has to be addressed by prospective clinical monitoring and extensive correlative science. In this review we discuss the current standard of care of patients with MGUS and SMM, the use of risk models, including flow cytometry and free-light chain analyses, for predicting risk of progression. Emerging evidence from molecular studies on MGUS and SMM, involving cytogenetics, gene-expression profiling, and microRNA as well as molecular imaging is described. Finally, future directions for improving individualized management of MGUS and SMM patients, as well as the potential for developing early treatment strategies designed to delay and prevent development of MM are discussed.

  16. Low endogenous glucocorticoid allows induction of kidney cortical cyclooxygenase-2 during postnatal rat development

    DEFF Research Database (Denmark)

    Madsen, Kirsten; Stubbe, Jane; Skøtt, Ole

    2004-01-01

    COX-2 in these cells. Thus low plasma concentrations of corticosterone allowed for cortical and medullary COX-2 induction during postnatal kidney development. Increased circulating glucocorticoid in the postnatal period may damage late renal development through inhibition of COX-2.......In postnatal weeks 2-4, cyclooxygenase-2 (COX-2) is induced in the rat kidney cortex where it is critically involved in final stages of kidney development. We examined whether changes in circulating gluco- or mineralocorticosteroids or in their renal receptors regulate postnatal COX-2 induction....... Plasma corticosterone concentration peaked at birth, decreased to low levels at days 3-13, and increased to adult levels from day 22. Aldosterone peaked at birth and then stabilized at adult levels. Gluco- and mineralocorticoid receptor (GR and MR) mRNAs were expressed stably in kidney before, during...

  17. Low level prenatal exposure to methylmercury disrupts neuronal migration in the developing rat cerebral cortex

    International Nuclear Information System (INIS)

    Guo, Bao-Qiang; Yan, Chong-Huai; Cai, Shi-Zhong; Yuan, Xiao-Bing; Shen, Xiao-Ming

    2013-01-01

    Highlights: ► Low level MeHg exposure causes migratory defect of rat cerebrocortical neurons. ► The migration defect is due to the impact of MeHg on the neuronal migration itself. ► Rho GTPases seem to be involved in MeHg-induced disruption of neuronal migration. -- Abstract: We determined the effects of low-level prenatal MeHg exposure on neuronal migration in the developing rat cerebral cortex using in utero electroporation. We used offspring rats born to dams that had been exposed to saline or various doses of MeHg (0.01 mg/kg/day, 0.1 mg/kg/day, and 1 mg/kg/day) from gestational day (GD) 11–21. Immunohistochemical examination of the brains of the offspring was conducted on postnatal day (PND) 0, PND3, and PND7. Our results showed that prenatal exposure to low levels of MeHg (0.1 mg/kg/day or 1 mg/kg/day) during the critical stage in neuronal migration resulted in migration defects of the cerebrocortical neurons in offspring rats. Importantly, our data revealed that the abnormal neuronal distribution induced by MeHg was not caused by altered proliferation of neural progenitor cells (NPCs), induction of apoptosis of NPCs and/or newborn neurons, abnormal differentiation of NPCs, and the morphological changes of radial glial scaffold, indicating that the defective neuronal positioning triggered by exposure to low-dose of MeHg is due to the impacts of MeHg on the process of neuronal migration itself. Moreover, we demonstrated that in utero exposure to low-level MeHg suppresses the expression of Rac1, Cdc42, and RhoA, which play key roles in the migration of cerebrocortical neurons during the early stage of brain development, suggesting that the MeHg-induced migratory disturbance of cerebrocortical neurons is likely associated with the Rho GTPases signal pathway. In conclusion, our results provide a novel perspective on clarifying the mechanisms underlying the impairment of neuronal migration induced by MeHg

  18. Brain manganese, catecholamine turnover, and the development of startle in rats prenatally exposed to manganese

    International Nuclear Information System (INIS)

    Kontur, P.J.; Fechter, L.D.

    1985-01-01

    Manganese (Mn) can be neurotoxic when present in high concentrations. Neonatal animals show differential absorption, accumulation, and excretion of Mn relative to adults. If similar kinetic differences exist during gestation, then fetal animals may be susceptible to Mn neurotoxicity. The objective of this study was to examine maternal-fetal Mn transfer and the susceptibility of prenatal animals to Mn neurotoxicity. This was approached by studying the ability of Mn to cross the placenta and reach the fetal central nervous system using radiotracer and atomic absorption spectroscopy techniques. Manganese is thought to disrupt catecholamine neurotransmission in the central nervous system. This was examined in newborn rats by alpha-methyl-para-tyrosine induced catecholamine turnover and the development of the acoustic startle response. The results suggest that there are limits on fetal Mn accumulation under conditions of both normal and excessive dietary Mn levels. Manganese accumulation in the fetal brain after exposure to increased dietary Mn does not alter either dopamine or norepinephrine turnover or the development of the acoustic startle response. Excess Mn does not appear to be neurotoxic to fetal rats in spite of its limited accumulation in nervous tissue after gestational exposure

  19. Development of a Physiologically-Based Pharmacokinetic Model of the Rat Central Nervous System

    Directory of Open Access Journals (Sweden)

    Raj K. Singh Badhan

    2014-03-01

    Full Text Available Central nervous system (CNS drug disposition is dictated by a drug’s physicochemical properties and its ability to permeate physiological barriers. The blood–brain barrier (BBB, blood-cerebrospinal fluid barrier and centrally located drug transporter proteins influence drug disposition within the central nervous system. Attainment of adequate brain-to-plasma and cerebrospinal fluid-to-plasma partitioning is important in determining the efficacy of centrally acting therapeutics. We have developed a physiologically-based pharmacokinetic model of the rat CNS which incorporates brain interstitial fluid (ISF, choroidal epithelial and total cerebrospinal fluid (CSF compartments and accurately predicts CNS pharmacokinetics. The model yielded reasonable predictions of unbound brain-to-plasma partition ratio (Kpuu,brain and CSF:plasma ratio (CSF:Plasmau using a series of in vitro permeability and unbound fraction parameters. When using in vitro permeability data obtained from L-mdr1a cells to estimate rat in vivo permeability, the model successfully predicted, to within 4-fold, Kpuu,brain and CSF:Plasmau for 81.5% of compounds simulated. The model presented allows for simultaneous simulation and analysis of both brain biophase and CSF to accurately predict CNS pharmacokinetics from preclinical drug parameters routinely available during discovery and development pathways.

  20. Perinatal methadone exposure produces physical dependence and altered behavioral development in the rat.

    Science.gov (United States)

    Kunko, P M; Smith, J A; Wallace, M J; Maher, J R; Saady, J J; Robinson, S E

    1996-06-01

    Pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that the following prenatal/postnatal exposure groups were obtained: water/water, methadone/water, water/methadone and methadone/methadone. Methadone slightly reduced litter size, particularly the number of male offspring, and reduced litter birth weight. The induction or maintenance of physical dependence in the postnatal methadone exposure groups was confirmed by an experiment in which PD19 pups were challenged with naloxone (1 mg/kg, s.c.). Methadone concentrations were assayed in pup brain on postnatal days 4, 10 and 22. Postnatal exposure to methadone via maternal milk produced measurable levels of methadone which decreased with age. Neuromuscular and physical development were assessed. Exposure to methadone accelerated acquisition of the righting reflex, but tended to delay the acquisition of the negative geotaxic response. Postnatal exposure to methadone was associated with decreased somatic growth as measured through postnatal day 21. The older pups (postnatal day 21) exposed to methadone exhibited variations in activity levels: pups exposed to methadone both prenatally and postnatally exhibited the least amount of spontaneous locomotor activity and pups exposed only postnatally exhibited the most activity. Therefore, it is possible to induce and/or maintain physical dependence via lactation in rat pups fostered to methadone-treated dams. Perinatal exposure to methadone by this route produces several subtle disruptions of pup development in the absence of gross maternal or fetal toxicity.

  1. Hip dysplasia: a significant risk factor for the development of hip osteoarthritis. A cross-sectional survey

    DEFF Research Database (Denmark)

    Jacobsen, Steffen; Sonne-Holm, Stig

    2005-01-01

    joint space width (JSW) /=60 yr of age. Of factors entered into logistic regression analyses, only age (P LT 0.001 for right hips and P LT 0.001 for left hips) and hip dysplasia (P LT 0.001 for right hips and P = 0.004 for left hips) were significantly associated with hip OA prevalence in women. In men......, only hip dysplasia was associated with hip OA prevalence, P LT 0.001 in right hips and P = 0.001 in left hips. CONCLUSIONS: Of the individual risk factors investigated in this study, only age and hip dysplasia were associated with the development of hip osteoarthritis.......OBJECTIVES: The aim of this cross-sectional survey of 2232 women and 1336 men (age range 20-91 yr) was to investigate individual risk factors for hip joint osteoarthritis (OA). METHODS: Standardized, weight-bearing pelvic radiographs were evaluated. Radiological hip joint OA was defined as minimum...

  2. Effect of environmental temperature on radioiodine uptake by the thyroid gland of rats during ontogenetic development

    International Nuclear Information System (INIS)

    Samel, M.

    1975-01-01

    Radioiodine uptake by the thyroid gland of young rats, aged 1 to 30 days, was studied at nest temperature (35degC) and at the temperature of the animal room (24degC). In animals younger than two weeks 131 I uptake was significantly lower at 24degC than at nest temperature. In older animals, these temperature differences did not result in significantly different uptake values. It is suggested that short-term cold does not activate the pituitary-thyroid gland axis in younger animals with unstable body temperature, and that functional changes in the circulatory system might be responsible for the differences observed in 131 I uptake. (author)

  3. Development of free statistical software enabling researchers to calculate confidence levels, clinical significance curves and risk-benefit contours

    International Nuclear Information System (INIS)

    Shakespeare, T.P.; Mukherjee, R.K.; Gebski, V.J.

    2003-01-01

    Confidence levels, clinical significance curves, and risk-benefit contours are tools improving analysis of clinical studies and minimizing misinterpretation of published results, however no software has been available for their calculation. The objective was to develop software to help clinicians utilize these tools. Excel 2000 spreadsheets were designed using only built-in functions, without macros. The workbook was protected and encrypted so that users can modify only input cells. The workbook has 4 spreadsheets for use in studies comparing two patient groups. Sheet 1 comprises instructions and graphic examples for use. Sheet 2 allows the user to input the main study results (e.g. survival rates) into a 2-by-2 table. Confidence intervals (95%), p-value and the confidence level for Treatment A being better than Treatment B are automatically generated. An additional input cell allows the user to determine the confidence associated with a specified level of benefit. For example if the user wishes to know the confidence that Treatment A is at least 10% better than B, 10% is entered. Sheet 2 automatically displays clinical significance curves, graphically illustrating confidence levels for all possible benefits of one treatment over the other. Sheet 3 allows input of toxicity data, and calculates the confidence that one treatment is more toxic than the other. It also determines the confidence that the relative toxicity of the most effective arm does not exceed user-defined tolerability. Sheet 4 automatically calculates risk-benefit contours, displaying the confidence associated with a specified scenario of minimum benefit and maximum risk of one treatment arm over the other. The spreadsheet is freely downloadable at www.ontumor.com/professional/statistics.htm A simple, self-explanatory, freely available spreadsheet calculator was developed using Excel 2000. The incorporated decision-making tools can be used for data analysis and improve the reporting of results of any

  4. Effects of prenatal X-irradiation on postnatal testicular development and function in the Wistar rat: development/teratology/behavior/radiation

    International Nuclear Information System (INIS)

    Jensh, R.P.; Brent, R.L.

