Single nucleotide polymorphism (SNP) rs4291 of the angiotensin-converting enzyme (ACE) gene is associated with the response to losartan treatment in hypertensive patients.

Arterial hypertension is characterized by systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mmHg and its treatment consists of the use of antihypertensive drugs, as losartan and hydrochlorothiazide. Blood pressure is regulated by angiotensin-converting enzyme (ACE) and polymorphisms in the ACE gene are associated to a greater predisposition to hypertension and response to treatment. The aim of this study was to evaluate the association of genetic polymorphisms of ACE rs4363, rs4291 and rs4335 and the response to antihypertensive drugs in hypertensive patients from Ouro Preto/MG, Brazil. A case-control study was carried out with 87 hypertensive patients being treated with losartan and 75 with hydrochlorothiazide, who answered a questionnaire and had blood samples collected. Biochemical analyzes were performed on serum using UV/Vis spectrophotometry and identification of ACE variants rs4363, rs4291 and rs4335 was performed by real-time PCR using the TaqMan® system. Univariate logistic regression test was performed to compare categorical data in STATA 13.0 software. The results showed that there was an influence of ACE polymorphisms on the response to losartan, demonstrating that AT or TT genotypes of rs4291 were more frequent in the group of controlled AH (54.9%), indicating that these individuals are 2.8 times more likely to of being controlled AH (95% CI 1.12-6.80, p. =0.026) compared to those with AA genotype. In contrast, no influence of ACE polymorphisms on the response to hydrochlorothiazide was observed. In conclusion, the presence of the T allele of the rs4291 variant was associated to controled blood pressure when losartan was used as an antihypertensive agent. These results show the importance of pharmacogenetic studies to detect genetic characteristics, enabling therapeutic individuality and reducing costs for the healthcare system.

Qualitative and quantitative changes in mitochondrial DNA associated with cervical cancer: A comprehensive review.

Cervical cancer is the fourth most commonly diagnosed cancer in women and is considered a preventable disease, as vaccination and screening programs effectively reduce its incidence and mortality rates. Disease physiopathology and malignant cell transformation is a complex process, but it is widely known that high-risk HPV (hrHPV) infection is a necessary risk factor for cancer development. Mitochondria, cell organelles with important bioenergetic and biosynthetic functions, are important for cell energy production, cell growth, and apoptosis. Mitochondrial DNA is a structure that is particularly susceptible to quantitative (mtDNA copy number variation) and qualitative (sequence variations) alterations that are associated with various types of cancer. Novel biomarkers with diagnostic and prognostic value in cervical cancer can be evaluated to provide higher specificity and complement hrHPV molecular testing, which is the most recommended method for primary screening. In accordance with this, this review aimed to assess mitochondrial alterations associated with cervical cancer in clinical cervicovaginal samples, in order to unravel their possible role as specific diagnostic and prognostic biomarkers for cervical malignancy, and also to guide the understanding of their involvement in carcinogenesis, HPV infection, and disease progression.

Yoga practice can reduce metabolic syndrome and cardiovascular risk in climacteric women.

To evaluate the effect of yoga on the frequency of MetS and its impact on cardiovascular risk markers in climacteric women. We recruited 84 sedentary women between 40 and 65 years diagnosed with MetS. Participants were randomly assigned to a 24-week yoga intervention or control group. We evaluated the frequency of MetS and changes in the individual components of MetS at baseline and after 24 weeks. We also assessed the impact of yoga practices on cardiovascular risk through the following markers: High-sensitivity C-reactive Protein (hs-CRP), Lipid Accumulation Product (LAP), Visceral Adiposity Index (VAI), and Atherogenic Index of Plasma (AIP). The frequency of MetS reduced significantly after 24 weeks of yoga practice (- 34.1%; p < 0.001). Statistical analysis showed that the frequency of MetS was significantly lower in the yoga group (65.9%; n = 27) than in the control group (93.0%; n = 40) after 24 weeks (p = 0.002). Regarding the individual components of MetS, yoga practitioners had statistically lower waist circumference, systolic blood pressure, triglycerides, HDLc, and glucose serum concentrations than the control group after 24 weeks. Yoga practitioners also had a significant decrease in hs-CRP serum concentrations (3.27 ± 2.95 mg/L vs. 2.52 ± 2.14 mg/L; p = 0.040) and a lower frequency of moderate or high cardiovascular risk (48.8% vs. 34.1%; p = 0.001) after 24 weeks of practice. The yoga group had LAP values significantly lower than the control group after the intervention period (55.8 ± 38.04 vs. 73.9 ± 40.7; p = 0.039). Yoga practice demonstrated to be an effective therapeutic to manage MetS and reduce cardiovascular risk in climacteric women.

G Protein Subunit Beta 3 (GNB3) Variant Is Associated with Biochemical Changes in Brazilian Patients with Hypertension. / Variante da Subunidade Beta 3 da Proteína G ( GNB3 ) Está Associada a Alterações Bioquímicas em Pacientes Brasileiros com Hipertensão.

