Sales Growth of New Pharmaceuticals Across the Globe: The Role of Regulatory Regimes

NARCIS (Netherlands)

S. Stremersch (Stefan); A. Lemmens (Aurélie)

2008-01-01

textabstractPrior marketing literature has overlooked the role of regulatory regimes in explaining international sales growth of new products. This paper addresses this gap in the context of new pharmaceuticals (15 new molecules in 34 countries) and sheds light on the effect regulatory regimes have

Role of the Regulatory Body in Implementing Defence in Depth in Nuclear Installations - Regulatory Oversight in Egypt

Energy Technology Data Exchange (ETDEWEB)

El-Sheikh, B. M., E-mail: badawymel@yahoo.com [Egyptian Nuclear and Radiological Regulatory Authority Cairo (Egypt)

2014-10-15

The fundamental objective of all nuclear safety regulatory bodies is to ensure that nuclear facilities are operated at all times in an acceptably safe manner including the safe conduct of decommissioning activities. Defence in depth is recognized as one of the fundamental safety principles that underlie the safety of nuclear power plants. Defence in depth is implemented to provide a graded protection against a wide variety of transients, incidents and accidents, including equipment failures and human errors within nuclear power plants and events initiated outside plants. The Regulator Body plays an important role in implementing defence in depth in nuclear installations in the context of a clear allocation of responsibilities with an operating organization. This role starting with setting safety objectives and by its own independent review and technical assessment of the safety justifications provided by the operating organization in addition to safety culture investigating within relevant organizations. This paper briefly reviews this role in normal operation and post accidents, and its effects on overall nuclear safety in nuclear installations with reference to Egyptian regulatory oversight. (author)

Regulatory focus at work : the moderating role of regulatory focus in the job demands-resources model

NARCIS (Netherlands)

Brenninkmeijer, V.; Demerouti, E.; Blanc, Le P.M.; Emmerik, van I.J.H.

2010-01-01

Purpose – The purpose of this study is to examine the moderating role of regulatory focus in the job demands-resources model. Design/methodology/approach – A questionnaire survey was conducted among 146 teachers in secondary education. It was expected that detrimental effects of job demands (i.e.

Role of cooperation activities for capacity building of Romanian Regulatory Authority (CNCAN)

International Nuclear Information System (INIS)

Biro, L.; Ciurea-Ercau, C.

2010-01-01

With a slow but active nuclear development program of sector since 1980, Romanian regulatory authority had to permanently adapt to the changes in national and international environment in order ensure continuously increase of capacity building and effectiveness, commensurate with the growing nuclear sector. Limited human resources available at the national level put the Romanian Regulatory Authority in the position of building the Technical Support Organization as part of its on organization. International cooperation played an important role in capacity building of Romanian regulatory body and providing necessary assistance in performing regulatory activities or support in development of regulatory framework. Fellowships and technical visits, workshops and training courses provided through IAEA TC at national or regional level, technical assistance provided by European Commission (EC) through PHARE Projects, all provided valuable contribution in assuring training of regulatory staff and development of proper regulatory framework in Romania. Therefore, Romanian Regulatory Authority is putting a strong accent on strengthening and promoting international cooperation through IAEA Technical Cooperation Programme, Molls between regulatory bodies, as one of the key elements in supporting capacity building of regulatory authorities in countries having small or embarking on nuclear power program. Building networks between training centers and research facilities and establishments of regional training centers represent one of the future viable options in preserving knowledge in nuclear field. (author)

Interpersonal goal support in achieving ideals and oughts: The role of dispositional regulatory focus

NARCIS (Netherlands)

Righetti, F.; Kumashiro, M.

2012-01-01

The present work examines the role of each partner's regulatory focus in the phenomenon of interpersonal goal support in close relationships. We examined the impact of regulatory orientation for interpersonal support of both ideal and ought self goals. Consistent with expectations, two studies

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...

Adolescent threat-related interpretive bias and its modification: the moderating role of regulatory control

NARCIS (Netherlands)

Salemink, E.; Wiers, R.W.

2012-01-01

Dual process models describe psychopathology as the consequence of an imbalance between a fast, impulsive system and a regulatory control system and have recently been applied to anxiety disorders. The aim of the current study was to specifically examine the role of a regulatory control system in

Regulatory effect of connexin 43 on basal Ca2+ signaling in rat ventricular myocytes.

Directory of Open Access Journals (Sweden)

Chen Li

Full Text Available BACKGROUND: It has been found that gap junction-associated intracellular Ca(2+ [Ca(2+](i disturbance contributes to the arrhythmogenesis and hyperconstriction in diseased heart. However, whether functional gaps are also involved in the regulation of normal Ca(2+ signaling, in particular the basal [Ca(2+](i activities, is unclear. METHODS AND RESULTS: Global and local Ca(2+ signaling and gap permeability were monitored in cultured neonatal rat ventricular myocytes (NRVMs and freshly isolated mouse ventricular myocytes by Fluo4/AM and Lucifer yellow (LY, respectively. The results showed that inhibition of gap communication by heptanol, Gap 27 and flufenamic acid or interference of connexin 43 (Cx43 with siRNA led to a significant suppression of LY uptake and, importantly, attenuations of global Ca(2+ transients and local Ca(2+ sparks in monolayer NRVMs and Ca(2+ sparks in adult ventricular myocytes. In contrast, overexpression of rat-Cx43 in NRVMs induced enhancements in the above measurements, and so did in HEK293 cells expressing rat Cx43. Additionally, membrane-permeable inositol 1,4,5-trisphosphate (IP(3 butyryloxymethyl ester and phenylephrine, an agonist of adrenergic receptor, could relieve the inhibited Ca(2+ signal and LY uptake by gap uncouplers, whereas blockade of IP(3 receptor with xestospongin C or 2-aminoethoxydiphenylborate mimicked the effects of gap inhibitors. More importantly, all these gap-associated effects on Ca(2+ signaling were also found in single NRVMs that only have hemichannels instead of gap junctions. Further immunostaining/immunoblotting single myocytes with antibody against Cx43 demonstrated apparent increases in membrane labeling of Cx43 and non-junctional Cx43 in overexpressed cells, suggesting functional hemichannels exist and also contribute to the Ca(2+ signaling regulation in cardiomyocytes. CONCLUSIONS: These data demonstrate that Cx43-associated gap coupling plays a role in the regulation of resting Ca(2

An analysis of pharmaceutical experience with decades of rat carcinogenicity testing: support for a proposal to modify current regulatory guidelines.

Science.gov (United States)

Sistare, Frank D; Morton, Daniel; Alden, Carl; Christensen, Joel; Keller, Douglas; Jonghe, Sandra De; Storer, Richard D; Reddy, M Vijayaraj; Kraynak, Andrew; Trela, Bruce; Bienvenu, Jean-Guy; Bjurström, Sivert; Bosmans, Vanessa; Brewster, David; Colman, Karyn; Dominick, Mark; Evans, John; Hailey, James R; Kinter, Lewis; Liu, Matt; Mahrt, Charles; Marien, Dirk; Myer, James; Perry, Richard; Potenta, Daniel; Roth, Arthur; Sherratt, Philip; Singer, Thomas; Slim, Rabih; Soper, Keith; Fransson-Steen, Ronny; Stoltz, James; Turner, Oliver; Turnquist, Susan; van Heerden, Marjolein; Woicke, Jochen; DeGeorge, Joseph J

2011-06-01

Data collected from 182 marketed and nonmarketed pharmaceuticals demonstrate that there is little value gained in conducting a rat two-year carcinogenicity study for compounds that lack: (1) histopathologic risk factors for rat neoplasia in chronic toxicology studies, (2) evidence of hormonal perturbation, and (3) positive genetic toxicology results. Using a single positive result among these three criteria as a test for outcome in the two-year study, fifty-two of sixty-six rat tumorigens were correctly identified, yielding 79% test sensitivity. When all three criteria were negative, sixty-two of seventy-six pharmaceuticals (82%) were correctly predicted to be rat noncarcinogens. The fourteen rat false negatives had two-year study findings of questionable human relevance. Applying these criteria to eighty-six additional chemicals identified by the International Agency for Research on Cancer as likely human carcinogens and to drugs withdrawn from the market for carcinogenicity concerns confirmed their sensitivity for predicting rat carcinogenicity outcome. These analyses support a proposal to refine regulatory criteria for conducting a two-year rat study to be based on assessment of histopathologic findings from a rat six-month study, evidence of hormonal perturbation, genetic toxicology results, and the findings of a six-month transgenic mouse carcinogenicity study. This proposed decision paradigm has the potential to eliminate over 40% of rat two-year testing on new pharmaceuticals without compromise to patient safety.

Eosinophilic spleen colonies are produced in rat-marrow-transplanted but not in murine-marrow-transplanted mice

International Nuclear Information System (INIS)

Szabo, L.G.; Kelemen, E.

1988-01-01

Differential counts of about 5000 splenic clusters and colonies developing in whole-body-irradiated mice and rats were made, using semi-serial histological sections prepared 9 to 12 d after transplantation with bone marrow haemopoietic cells. The investigated mouse and rat spleens were from syngeneically, allogeneically, or xenogeneically transplanted recipients. Splenic eosinophil clusters were always found when rat eosinophil-producing progenitors were present in the inoculum, whereas murine inocula failed to produce splenic eosinophilic clusters even in the syngeneic mouse. The limiting factor in the production pf splenic eosinophilic clusters was the appropriate donor progenitor/committed stem cell itself. Changes in the percentages of eosinophil clusters with the number of injected cells and with increased doses of irradiation, as well as formation of rat eosinophil colonies in mice, as against mainly clusters in rats, themselves show that regulatory mechanisms of the recipients also play a role. These regulatory mechanisms cannot be attributed to the splenic microenvironment. (author)

The role of serotoninergic neurons in rats agressive behaviour.

Science.gov (United States)

Czlonkowski, A; Kostowski, W; Markowska, L; Markiewicz, L; Wiśniewska, I

1975-10-01

Lesions of the dorsal and medial raphe nuclei that caused a marked decrease of the 5-HT level in the forebrain induced in groupped rats intraspecies aggressiveness but failed to increase mouse-killing behaviour. In rats isolated for 3 weeks lesions of the raphe nuclei did not change behaviour of "killers" and natural "non-killers". The role of 5-HT in mechanism of the aggressive behaviour is discussed.

Estrous cycle dependent fluctuations of regulatory neuropeptides in the lower urinary tract of female rats upon colon-bladder cross-sensitization.

Directory of Open Access Journals (Sweden)

Xiao-Qing Pan

Full Text Available Co-morbidity of bladder, bowel, and non-specific pelvic pain symptoms is highly prevalent in women. Little evidence is present on modulation of pelvic pain syndromes by sex hormones, therefore, the objective of this study was to clarify the effects of hormonal fluctuations within the estrous cycle on regulatory neuropeptides in female rats using a model of neurogenic bladder dysfunction. The estrous cycle in female rats (Sprague-Dawley, 230-250 g was assessed by vaginal smears and weight of uterine horns. Neurogenic bladder dysfunction was induced by a single inflammatory insult to the distal colon. Protein expression of calcitonin gene related peptide (CGRP, substance P (SP, nerve growth factor (NGF, and brain derived neurotrophic factor (BDNF in the pelvic organs, sensory ganglia and lumbosacral spinal cord was compared in rats in proestrus (high estrogen vs diestrus (low estrogen. Under normal physiological conditions, concentration of SP and CGRP was similar in the distal colon and urinary bladder during all phases of the estrous cycle, however, acute colitis induced a significant up-regulation of CGRP content in the colon (by 63% and urinary bladder (by 54%, p≤0.05 to control of rats in proestrus. These changes were accompanied by a significant diminution of CGRP content in L6-S2 DRG after colonic treatment, likely associated with its release in the periphery. In rats with high estrogen at the time of testing (proestrus, experimental colitis caused a significant up-regulation of BDNF colonic content from 26.1±8.5 pg/ml to 83.4±32.5 pg/ml (N = 7, p≤0.05 to control and also induced similar effects on BDNF in the urinary bladder which was also up-regulated by 5-fold in rats in proestrus (p≤0.05 to respective control. Our results demonstrate estrous cycle dependent fluctuations of regulatory neuropeptides in the lower urinary tract upon colon-bladder cross-sensitization, which may contribute to pain fluctuations in female patients

Deciphering Fur transcriptional regulatory network highlights its complex role beyond iron metabolism in Escherichia coli

DEFF Research Database (Denmark)

Seo, Sang Woo; Kim, Donghyuk; Latif, Haythem

2014-01-01

The ferric uptake regulator (Fur) plays a critical role in the transcriptional regulation of iron metabolism. However, the full regulatory potential of Fur remains undefined. Here we comprehensively reconstruct the Fur transcriptional regulatory network in Escherichia coli K-12 MG1655 in response...

The role of self-regulatory efficacy, moral disengagement and guilt on doping likelihood: A social cognitive theory perspective.

Science.gov (United States)

Ring, Christopher; Kavussanu, Maria

2018-03-01

Given the concern over doping in sport, researchers have begun to explore the role played by self-regulatory processes in the decision whether to use banned performance-enhancing substances. Grounded on Bandura's (1991) theory of moral thought and action, this study examined the role of self-regulatory efficacy, moral disengagement and anticipated guilt on the likelihood to use a banned substance among college athletes. Doping self-regulatory efficacy was associated with doping likelihood both directly (b = -.16, P self-regulatory efficacy influences the likelihood to use banned performance-enhancing substances both directly and indirectly via moral disengagement.

Sterol regulatory element binding protein 2 overexpression is associated with reduced adipogenesis and ectopic fat accumulation in transgenic spontaneously hypertensive rats

Czech Academy of Sciences Publication Activity Database

Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Šilhavý, Jan; Trnovská, J.; Kazdová, L.; Pravenec, Michal

2014-01-01

Roč. 63, č. 5 (2014), s. 587-590 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LH12061 Institutional support: RVO:67985823 Keywords : sterol regulatory element binding protein 2 * transgenic * spontaneously hypertensive rat * lipid metabolism Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.293, year: 2014

The regulatory effects of fish oil and chitosan on hepatic lipogenic signals in high-fat diet-induced obese rats.

Science.gov (United States)

Chiu, Chen-Yuan; Chang, Tien-Chia; Liu, Shing-Hwa; Chiang, Meng-Tsan

2017-10-01

The present study investigated the regulatory effects of fish oil and chitosan on the signals of hepatic lipid metabolism and the postulated mechanism in high-fat diet-induced obese rats. Diet supplementation of chitosan and fish oil efficiently suppressed the increased weights in body and livers of high-fat diet-fed rats. Supplementation of chitosan and fish oil significantly decreased the activities of hepatic lipid biosynthesis-related enzymes and efficiently regulated plasma lipoprotein homeostasis. Both chitosan and fish oil significantly ameliorated the alterations in the protein expressions of hepatic lipogenic transcription factors (LXRα and PPARα), and could also significantly regulate the downstream hepatic lipogenic genes (FAS, HMGCR, CYP7A1, FATP, FABP, AOX, and ABCA) expressions in high-fat diet-fed rats. These results suggest that both fish oil and chitosan exerts downregulative effects on hepatic lipid metabolism in high-fat diet-induced obese rats via the LXRα inhibition and PPARα activation, which further affect the expressions of hepatic lipogenesis-associated genes. Copyright © 2017. Published by Elsevier B.V.

Regulatory networks, legal federalism, and multi-level regulatory systems

OpenAIRE

Kerber, Wolfgang; Wendel, Julia

2016-01-01

Transnational regulatory networks play important roles in multi-level regulatory regimes, as e.g, the European Union. In this paper we analyze the role of regulatory networks from the perspective of the economic theory of legal federalism. Often sophisticated intermediate institutional solutions between pure centralisation and pure decentralisation can help to solve complex tradeoff problems between the benefits and problems of centralised and decentralised solutions. Drawing upon the insight...

The role of regulatory uncertainty in certificate markets: A case study of the Swedish/Norwegian market

International Nuclear Information System (INIS)

Fagiani, Riccardo; Hakvoort, Rudi

2014-01-01

Price volatility in green certificate markets reflects uncertainty over future prices, representing a major source of risk for renewable energy generators. Price risk is considered the principal deficiency of this market-based policy since it causes investors to require higher returns. Moreover, investors are exposed to regulatory risk; namely, the risk that a change in the regulation will materially impact the certificate price. Regulatory uncertainty is reflected in market volatility exacerbating certificate price risk. Using an econometric approach, we investigate the role of regulatory changes on price volatility in the Swedish certificate market. The results of our analysis indicate that regulatory changes strongly affect certificate markets, resulting in periods of higher volatility. Moreover, we analyze whether certificate price volatility has changed after creating a joint Swedish/Norwegian market. Results indicate that the ambivalence surrounding the creation of this bigger market led to a period of increased price volatility between 2010 and 2011. Overall, this article brings a better understanding of the role of regulatory uncertainty on certificate markets, and gives evidence for its negative impact in terms of increased price volatility. - Highlights: • Paper analyzes the impact of regulatory changes on certificate price volatility. • Regulatory changes affect market volatility and price risk. • Regulatory uncertainty harms certificate markets. • The bigger Swedish/Norwegian market has not resulted in lower volatility yet

Protective Effects of Total Glucosides of Paeony on N-nitrosodiethylamine-induced Hepatocellular Carcinoma in Rats via Down-regulation of Regulatory B Cells.

Science.gov (United States)

Song, S S; Yuan, P F; Li, P P; Wu, H X; Ni, W J; Lu, J T; Wei, W

2015-01-01

Total glucoside of paeony (TGP), extracted from the root of Paeonia Lactiflora, has been known to show anti-inflammatory, anti-oxidative, hepato-protective and immuno-regulatory activities. The aim of this present study was to determine the anti-tumor effect of TGP against N-nitrosodiethylamine (DEN)-induced hepatocellular carcinoma (HCC) in rats, and to find the related mechanisms. Rat HCC model was established by intragastrically administrating with DEN (8 mg/kg). We found the number of tumor nodules and the index of liver and spleen were increased in the model group compared with the normal group, and was significantly decreased by TGP. Additionally, TGP obviously improved the hepatic pathological lesions induced by DEN, and decreased the elevated levels of serum alanine aminotransferase (ALT), glutamic oxalacetic transaminase (AST), alkaline phosphatase (ALP) and alpha fetoprotein (AFP) by DEN. Moreover, TGP decreased the level of B cell-activating factor (BAFF) and the proportion of IL-10-producing regulatory B cells (Bregs), and the decrease of BAFF by TGP is positively correlated to the decrease of IL-10-producing Bregs by TGP. These results suggest that TGP had a good therapeutic action on DEN-induced HCC rats, which might be due to its down-regulation of Bregs through reducing the level of BAFF.

Role of technical and scientific support organization In Indonesian regulatory body

International Nuclear Information System (INIS)

Yusri Heni, N.A.; Zarkasih, A.S.; Liliana, Y.P.; Salman, S.

2007-01-01

Indonesian Nuclear Energy Regulatory Agency (BAPETEN) has the function in controlling the utility of nuclear energy through regulation, licensing and inspection, with the aim, interalia, to ensure the welfare, the security and the peace of people, to assure the safety and the health of workers and public, and the environmental protection, and to prevent diversion of purpose of the nuclear material utilization (Article 14 and 15 of Act no 10, 1997 on Nuclear Energy). The role and quality of technical and scientific expertise in supporting regulatory systems are importance increase the effectiveness and public confidence. The Center for Regulatory Assessment of Nuclear Installation and Nuclear Material and Center for Regulatory Assessment of Radiation Facilities and Radioactive Sources as part of BAPETEN organization has a function as technical and scientific support for regulatory systems. The purpose of this function is to provide technical and scientific basis for decisions and activities regarding nuclear and radiation safety during regulatory processes, such as in the developing and establishing regulation, technical verification for licensing, assessment of inspection funding and enforcement. In order to meet the quality and effectiveness of technical and scientific result activity, those two centers for regulatory assesment used internal and external technical experts and joint cooperation with universities, research institutes or laboratories. The development of technical and scientific strategic planning in enhancing nuclear and radiation safety is done by the following increasing of : Human resources and expertise by internal and external training or on the job training; number for computer code to perform safety analysis, capability and quality for review and assessment, national and international cooperation, etc. (author)

Antigen-induced pleural eosinophilia is suppressed in diabetic rats: role of corticosteroid hormones

Directory of Open Access Journals (Sweden)

Bruno L Diaz

1997-12-01

Full Text Available Previous studies have evidenced for the existence of interactive regulatory mechanisms between insulin and steroid hormones in different systems. In this study, we have investigated whether endogenous corticosteroids could be implicated in the hyporeactivity to antigen challenge observed in sensitized diabetic rats. Alloxinated rats showed a long-lasting increase in the blood glucose levels and a reduction in the number of pleural mast cells at 48 and 72 hr, but not at 24 hr after alloxan administration. In parallel, they also showed a significant elevation in the plasma levels of corticosterone together with an increase in the adrenal/body weight ratio. Antigen-evoked eosinophil accumulation appeared significantly reduced in rats pretreated with dexamethasone as well as in those rendered diabetic 72 hr after alloxan. In the same way, naive animals treated with dexamethasone also responded with a significant decrease in the number of pleural mast cells. Interestingly, when sensitized diabetic rats were pretreated with the steroid antagonist RU 38486 a reversion of the reduction in the allergen-induced eosinophil accumulation was noted. We conclude that the down-regulation of the allergic inflammatory response in diabetic rats is close-related to reduction in mast cell numbers and over expression of endogenous corticosteroids.

Altered expression of the cell cycle regulatory protein cyclin D1 in the rat dentate gyrus after adrenalectomy-induced granular cell lass

NARCIS (Netherlands)

Postigo, JA; Van der Werf, YD; Korf, J; Krugers, HJ

1998-01-01

The loss of dentate gyrus (DG) granular cells after removal of the rat adrenal glands (ADX) is mediated by a process that is apoptotic in nature. The present study was initiated to compare changes in the immunocytochemical distribution of the cell-cycle regulatory protein cyclin D1, which has been

The role of women in nuclear - attracting public participation in regulatory decision-making process

Science.gov (United States)

Mohamad Jais, Azlina; Hassan, Najwa

2018-01-01

Public participation is vital in demonstrating transparency and enhancing effectiveness of a nuclear regulatory process. As such, it is necessary for nuclear practitioners to involve the public in key nuclear delivery milestones. This paper specifically discusses challenges faced in attracting public participation throughout the nuclear regulatory decision-making process, and highlights the roles of women in nuclear (WiN) in initiating the said public discourse.

Free radicals in hypoxic rat diaphragm contractility: no role for xanthine oxidase.

NARCIS (Netherlands)

Heunks, L.M.A.; Machiels, H.A.; Abreu, R.A. de; Zhu, X.; Heijden, E. van der; Dekhuijzen, P.N.R.

2001-01-01

Recent evidence indicates that hypoxia enhances the generation of oxidants. Little is known about the role of free radicals in contractility of the rat diaphragm during hypoxia. We hypothesized that antioxidants improve contractility of the hypoxic rat diaphragm and that xanthine oxidase (XO) is an

[Changes of CD(4)(+) Foxp3+ regulatory T cells and CD(4)(+)IL-17+T cells in acrolein exposure rats].

Science.gov (United States)

Wei, Ming; Tu, Ling; Liang, Yinghong; Li, Jia; Gong, Yanjie; Zhang, Yihua; Yang, Lu

2015-09-01

To evaluate the changes of CD(4)(+) IL-17+T (Th17) and CD(4)(+)Foxp3+regulatory T (Treg) cells in peripheral blood and bronchoalveolar lavage fluid (BALF) , and therefore to explore the role of Th17 and Treg in acrolein exposure airway inflammation in rats. Forty male Wistar rats were randomly divided into 4 groups: a 2 wk acrolein exposure group, a 4 wk acrolein exposure group, a 2 wk control group and a 4 wk control group (n=10 each). Cells in BALF were collected and analyzed by absolute and differential cell counts.IL-17 and IL-6 levels in serum and BALF were tested by enzyme linked immunosorbent assay (ELISA). The proportion of CD(4)(+)IL-17+T and CD(4)(+) Foxp3+Treg in peripheral blood and BALF were determined by flow cytometry.The mRNA expressions of IL-17 and Foxp3 were measured by real-time PCR. Comparisons of the data between different groups were performed using one-way ANOVA, and SNK and Games-Howell test were used for comparison between 2 groups. Levels of IL-17 were remarkable increased in the 2 wk acrolein exposure group and the 4 wk acrolein exposure group in serum [(52.64 ± 1.89) ng/L, (76.73 ± 5.57) ng/L], and BALF [(79.07 ± 5.67) ng/L, (96.61 ± 6.44) ng/L] compared with the 2 wk control group [(40.05 ± 3.12) ng/L, (56.75 ± 4.37) ng/L] and the 4 wk control group [(38.75 ± 3.23) ng/L, (53.27 ± 4.48) ng/L], all Pcells and macrophages (r=0.5126, 0.5437, all Pcells and an vary of inflammatory cytokines were evident in airway inflammation of acrolein exposed rats, suggesting that Treg was involved in the immunological regulation and Th17 was associated with the persistent inflammation in acrolein induced airway inflammation in rats.

Moving through the stressed genome: Emerging regulatory roles for transposons in plant stress tolerance

Directory of Open Access Journals (Sweden)

Negi Pooja

2016-10-01

Full Text Available The recognition of a positive correlation between organism genome size with its transposable element (TE content, represents a key discovery of the field of genome biology. Considerable evidence accumulated since then suggests the involvement of TEs in genome structure, evolution and function. The global genome reorganization brought about by transposon activity might play an adaptive/regulatory role in the host response to environmental challenges, reminiscent of McClintock’s original ’Controlling Element’ hypothesis. This regulatory aspect of TEs is also garnering support in light of the recent evidences which project TEs as distributed genomic control modules. According to this view, TEs are capable of actively reprogramming host genes circuits and ultimately fine-tuning the host response to specific environmental stimuli. Moreover, the stress-induced changes in epigenetic status of TE activity may allow TEs to propagate their stress responsive elements to host genes; the resulting genome fluidity can permit phenotypic plasticity and adaptation to stress. Given their predominating presence in the plant genomes, nested organization in the genic regions and potential regulatory role in stress response, TEs hold unexplored potential for crop improvement programs. This review intends to present the current information about the roles played by TEs in plant genome organization, evolution and function, and highlight the regulatory mechanisms in plant stress responses. We will also briefly discuss the connection between TE activity, host epigenetic response and phenotypic plasticity as a critical link for traversing the translational bridge from a purely basic study of TEs, to the applied field of stress adaptation and crop improvement.

Moving through the Stressed Genome: Emerging Regulatory Roles for Transposons in Plant Stress Response.

Science.gov (United States)

Negi, Pooja; Rai, Archana N; Suprasanna, Penna

2016-01-01

The recognition of a positive correlation between organism genome size with its transposable element (TE) content, represents a key discovery of the field of genome biology. Considerable evidence accumulated since then suggests the involvement of TEs in genome structure, evolution and function. The global genome reorganization brought about by transposon activity might play an adaptive/regulatory role in the host response to environmental challenges, reminiscent of McClintock's original 'Controlling Element' hypothesis. This regulatory aspect of TEs is also garnering support in light of the recent evidences, which project TEs as "distributed genomic control modules." According to this view, TEs are capable of actively reprogramming host genes circuits and ultimately fine-tuning the host response to specific environmental stimuli. Moreover, the stress-induced changes in epigenetic status of TE activity may allow TEs to propagate their stress responsive elements to host genes; the resulting genome fluidity can permit phenotypic plasticity and adaptation to stress. Given their predominating presence in the plant genomes, nested organization in the genic regions and potential regulatory role in stress response, TEs hold unexplored potential for crop improvement programs. This review intends to present the current information about the roles played by TEs in plant genome organization, evolution, and function and highlight the regulatory mechanisms in plant stress responses. We will also briefly discuss the connection between TE activity, host epigenetic response and phenotypic plasticity as a critical link for traversing the translational bridge from a purely basic study of TEs, to the applied field of stress adaptation and crop improvement.

Moving through the Stressed Genome: Emerging Regulatory Roles for Transposons in Plant Stress Response

Science.gov (United States)

Negi, Pooja; Rai, Archana N.; Suprasanna, Penna

2016-01-01

The recognition of a positive correlation between organism genome size with its transposable element (TE) content, represents a key discovery of the field of genome biology. Considerable evidence accumulated since then suggests the involvement of TEs in genome structure, evolution and function. The global genome reorganization brought about by transposon activity might play an adaptive/regulatory role in the host response to environmental challenges, reminiscent of McClintock's original ‘Controlling Element’ hypothesis. This regulatory aspect of TEs is also garnering support in light of the recent evidences, which project TEs as “distributed genomic control modules.” According to this view, TEs are capable of actively reprogramming host genes circuits and ultimately fine-tuning the host response to specific environmental stimuli. Moreover, the stress-induced changes in epigenetic status of TE activity may allow TEs to propagate their stress responsive elements to host genes; the resulting genome fluidity can permit phenotypic plasticity and adaptation to stress. Given their predominating presence in the plant genomes, nested organization in the genic regions and potential regulatory role in stress response, TEs hold unexplored potential for crop improvement programs. This review intends to present the current information about the roles played by TEs in plant genome organization, evolution, and function and highlight the regulatory mechanisms in plant stress responses. We will also briefly discuss the connection between TE activity, host epigenetic response and phenotypic plasticity as a critical link for traversing the translational bridge from a purely basic study of TEs, to the applied field of stress adaptation and crop improvement. PMID:27777577

Role of the heme oxygenases in abnormalities of the mesenteric circulation in cirrhotic rats.

Science.gov (United States)

Sacerdoti, David; Abraham, Nader G; Oyekan, Adebayo O; Yang, Liming; Gatta, Angelo; McGiff, John C

2004-02-01

Carbon monoxide (CO), a product of heme metabolism by heme-oxygenase (HO), has biological actions similar to those of nitric oxide (NO). The role of CO in decreasing vascular responses to constrictor agents produced by experimental cirrhosis induced by carbon tetrachloride was evaluated before and after inhibition of HO with tin-mesoporphyrin (SnMP) in the perfused superior mesenteric vasculature (SMV) of cirrhotic and normal rats and in normal rats transfected with the human HO-1 (HHO-1) gene. Perfusion pressure and vasoconstrictor responses of the SMV to KCl, phenylephrine (PE), and endothelin-1 (ET-1) were decreased in cirrhotic rats. SnMP increased SMV perfusion pressure and restored the constrictor responses of the SMV to KCl, PE, and ET-1 in cirrhotic rats. The relative roles of NO and CO in producing hyporeactivity of the SMV to PE in cirrhotic rats were examined. Vasoconstrictor responses to PE were successively augmented by stepwise inhibition of CO and NO production, suggesting a complementary role for these gases in the regulation of reactivity of the SMV. Expression of constitutive but not of inducible HO (HO-1) was increased in the SMV of cirrhotic rats as was HO activity. Administration of adenovirus containing HHO-1 gene produced detection of HHO-1 RNA and increased HO activity in the SMV within 7 days. Rats transfected with HO-1 demonstrated reduction in both perfusion pressure and vasoconstrictor responses to PE in the SMV. We propose that HO is an essential component in mechanisms that modulate reactivity of the mesenteric circulation in experimental hepatic cirrhosis in rats.

[Regulatory role of NKT cells in the prevention of type 1 diabetes].

Science.gov (United States)

Ghazarian, Liana; Simoni, Yannick; Pingris, Karine; Beaudoin, Lucie; Lehuen, Agnès

2013-01-01

Type 1 diabetes is an autoimmune disease resulting from the destruction of pancreatic β cells by the immune system. NKT cells are innate-like T cells that can exert potent immuno-regulatory functions. The regulatory role of NKT cells was initially proposed after the observed decreased frequency of this subset in mouse models of type 1 diabetes, as well as in patients developing various autoimmune pathologies. Increasing NKT cell frequency and function prevent the development of type 1 diabetes in mouse models. Several mechanisms including IL-4 and IL-10 production by NKT cells and the accumulation of tolerogenic dendritic cells are critical for the dampening of pathogenic anti-islet T cell responses by NKT cells. Importantly, these cells can at the same time prevent diabetes and promote efficient immune responses against infectious agents. These results strengthen the potential role of NKT cells as a key target for the development of therapeutic strategies against type 1 diabetes. © 2013 médecine/sciences – Inserm.

Genetic control of differential acetylation in diabetic rats.

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Pamela J Kaisaki

Full Text Available Post-translational protein modifications such as acetylation have significant regulatory roles in metabolic processes, but their relationship to both variation in gene expression and DNA sequence is unclear. We address this question in the Goto-Kakizaki (GK rat inbred strain, a model of polygenic type 2 diabetes. Expression of the NAD-dependent deacetylase Sirtuin-3 is down-regulated in GK rats compared to normoglycemic Brown Norway (BN rats. We show first that a promoter SNP causes down-regulation of Sirtuin-3 expression in GK rats. We then use mass-spectrometry to identify proteome-wide differential lysine acetylation of putative Sirtuin-3 protein targets in livers of GK and BN rats. These include many proteins in pathways connected to diabetes and metabolic syndrome. We finally sequence GK and BN liver transcriptomes and find that mRNA expression of these targets does not differ significantly between GK and BN rats, in contrast to other components of the same pathways. We conclude that physiological differences between GK and BN rats are mediated by a combination of differential protein acetylation and gene transcription and that genetic variation can modulate acetylation independently of expression.

Electrical stimulation of the substantia nigra reticulata : Detection of neuronal extracellular GABA in the ventromedial thalamus and its regulatory mechanism using microdialysis in awake rats

NARCIS (Netherlands)

Timmerman, W; Westerink, B.H.C.

A combination of electrical stimulation and microdialysis was used to study the nigrothalamic gamma aminobutyric acid (GABA)ergic system and its regulatory mechanisms in awake rats. Extracellular GABA levels in the ventromedial nucleus of the thalamus were detected in S-min fractions collected

DMPD: The role of the interferon regulatory factor (IRF) family in dendritic celldevelopment and function. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17702640 The role of the interferon regulatory factor (IRF) family in dendritic celldevelopment and function...in dendritic celldevelopment and function. PubmedID 17702640 Title The role of th...e interferon regulatory factor (IRF) family in dendritic celldevelopment and function. Authors Gabriele L, O

Therapeutic Effect of CD4+CD25+ Regulatory T Cells Amplified In Vitro on Experimental Autoimmune Neuritis in Rats

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Feng-Jie Wang

2018-05-01

Full Text Available Background/Aims: This study aimed to explore whether the adoptive transfusion of autologous CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs has a therapeutic effect on Experimental autoimmune neuritis (EAN model rats, and it provides new experimental and theoretical bases for the immunotherapy of Guillain-Barre syndrome (GBS. Methods: CD4+CD25+ Tregs were sorted from the spleens of rats using immunomagnetic bead separation techniques combined with flow cytometry. Their in vitro inhibitory function was determined using a lymphocyte proliferation inhibition test, and their purity was confirmed by flow cytometry. Cells were stimulated using CD3/CD28 monoclonal antibodies and were cultured in culture medium containing interleukin 2 (IL-2, transforming growth factor-β (TGF-β and rapamycin. After 15 days of amplification, CD4+CD25+ Tregs were collected and transfused into EAN model rats. Changes in the pathology and electron microscopical morphology of rat sciatic nerves in the normal group, untreated group, low-dose group (2 × 107 and high-dose group (4 × 107 were observed, and the expression of CD4+CD25+FOXP3 in peripheral blood in the four groups of rats was detected by flow cytometry. Results: Compared with rats in the untreated group, rats in the treatment groups had significantly reduced infiltration of inflammatory cells in the sciatic nerve, as well as myelin and axonal damage. Additionally, the CD4+CD25+ Tregs levels in peripheral blood were significantly higher than those in the untreated group (P< 0. 05. Moreover, the therapeutic effect became more significant with an increase in the dose of adoptive transfusion. Conclusion: Adoptive transfusion of CD4+CD25+ Tregs into EAN model rats has significant therapeutic effects.

The Regulatory Role of Nuclear Factor Kappa B in the Heart of Hereditary Hypertriglyceridemic Rat

Czech Academy of Sciences Publication Activity Database

Vranková, S.; Barta, A.; Klimentová, J.; Dovinová, I.; Líšková, Silvia; Dobešová, Zdenka; Pecháňová, O.; Kuneš, Jaroslav; Zicha, Josef

2016-01-01

Roč. 2016, č. 2016 (2016), s. 9814038 ISSN 1942-0900 R&D Projects: GA MZd(CZ) NV15-25396A Institutional support: RVO:67985823 Keywords : nuclear factor-kB * nitric oxide * reactive oxygen species * heart * hereditary hypertriglyceridemic rats Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.593, year: 2016

Neurotoxic effects of carambola in rats: the role of oxalate.

Science.gov (United States)

Chen, Chien-Liang; Chou, Kang-Ju; Wang, Jyh-Seng; Yeh, Jeng-Hsien; Fang, Hua-Chang; Chung, Hsiao-Min

2002-05-01

Carambola (star fruit) has been reported to contain neurotoxins that cause convulsions, hiccups, or death in uremic patients, and prolong barbiturate-induced sleeping time in rats. The constituent responsible for these effects remains uncertain. Carambola contains a large quantity of oxalate, which can induce depression of cerebral function and seizures. This study was conducted to investigate the role of oxalate in carambola toxicity in rats. The effects on barbiturate-induced sleeping time and death caused by intraperitoneal administration of carambola juice were observed in Sprague-Dawley rats. To obtain a dose-dependent response curve and evaluate the lethal dose, rats were treated with serial amounts of pure carambola juice diluted with normal saline in a volume of 1:1. To test the role of oxalate in the neurotoxic effect of carambola, either 5.33 g/kg carambola after oxalate removal or 5.33 g/kg of pure carambola juice diluted with normal saline were administered intraperitoneally, while the control group was given normal saline before pentobarbital injection. The effects of carambola and oxalate-removed carambola on barbiturate-induced sleeping time were compared with those of saline. To assess the lethal effect of oxalate in carambola, we gave rats chemical oxalate at comparable concentrations to the oxalate content of carambola. Carambola juice administration prolonged barbiturate-induced sleeping time in a dose-dependent manner. The sleeping time of rats that received normal saline and 1.33 g/kg, 2.67 g/kg, 5.33 g/kg, and 10.67 g/kg of carambola juice were 66 +/- 16.6, 93.7 +/- 13.4, 113.3 +/- 11.4, 117.5 +/- 29.0, and 172.5 +/- 38.8 minutes, respectively. The three higher-dose groups had longer sleeping times than controls (p carambola juice. Four of eight rats in the 10.67-g/kg group and all rats in the 21.33 g/kg and chemical oxalate groups died after seizure. Lethal doses of carambola juice were rendered harmless by the oxalate removal procedure

[Changes of CD(4)(+)Foxp3(+) regulatory T cells and CD(4)(+)IL-17(+)T cells in cigarette smoke-exposed rats].

Science.gov (United States)

Meng, Jing-jing; Zhong, Xiao-ning; Bai, Jing; He, Zhi-yi; Zhang, Jian-quan; Huang, Qiu-pin

2012-01-01

To evaluate the changes of CD(4)(+)IL-17(+) T (Th17) and CD(4)(+)Foxp3(+) regulatory T (Treg) cells in peripheral blood and bronchoalveolar lavage fluid (BALF), and therefore to explore the role of Th17 and Treg in cigarette smoke-induced airway inflammation/COPD in rats. Forty male Wistar rats were randomly divided into 4 groups: a 12 wk smoke-exposure group, a 24 wk smoke-exposure group, a 12 wk control group and a 24 wk control group (n = 10 each). Cells in BALF were collected and analyzed by absolute and differential cell counts. IL-17 and IL-6 levels in serum and BALF were tested by enzyme linked immunosorbent assay (ELISA). The proportion of CD(4)(+)IL-17(+) T and CD(4)(+)Foxp3(+) Treg in peripheral blood and BALF were determined by flow cytometry. The mRNA expressions of IL-17 and Foxp3 were measured by real-time PCR. Comparisons of the data between different groups were performed using one-way ANOVA, and SNK and Games-Howell test were used for comparison between 2 groups. Levels of IL-17 were remarkable increased in the 12 wk smoke-exposure group and the 24 wk smoke-exposure group in serum [(52.6 ± 1.8) ng/L, (75.4 ± 6.0) ng/L] and BALF [(78.1 ± 5.8) ng/L, (95.0 ± 6.8) ng/L] compared with the 12 wk control group [(40.0 ± 3.2)ng/L, (54.5 ± 4.6) ng/L] and the 24 wk control group [(36.7 ± 3.2) ng/L, (53.9 ± 3.7) ng/L], all P cells and macrophages (r = 0.512, 0.543, all P cells and an increase of inflammatory cytokines were evident in airway inflammation of cigarette smoke-exposed rats, suggesting that Treg was involved in the immunological regulation and Th17 was associated with the persistent inflammation in cigarette smoke-induced airway inflammation in rats.

Information to Improve Public Perceptions of the Food and Drug Administration (FDA’s Tobacco Regulatory Role

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Amira Osman

2018-04-01

Full Text Available While the Food and Drug Administration (FDA has had regulatory authority over tobacco products since 2009, public awareness of this authority remains limited. This research examines several broad types of information about FDA tobacco regulatory mission that may improve the perceptions of FDA as a tobacco regulator. Using Amazon Mechanical Turk, 1766 adults, smokers and non-smokers, were randomly assigned to view a statement about FDA regulatory authority that varied three information types in a 2 × 2 × 2 between subjects experimental design: (1 FDA’s roles in regulating tobacco (yes/no; (2 The scientific basis of regulations (yes/no; and (3 A potential protective function of regulations (yes/no. Using factorial ANOVA, we estimated the main and interactive effects of all three types of information and of smoking status on the perceptions of FDA. Participants that were exposed to information on FDA roles reported higher FDA credibility and a greater perceived knowledge of FDA than those who did not. Exposure to information about the scientific basis of regulations led to more negative views of the tobacco industry. Participants who learned of the FDA’s commitment to protecting the public reported higher FDA credibility and more positive attitudes toward regulations than those who did not learn of this commitment. We observed no significant interaction effects. The findings suggest that providing information about the regulatory roles and protective characterization of the FDA’s tobacco regulatory mission positively influence public perceptions of FDA and tobacco regulations.

Teratology studies in the rat.

Science.gov (United States)

Leroy, Mariline; Allais, Linda

2013-01-01

The rat is the rodent species of choice for the regulatory safety testing of xenobiotics, such as medicinal products, food additives, and other chemicals. Many decades of experience and extensive data have accumulated for both general and developmental toxicology investigations in this species. The high fertility and large litter size of the rat are advantages for teratogenicity testing. The study designs are well defined in the regulatory guidelines and are relatively standardized between testing laboratories across the world. Teratology studies address maternal- and embryo-toxicity following exposure during the period of organogenesis. This chapter describes the design and conduct of a teratology study in the rat in compliance with the regulatory guidelines. The procedures for the handling and housing of the pregnant animals, the caesarean examinations and the sampling of fetuses for morphological examinations are described. The utility and design of preliminary studies and the inclusion of satellite animals in the main study for toxicokinetic sampling are discussed.

Regulatory impairments following selective 6-OHDA lesions of the neostriatum.

Science.gov (United States)

Dunnett, S B; Iversen, S D

1982-02-01

6-Hydroxydopamine lesions of the ventrolateral (VLC) but not anteromedial (AMC) caudate-putamen in rats resulted in a greater post-operative reduction in body weight and water intake than seen in animals with sham lesions. Once animals had fully resumed spontaneous food and water intake, a series of regulatory challenges were administered, and the AMC rats showed a reduced enhancement of drinking following injection of hypertonic saline. The results are interpreted in terms of a heterogeneous striatal convergence of nigrostriatal and cortical regulatory mechanisms.

Ischemia-reperfusion injury in rat fatty liver: role of nutritional status.

Science.gov (United States)

Caraceni, P; Nardo, B; Domenicali, M; Turi, P; Vici, M; Simoncini, M; De Maria, N; Trevisani, F; Van Thiel, D H; Derenzini, M; Cavallari, A; Bernardi, M

1999-04-01

Fatty livers are more sensitive to the deleterious effects of ischemia-reperfusion than normal livers. Nutritional status greatly modulates this injury in normal livers, but its role in the specific setting of fatty liver is unknown. This study aimed to determine the effect of nutritional status on warm ischemia-reperfusion injury in rat fatty livers. Fed and fasted rats with normal or fatty liver induced by a choline deficient diet underwent 1 hour of lobar ischemia and reperfusion. Rat survival was determined for 7 days. Serum transaminases, liver histology and cell ultrastructure were assessed before and after ischemia, and at 30 minutes, 2 hours, 8 hours, and 24 hours after reperfusion. Survival was also determined in fatty fasted rats supplemented with glucose before surgery. The preischemic hepatic glycogen was measured in all groups. Whereas survival was similar in fasted and fed rats with normal liver (90% vs. 100%), fasting dramatically reduced survival in rats with fatty liver (14% vs. 64%, P nutritional repletion procedure may be part of a treatment strategy aimed to prevent ischemia-reperfusion injury in fatty livers.

The role of the Nuclear Regulatory Commission in the management of nuclear waste

International Nuclear Information System (INIS)

Thompson, H.L. Jr.

1988-01-01

In general, the US Nuclear Regulatory Commission (NRC) is responsible for reviewing and making licensing decisions to ensure that the US Department of Energy's (DOE's) high-level waste repository is designed, constructed, and operated without unreasonable risk to public health and safety. In implementing this responsibility, however, the commission's guidance to the staff is that, in the absence of unresolved safety concerns, the NRC regulatory program will not delay the executive branch's program as set forth in the DOE project decision schedule. The NRC role for the next several years will be to develop its licensing framework and to consult with DOE on its plans. An essential ingredient in the success of both NRC's and DOE's respective missions is the need for free and open exchange of information, which will assure us that the concerns of all parties are addressed. With regard to low-level radioactive waste, the states have the lead responsibility for disposal. The NRC also provides assistance to the states and compacts on such items as regulatory programs, site characterization, and mixed waste disposal. Another of the NRC's roles is in the management of uranium mill tailings. Currently, most of the NRC's attention is focused on ensuring adequate long-term stabilization of tailings

The U.S. Nuclear Regulatory Commission's role in the management of radioactive wastes

International Nuclear Information System (INIS)

Bernero, R.M.; Kalman, K.L.

1991-01-01

This paper discusses the U.S. Nuclear Regulatory Commission's (NRC's) role in the management of radioactive waste. It provides an overview of the NRC's programs for the management of High-Level and Low-Level radioctive wastes and uranium mill tailings. (author) 7 refs

Activation of counter-regulatory mechanisms in a rat renal acute rejection model

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Salomon Daniel R

2008-02-01

Full Text Available Abstract Background Microarray analysis provides a powerful approach to identify gene expression alterations following transplantation. In patients the heterogeneity of graft specimens, co-morbidity, co-medications and the challenges in sample collection and preparation complicate conclusions regarding the underlying mechanisms of graft injury, rejection and immune regulation. Results We used a rat kidney transplantation model with strict transplant and sample preparation procedures to analyze genome wide changes in gene expression four days after syngeneic and allogeneic transplantation. Both interventions were associated with substantial changes in gene expression. After allogeneic transplantation, genes and pathways related to transport and metabolism were predominantly down-regulated consistent with rejection-mediated graft injury and dysfunction. Up-regulated genes were primarily related to the acute immune response including antigen presentation, T-cell receptor signaling, apoptosis, interferon signaling and complement cascades. We observed a cytokine and chemokine expression profile consistent with activation of a Th1-cell response. A novel finding was up-regulation of several regulatory and protective genes after allogeneic transplantation, specifically IL10, Bcl2a1, C4bpa, Ctla4, HO-1 and the SOCS family. Conclusion Our data indicate that in parallel with the predicted activation of immune response and tissue injury pathways, there is simultaneous activation of pathways for counter regulatory and protective mechanisms that would balance and limit the ongoing inflammatory/immune responses. The pathophysiological mechanisms behind and the clinical consequences of alterations in expression of these gene classes in acute rejection, injury and dysfunction vs. protection and immunoregulation, prompt further analyses and open new aspects for therapeutic approaches.

Role of in-house safety analysis and research activities in regulatory decision making

International Nuclear Information System (INIS)

Pradhan, Santosh K.; Nagrale, Dhanesh B.; Gaikwad, Avinash J.

2015-01-01

Achievement of an acceptable level of nuclear safety is an essential requirement for the peaceful utilization of nuclear energy. The success of Global Nuclear Safety Regime is built upon a foundation of research. Such research has been sponsored by Governments and industry and has led to improved designs, safer and more reliable plant operation, and improvements in operating plant efficiency. A key element of this research has been the nuclear safety research performed or sponsored by regulatory organizations. In part, it has been the safety research performed or sponsored by regulatory organizations that has contributed to improved safety and has laid the foundation for activities such as risk-informed regulation, plant life extension, improved plant performance (e.g. power uprates) and new plant designs. The regulatory research program is meant to improve the regulatory authority’s knowledge where uncertainty exists, where safety margins are not well-characterized, and where regulatory decisions need to be confirmed in existing or new designs and technologies. The regulatory body get research initiated either in-house or by the licensee or through technical support organizations (TSOs). Research and analysis carried out within the regulatory body is of immense value in this context. This could be in the form of analysis of safety significant events, analysis of severe accidents, review of operating experience, independent checks of critical designs and even review of operator responses under different situations towards arriving at modifications to training programmes and licensing procedures for operating personnel. A latent benefit of regulatory research carried out by the regulators themselves is that it improves their technical competence considerably which in turn leads to high quality safety reviews and improved regulation in general. The aim of the present paper is to provide an overview of role of regulatory research and the in-house regulatory safety

Role of Resistive Self-Regulatory Efficacy and Moral Disengagement in the Relationship between Values and Aggressiveness in Athletes

OpenAIRE

Albouza Y; d'Arripe-Longueville F; Corrion K

2017-01-01

This study examined whether athletes’ values are related to aggressiveness through self-regulatory mechanisms. Athletes (N=225) completed four questionnaires to assess their values, resistive self-regulatory efficacy, moral disengagement and aggressiveness. The results of structural equation modeling showed a good fit to the data and illustrated that: (a) The status and moral values were indirectly associated with aggressiveness through the mediating roles of resistive self-regulatory efficac...

The role of learning environment on high school chemistry students' motivation and self-regulatory processes

Science.gov (United States)

Judd, Jeffrey S.

Changes to the global workforce and technological advancements require graduating high school students to be more autonomous, self-directed, and critical in their thinking. To reflect societal changes, current educational reform has focused on developing more problem-based, collaborative, and student-centered classrooms to promote effective self-regulatory learning strategies, with the goal of helping students adapt to future learning situations and become life-long learners. This study identifies key features that may characterize these "powerful learning environments", which I term "high self-regulating learning environments" for ease of discussion, and examine the environment's role on students' motivation and self-regulatory processes. Using direct observation, surveys, and formal and informal interviews, I identified perceptions, motivations, and self-regulatory strategies of 67 students in my high school chemistry classes as they completed academic tasks in both high and low self-regulating learning environments. With social cognitive theory as a theoretical framework, I then examined how students' beliefs and processes changed after they moved from low to a high self-regulating learning environment. Analyses revealed that key features such as task meaning, utility, complexity, and control appeared to play a role in promoting positive changes in students' motivation and self-regulation. As embedded cases, I also included four students identified as high self-regulating, and four students identified as low self-regulating to examine whether the key features of high and low self-regulating learning environments played a similar role in both groups. Analysis of findings indicates that key features did play a significant role in promoting positive changes in both groups, with high self-regulating students' motivation and self-regulatory strategies generally remaining higher than the low self-regulating students; this was the case in both environments. Findings

Effects of Some Indigenous Plants of North Karnataka (India) on Cardiovascular and Glucose Regulatory Systems in Alloxan-Induced Diabetic Rats.

Science.gov (United States)

Das, Kusal K; Chadchan, Kailash S; Reddy, R Chandramouli; Biradar, M S; Kanthe, Pallavi S; Patil, Bheemshetty S; Ambekar, Jeevan G; Bagoji, Ishwar B; Das, Swastika

2017-11-08

Kenaf (Hibiscus cannabinus Linn, Pundi), Chick pea (Cicer arietinum Linn, Chana) and Prickly lettuce (Lactuca scariola Linn, Hattaraki) leaves are a few of indigenous plants which are routinely consumed by the people of north Karnataka in the diet. Studies on these plants showed some potential anti-diabetic efficacies. To examine the effect of leaves extracts of Hibiscus cannabinus Linn, Cicer arietinum Linn and Lactuca scariola Linn on cardiovascular integrity, glucose homeostasis and oxygen sensing cell signaling mechanisms in alloxan induced diabetic rats. In vitro and in vivo tests on glucose regulatory systems and molecular markers such as - NOS3, HIF- 1α and VEGF were conducted in alloxan induced diabetic rats supplemented with all the three plant extracts. Electrophysiological analysis (HRV, LF: HF ratio, baroreflex sensitivity, BRS) and histopathogy of myocardial tissues and elastic artery were evaluated in diabetic rats treated with L. scariola linn. Out of these three plant extracts, Lactuca scariola Linn supplementation showed significant beneficial effects on glucose homeostasis and oxygen sensing cell signaling pathways in alloxaninduced diabetic rats. Furthermore, effects of sub chronic supplementation of Lactuca scariola Linn aqueous extracts showed significant improvement in sympatho-vagal balance in diabetic rats by increase of Heart Rate Variability (HRV) and regaining of Baroreflex Sensitivity (BRS). These results were also corroborated with myocardial and elastic artery histopathology of Lactuca scariola Linn supplemented diabetic rats. These findings indicate an adaptive pathway for glucose homeostasis, oxygen sensing cell signaling mechanisms and cardio protective actions in alloxan - induced diabetic rats supplemented with Lactuca scariola Linn extracts. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The potential role of IGF-I receptor mRNA in rats with diabetic retinopathy

Institute of Scientific and Technical Information of China (English)

匡洪宇; 邹伟; 刘丹; 史榕荇; 程丽华; 殷慧清; 刘晓民

2003-01-01

Objective To evaluate the potential role of insulin-like growth factor-1 receptor mRNA(IGF-IR mRNA) in the onset and development of retinopathy in diabetic rats.Methods A diabetic model was duplicated in Wistar rats. The early changes in the retina were examined using light and transmission electron microscopy. Expression of IGF-IR mRNA was analyzed using in situ hybridization.Results Weak expression of IGF-IR mRNA(5%) was found in retinas of normal rats, but was significantly increased (15% and 18%) in the retinas of diabetic rats after 3 and 6 months of diabetes (P＜0.01). In situ hybridization and morphological study demonstrated that there was a positive correlation between IGF-IR mRNA expression and retinal changes at various stages.Conclusion Increased IGF-IR mRNA might play an important role in the onset and development of diabetic retinopathy.

Nuclear Regulatory Commission and its role in environmental standards

International Nuclear Information System (INIS)

Mattson, R.J.

1976-01-01

The NRC and its predecessors in the Atomic Energy Commission represent considerable experience in environmental standards setting. The Atomic Energy Act of 1954, the 1970 Supreme Court decision on Federal pre-emption of radiation standards, the Calvert Cliffs decision of 1971, the Energy Reorganization Act of 1974, and the Appendix I ''as low as reasonably achievable'' decision of 1975, to name a few of our landmarks, are representative of the scars and the achievements of being in a role of national leadership in radiation protection. The NRC, through a variety of legislative authorities, administrative regulations, regulatory guides, and national consensus standards regulates the commercial applications of nuclear energy. The purposes of regulation are the protection of the environment, public health and safety, and national security. To understand NRC's responsibilities relative to those of other Federal and state agencies concerned with environmental protection, we will briefly review the legislative authorities which underlie our regulatory program. Then we will examine the intent or the spirit of that program as embodied in our system of regulations, guides, and standards. Finally we will speak to what's happening today and what we see in the future for environmental standards

Intraperitoneal injection of neuropeptide Y (NPY) alters neurotrophin rat hypothalamic levels: Implications for NPY potential role in stress-related disorders.

Science.gov (United States)

Gelfo, Francesca; De Bartolo, Paola; Tirassa, Paola; Croce, Nicoletta; Caltagirone, Carlo; Petrosini, Laura; Angelucci, Francesco

2011-06-01

Neuropeptide Y (NPY) is a 36-amino acid peptide which exerts several regulatory actions within peripheral and central nervous systems. Among NPY actions preclinical and clinical data have suggested that the anxiolytic and antidepressant actions of NPY may be related to its antagonist action on the hypothalamic-pituitary-adrenal (HPA) axis. The neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are proteins involved in the growth, survival and function of neurons. In addition to this, a possible role of neurotrophins, particularly BDNF, in HPA axis hyperactivation has been proposed. To characterize the effect of NPY on the production of neurotrophins in the hypothalamus we exposed young adult rats to NPY intraperitoneal administration for three consecutive days and then evaluated BDNF and NGF synthesis in this brain region. We found that NPY treatment decreased BDNF and increased NGF production in the hypothalamus. Given the role of neurotrophins in the hypothalamus, these findings, although preliminary, provide evidence for a role of NPY as inhibitor of HPA axis and support the idea that NPY might be involved in pathologies characterized by HPA axis dysfunctions. Copyright © 2011 Elsevier Inc. All rights reserved.

Changes in Hypoxia-Inducible Factor-1 (HIF-1) and Regulatory Prolyl Hydroxylase (PHD) Enzymes Following Hypoxic-Ischemic Injury in the Neonatal Rat.

Science.gov (United States)

Chu, Hannah X; Jones, Nicole M

2016-03-01

Hypoxia leads to activation of many cellular adaptive processes which are regulated by the transcription factor hypoxia-inducible factor-1 (HIF-1). HIF-1 consists of HIF-1α and HIF-1ß subunits and levels of HIF-1α protein are regulated by HIF prolyl-hydroxylase enzymes (PHD1, 2, 3). The aim of the current study was to investigate the expression of HIF-1α and PHDs at various time points after hypoxia-ischemia (HI), using a neonatal rat model of HI brain injury. Sprague-Dawley rat pups (postnatal day 7) were anaesthetized and underwent right carotid artery occlusion and were then exposed to 6 % oxygen for 2.5 h at 37 °C. HI injured animals demonstrated a significant reduction in the size of the ipsilateral hemisphere, compared to sham controls. Protein analysis using western blotting and enzyme-linked immunosorbent assay showed that 24 h after HI, there was a significant increase in PHD3 protein and an increase of HIF-1α compared to controls. At the 72 h time point, there was a reduction in PHD3 protein, which appeared to relate to cellular loss. There were no changes in PHD1 or PHD2 protein levels after HI when compared to age-matched controls. Further studies are necessary to establish roles for the HIF-1 regulatory enzyme PHD3 in brain injury processes.

Pb exposure attenuates hypersensitivity in vivo by increasing regulatory T cells

Energy Technology Data Exchange (ETDEWEB)

Fang, Liang [Department of Immunology, Fourth Military Medical University, Xi' an 710032 (China); Zhao, Fang; Shen, Xuefeng [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Ouyang, Weiming [Laboratory of Cell Biology, Division of Monoclonal Antibodies, Office of Biotechnology Products, Center for Drug Evaluation and Research, United States Food and Drug Administration, Bethesda, MD (United States); Liu, Xinqin; Xu, Yan; Yu, Tao [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Jin, Boquan [Department of Immunology, Fourth Military Medical University, Xi' an 710032 (China); Chen, Jingyuan, E-mail: jy_chen@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Luo, Wenjing, E-mail: luowenj@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China)

2012-12-01

Pb is a common environmental pollutant affecting various organs. Exposure of the immune system to Pb leads to immunosuppression or immunodysregulation. Although previous studies showed that Pb exposure can modulate the function of helper T cells, Pb immunotoxicity remains incompletely understood. In this study, we investigated the effect of Pb exposure on T cell development, and the underlying mechanism of Pb-induced suppression of the delayed-type hypersensitivity (DTH) response in vivo. Sprague–Dawley rats were exposed to 300 ppm Pb-acetate solution via the drinking water for six weeks, and we found that Pb exposure significantly increased Pb concentrations in the blood by 4.2-fold (p < 0.05) as compared to those in the control rats. In Pb-exposed rats, the amount of thymic CD4{sup +}CD8{sup −} and peripheral CD4{sup +} T cells was significantly reduced, whereas, CD8{sup +} population was not affected. In contrast to conventional CD4{sup +} T cells, Foxp3{sup +} regulatory T cells (Tregs) were increased in both the thymus and peripheral lymphoid organs of Pb-exposed rats. In line with the increase of Tregs, the DTH response of Pb-exposed rats was markedly suppressed. Depletion of Tregs reversed the suppression of DTH response by Pb-exposed CD4{sup +} T cells in an adoptive transfer model, suggesting a critical role of the increased Tregs in suppressing the DTH response. Collectively, this study revealed that Pb-exposure may upregulate Tregs, thereby leading to immunosuppression. -- Highlights: ► Pb exposure impaired CD4{sup +} thymic T cell development. ► Peripheral T lymphocytes were reduced following Pb exposure. ► Pb exposure increases thymic and peripheral Treg cells in rats. ► Tregs played a critical role in Pb-exposure-induced immune suppression.

THE ROLE OF SELF-REGULATORY AUDITING ASSOCIATIONS IN ARRANGEMENT OF AUDIT ACTIVITIES QUALITY CONTROL

Directory of Open Access Journals (Sweden)

Zinaida P. Arharova

2013-01-01

Full Text Available The role of self-regulatory organizations in audit activities quality control is revealed in this article. Creation of a united audit association is the basis of certain regulating and auditing functions transfer from the government to the public sector.

Role of the vomeronasal organ on the estral cycle reduction by pheromones in the rat.

Science.gov (United States)

Mora, O A; Sánchez-Criado, J E; Guisado, S

1985-09-01

The role of he vomeronasal organ on the estral cycle reduction induced by pheromones is studied in adult female wistar rats. The animals were divided in three groups: I, intact rats; II, vomeronasalectomized rats (VNX); and III, sham operated rats (sham). Each group was submitted to another three distinct conditions from the day they were weaned (21 days old): Isolated female rats; with male odors from two adult males of tested sexual potency, and isolated rats again. The isolated intact rats show mainly 5 day length cycles. The groups I and III (intacts and sham) with male odors, show 4 day length cycles. The VNX animals show 5 day cycles in any one experimental conditions. These results support the idea that the vomeronasal organ is the receptor of the male reducing cycle pheromone in the female rat.

The Role of Advisory Committees on Regulatory functions: Argentine Experience

International Nuclear Information System (INIS)

Larcher, A. M.; Arias, C.; Kunst, J. J.; Perez, R. M.; Rudelli, M.

2004-01-01

The Argentine Nuclear Regulatory Authority (NRA) has appointed a consultants body that advises its Board of Directors on aspects related to authorization's granting to individuals for the use of radioisotopes and ionizing radiation in medicine, research and industry. Such committee, whose existence goes back to the year 1958, is integrated by prominent professionals knowledgeable about ionizing radiation and radioisotopes applications in the medical, biomedical and industrial fields, representing important professional associations or institutions related to the practices in question. Originally, the committee was conceived as a consultation body to fulfil two important functions: To produce, in a regular way, authorized opinions at experts level to settle down questions relative to the regulation of practices, new at that time in the country, and To submit to a peer review applications for individual authorization for different uses of ionizing radiation previously it's granting by the Regulatory Authority. In this paper the role of the advisory council is analyzed from a historical perspective trying to emphasize an outstanding aspect not sufficiently analyzed linked to the capability that advisory bodies, with representative users' presence, can reach in the interpretation of regulatory standards based on a performance philosophy. Such approach outlines the permanent dilemma about the performance level of the licensee that should satisfy the Regulatory Authority. Once the broad objectives of radiation protection has been defined professional criteria is required for applying them to different practices. Balance between flexibility and avoidance of excessive uncertainty is desirable. In the authors' opinion the inclusion, inside the regulator's structure of consultants bodies giving direct participation to qualified stakeholders, far from harming the necessary independence that should characterize the regulator, on the contrary, allows to have an excellent social

Hematopoietic chimerism and transplantation tolerance: a role for regulatory T cells

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Lise ePasquet

2011-12-01

Full Text Available The major obstacle in transplantation medicine is rejection of donor tissues by the host’s immune system. Immunosuppressive drugs can delay but not prevent loss of transplants, and their efficiency is strongly impacted by inter-individual pharmacokinetic differences. Moreover, due to the global immunosuppression induced and to the broad distribution of their targets amongst human tissues, these drugs have severe side effects. Induction of donor-specific non-responsiveness (i.e. immunological tolerance to transplants would solve these problems and would substantially ameliorate patients’ quality of life. It is widely believed that bone marrow or hematopoietic stem cell transplantation, and resulting (mixed hematopoietic chimerism, invariably leads to immunological tolerance to organs of the same donor. A careful analysis of the literature, reviewed here, indeed shows that chimerism consistently prolongs allograft survival. However, in absence of additional conditioning leading to the development of active regulatory mechanisms, it does not prevent chronic rejection. A central role for active tolerance in transplantation-tolerance is also supported by recent data showing that genuine immunological tolerance to organ allografts can be achieved by combining induction of hematopoietic chimerism with infusion of regulatory T lymphocytes. Therefore, conditioning regimens that lead to the establishment of hematopoietic chimerism plus active regulatory mechanisms appear required for induction of genuine tolerance to allogeneic grafts.

