Orientador: Sebastião Roberto Taboga / Banca: Lara Silvia Corradi Olhê Blanck / Banca: Ana Claudia Polli Lopes / Banca: Sérgio Luis Felisbino / Banca: Luis Antonio Justulin Junior / Resumo: A crisina é um composto natural biologicamente ativo encontrado predominantemente em flores de maracujá azul, em mel, camomila, própolis e casca de frutas. Possui propriedades potentes como efeito anti-inflamatório, antioxidante e tem sido empregada para o tratamento de desordens reprodutivas. Essa flavona tem o potencial de aumentar os níveis de testosterona endógena, tanto por inibir a enzima aromatase, quanto por estimular a esteroidogênese testicular. Alterações no metabolismo hormonal mediadas por interferências exógenas podem interferir na fisiologia prostática resultando em modificações na atividade secretora da glândula e na regulação dos receptores hormonais. Assim, o objetivo deste estudo foi avaliar os efeitos da exposição à crisina sobre a próstata e gônadas de gerbilos adultos. Para avaliar o potencial androgênico da crisina, nós analisamos, comparativamente, os efeitos da testosterona sobre estes mesmos órgãos. Machos e fêmeas de gerbilos com 90 dias de idade foram tratados com crisina (50 mg/kg/dia) ou com cipionato de testosterona (1 mg/kg/semana) e divididos tem 3 subgrupos que foram eutanasiados após 3, 7 e 21 dias de tratamento. As próstatas foram coletadas para análises morfológicas, morfométrico-estereológicas, imuno-histoquímicas e ultraestruturais. Testículos e ovários foram submetidos a análises morfológicas e morfométrico-estereológicas. Os níveis séricos de testosterona e 17β-estradiol foram mensurados por ELISA. Machos e fêmeas tratados com crisina... / Abstract: Chrysin is a naturally occurring biologically active compound found predominantly in blue passion flower, honey, chamomile, propolis and fruit peel. It has potent anti-inflammatory and antioxidant properties and has been used for the treatment of reproductive disorders. This flavone has the potential to increase endogenous testosterone levels both by inhibiting the aromatase enzyme and stimulating testicular steroidogenesis. Changes in hormone metabolism mediated by exogenous interferences may interfere with the prostatic physiology resulting in changes in the secretory activity of the gland and in the regulation of hormonal receptors. Thus, the objective of this study was to evaluate the effects of the exposure to chrysin on the prostate and gonads of adult gerbils. To evaluate the androgenic potential of chrysin, we comparatively analysed the effects of testosterone on these organs. Male and female gerbils aged 90 days were treated with either chrysin (50 mg/kg/day) or testosterone cypionate (1 mg/kg/week), subdivided into 3 subgroups and euthanized after 3, 7 and 21 days of treatment. The prostates and gonads were collected for morphological, morphometric-stereological, ultrastructural and immunehistochemical analyses. The testes and ovaries were subjected to morphological and morphometric-stereological analyses. Serum levels of testosterone and 17β-estradiol were determined using ELISA methods. Males and females treated with chrysin did not show increase in serum ... / Doutor

Made available in DSpace on 2014-06-11T19:22:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-07-04Bitstream added on 2014-06-13T20:10:01Z : No. of bitstreams: 1 crespilho_dm_me_rcla.pdf: 275859 bytes, checksum: 7d173afbc11a2f0b83977a420734397e (MD5) / Secretaria de Estado de Educação / Os objetivos do presente estudo foram investigar as adaptações endócrinometabólicas em ratos submetidos ao exercício físico de natação associado com a administração de testosterona durante 8 semanas. Ratos jovens Wistar foram divididos em 4 grupos: controle sedentário (CS), controle treinado (CT), testosterona sedentário (TS), testosterona treinado (TT). O protocolo de natação consistiu de 1 hora/dia, 5 dias/semanas, durante 8 semanas, suportando durante a natação uma sobrecarga de 5% do seu peso corporal. A testosterona foi administrada 3 dias/semana, na concentração de 5 mg/kg de peso corporal do animal, por via subcutânea, também por 8 semanas. Ao final da sétima semana de experimento, os ratos foram submetidos aos testes de tolerância à glicose (GTT) e teste de tolerância à insulina (ITT). Após 10 semanas os animais foram sacrificados na condição de repouso. Amostras de sangue foram coletadas para a determinação do hematócrito, glicose, insulina, proteínas totais, colesterol total e triglicérides. Os testículos, a próstata e vesícula seminal, os tecidos adiposos foram analisados em balança analítica. O tecido muscular e hepático foram usados para determinação do glicogênio e da razão proteína/DNA. As adrenais foram pesadas e usadas para determinar o conteúdo de colesterol e ácido ascórbico. A análise estatística foi feita por ANOVA e aplicação do teste de post-hoc de Newman-Keuls, onde adequado, com nível de significância pré-fixado em 5%. Os resultados indicam que os ratos treinados tiveram maior tolerância à glicose comparados com os animais sedentários durante o GTT. Nossos dados mostram que a administração crônica da testosterona mais o treinamento físico foi associada ao aumento da sensibilidade à insulina.O grupo treinado administrado com testosterona mostrou uma maior taxa de desaparecimento... / The aims of this study were to investigate the endocrine-metabolic adaptations in rats submitted to chronic swimming exercise associate to administration of testosterone during 8 weeks. Young Wistar rats were divided into four groups: sedentary control (CS), trained control (CT), sedentary testosterone (TS), trained testosterone (TT). Training protocol consisted of swimming 1h/day, 5 days/week, during 8 weeks, supporting a load of 5% body weight. Testosterone was administered 3 times a week, in concentration of 5 mg/kg body weight, during 8 weeks. After 7 weeks rats were submitted to glucose (GTT) and insulin (ITT) tolerance tests. After 8 weeks rats were sacrificed in rest. Blood samples were collected to determine hematocrit, glucose, insulin, total protein, total cholesterol and triglyceride. Hepatic and muscular tissues were used to determine glycogen and protein/DNA ratio. Adrenals were weighed and used to determine cholesterol and ascorbic acid contents. The results were analyzed by ANOVA and Newman- Keuls post-hoc test where appropriate and the significance level was 5%. The results indicate that trained rats showed higher glucose tolerance compared to sedentary animals during GTT. Our data showed that chronic exposure to testosterone plus physical training was associated with increase insulin sensitivity. The animals trained and administered with testosterone, showed higher glucose disappearance rates when compared to other groups. Testosterone administration promoted decrease in testicular mass and increase in prostate and seminal vesicle. Training promoted increase in muscle when compared to the sedentary groups, taking us to presuppose that training stimulated glycogen syntheses. The training protocol, testosterone administration or combination of two treatments, resulted in decrease of epididimal and perirrenal adipose tissues weight... (Complete abstract click electronic access below)

