National Institute of Hormones and Womens Health

Porto Alegre, Brazil

National Institute of Hormones and Womens Health

Porto Alegre, Brazil
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Santos B.R.,Federal University of Rio Grande do Sul | Mascarenhas L.P.G.,Federal University of Paraná | Boguszewski M.C.S.,National Institute of Hormones and Womens Health | Boguszewski M.C.S.,Federal University of Paraná | And 3 more authors.
Hormone Research in Paediatrics | Year: 2013

Background/Aims: Vitamin D deficiency has been recognized as a worldwide epidemic affecting several pediatric and adolescent populations. We determined the genotype and haplotype distribution of the rs4588 and rs7041 polymorphisms of the GC gene encoding vitamin D-binding protein (DBP) and investigated the associations between these gene variants and their haplotypes with 25-hydroxyvitamin D [25(OH)D] levels in girls from South Brazil. Methods: Cross-sectional study including 198 apparently healthy girls aged 10-18 years. Plasma levels of 25(OH)D were assessed by radioimmunoassay. Participants were genotyped for rs4588 and rs7041 by real-time PCR, with allelic discrimination assays. Results: Mean chronological age and BMI percentile were 13.17 ± 1.74 years and 57.81 ± 29.03, respectively. Sufficient circulating 25(OH)D levels (≥30 ng/ml) were found in 9.1% of the overall group, insufficient levels (20-29.9 ng/ml) in 59.6%, and deficient levels (<20 ng/ml) in 31.3%. The AA genotype of rs4588, TT genotype of rs7041 and CT-AT/AT-AT (GC 1f-2/2-2) diplotypes were significantly associated with lower 25(OH)D levels, even after adjustment for age and season at the time of blood collection. Conclusions: The GC gene genotype may be related to the susceptibility to low 25(OH)D levels in female children and adolescents. Copyright © 2013 S. Karger AG, Basel.


Santos B.R.,Federal University of Rio Grande do Sul | Mascarenhas L.P.G.,Federal University of Paraná | Satler F.,Federal University of Rio Grande do Sul | Boguszewski M.C.S.,Federal University of Paraná | And 3 more authors.
BMC Pediatrics | Year: 2012

Background: Vitamin D deficiency has been associated with a multitude of disorders including diabetes, defective insulin secretion as well as rickets and poor bone health. Vitamin D is also a concern during childhood and adolescence and has been reported in girls from South Brazil. We determined the prevalence of vitamin D deficiency in girls from South Brazil and investigated whether the genotypic distribution of the BsmI, ApaI and TaqI polymorphisms of the VDR gene and their haplotypes were associated with vitamin D levels.Methods: Cross-sectional study including 234 apparently healthy girls aged 7 to 18 years. Height and weight were measured for calculation of body mass index (BMI) percentiles for age. Plasma levels of 25-hydroxyvitamin D [25(OH)D] were assessed. Participants were genotyped for ApaI (rs7975232), TaqI (rs731236), and BsmI (rs1544410) SNPs.Results: The median and interquartile range (25-75%) of BMI percentile was 62.0 (33.3 - 84.9). The frequency of overweight/obesity was 24.9%. Circulating levels of 25(OH)D (≥ 30 ng/mL) were adequate in 9.4%; insufficient in 54.3% (20-29 ng/mL); and deficient in 36.3% (< 20 ng/mL). Genotype frequencies were GG = 47.0%, GA = 41.5%, and AA = 11.5% for BsmI; GG = 16.7%, GT = 52.6%, and TT = 30.8% for ApaI; TT = 46.2%, TC = 44.9% and CC = 9.0% for TaqI. Genotypes with no gene variance (ancestral wild genotype) of BsmI (GG vs. GA + AA, two-tailed Student's t-test p < 0.001), ApaI (GG vs. GT + TT, two-tailed Student's t-test p = 0.031) and TaqI (TT vs. TC + CC, two-tailed Student's t-test p = 0.005) SNPs and the GGT haplotype (two-tailed Student's t-test p = 0.036) were significantly associated with lower 25(OH)D levels.Conclusions: 25-hydroxyvitamin D deficiency and insufficiency were highly prevalent in this sample. The BsmI, ApaI and TaqI wild variants of the VDR gene, as well as the GGT haplotype, were associated with lower vitamin D levels, suggesting that VDR gene polymorphisms could be linked to higher susceptibility to vitamin D deficiency in a sub-population of children and adolescents. © 2012 Santos et al.; licensee BioMed Central Ltd.