BACKGROUND: Central Illustration : G Protein Subunit Beta 3 (GNB3) Variant Is Associated with Biochemical Changes in Brazilian Patients with Hypertension. BACKGROUND: Genes and their variants associated with environmental factors contribute to the development of the hypertensive phenotype. The G protein beta 3 subunit gene (GNB3) is involved in the intracellular signaling process, and its variants have been related to susceptibility to arterial hypertension. OBJECTIVE: To determine the association of the GNB3 variant (rs5443:C>T) with arterial hypertension, biochemical parameters, age, and obesity in hypertensive and normotensive individuals from Ouro Preto, Minas Gerais, Brazil. METHOD: The identification of variants was performed by real-time PCR, using the TaqMan® system, in 310 samples (155 hypertensive and 155 normotensive). Biochemical analyses (renal function, lipid profile and glycemia) were performed from the serum using UV/Vis spectrophotometry and ion-selective electrode. A multiple logistic regression model was used to identify factors associated with arterial hypertension. The analysis of continuous variables with normal distribution was performed using the unpaired Student's t test; non-normal data were analyzed using Mann-Whitney. P < 0.05 was considered significant. RESULTS: The rs5443:C>T variant was not associated with arterial hypertension in the evaluated population (p = 0.88). Regarding biochemical measures, the T allele was associated with high levels of triglycerides, glucose and uric acid in hypertensive individuals (p < 0.05). CONCLUSION: These results show the importance of genetic diagnosis to prevent the causes and consequences of diseases and imply that the GNB3 rs5443:C>T variant may be associated with changes in the biochemical profile in hypertensive individuals.

Variante da Subunidade Beta 3 da Proteína G ( GNB3 ) Está Associada a Alterações Bioquímicas em Pacientes Brasileiros com Hipertensão / G Protein Subunit Beta 3 (GNB3) Variant Is Associated with Biochemical Changes in Brazilian Patients with Hypertension

Resumo Fundamento Genes e suas variantes associadas a fatores ambientais contribuem para o desenvolvimento do fenótipo hipertenso. O gene da subunidade beta 3 da proteína G ( GNB3 ) está envolvido no processo de sinalização intracelular e suas variantes têm sido relacionadas à suscetibilidade à hipertensão arterial. Objetivo Determinar a associação da variante GNB3 (rs5443:C>T) com a hipertensão arterial, parâmetros bioquímicos, idade e obesidade em indivíduos hipertensos e normotensos de Ouro Preto, Minas Gerais. Método A identificação das variantes foi realizada por PCR em tempo real, utilizando o sistema TaqMan®, em amostras de 310 pacientes (155 hipertensos e 155 normotensos). Análises bioquímicas (função renal, perfil lipídico e glicemia) foram realizadas a partir do soro por meio de espectrofotometria UV/Vis e eletrodo íon-seletivo. Foi utilizado um modelo de regressão logística múltipla para identificar fatores associados à hipertensão arterial. A análise das variáveis contínuas com distribuição normal foi realizada usando o teste t de Student não pareado; dados não normais foram analisados usando o teste de Mann-Whitney. Valores de p < 0,05 foram considerados significativos. Resultados A variante rs5443:C>T não esteve associada à hipertensão arterial na população avaliada (p = 0,88). Em relação às medidas bioquímicas, o alelo T esteve associado a níveis elevados de triglicerídeos, glicose e ácido úrico em indivíduos hipertensos (p < 0,05). Conclusão Os presentes resultados mostram a importância do diagnóstico genético para prevenir as causas e consequências de doenças e sugerem que a variante GNB3 rs5443:C>T pode estar associada a alterações no perfil bioquímico em indivíduos hipertensos.

Abstract Background Genes and their variants associated with environmental factors contribute to the development of the hypertensive phenotype. The G protein beta 3 subunit gene (GNB3) is involved in the intracellular signaling process, and its variants have been related to susceptibility to arterial hypertension. Objective To determine the association of the GNB3 variant (rs5443:C>T) with arterial hypertension, biochemical parameters, age, and obesity in hypertensive and normotensive individuals from Ouro Preto, Minas Gerais, Brazil. Method The identification of variants was performed by real-time PCR, using the TaqMan® system, in 310 samples (155 hypertensive and 155 normotensive). Biochemical analyses (renal function, lipid profile and glycemia) were performed from the serum using UV/Vis spectrophotometry and ion-selective electrode. A multiple logistic regression model was used to identify factors associated with arterial hypertension. The analysis of continuous variables with normal distribution was performed using the unpaired Student's t test; non-normal data were analyzed using Mann-Whitney. P < 0.05 was considered significant. Results The rs5443:C>T variant was not associated with arterial hypertension in the evaluated population (p = 0.88). Regarding biochemical measures, the T allele was associated with high levels of triglycerides, glucose and uric acid in hypertensive individuals (p < 0.05). Conclusion These results show the importance of genetic diagnosis to prevent the causes and consequences of diseases and imply that the GNB3 rs5443:C>T variant may be associated with changes in the biochemical profile in hypertensive individuals.

Uric acid level in climacteric women and its association with clinical and metabolic parameters.

Climacteric women often experience unfavorable metabolic changes. Consequently, identifying markers that may contribute to such undesirable changes is imperative. This study aimed to evaluate serum uric acid (UA) concentration and its association with metabolic and clinical parameters in climacteric women. We selected 672 women between 40 and 65 years and performed interviews, biochemical analyses, blood pressure, and anthropometric measurements. UA levels were determined using the enzymatic-colorimetric method. We compared variables according to the quartiles of UA using the Kruskal-Wallis test. The mean UA level was 4.9 ± 1.5 mg/dl, ranging from 2.0 to 11.6 mg/dl. We found that UA levels greater than 4.8 mg/dl were associated with adverse metabolic parameters in climacteric women. For all anthropometric and biochemical variables, we observed significantly better results in women who had lower UA levels (p < 0.05). Similarly, we observed a significant increase in blood pressure, frequency of metabolic syndrome, and cardiovascular risk as UA levels increased (p < 0.05). Our findings showed that climacteric women with high levels of UA were more likely to have adverse metabolic and clinical parameters than those with lower UA levels. Further studies may determine the causal relationship between UA and metabolic changes in climacteric women.

