Vulvovaginitis in pregnant women.

• The balanced vaginal microbiome is the main factor defending the vaginal environment against infections. Lactobacilli play a key role in this regard, maintaining the vaginal pH within the normal range (3.8 to 4.5). •Hormonal and immune adaptations resulting from pregnancy influence changes in the vaginal microbiome during pregnancy. •An altered vaginal microbiome predisposes to human immunodeficiency virus (HIV) infection. •Bacterial vaginosis is the main clinical expression of an imbalanced vaginal microbiome. •Vulvovaginal candidiasis depends more on the host's conditions than on the etiological agent. •Trichomonas vaginalis is a protozoan transmitted during sexual intercourse. •The use of probiotics is not approved for use in pregnant women.

Association between development of severe COVID-19 and a polymorphism in the CIAS1 gene that codes for an inflammasome component.

An elevated pro-inflammatory cytokine response is associated with severe life-threatening symptoms in individuals with Coronavirus Disease-2019 (COVID). The inflammasome is an intracellular structure responsible for generation of interleukin (IL)-1ß and IL-18. NALP3, a product of the CIAS1 gene, is the rate-limiting component for inflammasome activity. We evaluated if a CIAS1 42 base pair length polymorphism (rs74163773) was associated with severe COVID. DNA from 93 individuals with severe COVID, 38 with mild COVID, and 98 controls were analyzed for this polymorphism. The 12 unit repeat allele is associated with the highest inflammasome activity. Five alleles, corresponding to 6, 7, 9, 12 or 13 repeat units, divided into 12 genotypes were identified. The frequency of the 12 unit repeat allele was 45.3% in those with severe disease as opposed to 30.0% in those with mild disease and 26.0% in controls (p < 0.0001, severe vs. controls). In contrast, the 7 unit repeat allele frequency was 30.1% in controls as opposed to 14.0% and 12.5% in those with severe or mild disease, respectively (p ≤ 0.0017). We conclude that individuals positive for the CIAS1 12 allele may be at elevated risk for development of severe COVID due to an increased level of induced pro-inflammatory cytokine production.

Effects of Melatonin Alone or Associated with Acyclovir on the Suppressive Treatment of Recurrent Genital Herpes: A Prospective, Randomized, and Double-Blind Study.

Suppressive therapy of recurrent genital herpes is a challenge, and melatonin may be an alternative. OBJECTIVE: To evaluate the action of melatonin, acyclovir, or the association of melatonin with acyclovir as a suppressive treatment in women with recurrent genital herpes. DESIGN: The study was prospective, double-blind, and randomized, including 56 patients as follows: (a) The melatonin group received 180 placebo capsules in the 'day' container and 180 melatonin 3 mg capsules in the 'night' container (n = 19); (b) The acyclovir group received 360 capsules of 400 mg acyclovir twice a day (one capsule during the day and another during the night) (n = 15); (c) the melatonin group received 180 placebo capsules in the 'day' container and 180 melatonin 3 mg capsules in the 'night' container (n = 22). The length of treatment was six months. The follow-up after treatment was six months. Patients were evaluated before, during, and after treatment through clinical visits, laboratory tests, and the application of four questionnaires (QSF-36, Beck, Epworth, VAS, and LANNS). RESULTS: No statistically significant difference was observed for the depression and sleepiness questionnaires. However, in the Lanns scale for pain, all groups decreased the mean and median values in time (p = 0.001), without differentiation among the groups (p = 0.188). The recurrence rates of genital herpes within 60 days after treatment were 15.8%, 33.3%, and 36.4% in the melatonin, acyclovir, and association of melatonin with acyclovir groups, respectively. CONCLUSION: Our data suggest that melatonin may be an option for the suppressive treatment of recurrent genital herpes.

The Medium Is the Message: Defining a "Normal" Vaginal Microbiome in Healthy Reproductive-Age Women.

