To see the other types of publications on this topic, follow the link: Rats; Human.
Dissertations / Theses on the topic 'Rats; Human'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Rats; Human.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Todd, Dorothy A. "A study of pyretics in rats and mice." Thesis, University of Aberdeen, 1986. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU004772.
Full textAbstract:
In this study, the suitability of rodents for the detection and assay of microbial pyrogens was investigated and the pathophysiology of the 'yeast rat' model, currently used for screening antipyretic drugs, was documented. Mice do not consistently develop pyrexia following systemic injections of bacterial endotoxin (BE). These findings are in contrast to the dose-dependent hyperthermia observed in mice following intrahypothalamic injections of prostaglandin E2 (PGE2), a putative central mediator of pyrexia. Hyperthermia was associated with a decrease in skin temperature or an increase in oxygen consumption depending on the ambient temperature. These results suggest that mice have the ability to co-ordinate thermoregulatory mechanisms to raise their body temperature. Unlike PGE2, BE injected into the preoptic and anterior hypothalamic nuclei did not consistently raise body temperature in mice. This suggests that the failure of systemically administered endotoxin to consistently induce pyrexia is not due to insufficient quantities of pyrogen reaching the central thermoregulatory centres. However, central injections of BE may not mimic the central events occurring during the development of pyrexia as a result of peripheral infection. The inconsistent effect of systemic endotoxin on body temperature in mice in this study suggests that this species is unsuitable for the assay of microbial pyrogens. Unlike mice, rats developed pyrexia following systemic injections of BE; the doses of BE required were at least 100 fold greater than those reported for the rabbit (see General Introduction), rendering rats less sensitive than other species as models for the detection and assay of microbial pyrogens. Yeast also raised body temperature in rats. Pyrexia coincided with the acute phase of a yeast-induced inflammatory response. An abscess was formed at the site of injection; this subsequently developed into a chronic granuloma. The pyrogenic response to yeast was not directly attributable to inflammatory mediators associated with increased vascular permeability, phagocytosis or granuloma formation. It is unlikely therefore, that antipyretic activity displayed by drugs tested in the 'yeast rat' model is due to peripheral anti-inflammatory activity. However, results from this study suggest that BE may be a suitable replacement for yeast as a pyrexic challenge in rats for screening antipyretics. BE would be less emotive than yeast and would not induce a chronic granuloma. No endogenous pyrogenic mediators were detected in yeast-treated rats. No endogenous pyrogen (EP) was obtained from rat blood or peritoneal exudates in vitro. Either rats do not release detectable EP or attempts in this study to activate rat white blood cells in vitro do not mimic events occurring in vivo. Athymic rats injected with yeast developed pyrexia which suggests that Interleukin 1 is not an endogenous pyrogenic mediator unless its release is independent of T-cell derived lymphokines. Changes in thermoregulatory behaviour following pyrogen administration in rats were studied as an alternative method for assaying pyrogens. Detectable changes in thermoregulatory behaviour can precede but do not always accompany changes in body temperature in rats. Therefore, body temperature was considered to be a more reliable measure of thermoregulatory changes than behaviour in this study.
2
Mabandla, Musa Vuyisile. "Exercise induced neuroprotection in spontaneuosly running rats." Doctoral thesis, University of Cape Town, 2007. http://hdl.handle.net/11427/3263.
Full textAbstract:
Includes bibliographical references (p. 182-205).We investigated the effects of voluntary exercise on neuroprotection after unilateral lesions with 6-hydroxydopamine. Rats were divided into runners (had access to running wheel) and non-runners (their running wheels were immobilised). Two weeks after injection of the neurotoxin, the rats were injected with apomorphine and the number of ipsilateral and contralateral rotations was counted with contralateral rotations of greater than 150 considered to represent striatal dopamine neuron destruction of 70% or above.
3
Katō, Norihiro. "Finding genes that cause essential hypertension." Thesis, University of Oxford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337601.
Full text
4
Kruszynska, Y. T. "Metabolic effects of portal and peripheral insulin delivery in streptozotocin diabetic rats." Thesis, University of Newcastle Upon Tyne, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.356789.
Full text
5
Rupanagudi, S. R. "Pathogenesis of thyroid enlargement and involution in rats treated with antithyroid compounds." Thesis, University of Surrey, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383301.
Full text
6
Conliffe, Phyllis R. (Phyllis Rowena). "Effects of maternal diabetes on fetal development in rats." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=39344.
Full textAbstract:
The mechanisms underlying the high incidence of fetal abnormalities including fetal lung immaturity during maternal diabetes are not fully understood. Utilizing streptozotocin-diabetic rats as the model, I have examined the role of fetal hyperglycemia and hyperinsulinemia and other factors on fetal adrenal and lung functions in culture. Insulin and glucose did not alter fetal adrenal and lung cell proliferation and adrenal corticosterone output. On the other hand, a novel protein-bound, low molecular weight non-proteinaceous cytotoxic factor was detected in the serum of diabetic animals. In addition, a novel protein with cytostatic activity was found in fetal lungs, the concentration of which increased during diabetes. Partial amino acid sequence and Western Blot analysis revealed this protein to be similar to histone H2B. An extra-nuclear role is suggested for this protein because it appears to be present in the microsomal fraction of fetal lungs. It is concluded that fetal lung immaturity during diabetes may be contributed by cytotoxic and cytostatic factors contained in the serum and fetal lungs, respectively.
7
Wan, J. M.-F. "The effect of E. coli endotoxin on the metabolic responses of Wistar rats." Thesis, University of Southampton, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376188.
Full text
8
Carter, Katharine Christine. "The specificity of the host's immunological response to invasive nematode parasites of rats." Thesis, University of Edinburgh, 1986. http://hdl.handle.net/1842/13330.
Full text
9
Hulme-Beaman, Ardern. "Exploring the human-mediated dispersal of commensal small mammals using dental morphology : Rattus exulans and Rattus rattus." Thesis, University of Aberdeen, 2014. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=215116.
Full textAbstract:
A handful of rat species are among the most pervasive mammal species across the globe, primarily because of their close relationship with humans. The processes involved in this relationship, commensalism, are described in detail. Two rat species, Rattus rattus and Rattus exulans, are the focus of this thesis and their biology and taxonomy are described and discussed. Their modern distributions are the direct result of some of the earliest and most extensive human migration events in human history. The archaeology of the Pacific and Indian Oceans is described and migration vectors and spheres of interaction are identified. These possible patterns of human migration and exchange networks provide testable hypotheses that can be investigated using the subject rat species as proxies for long distance human movement. Modern and archaeological tooth samples of R. exulans and modern samples of R. rattus are analysed using geometric morphometrics. The results reveal important aspects of human migration and differences between these species' biology. R. exulans was likely to have been transported out of Island Southeast Asia at a very early date. Human colonisation of the Pacific occurred in a series of complex pulses and pauses that are clearly reflected in the R. exulans data. For the first time it is possible to demonstrate, within one dataset, the multiple origins and directions of colonisation across the Pacific. The R. rattus data provides a striking comparison, showing very different results that allude to a different level of modern gene-‐ flow and therefore a difference in behaviour and biology. The results provide a framework for comparison with future archaeological material. The results presented and hypotheses raised have immediate application to existing archaeological material and areas of interest. Further commensal species should be examined following similar lines of questioning as applied here.
10
El-Shannawy, I. E. S. "Post-mortem changes in in-situ parenchyma cells in rats and humans." Thesis, University of Leeds, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.355699.
Full text
11
Amevor, Solomon Francis. "Renal physiology and aluminum biokinetics : studies in laboratory rats and human subjects /." [S.l.] : [s.n.], 1995. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=10972.
Full text
12
Shaw, Christine. "Temporal memory in human amnesic subjects and rats with specific brain lesions." Thesis, Durham University, 1992. http://etheses.dur.ac.uk/5755/.
Full textAbstract:
Temporal processing was assessed in a group of alcoholic Korsakoff subjects, post viral encephalitic subjects, alcoholic control and normal control subjects. Subjects were tested on their ability to reproduce and estimate intervals of time ranging from 3 to 96 seconds. Also, a computerised analogue of the fixed interval procedure used with animals was designed and used to test subjects' estimations of intervals of 15 and 30 seconds. Memory for temporal order was also assessed using an object recency task which also incorporated a recognition memory test. It was found that Korsakoff subjects were impaired at all intervals both in the temporal estimation tests and the fixed interval procedure compared to the alcoholic control subjects, whereas the post-encephalitic subjects performed similarly to the normal control group. Both amnesic groups, however, were severely impaired on the test of temporal order memory. The results suggested that these two aspects of temporal processing were unrelated and that neither was related to severity of amnesia. There was no evidence to support the view that amnesic subjects' temporal order deficits are a result of frontal lobe dysfunction, but the temporal duration judgments correlated significantly with tests of cognitive estimation suggesting a contribution of frontal lobe function to estimation of temporal duration. Temporal order memory was assessed in rats with either radiofrequency lesions of the fornix or aspiration lesions of medial prefrontal cortex using a delayed non-matching to sample procedure. Neither lesion group was impaired on this test of recency memory although both were impaired on a spatial non-matching task. These results are discussed in relation to previous animal studies and their implications for human amnesia.
13
Xu, Li Jing. "Oxygen and lung development in newborn rats and chick embryos." Thesis, McGill University, 1988. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=61955.
Full text
14
Ávila, Vanessa Perlin Ferraro de. "Efeito dos ruídos gerados por atividade humana em ratas wistar: avaliação da natimortalidade e desenvolvimento ponderal dos neonatos." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2012. http://hdl.handle.net/10183/48965.
