Thesis (doctoral)--University of Turku, 1990. / Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin, 1973. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph.D.)--University of Iowa, 2009. / Thesis supervisor: Ellen Lewin. Includes bibliographical references (leaves 213-234).

The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on October 2, 2009). Thesis advisor: Dr. David C. Geary. Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri--Columbia, 2005. / "July 2005" Typescript. Vita. Includes bibliographical references (l. 197-212). Also issued on the Internet.

Η τεστοστερόνη έχει πολυεπίπεδη αναβολική και ανδρογόνο δράση. Τα τελευταία χρόνια η άποψη ότι συμβάλει στην αύξηση της αθηρωμάτωσης, η οποία οδηγεί σε καρδιαγγειακά συμβάματα στο ανδρικό φύλο, άρχισε να κλονίζεται. Διάφορες μελέτες καταδεικνύουν ότι βασικές μεταβολικές παράμετροι που επηρεάζουν την εξέλιξη της αθηρωμάτωσης, όπως είναι το λιπιδαιμικό προφίλ και το βάρος μεταβάλλονται δυσμενώς με την πτώση των επιπέδων της τεστοστερόνης και αποκαθίστανται με την επάνοδο των επιπέδων της στο φυσιολογικό. Τα αποτελέσματα αυτών των ερευνών είναι όμως πολλές φορές αντιφατικά μεταξύ τους. Σημαντικό στοιχείο του συστήματος των λιπιδίων αποτελούν οι λιποπρωτεΐνες LDL και HDL καθώς και η απολιποπρωτεΐνη Ε και οι νυποδοχείς της LDL οι οποίοι είναι απαραίτητοι στην κάθαρση των LDL σωματιδίων στο ήπαρ. Στόχος της εργασίας αυτής ήταν η περαιτέρω διευκρίνιση του ρόλου της τεστοστερόνης σε βασικούς μεταβολικούς παράγοντες που εξελίσσουν την αθηρωματική διαδικασία. Για το σκοπό αυτό χρησιμοποιήθηκαν τρεις ομάδες μυών: μία με εξάλειψη του γονιδίου της ApoE (ApoE-/- ), μία με εξάλειψη του γονιδίου του υποδοχέα της LDL (LDLr-/- ) και μία αγρίου τύπου C57BL6. Οι μισοί μύες υπέστησαν ορχεκτομή και οι άλλοι μισοί ψευδοχειρουργείο και τέθηκαν σε δίαιτα δυτικού τύπου για 12 εβδομάδες. Οι LDLr-/- ορχεκτομηθέντες μύες είχαν σημαντικά μικρότερο ξηρό βάρος και λίπος από την ομάδα ελέγχου (9.1±0.9gr. και 19.0±1.4gr ξηρού βάρους καθώς και 8.8±0.9gr και 3.4±0.4gr λίπους αντίστοιχα ). Επιπλέον στους LDLr-/- μύες η δοκιμασία ανοχής γλυκόζης έδειξε χειρότερο γλυχαιμικό έλεγχο στην ομάδα ελέγχου αντίθετα με ότι συνέβαινε με την ομάδα των C57BL6. Παρεμφερής εικόνα υπήρξε και από τα τριγλυκερίδια του πλάσματος τα οποία ήταν αυξημένα στην ομάδα ελέγχου των LDLr-/- αντίθετα με τις ομάδες των ApoE-/- και C57BL6 στις οποίες δεν παρατηρήθηκε διαφορά. Τα ευρήματα αυτά καταδεικνύουν τον καθοριστικό ρόλο της τεστοστερόνης στην αύξηση του βάρους και την συνακόλουθη υπερτριγλυκεριδαιμία και διαταραχή στη δοκιμασία ανοχής γλυκόζης σε μύες LDLr-/-. Ειδικότερα, μπορεί να γίνει η υπόθεση ότι η παρουσία της τεστοστερόνης εξασφαλίζει ένα εναλλακτικό μοριακό μονοπάτι αναγκαίο για την αύξηση του βάρους σε LDLr-/- μύες. / Testosterone exhibits multiple anabolic and virilizing functions. Recently the classical view that testosterone contributes to the progression of atherosclerosis which leads to cardiovascular events is being doubted. Various studies have shown that a number of basic metabolic parameters affecting the progress of atherosclerosis such as blood lipid levels and body weight are deteriorated with the decrease of testosterone levels and restored after testosterone levels become normal again. Many of these studies provide contradicting results. The LDL and HDL lipoproteins constitute an important component to the lipid system as well as the Apolipoprotein E and the LDL receptors which are indispensable for the process of the LDL particle removal from circulation through the liver. The aim of this study was to further delineate the role of testosterone in affecting key metabolic parameters which in turn interfere with the rate of atherosclerosis progression. To achieve that, three groups of 10 mice each, were used: wild type C57BL6, ApoE deficient (ApoE-/-) and LDLr deficient (LDLr-/-). Half the mice were orchectomized and the rest were sham operated. After a four week recovery period the mice were fed western type diet. LDLr-/- orchectomized mice had significantly lower dry mass and body fat than the control group (9.1±0.9gr. και 19.0±1.4gr of dry mass and 8.8±0.9gr and 3.4±0.4gr