The microbial composition of the human vagina differs from that of all other mammals, likely as a consequence of the unique composition of vaginal constituents that promote the selective maintenance and proliferation of distinct bacterial species. Similarly, variations between individual healthy women in genetic, environmental, and medical variables also modify the vaginal lumen composition. The direction and magnitude of immune reactions to microorganisms present in the vagina, responses to stress and non-infectious stimuli, coupled with medical and pregnancy history and environmental exposures, can greatly differ between women. Adaptations to both internal and external pressures will determine the ability of select resident vaginal bacteria to numerically dominate and, therefore, the definition of a "normal" vaginal microbiota will substantially differ between individual healthy women.

The circulating 70 kDa heat shock protein (HSPA1A) level is a potential biomarker for breast carcinoma and its progression.

The early diagnosis of breast cancer can improve treatment and prognosis. We sought to evaluate whether the serum concentration of the 70 kDa heat shock protein (HSPA1A) was elevated in Brazilian women with breast cancer, and if levels correlated with tumor characteristics. This was a cross-sectional, analytical, case-control exploratory study performed at The University of São Paulo School of Medicine. From September 2017 to December 2018, 68 women with breast cancer and 59 controls were recruited. The HSPA1A concentration in serum samples was determined by ELISA by individuals blinded to the clinical data. The mean ages in the study and control groups were 54.9 and 52.0 years, respectively. The median serum levels of HSPA1A were elevated in women with breast cancer (1037 pg/ml) compared with controls (300 pg/ml) (p < 0.001). Elevated HSPA1A levels were associated with advanced histological tumor grade (p < 0.001) and with the cell proliferation index (KI67) (p = 0.0418). The HSPA1A concentration was similar in women with different histological subtypes, nuclear grade, hormone receptor expression, HER2 status and the presence or absence of angiolymphatic invasion. Elevated serum HSPA1A in Brazilian women with advanced histological grade and proliferation index breast cancer supports the potential value of additional investigation on larger and more varied populations to verify the value of HSPA1A detection as a component of breast cancer diagnosis and progression.

Lactobacilluscrispatus dominance in the vaginalmicrobiome reduces the occurrence of spontaneouspreterm birth in women with a short cervical length / Dominância de Lactobacillus crispatus no microbioma vaginal reduz a ocorrênciade parto prematuro espontâneo em mulheres com encurtamento do colo uterino

Introduction: The majority of pregnant women with a short cervix will deliver at term and, thus, may unnecessarily receive advanced monitoring and treatment. It is still necessary to define more accurately which sub-population of women with a short cervix is at elevated risk for early delivery. Objective: To determine if vaginal microbiome composition influenced the rate of spontaneous preterm birth in women with a short cervical length. Methods: In an exploratory, observational prospective study, vaginal secretions were obtained from 591 women at 21­24 week gestation. Vaginal microbiome composition was determined by analyzing the V1­V3 region of the bacterial 16S ribosomal RNA gene. Results: Lactobacillus crispatus was numerically dominant in the vagina in 41.7% of subjects, followed by L. iners in 32% and Gardnerella vaginalis in 12%. In women whose cervix was ≤25mm, the sensitivity to predict an spontaneous preterm birth was 11.8%. However, when L. crispatus was not the dominant vaginal bacterium, this sensitivity increased to 81.8%. Similarly, in women with a cervical length ≤30mm, the sensitivity to predict an spontaneous preterm birth increased from 21.7 to 78.3% when L. crispatus was not the dominant vaginal bacterium.In women with a prior spontaneous preterm birth and a cervix ≤25 or ≤30mm, L. crispatus dominance was also associated with a reduced rate of spontaneous preterm birth in the current pregnancy (p<0.001). Conclusion: In pregnant women with a cervix ≤25mm or ≤30mm, the risk for an spontaneous preterm birth is increased if L. crispatus is not dominant in the vagina.

