El objetivo de este trabajo es profundizar en el conocimiento de las bases fisiológicas de las respuestas de los cítricos a condiciones de estrés abiótico y biótico. Se ha diseñado un sistema que ha permitido el establecimiento de las condiciones óptimas para el cultivo in vitro de cítricos en condiciones de estrés abiótico. Los resultados obtenidos indican que pese a su sensibilidad, las plantas de citrange Carrizo sometidas a estrés hídrico mantienen su maquinaria antioxidante y su sistema de señalización hormonal intactos, incluso cuando se cultivan brotes sin raíz. Además, tras cultivar plantas de distintos genotipos in vitro en medio salinizado con o sin sistema radicular, se concluye que la tolerancia al estrés salino en cítricos no está relacionada con adaptaciones bioquímicas sino con la capacidad para excluir iones de la parte aérea. La infección con el virus de la tristeza provoca una reducción de la actividad fotosintética en plantas de lima mejicana que, unida a la incapacidad de activar mecanismos de disipación de energía en el fotosistema II, provoca daño oxidativo en los tejidos vegetales. Los datos también sugieren una precisa regulación hormonal de las respuestas de los cítricos al estrés biótico junto con una represión generalizada del metabolismo secundario.

This dissertation is based on seventeen months of ethnographic fieldwork that followed the development and diffusion of extended-cycle hormonal contraception, or birth control that is designed to eliminate monthly bleeding. It encompassed several sites and multiple constituencies: a clinical trial, documented medical conferences, users, potential users, and refusers of the pharmaceuticals, along with key academic and popular proponents of their adoption. Extended-cycle contraception is a critical topic because this new generation of pills, IUDs, shots, and implants is not only refiguring the length of women's cycles, but it is also augmenting the extent to which its users' bodies are medicalized, or subjected to a type of manipulation and regulation that was previously impossible. No longer just for pregnancy prevention, these regimens are increasingly touted as elective enhancement technologies that may improve on the human design, on the one hand, and as crucial preventative medicine for diseases such as reproductive cancers, on the other hand. Remarkably, these pharmaceuticals are as socially complex as they are chemically--they may facilitate the renegotiation of constructions of womanhood, nature, and progress.

La technique de clonage par transfert nucléaire de cellules somatiques (SCNT) présente une page importante dans les annales scientifiques, mais son application pratique demeure incertaine dû à son faible taux de succès. Les anomalies placentaires et de développement fœtal se traduisent par des pertes importantes de gestation et des mortalités néonatales. Dans un premier temps, la présente étude a caractérisé les changements morphologiques des membranes fœtales durant la gestation clonée en les comparant à des gestations contrôles obtenues à partir de l’insémination artificielle. Les différentes anomalies morphologiques des placentomes telles que l’œdème chorioallantoique, la présence de zones hyperéchoiques et irrégulières dans la membrane amniotique et la présence de cellules inflammatoires dégénérées compromettent le développement fœtal normal de la gestation clonée. L’examen ultrasonographique représente une technique diagnostique importante pour faire le suivi d’une gestation et de caractériser les changements placentaires dans le cadre d’évaluation globale du bien-être fœtal. Le profil hormonal de trois stéroïdes (progestérone (P4), estrone sulfate (E1S), et œstradiol (E2)) et de la protéine B spécifique de gestation (PSPB) dans le sérum des vaches porteuses de clones SCNT a été déterminé et associé aux anomalies de gestations clonées. Une diminution de la P4 sérique au jour 80, une élévation du niveau de la concentration de la PSPB au jour 150, et une augmentation de la concentration d’E2 sérique durant le deuxième et troisième tiers de la gestation clonée coïncident avec les anomalies de gestation déjà reportées. Ces changements du profil hormonal associés aux anomalies phénotypiques du placenta compromettent le déroulement normal de la gestation clonée et gênent le développement et le bien-être fœtal. Sur la base des observations faites sur le placenta de gestation clonée, le mécanisme moléculaire pouvant expliquer la disparition de l’épithélium du placenta (l’interface entre le tissue maternel et le placenta) a été étudié. L’étude a identifié des changements dans l’expression de deux protéines d’adhérence (E-cadhérin et β-catenin) de cellules épithéliales pouvant être associées aux anomalies du