The correlation of the fecal microbiome with the biochemical profile during menopause: a Brazilian cohort study.

BACKGROUND: Hormonal, biochemical, and metabolic changes after menopause may alter the quality of life of women, leading to vasomotor, psychological, and genitourinary symptoms, and changes in their gut microbiota, which regulates estrogen levels through the estroboloma. Fecal samples were used to investigate the changes in the gut microbiota during aging and hormonal changes in women. A balanced gut microbiota has been associated with health or disease conditions and remains poorly understood after menopause. This study identified the fecal microbiota, and their association with biochemical and hormonal parameters of a cohort of women in the climacteric in the city of Ouro Preto-MG, Brazil. METHODS: A total of 102 women aged 40 to 65 years old were recruited and distributed into three groups according to the STRAW criteria for reproductive stage: reproductive (n = 18), premenopausal (n = 26), and postmenopausal (n = 58). Blood samples were collected to measure their serum biochemical and hormone levels, and the participants answered a questionnaire. The gut microbiota was analyzed from fecal samples by qPCR using the genera Bifidobacterium, Bacteroides, Lactobacillus, and Clostridium. RESULTS: The following parameters showed differences among the groups: total cholesterol, triglycerides, VLDL, ApoB, urea, calcium, uric acid, and alkaline phosphatase (p < 0.05). qPCR revealed the genus Clostridium to be the most abundant in all three groups. In the reproductive age group, the significant correlations were: Bacteroides with glucose (r = -0.573 p = 0.0129), and SDHEA (r = -0.583 p = 0.0111). For the premenopausal group, they were: Bifidobacteria with total cholesterol (r = 0.396 p = 0.0451), LDL (r = 0.393 p = 0.0468), ApoB (r = 0.411 p = 0.0368); Lactobacillus and calcium (r = 0.443 p = 0.0232), ALP (r = 0.543 p = 0.0041), LPa (r =-0.442 p = 0.02336); and Bacteroides and urea (r =-0.461 p = 0.0176). In the postmenopausal group, they were Bifidobacterium and ALP (r =-0.315 p = 0.0159), Lactobacillus and urea (r =-0.276 p = 0.0356), and Clostridium and beta estradiol (r =-0.355 p = 0.0062). CONCLUSION: In conclusion, the hormonal and metabolic changes during menopause in the population studied were accompanied by a significant change in the fecal microbiota, especially of the genus Clostridium.

Correlation of serum anti-Mullerian hormone with hormonal and environmental parameters in Brazilian climacteric women.

This study aimed to identify the correlation among anti-Mullerian Hormone serum levels and 25-OH-D, obesity, metabolic syndrome (MetS), and sexual hormones in climacteric women classified according to stages of reproductive aging (SRA). A cross-sectional study was conducted with a total of 177 Brazilian climacteric women between 40 and 64 years old. Concentrations of AMH were measured using the Access 2 Immunoassay System. A multiple linear regression analysis was used to identify the relationship among AMH, 25-OH-D, obesity, MetS, sexual hormones, sociodemographic and lifestyle factors. AMH levels decreased with increased age (B = - 0.059; p < 0.001), and reproductive aging (B = - 0.483; p < 0.001). Obesity indicators, lifestyle characters, 25-OH-D levels and MetS were not significantly associated with AMH serum concentration. Negative correlation was found for FSH (B = - 0.009; p < 0.001) and LH (B = - 0.006; p = 0.004); positive correlation for E2 (B = 0.001; p = 0.011), DHEAS (B = 0.003; p < 0.001) and SHBG (B = 0.003; p = 0.005). In the model adjusted for SRA, FSH levels (p < 0.001) and DHEAS (p = 0.014) were associated with AMH. Although, with the adjustment for age, only FSH remained with a significant association (p = 0.001). Of the other analytes, none was associated with AMH, regardless of the model fit. Our findings confirm that serum AMH level decreased with age and FSH levels, but there is no correlation between AMH with obesity, 25-OH-D, MetS or other sexual hormones in Brazilian climacteric women.

Levels of Folate and Vitamin B12, and Genetic Polymorphisms Involved in One-Carbon Metabolism May Increase the Risk of Cervical Cytological Abnormalities.

To analyze the association of cervical cytological abnormalities with genetic polymorphisms of enzymes involved in folate metabolism, and the effect of micronutrients on association of polymorphisms with cervical carcinogenesis. Our samples were divided in Control (120 women with normal cytology), and Cases: 37 women with Atypical Squamous Cells of Undetermined Significance(ASC-US), 33 participants presenting Low-Grade Squamous Intraepithelial Lesion(LSIL), and 24 women presenting High-Grade cervical lesions(HSIL/ASC-H). We obtained cervical samples for cytological analysis, HPV detection, and analysis of polymorphisms and cervical cell folate. Blood samples were obtained for serum folate and vitamin B12 evaluation. To analyze all polymorphisms simultaneously, we calculated Genetic Risk Score(GRS). Median concentrations were used as cutoff for determination of micronutrient levels. We observed no differences of genotype or allelic frequencies of polymorphisms according to cervical lesions. However, high levels of cervical cell folate and high number of genetic alterations increased risk of High-Grade lesions [OR(IC95%):1.85(0.42-8.11)]. Instead, women with vitamin B12 ≤ 274 pg/ml and GRS ≥ 3 presented even greater risk of HSIL/ASC-H [OR(IC95%):2.91(0.46-18.62)]. High frequency of genetic polymorphisms involved in one-carbon metabolism associated with high levels of cell folate or low levels of serum vitamin B12, increased the risk of High-Grade lesion in uterine cervix.