Introdução: A maioria das mulheres grávidas com colo do útero curto dará à luz a termo e, portanto, pode receber desnecessariamente monitoramento e tratamento avançados. Permanece a necessidade de definir com mais precisão qual subpopulação de mulheres com colo do útero curto está em risco elevado de parto prematuro. Objetivo: Determinar se a composição do microbioma vaginal influenciou a taxa de parto prematuro espontâneo em mulheres com colo curto. Métodos: Em um estudo prospectivo exploratório observacional, os conteúdos vaginais foram obtidos de 591 mulheres com 21­24 semanas de gestação. A composição do microbioma vaginal foi determinada pela análise da região V1­V3 do gene de RNA ribossômico bacteriano 16S. Resultados: Lactobacilluscrispatus foi numericamente dominante na vagina em 41,7% dos indivíduos, seguido por L. iners em 32% e Gardnerella vaginalis em 12%. Em mulheres cujo colo do útero era <25 mm, a sensibilidade para prever uma taxa de parto prematuro espontâneo foi de 11,8%. No entanto, quando L. crispatus não era a bactéria vaginal dominante, essa sensibilidade aumentou para 81,8%. Da mesma forma, em mulheres com comprimento cervical <30 mm, a sensibilidade para prever uma taxa de parto prematuro espontâneo aumentou de 21,7 para 78,3% quando L. crispatus não era a bactéria vaginal dominante. Em mulheres com taxa de parto prematuro espontâneo anterior e colo do útero <25 ou <30 mm, a dominância de L. crispatus também foi associada a uma taxa reduzida de taxa de parto prematuro espontâneo na gravidez atual (p<0,001). Conclusão: Em mulheres grávidas com colo do útero <25 ou <30 mm, o risco de parto prematuro espontâneo é aumentado se L. crispatus não for dominante na vagina.

Comparative measurement of D- and L-lactic acid isomers in vaginal secretions: association with high-grade cervical squamous intraepithelial lesions.

PURPOSE: Identification of low-cost protocols to identify women at elevated susceptibility to develop cervical intra-epithelial abnormalities would aid in more individualized monitoring. We evaluated whether quantitation of the D- and L-lactic acid isomers in vaginal secretions could differentiate women with normal cervical epithelia from those with a low (LSIL) or high (HSIL) grade squamous intraepithelial lesion or with cervical cancer. METHODS: Vaginal samples, collected from 78 women undetgoing cervical colposcopy and biopsy, were tested for pH, bacterial composition by Gram stain (Nugent score) and concentrations of D- and L-lactic acid by a colorimetric assay. RESULTS: Subsequent diagnosis was 23 women with normal cervical epithelium, 10 with LSIL, 43 with HSIL and 2 with cervical cancer. Vaginal pH and Nugent score were comparable in all subject groups. The concentration of L-lactic acid, but not D-lactic acid, as well as the L/D-lactic acid ratio, were significantly elevated (p < 0.01) in women with HSIL and cervical cancer. CONCLUSION: Comparative measurement of vaginal D- and L-lactic acid isomers may provide a low-cost alternative to identification of women with an elevated susceptibility to cervical abnormalities.

Brazilian Protocol for Sexually Transmitted infections, 2020: pelvic inflammatory disease.

Pelvic Inflammatory Disease is a topic included in the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health in 2020. Pelvic inflammatory disease is an upper female genital tract acute infection due to canalicular spread of endogenous cervicovaginal microorganisms and especially the sexually transmitted microorganisms. Standing out among the etiological agents involved are Chlamydia trachomatis and Neisseria gonorrhoeae. The main sequelae are chronic pelvic pain, infertility, and ectopic pregnancy. Clinical diagnosis is the most important practical approach. Antibiotic treatment must start immediately after the clinical suspicion. Guidelines for health service managers and health professionals on diagnostic tests, treatment, follow-up, counseling, notification, handling sexual partners and special populations are described. Given the increased availability of the molecular biology techniques in Brazil, C. trachomatis and N. gonorrhoeae screening are recommended as a disease prevention strategy. Pelvic inflammatory disease is one of the most significant sexually transmitted infections, and in most cases, it is a main consequence of cervicitis.