    1988-01-01

    It is evident that significant permanent tissue hypoplasia can be produced following radiation exposure late in fetal development. Because two organs, brain and testes, are developmentally and functionally interrelated, it was of interest to determine whether fetal testicular hypoplasia was a primary or a secondary effect of fetal brain irradiation. Twenty-four pregnant Wistar strain rats were randomly assigned to one of four groups, and a laparotomy was performed on day 18 of gestation. The fetuses received sham irradiation, whole body irradiation, or only head/thorax or pelvic body irradiation at a dosage level of 1.5 Gy. Mothers were allowed to deliver and raise their offspring until postnatal day 30, when the offspring were weaned. At 60 days of age, 74 male offspring were allowed to mate with colony control females of similar age until successful insemination or until the males reached 90 days of age, when they were killed. Testes were weighed and processed for histologic examination. Direct radiation of testes, due to whole body or pelvic exposure, resulted in testicular growth retardation and significantly reduced spermatogenesis. Breeding activity of the males and the percent of positive inseminations were also slightly reduced. However, a significant percentage of male offspring receiving direct testicular radiation did produce offspring. Head/thorax-only irradiation did not adversely affect testicular growth or spermatogenesis. Therefore, the use of histologic analysis as the sole determinant of infertility may be misleading. This study indicates that testicular growth retardation and an increased infertility rate result from direct prenatal exposure of rat testes to X-radiation and are not necessarily mediated via X-irradiation effects on the central nervous system

  5. Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina

    Energy Technology Data Exchange (ETDEWEB)

    Rai, Nagendra Kumar; Ashok, Anushruti [Academy of Scientific and Innovative Research (India); Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India); Rai, Asit; Tripathi, Sachin [Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India); Nagar, Geet Kumar [Endocrinology, CSIR-Central Drug Research Institute (CSIR-CDRI) (India); Mitra, Kalyan [Electron Microscopy Unit, CSIR-CDRI, Lucknow 226001 (India); Bandyopadhyay, Sanghamitra, E-mail: sanghmitra@iitr.res.in [Academy of Scientific and Innovative Research (India); Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India)

    2013-12-01

    Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2′-, 3′-cyclic-nucleotide-3′-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology. - Highlights: • As, Cd and Pb-mixture, at human relevant dose, demyelinate developing rat CNS. • The attenuation in myelin and axon is synergistic. • The optic nerve and brain demonstrate reduced glutamine synthetase.

  6. Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina

    International Nuclear Information System (INIS)

    Rai, Nagendra Kumar; Ashok, Anushruti; Rai, Asit; Tripathi, Sachin; Nagar, Geet Kumar; Mitra, Kalyan; Bandyopadhyay, Sanghamitra

    2013-01-01

    Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2′-, 3′-cyclic-nucleotide-3′-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology. - Highlights: • As, Cd and Pb-mixture, at human relevant dose, demyelinate developing rat CNS. • The attenuation in myelin and axon is synergistic. • The optic nerve and brain demonstrate reduced glutamine synthetase.

  7. Long-Term Low Intensity Physical Exercise Attenuates Heart Failure Development in Aging Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Luana U. Pagan

    2015-04-01

    Full Text Available Background: Physical exercise is a strategy to control hypertension and attenuate pressure overload-induced cardiac remodeling. The influence of exercise on cardiac remodeling during uncontrolled hypertension is not established. We evaluated the effects of a long-term low intensity aerobic exercise protocol on heart failure (HF development and cardiac remodeling in aging spontaneously hypertensive rats (SHR. Methods: Sixteen month old SHR (n=50 and normotensive Wistar-Kyoto (WKY, n=35 rats were divided into sedentary (SED and exercised (EX groups. Rats exercised in treadmill at 12 m/min, 30 min/day, 5 days/week, for four months. The frequency of HF features was evaluated at euthanasia. Statistical analyses: ANOVA and Tukey or Mann-Whitney, and Goodman test. Results: Despite slightly higher systolic blood pressure, SHR-EX had better functional capacity and lower HF frequency than SHR-SED. Echocardiography and tissue Doppler imaging showed no differences between SHR groups. In SHR-EX, however, left ventricular (LV systolic diameter, larger in SHR-SED than WKY-SED, and endocardial fractional shortening, lower in SHR-SED than WKY-SED, had values between those in WKY-EX and SHR-SED not differing from either group. Myocardial function, assessed in LV papillary muscles, showed improvement in SHR-EX over SHR-SED and WKY-EX. LV myocardial collagen fraction and type I and III collagen gene expression were increased in SHR groups. Myocardial hydroxyproline concentration was lower in SHR-EX than SHR-SED. Lysyl oxidase gene expression was higher in SHR-SED than WKY-SED. Conclusion: Exercise improves functional capacity and reduces decompensated HF in aging SHR independent of elevated arterial pressure. Improvement in functional status is combined with attenuation of LV and myocardial dysfunction and fibrosis.

  8. Induction of glutathione S-transferase placental form positive foci in liver and epithelial hyperplasia in urinary bladder, but no tumor development in male Fischer 344 rats treated with monomethylarsonic acid for 104 weeks

    International Nuclear Information System (INIS)

    Shen Jun; Wanibuchi, Hideki; Salim, Elsayed I.; Wei Min; Doi, Kenichiro; Yoshida, Kaoru; Endo, Ginji; Morimura,; Fukushima, Shoji

    2003-01-01

    The carcinogenicity of monomethylarsonic acid (MMA(V)), a major metabolite of inorganic arsenics in human and experimental animals, was investigated in male Fischer 344 rats. A total of 129 rats at 10 weeks of age were randomly divided into three groups and received drinking water containing MMA(V) at doses of 0 (Control), 50, and 200 ppm ad libitum for 104 weeks. No significant differences were found between the control and the MMA(V)-treated groups regarding clinical signs, mortality, hematological, and serum biochemistry findings. Quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci in liver revealed a significant increase of numbers and areas in the 200 ppm MMA(V)-treated group. In the urinary bladder MMA(V) induced simple hyperplasia and significantly elevated the proliferating cell nuclear antigen (PCNA)-positive index in the urothelium. A variety of tumors developed in rats of all groups, including the controls, but all were histologically similar to those known to occur spontaneously in F344 rats and there were no significant differences among the groups. Thus, it could be concluded that, under the present experimental conditions, MMA(V) induced lesions in the liver and urinary bladder, but did not cause tumor development in male F344 rats even after 2 years exposure

  9. Normal development of the muscular region of the interventricular septum--I. The significance of the ventricular trabeculations.

    Science.gov (United States)

    Contreras-Ramos, A; Sánchez-Gómez, C; García-Romero, H L; Cimarosti, L O

    2008-10-01

    The structures that participate in normal ventricular septation, and to what extent they do so, are questions not yet clarified. Even less is known about how much each of the embryonic structures contributes to the topography of the mature interventricular septum (IVS). The aim of the present paper is to investigate the significance of ventricular trabeculations in the normal development of the muscular region (the middle and apical thirds) of the IVS and to determine the direction in which it grows during cardiac septation. Anatomical studies and in vivo labelling were carried out in chicken embryo hearts at stage 18HH, tracing the labels up to stage 36HH. We analysed the results by measuring the distance between the labelled structures at the beginning and end of the experiments. We demonstrate that the muscular region of the septum originates by the fusion of the ventricular trabeculations with evidence that during cardiac development, the IVS as well as the ventricular cavities grow in opposite direction to the atria.

  10. Lead nitrate-induced development of hypercholesterolemia in rats: sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis.

    Science.gov (United States)

    Kojima, Misaki; Masui, Toshimitsu; Nemoto, Kiyomitsu; Degawa, Masakuni

    2004-12-01

    Changes in the gene expressions of hepatic enzymes responsible for cholesterol homeostasis were examined during the process of lead nitrate (LN)-induced development of hypercholesterolemia in male rats. Total cholesterol levels in the liver and serum were significantly increased at 3-72 h and 12-72 h, respectively, after LN-treatment (100 micromol/kg, i.v.). Despite the development of hypercholesterolemia, the genes for hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and other enzymes (FPPS, farnesyl diphosphate synthase; SQS, squalene synthase; CYP51, lanosterol 14alpha-demethylase) responsible for cholesterol biosynthesis were activated at 3-24 h and 12-18 h, respectively. On the other hand, the gene expression of cholesterol 7alpha-hydroxylase (CYP7A1), a catabolic enzyme of cholesterol, was remarkably suppressed at 3-72 h. The gene expression levels of cytokines interleukin-1beta (IL-1beta) and TNF-alpha, which activate the HMGR gene and suppress the CYP7A1 gene, were significantly increased at 1-3 h and 3-24 h, respectively. Furthermore, gene activation of SREBP-2, a gene activator of several cholesterogenic enzymes, occurred before the gene activations of FPPS, SQS and CYP51. This is the first report demonstrating sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis in LN-treated male rats. The mechanisms for the altered-gene expressions of hepatic enzymes in LN-treated rats are discussed.

  11. Lung development and postnatal survival for rats exposed in utero to a high-boiling coal liquid

    Energy Technology Data Exchange (ETDEWEB)

    Springer, D.L.; Hackett, P.L.; Miller, R.A.; Buschbom, R.L.

    1986-01-01

    The study reported determines postnatal viability and development of survivors following in utero exposure to Harmarville process solvent (HPS), a wide-boiling-range (150 to > 455/sup 0/C) coal liquid. For this study, 0.74 g kg/sup -1/ of the coal liquid was administered (by intragastric intubation) to rats from 12 to 14 dg. Offspring were evaluated for postnatal survival, growth and lung and thymus weights. Fifty-four percent of the exposed pups and 9% of the control pups died between birth and 3 days postpartum. Of the treated pups that died, 10% (6/5; pups/litters) had cleft palate, 27% (17/9) had small lungs and 33% (21/8) had both cleft palate and small lungs. No gross malformations were observed in the remaining 30% of the dead pups. Microscopic examination of lungs from HPS-treated pups revealed no evident histological abnormalities. Body, lung and thymus weights for treated animals that died were significantly less than those of controls. Surviving exposed pups weighed significantly less than control pups from 0.25 to 21 days postpartum and their thymus weights were also depressed through 21 days postpartum. These data suggest that retarded lung growth during prenatal life as a result of in utero exposure to the coal liquid contributes to a significant portion of the observed neonatal mortality. Furthermore, lung weights of survivors, although significantly lower than control values through 7 days postpartum, appeared to have recovered by 21 days postpartum.

  12. Distribution of radiolabeled L-glutamate and D-aspartate from blood into peripheral tissues in naive rats: Significance for brain neuroprotection

    International Nuclear Information System (INIS)

    Klin, Yael; Zlotnik, Alexander; Boyko, Matthew; Ohayon, Sharon; Shapira, Yoram; Teichberg, Vivian I.