Induction of Foxp3-expressing regulatory T-cells by donor blood transfusion is required for tolerance to rat liver allografts.

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Yuta Abe

Full Text Available BACKGROUND: Donor-specific blood transfusion (DST prior to solid organ transplantation has been shown to induce long-term allograft survival in the absence of immunosuppressive therapy. Although the mechanisms underlying DST-induced allograft tolerance are not well defined, there is evidence to suggest DST induces one or more populations of antigen-specific regulatory cells that suppress allograft rejection. However, neither the identity nor the regulatory properties of these tolerogenic lymphocytes have been reported. Therefore, the objective of this study was to define the kinetics, phenotype and suppressive function of the regulatory cells induced by DST alone or in combination with liver allograft transplantation (LTx. METHODOLOGY/PRINCIPAL FINDINGS: Tolerance to Dark Agouti (DA; RT1(a rat liver allografts was induced by injection (iv of 1 ml of heparinized DA blood to naïve Lewis (LEW; RT1(l rats once per week for 4 weeks prior to LTx. We found that preoperative DST alone generates CD4(+ T-cells that when transferred into naïve LEW recipients are capable of suppressing DA liver allograft rejection and promoting long-term survival of the graft and recipient. However, these DST-generated T-cells did not express the regulatory T-cell (Treg transcription factor Foxp3 nor did they suppress alloantigen (DA-induced activation of LEW T-cells in vitro suggesting that these lymphocytes are not fully functional regulatory Tregs. We did observe that DST+LTx (but not DST alone induced the time-dependent formation of CD4(+Foxp3(+ Tregs that potently suppressed alloantigen-induced activation of naïve LEW T-cells in vitro and liver allograft rejection in vivo. Finally, we present data demonstrating that virtually all of the Foxp3-expressing Tregs reside within the CD4(+CD45RC(- population whereas in which approximately 50% of these Tregs express CD25. CONCLUSIONS/SIGNIFICANCE: We conclude that preoperative DST, in the absence of liver allograft

Modulatory role of allopurinol on xanthine oxidoreductase system and antioxidant status in irradiated rats

International Nuclear Information System (INIS)

Zahran, A.M.; Azab, Kh.Sh.; Abbady, M.I.

2006-01-01

Allopurinol is a xanthine oxidase (XO) inhibitor, used for management of hyperuricaema. It acts on purine catabolism without disrupting the biosynthesis of purine. The present work was conducted to examine the role of xanthine oxidase inhibitor (allopurinol) in minimizing radiation injuries in male albino rats. Allopurinol was given to rats via intraperitoneal (i.p) injection at a dose of 30 mg/kg body wt/day for 7 successive days before starting irradiation and 14 successive days during and in between exposure to gamma radiation. Rats were exposed to whole body gamma radiation, delivered as 1 Gy every other day up to total dose 8 Gy. Results demonstrate that treatment with allopurinol by the regime assumed in the present study minimized significantly the amount of thiobarbituric acid reactive substances (TBARS), product of lipid peroxidation, in liver, intestine and plasma. This effect was associated with significant amelioration in xanthine oxidoreductase (XOR) system as observed on the 1st and 7th days post last radiation fraction. The severity of changes in antioxidant parameters namely: superoxide dismutase (SOD), Catalase (CAT) and reduced glutathione (GSH) were less manifested in liver, intestine and blood as compared to irradiated rats. The levels of nitric oxide (NO) were significantly improved in plasma and the two investigated tissues as compared to irradiated rats. A significant decrease in plasma uric acid concentration was recorded on the 1st and 7th days post last allopurinol dose. However, significant amelioration was recorded in the plasma uric acid of rats treated with allopurinol before and during radiation exposure as compared to irradiated rats. Accordingly, it could be concluded that XO inhibitor (allopurinol) play a significant role in minimizing the tissue damages upon exposure to ionizing radiation via preventing the over production of reactive oxygen species (ROS) in irradiated cells through the XOR system of irradiation rats

KCNQ channels are involved in the regulatory volume decrease response in primary neonatal rat cardiomyocytes

DEFF Research Database (Denmark)

Calloe, Kirstine; Nielsen, Morten Schak; Grunnet, Morten

2007-01-01

of neonatal rat cardiomyocytes was studied in intact single cells attached to coverslips, i.e. with an intact cytoskeleton. The potential contribution of KCNQ (Kv7) channels to the RVD response and the possible involvement of the F-actin cytoskeleton were investigated. The rate of RVD was significantly...... changes the structure of the F-actin cytoskeleton, leading to a more rounded cell shape, less pronounced F-actin stress fibers and patches of actin. In the presence of cytochalasin D (1 microM), a potent inhibitor of actin polymerization, the RVD response was strongly reduced, confirming a possible role...... for an intact F-actin cytoskeleton in linking cell swelling to activation of ion transport in neonatal rat cardiomyocytes. Udgivelsesdato: 2007-Jun...

Intracellular [Ca2+] and Vo2 after manipulation of the free-energy of the Na+/Ca(2+)-exchanger in isolated rat ventricular myocytes

NARCIS (Netherlands)

Fiolet, J. W.; Baartscheer, A.; Schumacher, C. A.

1995-01-01

We have investigated whether the Na+/Ca(2+)-exchanger has a functional regulatory role in the control of oxidative metabolism in suspensions of isolated rat ventricular myocytes. Therefore we simultaneously measured intracellular [Ca2+] ([Ca2+]i) with Indo-1 and respiratory rate (Vo2) after abrupt

Pb exposure attenuates hypersensitivity in vivo by increasing regulatory T cells

International Nuclear Information System (INIS)

Fang, Liang; Zhao, Fang; Shen, Xuefeng; Ouyang, Weiming; Liu, Xinqin; Xu, Yan; Yu, Tao; Jin, Boquan; Chen, Jingyuan; Luo, Wenjing

2012-01-01

Pb is a common environmental pollutant affecting various organs. Exposure of the immune system to Pb leads to immunosuppression or immunodysregulation. Although previous studies showed that Pb exposure can modulate the function of helper T cells, Pb immunotoxicity remains incompletely understood. In this study, we investigated the effect of Pb exposure on T cell development, and the underlying mechanism of Pb-induced suppression of the delayed-type hypersensitivity (DTH) response in vivo. Sprague–Dawley rats were exposed to 300 ppm Pb-acetate solution via the drinking water for six weeks, and we found that Pb exposure significantly increased Pb concentrations in the blood by 4.2-fold (p + CD8 − and peripheral CD4 + T cells was significantly reduced, whereas, CD8 + population was not affected. In contrast to conventional CD4 + T cells, Foxp3 + regulatory T cells (Tregs) were increased in both the thymus and peripheral lymphoid organs of Pb-exposed rats. In line with the increase of Tregs, the DTH response of Pb-exposed rats was markedly suppressed. Depletion of Tregs reversed the suppression of DTH response by Pb-exposed CD4 + T cells in an adoptive transfer model, suggesting a critical role of the increased Tregs in suppressing the DTH response. Collectively, this study revealed that Pb-exposure may upregulate Tregs, thereby leading to immunosuppression. -- Highlights: ► Pb exposure impaired CD4 + thymic T cell development. ► Peripheral T lymphocytes were reduced following Pb exposure. ► Pb exposure increases thymic and peripheral Treg cells in rats. ► Tregs played a critical role in Pb-exposure-induced immune suppression.

Resistin enhances the expansion of regulatory T cells through modulation of dendritic cells

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Han Seung

2010-06-01

Full Text Available Abstract Background Resistin, a member of adipokine family, is known to be involved in the modulation of immune responses including inflammatory activity. Interestingly, resistin is secreted by adipocytes in mice and rats whereas it is secreted by leukocytes in humans. However, the mechanism behind the effect of resistin on the expansion of regulatory T cells (Tregs remains poorly understood. Therefore, we examined regulatory effect of resistin on the induction and cellular modification of Tregs. Results Both protein and mRNA expression of FoxP3, a representative marker of Tregs, increased in a dose-dependent manner when peripheral blood mononuclear cells were treated with resistin. At the same time, resistin had no direct effect on the induction of FoxP3 in CD4+ T cells, suggesting an indirect role through other cells type(s. Since DCs are an important player in the differentiation of T cells, we focused on the role of DCs in the modulation of Tregs by resistin. Resistin suppressed the expression of interferon regulatory factor (IRF-1 and its target cytokines, IL-6, IL-23p19 and IL-12p40, in DCs. Furthermore, FoxP3 expression is increased in CD4+ T cells when co-cultured with DCs and concomitantly treated with resistin. Conclusion Our results suggest that resistin induces expansion of functional Tregs only when co-cultured with DCs.

Negative emotions and behaviour: The role of regulatory emotional self-efficacy.

Science.gov (United States)

Mesurado, Belén; Vidal, Elisabeth Malonda; Mestre, Anna Llorca

2018-04-01

The objective of this study is to test a longitudinal model that analyses the direct effect of negative emotions (anger, depression and anxiety, wave 1) on prosocial and aggressive behaviour (wave 2) in adolescents. And the indirect effect of negative emotions (wave 1) on prosocial and aggressive behaviour (wave 2) through regulatory emotional self-efficacy. Data was obtained from 417 adolescents in a two-wave longitudinal study (225 girls, M age = 14.70 years) from schools located in Valencia, Spain. SEM was employed to explore longitudinal models. The results showed that anger had a direct relationship with prosocial behaviour and aggression, measured two years later. However, the depression and anxiety states did not predict prosociality and aggressiveness. The mediation role of regulatory emotional self-efficacy between negative emotion and behaviours was only partially confirmed. Finally, only the perception of self-efficacy in expressing positive affect is related to prosociality and aggressiveness. Copyright © 2018 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Gender-related difference in altered gene expression of a sterol regulatory element binding protein, SREBP-2, by lead nitrate in rats: correlation with development of hypercholesterolemia.

Science.gov (United States)

Kojima, Misaki; Degawa, Masakuni

2006-01-01

Changes in gene expression levels of hepatic sterol regulatory element binding protein-2 (SREBP-2) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) after a single i.v. injection of lead nitrate (LN, 100 micromol kg(-1) body weight) were examined comparatively by real time reverse transcriptase-polymerase chain reaction (RT-PCR) in male and female rats. Significant increases in the gene expression level of SREBP-2, a transcription factor for the HMGR gene, occurred at 6-12 h in male and at 24-36 h in female rats after LN-treatment. The gene expression level of HMGR, a rate-limiting enzyme for cholesterol biosynthesis, significantly increased at 3-48 h in male rats and 12-48 h in female rats. Subsequently, significant increases in the amount of hepatic total cholesterol in male and female rats were also observed at 3-48 h and 24-48 h, respectively. The present findings demonstrate that increases in gene expressions of hepatic SREBP-2 and HMGR and the amount of hepatic total cholesterol by LN occur earlier in male rats than in the females, and that increases in the gene expression level of HMGR and the amount of hepatic total cholesterol occur prior to the increase in the gene expression level of SREBP-2 in either sex of rats. Copyright (c) 2006 John Wiley & Sons, Ltd.

The kidneys play a central role in the clearance of rhGH in rats

DEFF Research Database (Denmark)

Vestergaard, Bill; Thygesen, Peter; Kreilgaard, Mads

2016-01-01

at treatment of patients with growth hormone disorders. The purpose of this study was to investigate the relative importance of the kidneys in the clearance of rhGH. The study employed a newly validated nephrectomy rat model and a population based pharmacokinetic approach to assess renal clearance of rh...... that renal clearance plays a pivotal role in the elimination of rhGH in rats....

Current role of the USNRC safety research program in support of the regulatory process

International Nuclear Information System (INIS)

Levine, S.

1979-01-01

The current role of the USNRC's safety research program is shown. Some aspects of this role in the wake of the TMI accident are discused as well as some historical perspective on the development of USNRC's program, its relationship with the NRC mission, an overview of the program activities and some recent research results, and finally the impact of the TMI accident in clarifiying needs for expedited and new research activities, including the need for a greatly enhanced use of probabilistic analysis techniques to improve the coherence of its regulatory process. (author)

Trust in regulatory regimes

NARCIS (Netherlands)

Six, Frédérique; Verhoest, Koen

2017-01-01

Within political and administrative sciences generally, trust as a concept is contested, especially in the field of regulatory governance. This groundbreaking book is the first to systematically explore the role and dynamics of trust within regulatory regimes. Conceptualizing, mapping and analyzing

Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma

International Nuclear Information System (INIS)

Valstar, Dingena L.; Schijf, Marcel A.; Nijkamp, Frans P.; Storm, Gert; Arts, Josje H.E.; Kuper, C. Frieke; Bloksma, Nanne; Henricks, Paul A.J.

2006-01-01

Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter inhaled compounds. These cells can produce many different mediators that have a putative role in asthma. In this study, we examined the role of AMs in lung function and airway inflammation of rats exposed to TMA. Female Brown Norway rats were sensitized by dermal application of TMA or received vehicle alone on days 0 and 7. One day before challenge, rats received intratracheally either empty or clodronate-containing liposomes to deplete the lungs of AMs. On day 21, all rats were challenged by inhalation of TMA in air. Lung function parameters were measured before, during, within 1 h after, and 24 h after challenge. IgE levels and parameters of inflammation and tissue damage were assessed 24 h after challenge. Sensitization with TMA led to decreased lung function parameters during and within 1 h after challenge as compared to non-sensitized rats. AM depletion alleviated the TMA-induced drop in lung function parameters and induced a faster recovery compared to sham-depleted TMA-sensitized rats. It also decreased the levels of serum IgE 24 h after challenge, but did not affect the sensitization-dependent increase in lung lavage fluid IL-6 and tissue TNF-α levels. In contrast, AM depletion augmented the TMA-induced tissue damage and inflammation 24 h after challenge. AMs seem to have a dual role in this model for TMA-induced occupational asthma since they potentiate the immediate TMA-induced decrease in lung function but tended to dampen the TMA-induced inflammatory reaction 24 h later

The role of basolateral amygdala adrenergic receptors in hippocampus dependent spatial memory in rat

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Vafaei A.L.

2008-03-01

Full Text Available Background and the purpose of the study: There are extensive evidences indicating that the noradrenergic system of the basolateral nucleus of the amygdala (BLA is involved in memory processes. The present study investigated the role of the BLA adrenergic receptors (ARs in hippocampus dependent spatial memory in place avoidance task in male rat. Material and Methods: Long Evans rats (n=150 were trained to avoid footshock in a 60° segment while foraging for scattered food on a circular (80-cm diameter arena. The rats were injected bilaterally in the BLA specific ARS (Adrenergic receptors agonist norepinephrine (NE, 0.5 and 1 µg/µl and specific β-ARs antagonist propranolol (PRO, 0.5 and 1 µg/µl before acquisition, after training or before retrieval of the place avoidance task. Control rats received vehicle at the same volume. The learning in a single 30-min session was assessed 24h later by a 30-min extinction trial in which the time to first entrance and the number of entrances to the shocked area measured the avoidance memory. Results: Acquisition and consolidation were enhanced and impaired significantly by NE and PRO when the drugs were injected 10 min before or immediately after training, respectively. In contrast, neither NE nor PRO influenced animal performances when injected before retention testing. Conclusion: Findings of this study indicates that adrenergic system of the BLA plays an important role in regulation of memory storage and show further evidences for the opinion that the BLA plays an important role in integrating hormonal and neurotransmitter influences on memory storage.

Regulatory focus and the family-work interface : the role of regulatory fit between cohabiting partners

NARCIS (Netherlands)

Demerouti, E.; Bakker, A.B.; Tetrick, L.

2014-01-01

The aim of the present study was to examine the impact of regulatory focus in goal pursuit and regulatory fit between marital partners on family conditions and the family–work interface. We hypothesized that when both partners are high on promotion focus (fit) they experience higher developmental

Institutions, regulatory role and economic growth of national economies

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Mladen Vedriš

2008-12-01

Full Text Available In the present time, characterized by the rapid disturbances in all time more connected global economy, territorially as well as structurally, the role of the state’s influence and responsibility with the adequate institutional addresses and procedures, defined in larger context, becomes the essential point not only of the further growth but also of the existing relations viability. It is simply because the encirclement does not function on the principle of status quo situation any more. Therefore, the role and significance of institutions, adequate regulatory role of these addresses, in the context of demand of permanent and stable economic growth, are of particular interest in the creation of this model. This analysis gains in importance studying the realized accelerated economic growth of states from some parts of the world, notably in the period after WW II. This question turned out to be exceptionally essential during the analysis of national strategies of accelerated economic growth (catch up strategy. On the other side of analysis are the transition period and the processes realized on the territory of the East and Central European states up to 1990 that were under the strong influence of the USSR. The attempts and mistakes in the quest for adequate balance of the market role were initially indoctrinated and led by the predominant conviction that the principles of Washington consensus will lead up to accelerated and efficient change of the entire structure of national economies and new frames for future behaviour. The problems that appeared very soon led to the establishment of significantly more balanced first the understanding and then to establishing significantly, more appropriate concept of balance and complementarity of market development with the permanently present role and responsibility of the state in this process and on this road.

Obesity-resistant S5B rats showed great cocaine conditioned place preference than the obesity-prone OM rats

Energy Technology Data Exchange (ETDEWEB)

Thanos, P.K.; Wang, G.; Thanos, P.K..; Kim, R.; Cho, J.; Michaelides, M.; Anderson, B.J.; Primeaux, S.D.; Bray, G.A.; Wang, G.-J.; Robinson, J.K.; Volkow, N.D.

2010-12-01

Dopamine (DA) and the DA D2 receptor (D2R) are involved in the rewarding and conditioned responses to food and drug rewards. Osborne-Mendel (OM) rats are genetically prone and S5B/P rats are genetically resistant to obesity when fed a high-fat diet. We hypothesized that the differential sensitivity of these two rat strains to natural rewards may also be reflected in sensitivity to drugs of abuse. Therefore, we tested whether OM and S5B/P rats showed a differential preference to cocaine using conditioned place preference (CPP). To also evaluate whether there is specific involvement of the D2R in this differential conditioning sensitivity, we then tested whether the D2R agonist bromocriptine (BC) would differentially affect the effects of cocaine in the two strains. OM and S5B/P rats were conditioned with cocaine (5 or 10 mg/kg) in one chamber and saline in another for 8 days. Rats were then tested for cocaine preference. The effects of BC (0.5, 1, 5, 10, 20 mg/kg) on cocaine preference were then assessed in subsequent test sessions. OM rats did not show a significant preference for the cocaine-paired chamber on test day. Only the S5B/P rats showed cocaine CPP. Later treatment with only the highest dose of BC resulted in reduced cocaine CPP in S5B/P rats when treated with 5 mg/kg cocaine and in OM rats treated with 10 mg/kg cocaine. Our results indicated that obesity-resistant S5B rats showed greater cocaine CPP than the obesity-prone OM rats. These findings do not support a theory of common vulnerability for reinforcer preferences (food and cocaine). However, they show that BC reduced cocaine conditioning effects supporting at least a partial regulatory role of D2R in conditioned responses to drugs.

Regulatory dendritic cells in autoimmunity: A comprehensive review.

Science.gov (United States)

Liu, Juan; Cao, Xuetao

2015-09-01

Dendritic cells (DCs) are professional antigen-presenting cells (APC) with significant phenotypic heterogeneity and functional plasticity. DCs play crucial roles in initiating effective adaptive immune responses for elimination of invading pathogens and also in inducing immune tolerance toward harmless components to maintain immune homeostasis. The regulatory capacity of DCs depends on their immature state and distinct subsets, yet not restricted to the immature state and one specialized subset. The tolerogenicity of DC is controlled by a complex network of environmental signals and cellular intrinsic mechanisms. Regulatory DCs play an important role in the maintenance of immunological tolerance via the induction of T cell unresponsiveness or apoptosis, and generation of regulatory T cells. DCs play essential roles in driving autoimmunity via promoting the activation of effector T cells such as T helper 1 and T helper 17 cells, and/or suppressing the generation of regulatory T cells. Besides, a breakdown of DCs-mediated tolerance due to abnormal environmental signals or breakdown of intrinsic regulatory mechanisms is closely linked with the pathogenesis of autoimmune diseases. Novel immunotherapy taking advantage of the tolerogenic potential of regulatory DCs is being developed for treatment of autoimmune diseases. In this review, we will describe the current understanding on the generation of regulatory DC and the role of regulatory DCs in promoting tolerogenic immune responses and suppressing autoimmune responses. The emerging roles of DCs dysfunction in the pathogenesis of autoimmune diseases and the potential application of regulatory DCs in the treatment of autoimmune diseases will also be discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ecological role of the giant root-rat (Tachyoryctes macrocephalus) in the Afroalpine ecosystem.

Science.gov (United States)

Šklíba, Jan; Vlasatá, Tereza; Lövy, Matěj; Hrouzková, Ema; Meheretu, Yonas; Sillero-Zubiri, Claudio; Šumbera, Radim

2017-07-01

Rodents with prevailing subterranean activity usually play an important role in the ecosystems of which they are a part due to the combined effect of herbivory and soil perturbation. This is the case for the giant root-rat Tachyoryctes macrocephalus endemic to the Afroalpine ecosystem of the Bale Mountains, Ethiopia. We studied the impact of root-rats on various ecosystem features within a 3.5-ha study locality dominated by Alchemilla pasture, which represents an optimal habitat for this species, in 2 periods of a year. The root-rats altered plant species composition, reducing the dominant forb, Alchemilla abyssinica, while enhancing Salvia merjame and a few other species, and reduced vegetation cover, but not the fresh plant biomass. Where burrows were abandoned by root-rats, other rodents took them over and A. abyssinica increased again. Root-rat burrowing created small-scale heterogeneity in soil compactness due to the backfilling of some unused burrow segments. Less compacted soil tended to be rich in nutrients, including carbon, nitrogen and phosphorus, which likely affected the plant growth on sites where the vegetation has been reduced as a result of root-rat foraging and burrowing. © 2016 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

Targeted resequencing of regulatory regions at schizophrenia risk loci: Role of rare functional variants at chromatin repressive states.

Science.gov (United States)

González-Peñas, Javier; Amigo, Jorge; Santomé, Luis; Sobrino, Beatriz; Brenlla, Julio; Agra, Santiago; Paz, Eduardo; Páramo, Mario; Carracedo, Ángel; Arrojo, Manuel; Costas, Javier

2016-07-01

There is mounting evidence that regulatory variation plays an important role in genetic risk for schizophrenia. Here, we specifically search for regulatory variants at risk by sequencing promoter regions of twenty-three genes implied in schizophrenia by copy number variant or genome-wide association studies. After strict quality control, a total of 55,206bp per sample were analyzed in 526 schizophrenia cases and 516 controls from Galicia, NW Spain, using the Applied Biosystems SOLiD System. Variants were filtered based on frequency from public databases, chromatin states from the RoadMap Epigenomics Consortium at tissues relevant for schizophrenia, such as fetal brain, mid-frontal lobe, and angular gyrus, and prediction of functionality from RegulomeDB. The proportion of rare variants at polycomb repressive chromatin state at relevant tissues was higher in cases than in controls. The proportion of rare variants with predicted regulatory role was significantly higher in cases than in controls (P=0.0028, OR=1.93, 95% C.I.=1.23-3.04). Combination of information from both sources led to the identification of an excess of carriers of rare variants with predicted regulatory role located at polycomb repressive chromatin state at relevant tissues in cases versus controls (P=0.0016, OR=19.34, 95% C.I.=2.45-2495.26). The variants are located at two genes affected by the 17q12 copy number variant, LHX1 and HNF1B. These data strongly suggest that a specific epigenetic mechanism, chromatin remodeling by histone modification during early development, may be impaired in a subset of schizophrenia patients, in agreement with previous data. Copyright © 2016 Elsevier B.V. All rights reserved.

Cardioprotective role of tadalafil against cisplatin-induced cardiovascular damage in rats.

Science.gov (United States)

Saleh, Rasha M; Awadin, Walaa F; El-Shafei, Reham A; Elseady, Yousef Y; Wehaish, Faheim E; Elshal, Mohamed F

2015-10-15

The present study investigated the possible cardioprotective effect of tadalafil (Tad) on cisplatin (CDDP)-induced cardiac and vascular damages in rats. A total number of seventy two healthy male albino rats initially weighting between 200 and 220 g were used and randomly divided into four groups,18 rats in each. The control group received no treatment; CDDP group received a single dose of CDDP (4 mg/kg) intraperitoneal (i.p.) per week for 4 weeks the duration of the experiment; Tad group received 0.4 mg/kg BW Tad i.p. daily and Tad +CDDP group received 0.4 mg/kg BW Tad i.p. +4 mg/kg BW CDDP i.p. The results showed that Tad was able to decrease blood pressure, heart rate, levels of serum cardiac troponin (cTn-I), malondialdehyde (MDA) and increased levels of reduced glutathione (GSH) and nitric oxide (NO) in the heart homogenate sample from CDDP treated rats. Semi-quantitative analysis showed that Tad was able to decrease the histopathological scores of cardiac muscular hyalinzation and fibrosis in three sacrifices in CDDP treated rats. CDDP treated rats showed significantly increased thickening in wall of aorta with an irregular luminal layer of endothelial cell linings in three sacrifices when it was compared to other groups. Moreover, immunohistochemical labeling of α- smooth muscle actin (α-SMA) in aorta revealed significant lower scores in Tad +CDDP group when they were compared to CDDP group. In conclusion, Tad alone did not induce any harmful effects on blood pressure, selective antioxidant, peroxidation markers or cardiac histology, in addition, Tad has a cardio-protective role against CDDP. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Role for macrophage inflammatory protein-2 in lipopolysaccharide-induced lung injury in rats

DEFF Research Database (Denmark)

Schmal, H; Shanley, T P; Jones, M L

1996-01-01

Macrophage inflammatory protein-2 (MIP-2) is a C-X-C chemokine that possesses chemotactic activity for neutrophils. Rat MIP-2 was cloned and expressed as a 7.9-kDa peptide that exhibited dose-dependent neutrophil chemotactic activity at concentrations from 10 to 250 nM. Rabbit polyclonal Ab to th...... instillation of LPS was found to be MIP-2-dependent. These data indicate that MIP-2 plays a significant role in LPS-induced inflammatory response in rat lungs and is required for the full recruitment of neutrophils....

Correlation of gut microbiota composition with resistance to experimental autoimmune encephalomyelitis in rats

Directory of Open Access Journals (Sweden)

Suzana Stanisavljevic

2016-12-01

Full Text Available Multiple sclerosis is a chronic inflammatory disease of the central nervous system (CNS. It is widely accepted that autoimmune response against the antigens of the CNS is the essential pathogenic force in the disease. It has recently become increasingly appreciated that activated encephalitogenic cells tend to migrate towards gut associated lymphoid tissues (GALT and that interrupted balance between regulatory and inflammatory immunity within the GALT might have decisive role in the initiation and propagation of the CNS autoimmunity. Gut microbiota composition and function has the major impact on the balance in the GALT. Thus, our aim was to perform analyses of gut microbiota in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis. Albino Oxford (AO rats that are highly resistant to EAE induction and Dark Agouti (DA rats that develop EAE after mild immunization were compared for gut microbiota composition in different phases after EAE induction. Microbial analyses of the genus Lactobacillus and related lactic acid bacteria showed higher diversity of Lactobacillus spp. in EAE-resistant AO rats, while some members of Firmicutes and Proteobacteria (Undibacterium oligocarboniphilum were detected only in faeces of DA rats at the peak of the disease (between 13 and 16 days after induction. Interestingly, Turicibacter sp. that was found exclusively in non-immunized AO, but not in DA rats in our previous study was detected in DA rats that remained healthy 16 days after induction. Similar observation was obtained for the members of Lachnospiraceae. As dominant presence of the members of Lachnospiraceae family in gut microbial community has been linked with mild symptoms of various diseases, it is tempting to assume that Turicibacter sp. and Lachnospiraceae contribute to the prevention of EAE development and the alleviation of the disease symptoms. Further, production of a typical regulatory cytokine interleukin-10 was

The role of adenosine in preconditioning by brief pressure overload in rats.

Science.gov (United States)

Huang, Cheng-Hsiung; Tsai, Shen-Kou; Chiang, Shu-Chiung; Lai, Chang-Chi; Weng, Zen-Chung

2015-08-01

Brief pressure overload of the left ventricle reduced myocardial infarct (MI) size in rabbits has been previously reported. Its effects in other species are not known. This study investigates effects of pressure overload and the role of adenosine in rats in this study. MI was induced by 40-minute occlusion of the left anterior descending coronary artery followed by 3-hour reperfusion. MI size was determined by triphenyl tetrazolium chloride staining. Brief pressure overload was induced by two 10-minute episodes of partial snaring of the ascending aorta. Systolic left ventricular pressure was raised 50% above the baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions. The MI size (mean ± standard deviation), expressed as percentage of area at risk, was significantly reduced in the pressure overload group as well as in the ischemic preconditioning group (17.4 ± 3.0% and 18.2 ± 1.5% vs. 26.6 ± 2.4% in the control group, p overload and ischemic preconditioning (18.3 ± 1.5% and 18.2 ± 2.0%, respectively, p overload of the left ventricle preconditioned rat myocardium against infarction. Because SPT did not significantly alter MI size reduction, our results did not support a role of adenosine in preconditioning by pressure overload in rats. Copyright © 2013. Published by Elsevier B.V.

The role of xanthine oxidase in ischemia/reperfusion damage of rat liver

NARCIS (Netherlands)

Frederiks, W. M.; Bosch, K. S.

1995-01-01

Oxygen radicals have been proposed to be involved in the induction of liver cell damage during reperfusion after ischemia. The role of xanthine oxidase in this process and the potential of the antioxidant system have been studied in a model of in vivo ischemia of rat liver followed by 1 h

Infantile 4-tert-octylphenol exposure transiently inhibits rat ovarian steroidogenesis and steroidogenic acute regulatory protein (StAR) expression

International Nuclear Information System (INIS)

Myllymaeki, S.A.; Karjalainen, M.; Haavisto, T.E.; Toppari, J.; Paranko, J.

2005-01-01

Phenolic compounds, such as 4-tert-octylphenol (OP), have been shown to interfere with rat ovarian steroidogenesis. However, little is known about steroidogenic effects of infantile OP exposure on immature ovary. The aim of the present study was to investigate the effects of infantile OP exposure on plasma FSH, LH, estradiol, and progesterone levels in 14-day-old female rats. The effect on ovarian steroidogenic acute regulatory protein (StAR) and FSH receptor (FSHr) expression was analyzed by Western blotting. Ex vivo analysis was carried out for follicular estradiol, progesterone, testosterone, and cAMP production. Sprague-Dawley rats were given OP (0, 10, 50, or 100 mg/kg) subcutaneously on postnatal days 6, 8, 10, and 12. On postnatal day 14, plasma FSH was decreased and progesterone increased significantly at a dose of 100 mg OP/kg. In addition, the highest OP dose advanced the time of vaginal opening in puberty. OP had no effect on infantile LH and estradiol levels or ovarian FSHr content. Ovarian StAR protein content and ex vivo hormone and cAMP production were decreased at all OP doses compared to controls. However, hormone levels recovered independent on FSH and even increased above the control level during a prolonged culture. On postnatal day 35, no statistically significant differences were seen between control and OP-exposed animals in plasma FSH, LH, estradiol, and progesterone levels, or in ovarian StAR protein content. The results indicate that the effect of OP on the infantile ovary is reversible, while more permanent effects in the hypothalamus and pituitary, as described earlier, are involved in the reduction of circulating FSH levels and premature vaginal opening

Possible regulatory role of phenylalanine ammonia-lyase in the production of anthocyanins in asparagus (Asparagus officinalis L)

NARCIS (Netherlands)

Flores, F.B.; Oosterhaven, J.; Martinez-Madrid, M.C.; Romojaro, F.

2005-01-01

The regulatory role of phenylalanine ammonia-lyase (PAL) in the light-induced accumulation of anthocyanins in the epidermis of asparagus spears has been analysed. A correlation between the stimulation of PAL activity and the rise in total anthocyanin content has been observed. Light radiation

Safeguards decision making in the public and regulatory environment, and the potential role of quantitative approaches

International Nuclear Information System (INIS)

Sherr, T.S.

1981-01-01

This paper briefly examines the nature of the safeguards program's objectives and constraints, and the inherent limitations on comprehensive quantification. It discusses the nature of the public and regulatory processes employed in safeguards decision making, and examines their implications regarding the potential role of quantitative approaches to safeguards policy and operational decision making

Effects of nonhypotensive endotoxemia in conscious rats: Role of prostaglandins

International Nuclear Information System (INIS)

Burnier, M.; Waeber, B.; Aubert, J.F.; Nussberger, J.; Brunner, H.R.

1988-01-01

A nonhypotensive dose of endotoxin was administered to normal conscious rats to evaluate the vascular and humoral effects of endotoxemia per se. Mean blood pressure and heart rate remained stable during the 45 min infusion of Escherichia coli endotoxin. However, a marked increase in plasma renin activity plasma epinephrine and plasma norepinephrine was observed during infusion in endotoxin-treated rats when compared with the vehicle-treated animals. In addition, the blood pressure response to exogenous norepinephrine was significantly reduced during nonhypotensive endotoxemia. Significant changes in regional blood flow distribution, as assessed by radiolabeled microspheres, were observed in endotoxemic rats; in particular a decrease in renal blood flow, and an increase in coronary blood flow were found. The role of prostaglandins in the vascular and humoral alterations induced by nonhypotensive endotoxemia was also examined. Pretreatment with indomethacin (5 mg) prevent the increase in plasma renin activity as well as plasma catecholamine levels. On the contrary, the decreased vascular reactivity and the reduction in renal blood flow observed during endotoxemia were not affected by prostaglandin synthesis inhibition. Thus significant vascular and humoral changes have been found during endotoxemia even in absence of hypotension. The humoral but not the vascular effects of endotoxemia were abolished when prostaglandin synthesis was inhibited

Balanites aegyptiaca ameliorates insulin secretion and decreases pancreatic apoptosis in diabetic rats: Role of SAPK/JNK pathway.

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Hassanin, Kamel M A; Mahmoud, Mohamed O; Hassan, Hossam M; Abdel-Razik, Abdel-Razik H; Aziz, Lourin N; Rateb, Mostafa E

2018-06-01

SAPK-JNK pathway performs a significant role in the pathogenesis of type 2 diabetes. Balanites aegyptiaca (BA) is used as an anti-diabetic agent in folk medicine however its hypoglycemic mechanism is not fully elucidated. The current study aimed to evaluate the effect of crude extract, butanol, and dichloromethane fractions from BA on the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK-JNK) pathway in experimental diabetic rats. Six groups of male Wistar rats were included: normal control, diabetic, diabetic rats treated with crude, butanol or dichloromethane fraction from BA (50 mg/kg BW) and diabetic rats treated with gliclazide as a reference drug for one month. Our results suggested a protective role of treatment of diabetic rats with BA against oxidative stress-induced SAPK-JNK pathway. Moreover, BA treatment produced a reduction in plasma glucose, HbA 1c , lactic acid, lipid profile, malondialdehyde levels and produced an increase in insulin, reduced glutathione levels, catalase and superoxide dismutase activities compared with untreated diabetic rats. Moreover, it decreased apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase 1, protein 53 and increased insulin receptor substrate 1 in rat pancreas while it increased glucose transporter 4 in rat muscle. Analysis of BA extracts by LC-HRMS revealed the presence of different saponins with reported hypoglycemic effect. In conclusion, BA exerted hypoglycemic, hypolipidemic, insulinotropic and antioxidant effects. Additionally, it reduced apoptosis in pancreatic β-cells and increased glucose uptake in muscle. These results suggest that the hypoglycemic effect of BA is due to the inhibition of the SAPK-JNK pathway. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Pharmacokinetics of warfarin in rats: role of serum protein binding and tissue distribution

International Nuclear Information System (INIS)

Cheung, W.K.

1985-01-01

The purpose of this study was to explore the role of serum protein binding and tissue distribution in the non-linear pharmacokinetics of warfarin in rats. The first phase of the research was an attempt to elucidate the causes of intersubject differences in serum protein binding of warfarin in rats. It was found that the distribution of S-warfarin between blood and liver, kidneys, muscle, or fatty tissue was non-linear. Based on the tissue distribution data obtained, a physiologically-based pharmacokinetic model was developed to describe the time course of S-warfarin concentrations in the serum and tissues of rats. The proposed model was able to display the dose-dependent pharmacokinetics of warfarin in rats. Namely a lower clearance and a smaller apparent volume of distribution with increasing dose, which appear to be due to the presence of capacity-limited, high-affinity binding sites for warfarin in various tissues. To determine if the binding of warfarin to the high-affinity binding sites in the liver of rats is reversible, concentrations of S-warfarin in the liver and serum of rats were monitored for a very long time after an intravenous injection of a 1 mg/kg dose. In another study in rats, non-radioactive warfarin was found to be able to displace tissue-bound C 14 -warfarin which was administered about 200 hours before the i.v. injection of the non-radioactive warfarin, showing that the binding of warfarin to the high-affinity binding sites in the body is persistent and reversible

Exendin-4 Plays a Protective Role in a Rat Model of Spinal Cord Injury Through SERCA2

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Zhonglei Sun

2018-05-01

Full Text Available Background/Aims: Current therapies for spinal cord injury (SCI have limited efficacy, and identifying a therapeutic target is a pressing need. Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2 plays an important role in regulating calcium homeostasis, which has been shown to inhibit apoptosis. Exendin-4 has been shown to inhibit the apoptosis of nerve cells in SCI, which can also improve SERCA2 expression. In this study, we sought to determine whether exendin-4 plays a protective role in a rat model of SCI via SERCA2. Methods: To investigate the effects of exendin-4 on SCI, a rat model of SCI was induced by a modified version of Allen’s method. Spinal cord tissue sections from rats and western blot analysis were used to examine SERCA2 expression after treatment with the long-acting glucagon-like peptide 1 receptor exendin-4 or the SERCA2 antagonist 5(6-carboxyfluorescein diacetate N-succinimidyl ester (CE. Locomotor function was evaluated using the Basso Beattie Bresnahan locomotor rating scale and slanting board test. Results: Cell apoptosis was increased with CE treatment and decreased with exendin-4 treatment. Upregulation of SERCA2 in female rats with SCI resulted in an improvement of motor function scores and histological changes. Conclusion: These findings suggest that exendin-4 plays a protective role in a rat model of SCI through SERCA2 via inhibition of apoptosis. Existing drugs targeting SERCA2 may be an effective therapeutic strategy for the treatment of SCI.

Security of handling radioactive sources and the role of the regulatory body in Egypt

International Nuclear Information System (INIS)

Salama, M.

1998-01-01

The motivation of the present paper was undertaken to discuss the system adopted by the National Centre for Nuclear Safety and Radiation Control (NCNSRC) in handling the radioactive sources inside the country. The system concentrates mainly on the role of the centre concerning three main categories namely regulations, licensing and training. The mutual co-operation between the regulatory body and the other agencies concerning this matter is going to be presented. (author)

Transfer RNA methylases in rat placenta

International Nuclear Information System (INIS)

Jagtiani, S.K.; Narurkar, L.M.; Narurkar, M.V.

1977-01-01

Presence of tRNA methylases (5-adenosylmethionine : tRNA methyltransferases) was demonstrated at various stages of gestation in rat placenta, the enzyme being 50-100% higher than that of adult rat liver during early gestation. Placental tRNA methylases were shown to differ from those of liver in the extent of methylation. Glycine methyltransferase (S-adenosylmethionine : glycine methyltransferase), a regulatory enzyme in adult rat liver, was absent in placenta throughout gestation. The placental tRNA methylases could be inhibited in vitro by semipurified glycine methyltransferase from adult rat liver. The high placental tRNA methylase activity was comparable with the inhibitor-free enzyme activity of the adult rat liver. S-adenosyl-[Me- 14 C]-methionine was used in the investigation. (author)

Dopamine receptors play distinct roles in sexual behavior expression of rats with a different sexual motivational tone.

Science.gov (United States)

Guadarrama-Bazante, Irma L; Canseco-Alba, Ana; Rodríguez-Manzo, Gabriela

2014-10-01

Dopamine (DA) plays a central role in the expression of male sexual behavior. The effects of DA-enhancing drugs on copulation seem to vary depending on the dose of the agonist used, the type of DA receptor activated, and the sexual condition of the animals. The aim of the present study was to carry out a systematic analysis of the effects of dopaminergic agonists on the expression of male sexual behavior by sexually competent rats in different sexual motivational states, that is when sexually active (sexually experienced) and when temporarily inhibited (sexually exhausted). To this end, the same doses of the nonselective DA receptor agonist apomorphine, the selective D2-like DA receptor agonist quinpirole, and the selective D1-like DA receptor agonist SKF38393 were injected intraperitoneally to sexually experienced or sexually exhausted male rats and their sexual behavior was recorded. Low apomorphine doses induced expression of sexual behavior in sexually satiated rats, but only reduced the intromission latency of sexually experienced rats. SKF38393 facilitated the expression of sexual behavior by sexually exhausted rats, but not that of sexually experienced males and quinpirole did not exert an effect in both types of animal. In line with these results, the apomorphine-induced reversal of sexual exhaustion was blocked by the D1-like receptor antagonist SCH23390. The data suggest that DA receptors play distinct roles in the expression of sexual behavior by male rats depending on their motivational state and that activation of D1-like receptors promotes the expression of sexual behavior in satiated rats.

Role of Renal Nerves in the Treatment of Renovascular Hypertensive Rats with L-Arginine

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Sonia Alves Gouvea

2014-01-01

Full Text Available The purpose was to determine the role of renal nerves in mediating the effects of antihypertensive treatment with L-arginine in a renovascular hypertension model. The 2K1C (two-kidney one-clip model hypertensive rats were submitted to bilateral surgical-pharmacological renal denervation. The animals were subdivided into six experimental groups: normotensive control rats (SHAM, 2K1C rats, 2K1C rats treated with L-arginine (2K1C + L-arg, denervated normotensive (DN rats, denervated 2K1C (2K1C + DN rats, and denervated 2K1C + L-arg (2K1C + DN + L-arg rats. Arterial blood pressure, water intake, urine volume, and sodium excretion were measured. The 2K1C rats exhibited an increase in the mean arterial pressure (MAP (from 106 ± 3 to 183 ± 5.8 mmHg, P<0.01, whereas L-arg treatment induced a reduction in the MAP (143 ± 3.4 mmHg without lowering it to the control level. Renal nerve denervation reduced the MAP to normotensive levels in 2K1C rats with or without chronic L-arg treatment. L-arg and denervation induced increases in water intake and urine volume, and L-arg caused a significant natriuretic effect. Our results suggest that renal sympathetic activity participates in the genesis and the maintenance of the hypertension and also demonstrate that treatment with L-arg alone is incapable of normalizing the MAP and that the effect of such treatment is not additive with the effect of kidney denervation.

Systematic Analysis of RNA Regulatory Network in Rat Brain after Ischemic Stroke

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Juan Liu

2018-01-01

Full Text Available Although extensive studies have identified large number of microRNAs (miRNAs and long noncoding RNAs (lncRNAs in ischemic stroke, the RNA regulation network response to focal ischemia remains poorly understood. In this study, we simultaneously interrogate the expression profiles of lncRNAs, miRNAs, and mRNAs changes during focal ischemia induced by transient middle cerebral artery occlusion. A set of 1924 novel lncRNAs were identified and may involve brain injury and DNA repair as revealed by coexpression network analysis. Furthermore, many short interspersed elements (SINE mediated lncRNA:mRNA duplexes were identified, implying that lncRNAs mediate Staufen1-mediated mRNA decay (SMD which may play a role during focal ischemia. Moreover, based on the competitive endogenous RNA (ceRNA hypothesis, a stroke regulatory ceRNA network which reveals functional lncRNA:miRNA:mRNA interactions was revealed in ischemic stroke. In brief, this work reports a large number of novel lncRNAs responding to focal ischemia and constructs a systematic RNA regulation network which highlighted the role of ncRNAs in ischemic stroke.

Depression of Complement Regulatory Factors in Rat and Human Renal Grafts Is Associated with the Progress of Acute T-Cell Mediated Rejection.

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Kazuaki Yamanaka

Full Text Available The association of complement with the progression of acute T cell mediated rejection (ATCMR is not well understood. We investigated the production of complement components and the expression of complement regulatory proteins (Cregs in acute T-cell mediated rejection using rat and human renal allografts.We prepared rat allograft and syngeneic graft models of renal transplantation. The expression of Complement components and Cregs was assessed in the rat grafts using quantitative real-time PCR (qRT-PCR and immunofluorescent staining. We also administered anti-Crry and anti-CD59 antibodies to the rat allograft model. Further, we assessed the relationship between the expression of membrane cofactor protein (MCP by immunohistochemical staining in human renal grafts and their clinical course.qRT-PCR results showed that the expression of Cregs, CD59 and rodent-specific complement regulator complement receptor 1-related gene/protein-y (Crry, was diminished in the rat allograft model especially on day 5 after transplantation in comparison with the syngeneic model. In contrast, the expression of complement components and receptors: C3, C3a receptor, C5a receptor, Factor B, C9, C1q, was increased, but not the expression of C4 and C5, indicating a possible activation of the alternative pathway. When anti-Crry and anti-CD59 mAbs were administered to the allograft, the survival period for each group was shortened. In the human ATCMR cases, the group with higher MCP expression in the grafts showed improved serum creatinine levels after the ATCMR treatment as well as a better 5-year graft survival rate.We conclude that the expression of Cregs in allografts is connected with ATCMR. Our results suggest that controlling complement activation in renal grafts can be a new strategy for the treatment of ATCMR.

The role of effective communications in Nuclear Regulatory Commission licensing

International Nuclear Information System (INIS)

Counsil, W.G.

1991-01-01

Communications are essential to the licensing and general regulatory program of the Nuclear Regulatory Commission. This paper attempts to identify and address certain aspects of, and approaches to, maintaining effective and efficient communications. It considers, from the perspective of the high-level radioactive waste repository program, both internal communication within the DOE itself and external communication with the Nuclear Regulatory Commission and interested parties. Many of the points presented are based on lessons learned from electric utility experience with nuclear plants

Involvement of Histone Lysine Methylation in p21 Gene Expression in Rat Kidney In Vivo and Rat Mesangial Cells In Vitro under Diabetic Conditions

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Xiangjun Li

2016-01-01

Full Text Available Diabetic nephropathy (DN, a common complication associated with type 1 and type 2 diabetes mellitus (DM, characterized by glomerular mesangial expansion, inflammation, accumulation of extracellular matrix (ECM protein, and hypertrophy, is the major cause of end-stage renal disease (ESRD. Increasing evidence suggested that p21-dependent glomerular and mesangial cell (MC hypertrophy play key roles in the pathogenesis of DN. Recently, posttranscriptional modifications (PTMs have uncovered novel molecular mechanisms involved in DN. However, precise regulatory mechanism of histone lysine methylation (HKme mediating p21 related hypertrophy associated with DN is not clear. We evaluated the roles of HKme and histone methyltransferase (HMT SET7/9 in p21 gene expression in glomeruli of diabetic rats and in high glucose- (HG- treated rat mesangial cells (RMCs. p21 gene expression was upregulated in diabetic rats glomeruli; chromatin immunoprecipitation (ChIP assays showed decreased histone H3-lysine9-dimethylation (H3K9me2 accompanied with enhanced histone H3-lysine4-methylation (H3K4me1/3 and SET7/9 occupancies at the p21 promoter. HG-treated RMCs exhibited increased p21 mRNA, H3K4me level, SET7/9 recruitment, and inverse H3K9me, which were reversed by TGF-β1 antibody. These data uncovered key roles of H3Kme and SET7/9 responsible for p21 gene expression in vivo and in vitro under diabetic conditions and confirmed preventive effect of TGF-β1 antibody on DN.

Reconstruction of the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator

DEFF Research Database (Denmark)

Usaite, Renata; Jewett, Michael Christopher; Soberano de Oliveira, Ana Paula

2009-01-01

Highly conserved among eukaryotic cells, the AMP-activated kinase (AMPK) is a central regulator of carbon metabolism. To map the complete network of interactions around AMPK in yeast (Snf1) and to evaluate the role of its regulatory subunit Snf4, we measured global mRNA, protein and metabolite...

The potential regulatory roles of NAD(+) and its metabolism in autophagy.

Science.gov (United States)

Zhang, Dong-Xia; Zhang, Jia-Ping; Hu, Jiong-Yu; Huang, Yue-Sheng

2016-04-01

(Macro)autophagy mediates the bulk degradation of defective organelles, long-lived proteins and protein aggregates in lysosomes and plays a critical role in cellular and tissue homeostasis. Defective autophagy processes have been found to contribute to a variety of metabolic diseases. However, the regulatory mechanisms of autophagy are not fully understood. Increasing data indicate that nicotinamide adenine nucleotide (NAD(+)) homeostasis correlates intimately with autophagy. NAD(+) is a ubiquitous coenzyme that functions primarily as an electron carrier of oxidoreductase in multiple redox reactions. Both NAD(+) homeostasis and its metabolism are thought to play critical roles in regulating autophagy. In this review, we discuss how the regulation of NAD(+) and its metabolism can influence autophagy. We focus on the regulation of NAD(+)/NADH homeostasis and the effects of NAD(+) consumption by poly(ADP-ribose) (PAR) polymerase-1 (PARP-1), NAD(+)-dependent deacetylation by sirtuins and NAD(+) metabolites on autophagy processes and the underlying mechanisms. Future studies should provide more direct evidence for the regulation of autophagy processes by NAD(+). A better understanding of the critical roles of NAD(+) and its metabolites on autophagy will shed light on the complexity of autophagy regulation, which is essential for the discovery of new therapeutic tools for autophagy-related diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of Thyroid Dysfunction on Reproductive Hormones in Female Rats.

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Liu, Juan; Guo, Meng; Hu, Xusong; Weng, Xuechun; Tian, Ye; Xu, Kaili; Heng, Dai; Liu, Wenbo; Ding, Yu; Yang, Yanzhou; Zhang, Cheng

2018-05-10

Thyroid hormones (THs) play a critical role in the development of ovarian cells. Although the effects of THs on female reproduction are of great interest, the mechanism remains unclear. We investigated the effects of TH dysregulation on reproductive hormones in rats. Propylthiouracil (PTU) and L-thyroxine were administered to rats to induce hypo- and hyper-thyroidism, respectively, and the reproductive hormone profiles were analyzed by radioimmunoassay. Ovarian histology was evaluated with H&E staining, and gene protein level or mRNA content was analyzed by western blotting or RT-PCR. The serum levels of gonadotropin releasing hormone (GnRH) and follicle stimulating hormone (FSH) in both rat models were significantly decreased on day 21, although there were no significant changes at earlier time points. There were no significant differences in luteinizing hormone (LH) or progesterone levels between the treatment and the control groups. Both PTU and L-thyroxine treatments downregulated estradiol concentrations; however, the serum testosterone level was increased only in hypothyroid rats at day 21. In addition, the expression levels of FSH receptor, cholesterol side-chain cleavage enzyme (P450scc), and steroidogenic acute regulatory protein were decreased in both rat models. Moreover, the onset of puberty was significantly delayed in the hypothyroid group. These results provide evidence that TH dysregulation alters reproductive hormone profiles, and that the initiation of the estrous cycle is postponed in hypothyroidism.

A new role for GABAergic transmission in the control of male rat sexual behavior expression.

Science.gov (United States)

Rodríguez-Manzo, Gabriela; Canseco-Alba, Ana

2017-03-01

GABAergic transmission in the ventral tegmental area (VTA) exerts a tonic inhibitory influence on mesolimbic dopaminergic neurons' activity. Blockade of VTA GABA A receptors increases dopamine release in the nucleus accumbens (NAcc). Increases in NAcc dopamine levels typically accompany sexual behavior display. Copulation to satiety is characterized by the instatement of a long lasting (72h) sexual behavior inhibition and the mesolimbic system appears to be involved in this phenomenon. GABAergic transmission in the VTA might play a role in the maintenance of this long lasting sexual inhibitory state. To test this hypothesis, in the present work we investigated the effect of GABA A receptor blockade in sexually exhausted males 24h after copulation to satiety, once the sexual inhibitory state is established, and compared it with its effect in sexually experienced rats. Results showed that low doses of systemically administered bicuculline induced sexual behavior expression in sexually exhausted rats, but lacked an effect on copulation of sexually experienced animals. Intra-VTA bilateral infusion of bicuculline did not modify sexual behavior of sexually experienced rats, but induced sexual behavior expression in all the sexually exhausted males. Hence, GABA plays a role in the control of sexual behavior expression at the VTA. The role played by GABAergic transmission in male sexual behavior expression of animals with distinct sexual behavior conditions is discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Protective role of radish oil (raphson sativus) against gamma radiation on lipids and carbohydrate in male rats

International Nuclear Information System (INIS)

Omran, M.F.; Soliman, N.K.I.

2005-01-01

The present work was carried out to investigate the effects of ionizing radiation on some biochemical parameters in rats. The rats were exposed to sublethal whole body gamma irradiation dose (1Gy x 4). The protective role of radish oil (Raphanus sativus) was evaluated by oral administration to rats before gamma radiation exposure and the lipid profile, serum glucose and liver glycogen were investigated. Exposed rats to gamma radiation showed significant alterations in the assayed parameters indicating disturbances in lipid and carbohydrate metabolisms. Oral administration of radish oil (Raphanus sativus) before gamma irradiation exerted marked ameliorations in the disorders induced by gamma radiation in most of the tested parameters such as lipid profile, serum glucose and liver glycogen

Evaluation of CART peptide level in rat plasma and CSF: Possible role as a biomarker in opioid addiction.

Science.gov (United States)

Bakhtazad, Atefeh; Vousooghi, Nasim; Garmabi, Behzad; Zarrindast, Mohammad Reza

2016-10-01

It has been shown previously that cocaine- and amphetamine-regulated transcript (CART) peptide has a modulatory role and homeostatic regulatory effect in motivation to and reward of the drugs of abuse specially psychostimulants. Recent data also showed that in addition to psychostimulants, CART is critically involved in the different stages of opioid addiction. Here we have evaluated the fluctuations in the level of CART peptide in plasma and CSF in different phases of opioid addiction to find out whether CART can serve as a suitable marker in opioid addiction studies. Male rats were randomly distributed in groups of control, acute low-dose (10mg/kg) morphine, acute high-dose morphine (80mg/kg), chronic escalating doses of morphine, withdrawal syndrome precipitated by administration of naloxone (1mg/kg), and abstinent after long-term drug-free maintenance of addicted animals. The level of CART peptide in CSF and plasma samples was measured by enzyme immunoassay. CART peptide concentration in the CSF and plasma was significantly elevated in acute high-dose morphine and withdrawal state animals and down-regulated in addicted rats. In abstinent group, CART peptide level was up-regulated in plasma but not in CSF samples. As the observed results are in agreement with data regarding the CART mRNA and protein expression in the brain reward pathway in opioid addiction phases, it may be suggested that evaluation of CART peptide level in CSF or plasma could be a suitable marker which reflects the rises and falls of the peptide concentration in brain in the development of opioid addiction. Copyright © 2016 Elsevier Inc. All rights reserved.

The role of estrogen G-protein coupled receptor 30 (GPR30) and sexual experience in sexual incentive motivation in male rats.

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Hawley, W R; Battista, C; Divack, S R; Morales Núñez, N B

2017-08-01

Male rats exhibit reductions in sexual motivation following systemic administration of drugs that inhibit the conversion of testosterone to estrogen, which indicates that estrogen signaling plays a role in male rat sexual motivation. Given that estrogen G-protein coupled receptor 30 (GPR30) is expressed in brain areas that are important for male sexual behaviors and endocrine function, the primary aim of the current study was to examine the role that GPR30 plays in sexual motivation in both sexually naïve and sexually experienced male rats. Following the final treatment with either a GPR30 antagonist (G-15) or vehicle control, male rats were placed into the center chamber of a larger three-chambered testing arena that was designed to assess sexual incentive motivation. A sexually receptive stimulus female rat and a stimulus male rat were individually confined to one of the two smaller chambers that were each separated by a perforated partition from the larger end chambers, which test rats had access to. Relative to vehicle treated rats, male rats treated with G-15 exhibited a reduction in the percentage of time spent in the vicinity of a sexually receptive female rat. Although G-15 reduced sexual incentive motivation independent of sexual experience, only sexually-naïve rats treated with G-15 did not exhibit a preference for the sexually receptive stimulus female rat. Collectively, these results indicate that interference with estrogen signaling at GPR30 reduces sexual motivation and that the lack of preference for a sexually receptive female rat over a male rat following G-15 treatment is abrogated by previous sexual experience. Copyright © 2017 Elsevier Inc. All rights reserved.

Increased expression of EMMPRIN and VEGF in the rat brain after gamma irradiation.

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Wei, Ming; Li, Hong; Huang, Huiling; Xu, Desheng; Zhi, Dashi; Liu, Dong; Zhang, Yipei

2012-03-01

The extracellular matrix metalloproteinase inducer (EMMPRIN) has been known to play a key regulatory role in pathological angiogenesis. A elevated activation of vascular endothelial growth factor (VEGF) following radiation injury has been shown to mediate blood-brain barrier (BBB) breakdown. However, the roles of EMMPRIN and VEGF in radiation-induced brain injury after gamma knife surgery (GKS) are not clearly understood. In this study, we investigated EMMPRIN changes in a rat model of radiation injury following GKS and examined potential associations between EMMPRIN and VEGF expression. Adult male rats were subjected to cerebral radiation injury by GKS under anesthesia. We found that EMMPRIN and VEGF expression were markedly upregulated in the target area at 8-12 weeks after GKS compared with the control group by western blot, immunohistochemistry, and RT-PCR analysis. Immunofluorescent double staining demonstrated that EMMPRIN signals colocalized with caspase-3 and VEGF-positive cells. Our data also demonstrated that increased EMMPRIN expression was correlated with increased VEGF levels in a temporal manner. This is the first study to show that EMMPRIN and VEGF may play a role in radiation injuries of the central nervous system after GKS.

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Impact of obesity on hypertension-induced cardiac remodeling: role of oxidative stress and its modulation by gemfibrozil treatment in rats.

Science.gov (United States)

Singh, Randhir; Singh, Amrit Pal; Singh, Manjeet; Krishan, Pawan

2011-01-15

This study investigated the possible synergistic role of obesity in hypertension-induced cardiac remodeling and its modulation by gemfibrozil treatment in rats. Male Wistar rats were fed a high-fat diet (HFD) for 90 days. Normal rats were subjected to hypertension by partial abdominal aortic constriction (PAAC) for 28 days. In the HFD+PAAC control group, rats on HFD were subjected to PAAC on the 62nd day and were sacrificed on the 90th day. HFD and PAAC individually resulted in significant cardiac hypertrophy and fibrosis along with increased oxidative stress and mean arterial blood pressure (MABP) in rats as evidenced by various morphological, biochemical, and histological parameters. Moreover, the HFD + PAAC control group showed marked cardiac remodeling compared to rats subjected to HFD or PAAC alone. The HFD+gemfibrozil and HFD+PAAC+gemfibrozil groups showed significant reduction in cardiac remodeling along with reduction in oxidative stress and MABP. Hence, it may be concluded that oxidative stress plays a key role in obesity-mediated synergistic effects on induction and progression of PAAC-induced cardiac remodeling, and its deleterious effects could be reversed by gemfibrozil treatment in rats through its antioxidant activity. Copyright © 2010 Elsevier Inc. All rights reserved.

Improving nuclear regulation. NEA regulatory guidance booklets volumes 1-14

International Nuclear Information System (INIS)

2011-01-01

A common theme throughout the series of NEA regulatory guidance reports, or 'green booklets', is the premise that the fundamental objective of all nuclear safety regulatory bodies is to ensure that nuclear facilities are continuously maintained and operated in an acceptably safe manner. In meeting this objective the regulator must bear in mind that it is the operator that has responsibility for safely operating the nuclear facility; the role of the regulator is to assess and to provide assurance regarding the operator's activities in terms of assuming that responsibility. The full series of these reports was brought together in one edition for the first time in 2009 and was widely found to be a useful resource. This second edition comprises 14 volumes, including the latest on The Nuclear Regulator's Role in Assessing Licensee Oversight of Vendor and Other Contracted Services. The reports address various challenges that could apply throughout the lifetime of a nuclear facility, including design, siting, manufacturing, construction, commissioning, operation, maintenance and decommissioning. The compilation is intended to serve as a knowledge management tool both for current regulators and the new nuclear professionals and organisations entering the regulatory field. Contents: Executive Summary; Regulatory Challenges: 1. The Role of the Nuclear Regulator in Promoting and Evaluating Safety Culture; 2. Regulatory Response Strategies for Safety Culture Problems; 3. Nuclear Regulatory Challenges Related to Human Performance; 4. Regulatory Challenges in Using Nuclear Operating Experience; 5. Nuclear Regulatory Review of Licensee Self-assessment (LSA); 6. Nuclear Regulatory Challenges Arising from Competition in Electricity Markets; 7. The Nuclear Regulatory Challenge of Judging Safety Back-fits; 8. The Regulatory Challenges of Decommissioning Nuclear Reactors; 9. The Nuclear Regulator's Role in Assessing Licensee Oversight of Vendor and Other Contracted Services

Role of insular cortex in visceral hypersensitivity model in rats subjected to chronic stress.

Science.gov (United States)

Yi, LiSha; Sun, HuiHui; Ge, Chao; Chen, Ying; Peng, HaiXia; Jiang, YuanXi; Wu, Ping; Tang, YinHan; Meng, QingWei; Xu, ShuChang

2014-12-30

Abnormal processing of visceral sensation at the level of the central nervous system has been proven to be important in the pathophysiologic mechanisms of stress related functional gastrointestinal disorders. However, the specific mechanism is still not clear. The insular cortex (IC) was considered as one important visceral sensory area. Moreover, the IC has been shown to be involved in various neuropsychiatric diseases such as panic disorders and post-traumatic stress disorder. However, whether the IC is important in psychological stress related visceral hypersensitivity has not been studied yet. In our study, through destruction of the bilateral IC, we explored whether the IC played a critical role in the formation of visceral hypersensitivity induced by chronic stress on rats. Chronic partial restraint stress was used to establish viscerally hypersensitive rat model. Bilateral IC lesions were generated by N-methyl-D-day (door) aspartate. After a recovery period of 7 days, 14-day consecutive restraint stress was performed. The visceromotor response to colorectal distension was monitored by recording electromyogram to measure rats׳ visceral sensitivity. We found that bilateral insular cortex lesion could markedly inhibit the formation of visceral hypersensitivity induced by chronic stress. The insular cortex plays a critical role in the pathophysiology of stress-related visceral hypersensitivity.

Ameliorative role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats.

Science.gov (United States)

Singh, Amrit Pal; Singh, Randhir; Krishan, Pawan

2015-04-01

Fibrates are peroxisome proliferator-activated receptor-α agonists and are clinically used for treatment of dyslipidemia and hypertriglyceridemia. Fenofibrate is reported as a cardioprotective agent in various models of cardiac dysfunction; however, limited literature is available regarding the role of gemfibrozil as a possible cardioprotective agent, especially in a non-obese model of cardiac remodelling. The present study investigated the role of gemfibrozil against partial abdominal aortic constriction-induced cardiac hypertrophy in rats. Cardiac hypertrophy was induced by partial abdominal aortic constriction in rats and they survived for 4 weeks. The cardiac hypertrophy was assessed by measuring left ventricular weight to body weight ratio, left ventricular wall thickness, and protein and collagen content. The oxidative stress in the cardiac tissues was assessed by measuring thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The haematoxylin-eosin and picrosirius red staining was used to observe cardiomyocyte diameter and collagen deposition, respectively. Moreover, serum levels of cholesterol, high-density lipoproteins, triglycerides, and glucose were also measured. Gemfibrozil (30 mg/kg, p.o.) was administered since the first day of partial abdominal aortic constriction and continued for 4 weeks. The partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy are indicated by significant change in various parameters used in the present study that were ameliorated with gemfibrozil treatment in rats. No significant change in serum parameters was observed between various groups used in the present study. It is concluded that gemfibrozil ameliorates partial abdominal aortic constriction-induced cardiac oxidative stress and hypertrophy and in rats.

The Role of Antioxidants in Biochemical Disorders Induced by Arsenic in Adult male Rats

International Nuclear Information System (INIS)

Hassanin, M.M.; Zaki, Z.T.; Emarah, E.A.M.; Hussein, A.M.M.

