Objetivo: Avaliar os efeitos dos estrogênios conjugados eqüinos (ECE), isolados ou associados ao acetato de medroxiprogesterona (AMP) sobre os glicosaminoglicanos do colo e do corno do útero de ratas. Métodos: 40 ratas adultas, após 30 dias de ooforectomia foram distribuídas em quatro grupos: GI - controle (veículo); GII - ECE (50 g/Kg, por dia); GIII - AMP (0,2 mg/Kg, por dia) e GIV - ECE (50 g/Kg, por dia) + AMP (0,2 mg/Kg, por dia). As substâncias foram administradas por gavagem por 28 dias consecutivos, sendo que ao final, após anestesia, o colo e o corpo do útero foram retirados e mergulhados em acetona para detecção e quantificação dos glicosaminoglicanos. Os glicosaminoglicanos sulfatados foram submetidos a eletroforese em gel de agarose e o ácido hialurônico a ensaio fluorimétrico (ELISA-like). Os resultados foram analisados pelo teste de t de Student e de ANOVA, complementado pelo teste de Tukey-Kramer (p<=0,05). Resultados: Foi detectada, em todos os grupos, maior concentração de glicosaminoglicanos sulfatados tanto no colo como nos cornos uterinos, em especial do dermatam sulfato. Já a concentração de ácido hialurônico foi maior no corno do que no colo. Com relação ao dermatam sulfato, os estrogênios promoveram incremento, tanto no colo quanto no corpo, sendo que a medroxiprogesterona bloqueou esta ação nos cornos uterinos. Os estrogênios e a medroxiprogesterona, por sua vez, apresentaram ação positiva nos níveis de heparam sulfato no colo do útero, já no corno este efeito foi atribuído à medroxiprogesterona. Conclusões: O perfil e a quantificação dos glicosaminoglicanos nas duas porções do útero de ratas são diferentes. Os glicosaminoglicanos sulfatados, em especial o dermatam sulfato, mostrou-se em maior concentração tanto no colo quanto no corno uterino. Os estrogênios e a medroxiprogesterona têm ação positiva nos glicosaminoglicanos sulfatados do colo, enquanto a medroxiprogesterona apresenta efeito antagônico no corno. O ácido hialurônico apareceu em maior concentração no corno do que no colo uterino. / Objective: To evaluate the effects of conjugated equine estrogens (CEE) alone or associated to medroxyprogesterone acetate (MPg) on glycosaminoglycans (GAGs) in the cervix and horns of the rat uterus. Methods: Thirty days after ovariectomy, 40 adult rats were randomly divided into four groups: GI, control (treated with drug vehicle); GII, CEE (50 ?g/Kg per day); GIII, MPg (0.2 mg/Kg per day), and GIV, CEE + MPg (doses as in GII and GIII). Drugs and vehicle were given by gavage during 28 days. After this the animals were euthanized, the uterine cervix and body were removed, fixed in acetone and further processed for GAGs quantification. Agarose gel electrophoresis was used for sulphated GAGs analyses; the hyaluronic acid was assayed with an ELISA-like method. Statistical analysis was done by the Student\'s t test and the Tukey-Kramer test. Significant differences were set at p<=0.05. Results: In all groups sulphated GAGs concentration (especially dermatan sulphate) was higher than that of nonsulphated GAGs, both in the cervix and in the uterine horns. Hyaluronic acid concentration in uterine horns was higher than in the cervix. With regard to dermatan sulphate, CEE exerted trophic effects both in horns and cervices, whereas MPg blocked this action in the uterine horn. The cervical concentration of heparan sulphate was rised by CEE and by MPg; in the uterine horns the same rise was observed, and this effect was attributed to MPg. Conclusions: The qualitative and quantitative profiles of GAGs in the horns and cervix of rat uterus are distinct. Sulphated GAGs (especially dermatan sulphate) are more concentrated than the non-sulphated ones in both uterine regions. With regard to sulphated GAGs, estrogens and medroxyprogesterone have trophic actions on sulphated GAGs at the cervix, whereas at the uterine horn MPg shows an antagonistic action. The concentration of hyaluronic acid in the uterine horns was higher than in the cervix.