Vieira C.S.,University of Sao Paulo | Vieira C.S.,National Institute of Hormones and Womens Health | Bahamondes M.V.,National Institute of Hormones and Womens Health | Bahamondes M.V.,University of Campinas | And 11 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2014

Objective:: Data on the interaction between the etonogestrel (ENG) implant and antiretroviral therapy are lacking. We evaluated the effect of 2 highly active antiretroviral therapy (HAART) regimens (1 including efavirenz and the other ritonavir-boosted lopinavir) on the pharmacokinetic (PK) parameters of an ENG-releasing implant in HIV-positive women. Design:: Prospective nonrandomized PK study. Methods:: Forty-five HIV-positive women who desired to use ENG implants were included: 15 had received zidovudine/lamivudine + lopinavir/ritonavir for ≥3 months (LPV/r-based HAART group), 15 had received zidovudine/lamivudine + efavirenz for ≥3 months (EFV-based HAART group), and 15 had not received HAART (non-HAART group). PK parameters were measured using ultra-performance liquid chromatography-mass spectrometry at baseline and 2, 4, 6, 8, 10, 12, 16, 20, and 24 weeks after implant placement. Results:: The EFV-based HAART regimen was associated with a reduction in the bioavailability of ENG, which showed decreases of 63.4%, 53.7%, and 70% in the area under the curve (AUC), maximum concentration (Cmax), and minimum concentration (Cmin) of ENG, respectively, compared with the non-HAART group. The LPV/r-based HAART regimen was associated with an increase in ENG bioavailability, which showed 52%, 60.6%, and 33.8% increases in the ENG AUC, Cmax, and Cmin, respectively, compared with the non-HAART group. Conclusions:: The coadministration of EFV decreased the bioavailability of ENG released from the implant, which could impair contraceptive efficacy. However, the coadministration of LPV/r increased the bioavailability of ENG released from the implant, which suggests that this antiretroviral combination does not impair the ENG implant efficacy. Copyright © 2014 by Lippincott Williams & Wilkins.


Colpani V.,Hospital Of Clinicas Of Porto Alegre | Oppermann K.,University Of Passo Fundo | Oppermann K.,National Institute of Hormones and Womens Health | Spritzer P.M.,Hospital Of Clinicas Of Porto Alegre | And 2 more authors.
Menopause | Year: 2013

Objective: Menopause is associated with an increased risk of cardiovascular disease. Habitual physical activity, defined as any form of body movement with energy expenditure above resting levels, may improve health parameters. We assessed the level of habitual physical activity and its effect on anthropometric measures and cardiovascular risk factors in a cohort of premenopausal, perimenopausal, and postmenopausal women. Methods: This cross-sectional study is nested on a longitudinal population-based study that was begun in 1995 in the city of Passo Fundo, Brazil. For the present analysis, 292 women were included. Anthropometric and metabolic profile was evaluated. Habitual physical activity was assessed by a digital pedometer for 7 days, and participants were stratified into active and inactive (≥6,000 and <6,000 steps/day, respectively). Results: The mean (SD) age was 57.1 (5.4) years. The average number of steps per day for the total sample was 5,250.7 (3,372.9): 3,472.4 (1,570.2) in the inactive group (61.8%) and 9,055.9 (3,033.4) in the active group (31.9%). A negative and statistically significant correlation was found between physical activity and smoking (P = -0.019), body mass index (P = -0.006), waist circumference (P = -0.013), and waist-to-hip ratio of 0.85 or higher (P = -0.043). Inactive women presented a higher risk of overweight/obesity (odds ratio [OR], 2.1; 95% CI, 1.233-3.622; P = 0.006) and waist circumference larger than 88 cm (OR, 1.7; 95% CI, 1.054-2.942; P = 0.03), even after adjustment for age, menopause status, smoking, and hormone therapy. Inactive women also had a higher risk of diabetes mellitus (OR, 2.7; 95% CI, 1.233-6.295; P = 0.014) and metabolic syndrome (OR, 2.5, 95% CI, 1.443-4.294; P = 0.001). Conclusions: Habitual physical activity, specifically walking 6,000 or more steps daily, was associated with a decreased risk of cardiovascular disease and diabetes in middle-aged women, independently of menopause status. © 2012 by The North American Menopause Society.


