Causas de hemorragia uterina anormal en mujeres de 35 a 50 años que acudieron al departamento de ginecología en el Hospital José Carrasco Arteaga desde junio-diciembre del 2014

ANTECEDENTES: La hemorragia uterina anormal (HUA) es un problema común de mujeres en edad reproductiva, perimenopáusica y menopausia, por lo cual se realizó el presente estudio para conocer las causas de la hemorragia uterina anormal en nuestra población además de sus características demográficas y consecuencia del sangrado. OBJETIVO GENERAL: Determinar las diferentes causas del sangrado uterino anormal en mujeres de 35 a 50 años del departamento de gineco-obstetricia del hospital José Carrasco Arteaga en el periodo de junio-diciembre del 2014. METODOLOGÍA: Es un estudio cuantitativo descriptivo donde se indagó las historias clínicas de pacientes con diagnósticos de hemorragia uterina anormal en el Hospital “José Carrasco Arteaga”, del departamento de Ginecología en el periodo junio-diciembre 2014. La recolección de variables fue procesada, elaborada y codificada en el programa SPSS. RESULTADOS: Se identificaron 178 casos, con una media de 43,47 años, de la región urbana (88,8%), la mayor frecuencia fue empleadas formal(72,5%), casadas (60,1%), con una media de gestas de 3, 91% con Papanicolaou en el ultimo año, 65,7% no tuvo planificación familiar, el principal diagnóstico fue hiperplasia endometrial (41%), segundo Leiomioma (36,7%), y el principal tratamiento fue: legrado (46,1%), seguida de histerectomía (43,3%), y 27,5% presento anemia moderada, a continuación, anemia leve (11,8%) y grave (9,6%). CONCLUCIONES: La causa más frecuente de hemorragia uterina anormal fue hiperplasia endometrial y el tipo de tratamiento escogido fue el legrado intrauterino

Genetic Polymorphisms in Replication-related Genes and Risk of Breast Cancer Among European and East Asian Women

Background: The role of common, low to intermediate risk alleles in breast cancer need to be examined due to their relatively high prevalence. Among many cellular pathways, replication has a pivotal role in cell division and frequently targeted during carcinogenesis. Replication is governed by a host of genes involved in a number of different pathways. This study investigates the effects of replication-gene variants in relation to breast cancer and how this relationship is affected by ethnicity, menopausal status and breast tumour subtype. Methods: Data from a case-control study with 997 incident breast cancer cases and 1,050 age frequency matched controls in Vancouver, British Columbia and Kingston, Ontario were used. Unconditional logistic regression was used to calculate odds ratios between 45 replication gene variants and breast cancer risk, assuming an additive genetic model adjusted for age and centre, presented for Europeans and East Asians separately. Polytomous logistic regression was used to assess odds ratios between each SNP and four breast cancer subtypes defined by hormone receptor status among Europeans. All analyses were stratified by menopausal status. The Benjamini–Hochberg false discovery rate (FDR) was used to address multiple comparisons. Results: Among Europeans, the SNPs in FGFR2, TOX3 and 11q13 loci were associated with breast cancer after controlling for multiple comparisons. Test of heterogeneity showed the SNPs rs1045185, rs4973768, rs672888, rs1219648, rs2420946 among Europeans and rs889312 among East Asians conferred differential risk across the tumour subtypes. Conclusions: Specific SNPs in replication genes were associated with breast cancer, and the risk level differed by tumour subtype defined by ER/PR/Her2 status and ethnicity.