Tyrimo tikslas buvo išanalizuoti maisto produktų užterštumą kai kuriomis A grupės farmakologiškai aktyviomis medžiagomis Lietuvoje. Darbo metu atlikta A grupės farmakologiškai aktyvių medžiagų patekimo į organizmą jų sukeliamą žalą bei kiekius maisto produktuose liečiančią mokslinę literatūrą. Aptartas farmakologiškai aktyvių medžiagų teisinis reglamentavimas LR bei ES, išanalizuoti 1998-2006 metų literatūroje rasti farmakologiškai aktyvių medžiagų monitoringo duomenys, bei 1998-1999 ir 2004-2006 metais sukauptų visų farmakologiškai aktyvių A grupės medžiagų stebėsenos rezultatai pagal maisto žaliavų grupes. Informacija ir tyrimų medžiaga gauti iš Nacionalinės veterinarijos laboratorijos ir atlikta jų statistinė analizė SPSS statistiniu paketu (SPSS Inc, 1995-2007). Analizuojant 1998-2006 metų A grupės farmakologiškai aktyvių medžiagų stebėsenos aprašomosios statistikos rezultatus nustatyta, kad daugiausiai mėginių ištirta ieškant chloramfenikolio likučių maisto produktuose (1271). Daugiausiai maisto produktų tyrimų nustatant A grupės medžiagas atlikta 2003 metais (1476). Per analizuojamą laikotarpį daugiausiai ištirta galvijienos (3024) ir kiaulienos (1069) mėginių, mažiausiai – medaus, avienos, triušienos, žvėrienos ir vandens mėginių. Daugumos A grupės medžiagų - stilbeno ir stilbeno produktų, antitiroidinių agentų, steroidų (išskyrus estradiolį ir testosteroną), rezorcilo rūgšties laktinų, beta-antagonistų zeranolio, farmakologiškai aktyvių junginių (chloramfenikolio... [toliau žr. visą tekstą] / The purpose of research was to analyze the contamination of food products with some pharmacologically active substances of group A in Lithuania. The work analyzed the getting of pharmacologically active substances of group A into the organism, the damage that they cause, and the scientific literature related to their amounts in the food products. The legal regulation of pharmacologically active substances in Lithuania and the EU was discussed, the monitoring data on the pharmacologically active substances found in the literature of the years 1998-2006 was analyzed together with the monitoring results of pharmacologically active substances of group A accumulated in 2004-2006, according to the groups of raw food materials. The information and research’s material was received from the National Laboratory of Veterinary and its statistical analysis was done with the help of SPSS statistical package (SPSS Inc, 1995-2007). While analyzing the results of the descriptive statistics of the monitoring of pharmacologically active substances of group A in the years 1998-2006, it was determined that the majority of samples were analyzed in search for the remains of chloramphenicol in the food products (1271). The majority of tests with food products determining the substances of group A was done in 2003 (1476). During the analyzed period the number of samples of cattle meat (3024) and pork (1069) was the biggest, while that of honey, lamb, rabbit, game and water was the smallest. The... [to full text]

Made available in DSpace on 2015-12-06T23:05:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2005 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Programa de Apoio a Núcleos de Excelência (PRONEX) / Fundo de Auxílio aos docentes e Alunos (FADA) / 0 modelo experimental de epilepsia, induzido por pilocarpina, em fêmeas inicialmente descrito por Amado e cols., (1993). Após esses achados, vários estudos continuaram a ser efetuados na tentativa de se obter um conhecimento maior do envolvimento hormonal no fenômeno epileptogênico. Nesse sentido, este trabalho teve como objetivo, estudar a função dos hormônios sexuais no modelo de epilepsia induzido por pilocarpina, em ratas castradas. Utilizamos como grupo de estudos: (a) animais controles (estro, metaestro, diestro, proestro e castradas), (b) animais experimentais, que receberam pilocar pina e foram estudados na fase crônica do modelo (intacta crônica e castrada crônica) e (c) animais castrados, que na fase crônica do modelo foram submetidas à terapia de reposição hormonal (castrada crônica tratada com acetato de medroxiprogesterona, castrada crônica tratada com 17beta-estradiol e castrada crônica tratada com acetato de medroxiprogesterona + 17beta-estradiol. Pudemos verificar que todos os animais castrados tiveram atrofia genital após 4 dias do procedimento cirúrgico. Além disso, todos os animais que receberam pilocarpina apresentaram crises espontâneas e recorrentes na fase crônica. O estudo da distribuição hipocampal de parvalbumina mostrou que a marcação para esta proteína sofre flutuações durante as fases ao ciclo estral e apresenta maior marcação no grupo de ratas castradas que receberam acetato de medoxiprogesterona + 17beta-estradiol. Em relação à freqüência de crises o melhor tratamento após a castração foi aquele onde houve reposição de acetato de medoxiprogesterona + 17beta-estradiol. Entretanto, animais que receberam a reposição somente com acetato de medoxiprogesterona também tiveram redução do número de crises. Além disso, o tratamento hormonal também foi capaz de estabilizar o brotamento supragranular de fibras musgosas, mostrando a importância desses hormônios no desenvolvimento da epilepsia em fêmeas. / The epilepsy model, induced by pilocarpine, in females was described by Amado et al., (1993) and was been used to understand the effect of hormones in epileptogenesis. Therefore this work was as objective, to study the function of sexual hormones in the epilepsy model induced by pilocarpine in castrated rats. We use as groups: (a) controls animals (estrus, metaestrus, diestrus, proestrus and castrated), (b) experimental animals, that was received pilocarpine and it was studied in the chronic phase of the model (normal chronic and castrated chronic) and (c) castrated animals, that in the chronic phase it was submitted to the hormonal replace therapy (castrated chronic treated with medroxiprogesterone acetate, castrated chronic treated with 17β- estradiol and castrated chronic treated with medroxiprogesterone acetate + 17β-estradiol. We could verify that all the castrated