2010-01-01

The present investigation included biochemical, radiometric, molecular studies and histopathological examination to evaluate the protective role of Antox tablets toward Arsenic toxicity in adult male albino rats (Rattus rattus). Arsenic were given as sodium arsenate to different groups in drinking water at a dose of 100 mg/L, for 3 and 6 weeks led to severe tissue damage as revealed by an elevation of serum total protein and alteration of serum protein fractions. Using radioimmunoassay it was found that serum total testosterone level was significantly decreased. The decreased level of total testosterone paralleled the observed testicular damage. Treatment of male rats with antioxidant (Antox) along with arsenic led to an improvement in both the biochemical and histological alterations induced by arsenic. Thus the protective role of Antox is attributed to its antioxidant and free radicals scavenging properties of its components (selenium, vitamin A acetate, ascorbic acid and vitamin E).

Excessive endoplasmic reticulum stress and decreased neuroplasticity-associated proteins in prefrontal cortex of obese rats and the regulatory effects of aerobic exercise.

Science.gov (United States)

Li, Feng; Liu, Bei Bei; Cai, Ming; Li, Jing Jing; Lou, Shu-Jie

2018-04-06

Studies have shown high fat diet induced obesity may cause cognition impairment and down-regulation of neuroplasticity-associated proteins, while aerobic exercise could improve that damage. Endoplasmic reticulum stress (ERS) has been reported to play a key role in regulating neuroplasticity-associated proteins expression, folding and post-translational modification in hippocampus of obese rodent models, however, the effects of ERS on neuroplasticity-associated proteins and possible underlying mechanisms in prefrontal cortex are not fully clear. In order to clarify changes of neuroplasticity-associated proteins and ERS in the prefrontal cortex of obese rats, male SD rats were fed on high fat diet for 8 weeks to establish the obese model. Then, 8 weeks of aerobic exercise treadmill intervention was arranged for the obese rats. Results showed that high fat diet induced obesity caused hyperlipidemia, and significantly promoted FATP1 expression in the prefrontal cortex, meanwhile, we found up-regulation of GRP78, p-PERK, p-eIF2α, caspase-12, CHOP, and Bax/Bcl-2, reflecting the activation of ERS and ERS-mediated apoptosis. Moreover, reduced BDNF and SYN was found in obese rats. However, FATP1, GRP78, p-PERK, p-eIF2α, caspase-12, CHOP, and Bax/Bcl-2 expressions were obviously reversed by aerobic exercise intervention. These results suggested that dietary obesity could induce Prefrontal ERS in SD rats and excessive ERS may play a critical role in decreasing the levels of neuroplasticity-associated proteins. Moreover, aerobic exercise could relieve ERS, thus promoted the expression of neuroplasticity-associated proteins. Copyright © 2018. Published by Elsevier Inc.

Role of Estrogen on Prevention of Morphine Addiction in Ovarectomized Female Rats

Directory of Open Access Journals (Sweden)

A Rafati

2008-04-01

Full Text Available ABSTRACT: Introduction & Objective: Evidence indicates that the biological response and the causes of drug abuse may be different between women and men. These sex differences in drug abuse may be due to socio-cultural factors or biological (hormonal differences. Estrogen is one of the hormones which involves in dopamine release in striatum and nucleus accumbency and also is one of the most important neurotransmitters in central nervous system which has critical role in morphine addiction. So, in this study we survey the role of estrogen on dependency and tendency to morphine in rat as a factor of sex differences in addiction. Materials & Methods: This experimental study was carried out in Yazd University of Medical Sciences. Behavioral changes like morphine craving was evaluated by self-administration as a criterion for tendency and for assessment of dependency. we evaluated withdrawal syndrome sings (e.g. jumping, wet dog shaking, etc in control group (ovarectomized female rats receiving morphine sulfate solution and test group (ovarectomized female rats, pretreated with estradiol benzoate before receiving daily morphine sulfate solution. Data obtained were analyzed by SPSS software, using T-test analysis Results: Results showed that although pretreatment with estradiol in test group might lead to a significant decline in withdrawal syndrome sings in comparison with control group, differences in morphine craving as a criterion for tendency was not significant between the two groups. Conclusion: According to our findings, it seems that estrogen, through central mechanisms and its effect on brain dopaminergic system, reduces the physical dependency to morphine.

Identification and target prediction of miRNAs specifically expressed in rat neural tissue

Directory of Open Access Journals (Sweden)

Tu Kang

2009-05-01

Full Text Available Abstract Background MicroRNAs (miRNAs are a large group of RNAs that play important roles in regulating gene expression and protein translation. Several studies have indicated that some miRNAs are specifically expressed in human, mouse and zebrafish tissues. For example, miR-1 and miR-133 are specifically expressed in muscles. Tissue-specific miRNAs may have particular functions. Although previous studies have reported the presence of human, mouse and zebrafish tissue-specific miRNAs, there have been no detailed reports of rat tissue-specific miRNAs. In this study, Home-made rat miRNA microarrays which established in our previous study were used to investigate rat neural tissue-specific miRNAs, and mapped their target genes in rat tissues. This study will provide information for the functional analysis of these miRNAs. Results In order to obtain as complete a picture of specific miRNA expression in rat neural tissues as possible, customized miRNA microarrays with 152 selected miRNAs from miRBase were used to detect miRNA expression in 14 rat tissues. After a general clustering analysis, 14 rat tissues could be clearly classified into neural and non-neural tissues based on the obtained expression profiles with p values Conclusion Our work provides a global view of rat neural tissue-specific miRNA profiles and a target map of miRNAs, which is expected to contribute to future investigations of miRNA regulatory mechanisms in neural systems.

Evidence for a role of proline and hypothalamic astrocytes in the regulation of glucose metabolism in rats.

Science.gov (United States)

Arrieta-Cruz, Isabel; Su, Ya; Knight, Colette M; Lam, Tony K T; Gutiérrez-Juárez, Roger

2013-04-01

The metabolism of lactate to pyruvate in the mediobasal hypothalamus (MBH) regulates hepatic glucose production. Because astrocytes and neurons are functionally linked by metabolic coupling through lactate transfer via the astrocyte-neuron lactate shuttle (ANLS), we reasoned that astrocytes might be involved in the hypothalamic regulation of glucose metabolism. To examine this possibility, we used the gluconeogenic amino acid proline, which is metabolized to pyruvate in astrocytes. Our results showed that increasing the availability of proline in rats either centrally (MBH) or systemically acutely lowered blood glucose. Pancreatic clamp studies revealed that this hypoglycemic effect was due to a decrease of hepatic glucose production secondary to an inhibition of glycogenolysis, gluconeogenesis, and glucose-6-phosphatase flux. The effect of proline was mimicked by glutamate, an intermediary of proline metabolism. Interestingly, proline's action was markedly blunted by pharmacological inhibition of hypothalamic lactate dehydrogenase (LDH) suggesting that metabolic flux through LDH was required. Furthermore, short hairpin RNA-mediated knockdown of hypothalamic LDH-A, an astrocytic component of the ANLS, also blunted the glucoregulatory action of proline. Thus our studies suggest not only a new role for proline in the regulation of hepatic glucose production but also indicate that hypothalamic astrocytes are involved in the regulatory mechanism as well.

Through the regulatory hoop

International Nuclear Information System (INIS)

Kirner, N.P.

1985-01-01

There are many regulatory hoops through which waste generators, brokers, and disposal site operators must jump to dispose of waste safely. As the proposed exclusionary date of January 1, 1986, approaches, these regulatory hoops have the distinct possibility of multiplying or at least changing shape. The state of Washington, in its role as an Agreement State with the US Nuclear Regulatory Commission, licenses and inspects the commercial operator of the Northwest Compact's low-level radioactive waste disposal site on the Hanford Reservation. Washington has received as much as 53%, or 1.4 million cubic feet per year, of the nation's total volume of waste disposed. To control such a large volume of waste, a regulatory program involving six agencies has developed over the years in Washington

Mimicry of the regulatory role of urokinase in lamellipodia formation by introduction of a non-native interdomain disulfide bond in its receptor

DEFF Research Database (Denmark)

Gårdsvoll, Henrik; Kjærgaard, Magnus; Jacobsen, Benedikte

2011-01-01

The high-affinity interaction between the urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) plays a regulatory role for both extravascular fibrinolysis and uPAR-mediated adhesion and migration on vitronectin-coated surfaces. We have recently proposed that the ......The high-affinity interaction between the urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) plays a regulatory role for both extravascular fibrinolysis and uPAR-mediated adhesion and migration on vitronectin-coated surfaces. We have recently proposed...... that the adhesive function of uPAR is allosterically regulated via a "tightening" of its three-domain structure elicited by uPA binding. To challenge this proposition, we redesigned the uPAR structure to limit its inherent conformational flexibility by covalently tethering domains DI and DIII via a non...... adhering to vitronectin. In this respect, the engineered constraint in uPAR(H47C-N259C) thus bypasses the regulatory role of uPA binding, resulting in a constitutively active uPAR. In conclusion, our data argue for a biological relevance of the interdomain dynamics of the glycolipid-anchored u...

Reduced expression of Nogo-A leads to motivational deficits in rats

Directory of Open Access Journals (Sweden)

Thomas eEnkel

2014-01-01

Full Text Available Nogo-A is an important neurite growth-regulatory protein in the adult and developing nervous system. Mice lacking Nogo-A, or rats with neuronal Nogo-A deficiency, exhibit behavioral abnormalities such as impaired short-term memory, decreased prepulse inhibition and behavioral inflexibility. In the current study we extended the behavioral profile of the Nogo-A deficient rat line with respect to reward sensitivity and motivation and determined the concentrations of the monoamines dopamine and serotonin in the prefrontal cortex, dorsal striatum and nucleus accumbens. Using a limited access consumption task, we found similar intake of a sweet condensed milk solution following ad libitum or restricted feeding in wild-type and Nogo-A deficient rats, indicating normal reward sensitivity and translation of hunger into feeding behavior. When tested for motivation in a spontaneous progressive ratio task, Nogo-A rats exhibited lower break points and tended to have lower ‘highest completed ratios’. Further, under extinction conditions responding ceased substantially earlier in these rats. Finally, in the prefrontal cortex we found increased tissue levels of serotonin, while dopamine was unaltered. Dopamine and serotonin levels were also unaltered in the dorsal striatum and the nucleus accumbens. In summary, these results suggest a role for Nogo-A regulated processes in motivated behavior and related neurochemistry. The behavioral pattern observed resembles aspects of the negative symptomatology of schizophrenia.

Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

Energy Technology Data Exchange (ETDEWEB)

Takaoka, Yuki [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Kawamoto, Seiji, E-mail: skawa@hiroshima-u.ac.jp [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Katayama, Akiko [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Nakano, Toshiaki [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Yamanaka, Yasushi; Takahashi, Miki [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Shimada, Yayoi; Chiang, Kuei-Chen [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Ohmori, Naoya [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Faculty of Nursing, Josai International University, Togane (Japan); Aki, Tsunehiro [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan); Goto, Takeshi; Sato, Shuji [Kazusa Institute for Drug Discovery, Josai International University, Kisarazu (Japan); Faculty of Nursing, Josai International University, Togane (Japan); Goto, Shigeru [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Iwao Hospital, Yufuin (Japan); Chen, Chao-Long [Liver Transplantation Program, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (China); Ono, Kazuhisa [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima (Japan)

2013-02-08

Highlights: ► Anti-histone H1 autoantibody (anti-H1) acts on T cells to inhibit their activation. ► Anti-H1 suppresses T cell activation in Treg cell-dependent and -independent manners. ► Suboptimal dose of anti-H1 enhances suppressor function of Treg cells. ► High dose of anti-H1 directly inhibits T cell receptor signaling. -- Abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4{sup +}Foxp3{sup +} Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings.

Unexpected T cell regulatory activity of anti-histone H1 autoantibody: Its mode of action in regulatory T cell-dependent and -independent manners

International Nuclear Information System (INIS)

Takaoka, Yuki; Kawamoto, Seiji; Katayama, Akiko; Nakano, Toshiaki; Yamanaka, Yasushi; Takahashi, Miki; Shimada, Yayoi; Chiang, Kuei-Chen; Ohmori, Naoya; Aki, Tsunehiro; Goto, Takeshi; Sato, Shuji; Goto, Shigeru; Chen, Chao-Long; Ono, Kazuhisa

2013-01-01

Highlights: ► Anti-histone H1 autoantibody (anti-H1) acts on T cells to inhibit their activation. ► Anti-H1 suppresses T cell activation in Treg cell-dependent and -independent manners. ► Suboptimal dose of anti-H1 enhances suppressor function of Treg cells. ► High dose of anti-H1 directly inhibits T cell receptor signaling. -- Abstract: Induction of anti-nuclear antibodies against DNA or histones is a hallmark of autoimmune disorders, but their actual contribution to disease predisposition remains to be clarified. We have previously reported that autoantibodies against histone H1 work as a critical graft survival factor in a rat model of tolerogeneic liver transplantation. Here we show that an immunosuppressive anti-histone H1 monoclonal antibody (anti-H1 mAb) acts directly on T cells to inhibit their activation in response to T cell receptor (TCR) ligation. Intriguingly, the T cell activation inhibitory activity of anti-H1 mAb under suboptimal dosages required regulatory T (Treg) cells, while high dose stimulation with anti-H1 mAb triggered a Treg cell-independent, direct negative regulation of T cell activation upon TCR cross-linking. In the Treg cell-dependent mode of immunosuppressive action, anti-H1 mAb did not induce the expansion of CD4 + Foxp3 + Treg cells, but rather potentiated their regulatory capacity. These results reveal a previously unappreciated T cell regulatory role of anti-H1 autoantibody, whose overproduction is generally thought to be pathogenic in the autoimmune settings

Increased CD147 (EMMPRIN) expression in the rat brain following traumatic brain injury.

Science.gov (United States)

Wei, Ming; Li, Hong; Shang, Yanguo; Zhou, Ziwei; Zhang, Jianning

2014-10-17

The extracellular matrix metalloproteinase inducer (EMMPRIN), or CD147, has been known to play a key regulatory role in vascular permeability and leukocyte activation by inducing the expression of matrix metalloproteinases (MMPs). The effects of traumatic brain injury on the expression of EMMPRIN remain poorly understood. In this study, we investigated changes in EMMPRIN expression in a rat model of fluid percussion injury (FPI) and examined the potential association between EMMPRIN and MMP-9 expression. Adult male rats were subjected to FPI. EMMPRIN expression was markedly up-regulated in the brain tissue surrounding the injured region 6-48 h after TBI, as measured by immunoblot and immunohistochemistry. EMMPRIN expression was localized to inflammatory cells. The increase in EMMPRIN expression was temporally correlated with an increase in MMP-9 levels. These data demonstrate, for the first time, changes in CD147 and MMP-9 expression following TBI. These data also suggest that CD147 and MMP-9 may play a role in vascular injuries after TBI. Copyright © 2014 Elsevier B.V. All rights reserved.

Mapping of carbonic anhydrase and estrone sulphatase in rat brain using 16-α-[18F]fluoroestradiol-3,17-β-disulphamate ([18F]FESDS)

International Nuclear Information System (INIS)

Rodig, H.; Brust, P.; Bergmann, R.; Roemer, J.; Fuechtner, F.; Steinbach, J.; Kasch, H.

2002-01-01

16α-[ 18 F]Fluoroestradiol-3,17β-disulphamate ([ 18 F]FESDS) was recently found to display affinities to carbonic anhydrase (CA) and estrone sulphatase (ES), enzymes which are expressed in the CNS and probably play a regulatory role in various brain diseases. In this study the radioligand was used to provide quantitative data on the regional distribution of these enzymes in the rat brain. (orig.)

Legal principles of regulatory administration and nuclear safety regulation

Energy Technology Data Exchange (ETDEWEB)

Lee, Kyeong Hui; Cheong, Sang Kee [Hannam Univ., Taejon (Korea, Republic of)

2000-12-15

This research presents a critical analysis and evaluation of principles of administrative laws in order to provide framework of structural reform on the nuclear safety regulation system. The focus of this analysis and evaluation is centered around the area of origin of regulatory administrative laws; authorities of regulation; procedures of regulatory actions; regulatory enforcement; and administrative relief system. In chapter 2 the concept of regulatory administration is analysed. Chapter 3 identifies the origin of regulatory administration and the principles of administration laws. It also examines legal nature of the nuclear safety standard. In relation to regulatory authorities. Chapter 4 identifies role and responsibility of administration authorities and institutions. It also examines fundamental principles of delegation of power. Then the chapter discusses the nuclear safety regulation authorities and their roles and responsibilities. Chapter 5 classifies and examines regulatory administration actions. Chapter 6 evaluates enforcement measure for effectiveness of regulation. Finally, chapter 7 discusses the administrative relief system for reviewing unreasonable regulatory acts.

Cypermethrin induced reproductive toxicity in male Wistar rats: protective role of Tribulus terrestris.

Science.gov (United States)

Sharma, Poonam; Huq, Amir Ul; Singh, Rambir

2013-09-01

The present study was designed to investigate role of ethanolic extract of Tribulus terrestris (EETT) against alpha-cypermethrin induced reproductive toxicity in male Wistar rats. 24 male Wistar rats weighing about 250-300g were divided in four groups. Group-I was control. alpha-cypermethrin (3.38 mg kg-1b.wt.) was given to group-IlI for 28 days. In Group-Ill, alpha-cypermethrin and EETT (100 mg kg -1b.wt.) were administered in combination for 28 days. Rats in group-IV were given EETT for 28 days. At the end of the experiment, rats were sacrificed, testes and epididymis were removed and sperm characteristics, sex hormones and various biochemical parameters were studied. Decrease in weight of testes and epididymis, testicular sperm head count, sperm motility, live sperm count, serum testosterone (T), follicle stimulating hormone (FSH), leutinizing hormone (LH), catalase (CAT), superoxide dismutase (SOD), glutathione S transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), total protein content and increase in sperm abnormalities and lipid peroxidation (LPO) level was observed in rats exposed to cypermethrin. In combination group-Ill, EETT treatment ameliorated alpha-cypermethrin induced damage. EETT treatment in group-IV increased testes and epididymis weight, sperm head counts, sperm motility, live sperm counts, testosterone, FSH, LH, GSH, CAT, SOD, GST, GR, GPx and total protein content. The study suggested that Tribulus terrestris plant possess reproductive system enhancement and antioxidant activity.

Induction of regulatory T cells: A role for probiotics and prebiotics to suppress autoimmunity.

Science.gov (United States)

Dwivedi, Mitesh; Kumar, Prasant; Laddha, Naresh C; Kemp, E Helen

2016-04-01

Regulatory T cells (Tregs) are comprised of a heterogeneous population of cells that play a vital role in suppressing inflammation and maintaining immune tolerance. Given the crucial role of Tregs in maintaining immune homeostasis, it is probably not surprising that many microbial species and their metabolites have the potential to induce Tregs. There is now great interest in the therapeutic potential of probiotics and prebiotics based strategies for a range of autoimmune disorders. This review will summarise recent findings concerning the role of probiotics and prebiotics in induction of Tregs to ameliorate the autoimmune conditions. In addition, the article is focused to explain the different mechanisms of Treg induction and function by these probiotics and prebiotics, based on the available studies till date. The article further proposes that induction of Tregs by probiotics and prebiotics could lead to the development of new therapeutic approach towards curbing the autoimmune response and as an alternative to detrimental immunosuppressive drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

Role of Oestrogen α Receptors in Sociosexual Behaviour in Female Rats Housed in a Seminatural Environment.

Science.gov (United States)

Snoeren, E M S; Antonio-Cabrera, E; Spiteri, T; Musatov, S; Ogawa, S; Pfaff, D W; Ågmo, A

2015-11-01

The present study investigated the role of oestrogen receptor (ER)α in the ventromedial nucleus of the hypothalamus (VMN), the preoptic area (POA), the medial amygdala (MePD) and the bed nucleus of stria terminalis (BNST) in sociosexual behaviour in female rats. This was conducted in two sets of experiments, with the VMN and POA investigated in the first set, and the MePD and BNST in the second set. The VMN and POA received intense projections from the MePD and BNST. We used a short hairpin RNA encoded within an adeno-associated viral vector directed against the gene for ERα to reduce the number of ERα in the VMN or POA (first set of experiments) or in the BNST or MePD (second set of experiments) in female rats. The rats were housed in groups of four ovariectomised females and three males in a seminatural environment for 8 days. Compared with traditional test set-ups, the seminatural environment provides an arena in which the rats can express their full behavioural repertoire, which allowed us to investigate multiple aspects of social and sexual behaviour in groups of rats. Behavioural observation was performed after oestrogen and progesterone injections. A reduction of ERα expression in the VMN or POA diminished the display of paracopulatory behaviours and lordosis responses compared to controls, whereas the lordosis quotient remained unaffected. This suggests that ERα in the VMN and POA play an important role in intrinsic sexual motivation. The reduction in ERα did not affect the social behaviour of the females, although the males sniffed and pursued the females with reduced ERα less than the controls. This suggests that the ERα in the VMN and POA is involved in the regulation of sexual attractiveness of females. The ERα in the MePD and BNST, on the other hand, plays no role in sociosexual behaviour. © 2015 British Society for Neuroendocrinology.

TSO Role in Supporting the Regulatory Authority in View of Safety Culture

International Nuclear Information System (INIS)

Khamaza, A.; Vasilishin, A.

2016-01-01

Human and organizational factors are always of paramount importance at nuclear and radiation safety as well as in the safety regulation provision. Major NPP accidents occurred merely reaffirm this fact. The role of an authority that regulates nuclear safety increases each time in the aftermath of accidents perceived as a shock together with the importance of scientific and technical support. SEC NRS was established in 1987, the next year after the Chernobyl NPP accident aiming to strengthen supervision over works carried out at the nuclear industry enterprises. Currently SEC NRS provides comprehensive scientific and technical support to Rostechnadzor including safety review and regulatory legal documents development to regulate safety along with safety culture.

Early prophylactic and treatment role of melatonin against certain biochemical disorders in irradiated rats

International Nuclear Information System (INIS)

El-Massry, F.S.

2005-01-01

The aim of the present study is to evaluate the possible early prophylactic and therapeutic role of melatonin on irradiated rats. The experimental animals were divided into five groups: control, injected intraperitoneally with melatonin (10 mg/ kg b.wt.), irradiated at 6 Gy, injected with melatonin before irradiation and injected with melatonin after gamma irradiation. Blood, liver and brain samples from rats were collected at three time intervals of 7, 10, 14 days after terminating all treatments. Protein content and glutathione were estimated in blood and tissues, whereas testosterone and cortisol were assayed in blood of rats after whole body gamma irradiation at 6 Gy. Administration of melatonin (10 mg/kg) before whole body gamma irradiation markedly reduced the radiation injury and controlled the changes in most of the studied parameters, but following the administration of melatonin after irradiation, there were no changes in these parameters

Periodontitis promotes the diabetic development of obese rat via miR-147 induced classical macrophage activation.

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Xu, Ran; Zeng, Guang; Wang, Shuyong; Tao, Hong; Ren, Le; Zhang, Zhe; Zhang, Qingna; Zhao, Jinxiu; Gao, Jing; Li, Daxu

2016-10-01

Emerging evidence has indicated the bad effect of periodontal inflammation on diabetes control. However, the exact regulatory mechanisms within the association between periodontitis and diabetic development remain unclear. This study aims to investigate the function of microRNAs in regulating periodontitis-induced inflammation in an obese rat model. Experimental periodontitis was introduced into OLETF and LETO rat. Intraperitoneal glucose tolerance test was performed to detect diabetic development. Serum cytokines levels and microRNAs expression were detected by ELISA and RT-PCR analysis respectively. And, macrophages were isolated for gain- and loss-of-function studies, to investigate the regulatory mechanism of miR-147 in periodontitis-induced inflammation. Periodontitis induced proinflammatory response with classical activated macrophages in both rats, but distinctively aggravated the impaired glucose tolerance of OLETF rat with spontaneous type 2 diabetes. Analysis for serum microRNAs expression showed the distinctive and synergistic upregulation of miR-147 with periodontitis-induced effects in rats, while further experiments demonstrated the positive regulatory mechanism of miR-147 on classical activated macrophages with overexpressed proinflammatory markers, showing M1 phenotype. This study provided new evidence for the positive effect of periodontal inflammation on diabetic development, while the regulatory mechanism of miR-147 on classical macrophage activation, was verified, and presumed to contribute to the impaired glucose tolerance aggravated by periodontitis in obese rats. Besides, this study indicated the application of miR-147 for therapeutic approach in the treatment of diabetes with periodontitis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

RNA SURVEILLANCE– AN EMERGING ROLE FOR RNA REGULATORY NETWORKS IN AGING

OpenAIRE

Montano, Monty; Long, Kimberly

2010-01-01

In this review, we describe recent advances in the field of RNA regulatory biology and relate these advances to aging science. We introduce a new term, RNA surveillance, an RNA regulatory process that is conserved in metazoans, and describe how RNA surveillance represents molecular cross-talk between two emerging RNA regulatory systems – RNA interference and RNA editing. We discuss how RNA surveillance mechanisms influence mRNA and microRNA expression and activity during lifespan. Additionall...

Uncaria rhynchophylla (miq) Jack plays a role in neuronal protection in kainic acid-treated rats.

Science.gov (United States)

Tang, Nou-Ying; Liu, Chung-Hsiang; Su, Shan-Yu; Jan, Ya-Min; Hsieh, Ching-Tou; Cheng, Chin-Yi; Shyu, Woei-Cherng; Hsieh, Ching-Liang

2010-01-01

Uncaria rhynchophylla (Miq) Jack (UR) is one of many Chinese herbs. Our previous studies have shown that UR has both anticonvulsive and free radical-scavenging activities in kainic acid (KA)-treated rats. The aim of the present study was to use the effect of UR on activated microglia, nitric oxide synthase, and apoptotic cells to investigate its function in neuroproction in KA-treated rats. UR of 1.0 or 0.5 g/kg was orally administered for 3 days (first day, second day, and 30 min prior to KA administration on the third day), or 10 mg/kg (intraperitoneal injection, i.p.) N-nitro-L-arginine methyl ester (L-NAME) 30 min prior to KA (2 microg/2 microl) was injected into the right hippocampus region of Sprague-Dawly rats. ED1 (mouse anti rat CD68), neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS) immunoreactive cells and apoptotic cells were observed in the hippocampus region. The results indicated that 1.0 g/kg, 0.5 g/kg of UR and 10 mg/kg of L-NAME reduced the counts of ED1, nNOS, iNOS immunoreactive cells and apoptotic cells in KA-treated rats. This study demonstrates that UR can reduce microglia activation, nNOS, iNOS and apoptosis, suggesting that UR plays a neuro-protective role against neuronal damage in KA-treated rats.

Regulatory role of XynR (YagI) in catabolism of xylonate in Escherichia coli K-12.

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Shimada, Tomohiro; Momiyama, Eri; Yamanaka, Yuki; Watanabe, Hiroki; Yamamoto, Kaneyoshi; Ishihama, Akira

2017-12-01

The genome of Escherichia coli K-12 contains ten cryptic phages, altogether constituting about 3.6% of the genome in sequence. Among more than 200 predicted genes in these cryptic phages, 14 putative transcription factor (TF) genes exist, but their regulatory functions remain unidentified. As an initial attempt to make a breakthrough for understanding the regulatory roles of cryptic phage-encoded TFs, we tried to identify the regulatory function of CP4-6 cryptic prophage-encoded YagI with unknown function. After SELEX screening, YagI was found to bind mainly at a single site within the spacer of bidirectional transcription units, yagA (encoding another uncharacterized TF) and yagEF (encoding 2-keto-3-deoxy gluconate aldolase, and dehydratase, respectively) within this prophage region. YagEF enzymes are involved in the catabolism of xylose downstream from xylonate. We then designated YagI as XynR (regulator of xylonate catabolism), one of the rare single-target TFs. In agreement with this predicted regulatory function, the activity of XynR was suggested to be controlled by xylonate. Even though low-affinity binding sites of XynR were identified in the E. coli K-12 genome, they all were inside open reading frames, implying that the regulation network of XynR is still fixed within the CR4-6 prophage without significant influence over the host E. coli K-12. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Dietary isoflavones alter regulatory behaviors, metabolic hormones and neuroendocrine function in Long-Evans male rats

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Bu Lihong

2004-12-01

Full Text Available Abstract Background Phytoestrogens derived from soy foods (or isoflavones have received prevalent usage due to their 'health benefits' of decreasing: a age-related diseases, b hormone-dependent cancers and c postmenopausal symptoms. However, little is known about the influence of dietary phytoestrogens on regulatory behaviors, such as food and water intake, metabolic hormones and neuroendocrine parameters. This study examined important hormonal and metabolic health issues by testing the hypotheses that dietary soy-derived isoflavones influence: 1 body weight and adipose deposition, 2 food and water intake, 3 metabolic hormones (i.e., leptin, insulin, T3 and glucose levels, 4 brain neuropeptide Y (NPY levels, 5 heat production [in brown adipose tissue (BAT quantifying uncoupling protein (UCP-1 mRNA levels] and 6 core body temperature. Methods This was accomplished by conducting longitudinal studies where male Long-Evans rats were exposed (from conception to time of testing or tissue collection to a diet rich in isoflavones (at 600 micrograms/gram of diet or 600 ppm vs. a diet low in isoflavones (at approximately 10–15 micrograms/gram of diet or 10–15 ppm. Body, white adipose tissue and food intake were measured in grams and water intake in milliliters. The hormones (leptin, insulin, T3, glucose and NPY were quantified by radioimmunoassays (RIA. BAT UCP-1 mRNA levels were quantified by PCR and polyacrylamide gel electrophoresis while core body temperatures were recorded by radio telemetry. The data were tested by analysis of variance (ANOVA (or where appropriate by repeated measures. Results Body and adipose tissue weights were decreased in Phyto-600 vs. Phyto-free fed rats. Food and water intake was greater in Phyto-600 animals, that displayed higher hypothalamic (NPY concentrations, but lower plasma leptin and insulin levels, vs. Phyto-free fed males. Higher thyroid levels (and a tendency for higher glucose levels and increased uncoupling

The role of oxidative stress in streptozotocin-induced diabetic nephropathy in rats.

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Fernandes, Sheila Marques; Cordeiro, Priscilla Mendes; Watanabe, Mirian; Fonseca, Cassiane Dezoti da; Vattimo, Maria de Fatima Fernandes

2016-10-01

The objective of this study was to evaluate the role of oxidative stress in an experimental model of streptozotocin-induced diabetic nephropathy in rats. Wistar, adult, male rats were used in the study. Animals were divided in the following groups: Citrate (control, citrate buffer 0.01M, pH 4.2 was administrated intravenously - i.v - in the caudal vein), Uninephrectomy+Citrate (left uninephrectomy-20 days before the study), DM (streptozotocin, 65 mg/kg, i.v, on the 20th day of the study), Uninephrectomy+DM. Physiological parameters (water and food intake, body weight, blood glucose, kidney weight, and relative kidney weight); renal function (creatinine clearance), urine albumin (immunodiffusion method); oxidative metabolites (urinary peroxides, thiobarbituric acid reactive substances, and thiols in renal tissue), and kidney histology were evaluated. Polyphagia, polydipsia, hyperglycemia, and reduced body weight were observed in diabetic rats. Renal function was reduced in diabetic groups (creatinine clearance, p < 0.05). Uninephrectomy potentiated urine albumin and increased kidney weight and relative kidney weight in diabetic animals (p < 0.05). Urinary peroxides and thiobarbituric acid reactive substances were increased, and the reduction in thiol levels demonstrated endogenous substrate consumption in diabetic groups (p < 0.05). The histological analysis revealed moderate lesions of diabetic nephropathy. This study confirms lipid peroxidation and intense consumption of the antioxidant defense system in diabetic rats. The association of hyperglycemia and uninephrectomy resulted in additional renal injury, demonstrating that the model is adequate for the study of diabetic nephropathy.

An essential regulatory role of downstream of kinase-1 in the ovalbumin-induced murine model of asthma.

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Chang-Min Lee

Full Text Available The downstream of kinase (DOK-1 is involved in the protein tyrosine kinase (PTK pathway in mast cells, but the role of DOK-1 in the pathogenesis of asthma has not been defined. In this study, we have demonstrated a novel regulatory role of DOK-1 in airway inflammation and physiologic responses in a murine model of asthma using lentiviral vector containing DOK-1 cDNA or DOK-1-specific ShRNA. The OVA-induced inflammatory cells, airway hyperresponsiveness, Th2 cytokine expression, and mucus response were significantly reduced in DOK-1 overexpressing mice compared to OVA-challenged control mice. The transgenic introduction of DOK-1 significantly stimulated the activation and expression of STAT-4 and T-bet, while impressively inhibiting the activation and expression of STAT-6 and GATA-3 in airway epithelial cells. On the other hand, DOK-1 knockdown mice enhanced STAT-6 expression and its nuclear translocation compared to OVA-challenged control mice. When viewed in combination, our studies demonstrate DOK-1 regulates allergen-induced Th2 immune responses by selective stimulation and inhibition of STAT-4 and STAT-6 signaling pathways, respectively. These studies provide a novel insight on the regulatory role of DOK-1 in allergen-induced Th2 inflammation and airway responses, which has therapeutic potential for asthma and other allergic diseases.

The Protective Role of Zinc Sulphate on Ethanol -Induced Liver and Kidney Damages in Rats

International Nuclear Information System (INIS)

Al-Damegh, Mona Abdalla

2007-01-01

Around the world more and more people suffer from alcoholism. Addiction problems, alcoholism and excessive use of drugs both medical and nonmedical, are major causes of liver and kidney damage in adults. The purpose of this study was to investigate on the protective role of zinc sulphate on liver and kidney in rats with acute alcoholism. Wistar albino rats were divided into four groups. Group I; control group, group 2; given only Zinc Sulphate (100 mg/kg/day for 3days), group 3; rats given absolute ethanol (1 ml of absolute ethanol administrated by gavage technique to each rat), group 4 given Zinc sulphate prior to the administration of absolute ethanol. The results of this study revealed that acute ethanol exposure caused degenerative morphological changes in the liver and kidney. Significant difference were found in the levels of serum, liver, kidney super oxide dismutase(SOD), catalase (CAT), nitric oxide(NO), and malondialdehyde (MDA) in the ethanol group compared to the control group. Moreover ,serum urea, creatnine, uric acid, alkaline phoshpatase and transaminases activities (GOTand GPT) were increased in the ethanol group compared to the control group. On the other hand,administration of zinc sulphate in the ethanol group caused a significant decrease in the degenerative changes, lipid peroxidation, antioxidant enzymes, and nitric oxide in serum, liver, and kidney. It can be concluded that zinc Sulphate has a protective role on the ethanol induced liver and kidney injury. In addition ,nitric oxide is involved in the mechanism of acute alcohol intoxication. (author)

Locus coeruleus lesions and PCOS: role of the central and peripheral sympathetic nervous system in the ovarian function of rat

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Farideh Zafari Zangeneh

2012-01-01

Full Text Available Polycystic ovary syndrome (PCOS is a complex endocrine and metabolic disorder associated with ovulatory dysfunction”. “Autonomic and central nervous systems play important roles in the regulation of ovarian physiology”. The noradrenergic nucleus locus coeruleus (LC plays a central role in the regulation of the sympathetic nervous system and synaptically connected to the preganglionic cell bodies of the ovarian sympathetic pathway and its activation is essential to trigger spontaneous or induced LH surges. This study evaluates sympathetic outflow in central and peripheral pathways in PCO rats. Objective: Our objectives in this study were (1 to estimate LC activity in rats with estradiol valerate (EV-induced PCO; (2 to antagonized alpha2a adrenoceptor in systemic conditions with yohimbine. Materials and Methods: Forty two rats were divided into two groups: 1 LC and yohimbine and 2 control. Every group subdivided in two groups: eighteen rats were treated with estradiol valerate for induction of follicular cysts and the remainders were sesame oil groups. Results: Estradiol concentration was significantly augmented by the LC lesion in PCO rats (p<0.001, while LC lesion could not alter serum concentrations of LH and FSH, like yohimbine. The morphological observations of ovaries of LC lesion rats showed follicles with hyperthecosis, but yohimbine reduced the number of cysts, increased corpus lutea and developed follicles. Conclusion: Rats with EV-induced PCO increased sympathetic activity. LC lesion and yohimbine decreased the number of cysts and yohimbine increased corpus lutea and developed follicles in PCO rats.

Expression and role of neuroglobin in rats with sepsis-associated encephalopathy.

Science.gov (United States)

Zhang, Li-Na; Ai, Yu-Hang; Gong, Hua; Guo, Qu-Lian; Huang, Li; Liu, Zhi-Yong; Yao, Bo

2014-01-01

To determine the role of neuroglobin in the pathology of sepsis-associated encephalopathy and ascertain if neuroglobin has any protective effects against sepsis-associated encephalopathy. Randomized laboratory animal study. Research university animal laboratory. Two hundred and forty adult male Sprague-Dawley rats. Rats received cecal puncture and ligation (or sham) surgery to induce sepsis, then broken up into groups based on whether or not the rat developed sepsis-associated encephalopathy as determined by electroencephalograph and evoked potential recordings. The rats were then left untreated to examine the effect of sepsis-associated encephalopathy on neuroglobin, treated with a neuroglobin antisense nucleotide to block gene expression, or given hemin, a neuroglobin inducer. Following sepsis induction, diagnosis, and treatment, the brains were analyzed for both gross and ultrastructural morphology. Also, neuronal neuroglobin immunoreactivity and apoptosis (via terminal uridine nucleotide end-labeling) were examined. Blood serum levels were then analyzed for neuroglobin, superoxide dismutase, and malondialdehyde levels. We determined that sepsis-associated encephalopathy induces damage evident when examining both gross and ultrastructural morphology, as well as induces neuronal neuroglobin expression. Also, blockade of neuroglobin expression via antisense treatment will exacerbate these pathological effects, while increasing neuroglobin levels via hemin will ameliorate them. Blood analysis found that levels of superoxide dismutase and malondialdehyde mirrored the level of pathology found in the brain, while plasma neuroglobin levels reflected the amount of neuronal neuroglobin immunoreactivity. We conclude that neuroglobin is involved in the pathogenesis of sepsis-associated encephalopathy and has neuroprotective effects. We also determined that hemin has protective effects against sepsis-associated encephalopathy as well, most probably due to its effect on

role of conjugated linoleic acid in the prevention of radiation hazard in male rats

International Nuclear Information System (INIS)

Hussien, E.M.; Osman, N.N.; Haggag, A.M.

2009-01-01

the objective of the present study was to examine the effect of conjugated linoleic acid (CLA) as a natural product in minimizing the radiation hazards. male rats were assigned to six groups each of 7 animals throughout six weeks, fed 1% CLA (wt/wt)added to commercial diet in the form of milk powder 182 g/kg diet. rats exposed to 6 Gy whole body gamma irradiation showed significant increase in total cholesterol (TC), low density lipoprotein cholesterol (LDL-C).triglycerides (TG), atherosclerosis index, total lipid (TL), phospholipids (ph-lipids), malondialdehyde (MDA), urea,creatinine, uric acid, calcium (Ca) and phosphorous levels associated with decrease in high density lipoprotein-cholesterol (HDL-C), activity of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), total antioxidant status, body weight, testes weight and testosterone both irradiated and non-irradiated milk powder administrated to irradiated rat groups minimized the radiation damage in the assayed parameters indicating its beneficial role as a promising antioxidant in scavenging free radicals and reactive oxygen species

Role of the regulatory authority in preparation of the NPP self assessment of safety culture

Energy Technology Data Exchange (ETDEWEB)

Gantchev, T [Committee on the Use of Atomic Energy for Peaceful Purposes, Sofia (Bulgaria)

1997-12-31

We believe that with the assistance of the IAEA(ASSET Training Mission) the plant personnel will be able to prepare high quality Self Assessment Report. The main role of the Regulatory Body is to ensure correspondence with the IAEA requirements and to provide clear guidance for the most important items of the Plant Self Assessment Report. The involvement of the Operating Organization is also desirable in order to ensure the necessary resources for the implementation of the action plan. Figs.

Role of the regulatory authority in preparation of the NPP self assessment of safety culture

International Nuclear Information System (INIS)

Gantchev, T.

1996-01-01

We believe that with the assistance of the IAEA(ASSET Training Mission) the plant personnel will be able to prepare high quality Self Assessment Report. The main role of the Regulatory Body is to ensure correspondence with the IAEA requirements and to provide clear guidance for the most important items of the Plant Self Assessment Report. The involvement of the Operating Organization is also desirable in order to ensure the necessary resources for the implementation of the action plan. Figs

The lateral neostriatum is necessary for compensatory ingestive behaviour after intravascular dehydration in female rats.

Science.gov (United States)

Lelos, M J; Harrison, D J; Rosser, A E; Dunnett, S B

2013-12-01

Aberrant striatal function results in an array of physiological symptoms, including impaired consummatory and regulatory behaviours, which can lead to weight loss and dehydration. It was hypothesised, therefore, that cell loss in the neostriatum may contribute to altered fluid intake by regulating physiological signals related to dehydration status. To test this theory, rats with lesions of the lateral neostriatum and sham controls underwent a series of physiological challenges, including the experimental induction of intracellular and intravascular dehydration. No baseline differences in prandial or non-prandial drinking were observed, nor were differences in locomotor activity evident between groups. Furthermore, intracellular dehydration increased water intake in lesion rats in a manner comparable to sham rats. Interestingly, a specific impairment was evident in lesion rats after subcutaneous injection of poly-ethylene glycol was used to induce intravascular dehydration, such that lesion rats failed to adapt their water intake to this physiological change. The results suggest that the striatal lesions resulted in regulatory dysfunction by impairing motivational control over compensatory ingestive behaviour after intravascular hydration, while the physiological signals related to dehydration remain intact. Loss of these cells in neurodegenerative disorders, such Huntington's disease, may contribute to regulatory changes evident in the course of the disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neuroprotective role of curcumin on the hippocampus against the structural and serological alterations of streptozotocin-induced diabetes in Sprague Dawely rats.

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Faheem, Nermeen Mohammed; El Askary, Ahmad

2017-06-01

Diabetes mellitus causes impaired memory and cognitive functions. The hippocampus plays a key role in memory and learning. Curcumin attenuates diabetic nephropathy in vivo . Curcumin has shown a neurogenic effect and cognition-enhancing potential in aged rats. The aim of this study is to evaluate the possible protective role of curcumin on the histological and serological changes of the hippocampus in diabetic rats. Forty albino rats were divided into four groups, ten rats each. Group 1 control rats, group 2 rats received curcumin orally (200 mg/kg/day for six weeks), group 3 rats were injected intraperitoneally with streptozotocin (STZ) (100 mg/kg, single dose), group 4 received a single injection of STZ and received curcumin orally for six weeks. Paraffin sections of hippocampus were prepared and stained with hematoxylin and eosin stain, and immnunohistochemical staining for GFAP and caspase-3. Morphometrical and statistical analyses were performed. Glycemic status and parameters of oxidative stress was measured. Examination of hippocampus of diabetic rats showed disorganization of small pyramidal cells in CA1, many cellular losses in the pyramidal cells of CA3, many degenerated granule cells in the dentate gyrus. GFAP positive astrocyte and caspase-3 positive neuron counts were significantly increased. There were significant serum glucose elevation and significant lowered levels of oxidative stress parameters as compared to control rats. Curcumin administration improved the structural and serological alterations of the hippocampus with significant reduction in serum glucose level. Curcumin ameliorates the deterious effect of diabetes on the hippocampus through its antioxidant, antiapoptotic and anti-inflammatory efficacies.

Role of Sodium Bicarbonate Cotransporters in Intracellular pH Regulation and Their Regulatory Mechanisms in Human Submandibular Glands.

Science.gov (United States)

Namkoong, Eun; Shin, Yong-Hwan; Bae, Jun-Seok; Choi, Seulki; Kim, Minkyoung; Kim, Nahyun; Hwang, Sung-Min; Park, Kyungpyo

2015-01-01

Sodium bicarbonate cotransporters (NBCs) are involved in the pH regulation of salivary glands. However, the roles and regulatory mechanisms among different NBC isotypes have not been rigorously evaluated. We investigated the roles of two different types of NBCs, electroneutral (NBCn1) and electrogenic NBC (NBCe1), with respect to pH regulation and regulatory mechanisms using human submandibular glands (hSMGs) and HSG cells. Intracellular pH (pHi) was measured and the pHi recovery rate from cell acidification induced by an NH4Cl pulse was recorded. Subcellular localization and protein phosphorylation were determined using immunohistochemistry and co-immunoprecipitation techniques. We determined that NBCn1 is expressed on the basolateral side of acinar cells and the apical side of duct cells, while NBCe1 is exclusively expressed on the apical membrane of duct cells. The pHi recovery rate in hSMG acinar cells, which only express NBCn1, was not affected by pre-incubation with 5 μM PP2, an Src tyrosine kinase inhibitor. However, in HSG cells, which express both NBCe1 and NBCn1, the pHi recovery rate was inhibited by PP2. The apparent difference in regulatory mechanisms for NBCn1 and NBCe1 was evaluated by artificial overexpression of NBCn1 or NBCe1 in HSG cells, which revealed that the pHi recovery rate was only inhibited by PP2 in cells overexpressing NBCe1. Furthermore, only NBCe1 was significantly phosphorylated and translocated by NH4Cl, which was inhibited by PP2. Our results suggest that both NBCn1 and NBCe1 play a role in pHi regulation in hSMG acinar cells, and also that Src kinase does not regulate the activity of NBCn1.

Role of Sodium Bicarbonate Cotransporters in Intracellular pH Regulation and Their Regulatory Mechanisms in Human Submandibular Glands.

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Eun Namkoong

Full Text Available Sodium bicarbonate cotransporters (NBCs are involved in the pH regulation of salivary glands. However, the roles and regulatory mechanisms among different NBC isotypes have not been rigorously evaluated. We investigated the roles of two different types of NBCs, electroneutral (NBCn1 and electrogenic NBC (NBCe1, with respect to pH regulation and regulatory mechanisms using human submandibular glands (hSMGs and HSG cells. Intracellular pH (pHi was measured and the pHi recovery rate from cell acidification induced by an NH4Cl pulse was recorded. Subcellular localization and protein phosphorylation were determined using immunohistochemistry and co-immunoprecipitation techniques. We determined that NBCn1 is expressed on the basolateral side of acinar cells and the apical side of duct cells, while NBCe1 is exclusively expressed on the apical membrane of duct cells. The pHi recovery rate in hSMG acinar cells, which only express NBCn1, was not affected by pre-incubation with 5 μM PP2, an Src tyrosine kinase inhibitor. However, in HSG cells, which express both NBCe1 and NBCn1, the pHi recovery rate was inhibited by PP2. The apparent difference in regulatory mechanisms for NBCn1 and NBCe1 was evaluated by artificial overexpression of NBCn1 or NBCe1 in HSG cells, which revealed that the pHi recovery rate was only inhibited by PP2 in cells overexpressing NBCe1. Furthermore, only NBCe1 was significantly phosphorylated and translocated by NH4Cl, which was inhibited by PP2. Our results suggest that both NBCn1 and NBCe1 play a role in pHi regulation in hSMG acinar cells, and also that Src kinase does not regulate the activity of NBCn1.

MicroRNA profiling in the dentate gyrus in epileptic rats: The role of miR-187-3p.

Science.gov (United States)

Zhang, Suya; Kou, Yubin; Hu, Chunmei; Han, Yan

2017-06-01

This study aimed to explore the role of aberrant miRNA expression in epilepsy and to identify more potential genes associated with epileptogenesis.The miRNA expression profile of GSE49850, which included 20 samples from the rat epileptic dentate gyrus at 7, 14, 30, and 90 days after electrical stimulation and 20 additional samples from sham time-matched controls, was downloaded from the Gene Expression Omnibus database. The significantly differentially expressed miRNAs were identified in stimulated samples at each time point compared to time-matched controls, respectively. The target genes of consistently differentially expressed miRNAs were screened from miRDB and microRNA.org databases, followed by Gene Ontology (GO) and pathway enrichment analysis and regulatory network construction. The overlapping target genes for consistently differentially expressed miRNAs were also identified from these 2 databases. Furthermore, the potential binding sites of miRNAs and their target genes were analyzed.Rno-miR-187-3p was consistently downregulated in stimulated groups compared with time-matched controls. The predicted target genes of rno-miR-187-3p were enriched in different GO terms and pathways. In addition, 7 overlapping target genes of rno-miR-187-3p were identified, including NFS1, PAQR4, CAND1, DCLK1, PRKAR2A, AKAP3, and KCNK10. These 7 overlapping target genes were determined to have a different number of matched binding sites with rno-miR-187-3p.Our study suggests that miR-187-3p may play an important role in epilepsy development and progression via regulating numerous target genes, such as NFS1, CAND1, DCLK1, AKAP3, and KCNK10. Determining the underlying mechanism of the role of miR-187-3p in epilepsy may make it a potential therapeutic option.

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

Energy Technology Data Exchange (ETDEWEB)

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

2010-09-15

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

Broadening the cancer and cognition landscape: the role of self-regulatory challenges.

Science.gov (United States)

Arndt, Jamie; Das, Enny; Schagen, Sanne B; Reid-Arndt, Stephanie A; Cameron, Linda D; Ahles, Tim A

2014-01-01

The potentially detrimental effects of cancer and related treatments on cognitive functioning have emerged as one of the key foci of cancer survivorship research, but little is known about how psychological variables other than depression influence these relationships. To illustrate the potential of social psychological perspectives, we examine how a self-regulatory analysis and specific self-regulatory challenges of contending with cancer-related expectancies and stereotypes provide conceptual frameworks for understanding some of the potential causes and consequences of cancer-related cognitive deficits. Literatures on cancer-related cognitive deficits, self-regulatory ego depletion, expectancy stereotypes, and their points of convergence are briefly reviewed. A review and conceptual integration of relevant literatures suggest that coping with cancer can impair self-regulatory capacity. There is an overlap between cognitive deficits associated with self-regulatory challenge and with cancer and its treatment, and restoring self-regulatory resources can attenuate cancer-related cognitive deficits. Examination of specific regulatory challenges of contending with expectancies and stereotypes related to treatment suggests insights that can inform when and among whom cognitive deficits may most likely emerge. Integrating social psychological ideas with a substantial knowledge base can illustrate novel research trajectories that can deepen our understanding of cancer-related cognitive deficits and their impact on psychosocial well-being. Copyright © 2013 John Wiley & Sons, Ltd.

Development of multipurpose regulatory PSA model

International Nuclear Information System (INIS)

Lee, Chang Ju; Sung, Key Yong; Kim, Hho Jung; Yang, Joon Eon; Ha, Jae Joo

2004-01-01

Generally, risk information for nuclear facilities comes from the results of Probabilistic safety assessment (PSA). PSA is a systematic tool to ensure the safety of nuclear facilities, since it is based on thorough and consistent application of probability models. In particular, the PSA has been widely utilized for risk-informed regulation (RIR), including various licensee-initiated risk-informed applications (RIA). In any regulatory decision, the main goal is to make a sound safety decision based on technically defensible information. Also, due to the increased public requests for giving a safety guarantee, the regulator should provide the visible means of safety. The use of PSA by the regulator can give the answer on this problem. Therefore, in order to study the applicability of risk information for regulatory safety management, it is a demanding task to prepare a well-established regulatory PSA model and tool. In 2002, KINS and KAERI together made a research cooperation to form a working group to develop the regulatory PSA model - so-called MPAS model. The MPAS stands for multipurpose probabilistic analysis of safety. For instance, a role of the MPAS model is to give some risk insights in the preparation of various regulatory programs. Another role of this model is to provide an independent risk information to the regulator during regulatory decision-making, not depending on the licensee's information

Increased in vivo glucose utilization in 30-day-old obese Zucker rat: Role of white adipose tissue

International Nuclear Information System (INIS)

Krief, S.; Bazin, R.; Dupuy, F.; Lavau, M.

1988-01-01

In vivo whole-body glucose utilization and uptake in multiple individual tissues were investigated in conscious 30-day-old Zucker rats, which when obese are hyperphagic, hyperinsulinemic, and normoglycemic. Whole-body glucose metabolism (assessed by [3- 3 H]glucose) was 40% higher in obese (fa/fa) than in lean (Fa/fa) rats, suggesting that obese rats were quite responsive to their hyperinsulinemia. In obese compared with lean rats, tissue glucose uptake was increased by 15, 12, and 6 times in dorsal, inguinal, perigonadal white depots, respectively; multiplied by 2.5 in brown adipose tissue; increased by 50% in skin from inguinal region but not in that from cranial, thoracic, or dorsal area; and increased twofold in diaphragm but similar in heart in proximal intestine, and in total muscular mass of limbs. The data establish that in young obese rats the hypertrophied white adipose tissue was a major glucose-utilizing tissue whose capacity for glucose disposal compared with that of half the muscular mass. Adipose tissue could therefore play an important role in the homeostasis of glucose in obese rats in the face of their increased carbohydrate intake

α-Estrogen and Progesterone Receptors Modulate Kisspeptin Effects on Prolactin: Role in Estradiol-Induced Prolactin Surge in Female Rats.

Science.gov (United States)

Aquino, Nayara S S; Araujo-Lopes, Roberta; Henriques, Patricia C; Lopes, Felipe E F; Gusmao, Daniela O; Coimbra, Candido C; Franci, Celso R; Reis, Adelina M; Szawka, Raphael E

2017-06-01

Kisspeptin (Kp) regulates prolactin (PRL) in an estradiol-dependent manner. We investigated the interaction between ovarian steroid receptors and Kp in the control of PRL secretion. Intracerebroventricular injections of Kp-10 or Kp-234 were performed in ovariectomized (OVX) rats under different hormonal treatments. Kp-10 increased PRL release and decreased 3,4-dihydroxyphenylacetic acid levels in the median eminence (ME) of OVX rats treated with estradiol (OVX+E), which was prevented by tamoxifen. Whereas these effects of Kp-10 were absent in OVX rats, they were replicated in OVX rats treated with selective agonist of estrogen receptor (ER)α, propylpyrazole triol, but not of ERβ, diarylpropionitrile. Furthermore, the Kp-10-induced increase in PRL was two times higher in OVX+E rats also treated with progesterone (OVX+EP), which was associated with a reduced expression of both tyrosine hydroxylase (TH) and Ser40-phosphorylated TH in the ME. Kp-10 also reduced dopamine levels in the ME of OVX+EP rats, an effect blocked by the progesterone receptor (PR) antagonist RU486. We also determined the effect of Kp antagonism with Kp-234 on the estradiol-induced surges of PRL and luteinizing hormone (LH), using tail-tip blood sampling combined with ultrasensitive enzyme-linked immunosorbent assay. Kp-234 impaired the early phase of the PRL surge and prevented the LH surge in OVX+E rats. Thus, we provide evidence that Kp stimulation of PRL release requires ERα and is potentiated by progesterone via PR activation. Moreover, alongside its essential role in the LH surge, Kp seems to play a role in the peak phase of the estradiol-induced PRL surge. Copyright © 2017 Endocrine Society.

[Effect of baicalin on ATPase and LDH and its regulatory effect on the AC/cAMP/PKA signaling pathway in rats with attention deficit hyperactivity disorder].

Science.gov (United States)

Zhou, Rong-Yi; Wang, Jiao-Jiao; You, Yue; Sun, Ji-Chao; Song, Yu-Chen; Yuan, Hai-Xia; Han, Xin-Min

2017-05-01

To study the effect of baicalin on synaptosomal adenosine triphosphatase (ATPase) and lactate dehydrogenase (LDH) and its regulatory effect on the adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway in rats with attention deficit hyperactivity disorder (ADHD). A total of 40 SHR rats were randomly divided into five groups: ADHD model, methylphenidate hydrochloride treatment (0.07 mg/mL), and low-dose (3.33 mg/mL), medium-dose (6.67 mg/mL), and high-dose (10 mg/mL) baicalin treatment (n=8 each). Eight WKY rats were selected as normal control group. Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structure. Colorimetry was used to measure the activities of ATPase and LDH in synaptosomes. ELISA was used to measure the content of AC, cAMP, and PKA. Compared with the normal control group, the ADHD model group had a significant reduction in the ATPase activity, a significant increase in the LDH activity, and significant reductions in the content of AC, cAMP, and PKA (PATPase activity (PATPase activity (PATPase activity (PATPase and LDH activities in rats with ADHD. The effect of baicalin is dose-dependent, and high-dose baicalin has a significantly greater effect than methylphenidate hydrochloride. Baicalin exerts its therapeutic effect possibly by upregulating the AC/cAMP/PKA signaling pathway.

Adenylyl cyclase plays a regulatory role in development, stress resistance and secondary metabolism in Fusarium fujikuroi.

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Jorge García-Martínez

Full Text Available The ascomycete fungus Fusarium fujikuroi (Gibberella fujikuroi MP-C produces secondary metabolites of biotechnological interest, such as gibberellins, bikaverin, and carotenoids. Production of these metabolites is regulated by nitrogen availability and, in a specific manner, by other environmental signals, such as light in the case of the carotenoid pathway. A complex regulatory network controlling these processes is recently emerging from the alterations of metabolite production found through the mutation of different regulatory genes. Here we show the effect of the targeted mutation of the acyA gene of F. fujikuroi, coding for adenylyl cyclase. Mutants lacking the catalytic domain of the AcyA protein showed different phenotypic alterations, including reduced growth, enhanced production of unidentified red pigments, reduced production of gibberellins and partially derepressed carotenoid biosynthesis in the dark. The phenotype differs in some aspects from that of similar mutants of the close relatives F. proliferatum and F. verticillioides: contrary to what was observed in these species, ΔacyA mutants of F. fujikuroi showed enhanced sensitivity to oxidative stress (H(2O(2, but no change in heavy metal resistance or in the ability to colonize tomato tissue, indicating a high versatility in the regulatory roles played by cAMP in this fungal group.

Advancing the use of noncoding RNA in regulatory toxicology: Report of an ECETOC workshop.

Science.gov (United States)

Aigner, Achim; Buesen, Roland; Gant, Tim; Gooderham, Nigel; Greim, Helmut; Hackermüller, Jörg; Hubesch, Bruno; Laffont, Madeleine; Marczylo, Emma; Meister, Gunter; Petrick, Jay S; Rasoulpour, Reza J; Sauer, Ursula G; Schmidt, Kerstin; Seitz, Hervé; Slack, Frank; Sukata, Tokuo; van der Vies, Saskia M; Verhaert, Jan; Witwer, Kenneth W; Poole, Alan

2016-12-01

The European Centre for the Ecotoxicology and Toxicology of Chemicals (ECETOC) organised a workshop to discuss the state-of-the-art research on noncoding RNAs (ncRNAs) as biomarkers in regulatory toxicology and as analytical and therapeutic agents. There was agreement that ncRNA expression profiling data requires careful evaluation to determine the utility of specific ncRNAs as biomarkers. To advance the use of ncRNA in regulatory toxicology, the following research priorities were identified: (1) Conduct comprehensive literature reviews to identify possibly suitable ncRNAs and areas of toxicology where ncRNA expression profiling could address prevailing scientific deficiencies. (2) Develop consensus on how to conduct ncRNA expression profiling in a toxicological context. (3) Conduct experimental projects, including, e.g., rat (90-day) oral toxicity studies, to evaluate the toxicological relevance of the expression profiles of selected ncRNAs. Thereby, physiological ncRNA expression profiles should be established, including the biological variability of healthy individuals. To substantiate the relevance of key ncRNAs for cell homeostasis or pathogenesis, molecular events should be dose-dependently linked with substance-induced apical effects. Applying a holistic approach, knowledge on ncRNAs, 'omics and epigenetics technologies should be integrated into adverse outcome pathways to improve the understanding of the functional roles of ncRNAs within a regulatory context. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

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Camilla Figueiredo Grans

2014-07-01

Full Text Available Background: Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. Objective: To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Methods: Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week. At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. Results: The maximum load test increased in groups trained control (+32% and trained infarcted (+46% in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%, myocardial performance index (-39% and systolic blood pressure (+6% improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%, as well as in the low frequency band of systolic blood pressure (-46% in rats from group trained infarcted in relation to group sedentary infarcted. Conclusion: Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats.

Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

International Nuclear Information System (INIS)

Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins; Mostarda, Cristiano; Figueroa, Diego Mendrot; Angelis, Kátia De; Irigoyen, Maria Cláudia; Rodrigues, Bruno

2014-01-01

Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats

Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

Energy Technology Data Exchange (ETDEWEB)

Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins [Laboratório do Movimento Humano, Universidade São Judas Tadeu (USJT), São Paulo, SP (Brazil); Mostarda, Cristiano [Departamento de Educação Física, Universidade Federal do Maranhão (UFMA), São Luís, MA (Brazil); Figueroa, Diego Mendrot [Laboratório de Hipertensão Experimental, Instituto do Coração (InCor), Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP (Brazil); Angelis, Kátia De [Laboratório de Fisiologia Translacional, Universidade Nove de Julho (Uninove), São Paulo, SP (Brazil); Irigoyen, Maria Cláudia [Laboratório de Hipertensão Experimental, Instituto do Coração (InCor), Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP (Brazil); Rodrigues, Bruno, E-mail: bruno.rodrigues@incor.usp.br [Laboratório do Movimento Humano, Universidade São Judas Tadeu (USJT), São Paulo, SP (Brazil)

2014-07-15

Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats.

Resistance Training After Myocardial Infarction in Rats: Its Role on Cardiac and Autonomic Function

Science.gov (United States)

Grans, Camilla Figueiredo; Feriani, Daniele Jardim; Abssamra, Marcos Elias Vergilino; Rocha, Leandro Yanase; Carrozzi, Nicolle Martins; Mostarda, Cristiano; Figueroa, Diego Mendrot; Angelis, Kátia De; Irigoyen, Maria Cláudia; Rodrigues, Bruno

2014-01-01

Background Although resistance exercise training is part of cardiovascular rehabilitation programs, little is known about its role on the cardiac and autonomic function after myocardial infarction. Objective To evaluate the effects of resistance exercise training, started early after myocardial infarction, on cardiac function, hemodynamic profile, and autonomic modulation in rats. Methods Male Wistar rats were divided into four groups: sedentary control, trained control, sedentary infarcted and trained infarcted rats. Each group with n = 9 rats. The animals underwent maximum load test and echocardiography at the beginning and at the end of the resistance exercise training (in an adapted ladder, 40% to 60% of the maximum load test, 3 months, 5 days/week). At the end, hemodynamic, baroreflex sensitivity and autonomic modulation assessments were made. Results The maximum load test increased in groups trained control (+32%) and trained infarcted (+46%) in relation to groups sedentary control and sedentary infarcted. Although no change occurred regarding the myocardial infarction size and systolic function, the E/A ratio (-23%), myocardial performance index (-39%) and systolic blood pressure (+6%) improved with resistance exercise training in group trained infarcted. Concomitantly, the training provided additional benefits in the high frequency bands of the pulse interval (+45%), as well as in the low frequency band of systolic blood pressure (-46%) in rats from group trained infarcted in relation to group sedentary infarcted. Conclusion Resistance exercise training alone may be an important and safe tool in the management of patients after myocardial infarction, considering that it does not lead to significant changes in the ventricular function, reduces the global cardiac stress, and significantly improves the vascular and cardiac autonomic modulation in infarcted rats. PMID:25014059

The role of the dopamine D1 receptor in social cognition: studies using a novel genetic rat model­

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Judith R. Homberg

2016-10-01

Full Text Available Social cognition is an endophenotype that is impaired in schizophrenia and several other (comorbid psychiatric disorders. One of the modulators of social cognition is dopamine, but its role is not clear. The effects of dopamine are mediated through dopamine receptors, including the dopamine D1 receptor (Drd1. Because current Drd1 receptor agonists are not Drd1 selective, pharmacological tools are not sufficient to delineate the role of the Drd1. Here, we describe a novel rat model with a genetic mutation in Drd1 in which we measured basic behavioural phenotypes and social cognition. The I116S mutation was predicted to render the receptor less stable. In line with this computational prediction, this Drd1 mutation led to a decreased transmembrane insertion of Drd1, whereas Drd1 expression, as measured by Drd1 mRNA levels, remained unaffected. Owing to decreased transmembrane Drd1 insertion, the mutant rats displayed normal basic motoric and neurological parameters, as well as locomotor activity and anxiety-like behaviour. However, measures of social cognition like social interaction, scent marking, pup ultrasonic vocalizations and sociability, were strongly reduced in the mutant rats. This profile of the Drd1 mutant rat offers the field of neuroscience a novel genetic rat model to study a series of psychiatric disorders including schizophrenia, autism, depression, bipolar disorder and drug addiction.