Full textAbstract:
Animais de laboratório estão sujeitos a uma variedade de ruídos diários que podem afetar seu bem estar, havendo estudos que apontam o trabalho humano nas salas de animais como uma importante fonte de ruídos com intensidades e frequências variáveis capazes de causar alterações comportamentais e fisiológicas nesses animais. Este trabalho teve como objetivo analisar os possíveis efeitos dos ruídos gerados durante a atividade humana na gestação de ratas wistar e no crescimento ponderal dos neonatos. Quarenta e quatro ratas wistar de 120 dias de idade, alojadas em sistema de gaiola aberta, oriundas do CREAL/UFRGS, foram acasaladas e submetidas à rotina de trabalho normal (grupo controle) ou expostas a ruídos em duas sessões de 20 minutos/dia com intervalo de 15 segundos entre cada ruído (grupo tratado) durante toda a gestação e na primeira semana de vida dos filhotes. Os ruídos foram previamente selecionados com base no trabalho humano realizado nas salas de animais e registrados por meio do microfone de um medidor de nível de pressão sonora com resposta de frequência 20 Hz-20kHz. As frequências foram avaliadas utilizando-se um software editor de áudio (Audacity® 1.3). Os partos de ambos os grupos (tratado e controle) foram acompanhados e durante os mesmos anotou-se o número de filhotes vivos e natimortos. Para avaliação do peso ponderal dos neonatos pesaram-se os três filhotes maiores de cada ninhada das fêmeas uma vez ao dia entre 14:00 e 16:00 hs. Utilizou-se o teste- T para análise do número de natimortos no qual demonstrou diferença significativa (p= 0,021) entre os grupos. O teste de variância Anova para medidas repetidas e o Tukey-Kramer foram utilizados para comparar o peso médio dos três filhotes maiores, o qual foi observado diferença significativa do peso médio dos três filhotes maiores nos dias 4 (p= 0,0026),5 (p<0,001),6 (p=0,0005) e 7 (p< 0,0001). Este estudo demonstra que ruídos gerados por atividade humana podem gerar filhotes natimortos e interferir no comportamento materno diminuindo o peso do filhote a partir do quarto dia na primeira semana de vida.Laboratory animals are subjected to a variety of daily noises which can affect their well-being. There are studies that suggest the human work in animal rooms is an important source of noise with varying frequencies and intensities which may cause physiological and behavioral changes in the animals. This work had as its main objective the analysis of the possible effects that the noise generated by professionals while doing their activities may have on pregnancy of Wistar rats, evaluating the natimortality and the weight development of newborns. Fourty-for 120 days old Wistar rats from CREAL/UFRGS accommodated in an open cage system have been paired and have undergone a normal work routine (control group) or have been exposed to noise in two sessions of 20 minutes/day with interval of 15 seconds between each noise (treated group) throughout their pregnancy and in the first week of their offspring’s life. The noises were previously selected on the basis of the human work carried out in animal rooms and recorded through the use of a microphone sound pressure level meter frequency response of 20 Hz-20kHz. The frequencies were evaluated using an audio editor software (Audacity® 1.3). The delivery in both groups (treated and control) were accompanied and during them it was taken note the number of living and stillborn offspring. To evaluate the weight of newborns, the three biggest ones of each litter rats were weighed up once a day between 2:00 and 4:00 p.m. It was used the T-test for examining the number of stillborns which showed a significant difference (p = 0.021) between the groups. The Anova variance test for repeated measures and the Tukey- Kramer test were used to compare the average weight of the three biggest offspring. It was observed significant difference of average weight in the three biggest ones on day 4 (p = 0.0026), 5 (p < 0.001), 6 (p = 0.0005) and 7 (p < 0.0001). This study shows that noise generated by human activity may cause stillborn offspring and interfere with maternal behavior by decreasing the weight of the new born from the fourth day the first week of life.
15
Ruivo, Pedro Reis. "Aging pathology in sprague dawley rats : background lesions and comparative study between wild type and transgenic rats with neuronal overexpression of human adenosine A2A receptors." Master's thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2018. http://hdl.handle.net/10400.5/16691.
Full textAbstract:
Dissertação de Mestrado Integrado em Medicina VeterináriaAging is a complex phenomenon defined as a time-dependent functional decline, progressive loss of physiological integrity and progressive increase in disease susceptibly. Adenosine A2A receptors (A2AR) are G protein-couple receptors that, upon binding of adenosine, lead to different transducing signals. Although having a protective effect, A2AR also play an important role in neurodegenerative disorders and are upregulated in the brain of Alzheimer and Parkinson patients. Previous studies from our collaborators showed that transgenic rats with neuronal overexpression of human A2AR (Tg (CaMKIIhA2AR)) have depressive-like behavior, impaired hypothalamic-pituitary-adrenal (HPA) axis and, as a result of this, increased levels of circulating corticosteroids. The aim of this work was to evaluate, by histopathology, the impact of the neuronal overexpression of human A2AR in the onset of specific or age-associated lesions in transgenic Sprague Dawley rats. Comprehensive necropsy and histopathology were performed in 37 Wild-type (Wt) and 39 transgenic (Tg) rats, at specific time-points, ranging from 12 to 126 weeks of age. Univariate and multivariate statistical analysis were performed to investigate the association between the phenotype and genotype. Briefly we found that Tg rats are 2.7 times more likely to develop systemic pathology than Wt rats [Odds ratio (OR) 2.745, IC 95% 1.0.07-6.997; (p<0.05)]. In the heart cardiomyopathy was the most frequent lesion both in Wt and Tg rats, and its incidence did not differ between groups [OR 0.82; IC 95% 0.315-2.139, (p>0.05)]. In blood vessels, mineralization was the most frequent lesion and Tg rats were 5.5 times more likely to develop this lesion than Wt [OR 5.486, IC 95% 1.776- 17.074; (p<0.05)]. In lung, alveolar histiocytosis and alveolar septa mineralization were the most frequent lesions and Tg rats were 7.7 times more likely to develop lung pathology than Wt [OR 7.7, IC 95% 1.604-37.19; (p<0.05)]. In kidney, chronic progressive nephropathy was the most frequent lesion both in Wt and Tg rats, and its incidence did not differ between groups [OR 2.5, IC 95% 0.919-6.923; (p>0.05)]. Regarding adrenal gland pathology, vacuolation of the cortical cells was the most frequent lesion and Tg rats were 4.3 times more likely to develop this pathology than Wt [OR 4.3, IC 95% 1.156-16.248; (p<0.05)]. Mammary fibroadenoma was the most common tumor in our sample, being observed in one Wt and five Tg rats. Even in cases where no difference was seen when comparing Tg and Wt rats, all lesions found in our study were age-associated lesions, typical for this species, and their incidence correlated with age. Our results show a clear correlation between increased A2AR signaling in the brain and accelerated aging, in our sample, and although herein we did not explore the precise mechanism(s) through which this occurs, it could be linked to the fact that Tg rats have HPA-axis dysfunction and increased circulating levels of corticosterone, which translated into chronic stress. To our knowledge, this is the first study to characterize the systemic repercussion of neuronal overexpression of adenosine A2A receptors, which is seen in several degenerative disorders during the aging process.
RESUMO - O envelhecimento é um fenómeno complexo definido como um declínio funcional dependente do tempo, com perda progressiva da integridade fisiológica e aumento gradual da suscetibilidade a doenças. Os recetores de adenosina A2A (A2AR) são recetores acoplados à proteína G cuja ligação à adenosina leva a diferentes sinais de transdução. Apesar do seu efeito protetor, os recetores de adenosina A2A têm também um papel crítico em doenças neurodegenerativas e estão sobre expressos no cérebro de doentes de Alzheimer e Parkinson. Estudos recentes demostraram que ratos transgénicos com sobre expressão neuronal de A2AR (Tg (CaMKIIhA2AR)) apresentam comportamento depressivo e disfunção do eixo hipotálamo-hipófise-adrenal, resultando em níveis elevados de corticosteroides circulante. O objetivo deste estudo foi avaliar, por histopatologia, o impacto da sobre expressão neuronal de A2AR no fenótipo de envelhecimento de vários órgãos e sistemas, em ratos Sprague Dawley. Foi efetuada a necrópsia compreensiva e histopatologia em 37 ratos “Wild type” (Wt) e 39 transgénicos (Tg) com idade variável entre as 12 e as 126 semanas. Foi efetuada análise estatística univariável e multivariável para investigar a associação entre o fenótipo e o genótipo. Resumidamente, descobrimos que os ratos Tg foram 2.7 vezes mais suscetíveis a desenvolver patologia sistémica, comparativamente aos Wt [Odds ratio (OR) 2.745, IC 95% 1.0.07-6.997; (p<0.05)]. No coração, a lesão mais frequentemente diagnosticada foi cardiomiopatia e a sua incidência não variou entre Wt e Tg [OR 0.82; IC 95% 0.315-2.139, (p>0.05)]. Nos vasos sanguíneos, a lesão mais frequente foi a mineralização da parede, sendo que os ratos Tg foram 5.5 vezes mais suscetíveis a desenvolver esta lesão que os Wt [OR 5.486, IC 95% 1.776- 17.074; (p<0.05)]. Relativamente ao pulmão, as lesões mais frequentes foram a histiocitose alveolar e a mineralização dos septos alveolares. Os ratos Tg foram 7.7 vezes mais suscetíveis a desenvolver estas lesões que os Wt [OR 7.7, IC 95% 1.604-37.19; (p<0.05)]. Relativamente ao rim, a lesão mais frequente foi a nefropatia crónica progressiva e a sua incidência não variou entre os ratos Wt e Tg [OR 2.5, IC 95% 0.919-6.923; (p>0.05)]. Relativamente às adrenais, a lesão mais frequente foi a vacuolização das células da cortical e os ratos Tg foram 4.3 vezes mais suscetíveis para o desenvolvimento desta lesão que os Wt [OR 4.3, IC 95% 1.156-16.248; (p<0.05)]. Fibroadenoma mamário foi o tumor mais frequente, tendo sido observado em um rato Wt e cinco ratos Tg. Mesmo em casos onde não foi observada diferença entre ratos Wt e Tg, todas as lesões encontradas neste estudo são lesões muitas vezes associadas ao envelhecimento, típicas desta espécie e a sua incidência correlacionou-se com a idade. Os nossos resultados mostram uma relação clara entre a sobre expressão neuronal de A2AR e envelhecimento acelerado na nossa amostra, e apesar de não termos explorado os mecanismos específicos para tal acontecimento, poderá estar ligado ao facto dos ratos Tg terem disfunção do eixo hipotálamo-hipófise-adrenal e níveis elevados de corticosterona, o que se traduz em stress crónico. A conhecimento dos autores, este é o primeiro estudo a caracterizar as repercussões sistémicas da sobre expressão neuronal de A2AR, que é observada em várias doenças degenerativas durante o envelhecimento.