[Brazilian Protocol for Sexually Transmitted Infections 2020: pelvic inflammatory disease]. / Protocolo Brasileiro para Infecções Sexualmente Transmissíveis 2020: doença inflamatória pélvica.

Pelvic Inflammatory Disease is a topic included in the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health in 2020. Pelvic inflammatory disease is an acute infection of the upper female genital tract due to canalicular spread of endogenous cervicovaginal microorganisms, in particular sexually transmitted organisms. Standing out among the etiological agents involved are Chlamydia trachomatis and Neisseria gonorrhoeae. The most important sequels are chronic pelvic pain, infertility and ectopic pregnancy. Clinical diagnosis is the most important practical approach. Antibiotic treatment should start immediately upon clinical suspicion. The article contains guidance for health service managers and health professionals on diagnostic tests, treatment, follow-up, counseling, notification, handling of sexual partnerships and special populations. In view of increased availability of the molecular biology technique in Brazil, C. trachomatis and N. gonorrhoeae screening is recommended as a disease prevention strategy.

O tema doença inflamatória pélvica está contemplado no Protocolo Clínico e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Infecções Sexualmente Transmissíveis, publicado pelo Ministério da Saúde do Brasil em 2020. A doença inflamatória pélvica é a infecção aguda do trato genital superior feminino decorrente da ascensão canalicular de microrganismos cervicovaginais endógenos e, principalmente, os de transmissão sexual. Entre os agentes etiológicos envolvidos, destacam-se Chlamydia trachomatis e Neisseria gonorrhoeae. As sequelas mais importantes são dor pélvica crônica, infertilidade e gravidez ectópica. O diagnóstico clínico apresenta-se como a abordagem prática mais importante. O tratamento com antibióticos deve ser iniciado imediatamente diante da suspeição clínica. Descrevem-se orientações para gestores e profissionais de saúde sobre testes diagnósticos, tratamento preconizado, seguimento, aconselhamento, notificação, manejo de parcerias sexuais e de populações especiais. Com a maior disponibilidade da técnica de biologia molecular no Brasil, recomenda-se o rastreio de C. trachomatis e N. gonorrhoeae como estratégia preventiva da doença.

El tema de la enfermedad inflamatoria pélvica está incluido en el Protocolo Clínico y Directrices Terapéuticas para la Atención Integral para Personas con Infecciones de Transmisión Sexual, publicado por el Ministerio de Salud de Brasil en 2020. La enfermedad inflamatoria pélvica es una infección aguda del tracto genital superior femenino resultante del ascenso canalicular de microorganismos cervicovaginales endógenos y, principalmente, los de transmisión sexual. Entre los agentes etiológicos involucrados, se destacan Chlamydia trachomatis y Neisseria gonorrhoeae. Las secuelas más importantes son: dolor pélvico crónico, infertilidad y embarazo ectópico. El diagnóstico clínico es el enfoque práctico más importante. El tratamiento con antibiótico debe iniciarse inmediatamente ante la sospecha clínica. Se describen pautas para gestores y profesionales de la salud sobre pruebas de diagnóstico, tratamiento, seguimiento, asesoramiento, notificación, manejo de parejas sexuales y poblaciones especiales. Con la mayor disponibilidad de la técnica de biología molecular, se recomienda el cribado de C. trachomatis y N. gonorrhoeae como estrategia preventiva para la enfermedad.

The Torque Teno Virus Titer in Saliva Reflects the Level of Circulating CD4+ T Lymphocytes and HIV in Individuals Undergoing Antiretroviral Maintenance Therapy.