Newsholme P.,Curtin University Australia | De Bittencourt P.I.H.,Federal University of Rio Grande do Sul | De Bittencourt P.I.H.,National Institute of Hormones and Womens Health
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2014

Obesity is a chronic inflammatory disease in which the physiological resolution of inflammation is attenuated, leading to low-grade inflammation throughout the body. However, the heat shock response, which is a key component of the physiological response to resolve inflammation, is seriously hampered in adipose tissue and other metabolic organs (e.g. skeletal muscle, liver, pancreatic β-cells) in metabolic diseases. In this review, we hypothesize that adipocyte metabolic stress triggers the onset of fat cell senescence, and companion senescence-Associated secretory phenotype (SASP), and that such a scenario is responsible for attenuating the resolution of inflammation. RECENT FINDINGS: We shall discuss the role of the heat shock response in the context of the resolution of inflammation and the relevance of heat shock response blockade in chronic inflammatory diseases. Sirtuin-1 is responsible for the induction of heat shock transcription factor-1 mRNA expression and for the stabilization of heat shock transcription factor-1 in a high-profile activity state. However, adipose tissue-emanated SASP depress sirtuin-1 expression, leading adipocytes to a perpetual state of unresolved inflammation, due to a dampening of the heat shock response. SUMMARY: The advance of inflammasome-mediated SASP from adipose to other tissues promotes cellular senescence in many other cells of the organism, aggravating obesity-dependent chronic inflammation. Inducers of heat shock response (e.g. heat shock itself, physical exercise and calorie restriction) may efficiently interrupt this vicious cycle and are envisaged as the best and also the most economical treatment for obesity-related chronic diseases.Copyright © Lippincott Williams &Wilkins.


Lecke S.B.,Hospital Of Clinicas Of Porto Alegre | Mattei F.,Hospital Of Clinicas Of Porto Alegre | Mattei F.,Federal University of Rio Grande do Sul | Morsch D.M.,Hospital Of Clinicas Of Porto Alegre | And 3 more authors.
Fertility and Sterility | Year: 2011

Objective: To determine leptin and adiponectin serum levels and gene expression in subcutaneous adipose tissue from women with polycystic ovary syndrome (PCOS) and nonhirsute, ovulatory women; and leptin/adiponectin (L/A) ratio. Design: Case-control study. Setting: University hospital gynecologic endocrinology unit. Patient(s): Thirty-one women with PCOS and 57 controls. Intervention(s): Anthropometric, hormonal, and metabolic assessment; subcutaneous adipose tissue biopsy. Main Outcome Measure(s): Leptin and adiponectin serum levels, L/A ratio, controlled by age, and gene expression in women with PCOS and controls, stratified by body mass index and variables associated with androgen excess and insulin resistance. Result(s): Serum leptin was higher in overweight/obese patients with PCOS than in all normal-weight control women. Adiponectin levels were similar in all subgroups. The L/A ratio was lower in normal-weight controls (1.80; range 0.94-3.72) than in overweight/obese controls (5.27; range 2.66-13.58) and patients with PCOS (7.73; range 3.81-15.04). Subcutaneous leptin messenger RNA was higher in overweight/obese women with PCOS than in normal-weight controls (2.316 [range 1.987-2.580] vs. 1.687 [range 1.518-2.212]). Adiponectin gene expression was similar in all groups. Positive correlations were found between serum and messenger RNA levels for both leptin and adiponectin. On multiple regression analysis, percentage of body fat contributed significantly to L/A ratio in PCOS, independently of body mass index and free androgen index. Conclusion(s): In PCOS, altered adipocyte secretion seems to relate to adiposity rather than to androgen excess. © 2011 by American Society for Reproductive Medicine.


Graff S.K.,Hospital Of Clinicas Of Porto Alegre Hcpa | Mario F.M.,Hospital Of Clinicas Of Porto Alegre Hcpa | Alves B.C.,Hospital Of Clinicas Of Porto Alegre Hcpa | Spritzer P.M.,Hospital Of Clinicas Of Porto Alegre Hcpa | And 2 more authors.
Fertility and Sterility | Year: 2013