Neuroprotective role of curcumin on the hippocampus against the structural and serological alterations of streptozotocin-induced diabetes in sprague dawely rats

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Nermeen Mohammed Faheem

2017-06-01

Full Text Available Objective(s: Diabetes mellitus causes impaired memory and cognitive functions. The hippocampus plays a key role in memory and learning. Curcumin attenuates diabetic nephropathy in vivo. Curcumin has shown a neurogenic effect and cognition-enhancing potential in aged rats. The aim of this study is to evaluate the possible protective role of curcumin on the histological and serologicalchanges of the hippocampus in diabetic rats. Materials and Methods: Forty albino rats were divided into four groups, ten rats each. Group 1 control rats, group 2 rats received curcumin orally (200 mg/kg/day for six weeks, group 3 rats were injected intraperitoneally with streptozotocin (STZ (100 mg/kg, single dose, group 4 received a single injection of STZ and received curcumin orally for six weeks. Paraffin sections of hippocampus were prepared and stained with hematoxylin and eosin stain, and immnunohistochemical staining for GFAP and caspase-3. Morphometrical and statistical analyses were performed. Glycemic status and parameters of oxidative stress was measured. Results: Examination of hippocampus of diabetic rats showed disorganization of small pyramidal cells in CA1, many cellular losses in the pyramidal cells of CA3, many degenerated granule cells in the dentate gyrus. GFAP positive astrocyte and caspase-3 positive neuron counts were significantly increased.  There were significant serum glucose elevation and significant lowered levels of oxidative stress parameters as compared to control rats. Curcumin administration improved the structural and serological alterationsof the hippocampuswith significant reduction in serum glucose level. Conclusion: Curcumin ameliorates the deterious effect of diabetes on the hippocampus through its antioxidant, antiapoptotic and anti-inflammatory efficacies.

Dual Role of GM-CSF as a Pro-Inflammatory and a Regulatory Cytokine: Implications for Immune Therapy

Science.gov (United States)

Bhattacharya, Palash; Budnick, Isadore; Singh, Medha; Thiruppathi, Muthusamy; Alharshawi, Khaled; Elshabrawy, Hatem; Holterman, Mark J.

2015-01-01

Granulocyte macrophage colony stimulating factor (GM-CSF) is generally recognized as an inflammatory cytokine. Its inflammatory activity is primarily due its role as a growth and differentiation factor for granulocyte and macrophage populations. In this capacity, among other clinical applications, it has been used to bolster anti-tumor immune responses. GM-CSF-mediated inflammation has also been implicated in certain types of autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. Thus, agents that can block GM-CSF or its receptor have been used as anti-inflammatory therapies. However, a review of literature reveals that in many situations GM-CSF can act as an anti-inflammatory/regulatory cytokine. We and others have shown that GM-CSF can modulate dendritic cell differentiation to render them “tolerogenic,” which, in turn, can increase regulatory T-cell numbers and function. Therefore, the pro-inflammatory and regulatory effects of GM-CSF appear to depend on the dose and the presence of other relevant cytokines in the context of an immune response. A thorough understanding of the various immunomodulatory effects of GM-CSF will facilitate more appropriate use and thus further enhance its clinical utility. PMID:25803788

Risk literacy for scientists. Invitation to regulatory science

International Nuclear Information System (INIS)

Ono, Kyoko

2012-01-01

This paper discusses a regulatory science, which fills a gap between scientific knowledge and regulatory actions. The author provides examples of the regulatory science employed in chemical risk assessment, such as the linear non-threshold theory. In the regulatory science, scientific data as well as scientific reasoning based on scientific knowledge - or regulatory rules - should play an important role. It is important to recognize that the rules facilitate transparent decision making under conditions of uncertainty and time constraints. Furthermore, the development of traditional or pure science results in the validation of regulatory rules, and subsequently, the regulatory science procedure develops more systematically. The concept of this science should be understood by those engaged in governmental decision making. (author)

Functional adaptation in female rats: the role of estrogen signaling.

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Susannah J Sample

Full Text Available Sex steroids have direct effects on the skeleton. Estrogen acts on the skeleton via the classical genomic estrogen receptors alpha and beta (ERα and ERβ, a membrane ER, and the non-genomic G-protein coupled estrogen receptor (GPER. GPER is distributed throughout the nervous system, but little is known about its effects on bone. In male rats, adaptation to loading is neuronally regulated, but this has not been studied in females.We used the rat ulna end-loading model to induce an adaptive modeling response in ovariectomized (OVX female Sprague-Dawley rats. Rats were treated with a placebo, estrogen (17β-estradiol, or G-1, a GPER-specific agonist. Fourteen days after OVX, rats underwent unilateral cyclic loading of the right ulna; half of the rats in each group had brachial plexus anesthesia (BPA of the loaded limb before loading. Ten days after loading, serum estrogen concentrations, dorsal root ganglion (DRG gene expression of ERα, ERβ, GPER, CGRPα, TRPV1, TRPV4 and TRPA1, and load-induced skeletal responses were quantified. We hypothesized that estrogen and G-1 treatment would influence skeletal responses to cyclic loading through a neuronal mechanism. We found that estrogen suppresses periosteal bone formation in female rats. This physiological effect is not GPER-mediated. We also found that absolute mechanosensitivity in female rats was decreased, when compared with male rats. Blocking of adaptive bone formation by BPA in Placebo OVX females was reduced.Estrogen acts to decrease periosteal bone formation in female rats in vivo. This effect is not GPER-mediated. Gender differences in absolute bone mechanosensitivity exist in young Sprague-Dawley rats with reduced mechanosensitivity in females, although underlying bone formation rate associated with growth likely influences this observation. In contrast to female and male rats, central neuronal signals had a diminished effect on adaptive bone formation in estrogen-deficient female rats.

WTO+ commitments on services in Asian PTAs: The role of regulatory homogeneity and goods trade complementarity

OpenAIRE

Shingal, Anirudh; Ro, Martin; Sauvé, Pierre

2018-01-01

This paper looks at the role of applied services regulations in accounting for WTO+ commitments on trade in services in preferential trade agreements (PTAs) among Asian economies. The empirical findings suggest that Asian trading dyads with regulatory frameworks that are more similar and more trade-restrictive tend to undertake higher levels of WTO+ commitments on services in their PTAs. There is also evidence in the results for such WTO+ commitments being driven by goods trade complementarit...

Role of amygdala kisspeptin in pubertal timing in female rats.

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Daniel A Adekunbi

Full Text Available To investigate the mechanism by which maternal obesity disrupts reproductive function in offspring, we examined Kiss1 expression in the hypothalamic arcuate (ARC and anteroventral periventricular (AVPV nuclei, and posterodorsal medial amygdala (MePD of pre-pubertal and young adult offspring. Sprague-Dawley rats were fed either a standard or energy-dense diet for six weeks prior to mating and throughout pregnancy and lactation. Male and female offspring were weaned onto normal diet on postnatal day (pnd 21. Brains were collected on pnd 30 or 100 for qRT-PCR to determine Kiss1 mRNA levels. Maternal obesity increased Kiss1 mRNA expression in the MePD of pre-pubertal male and female offspring, whereas Kiss1 expression was not affected in the ARC or AVPV at this age. Maternal obesity reduced Kiss1 expression in all three brain regions of 3 month old female offspring, but only in MePD of males. The role of MePD kisspeptin on puberty, estrous cyclicity and preovulatory LH surges was assessed directly in a separate group of post-weanling and young adult female rats exposed to a normal diet throughout their life course. Bilateral intra-MePD cannulae connected to osmotic mini-pumps for delivery of kisspeptin receptor antagonist (Peptide 234 for 14 days were chronically implanted on pnd 21 or 100. Antagonism of MePD kisspeptin delayed puberty onset, disrupted estrous cyclicity and reduced the incidence of LH surges. These data show that the MePD plays a key role in pubertal timing and ovulation and that maternal obesity may act via amygdala kisspeptin signaling to influence reproductive function in the offspring.

Effect of Ethanolic Extract of Emblica officinalis (Amla on Glucose Homeostasis in Rats Fed with High Fat Diet

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Pallavi S. Kanthe

2017-07-01

Full Text Available Background: Emblica officinalis contains many biological active components which are found to have some medicinal properties against diseases. Aim and Objectives: To assess hypolipidemic and glucose regulatory actions of Ethanolic Extract of Emblica officinalis (EEO on High Fat Diet (HFD fed experimental rats. Material and Methods: Twenty four rats were divided into four groups, having six rats in each group as following; Group I- Control (20% fat; Group II (EEO 100 mg/kg/b w; Group III (30% fat and Group IV (30% fat + EEO 100 mg/kg/b w. The treatment was continued for 21 days. Gravimetric parameters and lipid profiles of all the groups were measured. Oral Glucose Tolerance Test (OGTT, fasting and postprandial glucose and fasting insulin levels were estimated. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR was calculated. Statistical analysis was done. Results: Significant alteration in serum lipid profile, fasting and post prandial blood glucose levels and fasting insulin level were observed in rats of Group III fed with high fat diet. Supplementation of EEO improved both of glycemic and lipid profiles in rats of Group IV fed with high fat diet. Conclusion: Results from the study indicate the beneficial role of EEO on dyslipidemia and glucose homeostasis in rats treated with high fat diet.

Role of sex steroids in progesterone and corticosterone response to acute restraint stress in rats: sex differences.

Science.gov (United States)

Kalil, B; Leite, C M; Carvalho-Lima, M; Anselmo-Franci, J A

2013-07-01

Adrenal progesterone secretion increases along with corticosterone in response to stress in male and female rats to modulate some stress responses. Here we investigated the role of sex steroids in sex differences in the progesterone response to 60 min of restraint stress in adult male and female rats. Comparisons between males and females in the progesterone response were evaluated in parallel with corticosterone responses. From day 5 to 7 after gonadectomy, female and male rats were treated with estradiol or testosterone, respectively (OVX-E and ORCH-T groups), or oil (OVX and ORCH groups). Female rats in proestrus, intact and 7 d adrenalectomized (ADX) male rats were also studied. At 10:00 h, blood samples were withdrawn via an implanted jugular cannula before (-5 min), during (15, 30, 45, 60 min) and after (90 and 120 min) restraint stress to measure plasma progesterone and corticosterone concentrations by radioimmunoassay. Intact male and proestrus female rats exhibited similar progesterone responses to stress. Gonadectomy did not alter the amount of progesterone secreted during stress in female rats but decreased secretion in male rats. Unlike corticosterone, the progesterone response to stress in females was not influenced by estradiol. In males, testosterone replacement attenuated the progesterone and corticosterone responses to stress. Basal secretion of progesterone among intact, ORCH and ADX males was similar, but ADX-stressed rats secreted little progesterone. Hence, the gonads differently modulate adrenal progesterone and corticosterone responses to stress in female and male rats. The ovaries enhance corticosterone but not progesterone secretion, while the testes stimulate progesterone but not corticosterone secretion.

Efficacy of Mesenchymal Stem Cells in Suppression of Hepatocarcinorigenesis in Rats: Possible Role of Wnt Signaling

LENUS (Irish Health Repository)

Abdel Aziz, Mohamed T

2011-05-05

Abstract Background The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs) in an experimental hepatocellular carcinoma (HCC) model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis. Methods Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA) and CCl 4 , rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR) in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups. Results Histopathological examination of liver tissue from animals which received DENA-CCl4 only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated β-catenin, proliferating cell nuclear antigen (PCNA), cyclin D and survivin genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect. Conclusions Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell proliferation

Role of garlic oil and selenium as stimulators to some antioxidant defense system in irradiated male rats

International Nuclear Information System (INIS)

El-Gawish, M.A.; Abdel-Azeem, M.G.

2002-01-01

The increased level of lipid peroxide product; malondialdehyde (MDA) in various tissues of irradiated animals, may play a crucial role in damaging effects of exposure to ionizing radiation mediated by reactive free radicals generation. The protective efficiency of oral administration of garlic oil (500 mg/kg b.wt) three times weekly together with a single intraperitoneal injection of selenium (0.5 mg/kg b.wt) weekly for two weeks was examined on some antioxidant defense system as well as ultrastructural study in rats subjected to fractionated doses of gamma radiation up to a dose level of 6 Gy (1.5 Gy day after day). Exposure to gamma radiation induced a significant elevation in the level of malondialdehyde in plasma and liver and non-significant change was observed in superoxide dismutase activity (SOD). Also a significant increase was occurred in hepatic glutathione (GSH) content and glutathione peroxidase (GSHPx) activity. The pretreatment of irradiated rats with garlic oil and selenium caused a significant decrease in elevated level of MDA and a significant increase in the activity of SOD, GSHPx and GSH contents in both blood and liver. Concerning the ultrastructure studies, liver of irradiated rats showed abnormal shape of nucleus and nucleus membrane, swollen mitochondria with ruptured cristae, rupture of endoplasmic reticulum and vaculated cytoplasm, while intestine of irradiated rats exhibited deformed, shortened and abnormal structure of microvilli, accumulation of nuclear chromatin and dilatation of terminal web layer. In group of rats treated with garlic oil and selenium before exposure to gamma radiation, noticeable amelioration in ultrastructure changes of liver and intestine induced by irradiation was observed indicating a beneficial radioprotective role of both garlic oil and selenium

Regulatory Expectations for Safety Culture

Energy Technology Data Exchange (ETDEWEB)

Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2014-05-15

The oversight of licensee's safety culture becomes an important issue that attracts great public and political concerns recently in Korea. Beginning from the intended violation of rules, a series of corruptions, documents forgery and disclosure of wrong-doings made the public think that the whole mindset of nuclear workers has been inadequate. Thus, they are demanding that safety culture shall be improved and that regulatory body shall play more roles and responsibilities for the improvements and oversight for them. This paper introduces, as an effort of regulatory side, recent changes in the role of regulators in safety culture, regulatory expectations on the desired status of licensee's safety culture, the pilot inspection program for safety culture and research activity for the development of oversight system. After the Fukushima accident in Japan 2011, many critics has searched for cultural factors that caused the unacceptable negligence pervaded in Japan nuclear society and the renewed emphasis has been placed on rebuilding safety culture by operators, regulators, and relevant institutions globally. Significant progress has been made in how to approach safety culture and led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety.

Regulatory Expectations for Safety Culture

International Nuclear Information System (INIS)

Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung

2014-01-01

The oversight of licensee's safety culture becomes an important issue that attracts great public and political concerns recently in Korea. Beginning from the intended violation of rules, a series of corruptions, documents forgery and disclosure of wrong-doings made the public think that the whole mindset of nuclear workers has been inadequate. Thus, they are demanding that safety culture shall be improved and that regulatory body shall play more roles and responsibilities for the improvements and oversight for them. This paper introduces, as an effort of regulatory side, recent changes in the role of regulators in safety culture, regulatory expectations on the desired status of licensee's safety culture, the pilot inspection program for safety culture and research activity for the development of oversight system. After the Fukushima accident in Japan 2011, many critics has searched for cultural factors that caused the unacceptable negligence pervaded in Japan nuclear society and the renewed emphasis has been placed on rebuilding safety culture by operators, regulators, and relevant institutions globally. Significant progress has been made in how to approach safety culture and led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety

Social defeat alters the acquisition of cocaine self-administration in rats: role of individual differences in cocaine-taking behavior.

Science.gov (United States)

Kabbaj, M; Norton, C S; Kollack-Walker, S; Watson, S J; Robinson, T E; Akil, H

2001-12-01

It is known that social defeat can modulate cocaine self-administration. However, it is unclear whether this psychosocial stressor affects drug-taking behavior to the same extent across all individual animals, particularly those with differing propensities to self-administer psychostimulants. This study examined the effect of social defeat on cocaine self-administration in animals that differ in novelty-seeking behavior that predicts differences in drug self-administration. Male Sprague-Dawley rats were first classified into high-responder (HR) and low-responder (LR) groups. HR and LR rats were categorized based on their locomotor activity in a novel environment, with HR rats exhibiting higher locomotor activity than LR rats. Then, male rats were exposed on four occasions to an aggressive Long Evans male rat over the course of 4 days. Control rats were not exposed to the social defeat. All rats were subsequently implanted with jugular catheters and 3 days later placed into the self-administration box to study the acquisition of cocaine self-administration (0.25 mg per infusion). HR non-defeated animals self-administered more cocaine than the LR non-defeated animals. Following social defeat, the acquisition of cocaine self-administration is significantly delayed in HR rats and enhanced in LR rats. CONCLUSION The unique patterns of responsiveness in the HR and LR animals suggest that social defeat plays a role of equalizer of individual differences in drug-taking behavior.

Regulatory T-cells and autoimmunity.

LENUS (Irish Health Repository)

Ni Choileain, Niamh

2012-02-03

Approximately 20% of the population is affected by autoimmune or inflammatory diseases mediated by an abnormal immune response. A characteristic feature of autoimmune disease is the selective targeting of a single cell type, organ or tissue by certain populations of autoreactive T-cells. Examples of such diseases include rheumatoid arthritis, insulin-dependent diabetes mellitus, and systemic lupus erythematosus (SLE), all of which are characterized by chronic inflammation, tissue destruction and target organ malfunction. Although strong evidence links most autoimmune diseases to specific genes, considerable controversy prevails regarding the role of regulatory T-cell populations in the disease process. These cells are now also believed to play a key role in mediating transplantation tolerance and inhibiting the induction of tumor immunity. Though the concept of therapeutic immune regulation aimed at treating autoimmune pathology has been validated in many animal models, the development of strategies for the treatment of human autoimmune disorders remains in its infancy. The main obstacles to this include the conflicting findings of different model systems, as well as the contrasting functions of regulatory T-cells and cytokines involved in the development of such disorders. This review examines the role of regulatory T-cells in the pathogenesis of autoimmunity and describes the therapeutic potential of these cells for the prevention of immune-mediated pathologies in the future. Although much remains to be learned about such pathologies, a clearer understanding of the mechanisms by which regulatory T-cells function will undoubtedly lead to exciting new possibilities for immunotherapeutics.

Application of physiologically-based pharmacokinetic modeling to explore the role of kidney transporters in renal reabsorption of perfluorooctanoic acid in the rat

Energy Technology Data Exchange (ETDEWEB)

Worley, Rachel Rogers, E-mail: idz7@cdc.gov [Agency for Toxic Substances and Disease Registry, Division of Community Health Investigations, 4770 Buford Highway, Atlanta, GA 30341 (United States); Interdisciplinary Toxicology Program, University of Georgia, 341 Pharmacy South, Athens, GA 30602 (United States); Fisher, Jeffrey [Interdisciplinary Toxicology Program, University of Georgia, 341 Pharmacy South, Athens, GA 30602 (United States); Food and Drug Administration, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079 (United States)

2015-12-15

ABSTRACT: Renal elimination and the resulting clearance of perfluorooctanoic acid (PFOA) from the serum exhibit pronounced sex differences in the adult rat. The literature suggests that this is largely due to hormonally regulated expression of organic anion transporters (OATs) on the apical and basolateral membranes of the proximal tubule cells that facilitate excretion and reabsorption of PFOA from the filtrate into the blood. Previously developed PBPK models of PFOA exposure in the rat have not been parameterized to specifically account for transporter-mediated renal elimination. We developed a PBPK model for PFOA in male and female rats to explore the role of Oat1, Oat3, and Oatp1a1 in sex-specific renal reabsorption and excretion of PFOA. Descriptions of the kinetic behavior of these transporters were extrapolated from in vitro studies and the model was used to simulate time-course serum, liver, and urine data for intravenous (IV) and oral exposures in both sexes. Model predicted concentrations of PFOA in the liver, serum, and urine showed good agreement with experimental data for both male and female rats indicating that in vitro derived physiological descriptions of transporter-mediated renal reabsorption can successfully predict sex-dependent excretion of PFOA in the rat. This study supports the hypothesis that sex-specific serum half-lives for PFOA are largely driven by expression of transporters in the kidney and contribute to the development of PBPK modeling as a tool for evaluating the role of transporters in renal clearance. - Highlights: • The PBPK model for PFOA in the rat explores the role of OATs in sex-specific clearance. • Descriptions of OAT kinetics were extrapolated from in vitro studies. • Model predictions showed good fit with experimental data for male and female rats.

Application of physiologically-based pharmacokinetic modeling to explore the role of kidney transporters in renal reabsorption of perfluorooctanoic acid in the rat

International Nuclear Information System (INIS)

Worley, Rachel Rogers; Fisher, Jeffrey

2015-01-01

ABSTRACT: Renal elimination and the resulting clearance of perfluorooctanoic acid (PFOA) from the serum exhibit pronounced sex differences in the adult rat. The literature suggests that this is largely due to hormonally regulated expression of organic anion transporters (OATs) on the apical and basolateral membranes of the proximal tubule cells that facilitate excretion and reabsorption of PFOA from the filtrate into the blood. Previously developed PBPK models of PFOA exposure in the rat have not been parameterized to specifically account for transporter-mediated renal elimination. We developed a PBPK model for PFOA in male and female rats to explore the role of Oat1, Oat3, and Oatp1a1 in sex-specific renal reabsorption and excretion of PFOA. Descriptions of the kinetic behavior of these transporters were extrapolated from in vitro studies and the model was used to simulate time-course serum, liver, and urine data for intravenous (IV) and oral exposures in both sexes. Model predicted concentrations of PFOA in the liver, serum, and urine showed good agreement with experimental data for both male and female rats indicating that in vitro derived physiological descriptions of transporter-mediated renal reabsorption can successfully predict sex-dependent excretion of PFOA in the rat. This study supports the hypothesis that sex-specific serum half-lives for PFOA are largely driven by expression of transporters in the kidney and contribute to the development of PBPK modeling as a tool for evaluating the role of transporters in renal clearance. - Highlights: • The PBPK model for PFOA in the rat explores the role of OATs in sex-specific clearance. • Descriptions of OAT kinetics were extrapolated from in vitro studies. • Model predictions showed good fit with experimental data for male and female rats.

Hormone therapy alters the composition of the vaginal microflora in ovariectomized rats.

Science.gov (United States)

Bezirtzoglou, E; Voidarou, Ch; Papadaki, A; Tsiotsias, A; Kotsovolou, O; Konstandi, M

2008-05-01

The aim of the present study was to evaluate the alterations that may take place in the bacterial genital tract flora in the absence of ovarian hormones. The role of hormone replacement therapy was also assessed. For this purpose, various bacteria were identified from the vaginal flora of ovariectomized and sham operated female rats, following the Bergey's manual criteria. The data of this study showed that substantial differences exist in the vaginal bacterial microflora between ovariectomized and normal cyclic rats. Ovariectomy was associated with a lower total bacterial load that may be due mainly to the absence of Lactobacillus. Anaerobic bacteria were also absent. Streptococcus and Enterococcus were also not favored in an environment lacking the ovarian hormones. In contrast, C. perfringens, Bacteroides, S. epidermidis, and S. aureus were detected in high numbers in ovariectomized rats. In terms of the impact of hormone replacement therapy on vaginal flora, only estradiol (EE2) restored Lactobacillus levels in ovariectomized rats, whereas all hormonal schemes used brought Streptococcus, Clostridium lec (-), and C. perfringens, the spore and vegetative forms, close to those detected in normal cyclic female rats. In conclusion, ovarian hormones appeared to be regulatory factors that favor the presence of a broad variety of bacteria, which are members of the normal genital tract flora. On the other hand, ovariectomy modifies the vaginal microbial profile, and hormone replacement therapy based mainly on schemes containing EE2 could alleviate this disturbance.

Effect of pregabalin on apoptotic regulatory genes in hippocampus of rats with chronic temporal lobe epilepsy

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ZHANG Yi-dan

2012-04-01

Full Text Available Objective To observe the effect of pregabalin on the expression of Bcl-2 and Bax in hippocampus of chronic epileptic rats induced by pilocarpine, to explore the anti-epileptic pharmacology mechanism of pregabalin, and its anti-apoptotic effect on hippocampal neurons of rats. Methods The model of chronic temporal lobe epileptic rats induced by lithium-pilocarpine was established, then the rats in pregabalin treatment group received intraperitoneal injection of pregabalin (40 mg/kg once daily for three weeks. The expression of Bcl-2 and Bax in hippocampus of all rats was detected by immunohistochemical technique and Western blotting. Results Compared with normal saline group rats, the expression of Bcl-2 and Bax in hippocampus of rats with chronic temporal lobe epilepsy was significantly increased (P = 0.000, for all. Pregabalin can down-regulate the expression of Bax and up-regulate the expression of Bcl-2 in hippocampus of rats compared to model group rats (P = 0.000, for all. Conclusion Pregabalin may have the effects of inhibiting cell apoptosis and protecting neurons through lowing Bax level and increasing Bcl-2 level in hippocampus of chronic temporal lobe epileptic rats.

Use of a specific cholecystokinin receptor antagonist (L-364,718) to determine the role of cholecystokinin on feeding and body weight in rats with obstructive jaundice.

Science.gov (United States)

Tangoku, A; Doi, R; Chowdhury, P; Pasley, J N; McKay, D W; Rayford, P L

1992-01-01

We conducted a study to examine the role of cholecystokinin in feeding behavior and weight change in rats with obstructive jaundice. Daily food and water intake, body weight, and short-term food intake were determined in two groups of rats with surgically induced obstructive jaundice and in control rats. One group of rats with obstructive jaundice was given L-364,718, a selective cholecystokinin receptor antagonist. Plasma bilirubin and cholecystokinin levels were measured in each rat before and 7 days after surgery. Daily food intake and body weight were decreased in obstructive jaundice rats compared with control rats during the first week after surgery (P less than .05); however, obstructive jaundice rats treated with L-364,718 had increased food intake and body weight (P less than .05). Short-term food intake measured for 30 minutes and 120 minutes in food-deprived obstructive jaundice rats was decreased when compared with control rats (P less than .05), but the obstructive jaundice rats given L-364,718 had increased short-term food intake (P less than .05). Water intake was similar between the two groups of rats. Plasma levels of cholecystokinin and bilirubin were increased in obstructive jaundice rats with and without L-364,718 treatment (P less than .05). The results support the concept that endogenously elevated levels of plasma cholecystokinin play an important role in decreased food intake and subsequent loss of body weight in rats with obstructive jaundice.

Cardioprotection after acute exposure to simulated high altitude in rats. Role of nitric oxide.

Science.gov (United States)

La Padula, Pablo H; Etchegoyen, Melisa; Czerniczyniec, Analia; Piotrkowski, Barbara; Arnaiz, Silvia Lores; Milei, Jose; Costa, Lidia E

2018-02-28

In previous studies, upregulation of NOS during acclimatization of rats to sustained hypobaric hypoxia was associated to cardioprotection, evaluated as an increased tolerance of myocardium to hypoxia/reoxygenation. The objective of the present work was to investigate the effect of acute hypobaric hypoxia and the role of endogenous NO concerning cardiac tolerance to hypoxia/reoxygenation under β-adrenergic stimulation. Rats were submitted to 58.7 kPa in a hypopressure chamber for 48 h whereas their normoxic controls remained at 101.3 kPa. By adding NOS substrate L-arg, or blocker L-NNA, isometric mechanical activity of papillary muscles isolated from left ventricle was evaluated at maximal or minimal production of NO, respectively, under β-adrenergic stimulation by isoproterenol, followed by 60/30 min of hypoxia/reoxygenation. Activities of NOS and cytochrome oxidase were evaluated by spectrophotometric methods and expression of HIF1-α and NOS isoforms by western blot. Eosin and hematoxiline staining were used for histological studies. Cytosolic expression of HIF1-α, nNOS and eNOS, and NO production were higher in left ventricle of hypoxic rats. Mitochondrial cytochrome oxidase activity was decreased by hypobaric hypoxia and this effect was reversed by L-NNA. After H/R, recovery of developed tension in papillary muscles from normoxic rats was 51-60% (regardless NO modulation) while in hypobaric hypoxia was 70% ± 3 (L-arg) and 54% ± 1 (L-NNA). Other mechanical parameters showed similar results. Preserved histological architecture was observed only in L-arg papillary muscles of hypoxic rats. Exposure of rats to hypobaric hypoxia for only 2 days increased NO synthesis leading to cardioprotection. Copyright © 2017 Elsevier Inc. All rights reserved.

The Protective Role of Lettuce oil (Lactuca sativa) against Radiation induced Biological Hazards in Male Rats

International Nuclear Information System (INIS)

Abdel-Magied, N.; Ahmed, A.G.

2011-01-01

This study was conducted to clarify the potential role of lettuce oil against damages induced in rats due to exposure to gamma radiation. Adult male albino rats (120-150 g) were divided into 4 groups each of 12 animals. The first group was considered control animals. The second group received, via gavages, lettuce oil (200 mg/Kg body weight) for 3 weeks. The third group was subjected to a single dose of 6.5Gy whole body gamma irradiation. The fourth group received lettuce oil for 3 weeks then was exposed to radiation. Blood samples were collected 1 and 7 days post irradiation. Exposure of rats to gamma irradiation caused a significant increase in the level of glucose, total cholesterol (TC), triglycerides (TG), malondialdehyde (MDA) and follicle stimulating hormone (FSH) while a significant decrease was recorded in glutathione content (GSH), superoxide dismutase (SOD) and catalase activities, white blood cells (WBCs), red blood cells (RBCs), haemoglobin content (Hb), haematocrit percentage (Hct%), mean corpuscular volume (MCV), platelets (PLT), leutinizing hormone (LH) and testosterone hormone . In rats treated with lettuce oil then exposed to radiation, the results showed an improvement in all previous parameters. It could be concluded that lettuce oil might reduce the biological hazards in rats induced by gamma irradiation

Anxiety-related behavior in hyperhomocysteinemia induced by methionine nutritional overload in rats: role of the brain oxidative stress.

Science.gov (United States)

Hrncic, Dragan; Mikić, Jelena; Rasic-Markovic, Aleksandra; Velimirović, Milica; Stojković, Tihomir; Obrenović, Radmila; Rankov-Petrović, Bojana; Šušić, Veselinka; Djuric, Dragan; Petronijević, Nataša; Stanojlovic, Olivera

2016-10-01

The aim of this study was to examine the effects of a methionine-enriched diet on anxiety-related behavior in rats and to determine the role of the brain oxidative status in these alterations. Adult male Wistar rats were fed from the 30th to 60th postnatal day with standard or methionine-enriched diet (double content comparing with standard diet: 7.7 g/kg). Rats were tested in open field and light-dark tests and afterwards oxidative status in the different brain regions were determined. Hyperhomocysteinemia induced by methionine-enriched diet in this study decreased the number of rearings, as well as the time that these animals spent in the center of the open field, but increased index of thigmotaxy. Oxidative status was selectively altered in the examined regions. Lipid peroxidation was significantly increased in the cortex and nc. caudatus of rats developing hyperhomocysteinemia, but unaltered in the hippocampus and thalamus. Based on the results of this research, it could be concluded that hyperhomocysteinemia induced by methionine nutritional overload increased anxiety-related behavior in rats. These proanxiogenic effects could be, at least in part, a consequence of oxidative stress in the rat brain.

The role of periodontal ASIC3 in orofacial pain induced by experimental tooth movement in rats.

Science.gov (United States)

Gao, Meiya; Long, Hu; Ma, Wenqiang; Liao, Lina; Yang, Xin; Zhou, Yang; Shan, Di; Huang, Renhuan; Jian, Fan; Wang, Yan; Lai, Wenli

2016-12-01

This study aimed to clarify the roles of Acid-sensing ion channel 3 (ASIC3) in orofacial pain following experimental tooth movement. Sixty male Sprague-Dawley rats were divided into the experimental group (40g, n = 30) and the sham group (0g, n = 30). Closed coil springs were ligated between maxillary incisor and molars to achieve experimental tooth movement. Rat grimace scale (RGS) scores were assessed at 0, 1, 3, 5, 7, and 14 days after the placement of the springs. ASIC3 immunostaining was performed and the expression levels of ASIC3 were measured through integrated optical density/area in Image-Pro Plus 6.0. Moreover, 18 rats were divided into APETx2 group (n = 6), amiloride group (n = 6), and vehicle group (n = 6), and RGS scores were obtained compared among them to verify the roles of ASIC3 in orofacial pain following tooth movement. ASIC3 expression levels became significantly higher in the experimental group than in sham group on 1, 3, and 5 days and became similar on 7 and 14 days. Pain levels (RGS scores) increased in both groups and were significantly higher in the experimental group on 1, 3, 5, and 7 days and were similar on 14 days. Periodontal ASIC3 expression levels were correlated with orofacial pain levels following experimental tooth movement. Periodontal administrations of ASIC3 antagonists (APETx2 and amiloride) could alleviate pain. This study needs to be better evidenced by RNA interference of ASIC3 in periodontal tissues in rats following experimental tooth movement. Moreover, we hope further studies would concentrate on the pain perception of ASIC3 knockout (ASIC3 -/- ) mice. Our results suggest that periodontal ASIC3 plays an important role in orofacial pain induced by experimental tooth movement. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The roles of antitrust law and regulatory oversight in the restructured electricity industry

Energy Technology Data Exchange (ETDEWEB)

Glazer, C.A.; Little, M.B.

1999-05-01

The introduction of retail wheeling is changing the roles of regulators and the courts. When states unbundle the vertically integrated investor-owned utility (IOU) into generation companies, transmission companies, and distribution companies, antitrust enforcement and policy setting by the state public utility/service commissions (PUCs) will be paramount. As was seen in the deregulation of the airline industry, vigorous enforcement of antitrust laws by the courts and proper policy setting by the regulators are the keys to a successful competitive market. Many of the problems raised in the airline deregulation movement came about due to laxity in correcting clear antitrust violations and anti-competitive conditions before they caused damage to the market. As retail wheeling rolls out, it is critical for state PUCs to become attuned to these issues and, most of all, to have staff trained in these disciplines. The advent of retail wheeling changes the application of the State Action Doctrine and, in turn, may dramatically alter the role of the state PUC--meaning antitrust law and regulatory oversight must step in to protect competitors and consumers from monopolistic abuse.

Role of insulin on exercise-induced GLUT-4 protein expression and glycogen supercompensation in rat skeletal muscle.

Science.gov (United States)

Kuo, Chia-Hua; Hwang, Hyonson; Lee, Man-Cheong; Castle, Arthur L; Ivy, John L

2004-02-01

The purpose of this study was to investigate the role of insulin on skeletal muscle GLUT-4 protein expression and glycogen storage after postexercise carbohydrate supplementation. Male Sprague-Dawley rats were randomly assigned to one of six treatment groups: sedentary control (Con), Con with streptozocin (Stz/C), immediately postexercise (Ex0), Ex0 with Stz (Stz/Ex0), 5-h postexercise (Ex5), and Ex5 with Stz (Stz/Ex5). Rats were exercised by swimming (2 bouts of 3 h) and carbohydrate supplemented immediately after each exercise session by glucose intubation (1 ml of a 50% wt/vol). Stz was administered 72-h before exercise, which resulted in hyperglycemia and elimination of the insulin response to the carbohydrate supplement. GLUT-4 protein of Ex0 rats was 30% above Con in fast-twitch (FT) red and 21% above Con in FT white muscle. In Ex5, GLUT-4 protein was 52% above Con in FT red and 47% above Con in FT white muscle. Muscle glycogen in FT red and white muscle was also increased above Con in Ex5 rats. Neither GLUT-4 protein nor muscle glycogen was increased above Con in Stz/Ex0 or Stz/Ex5 rats. GLUT-4 mRNA in FT red muscle of Ex0 rats was 61% above Con but only 33% above Con in Ex5 rats. GLUT-4 mRNA in FT red muscle of Stz/C and Stz/Ex0 rats was similar but significantly elevated in Ex5/Stz rats. These results suggest that insulin is essential for the increase in GLUT-4 protein expression following postexercise carbohydrate supplementation.

The Role of Calcium in Ameliorating the Oxidative Stress of Fluoride in Rats.

Science.gov (United States)

Mohamed, N E

2016-03-01

The present study was carried out to investigate the effects of fluoride toxicity on some biochemical, hormonal, and histological parameters of female rats and the protective role of calcium against such effects. Adult female albino rats were divided into five groups; control group received distilled water for 60 days, calcium group received calcium carbonate with dose of 50 mg/kg three times per week for 60 days, fluoride group received sodium fluoride with dose of 20 mg/kg three times per week for 60 days, calcium + fluoride group received calcium carbonate (50 mg/kg) then after 2 h received sodium fluoride (20 mg/kg) three times per week for 60 days, and fluoride + calcium group received sodium fluoride (20 mg/kg) three times per week for 30 days then received calcium carbonate (50 mg/kg) three times per week for another 30 days. The results showed that the levels of thiobarbituric acid reactive substances, urea, creatinine, alkaline phosphatase, triiodothyronine, thyroxine, parathormone, phosphorous, magnesium, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma glutamyl transferase were significantly increased in rats treated with fluoride while serum estradiol, calcium, and organ glutathione were significantly decreased. The histological examination of the femur bone revealed that fluoride treatment induced thinning of bone trabeculae with wilding of marrow space, demineralization, and loss of trabeculae interconnections. Also, the histological examination of hepatic and renal tissues of fluoride-treated rats showed some damages in these tissues while administration of calcium carbonate for 30 or 60 days during fluoride treatment minimized such damages. It could be concluded that administration of calcium to female rats can ameliorate the hazardous effects of fluoride observed in the biochemical, hormonal, and histological parameters.

Role of (Pro)Renin Receptor in Albumin Overload-Induced Nephropathy in Rats.

Science.gov (United States)

Fang, Hui; Deng, Mokan; Zhang, Linlin; Lu, Aihua; Su, Jiahui; Xu, Chuanming; Zhou, Li; Wang, Lei; Ou, Jing-Song; Wang, Weidong; Yang, Tianxin

2018-05-30

Proteinuria is not only a common feature of chronic kidney diseases (CKD) but also an independent risk factor promoting CKD progression to end-stage renal failure. However, the underlying molecular mechanisms for protein overload-induced renal injury remain elusive. The present study examined the role of (pro)renin receptor (PRR) in pathogenesis of albumin overload (AO)-induced nephropathy and activation of intrarenal renin-angiotensin system (RAS) in rats. Wistar rats underwent unilateral nephrectomy and were treated for 7 weeks with vehicle, bovine serum albumin (5 g/kg/d via a single i.p. injection) alone or in conjunction with a PRR decoy inhibitor PRO20 (500 μg/kg/d via 3 s.c. injections). The AO rat model exhibited severe proteinuria, tubular necrosis, and interstitial fibrosis, oxidative stress, inflammation, accompanied by elevated urinary N-acetyl-beta-D-glucosaminidase activity and urinary β2-microglobulin secretion, all of which were significantly attenuated by PRO20. Urinary and renal levels of renin, angiotensinogen (AGT), and Ang II were elevated by AO and suppressed by PRO20, contrasting to largely unaltered plasma levels of the RAS parameters. The AO model also showed increased renal expression of full-length PRR and soluble PRR (sPRR) and urinary excretion of sPRR. Taken together, we conclude that PRR antagonism with PRO20 alleviates AO-induced nephropathy via inhibition of intrarenal RAS.

Developing regulatory approaches

International Nuclear Information System (INIS)

Axelsson, Lars

2012-01-01

Lars Axelsson presented SSM progress on oversight of LMfS/SC since the Chester 1 Workshop in 2007. Current SSM approaches for safety culture oversight include targeted safety management and safety culture inspections, compliance inspections which cover aspects of safety management/safety culture and multi-disciplinary team inspections. Examples of themes for targeted inspections include management of ambiguous operational situations or other weak signals, understanding of and attitudes to Human Performance tools, the Safety Department's role and authority and Leadership for safety. All regulatory activities provide inputs for the SSM yearly safety evaluation of each licensee. A form has been developed to capture safety culture observations from inspections and other interactions with licensees. Analysis will be performed to identify patterns and provide information to support planning of specific Safety Culture activities. Training has been developed for regulatory staff to enhance the quality of regulatory interventions on safety culture. This includes a half-day seminar to provide an overview of safety culture, and a workshop which provides more in-depth discussion on cultural issues and how to capture those during regulatory activities. Future plans include guidance for inspectors, and informal seminars on safety culture with licensees

The Tumorigenic Roles of the Cellular REDOX Regulatory Systems

Directory of Open Access Journals (Sweden)

Stéphanie Anaís Castaldo

2016-01-01

Full Text Available The cellular REDOX regulatory systems play a central role in maintaining REDOX homeostasis that is crucial for cell integrity, survival, and proliferation. To date, a substantial amount of data has demonstrated that cancer cells typically undergo increasing oxidative stress as the tumor develops, upregulating these important antioxidant systems in order to survive, proliferate, and metastasize under these extreme oxidative stress conditions. Since a large number of chemotherapeutic agents currently used in the clinic rely on the induction of ROS overload or change of ROS quality to kill the tumor, the cancer cell REDOX adaptation represents a significant obstacle to conventional chemotherapy. In this review we will first examine the different factors that contribute to the enhanced oxidative stress generally observed within the tumor microenvironment. We will then make a comprehensive assessment of the current literature regarding the main antioxidant proteins and systems that have been shown to be positively associated with tumor progression and chemoresistance. Finally we will make an analysis of commonly used chemotherapeutic drugs that induce ROS. The current knowledge of cancer cell REDOX adaptation raises the issue of developing novel and more effective therapies for these tumors that are usually resistant to conventional ROS inducing chemotherapy.

The effects of heated vegetable oils on blood pressure in rats

Directory of Open Access Journals (Sweden)

Kamsiah Jaarin

2011-01-01

Full Text Available OBJECTIVES: The goal of this study was to determine the possible mechanism that is involved in the blood pressureraising effect of heated vegetable oils. METHODS: Adult male Sprague-Dawley rats were divided into 11 groups; the control group was fed with rat chow, and the other groups were fed with chow that was mixed with 15% weight/weight palm or soy oils, which were either in a fresh form or heated once, twice, five, or ten times. Blood pressures were measured at the baseline and throughout the 24-week study. Plasma nitric oxide levels were assessed prior to treatment and at the end of the study. Following 24 weeks, the rats were sacrificed to investigate their vascular reactivity using the thoracic aorta. RESULTS: Palm and soy oils had no detrimental effects on blood pressure, and they significantly elevated the nitric oxide contents and reduced the contractile responses to phenylephrine. However, trials using palm and soy oils that were repeatedly heated showed an increase in blood pressure, enhanced phenylephrine-induced contractions, reduced acetylcholine- and sodium nitroprusside-induced relaxations relative to the control and rats that were fed fresh vegetable oils. CONCLUSIONS: The blood pressure-raising effect of the heated vegetable cooking oils is associated with increased vascular reactivity and a reduction in nitric oxide levels. The chronic consumption of heated vegetable oils leads to disturbances in endogenous vascular regulatory substances, such as nitric oxide. The thermal oxidation of the cooking oils promotes the generation of free radicals and may play an important contributory role in the pathogenesis of hypertension in rats.

Protective effect of Chinese prescription Kangen-karyu and its crude drug Tanjin against age-related lipidosis in rats.

Science.gov (United States)

Cho, Eun Ju; Yokozawa, Takako; Okamoto, Takuya

2007-05-01

We have investigated the effect of the Chinese prescription Kangen-karyu and its crude drug Tanjin against age-related lipidosis in-vivo in a rat model. The serum and hepatic triglyceride levels were remarkably elevated in 12-month-old compared with two-month-old rats. However, the administration of Kangen-karyu and Tanjin extracts significantly decreased these levels. This suggested a protective role against related pathological conditions as well as hyperlipidaemia. On the other hand, the reduction of the levels of adiponectin in serum with ageing did not show significant changes in rats given diets supplemented with Kangen-karyu and Tanjin extracts. Furthermore, the expression of transcription factors in nuclear hepatic tissue related to lipid metabolism was investigated. The decline in the expression of nuclear peroxisome proliferator-activated receptor alpha protein in hepatic tissue with age was ameliorated by the administration of Kangen-karyu and Tanjin supplements. On the other hand, the overexpression of sterol regulatory element-binding proteins (SREBP)-1 and SREBP-2 in old rats compared with young rats showed a tendency to decrease with Kangen-karyu and Tanjin administration. The decline of hepatic function with ageing was attenuated by Kangen-karyu and Tanjin, suggesting the beneficial role of Kangen-karyu and Tanjin on lipid metabolism through the improvement of hepatic function. This study has demonstrated that Kangen-karyu and Tanjin inhibited the accumulation of triglyceride with regulation of related protein expressions and they improved hepatic function. Evidence has been provided for the anti-ageing activity of Kangen-karyu and its crude drug Tanjin against age-related lipidosis.

Supplementation of chitosan alleviates high-fat diet-enhanced lipogenesis in rats via adenosine monophosphate (AMP)-activated protein kinase activation and inhibition of lipogenesis-associated genes.

Science.gov (United States)

Chiu, Chen-Yuan; Chan, Im-Lam; Yang, Tsung-Han; Liu, Shing-Hwa; Chiang, Meng-Tsan

2015-03-25

This study investigated the role of chitosan in lipogenesis in high-fat diet-induced obese rats. The lipogenesis-associated genes and their upstream regulatory proteins were explored. Diet supplementation of chitosan efficiently decreased the increased weights in body, livers, and adipose tissues in high-fat diet-fed rats. Chitosan supplementation significantly raised the lipolysis rate; attenuated the adipocyte hypertrophy, triglyceride accumulation, and lipoprotein lipase activity in epididymal adipose tissues; and decreased hepatic enzyme activities of lipid biosynthesis. Chitosan supplementation significantly activated adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and attenuated high-fat diet-induced protein expressions of lipogenic transcription factors (PPAR-γ and SREBP1c) in livers and adipose tissues. Moreover, chitosan supplementation significantly inhibited the expressions of downstream lipogenic genes (FAS, HMGCR, FATP1, and FABP4) in livers and adipose tissues of high-fat diet-fed rats. These results demonstrate for the first time that chitosan supplementation alleviates high-fat diet-enhanced lipogenesis in rats via AMPK activation and lipogenesis-associated gene inhibition.

Automated Identification of Core Regulatory Genes in Human Gene Regulatory Networks.

Directory of Open Access Journals (Sweden)

Vipin Narang

Full Text Available Human gene regulatory networks (GRN can be difficult to interpret due to a tangle of edges interconnecting thousands of genes. We constructed a general human GRN from extensive transcription factor and microRNA target data obtained from public databases. In a subnetwork of this GRN that is active during estrogen stimulation of MCF-7 breast cancer cells, we benchmarked automated algorithms for identifying core regulatory genes (transcription factors and microRNAs. Among these algorithms, we identified K-core decomposition, pagerank and betweenness centrality algorithms as the most effective for discovering core regulatory genes in the network evaluated based on previously known roles of these genes in MCF-7 biology as well as in their ability to explain the up or down expression status of up to 70% of the remaining genes. Finally, we validated the use of K-core algorithm for organizing the GRN in an easier to interpret layered hierarchy where more influential regulatory genes percolate towards the inner layers. The integrated human gene and miRNA network and software used in this study are provided as supplementary materials (S1 Data accompanying this manuscript.

Modulatory Role of Aloe vera on Gamma Irradiation Induced Histological Changes in Different Tissues of Rats

International Nuclear Information System (INIS)

Rezk, R.G.

2005-01-01

Aloe Vera is known for its wide medicinal properties. This study was performed to evaluate the role of Aloe vera (Aloe barbadensis Miller) in the amelioration of the histological disorders that occurr in different tissues of albino rats exposed to 7 Gy whole body gamma irradiation, delivered as a single dose. Aloe vera (leaf juice filtrate) was supplemented daily to rats (0.25 ml/kg b wt/day) by gavage, 5 days before irradiation and 10 days after irradiation. Experimental investigations performed 7 and 10 days after exposure to radiation showed that Aloe vera treatment has significantly improved the radiation-induced inflammation, haemorrhage, widening and dilated blood vessela, necrosis, atrophy sloughing in liver, spleen and small intestine (jejenum) tissues of irradiated rats. It is concluded that the synergistic relationship between the elements found in the leaf of Aloe vera could be a useful adjunct for maintaining the integrity of histological architecture

Regulatory agencies and regulatory risk

OpenAIRE

Knieps, Günter; Weiß, Hans-Jörg

2008-01-01

The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

The Role of Level-3 PSA in the Regulatory Structure for the Licensing of Future NPPs

International Nuclear Information System (INIS)

Jeong, Jong Tae; Han, Sang Hoon

2008-01-01

The probabilistic safety assessment (PSA) provides a systematic analysis to identify and quantify all risks that the plant imposed to the operators, general public and the environment and thus demonstrates compliance to regulatory risk criteria. Therefore, the PSA has been being played an important role in the development of safety requirements for the existing plants, mainly reactors using light water technology. However, the existing safety requirements may not be fully applicable to the future reactors due to the advances in technology, new safety options, and new strategies for managing abnormal plant conditions. Therefore, a comprehensive set of technology-neutral safety requirements are being developed by the IAEA and USNRC. Especially, USNRC is developing a basis for a regulatory structure that is applicable to all types of reactor designs, including gas-cooled, liquid metal, and heavy and light water-moderated reactors because metrics such as core damage and large early release may not be applicable to some advanced reactor designs. They are developing this kind of basis for a regulatory structure in order to provide a technology neutral safety approach that will guide the design, construction and operation, as well as safety assessment, of innovative reactors. They are using the quantitative safety goals expressed by means of a frequency-consequence diagram. Within this approach, the scope of the PSA needs to encompass a whole spectrum of off-normal events including frequent, infrequent, and rare initiating events and event sequences. These events include a spectrum of releases from minor to major, and sequences that address conditions less than the core damage sequences. It also needs to address the dose consequences of these event sequences as measured at the exclusion area boundary (EAB). In order to obtain dose consequences for the whole spectrum of off-normal events, the dose evaluation by using the deterministic and probabilistic approaches has to be

Altered alkaline phosphatase activity in obese Zucker rats liver respect to lean Zucker and Wistar rats discussed in terms of all putative roles ascribed to the enzyme

Directory of Open Access Journals (Sweden)

V. Bertone

2011-02-01

Full Text Available Biliary complications often lead to acute and chronic liver injury after orthotopic liver transplantation (OLT. Bile composition and secretion depend on the integrated action of all the components of the biliary tree, starting from hepatocytes. Fatty livers are often discarded as grafts for OLT, since they are extremely vulnerable to conventional cold storage (CS. However, the insufficiency of donors has stimulated research to improve the usage of such marginal organs as well as grafts. Our group has recently developed a machine perfusion system at subnormothermic temperature (20°C; MP20 that allows a marked improvement in preservation of fatty and even of normal rat livers as compared with CS. We sought to evaluate the response of the biliary tree of fatty liver to MP20, and a suitable marker was essential to this purpose. Alkaline phosphatase (AlkP, EC 3.1.3.1, frequently used as marker of membrane transport in hepatocytes and bile ducts, was our first choice. Since no histochemical data were available on AlkP distribution and activity in fatty liver, we have first settled to investigate AlkP activity in the steatotic liver of fatty Zucker rats (fa/fa, using as controls lean Zucker (fa/+ and normal Wistar rats. The AlkP reaction in Wistar rats was in accordance with the existing data and, in particular, was present in bile canaliculi of hepatocytes in the periportal region and midzone, in the canals of Hering and in small bile ducts but not in large bile ducts. In lean ZR liver the AlkP reaction in Hering canals and small bile ducts was similar to Wistar rat liver but hepatocytes had lower canalicular activity and besides presented moderate basolateral reaction. The difference between lean Zucker and Wistar rats, both phenotypically normal animals, could be related to the fact that lean Zucker rats are genotypically heterozygous for a recessive mutated allele. In fatty liver, the activity in ductules and small bile ducts was unchanged, but

Altered alkaline phosphatase activity in obese Zucker rats liver respect to lean Zucker and Wistar rats discussed in terms of all putative roles ascribed to the enzyme.

Science.gov (United States)

Bertone, V; Tarantola, E; Ferrigno, A; Gringeri, E; Barni, S; Vairetti, M; Freitas, I

2011-02-08

Biliary complications often lead to acute and chronic liver injury after orthotopic liver transplantation (OLT). Bile composition and secretion depend on the integrated action of all the components of the biliary tree, starting from hepatocytes. Fatty livers are often discarded as grafts for OLT, since they are extremely vulnerable to conventional cold storage (CS). However, the insufficiency of donors has stimulated research to improve the usage of such marginal organs as well as grafts. Our group has recently developed a machine perfusion system at subnormothermic temperature (20°C; MP20) that allows a marked improvement in preservation of fatty and even of normal rat livers as compared with CS. We sought to evaluate the response of the biliary tree of fatty liver to MP20, and a suitable marker was essential to this purpose. Alkaline phosphatase (AlkP, EC 3.1.3.1), frequently used as marker of membrane transport in hepatocytes and bile ducts, was our first choice. Since no histochemical data were available on AlkP distribution and activity in fatty liver, we have first settled to investigate AlkP activity in the steatotic liver of fatty Zucker rats (fa/fa), using as controls lean Zucker (fa/+) and normal Wistar rats. The AlkP reaction in Wistar rats was in accordance with the existing data and, in particular, was present in bile canaliculi of hepatocytes in the periportal region and midzone, in the canals of Hering and in small bile ducts but not in large bile ducts. In lean ZR liver the AlkP reaction in Hering canals and small bile ducts was similar to Wistar rat liver but hepatocytes had lower canalicular activity and besides presented moderate basolateral reaction. The difference between lean Zucker and Wistar rats, both phenotypically normal animals, could be related to the fact that lean Zucker rats are genotypically heterozygous for a recessive mutated allele. In fatty liver, the activity in ductules and small bile ducts was unchanged, but most hepatocytes

Even Giants Need A Club: Domestic Institutions, Market Size, And Regulatory Influence

OpenAIRE

DAVID BACH

2005-01-01

This paper show that work on international market regulation has paid insufficient attention to the critical role played by domestic political and regulatory institutions. Existing literature emphasizes the role of market power, determined by market size, in analyzing international regulatory influence. While we do not contest the importance of market power, we introduce the notion of domestic regulatory capacity to capture the domestic institutional side of international market regulation th...

Functional and topological characteristics of mammalian regulatory domains

Science.gov (United States)

Symmons, Orsolya; Uslu, Veli Vural; Tsujimura, Taro; Ruf, Sandra; Nassari, Sonya; Schwarzer, Wibke; Ettwiller, Laurence; Spitz, François

2014-01-01

Long-range regulatory interactions play an important role in shaping gene-expression programs. However, the genomic features that organize these activities are still poorly characterized. We conducted a large operational analysis to chart the distribution of gene regulatory activities along the mouse genome, using hundreds of insertions of a regulatory sensor. We found that enhancers distribute their activities along broad regions and not in a gene-centric manner, defining large regulatory domains. Remarkably, these domains correlate strongly with the recently described TADs, which partition the genome into distinct self-interacting blocks. Different features, including specific repeats and CTCF-binding sites, correlate with the transition zones separating regulatory domains, and may help to further organize promiscuously distributed regulatory influences within large domains. These findings support a model of genomic organization where TADs confine regulatory activities to specific but large regulatory domains, contributing to the establishment of specific gene expression profiles. PMID:24398455

Role of CC chemokines (macrophage inflammatory protein-1 beta, monocyte chemoattractant protein-1, RANTES) in acute lung injury in rats

DEFF Research Database (Denmark)

Bless, N M; Huber-Lang, M; Guo, R F

2000-01-01

The role of the CC chemokines, macrophage inflammatory protein-1 beta (MIP-1 beta), monocyte chemotactic peptide-1 (MCP-1), and RANTES, in acute lung inflammatory injury induced by intrapulmonary deposition of IgG immune complexes injury in rats was determined. Rat MIP-1 beta, MCP-1, and RANTES...... were cloned, the proteins were expressed, and neutralizing Abs were developed. mRNA and protein expression for MIP-1 beta and MCP-1 were up-regulated during the inflammatory response, while mRNA and protein expression for RANTES were constitutive and unchanged during the inflammatory response....... Treatment of rats with anti-MIP-1 beta Ab significantly decreased vascular permeability by 37% (p = 0.012), reduced neutrophil recruitment into lung by 65% (p = 0.047), and suppressed levels of TNF-alpha in bronchoalveolar lavage fluids by 61% (p = 0.008). Treatment of rats with anti-rat MCP-1 or anti...

[Regulatory effect of Erbao granules on brain-gut peptide in juvenile animal model of anorexia].

Science.gov (United States)

Zhang, Y; Du, Y; Wang, S

2000-10-01

To study the regulatory effect of Erbao granules (EBG) on central and peripheral brain-gut peptide in juvenile animal model of anorexia. Juvenile rat model of anorexia was established by imitating the major cause of infantile anorexia and treated with EBG. The cholocystokinin-octapeptide (CCK-8) and beta-endorphin (beta-EP) concentration in hypothalamus, antrum pyloricum and peripheral blood were examined by radioimmunoassay. CCK-8 concentration in hypothalamus and plasma in the model rats increased (P anorexia model.

The role of adrenal hormones in the response of glutamine synthetase to fasting in adult and old rats.

Science.gov (United States)

Mezzarobba, V; Torrent, A; Leydier, I; Alles, S; Brajon, B; Mignon, M; Attaix, D; Meynial-Denis, D

2003-12-01

During fasting, skeletal muscle exports increased amounts of glutamine (Gln) while increasing the production of this amino acid by glutamine synthetase (GS) in order to maintain the intramuscular Gln pool. Glucocorticoid hormones are believed to be the principal mediators of GS induction during stress conditions. The aim of this study was to evaluate (1) the effect of fasting on GS activity and expression in skeletal muscle during aging and consequently, (2) the role of glucocorticoids in fasting-induced GS activity. Male Wistar rats (6-, 22-month old) were fasted for 5 days and both the activity and expression of GS were measured in tibialis anterior muscle. To better demonstrate the role of glucocorticoids in the response of GS to fasting, we suppressed their action by RU38486 administration (a potent glucocorticoid antagonist) and their production by adrenalectomy in fed and fasted rats. An increase in fasting-induced GS activity was observed in skeletal muscles from both adult and aged rats. Adrenalectomy, but surprisingly not RU38486, suppressed the fasting-induced increase in GS activity and expression. The data clearly show that the GS responsiveness to fasting was not modified by aging in skeletal muscle.

Nuclear Regulatory Commission: more aggressive leadership needed

International Nuclear Information System (INIS)

Staats, E.B.

1980-01-01

The Energy Reorganization Act of 1974 which established the Nuclear Regulatory Commission required GAO to evaluate the Commission's performance by January 18, 1980. This report responds to that requirement. GAO concluded that, although improvements have been made, the Commission's nuclear regulatory performance can be characterized best as slow, indecisive, cautious - in a word, complacent. This has largely resulted from a lack of aggressive leadership as evidenced by the Commissioners' failure to establish regulatory goals, control policymaking, and most importantly, clearly define their roles in nuclear regulation

Network perturbation by recurrent regulatory variants in cancer.

Directory of Open Access Journals (Sweden)

Kiwon Jang

2017-03-01

Full Text Available Cancer driving genes have been identified as recurrently affected by variants that alter protein-coding sequences. However, a majority of cancer variants arise in noncoding regions, and some of them are thought to play a critical role through transcriptional perturbation. Here we identified putative transcriptional driver genes based on combinatorial variant recurrence in cis-regulatory regions. The identified genes showed high connectivity in the cancer type-specific transcription regulatory network, with high outdegree and many downstream genes, highlighting their causative role during tumorigenesis. In the protein interactome, the identified transcriptional drivers were not as highly connected as coding driver genes but appeared to form a network module centered on the coding drivers. The coding and regulatory variants associated via these interactions between the coding and transcriptional drivers showed exclusive and complementary occurrence patterns across tumor samples. Transcriptional cancer drivers may act through an extensive perturbation of the regulatory network and by altering protein network modules through interactions with coding driver genes.

Impact of regulatory science on global public health

OpenAIRE

Meghal Patel; Margaret Ann Miller

2012-01-01

Regulatory science plays a vital role in protecting and promoting global public health by providing the scientific basis for ensuring that food and medical products are safe, properly labeled, and effective. Regulatory science research was first developed for the determination of product safety in the early part of the 20th Century, and continues to support innovation of the processes needed for regulatory policy decisions. Historically, public health laws and regulations were enacted followi...

Purinergic 2X receptors play a role in evoking the exercise pressor reflex in rats with peripheral artery insufficiency.

Science.gov (United States)

Stone, Audrey J; Yamauchi, Katsuya; Kaufman, Marc P

2014-02-01

Purinergic 2X (P2X) receptors on the endings of thin fiber afferents have been shown to play a role in evoking the exercise pressor reflex in cats. In this study, we attempted to extend this finding to decerebrated, unanesthetized rats whose femoral arteries were either freely perfused or were ligated 72 h before the start of the experiment. We first established that our dose of pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 10 mg/kg), a P2X receptor antagonist, attenuated the pressor response to α,β-methylene ATP (10 μg/kg), a P2X receptor agonist. We then compared the exercise pressor reflex before and after infusing PPADS into the arterial supply of the hindlimb muscles that were statically contracted. In rats with freely perfused femoral arteries, the peak pressor responses to contraction were not significantly attenuated by PPADS (before PPADS: 19 ± 2 mmHg, 13 min after PPADS: 17 ± 2 mmHg, and 25 min after PPADS: 17 ± 3 mmHg). Likewise, the cardioaccelerator and renal sympathetic nerve responses were not significantly attenuated. In contrast, we found that in rats whose femoral arteries were ligated PPADS significantly attenuated the peak pressor responses to contraction (before PPADS: 37 ± 5 mmHg, 13 min after PPADS: 27 ± 6 mmHg, and 25 min after PPADS: 25 ± 5 mmHg; P reflex in rats whose femoral arteries were ligated but play only a minimal role in evoking the reflex in rats whose femoral arteries were freely perfused.

Where we stand, where we are moving: Surveying computational techniques for identifying miRNA genes and uncovering their regulatory role

KAUST Repository

Kleftogiannis, Dimitrios A.; Korfiati, Aigli; Theofilatos, Konstantinos A.; Likothanassis, Spiridon D.; Tsakalidis, Athanasios K.; Mavroudi, Seferina P.

2013-01-01

Traditional biology was forced to restate some of its principles when the microRNA (miRNA) genes and their regulatory role were firstly discovered. Typically, miRNAs are small non-coding RNA molecules which have the ability to bind to the 3'untraslated region (UTR) of their mRNA target genes for cleavage or translational repression. Existing experimental techniques for their identification and the prediction of the target genes share some important limitations such as low coverage, time consuming experiments and high cost reagents. Hence, many computational methods have been proposed for these tasks to overcome these limitations. Recently, many researchers emphasized on the development of computational approaches to predict the participation of miRNA genes in regulatory networks and to analyze their transcription mechanisms. All these approaches have certain advantages and disadvantages which are going to be described in the present survey. Our work is differentiated from existing review papers by updating the methodologies list and emphasizing on the computational issues that arise from the miRNA data analysis. Furthermore, in the present survey, the various miRNA data analysis steps are treated as an integrated procedure whose aims and scope is to uncover the regulatory role and mechanisms of the miRNA genes. This integrated view of the miRNA data analysis steps may be extremely useful for all researchers even if they work on just a single step. © 2013 Elsevier Inc.

Where we stand, where we are moving: Surveying computational techniques for identifying miRNA genes and uncovering their regulatory role

KAUST Repository

Kleftogiannis, Dimitrios A.

2013-06-01

Traditional biology was forced to restate some of its principles when the microRNA (miRNA) genes and their regulatory role were firstly discovered. Typically, miRNAs are small non-coding RNA molecules which have the ability to bind to the 3\\'untraslated region (UTR) of their mRNA target genes for cleavage or translational repression. Existing experimental techniques for their identification and the prediction of the target genes share some important limitations such as low coverage, time consuming experiments and high cost reagents. Hence, many computational methods have been proposed for these tasks to overcome these limitations. Recently, many researchers emphasized on the development of computational approaches to predict the participation of miRNA genes in regulatory networks and to analyze their transcription mechanisms. All these approaches have certain advantages and disadvantages which are going to be described in the present survey. Our work is differentiated from existing review papers by updating the methodologies list and emphasizing on the computational issues that arise from the miRNA data analysis. Furthermore, in the present survey, the various miRNA data analysis steps are treated as an integrated procedure whose aims and scope is to uncover the regulatory role and mechanisms of the miRNA genes. This integrated view of the miRNA data analysis steps may be extremely useful for all researchers even if they work on just a single step. © 2013 Elsevier Inc.

Omega-3 polyunsaturated fatty acid docosahexaenoic acid and its role in exhaustive-exercise-induced changes in female rat ovulatory cycle.

Science.gov (United States)

Mostafa, Abeer F; Samir, Shereen M; Nagib, R M

2018-04-01

Exhaustive exercises can cause delayed menarche or menstrual cycle irregularities in females. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are incorporated into a wide range of benefits in many physiological systems. Our work aimed to assess the role of ω-3 PUFA docosahexaenoic acid (DHA) on the deleterious effects of exhaustive exercise on the female reproductive system in rats. Virgin female rats were randomly divided into 4 groups (12 rats in each): control group, omega-3 group treated with DHA, exhaustive exercise group, and exhaustive exercised rats treated with DHA. Omega-3 was given orally to the rats once daily for 4 estrous cycles. Exhaustive exercises revealed lower levels in progesterone and gonadotropins together with histopathological decrease in number of growing follicles and corpora lutea. Moreover, the exercised rats showed low levels of ovarian antioxidants with high level of caspase-3 and plasma cortisol level that lead to disruption of hypothalamic-pituitary-gonadal axis. ω-3 PUFA DHA has beneficial effects on the number of newly growing follicles in both sedentary and exercised rats with decreasing the level of caspase-3 and increasing the antioxidant activity in ovaries. Exhaustive exercises can cause ovulatory problems in female rats that can be improved by ω-3 supplementation.