Climacteric symptoms and quality of life in yoga practitioners.

BACKGROUND: Yoga is among the most commonly studied complementary therapies for managing climacteric symptoms. However, it is unclear whether yoga practices in premenopause can affect the occurrence of symptoms when women reach menopause. OBJECTIVE: To assess climacteric symptoms and quality of life in regular yoga practitioners and to determine whether yoga practices before menopause may avoid or mitigate climacteric-related symptoms. DESIGN: This study of 108 women between 40 and 65 years old included 28 women who started to practice yoga in premenopause and had already practiced for at least five years, and as controls 30 physical activity practitioners (PA) who had practiced for at least five years, and 50 sedentary women. MAIN OUTCOME MEASURES: Climacteric symptoms were evaluated with the Kupperman Menopausal Index (KMI) and the Women's Health Questionnaire (WHQ). Moreover, we measured the quality of life with the WHQ. RESULTS: The KMI showed that 39.3% of yoga practitioners had no menopausal symptoms, and none reported severe symptoms. The WHQ indicated a few symptoms and a good quality of life for yoga practitioners (3.56; 3.35-3.80). In addition, we found that the yoga group had significantly less moderate and severe symptoms (p = 0.002) compared with the sedentary group. We also observed that yoga practitioners had less vasomotor symptoms and memory/concentration disorders than PA practitioners (p = 0.010 and p = 0.047) and sedentary women (p = 0.001 and p = 0.001) and also used fewer drugs than the PA (p < 0.001) and the sedentary groups (p = 0.001). CONCLUSIONS: Yoga practitioners who started to practice in premenopause had satisfactory results on the frequency and intensity of climacteric symptoms and quality of life. Although further research is required to support our findings, we conclude that yoga practice may represent an efficient non-pharmacological approach to manage and prevent climacteric symptoms.

Bacterial vaginosis: prevalence, risk profile and association with sexually transmitted infections / Vaginose bacteriana: prevalência, perfil de risco e associação com infecções sexualmente transmissíveis / Vaginosis bacteriana: prevalencia, perfil de riesgo y asociación con infecciones de transmisión sexual

Background and Objectives: Bacterial vaginosis (BV) is the most common cause of vaginal discharge in the world. The study aimed to estimate the prevalence and to identify risk factors associated with bacterial vaginosis. Methods: A cross-sectional study was conducted in Ouro Preto, Brazil, between February and December 2017. Three hundred and forty-one women aged 18 years or older, users of the Brazilian Unified Health System, participated in this study. Women who used oral or topical antibiotics in the four weeks prior to the sample collection and women who had undergone a total hysterectomy were excluded from the study. After signing the Informed Consent Form and filling out a questionnaire containing sociodemographic, behavioral and sexual data, the participants were directed to the collection room, where the nurse collected the samples for the preventive examination of the cervix and also two vaginal swabs. Vaginal swabs and cervical samples were analyzed for cytological abnormalities and BV using Gram staining and cytology. Pathogens causing sexually transmitted infections (STIs) were identified by Polymerase Chain Reaction (PCR). For the analysis of the data, statistical package STATA version 10.0 was used. This study was approved by the Research Ethics Committee of the Federal University of Ouro Preto (UFOP). Results: During the study, 341 women were evaluated. The prevalence of BV using Gram staining (32.5% [CI95% 27.7-37.7%]) and cytology (27.7% [CI95% 23.032.8%]) was similar, however, the sensitivity of cytology was lower (77.8%). Risk factors associated with BV were smoking (IRR 1.5 [CI95%: 1.1  2.1]), use of an intrauterine device (IRR 2.8 [CI95%: 1.2 - 6.5]), and past medical history of BV (IRR 1.5 [CI95%: 1.1 - 2.1]). Correlation between the presence of BV and Trichomonas vaginalis (TV) infection (r=0.24) was observed. Conclusion: The prevalence of BV was affected by life habits and was prevalent in women with TV. Thus, behavioral and social prevention approaches to women with diverse risk profiles may help mitigate TV/BV prevalence and recurrence of BV.(AU)