    2010-01-01

    Research highlights: → Blood glutamate has a half-life time of 2-3 min. → Blood glutamate is submitted to rapid decarboxylation. → Blood glutamate and its metabolites are mainly absorbed in skeletal muscle and liver. → The skeletal muscle and liver are now targets for potential drugs affording brain neuroprotection. -- Abstract: Excess L-glutamate (glutamate) levels in brain interstitial and cerebrospinal fluids (ISF and CSF, respectively) are the hallmark of several neurodegenerative conditions such as stroke, traumatic brain injury or amyotrophic lateral sclerosis. Its removal could prevent the glutamate excitotoxicity that causes long-lasting neurological deficits. As in previous studies, we have established the role of blood glutamate levels in brain neuroprotection, we have now investigated the contribution of the peripheral organs to the homeostasis of glutamate in blood. We have administered naive rats with intravenous injections of either L-[1- 14 C] Glutamic acid (L-[1- 14 C] Glu), L-[G- 3 H] Glutamic acid (L-[G- 3 H] Glu) or D-[2,3- 3 H] Aspartic acid (D-[2,3- 3 H] Asp), a non-metabolized analog of glutamate, and have followed their distribution into peripheral organs. We have observed that the decay of the radioactivity associated with L-[1- 14 C] Glu and L-[G- 3 H] Glu was faster than that associated with glutamate non-metabolized analog, D-[2,3- 3 H] Asp. L-[1- 14 C] Glu was subjected in blood to a rapid decarboxylation with the loss of 14 CO 2 . The three major sequestrating organs, serving as depots for the eliminated glutamate and/or its metabolites were skeletal muscle, liver and gut, contributing together 92% or 87% of total L-[U- 14 C] Glu or D-[2,3- 3 H] Asp radioactivity capture. L-[U- 14 C] Glu and D-[2,3- 3 H] Asp showed a different organ sequestration pattern. We conclude that glutamate is rapidly eliminated from the blood into peripheral tissues, mainly in non-metabolized form. The liver plays a central role in glutamate metabolism

  13. Distribution of radiolabeled L-glutamate and D-aspartate from blood into peripheral tissues in naive rats: Significance for brain neuroprotection

    Energy Technology Data Exchange (ETDEWEB)

    Klin, Yael [Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100 (Israel); Zlotnik, Alexander; Boyko, Matthew; Ohayon, Sharon; Shapira, Yoram [The Division of Anesthesiology, Soroka Medical Center and Ben Gurion University of the Negev, Beer-Sheva (Israel); Teichberg, Vivian I., E-mail: Vivian.teichberg@weizmann.ac.il [Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100 (Israel)

    2010-09-03

    Research highlights: {yields} Blood glutamate has a half-life time of 2-3 min. {yields} Blood glutamate is submitted to rapid decarboxylation. {yields} Blood glutamate and its metabolites are mainly absorbed in skeletal muscle and liver. {yields} The skeletal muscle and liver are now targets for potential drugs affording brain neuroprotection. -- Abstract: Excess L-glutamate (glutamate) levels in brain interstitial and cerebrospinal fluids (ISF and CSF, respectively) are the hallmark of several neurodegenerative conditions such as stroke, traumatic brain injury or amyotrophic lateral sclerosis. Its removal could prevent the glutamate excitotoxicity that causes long-lasting neurological deficits. As in previous studies, we have established the role of blood glutamate levels in brain neuroprotection, we have now investigated the contribution of the peripheral organs to the homeostasis of glutamate in blood. We have administered naive rats with intravenous injections of either L-[1-{sup 14}C] Glutamic acid (L-[1-{sup 14}C] Glu), L-[G-{sup 3}H] Glutamic acid (L-[G-{sup 3}H] Glu) or D-[2,3-{sup 3}H] Aspartic acid (D-[2,3-{sup 3}H] Asp), a non-metabolized analog of glutamate, and have followed their distribution into peripheral organs. We have observed that the decay of the radioactivity associated with L-[1-{sup 14}C] Glu and L-[G-{sup 3}H] Glu was faster than that associated with glutamate non-metabolized analog, D-[2,3-{sup 3}H] Asp. L-[1-{sup 14}C] Glu was subjected in blood to a rapid decarboxylation with the loss of {sup 14}CO{sub 2}. The three major sequestrating organs, serving as depots for the eliminated glutamate and/or its metabolites were skeletal muscle, liver and gut, contributing together 92% or 87% of total L-[U-{sup 14}C] Glu or D-[2,3-{sup 3}H] Asp radioactivity capture. L-[U-{sup 14}C] Glu and D-[2,3-{sup 3}H] Asp showed a different organ sequestration pattern. We conclude that glutamate is rapidly eliminated from the blood into peripheral tissues

  14. Development and evaluation of polymer nanoparticles for oral delivery of estradiol to rat brain in a model of Alzheimer's pathology.

    Science.gov (United States)

    Mittal, G; Carswell, H; Brett, R; Currie, S; Kumar, M N V Ravi

    2011-03-10

    The purpose of this study was to develop tween 80 (T-80) coated polylactide-co-glycolide (PLGA) nanoparticles that can deliver estradiol to the brain upon oral administration. Estradiol containing nanoparticles were made by a single emulsion technique and T-80 coating was achieved by incubating the re-constituted nanoparticles at different concentrations of T-80. The process of T-80 coating on the nanoparticles was optimized and the pharmacokinetics of estradiol nanoparticles was studied as a function of T-80 coating. The nanoparticles were then evaluated in an ovariectomized (OVX) rat model of Alzheimer's disease (AD) that mimics the postmenopausal conditions. The nanoparticles bound T-80 were found to proportionally increase from 9.72 ± 1.07 mg to 63.84 ± 3.59 mg with an increase in the initial concentration T-80 from 1% to 5% and were stable in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Orally administered T-80 coated nanoparticles resulted in significantly higher brain estradiol levels after 24h (1.969 ± 0.197 ng/g tissue) as compared to uncoated ones (1.105 ± 0.136 ng/g tissue) at a dose of 0.2mg/rat, suggesting a significant role of surface coating. Moreover, these brain estradiol levels were almost similar to those obtained after administration of the same dose of drug suspension via 100% bioavailable intramuscular route (2.123 ± 0.370 ng/g tissue), indicating the increased fraction of bioavailable drug reaching the brain when administered orally. Also, the nanoparticle treated group was successful in preventing the expression of amyloid beta-42 (Aβ42) immunoreactivity in the hippocampus region of brain. Together, the results indicate the potential of nanoparticles for oral delivery of estradiol to brain. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. Reduction of abdominal fat accumulation in rats by 8-week ingestion of a newly developed sweetener made from high fructose corn syrup.

    Science.gov (United States)

    Iida, Tetsuo; Yamada, Takako; Hayashi, Noriko; Okuma, Kazuhiro; Izumori, Ken; Ishii, Reika; Matsuo, Tatsuhiro

    2013-06-01

    Many studies have shown that ingestion of high-fructose corn syrup (HFCS) may cause an increase in body weight and abdominal fat. We recently developed a new sweetener containing rare sugars (rare sugar syrup; RSS) by slight isomerization of HFCS. Here, the functional effects of RSS on body weight and abdominal fat, and biochemical parameters in Wistar rats were examined. Rats (n=30) were randomly divided into three groups and maintained for 8-weeks on starch, starch+HFCS (50:50), and starch+RSS (50:50) diets. Rats in the Starch and HFCS groups gained significantly more body weight and abdominal fat than the RSS group. Fasting serum insulin in the RSS group was significantly lower than in the Starch and HFCS groups, although serum glucose in the HFCS and RSS groups was significantly lower than that in the Starch group. Thus, the substitution of HFCS with RSS prevents obesity induced by the consumption of HFCS. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Effect of hyperbaric oxygen on lipid peroxidation and visual development in neonatal rats with hypoxia-ischemia brain damage.

    Science.gov (United States)

    Chen, Jing; Chen, Yan-Hui; Lv, Hong-Yan; Chen, Li-Ting

    2016-07-01

    The aim of the present study was to investigate the effect of hyperbaric oxygen (HBO) on lipid peroxidation and visual development in a neonatal rat model of hypoxic-ischemic brain damage (HIBD). The rat models of HIBD were established by delayed uterus dissection and were divided randomly into two groups (10 rats each): HIBD and HBO-treated HIBD (HIBD+HBO) group. Another 20 rats that underwent sham-surgery were also divided randomly into the HBO-treated and control groups. The rats that underwent HBO treatment received HBO (0.02 MPa, 1 h/day) 24 h after the surgery and this continued for 14 days. When rats were 4 weeks old, their flash visual evoked potentials (F-VEPs) were monitored and the ultrastructures of the hippocampus were observed under transmission electron microscope. The levels of superoxide dismutase (SOD) and malonyldialdehyde (MDA) in the brain tissue homogenate were detected by xanthine oxidase and the thiobarbituric acid colorimetric method. Compared with the control group, the ultrastructures of the pyramidal neurons in the hippocampal CA3 area were distorted, the latencies of F-VEPs were prolonged (P0.05). HBO enhances antioxidant capacity and reduces the ultrastructural damage induced by hypoxic-ischemia, which may improve synaptic reconstruction and alleviate immature brain damage to promote the habilitation of brain function.

  17. Development of an Assay Based on the Effects of PGBx on the Isolated Perfused Rat Heart and Rat Skeletal Muscle.

    Science.gov (United States)

    1980-09-01

    had no effect on discphe- nol induced alterations in spontaneous heart rate, but did appear to prevent the increase in coronary flow caused by...Phosphorylase a i -24 activity was also the same in each of the groups examined (Table 2-4). DISCUSSION The ability of PGBx to prevent 2,4-dinitrophenol-induced...euthyroid and hyperthyroid rats. Eur. J. Pharmac. 19, 12-17. Aronson, C. E. and Serlick, E. R. (1977a) Effects of chlorpromazine on the isolated

  18. Development and characterization of an effective food allergy model in Brown Norway rats.

    Science.gov (United States)

    Abril-Gil, Mar; Garcia-Just, Alba; Pérez-Cano, Francisco J; Franch, Àngels; Castell, Margarida

    2015-01-01

    Food allergy (FA) is an adverse health effect produced by the exposure to a given food. Currently, there is no optimal animal model of FA for the screening of immunotherapies or for testing the allergenicity of new foods. The aim of the present study was to develop an effective and rapid model of FA in Brown Norway rats. In order to establish biomarkers of FA in rat, we compared the immune response and the anaphylactic shock obtained in this model with those achieved with only intraperitoneal immunization. Rats received an intraperitoneal injection of ovalbumin (OVA) with alum and toxin from Bordetella pertussis, and 14 days later, OVA by oral route daily for three weeks (FA group). A group of rats receiving only the i.p. injection (IP group) were also tested. Serum anti-OVA IgE, IgG1, IgG2a, IgG2b and IgA antibodies were quantified throughout the study. After an oral challenge, body temperature, intestinal permeability, motor activity, and mast cell protease II (RMCP-II) levels were determined. At the end of the study, anti-OVA intestinal IgA, spleen cytokine production, lymphocyte composition of Peyer's patches and mesenteric lymph nodes, and gene expression in the small intestine were quantified. Serum OVA-specific IgG1, IgG2a and IgG2b concentrations rose with the i.p. immunization but were highly augmented after the oral OVA administration. Anti-OVA IgE increased twofold during the first week of oral OVA gavage. The anaphylaxis in both IP and FA groups decreased body temperature and motor activity, whereas intestinal permeability increased. Interestingly, the FA group showed a much higher RMCP II serum protein and intestinal mRNA expression. These results show both an effective and relatively rapid model of FA assessed by means of specific antibody titres and the high production of RMCP-II and its intestinal gene expression.