animals were genital atrophy 4 days of the surgical procedure. Moreover, all the animals that were received pilocarpine presented spontaneous recurrent seizures in the chronic phase. The study of the hipocampal distribution of parvalbumine showed that the staining for this protein presents fluctuations during the phases from the estrous cycle and presents greater staining in the group of castrated rats that was received medoxiprogesterone acetate + 17β-estradiol. In the frequency of seizures the best treatment after the castration was that one where medoxiprogesterone acetate + 17β-estradiol. However, animals that received the replacement only medoxiprogesterone acetate also was reduction of the number of seizures. Moreover, the hormonal treatment also was capable os stabilize the sprouting mossy fibers, showing the importance of these hormones in the development of the epilepsy in females rats. / BV UNIFESP: Teses e dissertações

Orientador: Luis Guillermo Bahamondes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-12T11:48:13Z (GMT). No. of bitstreams: 1 Sanches_Luciana_M.pdf: 2162409 bytes, checksum: b3edab8c6bcc59cc639d9b6b5d09e971 (MD5) Previous issue date: 2008 / Resumo: Introdução: Diante da relevância da contracepção na saúde reprodutiva, muitos estudos sobre segurança e eficácia contraceptiva são realizados a cada ano. O contraceptivo injetável com acetato de medroxiprogesterona de depósito (AMP-D) é um método reversível e eficaz. Entretanto, seu uso provoca hipoestrogenismo e pode afetar a densidade mineral óssea (DMO) durante seu uso ou após a descontinuação, levando à osteopenia e osteoporose. A osteoporose é uma doença caracterizada pela diminuição absoluta da quantidade de osso, tornando-o frágil, sendo um dos maiores problemas de saúde, pois está associada com o aumento no risco de fraturas. O efeito do uso do AMP-D durante a vida reprodutiva sobre a DMO na pós-menopausa ainda é controverso. Objetivo: Avaliar a DMO em mulheres na pós-menopausa que usaram o AMP-D como contraceptivo até a menopausa e comparar com mulheres na pós-menopausa que usaram o dispositivo intra-uterino (DIU) com cobre. Sujeitos e métodos: Estudo com 135 mulheres na pós-menopausa, com idade entre 43 e 58 anos, compreendendo 36 usuárias de AMP-D e 99 usuárias de DIU com cobre como grupo comparativo. A DMO foi avaliada nas porções distal e ultradistal do rádio do antebraço não dominante, usando a técnica da energia dupla de Raios-X, até 3 anos após a menopausa. Todos os valores foram expressos em média ± erro-padrão da média (EPM). Resultados: O tempo de uso de ambos os contraceptivos foi de 9,4 ± 3,8 e 14,7 ± 6,2 anos para o AMP-D e DIU, respectivamente. As DMO na seção distal nos anos 1 e 2-3 após a menopausa foram 0,435 e 0,449 e 0,426 e 0,447 nas usuárias de AMP-D e DIU, respectivamente. Na seção ultradistal os valores foram: 0,369 e 0,384 e 0,340 e 0,383, respectivamente. Todos sem significância estatística. Conclusões: Mulheres com idade entre 43 e 58 anos, na pós-menopausa, ex-usuárias de AMP-D, apresentaram DMO, no ano 1 ou 2-3 após a menopausa, similar ao grupo de controle. / Abstract: Objetive: The aim of the study was to compare bone mineral density (BMD) in post menopausal women who were users of depot-medroxyprogesterone acetate (DMPA) or copper intrauterine device (IUD) up to the menopause. Volunteers and methods: This study included 135 postmenopausal women, aged 43 to 58 year divided on a group of formers users of DMPA (36 women) and the control group of formers users of the copper IUD (99 women). BMD was measured at the nondominant forearm using double X-ray absorptiometry up to 3 years after the menopause. Results: The mean time of previous use of both contraceptives was (Mean ± SEM) 9.4 ± 3.8 and 14.7 ± 6.2 years for DMPA and IUD, respectively. The mean BMD at the distal section at years 1 and 2-3 after the menopause among DMPA and IUD users were 0.435 and 0.449 and 0.426 and 0.447, respectively. At the ultradistal section the values were 0.369 and 0.384 and 0.340 and 0.383, respectively, without statistically significance. Conclusions: Postmenopausal women aged 43 to 58 former users of either DMPA or copper IUD up to the onset of menopause presented similar BMD at 1 or 2-3 years after the menopause. / Mestrado / Ciencias Biomedicas / Mestre em Tocoginecologia

Orientador: Ilza Maria Urbano Monteiro / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-27T21:47:52Z (GMT). No. of bitstreams: 1 Souza_NataliaDal'Avade_D.pdf: 1420906 bytes, checksum: a2935c71ee1a1153564862074a4b592f (MD5) Previous issue date: 2015 / Resumo: INTRODUÇÃO: O ganho de peso associado ao uso de métodos contraceptivos contendo apenas progestágenos pode levar à descontinuação do uso. A avaliação da composição corporal (CC) pode auxiliar na compreensão e monitoração do ganho de peso. A mensuração da CC pela técnica de absorciometria de duplo feixe de raios-X (DEXA) permite quantificar os diferentes componentes da CC - massa gorda (MG), massa magra (MM). OBJETIVOS: Estimar a CC de mulheres na menacme e avaliar sua variação entre usuárias de acetato de medroxiprogesterona de depósito (AMPD) comparadas com usuárias de dispositivo intrauterino TCu380A (DIU TCu380A). SUJEITOS E MÉTODOS: Foram realizados dois estudos de avaliação da CC pela técnica DEXA. As participantes dos estudos foram selecionadas no Ambulatório de Planejamento Familiar do Departamento de Tocoginecologia da UNICAMP. Estudo 1: Estudo de corte transversal com 639 mulheres, entre 20 e 50 anos, divididas por faixas etárias (20-25, 26-30, 31-35, 36-40, 41-45, 46-50), no qual foi avaliado o peso corporal (kg), índice de massa corpórea (IMC kg/m2) e as variáveis de CC: MG (kg) e MM (kg), percentual de MG e de MM, índice de MG (IMG kg/m²) e índice de MM (IMM kg/m²). Estudo 2: Estudo de coorte prospectivo com acompanhamento de um ano, composto por dois grupos: 26 usuárias de AMPD como grupo-estudo e 26 usuárias de DIU TCu380A como grupo-controle , pareadas por peso (±2kg) e idade (±2 anos). Para avaliação da mudança de CC utilizaram-se variações percentuais de MG e MM e do peso (kg). A primeira avaliação foi realizada antes de se iniciar o uso do método contraceptivo e a segunda após 12 meses de uso. RESULTADOS: Estudo 1: Houve aumento absoluto de peso de 8kg (p=0,0001), 4,7kg de MG (p=0,003) e 1,9kg de MM (p=0,124) concomitante com a idade, embora não tenha ocorrido mudança significativa nos percentuais de MG e MM. O IMC(kg/m²) médio foi de 26,18(±4,6), sendo que as mulheres apresentaram sobrepeso desde a faixa etária de 26 a 30 anos e altos percentuais de gordura, atingindo valor médio de 41,6%(±7,4). O IMG médio das mulheres foi 10,5(±3,5). Estudo 2: Aos 12 meses de uso, as usuárias de AMPD tiveram aumento de peso de 1,9kg (p=0,02), resultante do ganho de 1,6kg (p=0,03) de MG. Nas usuárias de DIU TCu380A não houve alteração de peso; entretanto, houve ganho de 1,2kg de MM aos 12 meses de uso (p=0,001). O número de mulheres praticantes de atividade física aumentou neste grupo. Houve diferença significativa entre os grupos na variação do percentual de gordura central (p=0,04). CONCLUSÕES: As mulheres avaliadas apresentaram sobrepeso desde a idade jovem e ganho de peso, concomitantemente ao aumento da idade. Embora os percentuais de MG e MM não tenham se modificado, a quantidade absoluta de MG e de MM aumentou com o aumento da idade. O ganho de peso ocorrido nas usuárias de AMPD deveu-se ao ganho de MG, enquanto que as usuárias de DIU TCu380A tiveram aumento de MM e diminuição na MG abdominal / Abstract: INTRODUCTION: Weight gain associated with the use progestin-only contraceptive methods can lead women to discontinue the use. The boody composition assessment (BC) could assist to understand and to monitor weight gain. Evaluation of body composition by the technique dual-energy X-ray absorptiometry (DXA) allows to quantify the different components of CC: fat mass (FM) and lean mass (LM). OBJECTIVE: This study estimated body composition in women at reproductive age and evaluated body composition (BC) changes in users of depot medroxyprogesterone acetate (DMPA) and compared to TCu380A intrauterine device (IUD) users. SUJEITOS E MÉTODOS: It was performed two studies of BC assessment by DXA. Women of both studies were recruited at Woman Hospital of University of Campinas (Unicamp). Study 1: Cross-sectional study assessed BC of 639 women, between 20 - 50 years into age brackets (20-25, 26-30, 31-35, 36-40, 41-45, 46-50). It was evaluated weight, body mass index (BMI kg/m²), fat (FM) and lean mass (LM), percentage of fat (%FM) and lean mass (%FFM), fat mass index (FMI kg/m²) and fat-free mass index (FFMI kg/m²). Study 2: Prospective study was performed to compare body weight (BW) and BC in DMPA and IUD users at baseline and after one year of use. We enrolled 26 new DMPA users and age (± 2) and weight (± 2) matched 26 new IUD users. Weight and height were measured, BC (fat and lean mass), and physical activity was assessed at baseline and at 12 months. RESULTS: Study 1: It was an increase of 8kg of BW (p=0.0001), 4.7kg of FM (p= 0.003) of 1.9kg of LM (p= 0.124) concomitantly with increasing age, however it was no significant changes in %FM and %LM. Mean BMI (kg/m²) was 26.18 (±4.6), and women presented overweight since 26 years and elevated %FM, mean of 41.6% (±7.4). Mean FMI was (kg/m²) 10.5 (±3.5). Study 2: An increase of 1.9 kg occurred in BW (p=0.02) in DMPA users at 12 months of use, resulting from an increase in fat mass of 1.6 kg (p=.03). Weight remained stable in IUD users; however, there was an increase in lean mass of 1.2kg at 12 months of use (p=0.001). The number of women practicing physical activity increased in this group. There was a significant difference between the groups regarding the variation in the percentage of central fat (p=0.04). CONCLUSIONS: The women evaluated were overweight from the range of 26-30 years and presented weight gain concomitantly with increasing age. Although the percentage of fat and lean body mass has not changed, the absolute amount of fat and lean body mass increased with increasing age. Weight gain in the DMPA group resulted from an increase in fat mass. Weight remained stable in the IUD group; however, an increase in lean mass and a reduction in localized abdominal fat mass occurred / Doutorado / Fisiopatologia Ginecológica / Doutora em Ciências da Saúde

Thesis (MScMedSc (Pathology. Medical Microbiology))--University of Stellenbosch, 2005. / The aim of this study was to investigate the anti-inflammatory and immunosuppressive effects of the synthetic progestins, MPA and NET-A on human cells in vitro. These injectable contraceptives are used extensively throughout the world, including Africa. The potential of these two synthetic hormones to have certain immunosuppressive and GC properties have previously been shown. Therefore, it was of concern to us to investigate whether these two hormones could possibly demonstrate any of these GC-like properties at contraceptive doses. This was achieved by determining the effects of these two synthetic hormones in vitro on certain immunologic parameters. Chapter 1 is a literature review on MPA, NET and GCs. This chapter starts with a short introduction that sets the scene. The mode of action, effectiveness, sideeffects as well as previously reported relevant data on both MPA and NET-A is portrayed in this review. Research on the known GC, Dex, is also included in the section dealing with GCs, because this synthetic hormone was used as a comparative GC in all our experiments. This chapter soon makes the reader realize how much evidence exists that indicate the possible immunosuppressive effects these two contraceptive hormones, in particular MPA, could have. The possible anti-inflammatory or pro-inflammatory effects of MPA and NET-A are investigated in Chapter 2. This was done in vitro by measuring the effects of these two synthetic hormones on the inflammatory markers, IL-6 and TNFα, by means of ELISA. In this chapter we demonstrate that MPA, even at contraceptive doses, exhibits significant anti-inflammatory properties on both cytokines tested, while NETA displayed considerably less anti-inflammatory tendencies. In