Thesis (Ph. D.)--University of Missouri-Columbia, 1999. / Typescript. Vita. Includes bibliographical references. Also available on the Internet.

In vivo experiments were conducted to determine if elevated plasma glucocorticoid concentrations would suppress intrafollicular prostaglandin F2$ alpha$ (PGF2$ alpha$) synthesis and, thereby, inhibit ovulation in the pig. Following ACTH administration, PGF2$ alpha$ concentrations in FF tended to be lower than in controls. Injections of betamethasone partially suppressed the preovulatory rise of PGF2$ alpha$ in FF at 40h, although the effect was less marked than that produced by indomethacin. While no ovulations occurred in the indomethacin-treated group at any time, betamethasone resulted in a lower number of ovulated follicles at 44h than in the control animals. Progesterone concentrations were unaffected by the treatments. / In vitro studies were conducted with a spontaneously established cell line developed through continuous culturing of primary granulosa cells collected from prepuberal gilts six hours after they had received PMSG. Characterization of these cells revealed that aromatase and steroidogenesis were functional but gonadotropin receptors were not present. When extracellular PGF2$ alpha$ levels were measured, dexamethasone was able to significantly suppress PGF$ sb{2 alpha}$ concentrations, but not as effectively as with indomethacin. (Abstract shortened by UMI.)

Thesis (MSc)--University of Stellenbosch, 2001. / ENGLISH ABSTRACT: SEPARATION STUDY Traumatic experiences during childhood can have a negative impact on behaviour later in life. Kendier et al. (1992) found that the loss of a parent during childhood increased the risk to develop major anxiety disorders and could also lead to depressive-like behaviour (Furukawa et al., 1999). Methods: We subjected rat pups to maternal separation and determined the effects thereof on adult behaviour. We removed rat pups from their mothers for 3 hours daily from postnatal day 2 to 14. On day 60, the behaviours of the rats were tested using the elevated plus-maze and the open field test. Controls were reared normally. Behaviours: Amount of time spent and the number of entries into the arms of the maze were noted on the elevated plus-maze, while the total time spent in each zone (inner versus outer) and the number of zone crossings were noted for each rat on the open field arena. The latency to move from the initial placement in the outer zone to the inner zone as well as the number of quadrant crossings was also determined. Defecation, freezing, rearing and grooming behaviours were also noted. Neurotransmitter levels: Noradrenaline, serotonin and their metabolites were evaluated in maternally separated rats and compared to controls. Their concentrations at basal level, immediately after restraint stress and 15 minutes after restraint stress, were also determined. A HPLC method was followed in these determinations. ACTH Determinations: All rats were subjected to restraint stress for a lO-minute period. Trunk blood was collected for basal, as well as 15 and 60 minutes postrestraint stress for ACTH determinations. Results: Behaviours: The amount of entries was significantly reduced in the separated animals, indicating decreased locomotion. They spent significantly more time in the closed maze arms. A significant increase in defecation frequency and rearing behaviour was noted. These observations are typical of anxious behaviour. In the open field test, the behavioural results were less convincing. Only a significant increase in defecation frequency and a significant decrease in rearing behaviour in separated animals, were observed. Neurotransmitter levels: No significant differences were noted between separated animals and controls with respect to basal monoamine levels. However, noradrenaline levels were significantly decreased in the frontal cortex 15 minutes after restraint stress and immediately after restraint stress in the hypothalamus and hippocampus