of body fat respectively). Furthermore, glucose tolerance test revealed impaired control in the LDLr-/- control group contrary to what happened with the orchectomized LDLr-/- and C57BL6 mice. Likewise, triglyceride plasma levels were elevated in the LDLr-/- control group in contrast to their ApoE-/- and C57BL6 and, LDLr-/-orchectomized counterparts whose levels did not deviate significantly from their basal state. These findings underline the crucial role testosterone plays in hyperlipedaemia, weight gain and glucose tolerance. Specifically, testosterone seems to provide an alternative molecular route which is crucial for weight gain in LDLr-/- mice.

Orientador: Agnaldo Bruno Chies / Coorientador: Oduvaldo Câmara Marques Pereira / Banca: Liliam Fernandes / Banca: Carlos Alan Cândido Dias Junior / Banca: André Sampaio Pupo / Banca: Osni Lázaro Pinheiro / Resumo: As repercussões fisiológicas da redução a longo prazo dos níveis plasmáticos de testosterona têm sido sistematicamente estudadas, uma vez que retratam algumas situações clínicas comumente observadas em homens, tais como o hipogonadismo e o envelhecimento. Um dos importantes alvos das ações androgênicas é o sistema cardiovascular. Particularmente, existe uma importante lacuna de conhecimento em relação à ação da testosterona em leitos venosos. Observamos anteriormente que a orquidectomia promove aumento das ações vasomotoras da fenilefrina em veia porta de rato e que mecanismos relacionados à endotelina-1 poderiam estar envolvidos neste fenômeno. Assim, o objetivo do presente trabalho foi estudar a influência da orquidectomia, seguida ou não de reposição hormonal com testosterona, sobre as respostas vasomotoras de diferentes veias isoladas de rato a agonistas simpatomiméticos. Para isto, utilizaram-se ratos Wistar machos adultos controles e orquidectomizados, seguidos ou não de reposição hormonal (propionato de testosterona, 10mg/kg, i.p., por 3 semanas, com intervalo de 5 dias entre as doses). Destes animais, anéis (4-5 mm) de veias pulmonar, renal, femoral, mesentérica, assim como de artérias, pulmonar, femoral, mesentérica, aorta torácica e abdominal foram estudados em cubas de órgão isolado. Obtiveram-se curvas concentração-resposta para fenilefrina, noradrenalina, clonidina, metoxamina, assim como para endotelina-1, calculando-se pEC50 e resposta máxima (Rmax). Além disso, determinou-se a expressão do mRNA para endotelina-1 e para os receptores ETA e ETB. Os resultados mostraram que a orquidectomia seguida ou não de reposição hormonal não alterou a capacidade contrátil de veia porta frente à clonidina e metoxamina, tampouco frente à noradrenalina na presença de timolol... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The physiological repercussions of a long term reduction in testosterone levels have been systematically investigated, once it can be related with some clinical situations frequently seen in men such as hypogonadism and aging. One of the most important targets of androgen actions is the cardiovascular system. However, androgenic actions upon this system remain controversial especially in venous bed. We have previously observed that orchidectomy induces an increase in vasomotor responses of phenylephrine in rat portal vein. Probably mechanisms related to endothelin-1 could be involved in this phenomenon. Thus, the presented study aimed to investigate the influence of orchidectomy, followed or not by testosterone replacement, upon the response of different isolated veins to sympathomimetic agonists. In this manner, we used control and orchidectomized adult male Wistar rats, with the latter group followed or not by testosterone replacement (testosterone propionate, 10mg/kg, i.p., for 3 weeks, with 5-day intervals between the doses). Rings (3-4 mm) of pulmonary, renal, femoral and mesenteric veins and pulmonary, femoral and mesenteric arteries, as well as thoracic and abdominal aorta were studied in organ baths. Concentration-response curves were obtained to phenylephrine, norepinephrine, clonidine, methoxamine, and to endothelin-1. The maximum response (Rmax) and EC50 were calculated. Furthermore, we determined the mRNA expression of endothelin-1 and the ETA and ETB receptors. The results showed that orchiectomy, followed or not by testosterone replacement did not alter the contractile response of portal vein to clonidine and methoxamine, either face to noradrenaline in the presence of timolol (10-6M) or timolol (10-6M) + yohimbine (10-6M). However, although modifications of portal vein responses to endothelin-1 were not induced by orchidectomy... (Complete abstract click electronic access below) / Doutor