placenta chez les gestations clonées. Le tissu de cotylédons provenant de gestations clonées et contrôles a été analysé par Western blot, RT-PCR quantitatif, et par immunohistochimie. Les résultats présentaient une diminution significative (p<0.05) de l’expression des dites protéines dans les cellules trophoblastiques chez les gestations clonées. Le RT-PCR quantitatif démontrait que les gènes CCND1, CLDN1 et MSX1 ciblés par la voie de signalisation de la Wnt/β-catenin étaient significativement sous exprimés. La diminution de l’expression des protéines E-cadherin et β-catenin avec une réduction de l’activation de la protéine β-catenin durant le période d’attachement de l’embryon peut potentiellement expliquer l’absence totale ou partielle de l’attachement des membranes fœtales au tissu maternel et éventuellement, l’insuffisance placentaire caractéristique des gestations clonées chez la vache. La caractérisation morphologique et fonctionnelle du placenta durant les gestations clonées à haut risque est essentielle pour évaluer le statut de la gestation. Les résultats de la présente étude permettront de prédire le développement et le bien-être fœtal de façon critique à travers un protocole standardisé et permettre des interventions médicales pour améliorer le taux de succès des gestations clonées chez les bovins. / Although somatic cell nuclear transfer (SCNT) has been shown to be successful, there are still problems with this technique that is inhibiting its use in industry. Altered placental formation and development results in the high incidence of pregnancy loss and prenatal morbidity and mortality found in SCNT pregnancies. The objective of the initial study was to characterize morphological changes in fetal membranes of a group of bovine recipients carrying cloned fetuses and comparing them with control AI fetuses at various stages of gestation. Several morphological anomalies of placentomes such as edematous chorioallantoic membrane, hyper-echodense spikes or irregularities in the amniotic membrane as well as the pathological presence of degenerated inflammatory cells accompanied by disappearance of the placental epithelium were observed. It was concluded that these anomalies compromise fetal development. The results of this work also showed that ultrasonography may be a reliable technique to monitor and to characterize the placental changes in bovine pregnancies that can be used to assess fetal well-being. The next study compared the functionality of the placenta of cloned fetuses with controls. The concentration of three steroids (progesterone (P4), estrone sulphate (E1S), and estradiol (E2)) and pregnancy-specific protein B (PSPB) in maternal peripheral circulation were assessed and their associations with gestational anomalies were determined. The hormones profiles in the SCNT recipients deviated from the control group at certain stages of pregnancy. We observed higher concentrations of E2 throughout the study period, lower levels of P4 at day 80 as well as elevated PSPB concentrations at day 150 in SCNT recipients which coincided with high rate of abortion in these animals shortly after this stage. So, it is proposed that these hormonal changes together with the morphological anomalies of the placenta result in compromised fetal development. Finally, the molecular mechanism that could be responsible for the abnormal disappearance of the epithelial layer observed in SCNT placenta was investigated. To do so, we measured the expression of two major epithelial adherens junction proteins (E-cadherin and β-catenin) and determined if their expression is altered in relation to the aberrant placentation in SCNT embryos. Cotyledonary tissues from SCNT gestations and control pregnancies were analyzed by Western blot, quantitative RT-PCR and immunohistochemical analysis. Both candidates were significantly (P < 0.05) under-expressed in SCNT trophoblast cells at the protein level. Also, qRT-PCR confirmed that the Wnt/β-catenin signaling pathway target genes CCND1, CLDN1 and MSX1 were significantly down-regulated in SCNT placentas. So, we inferred that impaired E-cadherin and β-catenin protein expression, along with defective β-catenin signaling during embryo attachment, specifically in the window of placentation, results in loose attachment and contributes to insufficient placentation in bovine SCNT-derived embryos. Overall, we concluded that during the high-risk pregnancy of cloned fetuses, characterization of the morphological and functional changes of the placenta is critical to enable us to predict normal fetal development and wellbeing through a standardized procedure during clone gestations and to intervene medically in emergency cases to improve the overall efficiency of cloning in cattle.