Contexte et objectifs: La vaginose bactérienne (VB) est la cause la plus fréquente de pertes vaginales dans le monde. Le but de cette étude était d'évaluer la prévalence et les facteurs associés à la vaginose bactérienne. Méthodes: Il s'agit d'une approche descriptive, transversale et quantitative réalisée à Ouro Preto, Minas Gerais, Brésil, entre février et décembre 2017. 341 femmes ont participé à cette étude, âgées de 18 ans ou plus, utilisatrices du Système de santé unifié. Les femmes ayant utilisé des antibiotiques oraux ou topiques dans les quatre semaines précédant le prélèvement et les femmes ayant subi une hystérectomie totale ont été exclues de l'étude. Après avoir signé le formulaire de consentement éclairé et rempli un questionnaire contenant des données sociodémographiques, comportementales et sexuelles, les participants ont été dirigés vers la salle de collecte, où l'infirmière a prélevé les échantillons pour l'examen préventif du col de l'utérus. et aussi deux écouvillons vaginaux. Les échantillons de frottis vaginaux et cervicaux ont été analysés pour les anomalies cytologiques et VB en utilisant la coloration de Gram et la cytologie. Les agents pathogènes causant des infections sexuellement transmissibles (IST) ont été identifiés par réaction en chaîne par polymérase. Pour l'analyse des données, le progiciel statistique STATA version 10.0 a été utilisé. Cette étude a été approuvée par le Comité d'éthique de la recherche de l'Université fédérale d'Ouro Preto (UFOP). Résultats: Au cours de l'étude, 341 femmes ont été évaluées. La prévalence de la VB avec coloration de Gram (32,5% [IC 95% 27,7 - 37,7%]) et de la cytologie (27,7% [IC 95% 23,0 - 32,8%]) était similaire, cependant la sensibilité cytologique était plus faible (77,8%). Les facteurs de risque associés à la VB étaient le tabagisme (IRR 1,5 [IC 95%: 1,1 - 2,1]), l'utilisation d'un dispositif intra-utérin (IRR 2,8 [IC 95%: 1,2 - 6,5] ) et antécédents médicaux de VB (IRR 1,5 [IC 95%: 1,1 - 2,1]). Il y avait une corrélation entre la présence d'une infection à VB et Trichomonas vaginalis (TV) (r = 0,24). Conclusion: La prévalence de la VB était affectée par le mode de vie et l'infection TV. Ainsi, les approches de prévention comportementale et sociale pour les femmes présentant des profils de risque différents peuvent aider à atténuer la prévalence de la TV / VB et la récurrence de la VB.(AU)

Justificativa e Objetivos: A vaginose bacteriana (VB) é a causa mais comum de corrimento vaginal no mundo. O objetivo desse estudo foi avaliar a prevalência e os fatores associados à vaginose bacteriana. Métodos: Trata-se de um descritivo, de forma transversal e abordagem quantitativa realizado em Ouro Preto, Minas Gerais, Brasil, entre fevereiro a dezembro de 2017. Participaram desse estudo 341 mulheres com idade igual ou superior a 18 anos, usuárias do Sistema Único de Saúde (SUS). Mulheres que usaram antibióticos orais ou tópicos nas quatro semanas anteriores à coleta e mulheres que haviam sido submetidas a uma histerectomia total foram excluídas do estudo. Após a assinatura do Termo de Consentimento Livre e Esclarecido e preenchimento de questionário contendo dados sócio-demográfico, comportamental e sexual, as participantes foram encaminhadas para a sala de coleta, onde a enfermeira realizou a coleta das amostras para o exame preventivo do colo do útero e também de dois swabs vaginais. As amostras de esfregaço vaginal e cervical foram analisadas quanto às anormalidades citológicas e VB usando coloração de Gram e citologia. Patógenos causadores de infecções sexualmente transmissíveis (ISTs) foram identificados por Reação em Cadeia da Polimerase (PCR). Para a análise dos dados foi utilizado o pacote estatístico STATA versão 10.0. O presente estudo foi aprovado pelo Comitê de Ética em Pesquisa da Universidade Federal de Ouro Preto (UFOP). Resultados: Durante o estudo, 341 mulheres foram avaliadas. A prevalência de VB com coloração de Gram (32,5% [IC95% 27,7 - 37,7%]) e citologia (27,7% [IC95% 23,0 - 32,8%]) foi semelhante, porém a sensibilidade da citologia foi menor (77,8%). Os fatores de risco associados ao VB foram tabagismo (IRR 1,5 [IC95%: 1,1 - 2,1]), uso de dispositivo intrauterino (IRR 2,8 [IC 95%: 1,2 - 6,5]) e história médica pregressa de VB (IRR 1,5 [IC95%: 1,1 - 2.1]). Observou-se correlação entre a presença de infecção por VB e Trichomonas vaginalis (TV) (r = 0,24). Conclusão: A prevalência de VB foi afetada por hábitos de vida e infecção por TV. Assim, abordagens de prevenção comportamental e social para mulheres com diversos perfis de risco podem ajudar a mitigar a prevalência de TV / VB e recorrência de VB.(AU)

Association of serum folate and vitamin B12 with pre-neoplastic cervical lesions.

BACKGROUND & AIMS: Diet and lifestyle play an important role in etiology of various tumors. Serum concentration of folate and vitamin B12may be associated with carcinogenesis since they are involved in DNA methylation and nucleotide synthesis. However, the role of these micronutrients on development of cervical cancer is still controversial. Thus, the aim of this study was to analyze the association of lower status of folate and vitamin B12 with the risk of pre-neoplastic cervical lesions. METHODS: Our sample group was divided in Control group (n = 120) - women with normal cytology, and Case groups (n = 57) - women presenting Atypical Squamous Cells of Undetermined Significance (ASC-US, n = 21), Low Grade Squamous Intraepithelial Lesion (LSIL; n = 16), and High-Grade lesions (n = 20). We obtained cervical samples for cytology analysis and HPV detection, and blood samples for evaluation of serum concentration of folate and vitamin B12. RESULTS: No difference of serum folate was observed among Cases and Control groups. On the other hand, women with High-Grade lesions presented significant lower median concentration of vitamin B12 if compared to another groups. Then, we observed increased risk of High-Grade lesions among participants with low vitamin B12 levels was observed in relation to women that presented high levels of the micronutrient and from Control group [OR (95% CI): 2.09 (0.65-6.76), p = 0.216], ASC-US [OR (95% CI): 3.15 (0.82-12.08), p = 0.095], and LSIL [OR (95% CI): 3.10 (0.76-12.70), p = 0.116]. CONCLUSIONS: Low concentration of vitamin B12 was associated with an increased risk of High-Grade cervical lesions. Besides, we did not observe any difference of serum folate among women with normal cytology and women with pre-neoplastic cervical lesions.