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No. of bitstreams: 1 talita_emanuela_domingues.pdf: 1944980 bytes, checksum: c19178f686ffe12e73375417db38510c (MD5) Previous issue date: 2015 / A doen?a renal cr?nica consiste em les?o renal com perda progressiva e irrevers?vel da fun??o dos rins. Nesta fase, os pacientes recebem indica??o de terapia renal substitutiva sendo a Hemodi?lise o recurso mais utilizado. Evid?ncias indicam que a pr?tica de exerc?cio f?sico intradial?tico ? ben?fica. Entretanto, os benef?cios desta modalidade de exerc?cio sobre par?metros end?crino-metab?licos e de estresse oxidativo ainda s?o poucos conhecidos. Objetivo: Avaliar o efeito de uma sess?o de exerc?cio f?sico de intensidade leve a moderada, sobre par?metros end?crino-metab?licos e de estresse oxidativo de pacientes com doen?a renal cr?nica submetidos ? hemodi?lise. M?todos: Doze volunt?rios, alocados de forma randomizada, do Servi?o de Hemodi?lise da Santa Casa de Caridade de Diamantina/MG participaram do estudo. Todos foram cross-over durante o experimento, a fim de comparar os resultados entre os dias de hemodi?lise sem exerc?cio (HD s/ exc) e hemodi?lise com exerc?cio (HD c/exc), e os dias posterior ? sess?o de hemodi?lise sem exerc?cio (P-HD s/ exc) e posterior ? sess?o de hemodi?lise com exerc?cio (P-HD c/exc), para cada volunt?rio. O exerc?cio f?sico intradial?tico ocorreu de maneira supervisionada, e por meio de um cicloerg?metro port?til. A coleta de saliva para avalia??o dos par?metros end?crino-meteb?licos cortisol e testosterona ocorreu durante todos os dias do protocolo experimental, em seis momentos ao longo do dia, a saber: ao acordar (T1) e trinta minutos ap?s (T2), 12:00h (T3), 14:00h (T4), 16:00h (T5) e ?s 19h (T6). As amostras de sangue para avalia??o dos par?metros de estresse oxidativo foram coletadas apenas em dias de hemodi?lise, em dois momentos: antes (T3) e ap?s (T4) a sess?o de hemodi?lise. Resultados: As concentra??es de cortisol e testosterona para os dias de hemodi?lise com exerc?cio f?sico (HD c/exc) n?o se elevaram significativamente em rela??o ?s concentra??es apresentadas no dia de hemodi?lise sem exerc?cio f?sico (HD s/exc), o que tamb?m ocorreu para os dias posteriores ? aplica??o do protocolo de exerc?cio intradial?tico (PHD c/ exc e P-HD s/ exc). Entretanto, a raz?o testosterona/cortisol aumentou significativamente no dia posterior ? sess?o de hemodi?lise com exerc?cio (P-HD c/ exc) quando comparada ao dia posterior ? sess?o de hemodi?lise sem exerc?cio (P-HD s/ exc). Os par?metros de estresse oxidativo n?o apresentaram altera??es induzidas pelo protocolo de exerc?cio f?sico. Conclus?o: O exerc?cio f?sico intradial?tico alterou o status anab?lico 24 horas ap?s ? sua realiza??o e n?o induziu altera??es significativas nos par?metros de estresse oxidativo.sumo / Programa Multic?ntrico de P?s-gradua??o em Ci?ncias Fisiol?gicas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2015. / Chronic kidney disease is a kidney injury with progressive and irreversible loss of kidney function. At the severe stage, patients undergo renal replacement therapy and the hemodialysis being the most used medical resource. Evidence indicates that the practical of physical exercise during the hemodialysis sessions is beneficial. However, the benefits of this exercise modality on endocrine-metabolic parameters and on oxidative stress remains unknown. Objective: To evaluate the effect of an exercise session mild to moderate intensity, on endocrine-metabolic parameters and oxidative stress in patients with chronic renal failure undergoing hemodialysis. Methods: Twelve users of the Hemodialysis Service of Santa Casa de