Adjuvant hormonal therapy has been demonstrated to be able to delay disease progression in nonmetastatic prostate cancer. To date, however, a favorable impact on survival has only been demonstrated in lymph-node-positive disease and in external-beam radiotherapy series with locally advanced and probably mainly micrometastatic tumors. The Bicalutamide Early Prostate Cancer Program is the largest study under way to define the role of adjuvant treatment in early prostate cancer and identify subgroups of patients likely to benefit from immediate hormonal therapy. At the time of the most recently published analysis, the risk of objective clinical progression was significantly reduced in the bicalutamide arm (hazards ratio 0.58, 95% confidence interval 0.51–0.66, p < 0.0001). However, further maturation of data is needed to see whether this difference will lead to a survival advantage. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

The treatment of clinically locally advanced prostate carcinoma (stage cT3) remains controversial. One of the main reasons for this controversy results from the substantial staging error attached to the clinical diagnosis cT3 with overstaged T2 tumors and understaged node-positive cases. Treatment options in this situation include radical prostatectomy, external beam radiotherapy, immediate or delayed androgen deprivation treatment and the so-called ‘watchful waiting’. Acceptable and often surprisingly good tumor-specific survival rates have been reported for radical prostatectomy in pT3 series – based on good clinical case selection – approaching those of pT2 series. In lymph node-positive pT3 cases, adjuvant hormone deprivation seems to prolong survival which it does not in lymph node-negative pT3 disease. A benefit of adjuvant external beam radiotherapy after radical prostatectomy for pT3 cases in prolonging overall survival has not been shown, despite the fact that it can prevent or delay biochemical and local recurrence. External beam radiotherapy as the only treatment for cT3 disease results in unfavorable tumor-specific survival rates, which can be significantly improved with adjuvant hormonal treatment with LHRH agonists. If, in case of advanced age and/or significant comorbidity, primary hormonal treatment is chosen, early hormonal deprivation therapy seems to offer marginal benefits in survival compared to delayed treatment. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Diss. (sammanfattning) Stockholm : Karolinska institutet 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Linköping : Univ., 2002. / Härtill 4 uppsatser.

INTRODUÇÃO. Mulheres pós-menopáusicas apresentam maior risco de desenvolvimento de doença arterial coronariana. Estudos observacionais demonstraram que a terapia de reposição hormonal produz efeitos benéficos no perfil lipídico e na modulação autonômica cardíaca. O aumento da variabilidade da freqüência cardíaca (VFC), até então atribuído à reposição hormonal, não foi testado em estudos randomizados, placebo-controlados, delineados para permitir a comparação entre as duas formas mais utilizadas de reposição hormonal. A VFC de 24 horas calculada pelo método não linear Mapa de Retorno Tridimensional permite avaliar tanto a modulação vagal como a simpática. OBJETIVOS Avaliar a modulação autonômica cardíaca de mulheres pósmenopáusicas através da análise da VFC no domínio do tempo e dos índices do Mapa de Retorno Tridimensional no ECG de 24 horas. Testar a hipótese de que a reposição hormonal contínua, seja com estradiol isolado (TRE), seja com estradiol associado à noretisterona (TRH), por um período de três meses, aumenta a VFC nessas mulheres. MÉTODOS Quarenta mulheres pós-menopáusicas (46 a 63 anos; média = 54,6 ± 4,2) foram randomizadas para um dos três tratamentos, de forma contínua: TRH, estrogenioterapia (TRE) ou placebo, por três meses consecutivos. Previamente, todas as mulheres foram submetidas a exames clínico, ginecológico e laboratorial (glicose, estradiol, HDL, LDL, triglicerídios; mamografia e ultrassonografia transvaginal). O ECG de 24 horas foi gravado em cada paciente, antes e após o tratamento, para calcular os índices da VFC. RESULTADOS Não houve diferença estatisticamente significativa entre os três grupos, após 3 meses de tratamento, nos índices da VFC e do Mapa de Retorno Tridimensional. A TRH diferiu da TRE apenas quanto ao perfil lipídico. A associação com a noretisterona provocou uma redução de 12,4 % no HDL (p = 0,008). CONCLUSÃO Em mulheres pós-menopáusicas, a terapia de reposição hormonal contínua com estradiol, ou com estradiol associado à noretisterona, por um período de 3 meses, não altera a modulação autonômica cardíaca avaliada pela VFC. / Background: Postmenopausal women are at greater risk of coronary heart disease. Observational studies have demonstrated that hormone replacement therapy (HRT) improves lipid profile and cardiac autonomic modulation. The cardioprotective effect attributed to HRT has not been tested in randomized, placebo-controlled trials to compare the two most frequently used regimens. This study evaluates cardiac autonomic modulation in postmenopausal women using time domain indices of heart rate variability (HRV) and indices derived from the three-dimensional return map, and investigates whether continuous