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

The Role of Sulfur Dioxide in the Regulation of Mitochondrion-Related Cardiomyocyte Apoptosis in Rats with Isopropylarterenol-Induced Myocardial Injury

Directory of Open Access Journals (Sweden)

Junbao Du

2013-05-01

Full Text Available The authors investigated the regulatory effects of sulfur dioxide (SO2 on myocardial injury induced by isopropylarterenol (ISO hydrochloride and its mechanisms. Wistar rats were divided into four groups: control group, ISO group, ISO plus SO2 group, and SO2 only group. Cardiac function was measured and cardiomyocyte apoptosis was detected. Bcl-2, bax and cytochrome c (cytc expressions, and caspase-9 and caspase-3 activities in the left ventricular tissues were examined in the rats. The opening status of myocardial mitochondrial permeability transition pore (MPTP and membrane potential were analyzed. The results showed that ISO-treated rats developed heart dysfunction and cardiac injury. Furthermore, cardiomyocyte apoptosis in the left ventricular tissues was augmented, left ventricular tissue bcl-2 expression was down-regulated, bax expression was up-regulated, mitochondrial membrane potential was significantly reduced, MPTP opened, cytc release from mitochondrion into cytoplasm was significantly increased, and both caspase-9 and caspase-3 activities were increased. Administration of an SO2 donor, however, markedly improved heart function and relieved myocardial injury of the ISO-treated rats; it lessened cardiomyocyte apoptosis, up-regulated myocardial bcl-2, down-regulated bax expression, stimulated mitochondrial membrane potential, closed MPTP, and reduced cytc release as well as caspase-9 and caspase-3 activities in the left ventricular tissue. Hence, SO2 attenuated myocardial injury in association with the inhibition of apoptosis in myocardial tissues, and the bcl-2/cytc/caspase-9/caspase-3 pathway was possibly involved in this process.

Fragmentation of Protein Kinase N (PKN) in the Hydrocephalic Rat Brain

International Nuclear Information System (INIS)

Okii, Norifumi; Amano, Taku; Seki, Takahiro; Matsubayashi, Hiroaki; Mukai, Hideyuki; Ono, Yoshitaka; Kurisu, Kaoru; Sakai, Norio

2007-01-01

PKN (protein kinase N; also called protein kinase C-related kinase (PRK-1)), is a serine/threonine protein kinase that is ubiquitously expressed in several organs, including the brain. PKN has a molecular mass of 120 kDa and has two domains, a regulatory and a catalytic domain, in its amino-terminals and carboxyl-terminus, respectively. Although the role of PKN has not been fully elucidated, previous studies have revealed that PKN is cleaved to a constitutively active catalytic fragment of 55 kDa in response to apoptotic signals. Hydrocephalus is a pathological condition caused by insufficient cerebrospinal fluid (CSF) circulation and subsequent excess of CSF in the brain. In this study, in order to elucidate the role of PKN in the pathophysiology of hydrocephalus, we examined PKN fragmentation in hydrocephalic model rats. Hydrocephalus was induced in rats by injecting kaolin into the cisterna magna. Kaolin-induced rats (n=60) were divided into three groups according to the observation period after treatment (group 1: 3–6 weeks, group 2: 7–12 weeks, and group 3: 13–18 weeks). Sham-treated control rats, injected with sterile saline (n=20), were similarly divided into three groups. Spatial learning ability was estimated by a modified water maze test. Thereafter, brains were cut into slices and ventricular dilatation was estimated. Fragmentation of PKN was observed by Western blotting in samples collected from the parietal cortex, striatum, septal nucleus, hippocampus, and periaqueductal gray matter. All kaolin-induced rats showed ventricular dilatation. Most of them showed less spatial learning ability than those of sham-treated controls. In most regions, fragmentation of PKN had occurred in a biphasic manner more frequently than that in controls. The appearance of PKN fragmentation in periaqueductal gray matter was correlated with the extent of ventricular dilation and spatial learning disability. These results revealed that PKN fragmentation was observed in

Circular RNA Profiling and Bioinformatic Modeling Identify Its Regulatory Role in Hepatic Steatosis.

Science.gov (United States)

Guo, Xing-Ya; He, Chong-Xin; Wang, Yu-Qin; Sun, Chao; Li, Guang-Ming; Su, Qing; Pan, Qin; Fan, Jian-Gao

2017-01-01

Circular RNAs (circRNAs) exhibit a wide range of physiological and pathological activities. To uncover their role in hepatic steatosis, we investigated the expression profile of circRNAs in HepG2-based hepatic steatosis induced by high-fat stimulation. Differentially expressed circRNAs were subjected to validation using QPCR and functional analyses using principal component analysis, hierarchical clustering, target prediction, gene ontology (GO), and pathway annotation, respectively. Bioinformatic integration established the circRNA-miRNA-mRNA regulatory network so as to identify the mechanisms underlying circRNAs' metabolic effect. Here we reported that hepatic steatosis was associated with a total of 357 circRNAs. Enrichment of transcription-related GOs, especially GO: 0006355, GO: 004589, GO: 0045944, GO: 0045892, and GO: 0000122, demonstrated their specific actions in transcriptional regulation. Lipin 1 (LPIN1) was recognized to mediate the transcriptional regulatory effect of circRNAs on metabolic pathways. circRNA-miRNA-mRNA network further identified the signaling cascade of circRNA_021412/miR-1972/LPIN1, which was characterized by decreased level of circRNA_021412 and miR-1972-based inhibition of LPIN1. LPIN1-induced downregulation of long chain acyl-CoA synthetases (ACSLs) expression finally resulted in the hepatosteatosis. These findings identify circRNAs to be important regulators of hepatic steatosis. Transcription-dependent modulation of metabolic pathways may underlie their effects, partially by the circRNA_021412/miR-1972/LPIN1 signaling.

Posttraumatic Stress Disorder Disturbs Coronary Tone and Its Regulatory Mechanisms.

Science.gov (United States)

Lazuko, Svetlana S; Kuzhel, Olga P; Belyaeva, Lyudmila E; Manukhina, Eugenia B; Fred Downey, H; Tseilikman, Olga B; Komelkova, Maria V; Tseilikman, Vadim E

2018-01-01

Posttraumatic stress disorder (PTSD) is associated with myocardial injury, but changes in coronary regulatory mechanisms in PTSD have not been investigated. This study evaluated the effect of PTSD-inducing stress on coronary tone and its regulation by nitric oxide (NO) and voltage-gated K + channels. PTSD was induced by exposing rats to predator stress, 15 min daily for 10 days, followed by 14 stress-free days. Presence of PTSD was confirmed by the elevated plus-maze test. Coronary tone was evaluated from changes in coronary perfusion pressure of Langendorff isolated hearts. Predator stress induced significant decreases in coronary tone of isolated hearts and in blood pressure of intact rats. L-NAME, a non-selective NO synthase (NOS) inhibitor, but not S-MT, a selective iNOS inhibitor, and increased coronary tone of control rats. In PTSD rats, both L-NAME and S-MT increased coronary tone. Therefore, the stress-induced coronary vasodilation resulted from NO overproduction by both iNOS and eNOS. NOS induction was apparently due to systemic inflammation as evidenced by increased serum interleukin-1β and C-reactive protein in PTSD rats. Decreased corticosterone in PTSD rats may have contributed to inflammation and its effect on coronary tone. PTSD was also associated with voltage-gated K + channel dysfunction, which would have also reduced coronary tone.

The role and molecular mechanism of D-aspartic acid in the release and synthesis of LH and testosterone in humans and rats

Directory of Open Access Journals (Sweden)

Ronsini Salvatore

2009-10-01

Full Text Available Abstract Background D-aspartic acid is an amino acid present in neuroendocrine tissues of invertebrates and vertebrates, including rats and humans. Here we investigated the effect of this amino acid on the release of LH and testosterone in the serum of humans and rats. Furthermore, we investigated the role of D-aspartate in the synthesis of LH and testosterone in the pituitary and testes of rats, and the molecular mechanisms by which this amino acid triggers its action. Methods For humans: A group of 23 men were given a daily dose of D-aspartate (DADAVIT® for 12 days, whereas another group of 20 men were given a placebo. For rats: A group of 10 rats drank a solution of either 20 mM D-aspartate or a placebo for 12 days. Then LH and testosterone accumulation was determined in the serum and D-aspartate accumulation in tissues. The effects of D-aspartate on the synthesis of LH and testosterone were gauged on isolated rat pituitary and Leydig cells. Tissues were incubated with D-aspartate, and then the concentration (synthesis of LH and cGMP in the pituitary and of testosterone and cAMP in the Leydig cells was determined. Results In humans and rats, sodium D-aspartate induces an enhancement of LH and testosterone release. In the rat pituitary, sodium D-aspartate increases the release and synthesis of LH through the involvement of cGMP as a second messenger, whereas in rat testis Leydig cells, it increases the synthesis and release of testosterone and cAMP is implicated as second messenger. In the pituitary and in testes D-Asp is synthesized by a D-aspartate racemase which convert L-Asp into D-Asp. The pituitary and testes possesses a high capacity to trapping circulating D-Asp from hexogen or endogen sources. Conclusion D-aspartic acid is a physiological amino acid occurring principally in the pituitary gland and testes and has a role in the regulation of the release and synthesis of LH and testosterone in humans and rats.

The role of nesfatin-1 expression in letrozole-induced polycystic ovaries in the rat.

Science.gov (United States)

Xu, Yingqiao; Zhang, Hua; Li, Qingchun; Lao, Kaixue; Wang, Yanlin

2017-06-01

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disorder, generally exhibiting the characteristic features of hyperandrogenemia, insulin resistance (IR) and obesity. Nesfatin-1 is derived from the precursor nucleobindin2 (NUCB2), and plays an active role in energy balance, glucose metabolism and most likely gonadal function. In order to explore the role of nesfatin-1, we employed a rat model that uses letrozole to induce PCOS. The PCOS rats exhibited increased body weight, irregular cycles, polycystic ovaries characterized by cysts formed from atretic follicles, and a diminished granulosa layer. The expression of both nesfatin-1 mRNA and protein in the ovarian tissues of PCOS group decreased significantly compared to the control group (p < 0.05). Nesfatin-1 expression in peripheral blood also decreased in the PCOS group, in contrast with the control group. Furthermore, we found that nesfatin-1 had a positive correlation with FSH, E 2 and P, whereas it had a negative correlation with LH, and total T (p < 0.05). When taken together, these data indicated that the decrease in nesfatin-1 may contribute to the mechanism governing PCOS, and might provide a new potential target for therapies aimed at treating PCOS.

Tissue-specific expression and regulatory networks of pig microRNAome.

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Paolo Martini

Full Text Available BACKGROUND: Despite the economic and medical importance of the pig, knowledge about its genome organization, gene expression regulation, and molecular mechanisms involved in physiological processes is far from that achieved for mouse and rat, the two most used model organisms in biomedical research. MicroRNAs (miRNAs are a wide class of molecules that exert a recognized role in gene expression modulation, but only 280 miRNAs in pig have been characterized to date. RESULTS: We applied a novel computational approach to predict species-specific and conserved miRNAs in the pig genome, which were then subjected to experimental validation. We experimentally identified candidate miRNAs sequences grouped in high-confidence (424 and medium-confidence (353 miRNAs according to RNA-seq results. A group of miRNAs was also validated by PCR experiments. We established the subtle variability in expression of isomiRs and miRNA-miRNA star couples supporting a biological function for these molecules. Finally, miRNA and mRNA expression profiles produced from the same sample of 20 different tissue of the animal were combined, using a correlation threshold to filter miRNA-target predictions, to identify tissue-specific regulatory networks. CONCLUSIONS: Our data represent a significant progress in the current understanding of miRNAome in pig. The identification of miRNAs, their target mRNAs, and the construction of regulatory circuits will provide new insights into the complex biological networks in several tissues of this important animal model.

Role of Some Antioxidants in Ameliorating Disturbances Caused by Gamma Radiation in Female Rats

International Nuclear Information System (INIS)

El-Sherbiny, E. M.; Bayomi, M. M.; Addel-Aziz, S. M.

2007-01-01

The aim of this research is to investigate the role of supplemental antioxidant vitamins against some sex hormone and trace element disturbances in female rats 1 hour post exposure to 7.0 Gy of gamma radiation as a single dose using 60 Co source. Vitamins C and E were orally administered daily for 2 weeks in doses of 100 mg/kg and 25 mg/kg body weight, respectively. Total number of 48 female albino rats were equally divided into 4 groups; irradiated group (n = 12), vitamin C administered group (n = 12), vitamin E administered group (n = 12) and rats administered vitamin C followed immediately by vitamin E (n =12) post irradiation, in addition to the normal control group (n = 10). The results of this study revealed a significant reduction in serum estradiol level and highly significant reductions in serum progesterone level, zinc and selenium concentrations of female rats exposed to gamma rays, compared to control. Concerning groups administered vitamins, rats administered vitamin C showed a significant improvement in estradiol and progesterone levels, reaching the levels of control group and a non-significant improvement in serum zinc and selenium concentrations was recorded. Vitamin E administered group revealed a high significant increase in serum estradiol level accompanied with an improvement in progesterone, whereas a significant decrease in zinc was found and a significant amelioration in selenium concentration was recorded in comparison with control values. Administration of vitamin E followed immediately by vitamin C resulted in a significant increase in estradiol level and a remarkable improvement in the level of progesterone. Slight significant reduction in zinc was noticed, whereas selenium concentrations were reached normal levels in both E and C and and E groups in comparison with the other groups

Enhancing Tissue Engineering and Regenerative Medicine Product Commercialization: The Role of Science in Regulatory Decision-Making for the TE/RM Product Development.

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Bertram, Timothy A; Johnson, Peter C; Tawil, Bill J; Van Dyke, Mark; Hellman, Kiki B

2015-10-01

TERMIS-AM Industry Committee (TERMIS-AM/IC), in collaboration with the TERMIS-Europe (EU)/IC, conducted a symposium involving the European Medicines Agency and the U.S. Food and Drug Administration (FDA) toward building an understanding of the rational basis for regulatory decision-making and providing a framework for decisions made during the evaluation of safety and efficacy of TE/RM technologies. This symposium was held in August 2012 during the TERMIS-WC in Vienna, Austria. Emerging from this international initiative by the European Union and the United States, representatives from the respective agencies demonstrated that there are ongoing interagency efforts for developing common national practices toward harmonization of regulatory requirements for the TE/RM products. To extend a broad-based understanding of the role of science in regulatory decision-making, TERMIS-AM/IC, in cooperation with the FDA, organized a symposium at the 2014 TERMIS-AM Annual Meeting, which was held in Washington, DC. This event provided insights from leaders in the FDA and TERMIS on the current status of regulatory approaches for the approved TE/RM products, the use of science in making regulatory decisions, and TE/RM technologies that are in the development pipeline to address unmet medical needs. A far-ranging discussion with FDA representatives, industrialists, physicians, regenerative medicine biologists, and tissue engineers considered the gaps in today's scientific and regulatory understanding of TE/RM technologies. The identified gaps represent significant opportunities to advance TE/RM technologies toward commercialization.

Role of the orexin (hypocretin) system in contextual fear conditioning in rats.

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Wang, Huiying; Li, Sa; Kirouac, Gilbert J

2017-01-01

Orexin (hypocretin) neurons located in the posterior hypothalamus send projections to multiple areas of the brain involved in arousal and experimental evidence indicates that these neurons play a role in the physiological and behavioral responses to stress. This study was done to determine if the orexin system was involved in mediating the fear associated with shock context (5×2s of 1.5mA). First, real-time RT-PCR was used to examine changes in the mRNA levels for prepro-orexin (ppOX), the orexin-1 receptor (OX1R) and the orexin-2 receptor (OX2R) at two weeks post-shock. We found that the mRNA levels for ppOX and OX1R were increased in the posterior hypothalamus of shocked rats. In contrast, no significant difference was found in the midline thalamus or the locus coeruleus/parabrachial region. Second, the study examined if systemic injections of antagonists for orexin receptors attenuated the freezing related to contextual fear. The OX1R antagonist SB334867 (20 or 30mg/kg; i.p.) decreased freezing while the same doses of the OX2R antagonist TCSOX229 had no effect. The dual orexin antagonist TCS1102 (20mg/kg; i.p.) also decreased the freezing to the shock context. The results of the present study show upregulation of orexin activity and of the OX1R in the hypothalamus following exposure of rats to footshocks and highlight a specific role of OX1R in contextual fear. Copyright © 2016 Elsevier B.V. All rights reserved.

Perceptions of regulatory approaches

International Nuclear Information System (INIS)

Halin, Magnus; Leinonen, Ruusaliisa

2012-01-01

Ms. Ruusaliisa Leinonen and Mr. Magnus Halin from Fortum gave a joint presentation on industry perceptions of regulatory oversight of LMfS/SC. It was concluded that an open culture of discussion exists between the regulator (STUK) and the licensee, based on the common goal of nuclear safety. An example was provided of on how regulatory interventions helped foster improvements to individual and collective dose rate trends, which had remained static. Regulatory interventions included discussions on the ALARA concept to reinforce the requirement to continuously strive for improvements in safety performance. Safety culture has also been built into regulatory inspections in recent years. Training days have also been organised by the regulatory body to help develop a shared understanding of safety culture between licensee and regulatory personnel. Fortum has also developed their own training for managers and supervisors. Training and ongoing discussion on LMfS/SC safety culture is considered particularly important because both Fortum and the regulatory body are experiencing an influx of new staff due to the demographic profile of their organisations. It was noted that further work is needed to reach a common understanding of safety culture on a practical level (e.g., for a mechanic setting to work), and in relation to the inspection criteria used by the regulator. The challenges associated with companies with a mix of energy types were also discussed. This can make it more difficult to understand responsibilities and decision making processes, including the role of the parent body organisation. It also makes communication more challenging due to increased complexity and a larger number of stakeholders

The Regulatory Roles of MicroRNAs in Bone Remodeling and Perspectives as Biomarkers in Osteoporosis

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Mengge Sun

2016-01-01

Full Text Available MicroRNAs are involved in many cellular and molecular activities and played important roles in many biological and pathological processes, such as tissue formation, cancer development, diabetes, neurodegenerative diseases, and cardiovascular diseases. Recently, it has been reported that microRNAs can modulate the differentiation and activities of osteoblasts and osteoclasts, the key cells that are involved in bone remodeling process. Meanwhile, the results from our and other research groups showed that the expression profiles of microRNAs in the serum and bone tissues are significantly different in postmenopausal women with or without fractures compared to the control. Therefore, it can be postulated that microRNAs might play important roles in bone remodeling and that they are very likely to be involved in the pathological process of postmenopausal osteoporosis. In this review, we will present the updated research on the regulatory roles of microRNAs in osteoblasts and osteoclasts and the expression profiles of microRNAs in osteoporosis and osteoporotic fracture patients. The perspective of serum microRNAs as novel biomarkers in bone loss disorders such as osteoporosis has also been discussed.

Role of AC-cAMP-PKA Cascade in Antidepressant Action of Electroacupuncture Treatment in Rats

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Jian-hua Liu

2012-01-01

Full Text Available Adenylyl cyclase (AC-cyclic adenosine monophosphate (cAMP-cAMP-dependent protein kinase A (PKA cascade is considered to be associated with the pathogenesis and treatment of depression. The present study was conducted to explore the role of the cAMP cascade in antidepressant action of electroacupuncture (EA treatment for chronic mild stress (CMS-induced depression model rats. The results showed that EA improved significantly behavior symptoms in depression and dysfunction of AC-cAMP-PKA signal transduction pathway induced by CMS, which was as effective as fluoxetine. Moreover, the antidepressant effects of EA rather than Fluoxetine were completely abolished by H89, a specific PKA inhibitor. Consequently, EA has a significant antidepressant treatment in CMS-induced depression model rats, and AC-cAMP-PKA signal transduction pathway is crucial for it.

Perspectives on Regulatory T Cell Therapies.

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Probst-Kepper, Michael; Kröger, Andrea; Garritsen, Henk S P; Buer, Jan

2009-01-01

Adoptive transfer in animal models clearly indicate an essential role of CD4+ CD25+ FOXP3+ regulatory T (T(reg)) cells in prevention and treatment of autoimmune and graft-versus-host disease. Thus, T(reg) cell therapies and development of drugs that specifically enhance T(reg) cell function and development represent promising tools to establish dominant tolerance. So far, lack of specific markers to differentiate human T(reg) cells from activated CD4+ CD25+ effector T cells, which also express FOXP3 at different levels, hampered such an approach. Recent identification of the orphan receptor glycoprotein-A repetitions predominant (GARP or LRRC32) as T(reg) cell-specific key molecule that dominantly controls FOXP3 via a positive feedback loop opens up new perspectives for molecular and cellular therapies. This brief review focuses on the role of GARP as a safeguard of a complex regulatory network of human T(reg) cells and its implications for regulatory T cell therapies in autoimmunity and graft-versus-host disease.

Role of cytochrome P-450 4A in oxygen sensing and NO production in rat cremaster resistance arteries

NARCIS (Netherlands)

Kerkhof, C. J.; Bakker, E. N.; Sipkema, P.

1999-01-01

The role of arachidonic acid metabolism and nitric oxide (NO) in hypoxia-induced changes of vascular tone was investigated in first-order cannulated rat cremaster muscle resistance arteries. Spontaneous tone reduced arterial diameter from 179 +/- 2 micrometer (fully dilated) to 98 +/- 3 micrometer

Reflections on the role of the pharmacy regulatory authority in enhancing quality related event reporting in community pharmacies.

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Boyle, Todd A; Bishop, Andrea C; Mahaffey, Thomas; Mackinnon, Neil J; Ashcroft, Darren M; Zwicker, Bev; Reid, Carolyn

2014-01-01

Given the demanding nature of providing pharmacy services, coupled with the expanded scope of practice of the professions in jurisdictions around the world, greater commitment to continuous quality improvement through adoption of quality-related event (QRE) reporting is necessary to ensure patient safety. Pharmacy regulatory authorities (PRAs) are in a unique position to enhance QRE reporting and learning through the standardization of expected practice. This study was aimed to gain a better understanding of the perceived roles of PRAs in enhancing QRE reporting and learning in community pharmacies, and identifying regulatory best practices to execute such roles. A purposive case sampling approach was used to identify PRA staff members from two groups (Deputy registrars and pharmacy inspectors) in 10 Canadian jurisdictions to participate in focus groups in the fall of 2011. Focus groups were used to explore perceptions of the role of PRAs in enhancing and promoting QRE reporting and learning, and perceived barriers to effective implementation in practice. Thematic analysis was used to analyze the qualitative data. Two focus groups were conducted, one with seven Deputy registrars/Practice managers, and one with nine pharmacy inspectors. Five themes were identified, including (1) defining QRE reporting and compliance, (2) navigating role conflict, (3) educating for enhanced QRE reporting and learning, (4) promoting the positive/removing the fear of QREs, and (5) tailoring QRE reporting and learning consistency. Overall, participants perceived a strong role for PRAs in enhancing QRE reporting and learning and providing education for pharmacies to support their compliance with reporting standards. However, PRAs must navigate the conflict inherent in both educating and promoting a process for achieving a standard while simultaneously inspecting compliance to that standard. Ensuring pharmacies have autonomy in operationalizing standards may help to mitigate this conflict

REFLECTIONS ON THE ROLE OF THE PHARMACY REGULATORY AUTHORITY IN ENHANCING QUALITY RELATED EVENT REPORTING IN COMMUNITY PHARMACIESi

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Boyle, Todd A.; Bishop, Andrea C.; Mahaffey, Thomas; MacKinnon, Neil J.; Ashcroft, Darren; Zwicker, Bev; Reid, Carolyn

2016-01-01

Background Given the demanding nature of providing pharmacy services, coupled with the expanded scope of practice of the professions in jurisdictions around the world, greater commitment to continuous quality improvement through adoption of quality related event (QRE) reporting is necessary to ensure patient safety. Pharmacy regulatory authorities (PRAs) are in a unique position to enhance QRE reporting and learning through the standardization of expected practice Objective This study aims to better understand the perceived roles of PRAs in enhancing QRE reporting and learning in community pharmacies and identifying regulatory best practices to execute such roles. Methods A purposive case sampling approach was used to identify PRA staff members from two groups (deputy registrars and pharmacy inspectors) in 10 Canadian jurisdictions to participate in focus groups in the fall of 2011. Focus groups were used to explore perceptions of the role of PRAs in enhancing and promoting QRE reporting and learning, and perceived barriers to effective implementation in practice. Thematic analysis was used to analyze the qualitative data. Results Two focus groups were conducted, one with seven deputy registrars/practice managers and one with nine pharmacy inspectors. Five themes were identified, including (1) defining QRE reporting and compliance, (2) navigating role conflict, (3) educating for enhanced QRE reporting and learning, (4) promoting the positive/removing the fear of QREs, and (5) tailoring QRE reporting and learning consistency. Conclusions Overall, participants perceived a strong role for PRAs in enhancing QRE reporting and learning and providing education for pharmacies to support their compliance with reporting standards. However, PRAs must navigate the conflict inherent in both educating and promoting a process for achieving a standard while simultaneously inspecting compliance to that standard. Ensuring pharmacies have autonomy in operationalizing standards may

Interactive toxicity of chlorpyrifos and parathion in neonatal rats: Role of esterases in exposure sequence-dependent toxicity

International Nuclear Information System (INIS)

Kacham, R.; Karanth, S.; Baireddy, P.; Liu, J.; Pope, C.

2006-01-01

capable than adults at detoxifying many organophosphorus insecticides including chlorpyrifos and parathion, toxicant-selective differences in detoxification play a role in sequence-dependent toxicity in both neonatal and adult rats with these two insecticides

The Spot 42 RNA: A regulatory small RNA with roles in the central metabolism

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Bækkedal, Cecilie; Haugen, Peik

2015-01-01

The Spot 42 RNA is a 109 nucleotide long (in Escherichia coli) noncoding small regulatory RNA (sRNA) encoded by the spf (spot fourty-two) gene. spf is found in gamma-proteobacteria and the majority of experimental work on Spot 42 RNA has been performed using E. coli, and recently Aliivibrio salmonicida. In the cell Spot 42 RNA plays essential roles as a regulator in carbohydrate metabolism and uptake, and its expression is activated by glucose, and inhibited by the cAMP-CRP complex. Here we summarize the current knowledge on Spot 42, and present the natural distribution of spf, show family-specific secondary structural features of Spot 42, and link highly conserved structural regions to mRNA target binding. PMID:26327359

The Spot 42 RNA: A regulatory small RNA with roles in the central metabolism.

Science.gov (United States)

Bækkedal, Cecilie; Haugen, Peik

2015-01-01

The Spot 42 RNA is a 109 nucleotide long (in Escherichia coli) noncoding small regulatory RNA (sRNA) encoded by the spf (spot fourty-two) gene. spf is found in gamma-proteobacteria and the majority of experimental work on Spot 42 RNA has been performed using E. coli, and recently Aliivibrio salmonicida. In the cell Spot 42 RNA plays essential roles as a regulator in carbohydrate metabolism and uptake, and its expression is activated by glucose, and inhibited by the cAMP-CRP complex. Here we summarize the current knowledge on Spot 42, and present the natural distribution of spf, show family-specific secondary structural features of Spot 42, and link highly conserved structural regions to mRNA target binding.

[A study on the role of vascular endothelial growth factor in emphysema of rat caused by smog exposure].

Science.gov (United States)

Chen, Jin-long; Ran, Pi-xin

2003-11-01

To explore the role of vascular endothelial growth factor (VEGF) in emphysema of rat caused by smog exposure. Thirty-six 12-week male rats were randomly divided into 2 groups: a smog exposure group (S group), and a normal control group (N group). S group rats were randomly subdivided into 3 groups: S(1) group, S(2) group, S(3) group, which were exposed to smog for 2 weeks, 4 weeks, 8 weeks, respectively; N group rats were randomly subdivided into 3 groups: N(1) group, N(2) group, N(3) group, which were raised in normal oxygen condition for 0 week, 4 weeks, 8 weeks, respectively. The expressions of VEGF mRNA and VEGF protein and kinase-insert domain containing receptor (KDR) protein were determined by reverse transcription-polymerase chain reaction (RT-PCR) and modified SABC immunohistochemistry assay separately. The pathological change in smog exposure rat lung was determined by HE staining. MLI and MAN were determined as an index of emphysema. Variance analysis, nonparametric analysis and correlate analysis were conducted in SPSS 10.0. (1) There were airway inflammation in S group rat lungs, and an early-emphysema-like change in S(3) group rat lungs: MAN in S(3) group was significantly decreased compared with N(3) group, MLI in S(3) group was significantly increased compared with N(3) group (P 0.05). (3) VEGF protein expression in alveolar epithelium and bronchial epithelium had a positive correlation with MAN (r = 0.43, r = 0.37, P Smog exposure decrease the expression of VEGF and KDR in rat lung. VEGF might involve in the pathology of emphysema caused by smog exposure.

Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis.

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Stanisavljević, Suzana; Dinić, Miroslav; Jevtić, Bojan; Đedović, Neda; Momčilović, Miljana; Đokić, Jelena; Golić, Nataša; Mostarica Stojković, Marija; Miljković, Đorđe

2018-01-01

Albino Oxford (AO) rats are extremely resistant to induction of experimental autoimmune encephalomyelitis (EAE). EAE is an animal model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS), with established autoimmune pathogenesis. The autoimmune response against the antigens of the CNS is initiated in the peripheral lymphoid tissues after immunization of AO rats with CNS antigens. Subsequently, limited infiltration of the CNS occurs, yet without clinical sequels. It has recently become increasingly appreciated that gut-associated lymphoid tissues (GALT) and gut microbiota play an important role in regulation and propagation of encephalitogenic immune response. Therefore, modulation of AO gut microbiota by antibiotics was performed in this study. The treatment altered composition of gut microbiota in AO rats and led to a reduction in the proportion of regulatory T cells in Peyer's patches, mesenteric lymph nodes, and in lymph nodes draining the site of immunization. Upregulation of interferon-γ and interleukin (IL)-17 production was observed in the draining lymph nodes. The treatment led to clinically manifested EAE in AO rats with more numerous infiltrates and higher production of IL-17 observed in the CNS. Importantly, transfer of AO gut microbiota into EAE-prone Dark Agouti rats ameliorated the disease. These results clearly imply that gut microbiota is an important factor in AO rat resistance to EAE and that gut microbiota transfer is an efficacious way to treat CNS autoimmunity. These findings also support the idea that gut microbiota modulation has a potential as a future treatment of multiple sclerosis.

The protective role of bee honey against the toxic effect of melamine in the male rat kidney.

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Al-Seeni, Madeha N; El Rabey, Haddad A; Al-Solamy, Suad M

2015-06-01

This study aimed to test the protective role of natural bee honey against melamine toxicity in the kidney of male albino rats. The dietary supplementation of melamine at a dose of 20,000 ppm for 28 days induced renal dysfunction, as reflected by a significant increase in kidney function parameters (urea, creatinine, and uric acid) and an increase in potassium levels. In addition, a decrease in catalase and glutathione-S-transferase and an increase in lipid peroxide in the kidney tissue homogenate were also observed. Histological changes in the melamine-treated group revealed hyperplasia and damage in kidney cells and the accumulation of melamine crystals in kidney tissues. Honey treatment for 28 days in rats concurrently administered melamine at a dose of 2.5 g/kg body weight for 28 days improved the kidney function, increased antioxidant enzymes, and decreased lipid peroxide levels. The morphology of the kidney cells of the melamine-fed rats was also improved as a result of honey treatment. In conclusion, this study revealed that natural bee honey protects the kidney against the adverse effects induced by melamine toxicity in male albino rats. © The Author(s) 2014.

Cell-intrinsic role for NF-kappa B-inducing kinase in peripheral maintenance but not thymic development of Foxp3+ regulatory T cells in mice.

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Susan E Murray

Full Text Available NF-κB inducing kinase (NIK, MAP3K14 is a key signaling molecule in non-canonical NF-κB activation, and NIK deficient mice have been instrumental in deciphering the immunologic role of this pathway. Global ablation of NIK prevents lymph node development, impairs thymic stromal development, and drastically reduces B cells. Despite altered thymic selection, T cell numbers are near normal in NIK deficient mice. The exception is CD4(+ regulatory T cells (Tregs, which are reduced in the thymus and periphery. Defects in thymic stroma are known to contribute to impaired Treg generation, but whether NIK also plays a cell intrinsic role in Tregs is unknown. Here, we compared intact mice with single and mixed BM chimeric mice to assess the intrinsic role of NIK in Treg generation and maintenance. We found that while NIK expression in stromal cells suffices for normal thymic Treg development, NIK is required cell-intrinsically to maintain peripheral Tregs. In addition, we unexpectedly discovered a cell-intrinsic role for NIK in memory phenotype conventional T cells that is masked in intact mice, but revealed in BM chimeras. These results demonstrate a novel role for NIK in peripheral regulatory and memory phenotype T cell homeostasis.

Regulatory role of prolactin in paternal behavior in male parents: A narrative review

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F Hashemian

2016-01-01

Full Text Available In all mammalian species, a combination of neuroendocrine and experiential factors contributes to the emergence of remarkable behavioral changes observed in parental behavior. Yet, our understanding of neuroendocrine bases of paternal behavior in humans is still preliminary and more research is needed in this area. In the present review, the authors summarized hormonal bases of paternal behavior in both human and nonhuman mammalian species and focused on studies on the regulatory role of prolactin in occurrence of paternal behavior. All peer-reviewed journal articles published before 2015 for each area discussed (parental brain, hormonal bases of maternal behavior, hormonal bases of paternal behavior and the role of prolactin in regulation of paternal behavior in nonhuman mammalian species, hormonal bases of paternal behavior and the role of prolactin in regulation of paternal behavior in humans were searched by PubMed, Medline, and Scopus for original research and review articles. Publications between 1973 and 2015 were included. Similar to female parents, elevated prolactin levels in new fathers most probably contribute to child-caring behavior and facilitate behavioral and emotional states attributed to child care. Moreover, elevated parental prolactin levels after childbirth decrease the parents′ libidos so that they invest more in parental care than in fertility behavior. According to the available clinical studies, elevation in the amounts of prolactin levels after childbirth in male parents are probably associated with paternal behavior observed in humans.

Small RNA expression and strain specificity in the rat

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de Bruijn Ewart

2010-04-01

Full Text Available Abstract Background Digital gene expression (DGE profiling has become an established tool to study RNA expression. Here, we provide an in-depth analysis of small RNA DGE profiles from two different rat strains (BN-Lx and SHR from six different rat tissues (spleen, liver, brain, testis, heart, kidney. We describe the expression patterns of known and novel micro (miRNAs and piwi-interacting (piRNAs. Results We confirmed the expression of 588 known miRNAs (54 in antisense orientation and identified 56 miRNAs homologous to known human or mouse miRNAs, as well as 45 new rat miRNAs. Furthermore, we confirmed specific A to I editing in brain for mir-376a/b/c and identified mir-377 as a novel editing target. In accordance with earlier findings, we observed a highly tissue-specific expression pattern for all tissues analyzed. The brain was found to express the highest number of tissue-specific miRNAs, followed by testis. Notably, our experiments also revealed robust strain-specific differential miRNA expression in the liver that is caused by genetic variation between the strains. Finally, we identified two types of germline-specific piRNAs in testis, mapping either to transposons or in strand-specific clusters. Conclusions Taken together, the small RNA compendium described here advances the annotation of small RNAs in the rat genome. Strain and tissue-specific expression patterns furthermore provide a strong basis for studying the role of small RNAs in regulatory networks as well as biological process like physiology and neurobiology that are extensively studied in this model system.

Zinc prevents sickness behavior induced by lipopolysaccharides after a stress challenge in rats.

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Thiago B Kirsten

Full Text Available Sickness behavior is considered part of the specific beneficial adaptive behavioral and neuroimmune changes that occur in individuals in response to infectious/inflammatory processes. However, in dangerous and stressful situations, sickness behavior should be momentarily abrogated to prioritize survival behaviors, such as fight or flight. Taking this assumption into account, we experimentally induced sickness behavior in rats using lipopolysaccharides (LPS, an endotoxin that mimics infection by gram-negative bacteria, and then exposed these rats to a restraint stress challenge. Zinc has been shown to play a regulatory role in the immune and nervous systems. Therefore, the objective of this study was to examine the effects of zinc treatment on the sickness response of stress-challenged rats. We evaluated 22-kHz ultrasonic vocalizations, open-field behavior, tumor necrosis factor α (TNF-α, corticosterone, and brain-derived neurotrophic factor (BDNF plasma levels. LPS administration induced sickness behavior in rats compared to controls, i.e., decreases in the distance traveled, average velocity, rearing frequency, self-grooming, and number of vocalizations, as well as an increase in the plasma levels of TNF-α, compared with controls after a stressor challenge. LPS also decreased BDNF expression but did not influence anxiety parameters. Zinc treatment was able to prevent sickness behavior in LPS-exposed rats after the stress challenge, restoring exploratory/motor behaviors, communication, and TNF-α levels similar to those of the control group. Thus, zinc treatment appears to be beneficial for sick animals when they are facing risky/stressful situations.

Distinct roles of the endocannabinoids anandamide and 2-arachidonoylglycerol in social behavior and emotionality at different developmental ages in rats.

Science.gov (United States)

Manduca, Antonia; Morena, Maria; Campolongo, Patrizia; Servadio, Michela; Palmery, Maura; Trabace, Luigia; Hill, Matthew N; Vanderschuren, Louk J M J; Cuomo, Vincenzo; Trezza, Viviana

2015-08-01

To date, our understanding of the relative contribution and potential overlapping roles of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the regulation of brain function and behavior is still limited. To address this issue, we investigated the effects of systemic administration of JZL195, that simultaneously increases AEA and 2-AG signaling by inhibiting their hydrolysis, in the regulation of socio-emotional behavior in adolescent and adult rats. JZL195, administered at the dose of 0.01mg/kg, increased social play behavior, that is the most characteristic social activity displayed by adolescent rats, and increased social interaction in adult animals. At both ages, these behavioral effects were antagonized by the CB1 cannabinoid receptor antagonist SR141716A and were associated with increased brain levels of 2-AG, but not AEA. Conversely, at the dose of 1mg/kg, JZL195 decreased general social exploration in adolescent rats without affecting social play behavior, and induced anxiogenic-like effects in the elevated plus-maze test both in adolescent and adult animals. These effects, mediated by activation of CB1 cannabinoid receptors, were paralleled by simultaneous increase in AEA and 2-AG levels in adolescent rats, and by an increase of only 2-AG levels in adult animals. These findings provide the first evidence for a role of 2-AG in social behavior, highlight the different contributions of AEA and 2-AG in the modulation of emotionality at different developmental ages and suggest that pharmacological inhibition of AEA and 2-AG hydrolysis is a useful approach to investigate the role of these endocannabinoids in neurobehavioral processes. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Competitive mindsets, creativity, and the role of regulatory focus

NARCIS (Netherlands)

Bittner, Jenny; Heidemeier, Heike

2013-01-01

We examined how regulatory focus and intentions to compete rather than cooperate with group members relate to creativity. Study 1 showed that a promotion focus (i.e., a focus on ideals) activated a cooperative mindset, whereas a prevention focus (i.e., a focus on responsibilities) activated a

Environment and T regulatory cells in allergy.

Science.gov (United States)

Braga, M; Schiavone, C; Di Gioacchino, G; De Angelis, I; Cavallucci, E; Lazzarin, F; Petrarca, C; Di Gioacchino, M

2012-04-15

The central role of T regulatory cells in the responses against harmless environmental antigens has been confirmed by many studies. Impaired T regulatory cell function is implicated in many pathological conditions, particularly allergic diseases. The "hygiene hypothesis" suggests that infections and infestations may play a protective role for allergy, whereas environmental pollutants favor the development of allergic diseases. Developing countries suffer from a variety of infections and are also facing an increasing diffusion of environmental pollutants. In these countries allergies increase in relation to the spreading use of xenobiotics (pesticides, herbicides, pollution, etc.) with a rate similar to those of developed countries, overcoming the protective effects of infections. We review here the main mechanisms of non-self tolerance, with particular regard to relations between T regulatory cell activity, infections and infestations such as helminthiasis, and exposure to environmental xenobiotics with relevant diffusion in developing countries. Copyright © 2010 Elsevier B.V. All rights reserved.

Antioxidant role of inositol hexaphosphate on male rats after short-term exposure to ionizing radiation

International Nuclear Information System (INIS)

Mansour, S.Z.; Aly, S.M.E.; Ibrahim, N.K.

2006-01-01

This study was conducted to evaluate the potency of Inositol hexaphosphate (IP6) as a natural protective agent against gamma-irradiation induced intracellular free radical such as superoxide anion and hydroxyl radical. Swiss albino rats were gavaged by orally tube with 6 doses (day after day) with IP6 mg/kg body wt) alone or even before exposure the animals to whole body gamma-radiation with single dose of 6 Gy 30 min post the last injection of IP6. Lipid peroxide (LP), Glutathione (GSH) levels and the activity of the antioxidant scavenger enzyme Catalase were estimated in blood, liver, kidney and spleen at day 1 post-irradiation. Some metals concentrations were determined to demonstrate the role of IP6 as chelating agent. Radiation exposure showed marked elevation in LP level accompanied by decline in GSH content and in the activity of related antioxidant enzyme Pretreatment with IP6 potentially reversed the investigated parameters in irradiated rats. It modulated LP, and ameliorated to a great extent GSH content and the activity of Catalase enzyme in blood, liver, kidney and spleen of rats exposed to gamma-irradiation

A PTEN-COL17A1 fusion gene and its novel regulatory role in Collagen XVII expression and GBM malignance.

Science.gov (United States)

Yan, Xiaoyan; Zhang, Chuanbao; Liang, Tingyu; Yang, Fan; Wang, Haoyuan; Wu, Fan; Wang, Wen; Wang, Zheng; Cheng, Wen; Xu, Jiangnan; Jiang, Tao; Chen, Jing; Ding, Yaozhong

2017-10-17

Collagen XVII expression has recently been demonstrated to be correlated with the tumor malignance. While Collagen XVII is known to be widely distributed in neurons of the human brain, its precise role in pathogenesis of glioblastoma multiforme (GBM) is unknown. In this study, we identified and characterized a new PTEN-COL17A1 fusion gene in GMB using transcriptome sequencing. Although fusion gene did not result in measurable fusion protein production, its presence is accompanied with high levels of COL17A1 expression, revealed a novel regulatory mechanism of Collagen XVII expression by PTEN-COL17A1 gene fusion. Knocked down Collagen XVII expression in glioma cell lines resulted in decreased tumor invasiveness, along with significant reduction of MMP9 expression, while increased Collagen XVII expression promotes invasive activities of glioma cells and associated with GBM recurrences. Together, our results uncovered a new PTEN-COL17A1 fusion gene and its novel regulatory role in Collagen XVII expression and GBM malignance, and demonstrated that COL17A1 could serve as a useful prognostic biomarker and therapeutic targets for GBM.

Parameters of Blood Flow in Great Arteries in Hypertensive ISIAH Rats with Stress-Dependent Arterial Hypertension.

Science.gov (United States)

Seryapina, A A; Shevelev, O B; Moshkin, M P; Markel', A L

2016-08-01

Magnetic resonance angiography was used to examine blood flow in great arteries of hypertensive ISIAH and normotensive Wistar rats. In hypertensive ISIAH rats, increased vascular resistance in the basin of the abdominal aorta and renal arteries as well as reduced fraction of total renal blood flow were found. In contrast, blood flow through both carotid arteries in ISIAH rats was enhanced, which in suggests more intensive blood supply to brain regulatory centers providing enhanced stress reactivity of these rats characterized by stress-dependent arterial hypertension.

Protective role of selenium and vitamins A, C and E against gamma irradiation-induced oxidative stress in diabetic rats

International Nuclear Information System (INIS)

Nagiub, N.I.; Abd El-maguid, A.; Saad, T.M.M.

2006-01-01

This study was designed to evaluate the protective effect of selenium and vitamins A, C and E on the oxidative stress in alloxan injected and/or irradiated rats. Rats were received a daily intraperitoneal administration of selenium (0.9 mg/rat) and vitamin A (14 IU/rat), vitamin C (0.8 mg/rat) and vitamin E (0.25 mg/rat) daily for one week before intraperitoneal injection with alloxan (60 mg/kg body weight) and/or gamma irradiation exposure (6.5 Gy). Animals were sacrificed on the tenth day post-irradiation and/or alloxan treatment. Histological examinations were made on eye tissue and blood was removed for biochemical analysis. The histological results obtained revealed that exposure to ionizing radiation or treatment with alloxan caused histopathological damage in the eye tissue manifested as a congestion in retinal blood capillaries, vacuolation in ganglionic cells and degeneration in nuclear cells of retina. The lens became coagulated, homogenous and oesinophilic while the cornea showed vacuolations in its epithelium, edema and hyalinosis of substantia propria.The biochemical results showed that exposure to single dose (6.5 Gy) of ionizing radiation or treatment with alloxan caused significant elevation in lipid peroxide content (MDA), glucose level, total cholesterol (TC), triacylglycerol (TAG), low density lipoprotein (LDL), accompanied with significant depletion in reduced glutathione content (GSH), superoxide dismutase (SOD) activity and high density lipoprotein (HDL) in blood samples. Administration of selenium and vitamin A, C and E before gamma radiation exposure and/or alloxan treatment exerted marked amelioration of the histological changes in the eye and of the biochemical changes in rats induced by radiation but did not ameliorate that due to alloxan treatment in the tested parameters, thus diminishing the magnitude of injury due to radiation only. According to the results obtained, it could be concluded that selenium and vitamin A, C and E (a

Conducted vasoconstriction in rat mesenteric arterioles: role for dihydropyridine-insensitive Ca(2+) channels

DEFF Research Database (Denmark)

Gustafsson, F; Andreasen, D; Salomonsson, Max

2001-01-01

The aim of this study was to evaluate the role of voltage-operated Ca(2+) channels in the initiation and conduction of vasoconstrictor responses to local micropipette electrical stimulation of rat mesenteric arterioles (28 +/- 1 microm, n = 79) in vivo. Local and conducted (600 microm upstream from...... the pipette) vasoconstriction was not blocked by TTX (1 micromol/l, n = 5), nifedipine, or nimodipine (10 micromol/l, n = 9). Increasing the K(+) concentration of the superfusate to 75 mmol/l did not evoke vasoconstriction, but this depolarizing stimulus reversibly abolished vasoconstrictor responses...

Role of wheat germ oil in radiation-induced oxidative stress and alteration in energy metabolism in rats

Energy Technology Data Exchange (ETDEWEB)

Shedid, S M.E. [National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo (Egypt)

2008-07-01

The liver is essential in keeping the body functioning properly while muscular strength is important in sport as well as in daily activities. Exposure to ionizing radiation is thought to increase oxidative stress and damage liver and muscle tissues. Wheat germ oil is a natural unrefined vegetable oil. It is an excellent source of vitamin E, octacosanol, linoleic and linolenic essential fatty acids, which may be beneficial in neutralizing the free oxygen radicals. This study was designed to investigate the efficacy of wheat germ oil, on radiation induced oxidative damage in rat's liver and skeletal muscle. Wheat germ oil was supplemented orally via gavage to rats at a dose of 54 mg/ kg body weight for 14 successive days pre- and 7 days post-exposure to 5 Gy (single dose) of whole body gamma irradiation. Animals were sacrificed 7, 14 and 21 days post radiation exposure. The results revealed that whole body gamma irradiation of rats induces oxidative stress in liver and skeletal muscles obvious by significant elevation in the levels of xanthine oxidase and thiobarbituric acid reactive substances (TBARS) associated with significant decreases in the content of reduced glutathione, as well as decreases in xanthine dehydrogenase, superoxide dismutase, catalase and glutathione peroxidase activities. Irradiated rats showed also significant decreases in creatine phosphokinase, glutamate dehydrogenase and glucose-6- phosphate dehydrogenase activities while lactate dehydrogenase were significantly increased. Total iron, total copper and total calcium levels significantly increased in the liver and skeletal muscles of irradiated rats group compared to control group. Wheat germ oil treated-irradiated rats showed significantly less severe damage and remarkable improvement in all the measured parameters, compared to irradiated rats. It could be concluded that wheat germ oil by attenuating radiation-induced oxidative stress might play a role in maintaining liver and skeletal muscle

Role of wheat germ oil in radiation-induced oxidative stress and alteration in energy metabolism in rats

International Nuclear Information System (INIS)

Shedid, S.M.E.

2008-01-01

The liver is essential in keeping the body functioning properly while muscular strength is important in sport as well as in daily activities. Exposure to ionizing radiation is thought to increase oxidative stress and damage liver and muscle tissues. Wheat germ oil is a natural unrefined vegetable oil. It is an excellent source of vitamin E, octacosanol, linoleic and linolenic essential fatty acids, which may be beneficial in neutralizing the free oxygen radicals. This study was designed to investigate the efficacy of wheat germ oil, on radiation induced oxidative damage in rat's liver and skeletal muscle. Wheat germ oil was supplemented orally via gavage to rats at a dose of 54 mg/ kg body weight for 14 successive days pre- and 7 days post-exposure to 5 Gy (single dose) of whole body gamma irradiation. Animals were sacrificed 7, 14 and 21 days post radiation exposure. The results revealed that whole body gamma irradiation of rats induces oxidative stress in liver and skeletal muscles obvious by significant elevation in the levels of xanthine oxidase and thiobarbituric acid reactive substances (TBARS) associated with significant decreases in the content of reduced glutathione, as well as decreases in xanthine dehydrogenase, superoxide dismutase, catalase and glutathione peroxidase activities. Irradiated rats showed also significant decreases in creatine phosphokinase, glutamate dehydrogenase and glucose-6- phosphate dehydrogenase activities while lactate dehydrogenase were significantly increased. Total iron, total copper and total calcium levels significantly increased in the liver and skeletal muscles of irradiated rats group compared to control group. Wheat germ oil treated-irradiated rats showed significantly less severe damage and remarkable improvement in all the measured parameters, compared to irradiated rats. It could be concluded that wheat germ oil by attenuating radiation-induced oxidative stress might play a role in maintaining liver and skeletal muscle

Regulatory dendritic cell therapy: from rodents to clinical application

OpenAIRE

Raïch-Regué, Dalia; Glancy, Megan; Thomson, Angus W.

2013-01-01

Dendritic cells (DC) are highly-specialized, bone marrow-derived antigen-presenting cells that induce or regulate innate and adaptive immunity. Regulatory or “tolerogenic” DC play a crucial role in maintaining self tolerance in the healthy steady-state. These regulatory innate immune cells subvert naïve or memory T cell responses by various mechanisms. Regulatory DC (DCreg) also exhibit the ability to induce or restore T cell tolerance in many animal models of autoimmune disease or transplant...

AMP deaminase histochemical activity and immunofluorescent isozyme localization in rat skeletal muscle

Science.gov (United States)

Thompson, J. L.; Sabina, R. L.; Ogasawara, N.; Riley, D. A.

1992-01-01

The cellular distribution of AMP deaminase (AMPda) isozymes was documented for rat soleus and plantaris muscles, utilizing immunofluorescence microscopy and immunoprecipitation methods. AMPda is a ubiquitous enzyme existing as three distinct isozymes, A, B and C, which were initially purified from skeletal muscle, liver (and kidney), and heart, respectively. AMPda-A is primarily concentrated subsarcolemmally and intermyofibrillarly within muscle cells, while isozymes B and C are concentrated within non-myofiber elements of muscle tissue. AMPda-B is principally associated with connective tissues surrounding neural elements and the muscle spindle capsule, and AMPda-C is predominantly associated with circulatory elements, such as arterial and venous walls, capillary endothelium, and red blood cells. These specific localizations, combined with documented differences in kinetic properties, suggest multiple functional roles for the AMPda isozymes or temporal segregation of similar AMPda functions. Linkage of the AMPda substrate with adenosine production pathways at the AMP level and the localization of isozyme-C in vascular tissue suggest a regulatory role in the microcirculation.

The role of substance P in the maintenance of colonic hypermotility induced by repeated stress in rats.

Science.gov (United States)

Lu, Ping; Luo, Hesheng; Quan, Xiaojing; Fan, Han; Tang, Qincai; Yu, Guang; Chen, Wei; Xia, Hong

2016-04-01

The mechanism underlying chronic stress-induced gastrointestinal (GI) dysmotility has not been fully elucidated and GI hormones have been indicated playing a role in mediating stress-induced changes in GI motor function. Our objective was to study the possible role of substance P (SP) in the colonic hypermotility induced by repeated water avoidance stress (WAS) which mimics irritable bowel syndrome. Male Wistar rats were submitted to WAS or sham WAS (SWAS) (1h/day) for up to 10 consecutive days. Enzyme Immunoassay Kit was used to detect the serum level of SP. The expression of neurokinin-1 receptor (NK1R) was investigated by Immunohistochemistry and Western blotting. The spontaneous contraction of muscle strip was studied in an organ bath system. L-type calcium channel currents (ICa,L) of smooth muscle cells (SMCs) were recorded by whole-cell patch-clamp technique. Fecal pellet expulsion and spontaneous contraction of proximal colon in rats were increased after repeated WAS. The serum level of SP was elevated following WAS. Immunohistochemistry proved the expression of NK1R in mucosa, muscularis and myenteric plexus. Western blotting demonstrated stress-induced up-regulation of NK1R in colon devoid of mucosa and submucosa. Repeated WAS increased the contractile activities of longitudinal muscle and circular muscle strips induced by SP and this effect was reversed by a selective NK1R antagonist. The ICa,L of SMCs in the WAS rats were drastically increased compared to controls after addition of SP. Increased serum SP level and up-regulated NK1R in colon may contribute to stress-induced colonic hypermotility. And L-type calcium channels play a potentially important role in the process of WAS-induced dysmotility. Copyright © 2016 Elsevier Ltd. All rights reserved.

Food safety regulatory systems in Europe and China：A study of how co-regulation can improve regulatory effectiveness

Institute of Scientific and Technical Information of China (English)

Kevin Chen; WANG Xin-xin; SONG Hai-ying

2015-01-01

Food safety has received a great deal of attention in both developed and developing countries in recent years. In China, the numerous food scandals and scares that have struck over the past decade have spurred signiifcant food safety regulatory reform, which has been increasingly oriented towards the public-private partnership model adopted by the Europe Union’s (EU) food safety regulatory system. This paper analyzes the development of both the EU’s and China’s food safety regu-latory systems, identiifes the current chalenges for China and additionaly considers the role of public-private partnership. The success of co-regulation in the food regulatory system would bring signiifcant beneifts and opportunities for China. Finaly, this paper recommends additional measures like training and grants to improve the private’s sector effectiveness in co-regulating China’s food safety issues.

Uncovering a Dual Regulatory Role for Caspases During Endoplasmic Reticulum Stress-induced Cell Death.

Science.gov (United States)

Anania, Veronica G; Yu, Kebing; Gnad, Florian; Pferdehirt, Rebecca R; Li, Han; Ma, Taylur P; Jeon, Diana; Fortelny, Nikolaus; Forrest, William; Ashkenazi, Avi; Overall, Christopher M; Lill, Jennie R

2016-07-01

Many diseases are associated with endoplasmic reticulum (ER) stress, which results from an accumulation of misfolded proteins. This triggers an adaptive response called the "unfolded protein response" (UPR), and prolonged exposure to ER stress leads to cell death. Caspases are reported to play a critical role in ER stress-induced cell death but the underlying mechanisms by which they exert their effect continue to remain elusive. To understand the role caspases play during ER stress, a systems level approach integrating analysis of the transcriptome, proteome, and proteolytic substrate profile was employed. This quantitative analysis revealed transcriptional profiles for most human genes, provided information on protein abundance for 4476 proteins, and identified 445 caspase substrates. Based on these data sets many caspase substrates were shown to be downregulated at the protein level during ER stress suggesting caspase activity inhibits their cellular function. Additionally, RNA sequencing revealed a role for caspases in regulation of ER stress-induced transcriptional pathways and gene set enrichment analysis showed expression of multiple gene targets of essential transcription factors to be upregulated during ER stress upon inhibition of caspases. Furthermore, these transcription factors were degraded in a caspase-dependent manner during ER stress. These results indicate that caspases play a dual role in regulating the cellular response to ER stress through both post-translational and transcriptional regulatory mechanisms. Moreover, this study provides unique insight into progression of the unfolded protein response into cell death, which may help identify therapeutic strategies to treat ER stress-related diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The Regulatory Independence of FANR

International Nuclear Information System (INIS)

ALNuaimi, Fatema; Choi, Kwang Shik

2012-01-01

Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

The Regulatory Independence of FANR

Energy Technology Data Exchange (ETDEWEB)

ALNuaimi, Fatema; Choi, Kwang Shik [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

2012-05-15

Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

Localization of phosphatidylinositol signaling components in rat taste cells: Role in bitter taste transduction

International Nuclear Information System (INIS)

Hwang, P.M.; Verma, A.; Bredt, D.S.; Snyder, S.H.

1990-01-01

To assess the role of phosphatidylinositol turnover in taste transduction we have visualized, in rat tongue, ATP-dependent endoplasmic reticular accumulation of 45 Ca 2+ , inositol 1,4,5-trisphosphate receptor binding sites, and phosphatidylinositol turnover monitored by autoradiography of [ 3 H]cytidine diphosphate diacylglycerol formed from [ 3 H]cytidine. Accumulated 45 Ca 2+ , inositol 1,4,5-trisphosphate receptors, and phosphatidylinositol turnover are selectively localized to apical areas of the taste buds of circumvallate papillae, which are associated with bitter taste. Further evidence for a role of phosphatidylinositol turnover in bitter taste is our observation of a rapid, selective increase in mass levels of inositol 1,4,5-trisphosphate elicited by low concentrations of denatonium, a potently bitter tastant

Testing stem cell therapy in a rat model of inflammatory bowel disease: role of bone marrow stem cells and stem cell factor in mucosal regeneration.

Science.gov (United States)

Qu, Bo; Xin, Guo-Rong; Zhao, Li-Xia; Xing, Hui; Lian, Li-Ying; Jiang, Hai-Yan; Tong, Jia-Zhao; Wang, Bei-Bei; Jin, Shi-Zhu

2014-01-01

The gastrointestinal (GI) mucosal cells turnover regularly under physiological conditions, which may be stimulated in various pathological situations including inflammation. Local epithelial stem cells appear to play a major role in such mucosal renewal or pathological regeneration. Less is clear about the involvement of multipotent stem cells from blood in GI repair. We attempted to explore a role of bone marrow mesenchymal stromal cells (BMMSCs) and soluble stem cell factor (SCF) in GI mucosa regeneration in a rat model of inflammatory bowel diseases (IBD). BMMSCs labelled with the fluorescent dye PKH26 from donor rats were transfused into rats suffering indomethacin-induced GI injury. Experimental effects by BMMSCs transplant and SCF were determined by morphometry of intestinal mucosa, double labeling of PKH26 positive BMMSCs with endogenous proliferative and intestinal cell markers, and western blot and PCR analyses of the above molecular markers in the recipient rats relative to controls. PKH26 positive BMMSCs were found in the recipient mucosa, partially colocalizing with the proliferating cell nuclear antigen (PCNA), Lgr5, Musashi-1 and ephrin-B3. mRNA and protein levels of PCNA, Lgr5, Musashi-1 and ephrin-B3 were elevated in the intestine in BMMSCs-treated rats, most prominent in the BMMSCs-SCF co-treatment group. The mucosal layer and the crypt layer of the small intestine were thicker in BMMSCs-treated rats, more evident in the BMMSCs-SCF co-treatment group. BMMSCs and SCF participate in but may play a synergistic role in mucosal cell regeneration following experimentally induced intestinal injury. Bone marrow stem cell therapy and SCF administration may be of therapeutic value in IBD.

Role of the availability of substrates on hepatic and renal gluconeogenesis in the fasted late pregnant rat

International Nuclear Information System (INIS)

Zorzano, A.; Lasuncion, M.A.; Herrera, E.

1986-01-01

Studies were conducted to examine the role of gluconeogenetic substrate availability on glucose production in the fasted late pregnant rat. Virgin and 21-day pregnant rats were studied after 24 hours' food deprivation. Pregnant animals showed decreased circulating glucose and gluconeogenic amino acid and increased plasma glycerol concentration. Glucose formation was studied in vivo two, five, and ten minutes after the intravenous administration of two concentrations of 14 C-alanine, 14 C-pyruvate, or 14 C-glycerol. Concentrations of 0.2 mmols of 14 C-glycerol or 14 C-pyruvate, but not of 14 C-alanine, enhanced 14 C-glucose production in pregnant rats, whereas 1 mmol of any of the three 14 C-substrates always enhanced 14 C-glucose production in these rats. Both 1 mmol/L and 5 mmol/L 14 C-alanine increased 14 C-glucose formation in 90-minute-incubated liver slices of fasted pregnant rats, in spite of decreased cytosolic activity of alanine aminotransferase. The three substrates enhanced in vitro renal gluconeogenesis in pregnant rats. Under all experimental conditions studied, labeled glycerol was converted more efficiently into glucose than equivalent amounts of any other substrate used, and this difference was greater in pregnant, than in virgin animals. Results indicate that, in spite of enhanced gluconeogenetic activity, maternal glucose production in the fasted state at late gestation is limited by the deficiency of certain substrates, such as amino acids. It is proposed that glycerol derived from enhanced maternal adipose tissue lipolysis constitutes a preferential gluconeogenetic substrate in comparison with others, such as alanine, that are more efficiently transferred through the placenta to the fetus

Protective role of curcumin against sulfite-induced structural changes in rats' medial prefrontal cortex.

Science.gov (United States)

Noorafshan, Ali; Asadi-Golshan, Reza; Abdollahifar, Mohammad-Amin; Karbalay-Doust, Saied

2015-08-01

Sodium metabisulfite as a food preservative can affect the central nervous system. Curcumin, the main ingredient of turmeric has neuroprotective activity. This study was designed to evaluate the effects of sulfite and curcumin on the medial prefrontal cortex (mPFC) using stereological methods. Thirty rats were randomly divided into five groups. The rats in groups I-V received distilled water, olive oil, curcumin (100 mg/kg/day), sodium metabisulfite (25 mg/kg/day), and sulfite + curcumin, respectively, for 8 weeks. The brains were subjected to the stereological methods. Cavalieri and optical disector techniques were used to estimate the total volume of mPFC and the number of neurons and glial cells. Intersections counting were applied on the thick vertical uniform random sections to estimate the dendrites length, and classify the spines. Non-parametric tests were used to analyze the data. The mean mPFC volume, neurons number, glia number, dendritic length, and total spines per neuron were 3.7 mm(3), 365,000, 180,000, 1820 µm, and 1700 in distilled water group, respectively. A reduction was observed in the volume of mPFC (∼8%), number of neurons (∼15%), and number of glia (∼14%) in mPFC of the sulfite group compared to the control groups (P curcumin had a protective role against the changes in the rats.

Discussion on building safety culture inside a nuclear safety regulatory body

International Nuclear Information System (INIS)

Fan Yumao

2013-01-01

A strong internal safety culture plays a key role in improving the performance of a nuclear regulatory body. This paper discusses the definition of internal safety culture of nuclear regulatory bodies, and explains the functions that the safety culture to facilitate the nuclear safety regulation and finally puts forward some thoughts about building internal safety culture inside regulatory bodies. (author)

CPEB1 modulates lipopolysaccharide-mediated iNOS induction in rat primary astrocytes

International Nuclear Information System (INIS)

Kim, Ki Chan; Hyun Joo, So; Shin, Chan Young

2011-01-01

Highlights: → Expression and phosphorylation of CPEB1 is increased by LPS stimulation in rat primary astrocytes. → JNK regulates expression and phosphorylation of CPEB1 in reactive astrocytes. → Down-regulation of CPEB1 using siRNA inhibits oxidative stress and iNOS induction by LPS stimulation. → CPEB1 may play an important role in regulating inflammatory responses in reactive astrocytes induced by LPS. -- Abstract: Upon CNS damage, astrocytes undergo a series of biological changes including increased proliferation, production of inflammatory mediators and morphological changes, in a response collectively called reactive gliosis. This process is an essential part of the brains response to injury, yet much is unknown about the molecular mechanism(s) that induce these changes. In this study, we investigated the role of cytoplasmic polyadenylation element binding protein 1 (CPEB1) in the regulation of inflammatory responses in a model of reactive gliosis, lipopolysaccharide-stimulated astrocytes. CPEB1 is an mRNA-binding protein recently shown to be expressed in astrocytes that may play a role in astrocytes migration. After LPS stimulation, the expression and phosphorylation of CPEB1 was increased in rat primary astrocytes in a JNK-dependent process. siRNA-induced knockdown of CPEB1 expression inhibited the LPS-induced up-regulation of iNOS as well as NO and ROS production, a hallmark of immunological activation of astrocytes. The results from the study suggest that CPEB1 is actively involved in the regulation of inflammatory responses in astrocytes, which might provide new insights into the regulatory mechanism after brain injury.