Diamantina Charity / MG participated, were assigned randomly as volunteers in the study and were cross-over during all the experiment in order to compare the results between the days of hemodialysis session without exercise (HD s/ exc) and hemodialysis session with exercise (HD c/ exc), and the subsequent days of hemodialysis session without exercise (P-HD s/ exc) and after the hemodialysis session with exercise (P-HD w / exc) for each volunteer. The exercise protocol was performed in a portable bicycle ergometer and its intensity was previously determined for each volunteer as mild to moderate. Saliva samples were collected during all days of the experimental protocol, six times throughout the day, namely on waking (T1) and thirty minutes after (T2), 12: 00 (T3), 14 : 00 (T4), 16: 00h (T5) and 19h (T6) to determine the salivary cortisol concentrations and salivary testosterone concentrations. Blood samples were collected in days of hemodialysis sessions, in two times: pre (T3) and after (T4) hemodialysis session to determine the REDOX status parameters. Results: The concentrations of cortisol and testosterone on the days of hemodialysis with exercise (HD c / exc ) did not increase significantly in relation to the concentrations shown on hemodialysis day without exercise (HD s / exc ), which also happened after the exercise protocol application days (P-HD c/ exc and PHD s/exc). However, the reason testosterone/cortisol increased significantly on the day after the hemodialysis session with exercise (P-HD w / exc) when compared to the day after the hemodialysis session without exercise (P-HD s / exc). The oxidative stress parameters did not show induced changes by the physical exercise protocol. Conclusion: It was shown that the exercise protocol induced changes in the anabolic status 24 hours after its realization and did not induce changes in oxidative stress parameters.

This project involved the study of mechanisms which modulate autonomic transmission within the sympathetic nervous system using the mouse vas deferens as a model tissue. Data was collected using contraction studies, electrophysiological techniques with sharp microelectrodes, and fluorescent calcium imaging of both smooth muscle cells and nerve terminal varicosities. An additional series of experiments was conducted using the PC12 cell line, derived from a phaeochromocytoma of the rat adrenal medulla, for flow cytometry experiments using fluorescence-activated cell sorting. During the course of this project a novel technique for studying the activity of the norepinephrine transporter within a whole organ preparation was developed using the neurotransmitter uptake assay. The uptake of this assay within the nerve terminals of the vas deferens was abolished by desipramine whilst its rate of washout was increased by amphetamine. However, some non-neuronal, peri-nuclear staining which could not be prevented by a range of pharmacological means was also observed. This new technique was then used in other work exploring putative NET regulation by cannabinoids. The modulatory effects of two pharmacological groups were assessed: testosterone and cannabinoids. Testosterone was found to have a rapid, non-genomic effect inhibiting neurotransmission within the vas deferens. This was a postjunctional effect which appeared to involve modulation of the opening of L-type calcium channels on the smooth muscle cells. For the studies of cannabinoids, two broad areas of research were conducted. First the effects of Δ⁹-tetrahydrocannabinol were investigated with regard to the pre-junctional release of neurotransmitters and the effect of THC on calcium dynamics within individual nerve terminal varicosities. Secondly, a surprising novel effect upon the norepinephrine transporter was identified and examined. This inhibitory effect was revealed initially by contraction experiments demonstrating a decrease in the rate of uptake of noradrenaline from the junction. This work demonstrates that there are still novel modes of regulation of sympathetic transmission to be uncovered. The ongoing challenge is to establish their role within physiology and pathophysiology.