N/A
16
Ouyang, Xuesong. "Differential gene expression during sex hormone-induced prostate carcinogenesis in the rat with emphasis on ID-1 gene and its role in human prostate cancer /." Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk/hkuto/record.jsp?B24738694.
Full text
17
Moazzami, Ali A. "Sesame seed lignans : diversity, human metabolism and bioactivities /." Uppsala : Department of Food Science, Swedish University of Agricultural Sciences, 2006. http://epsilon.slu.se/200698.pdf.
Full text
18
Schrader, Lauran N. "Does ANA-positive SLE human serum promote development of Libman-Sacks endocarditis in the NP-SLE Lewis rat model?" Muncie, IN : Ball State University, 2009. http://cardinalscholar.bsu.edu/675.
Full text
19
Chow, Ka-man. "The antioxidant effect of lycium fruit extract on hyperglycemia-induced oxidative stress in human liver and rat muscle cell lines." View the Table of Contents & Abstract, 2005. http://sunzi.lib.hku.hk/hkuto/record/B36186132.
Full text
20
Dubois, Axel. "Convergent antibody signatures for the measles virus in transgenic rats expressing a human B cell IG repertoire." Thesis, Université de Lorraine, 2015. http://www.theses.fr/2015LORR0317/document.
Full textAbstract:
L’énorme diversité des immunoglobulines (IG) permet la reconnaissance spécifique d’un nombre presqu’infini d’antigènes, et assure à l’organisme une protection à long-terme envers les pathogènes déjà rencontrés. La région déterminant de la complémentarité 3 (CDR3) de la chaine lourde des IG est le principal déterminant de la spécificité de l’IG. A l’aide des technologies de séquençage à haut débit, nous avons évalué si une vaccination peut conduire à la production d’IG antigène-spécifiques et partagées entre individus (réponse humorale publique), en nous intéressant particulièrement à la région CDR3. Ces «signatures» antigène-spécifiques peuvent potentiellement être utilisées pour reconstruire a posteriori l’histoire immunitaire d’un individu. Pour tester cette hypothèse, des rats transgéniques produisant des anticorps humains (OmniRatTM) ont été vaccinés avec divers antigènes, en particulier du virus de la rougeole (souche vaccinale et sauvage). Une forte réponse immunitaire publique a été observée au sein de différents groupes de rats, caractérisée par des séquences CDR3 partagées entre les animaux ayant reçu le même vaccin. Ces groupes de CDR3s constituent des signatures complexes antigène-spécifiques. De futures études de suivi vaccinal et d’infection devraient nous permettre de déterminer si les signatures identifiées se retrouvent également chez l’humain. Ces outils pourront se révéler précieux dans le cadre de la campagne de l'Organisation mondiale de la Santé en vue de l’éradication de la rougeole, en permettant de distinguer entre les individus vaccinés et infectésThe enormous diversity of immunoglobulins (IG) allows the specific recognition of an almost infinite number of antigens, and ensure a long-term protection against pathogens previously encountered by the organism. The complementarity-determining region 3 (CDR3) of the immunoglobulin heavy chain (IGH) is the major antigen binding domain and determinant of antigen-specificity of the antibody molecule. Using next-generation sequencing, we tested whether immunization resulted in the generation and accumulation of similar IGH CDR3 sequences that are antigen-specific and shared across individuals, i.e. public IGH CDR3s. Such public "antigen-specific signatures" can potentially be used to retrospectively reconstruct past antigenic challenges. To test this hypothesis, transgenic rats with fully functional human Ig heavy and light chain loci (OmniRatTM) have been immunized with diverse antigens, and particularly measles virus (MV)-derived antigen. We demonstrated a strong public immune response within the different groups of rats characterized by convergent IGH CDR3 amino acid sequences in the animals that received the same vaccine. These clusters of CDR3s represent complex antigen-specific IGH CDR3 signatures. We are now transposing this concept to human studies by performing infection and vaccination follow ups to test whether similar CDR3 signatures can also be found in peripheral blood B cells. In the context of the MV eradication campaign of the World Health Organization, new epidemiological tools that enable to distinguish between immunized and infected individuals would be valuable assets
21
Uwimana, Eric. "Probing the PCB metabolome: metabolism of chiral and non-chiral polychlorinated biphenyls to chiral hydroxylated metabolites in humans and rats." Diss., University of Iowa, 2018. https://ir.uiowa.edu/etd/6657.
Full textAbstract:
Polychlorinated biphenyls (PCBs) continue to pose a health concern because of their predominance in the diet and air as well as in environmental samples and humans. PCB congeners with 3 or 4 chlorine substituents in ortho position have been associated with neurodevelopmental disorders. Hydroxylated metabolites (OH-PCBs) of these PCBs are also potentially toxic to the developing brain. Metabolism studies have mainly focused on animal models. However, preliminary data from this dissertation work have revealed PCB metabolism differences between laboratory animal models and humans in terms of metabolite profiles, chiral signatures. More concerning, biotransformation of chiral PCBs is poorly investigated in humans. The objective of this dissertation research was to study the biotransformation of chiral and prochiral PCBs to chiral hydroxylated metabolites in humans and rats and to identify individual human P450 enzymes involved in the metabolism of these PCBs. I chose chiral PCB congeners 2,2',3,4',6-pentachlorobiphenyl (PCB 91); 2,2',3,5',6-pentachlorobiphenyl (PCB 95), 2,2',3,3',4,6'-hexachlorobiphenyl (PCB 132) and 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) for this investigation because they are environmentally relevant and their metabolism has been studied in rodents and other laboratory animal species (Kania-Korwel et al., 2016a). Prochiral PCB congeners 2,2′,4,6′-tetrachlorobiphenyl (PCB 51) and 2,2′,4,5,6′-pentachlorobiphenyl (PCB 102) were selected because their considerable presence in technical PCB mixtures.
To test the hypothesis that P450 enzyme and species differences mediate the congener-specific enantioselective metabolism of chiral PCBs to hydroxylated metabolites, I sought to establish structure-metabolism relationships by studying the enantioselective metabolism of structurally diverse chiral PCBs by human liver microsomes (HLMs). Racemic PCB 91, PCB 95 and PCB 132 were incubated in vitro with pooled or individual donor HLMs at 37 °C, and levels and chiral signatures of the parent PCB and its hydroxylated metabolites were determined by high-resolution gas chromatography equipped with time-of-flight mass spectrometry (GC/TOF-MS) or electron capture detection (GC-ECD). Hydroxylated metabolites formed were identified and metabolic schemes for these PCBs proposed. I found inter-individual differences in the formation of OH-PCBs by individual donor HLMs. Comparison of the metabolite profiles of PCB 91, PCB 95, PCB 132 and PCB 136 (PCB 136 metabolism by HLMs was investigated by other researchers) revealed congener-specific differences in the oxidation of PCBs by human cytochrome P450 enzymes. PCB 91 and PCB 132 were mainly hydroxylated in meta position, with the 1,2-shift metabolites being the major metabolites formed from both PCB congeners by HLMs. In contrast, PCB 95 and PCB 136 were primarily hydroxylated in the para position. Moreover, we determined human P450 isoforms involved in the metabolism of neurotoxic PCBs using in silico and in vitro approaches. In silico predictions suggested that chiral PCBs are metabolized by CYP1A2, CYP2A6, CYP2B6, CYP2E1, and CYP3A4. Experimentally we found that CYP2A6, CYP2B6 and to a minor extent CYP2E1 were the enzymes involved in the metabolism of these chiral PCBS.
We also investigated nonchiral sources of chiral OH-PCBs by studying the P450- and species-dependent biotransformation of prochiral PCB 51 and PCB 102 to chiral OH-PCB metabolites. Prochiral PCB 51 and PCB 102 were incubated with liver microsomes prepared from male Sprague-Dawley rats pretreated with various inducers of P450 enzymes including phenobarbital (PB), dexamethasone (DEX), isoniazid (INH), β-naphthoflavone (BNF), clofibric acid (CFA) or corn oil (CO); and untreated male cynomolgus monkeys, Hartley albino guinea pigs, New Zealand rabbits, golden Syrian hamsters; and untreated female Beagle dogs. PCB 51 and PCB 102 were metabolized to 2,2',4,6'-tetrachlorobiphenyl-3'-ol (OH-PCB 51) and 2,2',4,5,6'-pentachlorobiphenyl-3'-ol (OH-PCB 102), respectively. The formation of both metabolites was P450 isoforms- and species-dependent. Moreover, OH-PCB 51 and OH-PCB 102 were chiral and were formed enantioselectively in all microsomes investigated.