in separated animals. MHPG levels were significantly decreased in the frontal cortex immediately after restraint stress. No significant differences were found with respect to serotonin levels. However, significant increases were found in 5HIAA levels in the frontal cortex and hippocampus of separated rats, 15 minutes after restraint stress. The basal turnover ratios of serotonin (5HIAA/5HT) and noradrenaline (MHPGINA) did not yield significant results. However, immediately after restraint stress, a significant increase was found in serotonin turnover in the hypothalamus of separated rats when compared to controls. This turnover rate was also increased in separated rats, 15 minutes after restraint stress in the frontal cortex and hypothalamus. ACTH Determinations: Basal ACTH levels were significantly higher in separated animals. At 15 minutes post-restraint stress, the levels were significantly lower than controls, indicating a blunted stress response. Our results therefore showed that maternal separation could lead to anxious behaviours in adult life. These behavioural abnormalities were associated with alterations in the central nervous and neuroendocrinological systems, particularly in response to stressful situations. CRF STUDY The maternal separation study indicated that elevated CRF levels could possibly be causally related to abnormalities observed in the anxious animals. We therefore hypothesised that adverse development factors, such as maternal separation, predisposes individuals to develop psychopathologies later in life and that this process was driven by a presence of high CRF levels. Methods: Cannulas were implanted into the left lateral ventricles of normal rats, making use of stereotaxic procedures. CRF (3 flg/fll) was injected into the ventricles daily for 5 days. Saline controls were handled similarly, but only injected with saline for the same time period. Both groups of animals were then compared to naïve controls. Histology was performed to determine the correct placement of the cannulas. Behaviours: The Elevated Plus-maze was employed to determine whether their behaviours were anxious. The number of entries into the various arms of the maze as well as the amount of time spent in the open and closed arms was accumulated. Rearing, freezing, defecation and grooming were also noted. ACTH Determinations: The ACTH levels ofCRF-injected, saline-injected and naïve rats were determined 15 minutes after restraint stress. Results: Behaviours: A decrease in the number of entries into the closed arms of the maze was noted in the CRF-injected rats when compared to naïve controls. No significant differences were found between the groups with respect to the amount of time spent in the various arms and the behaviours noted during the experiment. ACTH Determinations: A decrease in ACTH levels was noted in CRF-injected rats 15 minutes after restraint stress when compared to naïve controls. Therefore, although the CRF injections did not alter the behaviour of the rat, they did exhibit a blunted stress response to the stressor. Conclusion: Our experiments led us to conclude that early adverse experiences, such as maternal separation, can lead to the development of psychopathologies later in life. CRF, however, is not pivotal in the development of these abnormalities; rather it seems that the neurochemical abnormalities (serotonin and noradrenaline) play a more important role in the development of these mental disturbances. Finally, we hypothesise that combination drug therapy that targets both the noradrenergic and serotonergic neurotransmitter systems could be preferred above those aimed at rectifying the individual neurotransmitter systems in the treatment of psychopathologies, such as anxiety disorders. / AFRIKAANSE OPSOMMING: MOEDERLIKE SKEIDINGS STUDIE Traumatiese gebeurtenisse wat gedurende kinderjare ervaar word, kan 'n negatiewe impak op die gedrag van dieselfde individue hê, as hulle volwassenheid bereik het. Kendier et al. (1992) het