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The vagina is the port of entry for sexually transmitted diseases in women. Its epithelium constitutes the luminal border, thus comprising an important defence barrier. The objective of this work was to investigate the mechanisms of importance in the immune defence of the vaginal epithelium of healthy, fertile women, and possible menstrual cycle changes. Effects of hormonal contraceptive usage on oestrogen receptor (ER) and progesterone receptor (PR) expression were studied. The contribution of epithelial cell to the immune defence was estimated by assaying their expression of antimicrobial defensins and the epithelial thickness. Vaginal biopsies and serum samples were collected during the follicular and luteal phases in regularly menstruating women (controls) and in users of combined oral contraceptives (COCs), levonorgestrel implants (LNGs), or depot-medroxyprogesterone acetate injections (DMPAs). Fifteen healthy women (aged 20–34 years) were enrolled in each group. Morphometry was performed on vaginal tissue stained with haematoxylin/eosin and by immunohistochemistry using monoclonal antibodies against immune cell markers, PR, and ER. Expression of mRNA for human α-defensins HD-5 and HD-6, and human β-defensins (HBD) 1 to 4 were determined by real-time qRT-PCR and in situ hybridization. In controls, the epithelium was 261 ± 16 μm thick and harboured 241 ± 35 leukocytes (CD45+) per mm2. T lymphocytes (CD3+) dominated. Both αβ T cells and γδ T cells were present with an approximate 4-fold dominance of αβ T cells. Cytotoxic T cells (CD8+) were more frequent than T helper cells (CD4:CD8 ratio: 0.7 ± 0.1). Macrophages (CD68+) constituted the second-largest population, followed by Langerhans cells (CD1a+). B cells, natural killer cells, monocytes and granulocytes were generally absent. No differences were found between the follicular and luteal phase. All four β-defensins analysed for were detected in vaginal epithelium and most samples expressed at least two. HBD-2 and HBD-3 were most frequent. HBD-3 and HBD-4 expressing cells were localized in the parabasal and intermediate cell layers. α-defensins were not detected. The epithelium was significantly thicker (333 ± 9 μm) in COC, LNG, and DMPA users than in controls, and commonly showed hyperplasia. In DMPA and LNG users the frequency of intraepithelial leukocytes (CD45+) was increased, explained by increased frequencies of both αβ and γδ T cells. In DMPA users there was also a selective increase in CD8+ T cells. PR expression was significantly reduced in DMPA users compared with controls, COC and LNG users. COC and particularly DMPA users often had undetectable levels of serum E2. In conclusion, both adaptive immunity, i.e. intraepithelial T cells, and innate defence mechanisms, i.e. intraepithelial macrophages and β-defensins, are believed to contribute to the immune defence in the human female lower genital tract. These parameters did not change during the menstrual cycle but hormonal contraceptive usage, especially DMPA, affected the quality of the epithelium. The use of DMPA and LNG was correlated with the accumulation of T cells within the epithelium. The effects of these changes on the risk of contracting infections are yet to be determined.

Background: Teen pregnancy is associated with an array of negative social and health related outcomes for the mother as well as the baby. The risk of becoming a parent before the age of 20 is clearly elevated for former child welfare clients. Aim: The aim of this study is therefore to investigate the elevated birth rates among female adolescent child welfare clients by examining the relationship between contraceptive behaviour and pregnancies. Method: The study was based on a set of compiled register data. The study population were all females between the ages 14 and 19 during the years 2006-2008 (n. 487 115). The study group of main interest were child welfare clients who were compared to peers in the majority population as well as international and national adoptees. Analysis was conducted with multivariate logistic regression and the observed association was controlled for maternal, socio-demographic and behavioural factors. Results: The two sub-populations of child welfare clients both had much higher rates of retrieved hormonal contraceptives compared to the majority population, the international and the national adoptees up to age 17. In the ages 18 and 19 the rates were instead lower than the majority population. The child welfare clients had a stronger association to births than all groups of comparison, which was consistent with earlier research. All findings persisted after controlling for socio-demographic, maternal and behavioural factors. Conclusion: The child welfare clients showed a specific pattern of contraceptive behaviour over the age groups which was not consistent with the groups of comparison or with the expected relationship to birth rates. This suggests that teenage births cannot unanimously be predicted by the rates of retrieved hormonal contraceptives. The results imply that other factors than those investigated in this study are more influential regarding the contraceptive behaviour of this adolescent population.