INTRODUCTION: Torque teno virus (TTV) is a non-pathogenic virus present in body fluids. Its titer in the circulation increases in association with immune suppression, such as in HIV-infected individuals. We evaluated if the TTV titer in saliva from HIV-positive individuals undergoing antiretroviral therapy (ART) was related to the circulating CD4+ T lymphocyte concentration and the HIV titer. METHODS: Saliva was collected from 276 asymptomatic individuals undergoing ART, and an additional 48 individuals positive for AIDS-associated Kaposi's Sarcoma (AIDS-KS). The salivary TTV titer was measured by gene amplification analysis. The circulating CD4+ T lymphocyte and HIV levels were obtained by chart review. RESULTS: TTV was detectable in saliva from 80% of the asymptomatic subjects and 87% of those with AIDS-KS. In the asymptomatic group the median log10 TTV titer/ml was 3.3 in 200 males vs. 2.4 in 76 females (p < 0.0001). TTV titer/ml was 3.7 when HIV was acquired by intravenous drug usage, 3.2 when by sexual acquisition and 2.4 when blood transfusion acquired. The salivary TTV titer was inversely correlated with the circulating CD4+ T lymphocyte level (p < 0.0001) and positively correlated with the circulating HIV concentration (p = 0.0005). The median salivary TTV titer and circulating HIV titer were higher, and the CD4+ count was lower, in individuals positive for AIDS-KS than in the asymptomatic subjects (p < 0.0001). CONCLUSION: The TTV titer in saliva is a potential biomarker for monitoring immune status in individuals undergoing ART.

Protocolo Brasileiro para Infecções Sexualmente Transmissíveis 2020: doença inflamatória pélvica / Brazilian Protocol for Sexually Transmitted Infections 2020: pelvic inflammatory disease / Protocolo Brasileño para Infecciones de Transmisión Sexual 2020: enfermedad inflamatoria pélvica

O tema doença inflamatória pélvica está contemplado no Protocolo Clínico e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Infecções Sexualmente Transmissíveis, publicado pelo Ministério da Saúde do Brasil em 2020. A doença inflamatória pélvica é a infecção aguda do trato genital superior feminino decorrente da ascensão canalicular de microrganismos cervicovaginais endógenos e, principalmente, os de transmissão sexual. Entre os agentes etiológicos envolvidos, destacam-se Chlamydia trachomatis e Neisseria gonorrhoeae. As sequelas mais importantes são dor pélvica crônica, infertilidade e gravidez ectópica. O diagnóstico clínico apresenta-se como a abordagem prática mais importante. O tratamento com antibióticos deve ser iniciado imediatamente diante da suspeição clínica. Descrevem-se orientações para gestores e profissionais de saúde sobre testes diagnósticos, tratamento preconizado, seguimento, aconselhamento, notificação, manejo de parcerias sexuais e de populações especiais. Com a maior disponibilidade da técnica de biologia molecular no Brasil, recomenda-se o rastreio de C. trachomatis e N. gonorrhoeae como estratégia preventiva da doença.

Pelvic Inflammatory Disease is a topic included in the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health in 2020. Pelvic inflammatory disease is an acute infection of the upper female genital tract due to canalicular spread of endogenous cervicovaginal microorganisms, in particular sexually transmitted organisms. Standing out among the etiological agents involved are Chlamydia trachomatis and Neisseria gonorrhoeae. The most important sequels are chronic pelvic pain, infertility and ectopic pregnancy. Clinical diagnosis is the most important practical approach. Antibiotic treatment should start immediately upon clinical suspicion. The article contains guidance for health service managers and health professionals on diagnostic tests, treatment, follow-up, counseling, notification, handling of sexual partnerships and special populations. In view of increased availability of the molecular biology technique in Brazil, C. trachomatis and N. gonorrhoeae screening is recommended as a disease prevention strategy.