waargeneem dat die verlies van 'n ouer tydens die kinderjare, die risiko om angssteumisse te ontwikkel, dramaties verhoog en kan ook lei tot 'n depressiewe gemoedtoestand (Furukawa et al., 1999). Metodes: Ons het neonatale rotte aan moederlike skeiding blootgestel en die effekte daarvan op gedrag tydens hul volwasse lewe beoordeel. Ons het daagliks die moeders vir 3 ure van die kleintjies afweggeneem, vanafpostnatale dag 2 tot 14. Op dag 60, het ons die gedrag van die diere op die "elevated plus-maze" en die" open field test" getoets. Kontrole rotte het onder normale omstandighede opgegroei. Gedrag parameters: Die hoeveelheid tyd en aantal kere wat die rotte in die verskillende arms van die "elevated plus-maze" gespandeer het, was waargeneem. Die totale tyd in die "open field" toets se binneste ofbuitenste sones, die hoeveelheid kruisings tussen die twee sones, die tyd wat dit neem om beweging in die binneste sone te inisiëer, sowel as die hoeveelheid kwadrante wat gekruis was, is genotuleer. Defekasie, botstilstande, steiering, en versorgingsgedragte was ook waargeneem terwyl die rotte in die doolhowe was. Neurochemiese oordragstowwe: Die hippokampus, hipotalamus en frontale korteks van moerderlik-geskeide rotte en kontroles, was uit hul brein gedissekteer om die vlakke van noradrenalien, serotonien en hul metaboliete daarin te bepaal. Basale vlakke sowel as hul konsentrasies onmiddelik na stres en 15 minute na stres, was gedetermineer. 'n HPLC metode was gebruik vir hierdie bepalings. ACTH bepalings: Rotte, moederlik-geskei en kontroles, was onderwerp aan beperkingstres vir 'n tydsduur van 10 minute. Bloed was op die volgende tydsintervalle gekollekteer vir die bepaling van ACTH vlakke, naamlik basaal, 15 minute en 60 minute na die einde van stresperiode. Resultate: Gedrag: Op die "elevated plus-maze" was moederlik-geskeide rotte minder beweeglik omdat hul aanmerklik minder die arms van die doolhowe binne gegaan het. Hulle het ook baie meer tyd in die geslote arms gespandeer. Verder het die eksperimentele rotte meer defekasie bolusse uitgeskei en was die aantal steieringe uitgevoer, ook aanmerklik verhoog. Hierdie patroon van gedrag is tipies die van angstigheid. Neurochemiese oordragstowwe: Daar was geen betekenisvolle verskil tussen die basale neurotransmitter vlakke van moederlik-geskeide rotte en hul kontroles. Daarenteen was die vlakke van noradrenalien in die frontale korteks dramaties verhoog by die 15 minute tydsinterval na die stres, asook onmiddelik na die stres in die hipotalamus en hippokampus. MHPG vlakke was egter aanmerklik verlaag in die frontale korteks onmiddelik na die stres. Terwyl daar geen noemenswaardige verskil in serotonien vlakke waargeneem is nie, was die vlakke van 5HlAA betekenisvol verhoog in die frontale korteks en hippokampus van moederlik-geskeide rotte, 15 minute na die beperkingstres. Geen verskil in die omsettingsverhoudinge van basale serotonien (5HlAA/5HT) ofnoradrenalien (MHPGINA) vlakke is gevind nie. Daar was egter 'n betekenisvolle verhoging in die serotonien omset in die hipotalamus van moerdlik-geskeide rotte, onmiddelik na beperkingstres. Hierdie verskil het ook voorgekom 15 minute na die stresperiode in die hipotalamus, sowel as in die frontale korteks. ACTH bepalings: Rotte wat onderwerp was aan moederlike skeiding het verhoogde basale konsentrasies van ACTH getoon. Die ACTH vlakke was egter aanmerklik laer 15 minute na stres toe dit met kontrole groepe vergelyk is. Ons resultate toon dus dat moerderlike-skeiding wel tot angstige gedrag tydens die volwasse lewe kan lei. Hierdie afwyking in gedrag was geassosieër met abnormaliteite in die sentrale senuwee sisteem sowel as die neuroendokrienologiese sisteem van die dier, veralonder toestande van stres. Na gelang van ons bevindinge in die moerderlike skeidingstudie, het dit geblyk dat CRF 'n belangrike rol speel tot daarstelling van angstige gedrag. Daarom het ons in die tweede deel van ons studie gaan kyk ofverhoogde vlakke van CRF in die brein