Interleukin-2 and STAT5 in regulatory T cell development and function

OpenAIRE

Mahmud, Shawn A.; Manlove, Luke S.; Farrar, Michael A.

2013-01-01

Interleukin-2 and its downstream target STAT5 have effects on many aspects of immune function. This has been perhaps best documented in regulatory T cells. In this review we summarize the initial findings supporting a role for IL2 and STAT5 in regulatory T cell development and outline more recent studies describing how this critical signaling pathway entrains regulatory T cell differentiation and affects regulatory T cell function.

A Novel Gibberellin-Induced Gene from Rice and Its Potential Regulatory Role in Stem Growth1

Science.gov (United States)

van der Knaap, Esther; Kim, Jeong Hoe; Kende, Hans

2000-01-01

Os-GRF1 (Oryza sativa-GROWTH-REGULATING FACTOR1) was identified in a search for genes that are differentially expressed in the intercalary meristem of deepwater rice (Oryza sativa L.) internodes in response to gibberellin (GA). Os-GRF1 displays general features of transcription factors, contains a functional nuclear localization signal, and has three regions with similarities to sequences in the database. One of these regions is similar to a protein interaction domain of SWI2/SNF2, which is a subunit of a chromatin-remodeling complex in yeast. The two other domains are novel and found only in plant proteins of unknown function. To study its role in plant growth, Os-GRF1 was expressed in Arabidopsis. Stem elongation of transformed plants was severely inhibited, and normal growth could not be recovered by the application of GA. Our results indicate that Os-GRF1 belongs to a novel class of plant proteins and may play a regulatory role in GA-induced stem elongation. PMID:10712532

Helminth parasites in black rats (Rattus rattus) and brown rats (Rattus norvegicus) from different environments in the Netherlands

NARCIS (Netherlands)

Franssen, Frits; Swart, Arno; van Knapen, Frans|info:eu-repo/dai/nl/070114749; van der Giessen, Joke

2016-01-01

BACKGROUND: Rattus norvegicus (brown rat) and Rattus rattus (black rat) are known carriers of bacteria, viruses, and parasites of zoonotic and veterinary importance. Moreover, rats may play a role in the transmission of muscle larvae of the zoonotic nematode Trichinella spiralis to farm animals. We

Pivotal Role of Brain-Derived Neurotrophic Factor Secreted by Mesenchymal Stem Cells in Severe Intraventricular Hemorrhage in Newborn Rats.

Science.gov (United States)

Ahn, So Yoon; Chang, Yun Sil; Sung, Dong Kyung; Sung, Se In; Ahn, Jee-Yin; Park, Won Soon

2017-01-24

Mesenchymal stem cell (MSC) transplantation protects against neonatal severe intraventricular hemorrhage (IVH)-induced brain injury by a paracrine rather than regenerative mechanism; however, the paracrine factors involved and their roles have not yet been delineated. This study aimed to identify the paracrine mediator(s) and to determine their role in mediating the therapeutic effects of MSCs in severe IVH. We first identified significant upregulation of brain-derived neurotrophic factor (BDNF) in MSCs compared with fibroblasts, in both DNA and antibody microarrays, after thrombin exposure. We then knocked down BDNF in MSCs by transfection with small interfering (si)RNA specific for human BDNF. The therapeutic effects of MSCs with or without BDNF knockdown were evaluated in vitro in rat neuronal cells challenged with thrombin, and in vivo in newborn Sprague-Dawley rats by injecting 200 μl of blood on postnatal day 4 (P4), and transplanting MSCs (1 × 105 cells) intraventricularly on P6. siRNA-induced BDNF knockdown abolished the in vitro benefits of MSCs on thrombin-induced neuronal cell death. BDNF knockdown also abolished the in vivo protective effects against severe IVH-induced brain injuries such as the attenuation of posthemorrhagic hydrocephalus, impaired behavioral test performance, increased astrogliosis, increased number of TUNEL cells, ED-1+ cells, and inflammatory cytokines, and reduced myelin basic protein expression. Our data indicate that BDNF secreted by transplanted MSCs is one of the critical paracrine factors that play a seminal role in attenuating severe IVH-induced brain injuries in newborn rats.

Prohibitin regulates the FSH signaling pathway in rat granulosa cell differentiation.

Science.gov (United States)

Chowdhury, Indrajit; Thomas, Kelwyn; Zeleznik, Anthony; Thompson, Winston E

2016-05-01

Published results from our laboratory identified prohibitin (PHB), a gene product expressed in granulosa cells (GCs) that progressively increases during follicle maturation. Our current in vitro studies demonstrate that follicle-stimulating hormone (FSH) stimulates Phb expression in rat primary GCs. The FSH-dependent expression of PHB was primarily localized within mitochondria, and positively correlates with the morphological changes in GCs organelles, and synthesis and secretions of estradiol (E2) and progesterone (P4). In order to confirm that PHB plays a regulatory role in rat GC differentiation, endogenous PHB-knockdown studies were carried out in undifferentiated GCs using adenoviral (Ad)-mediated RNA interference methodology. Knockdown of PHB in GCs resulted in the suppression of the key steroidogenic enzymes including steroidogenic acute regulatory protein (StAR), p450 cholesterol side-chain cleavage enzyme (p450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), and aromatase (Cyp19a1); and decreased E2 and P4 synthesis and secretions in the presence of FSH stimulation. Furthermore, these experimental studies also provided direct evidence that PHB within the mitochondrial fraction in GCs is phosphorylated at residues Y249, T258, and Y259 in response to FSH stimulation. The observed levels of phosphorylation of PHB at Y249, T258, and Y259 were significantly low in GCs in the absence of FSH stimulation. In addition, during GC differentiation FSH-induced expression of phospho-PHB (pPHB) requires the activation of MEK1-ERK1/2 signaling pathway. Taken together, these studies provide new evidence supporting FSH-dependent PHB/pPHB upregulation in GCs is required to sustain the differentiated state of GCs. © 2016 The authors.

Zooming in on regulatory intermediaries: The impact of non-state regulators on sustainable construction practice

NARCIS (Netherlands)

van der Heijden, J.

2014-01-01

Levi-Faur and Starobin (2013) have recently drawn our attention to the important role of regulatory intermediates in contemporary regulatory regimes. Among others they argue that regulatory intermediaries come in a wide variety of appearances, and that these can influence the outcomes of regulatory

Role of Ginkgo Biloba in Hyperhomocysteinemia Induced in Rats By L-Methionine and Gamma Irradiation

International Nuclear Information System (INIS)

Mansour, S.Z.

2011-01-01

The objective of this study is to evaluate the role of Ginkgo biloba in hyperhomocysteinemia and oxidative stress. Methionine was supplied orally to adult male albino rats with a dose of 1.7 g/kg/day during 4 weeks. Irradiation was applied to rats by whole body gamma irradiation with a dose of 2 Gy/week up to a total dose of 8 Gy. Ginkgo biloba (100 mg/kg/day) was supplemented orally to rats, daily, during the period of methionine administration and/or radiation exposure. Biochemical analysis in blood and brain tissues showed that methionine and/or gamma irradiation produced significant increases in homocysteine and acetylcholine esterase levels and significant decrease in nitric oxide (NO). Significant increase in malondialdehyde (MDA) with significant decreases in glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase levels were observed and alteration in plasma lipid profile was also recorded. Ginkgo biloba supplementation has significantly decreased homocysteine and acetylcholine esterase levels and increased NO while was associated with significant improvement of oxidative stress and lipid profile. It could be concluded that the protective effect of Gingko biloba against hyperhomocysteinemia and oxidative stress is attributed to its antioxidant and free radicals scavenging properties.

The Role of the Rat Medial Prefrontal Cortex in Adapting to Changes in Instrumental Contingency

Science.gov (United States)

Coutureau, Etienne; Esclassan, Frederic; Di Scala, Georges; Marchand, Alain R.

2012-01-01

In order to select actions appropriate to current needs, a subject must identify relationships between actions and events. Control over the environment is determined by the degree to which action consequences can be predicted, as described by action-outcome contingencies – i.e. performing an action should affect the probability of the outcome. We evaluated in a first experiment adaptation to contingency changes in rats with neurotoxic lesions of the medial prefrontal cortex. Results indicate that this brain region is not critical to adjust instrumental responding to a negative contingency where the rats must refrain from pressing a lever, as this action prevents reward delivery. By contrast, this brain region is required to reduce responding in a non-contingent situation where the same number of rewards is freely delivered and actions do not affect the outcome any more. In a second experiment, we determined that this effect does not result from a different perception of temporal relationships between actions and outcomes since lesioned rats adapted normally to gradually increasing delays in reward delivery. These data indicate that the medial prefrontal cortex is not directly involved in evaluating the correlation between action-and reward-rates or in the perception of reward delays. The deficit in lesioned rats appears to consist of an abnormal response to the balance between contingent and non-contingent rewards. By highlighting the role of prefrontal regions in adapting to the causal status of actions, these data contribute to our understanding of the neural basis of choice tasks. PMID:22496747

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.

The Regulatory Role of MicroRNAs in EMT and Cancer

Directory of Open Access Journals (Sweden)

Apostolos Zaravinos

2015-01-01

Full Text Available The epithelial to mesenchymal transition (EMT is a powerful process in tumor invasion, metastasis, and tumorigenesis and describes the molecular reprogramming and phenotypic changes that are characterized by a transition from polarized immotile epithelial cells to motile mesenchymal cells. It is now well known that miRNAs are important regulators of malignant transformation and metastasis. The aberrant expression of the miR-200 family in cancer and its involvement in the initiation and progression of malignant transformation has been well demonstrated. The metastasis suppressive role of the miR-200 members is strongly associated with a pathologic EMT. This review describes the most recent advances regarding the influence of miRNAs in EMT and the control they exert in major signaling pathways in various cancers. The ability of the autocrine TGF-β/ZEB/miR-200 signaling regulatory network to control cell plasticity between the epithelial and mesenchymal state is further discussed. Various miRNAs are reported to directly target EMT transcription factors and components of the cell architecture, as well as miRNAs that are able to reverse the EMT process by targeting the Notch and Wnt signaling pathways. The link between cancer stem cells and EMT is also reported and the most recent developments regarding clinical trials that are currently using anti-miRNA constructs are further discussed.

Antifibrogenic role of valproic acid in streptozotocin induced diabetic rat penis.

Science.gov (United States)

Kutlu, O; Karaguzel, E; Gurgen, S G; Okatan, A E; Kutlu, S; Bayraktar, C; Kazaz, I O; Eren, H

2016-05-01

We investigated the therapeutic effects of valproic acid (VPA) on erectile dysfunction and reducing penile fibrosis in streptozocin (STZ)-induced diabetic rats. Eighteen male rats were divided into three experimental groups (Control, STZ-DM, STZ-DM plus VPA) and diabetes was induced by transperitoneal single dose STZ. Eight weeks after, VPA and placebo treatments were given according to groups for 15 days. All rats were anesthetised for the measurement of in vivo erectile response to cavernous nerve stimulation. Afterward penes were evaluated histologically in terms of immune labelling scores of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1). Slides were also evaluated in terms of collagen/smooth muscle ratio and penile apoptosis. After the treatment with VPA, erectile responses were found as improved when compared with STZ-DM rats but not statistically meaningful. eNOS and VEGF immune expressions diminished in penile corpora of STZ-DM rats and improved with VPA treatment. VPA led to decrease in TGF-β1 expression and collagen content of diabetic rats' penes. Penile apoptosis was not diminished with VPA. In conclusion, VPA treatment seems to be effective for reducing penile fibrosis in diabetic rats and more prolonged treatment period may enhance erectile functions. © 2015 Blackwell Verlag GmbH.

Role of Growth Hormone, Exercise and Serum Phosphorus in Unloaded Bone of Young Rats

Science.gov (United States)

Arnnaud, Sara B.; Harper, J. S.; Gosselink, K. L.; Navidi, M.; Fung, P.; Grindeland, R. E.; Wade, Charles E. (Technical Monitor)

1994-01-01

Growth hormone, known to be stimulated by exercise, is suppressed in rats after space flight and in a ground-based model in which the hind-limbs are unloaded (S). To determine the role of GH in the osteopenia of unloaded bones of S rats, young males were treated with GH combined with insulin-like growth factor-1 (IGF-1), a peptide that mediates the local actions of the hormone. 200 g rats, hypophysectomized (hypox) 17 d earlier, were treated with 1 mg/kg/d GH/IGF-1 (H) or saline (C) in 3 divided daily doses x10 d. Hind-limb bones were unloaded (S), ambulated (A) or exercised (X) by climbing a ladder while carrying a weight. Growth was monitored daily. Tibial growth plate (Tepi) was measured with a micrometer, and femoral (F) area, length, and mineral content (BMC) by DEXA. Parameters of calcium metabolism were measured by autoanalyzer and calciotropic hormones by radioimmunoassay. F bone density, g/square cm, (BMD) or BW were not affected by S in Hypox. However, FBMD was lower in S+H than A+H (p is less than 0.002) and H stimulated whole body growth in S (5.2 g/d) and SX (5.6 g/d) to a lesser extent than in A (6.6 g/d) (p is less than 0.05). Adjusted for BW, Tepi showed the greatest increase in S+H+X (64%), the next highest increase in S+H (50%) and no change in S+X. F area, length and BMC/100 g BW were lower in all H groups than respective C's. By multiple regression analysis, serum phosphorus (Pi) which correlated with Tepi (r = 0.88, p is less than 0.001) and was inversely related to FBMC (r = -0.68, p is less than 0.001) proved to be the most significant determinant of BMC. This illustrates the dependence of osteopenia in S on GH, the maximizing effect of X for epiphyseal growth and the major role of Pi metabolism on BMC in weight bearing bone during growth.

Safety Committees for Argentinean Research Reactor - Regulatory Issues

International Nuclear Information System (INIS)

Perrin, Carlos D.

2009-01-01

In the field of radiological and nuclear safety, the Nuclear Regulatory Authority (ARN) of Argentina controls three research reactors and three critical assemblies, by means of evaluations, audits and inspections, in order to ensure the fulfillment of the requirements established in the Licenses, in the Regulatory Standards and in the Mandatory Documentation in general. From the Nuclear Regulatory Authority's point of view, within the general process of research reactors safety management, the Operational Organization self verification of radiological and nuclear safety plays an outstanding role. In this aspect the ARN has established specific requirements in the Regulatory Standards, in the Operation Licenses and in the Operational Limits and Conditions. These requirements include the figure of different safety committees, which act as reviewers or advisers in diverse situations. This paper describes the main characteristics of the committees, their function, scope and the regulatory documents where the requirements are included. (author)

Regulatory control of nuclear power plants

International Nuclear Information System (INIS)

2002-01-01

The purpose of this book is to support IAEA training courses and workshops in the field of regulatory control of nuclear power plants as well as to support the regulatory bodies of Member States in their own training activities. The target group is the professional staff members of nuclear safety regulatory bodies supervising nuclear power plants and having duties and responsibilities in the following regulatory fields: regulatory framework; regulatory organization; regulatory guidance; licensing and licensing documents; assessment of safety; and regulatory inspection and enforcement. Important topics such as regulatory competence and quality of regulatory work as well as emergency preparedness and public communication are also covered. The book also presents the key issues of nuclear safety such as 'defence-in-depth' and safety culture and explains how these should be taken into account in regulatory work, e.g. during safety assessment and regulatory inspection. The book also reflects how nuclear safety has been developed during the years on the basis of operating experience feedback and results of safety research by giving topical examples. The examples cover development of operating procedures and accident management to cope with complicated incidents and severe accidents to stress the importance of regulatory role in nuclear safety research. The main target group is new staff members of regulatory bodies, but the book also offers good examples for more experienced inspectors to be used as comparison and discussion basis in internal workshops organized by the regulatory bodies for refreshing and continuing training. The book was originally compiled on the basis of presentations provided during the two regulatory control training courses in 1997 and 1998. The textbook was reviewed at the beginning of the years 2000 and 2002 by IAEA staff members and consistency with the latest revisions of safety standards have been ensured. The textbook was completed in the

Strengthening Regulatory Competence in Pakistan

International Nuclear Information System (INIS)

Sadiq, M.

2016-01-01

Capacity building of Pakistan Nuclear Regulatory Authority is considered an essential element in pursuit of its vision to become a world class regulatory body. Since its inception in 2001, PNRA has continuously endeavoured to invest in its people, develop training infrastructure and impart sound knowledge and professional skills with the aim to improve its regulatory effectiveness. The use of nuclear and radioactive material in Pakistan has increased manifold in recent years, thus induction of more manpower was needed for regulatory oversight. PNRA adopted two pronged approach for meeting the manpower demand (a) employment of university graduates through fast track recruitment drive and (b) induction of graduates by offering fellowships for Master degree programs. Although, the newly employed staff was selected on the basis of their excellent academic qualifications in basic and applied sciences, but they required rigorous knowledge and skills in regulatory perspectives. In order to implement a structured training program, PNRA conducted Training Needs Assessment (TNA) and identified competency gaps of the regulatory staff in legal, technical, regulatory practice and behavioural domains. PNRA took several initiatives for capacity building which included establishment of a training centre for sustainability of trainings, initiation of a fellowship scheme for Master program, attachment of staff at local institutes for on-the-job training and placement at foreign regulatory bodies and organizations for technical development with the assistance of IAEA. The above strategies have been very beneficial in competence building of the PNRA staff to perform all regulatory activities indigenously for nuclear power plants, research reactors and radiation facilities. Provision of vibrant technical support to IAEA and Member States in various programs by PNRA is a landmark of these competence development efforts. This paper summarizes PNRA initiatives and the International Atomic

Regulatory governance of telecommunications liberalisation in Taiwan

International Nuclear Information System (INIS)

Cheng, Kuo-Tai; Hebenton, Bill

2008-01-01

This paper examines the changing role of government and market in regulating the telecommunications sector from since 1996 in Taiwan. It contextualises the theoretical aspects of regulatory governance for institutional design and practices, and reviews the concepts and mechanisms for appraising privatisation and regulatory systems. Using a conceptual framework for researching privatisation and regulation, it describes the process and issues pertinent to telecommunications liberalisation and privatisation in Taiwan, supported by a brief presentation of theoretical points of view as well as practitioners' views. The paper presents results concerning criteria for appraising privatisation and regulatory governance and considers policy lessons that can be learned from the experiences of the Taiwanese telecommunications sector's liberalisation. (author)

Regulatory governance of telecommunications liberalisation in Taiwan

Energy Technology Data Exchange (ETDEWEB)

Cheng, Kuo-Tai [Department of Regional Studies in Humanity and Social Sciences, National Hsin-Chu University of Education, No. 521 Nan-Da Road, Hsin-Chu 300 (China); Hebenton, Bill [School of Law, University of Manchester, M13 9PP (United Kingdom)

2008-12-15

This paper examines the changing role of government and market in regulating the telecommunications sector from since 1996 in Taiwan. It contextualises the theoretical aspects of regulatory governance for institutional design and practices, and reviews the concepts and mechanisms for appraising privatisation and regulatory systems. Using a conceptual framework for researching privatisation and regulation, it describes the process and issues pertinent to telecommunications liberalisation and privatisation in Taiwan, supported by a brief presentation of theoretical points of view as well as practitioners' views. The paper presents results concerning criteria for appraising privatisation and regulatory governance and considers policy lessons that can be learned from the experiences of the Taiwanese telecommunications sector's liberalisation. (author)

The role of L-type calcium channels in the vascular effect of Trigonella foenum-graecum L. in diabetic rats

Directory of Open Access Journals (Sweden)

Mehrdad Roghani

2006-03-01

Full Text Available Some ion channels like voltage-operated calcium channels (VOCC within the plasma membrane of vascular muscle cells from the walls of resistance arteries and arterioles play a central role in the regulation of vascular tone. On the basis of reports about the beneficial attenuating effect of fenugreek (Trigonella foenum-graecum L.; TFG on the contractile reactivity of aortic rings of diabetic rats, this study was carried out to evaluate the possible involvement of L-type voltage-operated calcium channels in the vascular effect of this medicinal plant. For this purpose, male Wistar rats were made diabetic using streptozotocin (STZ, 60 mg/Kg, i.p. The extract-treated control and diabetic rats received aqueous leaf extract of TFG (200 mg/Kg, i.p. every other day for two months. At the end of the study, contractile response of isolated aortic rings to KCl and noreadrenaline (NA was determined in the absence and presence of the calcium channel blocker nifedipine. The results showed that aortic rings from diabetic rats are more responsive to the effect of KCl and NA than those of controls, TFG extract treatment could attenuate the enhanced contractile response of aortic rings of diabetic rats, and nifedipine pretreatment could partially neutralize the beneficial effect of this extract. It is concluded that TFG extract attenuates the enhanced vascular reactivity in chronic diabetic rats and voltage-operated calcium channels are in part responsible for this effect of TFG extract.

The role of trigeminal nucleus caudalis orexin 1 receptors in orofacial pain transmission and in orofacial pain-induced learning and memory impairment in rats.

Science.gov (United States)

Kooshki, Razieh; Abbasnejad, Mehdi; Esmaeili-Mahani, Saeed; Raoof, Maryam

2016-04-01

It is widely accepted that the spinal trigeminal nuclear complex, especially the subnucleus caudalis (Vc), receives input from orofacial structures. The neuropeptides orexin-A and -B are expressed in multiple neuronal systems. Orexin signaling has been implicated in pain-modulating system as well as learning and memory processes. Orexin 1 receptor (OX1R) has been reported in trigeminal nucleus caudalis. However, its roles in trigeminal pain modulation have not been elucidated so far. This study was designed to investigate the role of Vc OX1R in the modulation of orofacial pain as well as pain-induced learning and memory deficits. Orofacial pain was induced by subcutaneous injection of capsaicin in the right upper lip of the rats. OX1R agonist (orexin-A) and antagonist (SB-334867-A) were microinjected into Vc prior capsaicin administration. After recording nociceptive times, learning and memory was investigated using Morris water maze (MWM) test. The results indicated that, orexin-A (150 pM/rat) significantly reduced the nociceptive times, while SB334867-A (80 nM/rat) exaggerated nociceptive behavior in response to capsaicin injection. In MWM test, capsaicin-treated rats showed a significant learning and memory impairment. Moreover, SB-334867-A (80 nM/rat) significantly exaggerated learning and memory impairment in capsaicin-treated rats. However, administration of orexin-A (100 pM/rat) prevented learning and memory deficits. Taken together, these results indicate that Vc OX1R was at least in part involved in orofacial pain transmission and orexin-A has also a beneficial inhibitory effect on orofacial pain-induced deficits in abilities of spatial learning and memory. Copyright © 2016 Elsevier Inc. All rights reserved.

Regulation of renal Na+-K-ATPase in the rat: role of increased potassium transport

International Nuclear Information System (INIS)

Mujais, S.K.; Chekal, M.A.; Hayslett, J.P.; Katz, A.I.

1986-01-01

The purpose of this study was to characterize the alterations in collecting tubule Na + -K + -ATPase activity produced by sustained increments in dietary potassium in the rat and to evaluate the role of aldosterone in their generation. In adrenal-intact animals, feeding a high-potassium diet or administration of a high physiological dose of aldosterone, which simulates the delivery rate of this hormone during potassium loading, caused marked increments in Na + -K + -ATPase activity in the cortical collecting tubule (CCT) but had no effect on the enzyme in the inner stripe of the medullary collecting tubule (MCT). A significant increase in enzyme activity was also observed after smaller dietary potassium increments and after 4 days of dietary potassium load. In adrenalectomized rats provided with physiological replacement doses of corticosterone and aldosterone, Na + -K + -ATPase activity in both CCT and MCT was similar to that of adrenal-intact controls but remained unchanged after 7 days on the potassium-enriched (10-fold) diet. In contrast, adrenalectomized animals receiving the high physiological dose of aldosterone displayed an increase in Na + -K + -ATPase activity of CCT comparable with that of adrenal-intact animals, whereas the enzyme activity in the MCT was unaffected. In conclusion, 1) following chronic potassium loading Na + -K + -ATPase activity increases significantly in the CCT with no change in its activity in the inner stripe of the MCT; 2) this increase in enzyme activity occurs in a time-dependent fashion and in proportion to the potassium load; and 3) the stimulation of Na + -K + -ATPase activity in adrenal-replaced rats is facilitated by augmented levels of aldosterone, such as those actually observed in adrenal-intact rats subjected to chronic potassium loading

Regulation of renal Na -K-ATPase in the rat: role of increased potassium transport

Energy Technology Data Exchange (ETDEWEB)

Mujais, S.K.; Chekal, M.A.; Hayslett, J.P.; Katz, A.I.

1986-08-01

The purpose of this study was to characterize the alterations in collecting tubule Na -K -ATPase activity produced by sustained increments in dietary potassium in the rat and to evaluate the role of aldosterone in their generation. In adrenal-intact animals, feeding a high-potassium diet or administration of a high physiological dose of aldosterone, which simulates the delivery rate of this hormone during potassium loading, caused marked increments in Na -K -ATPase activity in the cortical collecting tubule (CCT) but had no effect on the enzyme in the inner stripe of the medullary collecting tubule (MCT). A significant increase in enzyme activity was also observed after smaller dietary potassium increments and after 4 days of dietary potassium load. In adrenalectomized rats provided with physiological replacement doses of corticosterone and aldosterone, Na -K -ATPase activity in both CCT and MCT was similar to that of adrenal-intact controls but remained unchanged after 7 days on the potassium-enriched (10-fold) diet. In contrast, adrenalectomized animals receiving the high physiological dose of aldosterone displayed an increase in Na -K -ATPase activity of CCT comparable with that of adrenal-intact animals, whereas the enzyme activity in the MCT was unaffected. In conclusion, 1) following chronic potassium loading Na -K -ATPase activity increases significantly in the CCT with no change in its activity in the inner stripe of the MCT; 2) this increase in enzyme activity occurs in a time-dependent fashion and in proportion to the potassium load; and 3) the stimulation of Na -K -ATPase activity in adrenal-replaced rats is facilitated by augmented levels of aldosterone, such as those actually observed in adrenal-intact rats subjected to chronic potassium loading.

Aberrant rhythmic expression of cryptochrome2 regulates the radiosensitivity of rat gliomas.

Science.gov (United States)

Fan, Wang; Caiyan, Li; Ling, Zhu; Jiayun, Zhao

2017-09-29

In this study, we investigated the role of the clock regulatory protein cryptochrome 2 (Cry2) in determining the radiosensitivity of C6 glioma cells in a rat model. We observed that Cry2 mRNA and protein levels showed aberrant rhythmic periodicity of 8 h in glioma tissues, compared to 24 h in normal brain tissue. Cry2 mRNA and protein levels did not respond to irradiation in normal tissues, but both were increased at the ZT4 (low Cry2) and ZT8 (high Cry2) time points in gliomas. Immunohistochemical staining of PCNA and TUNEL assays demonstrated that high Cry2 expression in glioma tissues was associated with increased cell proliferation and decreased apoptosis. Western blot analysis showed that glioma cell fate was independent of p53, but was probably dependent on p73, which was more highly expressed at ZT4 (low Cry2) than at ZT8 (high Cry2). Levels of both p53 and p73 were unaffected by irradiation in normal brain tissues. These findings suggest aberrant rhythmic expression of Cry2 influence on radiosensitivity in rat gliomas.

Modernizing the Regulatory System for Biotechnology Products

Science.gov (United States)

This Web page describes the continuing effort to modernize the federal regulatory system for biotechnology products as well as clarify various roles of EPA, FDA and USDA in evaluating new biotechnology products.

Take it of leave it : Mechanisms underlying bacterial bistable regulatory networks

NARCIS (Netherlands)

Siebring, Jeroen; Sorg, Robin; Herber, Martijn; Kuipers, Oscar; Filloux, Alain A.M.

2012-01-01

Bistable switches occur in regulatory networks that can exist in two distinct stable states. Such networks allow distinct switching of individual cells. In bacteria these switches coexist with regulatory networks that respond gradually to environmental input. Bistable switches play key roles in high

The role of dopamine in the nucleus accumbens and striatum during sexual behavior in the female rat.

Science.gov (United States)

Becker, J B; Rudick, C N; Jenkins, W J

2001-05-01

Dopamine in dialysate from the nucleus accumbens (NAcc) increases during sexual and feeding behavior and after administration of drugs of abuse, even those that do not directly activate dopaminergic systems (e.g., morphine or nicotine). These findings and others have led to hypotheses that propose that dopamine is rewarding, predicts that reinforcement will occur, or attributes incentive salience. Examining increases in dopamine in NAcc or striatum during sexual behavior in female rats provides a unique situation to study these relations. This is because, for the female rat, sexual behavior is associated with an increase in NAcc dopamine and conditioned place preference only under certain testing conditions. This experiment was conducted to determine what factors are important for the increase in dopamine in dialysate from NAcc and striatum during sexual behavior in female rats. The factors considered were the number of contacts by the male, the timing of contacts by the male, or the ability of the female to control contacts by the male. The results indicate that increased NAcc dopamine is dependent on the timing of copulatory stimuli, independent of whether the female rat is actively engaged in regulating this timing. For the striatum, the timing of copulatory behavior influences the magnitude of the increase in dopamine in dialysate, but other factors are also involved. We conclude that increased extracellular dopamine in the NAcc and striatum conveys qualitative or interpretive information about the rewarding value of stimuli. Sexual behavior in the female rat is proposed as a model to determine the role of dopamine in motivated behavior.

Activity of cAMP-dependent protein kinases and cAMP-binding proteins of rat kidney cytosol during dehydration

International Nuclear Information System (INIS)

Zelenina, M.N.; Solenov, E.I.; Ivanova, L.N.

1985-01-01

The activity of cAMP-dependent protein kinases, the binding of cAMP, and the spectrum of cAMP-binding proteins in the cytosol of the renal papilla was studied in intact rats and in rats after 24 h on a water-deprived diet. It was found that the activation of protein kinases by 10 -6 M cAMP is significantly higher in the experimental animals than in the intact animals. In chromatography on DEAE-cellulose, the positions of the peaks of specific reception of cAMP corresponded to the peaks of the regulatory subunits of cAMP-dependent protein kinases of types I and II. In this case, in intact animals more than 80% of the binding activity was detected in peaks II, whereas in rats subjected to water deprivation, more than 60% of the binding was observed in peak I. The general regulatory activity of the cytosol was unchanged in the experimental animals in comparison with intact animals. It is suggested that during dehydration there is an induction of the synthesis of the regulatory subunit of type I cAMP-dependent protein kinase in the renal papilla

Phosphorylation of CaMKII in the rat dorsal raphe nucleus plays an important role in sleep-wake regulation.

Science.gov (United States)

Cui, Su-Ying; Li, Sheng-Jie; Cui, Xiang-Yu; Zhang, Xue-Qiong; Yu, Bin; Sheng, Zhao-Fu; Huang, Yuan-Li; Cao, Qing; Xu, Ya-Ping; Lin, Zhi-Ge; Yang, Guang; Song, Jin-Zhi; Ding, Hui; Wang, Zi-Jun; Zhang, Yong-He

2016-02-01

The Ca(2+) modulation in the dorsal raphe nucleus (DRN) plays an important role in sleep-wake regulation. Calmodulin-dependent kinase II (CaMKII) is an important signal-transducing molecule that is activated by Ca(2+) . This study investigated the effects of intracellular Ca(2+) /CaMKII signaling in the DRN on sleep-wake states in rats. Maximum and minimum CaMKII phosphorylation was detected at Zeitgeber time 21 (ZT 21; wakefulness state) and ZT 3 (sleep state), respectively, across the light-dark rhythm in the DRN in rats. Six-hour sleep deprivation significantly reduced CaMKII phosphorylation in the DRN. Microinjection of the CAMKII activation inhibitor KN-93 (5 or 10 nmol) into the DRN suppressed wakefulness and enhanced rapid-eye-movement sleep (REMS) and non-REM sleep (NREMS). Application of a high dose of KN-93 (10 nmol) increased slow-wave sleep (SWS) time, SWS bouts, the mean duration of SWS, the percentage of SWS relative to total sleep, and delta power density during NREMS. Microinjection of CaCl2 (50 nmol) in the DRN increased CaMKII phosphorylation and decreased NREMS, SWS, and REMS. KN-93 abolished the inhibitory effects of CaCl2 on NREMS, SWS, and REMS. These data indicate a novel wake-promoting and sleep-suppressing role for the Ca(2+) /CaMKII signaling pathway in DRN neurons. We propose that the intracellular Ca(2+) /CaMKII signaling in the dorsal raphe nucleus (DRN) plays wake-promoting and sleep-suppressing role in rats. Intra-DRN application of KN-93 (CaMKII activation inhibitor) suppressed wakefulness and enhanced rapid-eye-movement sleep (REMS) and non-REMS (NREMS). Intra-DRN application of CaCl2 attenuated REMS and NREMS. We think these findings should provide a novel cellular and molecular mechanism of sleep-wake regulation. © 2015 International Society for Neurochemistry.

Differential effects of B7-1 blockade in the rat experimental autoimmune encephalomyelitis model

DEFF Research Database (Denmark)

Gallon, L; Chandraker, A; Issazadeh-Navikas, Shohreh

1997-01-01

that CD28-B7 blockade by systemic administration of CTLA4Ig prevents actively induced EAE. Since CTLA4Ig binds to both B7-1 and B7-2, we used a mutant form of CTLA4Ig (CTLA4IgY100F) that binds only B7-1, to study the role of B7-1 blockade in this model. Such a reagent avoids the potential of signaling...... treated with systemic CTLA4gY100F did not. More importantly, systemic administration of CTLA4IgY100F abrogated the protective effect of ex vivo treated APCs. These data suggest an important regulatory role for B7-1, perhaps through binding to CTLA4, in this model of EAE. Understanding the role......Blocking the CD28-B7 T cell costimulatory activation pathway protects animals from developing experimental autoimmune encephalomyelitis (EAE). In the mouse EAE model, selective blockade of B7-1 by specific mAbs has been shown to protect animals from EAE. In the Lewis rat model, we have shown...

Hormesis in Regulatory risk assessment - Science and Science Policy.

Science.gov (United States)

Gray, George

2011-01-01

This brief commentary will argue that whether hormesis is considered in regulatory risk assessment is a matter less of science than of science policy. I will first discuss the distinction between science and science policy and their roles in regulatory risk assessment. Then I will focus on factors that influence science policy, especially as it relates to the conduct of risk assessments to inform regulatory decisions, with a focus on the U.S. Environmental Protection Agency (EPA). The key questions will then be how does hormesis interact with current concepts of science and science policy for risk assessment? Finally, I look ahead to factors that may increase, or decrease, the likelihood of hormesis being incorporated into regulatory risk assessment.

Sex differences in the enhanced responsiveness to acute angiotensin II in growth-restricted rats: role of fasudil, a Rho kinase inhibitor.

Science.gov (United States)

Ojeda, Norma B; Royals, Thomas P; Alexander, Barbara T

2013-04-01

This study tested the hypothesis that Rho kinase contributes to the enhanced pressor response to acute angiotensin II in intact male growth-restricted and gonadectomized female growth-restricted rats. Mean arterial pressure (MAP) and renal function were determined in conscious animals pretreated with enalapril (250 mg/l in drinking water) for 1 wk to block the endogenous renin-angiotensin system and normalize blood pressure (baseline). Blood pressure and renal hemodynamics did not differ at baseline. Acute Ang II (100 ng·kg(-1)·min(-1)) induced a greater increase in MAP and renal vascular resistance and enhanced reduction in glomerular filtration rate in intact male growth-restricted rats compared with intact male controls (P back to baseline in male growth-restricted rats, and yet glomerular filtration rate remained significantly reduced (P < 0.05). Thus, these data suggest a role for enhanced renal sensitivity to acute Ang II in the developmental programming of hypertension in male growth-restricted rats. However, inhibition of Rho kinase had no effect on the basal or enhanced increase in blood pressure induced by acute Ang II in the gonadectomized female growth-restricted rat. Therefore, these studies suggest that Rho kinase inhibition exerts a sex-specific effect on blood pressure sensitivity to acute Ang II in growth-restricted rats.

A Role for Matrix Metalloproteinases in Nicotine-Induced Conditioned Place Preference and Relapse in Adolescent Female Rats

Directory of Open Access Journals (Sweden)

Reka Natarajan

2013-01-01

Full Text Available Reconfiguration of extracellular matrix proteins appears to be necessary for the synaptic plasticity that underlies memory consolidation. The primary candidates involved in controlling this process are a family of endopeptidases called matrix metalloproteinases (MMPs; however, the potential role of MMPs in nicotine addiction-related memories has not been adequately tested. Present results indicate transient changes in hippocampal MMP-2, -3, and -9 expression following context dependent learning of nicotine-induced conditioned place preference (CPP. Members of a CPP procedural control group also indicated similar MMP changes, suggesting that memory activation occurred in these animals as well. However, hippocampal MMP-9 expression was differentially elevated in members of the nicotine-induced CPP group on days 4 and 5 of training. Inhibition of MMPs using a broad spectrum MMP inhibitor (FN439 during nicotine-induced CPP training blocked the acquisition of CPP. Elevations in hippocampal and prefrontal cortex MMP-3 expression—but not MMP-2 and -9—accompanied reactivation of a previously learned drug related memory. Decreases in the actin regulatory cytoskeletal protein cortactin were measured in the HIP and PFC during the initial two days of acquisition of CPP; however, no changes were seen following re-exposure to the drug related environment. These results suggest that MMP-9 may be involved in facilitating the intracellular and extracellular events required for the synaptic plasticity underlying the acquisition of nicotine-induced CPP. Furthermore, MMP-3 appears to be important during re-exposure to the drug associated environment. However, rats introduced into the CPP apparatus and given injections of vehicle rather than nicotine during training also revealed a pattern of MMP expression similar to nicotine-induced CPP animals.

Role of Carnosine and Melatonin in Ameliorating Cardiotoxicity of Titanium Dioxide Nanoparticles in the Rats

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Nouf Al-Rasheed

2015-08-01

Full Text Available The aim of this work was to study the possible cardiotoxicity of two different doses of 50 nm nano titanium dioxide (n-TiO2 and the possible modulating effects of the use of two natural antioxidants carnosine and melatonin. The results showed that TiO2- NPs produced deleterious effects on rat cardiac tissue as confirmed by the increased levels of serum myoglobin, troponin-T and CK-MB. Increased levels of serum Inflammatory markers represented by the tumor necrosis factor alpha (TNF-α and Interleukin-6 (IL-6 was also noticed. Caspase3 and IGg were elevated compared to the control group in a dose dependant manner. treatment of the rats with Carnosine or melatonin. along with TiO2- NPs administration significantly improved most of the elevated biochemical markers. It was concluded that the use of Carnosine or melatonin could play a beneficial role against deleterious effects of TiO2- NPs

Antiapoptotic and neuroprotective role of Curcumin in Pentylenetetrazole (PTZ) induced kindling model in rat.

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Saha, Lekha; Chakrabarti, Amitava; Kumari, Sweta; Bhatia, Alka; Banerjee, Dibyojyoti

2016-02-01

Kindling, a sub threshold chemical or electrical stimulation, increases seizure duration and enhances accompanied behavior until it reaches a sort of equilibrium state. The present study aimed to explore the effect of curcumin on the development of kindling in PTZ kindled rats and its role in apoptosis and neuronal damage. In a PTZ kindled Wistar rat model, different doses of curcumin (100, 200 and 300 mg/kg) were administrated orally one hour before the PTZ injections on alternate day during the whole kindling days. The following parameters were compared between control and experimental groups: the course of kindling, stages of seizures, Histopathological scoring of hippocampus, antioxidant parameters in the hippocampus, DNA fragmentation and caspase-3 expression in hippocampus, and neuron-specific enolase in the blood. One way ANOVA followed by Bonferroni post hoc analysis and Fischer's Exact test were used for statistical analyses. PTZ, 30 mg/kg, induced kindling in rats after 32.0 ± 1.4 days. Curcumin showed dose-dependent anti-seizure effect. Curcumin (300 mg/kg) significantly increased the latency to myoclonic jerks, clonic seizures as well as generalized tonic-clonic seizures, improved the seizure score and decreased the number of myoclonic jerks. PTZ kindling induced a significant neuronal injury, oxidative stress and apoptosis which were reversed by pretreatment with curcumin in a dose-dependent manner. Our study suggests that curcumin has a potential antiepileptogenic effect on kindling-induced epileptogenesis.

As to achieve regulatory action, regulatory approaches

International Nuclear Information System (INIS)

Cid, R.; Encinas, D.

2014-01-01

The achievement of the effectiveness in the performance of a nuclear regulatory body has been a permanent challenge in the recent history of nuclear regulation. In the post-Fukushima era this challenge is even more important. This article addresses the subject from two complementary points of view: the characteristics of an effective regulatory body and the regulatory approaches. This work is based on the most recent studies carried out by the Committee on Nuclear Regulatory Activities, CNRA (OECD/NEA), as well as on the experience of the Consejo de Seguridad Nuclear, CSN, the Spanish regulatory body. Rafael Cid is the representative of CSN in these project: Diego Encinas has participated in the study on regulatory approaches. (Author)

The Role of the Two-Pore Domain Potassium Channel TREK-1 in the Therapeutic Effects of Escitalopram in a Rat Model of Poststroke Depression.

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Lin, Dai-Hua; Zhang, Xiang-Rong; Ye, Dong-Qing; Xi, Guang-Jun; Hui, Jiao-Jie; Liu, Shan-Shan; Li, Lin-Jiang; Zhang, Zhi-Jun

2015-06-01

Poststroke depression (PSD) is one of the most common neuropsychiatric complications after stroke. TREK-1, a two-pore-domain potassium channel, has been implicated in the pathogenesis of stroke and depression. The aim of this study was to investigate whether TREK-1 plays a role in the therapeutic effects of the selective serotonin reuptake inhibitor (SSRI) escitalopram in a rat PSD model. The whole-cell patch-clamp technique was performed to assess the effect of escitalopram on recombinant TREK-1 currents in HEK293 cells. The expression of TREK-1 mRNA and protein was measured in the hippocampus and prefrontal cortex (PFC), and neural stem cell (NSC) proliferation was detected in the hippocampal dentate gyrus (DG) in PSD rats after 3 weeks of escitalopram administration. Escitalopram reversibly inhibited TREK-1 currents in a concentration-dependent manner. Chronic treatment with escitalopram significantly reversed the reductions in weight gain, locomotor activity, and sucrose preference in PSD rats. The expressions of TREK-1 mRNA and protein were significantly increased in hippocampal CA1, CA3, DG, and PFC in PSD rats, with the exception of TREK-1 mRNA in hippocampal CA1. NSC proliferation was significantly decreased in hippocampal DG of PSD rats. Escitalopram significantly reversed the regional increases of TREK-1 expression and the reduction of hippocampal NSC proliferation in PSD rats. TREK-1 plays an important role in the therapeutic effects of the SSRI escitalopram in PSD model, making TREK-1 an attractive candidate molecule for further understanding the pathophysiology and treatment of PSD. © 2015 John Wiley & Sons Ltd.

The role of the US regulatory process in public acceptance of nuclear power

International Nuclear Information System (INIS)

Rowden, M.A.

1977-01-01

This paper focuses, on NRC's regulatory responsibilities in relation to public acceptance of nuclear power. Since public attitudes in the United States may influence reaction to nuclear power in other nations, it is fair to say that the credibility of our regulatory program has international significance. Stated simply, unless the public is convinced that the regulatory process is effective in assuring safety, safeguarding nuclear facilities and materials, and protecting the environment, the use of nuclear power could be curtailed or even brought to a halt. Not only must the regulatory process be effective, it must at the same time be recognized by the public as being effective. Opinion polls in the United States have shown consistently that a majority of Americans believe it is important to develop nuclear power to help meet our future energy needs. The direction of public concern has shifted from year to year. Most recently, public apprehension has been expressed about the potential hazards of long-term storage of the high-level wastes from spent fuel reprocessing, and about the risks that nuclear materials and facilities may be subject to theft or diversion or sabotage. Uppermost in the public mind is the question whether the regulatory process can cope with these potential threats to public health and safety. The licensing process of the NRC is conducted in full public view. Issues of a generic nature are aired in rulemaking hearings, while each proposal to construct and operate a nuclear power plant or a facility such as fuel reprocessing plant is the subject of public hearings, which are held near the site of the proposed plant. During the last two years, we have noted that some persons who object to nuclear power plants have indicated that they believe that decisions to permit construction of such plants should be made at the State government level, rather than by a Federal agency. As a result, there now are movements to enact State laws and to set up State

The role of hypothalamus tuberomammillary nucleus on the regulation of respiratory movement of rats with asthma

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Chen CHEN

2016-01-01

Full Text Available Objective 　To explore the role of central histaminergic neurons in the tuberomammillary nucleus (TMN of posterior hypothalamus on asthma. Methods 　Seventy-two healthy male SD rats were served as study objects. Sixty-four rats were sensitized with ovalbumin (OA solution intraperitoneally and challenged with OA aerosol inhalation to prepare asthma model. Asthma attack was evoked in asthmatic rats by OA solution injected intravenously, the electrical activities of TMN in posterior hypothalamus were recorded with biological signal collecting system and the power spectra were analyzed. TMN was lesioned or stimulated electrically by central stereo positioning technology. Histamine H3 receptor agonist R-(α-methylhistamine (RMHA or antagonist thioperamide (THIO was microinjected into TMN by central nuclear group microinjection technology, and the pulmonary function indexes were detected including diaphragm electromyography (EMGdi frequency, EMGdi integral, minute ventilation volume (MVV, expiratory time/inspiratory time (TE/TI, airway resistance (Raw and dynamic pulmonary compliance (Cdyn. Results 　Compared with control group, the percentage of α, β1 and β2 wave in the electrical activities of TMN of asthmatic rats increased significantly, while the percentage of δ and θ wave decreased and the total discharge power increased. Compared with the corresponding control group, electric lesion of TMN or TMN microinjected with histamine H3 receptor antagonist increased EMGdi frequency, TE/TI, Raw, and decreased EMGdi integral, MVV and Cdyn. Compared with the corresponding control group, electric stimulation of TMN or TMN microinjected with histamine H3 receptor agonist decreased EMGdi frequency, TE/TI, Raw, and increased EMGdi integral, MVV and Cdyn. Conclusion 　Central histaminergic neurons in tuberomammillary nucleus of posterior hypothalamus are activated in asthmatic rats. DOI: 10.11855/j.issn.0577-7402.2015.12.09

Role of spared pathways in locomotor recovery after body-weight-supported treadmill training in contused rats.

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Singh, Anita; Balasubramanian, Sriram; Murray, Marion; Lemay, Michel; Houle, John

2011-12-01

Body-weight-supported treadmill training (BWSTT)-related locomotor recovery has been shown in spinalized animals. Only a few animal studies have demonstrated locomotor recovery after BWSTT in an incomplete spinal cord injury (SCI) model, such as contusion injury. The contribution of spared descending pathways after BWSTT to behavioral recovery is unclear. Our goal was to evaluate locomotor recovery in contused rats after BWSTT, and to study the role of spared pathways in spinal plasticity after BWSTT. Forty-eight rats received a contusion, a transection, or a contusion followed at 9 weeks by a second transection injury. Half of the animals in the three injury groups were given BWSTT for up to 8 weeks. Kinematics and the Basso-Beattie-Bresnahan (BBB) test assessed behavioral improvements. Changes in Hoffmann-reflex (H-reflex) rate depression property, soleus muscle mass, and sprouting of primary afferent fibers were also evaluated. BWSTT-contused animals showed accelerated locomotor recovery, improved H-reflex properties, reduced muscle atrophy, and decreased sprouting of small caliber afferent fibers. BBB scores were not improved by BWSTT. Untrained contused rats that received a transection exhibited a decrease in kinematic parameters immediately after the transection; in contrast, trained contused rats did not show an immediate decrease in kinematic parameters after transection. This suggests that BWSTT with spared descending pathways leads to neuroplasticity at the lumbar spinal level that is capable of maintaining locomotor activity. Discontinuing training after the transection in the trained contused rats abolished the improved kinematics within 2 weeks and led to a reversal of the improved H-reflex response, increased muscle atrophy, and an increase in primary afferent fiber sprouting. Thus continued training may be required for maintenance of the recovery. Transected animals had no effect of BWSTT, indicating that in the absence of spared pathways this

Building Nuclear Safety and Security Culture Within Regulatory Body

International Nuclear Information System (INIS)

Huda, K.

2016-01-01

To achieve a higher level of nuclear safety and security, it needs to develop the safety and security culture not only in the facility but also in the regulatory body. The regulatory body, especially needs to develop the safety and security culture within the organization, because it has a function to promote and oversee the culture in the facilities. In this sense, the regulatory body should become a role model. Development of the nuclear safety and security culture should be started by properly understanding its concept and awakening the awareness of individual and organization on the importance of nuclear safety and security. For effectiveness of the culture development in the regulatory body, the following steps are suggested to be taken: setting up of the regulatory requirements, self-assessment, independent assessment review, communication with the licensee, oversight of management system implementation, and integration with regulatory activities. The paper discusses those steps in the framework of development of nuclear safety and security culture in the regulatory body, as well as some important elements in building of the culture in the nuclear facilities. (author)

Characterization of noncoding regulatory DNA in the human genome.

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Elkon, Ran; Agami, Reuven

2017-08-08

Genetic variants associated with common diseases are usually located in noncoding parts of the human genome. Delineation of the full repertoire of functional noncoding elements, together with efficient methods for probing their biological roles, is therefore of crucial importance. Over the past decade, DNA accessibility and various epigenetic modifications have been associated with regulatory functions. Mapping these features across the genome has enabled researchers to begin to document the full complement of putative regulatory elements. High-throughput reporter assays to probe the functions of regulatory regions have also been developed but these methods separate putative regulatory elements from the chromosome so that any effects of chromatin context and long-range regulatory interactions are lost. Definitive assignment of function(s) to putative cis-regulatory elements requires perturbation of these elements. Genome-editing technologies are now transforming our ability to perturb regulatory elements across entire genomes. Interpretation of high-throughput genetic screens that incorporate genome editors might enable the construction of an unbiased map of functional noncoding elements in the human genome.

Role of Mas receptor in renal blood flow response to angiotensin-(1-7) in ovariectomized estradiol treated rats.

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Saberi, Shadan; Dehghani, Aghdas; Nematbakhsh, Mehdi

2016-01-01

The angiotensin 1-7 (Ang 1-7), is abundantly produced in kidneys and antagonizes the function of angiotensin II through Mas receptor (MasR) or other unknown mechanisms. In the current study, the role of MasR and steroid hormone estrogen on renal blood flow response to Ang 1-7 administration was investigated in ovariectomized (OV) female rats. OV female Wistar-rats received estradiol (500 μg/kg/week) or vehicle for two weeks. In the day of the experiment, the animals were anesthetized, cannulated, and the responses including mean arterial pressure, renal blood flow (RBF), and renal vascular resistance at the constant level of renal perfusion pressure to graded infusion of Ang 1-7 at 0, 100 and 300 ng/kg/min were determined in OV and OV estradiol-treated (OVE) rats, treated with vehicle or MasR antagonist; A779. RBF response to Ang 1-7 infusion increased dose-dependently in vehicle (Pdose <0.001) and A779-treated (Pdose <0.01) animals. However, when MasR was blocked, the RBF response to Ang 1-7 significantly increased in OV animals compared with OVE rats (P<0.05). When estradiol was limited by ovariectomy, A779 increased RBF response to Ang 1-7 administration, while this response was attenuated in OVE animals.

Abatement by Naringenin of Doxorubicin-Induced Cardiac Toxicity in Rats

International Nuclear Information System (INIS)

Arafa, H.M.; Abd-Ellah, M.F.; Hafez, H.F.

2005-01-01

Doxorubicin is one of the most active cytotoxic agents in current use. It has proven efficacy in various malignancies either alone or combined with other cytocidal agents. The clinical usefulness of the anthracycline drug has been precluded by cardiac toxicity. Many therapeutic interventions have been attempted to improve the therapeutic benefits of the drug. Few, however, have been efficacious in this setting. Purpose: We have addressed in the current study the possible protective effects of naringenin, a flavonoid known to have anti-oxidant properties, on doxorubicin induced cardiac toxicity in male Swiss albino rats. Methods: Forty male Swiss albino rats were used in this study. Naringenin (25 mg/kg body weight) was administered daily by gavage for 7 consecutive days before a cumulative single dose of doxorubicin (15 mg/kg body weight, ip). Doxorubicin induced marked biochemical alterations characteristic of cardiac toxicity including, elevated activities of serum total lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), enhanced lipid peroxidation measured as malonaldehyde (MDA). The anthracycline drug has also reduced the cardiac enzymatic activities of superoxide dismutase (SOD), glutathione-Stransferase (GST) and catalase (CAT). Besides, it reduced significantly the reduced glutathione (GSH) level, but it increased the total NO content in heart tissue. Prior administration of naringenin ahead of doxorubicin challenge ameliorated all these biochemical markers. Taken together, one could conclude that naringenin has a protective role in the abatement of doxorubicin-induced cardiac toxicity that resides, at least in part, on its anti-radical effects and regulatory role on NO production

The Role of Regulatory Pressure in Banks’ Capital and Risk Decisions

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Alessandra Tanda

2015-06-01

Full Text Available Capital regulation represents the core of prudential regulation in banking. Despite the aim of the regulators to have a safer and more robust banking industry, the effects of capital regulation on banks’ capital and risk decisions appear ambiguous. The paper analyses the relationship between capital and risk changes and the impact of regulatory pressure for a sample of European banks during the period 2006–2010, which encompasses the start of the latest financial crisis. Results highlight that banks tend to adopt a different behaviour depending on the capital ratio considered, supporting the so-called ‘gamble for resurrection’ hypothesis. Evidence supports the rethinking of the regulatory framework, especially with reference to higher and stricter capital requirements.

Calpain inhibition reduces NMDA receptor rundown in rat substantia nigra dopamine neurons.

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Zhao, Jerry; Baudry, Michel; Jones, Susan

2018-05-04

Repeated activation of N-Methyl-d-aspartate receptors (NMDARs) causes a Ca 2+ -dependent reduction in NMDAR-mediated current in dopamine (DA) neurons of the substantia nigra pars compacta (SNc) in one week old rats; however, a Ca 2+ -dependent regulatory protein has not been identified. The role of the Ca 2+ -dependent cysteine protease, calpain, in mediating NMDAR current rundown was investigated. In brain slices from rats aged postnatal day 7-9 ('P7'), bath application of either of the membrane permeable calpain inhibitors, N-Acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN, 20 μM) or MDL-28170 (30 μM) significantly reduced whole-cell NMDAR current rundown. To investigate the role of the calpain-2 isoform, the membrane permeable calpain-2 inhibitor, Z-Leu-Abu-CONH-CH2-C6H3 (3, 5-(OMe)2 (C2I, 200 nM), was applied; C2I application significantly reduced whole cell NMDAR current rundown. Interestingly, ALLN but not C2I significantly reduced rundown of NMDA-EPSCs. These results suggest the calpain-2 isoform mediates Ca 2+ -dependent regulation of extrasynaptic NMDAR current in the first postnatal week, while calpain-1 might mediate rundown of synaptic NMDAR currents. One week later in postnatal development, at P12-P16 ('P14'), there was significantly less rundown in SNc-DA neurons, and no significant effect on rundown of either Ca 2+ chelation or treatment with the calpain inhibitor, ALLN, suggesting that the rundown observed in SNc-DA neurons from two week-old rats might be Ca 2+ -independent. In conclusion, Ca 2+ -dependent rundown of extrasynaptic NMDAR currents in SNc DA neurons involves calpain-2 activation, but Ca 2+ - and calpain-2-dependent NMDAR current rundown is developmentally regulated. Copyright © 2018 Elsevier Ltd. All rights reserved.

Potential role of Saudi red propolis in alleviating lung damage induced by methicillin resistant Staphylococcus aureus virulence in rats.

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Saddiq, Amna Ali; Mohamed, Azza Mostafa

2016-07-01

The aim of this study was to explore the protective impact of aqueous extract of Saudi red propolis against rat lung damage induced by the pathogenic bacteria namely methicillin resistant Staphylococcus aureus (MRSA) ATCC 6538 strain. Infected rats were received a single intraperitoneal (i.p.) injection of bacterial suspension at a dose of 1 X 10(6) CFU / 100g body weight. Results showed that oral administration of an aqueous extract of propolis (50mg/100g body weight) daily for two weeks to infected rats simultaneously with bacterial infection, effectively ameliorated the alteration of oxidative stress biomarker, malondialdehyde (MDA), as well as the antioxidant markers, glutathione peroxidase (GPx) and superoxide dismutase (SOD), in lungs of infected rats compared with infected untreated ones. Also, the used propolis extract successfully modulated the alterations in proinflammatory mediators, tumor necrosis factor-α (TNF- α) and vascular endothelial growth factor (VEGF) in serum. In addition, the propolis extract successfully modulated the oxidative DNA damage and the apoptosis biomarker, caspase 3, in lungs of S aureus infected rats compared with infected untreated animals. The biochemical results were supported by histo-pathological observation of lung tissues. In conclusion, the beneficial prophylactic role of the aqueous extract of Saudi red propolis against lung damage induced by methicillin resistant S aureus may be related to the antioxidant, anti-inflammatory, immunomodulatory and antiapoptosis of its active constituents.

ROLE OF MELATONIN IN EXPRESSION OF MALONDIALDEHYDE ON MICROGLIA CELLS OF RAT INDUCED HEAD INJURY

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K. I. Nasution

2015-08-01

Full Text Available Background: brain injury is condition that harm human life. This study examines the application of melatonin in reducing oxidant status and barriers to the formation of cerebral edema in a rat brain injury model. The main purpose of this study is to prove the role of melatonin on the expression of Malondialdehyde (MDA and histological injury in a rat head injury model. Methods: This study was a randomized experimental posttest only control group design. This experimental was carried out on male Sprague Dawley strain Rattus novergicus, aged of 10-12 weeks, and weight of 300 g. Rat brain injury model was performed based on Marmarou (1994.1 Histology were observed using hematoxilen-eosin staining and immunohistochemistry, MDA was assessed using antibodies specific to each MDA protein. Observation and calculation of immunohistochemistry studies were also performed. Results: In this study, histological observation area covers an area of bleeding, number of immune-competent cells and the diameter of the arteries. Histology observation results showed that there is a significant reduction in diameter of arterial blood vessels of the brain injury tissue. Immunohisto-chemistry results showed that there is a significant reduction of MDA expression amount microglia cells of brain injury tissue. Conclusion: From this study, it can be concluded that Melatonin is a potent hydrogen peroxide scavenger that reduce the production of MDA. 

Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock.

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Sophie Joly

Full Text Available Interferon Regulatory Factor (IRF 6, a member of the IRF family, is essential for epidermal and orofacial embryonic development. Irf6 is strongly expressed in keratinocytes, in which it regulates epidermal proliferation, differentiation, and migration. A recent role for Irf6 in Toll-like receptor 2-dependent chemokine gene expression was also reported in an epithelial cell line. However, a function for Irf6 in innate immune cells was not previously reported. In the present study, we investigated the expression and function of Irf6 in bone marrow-derived neutrophils and macrophages. We show here, using a conditional knockout of Irf6 in lysosymeM expressing cells, that Irf6 is required for resistance to LPS-induced endotoxic shock. In addition, Irf6-deficient bone marrow-derived neutrophils exhibited increased chemotactic index and velocity compared with wild-type cells in vitro. TLR4-specific KC and IL6 secretions were upregulated in Irf6-deficient bone marrow-derived macrophages in vitro. These cells also exhibited an increased level of phosphorylated IkBa. Collectively, our findings suggest a role for Irf6 in the resistance to endotoxic shock due to NFk-B-mediated alteration of cytokine production.

Analysing success of regulatory policy transfers: Evidence from Turkish energy markets

International Nuclear Information System (INIS)

Dastan, Seyit Ali

2011-01-01

Economic regulation of public utilities has become a worldwide phenomenon with the preceding privatisation stream. It is questionable to transfer regulatory models hastily without customising the policy options or introducing necessary institutional reforms enabling the achievement of expected results of regulatory reform. Institutional configuration of a country affects credibility of regulatory commitments, quality of regulatory design, and way of policy transfer. Turkey’s energy market regulation experience confirms the decisive role of institutions in shaping the regulatory framework. - Highlights: ► The last quarter of the 20th century witnessed public sector reforms all over the world. ► The British model of utility regulation swept globally. ► In Turkey’s adoption of the utility regulation model, different factors affected in various ways. ► Higher political stability and regulatory experience provide faith in the regulatory framework.

U.S. Nuclear Regulatory Commission natural analogue research program

International Nuclear Information System (INIS)

Kovach, L.A.; Ott, W.R.

1995-01-01

This article describes the natural analogue research program of the U.S. Nuclear Regulatory Commission (US NRC). It contains information on the regulatory context and organizational structure of the high-level radioactive waste research program plan. It also includes information on the conditions and processes constraining selection of natural analogues, describes initiatives of the US NRC, and describes the role of analogues in the licensing process

The role of regulatory council in the energy sector from the aspect of consumers' protection

International Nuclear Information System (INIS)

Banovac, E.; Pavlovic, D.; Boljesic, K.

2003-01-01

The consumers' protection legal base, with few factors of new legislative consumers' protection legislation in European Union, in the Law on Consumers' Protection, and in the set of the Croatian Energy Laws is shown in this paper. Special attention in this paper is paid on five factors of regulatory body's orientation to the consumers' protection field, which energy regulatory body's policy should be included. The model of consumers' protection in the energy sector is shown, with the scheme of Three-component interactive subsystems: basic legislation which is determined consumers' protection policy, planning activities for consumers' protection (short and long time plans), and performing activities for consumers' protection. Furthermore, the approach of consumers' protection in the energy sectors in European Union are described. The paper gives the model of consumers' protection in the Croatian energy sector, and Croatian Energy Regulatory Council' approach to this issue. The table, with the data of specific consumers' protection problems in practice, those the Croatian Energy Regulatory Council as a regulatory body have been settled, is shown.(author)

Protective Role Of Fresh Pomegranate Against Oxidative Damage In Whole Body Gamma Irradiated Male Albino Rats

International Nuclear Information System (INIS)

Kassab, F.M.A.; Taha, M.S.

2013-01-01

Twenty four male albino rats, body weight 100-130 g, were used to evaluate the protective role of fresh pomegranate fruit intake for 30 days on the damage induced by single dose of 6 Gy whole body gamma irradiation. The rats were randomly and equally divided into four groups: group (1): control, group (2): irradiated with 6 Gy, group (3): pomegranate for 30 days and group (4): pomegranate for 30 days followed by 6 Gy whole body irradiation. At the end of the experiment, all rats were sacrificed after 12 hours fasting then sera were separated for the determination of sugar, total antioxidant, lipid profile and liver and kidney functions. Results showed that gamma radiation caused significant decline (P<0.05) in serum total antioxidant, total protein, albumin, HDL-C and blood glucose with significant elevation (P<0.05) in other hepato-renal markers in addition to serum total cholesterol, triglycerides and LDL-C. These changes were significantly attenuated in irradiated animals pre-treated with whole fresh pomegranate fruit leading to the conclusion that pre-intake of pomegranate fruit had a radio- protective effect. This protection of this whole fruit may be due to the increased total antioxidant level leading to free radical scavenging

Aggravation of serum Hepatocyte Growth Factor levels during hepato carcinogenesis in Rats

International Nuclear Information System (INIS)

Abdelgawad, M.R.; Ghareeb, N.A.

2010-01-01

Hepatocyte growth factor (HGF) has an essential role during liver development and it plays an important role in the regeneration and repair of injured tissues and acting as a mitogen, motogen and morphogens for a variety of epithelial cells. The role of HGF in carcinogenesis is in straggle and so, the present study aimed to through light through the level of HGF during different steps of carcinogenesis. Forty male rats were given diethylnitrosamine (DEN) in drinking water (100 mg/l) for up to 16 weeks. Eight rats were sacrificed at 8, 12 and 16 weeks. Besides, 8 hepatoma bearing rats were exposed to a single dose gamma irradiation (3 Gy) were sacrificed after 2 weeks from exposure (2 rats died, 36 hrs post irradiation) and 8 hepatoma bearing rats were sacrificed after 4 weeks from receiving a combined antioxidant (N-acetylcysteine and Lmethionine). Serum HGF was assayed by enzyme linked immunosorbent assay (ELISA). Serum HGF level in DEN treated rats and in exposed hepatoma bearing rats was significantly higher than in control rats whereas, serum HGF level after treatment with N acetylcysteine and L-methionine for 4 weeks was significantly decreased than DEN treated rats and concluded that serum HGF may play a role during promotion and progression of hepatocellular carcinoma (HCC) and during treatment

Differential expression of FGF receptors and of myogenic regulatory factors in primary cultures of satellite cells originating from fast (EDL) and slow (Soleus) twitch rat muscles.