its true antiinflammatory manner, we found that Dex significantly inhibited the release of both inflammatory markers from human monocytes. In Chapter 3, we investigated the effects of MPA and NET-A on the activation of human lymphocytes. This was achieved by flow cytometric measurement of the expression of the activation membrane marker CD69 by CD4 and CD8 T cells. Here we discovered that MPA had a very significant inhibitory effect on the activation of both CD4+ and CD8+ T cells, while NET-A only significantly inhibited the activation of CD8+ T cells. In addition, we found that the inhibition of CD4+ and CD8+ T cell activation by MPA was more or less the same as the known GC, Dex, and in some cases even more potent. Chapter 4 consists of an investigation of the effects of MPA and NET-A on the cytokines belonging to TH1 and TH2 subsets of CD4 T cells. This was achieved by determining whether MPA and/or NET-A targeted specific subsets of T helper cells by measuring the distinct regulatory cytokines, IFNγ and IL-4. The mechanism and role of the T helper subsets are discussed in the introduction of this chapter. Our results were portrayed as a ratio of TH2: TH1 on which the statistical analysis was done. In addition to the analysis done on the ratio, we analyzed the helper subsets separately in order to determine which subset(s) were influenced. The results of this chapter showed that neither MPA nor NET-A significantly affected either one of the helper subsets, while Dex significantly decreased this ratio. After our observed effects of MPA and NET-A on CD8 T cells, it became of interest in Chapter 5 to investigate the effects of these two synthetic hormones on the CD8 T cell-specific chemokine, RANTES. This was achieved by measuring the effects MPA and NET-A had on RANTES production in vitro by means of ELISA. Surprisingly, we discovered in this chapter that MPA and NET-A enhanced RANTES production before and after activation of CD8 T cells. We also found that Dex had the same effect on RANTES production, but to a lesser degree. Finally, a general conclusion depicting the significance and implications of our results as well as possible future research that is required is presented in Chapter 6. It was of great importance to discuss and interpret the magnitude of data generated out of all our experiments to the utmost of our capabilities. We found that MPA, even at contraceptive doses, displayed significant immunosuppressive as well as anti-inflammatory properties. NET-A, on the other hand, demonstrated weaker immunosuppressive properties in our research and no significant anti-inflammatory properties. These findings could have clinical implications in females being treated with these synthetic contraceptives. We also demonstrated significant variation found amongst genders in response to MPA, NET-A and Dex.

Orientador: Sarah Monte Alegre / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T08:26:23Z (GMT). No. of bitstreams: 1 Batista_GiseleAlmeida_M.pdf: 1859346 bytes, checksum: 3cb1bc28cbd20d9ddb7e8e3a58874a1e (MD5) Previous issue date: 2014 / Resumo: Introdução: O acetato de medroxiprogesterona de depósito (AMPD, Depoprovera®) é um método contraceptivo de alta eficácia e segurança; seu uso tem se difundido amplamente e vem sendo utilizado por milhões de mulheres. Existem poucos estudos na literatura sobre o gasto energético em repouso nas usuárias de Depoprovera®, e é possível que existam variações especialmente naquelas que ganham peso em uso do método. Objetivo: Avaliar as alterações no peso, composição corporal e gasto energético em repouso de mulheres em uso de acetato de medroxiprogesterona de depósito e DIU TCu 380 no período de 12 meses. Métodos: Estudo prospectivo com 20 usuárias de Depoprovera® e 17 usuárias de DIU TCu380, como controle, no período de um ano. Mulheres atendidas no ambulatório de Planejamento Familiar do CAISM/UNICAMP em idade fértil, que optaram como método contraceptivo o injetável Depoprovera®, sem uso prévio deste método, e que apresentavam Índice de Massa Corporal (IMC) < 30 kg/m², além de mulheres que utilizavam o método contraceptivo não hormonal DIU TCu 380A foram convidadas a participar do estudo. Resultados: Os grupos foram pareados no período basal, tornando-se um grupo homogêneo em relação a peso, idade e IMC. Após 12 meses de avaliação, pode-se observar aumento de peso, IMC e superfície corporal de forma significativa no grupo Depo. Em relação ao gasto energético em repouso e quociente respiratório, houve aumento significativo da taxa metabólica basal nos dois grupos. O quociente respiratório reduziu de forma significante nos dois grupos. Quando o grupo Depo foi subdividido por ganho de peso, o subgrupo que ganhou < 3 kg após 12 meses teve aumento significativo de peso, IMC, superfície corporal e quociente respiratório, já o subgrupo que ganhou > 3 kg aumentou significativamente peso, IMC, superfície corporal, peso de massa magra, peso de massa gorda, taxa metabólica basal, Leptina, HOMA-IR e circunferência da cintura e reduziu quociente respiratório após os 12 meses de acompanhamento. Conclusão: Nosso estudo encontrou alterações relevantes no peso, composição corporal e perfil metabólico da população estudada nos primeiros 12 meses de uso do contraceptivo. Essas alterações principalmente o aumento de peso corporal, aumento dos níveis de leptina e HOMA-IR, podem contribuir para o desenvolvimento de algumas complicações crônicas, entre elas a obesidade, resistência à insulina e diabetes mellitus / Abstract: Introduction: Depot Medroxyprogesterone Acetate (DMPA, Depoprovera®) is an high contraceptive efficacy and safety; its use has spread broadly and has been used by millions of women. There are few studies on the resting energy expenditure in Depoprovera® users, and it is possible that there are variations especially those who gain weight using the method. Objective: To evaluate the changes in weight, body composition and resting energy expenditure in women using depot medroxyprogesterone acetate and IUD TCu 380 in 12 months. Methods: This was a prospective study with 20 