  19. Development and characterization of an effective food allergy model in Brown Norway rats.

    Directory of Open Access Journals (Sweden)

    Mar Abril-Gil

    Full Text Available Food allergy (FA is an adverse health effect produced by the exposure to a given food. Currently, there is no optimal animal model of FA for the screening of immunotherapies or for testing the allergenicity of new foods.The aim of the present study was to develop an effective and rapid model of FA in Brown Norway rats. In order to establish biomarkers of FA in rat, we compared the immune response and the anaphylactic shock obtained in this model with those achieved with only intraperitoneal immunization.Rats received an intraperitoneal injection of ovalbumin (OVA with alum and toxin from Bordetella pertussis, and 14 days later, OVA by oral route daily for three weeks (FA group. A group of rats receiving only the i.p. injection (IP group were also tested. Serum anti-OVA IgE, IgG1, IgG2a, IgG2b and IgA antibodies were quantified throughout the study. After an oral challenge, body temperature, intestinal permeability, motor activity, and mast cell protease II (RMCP-II levels were determined. At the end of the study, anti-OVA intestinal IgA, spleen cytokine production, lymphocyte composition of Peyer's patches and mesenteric lymph nodes, and gene expression in the small intestine were quantified.Serum OVA-specific IgG1, IgG2a and IgG2b concentrations rose with the i.p. immunization but were highly augmented after the oral OVA administration. Anti-OVA IgE increased twofold during the first week of oral OVA gavage. The anaphylaxis in both IP and FA groups decreased body temperature and motor activity, whereas intestinal permeability increased. Interestingly, the FA group showed a much higher RMCP II serum protein and intestinal mRNA expression.These results show both an effective and relatively rapid model of FA assessed by means of specific antibody titres and the high production of RMCP-II and its intestinal gene expression.

  20. Infectivity and development of X-irradiated third-stage larvae of Angiostrongylus cantonensis in rats

    International Nuclear Information System (INIS)

    Fujiu, Yoshinori

    1989-01-01

    Angiostrongylus cantonensis third-stage larvae were exposed to less than 10Krad of X-radiation and then given orally to white rats to examine the effects of X-radiation on infectivity and development of the irradiated third-stage larvae and on fecundity of adults developing from the irradiated third-stage larvae. The deleterious effects of X-radiation were observed at relatively lower dosage in the above three parameters. A degree in susceptibility on X-radiation was shown to be radiation-dose-dependent. Comparing to the irradiation of larvae in vitro, the irradiation of larvae in snails caused less deleterious effects at the same dose of X-irradiation. Application of X-radiation to food hygiene was also discussed. (author)

  1. Development of spermatic granuloma in albino rats following administration of water extract of Heliotropium bacciferum Forssk.

    Science.gov (United States)

    Alanazi, Khalid; Alahmadi, Bassam A; Alhimaidi, Ahmed; Abou-Tarboush, Faisal M; Farah, Mohammad Abul; Mahmoud, Ahmed; Alfaifi, Mohamed

    2016-01-01

    A spermatic granuloma is a chronic inflammatory reaction produced in response to extravasated sperm within the intertubular connective tissue. The present study investigates the possible toxic effects of water extract of Heliotropium bacciferum on the reproductive system of male albino rats and the associated potential for the development of spermatic granulomas. H. bacciferum is a herbal plant used in traditional medicine and reported to have cytotoxic effects due to pyrrolizidine alkaloids. Histological examinations revealed no changes in the tissues of the testes, although, some changes were detected in the cauda epididymis, the most important of which was the development of small lesions of spermatic granulomas. Clear gaps were observed between the epithelial linings of the epididymal tubules.

  2. [THE STATUS OF CERTAIN PHYSIOLOGICAL ADRENERGIC RESPONSES IN ALBINO RATS DURING DEVELOPMENT OF EXPERIMENTAL HYPERTHYROIDISM].

    Science.gov (United States)

    Osman, Nizar Salim; Ismail, Mohsen

    2015-01-01

    In this paper we investigated the effects of thyroid hormones on the expression of physiological reactions during adrenergic stimulation (20 min at a dose of 2.0 mg x kg(-1) x min(-1)) during the development of experimental hyperthyroidism. Rats were divided into two groups. The animals in Group 1 were injected woth triiodothyronine. The duration of injection ranged from 1 to 12 days. Consequently, 12 subgroups were formed. The second group was the control group. It is shown that in the process of development of experimental hyperthyroidism all physiological responses vary in accordance with the law, which can be described by a parabola of general form with the value of the degree in the equation equal to three.

  3. Relationship between histology, development and tumorigenesis of mammary gland in female rat

    Science.gov (United States)

    LÍŠKA, Ján; BRTKO, Július; DUBOVICKÝ, Michal; MACEJOVÁ, Dana; KISSOVÁ, Viktória; POLÁK, Štefan; UJHÁZY, Eduard

    2015-01-01

    The mammary gland is a dynamic organ that undergoes structural and functional changes associated with growth, reproduction, and post-menopausal regression. The postnatal transformations of the epithelium and stromal cells of the mammary gland may contribute to its susceptibility to carcinogenesis. The increased cancer incidence in mammary glands of humans and similarly of rodents in association with their development is believed to be partly explained by proliferative activity together with lesser degree of differentiation, but it is not completely understood how the virgin gland retains its higher susceptibility to carcinogenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer. An early first full-term pregnancy may have a protective effect. Rodent models are useful for investigating potential breast carcinogens. The purpose of this review is to help recognizing histological appearance of the epithelium and the stroma of the normal mammary gland in rats, and throughout its development in relation to tumorigenic potential. PMID:26424555

  4. Early development influences ontogeny of personality types in young laboratory rats.

    Science.gov (United States)

    Rödel, Heiko G; Meyer, Susann

    2011-09-01

    Features of an individual's early development are frequently reported to alter the postnatal ontogeny in litter-bearing mammals with respect to various physiological parameters. We hypothesized that such effects might also apply to the ontogeny of personality types. On the one hand, litter size effects by means of more contacts with littermates, might lead to the development of more offensive types. On the other hand, smaller and less developed young from larger litters might be less offensive due to their lower physical capabilities to deal with challenging situations. We studied these contrasting hypotheses in young rats, which we tested in a battery of emotionality tests. There were clear indications for the existence of distinct behavioral types by means of consistencies in behavioral responses within and across contexts. Based on these responses, we calculated three new variables by PCA, which we interpreted to mainly reflect boldness, exploration, and anxiety. Overall, our results strongly suggest that the early development alters the ontogeny of personality types, with heavier individuals being bolder and more explorative. Furthermore, body mass and litter size influenced the changes in the behavioral responses in successive tests, further supporting the importance of the litter size-dependent body mass for the ontogeny of personalities. Anxiety also depended on litter size, however, in a nonlinear way. Animals born to litters of small or large sizes had higher scores, whereas individuals from medium-sized litters were less anxious. This optimum curve indicates that opposing effects of litter size are involved in shaping personalities in young rats. Copyright © 2011 Wiley Periodicals, Inc.

  5. Prenatal exposure to a low fipronil dose disturbs maternal behavior and reflex development in rats.

    Science.gov (United States)

    Udo, Mariana S B; Sandini, Thaísa M; Reis, Thiago M; Bernardi, Maria Martha; Spinosa, Helenice S

    2014-01-01

    Fipronil (FPN) is a phenylpyrazole insecticide used in veterinary services and agriculture, and it is of considerable concern to public health. It inhibits the chloride channels associated with gamma-amino butyric acid (GABA) receptors in mammals and also inhibits the chloride channels associated with GABA and glutamate (Glu) receptors in insects. In this study, a commercial product containing fipronil was orally administered to pregnant Wistar rats at dose levels of 0.1, 1.0, or 10.0mg/kg/day from the sixth to twentieth day of gestation (n=10 pregnant rats/group). Its toxicity was evaluated based on maternal toxicity, reproductive quality, maternal behavior, and offspring physical as well as reflex development. All parameters observed in the observed offspring were assigned to one ink-marked couple in each litter (n=20 animals/group - 10 males and 10 females). The offspring couple represented the litter. Slight maternal toxicity presented during the second week of gestation for each fipronil dose and during the third gestational week at the highest dose due to lower chow intake. However, no effects were observed for gestational weight gain or gestation time, and the reproductive quality was not impaired, which suggests no adverse maternal effects from the doses during pregnancy. Moreover, the lowest fipronil dose compromised the active and reflexive maternal responses, but the highest dose induced a stereotyped active response without interfering in the reflexive reaction. For offspring development, no differences in physical growth parameters were observed between the groups. However, considering reflex development, our results showed that negative geotaxis reflex development was delayed in the offspring at the lowest fipronil dose, and palmar grasp was lost earlier at the lowest and intermediate fipronil doses. These results suggest that the alterations observed herein may be due to either the GABAergic system or endocrine disruption, considering that fipronil

  6. Early-life exposure to fibroblast growth factor-2 facilitates context-dependent long-term memory in developing rats.

    Science.gov (United States)

    Graham, Bronwyn M; Richardson, Rick

    2010-06-01

    Fibroblast growth factor-2 (FGF2) is a potent neurotrophic factor that is involved in brain development and the formation of long-term memory. It has recently been shown that acute FGF2, administered at the time of learning, enhances long-term memory for contextual fear conditioning as well as extinction of conditioned fear in developing rats. As other research has shown that administering FGF2 on the first day of life leads to long-term morphological changes in the hippocampus, in the present study we investigated whether early life exposure to FGF2 affects contextual fear conditioning, and renewal following extinction, later in life. Experiment 1 demonstrated that a single injection of FGF2 on Postnatal Day (PND) 1 did not lead to any detectable changes in contextual fear conditioning in PND 16 or PND 23 rats. Experiments 2 and 3 demonstrated that 5 days of injections of FGF2 (from PND 1-5) facilitated contextual fear conditioning in PND 16 and PND 23 rats. Experiment 4 demonstrated that the observed facilitation of memory was not due to FGF2 increasing rats' sensitivity to foot shock. Experiment 5 showed that early life exposure to FGF2 did not affect learning about a discrete conditioned stimulus, but did allow PND 16 rats to use contextual information in more complex ways, leading to context-dependent extinction of conditioned fear. These results further implicate FGF2 as a critical signal involved in the development of learning and memory.

  7. Dahl salt-sensitive rats develop hypovitaminosis D and hyperparathyroidism when fed a standard diet

    Science.gov (United States)

    Thierry-Palmer, Myrtle; Cephas, Stacy; Sayavongsa, Phouyong; Doherty, Akins; Arnaud, Sara B.

    2005-01-01

    The Dahl salt-sensitive rat (S), a model for salt-sensitive hypertension, excretes protein-bound 25-hydroxyvitamin D (25-OHD) into urine when fed a low salt diet. Urinary 25-OHD increases during high salt intake. We tested the hypothesis that continuous loss of 25-OHD into urine would result in low plasma 25-OHD concentration in mature S rats raised on a standard diet. Dahl S and salt-resistant (R) male rats were raised to maturity (12-month-old) on a commercial rat diet (1% salt) and switched to 0.3% (low) or 2% (high) salt diets 3 weeks before euthanasia. Urine (24 h) was collected at the end of the dietary treatments. Urinary 25-OHD and urinary 25-OHD binding activity of S rats were three times that of R rats, resulting in lower plasma 25-OHD and 24,25-dihydroxyvitamin D concentrations in S rats than in R rats (P D concentrations than those fed 0.3% salt (P = 0.002). S rats excreted more calcium into urine than R rats (P D and high plasma 1,25-dihydroxyvitamin D and PTH concentrations seen in the mature S rats have also been reported for elderly patients with low-renin (salt-induced) hypertension. An implication of this study is that low vitamin D status may occur with age in salt-sensitive individuals, even when salt intake is normal.