Made available in DSpace on 2014-10-09T12:49:59Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:03:46Z (GMT). No. of bitstreams: 1 00823.pdf: 1156642 bytes, checksum: 3967a87a081af8fede649a131568f486 (MD5) / Tese (Doutoramento) / IEA/T / Instituto de Biociencias, Universidade de São Paulo

Made available in DSpace on 2014-10-09T12:49:59Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:03:46Z (GMT). No. of bitstreams: 1 00823.pdf: 1156642 bytes, checksum: 3967a87a081af8fede649a131568f486 (MD5) / Tese (Doutoramento) / IEA/T / Instituto de Biociencias, Universidade de São Paulo

Orientadoesr: Wagner Eduardo Matheus, Ubirajara Ferreira / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-20T13:05:18Z (GMT). No. of bitstreams: 1 Silva_ElcioDias_D.pdf: 1974038 bytes, checksum: e1e7b084d346a50a85fec60666fbf526 (MD5) Previous issue date: 2012 / Resumo: Objetivo: avaliar a eficácia relativa do leuprolide 3,75 mg, leuprolide 7,5 mg e goserelina 3,6 mg quanto à redução da testosterona sérica, em níveis de castração. Método: foram avaliados 60 pacientes com carcinoma avançado de próstata, com indicação de bloqueio hormonal. Os pacientes foram divididos em 3 grupos de 20: Grupo 1) pacientes que receberam leuprolide na dose 3,75 mg; Grupo 2) receberam leuprolide 7,5 mg, Grupo 3) receberam goserelina 3,6 mg. Todos os grupos foram tratados por aplicação mensal das respectivas medicações. Os pacientes foram avaliados com dosagens de testosterona sérica em 2 momentos: pré-tratamento e após 3 meses de tratamento. Resultados: a idade dos pacientes foi semelhante nos três grupos, com mediana de 72, 70 e 70 anos, respectivamente aos grupos 1, 2 e 3. Dos pacientes que receberam leuprolide 3,75 mg, leuprolide 7,5 mg e goserelina 3,6 mg, 26,3%, 25% e 35%, respectivamente, não obtiveram nível de castração, considerando nível de corte de testosterona ? 50 ng/dl; e 68,4%, 30% e 45%, respectivamente, não obtiveram nível de castração, considerando nível de corte de testosterona ? 20 ng/dl. Conclusão: não houve diferença significativa na obtenção de níveis de castração com leuprolide 3,75 mg, leuprolide 7,5 mg e goserelina 3,6 mg, quando comparadas as três substâncias em conjunto. Quando comparados os grupos dois a dois, houve diferença estatisticamente significativa na análise do leuprolide 3,75 mg com o leuprolide 7,5 mg, havendo maior obtenção de nível de castração com 7,5 mg, quando se considera este nível como igual ou menor que 20 ng/dl. A importância dessa eventual diferença, no entanto, deve ser vista com cautela, já que a comparação dos três grupos simultaneamente, muito embora próximo, não atingiu o nível de significância estabelecido / Abstract: Purpose: to evaluate the relative efficiency of leuprolide 3.75 mg, leuprolide 7.5 mg, and goserelin 3.6 mg in relation to the reduction of serum testosterone, regarding the levels of castration. Methods: we evaluated prospectively 60 randomized patients with advanced prostate carcinoma, with indication for hormone blockade. The patients were divided into 3 groups of 20: Group 1) received leuprolide 3.75 mg; Group 2) received leuprolide 7.5 mg; group 3) received goserelin 3.6 mg. All groups were treated with monthly application of the respective drugs. Results: the patients' ages were similar within the three groups, with a median of 72, 70, and 70 in groups 1, 2, and 3, respectively. Of the patients that received leuprolide 3.75 mg, leuprolide 7.5 mg, and goserelin 3.6 mg, 26.3%, 25%, and 35%, respectively, did not reach castration levels, considering a testosterone cut of ?50 ng/dl. 68.4%, 30%, and 45%, respectively, did not reach castration levels, considering a testosterone cut of ?20 ng/dl. Conclusions: There were no statiscally significant differences in the levels of castration when comparing with leuprolide 3.75 mg, leuprolide 7.5 mg, and goserelin 3.6 mg, when comparing the three substances altogether. When compared in groups of two, there was a statiscally significant difference between leuprolide 3.75 mg and leuprolide 7.5 mg, in which the latter presented better results in reaching castration levels, when considered equal or less than 20ng/dl. The importance of this difference, however, must be measured with caution, since the comparison of the three groups simultaneously did not reach the established significance level, even though it came close / Doutorado / Fisiopatologia / Doutor em Ciências