El tema de la enfermedad inflamatoria pélvica está incluido en el Protocolo Clínico y Directrices Terapéuticas para la Atención Integral para Personas con Infecciones de Transmisión Sexual, publicado por el Ministerio de Salud de Brasil en 2020. La enfermedad inflamatoria pélvica es una infección aguda del tracto genital superior femenino resultante del ascenso canalicular de microorganismos cervicovaginales endógenos y, principalmente, los de transmisión sexual. Entre los agentes etiológicos involucrados, se destacan Chlamydia trachomatis y Neisseria gonorrhoeae. Las secuelas más importantes son: dolor pélvico crónico, infertilidad y embarazo ectópico. El diagnóstico clínico es el enfoque práctico más importante. El tratamiento con antibiótico debe iniciarse inmediatamente ante la sospecha clínica. Se describen pautas para gestores y profesionales de la salud sobre pruebas de diagnóstico, tratamiento, seguimiento, asesoramiento, notificación, manejo de parejas sexuales y poblaciones especiales. Con la mayor disponibilidad de la técnica de biología molecular, se recomienda el cribado de C. trachomatis y N. gonorrhoeae como estrategia preventiva para la enfermedad.

Protocolo Brasileiro para Infecções Sexualmente Transmissíveis 2020: doença inflamatória pélvica / Brazilian Protocol for Sexually Transmitted Infections 2020: pelvic inflammatory disease / Protocolo Brasileño para Infecciones de Transmisión Sexual 2020: enfermedad inflamatoria pélvica

Resumo O tema doença inflamatória pélvica está contemplado no Protocolo Clínico e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Infecções Sexualmente Transmissíveis, publicado pelo Ministério da Saúde do Brasil em 2020. A doença inflamatória pélvica é a infecção aguda do trato genital superior feminino decorrente da ascensão canalicular de microrganismos cervicovaginais endógenos e, principalmente, os de transmissão sexual. Entre os agentes etiológicos envolvidos, destacam-se Chlamydia trachomatis e Neisseria gonorrhoeae. As sequelas mais importantes são dor pélvica crônica, infertilidade e gravidez ectópica. O diagnóstico clínico apresenta-se como a abordagem prática mais importante. O tratamento com antibióticos deve ser iniciado imediatamente diante da suspeição clínica. Descrevem-se orientações para gestores e profissionais de saúde sobre testes diagnósticos, tratamento preconizado, seguimento, aconselhamento, notificação, manejo de parcerias sexuais e de populações especiais. Com a maior disponibilidade da técnica de biologia molecular no Brasil, recomenda-se o rastreio de C. trachomatis e N. gonorrhoeae como estratégia preventiva da doença.

Abstract Pelvic Inflammatory Disease is a topic included in the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health in 2020. Pelvic inflammatory disease is an acute infection of the upper female genital tract due to canalicular spread of endogenous cervicovaginal microorganisms, in particular sexually transmitted organisms. Standing out among the etiological agents involved are Chlamydia trachomatis and Neisseria gonorrhoeae. The most important sequels are chronic pelvic pain, infertility and ectopic pregnancy. Clinical diagnosis is the most important practical approach. Antibiotic treatment should start immediately upon clinical suspicion. The article contains guidance for health service managers and health professionals on diagnostic tests, treatment, follow-up, counseling, notification, handling of sexual partnerships and special populations. In view of increased availability of the molecular biology technique in Brazil, C. trachomatis and N. gonorrhoeae screening is recommended as a disease prevention strategy.