  8. Fetal development and renal function in adult rats prenatally subjected to sodium overload.

    Science.gov (United States)

    Cardoso, Henriqueta D; Cabral, Edjair V; Vieira-Filho, Leucio D; Vieyra, Adalberto; Paixão, Ana D O

    2009-10-01

    The aims of this study were (1) to evaluate two factors that affect fetal development--placental oxidative stress (Ox) and plasma volume (PV)--in dams with sodium overload and (2) to correlate possible alterations in these factors with subsequent modifications in the renal function of adult offspring. Wistar dams were maintained on 0.17 M NaCl instead of water from 20 days before mating until either the twentieth pregnancy day/parturition or weaning. Colorimetric methods were used to measure Ox in maternal and offspring tissues, PV, 24-h urinary protein (U(Prot24 h)) and serum triacylglycerols (TG) and cholesterol (Chol). Renal hemodynamics was evaluated in the offspring at 90 days of age using a blood pressure transducer, a flow probe and inulin clearance to measure mean arterial pressure (MAP), renal blood flow and glomerular filtration rate (GFR), respectively. The number of nephrons (NN) was counted in kidney suspensions. Dams showed unchanged PV, placental Ox and fetal weight but increased U(Prot24 h) (150%, P sodium-overloaded pups showed increased U(Prot24 h) (45%, P sodium-overloaded rats showed increased U(Prot24 h) (27%, P sodium-overloaded group. We conclude that salt overload from the prenatal stage until weaning leads to alterations in lipid metabolism and in the renal function of the pups, which are additional to those alterations seen in rats only overloaded prenatally.

  9. The effects of low dose ionizing radiation on the development of rat cerebral cortex, (1)

    International Nuclear Information System (INIS)

    Matsushita, Koji

    1993-01-01

    We obtained the following results with regards to the effects of low dose ionizing radiation (5, 10, 15 and 20 cGy) on neuronal migration of developing rat cerebral cortex. Neuronal migration delay was found by autoradiography after intraperitoneal labeling with 3 H-thymidine to pregnant Wistar rats embryonic 16, and low dose radiation an hour or 48 hours after labeling. In 15-20 cGy, N-CAM (neural cell adhesion molecules) staining patterns changed with immunohistochemical method, whereas those of L1 and cytoskeleton neurofilament (160 KD), tauprotein, MAP2 (microtubule associated protein 2) did not. After 24-48 hours of radiation, N-CAM were not detected on the matrix cell layer. After 72-96 hours of radiation, N-CAM staining recovered to a normal pattern. In conclusion, low dose radiation of 15-20 cGy gave rise to neuronal migration delay and it was suggested that N-CAM may be related to neuronal migration as one of the mechanisms involved. (author)

  10. Hepatic steatosis development with four weeks of physical inactivity in previously active, hyperphagic OLETF rats.

    Science.gov (United States)

    Linden, Melissa A; Meers, Grace M; Ruebel, Meghan L; Jenkins, Nathan T; Booth, Frank W; Laughlin, M Harold; Ibdah, Jamal A; Thyfault, John P; Rector, R Scott

    2013-05-01

    Physical activity-induced prevention of hepatic steatosis is maintained during short-term (7-day) transitions to an inactive state; however, whether these protective effects are present under a longer duration of physical inactivity is largely unknown. Here, we sought to determine whether previous physical activity had protective effects on hepatic steatosis and metabolic health following 4 wk of physical inactivity. Four-week old, hyperphagic, male Otsuka Long-Evans Tokushima fatty (OLETF) rats were randomly assigned to either a sedentary group for 16 wk (OLETF-SED), given access to running wheels for 16 wk with wheels locked 5 h (OLETF-WL5hr) or given access to running wheels for 12 wk with wheels locked 4 wk (OLETF-WL4wk) prior to death. Four weeks of physical inactivity caused hepatic steatosis development, but liver triglycerides remained 60% lower than OLETF-SED (P inactivity, whereas markers of fatty acid uptake and lipogenesis remained relatively suppressed following 4 wk of inactivity. In addition, 4 wk of inactivity caused a complete loss of activity-induced increases in serum IL-6 and reductions in regulated upon activation, normal T-cell expressed, and secreted (RANTES), and a partial loss in reductions in leptin, monocyte chemoattractant protein-1, and TNF-α. In conclusion, 4 wk of physical inactivity does not result in a complete loss in physical activity-induced benefits but does cause deterioration in the liver phenotype and overall metabolic health in hyperphagic OLETF rats.

  11. Administration of imatinib mesylate in rats impairs the neonatal development of intramuscular interstitial cells in bladder and results in altered contractile properties.

    Science.gov (United States)

    Gevaert, Thomas; Hutchings, Graham; Everaerts, Wouter; Prenen, Hans; Roskams, Tania; Nilius, Bernd; De Ridder, Dirk

    2014-04-01

    The KIT receptor is considered as a reliable marker for a subpopulation of interstitial cells (IC), and by persistent neonatal inhibition of KIT we have investigated the role of this receptor in the development of IC-networks in bladder and we have observed the functional consequences of this inhibition. Newborn rat pups were treated daily with the KIT inhibitor imatinib mesylate (IM). After 7 days animals were sacrificed and bladder samples were dissected for morphological and functional studies. Morphological research consisted of immunohistochemistry with IC specific antigens (KIT and vimentin) and electron microscopy. The functional studies were based on isolated bladder strips in organ baths, in which spontaneous bladder contractility and the response to a non-subtype selective muscarinic agonist was evaluated. Suburothelial and intramuscular IC were found and characterized in neonatal rat bladder. IM-treatment induced a significant decrease in numbers of IC based on specific immunohistochemical markers, and electron microscopy revealed evidence of IC cell injury. These morphological alterations were observed on intramuscular IC only and not on IC in the suburothelium. Isolated muscle strips from IM-treated animals had a lower contractile frequency and an altered response to muscarinic agonists. The present study shows the presence of regional subpopulations of IC in neonatal rat bladder, provides evidence for a dependence on KIT of the development of intramuscular IC and supports the hypothesis that a poor development of networks of intramuscular IC might have repercussions on spontaneous and muscarinic-induced bladder contractility. © 2013 Wiley Periodicals, Inc.

  12. Effect of maternal lipopolysaccharide administration on the development of dopaminergic receptors and transporter in the rat offspring.

    Directory of Open Access Journals (Sweden)

    Moogeh Baharnoori

    Full Text Available Epidemiological evidence supports that maternal infection during gestation are notable risk factors for developmental mental illnesses including schizophrenia and autism. In prenatal lipopolysaccharide (LPS model of immune activation in rats, the offspring exhibit significant impairments in behaviors mediated by central dopamine (DA system. This study aimed to examine the temporal and regional pattern of postnatal DA development in the male offspring of pregnant Sprague-Dawley rats administered with 100 µg/kg LPS or saline at gestational days 15/16. Using ligand autoradiography, D1 and D2 dopamine receptors (D1R, D2R and dopamine transporter (DAT binding levels were measured in the prefrontal cortex (PFC and sub cortical regions (dorsal striatum and nucleus accumbens core and shell at pre pubertal (P35 and post pubertal ages (P60. We found a significant decrease in D2R ligand [(3H] YM-90151-2 binding in the medial PFC (mPFC in prenatal LPS-treated animals at P35 and P60 compared to respective saline groups. The decrease in D2R levels was not observed in the striatum or accumbens of maternal LPS-treated animals. No significant changes were observed in [(3H] SCH23390 binding to D1R. However, the level of [(125I] RTI-121 binding to DAT was selectively reduced in the nucleus accumbens core and shell at P35 in the prenatal LPS group. Immunohistochemical analysis showed that number of D2R immunopositive cells in infralimbic/prelimbic (IL/PL part of mPFC was significantly reduced in the LPS group at P60. Prenatal LPS treatment did not significantly affect either the total number of mature neurons or parvalbumin (PV-immunopositive interneurons in this region. However the number of PV and D2R co-labeled neurons was significantly reduced in the IL/PL subregion of PFC of LPS treated animals. Our data suggests D2R deficit in the PFC and PV interneurons may be relevant to understanding mechanisms of cortical dysfunctions described in prenatal infection

  13. Early postnatal development of electrophysiological and histological properties of sensory sural nerves in male rats that were maternally deprived and artificially reared: Role of tactile stimulation.

    Science.gov (United States)

    Zempoalteca, Rene; Porras, Mercedes G; Moreno-Pérez, Suelem; Ramirez-Funez, Gabriela; Aguirre-Benítez, Elsa L; González Del Pliego, Margarita; Mariscal-Tovar, Silvia; Mendoza-Garrido, Maria E; Hoffman, Kurt Leroy; Jiménez-Estrada, Ismael; Melo, Angel I

    2018-04-01

    Early adverse experiences disrupt brain development and behavior, but little is known about how such experiences impact on the development of the peripheral nervous system. Recently, we found alterations in the electrophysiological and histological characteristics of the sensory sural (SU) nerve in maternally deprived, artificially reared (AR) adult male rats, as compared with maternally reared (MR) control rats. In the present study, our aim was to characterize the ontogeny of these alterations. Thus, male pups of four postnatal days (PND) were (1) AR group, (2) AR and received daily tactile stimulation to the body and anogenital region (AR-Tactile group); or (3) reared by their mother (MR group). At PND 7, 14, or 21, electrophysiological properties and histological characteristics of the SU nerves were assessed. At PND 7, the electrophysiological properties and most histological parameters of the SU nerve did not differ among MR, AR, and AR-Tactile groups. By contrast, at PND 14 and/or 21, the SU nerve of AR rats showed a lower CAP amplitude and area, and a significant reduction in myelin area and myelin thickness, which were accompanied by a reduction in axon area (day 21 only) compared to the nerves of MR rats. Tactile stimulation (AR-Tactile group) partially prevented most of these alterations. These results suggest that sensory cues from the mother and/or littermates during the first 7-14 PND are relevant for the proper development and function of the adult SU nerve. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 78: 351-362, 2018. © 2017 Wiley Periodicals, Inc.

  14. Development and evaluation of novel biodegradable chitosan based metformin intrapocket dental film for the management of periodontitis and alveolar bone loss in a rat model.

    Science.gov (United States)

    Khajuria, Deepak Kumar; Patil, Omprakash Nandikamba; Karasik, David; Razdan, Rema

    2018-01-01

    The aim of this study was to develop a chitosan-metformin based intrapocket dental film (CMIDF) for applications in the treatment of periodontitis and alveolar bone loss in an rat model of periodontitis. CMIDF inserts were fabricated by the solvent casting technique. The fabricated inserts were evaluated for physical characteristics such as folding endurance, surface pH, mucoadhesive strength, metformin content uniformity, and release. X-ray diffraction analysis indicates no crystallinity of metformin in presence of chitosan which confirmed successful entrapment of metformin into the CMIDF. Fourier-transform infrared spectroscopy revealed stability of CMIDF and compatibility between metformin and chitosan. Periodontitis was induced by a combination of Porphyromonas gingivalis- lipopolysaccharide injections in combinations with ligatures around the mandibular first molar. We divided rats into 5 groups (8 rats/group): healthy, untreated periodontitis; periodontitis plus CMIDF-A (1.99±0.09mg metformin; total mass-4.01±0.05mg), periodontitis plus CMIDF-B (2.07±0.06mg metformin; total mass-7.56±0.09mg), and periodontitis plus chitosan film (7.61±0.08mg). After four weeks, mandibles were extracted to evaluate alveolar bone loss by micro-computerized tomography and histological techniques. Alveolar bone was intact in the healthy group. Local administration of CMIDF resulted in significant improvements in the alveolar bone properties when compared to the untreated periodontitis group. The study reported here demonstrates that novel CMIDF showed good antibacterial activity and effectively reduced alveolar bone destruction in a rat model of experimental periodontitis. Novel CMIDF showed good antibacterial activity and improved alveolar bone properties in a rat model. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Religious Freedom and Equality as Celebration of Difference: A Significant Development in Recent South African Constitutional Case-Law

    Directory of Open Access Journals (Sweden)

    L du Plessis

    2009-12-01

    Full Text Available This contribution focuses on the way in which the South African Constitutional Court has, since 1997, been dealing with the (seemingly eccentric claims of (assumedly idiosyncratic 'religious Others'. Developments in this regard have, for the time being at least, culminated in the Constitutional Court's landmark judgment in MEC for Education: KwaZulu Natal v Pillay 2008 (2 BCLR 99 (CC, 2008 (1 SA 474 (CC (hereafter Pillay. Constitutional Court judgments since 1997 manifesting the adjudication of such unconventional claims are assessed, eventually getting to Pillay as benchmark. This remarkable judgment, dealing with a deceptively mundane issue, has played a considerable role in fleshing out a jurisprudence of difference, putting an adherent of a vulnerable, minority religion in the right. This is not just a high point in the adjudication of constitutional entitlements of the religious (and cultural Other in South Africa, but also a significant contribution to the growth of a jurisprudence sensitive to the predicaments and constitutional entitlements of unconventional, 'non-mainstream' claimants of religious (and cultural rights. Finally Pillay illustrates that the constitutional guarantee of the right to freedom of religion, conscience, belief and opinion (entrenched in section 15(1 of the Constitution of Republic of South Africa 1996 can be crucially dependent upon due effect being given to the proscription of unfair discrimination on the grounds of religion, conscience, belief and opinion elsewhere (namely in section 9(3 of the Constitution.