Role of 17β-Hydroxysteroid Dehydrogenase Type 5 in Breast Cancer Studied by Intracrinology

Dans cette thèse, je présente une étude (1) du rôle de la 17β-HSD5 dans la modulation des taux d’hormones et dans la prolifération, et l’impact de l’expression de la 17β-HSD5 sur d’autres protéines de BC cellules; (2) une étude comparative sur trois enzymes (17β-HSD1, 17β-HSD7 et 3α-HSD3) avec la provision de DHEA et ses substrats directes soit l’E1 ou la DHT. Les principaux résultats obtenus dans cette étude sont les suivants: (1) en utilisant l’ARN d’interférence de la 17β-HSD5, des immunodosages enzymatiques et des tests de prolifération de cellules démontrent que l’expression de la 17β-HSD5 est positivement corrélée à un niveau de T et de DHT dans les BCC, mais négativement corrélée pour l’E2 et la prolifération des cellules de BC (2) les analyses quantitatives de PCR en temps réel et de Western blot ont démontré que l’inhibition de l’expression de la 17β-HSD5 régule à la hausse l’expression de l’aromatase dans les cellules MCF-7. (3) L’analyse d’ELISA de la prostaglandine E2 a vérifié que l’expression accrue de l’aromatase a été modulée par des niveaux élevés de PGE2 après l’inactivation de l’expression du gène de la 17β-HSD5. (4) Le test de cicatrisation a montré que l’inactivation de l’expression du gène de la 17β-HSD5 favorise l’augmentation de la migration cellulaire. (5) L’expression du gène 17β-HSD5 dans des échantillons cliniques, à partir de l’analyse de base de données ONCOMINE, a montré que sa plus faible expression a été corrélée avec le statut de l’HER-2 et de la métastase de la tumeur. (6) Les données protéomiques révèlent également que des protéines impliquées dans les voies métaboliques sont fortement exprimées dans les cellules MCF-7 après l’inactivation de l’expression du gène de la 17β-HSD5. (7) L’étude n’a démontré aucune différence dans la fonction biologique de la 17β-HSD1 et de la 17β-HSD7 lorsqu’elles sont cultivées avec différentes stéroïdes: tel que les niveaux de stéroides, la prolifération cellulaire et les protéines régulées. (8) Toutefois, la supplémentation du milieu de culture se révèle avoir un impact marqué sur l’étude de la 3α-HSD3. (9). Nous avons proposé que l’utilisation de la DHEA comme source d’hormone puisse entraîner une meilleure imitation des conditions physiologiques post-ménopausales en culture cellulaire selon l’intracrinologie.

Genomic and functional insights into the interactions between vaginal Lactobacillus strains and pathogens

The vaginal microbiota of healthy pre-menopausal women is typically dominated by one Lactobacillus species among L. crispatus, L. gasseri, L. jensenii and L. iners. Thanks to a series of antimicrobial activities, strains belonging to these species represent the first barrier against infections and maintain niche homeostasis. On the other hands, the increase abundance in pathogen species is associated with the onset of numerous diseases, leading also to an increase risk of other infections acquisition. The deciphering of factors which influence Lactobacillus survival, as well as the interactions between lactobacilli-pathogens and pathogens-pathogens represent an important topic of study for improving woman health and investigating effective probiotic strategies. Here, we investigated environmental factors and genetic traits that lead to the dominance of either L. crispatus or L. gasseri in the vaginal niche and the possible applications of liposomes loaded with L. gasseri biosurfactants for the treatment and prevention of Staphylococcus aureus biofilm infections. Furthermore, considering the increasing relevance acquired by bacterial extracellular vesicles (EVs) we analysed the role of EVs derived from vaginal lactobacilli and pathogens on both bacterial growth and HIV-1 infections. As a result, we reported for the first time i) common and species-specific genotypic and phenotypic features of L. crispatus and L. gasseri ii) significant antibiofilm activity of liposomes loading vaginal Lactobacillus biosurfactants against multi-drug resistant S. aureus strains iii) absence of growth regulation mediated by EVs derived from lactobacilli on pathogen cultures and vice versa iv) anti-HIV-1 activity of protein derived from L. gasseri EVs and unexpected antiviral effect of pathogen-derived EVs on HIV-1 infections in vitro. In conclusion, this PhD thesis explored characteristics and possible applications of vaginal lactobacilli for the human health, as well as promising antiviral effects of both lactobacilli and pathogen derived EVs.