moontlik die gedrag van die rot kon verander. CRF STUDIE Metodes: Kannules was in die linker ventrikel van die breine van normale rotte geïmplanteer deur gebruik te maak van stereotaktiese prosedures. CRF (3 Ilg/IlI) was daagliks vir 5 dae aan die rotte toegedien. Rotte wat presies dieselfde gehanteer was het 'n fisiologiese soutoplossing ontvang. Hierdie rotte was met naïewe rotte vergelyk. Die korrekte plasing van kannules was met histologiese metodes bevestig. Gedrag: Die "elevated plus-maze" was gebruik om te bepaal of angstige gedragte by behandelde rotte ontlok was. Die aantal kere wat 'n rot die verskillende arms van die doolhofbinne gaan, sowel as die tyd wat die dier op elke arm deurbring was genotuleer. Die aantal steierings, botstilstande, defekasies en versorgingsbewegings was weereens waargeneem. ACTH bepalings: Die vlakke van ACTH was bepaal in al die rotgroepe, 15 minute nadat hulle aan 10 minute beperkingstres onderwerp was. Resultate: Gedrag: Rotte wat met CRF toegedien was, het op minder geleenthede die toe arms van die "elevated plus-maze" binne gegaan toe hulle met die naïewe groep rotte vergelyk was. Hierdie verskil was betekenisvol. Daar was geen ander noemenswaardige verskille ten opsigte van die ander gedragsparameter nie. ACTH bepalings: Daar was 'n afname in die ACTH vlakke, 15 minute na die stres toegedien was in rotte wat CRF ontvang het, in vergelyking tot die naïewe kontrole groep. Hierdie resultate dui daarop dat die toediening van CRF in die brein nie die rot se gedrag, maar wel die dier se respons op stres, beïnvloed het. Gevolgtrekking: In die lig van die voorafgaande resultate verky, blyk dit dat moederlike-skeiding tydens die vroeë kinderjare wel kan aanleiding gee tot angstige gedrag tydens volwassenheid. Ons studies dui ook aan dat CRF nie die primêre bron van hierdie gedrags afwykings is nie, maar dat abnormaliteite in die neurochemiese oordragstowwe (serotonien en noradrenalien) eerder die bepalende faktore is. Ten slotte, ons beveel aan dat geneesmiddels wat geskoei is om die serotonerge sowel as die noradrenerge sisteme aan te spreek, voordeel moet geniet in die behandeling van gedragstoomisse, soos angs.

Thesis (Ph.D.)--Tufts University, 2003. / Adviser: L. Michael Romero. Submitted to the Dept. of Biology. Includes bibliographical references (leaves 158-180). Access restricted to members of the Tufts University community. Also available via the World Wide Web;

Thèse (M.Sc.)--Université Laval, 2003. / Bibliogr.: f. 71-81. Publié aussi en version électronique.

Thesis (M. Sc.)--University of Canterbury, 2006. / Typescript (photocopy). "June 2006." Includes bibliographical references (leaves 67-75). Also available via the World Wide Web.

Made available in DSpace on 2014-06-11T19:30:31Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-05-18Bitstream added on 2014-06-13T19:40:15Z : No. of bitstreams: 1 cericato_l_dr_jabo.pdf: 310501 bytes, checksum: 917bfed91edc7c58d80704c91dc52a3f (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Universidade Estadual Paulista (UNESP) / A intensificação das práticas agrícolas e o aumento da produção geralmente dependem da aplicação de agrotóxicos, que podem direta ou indiretamente contaminar as fontes de água, córregos, açudes e lençóis freáticos. O peixe jundiá (Rhamdia quelen) é uma espécie da família Siluridae que ocorre no sul da América do Sul. Devido a sua prolificidade, robustez e bom ganho de peso, a espécie tem sido intensivamente estudada. A resposta ao estresse é uma reação do organismo a uma variedade de fatores adversos e compreende uma série de processos fisiológicos adaptativos coordenados pelo eixo hipotálamohipófise- interrenal (eixo HHI). O impacto de contaminantes sobre a síntese dos hormônios corticosteróides ainda é pouco conhecido para peixes tropicais. Estes hormônios possuem importante papel em processos fisiológicos como crescimento, metabolismo, balanço hidromineral, reprodução e sistema imune. Assim, qualquer impacto no seu eixo neuroendócrino