Les travaux de Melançon (Melançon 2005) ont montré que le récepteur au glucagon (RG) peut être modulé rapidement par 180 minutes d'exercice ou 24 heures de jeûne. Cette modulation provient en partie de la hausse de la densité des récepteurs au glucagon membranaire. Plus récemment, les travaux de Merlen (Merlen, Fabrega et al., 2006) ont montré l'endocytose du récepteur au glucagon suite à un bolus de glucagon. Le présent projet vise à établir une cinétique de protéines reliées à la signalisation et à l'internalisation du RG. Spécifiquement, nous avons effectué une cinétique sur 24 heures suivant un exercice intense et un jeûne prolongé pour analyser par immunobuvardage l'AMPK, la LKB1, la GRK, la PKC et la β-arrestine. Des rats mâles Sprague-Dawley ont été aléatoirement assignés à des groupes contrôle, d'exercice (90 min et 180 min d'exercice, 180 min + 1 h, + 3 h, + 12 h et + 24 h de récupération au repos post-exercice) ou de jeûne (6 h, 12 h et 24 h de jeûne, 24 h jeûne + 6 h, + 12 h et + 24 h de récupération nourrie post-jeûne). Aucun changement statistiquement significatif n'est observé au niveau de la glycémie. Cependant, les niveaux de glycogène hépatique sont grandement diminués dans les deux cas, 98% de déplétion après 24 heures de jeûne et 74% après 3 heures d'exercice en comparaison à leur groupe contrôle respectif. Une période d'exercice induit, chez des rats sains, une augmentation significative de 244% des récepteurs membranaires au glucagon alors qu'il n'y a aucune variation significative de l'expression des récepteurs totaux. Ces données permettent de formuler l'hypothèse d'un mécanisme de sensibilisation/désensibilisation des récepteurs au glucagon expliquant cette grande mobilité lors de l'exercice. Le mécanisme de sensibilisation apparait en même temps qu'une augmentation des quantités d'AMPK et de GRK de l'ordre de 183 et 158% respectivement. Le mécanisme de désensibilisation en récupération s'opère simultanément avec une augmentation de l'expression de PKC de 207% et une diminution d'AMPK de l'ordre de 60%. Une période de jeûne prolongé induit chez des rats sains une augmentation significative de 165% des récepteurs membranaires au glucagon. Cette augmentation n'est accompagnée d'aucun changement significatif dans l'expression des protéines étudiées ouvrant la voie à la synthèse de l'ARNm pour contribuer à l'augmentation des RG membranaires lors du jeûne. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Récepteur au glucagon, AMPK, LKB1, GRK, PKC, β-arrestine, jeûne, exercice

Female athletes are known to have a higher rate of ACL injuries than male athletes in similar sports. Anatomical, neuromuscular, and strength factors have all been proposed as potential causes of this difference. The purpose of this investigation was to determine, through a series of three studies, the magnitude of sex differences, which exist in these potential risk factors. The first study investigated sex differences in anatomical risk factors. Male and female athletes from the Queensland Academy of Sport (Basketball: M = 14; F = 16; Soccer: F = 14) as well as the Men’s Lions Soccer club (n = 10) were recruited to participate in the study. A physical examination was completed which included: anthropometric measurements; lower extremity alignment measurements such as Q-Angle, knee recurvatum, and foot pronation; knee ligamentous laxity and muscle flexibility measurements; intercondylar notch width measurements using MRI; and an orthopedic examination. Our investigation found that anatomical differences do exist between healthy uninjured male and females. Females had larger Q-Angles, excessive foot pronation, decreased intercondylar notch width and increased ligamentous laxity and muscular flexibility compared to males. However, when examining the likely magnitude of these difference between the sexes, only a moderate effect was found (0.60 < ES ≤ 1.2). The second study investigated sex differences in strength measures that included knee flexion and extension peak torque values as measured using an isokinetic dynamometer, thigh muscle volume and cross sectional area (CSA) determined by Magnetic Resonance Imaging (MRI), and single leg hop for distance. Male and female athletes were recruited from the Queensland Academy of Sport (QAS) basketball program (M= 13; F = 13). Males were found to be significantly stronger than