3'UTR polymorphism of Thymidylate Synthase gene increased the risk of persistence of pre-neoplastic cervical lesions.

BACKGROUND: Cervical cancer is caused by high-risk Human Papillomavirus (hr-HPV) infection associated with cofactors that has been analyzed as predictors of the remission or persistence of cytological abnormalities remission or persistence. These cofactors can be either environmental, epigenetic, or genetic. Polymorphism in genes of enzymes that act on one-carbon metabolism alter their activity and also may be associated with cervical carcinogenesis because they affect DNA synthesis and repair, and gene expression. Therefore, this study aimed to analyze the risk of persistence of pre-neoplastic cervical lesions according to genetic polymorphisms involved in one-carbon metabolism. METHODS: Our sample consisted of 106 women, divided into two groups - Remission (n = 60), i.e., with the presence of pre-neoplastic lesions at first meeting (T1) and normal cytology after 6 months of follow-up (T2), and Persistence (n = 46), i.e., with the presence of pre-neoplastic lesions at T1 and T2. We obtained cervical samples for cytological analysis (T1 and T2), HPV detection (T1), and evaluation of polymorphism C667T of Methylenetetrahydrofolate Reductase (MTHFR C677T), A2756G of Methionine Synthase (MS A2756G), A66G of Methionine Synthase Reductase (MTRR A66G), double or triple 28 bp tandem repeat in 5'-untranslated enhanced region of Thymidylate Synthase (TSER), and 6 bp deletion at nucleotide 1494 in TS 3'-untranslated region (TS3'UTR). To analyze all genetic polymorphisms simultaneously, we calculated the Genetic Risk Score (GRS). RESULTS: We observed no differences between the Remission and Persistence groups regarding the GRS. Also, there were no differences in the genotypic and allelic distribution of MTHFR C677T and MS A2756G polymorphisms. However, the risk of persistence was higher among women with the heterozygote genotype - ins/del [OR (IC95%): 3.22 (1.19-8.69), p = 0.021], or the polymorphic genotype - del/del [OR (IC95%): 6.50 (1.71-24.70), p = 0.006] of TS3'UTR. CONCLUSIONS: The presence of the TS3'UTR polymorphism increased the risk of persistence of cervical abnormalities. This genetic variant could be a potential marker of cervical carcinogenesis and therefore assist the follow-up of women with persistent pre-neoplastic cervical lesions.

Knowledge about cervical cancer and HPV immunization dropout rate among Brazilian adolescent girls and their guardians.

BACKGROUND: Infections with Human Papillomavirus (HPV) are the main cause of cervical cancer. Since 2014, the HPV vaccine was introduced in the Brazilian National Vaccination Calendar. The purpose of this study was to assess the knowledge of adolescent girls and their mothers/guardians about HPV and HPV vaccine, identify the factors associated with this knowledge, and evaluate immunization dropout rate. METHODS: This was a cross-sectional study involving adolescent girls and their mothers/guardians. Participants underwent an interview that addressed sociodemographic data, sexual and gynecological history, and knowledge about HPV, HPV vaccine and cervical cancer. The third quartile of the total score was established as a cutoff for assessing knowledge. Adolescents who correctly answered more than four questions and mothers/guardians who obtained more than five correct responses were categorized into high knowledge. Poisson regression analysis was performed to identify variables associated with low knowledge. Vaccination records were used to assess immunization dropout rates. Any adolescent who did not complete the two-dose vaccination schedule was considered dropout. RESULTS: A total of 666 adolescent girls and 623 mothers/guardians were interviewed. Low knowledge was observed in 76.7% of adolescents and 79.8% of mothers/guardians. Most were unaware of the causal relationship between HPV and cervical cancer, signs and symptoms of HPV infection, and had limited knowledge about the HPV vaccine. Factors associated with low knowledge of adolescents were aged 12 years [IRR 1.2 (95% CI 1. 1-1.3)] or less [IRR 1.3 (95% CI (1. 2-1.4)]; household income lower than US$750 [IRR 1.7 (95% CI 1. 1-2.6)] and household income between US$751 and US$1500 [IRR 1.6 (95% CI 1.0-2.6)]. Among mothers/guardians, low knowledge was related to having completed elementary school or less [IRR 1.5 (95% CI 1. 2-2.0)]; and household income lower than US$750 [IRR 1.2 (95% CI 1.0-1.4)]. Knowledge of adolescents and mothers/guardians was not associated with vaccine uptake. HPV immunization dropout rate was considered high (32.3%). CONCLUSION: Knowledge about HPV and cervical cancer as well as vaccine uptake was low. Results highlight the need for educational interventions about HPV and cervical cancer. These actions may contribute to improve adherence to HPV vaccination.

Lack of association between methylenetetrahydrofolate reductase C677T polymorphism, HPV infection and cervical intraepithelial neoplasia in Brazilian women.