Resumen El tema de la enfermedad inflamatoria pélvica está incluido en el Protocolo Clínico y Directrices Terapéuticas para la Atención Integral para Personas con Infecciones de Transmisión Sexual, publicado por el Ministerio de Salud de Brasil en 2020. La enfermedad inflamatoria pélvica es una infección aguda del tracto genital superior femenino resultante del ascenso canalicular de microorganismos cervicovaginales endógenos y, principalmente, los de transmisión sexual. Entre los agentes etiológicos involucrados, se destacan Chlamydia trachomatis y Neisseria gonorrhoeae. Las secuelas más importantes son: dolor pélvico crónico, infertilidad y embarazo ectópico. El diagnóstico clínico es el enfoque práctico más importante. El tratamiento con antibiótico debe iniciarse inmediatamente ante la sospecha clínica. Se describen pautas para gestores y profesionales de la salud sobre pruebas de diagnóstico, tratamiento, seguimiento, asesoramiento, notificación, manejo de parejas sexuales y poblaciones especiales. Con la mayor disponibilidad de la técnica de biología molecular, se recomienda el cribado de C. trachomatis y N. gonorrhoeae como estrategia preventiva para la enfermedad.

Brazilian protocol for sexually transmitted infections, 2020: pelvic inflammatory disease

Abstract Pelvic Inflammatory Disease is a topic included in the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health in 2020. Pelvic inflammatory disease is an upper female genital tract acute infection due to canalicular spread of endogenous cervicovaginal microorganisms and especially the sexually transmitted microorganisms. Standing out among the etiological agents involved are Chlamydia trachomatis and Neisseria gonorrhoeae. The main sequelae are chronic pelvic pain, infertility, and ectopic pregnancy. Clinical diagnosis is the most important practical approach. Antibiotic treatment must start immediately after the clinical suspicion. Guidelines for health service managers and health professionals on diagnostic tests, treatment, follow-up, counseling, notification, handling sexual partners and special populations are described. Given the increased availability of the molecular biology techniques in Brazil, C. trachomatis and N. gonorrhoeae screening are recommended as a disease prevention strategy.

Mannose-binding lectin gene polymorphism and risk factors for cardiovascular disease in postmenopausal women.

BACKGROUND: Inflammatory responses may be altered in postmenopausal women and predispose to cardiovascular disease (CVD). Genetic factors can also influence susceptibility to CVD. Mannose-binding lectin (MBL) is a component of the innate immune system and an activator of the complement cascade. We evaluated the association of genetic polymorphism of MBL (MBL2) on risk factors for CVD in postmenopausal women. METHODS: In this cross-sectional study, 311 Brazilian women (age ≥45 years and amenorrhea ≥12 months) were included. EXCLUSION CRITERIA: presence of previous or current CVD, insulin dependent diabetes, chronic kidney disease, autoimmune diseases and cancer. Clinical, anthropometric and biochemical assessments were performed to evaluate the cardiovascular risk factors. DNA was extracted from buccal cell and polymorphisms at codons 54 and 57 in the MBL2 were determined by polymerase chain reaction (PCR). For statistical analysis, the chi-square and logistic regression (odds ratio, OR) were used. RESULTS: The presence of the polymorphic allele for codon 54 was found in 25.8% of women (A/B=22.6%, B/B=3.2%) and for codon 57 in 12.2% (A/C=10.8%, C/C=1.4%). The polymorphism at codon 54 was significantly associated with the presence of hypertension (OR 0.55, 95% CI 0.31-0.99, p=0.044) and insulin resistance assessed by HOMA-IR (OR 0.46, 95% CI 0.24-0.91, p=0.025). No significant associations were observed between the polymorphism at codon 57 with risk factors for CVD. CONCLUSION: In postmenopausal women, the polymorphism at codon 54 of the MBL2 was associated with lower risk for hypertension and insulin resistance that are important risk factors for CVD.

Uterine cervical ectopy during reproductive age: cytological and microbiological findings.