females even when all strength measurements were normalized to account for sex differences in anthropometrics (p < 0.05). Males generated greater peak forces in their knee extensors and flexors, greater hop distances and had larger muscle volumes and maximal cross sectional areas as determined by MRI analysis. When examining the likely magnitude of these difference between the sexes, a moderate to large effect was found (1.00 < ES ≤ 2.8). The final study investigated sex differences in lower limb neuromuscular factors, viz: body-segmental motions; ground reaction forces; and muscle timing and recruitment patterns in response to a drop-landing task in a laboratory setting. Participants recruited for the study were male and female university students (M= 11, F = 11), currently attending the University of Queensland. Participants performed a drop-landing task that consisted of performing a total of eight vertical drop landings from a box, 40cm in height, onto a force platform. Lower extremity sagittal plane marker kinetics and kinematics for the hip, knee and ankle were collected to determine joint angles at impact of landing and then maximum angle reached, ROM from initial ground contact to maximum angle as well as joint angular velocities. Thigh muscle activation patterns (i.e. recruitment order) in response to the drop-landing task were also collected. Results found that the female group landed with decreased knee flexion angles and higher ground reaction forces per body weight during the impact of landing compared to the males. After initial impact, the females also reached the greatest angles at the hip and knee therefore producing the greatest ROM at these joints. In regards to thigh muscle activation patterns, both male and female groups activated the hamstring muscles, prior to quadriceps activation, a result that was not expected. In conclusion, several anatomical, neuromuscular and strength differences exist between male and female athletes with the greatest differences observed in the kinematic and strength data. Females could potentially best benefit from training programs that include strength and proprioception components as well as technique awareness in an attempt to reduce the current ACL incidence rates observed in female athletes.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 6 uppsatser.

Thesis (Ph. D.)--Cornell University, January, 2009. / Vita. Includes bibliographical references.

Made available in DSpace on 2016-08-10T10:55:45Z (GMT). No. of bitstreams: 1 Ary Henrique de Souza Junior.pdf: 593464 bytes, checksum: 97cf99e0707363cc47b40b7b24df7ef3 (MD5) Previous issue date: 2005-04-14 / This work proposes an informational system for a clinical laboratory to control the post analytical phase of the exams. The system can automatically liberate the results of clinical exams. To assess the system we developed a prototype able to liberate FSH and Estradiol hormones based on rules that confront FSH and Estradiol results. The prototype was able to autonomously liberate 67,10% of the FSH results and 98,38% of the Estradiol results when analyzed independently and 82,74% of the results when applying the confrontations rules. The rules are based on elements of fuzzy logic and can provide a reduction in therapeutic length and costs, reduction of the diagnosis time and increase the safety of the procedures involved. / Foi proposto um sistema de informatização de laboratório clínico com aplicação na fase pós-analítica, com a capacidade de liberar clínico laboratorialmente resultados de exames. Para demonstrar a funcionalidade do projeto foi desenvolvido um protótipo para liberar resultado de exames de FSH e Estradiol. Em teste, o protótipo foi capaz de liberar 67,10% dos resultados de FSH e 98,38% de E2, atendendo ao conjunto de regras estabelecidas. Quando utilizados os preceitos de confrontação de resultados de FSH contra os de E2, baseados no comportamento fisiológico dos hormônios, a liberação ocorre em 82,74% dos resultados. Os 17,25% dos resultados restantes são colocados em arquivo próprio para a liberação supervisionada. O uso de regras baseadas em elementos de lógica difusa na liberação de resultados de exames laboratoriais pode oferecer, dentre outros ganhos, diminuição de prazo terapêutico e custos, aumento da rapidez do diagnóstico e da segurança de todos os envolvidos nas ações de saúde.