  16. Pressure sores significantly increase the risk of developing a Fournier's gangrene in patients with spinal cord injury.

    Science.gov (United States)

    Backhaus, M; Citak, M; Tilkorn, D-J; Meindl, R; Schildhauer, T A; Fehmer, T

    2011-11-01

    Retrospective chart review. The aim of our study was to evaluate the mortality rate and further specific risk factors for Fournier's gangrene in patients with spinal cord injury (SCI). Division of Spinal Cord Injury, BG-University Hospital Bergmannsheil Bochum, Ruhr-University Bochum, Germany. All patients with a SCI and a Fournier's gangrene treated in our hospital were enrolled in this study. Following parameters were taken form patients medical records: age, type of SCI, cause of Fournier's gangrene, number of surgical debridements, length of hospital and intensive care unit stay, co morbidity factors and mortality rate. In addition, laboratory parameter including the laboratory risk indicator for necrotizing fasciitis (LRINEC) score and microbiological findings were analyzed. Clinical diagnosis was made via histological examination. A total of 16 male patients (15 paraplegic and one tetraplegic) were included in the study. In 81% of all cases, the origin of Fournier's gangrene was a pressure sore. The median LRINEC score on admission was 6.5. In the vast majority of cases, a polybacterial infection was found. No patient died during the hospital stay. The mean number of surgical debridements before soft tissue closure was 1.9 and after a mean time interval of 39.1 days wound closure was performed in all patients. Pressure sores significantly increase the risk of developing Fournier's gangrene in patients with SCI. We reported the results of our patients to increase awareness among physicians and training staff working with patients with a SCI in order to expedite the diagnosis.

  17. Large diameter femoral heads impose significant alterations on the strains developed on femoral component and bone: a finite element analysis.

    Science.gov (United States)

    Theodorou, E G; Provatidis, C G; Babis, G C; Georgiou, C S; Megas, P D

    2011-01-01

    Total Hip Arthroplasty aims at fully recreating a functional hip joint. Over the past years modular implant systems have become common practice and are widely used, due to the surgical options they provide. In addition Big Femoral Heads have also been implemented in the process, providing more flexibility for the surgeon. The current study aims at investigating the effects that femoral heads of bigger diameter may impose on the mechanical behavior of the bone-implant assembly. Using data acquired by Computed Tomographies and a Coordinate Measurement Machine, a cadaveric femur and a Profemur-E modular stem were fully digitized, leading to a three dimensional finite element model in ANSYS Workbench. Strains and stresses were then calculated, focusing on areas of clinical interest, based on Gruen zones: the calcar and the corresponding below the greater trochanter area in the proximal femur, the stem tip region and a profile line along linea aspera. The performed finite elements analysis revealed that the use of large diameter heads produces significant changes in strain development within the bone volume, especially in the lateral side. The application of Frost's law in bone remodeling, validated the hypothesis that for all diameters normal bone growth occurs. However, in the calcar area lower strain values were recorded, when comparing with the reference model featuring a 28mm femoral head. Along line aspera and for the stem tip area, higher values were recorded. Finally, stresses calculated on the modular neck revealed increased values, but without reaching the yield strength of the titanium alloy used.

  18. Lactational exposure to hexavalent chromium delays puberty by impairing ovarian development, steroidogenesis and pituitary hormone synthesis in developing Wistar rats

    International Nuclear Information System (INIS)

    Banu, Sakhila K.; Samuel, Jawahar B.; Arosh, Joe A.; Burghardt, Robert C.; Aruldhas, Michael M.

    2008-01-01

    Hexavalent chromium (Cr-VI) is used in a wide range of industries. Cr-VI from chromate industries and atmospheric emissions contribute to the Cr contamination in the environment. Cr is a reproductive metal toxicant that can traverse the placental barrier and cause a wide range of fetal effects including ovotoxicity. Therefore, the goal of this study was to investigate the basic mechanisms involved in Cr(VI)-induced ovotoxicity, and the protective role of vitamin C on ovarian follicular development and function in Cr(VI)-induced reproductive toxicity using both in vivo and in vitro approaches. Lactating rats received potassium dichromate (200 mg/L) with or without vitamin C (500 mg/L), through drinking water from postpartum days 1-21. During postnatal days (PND) 1-21 the pups received Cr(VI) via the mother's milk. Pups from both control and treatment groups were continued on regular diet and water from PND-21 onwards, and euthanized on PND-21, -45 and -65. Cr(VI) decreased steroidogenesis, GH and PRL, increased FSH and did not alter LH. Cr(VI) delayed puberty, decreased follicle number, and extended estrous cycle. Spontaneously immortalized rat granulosa cells were treated with 12.5 μM (IC 50 ) potassium dichromate for 12 and 24 h, with or without vitamin C pre-treatment. Cr(VI) decreased the mRNA expressions of StAR, SF-1, 17β-HSD-1, 17β-HSD-2, FSHR, LHR, ERα and ERβ. Vitamin C pre-treatment protected ovary and granulosa cells from the deleterious effects of Cr(VI) toxicity, both in vivo and in vitro. Therefore, Cr(VI) toxicity could be a potential risk to the reproductive system in developing females, and vitamin C plays a protective role against Cr(VI)-induced ovotoxicity

  19. Postnatal development of rat pups is altered by prenatal methamphetamine exposure.

    Science.gov (United States)

    Slamberová, Romana; Pometlová, Marie; Charousová, Petra

    2006-01-01

    There are studies showing that drug abuse during pregnancy may have impairing effect on progeny of drug-abusing mothers. Methamphetamine (MA) is one of the most common illicit drugs throughout the world. The purpose of the present study was to assess the effect of prenatal MA exposure on postnatal development of rat pups before the time of separation from their mothers. Female rats were injected with MA (5 mg/kg daily) for the duration of their pregnancy. Pups were then tested throughout the lactation period. They were weighed daily and the ano-genital distance was measured on postnatal day (PD) 1. Development of postural motor reaction was tested by righting reflex on surface between PD 1 and 12, and righting reflex in mid-air after PD 12 until successfully accomplished. On PD 15 homing test was examined as a test of pup acute learning. On PD 23 sensory-motor coordination was examined using the rotarod and bar-holding tests. Additionally, the markers of physical maturation, such as eye opening, testes descent in males and vaginal opening in females were also recorded. The birth weight in prenatally MA-exposed pups was lower than in controls or saline-exposed pups regardless of sex. There were no changes induced by prenatal MA exposure in weight gain or in sexual maturation. In righting reflexes, we demonstrated that pups exposed prenatally to MA were slower in righting reflex on surface and that they accomplished the test of righting reflex in mid-air later than controls or saline-exposed pups. The performance of homing test was not affected by prenatal drug exposure. The sensory-motor coordination was impaired in prenatally MA-exposed pups when testing in the rotarod test. Also, the number of falls in the bar-holding test was higher in MA-exposed pups than in controls. There were no sex differences in any measures. Thus, the present study demonstrated that prenatal MA exposure impairs development of postural motor movements of rat pups during the first 3 weeks

  20. Spatial learning and memory is preserved in rats after early development in a microgravity environment

    Science.gov (United States)

    Temple, Meredith D.; Kosik, Kenneth S.; Steward, Oswald

    2002-01-01

    This study evaluated the cognitive mapping abilities of rats that spent part of their early development in a microgravity environment. Litters of male and female Sprague-Dawley rat pups were launched into space aboard the National Aeronautics and Space Administration space shuttle Columbia on postnatal day 8 or 14 and remained in space for 16 days. These animals were designated as FLT groups. Two age-matched control groups remained on Earth: those in standard vivarium housing (VIV) and those in housing identical to that aboard the shuttle (AGC). On return to Earth, animals were tested in three different tasks that measure spatial learning ability, the Morris water maze (MWM), and a modified version of the radial arm maze (RAM). Animals were also tested in an open field apparatus to measure general activity and exploratory activity. Performance and search strategies were evaluated in each of these tasks using an automated tracking system. Despite the dramatic differences in early experience, there were remarkably few differences between the FLT groups and their Earth-bound controls in these tasks. FLT animals learned the MWM and RAM as quickly as did controls. Evaluation of search patterns suggested subtle differences in patterns of exploration and in the strategies used to solve the tasks during the first few days of testing, but these differences normalized rapidly. Together, these data suggest that development in an environment without gravity has minimal long-term impact on spatial learning and memory abilities. Any differences due to development in microgravity are quickly reversed after return to earth normal gravity.

  1. Different dietary omega-3 sources during pregnancy and DHA in the developing rat brain

    Directory of Open Access Journals (Sweden)

    Childs Caroline E.

    2011-09-01

    Full Text Available The essential n-3 fatty acid α-linolenic acid (ALA can be converted into eicosapentaenoic acid (EPA, docosapentaenoic acid (DPA and docosahexaenoic acid (DHA under the action of desaturase and elongase enzymes. Human studies have demonstrated that females convert a higher proportion of ALA into EPA and DHA than males. We have demonstrated that when fed upon an ALA rich diet, female rats have a significantly higher EPA content of plasma and liver lipids than males. When fetal tissues were collected, it was observed that pups from dams fed the ALA rich diet had a comparable brain DHA status to those from dams fed on a salmon-oil based diet, indicating that conversion of ALA to DHA during pregnancy was efficient, and that DHA accumulated in a tissue-specific manner. Similar efficacy of dietary ALA in women during pregnancy would mean that plant n-3 fatty acids would be useful alternatives to preformed EPA and DHA.

  2. EVOLUTION OF NEUROENDOCRINE CELL POPULATION AND PEPTIDERGIC INNERVATION, ASSESSED BY DISCRIMINANT ANALYSIS, DURING POSTNATAL DEVELOPMENT OF THE RAT PROSTATE

    Directory of Open Access Journals (Sweden)

    Rosario Rodríguez

    2011-05-01

    Full Text Available Serotonin immunoreactive neuroendocrine cells and peptidergic nerves (NPY and VIP could have a role in prostate growth and function. In the present study, rats grouped by stages of postnatal development (prepubertal, pubertal, young and aged adults were employed in order to ascertain whether age causes changes in the number of serotoninergic neuroendocrine cells and the length of NPY and VIP fibres. Discriminant analysis was performed in order to ascertain the classificatory power of stereologic variables (absolute and relative measurements of cell number and fibre length on age groups. The following conclusions were drawn: a discriminant analysis confirms the androgen-dependence of both neuroendocrine cells and NPYVIP innervation during the postnatal development of the rat prostate; b periglandular innervation has more relevance than interglandular innervation in classifying the rats in age groups; and c peptidergic nerves from ventral, ampullar and periductal regions were more age-dependent than nerves from the dorso-lateral region.