pode afetar o desempenho do animal. O efeito deletério dos contaminantes sobre o eixo HHI pode ser classificado como interrupção endócrina. Neste caso, um peixe sob estresse tem significativamente reduzida sua capacidade de elevar o cortisol plasmático e, assim, fica fisiologicamente comprometido e não responde adequadamente aos estressores comuns em seu ambiente. Assim, este trabalho avaliou a resposta de estresse de jundiás quando expostos á cinco agrotóxicos, por meio da avaliação da resposta cortisolêmica a estressor padrão e pelo teste de sensibilidade ao hormônio adrenocorticotrófico (ACTH). Com os resultados obtidos pode-se perceber que, a exposição sub-letal ao metil-paration, atrazine+simazine e glifosato exercem um efeito deletério na resposta cortisolêmica a um estressor adicional em jundiá (Rhamdia quelen) e que em teste... / Exposure to agrichemicals can have deleterious effects on fish, such as disruption of the hypothalamus–pituitary–inter-renal axis (HPI) that could impair the ability of fish to respond to stressors. In this study, fingerlings of the teleost jundiá (Rhamdia quelen) were used to investigate the effects of the commonly used agrichemicals on the fish response to stress. Five agrichemicals were tested: the fungicide (tebuconazole), the insecticide (methyl-parathion), and the herbicide (atrazine, atrazine+simazine, and glyphosate). Control fishes were not exposed to agrichemicals and standard stressors. In treatments 2– 4, the fishes were exposed to sub-lethal concentrations (16.6%, 33.3%, and 50% of the LC50) of each agrichemical for 96 h, and at the end of this period, were subjected to an acute stress-handling stimulus by chasing them with a pen net. In treatments 5–7 (16.6%, 33.3%, and 50% of the LC50), the fishes were exposed to the same concentrations of the agrichemicals without stress stimulus. Treatment 8 consisted of jundiás not exposed to agrichemicals, but was subjected to an acute stress-handling stimulus. Jundiás exposed to methyl-parathion, atrazine+simazine, and glyphosate presented a decreased capacity in exhibiting an adequate response to cope with stress and in maintaining the homeostasis, with cortisol level lower than that in the control fish (P<0.01). In conclusion, the results of this study clearly demonstrate that the acute exposure to sub-lethal concentrations of methyl parathion, atrazine+simazine, and glyphosate exert a deleterious effect on the cortisol response to an additional acute stressor in the jundiá fingerlings.

A doença de Cushing (DC) permanece um desafio médico, com muitas questões ainda não respondidas. O sucesso terapêutico dos pacientes com DC está intimamente ligado à correta investigação diagnóstica sindrômica e etiológica e à escolha da melhor opção terapêutica. Várias são as alternativas terapêuticas, entre elas, as medicações anti-esteroidogênicas e as supressoras dos corticotrofos, a radioterapia, a adrenalectomia e a cirurgia hipofisária. No entanto, a adenomectomia hipofisária transesfenoidal constitui-se no tratamento de escolha para a DC. A avaliação da remissão da doença no pós-operatório e da recorrência em longo prazo constitui um desafio ainda maior, com grande divergência entre os centros médicos especializados sobre qual a melhor maneira de avaliar a atividade da doença e quais são os parâmetros indicadores de remissão e de recidiva ao longo do seguimento. Neste sentido, especial destaque deve ser dado para o papel do cortisol sérico no pós-operatório como um marcador de remissão da DC em longo prazo. Adicionalmente, a utilização de glicorticoide exógeno no pós-operatório apenas em situações de insuficiência adrenal tem sido sugerida por alguns autores, como prática fundamental para permitir a utilização do cortisol sérico neste cenário. Neste artigo, revisamos as formas de avaliação da atividade da DC e os marcadores de remissão e recidiva em longo prazo, após a realização da cirurgia transesfenoidal.

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