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Martelly, I; Soulet, L; Bonnavaud, S; Cebrian, J; Gautron, J; Barritault, D

2000-11-01

In the rat, the fast and slow twitch muscles respectively Extensor digitorum longus (EDL) and Soleus present differential characteristics during regeneration. This suggests that their satellite cells responsible for muscle growth and repair represent distinct cellular populations. We have previously shown that satellite cells dissociated from Soleus and grown in vitro proliferate more readily than those isolated from EDL muscle. Fibroblast growth factors (FGFs) are known as regulators of myoblast proliferation and several studies have revealed a relationship between the response of myoblasts to FGF and the expression of myogenic regulatory factors (MRF) of the MyoD family by myoblasts. Therefore, we presently examined the possibility that the satellite cells isolated from EDL and Soleus muscles differ in the expression of FGF receptors (FGF-R) and of MRF expression. FGF-R1 and -R4 were strongly expressed in proliferating cultures whereas FGF-R2 and R3 were not detected in these cultures. In differentiating cultures, only -R1 was present in EDL satellite cells while FGF-R4 was also still expressed in Soleus cells. Interestingly, the unconventional receptor for FGF called cystein rich FGF receptor (CFR), of yet unknown function, was mainly detected in EDL satellite cell cultures. Soleus and EDL satellite cell cultures also differed in the expression MRFs. These results are consistent with the notion that satellite cells from fast and slow twitch muscles belong to different types of myogenic cells and suggest that satellite cells might play distinct roles in the formation and diversification of fast and slow fibres.

Regulatory T cells as suppressors of anti-tumor immunity: Role of metabolism.

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De Rosa, Veronica; Di Rella, Francesca; Di Giacomo, Antonio; Matarese, Giuseppe

2017-06-01

Novel concepts in immunometabolism support the hypothesis that glucose consumption is also used to modulate anti-tumor immune responses, favoring growth and expansion of specific cellular subsets defined in the past as suppressor T cells and currently reborn as regulatory T (Treg) cells. During the 1920s, Otto Warburg and colleagues observed that tumors consumed high amounts of glucose compared to normal tissues, even in the presence of oxygen and completely functioning mitochondria. However, the role of the Warburg Effect is still not completely understood, particularly in the context of an ongoing anti-tumor immune response. Current experimental evidence suggests that tumor-derived metabolic restrictions can drive T cell hyporesponsiveness and immune tolerance. For example, several glycolytic enzymes, deregulated in cancer, contribute to tumor progression independently from their canonical metabolic activity. Indeed, they can control apoptosis, gene expression and activation of specific intracellular pathways, thus suggesting a direct link between metabolic switches and pro-tumorigenic transcriptional programs. Focus of this review is to define the specific metabolic pathways controlling Treg cell immunobiology in the context of anti-tumor immunity and tumor progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Role of slow oscillatory activity and slow wave sleep in consolidation of episodic-like memory in rats.

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Oyanedel, Carlos N; Binder, Sonja; Kelemen, Eduard; Petersen, Kimberley; Born, Jan; Inostroza, Marion

2014-12-15

Our previous experiments showed that sleep in rats enhances consolidation of hippocampus dependent episodic-like memory, i.e. the ability to remember an event bound into specific spatio-temporal context. Here we tested the hypothesis that this enhancing effect of sleep is linked to the occurrence of slow oscillatory and spindle activity during slow wave sleep (SWS). Rats were tested on an episodic-like memory task and on three additional tasks covering separately the where (object place recognition), when (temporal memory), and what (novel object recognition) components of episodic memory. In each task, the sample phase (encoding) was followed by an 80-min retention interval that covered either a period of regular morning sleep or sleep deprivation. Memory during retrieval was tested using preferential exploration of novelty vs. familiarity. Consistent with previous findings, the rats which had slept during the retention interval showed significantly stronger episodic-like memory and spatial memory, and a trend of improved temporal memory (although not significant). Object recognition memory was similarly retained across sleep and sleep deprivation retention intervals. Recall of episodic-like memory was associated with increased slow oscillatory activity (0.85-2.0Hz) during SWS in the retention interval. Spatial memory was associated with increased proportions of SWS. Against our hypothesis, a relationship between spindle activity and episodic-like memory performance was not detected, but spindle activity was associated with object recognition memory. The results provide support for the role of SWS and slow oscillatory activity in consolidating hippocampus-dependent memory, the role of spindles in this process needs to be further examined. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Mechanism of immune tolerance induced by donor derived immature dendritic cells in rat high-risk corneal transplantation

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Xu-Dong Zhao

2013-06-01

Full Text Available AIM: To study the role of immature dendritic cells (imDCs on immune tolerance in rat penetrating keratoplasty (PKP in high-risk eyes and to investigate the mechanism of immune hyporesponsiveness induced by donor-derived imDCs. METHODS: Seventy-five SD rats (recipient and 39 Wistar rats (donor were randomly divided into 3 groups: control, imDC and mature dendritic cell (mDC group respectively. Using a model of orthotopic corneal transplantation in which allografts were placed in neovascularized high-risk eyes of recipient rat. Corneal neovascularization was induced by alkaline burn in the central cornea of recipient rat. Recipients in imDC group or mDC group were injected donor bone marrow-derived imDCs or mDCs of 1×106 respectively 1 week before corneal transplantation via tail vein. Control rat received the same volume of PBS. In each group, 16 recipients were kept for determination of survival time and other 9 recipients were executed on day 3, 7 and 14 after transplantation. Cornea was harvested for hematoxylin-eosin staining and acute rejection evaluation, Western blot was used to detect the expression level of Foxp3. RESULTS: The mean survival time of imDC group was significantly longer than that of control and mDC groups (all P<0.05. The expression level of Foxp3 on CD4+CD25+T cells of imDC group (2.24±0.18 was significantly higher than that in the control (1.68±0.09 and mDC groups (1.46±0.13 (all P<0.05. CONCLUSION: Donor-derived imDC is an effective treatment in inducing immune hyporesponsiveness in rat PKP. The mechanism of immune tolerance induced by imDC might be inhibit T lymphocytes responsiveness by regulatory T cells.

Experimental studies on possible regulatory role of nitric oxide on the differential effects of chronic predictable and unpredictable stress on adaptive immune responses.

Science.gov (United States)

Thakur, Tarun; Gulati, Kavita; Rai, Nishant; Ray, Arunabha

2017-09-01

The present study was designed to investigate the effects of chronic predictable stress (CPS) and chronic unpredictable stress (CUS) on immunological responses in KLH-sensitized rats and involvement of NOergic signaling pathways mediating such responses. Male Wistar rats (200-250g) were exposed to either CPS or CUS for 14days and IgG antibody levels and delayed type hypersensitivity (DTH) response was determined to assess changes in adaptive immunity. To evaluate the role of nitric oxide during such immunomodulation, biochemical estimation of stable metabolite of nitric oxide (NOx) and 3-nitrotyrosine (3-NT, a marker of peroxynitrite formation) were done in both blood and brain. Chronic stress exposure resulted in suppression of IgG and DTH response and elevated NOx and 3-NT levels, with a difference in magnitude of response in CPS vs CUS. Pretreatment with aminoguanidine (iNOS inhibitor) caused further reduction of adaptive immune responses and attenuated the increased NOx and 3-NT levels in CPS or CUS exposed rats. On the other hand 7-NI (nNOS inhibitor) did not significantly affect these estimated parameters. The results suggest involvement of iNOS and lesser/no role of nNOS during modulation of adaptive immunity to stress. Thus, the result showed that predictability of stressors results in differential degree of modulation of immune responses and complex NO-mediated signaling mechanisms may be involved during responses. Copyright © 2017. Published by Elsevier B.V.

Modulatory role of chelating agents in diet-induced hypercholesterolemia in rats

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Heba M. Mahmoud

2014-06-01

Conclusion: Pretreatment of hypercholesterolemic rats with simvastatin, CaNa2EDTA or DMSA attenuated most of the changes induced by feeding rats with cholesterol-rich diet owing to their observed anti-hyperlipidemic and antioxidant properties.

Strengthening Regulatory Competence through Techno-managerial Knowledge Integration: Indian Experience

International Nuclear Information System (INIS)

Kuchibhotla, S.

2016-01-01

Competence development is the process of identifying the competencies required to perform a given job, role or set of tasks successfully at workplace. Strengthening regulatory competence, for the nuclear regulator, is essential to ensure skilled and competent human resources for performing the functions of the Regulatory Body. The strengthening of existing competence level for the Indian nuclear regulator, takes into account the understanding of the elements such as legal basis and regulatory processes governing operations of regulatory body, technological competences for performing regulatory functions, competences pertinent to regulatory practices, and competences related to personal and interpersonal effectiveness within the organization. Competency data from AERB divisions was compiled to identify gaps at various positions with recommendations for making specialized training modules and modifications to basic and refresher training modules. The exercise is aimed at providing continual improvement in skills and knowledge of human resources at AERB in a phased manner. (author)

Regulatory aspects of radiopharmaceuticals

International Nuclear Information System (INIS)

Kristensen, K.

1985-01-01

Regulatory systems in the field of radiopharmaceuticals have two main purposes: efficacy and safety. Efficacy expresses the quality of the diagnostic and therapeutic process for the patient. Safety involves the patient, the staff, and the environment. The world situation regarding regulations for radiopharmaceuticals is reviewed on the basis of a survey in WHO Member States. The main content of such regulations is discussed. The special properties of radiopharmaceuticals compared with ordinary drugs may call for modified regulations. Several countries are preparing such regulations. Close co-operation and good understanding among scientists working in hospital research, industry and regulatory bodies will be of great importance for the fast and safe introduction of new radiopharmaceuticals for the benefit of the patient. Before introducing new legislation in this field, a radiopharmaceutical expert should analyse the situation in the country and the relationship to the existing regulations. It is expected that the most important factor in promoting the fast introduction of new, safe and effective radiopharmaceuticals will be the training of people working within the regulatory bodies. It is foreseen that the IAEA and WHO will have an important role to play by providing expert advice and training in this area. (author)

The protective role of crocin in tartrazine induced nephrotoxicity in Wistar rats.

Science.gov (United States)

Erdemli, Mehmet Erman; Gul, Mehmet; Altinoz, Eyup; Zayman, Emrah; Aksungur, Zeynep; Bag, Harika Gozukara

2017-12-01

The present study was conducted to investigate the changes in rat kidney tissues after administration of tartrazine (T) and crocine (Cr). The latter was applied for its protective properties. The present study was conducted with the approval of Inonu University, Faculty of Medicine, Experimental Animals Ethics Committee. Forty rats were randomly divided into 4 equal groups (Control, T, Cr, T + Cr). At the end of the experiment, the rats were decapitated. Biochemical and histopathological studies were conducted on excised rat kidney tissues. It was determined that there was a significant increase in MDA, TOS, SOD, CAT, Bun, Creatinine levels in tartrazine administered rat kidney tissues for 21 days, while GSH and TAS levels decreased (P ≤ 0.05) when compared to all other groups. On the other hand, it was identified that Cr administration statistically significantly increased GSH and TAS levels in rat kidney tissues when compared to all other groups and decreased MDA and TOS levels to control group levels (P tartrazine toxicity agent. Copyright © 2017. Published by Elsevier Masson SAS.

Study on the Mechanism Underlying the Regulation of the NMDA Receptor Pathway in Spinal Dorsal Horns of Visceral Hypersensitivity Rats by Moxibustion

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L. D. Wang

2016-01-01

Full Text Available Visceral hypersensitivity is enhanced in irritable bowel syndrome (IBS patients. Treatment of IBS visceral pain by moxibustion methods has a long history and rich clinical experience. In the clinic, moxibustion on the Tianshu (ST25 and Shangjuxu (ST37 acupoints can effectively treat bowel disease with visceral pain and diarrhea symptoms. To investigate the regulatory function of moxibustion on the Tianshu (ST25 and Shangjuxu (ST37 acupoints on spinal cord NR1, NR2B, and PKCε protein and mRNA expression in irritable bowel syndrome (IBS visceral hypersensitivity rats, we did some research. In the study, we found that moxibustion effectively relieved the IBS visceral hyperalgesia status of rats. Analgesic effect of moxibustion was similar to intrathecal injection of Ro 25-6981. The expression of NR1, NR2B, and PKCε in the spinal dorsal horns of IBS visceral hyperalgesia rats increased. Moxibustion on the Tianshu and Shangjuxu acupoints might inhibit the visceral hypersensitivity, simultaneously decreasing the expression of NR1, NR2B, and PKCε in spinal cord of IBS visceral hyperalgesia rats. Based on the above experimental results, we hypothesized NR1, NR2B, and PKCε of spinal cord could play an important role in moxibustion inhibiting the process of central sensitization and visceral hyperalgesia state.

RegRNA: an integrated web server for identifying regulatory RNA motifs and elements

OpenAIRE

Huang, Hsi-Yuan; Chien, Chia-Hung; Jen, Kuan-Hua; Huang, Hsien-Da

2006-01-01

Numerous regulatory structural motifs have been identified as playing essential roles in transcriptional and post-transcriptional regulation of gene expression. RegRNA is an integrated web server for identifying the homologs of regulatory RNA motifs and elements against an input mRNA sequence. Both sequence homologs and structural homologs of regulatory RNA motifs can be recognized. The regulatory RNA motifs supported in RegRNA are categorized into several classes: (i) motifs in mRNA 5′-untra...

Role of Omega 3 fatty acids on radiation-induced oxidative and structural damage in different tissues of male albino rats

International Nuclear Information System (INIS)

Rezk, R.G.; Abou Zaid, N.M.; Ahmed, A. G.

2011-01-01

Omega-3 fatty acids play a critical role in the development and function of the reproductive and central nervous systems. The aim of this study is to evaluate the effect of omega-3 fatty acids supplementation on lipid peroxidation and antioxidant enzyme levels associated with histopathologic changes induced by gamma irradiation in the testis and brain of male albino rats. Rats were whole body exposed to radiation at a single dose of 3 Gy. Omega-3 fatty acids (0.4 gm/kg b wt/day) were given to rats, by gavages, for 15 consecutive days before irradiation and for 15 days after irradiation. Rats were sacrificed one and 15 days post irradiation .Biochemical analysis of testis and cerebral cortex samples showed that irradiation induced a significant increase in xanthine oxidase (XO) activity and lipid peroxidation end product malondialdehyde (MDA) and a decrease in the content of reduced glutathione (GSH) and activity of antioxidant enzymes; glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT).Histological examination of testis and cerebral cortex tissues showed spermatogonia degeneration, apoptosis and necrosis in the testis and neurons cell bodies with ill defined and even ruptured cell membrane and damaged blood capillaries in the cerebral cortex. Omega-3 administration has attenuated the toxic effects of radiation by decreasing the levels of MDA, and XO, and increasing the activity of endogenous antioxidant enzymes, which was associated with amelioration of the histological injury markers in both testis and cerebral cortex. It could be postulated that omega-3 fatty acids as a multi-functional dietary supplement could exert a modulatory role in radiation- induced testis and cerebral cortex biochemical and histological changes through its antioxidant properties.

Effects of cisplatin on lipid peroxidation and the glutathione redox status in the liver of male rats: The protective role of selenium

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Trbojević Ivana S.

2010-01-01

Full Text Available The role of oxidative stress in cisplatin (CP toxicity and its prevention by pretreatment with selenium (Se was investigated. Male Wistar albino rats were injected with a single dose of cisplatin (7.5 mg CP/kg b.m., i.p. and selenium (6 mg Se/kg b.m, as Na2SeO3, i.p. alone or in combination. The results suggest that CP intoxication induces oxidative stress and alters the glutathione redox status: reduced glutathione (GSH, oxidized glutathione (GSSG and the GSH/GSSG ratio (GSH RI, resulting in increased lipid peroxidation (LPO in rat liver. The pretreatment with selenium prior to CP treatment showed a protective effect against the toxic influence of CP on peroxidation of the membrane lipids and an altering of the glutathione redox status in the liver of rats. From our results we conclude that selenium functions as a potent antioxidant and suggest that it can control CP-induced hepatotoxicity in rats.

Role of plant MicroRNA in cross-species regulatory networks of humans.

Science.gov (United States)

Zhang, Hao; Li, Yanpu; Liu, Yuanning; Liu, Haiming; Wang, Hongyu; Jin, Wen; Zhang, Yanmei; Zhang, Chao; Xu, Dong

2016-08-08

It has been found that microRNAs (miRNAs) can function as a regulatory factor across species. For example, food-derived plant miRNAs may pass through the gastrointestinal (GI) tract, enter into the plasma and serum of mammals, and interact with endogenous RNAs to regulate their expression. Although this new type of regulatory mechanism is not well understood, it provides a fresh look at the relationship between food consumption and physiology. To investigate this new type of mechanism, we conducted a systematic computational study to analyze the potential functions of these dietary miRNAs in the human body. In this paper, we predicted human and plant target genes using RNAhybrid and set some criteria to further filter them. Then we built the cross-species regulatory network according to the filtered targets, extracted central nodes by PageRank algorithm and built core modules. We summarized the functions of these modules to three major categories: ion transport, metabolic process and stress response, and especially some target genes are highly related to ion transport, polysaccharides and the lipid metabolic process. Through functional analysis, we found that human and plants have similar functions such as ion transport and stress response, so our study also indicates the existence of a close link between exogenous plant miRNA targets and digestive/urinary organs. According to our analysis results, we suggest that the ingestion of these plant miRNAs may have a functional impact on consuming organisms in a cross-kingdom way, and the dietary habit may affect the physiological condition at a genetic level. Our findings may be useful for discovering cross-species regulatory mechanism in further study.

The effects of seeds with hot and cold temperaments on serum thyroid hormones, corticosterone and urine vanillylmandelic acid concentrations of healthy rats.

Science.gov (United States)

Parvinroo, Shirin; Naghibi, Farzaneh; Zahediasl, Saleh; Kamalinejad, Mohammad; Sabetkasaei, Masoumeh

2014-10-28

Hot and cold temperaments are the basic concepts of Iranian traditional medicine (ITM). Nevertheless, studies on the functional mechanisms of medicinal herbs based on hot and cold temperaments are not very extensive. This study aimed to evaluate the effects of diets containing hot or cold temperament seeds according to ITM on some hormonal and neuromediator parameters with a regulatory role in thermogenesis and energy metabolism in acute (24 hr) and subacute (7-day) experiments that were performed on rats. Each experiment was performed on 42 male Wistar rats, which were randomly divided into 7 groups. while 1 group received usual diet (controls), 6 other groups were fed with a diet containing 10% seeds, namely, anise, fennel, or ajowan (hot temperament groups) or cucumber, pumpkin, or watermelon (cold temperament groups), respectively. The levels of the rats׳ serum free thyroxin (FT4), free triiodothyronin (FT3), triiodothyronin (T3), thyroxin (T4), corticosterone and urine vanillylmandelic acid (VMA) were analyzed. After 24 hours, a significant decrease in FT3 was observed in groups that were fed anise or fennel seeds. However, a significant increase in T3 was observed in the ajowan seed-fed group, and no changes in other parameters were observed in this group. On the 7th day, FT4 was significantly increased in fennel seed-fed group; T3 was significantly increased in the anise, fennel, ajowan and watermelon seed-fed groups; corticosterone was significantly increased in the watermelon and pumpkin seed-fed groups; and VMA was significantly increased in the fennel seed-fed group and significantly decreased in the cucumber seed-fed group. Alterations induced by hot and cold temperament seeds in measured hormonal and neuromediator levels that have a regulatory role in thermogenesis and the body׳s energy metabolism revealed that hot and cold temperament characteristics of studied seeds may most likely be related to their intervention in the body׳s energy metabolism

Regulatory Powers in Public Procurement Law of Peruvian Administrative Agencies

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Juan Carlos Morón Urbina

2017-12-01

Full Text Available Peruvian law has explicitly recognized regulatory powers to administrative agencies, which allows them to have a preponderant role in the production of rules in public procurement. Although these delegations of legislative authority are positively defined, distortions in the system of legal sources arise when agencies exceed delegated powers or when measures issued by administrative entities are mistaken for regulations. This paper aims to identify regulatory powers of Peruvian administrative agencies, as well as the regulatory measures they issue, and their relation with other sources of law.

Evidence for role of acid-sensing ion channels in nucleus ambiguus neurons: essential differences in anesthetized versus awake rats.

Science.gov (United States)

Brailoiu, G Cristina; Deliu, Elena; Altmann, Joseph B; Chitravanshi, Vineet; Brailoiu, Eugen

2014-08-01

Acid-sensing ion channels (ASIC) are widely expressed in several brain regions including medulla; their role in physiology and pathophysiology is incompletely understood. We examined the effect of acidic pH of 6.2 on the medullary neurons involved in parasympathetic cardiac control. Our results indicate that retrogradely labeled cardiac vagal neurons of nucleus ambiguus are depolarized by acidic pH. In addition, acidic saline of pH 6.2 increases cytosolic Ca(2+) concentration by promoting Ca(2+) influx in nucleus ambiguus neurons. In vivo studies indicate that microinjection of acidic artificial cerebrospinal fluid (pH 6.2) into the nucleus ambiguus decreases the heart rate in conscious rats, whereas it has no effect in anesthetized animals. Pretreatment with either amiloride or benzamil, two widely used ASIC blockers, abolishes both the in vitro and in vivo effects elicited by pH 6.2. Our findings support a critical role for ASIC in modulation of cardiac vagal tone and provide a potential mechanism for acidosis-induced bradycardia, while identifying important differences in the response to acidic pH between anesthetized and conscious rats.

The role of adrenal hormones in the activation of tryptophan 2,3-dioxygenase by nicotinic acid in rat liver.

Science.gov (United States)

Sainio, E L

1997-09-01

In this study, our previous finding that nicotinic acid activates tryptophan 2,3-dioxygenase as strongly as tryptophan was investigated in further detail. This study focused on the role of the adrenals in the activation process. Adrenalectomy abolished the activation due to nicotinic acid, but not the activation caused by tryptophan. The role of corticoids and/or adrenomedullary hormones in the enzyme activation was studied, by supplementing these hormones in adrenalectomized rats using minipumps implanted under the skin. The results showed that the enhanced activity of tryptophan 2,3-dioxygenase caused by nicotinic acid was partly restored by adrenaline following adrenalectomy but not by corticosterone supplementation. The results were supported by further experiments in which the rats were treated with adrenaline or corticosterone intraperitoneally before nicotinic acid administration. The conclusion that adrenaline participates in the regulation of tryptophan 2,3-dioxygenase should promote further study to determine whether adrenaline is a general modulator of this enzyme. This experimental model generated new information on the activation mechanism of tryptophan 2,3-dioxygenase by nicotinic acid.

Regulatory role for the memory B cell as suppressor-inducer of feedback control

International Nuclear Information System (INIS)

Kennedy, M.W.; Thomas, D.B.

1983-01-01

A regulatory role is proposed for the antigen-responsive B cell, as suppressor-inducer of feedback control during the secondary response in vivo. In a double adoptive transfer of memory cells primed to a thymus-dependent antigen from one irradiated host to another, antigen-specific suppressors are generated after a critical time in the primary recipient, able to entirely ablate a secondary anti-hapten response. Positive cell selection in the fluorescence-activated cell sorter confirmed that suppression was mediated by an Lyt-2+ T cell; however, positively selected B cells were also inhibitory and able to induce suppressors in a carrier-specific manner: B hapten induced suppressors in a carrier-primed population, and B carrier induced suppressors in a hapten-carrier population. At the peak of the antibody response in the primary host, memory B cells and their progeny were unable to differentiate further to plasma cells due to their intrinsic suppressor-inducer activity, but this autoregulatory circuit could be severed by adoptive transfer to carrier-primed, X-irradiated recipients

Prophylactic Role of Spermine in Rats Intoxicated With Lead and/or Gamma Irradiation

International Nuclear Information System (INIS)

Habieb, M.E.; Mohamed, M.A.; Hawas, A.M.; Abu-Khudir, R.; Mohamed, T.M.

2017-01-01

The current study was conducted to investigate the protective effect of spermine, a natural polyamine against toxicity of lead and /or gamma irradiation in male rats. Eight groups of rats were used in this study (control, irradiated group (6 GY), lead (40 mg/kg bw), spermine (10 mg/kg bw), lead plus irradiation, irradiation plus spermine, lead plus spermine, irradiation plus lead co-treated with spermine) for consecutive 14 days. Blood samples were used for complete blood count (CBC) and glucose 6-phosphate-dehydrogenase (G6PD) levels. Moreover, malondialdhyde (MDA), glutathione (GSH), metallothionein (MT) levels and catalase (CAT) activity were investigated in liver, kidney and brain. G6PD activity significantly decreased post exposure to lead and /or gamma irradiation. Hepatic, renal and brain MDA, GSH, MT and CAT were significantly increased in lead intoxicated group, while GSH, MT and CAT activity were significantly decreased in gamma-irradiated group. Spermine administration alleviated changes in CBC, G6PD, MDA, MT and CAT to normal control levels, but with significant increase in G6PD activity and platelets count. In conclusion, spermine acts as an antioxidant and plays a prophylactic role against intoxication with lead and/or gamma irradiation exposure.

Reduced incidence of stress ulcer in germ-free Sprague Dawley rats.

Science.gov (United States)

Paré, W P; Burken, M I; Allen, E D; Kluczynski, J M

1993-01-01

Recent findings with respect to the role of spiral gram-negative bacteria in peptic ulcer disease have stimulated interest in discerning the role of these agents in stress ulcer disease. We tested the hypothesis that a standard restraint-cold ulcerogenic procedure would fail to produce ulcers in axenic rats. Axenic, as well as normal Sprague Dawley rats, were exposed to a cold-restraint procedure. The germ-free condition was maintained throughout the study in the axenic rats. Axenic rats had significantly fewer ulcers as compared to normal rats exposed to the standard cold-restraint procedure, as well as handling control rats. The data represent the first report suggesting a microbiologic component in the development of stress ulcer using the rat model.

Methodology For Evaluation Of Regulatory Effectiveness In Physical Protection

International Nuclear Information System (INIS)

Izmaylov, Alexander; Valente, John; Griggs, James R.; Rexroth, Paul; Piskarev, Alexander; Babkin, Vladimir; Sokolov, Egor; Melton, Ronald B.; Cunningham, Mitchel E.; Baker, Kathryn A.; Brothers, Alan J.

2005-01-01

Material protection, control, and accounting (MPC and A) regulatory documents play an important role in securing and protecting nuclear material by regulating a variety of activities at different hierarchical levels. The development, implementation, and practical application of these regulatory documents requires a significant investment of financial and material resources. Therefore, it is important to evaluate the effectiveness of the regulatory development process and the extent to which regulations improve the effectiveness of MPC and A at nuclear sites. The joint Russian and U.S. Regulatory Development Project has a goal of evaluating the effectiveness of regulatory documents developed for MPC and A. As part of this joint Project, a methodology for evaluating effectiveness has been developed. This methodology was developed around physical protection objectives. The developed methodology specifies physical protection objectives to be accomplished through the implementation of a regulatory system based on the physical protection goals at the nuclear sites. It includes approaches to assessing regulatory effectiveness, the hierarchical structure of physical protection objectives to be accomplished through implementing regulations, a 'mapping' of the physical protection objectives to the regulatory framework, a list of criteria for evaluating the effectiveness of physical protection regulations and effectiveness indicators, as well as means and methods for gathering information and implementation of this evaluation.

Role of liver nerves and adrenal medulla in glucose turnover of running rats

DEFF Research Database (Denmark)

Sonne, B; Mikines, K J; Richter, Erik

1985-01-01

Sympathetic control of glucose turnover was studied in rats running 35 min at 21 m X min-1 on the level. The rats were surgically liver denervated, adrenodemedullated, or sham operated. Glucose turnover was measured by primed constant infusion of [3-3H]glucose. At rest, the three groups had...... identical turnover rates and concentrations of glucose in plasma. During running, glucose production always rose rapidly to steady levels. The increase was not influenced by liver denervation but was halved by adrenodemedullation. Similarly, hepatic glycogen depletion was identical in denervated and control...... rats but reduced after adrenodemedullation. Early in exercise, glucose uptake rose identically in all groups and, in adrenodemedullated rats, matched glucose production. Accordingly, plasma glucose concentration increased in liver-denervated and control rats but was constant in adrenodemedullated rats...

Oxytocin differently regulates pressor responses to stress in WKY and SHR rats: the role of central oxytocin and V1a receptors.

Science.gov (United States)

Wsol, A; Szczepanska-Sadowska, E; Kowalewski, S; Puchalska, L; Cudnoch-Jedrzejewska, A

2014-01-01

The role of central oxytocin in the regulation of cardiovascular parameters under resting conditions and during acute stress was investigated in male normotensive Wistar-Kyoto (WKY; n = 40) and spontaneously hypertensive rats (SHR; n = 28). In Experiment 1, mean arterial blood pressure (MABP) and heart rate (HR) were recorded in WKY and SHR rats at rest and after an air-jet stressor during intracerebroventricular (ICV) infusions of vehicle, oxytocin or oxytocin receptor (OTR) antagonist. In Experiment 2, the effects of vehicle, oxytocin and OTR antagonist were determined in WKY rats after prior administration of a V1a vasopressin receptor (V1aR) antagonist. Resting MABP and HR were not affected by any of the ICV infusions either in WKY or in SHR rats. In control experiments (vehicle), the pressor response to stress was significantly higher in SHR. Oxytocin enhanced the pressor response to stress in the WKY rats but reduced it in SHR. During V1aR blockade, oxytocin infusion entirely abolished the pressor response to stress in WKY rats. Combined blockade of V1aR and OTR elicited a significantly greater MABP response to stress than infusion of V1a antagonist and vehicle. This study reveals significant differences in the regulation of blood pressure in WKY and SHR rats during alarming stress. Specifically, the augmentation of the pressor response to stress by exogenous oxytocin in WKY rats is caused by its interaction with V1aR, and endogenous oxytocin regulates the magnitude of the pressor response to stress in WKY rats by simultaneous interaction with OTR and V1aR.

Lupine Alleviate Hyperglycemia in Streptozotocin Diabetic gamma- Irradiated Rats

International Nuclear Information System (INIS)

El-Sayed, S.M.

2010-01-01

This study was to examine the regulatory effect of lupine on the diabetic profile developed in Streptozotocin (STZ) induced diabetic albino rats. The effectiveness of lupine against diabetes in gamma irradiated rats was purposed in the present study. Rats were received lupine seeds powder suspension (1 g/kg body weight for 14 consecutive days) before whole body exposure to 8 Gy of gamma radiation and /or STZ (55 mg/kg body weight, single dose) injection. The results pointed out that radiation exposure sustained the diabetic profile in rats received STZ comparing with STZ diabetic not irradiated rats. The prolonged administration of lupine suspension before STZ induction of diabetic and/or irradiated rats reduced the changes in the level of blood glucose, insulin concentration, liver glycogen, and the activity of glucose-6-phosphatase associated with significant amelioration in blood antioxidant status (superoxide dismutase, SOD; catalase, CAT; glucose-6-phosphate dehydrogenase, G-6-PD activities and reduced glutathione concentration GSH). Also, the level of blood lipid peroxides (TBARS) were reduced greatly when compared with its matched value in diabetic and /or gamma irradiated rats. It could be postulated that lupine powder suspension might be attenuate the diabetic profile development throughout reducing oxidative damages and modulating the antioxidant status. In addition, lupine could be considered as one of a remarkable radio protective agent owing to its antioxidants property

Nerve growth factor induces facial heat hyperalgesia and plays a role in trigeminal neuropathic pain in rats.

Science.gov (United States)

Dos Reis, Renata C; Kopruszinski, Caroline M; Nones, Carina F M; Chichorro, Juliana G

2016-09-01

There is preclinical evidence that nerve growth factor (NGF) contributes toward inflammatory hyperalgesia in the orofacial region, but the mechanisms underlying its hyperalgesic effect as well as its role in trigeminal neuropathic pain require further investigation. This study investigated the ability of NGF to induce facial heat hyperalgesia and the involvement of tyrosine kinase receptor A, transient receptor potential vanilloid 1, and mast cells in NGF pronociceptive effects. In addition, the role of NGF in heat hyperalgesia in a model of trigeminal neuropathic pain was evaluated. NGF injection into the upper lip of naive rats induced long-lasting heat hyperalgesia. Pretreatment with an antibody anti-NGF, antagonists of tyrosine kinase receptor A, and transient receptor potential vanilloid 1 receptors or compound 48/80, to induce mast-cell degranulation, all attenuated NGF-induced hyperalgesia. In a rat model of trigeminal neuropathic pain, local treatment with anti-NGF significantly reduced heat hyperalgesia. In addition, increased NGF levels were detected in the ipsilateral infraorbital nerve branch at the time point that represents the peak of heat hyperalgesia. The results suggest that NGF is a prominent hyperalgesic mediator in the trigeminal system and it may represent a potential therapeutic target for the management of painful orofacial conditions, including trigeminal neuropathic pain.

Comparison of rat and rabbit embryo-fetal developmental ...

Science.gov (United States)

Regulatory non-clinical safety testing of human pharmaceutical compounds typically requires embryo fetal developmental toxicity (EFDT) testing in two species, (one rodent and one non-rodent, usually the rat and the rabbit). The question has been raised whether under some conditions EFDT testing could be limited to one species, or whether the need for testing in a second species could be decided on a case by case basis. As part of an RIVM/CBG-MEB/HESI/US EPA consortium initiative, we built and queried a database of 379 EFDT studies conducted for marketed and non-marketed pharmaceutical compounds. The animal models (rat and rabbit) were assessed for their potential for adverse developmental and maternal outcomes. The database was analyzed for the prevalence of EFDT incidence and the nature and severity of adverse findings in the two species. Some manifestation of EFDT in either one or both species (rat and rabbit) was demonstrated for 282 compounds (74%), and EFDT was detected in only one species (rat or rabbit) in almost a third (31%, 118 compounds), with approximately 58% rat and 42% rabbit studies identifying an EFDT signal among the 379 compounds tested. For 24 compounds (6%), fetal malformations were observed in one species (rat or rabbit) in the absence of any EFDT in the second species. In general, growth retardation, fetal variations, and malformations were more prominent in the rat, whereas embryo-fetal death was observed more often in the rabbit. Discor

Cobalamin (Vitamin B12) Role on the Biochemical, Histological and Teratological Changes Induced in Diabetic Irradiated Pregnant Rats

International Nuclear Information System (INIS)

Ramadan, F.L.

2013-01-01

Vitamin B 12 called Cobalamin, is a water soluble vitamin with a key role in the normal function of the brain, nervous system, cell division and for the formation of blood. It is normally involved in the metabolism of every cell of the human body especially affecting DNA synthesis and regulation, fatty acid synthesis and energy production.The aim of the present study was to evaluate the role of vitamin B 12 intake on radiation induced damage in diabetic mothers.Diabetes was induced in female rats by intra-peritoneal injection of alloxan 150 mg/kg b.wt. dissolved in saline. Pregnant diabetic mothers were received vitamin B 12 0.1 mg/100 g b.wt. from the 1st up to 19th day of gestation. Meanwhile, pregnant diabetic rats were exposed to 0.6 Gy on the 7th and the 14th days of gestation. The increased incidence of malformations in diabetic pregnancy with an excess of free oxygen radicals in the embryos was recorded .Vitamin B12 supplementation to diabetic mother ameliorated radiation-induced damage which was obvious by diminishing the increase in glucose level, improving serum insulin level, glycogen content in the liver and ameliorating the decrease in glutathione (GSH) content in the liver of pregnant rats and their fetuses.In addition, vitamin B 12 treatment improved the decrease in red blood cells (RBCs), white blood cells (WBCs) and hemoglobin (Hb) of fetuses and DNA content in the liver tissues. Moreover, vitamin B 12 treatment lead to the regeneration of normal architecture of maternal and fetuses hepatic cells and blood vessels. It could be concluded that vitamin B 12 supplementation to diabetic mothers ameliorated the radiation effect which induced biochemical, histochemical, histological and teratological disorders.Furthermore, the results obtained showed that vitamin B 12 administration caused a protection to diabetic pregnant rats against embryo malformations induced by gamma rays

Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney

International Nuclear Information System (INIS)

Graceli, J.B.; Cicilini, M.A.; Bissoli, N.S.; Abreu, G.R.; Moysés, M.R.

2013-01-01

The maintenance of extracellular Na + and Cl - concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na + and Cl - reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg·kg -1 ·day -1 , sc) and progesterone (OVP, 1.7 mg·kg -1 ·day -1 , sc). We assessed Na + and Cl - fractional excretion (FE Na + and FE Cl - , respectively) and renal and plasma catecholamine release concentrations. FE Na + , FE Cl - , water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FE Na + , FE Cl - , water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6±36.1 ng/g) and denervated rat groups (D: 102.1±15.7; ODE: 108.7±23.2; ODP: 101.1±22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9±25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function

Scientific underpinnings of biotechnology regulatory frameworks.

Science.gov (United States)

Gleim, Savannah; Smyth, Stuart J

2018-05-25

Part of what is presently missing at domestic regulatory levels (and that is important at the international level as well) is a detailed understanding of what the rules of, and for, regulation should be, who the actors, stakeholders and major decision makers are and finally, how to get agreement about the rules. Greater insights into the system of rules that underpin regulatory frameworks for agri-food and biotechnology products in genetically modified (GM) crop- adopting nations will provide value by clarifying the evidence used to commercialize these technologies. This article examines the public documents available from Canada, the United States, the European Union and the Organisation for Economic Cooperation and Development regarding the development of regulatory risk assessment frameworks for products of biotechnology to determine what science grounds these frameworks. The documentation used to provide the initial structure to the existing regulatory frameworks identifies the linkages, connections and relationships that exist between science, risk assessment and regulatory policy. The relationship between risk and regulation has never been more critical to the commercialization of innovative agricultural products. Documenting the role of science-based risk assessment in regulations and how this has changed over the 20 years of experience in regulating GM crops will identify changes in the risk/regulation relationship. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Safety Culture Implementation in Indonesian Nuclear Energy Regulatory Agency (BAPETEN)

International Nuclear Information System (INIS)

Nurwidi Astuti, Y.H.; Dewanto, P.

2016-01-01

The Indonesia Nuclear Energy Act no. 10 of 1997 clearly stated that Nuclear Energy Regulatory Agency (BAPETEN) is the Nuclear Regulatory Body. This is the legal basis of BAPETEN to perform regulatory functions on the use of nuclear energy in Indonesia, including regulation, authorisation, inspection and enforcement. The Independent regulatory functions are stipulated in Article 4 and Article 14 of the Nuclear Energy Act no. 10 (1997) which require the government to establish regulatory body that is reporting directly to the president and has responsibility to control of the use of nuclear energy. BAPETEN has been start fully its functioning on January 4, 1999. In it roles as a regulatory body, the main aspect that continues and always to be developed is the safety culture. One of the objectives of regulatory functions is “to increase legal awareness of nuclear energy of the user to develop safety culture” (Article 15, point d), while in the elucidation of article 15 it is stipulated that “safety culture is that of characteristics and attitudes in organizations and individual that emphasise the importance of safety”.

Enhanced muscarinic M1 receptor gene expression in the corpus striatum of streptozotocin-induced diabetic rats

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Mathew Jobin

2009-04-01

Full Text Available Abstract Acetylcholine (ACh, the first neurotransmitter to be identified, regulate the activities of central and peripheral functions through interactions with muscarinic receptors. Changes in muscarinic acetylcholine receptor (mAChR have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS. Previous reports from our laboratory on streptozotocin (STZ induced diabetic rats showed down regulation of muscarinic M1 receptors in the brainstem, hypothalamus, cerebral cortex and pancreatic islets. In this study, we have investigated the changes of acetylcholine esterase (AChE enzyme activity, total muscarinic and muscarinic M1 receptor binding and gene expression in the corpus striatum of STZ – diabetic rats and the insulin treated diabetic rats. The striatum, a neuronal nucleus intimately involved in motor behaviour, is one of the brain regions with the highest acetylcholine content. ACh has complex and clinically important actions in the striatum that are mediated predominantly by muscarinic receptors. We observed that insulin treatment brought back the decreased maximal velocity (Vmax of acetylcholine esterase in the corpus striatum during diabetes to near control state. In diabetic rats there was a decrease in maximal number (Bmax and affinity (Kd of total muscarinic receptors whereas muscarinic M1 receptors were increased with decrease in affinity in diabetic rats. We observed that, in all cases, the binding parameters were reversed to near control by the treatment of diabetic rats with insulin. Real-time PCR experiment confirmed the increase in muscarinic M1 receptor gene expression and a similar reversal with insulin treatment. These results suggest the diabetes-induced changes of the cholinergic activity in the corpus striatum and the regulatory role of insulin on binding parameters and gene expression of total and muscarinic M1 receptors.

A physiological increase of insulin in the olfactory bulb decreases detection of a learned aversive odor and abolishes food odor-induced sniffing behavior in rats.

Directory of Open Access Journals (Sweden)

Pascaline Aimé

Full Text Available Insulin is involved in multiple regulatory mechanisms, including body weight and food intake, and plays a critical role in metabolic disorders such as obesity and diabetes. An increasing body of evidence indicates that insulin is also involved in the modulation of olfactory function. The olfactory bulb (OB contains the highest level of insulin and insulin receptors (IRs in the brain. However, a role for insulin in odor detection and sniffing behavior remains to be elucidated. Using a behavioral paradigm based on conditioned olfactory aversion (COA to isoamyl-acetate odor, we demonstrated that an intracerebroventricular (ICV injection of 14 mU insulin acutely decreased olfactory detection of fasted rats to the level observed in satiated animals. In addition, whereas fasted animals demonstrated an increase in respiratory frequency upon food odor detection, this effect was absent in fasted animals receiving a 14 mU insulin ICV injection as well as in satiated animals. In parallel, we showed that the OB and plasma insulin levels were increased in satiated rats compared to fasted rats, and that a 14 mU insulin ICV injection elevated the OB insulin level of fasted rats to that of satiated rats. We further quantified insulin receptors (IRs distribution and showed that IRs are preferentially expressed in the caudal and lateral parts of the main OB, with the highest labeling found in the mitral cells, the main OB projection neurons. Together, these data suggest that insulin acts on the OB network to modulate olfactory processing and demonstrate that olfactory function is under the control of signals involved in energy homeostasis regulation and feeding behaviors.

[The role of nitric oxide on the dysfunction of intestinal motility in rats subjected to hemorrhagic shock].

Science.gov (United States)

Zhang, Yu-ping; Wang, Xiao-rong; Zhao, Xiao-qi; Qiao, Hai-xia

2013-09-01

To determine the role of nitric oxide (NO) in intestinal motility dysfunction in rats subjected to hemorrhagic shock (HS). Sixteen male Wistar rats were randomly and equally divided into two groups. The HS model of rat was induced by bleeding from femoral artery. After animal models were made, different inducers were added, and duodenum samples were harvested for the determination of contractile response to acetylcholine (ACh) in vitro, activities of inducible nitric oxide synthase (iNOS), contents of NO in tissue, and morphological changes. The spontaneous contraction of intestinal smooth muscle and contractile response induced by ACh were significantly decreased at 180 minutes in HS group, compared with control group, the contractile response induced by ACh of intestinal smooth muscle was decreased by almost 60% (0.40±0.11 g×mm(-2)×s(-1) vs. 1.00±0.20 g×mm(-2)×s(-1), Phydrochloride (L-NAME) could significantly restore the suppressed contractile response of smooth muscle strips obtained from HS rats (0.97±0.25 vs. 0.40±0.11, P0.05). Compared with those of control group, iNOS activities (2.295±0.310 U/g vs. 1.319±0.322 U/g) and NO contents (2.880±0.353 μmol/g vs. 1.505±0.387 μmol/g) in duodenum of HS rats were both significantly increased (both P<0.01). Under light microscopy, the most significant morphological change in duodenum following HS was the infiltration of obvious inflammatory cells. The NO produced by the overexpression of iNOS induced by HS involves in the motility dysfunction of intestine through the mechanism of cyclic guanosine monophosphate (cGMP) system. Moreover, NO-mediated infiltration of inflammatory cells in tissue may also contribute to the development of motility dysfunction of intestine following HS.

Therapeutic role of niacin in the prevention and regression of hepatic steatosis in rat model of nonalcoholic fatty liver disease.

Science.gov (United States)

Ganji, Shobha H; Kukes, Gary D; Lambrecht, Nils; Kashyap, Moti L; Kamanna, Vaijinath S

2014-02-15

Nonalcoholic fatty liver disease (NAFLD), a leading cause of liver damage, comprises a spectrum of liver abnormalities including the early fat deposition in the liver (hepatic steatosis) and advanced nonalcoholic steatohepatitis. Niacin decreases plasma triglycerides, but its effect on hepatic steatosis is elusive. To examine the effect of niacin on steatosis, rats were fed either a rodent normal chow, chow containing high fat (HF), or HF containing 0.5% or 1.0% niacin in the diet for 4 wk. For regression studies, rats were first fed the HF diet for 6 wk to induce hepatic steatosis and were then treated with niacin (0.5% in the diet) while on the HF diet for 6 wk. The findings indicated that inclusion of niacin at 0.5% and 1.0% doses in the HF diet significantly decreased liver fat content, liver weight, hepatic oxidative products, and prevented hepatic steatosis. Niacin treatment to rats with preexisting hepatic steatosis induced by the HF diet significantly regressed steatosis. Niacin had no effect on the mRNA expression of fatty acid synthesis or oxidation genes (including sterol-regulatory element-binding protein 1, acetyl-CoA carboxylase 1, fatty acid synthase, and carnitine palmitoyltransferase 1) but significantly inhibited mRNA levels, protein expression, and activity of diacylglycerol acyltrasferase 2, a key enzyme in triglyceride synthesis. These novel findings suggest that niacin effectively prevents and causes the regression of experimental hepatic steatosis. Approved niacin formulation(s) for other indications or niacin analogs may offer a very cost-effective opportunity for the clinical development of niacin for treating NAFLD and fatty liver disease.

Shen-Qi-Jie-Yu-Fang exerts effects on a rat model of postpartum depression by regulating inflammatory cytokines and CD4+CD25+ regulatory T cells

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Li JY

2016-04-01

Full Text Available Jingya Li,1,* Ruizhen Zhao,1,* Xiaoli Li,1 Wenjun Sun,1 Miao Qu,1 Qisheng Tang,1 Xinke Yang,1 Shujing Zhang2 1Third Affiliated Hospital, 2School of Basic Medical Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of China *These authors contributed equally to this work Background: Shen-Qi-Jie-Yu-Fang (SJF is composed of eight Chinese medicinal herbs. It is widely used in traditional Chinese medicine for treating postpartum depression (PPD. Previous studies have shown that SJF treats PPD through the neuroendocrine mechanism. Aim: To further investigate the effect of SJF on the immune system, including the inflammatory response system and CD4+CD25+ regulatory T (Treg cells. Materials and methods: Sprague Dawley rats were used to create an animal model of PPD by inducing hormone-simulated pregnancy followed by hormone withdrawal. After hormone withdrawal, the PPD rats were treated with SJF or fluoxetine for 1, 2, and 4 weeks. Levels of Treg cells in peripheral blood were measured by flow cytometry analysis. Serum interleukin (IL-1β and IL-6 were evaluated by enzyme-linked immunosorbent assay, and gene and protein expressions of IL-1RI, IL-6Rα, and gp130 in the hippocampus were observed by reverse-transcription polymerase chain reaction and Western blot. Results: Serum IL-1β in PPD rats increased at 2 weeks and declined from then on, while serum IL-6 increased at 1, 2, and 4 weeks. Both IL-1β and IL-6 were downregulated by SJF and fluoxetine. Changes in gene and protein expressions of IL-1RI and gp130 in PPD rats were consistent with changes in serum IL-1β, and were able to be regulated by SJF and fluoxetine. The levels of Treg cells were negatively correlated with serum IL-1β and IL-6, and were decreased in PPD rats. The levels of Treg cells were increased by SJF and fluoxetine. Conclusion: Dysfunction of proinflammatory cytokines and Tregs in different stages of PPD was attenuated by SJF and fluoxetine through

Contrasting Roles of Dopamine and Noradrenaline in the Motivational Properties of Social Play Behavior in Rats.

Science.gov (United States)

Achterberg, E J Marijke; van Kerkhof, Linda W M; Servadio, Michela; van Swieten, Maaike M H; Houwing, Danielle J; Aalderink, Mandy; Driel, Nina V; Trezza, Viviana; Vanderschuren, Louk J M J

2016-02-01

Social play behavior, abundant in the young of most mammalian species, is thought to be important for social and cognitive development. Social play is highly rewarding, and as such, the expression of social play depends on its pleasurable and motivational properties. Since the motivational properties of social play have only sporadically been investigated, we developed a setup in which rats responded for social play under a progressive ratio schedule of reinforcement. Dopaminergic neurotransmission plays a key role in incentive motivational processes, and both dopamine and noradrenaline have been implicated in the modulation of social play behavior. Therefore, we investigated the role of dopamine and noradrenaline in the motivation for social play. Treatment with the psychostimulant drugs methylphenidate and cocaine increased responding for social play, but suppressed its expression during reinforced play periods. The dopamine reuptake inhibitor GBR-12909 increased responding for social play, but did not affect its expression, whereas the noradrenaline reuptake inhibitor atomoxetine decreased responding for social play as well as its expression. The effects of methylphenidate and cocaine on responding for social play, but not their play-suppressant effects, were blocked by pretreatment with the dopamine receptor antagonist α-flupenthixol. In contrast, pretreatment with the α2-adrenoceptor antagonist RX821002 prevented the play-suppressant effect of methylphenidate, but left its effect on responding for social play unaltered. In sum, the present study introduces a novel method to study the incentive motivational properties of social play behavior in rats. Using this paradigm, we demonstrate dissociable roles for dopamine and noradrenaline in social play behavior: dopamine stimulates the motivation for social play, whereas noradrenaline negatively modulates the motivation for social play behavior and its expression.

Genome Editing in Rats Using TALE Nucleases.

Science.gov (United States)

Tesson, Laurent; Remy, Séverine; Ménoret, Séverine; Usal, Claire; Thinard, Reynald; Savignard, Chloé; De Cian, Anne; Giovannangeli, Carine; Concordet, Jean-Paul; Anegon, Ignacio

2016-01-01

The rat is an important animal model to understand gene function and model human diseases. Since recent years, the development of gene-specific nucleases has become important for generating new rat models of human diseases, to analyze the role of genes and to generate human antibodies. Transcription activator-like (TALE) nucleases efficiently create gene-specific knockout rats and lead to the possibility of gene targeting by homology-directed recombination (HDR) and generating knock-in rats. We describe a detailed protocol for generating knockout and knock-in rats via microinjection of TALE nucleases into fertilized eggs. This technology is an efficient, cost- and time-effective method for creating new rat models.

Transcriptional Regulatory Network Analysis of MYB Transcription Factor Family Genes in Rice

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Shuchi eSmita

2015-12-01

Full Text Available MYB transcription factor (TF is one of the largest TF families and regulates defense responses to various stresses, hormone signaling as well as many metabolic and developmental processes in plants. Understanding these regulatory hierarchies of gene expression networks in response to developmental and environmental cues is a major challenge due to the complex interactions between the genetic elements. Correlation analyses are useful to unravel co-regulated gene pairs governing biological process as well as identification of new candidate hub genes in response to these complex processes. High throughput expression profiling data are highly useful for construction of co-expression networks. In the present study, we utilized transcriptome data for comprehensive regulatory network studies of MYB TFs by top down and guide gene approaches. More than 50% of OsMYBs were strongly correlated under fifty experimental conditions with 51 hub genes via top down approach. Further, clusters were identified using Markov Clustering (MCL. To maximize the clustering performance, parameter evaluation of the MCL inflation score (I was performed in terms of enriched GO categories by measuring F-score. Comparison of co-expressed cluster and clads analyzed from phylogenetic analysis signifies their evolutionarily conserved co-regulatory role. We utilized compendium of known interaction and biological role with Gene Ontology enrichment analysis to hypothesize function of coexpressed OsMYBs. In the other part, the transcriptional regulatory network analysis by guide gene approach revealed 40 putative targets of 26 OsMYB TF hubs with high correlation value utilizing 815 microarray data. The putative targets with MYB-binding cis-elements enrichment in their promoter region, functional co-occurrence as well as nuclear localization supports our finding. Specially, enrichment of MYB binding regions involved in drought-inducibility implying their regulatory role in drought

Trust in regulatory regimes: scoping the field

NARCIS (Netherlands)

Six, F.E.; Verhoest, Koen

2017-01-01

This edited volume is the first endeavour to systematically investigate the role of trust in the different relations within regulatory regimes. Trust as a multifaceted concept is contested within public administration and political science in general and especially within the relation between

Aboriginal and invasive rats of genus Rattus as hosts of infectious agents.

Science.gov (United States)

Kosoy, Michael; Khlyap, Lyudmila; Cosson, Jean-Francois; Morand, Serge

2015-01-01

From the perspective of ecology of zoonotic pathogens, the role of the Old World rats of the genus Rattus is exceptional. The review analyzes specific characteristics of rats that contribute to their important role in hosting pathogens, such as host-pathogen relations and rates of rat-borne infections, taxonomy, ecology, and essential factors. Specifically the review addresses recent taxonomic revisions within the genus Rattus that resulted from applications of new genetic tools in understanding relationships between the Old World rats and the infectious agents that they carry. Among the numerous species within the genus Rattus, only three species-the Norway rat (R. norvegicus), the black or roof rat (R. rattus), and the Asian black rat (R. tanezumi)-have colonized urban ecosystems globally for a historically long period of time. The fourth invasive species, R. exulans, is limited to tropical Asia-Pacific areas. One of the points highlighted in this review is the necessity to discriminate the roles played by rats as pathogen reservoirs within the land of their original diversification and in regions where only one or few rat species were introduced during the recent human history.

Fetal hypothalamic transplants into brain irradiated rats: Graft morphometry and host behavioral responses

International Nuclear Information System (INIS)

Pearlman, S.H.; Rubin, P.; White, H.C.; Wiegand, S.J.; Gash, D.M.

1990-01-01

This study was designed to test the hypothesis that neural implants can ameliorate or prevent some of the long-term changes associated with CNS irradiation. Using a rat model, the initial study focused on establishing motor, regulatory, and morphological changes associated with brain radiation treatments. Secondly, fetal hypothalamic tissue grafts were placed into the third ventricle of rats which had been previously irradiated. Adult male Long Evans rats received one of three radiation doses (15, 22.5, ampersand 30 Gy) or no radiation. Three days after irradiation, 7 animals in each dose group received an embryonic day 17 hypothalamic graft into the third ventricle while the remaining 8-9 animals in each group received injections of vehicle solution (sham). Few changes were observed in the 15 and 22.5 Gy animals, however rats in the 30 Gy treatment group showed stereotypic and ambulatory behavioral hyperactivity 32 weeks after irradiation. Regulatory changes in the high dose group included decreased growth rate and decreased urine osmolalities, but these measures were extremely variable among animals. Morphological results demonstrated that 30 Gy irradiated animals showed extensive necrosis primarily in the fimbria, which extended into the internal capsule, optic nerve, hippocampus, and thalamus. Hemorrhages were found in the hippocampus, thalamus, and fimbria. Defects in the blood-brain barrier also were evident by entry of intravascularly injected horseradish peroxidase into the parenchyma of the brain. Animals in the 30 Gy grafted group showed fewer behavioral changes and less brain damage than their sham grafted counterparts. Specifically, activity measures were comparable to normal levels, and a dilute urine was not found in the 30 Gy implanted rats. Morphological changes support these behavioral results since only two 30 Gy implanted rats showed necrosis

Collective statement on the role of research in a nuclear regulatory context

International Nuclear Information System (INIS)

2001-01-01

In the present context of deregulation and privatisation of the nuclear industry, maintaining an adequate level of nuclear safety research is a primary concern for nuclear regulators, researchers and nuclear power plant licensees, as well as for government officials and the public. While these different stakeholders may have common concerns and interests, there may also be differences. At the international level, it is important to understand that divisions exist both within and among countries, not only in national cultures but also in the way regulators, researchers and licensees view the rote of research. An international gathering under the auspices of the OECD Nuclear Energy Agency (NEA) took place in June 2001, bringing together heads of nuclear regulatory bodies of NEA Member countries, senior regulators, senior executives of research organisations and leaders from the nuclear industry to discuss their perceptions of the rote of research in a nuclear regulatory context. This collective statement represents an international consensus on a rationale for regulatory research for currently operating nuclear reactors and for future reactors, and sets forth specific recommendations to NEA standing technical committees and Member countries. The intended audience is primarily nuclear safety regulators, senior researchers and industry leaders. Government authorities, nuclear power plant operators and the general public may also be interested. (author)

The Chinese health care regulatory institutions in an era of transition.

Science.gov (United States)

Fang, Jing

2008-02-01

The purpose of this paper is to contribute to a better understanding of Chinese health care regulation in an era of transition. It describes the major health care regulatory institutions operating currently in China and analyzes the underlying factors. The paper argues that in the transition from a planned to a market economy, the Chinese government has been employing a hybrid approach where both old and new institutions have a role in the management of emerging markets, including the health care market. This approach is consistent with the incremental reform strategy adopted by the Party-state. Although a health care regulatory framework has gradually taken shape, the framework is incomplete, with a particular lack of emphasis on professional self-regulation. In addition, its effectiveness is limited despite the existence of many regulatory institutions. In poor rural areas, the effectiveness of the regulatory framework is further undermined or distorted by the extremely difficult financial position that local governments find themselves in. The interpretations of the principle of 'rule of law' by policy makers and officials at different levels and the widespread informal network of relations between known individuals (Guanxi) play an important role in the operation of the regulatory framework. The findings of this paper reveal the complex nature of regulating health care in transitional China.

Early growth and postprandial appetite regulatory hormone responses

DEFF Research Database (Denmark)

Perälä, Mia-Maria; Kajantie, Eero; Valsta, Liisa M

2013-01-01

Strong epidemiological evidence suggests that slow prenatal or postnatal growth is associated with an increased risk of CVD and other metabolic diseases. However, little is known whether early growth affects postprandial metabolism and, especially, the appetite regulatory hormone system. Therefore......, we investigated the impact of early growth on postprandial appetite regulatory hormone responses to two high-protein and two high-fat content meals. Healthy, 65-75-year-old volunteers from the Helsinki Birth Cohort Study were recruited; twelve with a slow increase in BMI during the first year of life......, early growth may have a role in programming appetite regulatory hormone secretion in later life. Slow early growth is also associated with higher postprandial insulin and TAG responses but not with incretin levels....

Role of some selected Bifidobacterium strains in modulating immunosenescence of aged albino rats

Directory of Open Access Journals (Sweden)

Hanan A. El-Bakry

2013-10-01

Full Text Available Probiotic administration has been associated with enhanced immune function in elderly subjects. However, approaches for selection of an “ideal” strain of bifidobacteria are still difficult. The aim of the present study is to investigate the possible modulatory effects of three strains of Bifidobacterium species (Bifidobacterium adolescentis ATCC 15704, Bifidobacterium breve ATCC 15700 and Bifidobacterium longum ATCC 15707 on haematological and immunological parameters of aged albino rats corresponding to normal adult ones. The animals were divided into six groups; three groups of aged rats were fed yoghurt inoculated with one of the Bifidobacterium strains; one group of aged rats was fed yoghurt alone (control aged; two groups of adult and aged rats were provided with normal diet and assigned as normal groups. The total leucocyte count was significantly increased in the three bifidobacteria-treated aged groups as compared with both normal and control aged rats. Serum IgA level was considerably increased in all treated rats. On the contrary, serum IgE level was significantly decreased in rats supplemented with yoghurt inoculated with B. adolescentis or B. breve. Both B. adolescentis and B. breve groups showed significant enhanced production of TNF-α. Furthermore, the production of cytokine IL-8 was significantly increased in the B. adolescentis group. Interestingly, it was apparent that only B. adolescentis had the most pronounced effect on aged rats to regain nearly normal values as measured in normal adult rats. Conclusively, the present work indicates that dietary consumption of selected bifidobacteria strains may have a particular application in the elderly especially in terms of immunomodulation.

Possible role of licorice roots (glycyrrhiza glabra) as a natural radioprotector against oxidative damage in rats

International Nuclear Information System (INIS)

Darwish, M. M.; Hussien, E. M.; Haggag, A. M.

2007-01-01

This study was conducted to investigate the possible role of Licorice against damages induced by gamma rays. Adult female albino rats (130-140 g) were divided into four groups. Group 1: control animals, group 2: rats whole body exposed to gamma radiations (6.5 Gy), group 3: animals received Licorice in drinking water for four weeks (100 mg/ kg body wt/ day), and group 4: received Licorice two weeks before and two weeks after irradiation. Blood and liver samples were obtained two weeks post-irradiation. Total cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C), glucose, sodium (Na + ) and potassium (K + ) levels were determined in serum. Per oxidative hepatic damage was studied by assessing; thiobarbituric acid reactive substances (TBARs) and reduced glutathione (GSH) contents, as well as, superoxide dismutase (SOD) and catalase (CAT) activities in liver tissue. The data obtained revealed a significant increase in serum glucose, K + , TC, TG and LDL-C and liver TABRs. While, significant decreases were recorded for serum Na + and HDL-C levels, liver GSH content, SOD and CAT activities. On the other hand, Licorice treated irradiation rats showed a significant amelioration in the changes produced by gamma radiation with variable degree. Thus, it could be concluded that Licorice might provide protection against radiation-induced disturbances in metabolic activities and oxidative damage in liver tissues

Role of Vitamin C As A Potent Antioxidant in Acute Radiation Induced Liver Disease (RILD) Among Male Albino Rats

International Nuclear Information System (INIS)

Ezz El Arab, A.; Ayad, S.K.Y.; El Fouly, A.

2012-01-01

Recent studies demonstrated the role of vitamin C as antioxidant in alleviating organ damage caused by gamma irradiation. The present study was conducted to find out the effect of vitamin C on liver biochemical functions such as serum ALT, AST, albumin and bilirubin after experimental liver damage induced by gamma irradiation. Rats irradiated with gamma radiation were used as a model of liver injury terminating with necro inflammatory activity and acute hepatitis. Forty male albino rats were classified into 6 groups (G0-G5). G0 included 8 male albino rats that were divided to 2 subgroups (4 rats/subgroup). Both subgroups were exposed to gamma irradiation with 6 Gy as a single dose. The first subgroup was left for 3 weeks then serum and liver samples were collected while in the second subgroup, 2 rats were died and the remaining 2 rats were left for 6 weeks then serum and liver samples were collected. G1 was the negative control while in the rest groups, the whole body of rats was exposed to gamma irradiation of dose 8 Gy divided to 2 doses (4 Gy/one dose) at one week interval in between. G2 included 12 albino rats divided into 3 subgroups (4 rats/subgroup). The whole body of albino rats of G2 was exposed to 8 Gy gamma irradiation that divided as mentioned before. Serum and liver samples were collected after one day, two days and four days after last dose of irradiation. G3 also included 8 rats that were divided into 2 subgroups (4 rats/subgroup) and whole body was exposed to 8 Gy gamma irradiation that were divided as mentioned before. Serum and liver samples were collected after one week for one subgroup and 2 weeks for other subgroup after last dose of irradiation. The rest 2 groups (4 rats/group) were exposed to 8Gy gamma irradiation divided as before, but the rats in one group were orally supplemented with low dose of vitamin C. G4 and the others were supplemented with high dose of vitamin C for 2 weeks starting after last dose of irradiation (G5) then serum

Reconstruction of the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator

Science.gov (United States)

Usaite, Renata; Jewett, Michael C; Oliveira, Ana Paula; Yates, John R; Olsson, Lisbeth; Nielsen, Jens

2009-01-01

Highly conserved among eukaryotic cells, the AMP-activated kinase (AMPK) is a central regulator of carbon metabolism. To map the complete network of interactions around AMPK in yeast (Snf1) and to evaluate the role of its regulatory subunit Snf4, we measured global mRNA, protein and metabolite levels in wild type, Δsnf1, Δsnf4, and Δsnf1Δsnf4 knockout strains. Using four newly developed computational tools, including novel DOGMA sub-network analysis, we showed the benefits of three-level ome-data integration to uncover the global Snf1 kinase role in yeast. We for the first time identified Snf1's global regulation on gene and protein expression levels, and showed that yeast Snf1 has a far more extensive function in controlling energy metabolism than reported earlier. Additionally, we identified complementary roles of Snf1 and Snf4. Similar to the function of AMPK in humans, our findings showed that Snf1 is a low-energy checkpoint and that yeast can be used more extensively as a model system for studying the molecular mechanisms underlying the global regulation of AMPK in mammals, failure of which leads to metabolic diseases. PMID:19888214

Assessment of regulatory effectiveness. Peer discussions on regulatory practices

International Nuclear Information System (INIS)

1999-09-01

This report arises from the seventh series of peer discussions on regulatory practices entitled 'Assessment of Regulatory Effectiveness'. The term 'regulatory effectiveness' covers the quality of the work and level of performance of a regulatory body. In this sense, regulatory effectiveness applies to regulatory body activities aimed at preventing safety degradation and ensuring that an acceptable level of safety is being maintained by the regulated operating organizations. In addition, regulatory effectiveness encompasses the promotion of safety improvements, the timely and cost effective performance of regulatory functions in a manner which ensures the confidence of the operating organizations, the general public and the government, and striving for continuous improvements to performance. Senior regulators from 22 Member States participated in two peer group discussions during March and May 1999. The discussions were focused on the elements of an effective regulatory body, possible indicators of regulatory effectiveness and its assessment. This report presents the outcome of these meetings and recommendations of good practices identified by senior regulators, which do not necessarily reflect those of the governments of the nominating Member States, the organizations they belong to, or the International Atomic Energy Agency. In order to protect people and the environment from hazards associated with nuclear facilities, the main objective of a nuclear regulatory body is to ensure that a high level of safety in the nuclear activities under its jurisdiction is achieved, maintained and within the control of operating organizations. Even if it is possible to directly judge objective safety levels at nuclear facilities, such safety levels would not provide an exclusive indicator of regulatory effectiveness. The way the regulatory body ensures the safety of workers and the public and the way it discharges its responsibilities also determine its effectiveness. Hence the

Feather development genes and associated regulatory innovation predate the origin of Dinosauria.