  3. Role of major histocompatibility complex class II in the development of autoimmune type 1 diabetes and thyroiditis in rats

    Science.gov (United States)

    Yokoi, N; Hidaka, S; Tanabe, S; Ohya, M; Ishima, M; Takagi, Y; Masui, N; Seino, S

    2012-01-01

    Although the MHC class II ‘u' haplotype is strongly associated with type 1 diabetes (T1D) in rats, the role of MHC class II in the development of tissue-specific autoimmune diseases including T1D and autoimmune thyroiditis remains unclear. To clarify this, we produced a congenic strain carrying MHC class II ‘a' and ‘u' haplotypes on the Komeda diabetes-prone (KDP) genetic background. The u/u homozygous animals developed T1D similar to the original KDP rat; a/u heterozygous animals did develop T1D but with delayed onset and low frequency. In contrast, none of the a/a homozygous animals developed T1D; about half of the animals with a/u heterozygous or a/a homozygous genotypes showed autoimmune thyroiditis. To investigate the role of genetic background in the development of thyroiditis, we also produced a congenic strain carrying Cblb mutation of the KDP rat on the PVG.R23 genetic background (MHC class II ‘a' haplotype). The congenic rats with homozygous Cblb mutation showed autoimmune thyroiditis without T1D and slight to severe alopecia, a clinical symptom of hypothyroidism such as Hashimoto's thyroiditis. These data indicate that MHC class II is involved in the tissue-specific development of autoimmune diseases, including T1D and thyroiditis. PMID:21918539

  4. Dietary gamma oryzanol plays a significant role in the anti-inflammatory activity of rice bran oil by decreasing pro-inflammatory mediators secreted by peritoneal macrophages of rats.

    Science.gov (United States)

    Rao, Y Poorna Chandra; Sugasini, D; Lokesh, B R

    2016-10-28

    Ricebran oil (RBO) is promoted as heart friendly oil because of its ability to maintain serum lipids at desirable levels. Inflammation also plays an important role on cardiovascular health. The role of minor constituents present in unsaponifiable fraction (UF) of RBO on inflammatory markers is not well understood. To evaluate this, we have taken RBO with UF (RBO-N), RBO stripped of UF (RBO-MCR) and RBO-MCR supplemented with UF from RBO (UFRBO) or Gamma-Oryzanol (γ-ORY) were added in AIN-93 diets which was then fed to Wistar rats for a period of 60 days. Groundnut oil with UF (GNO-N), UF removed GNO (GNO-MCR) and GNO-MCR supplemented with UF from RBO or γ-ORY was also used for comparison. The peritoneal macrophages from the rats were activated and pro-inflammatory mediators such as Reactive Oxygen Species (ROS), eicosanoids, cytokines, hydrolytic enzymes of lysosomal origin were monitored. The results indicated that UF of RBO and γ-ORY supplemented in the dietary oils play a significant role in reducing the secretion of pro-inflammatory mediators by macrophages. Hence γ-ORY in RBO significantly contributed to the anti-inflammatory properties of RBO. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Hyperthyroidism modifies ecto-nucleotidase activities in synaptosomes from hippocampus and cerebral cortex of rats in different phases of development.

    Science.gov (United States)

    Bruno, Alessandra Nejar; Da Silva, Rosane Souza; Bonan, Carla Denise; Battastini, Ana Maria Oliveira; Barreto-chaves, Maria Luiza M; Sarkis, João José Freitas

    2003-11-01

    Here we investigate the possible effects of the hyperthyroidism on the hydrolysis of the ATP to adenosine in the synaptosomes of hippocampus, cerebral cortex and blood serum of rats in different developmental phases. Manifestations of hyperthyroidism include anxiety, nervousness, tachycardia, physical hyperactivity and weight loss amongst others. The thyroid hormones modulate a number of physiological functions in central nervous system, including development, function, expression of adenosine A(1) receptors and transport of neuromodulator adenosine. Thus, hyperthyroidism was induced in male Wistar rats (5-, 60-, 150- and 330-day old) by daily injections of L-thyroxine (T4) for 14 days. Nucleotide hydrolysis was decreased by about 14-52% in both hippocampus and cerebral cortex in 5 to 60-day-old rats. These changes were also observed in rat blood serum. In addition, in 11-month-old rats, inhibition of ADP and AMP hydrolysis persisted in the hippocampus, whereas, in cerebral cortex, an increase in AMP hydrolysis was detected. Thus, hyperthyroidism affects the extracellular nucleotides balance and adenosine production, interfering in neurotransmitter release, development and others physiological processes in different systems.

  6. Role of reactive oxygen species and poly-ADP-ribose polymerase in the development of AZT-induced cardiomyopathy in rat.

    Science.gov (United States)

    Szabados, E; Fischer, G M; Toth, K; Csete, B; Nemeti, B; Trombitas, K; Habon, T; Endrei, D; Sumegi, B

    1999-02-01

    The short term cardiac side-effects of AZT (3'-azido-3'-deoxythymidine, zidovudine) was studied in rats to understand the biochemical events contributing to the development of AZT-induced cardiomyopathy. Developing rats were treated with AZT (50 mg/kg/day) for 2 wk and the structural and functional changes were monitored in the cardiac muscle. AZT treatment provoked a surprisingly fast appearance of cardiac malfunctions in developing animals characterized by prolonged RR, PR and QT intervals and J point depression. Electron microscopy showed abnormal mitochondrial structure but the cardiomyocyte had normal myofibers. The AZT treatment of rats significantly increased ROS and peroxynitrite formation in heart tissues as determined by the oxidation of nonfluorescent dihydrorhodamine123 and dichlorodihydro-fluorescein diacetate (H2DCFDA) to fluorescent dyes, and induced single-strand DNA breaks. Lipid peroxidation and oxidation of cellular proteins determined from protein carbonyl content were increased as a consequence of AZT treatment. Activation of the nuclear poly-ADP-ribose polymerase and the accelerated NAD+ catabolism were also observed in AZT-treated animals. Western blot analysis showed that mono-ADP-ribosylation of glucose regulated protein (GRP78/BIP) was enhanced by AZT treatment, that process inactivates GRP78. In this way moderate decrease in the activity of respiratory complexes was detected in the heart of AZT-treated animals indicating a damaged mitochondrial energy production. There was a significant decrease in creatine phosphate concentration resulting in a decrease in creatine phosphate/creatine ratio from 2.08 to 0.58. ATP level remained close to normal but the total extractable ADP increased with 45%. The calculated free ATP/ADP ratio decreased from 340 to 94 in the heart of AZT-treated rats as a consequence of increased free ADP concentration. It was assumed that the increased free ADP in AZT-treated cardiomyocyte may help cells to compensate the

  7. Sex differences and left-right asymmetries in expression of insulin and insulin-like growth factor-1 receptors in developing rat hippocampus.

    Science.gov (United States)

    Hami, Javad; Sadr-Nabavi, Ariane; Sankian, Mojtaba; Haghir, Hossein

    2012-04-01

    Sex differences and laterality of rat hippocampus with respect to insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (InsR) expression as two important contributors to/regulators of developmental and cognitive functions were examined using real-time PCR and western blot analysis at P0, P7 and P14. Expression of the IGF-1R gene was lowest at P0 in all studied hippocampi. In males, we found the highest expression at P7 in the right hippocampus, and at P14 in the left one. In contrast, the peaked IGF-1R expression occurred at P7 in female hippocampi independent of laterality. Hippocampal InsR expression in males decreased significantly between P0 and P7, followed by a marked upregulation at P14. Conversely, the expression of InsR in females peaked at P7 and then decreased again significantly at P14. We found significant interhemispheric differences in IGF-1R mRNA levels in both male and female hippocampi at different time points. In contrast, we only found significant interhemispheric differences in InsR mRNA expression in P14 male rats, with higher values in the left hippocampus. Interestingly, changes in mRNA expression and in protein levels followed the same developmental pattern, indicating that IGF-1R and InsR transcription is not subject to modulatory effects during the first two weeks of development. These findings indicate that there are prominent interhemispheric and sex differences in IGF-1R and InsR expression in the developing rat hippocampus, suggesting a probable mechanism for the control of gender and laterality differences in development and function of the hippocampus.

  8. Effects of prenatal exposure to a low dose atrazine metabolite mixture on pubertal timing and prostate development of male Long-Evans rats

    Energy Technology Data Exchange (ETDEWEB)

    Stanko, Jason [National Institute of Environmental Health Sciences (NIEHS); Enoch, Rolondo [North Carolina Central University, Durham; Rayner, Jennifer L [ORNL; Davis, Christine [U.S. Environmental Protection Agency; Wolf, Douglas [U.S. Environmental Protection Agency; Malarkey, David [University of North Carolina, Chapel Hill; Fenton, Suzanne [National Institute of Environmental Health Sciences (NIEHS)

    2010-12-01

    The present study examines the postnatal reproductive development of male rats following prenatal exposure to an atrazine metabolite mixture (AMM) consisting of the herbicide atrazine and its environmental metabolites diaminochlorotriazine, hydroxyatrazine, deethylatrazine, and deisopropylatrazine. Pregnant Long-Evans rats were treated by gavage with 0.09, 0.87, or 8.73 mg AMM/kg body weight (BW), vehicle, or 100 mg ATR/kg BW positive control, on gestation days 15 19. Preputial separation was significantly delayed in 0.87 mg and 8.73 mg AMM-exposed males. AMM-exposed males demonstrated a significant treatment-related increase in incidence and severity of inflammation in the prostate on postnatal day (PND) 120. A dose-dependent increase in epididymal fat masses and prostate foci were grossly visible in AMM-exposed offspring. These results indicate that a short, late prenatal exposure to mixture of chlorotriazine metabolites can cause chronic prostatitis in male LE rats. The mode of action for these effects is presently unclear.

  9. Regional alterations of brain biogenic amines and GABA/glutamate levels in rats following chronic lead exposure during neonatal development

    Energy Technology Data Exchange (ETDEWEB)

    Shailesh Kumar, M V; Desiraju, T [National Inst. of Mental Health and Neuro Sciences, Bangalore (India). Dept. of Neurophysiology

    1990-06-01

    Wistar rat pups were administered either a high dose of lead acetate (400 {mu}g lead-g body weight/day) or a low dose (100 {mu}g lead/g body weight/day) by gastric intubation, from 2 days through 60 days of age. The rats on both these doses exhibited statistically significant decreases in body and brain weights throughout the lead treatment period. A group of rats on high dose was also rehabilitated by discontinuing the lead from 60 days of age. In these rats, at 160 days of age, the body weight but not the brain weight recovered to normal levels. During the lead intake, the rats on high dose revealed significant elevations in the levels of noradrenaline (NA) in the hippocampus (HI), cerebellum (CE), hypothalamus (HY), brainstem (BS), and accumbens-striatum (SA). The elevated levels in all the above regions except in the HY persisted even after rehabilitation. The dopamine (DA) levels changed significantly in opposite directions in HY (elevation) and BS (reduction) during the lead treatment, and the HY recovered after rehabilitation. Under lead, the serotonin (5HT) levels were elevated significantly in the HI, BS and MC (motor cortex), while after rehabilitation the abnormality persisted only in the MC. Low dose lead treatment was also effective on the same areas of brain. In the low dose group, estimation of the levels of GABA and glutamate were also done, and a significant decrease of GABA in CE and glutamate in MC was observed. The differences observed in the neurotoxic effects (none or significant) of lead in the different regions for each of the transmitters (NA, DA, 5HT) supports the interesting conclusion that the vulnerability of the axon terminals of any given type is dependent on some regional factors, although the projections of the different regions originate from an apparently similar category of neurons in the brain stem. (orig.).