Made available in DSpace on 2014-06-11T19:32:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-08-30Bitstream added on 2014-06-13T18:43:04Z : No. of bitstreams: 1 rossignoli_ps_dr_botib_parcial.pdf: 102153 bytes, checksum: d8a43ae97f1572f4a15916ef299ec5df (MD5) Bitstreams deleted on 2014-11-14T12:16:55Z: rossignoli_ps_dr_botib_parcial.pdf,Bitstream added on 2014-11-14T12:17:44Z : No. of bitstreams: 1 000708975.pdf: 551554 bytes, checksum: 67f6e5c14cf654e1e8d2efbd9933a82c (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / As repercussões fisiológicas da redução a longo prazo dos níveis plasmáticos de testosterona têm sido sistematicamente estudadas, uma vez que retratam algumas situações clínicas comumente observadas em homens, tais como o hipogonadismo e o envelhecimento. Um dos importantes alvos das ações androgênicas é o sistema cardiovascular. Particularmente, existe uma importante lacuna de conhecimento em relação à ação da testosterona em leitos venosos. Observamos anteriormente que a orquidectomia promove aumento das ações vasomotoras da fenilefrina em veia porta de rato e que mecanismos relacionados à endotelina-1 poderiam estar envolvidos neste fenômeno. Assim, o objetivo do presente trabalho foi estudar a influência da orquidectomia, seguida ou não de reposição hormonal com testosterona, sobre as respostas vasomotoras de diferentes veias isoladas de rato a agonistas simpatomiméticos. Para isto, utilizaram-se ratos Wistar machos adultos controles e orquidectomizados, seguidos ou não de reposição hormonal (propionato de testosterona, 10mg/kg, i.p., por 3 semanas, com intervalo de 5 dias entre as doses). Destes animais, anéis (4–5 mm) de veias pulmonar, renal, femoral, mesentérica, assim como de artérias, pulmonar, femoral, mesentérica, aorta torácica e abdominal foram estudados em cubas de órgão isolado. Obtiveram-se curvas concentração-resposta para fenilefrina, noradrenalina, clonidina, metoxamina, assim como para endotelina-1, calculando-se pEC50 e resposta máxima (Rmax). Além disso, determinou-se a expressão do mRNA para endotelina-1 e para os receptores ETA e ETB. Os resultados mostraram que a orquidectomia seguida ou não de reposição hormonal não alterou a capacidade contrátil de veia porta frente à clonidina e metoxamina, tampouco frente à noradrenalina na presença de timolol... / The physiological repercussions of a long term reduction in testosterone levels have been systematically investigated, once it can be related with some clinical situations frequently seen in men such as hypogonadism and aging. One of the most important targets of androgen actions is the cardiovascular system. However, androgenic actions upon this system remain controversial especially in venous bed. We have previously observed that orchidectomy induces an increase in vasomotor responses of phenylephrine in rat portal vein. Probably mechanisms related to endothelin-1 could be involved in this phenomenon. Thus, the presented study aimed to investigate the influence of orchidectomy, followed or not by testosterone replacement, upon the response of different isolated veins to sympathomimetic agonists. In this manner, we used control and orchidectomized adult male Wistar rats, with the latter group followed or not by testosterone replacement (testosterone propionate, 10mg/kg, i.p., for 3 weeks, with 5-day intervals between the doses). Rings (3-4 mm) of pulmonary, renal, femoral and mesenteric veins and pulmonary, femoral and mesenteric arteries, as well as thoracic and abdominal aorta were studied in organ baths. Concentration-response curves were obtained to phenylephrine, norepinephrine, clonidine, methoxamine, and to endothelin-1. The maximum response (Rmax) and EC50 were calculated. Furthermore, we determined the mRNA expression of endothelin-1 and the ETA and ETB receptors. The results showed that orchiectomy, followed or not by testosterone replacement did not alter the contractile response of portal vein to clonidine and methoxamine, either face to noradrenaline in the presence of timolol (10-6M) or timolol (10-6M) + yohimbine (10-6M). However, although modifications of portal vein responses to endothelin-1 were not induced by orchidectomy... (Complete abstract click electronic access below)