Magister Scientiae (Medical Bioscience) - MSc(MBS) / This study investigated the effect of the C. capensis extract (0.001, 0.01, 0.1, 1, 10, 100 1000 μg/ml) on LNCaP prostate cancer, TM3 Leydig and TM4 Sertoli cells for 24 and 96 hours. The following parameters were investigated: morphology, cell viability (XTT), testosterone modulation, DNA fragmentation (TUNEL), lactate dehydrogenase activity (LDH), testosterone production, anti-cancer drug combination. In a separate set of experiments, parameters affecting the initiation, progression and metastasis of cancer were investigated. These included the ability of the aqueous C. capensis rhizome extract to inhibit of reactive oxygen species (ROS) and reactive nitrogen species (RNS) production, and to inhibit collagenase and elastase activity.

The influence of the gonadal sex steroids namely, estradiol, progesterone and testosterone on the two major enzymes responsible for the synthesis of melatonin in the pineal gland was investigated. These enzymes are Serotonin-N-acetyltransferase (SNAT) and Hydroxyindole-O-methyltransferase (Hl0MT). Testosterone was found to be the only sex steroid capable of influencing SNAT activity whereas all three of the sex steroids were found to influence Hl0MT activity in a biphasic dose-dependent manner. The influence of these sex steroids on radiolabeled serotonin metabolism by pineals in organ culture was also investigated. Ovariectomy, castration and the sex steroids were all found to alter the pattern of the radiolabeled serotonin metabolism by these pineal glands in organ culture. / KMBT_363 / Adobe Acrobat 9.53 Paper Capture Plug-in

Testosterone products comprise a multi-billion dollar industry; however, Health Canada and the United States Food and Drug Administration have issued statements of concern about their safety, and their benefits are unclear. In the first phase of this study, we performed a systematic review of the current evidence for the benefits of testosterone replacement therapy. In the second phase, we analyzed the evidence from randomized controlled trials for the benefits of testosterone replacement therapy (depression, quality of life, erectile function, libido, total testosterone level). In the third phase, we analyzed data for harms (cardiovascular death, myocardial infarction, stroke, newly diagnosed prostate cancer, coronary artery disease or diabetes, serious adverse events, withdrawals due to adverse events, erythrocytosis) from randomized controlled trials and non-randomized studies. In general, most included studies had a short duration and were poorly reported. Additional high-quality research into the long-term safety of testosterone products is needed.

Magister Scientiae (Medical Bioscience) - MSc(MBS) / The aim of this study is to be the first to ascertain the effects of silver nanoparticles on testosterone production. The Ag NPs used for this study have the following characteristics; purity ≥ 99.5%; 66.7 % of particles have a diameter between 20-40 nm in aqueous solution. Three month old male Balb/C mice were sacrificed and testicular cell cultures were prepared. The cells were subsequently treated with various concentrations of Ag NPs (with or without luteinizing hormone (LH)-treatment) and incubated for 4 hours. Testosterone secretion in the culture supernantant was then determined using a testosterone ELISA kit. Ag NPs (at 20 μg/ml) significantly (p < 0.001) decreased LH-stimulated testosterone production as compared to the control. This study showed that Ag NPs adversely affect testosterone synthesis in vitro and can therefore pose a risk for male reproduction.

Magister Scientiae (Medical Bioscience) - MSc(MBS) / Obesity is a growing public health concern globally, particularly in developed countries such as the United States (US). More than 30% of Americans are considered obese. In the past 20 years in America, incidence of obesity has increased significantly (Mokdad et al., 2003). As a consequence, the Centers for Disease Control (CDC) anticipates that 1 in 3 American adults will be diabetic by 2050 (Boyle et al., 2001; Hedley et al., 2004). The most important cause of obesity is poor nutrition, absence of physical exercise and unfavourable lifestyle changes (James et al., 2001).