  10. Galantamine counteracts development of learning impairment in guinea pigs exposed to the organophosphorus poison soman: Clinical significance

    Science.gov (United States)

    Mamczarz, Jacek; Kulkarni, Girish S.; Pereira, Edna F. R.; Albuquerque, Edson X.

    2017-01-01

    Galantamine, a drug used to treat Alzheimer’s disease, protects guinea pigs against the acute toxicity and lethality of organophosphorus (OP) compounds, including soman. Here, we tested the hypothesis that a single exposure of guinea pigs to 1xLD50 soman triggers cognitive impairments that can be counteracted by galantamine. Thus, animals were injected intramuscularly with saline (0.5 ml/kg) or galantamine (8 mg/kg) and 30 min later injected subcutaneously with soman (26.3 µg/kg) or saline. Cognitive performance was analyzed in the Morris water maze (MWM) four days or three months after the soman challenge. Fifty percent of the saline-injected animals that were challenged with soman survived with mild-to-moderate signs of acute toxicity that subsided within a few hours. These animals showed no learning impairment and no memory retention deficit, when training in the MWM started four days post-soman challenge. In contrast, animals presented significant learning impairment when testing started three months post-challenge. Though the magnitude of the impairment correlated with the severity of the acute toxicity, animals that presented no or only mild signs of toxicity were also learning impaired. All guinea pigs that were treated with galantamine survived the soman challenge with no signs of acute toxicity and learned the MWM task as control animals, regardless of when testing began. Galantamine also prevented memory extinction in both saline-and soman-challenged animals. In conclusion, learning impairment develops months after a single exposure to 1xLD50 soman, and galantamine prevents both the acute toxicity and the delayed cognitive deficits triggered by this OP poison. PMID:21784098

  11. Upregulation of EMMPRIN (OX47 in Rat Dorsal Root Ganglion Contributes to the Development of Mechanical Allodynia after Nerve Injury

    Directory of Open Access Journals (Sweden)

    Qun Wang

    2015-01-01

    Full Text Available Matrix metalloproteinases (MMPs are widely implicated in inflammation and tissue remodeling associated with various neurodegenerative diseases and play an important role in nociception and allodynia. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN plays a key regulatory role for MMP activities. However, the role of EMMPRIN in the development of neuropathic pain is not clear. Western blotting, real-time quantitative RT-PCR (qRT-PCR, and immunofluorescence were performed to determine the changes of messenger RNA and protein of EMMPRIN/OX47 and their cellular localization in the rat dorsal root ganglion (DRG after nerve injury. Paw withdrawal threshold test was examined to evaluate the pain behavior in spinal nerve ligation (SNL model. The lentivirus containing OX47 shRNA was injected into the DRG one day before SNL. The expression level of both mRNA and protein of OX47 was markedly upregulated in ipsilateral DRG after SNL. OX47 was mainly expressed in the extracellular matrix of DRG. Administration of shRNA targeted against OX47 in vivo remarkably attenuated mechanical allodynia induced by SNL. In conclusion, peripheral nerve injury induced upregulation of OX47 in the extracellular matrix of DRG. RNA interference against OX47 significantly suppressed the expression of OX47 mRNA and the development of mechanical allodynia. The altered expression of OX47 may contribute to the development of neuropathic pain after nerve injury.

  12. The development of the cholinergic system in rat hippocampus following postnatal X-irradiation

    International Nuclear Information System (INIS)

    Ben-Barak, J.

    1981-01-01

    Postnatal X-irradiation of the rat hippocampus results in a marked reduction in the number of the postnatally developing granular neurons in the dentate gyrus and also caused a marked increase in the specific activity of acetylcholinesterase (AChE) and choline acetyltransferase (CAT) and a slight but consistent increase in the activity per whole hippocampus of AChE. The effect of irradiation on the granular neurons and on the cholinergic enzymes was found to be dose and age dependent. Drastic increase in specific enzymatic activities is also observed in the irradiated cerebellum whose granular neurons differentiate postnatally and to a lesser extent in the cerebral cortex in which cell formation is accomplished prior to birth. (Auth.)

  13. Ultrastructural study of the development of Sarcocystis singaporensis sarcocysts in the muscles of its rat host

    Directory of Open Access Journals (Sweden)

    Paperna I.

    2002-06-01

    Full Text Available Laboratory rats fed sporocysts of Sarcocystis singaporensis (Zaman & Colley, 1975 Zaman & Colley, 1976 originating from Singapore were euthanized 22, 23, 33 and 80 days later. Sporocysts were extracted from feces of either naturally or laboratory-infected Python reticulatus. Electron microscopically examined tongue and esophageal muscles yielded images of successive developing stages of sarcocysts. The primary wall evolved from a continuous thin layer into folds and later, into villar protrusions. At all stages the wall was interrupted by pinocytotic-like indentations. Young sarcocysts contained only metrocytes, they divided by endodyogeny into daughter metrocytes. The first bradyzoites appeared only 33 d.p.i. Sarcocysts by 80 d.p.i. were enclosed in a fully differentiated primary wall and contained almost entirely bradyzoites.

  14. Distribution of aromatase and sex steroid receptors in the baculum during the rat life cycle: effects of estrogen during the early development of the baculum.

    Science.gov (United States)

    Yonezawa, Tomohiro; Higashi, Mayuko; Yoshioka, Kazuki; Mutoh, Ken-ichiro

    2011-07-01

    The baculum, also called os penis, plays an important role during copulation. However, the hormonal regulation of its development remains to be elucidated. To determine the direct involvement of sex steroids in the development of the baculum of rats, the distributions of androgen receptors (ARs), aromatase, and estrogen receptor alpha (ESR1) were observed immunohistochemically. On Postnatal Day 1, the rudiment of the baculum expressed ARs, aromatase, and ESR1. In the proximal segment of the baculum of neonatal rats, ARs were expressed in the parosteal layer but not in the periosteum or osteoblasts. Aromatase was expressed from the parosteal layer to the endosteum, particularly in the inner osteogenic layer. ESR1 was also abundantly expressed in almost all cells from the parosteal layer to the endosteum. ARs, aromatase, and ESR1 were all abundantly expressed during the neonatal period in the hyaline cartilage of the proximal segment and in fibrocartilage of the distal segment of the baculum. Expression in all the tissues was attenuated in an age-dependent manner and became quite weak at puberty. To determine the effect of estrogen on the growth of the baculum, the aromatase inhibitor 1,4,6-androstatrien-3,17-dione (ATD) was subcutaneously injected daily into pregnant rats from Days 19 to 23 of gestation and into pups on postnatal Days 1, 3, 5, 7, and 9. On Day 10, the length of the baculum in the ATD-treated rats was significantly shorter than that in the controls, although the body weight did not change. These findings suggest that not only androgen but also locally aromatized estrogen is involved in the early growth and development of the baculum.

  15. Expression of an Intestine-Specific Transcription Factor (CDX1) in Intestinal Metaplasia and in Subsequently Developed Intestinal Type of Cholangiocarcinoma in Rat Liver

    Science.gov (United States)

    Ren, Ping; Silberg, Debra G.; Sirica, Alphonse E.

    2000-01-01

    CDX1 is a caudal-type homeobox intestine-specific transcription factor that has been shown to be selectively expressed in epithelial cells in intestinal metaplasia of the human stomach and esophagus and variably expressed in human gastric and esophageal adenocarcinomas (Silberg DG, Furth EE, Taylor JK, Schuck T, Chiou T, Traber PG: Gastroenterology 1997, 113: 478–486). Through the use of immunohistochemistry and Western blotting, we investigated whether CDX1 is also uniquely associated with the intestinal metaplasia associated with putative precancerous cholangiofibrosis induced in rat liver during furan cholangiocarcinogenesis, as well as expressed in neoplastic glands in a subsequently developed intestinal type of cholangiocarcinoma. In normal, control adult rat small intestine, specific nuclear immunoreactivity for CDX1 was most prominent in enterocytes lining the crypts. In comparison, epithelium from intestinal metaplastic glands within furan-induced hepatic cholangiofibrosis and neoplastic epithelium from later developed primary intestinal-type cholangiocarcinoma each demonstrated strong nuclear immunoreactivity for CDX1. CDX1-positive cells were detected in hepatic cholangiofibrotic tissue as early as 3 weeks after the start of chronic furan treatment. We further determined that the percentages of CDX1-positive neoplastic glands and glandular nuclei are significantly higher in primary tumors than in a derived, transplantable cholangiocarcinoma serially-propagated in vivo. Western blotting confirmed our immunohistochemical results, and no CDX1 immunoreactivity was detected in normal adult rat liver or in hyperplastic biliary epithelial cells. These findings indicate that CDX1 is specifically associated with early intestinal metaplasia and a later developed intestinal-type of cholangiocarcinoma induced in the liver of furan-treated rats. PMID:10666391

  16. Developmental fluoride exposure influenced rat's splenic development and cell cycle via disruption of the ERK signal pathway.

    Science.gov (United States)

    Ma, Yanqin; Zhang, Kankan; Ren, Fengjun; Wang, Jundong

    2017-11-01

    Excessive fluoride exposure has been reported to cause damage to spleen. Neonatal period is characterized by rapid proliferation and differentiation of lymphocyte in the spleen. Children may be more sensitive to the toxicity of fluoride compared to the adults. The aim of this study was to investigate the effects of postnatal exposure (from neonatal period to early adulthood) to fluoride on the development of spleen on a regular basis and the underlying signal pathway. Results showed a marked decrease in spleen weight index and altered morphology in the spleen of fluoride-treated group on PND-84, which reflected fluoride inhibition of the development of spleen. Fluoride exposure induced cell cycle arrest of splenocytes and decreased the mRNA expression of IL-2, which indicated compromised baseline lymphocyte proliferation in the spleen. Time course research from 3-wk-of-age until 12-wk-of-age showed an adverse and cumulative impact of fluoride on the development of spleen. In view of the key role of MAPK/ERK pathway in lymphocyte development, Raf-1/MEK-1/ERK-2/c-fos mRNA expression and ERK/p-ERK protein expression were detected. Results showed despite a transitory increase in mRNA expression from PND-42 to PND-63 in fluoride-treated group, the expression of these genes on PND-84 decreased significantly compared with PND-42 or PND-63. NaF significantly inhibited the phosphorylation of ERK protein on PND-84. Taken together, these results emphasized the vital role of ERK pathway in the interfered development of spleen induced by a high dose of fluoride exposure in rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Liver antioxidant stores protect the brain from electromagnetic radiation (900 and 1800 MHz)-induced oxidative stress in rats during pregnancy and the development of offspring.

    Science.gov (United States)

    Çetin, Hasan; Nazıroğlu, Mustafa; Çelik, Ömer; Yüksel, Murat; Pastacı, Nural; Özkaya, Mehmet Okan

    2014-12-01

    The present study determined the effects of mobile phone (900 and 1800 MHz)-induced electromagnetic radiation (EMR) exposure on oxidative stress in the brain and liver as well as the element levels in growing rats from pregnancy to 6 weeks of age. Thirty-two rats and their offspring were equally divided into three different groups: the control, 900 MHz, and 1800 MHz groups. The 900 MHz and 1800 MHz groups were exposed to EMR for 60 min/d during pregnancy and neonatal development. At the 4th, 5th, and 6th weeks of the experiment, brain samples were obtained. Brain and liver glutathione peroxidase activities, as well as liver vitamin A and β-carotene concentrations decreased in the E