BACKGROUND: Cervical cancer has high prevalence and mortality rates in worldwide female population. Persistent infection by high-risk Human Papillomavirus (hr-HPV) is the main cause of this cancer. However, many environmental, genetical, and epigenetical cofactors can modulate viral infection and cervical carcinogenesis. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is a genetic factor that has been associated with many pathologies, including cancer. Nevertheless, studies with cervical cancer presented controversial results, and varied according to ethnicity. Thus, the aim of this study was to determine association between MTHFR C677T polymorphism, Human Papillomavirus (HPV) infection and cervical cancer. METHODS: A case-control study was performed with 150 histological cervical samples. Case group were divided in Cervical Intraepithelial Neoplasia (CIN) grade I (n = 30), CIN II (n = 30), CIN III (n = 30), and Squamous Cervical Carcinoma (SCC) (n = 30). Control group was composed by 30 samples without lesion, presenting cervicitis. HPV detection was performed by conventional Polymerase Chain Reaction (PCR) with SPF primers set, and by real-time PCR specific for HPV 16 and hr-HPV. MTHFR C677T polymorphism was analyzed by PCR followed by Restriction Fragment Length Polymorphism (RFLP). RESULTS: Frequency of MTHFR CC genotype was 72.7% (n = 109), CT 23.3% (n = 35) and TT 4.0% (n = 6). Polymorphic T allele frequency was 15.7%. No statistically significant association was observed between MTHFR C677T polymorphism and presence of pre-neoplastic or neoplastic cervical lesions. Similar frequencies of T allele was observed in control (23.3%) and cases (13.3%) groups (p = 0.174). In addition, there was no statistically significant association between MTHFR C677T polymorphism and viral infection, even considering hr-HPV or HPV 16 positivity. CONCLUSION: MTHFR C677T polymorphism was not associated with cervical cancer and HPV infection.

Antiproliferative and toxicogenomic effects of resveratrol in bladder cancer cells with different TP53 status.

The antitumor activity of resveratrol, a polyphenolic compound found mainly in grapes, has been studied in several types of cancer. In bladder cancer, its antiproliferative effects have already been demonstrated; however, its mechanism of action is not completely understood. The aim of this study was to evaluate resveratrol antitumor activity (12.5, 25, 50, 100, 150, 200, and 250 µM) and its possible mechanisms of action in bladder tumor cells with different TP53 gene status (RT4, grade 1, TP53 wild type; 5637-grade 2 and T24-grade 3, TP53 mutated). Cell proliferation, clonogenic survival, morphological changes, cell cycle progression, apoptosis rates, genotoxicity, global methylation, immunocytochemistry for p53 and PCNA and relative expression profiles of the AKT, mTOR, RASSF1A, HOXB3, SRC, PLK1, and DNMT1 were evaluated. Resveratrol decreased cell proliferation and induced DNA damage in all cell lines. Regarding the long-term effects, resveratrol reduced the number of colonies in all cell lines; however, TP53 wild type cells were more resistant. Increased rates of apoptosis were found in the TP53 wild type cells and this was accompanied by AKT, mTOR, and SRC downregulation. In addition, the resveratrol antiproliferative effects in wild type TP53 cells were accompanied by modulation of the DNMT1 gene. In the TP53 mutated cells, cell cycle arrest at S phase with PLK1 downregulation was observed. Additionally, there was modulation of the HOXB3/RASSF1A pathway and nuclear PCNA reduction in the highest-grade cells. In conclusion, resveratrol has antiproliferative activity in bladder tumor cells; however, the mechanisms of action are dependent on TP53 status. Environ. Mol. Mutagen., 60:740-751, 2019. © 2019 Wiley Periodicals, Inc.

Comparison of Capillary Electrophoresis, AGE, and PAGE for MTHFR Polymorphism Analysis in FFPE Cervical Samples.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism analysis could help in diagnosis, treatment, and prognosis of some pathologies, since it has been associated with the development of cardiovascular diseases, defects in neural tube formation, psychiatric disorders, and cancer. Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) is the most commonly used technique to analyze this polymorphism. Usually, RFLP products are evaluated by agarose gel electrophoresis (AGE) or polyacrylamide gel electrophoresis (PAGE). However, capillary electrophoresis (CE) may represent an alternative for MTHFR C677T polymorphism analysis by PCR-RFLP. Thus, the aim of this study was to compare CE, AGE, and PAGE to MTHFR C677T polymorphism analysis of Formalin-Fixed and Paraffin-Embedded (FFPE) cervical samples. METHODS: 150 biopsy blocks of cervical samples were analyzed. MTHFR polymorphism was evaluated by PCR-RFLP, and the products generated were analyzed by CE, AGE, and PAGE. Concordance between the methods was evaluated by rate agreement, Kappa coefficient, and McNemars's Test. RESULTS: Eight samples (5.4%) showed discordant results according to CE and PAGE or AGE. Differences of CC and CT frequencies were observed between CE and AGE (p=0.016): CC genotype varied from 68.0% to 72.7%, and CT varied from 23.3% to 27.3%. Besides, Kappa coefficient between CE and AGE, or PAGE was very high (κ>0.81). CONCLUSION: Capillary electrophoresis presented high agreement with PAGE and AGE, and may be an accurate, safe, and quick alternative method for MTHFR polymorphism analysis.

Fatores associados à qualidade de vida em mulheres no climatério / Factors associated with quality of life in climacteric women

Este trabalho foi composto por um estudo transversal, feito em Ouro Preto, Minas Gerais, Brasil, para avaliar os fatores associados à qualidade de vida em mulheres no climatério. Foram usados o questionário de qualidade de vida SF­36 e uma entrevista sobre dados socioeconômicos, demográficos, uso de medicamentos e hábitos de vida. A média de idade das 113 participantes foi de 53,3 ± 4,4 anos. Dessas, 49,6% conviviam com companheiro e 77,4% eram usuárias exclusivas do Sistema Único de Saúde. Foi observado que a renda de 54% delas era menor ou igual a um salário mínimo e 69% tinham baixa escolaridade. Na avaliação da associação entre as variáveis da entrevista e os oito domínios do questionário SF36, observou­se diferença significativa na qualidade de vida em relação a: (i) idade no domínio saúde mental; (ii) viver com ou sem companheiro nos domínios estado geral de saúde e limitação por aspecto emocional; (iii) presença de alguma doença crônica nos domínios estado geral de saúde e saúde mental; (iv) uso de medicamento contínuo no domínio saúde mental. Conclui­se que o aumento da idade, a presença de doenças crônicas e o uso de medicamentos agrava a qualidade de vida dessas mulheres. Entretanto, a convivência com parceiro modifica positivamente alguns domínios associados à qualidade de vida.