Depoprovera® users and 17 IUD users TCu380 as a control within one year. Women attending the outpatient clinic of CAISM / UNICAMP of childbearing age who chose the injectable contraceptive Depoprovera ® without previous use of this method, Body Mass Index (BMI) < 30kg / m², and women using non-hormonal contraception IUD TCu 380, were invited to participate in the study. Results: The groups were paired at baseline, becoming a homogeneous group in relation to age (± 1 year), and BMI (+1 kg/m²). After 12 months of evaluation, we could observe a significant increase in the DMPA group in weight, BMI and body surface. Relative to resting energy expenditure and respiratory quotient, there was an increase of baseline metabolic rate in both groups after one year. The respiratory quotient was significantly reduced after 12 months in groups DMPA and IUD. The sub-group DMPA that gained < 3kg had increased significant weight, BMI and body surface with respiratory quotient reduction, while the sub-group that gained > 3kg had a significant increase in weight, BMI, body surface, free fat mass, fat mass, baseline metabolic rate, Leptin, HOMA-IR and waist circumference, with respiratory quotient significantly reduced. Conclusion: Our study found significant changes in weight, body composition and metabolic profile of the population studied in the first 12 months of contraceptive use. These changes mainly increased body weight, leptin levels and HOMA-IR which can contribute to the development of some chronic complications, including obesity, insulin resistance and diabetes mellitus / Mestrado / Clinica Medica / Mestra em Clínica Médica

The androgen receptor (AR) fulfils important roles for both sexes. By mediating the biological function of androgens, the AR has remained the target for endocrine therapies treating prostate cancer. The AR also determines the effectiveness of medroxyprogesterone acetate (MPA) in treating AR positive breast cancer. Every man will be affected by prostate cancer if he lives long enough. Prostate cancer continues to be a leading cause of death for males despite research into this cancer covering more than 60 years since Huggins' seminal 1941 study showing that androgens play a key role in this cancer. Unfortunately, significant advances have not been forthcoming and the effect of treatment has remained largely the same over past decades, whereby initial treatment provides temporary remission but eventually advanced cases become refractory to further intervention and the disease recurs in a more aggressive form. A plethora of factors are exquisitely sensitive to minute changes in the AR's structural profile, which can be altered by a single mutation, resulting in aberrant activity. A principal feature of these variant ARs associated with prostate cancer, is enhanced capacity to bind a number of molecules other than its cognate ligand, dihydrotestosterone (DHT). The promiscuous activity of this receptor leads to continued AR signalling and stimulus for the cancer despite low androgen levels induced by treatment regimes. A key question is whether mutations occurring within the AR occur as a result of cancer or contribute to the propagation of the cancer. Recent research has demonstrated that treatments incorporating anti-androgens such as flutamide, which are designed to impede prostate cancer progression by inhibiting AR activity, may actually provide selective pressure favouring somatic mutation of the receptor to take place. The specific changes to the AR which are responsible for gains of function have not been resolved as their crystal structures, which are used to provide conformational analysis of proteins, are tremendously problematic to produce with little success found in literature. Generating representative crystals of the AR protein involves producing soluble recombinant protein. Unfortunately the AR is prone to aggregation and is highly unstable, especially in the presence of antagonistic molecules or absence of a stabilising ligand, preventing the protein from being maintained in the soluble state required for crystallization. In order to produce sufficient quantities of soluble material for crystallization, the androgen receptor's ligand binding domain (LBD) was produced as a recombinant protein in Escherichia coli bacteria strain BL21 (DE3) in the presence of DHT, flutamide, as well as in the absence of ligand. Since soluble unbound AR-LBD has not been produced until now, the bacterial culture containing no ligand was further processed to the stage of cleaving the purification tag from the recombinant protein and represents considerable progress into producing soluble material for crystallizing the troublesome yet considerably important AR in the absence of ligand. Although distinct from prostate cancer in males, AR activity in breast tissue is also a factor determining the action of drugs, such as MPA, included in therapies aimed at breast cancer. The use of MPA has declined primarily due to its adverse effects including unsuccessful generation of a biological response, as well as the advent of other drugs administered for hormonal therapies treating breast cancer. Alternative drugs are needed when breast cancer therapies fail as tumours develop resistance to primary drugs. Although there are a number of drugs on the market, success would be maximised if the determined therapy is matched with the patient, based for example, on their genetic makeup. There is a conundrum whereby some patients with an AR do not respond to MPA, a drug normally recognised by the receptor. In clinical trials it was discovered that an AR with threonine instead of methionine at residue 780 (M780T) fails to activate in response to MPA, but the exact mechanism has remained elusive and needs to be answered at the molecular level. The X-ray crystallographic studies that generate 3D images of macromolecules and wet chemistry, which have traditionally been used to provide insight into science in these dimensions, are incorporated with computer based molecular simulation. This is both complementary and distinct to traditional