Taken together, my findings demonstrate (1) considerable inter-individual variability in the congener-specific metabolism of PCBs to OH-PCBs; (2) the enantioselective formation of OH-PCBs by human CYP2A6, CYP2B6, and CYP2E1; and (3) that chiral PCB metabolites are formed enantioselectively from prochiral PCB congeners. Interestingly, the metabolism of PCBs by CYP2A6 appears to involve arene oxide intermediates, as suggested by the formation of 1,2-shift products as major metabolites of PCB 91 and PCB 132. In contrast, 1,2-shift products are minor PCB metabolites formed in rodents. Therefore extrapolation of hepatic metabolism across species may not be consistent and these differences should be considered in future toxicity and risk assessment studies.
22
Berggren, Sofia. "Drug Transport and Metabolism in Rat and Human Intestine." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Universitetsbiblioteket [distributör], 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7229.
Full text
23
Davis, Laura D. R. "The Biodistribution of 14C in the Digestive Organs of Rats Fed [14C]CD14 Protein." Thesis, Université d'Ottawa / University of Ottawa, 2010. http://hdl.handle.net/10393/12911.
Full textAbstract:
Human milk contains ~ 25 µg/mL of soluble cluster of differentiation 14 (sCD14) protein, a pattern recognition receptor (PRR) that triggers the innate immune system to respond to bacterial lipopolysaccharide (LPS). To date, the role of CD14 in the digestive tract of breast fed infants has not been well characterized and is the subject of this thesis.
To investigate the biodistribution of proteins such as CD14 in vivo, a novel method for 14C radiolabeling of proteins to high specific radioactivity was developed using in vacuo methylation. Bovine serum albumin (BSA) and casein were used as test proteins to determine the following: 1) The efficacy of the in vacuo radiolabeling procedure;
2) The extent of incorporation of the 14C-label into the organs of oro-gastric gavaged 10 day old Sprague Dawley rats. [14C]BSA, [14C]casein and [14C]CD14 were prepared with specific radioactivities of 10 400, 10 800 and 163 000 dpm/µg, respectively. After feeding 6.25 µg of 14C-labeled proteins, quantifiable levels of 14C were found in the stomach, jejunum, duodenum, ileum, large intestine, intestinal luminal flushes, blood, liver, spleen and kidneys of rats. The accumulation of radiolabel in the organs of [14C]CD14 fed rats was temporally and spatially distinct from [14C]BSA and [14C]casein. Most notably, the label persisted in the stomach 480 min post-gavage.
To design a neonate animal model for biodistribution, the segmental and total gastrointestinal transit times (GItt) were measured in two litters of 10 and 15 day old Sprague Dawley rat pups using barium sulfate. Ten day old rat pups that remained with and without the dam had a total gastrointestinal transit time of 13.8 ± 0.9 hr and 9.3 ± 0.7 hr, respectively. This decrease (p<0.05) in total gastrointestinal transit time in the absence of the dam was age dependent, as it was not observed (p>0.05) in the 15 day old rat pup litter.
The immunological impact of an exogenous sCD14 source was examined in human peripheral blood mononuclear cells (PBMC). Pre-treatment of CD14+ monocytes with sCD14 had a protective effect, one of reducing the production of proinflammatory cytokines (TNF-α, IL-6, IL-8, IL-1β) when challenged with LPS.
14C was absorbed by neonate rats upon ingestion of [14C]CD14 and exposure to relatively high concentrations of rCD14 led to a reduction in inflammation. This may be beneficial to initial gut colonization in breast-fed newborns.Alexander Graham Bell NSERC CGS M scholarship. Japan Society for the Promotion of Sciences, Summer in Japan Fellowship. Funded by the Canadian Institutes of Health Research, Institute of Nutrition Metabolism and Diabetes Grant #82816 “Fate and function of breast milk and recombinant human CD14 at mammary and newborn gastrointestinal mucosal epithelia”.
24
Yu-Täger, Libo [Verfasser], and Olaf [Akademischer Betreuer] Riess. "Generation and Characterization of BACHD Rats expressing full-length human mutant Huntingtin / Libo Yu-Täger ; Betreuer: Olaf Riess." Tübingen : Universitätsbibliothek Tübingen, 2013. http://d-nb.info/1160683638/34.
Full text
25
Miyawaki, Yoshifumi. "Zonisamide promotes survival of human induced pluripotent stem cell-derived dopaminergic neurons in the striatum of female rats." Kyoto University, 2020. http://hdl.handle.net/2433/259730.
Full text
26
Viljoen, Monet. "An integrative approach to the effect of interleukin-6 on adaptation to restraint stress in rats." Thesis, Stellenbosch : University of Stellenbosch, 2009. http://hdl.handle.net/10019.1/4365.
Full textAbstract:
Thesis (MSc (Physiological Sciences))--University of Stellenbosch, 2009.ENGLISH ABSTRACT: Bi-directional communication exists between HPA-axis activation and interleukin-6 (IL-6). However, the relative contribution of centrally versus peripherally secreted IL- 6 remains unclear, especially under psychological stress conditions. We hypothesised that the HPA response to mild psychological stress is dependent on IL- 6, both centrally and peripherally. 120 male Wistar rats were divided into four groups, depending on whether they received an anti-IL-6 antibody (Ab) (2μg/ml/kg body weight) or a placebo (sterile saline) injection and whether or not they were subjected to 1 hour of restraint stress for 1, 2 or 3 days. Rats were euthanized 24 hours after stress exposure. Plasma corticosteroid (GC) levels remained significantly increased 24 hours after a single stress exposure (control placebo (CP) versus stress placebo (SP): p < 0.05). The undetectable plasma IL-6 levels evident across all groups may be explained by the short half-life of IL-6. Plasma IL-1β levels decreased when IL-6 was blocked in unstressed animals (CP versus CAb: p < 0.05), suggesting a role for IL-6 in the maintenance of IL-1β levels under tonic physiological conditions. At tissue level, pituitary gland mass increased significantly at time point 2, independently of stress when blocking IL-6 (CAb: p < 0.05). This suggests that when normal homeostasis is threatened, immediate adaption or at least compensation may occur. It was observed that GR, IL-1β, IL-1βR, IL-6, IL-6R and GABAARα1 showed no response to stress alone in the pituitary. It is therefore more likely that resistance to adaptation exists centrally. IL-1β and IL-1βR (p < 0.05) and GABAARα1 (p < 0.005) expression increased in the CAb group in the pituitary, again suggesting a role for IL-6 under control conditions. In terms of the adrenal, blocking IL-6 resulted in decreased glandular mass at time point 1, independent of stress (CAb and SAb: p < 0.005). The up-regulation in GR expression seen in CAb and SAb (p < 0.05) may be the effect of a compensatory mechanism to increase IL-6 dependent bioactivity of GCs. The fact that expression of IL-6, IL-6R, IL-1β and IL- 1βR consistently increased in the Ab groups, and mostly in the zona fasciculata and zona reticularis, suggests that lack of local direct negative cytokine feedback occurred in response to very low plasma IL-6 levels and that this contributes more than GCs in the down-regulation of inflammatory cytokine release. In conclusion, consistent effects of the Ab were apparent in the tissues investigated, even in control conditions, suggesting that IL-6 plays a role in the maintenance of basal homeostasis, including its regulation of the response to psychological stress. We found differential regulation in terms of cytokines and GCs when comparing peripheral versus central effects of stress and Ab, as well as the levels of cytokines in the blood compartment, compared to within tissues.
AFRIKAANSE OPSOMMING: Daar bestaan twee-rigting kommunikasie tussen HPA-as aktivering en interleukin-6 (IL-6), allhoewel die relatiewe bydrae van sentraal versus perifeer afgeskeide IL-6 nog onduidelik is, veral gedurende sielkundige strestoestande. Ons hipotese is dat die HPA reaksie tot sielkundige stres afhanklik van IL-6 is, beide sentraal en in die periferie. 120 manlike Wistar rotte is in vier groepe verdeel, afhangende van of hulle ‘n anti-IL- 6 teenliggaampie (Ab) (2μg/ml/kg liggaamsgewig) of ‘n plasebo (steriele soutoplossing) inspuiting gekry het, en of hulle onderworpe was aan 1 uur van vaskeer-stres vir 1, 2 of 3 dae. Rotte is 24 uur na blootstelling aan stres aan genadedood onderwerp. Bloed kortikosteroïed (GC) vlakke het beduidend toegeneem binne 24 uur na ‘n eenmalige stres blootstelling (kontrole plasebo (CP) versus stres plasebo (SP): p < 0.05). Die onmeetbaar lae vlakke van IL-6 regoor al die groepe, kan verduidelik word na aanleiding van die kort half-leeftyd van IL-6. Bloed IL-1β vlakke het afgeneem in kontrole rotte wanneer IL-6 geblok is (CP versus CAb: p < 0.05). Dit kan beteken dat IL-6 noodsaaklik is vir die onderhoud van IL-1β vlakke gedurende basale toestande. Op weefselvlak het die hipofise massa toegeneem by tydpunt 2 toe IL-6 geblok is, onafhanklik van stres (CAb: p < 0.05). Dit dui aan dat wanneer normale homeostase bedreig word, daar onmiddelike aanpassing of kompensasie plaasvind. Dit is opvallend dat GR, IL-1β, IL-1βR, IL-6, IL-6R en GABAARα1 geen respons in terme van stres alleen in die hipofise getoon het nie. Na aanleiding daarvan is dit meer waarskynlik dat weerstand tot aanpassing sentraal bestaan. IL-1β and IL-1βR (p <0.05) en GABAARα1 (p < 0.005) uitdrukking in die hipofise het toegeneem in die CAb groep, wat weereens ‘n rol vir IL-6 onder kontrole toestande uitwys. In terme van die bynier, het die blok van IL-6 ‘n afname in massa veroorsaak by tydpunt 1, wat weer onafhanklik van stres was (CAb en SAb: p < 0.005). Die opregulering in die CAb en SAb groepe (p < 0.05), kan wees as gevolg van ‘n kompensasie meganisme om IL-6 afhanklike GC aktiwiteit te verhoog. Die feit dat die uitdrukking van IL-6, IL-6R, IL-1β and IL-1βR in die Ab groepe deurlopend verhoog was, en meeste in die zona fasciculata en zona reticularis, stel voor dat daar ‘n tekort aan plaaslike, direkte sitokien negatiewe terugvoering was, as gevolg van die merkwaardige lae bloed IL-6 vlakke en dat dit meer bydra as GCs in die afregulering van inflammatoriese sitokien vrystelling.