HRT for three months, either with estradiol alone (ERT) or with estradiol and norethisterone (HRT), increases HRV in postmenopausal women. Methods: Forty postmenopausal women aged 46 to 63 years were consecutively and randomly assigned to one of three treatment groups: HRT, ERT, or placebo. For all women, clinical, gynecological and laboratory data (glucose, estradiol, HDL, LDL, triglycerides, mammography and transvaginal sonography) were collected. Patients underwent 24-h ECG before and after the treatment to evaluate HRV indices. Results: Time domain indices of HRV as well as indices derived from the threedimensional return map presented no significant changes after interventions. The only significant difference between HRT and ERT groups was in lipid profile. HDL cholesterol levels decreased 12.4% (p = 0.008) for women who used HRT. Conclusion: In postmenopausal women, continuous hormone replacement therapy with estradiol or estradiol with norethisterone for 3 months does not affect cardiac autonomic modulation evaluated by HRV.

Objectif et problématique : Le transsexualisme ainsi que son traitement par la transformation hormonale et chirurgicale (THC) sont des phénomènes au carrefour de toutes les limites : corps, subjectivité, société, psyché… Face au constat de cette complexité, partant des approches structurale et déconstructiviste, cette thèse a pour objectif de définir et proposer une nouvelle approche « transversale » du transsexualisme, et dans la continuité de celle-ci de l’identité sexuée, avec les éléments de la théorie psychanalytique que sont la pulsion sexuelle de mort, la troisième topique de l’Inconscient clivé, la réalisation pulsionnelle par la perception et la clinique de l’extrême et de l’ordinaire.Matériel et méthode : Sur un échantillon de six sujets transsexuels masculin vers féminin ayant actuellement recours ou ayant eu recours à la THC depuis plus de deux ans, nous avons analysé les résultats à un entretien clinique inspiré de l’approche structurale, aux tests projectifs du rorschach et du TAT selon l’école projectiviste de Paris Descartes, ainsi qu’au MMPI-2. Nos trois hypothèses sont que la problématique identitaire transsexuelle renverrait à la pulsion sexuelle de mort, à l’Inconscient amential et à la clinique de l’extrême, puis que la THC aurait le potentiel d’agir telle une réalisation pulsionnelle par la perception.Résultats : Les résultats valident les deux premières hypothèses sur la pulsion sexuelle, l’Inconscient amential et la clinique de l’extrême, mais pas celle sur la réalisation pulsionnelle par la perception.Conclusion et discussion : Ces résultats montrent l’intérêt d’une approche transversale pour appréhender un phénomène limite comme le sont le transsexualisme et l’identité sexuée qui se voient éclairés par les éléments théoriques transversaux proposés (pulsion sexuelle de mort, Inconscient amential et clinique de l’extrême). Concernant, les effets de la THC au niveau psychique, il semble nécessaire de poursuivre notre investigation, la réalisation pulsionnelle par la perception ayant été validée chez un de nos deux sujets ayant terminé la THC depuis plus de deux ans, mais exclue chez l’autre. / Objective and problematic: the transsexualism as well as its treatment by the hormonal and surgical sex reassignment are phenomena in the crossroads of all the limits: body, subjectivity, society, psyche … In front of this complexity, running with the approaches structural and deconstructivist, this thesis has for objective to define and to propose a new "transversal" approach of the transsexualism, and in the continuity of this one of the sexed identity, with the elements of the psychoanalytical theory that are the sexual death drive, the third topical of the splited Unconscious, the impulsive realization by the perception and the clinical of the extreme and the ordinary.Material(Equipment) and method: on sample of six subjects transsexuals male to female resorting at present or having resorted to the sex reassignment for more than two years, we analyzed the results in a clinical interview inspired by the structural approach, in the projective tests of the rorschach and the TAT according to the projectivist method of Paris Descartes, as well as in the MMPI-2. Our three hypotheses are that the transsexual identity problematic would send back to the sexual death drive, to the amential Unconscious and to the clinical of the extreme, then that the sex reassignment would have the potential to act such as an impulsive realization by the perception.Results: the results validate both first ones hypothesis on the sex drive, the amential Unconscious and the clinical of the extreme, but not that one on the impulsive realization by the perception.Conclusion and discussion: these results show the interest of a transversal approach to dread a phenomenon borderline as are it the transsexualism and the sexed identity which see each other lit by the transversal theoretical proposed elements (sexual death drive, amential Unconscious and private hospital of the extreme). Concerning, the effects of psychic sex reassignment at the level, it seems necessary to pursue our investigation, the impulsive realization by the perception has been validated to one of our subject but excluded to the other one.