Science.gov (United States)

Lowe, Craig B; Clarke, Julia A; Baker, Allan J; Haussler, David; Edwards, Scott V

2015-01-01

The evolution of avian feathers has recently been illuminated by fossils and the identification of genes involved in feather patterning and morphogenesis. However, molecular studies have focused mainly on protein-coding genes. Using comparative genomics and more than 600,000 conserved regulatory elements, we show that patterns of genome evolution in the vicinity of feather genes are consistent with a major role for regulatory innovation in the evolution of feathers. Rates of innovation at feather regulatory elements exhibit an extended period of innovation with peaks in the ancestors of amniotes and archosaurs. We estimate that 86% of such regulatory elements and 100% of the nonkeratin feather gene set were present prior to the origin of Dinosauria. On the branch leading to modern birds, we detect a strong signal of regulatory innovation near insulin-like growth factor binding protein (IGFBP) 2 and IGFBP5, which have roles in body size reduction, and may represent a genomic signature for the miniaturization of dinosaurian body size preceding the origin of flight. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Elevated mitochondrial gene expression during rat liver regeneration after portal vein ligation.

Science.gov (United States)

Shimizu, Y; Suzuki, H; Nimura, Y; Onoue, S; Nagino, M; Tanaka, M; Ozawa, T

1995-10-01

We explored the molecular basis of mitochondrial energy production during rat liver regeneration after portal vein ligation. Ligation of the left branch of the portal vein induces an increase in the weight of the nonligated lobe, counterbalancing the reduced weight of the ligated lobe. Using this model, we investigated changes in mitochondrial DNA-binding proteins, mitochondrial DNA, and mitochondrial messenger RNA (mRNA) in rat hepatocytes of the nonligated lobes. The amount of mitochondrial DNA-binding protein increased maximally (200% to 300% of the preoperative level) at 12 hours after the operation, before an increase (390%) in mitochondrial DNA content at 24 hours, and parallel to an increase (240%) in mitochondrial mRNA levels at 12 hours. These results suggest that the energy supply for liver regeneration is achieved through enhancement of mitochondrial DNA replication as well as transcription, in which the mitochondrial DNA-binding proteins probably play regulatory roles. We also found that in the nonligated lobes, mRNA levels of hepatocyte growth factor increased to a detectable level only 12 hours after the operation. These molecular biochemical data help explain why preoperative portal vein embolization, which is a modification of portal vein branch ligation, is an effective method to prevent posthepatectomy liver failure.

The role of subcutaneous adipose tissue in supporting the copper balance in rats with a chronic deficiency in holo-ceruloplasmin.

Directory of Open Access Journals (Sweden)

Ekaterina Y Ilyechova

Full Text Available We have previously shown that (1 an acute deficiency in blood serum holo-ceruloplasmin (Cp developed in rats that were fed fodder containing silver ions (Ag-fodder for one month and (2 the deficiency in holo-Cp was compensated by non-hepatic holo-Cp synthesis in rats that were chronically fed Ag-fodder for 6 months (Ag-rats. The purpose of the present study is to identify the organ(s that compensate for the hepatic holo-Cp deficiency in the circulation. This study was performed on rats that were fed Ag-fodder (40 mg Ag·kg-1 body mass daily for 6 months. The relative expression levels of the genes responsible for copper status were measured by RT-PCR. The in vitro synthesis and secretion of [14C]Cp were analyzed using a metabolic labeling approach. Oxidase activity was determined using a gel assay with o-dianisidine. Copper status and some hematological indexes were measured. Differential centrifugation, immunoblotting, immunoelectrophoresis, and atomic absorption spectrometry were included in the investigation. In the Ag-rats, silver accumulation was tissue-specific. Skeletal muscles and internal (IAT and subcutaneous (SAT adipose tissues did not accumulate silver significantly. In SAT, the mRNAs for the soluble and glycosylphosphatidylinositol-anchored ceruloplasmin isoforms were expressed, and their relative levels were increased two-fold in the Ag-rats. In parallel, the levels of the genes responsible for Cp metallation (Ctr1 and Atp7a/b increased correspondingly. In the SAT of the Ag-rats, Cp oxidase activity was observed in the Golgi complex and plasma membrane. Moreover, full-length [14C]Cp polypeptides were released into the medium by slices of SAT. The possibilities that SAT is part of a system that controls the copper balance in mammals, and it plays a significant role in supporting copper homeostasis throughout the body are discussed.

Role of hypothalamic cannabinoid receptors in post-stroke depression in rats.

Science.gov (United States)

Wang, Shanshan; Sun, Hong; Liu, Sainan; Wang, Ting; Guan, Jinqun; Jia, Jianjun

2016-03-01

One of the most common psychological consequences of stroke is post-stroke depression (PSD). While more than 30 percent of stroke patients eventually develop PSD, the neurobiological mechanisms underlying such a phenomenon have not been well investigated. Given the critical involvement of hypothalamic-pituitary-adrenal axis and endocannabinoid system in response to stressful stimuli, we evaluated the hypothesis that cannabinoid receptors in the hypothalamus are critical for modulation of post-stroke depression-like behaviors in rats. To this end, rats were treated with middle cerebral artery occlusion (MCAO) followed by chronic unpredictable mild stress (CUMS) treatment procedure. We then assessed the expression of CB1 and CB2 receptors in the hypothalamus, and evaluated the effects of pharmacological stimulations of CB1 or CB2 receptors on the expression and development of depression-like behaviors in PSD rats. We found that PSD rats exhibited decreased the expression of CB1 receptor, but not CB2 receptor, in the ventral medial hypothalamus (VMH). Such an effect was not observed in the dorsally adjacent brain regions. Furthermore, intra-VMH injections of CB2 receptor agonist, but not CB1 receptor agonist, attenuated the expression of depression-like behaviors in PSD rats. Finally, repeated intraperitoneal injections of CB1 or CB2 receptor agonists during CUMS treatment inhibited the development of depression-like behaviors in PSD rats. Taken together, these results suggest that decreased CB1 receptor expression is likely associated with the development of post-stroke depression, and CB2 receptor may be a potential therapeutic target for the treatment post-stroke depressive disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Stimulation of estradiol biosynthesis by tributyltin in rat hippocampal slices.

Science.gov (United States)

Munetsuna, Eiji; Hattori, Minoru; Yamazaki, Takeshi

2014-01-01

Hippocampal functions are influenced by steroid hormones, such as testosterone and estradiol. It has been demonstrated that hippocampus-derived steroid hormones play important roles in neuronal protection and synapse formation. Our research groups have demonstrated that estradiol is de novo synthesized in the rat hippocampus. However, the mechanism(s) regulating this synthesis remains unclear. It has been reported that tributyltin, an environmental pollutant, binds to the retinoid X receptor (RXR) and modifies estrogen synthesis in human granulosa-like tumor cells. This compound can penetrate the blood brain barrier, and tends to accumulate in the brain. Based on these facts, we hypothesized that tributyltin could influence the hippocampal estradiol synthesis. A concentration of 0.1 μM tributyltin induced an increase in the mRNA content of P450(17α) and P450arom in hippocampal slices, as determined using real-time PCR. The transcript levels of other steroidogenic enzymes and a steroidogenic acute regulatory protein were not affected. The estradiol level in rat hippocampal slices was subsequently determined using a radioimmunoassay. We found that the estradiol synthesis was stimulated by ∼2-fold following a 48-h treatment with 0.1 μM tributyltin, and this was accompanied by transcriptional activation of P450(17α) and P450arom. Tributyltin stimulated de novo hippocampal estradiol synthesis by modifying the transcription of specific steroidogenic enzymes.

The changing regulatory environment

International Nuclear Information System (INIS)

Caron, G.

1999-01-01

The role and value of regulation in the energy sector was discussed, demonstrating how, despite common perception, regulation is an essential part of Canada's strategy to find and develop new opportunities. The future vision of regulation for industry participants was presented with particular focus on issues related to streamlining the regulatory process. As far as pipelines are concerned, regulatory actions are necessary to facilitate capacity increases and to ensure the line's integrity, safety and environmental record. Furthermore, regulation provides economic solutions where market forces cannot provide them, as for example where business has elements of monopoly. It arbitrates interests of landowners, business, consumers, and environmental groups. It looks for ways to ensure conditions under which competition can flourish. It acts as the guardian of citizens' rights in a democratic society by providing citizens with an opportunity to be heard on the building or expansion of pipelines and associated facilities. As citizens become more and more concerned about their property and the land that surrounds them, citizen involvement in decision making about how industry activity affects their quality of life will become correspondingly more important. Regulatory agencies are committed to facilitate this engagement by flexible hearing procedures and by making use of evolving communication and information technology

Roles and contributions of pharmacists in regulatory affairs at the Centers for Disease Control and Prevention for public health emergency preparedness and response.

Science.gov (United States)

Bhavsar, Tina R; Kim, Hye-Joo; Yu, Yon

To provide a general description of the roles and contributions of three pharmacists from the Regulatory Affairs program (RA) at the Centers for Disease Control and Prevention (CDC) who are involved in emergency preparedness and response activities, including the 2009 pandemic influenza A (H1N1) public health emergency. Atlanta, GA. RA consists of a staff of nine members, three of whom are pharmacists. The mission of RA is to support CDC's preparedness and emergency response activities and to ensure regulatory compliance for critical medical countermeasures against potential threats from natural, chemical, biological, radiological, or nuclear events. RA was well involved in the response to the H1N1 outbreak through numerous activities, such as submitting multiple Emergency Use Authorization (EUA) requests to the Food and Drug Administration, including those for medical countermeasures to be deployed from the Strategic National Stockpile, and developing the CDC EUA website (www.cdc.gov/h1n1flu/eua). RA will continue to support current and future preparedness and emergency response activities by ensuring that the appropriate regulatory mechanisms are in place for the deployment of critical medical countermeasures from the Strategic National Stockpile against threats to public health.

Hijacking Complement Regulatory Proteins for Bacterial Immune Evasion.

Science.gov (United States)

Hovingh, Elise S; van den Broek, Bryan; Jongerius, Ilse

2016-01-01

The human complement system plays an important role in the defense against invading pathogens, inflammation and homeostasis. Invading microbes, such as bacteria, directly activate the complement system resulting in the formation of chemoattractants and in effective labeling of the bacteria for phagocytosis. In addition, formation of the membrane attack complex is responsible for direct killing of Gram-negative bacteria. In turn, bacteria have evolved several ways to evade complement activation on their surface in order to be able to colonize and invade the human host. One important mechanism of bacterial escape is attraction of complement regulatory proteins to the microbial surface. These molecules are present in the human body for tight regulation of the complement system to prevent damage to host self-surfaces. Therefore, recruitment of complement regulatory proteins to the bacterial surface results in decreased complement activation on the microbial surface which favors bacterial survival. This review will discuss recent advances in understanding the binding of complement regulatory proteins to the bacterial surface at the molecular level. This includes, new insights that have become available concerning specific conserved motives on complement regulatory proteins that are favorable for microbial binding. Finally, complement evasion molecules are of high importance for vaccine development due to their dominant role in bacterial survival, high immunogenicity and homology as well as their presence on the bacterial surface. Here, the use of complement evasion molecules for vaccine development will be discussed.

One-electron reduction of mitomycin c by rat liver : role of cytochrome P-450 and NADPH-cytochrome P-450 reductase

NARCIS (Netherlands)

Vromans, R M; Van de Straat, R; Groeneveld, M.; Vermeulen, N P

1. The role of cytochrome P-450 in the one-electron reduction of mitomycin c was studied in rat hepatic microsomal systems and in reconstituted systems of purified cytochrome P-450. Formation of H2O2 from redox cycling of the reduced mitomycin c in the presence of O2 and the alkylation of

A response strategy predicts acquisition of schedule-induced polydipsia in rats.

Science.gov (United States)

Gregory, James Gardner; Hawken, Emily R; Banasikowski, Tomek J; Dumont, Eric C; Beninger, Richard J

2015-08-03

Schedule-induced polydipsia (SIP) is excessive, non-regulatory drinking. We aimed to identify phenotypic learning traits representative of neural circuitry that underlies SIP and hypothesized that rats that are response-learners will be more susceptible in developing compulsive water drinking. Using the Y-maze, the rats were characterized as either place- or response-learners. They were exposed to the SIP protocol for a period of 21days. Subsequent histological staining for FosB/ΔFosB examined neuronal activation associated with SIP in several brain regions. The rats with a preference for a response-learning strategy were more likely to develop SIP than the rats using a place-learning strategy. Furthermore amphetamine sensitization, observed to increase SIP, also shifted learning strategy to a response-learning strategy. No differences were observed in FosB/ΔFosB expression between SIP and non-SIP rats in the dorsolateral striatum (DLS) and CA1 region of the hippocampus. However, SIP rats had greater FosB/ΔFosB expression in prefrontal cortex regions. The rats that develop SIP have a preference for response-learning strategies and increased neuronal activation in frontal cortical regions associated with habit formation and compulsion. Copyright © 2015 Elsevier Inc. All rights reserved.

The role of T regulatory cells in kidney transplantation

OpenAIRE

Urbanová, Anna

2011-01-01

T regulatory lymphocytes (Treg) belong to the CD4+ cell group. They are an essential part of the immunity system. Treg cells prevent from excessive activation of effector T cells and they keep the tolerance to the tissues of the body. They have high expression of CD25 and the transcription factor Foxp3. We distinguish two basic populations of Treg cells: natural Treg cells (nTreg) created in the thym and representing 5-10 % of all CD4+ cells, and induced Treg cells (iTreg), created from naive...

c-Fos downregulation positively regulates EphA5 expression in a congenital hypothyroidism rat model.

Science.gov (United States)

Song, Honghua; Zheng, Yuqin; Cai, Fuying; Ma, Yanyan; Yang, Jingyue; Wu, Youjia

2018-04-01

The EphA5 receptor is well established as an axon guidance molecule during neural system development and plays an important role in dendritic spine formation and synaptogenesis. Our previous study has showed that EphA5 is decreased in the developing brain of congenital hypothyroidism (CH) and the EphA5 promoter methylation modification participates in its decrease. c-Fos, a well-kown transcription factor, has been considered in association with brain development. Bioinformatics analysis showed that the EphA5 promoter region contained five putative c-fos binding sites. The chromatin immunoprecipitation (ChIP) assays were used to assess the direct binding of c-fos to the EphA5 promoter. Furthermore, dual-luciferase assays showed that these three c-fos protein binding sites were positive regulatory elements for EphA5 expression in PC12 cells. Moreover, We verified c-fos positively regulation for EphA5 expression in CH model. Q-PCR and Western blot showed that c-fos overexpression could upregulate EphA5 expression in hippocampal neurons of rats with CH. Our results suggest that c-fos positively regulates EphA5 expression in CH rat model.

The role of the central histaminergic receptors in the exercise-induced improvements of the spatial learning and memory in rats.

Science.gov (United States)

Taati, Majid; Moghaddasi, Mehrnoush; Esmaeili, Masoumeh; Pourkhodadad, Soheila; Nayebzadeh, Hassan

2014-10-31

While it is well known that exercise can improve cognitive performance, the underlying mechanisms are not fully understood. There is now evidence that histamine can modulate learning and memory in different types of behavioral tasks. The present study was designed to examine the possible role of central histamine H1 and H2 receptors in forced treadmill running-induced enhancement of learning and memory in rats. For this purpose the animals received intracerebroventricularly chlorpheniramine (H1 receptor blocker) and cimetidine (H2 receptor blocker) before each day of fifteen consecutive days of exercise. Then their learning and memory were tested on the water maze task using a four-trial-per-day for 4 consecutive days. A probe trial was performed after the last training day. Our data showed that cimetidine reversed the exercise-induced improvement in learning and memory in rats; however, this was not the case regarding chlorpheniramine. Our findings indicate that central histamine H2 receptors play an important role in mediating the beneficial effects of forced exercise on learning and memory. Copyright © 2014 Elsevier B.V. All rights reserved.

Uncovering transcription factor and microRNA risk regulatory pathways associated with osteoarthritis by network analysis.

Science.gov (United States)

Song, Zhenhua; Zhang, Chi; He, Lingxiao; Sui, Yanfang; Lin, Xiafei; Pan, Jingjing

2018-05-01

Osteoarthritis (OA) is the most common form of joint disease. The development of inflammation have been considered to play a key role during the progression of OA. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, deciphering these risk regulatory pathways is critical for elucidating the mechanisms underlying OA. We constructed an OA-specific regulatory network by integrating comprehensive curated transcription and post-transcriptional resource involving transcription factor (TF) and microRNA (miRNA). To deepen our understanding of underlying molecular mechanisms of OA, we developed an integrated systems approach to identify OA-specific risk regulatory pathways. In this study, we identified 89 significantly differentially expressed genes between normal and inflamed areas of OA patients. We found the OA-specific regulatory network was a standard scale-free network with small-world properties. It significant enriched many immune response-related functions including leukocyte differentiation, myeloid differentiation and T cell activation. Finally, 141 risk regulatory pathways were identified based on OA-specific regulatory network, which contains some known regulator of OA. The risk regulatory pathways may provide clues for the etiology of OA and be a potential resource for the discovery of novel OA-associated disease genes. Copyright © 2018 Elsevier Inc. All rights reserved.

Protective role of wheat germ oil on some biochemical parameters in irradiated rats

International Nuclear Information System (INIS)

Atia, A.I.; Darwish, M.M.; Sallam, M.H.

2006-01-01

Wheat germ oil is an organic nutritionally rich vegetable oil. It is an excellent source of vitamin E and essential fatty acids (octacosanol, linoleic and linolenic). The study confirmed the beneficial role of the used anti-oxidation agents as recommended radio-protectors due to their ability of scavenging free radicals produced by ionizing radiation. The efficacy of daily oral treatment of rats with wheat germ oil (10 mg/ Kg body wt) for 15 days to control many of the damaging effects of ionizing radiation when male rats were subjected to fractionated 8 Gy (2 Gy day after day) of gamma irradiation were studied. Blood samples were collected from animals at 10 and 15 days after treatment and/or exposure. In blood, the data obtained revealed that, radiation exposure caused significant increases in levels of malondialdehyde (MDA), triacylglycerol (TG), total cholesterol (TC), low-density lipoproteins (LDL) and glucose at the 10th day. Meanwhile, significant reduction in contents of total protein, albumin, globulins, high-density lipoproteins (HDL), vitamin E and glucose were recorded at the 15th day. Also, the majority of these parameters were estimated in liver tissues. The results revealed that administration of the natural product wheat germ oil partially ameliorated the radiation-induced biochemical disturbances. These effects were explained in the light of the presumed different mechanisms of wheat germ oil actions

Role of epinephrine for muscular glycogenolysis and pancreatic hormonal secretion in running rats

DEFF Research Database (Denmark)

Richter, Erik; Sonne, B; Christensen, N J

1981-01-01

-E, but not in DM-S rats. In spite of the differences in blood glucose, plasma insulin was the same in all groups and plasma glucagon increased identically in all running rats. Plasma FFA and liver glycogen were similar in all groups. In conclusion. in running rats, epinephrine exerts an acute enhancing effect...

High mobility group box associated with cell proliferation appears to play an important role in hepatocellular carcinogenesis in rats and humans.

Science.gov (United States)

Suzuki, Shugo; Takeshita, Kentaro; Asamoto, Makoto; Takahashi, Satoru; Kandori, Hitoshi; Tsujimura, Kazunari; Saito, Fumiyo; Masuko, Kazuo; Shirai, Tomoyuki

2009-01-31

To identify genes important in hepatocellular carcinogenesis, especially processes involved in malignant transformation, we focused on differences in gene expression between adenomas and carcinomas by DNA microarray. Eighty-one genes for which expression was specific in carcinomas were analyzed using Ingenuity Pathway Analysis software and Gene Ontology, and found to be associated with TP53 and regulators of cell proliferation. In the genes associated with TP53, we selected high mobility group box (HMGB) for detailed analysis. Immunohistochemistry revealed expression of HMGBs in carcinomas to be significantly higher than in other lesions among both human and rat liver, and a positive correlation between HMGBs and TP53 was detected in rat carcinomas. Knock-down of HMGB 2 expression in a rat hepatocellular carcinoma cell line by RNAi resulted in inhibition of cell growth, although no effects on invasion were evident in vitro. These results suggest that acquisition of malignant potential in the liver requires specific signaling pathways related to high cell proliferation associated with TP53. In particular, HMGBs appear to have an important role for progression and cell proliferation associated with loss of TP53 function in rat and in human hepatocarcinogenesis.

High mobility group box associated with cell proliferation appears to play an important role in hepatocellular carcinogenesis in rats and humans

International Nuclear Information System (INIS)

Suzuki, Shugo; Takeshita, Kentaro; Asamoto, Makoto; Takahashi, Satoru; Kandori, Hitoshi; Tsujimura, Kazunari; Saito, Fumiyo; Masuko, Kazuo; Shirai, Tomoyuki

2009-01-01

To identify genes important in hepatocellular carcinogenesis, especially processes involved in malignant transformation, we focused on differences in gene expression between adenomas and carcinomas by DNA microarray. Eighty-one genes for which expression was specific in carcinomas were analyzed using Ingenuity Pathway Analysis software and Gene Ontology, and found to be associated with TP53 and regulators of cell proliferation. In the genes associated with TP53, we selected high mobility group box (HMGB) for detailed analysis. Immunohistochemistry revealed expression of HMGBs in carcinomas to be significantly higher than in other lesions among both human and rat liver, and a positive correlation between HMGBs and TP53 was detected in rat carcinomas. Knock-down of HMGB 2 expression in a rat hepatocellular carcinoma cell line by RNAi resulted in inhibition of cell growth, although no effects on invasion were evident in vitro. These results suggest that acquisition of malignant potential in the liver requires specific signaling pathways related to high cell proliferation associated with TP53. In particular, HMGBs appear to have an important role for progression and cell proliferation associated with loss of TP53 function in rat and in human hepatocarcinogenesis

Effect of electromagnetic waves from mobile phone on immune status of male rats: possible protective role of vitamin D.

Science.gov (United States)

El-Gohary, Ola Ahmed; Said, Mona Abdel-Azeem

2017-02-01

There are considerable public concerns about the relationship between mobile phone radiation and human health. The present study assesses the effect of electromagnetic field (EMF) emitted from a mobile phone on the immune system in rats and the possible protective role of vitamin D. Rats were randomly divided into six groups: Group I: control group; Group II: received vitamin D (1000 IU/kg/day) orally; Group III: exposed to EMF 1 h/day; Group IV: exposed to EMF 2 h/day; Group V: exposed to EMF 1 h/day and received vitamin D (1000 IU/kg/day); Group VI: exposed to EMF 2 h/day and received vitamin D (1000 IU/kg/day). After 30 days of exposure time, 1 h/day EMF exposure resulted in significant decrease in immunoglobulin levels (IgA, IgE, IgM, and IgG); total leukocyte, lymphocyte, eosinophil and basophil counts; and a significant increase in neutrophil and monocyte counts. These changes were more increased in the group exposed to 2 h/day EMF. Vitamin D supplementation in EMF-exposed rats reversed these results when compared with EMF-exposed groups. In contrast, 7, 14, and 21 days of EMF exposure produced nonsignificant differences in these parameters among all experimental groups. We concluded that exposure to mobile phone radiation compromises the immune system of rats, and vitamin D appears to have a protective effect.

Radioprotective role of vitamin E and urea in irradiated albino rats

International Nuclear Information System (INIS)

Mahdy, A.M.; Elkashef, H.S.

1991-01-01

The present study evaluates the action of vitamin E and urea as chemical radioprotectors for controlling the radiation induced changes in creatine and creatinine levels in the forebrain of female rats subjected to 7 Gy whole body gamma irradiation. The levels of creating and creatinine in the forebrain of normal control rats were±704±22 to±724±23 and 11.053 0.119 to 11.553 0.127 /g fresh tissue; respectively. The applied radiation dose caused a significant increase in the creating level of about 15%, 18%, 13% and 41% on the first,third,seventh and tenth days post irradiation; respectively. At the same post irradiation days, the level of creatinine generally increased, but not to the same extent as creatine. The treatment of rats either with vitamin E or with urea pre radiation exposure caused a remarkable recovery in both creatine and creatinine levels in the forebrain of irradiated rats.The results are discussed in the high of discussed in the high of available literatures. 2 tab

Childhood cumulative risk and obesity: the mediating role of self-regulatory ability.

Science.gov (United States)

Evans, Gary W; Fuller-Rowell, Thomas E; Doan, Stacey N

2012-01-01

We tested whether early childhood risk exposures are related to weight gain in adolescence and evaluate an underlying mechanism, self-regulatory behavior, for the risk-obesity link. Cumulative risk exposure to 9 sociodemographic (eg, poverty), physical (eg, substandard housing), and psychosocial (eg, family turmoil) stressors was assessed in 244 nine-year-old children. BMI was calculated at age 9 and then 4 years later. At age 9, children's ability to delay gratification as an index of self-regulatory behavior was assessed. Path analyses were then estimated to evaluate our mediational model (Cumulative risk → Self-regulation → BMI) over a 4-year period in a prospective, longitudinal design. Nine-year-old children exposed to a greater accumulation of multiple risk factors show larger gains in adiposity over the next four year period, net of their initial BMI. These gains in BMI during early adolescence are largely accounted for by deteriorated self-regulatory abilities among children facing more cumulative risks. Early childhood risk exposure leads to larger gains in BMI in adolescence. Given the importance of childhood adiposity to the development of obesity later in life, understanding the underlying mechanisms that link early experience to weight gain is an essential task. Deficiencies in self-regulation in response to chronic stress appears to be an important agent in the obesity epidemic.

Transient inhibitory effect of methoxychlor on testicular steroidogenesis in rat: an in vivo study

Energy Technology Data Exchange (ETDEWEB)

Vaithinathan, S.; Saradha, B.; Mathur, P.P. [Pondicherry University, Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry (India)

2008-11-15

Methoxychlor, an organochlorine pesticide, has been reported to induce reproductive abnormalities in male reproductive tract. To get more insight into the mechanism(s) of gonadal toxicity provoked by methoxychlor, we investigated whether treatment with methoxychlor at low observed adverse effect level (LOAEL) would alter the activities of steroidogenic enzymes such as {delta}{sup 5}3{beta}-hydroxysteroid dehydrogenase (3{beta}-HSD) and {delta}{sup 5}17{beta}-hydroxysteroid dehydrogenase (17{beta}-HSD), the expression levels of steroidogenic acute regulatory (StAR) protein and androgen binding protein (ABP) in the testis of adult male rats. The experimental rats were exposed to a single dose of methoxychlor (50 mg/kg body weight) orally. The rats were killed at 0, 3, 6, 12, 24 and 72 h following treatment using anesthetic ether and testes were collected, processed and used to measure the activities of 3{beta}-HSD, 17{beta}-HSD, levels of hydrogen peroxide produced and the expression levels of StAR protein, and ABP. Methoxychlor administration resulted in a sequential reduction in the expression of StAR protein and activities of 3{beta}-HSD, 17{beta}-HSD with concomitant increase in the levels of hydrogen peroxide in the testis. These changes were significant between 6-12 h following treatment. The levels of ABP declined at 6-12 h following exposure to methoxychlor. The present study demonstrates transient effect of methoxychlor at LOAEL on testicular steroidogenesis and the possible role of hydrogen peroxide in mediating these effects. (orig.)

Design reviews from a regulatory perspective

International Nuclear Information System (INIS)

Foster, B.D.

1991-01-01

This paper presents views on the role of the licensing engineer in the design process with specific emphasis on design reviews and the automated information management tools that support design reviews. The licensing engineer is seen as an important member of a design review team. The initial focus of the licensing engineer during design reviews is shown to be on ensuring that applicable regulatory requirements are addressed by the design. The utility of an automated tool, such as a commitments management system, to support regulatory requirements identification is discussed. The next responsibility of the licensing engineer is seen as verifying that regulatory requirements are transformed into measurable performance requirements. Performance requirements are shown to provide the basis for developing detailed design review criteria. Licensing engineer input during design reviews is discussed. This input is shown to be especially critical in cases where review findings may impact application of regulatory requirements. The use of automated tools in supporting design reviews is discussed. An information structure is proposed to support design reviews in a regulated environment. This information structure is shown to be useful to activities beyond design reviews. Incorporation of the proposed information structure into the Licensing Support System is proposed

Role of antioxidant supplements in adult male albino rats intoxicated with methomyl

International Nuclear Information System (INIS)

Tawfik, S.M.F.M.; EI-Sherbiny, E.M.; Afifi, E.A.A.

2007-01-01

The present investigation was undertaken to evaluate and determine the protective effect of intraperitoneal administration of trace mineral selenium (Se) and antioxidant vitamins E and pantothenic acid (PA) to male albino rats intoxicated with methomyl pesticide. Four groups of rats were used in this study. The data obtained revealed that methomyl caused disturbances in liver functions, which were elucidated through ALT and AST levels, and in the levels of serum glucose and insulin. Also, the levels of serum total protein, albumin, total lipids, triglycerides, cholesterol and acethylcholinesterase activity were significantly changed from those found in control rats for different periods. Treatment of rats with the antioxidant supplements ameliorated to some extent most of the disturbances in the mentioned biochemical parameter levels. The data concluded that such antioxidants could provide some protection against pesticide-induced toxicity

Role of the agranular insular cortex in contextual control over cocaine-seeking behavior in rats.

Science.gov (United States)

Arguello, Amy A; Wang, Rong; Lyons, Carey M; Higginbotham, Jessica A; Hodges, Matthew A; Fuchs, Rita A

2017-08-01

Environmental stimulus control over drug relapse requires the retrieval of context-response-cocaine associations, maintained in long-term memory through active reconsolidation processes. Identifying the neural substrates of these phenomena is important from a drug addiction treatment perspective. The present study evaluated whether the agranular insular cortex (AI) plays a role in drug context-induced cocaine-seeking behavior and cocaine memory reconsolidation. Rats were trained to lever press for cocaine infusions in a distinctive context, followed by extinction training in a different context. Rats in experiment 1 received bilateral microinfusions of vehicle or a GABA agonist cocktail (baclofen and muscimol (BM)) into the AI or the overlying somatosensory cortex (SSJ, anatomical control region) immediately before a test of drug-seeking behavior (i.e., non-reinforced lever presses) in the previously cocaine-paired context. The effects of these manipulations on locomotor activity were also assessed in a novel context. Rats in experiment 2 received vehicle or BM into the AI after a 15-min reexposure to the cocaine-paired context, intended to reactivate context-response-cocaine memories and initiate their reconsolidation. The effects of these manipulations on drug context-induced cocaine-seeking behavior were assessed 72 h later. BM-induced pharmacological inactivation of the AI, but not the SSJ, attenuated drug context-induced reinstatement of cocaine-seeking behavior without altering locomotor activity. Conversely, AI inactivation after memory reactivation failed to impair subsequent drug-seeking behavior and thus cocaine memory reconsolidation. These findings suggest that the AI is a critical element of the neural circuitry that mediates contextual control over cocaine-seeking behavior.

Radiation and the regulatory landscape of neo2-Darwinism

International Nuclear Information System (INIS)

Rollo, C. David

2006-01-01

Several recently revealed features of eukaryotic genomes were not predicted by earlier evolutionary paradigms, including the relatively small number of genes, the very large amounts of non-functional code and its quarantine in heterochromatin, the remarkable conservation of many functionally important genes across relatively enormous phylogenetic distances, and the prevalence of extra-genomic information associated with chromatin structure and histone proteins. All of these emphasize a paramount role for regulatory evolution, which is further reinforced by recent perspectives highlighting even higher-order regulation governing epigenetics and development (EVO-DEVO). Modern neo 2 -Darwinism, with its emphasis on regulatory mechanisms and regulatory evolution provides new vision for understanding radiation biology, particularly because free radicals and redox states are central to many regulatory mechanisms and free radicals generated by radiation mimic and amplify endogenous signalling. This paper explores some of these aspects and their implications for low-dose radiation biology

Radiation and the regulatory landscape of neo2-Darwinism.

Science.gov (United States)

Rollo, C David

2006-05-11

Several recently revealed features of eukaryotic genomes were not predicted by earlier evolutionary paradigms, including the relatively small number of genes, the very large amounts of non-functional code and its quarantine in heterochromatin, the remarkable conservation of many functionally important genes across relatively enormous phylogenetic distances, and the prevalence of extra-genomic information associated with chromatin structure and histone proteins. All of these emphasize a paramount role for regulatory evolution, which is further reinforced by recent perspectives highlighting even higher-order regulation governing epigenetics and development (EVO-DEVO). Modern neo2-Darwinism, with its emphasis on regulatory mechanisms and regulatory evolution provides new vision for understanding radiation biology, particularly because free radicals and redox states are central to many regulatory mechanisms and free radicals generated by radiation mimic and amplify endogenous signalling. This paper explores some of these aspects and their implications for low-dose radiation biology.

Role of the Nuclear Regulatory Authority in the final disposal of radioactive wastes in Argentina

International Nuclear Information System (INIS)

Petraitis, E.J.; Siraky, G.; Novo, R.G.

1998-01-01

This paper describes briefly the legislative and regulatory framework in which the final disposal of radioactive wastes is carried out in Argentina. The activities of the Nuclear Regulatory Authority (ARN) and the applied approaches in relation to inspection of facilities, safety assessments of associated systems and collaboration in the matter with international agencies are also exposed. (author) [es

Role of the collecting duct in the exaggerated natriuresis of spontaneously hypertensive rats

International Nuclear Information System (INIS)

Francisco, L.L.; DiBona, G.F.

1980-01-01

To carry out a comparative examination of exaggerated natriumresis in the kidneys with essential hypertonia, 2 rat populations consisting of 11 spontaneously hypertensive rats (SHR) and, for controlling, 9 Wistar Kyoto rats (WKY), were chosen. In rats of the same age and weight, there was a significant arterial difference in the blood pressure. After the intravenous administration of isotonic NaCl, the urinary flow rate and sodium excretion are increased. The end-distal tubule-microinjection showed the 14 C-inulin recovery while that of 22 Na was significantly higher in SHR than in WKY. (APR) [de

Impact of melatonin supplementation in the rat spermatogenesis subjected to forced swimming exercise.

Science.gov (United States)

Moayeri, A; Mokhtari, T; Hedayatpour, A; Abbaszadeh, H-A; Mohammadpour, S; Ramezanikhah, H; Shokri, S

2018-04-01

Oxygen consumption increases many times during exercise, which can increase reactive oxygen species. It negatively affects fertility in male athletes. Melatonin is exerting a regulatory role at different levels of the hypothalamic-pituitary-gonadal axis. However, there is no evidence that the protective effects of melatonin persist after long duration exercise on the spermatogenesis. Therefore, this study was conducted to examine the impacts of melatonin on the testis following the administration of swimming exercise. Rats were separated into five different groups, including Control, sham M: received the solvent of melatonin, M: received melatonin, S: the exercise protocol, MS: received melatonin and the exercise protocol. After 8 weeks, animals were scarified and antioxidant enzymes levels of testes, spermatogenic cells apoptosis and sperm quality were measured. Swimming decreased all parameters of spermatozoa. Nevertheless, melatonin could significantly improve the progressive motility of spermatozoa in MS rats. Swimming caused an increased apoptosis of S group and decreased all antioxidant enzymes. Melatonin could drastically reduce apoptosis and increased these enzymes. Therefore, melatonin seems to induce the production of antioxidant enzymes of testicular tissues and diminish the extent of apoptotic changes caused by forced exercise on the testis, which can, in turn, ameliorate the sperm parameters. © 2017 Blackwell Verlag GmbH.

Assessing the role of regulatory bodies in managing health professional issues and errors in Europe.

Science.gov (United States)

Risso-Gill, Isabelle; Legido-Quigley, H; Panteli, D; Mckee, M

2014-08-01

This paper explores how medical regulatory bodies in nine European countries manage professional issues involving quality and patient safety, to build on limited existing information on procedures for regulating medical professionals in Europe. Twelve vignettes describing scenarios of concerns about standards of physicians were developed, covering clinical, criminal and administrative matters. Medical regulatory bodies in nine European countries were asked what action they would normally take in each situation. Their responses were related to their regulatory mandate. Responses varied greatly across participating countries. Regulators are always involved where patients are at risk or where a criminal offence is committed within the clinical setting. Non-criminal medical issues were generally handled by the employer, if any, at their discretion. Countries varied in the use of punitive measures, the extent to which they took an interest in issues arising outside professional activities, and whether they dealt with issues themselves or referred cases to another regulatory authority or took no action at all. There is little consistency across Europe on the regulation of medical professionals. There is considerable diversity in the range of topics that regulatory bodies oversee, with almost all covering health care quality and safety and others encompassing issues related to reputation, respect and trust. These inconsistencies have significant implications for professional mobility, patient safety and quality of care. © The Author 2014. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.

Regulatory T cells (Treg and Their Roles in Immune System with Respect to Immunopathological Disorders

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Kateřina Kondělková

2010-01-01

Full Text Available Regulatory T cells (Tregs are a specialized subpopulation of T cells that act to suppress immune response, thereby maintaining homeostasis and self-tolerance. It has been shown that Tregs are able to inhibit T cell proliferation and cytokine production and play a critical role in preventing autoimmunity. Different subsets with various functions of Treg cells exist. Tregs can be usually identified by flow cytometry. The most specific marker for these cells is FoxP3, which is localized intracellulary. Selected surface markers such as CD25high (high molecular density and CD127low (low molecular density could serve as surrogate markers to detect Tregs in a routine clinical practice. Dysregulation in Treg cell frequency or functions may lead to the development of autoimmune disease. Therapeutical Treg modulation is considered to be a promising therapeutical approach to treat some selected disorders, such as allergies, and to prevent allograft rejection.

Neuron-mediated generation of regulatory T cells from encephalitogenic T cells suppresses EAE

DEFF Research Database (Denmark)

Liu, Yawei; Teige, Ingrid; Birnir, Bryndis

2006-01-01

Neurons have been neglected as cells with a major immune-regulatory function because they do not express major histocompatibility complex class II. Our data show that neurons are highly immune regulatory, having a crucial role in governing T-cell response and central nervous system (CNS) inflamma......Neurons have been neglected as cells with a major immune-regulatory function because they do not express major histocompatibility complex class II. Our data show that neurons are highly immune regulatory, having a crucial role in governing T-cell response and central nervous system (CNS......) inflammation. Neurons induce the proliferation of activated CD4+ T cells through B7-CD28 and transforming growth factor (TGF)-beta1-TGF-beta receptor signaling pathways, resulting in amplification of T-cell receptor signaling through phosphorylated ZAP-70, interleukin (IL)-2 and IL-9. The interaction between...... neurons and T cells results in the conversion of encephalitogenic T cells to CD25+ TGF-beta1+ CTLA-4+ FoxP3+ T regulatory (Treg) cells that suppress encephalitogenic T cells and inhibit experimental autoimmune encephalomyelitis. Suppression is dependent on cytotoxic T lymphocyte antigen (CTLA)-4...

Evolution of cichlid vision via trans-regulatory divergence

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O’Quin Kelly E

2012-12-01

Full Text Available Abstract Background Phenotypic evolution may occur through mutations that affect either the structure or expression of protein-coding genes. Although the evolution of color vision has historically been attributed to structural mutations within the opsin genes, recent research has shown that opsin regulatory mutations can also tune photoreceptor sensitivity and color vision. Visual sensitivity in African cichlid fishes varies as a result of the differential expression of seven opsin genes. We crossed cichlid species that express different opsin gene sets and scanned their genome for expression Quantitative Trait Loci (eQTL responsible for these differences. Our results shed light on the role that different structural, cis-, and trans-regulatory mutations play in the evolution of color vision. Results We identified 11 eQTL that contribute to the divergent expression of five opsin genes. On three linkage groups, several eQTL formed regulatory “hotspots” associated with the expression of multiple opsins. Importantly, however, the majority of the eQTL we identified (8/11 or 73% occur on linkage groups located trans to the opsin genes, suggesting that cichlid color vision has evolved primarily via trans-regulatory divergence. By modeling the impact of just two of these trans-regulatory eQTL, we show that opsin regulatory mutations can alter cichlid photoreceptor sensitivity and color vision at least as much as opsin structural mutations can. Conclusions Combined with previous work, we demonstrate that the evolution of cichlid color vision results from the interplay of structural, cis-, and especially trans-regulatory loci. Although there are numerous examples of structural and cis-regulatory mutations that contribute to phenotypic evolution, our results suggest that trans-regulatory mutations could contribute to phenotypic divergence more commonly than previously expected, especially in systems like color vision, where compensatory changes in the

The Protective Role of Starch on Modulating Toxic Effects of Citrullus Colocynthis on Rat Liver and Intestine

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Neda Eskandarzade

2018-01-01

Full Text Available Background: Despite using Citrullus colocynthis on treatment of various diseases, serious gastrointestinal disorders like bleeding are reported. In Traditional Iranian Medicine (TIM, administering equal weights of starch with this plant is suggested to produce more tolerable preparations from it. Hence, we assessed histopathological changes in rat liver and intestine after using starch as corrective agent. Methods: We designed three experiments in Veterinary Medicine School of Shahid Bahonar University in Kerman, Iran in 2016. The procedure was applied in 2016 for 15 days. In the first experiment, group No. 2 and 3 received single daily dose of alcoholic pulp extract of C. colocynthis at 300 and 600 mg/kg extract consecutively. In the second experiment, group No. 4 and 5 received 300 and 600 mg/kg extract plus the same amount of starch consecutively. In the third experiment, group No. 6 and 7 received extract at 300 and 600 mg/kg plus the three times weight of starch consecutively. The live rats were euthanized and their liver and intestine were removed for histopathology examination. The samples were stained with hematoxyline-eosin (H&E. Results: Rats in all of the groups died from bleeding and diarrhea except for group No.6 that showed no symptoms seen in other rats. Microscopic examination of their intestine showed no histopathological lesions or other degenerative changes of the epithelium. Conclusion: Clearly further works in modern phytotherapy will be required to delineate the role of starch in reducing C. colocynthis toxicity. Consumption of adequate weight of starch with the toxic dose of C. colocynthis make it safe for digestive system but could not prevent necrotic changes in the liver.

T-regulatory cells in chronic rejection versus stable grafts.

Science.gov (United States)

Al-Wedaie, Fatima; Farid, Eman; Tabbara, Khaled; El-Agroudy, Amgad E; Al-Ghareeb, Sumaya M

2015-04-01

Studying regulatory T cells in kidney allograft acceptance versus chronic rejection may help in the understanding of more mechanisms of immune tolerance and, in the future, may enable clinicians to induce immune tolerance and decrease the use of immunosuppressive drugs. The aim of the current study was to evaluate regulatory T cells in kidney transplant patients with stable graft versus transplant with biopsy-proven chronic rejection. The 3 groups that were studied included: kidney transplanted patients with no rejection episodes (n = 43); transplanted patients with biopsy-proven renal rejection (n = 27); and healthy age-matched nontransplanted individuals as controls (n = 42).The percentage of regulatory T cells (CD4+CD25+Foxp3+) in blood was determined by flow cytometry. The regulatory T cell percentage was significantly lower in chronic rejection patients than control or stable graft groups. No significant difference was observed in regulatory T cell percentage between the stable graft and control groups. In the stable graft group, patients on rapamycin had a significantly higher regulatory T cell percentage than patients on cyclosporine. No effect of donor type, infection, or duration after transplant was observed on regulatory T cell percentage. The results of the current study are consistent with previous studies addressing the function of regulatory T cells in inducing immunotolerance after kidney transplant. Considering the established role of regulatory T cells in graft maintenance and our observation of high regulatory T cell percentage in patients receiving rapamycin than cyclosporine, we recommend including rapamycin when possible in immunosuppressive protocols. The findings from the current study on the chronic rejection group support ongoing research of having treatment with regulatory T cells, which may constitute a novel, efficient antirejection therapy in the future.

Regulatory activities

International Nuclear Information System (INIS)

2001-01-01

This publication, compiled in 8 chapters, presents the regulatory system developed by the Nuclear Regulatory Authority (NRA) of the Argentine Republic. The following activities and developed topics in this document describe: the evolution of the nuclear regulatory activity in Argentina; the Argentine regulatory system; the nuclear regulatory laws and standards; the inspection and safeguards of nuclear facilities; the emergency systems; the environmental systems; the environmental monitoring; the analysis laboratories on physical and biological dosimetry, prenatal irradiation, internal irradiation, radiation measurements, detection techniques on nuclear testing, medical program on radiation protection; the institutional relations with national and international organization; the training courses and meeting; the technical information

Expression and role of 5-HT7 receptor in brain and intestine in rats with irritable bowel syndrome.

Science.gov (United States)

Zou, Bai-cang; Dong, Lei; Wang, Yan; Wang, Sheng-hao; Cao, Ming-bo

2007-12-05

The 5-hydroxytryptamine7 receptor (5-HT(7) receptor, 5-HT(7)R) plays an important role in the regulation of smooth muscle relaxation and visceral sensation and might be involved in the pathogenesis of the gastrointestinal dyskinesia, abdominal pain and visceral paresthesia in irritable bowel syndrome (IBS). The aim of this study was to investigate the role of the 5-HT(7) receptor in the pathogenesis of IBS. A rat model of irritable bowel syndrome with diarrhea (IBS-D) was established by colonic instillation of acetic acid and restraint stress. A rat model with irritable bowel syndrome with constipation (IBS-C) was established by stomach irrigated with 0 - 4 degrees C cool water daily for 14 days. The content and distribution of 5-HT in the brain and gut were examined by immunohistochemistry and the mRNA expression of the 5-HT(7) receptor was determined by fluorescent quantitative reverse transcription polymerase chain reaction. The accumulation of cyclic adenosine monophosphate (cAMP) in all the same tissues was measured by radioimmunity. The models of IBS were reliable by identification. The immunohistochemistry results showed that there were significantly more 5-HT positive cells in the IBS-D group than in the control group in the hippocampus, hypothalamus, jejunum, ileum, proximate colon and distal colon (P intestine is related to the IBS pathogenesis. The up-regulated expression of the 5-HT(7) receptor in the brain and colon might play an important role in the pathogenesis of IBS-C.

Regulatory philosophy and requirements for radiation control in Canadian uranium mine-mill facilities

International Nuclear Information System (INIS)

Dory, A.B.

1981-10-01

With the point made that radiation exposure is one of the health hazards of uranium mining and accordingly has to be controlled, the Canadian regulatory philosophy is outlined as it pertains to the uranium mining industry. Two extremes in regulatory approach are examined, and the joint regulatory process is explained. Two examples of poor management performance are given, and the role of mine unions in the regulatory process is touched upon. The development of new regulations to cover ventilation and employee training is sketched briefly. The author concludes with a general expression of objectives for the eighties which include improved personal dosimetry

Studies on the role of serotonin receptor subtypes in the effect of sibutramine in various feeding paradigms in rats

Science.gov (United States)

Grignaschi, G; Fanelli, E; Scagnol, I; Samanin, R

1999-01-01

The effect of the 5-hydroxytryptamine (5-HT) and noradrenaline (NA) reuptake inhibitor sibutramine was studied in food deprived, neuropeptide Y (NPY)- or muscimol-injected rats. Sibutramine dose-dependently reduced feeding caused by food-deprivation (ED50=5.1±0.8 mg kg−1) or by NPY injection into the paraventricular nucleus of the hypothalamus (ED50=6.0±0.5 mg kg−1). The increase in food intake caused by muscimol injected into the dorsal raphe was not modified by sibutramine (1–10 mg kg−1). The hypophagic effect of 5.1 mg kg−1 sibutramine in food-deprived rats was studied in rats pretreated with different serotonin receptor antagonists. Metergoline (non-selective, 0.3 and 1.0 mg kg−1), ritanserin (5-HT2A/2C, 0.5 and 1.0 mg kg−1) and GR127935 (5-HT1B/1D, 0.5 and 1.0 mg kg−1) did not modify the hypophagic effect of sibutramine, while SB206553 (5-HT2B/2C, 5 and 10 mg kg−1) slightly but significantly reduced it (Fint(2.53)=3.4; Psibutramine in NPY-injected rats was not modified by GR127935 (1.0 mg kg−1). The results suggest that, with the possible exception of a partial involvement of 5-HT2B/2C receptors in sibutramine's hypophagia in food-deprived rats, 5-HT1 and 5-HT2 receptor subtypes do not play an important role in the hypophagic effect of sibutramine, at least in the first 2 h after injection. PMID:10455265

Role of Mas Receptor Antagonist A799 in Renal Blood Flow Response to Ang 1-7 after Bradykinin Administration in Ovariectomized Estradiol-Treated Rats

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Aghdas Dehghani

2015-01-01

Full Text Available Background. The accompanied role of Mas receptor (MasR, bradykinin (BK, and female sex hormone on renal blood flow (RBF response to angiotensin 1-7 is not well defined. We investigated the role of MasR antagonist (A779 and BK on RBF response to Ang 1-7 infusion in ovariectomized estradiol-treated rats. Methods. Ovariectomized Wistar rats received estradiol (OVE or vehicle (OV for two weeks. Catheterized animals were subjected to BK and A799 infusion and mean arterial pressure (MAP, RBF, and renal vascular resistance (RVR responses to Ang 1-7 (0, 100, and 300 ng kg−1 min−1 were determined. Results. Percentage change of RBF (%RBF in response to Ang1-7 infusion increased in a dose-dependent manner. In the presence of BK, when MasR was not blocked, %RBF response to Ang 1-7 in OVE group was greater than OV group significantly (P<0.05. Infusion of 300 ng kg−1 min−1 Ang 1-7 increased RBF by 6.9±1.9% in OVE group versus 0.9±1.8% in OV group. However when MasR was blocked, %RBF response to Ang 1-7 in OV group was greater than OVE group insignificantly. Conclusion. Coadministration of BK and A779 compared to BK alone increased RBF response to Ang 1-7 in vehicle treated rats. Such observation was not seen in estradiol treated rats.

The pleasures and pains of distinct self-construals: the role of interdependence in regulatory focus.

Science.gov (United States)

Lee, A Y; Aaker, J L; Gardner, W L

2000-06-01

Regulatory focus theory distinguishes between self-regulatory processes that focus on promotion and prevention strategies for goal pursuit. Five studies provide support for the hypothesis that these strategies differ for individuals with distinct self-construals. Specifically, individuals with a dominant independent self-construal were predicted to place more emphasis on promotion-focused information, and those with a dominant interdependent self-construal on prevention-focused information. Support for this hypothesis was obtained for participants who scored high versus low on the Self-Construal Scale, participants who were presented with an independent versus interdependent situation, and participants from a Western versus Eastern culture. The influence of interdependence on regulatory focus was observed in both importance ratings of information and affective responses consistent with promotion or prevention focus.

A role for galanin N-terminal fragment (1-15) in anxiety- and depression-related behaviors in rats.

Science.gov (United States)

Millón, Carmelo; Flores-Burgess, Antonio; Narváez, Manuel; Borroto-Escuela, Dasiel O; Santín, Luis; Parrado, Concepción; Narváez, José Angel; Fuxe, Kjell; Díaz-Cabiale, Zaida

2014-10-31

Galanin (GAL) plays a role in mood regulation. In this study we analyzed the action of the active N-terminal fragment [GAL(1-15)] in anxiety- and depression-related behavioral tests in rats. The effect of GAL(1-15) was analyzed in the forced swimming test, tail suspension test, open field test, and light/dark test. The proximity of GAL1 and GAL2 receptors was examined with the proximity ligation assay (PLA). We tested the GAL receptors involved in GAL(1-15) effects with the GAL2 receptor antagonist M871 and with an in vivo model of siRNA GAL2 receptor knockdown or siRNA GAL1 receptor knockdown rats. The effects of GAL(1-15) were also studied in the cell line RN33B. GAL(1-15) induced strong depression-like and anxiogenic-like effects in all the tests. These effects were stronger than the ones induced by GAL. The involvement of the GAL2 receptor was demonstrated with M871 and with the siRNA GAL2 receptor knockdown rats. The PLA indicated the possible existence of GAL1 and GAL2 heteroreceptor complexes in the dorsal hippocampus and especially in the dorsal raphe nucleus. In the siRNA GAL1 receptor knockdown rats the behavioral actions of GAL(1-15) disappeared, and in the siRNA GAL2 receptor knockdown rats the reductions of the behavioral actions of GAL(1-15) was linked to a disappearance of PLA. In the cell line RN33B, GAL(1-15) decreased 5-HT immunoreactivity more strongly than GAL. Our results indicate that GAL(1-15) exerts strong depression-related and anxiogenic-like effects and may give the basis for the development of drugs targeting GAL1 and GAL2 heteroreceptor complexes in the raphe-limbic system for the treatment of depression and anxiety. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Integrating microRNA and mRNA expression profiles in response to radiation-induced injury in rat lung

International Nuclear Information System (INIS)

Xie, Ling; Zhou, Jundong; Zhang, Shuyu; Chen, Qing; Lai, Rensheng; Ding, Weiqun; Song, ChuanJun; Meng, XingJun; Wu, Jinchang

2014-01-01

Exposure to radiation provokes cellular responses, which are likely regulated by gene expression networks. MicroRNAs are small non-coding RNAs, which regulate gene expression by promoting mRNA degradation or inhibiting protein translation. The expression patterns of both mRNA and miRNA during the radiation-induced lung injury (RILI) remain less characterized and the role of miRNAs in the regulation of this process has not been studied. The present study sought to evaluate miRNA and mRNA expression profiles in the rat lung after irradiation. Male Wistar rats were subjected to single dose irradiation with 20 Gy using 6 MV x-rays to the right lung. (A dose rate of 5 Gy/min was applied). Rats were sacrificed at 3, 12 and 26 weeks after irradiation, and morphological changes in the lung were examined by haematoxylin and eosin. The miRNA and mRNA expression profiles were evaluated by microarrays and followed by quantitative RT-PCR analysis. A cDNA microarray analysis found 2183 transcripts being up-regulated and 2917 transcripts down-regulated (P ≤ 0.05, ≥2.0 fold change) in the lung tissues after irradiation. Likewise, a miRNAs microarray analysis indicated 15 miRNA species being up-regulated and 8 down-regulated (P ≤ 0.05). Subsequent bioinformatics anal -yses of the differentially expressed mRNA and miRNAs revealed that alterations in mRNA expression following irradiation were negatively correlated with miRNAs expression. Our results provide evidence indicating that irradiation induces alterations of mRNA and miRNA expression in rat lung and that there is a negative correlation of mRNA and miRNA expression levels after irradiation. These findings significantly advance our understanding of the regulatory mechanisms underlying the pathophysiology of radiation-induced lung injury. In summary, RILI does not develop gradually in a linear process. In fact, different cell types interact via cytokines in a very complex network. Furthermore, this study suggests that

Possible role of Arthrospira platensis in reversing oxidative stress-mediated liver damage in rats exposed to lead.

Science.gov (United States)

Khalil, Samah R; Elhady, Walaa M; Elewa, Yaser H A; Abd El-Hameed, Noura E; Ali, Sozan A

2018-01-01

Environmental pollutants, particularly metallic elements, mobilized and released into the environment, eventually accumulate in the food chain and thus pose a serious threat to human and animal health. In the present study, the role of Arthrospira (Spirulina platensis; SP) as a protector against oxidative stress-mediated liver damage induced by an exposure to lead acetate (LA; as a metallic pollutant) was assessed. To achieve this aim, rats were orally administered with 300 mg/kg bw SP for 15 days, before and concurrently with an intraperitoneal injection of 50 mg/kg bw LA (6 injections throughout 15 days). As a result, co-administration of SP with LA reduced the amount of lead that accumulated in both blood and liver tissue of the exposed rats and minimized the increased levels of lipid peroxidation, protein oxidation, DNA oxidative damage, and liver enzyme endpoints. In addition, because of SP administration, the levels of depleted biomarkers of antioxidant status and total antioxidant capacity in LA-exposed rats improved. Moreover, SP protected the liver tissue against the changes caused by LA exposure and also decreased the reactivity of HSP70 in the cytoplasm of hepatocytes. Collectively, our data suggest that SP has a potential use as a food supplement in the regions highly polluted with heavy metals such as lead. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Protective role of probiotic lactic acid bacteria against dietary fumonisin B1-induced toxicity and DNA-fragmentation in sprague-dawley rats.

Science.gov (United States)

Khalil, Ashraf A; Abou-Gabal, Ashgan E; Abdellatef, Amira A; Khalid, Ahmed E

2015-08-18

The genus Fusarium, especially F. verticillioides and F. proliferatum, has been found in several agricultural products worldwide, especially in maize. Regardless the occurrence of symptoms, the presence of Fusarium in maize constitutes an imminent risk due to its ability to produce fumonisins, mycotoxins with proven carcinogenic effect on rats, swine, and equines and already classified as possible carcinogens to humans. The toxicity of incremental levels of fumonisin B1 (FB1), that is, 50, 100, and 200 mg FB1/kg diet, and the role of Lactobacillus delbrueckii subsp. lactis DSM 20076 (LL) and Pediococcus acidilactici NNRL B-5627 (PA) supplementation in counteracting the FB1 effects in intoxicated rats were monitored over a period of 4 weeks. Effects on the feed intake and body weight gain were noticed. A significant (p ≤ 0.05) increase in the level of liver and kidney functions markers and DNA fragmentation was also noticed in rat groups T100 and T200. The lactic acid bacteria (LAB) supplementation could bring back the normal serum biochemical parameters in rats fed on fumonisin B1-contaminated diets (T50 and T100) compared to FB1-treated groups. In rats of high-dosage dietary groups supplemented with LAB (T200-LL and T200-PA), the supplementation reduced the serum activity levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and creatinine by 11.3, 11.9, 32, and 20%, respectively. DNA fragmentations were observed in the rat group treated with 200 mg FB1 after 3 weeks, while fragmentation was noticed in treated groups with 100 and 200 mg FB1 after 4 weeks. No DNA fragmentation was apparent in FB1-treated rats co-administered the LL or PA strain. These results suggest that in male rats consuming diets containing FB1, there is a time- and dose-dependent increase in serum enzyme activities and DNA lesions. Moreover, Lb. delbrueckii subsp. lactis (LL) and P. acidilactici (PA) strains have a protective effect

Regulatory mechanism of endothelin receptor B in the cerebral arteries after focal cerebral ischemia

DEFF Research Database (Denmark)

Grell, Anne-Sofie; Thigarajah, Rushani; Edvinsson, Lars

2014-01-01

BACKGROUND AND PURPOSE: Increased expression of endothelin receptor type B (ETBR), a vasoactive receptor, has recently been implied in the reduced cerebral blood flow and exacerbated neuronal damage after ischemia-reperfusion (I/R). The study explores the regulatory mechanisms of ETBR to identify...... drug targets to restore normal cerebral artery contractile function as part of successful neuroprotective therapy. METHODS: We have employed in vitro methods on human and rat cerebral arteries to study the regulatory mechanisms and the efficacy of target selective inhibitor, Mithramycin A (Mit...... the ETBR mRNA and protein levels. It also significantly reduced the ETBR mediated cerebrovascular contractility. Detailed analysis indicated that ERK1/2 mediated phosphorylation of Sp1 might be essential for ETBR transcription. CONCLUSION: Transcription factor Sp1 regulates the ETBR mediated...

Regulatory issues in the maintenance of Argentine nuclear power plants

International Nuclear Information System (INIS)

Castro, E.; Caruso, G.

1997-01-01

The influence of maintenance activities upon nuclear safety and their relevance as means to detect and prevent aging make them play an outstanding role among the fields of interest of the Argentine nuclear regulatory body (ENREN). Such interest is reinforced by the fact that the data obtained during maintenance are used - among other - as inputs in the Probabilistic Safety Analyses required for those nuclear power plants. This paper provides a brief description of the original requirements by the regulatory body concerning maintenance, of the factors that led to review the criteria involved in such requirements and of the key items identified during the reviewing process. The latter shall be taken into account in the maintenance regulatory policy, for the consequent issue of new requirements from the utilities and for the eventual publication of a specific regulatory standard. (author)

Differential Changes of Aorta and Carotid Vasodilation in Type 2 Diabetic GK and OLETF Rats: Paradoxical Roles of Hyperglycemia and Insulin

Directory of Open Access Journals (Sweden)

Mei-Fang Zhong

2012-01-01

Full Text Available We investigated large vessel function in lean Goto-Kakizaki diabetic rats (GK and Otsuka Long-Evans Tokushima Fatty diabetic rats (OLETF with possible roles of hyperglycemia/hyperosmolarity and insulin. Both young and old GK showed marked hyperglycemia with normal insulin level and well-preserved endothelium-dependent and endothelium-independent vasodilation in aorta and carotid artery. There were significant elevations in endothelial/inducible nitric oxide synthase (eNOS/iNOS and inducible/constitutive heme oxygenase (HO-1/HO-2 in GK. The endothelium-dependent vasodilation in GK was inhibited partly by NOS blockade and completely by simultaneous blocking of HO and NOS. In contrast, OLETF showed hyperinsulinemia and mild hyperglycemia but significant endothelium dysfunction beginning at early ages with concomitantly reduced eNOS. Insulin injection corrected hyperglycemia in GK but induced endothelium dysfunction and intima hyperplasia. Hyperglycemia/hyperosmolarity in vitro enhanced vessel eNOS/HO. We suggest that hyperinsulinemia plays a role in endothelium dysfunction in obese diabetic OLETF, while hyperglycemia/hyperosmolarity-induced eNOS/HO upregulation participates in the adaptation of endothelium function in lean diabetic GK.

The effects of freeze-dried Ganoderma lucidum mycelia on a recurrent oral ulceration rat model.

Science.gov (United States)

Xie, Ling; Zhong, Xiaohong; Liu, Dongbo; Liu, Lin; Xia, Zhilan

2017-12-01

Conventional scientific studies had supported the use of polysaccharides and β-glucans from a number of fungi, including Ganoderma lucidum for the treatment of recurrent oral ulceration (ROU). Our aim of the present study was to evaluate whether freeze-dried powder from G. lucidum mycelia (FDPGLM) prevents ROU in rats. A Sprague-Dawley (SD) rat model with ROU was established by autoantigen injection. The ROU rats were treated with three different dosages of FDPGLM and prednisone acetate (PA), and their effects were evaluated according to the clinical therapeutic evaluation indices of ROU. High-dose FDPGLM induced significantly prolonged total intervals and a reduction in the number of ulcers and ulcer areas, thereby indicating that the treatment was effective in preventing ROU. Enzyme-linked immunosorbent assay (ELISA) showed that high-dose FDPGLM significantly enhanced the serum transforming growth factor-β1 (TGF-β1) levels, whereas reduced those of interleukin-6 (IL-6) and interleukin-17 (IL-17). Flow cytometry (FCM) showed that the proportion of CD4 + CD25 + Foxp3 + (forkhead box P3) regulatory T cells (Tregs) significantly increased by 1.5-fold in the high-dose FDPGLM group compared to that in the rat model group (P < 0.01). The application of middle- and high-dose FDPGLM also resulted in the upregulation of Foxp3 and downregulation of retinoid-related orphan receptor gamma t(RORγt) mRNA. High-dose FDPGLM possibly plays a role in ROU by promoting CD4 + CD25 + Foxp3 + Treg and inhibiting T helper cell 17 differentiation. This study also shows that FDPGLM may be potentially used as a complementary and alternative medicine treatment scheme for ROU.

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