27
Takagishi, Yoshiko, 芳子 高岸, and Yoshiharu Murata. "Myosin Va mutation in rats is an animal model for the human hereditary neurological disease, Griscelli syndrome type 1." New York Academy of Sciences, 2006. http://hdl.handle.net/2237/10947.
Full text
28
Wang, Jiachao. "Bayesian analysis for quantification of individual rat and human behavioural patterns during attentional set-shifting tasks." Thesis, University of St Andrews, 2018. http://hdl.handle.net/10023/14843.
Full textAbstract:
Attentional set-shifting tasks, consisting of multiple stages of discrimination learning, have been widely used in animals and humans to investigate behavioural flexibility. However, there are several learning criteria (e.g., 6-correct-choice-in-a-row, or 10-out- of-12-correct) by which a subject might be judged to have learned a discrimination. Furthermore, the currently frequentist approach does not provide a detailed analysis of individual performance. In this PhD study, a large set of archival data of rats performing a 7-stage intra-dimensional/extra-dimensional (ID/ED) attentional set- shifting task was analysed, using a novel Bayesian analytical approach, to estimate each rat's learning processes over its trials within the task. The analysis showed that the Bayesian learning criterion may be an appropriate alternative to the frequentist n- correct-in-a-row criterion for studying performance. The individual analysis of rats' behaviour using the Bayesian model also suggested that the rats responded according to a number of irrelevant spatial and perceptual information sources before the correct stimulus-reward association was established. The efficacy of the Bayesian analysis of individual subjects' behaviour and the appropriateness of the Bayesian learning criterion were also supported by the analysis of simulated data in which the behavioural choices in the task were generated by known rules. Additionally, the efficacy was also supported by analysis of human behaviour during an analogous human 7-stage attentional set-shifting task, where participants' detailed learning processes were collected based on their trial-by-trial oral report. Further, an extended Bayesian approach, which considers the effects of feedback (correct vs incorrect) after each response in the task, can even help infer whether individual human participants have formed an attentional set, which is crucial when applying the set-shifting task to an evaluation of cognitive flexibility. Overall, this study demonstrates that the Bayesian approach can yield additional information not available to the conventional frequentist approach. Future work could include refining the rat Bayesian model and the development of an adaptive trial design.
29
Kunimasa, Junichi. "Pharmacokinetics and pharmacological effect of recombinant human granulocyte colony-stimulating factor conjugated to poly (styrene-co-maleic acid) in rats." Kyoto University, 2001. http://hdl.handle.net/2433/150596.
Full text
30
Chow, Ka-man, and 鄒嘉敏. "The antioxidant effect of lycium fruit extract on hyperglycemia-induced oxidative stress in human liver and rat muscle cell lines." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B36186132.
Full text
31
Yulius, Hermanto. "Transplantation of feeder-free human induced pluripotent stem cell-derived cortical neuron progenitors in adult male Wistar rats with focal brain ischemia." Kyoto University, 2019. http://hdl.handle.net/2433/242389.
Full text
32
Triandafillou, Joan. "Control of brown adipose tissue growth and function in rats and hamsters normalities in genetic models of human disease (obesity muscular dystrophy)." Thesis, University of Ottawa (Canada), 1985. http://hdl.handle.net/10393/4969.
Full text
33
Shobako, Naohisa. "Identification and characterization of a novel anti-hypertensive peptide derived from rice bran protein." Kyoto University, 2019. http://hdl.handle.net/2433/242924.
Full textAbstract:
Kyoto University (京都大学)0048
新制・課程博士
博士(農学)
甲第21973号
農博第2363号
新制||農||1071(附属図書館)
学位論文||R1||N5224(農学部図書室)
京都大学大学院農学研究科食品生物科学専攻
(主査)教授 井上 和生, 教授 谷 史人, 准教授 大日向 耕作
学位規則第4条第1項該当
34
Bridges, Kayla Marie. "The omega-3 fatty acid content of krill protein concentrate influences bioavailability, tissue deposition, peroxidation, and metabolism in young rats." Morgantown, W. Va. : [West Virginia University Libraries], 2009. http://hdl.handle.net/10450/10241.
Full textAbstract:
Thesis (M.S.)--West Virginia University, 2009.Title from document title page. Document formatted into pages; contains vii, 42 p. : ill. Includes abstract. Includes bibliographical references (p. 29-35).
35
Odendaal, Louise. "The effect of dietary Red Palm Oil on the functional recovery and the PKB/Akt pathway in the ischaemic/reperfused isolated rat heart." Thesis, Stellenbosch : Stellenbosch University, 2007. http://hdl.handle.net/10019.1/21745.
Full textAbstract:
Thesis (MSc)--University of Stellenbosch, 2007.ENGLISH ABSTRACT: Introduction Cardiovascular disease is one of the leading causes of death in the world. Formation of harmful reactive oxygen species (ROS) is associated with several pathological conditions, and contributes to ischaemia/reperfusion injury. Antioxidants can be added to the diet in an attempt to decrease the prevalence of cardiovascular disease by decreasing the harmful effects of ischaemia/reperfusion injury. Red Palm Oil (RPO) consists of saturated, monounsaturated and polyunsaturated fatty acids and is rich in antioxidants such as -carotene, tocopherols and tocotrienols. It has previously been shown that RPO-supplementation improved reperfusion mechanical function. In these studies it was found that RPO might exert its beneficial effects during reperfusion through increased PKB/Akt pathway activity, which may lead to inhibition of apoptosis and improved mechanical function. Aims The aims of this study were: 1) to determine whether RPO-supplementation protected against ischaemia/reperfusion injury in the isolated perfused rat heart, 2) to confirm RPO-supplementation’s effect on the PKB/Akt pathway activity and, 3) to elucidate the regulators in the PKB/Akt pathway that RPOsupplementation influenced. Methods Male Wistar rats were divided into 4 groups, 2 control groups and 2 experimental groups. The 2 control groups were fed a standard rat chow (SRC) for 4 weeks. The two experimental groups received SRC and RPOsupplementation for 4 weeks. Hearts were excised and transferred to a Langendorff perfusion apparatus and perfused with Krebs-Henseleit buffer. Mechanical functional recovery was measured after 25 min of total global noflow ischaemia. The following parameters were also measured during various time points in the protocol: left ventricular develop pressure, heart rate, coronary flow, rate pressure product. Hearts were also freeze-clamped for biochemical analysis at 10 min during reperfusion. The biochemical analysis was aimed at determining PKB/Akt involvement. In a second protocol, hearts were subjected to the same perfusion protocol, but wortmannin was also added to the perfusion fluid, in order to inhibit PI3- kinase. Results Hearts from the RPO-supplemented rats showed an improved RPP recovery (92.26 ± 5.89 % vs 63.86 ± 7.74 %) after 10 min of reperfusion. This finding corroborated the findings of previous studies. Hearts of the RPOsupplemented rats perfused with wortmannin, showed increased RPP recoveries at several time points. Biochemical results showed that wortmannin did indeed inhibit PI3-K phosphorylation in the RPO-supplemented group, as was expected. The RPO-supplemented group that was perfused with wortmannin had an increased PKB/Akt (Ser473) phosphoyrylation, when compared to the wortmannin control group. It was also found that the combination of RPO and wortmannin had prosurvival effects. Discussion This study showed that RPO-supplementation offered protection against ischaemia/reperfusion injury in the Langendorff-perfusion apparatus at 10 min into reperfusion. Thereafter the significance of the protection was lost. This protection has been confirmed in several previous studies and several mechanisms have been proposed for this protection. Since no conclusive evidence exists on the precise mechanism of protection, our investigation focused on the regulators of the pro-survival PKB/Akt pathway. An improved functional recovery was also seen in the RPO-supplemented group that was perfused with wortmannin. This was an unexpected finding, because Wortmannin is a known PI3-kinase inhibitor (as was confirmed by our biochemical data). PI3-kinase phosphorylation leads to PKB/Akt phosphorylation and therefore, activation of a pro-survival pathway. It would be expected that wortmannin would inhibit PKB/Akt and thus decrease the survival of the cells. The RPO-supplementation thus reversed wortmannin’s detrimental effect to such an extent that the functional recovery was far better than RPO-supplementation alone. In the RPO + wortmannin group, PKB/Akt (Ser473) phosphorylation was increased, contrary to previous findings. This is an indication that RPO may have the ability to override wortmannin’s inhibitory effect on PI3-kinase, or that PKB/Akt (Ser473) may be phosphorylated independently of PI3-kinase.