scientific methodologies, enabling further elucidation of protein-protein interactions, and the influence applied to such inter-relations by natural and drug ligands. This approach has been used, and is continually developed, to understand the binding mechanisms of current drugs as well as designing new drugs. In order to produce a receptor representing the M780T variant, the crystal structure representing the AR-LBD was mutated in silico, into which MPA was then docked. It was found that MPA binds into the M780T AR-LBD with considerably more spatial displacement compared to the position of DHT in the crystal structure, and is predicted to be the primary reason for the inability of MPA to activate this variant AR. The clarification of MPA binding and failure to elicit a response from the variant AR is significant for a cohort of breast cancer patients, as not only does the presence of an AR in the tumour determine the effectiveness of MPA, but correct composition of the AR, specifically, the absence of a M780T mutation. In the absence of this AR mutation, MPA could effectively be used either as an alternative to primary drugs, or in secondary therapies when primary therapies fail. Aberrant activity of variant ARs in response to MPA should also be taken into consideration when analysing drug studies about the effectiveness of MPA. The findings on the loss of response to MPA by the M780T variant AR have been included in the journal article &quotDecreased Androgen Receptor Levels and Receptor Function in Breast Cancer Contribute to the Failure of Response to Medroxyprogesterone Acetate" appearing in the September 2005 issue of Cancer Research journal.

Objetivo: O objetivo deste estudo foi avaliar em mulheres com tumores císticos de ovário, a proporção que, somente com o tratamento clínico e/ou punção, não necessitaram de cirurgia; a influência da medicação e das doenças associadas na indicação de cirurgia e se a punção reduziu significativamente o tamanho dos cistos. Casuística e métodos: Selecionaram-se 71 mulheres com idade entre 19 e 70 anos de idade, portadoras de tumores císticos de ovário maior que 5 cm, com características de benignidade ao ultra-som transvaginal com Doppler colorido e pulsado e com perfil endócrino e marcadores séricos tumorais normais. Foram divididas em cinco grupos: 1) Grupo A: 15 mulheres que fizeram uso de acetato de noretisterona; 2) Grupo B: 13 mulheres que fizeram uso de acetato de medroxiprogesterona; 3) Grupo C: 14 mulheres que utilizaram contraceptivo oral; 4) Grupo D: 15 mulheres que foram tratadas com análogo de GnRH e 5) Grupo E: 14 mulheres que não fizeram uso de medicação. Todos os grupos foram acompanhados por um ano. No final do primeiro trimestre, se o cisto persistiu, foi realizada a punção. No final do segundo trimestre, se houve recidiva do cisto, foi indicada cirurgia. As pacientes tiveram alta após um ano de acompanhamento com o tratamento do cisto concluído. Resultados: Não houve diferenças significantes entre os cinco grupos. Constatou-se que a condição de uso de medicação para doença associada teve influência significativa no resultado dos tratamentos. Verificou-se que a redução do tamanho do cisto com a punção foi efetiva após 9 meses de acompanhamento. Observou-se que 7% das mulheres tiveram indicação direta para cirurgia sem a punção, portanto, a proporção de recidiva da punção foi de 19,3% enquanto a porcentagem de mulheres que não fizeram a cirurgia foi de 73,2%. Conclusão: A proporção de mulheres que responderam adequadamente somente com o tratamento clínico e/ou a punção, não necessitando pois de cirurgia foi de 73,2%. A influência da medicação/ doença associada no tratamento não cirúrgico foi significativa. A redução do tamanho dos cistos benignos em função do tratamento instituído incluindo a punção foi significativa, a qual foi observada após 9 meses de tratamento. / Objectives: To evaluate the rate of women with ovarian cystic tumors submitted to diferent regimens of hormonal treatment and/or aspiration that didn’t need surgery. To access the effectiveness of ovarian cyst aspiration guided by ultrasonography (USG) and to study the influence of medication and associated diseases in the need for surgery. Patients and Methods: Seventy one (71) women, in an age range from 19 to 70 years, diagnosed with ovarian cysts larger than 5 cm in length, with benign aspect, examined using an ultrasonographic transvaginal probe and color Doppler. All the women have been submitted to measurements of ser um tumor markers and hormonal levels. They were grouped in five different categories: 1) Group A: 15 women treated with noretisterone acetate; 2) Group B: 13 subjects treated with medrooxiprogesterone acetate; 3) Group C: 14 patients treated with combined oral contraceptive; 4) Group D: 15 women treated with GnRH analog, and 5) Group E: 15 women with no treatment control). After 3 months, all the patients were reevaluated. In those ones whose cysts remained, cyst aspiration guided by ultrasonography was indicated. After 3 extra months, the women were submitted to a new USG examination and in those whose cysts still remained, surgery was performed. All the patients were followed for one year. Results: There was no significant difference among the groups of hormonal treatment. The use of medication promoted a significant influence in the treatment outcomes. We also noted that the cyst aspiration was effective in reducing the size of the cysts after 9 months of follow up. Seven per cent (7%) of the patients have had immediate indication for surgery. Among those who was submitted to cyst aspiration, 19.3% had to be resubmitted to treatment because of re-incidence of the cyst, whereas, 73.2% avoid the need for surgery. Conclusions: The proportion of subjects treated with hormones and/or cyst aspiration, with no need for surgery, was of 73.2%. The influence of medication/associated disease in the treatments without surgery was significant. The reduction of size of the cysts because of the hormonal and/or aspiration treatment was significant, which was observed after 9 months of therapy.