Cervical ectopy is common in adolescents, pregnant women, and those taking high doses of estrogen-containing contraceptives. The majority of cases have spontaneous reversion, but some cases can be persistent. Studies suggested that the adequacy of a Pap smear could be affected and there is an increased risk cervical infections. This study is a cross-sectional study conducted from December 2009 to February 2011 with 457 women with cervical ectopy and 736 without ectopy. Cervical samples were collected in vials for analysis by ThinPrep cytology (Hologic, Marlborough, MA). The Mann-Whitney test and Fisher's exact test (95% CI) were applied. The study was approved by the ethics committee of the Federal University of Ceará. The mean ages of the study group and control group were 28.7 (±14.8) and 33.6 (±7.5) years old, respectively (P < 0.0001). Negative diagnosis for malignancy and intraepithelial lesion was present in 399 (87%) cases and 705 (96%) in the study and control groups, respectively (P < 0.0001). Shift in the flora suggestive of bacterial vaginosis (BV) was observed more frequently in the study group: 74 (16.2%) than in the control group: 86(11.7%) (P = 0.017). The differences among the other morphotypes showed no significance. The smears were atypical in 12.7% (58/457) of the patients from the study group and in 4.2% (31/736) in the control group (P < 0.001; RR = 3 [2.033-4.712]). The association between ectopy and inflammatory cytology, the presence of the shift in the flora suggestive of BV and cytological atypia is evident.

Inhibition of autophagy by sera from pregnant women.

Autophagy is a process that maintains homeostasis by eliminating senescent or damaged intracellular organelles and proteins. Its role in pregnancy has been scarcely studied. We compared the influence of sera from pregnant and nonpregnant women on autophagy induction. Peripheral blood mononuclear cells (PBMCs) were incubated with sera from 35 pregnant or nonpregnant women in the presence or absence of the autophagy inducer, rapamycin. After 48 hours, the cells were assayed for p62, a cytoplasmic protein essential for autophagy induction. Its concentration in the cytoplasm is inversely proportional to the level of autophagy induction. Sera were tested for immune mediators by enzyme-linked immunosorbent assay. Median (range) p62 concentrations were 6.7 ng/mL (1.1-22.7) for PBMCs incubated with pregnancy sera versus 2.5 ng/mL (0.8-7.7) for nonpregnant sera (P < .0001). In the presence of rapamycin, median p62 levels were 1.3 ng/mL (<0.1-4.9) with pregnancy sera, when compared to 0.6 ng/mL (<0.1-3.3) with control sera (P = .0191). Among the pregnant patients, the p62 level was inversely proportional to the results of a 50-g glucose challenge test (r = -.5630, P = .0005). Sera from pregnant women had elevated levels of insulin-like growth factor 1 (IGF-1), interleukin 13 (IL-13), and transforming growth factor ß1 (TGF-ß1). Autophagy during pregnancy may be inhibited by IGF-1, IL-13, and/or TGF-ß1 and may influence insulin resistance.

Heat shock protein production and immunity and altered fetal development in diabetic pregnant rats.

We evaluated associations between the concentrations of heat shock proteins (hsp60 and hsp70) and their respective antibodies, alterations in maternal reproductive performance, and fetal malformations in pregnant rats with hyperglycemia. Mild diabetes (MD) or severe diabetes (SD) was induced in Sprague-Dawley rats prior to mating; non-treated non-diabetic rats (ND) served as controls. On day 21 of pregnancy, maternal blood was analyzed for hsp60 and hsp70 and their antibodies; and fetuses were weighed and analyzed for congenital malformations. Hsp and anti-hsp levels were correlated with blood glucose levels during gestation. There was a positive correlation between hsp60 and hsp70 levels and the total number of malformations (R = 0.5908, P = 0.0024; R = 0.4877, P = 0.0134, respectively) and the number of malformations per fetus (R = 0.6103, P = 0.0015; R = 0.4875, P = 0.0134, respectively). The anti-hsp60 IgG concentration was correlated with the number of malformations per fetus (R = 0.3887, P = 0.0451) and the anti-hsp70 IgG level correlated with the total number of malformations (R = 0.3999, P = 0.0387). Moreover, both hsp and anti-hsp antibodies showed negative correlations with fetal weight. The results suggest that there is a relationship between hsp60 and hsp70 levels and their respective antibodies and alterations in maternal reproductive performance and impaired fetal development and growth in pregnancies associated with diabetes.