AFRIKAANSE OPSOMMING: Inleiding Kardiovaskulêre siektes is een van die hoof oorsake van sterftes in die wêreld. Die vorming van skadelike reaktiewe suurstof spesies word geassosieer met verskeie patologiese kondisies en dra ook by tot isgemie/reperfusie skade. ‘n Moontlike manier om die voorkoms van isgemie/herperfusie skade asook kardiovaskulêre siektes te voorkom, is om antioksidante by die dieet te voeg. Rooi Palm Olie (RPO) bevat versadigde, mono-onversadigde en polionversadigde vetsure. RPO bevat ook ‘n oorvloed van antioksidante soos β- karoteen en tokoferole en tokotriënole. Dit is bewys in vorige studies dat RPO-aanvulling verbeter funksionele herstel. Hierdie voordelige effekte mag dalk wees agv verhoogde PKB/Akt pad aktiwiteit. Die PKB/Akt pad word geassosieer met die inhibisie van apoptose en verhoogde meganiese funksie. Doelwitte Die doelwitte van hierdie studie was om te bepaal of 1) RPO-aanvulling beskermende effekte teen isgemie/herperfusie skade in die geisoleerde rotharte het, 2) Bevestig of RPO-aanvulling wel die PKB/Akt pad beïnvloed 3). om die effekte wat RPO-aanvulling het op die reguleerders van die PKB/Akt pad te onthul. Metodes Manlike Wistar rotte is in 4 groepe verdeel. 2 Groepe kontrole rotte is ‘n standaard rotkosmengsel gevoer vir 4 weke. Die 2 eksperimentele groepe het ook ‘n standaard rotkosmengsel gekry plus ‘n RPO-aanvulling vir 4 weke. Harte is uitgesny en op ‘n Langendorff perfusie sisteem gemonteer en met Krebs-Henseleit buffer geperfuseer. Meganiese funksie herstel is gemeet na 25 min totale globale geen-vloei isgemie. Linker ventrikulêre ontwikkelde druk, harttempo, koronêre vloei en tempo druk produk is gemeet by verskillende tydpunte. Sommige harte is na 10 min herperfusie vir biochemiese analiese gevriesklamp. Die biochemiese analisiese was beoog om die PKB/Akt pad betrokkenheid te bepaal. ‘n Tweede stel harte is aan dieselfde perfusie protokol blootgestel, maar wortmannin (PI3-kinase inhibitor) is ook bygevoeg by die perfusie vloeistof. Resultate Die groep wat met RPO aangevul is, het na 10 min herperfusie, ‘n verbeterde tempo druk produk herstel getoon (92.26 ± 5.89 % vs 63.86 ± 7.74. Hierdie bevinding is ook met ander studies bevestig. ‘n Interessante bevinding was dat die groep wat met RPO aangevul is en met wortmannin geperfuseer is, ‘n verbeterde meganiese funksionele herstel getoon het. Biochemiese resultate het getoon dat wortmannin wel PI3-K fosforilering geinhibeer het. Die harte van die rotte in die groep wat aangevul is met RPO en daarna met wortmannin geperfuseer is, het ‘n toename in PKB/Akt (Ser473) fosforilering getoon, relatief tot die wortmannin geperfuseerde harte van die rotte in die kontrole groep. Hierdie groep (RPO-aanvulling en wortmannin perfusie) het beskermende effekte getoon. Bespreking Hierdie studie het getoon dat RPO-aanvulling beskerming gebied het teen isgemie/herperfusie skade in die Langendorff geperfuseerde rothart na 10 min herperfusie. Daarna is die beduidenheid van die beskerming verloor. Hierdie bevindings ondersteun die resultate van vorige studies. Verskeie moontlike meganismes is voorgestel vir die beskerming, maar die presiese meganisme is nog nie duidelik nie. In hierdie studie is daar gekyk na die reguleerders van die PKB/Akt pad. Geen vorige studies het al gefokus op RPO-aanvulling en sy effek op die reguleerders van die PKB/Akt pad nie. ‘n Onverwagte bevinding is dat harte van die rotte in die RPO + wortmannin groep ‘n verbeterde funksionele herstel getoon het. Wortmannin is ‘n PI3- kinase inhibitor. PI3-K fosforilering lei tot PKB/Akt fosforilering, wat tot sel beskerming lei. Dus, aangesien wortmannin PI3-K inhibeer, sou dit verwag word dat wortmannin sel beskerming sal verminder. Die RPO het egter die wortmannin se nadelige effekte tot so ‘n mate oorskrei dat die funksionele herstel baie beter was as die RPO-aanvulling alleen. Die verhoogde PKB/Akt (Ser473) fosforilering, wat gesien is in die RPO + wortmannin groep kan toegeskryf word aan RPO se vermoë om wortmannin se nadelige effekte te oorskrei. ‘n Moontlike verduideliking vir hierdie bevinding mag wees dat rooi palm olie PKB/Akt (Ser473) op ‘n PI3-K onafhanklike manier fosforileer.
36
Alvarenga, Cláudia Maria Domingues [UNESP]. "Avaliação dos mecanismos de ação interceptiva e/ou embriotóxica do extrato aquoso de Plectranthus barbatus Andr.(bolbo-brasileiro) administrado a ratas prenhez no período de pré-implantação." Universidade Estadual Paulista (UNESP), 2006. http://hdl.handle.net/11449/104597.
Full textAbstract:
Made available in DSpace on 2014-06-11T19:33:25Z (GMT). No. of bitstreams: 0
Previous issue date: 2006-08-24Bitstream added on 2014-06-13T18:45:06Z : No. of bitstreams: 1
alvarenga_cmd_dr_botfm_prot.pdf: 1786103 bytes, checksum: 14d9f0d294fb6c639b79eab0f8e823c6 (MD5)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
O objetivo do presente estudo foi verificar, experimentalmente, o possível mecanismo pelo qual o extrato aquoso de Plectranthus barbatus (boldo-brasileiro), planta utilizada popularmente como abortiva, atua sobre o organismo materno ou sobre o desenvolvimento do concepto durante o período de pré-implantação, correlacionando sua ingestão com possíveis alterações no transporte e desenvolvimento embrionário ou com alterações hormonais maternas...
The present study was conducted to determine the possible mechanism by which the aqueous extract of Plectranthus barbatus (brazilian-boldo), a plant used popularly as abortive agent, can lead to early loss of pregnancy, correlating this possible effect with morphological alterations in the embryo, oviductal motility dysfunctions or maternal hormonal level modifications...(Complete abstract, access undermentioned electronic address)
37
Sishi, Balindiwe J. N. (Balindiwe Jennifer Nonkosazana). "Anthracycline-induced cardiotoxicity : the role of proteolytic pathways." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/20305.
Full textAbstract:
Thesis (PhD)--Stellenbosch University, 2012.ENGLISH ABSTRACT: Introduction: The anthracyclines (ACs), daunorubicin (DNR) and doxorubicin (DXR) are two of the most effective drugs known for the treatment of systemic neoplasms and solid tumours. However, their clinical use is often hampered by their dosedependent cumulative cardiotoxicity, which leads to irreversible and fatal druginduced congestive heart failure. The mechanism by which ACs induces heart damage is not fully understood. Recent reports have indicated that DXR activates autophagy and ubiquitin proteasome-mediated degradation of specific transcription factors, however, no reports exists on the effect of ACs on the E3 ubiquitin ligases, MuRF-1 and MAFbx. The aim of the first part of the study was therefore to investigate the effect of DNR treatment on the protein and organelle degradation systems in the heart and to elucidate the signalling mechanisms involved. Although this model was ideal in allowing the investigation of the signalling pathways which are affected by DNR, it did not allow for further exploration or manipulation of signalling pathways that may be of potential benefit in this context. The in vitro model was therefore used to validate the hypothesis that increased autophagy alleviates AC-induced cardiotoxicity and delays the onset of cardiomyocyte death. The aims for the second part of the study were (i) to characterize the effect of DXR in H9C2 cells, (ii) to determine whether the induction/inhibition of autophagy in combination with DXR alleviates cytotoxicity and (iii) to investigate the influence of increased/decreased autophagy in combination with DXR on reactive oxygen species (ROS) production, mitochondrial function, endoplasmic reticulum (ER) stress and the ubiquitin proteasome pathway. In the final part of this study, an in vivo model was used to assess the potential benefit of autophagy in a novel GFP-LC-3 tumour bearing mouse model of acute DXR-induced cardiotoxicity. Material and Methods: Adult rats were divided into two groups where one group received six intraperitoneal injections of 2 mg/kg DNR on alternate days and the other group received saline injections as control. Hearts were excised and perfused on a working heart system the day after the last injection and freeze clamped for biochemical analysis. H9C2s were cultured and treated with Bafilomycin A1 (10 nM, inhibitor of autophagy) for 6 hrs, Rapamycin (50 μM, inducer of autophagy) for 24 hrs, DXR (3 μM) for 24 hrs or a combination of these drugs. Following treatment, cells were harvested and assessed for cell death, proteolytic activity and oxidative stress using western blotting, fluorescence microscopy and flow cytometry. In the final phase of the study, twenty-four female mice were injected at 8 weeks with a mouse breast cancer cell line (EO771) and after observation of tumour growth, animals were either treated with one injection (i.p.) of Rapamycin (4 mg/kg), two injections (i.p.) of DXR (10 mg/kg) or a combination of the two drugs. After the experimental protocol, mice were terminated and their hearts were rapidly excised. The hearts were divided cross-sectionally and utilized for biochemical and histological analyses. Results and Discussion: DNR treatment significantly attenuated myocardial function and increased apoptosis in the ex vivo heart model. DNR-induced cardiac cytotoxicity was associated with the upregulation of two E3 ubiquitin ligases, MuRF-1 and MAFbx as well as a significant increase in two markers of autophagy, beclin-1 and LC-3. These changes observed in the heart were also associated with attenuation of the PI3-kinase/Akt signalling pathway. The augmentation of autophagy with rapamycin before DXR treatment significantly reduced cell death in the in vitro model. Indeed, rapamycin treatment demonstrated to be a vital survival mechanism for acute DXR-induced cardiotoxicity as it decreased cellular ROS production, improved mitochondrial function and prevented nuclear translocation of DXR. Moreover, these changes in cardiomyocytes were also associated with a reduction in the ubiquitin-proteasome pathway (UPP). In the final part of this study, a novel tumour bearing GFP-LC3 mouse model was developed to confirm the results obtained in the in vitro study. It was demonstrated that acute DXR-induced cardiotoxicity resulted in increased apoptosis, the inhibition of autophagy and increased proteolysis via the UPP. These findings were associated with a reduction in body weight and cardiomyocyte cross-sectional area. The cardiotoxic effects of DXR were substantially reduced when autophagy was induced with rapamycin. Taken together, our data strongly indicates that it is possible to attenuate the cardiotoxic effects of doxorubicin in cancer patients by carefully controlling the levels of autophagy using rapamycin as adjuvant therapy.