Objetivo: O objetivo deste estudo foi avaliar em mulheres com tumores císticos de ovário, a proporção que, somente com o tratamento clínico e/ou punção, não necessitaram de cirurgia; a influência da medicação e das doenças associadas na indicação de cirurgia e se a punção reduziu significativamente o tamanho dos cistos. Casuística e métodos: Selecionaram-se 71 mulheres com idade entre 19 e 70 anos de idade, portadoras de tumores císticos de ovário maior que 5 cm, com características de benignidade ao ultra-som transvaginal com Doppler colorido e pulsado e com perfil endócrino e marcadores séricos tumorais normais. Foram divididas em cinco grupos: 1) Grupo A: 15 mulheres que fizeram uso de acetato de noretisterona; 2) Grupo B: 13 mulheres que fizeram uso de acetato de medroxiprogesterona; 3) Grupo C: 14 mulheres que utilizaram contraceptivo oral; 4) Grupo D: 15 mulheres que foram tratadas com análogo de GnRH e 5) Grupo E: 14 mulheres que não fizeram uso de medicação. Todos os grupos foram acompanhados por um ano. No final do primeiro trimestre, se o cisto persistiu, foi realizada a punção. No final do segundo trimestre, se houve recidiva do cisto, foi indicada cirurgia. As pacientes tiveram alta após um ano de acompanhamento com o tratamento do cisto concluído. Resultados: Não houve diferenças significantes entre os cinco grupos. Constatou-se que a condição de uso de medicação para doença associada teve influência significativa no resultado dos tratamentos. Verificou-se que a redução do tamanho do cisto com a punção foi efetiva após 9 meses de acompanhamento. Observou-se que 7% das mulheres tiveram indicação direta para cirurgia sem a punção, portanto, a proporção de recidiva da punção foi de 19,3% enquanto a porcentagem de mulheres que não fizeram a cirurgia foi de 73,2%. Conclusão: A proporção de mulheres que responderam adequadamente somente com o tratamento clínico e/ou a punção, não necessitando pois de cirurgia foi de 73,2%. A influência da medicação/ doença associada no tratamento não cirúrgico foi significativa. A redução do tamanho dos cistos benignos em função do tratamento instituído incluindo a punção foi significativa, a qual foi observada após 9 meses de tratamento. / Objectives: To evaluate the rate of women with ovarian cystic tumors submitted to diferent regimens of hormonal treatment and/or aspiration that didn’t need surgery. To access the effectiveness of ovarian cyst aspiration guided by ultrasonography (USG) and to study the influence of medication and associated diseases in the need for surgery. Patients and Methods: Seventy one (71) women, in an age range from 19 to 70 years, diagnosed with ovarian cysts larger than 5 cm in length, with benign aspect, examined using an ultrasonographic transvaginal probe and color Doppler. All the women have been submitted to measurements of ser um tumor markers and hormonal levels. They were grouped in five different categories: 1) Group A: 15 women treated with noretisterone acetate; 2) Group B: 13 subjects treated with medrooxiprogesterone acetate; 3) Group C: 14 patients treated with combined oral contraceptive; 4) Group D: 15 women treated with GnRH analog, and 5) Group E: 15 women with no treatment control). After 3 months, all the patients were reevaluated. In those ones whose cysts remained, cyst aspiration guided by ultrasonography was indicated. After 3 extra months, the women were submitted to a new USG examination and in those whose cysts still remained, surgery was performed. All the patients were followed for one year. Results: There was no significant difference among the groups of hormonal treatment. The use of medication promoted a significant influence in the treatment outcomes. We also noted that the cyst aspiration was effective in reducing the size of the cysts after 9 months of follow up. Seven per cent (7%) of the patients have had immediate indication for surgery. Among those who was submitted to cyst aspiration, 19.3% had to be resubmitted to treatment because of re-incidence of the cyst, whereas, 73.2% avoid the need for surgery. Conclusions: The proportion of subjects treated with hormones and/or cyst aspiration, with no need for surgery, was of 73.2%. The influence of medication/associated disease in the treatments without surgery was significant. The reduction of size of the cysts because of the hormonal and/or aspiration treatment was significant, which was observed after 9 months of therapy.