Selection of candidate probiotic strains from human microbial niches, for the development of tailored foods designed for specific consumers

My PhD project was intended, throughout the selection of probiotics from human milk and healthy vaginal environment, for the development of tailored fermented foods. According to this aim, several activities were carried out. The first one, concerning the isolation of Lactobacillus and Bifidobacterium strains from human milk to find new probiotic candidates to be included in food products showed promising results. Probiotics have been also proposed to improve female genital health and microbial strains isolated and connected with healthy vaginal ecosystem could be used to prevent or treat vaginal dysbiosis. In this context vaginal lactobacilli previously characterized for their technological features and antagonistic activity against several female uro-genital pathogens were investigated for their metabolic aptitude and additional probiotic features, showing interesting results hypothesizing their inclusion in foods. In addition, in order to preserve vaginal strains viability during food processing/digestion it was also evaluated the potential of microencapsulation by spray-drying. In this framework the results obtained were highly promising from the perspective of using encapsulated powders in food formulations. Another activity connected with the main idea to develop a food strategy for the administration of these vaginal strains was carried out. Lactobacillus crispatus BC4, was supplemented in a Squacquerone cheese, and its digestive fate was evaluated adopting SHIME® system. The results showed that during colonic fermentation, L. crispatus BC4 was metabolically active. Additionally, although probiotic delivery to humans has traditionally been associated with fermented dairy foods, recently the demand for non-dairy-alternatives as potential probiotics carrier is increasing. In this framework, my latest activity was connected with the development of fermented soy milks with encapsulated and non-encapsulated L. crispatus BC4 and L. gasseri BC9. The same fermented soy milks were also investigated for their nutritional qualities and after in vitro digestion for their specific functionality on post-menopausal fecal microbiota and protein bioaccessibility.

Climatério no ciclo de vida da mulher

Este objeto inicia destacando que é necessário capacitar e sensibilizar os profissionais de saúde para atender as mulheres que estão no climatério na atenção básica, aproveitando todas as ocasiões que a mulher busca a unidade de saúde, procurando desenvolver ações de promoção, prevenção e ou recuperação. Aponta dados que mostram que, no Brasil, aproximadamente 32% das mulheres estão na faixa etária em que ocorre o climatério. Destaca que a discriminação e os preconceitos são variáveis que devem ser consideradas. Lembra que, popularmente, o termo menopausa é utilizado como sinônimo de climatério, mas ela é somente a parada espontânea das menstruações durante, pelo menos, 12 (doze) meses consecutivos, sem que haja causas patológicas ou psicológicas e intervenções médicas. Apresenta uma animação sobre a o climatério, abordando também seus estágios, que são a transição menopausal, a perimenopausa e a pós-menopausa. Termina enfatizando que este período pode ser vivenciado de maneira saudável, constituindo-se numa oportunidade de viver experiências gratificantes, favorecendo a reflexão sobre a trajetória de vida, a renovação, o crescimento, a maturidade e a realização. Unidade 7 do módulo 6 que compõe o Curso de Especialização em Saúde da Família.

Climatério - principais alterações fisiológicas, emocionais e sociais que ocorrem nas mulheres

Este estudo teve por objetivo identificar as principais alterações fisiológicas, emocionais e sociais que ocorrem nas mulheres no período do climatério. Para tal, foi realizada uma revisão narrativa relativa às alterações fisiológicas e emocionais, à sexualidade e à qualidade de vida da mulher no período do climatério. A preocupação com a qualidade de vida em saúde ao longo do processo de envelhecimento tem aumentado nos últimos anos. O climatério também chamado de síndrome menopausal compreende o conjunto de sintomas e sinais que diminuem o bem-estar da mulher. A revisão da literatura apontou que a maioria das mulheres chega ao período do climatério com pouquíssima informação, ficando sujeitas a dúvidas, temores e inseguranças que poderiam ter sido evitados caso estivessem bem informadas sobre o assunto. Possibilitou ainda, identificar a relevância desta temática para as mulheres que estão no climatério, e também para os profissionais da Equipe de Saúde da Família. Em especial, os aspectos relacionados à sexualidade, saúde emocional e qualidade de vida.