AFRIKAANSE OPSOMMING: Inleiding: Die antrasikliene (AC’s), daunorubisien (DNR) en doksorubisien (DKS), is twee van die mees effektiewe AC wat bekend is vir die behandeling van sistemiese neoplasmas en soliede tumore. Hulle kliniese gebruik word egter deur dosis afhanklike kumulatiewe kardiotoksisiteit benadeel, wat tot onomkeerbare en dodelike kongestiewe hartversaking kan lei. Die meganisme waardeur AC’s hartversaking kan veroorsaak, word nog nie ten volle verstaan nie. Onlangse navorsing het aangetoon dat DKS autofagie en die ubikwitienproteosoom-bemiddelde degradasie van spesifieke transkripsie faktore aktiveer. Daar is egter geen literatuur wat die effek van AC’s op die E3-ubikwitienligases, MuRF-1 en MAFbx beskryfnie. Die doel van hierdie eerste afdeling van die studie is om die effek van DNR behandeling op die proteïen- en organel degradasie sisteme in die hart te ondersoek en om van die betrokke seinmeganismes te bepaal. Alhoewel hierdie model ideaal is om sommige seinweë wat deur DNR geaffekteer word, te ondersoek, kon seinoordragpaaie wat potensieël voordelig in hierdie konteks is, nie in bg. model gemanipuleer word nie. Die in vitro model is gebruik om die hipotese dat verhoogde outofagie AC-geïnduseerde kardiotoksisiteit verlaag en sodoende seldood verminder, te bevestig. Die doel van hierdie afdeling van die studie was: (i) om die effek van DKS op H9C2 selle te karakteriseer, (ii) om te bepaal of die induksie/inhibisie van outofagie in kombinasie met DKS kardiotoksisiteit verbeter (iii) om die invloed van verhoogde/verlaagde outofagie in kombinasie met DKS op reaktiwe suurstof species (ROS), mitokondriale funksie, endoplasmiese retikulum (ER) stress en die ubikwitienproteosoompad te ondersoek. In die finale deel van hierdie studie, is ‘n in vivo model gebruik om die moontlike voordelige effek van verhoogde outofagie in ‘n GFP-LC-3 tumor-draende muismodel met akute DKSgeïnduseerde kardiotoksisiteit, ondersoek. Materiaal en Metodes: Volwasse rotte is in twee groepe verdeel waar een groep ses intraperitoneale inspuitings van 2 mg/kg DNR op afwissellende dae ontvang het en die andergroep as ‘n kontrole, ‘n soutoplossing gekry het. Die harte is verwyder en geperfuseer op ‘n werkende hartsisteem een dag na die laaste inspuiting en gevriesklamp vir biochemiese analises. H9C2 selle is vir 6 uurgekweek en behandel met Bafilomisien A1 (10 nM, ‘n autofagie inhibitor), 24 uur met Rapamisien (50 μM, ‘n autofagie induseerder), 24 uur met DKS (3 μM) of ‘n kombinasie van hierdie middels. Na behandeling is selle ge-oes vir analises in seldood, proteolitiese aktiwiteit en oksidatiewe stress deur van westelike kladtegniek, fluoresensie mikroskopie en vloeisitometrie gebruik te maak. In die finale fase van hierdie studie is vier en twintig, agt weke oue wyfie muise ingespuit met ‘n muisborskankersellyn (E0771) en is tumorgroei waargeneem; die diere is of behandel met een rapamisien inspuiting (i.p) (4 mg/kg), of twee DKS inspuitings (i.p.) (10 mg/kg) of ‘n kombinasie van die twee middels. Na die eksperimentele protokol, is die muise van kant gemaak en hulle harte vinnig verwyder. Die harte is in twee verdeel en gebruik vir biochemiese- en histologiese analises. Resultate en Bespreking: DNR behandeling het kardiale funksie betekenisvol verswak en apoptose in die hart verhoog. DNR-geïnduseerde kardiotoksisiteit is geassosieer met die opregulering van E3-ligases, MuRF-1 en MAFbx en het ook ‘n betekenisvolle toename in twee outofagie merkers, beclin-1 en LC-3 veroorsaak. Hierdie veranderinge wat in die hart waargeneem is, is ook geassosieer met ‘n onderdrukking van die PI3-kinase/Akt seinweg. Die toename in outofagie met rapamisien voor DKS behandeling het seldood in die vorm van apoptose betekenisvol verlaag. Daarmee saam het verhoogde outofagie ‘n noodsaaklike oorlewings meganisme vir akute DKS-geïnduseerde kardiotoksisiteit gedemonstreer. Die rede hiervoor is dat dit ROS produksie verlaag het, mitokondriale funksie verbeter het en DKS translokasie vanuit die sitoplasma tot binne die nukleus verhoed het. Hierdie veranderinge in kardiomiosiete is ook met ‘n afname in die ubikwitienproteosoomseinweg (EPS) geassosieer. In die finale deel van hierdie studie, is ‘n nuwe tumor-draende muismodel ontwikkel om die resultate wat in die in vitro studie gekry is, te bevestig. Daar is bewys dat akute DKS-geïnduseerde kardiomiotoksisiteit aanleiding gegee het tot verhoogde apoptose, outofagie inhibisie en verhoogde proteolise via die EPS. Hierdie bevindinge is geassosieer met ‘n verlaging in liggaamsgewig en kardiomiosiet dwarssnit area. Die kardiotoksiese effekte van DKS is insiggewend verminder as autofagiege ïnduseer is met rapamisien. Om saam te vat: Ons data bevestig dat dit moontlik is om die kardiotoksiese effekte van DKS in kanker pasiënte te verminder deur outofagie vlakke te monitor en te kontroleer deur middel van rapamisien behandeling as bykomende terapie.
38
LUCO, DAYANE P. "Padronização de técnicas de isolamento de células de Langerhans imaturas e desenvolvimento de um modelo tridimensional de pele humana para testes de sensibilidade in vitro." reponame:Repositório Institucional do IPEN, 2014. http://repositorio.ipen.br:8080/xmlui/handle/123456789/23179.
Full textAbstract:
Submitted by Claudinei Pracidelli (cpracide@ipen.br) on 2014-12-19T17:52:28Z
No. of bitstreams: 0Made available in DSpace on 2014-12-19T17:52:28Z (GMT). No. of bitstreams: 0
Dissertação (Mestrado em Tecnologia Nuclear)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP
39
Schweininger, Johannes [Verfasser], Yves [Akademischer Betreuer] Muller, Yves [Gutachter] Muller, and Heinrich [Gutachter] Sticht. "Of rats and men: Structural and biophysical characterization of the immediate-early 1 proteins from rat and human cytomegalovirus / Johannes Schweininger ; Gutachter: Yves Muller, Heinrich Sticht ; Betreuer: Yves Muller." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2021. http://d-nb.info/1233010506/34.
Full text
40
Bott, Simone [Verfasser], and K. [Akademischer Betreuer] Amann. "Effekte einer oralen Therapie mit S 18886, einem TP-Rezeptor-Antagonisten, auf kardiovaskuläre Strukturveränderungen im Hypertonie-Modell der doppelt transgenen "human renin-angiotensinogen rats" (dTGR) / Simone Bott. Betreuer: K. Amann." Erlangen : Universitätsbibliothek der Universität Erlangen-Nürnberg, 2012. http://d-nb.info/1023597586/34.
Full text
41
Sá, Susana Isabel Ferreira da Silva de. "Estrogénios e Plasticidade Sináptica no Hipotálamo do Rato." Tese, Faculdade de Medicina da Universidade do Porto, 2010. http://hdl.handle.net/10216/55431.
Full text
42
Morgado, Carla Sofia da Costa. "O sistema somatossensitivo no rato com neuropatia diabética." Tese, Faculdade de Medicina da Universidade do Porto, 2010. http://hdl.handle.net/10216/56845.
Full text
43
Sá, Susana Isabel Ferreira da Silva de. "Estrogénios e Plasticidade Sináptica no Hipotálamo do Rato." Doctoral thesis, Faculdade de Medicina da Universidade do Porto, 2010. http://hdl.handle.net/10216/55431.
Full text
44
Morgado, Carla Sofia da Costa. "O sistema somatossensitivo no rato com neuropatia diabética." Doctoral thesis, Faculdade de Medicina da Universidade do Porto, 2010. http://hdl.handle.net/10216/56845.