O climatério afeta significativamente a vida de milhares de mulheres ao redor do mundo. A evolução do conhecimento em relação à segurança das opções medicamentosas utilizadas para manejo de seus sintomas se faz essencial no atual momento. A terapia hormonal usando estrógeno e progestágeno (TEP) tem sido amplamente prescrita para o manejo dos sintomas climatéricos. O uso da TEP foi recomendado no passado também com o objetivo de prevenção de doença cardiovascular. Porém, ensaios clínicos randomizados recentes falharam em comprovar os benefícios cardiovasculares do regime de TEP mais comumente utilizado (EEC 0.625mg + AMP 2.5mg /dia), tendo também sugerido que este regime está associado a significativo aumento de risco cardiovascular. A doença cardiovascular é a principal causa de mortalidade em países ditos desenvolvidos e em desenvolvimento, como o Brasil. Atualmente, mulheres brasileiras com faixa etária entre 50-59 anos apresentam taxa de mortalidade por DCV de 36%, aumentando este percentual gradativamente nas décadas que se seguem (60-69 anos = 40%, ≥70 anos = 46%). A população de mulheres pós-menopáusicas com Diabete Melito Tipo 2 (DM2) também vem crescendo significativamente em todo o mundo. O Brasil é um dos 10 países do mundo que apresentará o maior número de pessoas com diagnóstico de DM em 2025. A maioria desta população será de mulheres, moradoras de áreas urbanas, com idade entre 45-64 anos. Desta forma, mulheres pós-menopáusicas com DM2 representam um percentual significativo da população, e sabidamente apresentam risco cardiovascular aumentado. Além de ser um grupo de alto risco cardiovascular, estas mulheres freqüentemente necessitam manejo medicamentoso dos sintomas climatéricos. Este estudo visa revisar a literatura existente sobre o uso de TEP em mulheres pósmenopáusicas com DM2, analisando o impacto das diversas combinações sobre marcadores de risco de doença cardiovascular clássicos e não-clássicos. / The menopause has significant impact on thousands of women worldwide. The safety of pharmacological options in the management of menopause symptoms is an essential area of research and development. The hormonal therapy by means of estrogen and progestogen (EPT) has been widely prescribed to manage menopausal symptoms. The use of EPT had been also recommended in the past to prevent cardiovascular disease. However, recent large-scale randomized clinical trials have not only shown no cardiovascular benefit, but also have demonstrated that it is associated with significant increase in cardiovascular risk, at least with the most used regimen (CEE 0.625mg+MPA 2.5mg/day). Cardiovascular diseases (CVD) are the leading cause of death in developed world and in developing countries such as Brazil. Brazilian women, who are currently in the 50-59 age range, are expected to have a CVD mortality rate of 36%, with gradual increase in risk in the following decades (60-69 years-old = 40%, ≥ 70 years-old = 46%). The postmenopausal diabetic women population has also grown significantly worldwide. Brazil is one of the 10 countries in the world that will have the largest population of diabetics by 2025. The majority of this population will be female, living in urban areas and between 45 and 64 years-old. Therefore, post-menopausal diabetic women will represent a significant percentage of people, who knowingly have increased cardiovascular risk, these women frequently need medical management of their menopause symptoms. The aim of this study is to review the existing literature on EPT in post-menopausal diabetic women, analyzing the impact of several regimens over classic and non-classic CVD risk factors.