A cross­sectional study was conducted in Ouro Preto, Minas Gerais, Brazil to evaluate the factors associated with quality of life in climacteric women. It was used for this evaluation the questionnaire SF­36 of quality of life and one interview about socioeconomic, demographic, medicines used and living habits. The average age of the 113 participant was 53.3±4.4 years, 49.6% living with a partner and 77.4% using the public health system as the exclusive health insurance. It was observed that the income of 54% of them were less than or equal to the minimum wage and 69% had low education. Assessing the association between the variables of the interview and the eight domains of the SF­36, there was significant difference in the quality of life in relation to: (i) age, in the mental health domain; (ii) living with or without a partner, related to general health and limitation by emotional aspect; (iii) the presence of any chronic disease correlated to general health and mental health; (iv) continuous­use medication in the mental health domain. Concluding, the higher the age, in association with chronic diseases and medicines intake, the worse the quality of life of these women. Moreover, living with a partner positively modifies some areas associated with quality of life.

A qualidade, o custo e a dispensação de sinvastatina cápsulas em farmácias magistrais / Quality, cost and dispensing of simvastatin capsules at compounding pharmacies

Com base na RDC/ANVISA 67/2007, avaliou-se o serviço prestado na dispensação de sinvastatina cápsulas em farmácias magistrais. Vinte e quatro (16%) das 150 farmácias magistrais foram aleatoriamente selecionadas nas regiões de Belo Horizonte-MG, observando a distribuição geográfica. A qualidade do produto, os aspectos da dispensação e o custo foram considerados em estudos de correlação. Os resultados foram submetidos a análises estatísticas descritivas e inferenciais. Em apenas 25% destas farmácias, o fax da prescrição foi solicitado. Todos os pedidos foram entregues no prazo, porém sem comprovação da dispensação. Em uma das entregas, o medicamento era o incorreto. Seis (25%) dos produtos apresentaram rotulagem incompleta (ausência de posologia 16,3% ou de identificação do médico/paciente 8,7%). Apenas 11 (45,8%) das amostras apresentaram qualidade satisfatória. O custo do medicamento manipulado variou entre R$20,40 e R$44,00 com valor médio R$31,18. Não se observou associação entre a qualidade do medicamento e os aspectos do custo, prazo de entrega e localização geográfica. Verifica-se que a maioria das farmácias magistrais ainda precisa adequar-se à legislação para garantir à população uma assistência farmacêutica de qualidade.

The aim of the present study was to evaluate the dispensing of simvastatin capsules at compounding pharmacies in light of Brazilian public health regulations (RDC/ANVISA 67/2007). Twenty-four (16%) out of 150 compounding pharmacies were randomly selected in the city of Belo Horizonte based on geographic distribution among the different districts. Dispensing services, quality and cost were considered in the correlation studies. The results were submitted to descriptive and inferential statistical analyses. The prescription fax was requested in only 25% of the pharmacies. All orders were delivered on time, but without proof of dispensing. The medication was incorrect in one of the deliveries. Six (25%) product labels were incomplete (16.3% for absence of drug regimen; 8.7% for absence of physician/patient identification). Only 11 (45.8%) of the samples exhibited satisfactory quality. The cost of the compounded drug ranged from R$20.40 to R$44.00 (mean: R$31.18). No association was found between drug quality and cost, delivery or geographic location. In conclusion, the majority of compounding pharmacies need to make adjustments in order to meet the requirements of Brazilian legislation and ensure the quality of pharmaceutical services offered to the population.

Morphometric evaluation and nonclassical criteria for the diagnosis of HPV infection and cytological atypia in cervical samples.

Herein, we evaluated cervical samples from normal tissue or HPV-infected tissue, to determine if the relative nuclear/cytoplasmic ratio (NA/CA) and the presence of nonclassical cytological criteria are a novel cytological criterion for the diagnosis of HPV. Significantly, larger NA/CA ratios were found for the HPV-ATYPIA+ and HPV+ATYPIA+ groups compared with HPV-ATYPIA- group, regardless of collection method. For the samples collected with a spatula, only three samples from the HPV-ATIPIA- group showed four or more nonclassical parameters (i.e., were positive), while a larger number of the samples in the HPV-ATYPIA+, HPV+ATYPIA-, and HPV+ATYPIA+ groups were positive (13, 4, and 13 samples, respectively). Among those collected with a brush, no sample showed four or more nonclassical criteria in the HPV-ATYPIA- group, while a number of samples were positive in the HPV-ATYPIA+, HPV+ATYPIA-, and HPV+ATYPIA+ groups (4, 3, and 4 samples, respectively). HPV infection was associated with significant morphometrical changes; no increase in the NA/CA ratio was found in the HPV+ATYPIA- samples, compared with the HPV-ATIPIA- samples collected with either a spatula or a brush. In conclusion, by including nonclassical cytological criteria into the patient diagnosis, we were able to reduce the number of false negative and false positive HPV diagnoses made using conventional cytology alone.