Full text
45
Chwiesko, Caroline [Verfasser], Magdalena [Gutachter] Sauvage, and Boris [Gutachter] Suchan. "Bridging human and animal recognition memory : in search of hippocampal FMRI bold responses to familiarity and novelty in awake rats / Caroline Chwiesko ; Gutachter: Magdalena Sauvage, Boris Suchan ; International Graduate School of Neuroscience." Bochum : Ruhr-Universität Bochum, 2018. http://d-nb.info/1171521766/34.
Full text
46
Pu, Chang-En, and 蒲長恩. "Methamphetamine Induced Toxicities in Rats and Human." Thesis, 1994. http://ndltd.ncl.edu.tw/handle/66700949597882443626.
Full textAbstract:
碩士國防醫學院
解剖學研究所
82
Methamphetamine(MAP) is currently the major illicit drug in Taiwan. The fatal victims due to MAP abuse are increasing. The purposes of this study are to establish a database of these fatalities for epidemiology study and to establish animal models of self-administration (ingestion) of MAP that mimic the behaviors of human and to compare the MAP-induced toxicities in rats to that of human. 50 MAP- related fatalities from 1990 to 1992 were collected from Forensic Medicine Center. The definite lesions are hemorrhagic pulmonary edema (72%, n=36). 36 out 50 autopsy cases of The MAP concentration distribution from 0.36 to 80.70 μg/ml (mean 13.21 ±17.67 μ g/ml) in blood and 0.52 to 107.00 μ g/ml (mean 25.89 ±31.46 μ g/ml) in urine, the ratio is 1:2. Rats were fed with MAP (0.005-0.2 mg/ml) for a period of time. MAP concentration of ingestion, inhalation, urine excretion and blood level were monitored by Gas Chromatography / Mass Spectrophtometer method. The quantity of daily intake (ingestion) and output (urine) of MAP of self- administration rats fed with MAP 0.05, 0.1, 0.2 mg/ml were correlated. Chronic MAP ingestion with the concentration above 0.05 mg/ml induced intoxication. MAP concentration of blood and urine of rats after self-administration at 30 days are 4.68± 3.03 and 37.79±4.21 μ g/ml, the ratio is 1: 8. Chronic self-administrated and MAP rats showed delayed response to MAP induced hyperthermia and vasomotor effects. Spinal rats(T1) showed no significant reduce of hyperthermia induced by MAP, with low motality rate and mild hemorrahage pulmonary edema. These data shows that fatalities, hyperthermia and neurogenic pulmonary edema induced by MAP are correlated. These data are eligible for us to evaluate the progress of MAP-related fatalities and to explain the pathogenesis of MAP-induced toxicities.
47
Govender, Melvin M. "Oxidative stress of tissue in hypertensive rats." Thesis, 2006. http://hdl.handle.net/10413/1487.
Full textAbstract:
Oxidative stress, resulting from an antioxidant/free radical imbalance, is considered to be an important etiologic factor in the patho-physiological changes associated with salt sensitive hypertension. An important unresolved issue in hypertension research is the mechanism for organ damage during the development of the syndrome. Reactive oxygen species (ROS) such as the superoxide radical (02) , hydrogen peroxide (H202), and the hydroxyl radical (OH), may playa critical role in the pathogenesis of hypertension by targeting the very tissue that is responsible for regulating blood pressure, during the hypertensive state. Thus, this study was undertaken to evaluate the antioxidant and free radical status in the DSS rat strain, which has been shown to be an excellent model of salt sensitive hypertension. The antioxidant status was evaluated on the basis of the vascular superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels, and the free radical status was evaluated on the basis of the plasma H20 2 concentration. The levels of malonyldialdehyde (MDA), which is a bio-marker for lipid peroxidation was used to determine the level of oxidative stress in the kidney, liver and brain. The kidney and liver were also subjected to an induced free radical mediated lipid peroxidation, by exposing the tissue to increasing known concentrations of H202 (2.5mM - 15mM). The level of lipid peroxidation was used to assess the tissues antioxidant buffering capacity to an induced free radical "attack". The results have shown that the DSS strain may have a compensatory increase in vascular SOD levels, to counter an increase in 02-. SOD levels were significantly lower during salt loading. The GPx levels were significantly lower in the DSS strain, and showed a slight increase during salt loading. The results demonstrate that the DSS strain has a compromised antioxidant status compared to the DSR strain. The plasma H202concentration displayed non-significant changes in the DSS strain, however salt loading did result in a non-significant increase in the plasma H202 concentration in the DSS strain. The GPx : HZ02 ratio, demonstrated an inadequate increase in GPx levels during salt loading to neutralise this non-significant increase in HzOz concentration. The kidney showed an increased level of in vivo lipid peroxidation, which could implicate increased tissue damage, and thus confirm the kidney as being a target organ during the hypertensive state. The liver and brain showed non-significant differences in the level of in vivo lipid peroxidation and are therefore thought not to be target tissue in the hypertensive state. The kidney displayed a decreased antioxidant buffering capacity to the induced free radical "attack", thereby demonstrating the tissue's decreased ability to neutralise an increased free radical level. Although the liver displayed a "normal" level of in vivo lipid peroxidation, it also displayed a decreased antioxidant buffering capacity to an induced free radical "attack", showing that the liver is able to cope with in vivo free radical levels, but at higher free radical levels, its loses its ability to quench a free radical "attack" and thereby minimise lipid peroxidation. The in vivo lipid peroxidation levels of the kidney, liver and brain have shown that tissues have varying abilities to cope with tissue oxidative stress, and behave differently, in their free radical quenching abilities. These results have shown that a compromised free radical and antioxidant status results in oxidative damage to the tissue responsible for regulating blood pressure.Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Westville, 2006.
48
Lee, Jyun-Lin, and 李俊霖. "Effects of Human Chorionic Gonadotropin on Gastrointestinal Motility in Ovariectomized Rats." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/at5hu3.
Full textAbstract:
碩士國立陽明大學
生理學研究所
97
Vomiting concurs with high levels of human chorionic gonadotropin (hCG) and a prolongation of GI transit has been reported during pregnancy, but the mechanism is uncertain. These observations have led to speculation about the possible role of hCG on gastrointestinal (GI) function. In addition, cholecystokinin (CCK) is well known to inhibit gastric emptying. Therefore, the aims of this study were to investigate the effects of hCG on GI motility in ovariectomized (Ovx) rats, and to clarify the role of CCK in regulating the hCG effects on GI motility. GI motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal and Na251CrO4. Gastric emptying was determined by measuring the amount of labeled chromium contained in the small intestine as a percentage of the initial amount received. Intestinal transit was assessed by calculating the geometric center of distribution of the radiolabeled marker. CCK concentrations in the plasma were measured by enzymeimmunoassay. The results showed that after intraperitoneal administration of hCG (50, 100 and 200 IU) 3 days, gastric emptying was decreased in a dose-dependence manner but intestinal transit was not affected. Plasma CCK levels were increased dose-dependently by hCG. Peripheral administration of lorglumide, a selective CCK1 receptor antagonist, effectively attenuated the hCG-induced inhibition of gastric emptying. Central administration of lorglumide did not alter the hCG -induced inhibition of gastric emptying. These results suggest that hCG inhibits gastric emptying in Ovx rats via a peripheral mechanism involving the stimulation of CCK release and the activation of CCK1 receptor.
49
蔡家雄. "Disposition of benzene in mice, rats, and human by PBPK model." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/94563433617020792049.
Full text
50
Huang, Pei-Yu, and 黃佩宇. "Functional roles of human umbilical mesenchymal stem cell transplantation in adult epileptic rats." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/2596u6.
Full textAbstract:
碩士國立陽明大學
生理學研究所
97
Temporal lobe epilepsy (TLE) is a common neurological disease characterized by spontaneous recurrent motor seizure (SRMS) and impairment of learning and memory. However, most antiepileptic drugs provide symptom treatment without alleviating the process of epileptogenesis. In addition, the exact neuropathological mechanisms still remain unclear. We plan to investigate the effects of human umbilical mesenchymal stem cell (HUMSC) transplantation in rats with pilocarpine-induced epilepsy model. Specifically, the present study aimed to (1) examine the molecular and cellular changes of hippocampal cytoarchitecture, and (2) observe the behavioral manifestation of SRMS. Male Sprague-Dawley rats (200-300 g) were divided into four groups: (1) control rats, (2) control rats receiving HUMSC grafts, (3) epileptic rats receiving HUMSC grafts, and (4) epileptic rats receiving sham grafts. Status epilepticus (SE) was induced by pilocarpine (1.2 mg/μl; 2-3 μl) via intracerebroventricular administration, and was suppressed with diazepam at 1.5 hours later. HUMSCs (105; 10 μl) were injected into left hippocampal CA3 region at the first day after SE. Animals were sacrificed at the 28th day after SE. The survival and distribution of HUMSC in the hippocampal were confirmed by the detection of its surface marker (CD105). Hippocampal cell loss, aberrant mossy fiber sprouting (MFS), neuron-specific nuclear protein (NeuN) and neuropeptide Y (NPY) expression, were assessed by Nissl stain, Timm’s stain, and immunohistochemistry, respectively. The neuron loss in CA1 and CA3 regions were decreased and NPY expression was increased in the epileptic rats receiving HUMSC grafts. Additionally, in this group, half of rats did not reveal MFS. The behavioral performance of SRMS were not observed in epileptic rats receiving sham grafts and epileptic rats receiving HUMSC grafts from 2 to 11 weeks post SE, whereas we observed that only the epileptic rats receiving sham grafts began to demonstrate SRMS at 12th week. In conclusion, HUMSC transplantation may promote cell survival, modulate synaptic reorganization, and prolong the occurrence of SRMS in pilocarpine-induced rats.