Resumo: As espécies reofílicas apresentam, de modo geral, suas gônadas desenvolvidas até estágios avançados de maturação, porém as etapas finais do processo reprodutivo, tais como, a maturação final dos ovócitos, a ovulação, a desova e a liberação de sêmen, somente são atingidas mediante tratamentos hormonais. No entanto, a reprodução induzida de Leporinus macrocephalus apresenta algumas particularidades. Mesmo com a aplicação de duas doses de hormônio, os machos de L. macrocephalus geralmente liberam uma quantidade muito reduzida de sêmen, que freqüentemente é insuficiente para os procedimentos de reprodução induzida. Assim, o objetivo principal deste trabalho foi avaliar a evolução do processo de espermiação em reprodutores machos de L. macrocephalus, submetidos a tratamento hormonal. Para tanto, foram realizados estudos histológicos da estrutura testicular e da via seminífera, com inclusão de tecidos em historesina e coloração com azul de Toluidina. Estudos ultraestruturais das células germinativas foram realizados com processamento do material para rotina de microscopia eletrônica de transmissão. Análise da via seminífera foi também realizada com a injeção de acetato de vinila nos ductos testiculares e posterior análise em microscopia eletrônica de varredura. Para análise do epitélio germinativo ao longo do processo de indução hormonal, as preparações histológicas foram destinadas para estudos morfométricos, com utilização de sistema de análise de imagens. Após o tratamento hormonal foram realizadas análises seminais para verificação do volume total de sêmen liberado, concentração espermática, tempo de ativação e sobrevivência dos espermatozóides. Os estudos morfológicos evidenciaram que a estrutura testicular de L. macrocephalus é do tipo tubular anastomosado, espermatogonial irrestrito com espermatogênese do tipo cística... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Rheophilic species present, in general, their gonads developed to advanced stages of maturation, but the final stages of the reproductive process, such as the final maturation of oocytes, ovulation, spawning, and release of semen, are only achieved with hormonal treatments. However, the induced breeding of Leporinus macrocephalus has some peculiarities. Even with the application of two doses of hormone, males of L. macrocephalus usually release reduced semen, which is often insufficient for procedures of induced spawning. Thus, the objective of this study was to evaluate the progress of spermiation in males broodstocks of L. macrocephalus, undergoing hormonal treatment. For this, were performed histological studies of testicular structure and the seminal pathway with tissue inclusion into historesin and staining with toluidine blue. Ultrastructural studies of the stems cells were performed with material processing for routine of transmission electron microscopy. Analyses of seminal pathway were performed with the injection of vinyl acetate in the testicular ducts and subsequent analysis of scanning electron microscopy. For analysis of the germinal epithelium throughout the hormonal induction process, the histological preparations were destined for morphometric studies using an image analysis system. After hormone treatment seminal analysis was performed to verify the volume total release of semen, sperm concentration, time activation and survival of spermatozoa. Morphological studies evidence that the testicular structure of L. macrocephalus is anastomosed tubular type, espermatogonial unrestricted with a spermatogenesis of cystic type. The seminal pathway of this species comprises the seminiferous tubules anastomosing, the main testicular duct and spermatic duct. The histologic and ultrastructural studies showed that the connection of the seminiferous tubules occurs in different segments... (Complete abstract click electronic access below) / Orientador: Carlos Alberto Vicentini / Coorientador: Sérgio Ricardo Batlouni / Banca: Luciene Patrici Papa / Banca: João Paulo Mardegan Issa / Mestre

Baseado na hipótese de o que tratamento com 17b-Estradiol, reduz a modulação simpática, o estresse oxidativo e a participação do sistema renina angiotensina sobre o sistema cardiovascular, propomos estudar o balanço simpatovagal e o equilíbrio entre o óxido nítrico (NO) e as espécies reativas ao oxigênio (EROS) em ratas Wistar ovariectomizadas. Além disso, buscamos verificar a efetividade do 17b-Estradiol no controle da PA e na proteção cardiovascular contra os danos causados pelo estresse oxidativo usando doses menores do que as convencionais. Para isso, desenvolvemos três protocolos, usando ratas ovariectomizadas como um modelo experimental de menopausa, onde avaliamos parâmetros morfométricos, funcionais e bioquímicos que permitem a avaliação dos mecanismos relacionados ao objetivo deste trabalho de pesquisa. No primeiro protocolo (I) demonstramos o efeito do estrogênio, em uma dose alta, equivalente àquela praticada na clínica (5mg%), em melhorar o balanço autonômico para o sistema cardiovascular, provavelmente devido a uma melhora no equilíbrio entre as forcas vasodilatadoras, representadas pelo NO, e as forcas vasoconstritoras, representadas pelas EROS vasculares. O estudo também mostra uma forte associação entre o sistema nervoso simpático e a atividade da enzima NADPH oxidase neste modelo animal. No segundo protocolo (II) buscamos testar se 40% da dose convencional de estrogênio seria tão eficaz quanto a dose alta na melhora do controle da pressão arterial e estresse oxidativo cardíaco. Verificamos uma redução significativa na PA e nas concentrações de EROS, como ânion superóxido e peróxido de hidrogênio, um aumento das defesas antioxidantes não enzimáticas, avaliadas através do balanço redox e antioxidantes totais, e das enzimáticas, avaliadas pelas atividades das enzimas superóxido dismutase e catalase. Finalmente, realizamos o terceiro protocolo (III). Através deste testamos se uma dose de estrogênio ainda mais baixa, apenas 10% da dose convencional, seria tão eficaz quanto uma dose elevada para melhorar o controle da pressão arterial e diminuir o estresse oxidativo vascular. Verificamos que independente da dose usada, o estrogênio foi eficaz para reduzir a atividade da enzima NADPH oxidase, a concentração de peróxido de hidrogênio e a pressão arterial. Além de aumentar a concentração plasmática de nitritos totais e o estado redox. Dessa forma, demonstramos que uma dose baixa de estrogênio é tão eficaz como uma dose farmacológica para promover a proteção cardiovascular. / In this thesis was studied the sympathovagal and the nitric oxide (NO)/reactive oxygen species (ROS) balances in ovariectomized female rats. It was verified the effectiveness of 17b-estradiol in the blood pressure (BP) control and cardiovascular oxidative stress using low doses of estrogen. Then, we developed three protocols to evaluate morphometric, hemodynamic and biochemical parameters. In the first protocol (I), we demonstrate the estrogen effects with a pharmacological dose (5 mg%) to improve cardiovascular system autonomic balance. This result was probably due to an improvement in the balance between the vasodilator forces , represented by NO, and vasoconstrictive forces represented by vascular ROS. The study also showed a strong association between the sympathetic nervous system and the NADPH oxidase enzyme activity in this animal model. In the second protocol (II), we tested whether 40% of estrogen conventional dose would be as effective as a high dose in improving the control of blood pressure and oxidative stress. We found a significant reduction in BP and in ROS concentrations such as superoxide anion and hydrogen peroxide, an increase in non-enzymatic antioxidant defenses, as measured by the redox balance and total antioxidants, and enzymes, as assessed by the activities of superoxide dismutase and catalase. Finally, we performed the third protocol (III), which allowed us to test if a low estrogen dose (10% of conventional one), would be as effective as a high dose to improve the control of blood pressure and decrease the vascular oxidative stress. We found that estrogen was effective in reducing the activity of NADPH oxidase, the concentration of hydrogen peroxide and blood pressure in all dose used. Moreover, estrogen increased the total nitrite plasma concentration and redox state. Thus, we have demonstrated that a low dose of estrogen is as effective as a pharmacological dose to promote cardiovascular protection.