Objective To compare glycemic index (GI) in the usual diet of polycystic ovary syndrome (PCOS) and control women and to investigate whether dietary GI is associated with body composition and anthropometric and metabolic variables across PCOS phenotypes. Design Cross-sectional study. Setting University hospital outpatient clinic. Patient(s) Sixty-one women with PCOS and 44 nonhirsute women with ovulatory cycles. Intervention(s) Metabolic work-up, biochemical and hormonal assays, assessment of body composition and rest metabolic rate, physical activity (pedometer), and food consumption (food frequency questionnaire). Main outcome measure(s) GI, glycemic load, dietary intake, and hormone and metabolic profile in PCOS versus control and in PCOS women stratified by tertiles of GI and PCOS phenotype. Result(s) Mean age was 23.7 ± 6.3 years. Participants with PCOS had higher body fat percentage, fasting insulin, insulin resistance, lipid accumulation product, and androgen levels compared with control women. PCOS and control women in the highest tertile of GI had higher body mass index and waist circumference than those in the lowest tertile. Dietary GI was higher in the classic PCOS group. Obesity and this more severe PCOS phenotype explained 28.3% of variance in dietary GI. Conclusion(s) Dietary GI is increased in the classic PCOS phenotype and associated with a less favorable anthropometric and metabolic profile. Obesity and classic PCOS phenotype are age-independent predictors of higher dietary GI. Copyright © 2013 American Society for Reproductive Medicine, Published by Elsevier Inc.


Cangeri Di Naso F.,Federal University of Rio Grande do Sul | Rosa Porto R.,Federal University of Rio Grande do Sul | Rosa Porto R.,National Institute of Hormones and Womens Health | Sarubbi Fillmann H.,Federal University of Rio Grande do Sul | And 11 more authors.
Obesity | Year: 2015

Objectives To evaluate whether reduced activity of the anti-inflammatory HSP70 pathway correlates with nonalcoholic fatty liver disease (NAFLD) progression and with markers of oxidative stress because obesity activates inflammatory JNKs, whereas HSP70 exerts the opposite effect. Methods Adult obese patients (N-=-95) undergoing bariatric surgery were divided into steatosis (ST), steatohepatitis (SH), and fibrosis (SH+F) groups. The levels of HSP70, its major transcription factor, HSF1, and JNKs were assessed by immunoblotting hepatic and visceral adipose tissue; data were confirmed by immunohistochemistry. Plasma biochemistry (lipids, HbA1c, HOMA, hepatic enzymes, and redox markers) was also evaluated. Results In both liver and adipose tissue, decreased HSP70 levels, paralleled by similar reductions in HSF1 and reduced plasma antioxidant enzyme activities, correlated with insulin resistance and with NAFLD progression (expression levels were as follows: ST->-SH->-SH-+-F). The immunohistochemistry results suggested Kupffer cells as a site of HSP70 inhibition. Conversely, JNK1 content and phosphorylation increased. Conclusions Decreased HSF1 levels in the liver and fat of obese patients correlated with impairment of HSP70 in an NAFLD stage-dependent manner. This impairment may affect HSP70-dependent anti-inflammation, with consequent oxidative stress and insulin resistance in advanced stages of NAFLD. Possible causal effects of fat cell senescence are discussed. © 2014 The Obesity Society.


Ciarmela P.,Marche Polytechnic University | Islam M.S.,Marche Polytechnic University | Reis F.M.,University of Minas Gerais | Reis F.M.,National Institute of Hormones and Womens Health | And 5 more authors.
Human Reproduction Update | Year: 2011

Background: Growth factors are proteins secreted by a number of cell types that are capable of modulating cellular growth, proliferation and cellular differentiation. It is well accepted that uterine cellular events such as proliferation and differentiation are regulated by sex steroids and their actions in target tissues are mediated by local production of growth factors acting through paracrine and/or autocrine mechanisms. Myometrial mass is ultimately modified in pregnancy as well as in tumour conditions such as leiomyoma and leiomyosarcoma. Leiomyomas, also known as fibroids, are benign tumours of the uterus, considered to be one of the most frequent causes of infertility in reproductive years in women. Methods: For this review, we searched the database MEDLINE and Google Scholar for articles with content related to growth factors acting on myometrium; the findings are hereby reviewed and discussed. RESULTS: Different growth factors such as epidermal growth factor (EGF), transforming growth factor-α (TGF-α), heparin-binding EGF (HB-EGF), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF) and TGF-β perform actions in myometrium and in leiomyomas. In addition to these growth factors, activin and myostatin have been recently identified in myometrium and leiomyoma. Conclusions: Growth factors play an important role in the mechanisms involved in myometrial patho-physiology. © The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.


Reis F.M.,Federal University of Minas Gerais | Reis F.M.,National Institute of Hormones and Womens Health | Bouissou D.R.,Federal University of Minas Gerais | Pereira V.M.,Federal University of Minas Gerais | And 4 more authors.
Fertility and Sterility | Year: 2011

Objective: To investigate whether angiotensin (Ang)-(1-7), its receptor Mas, and angiotensin-converting enzyme type 2 (ACE2) are present in human ovary. Design: Cross-sectional study. Setting: Academic hospital. Patient(s): Twelve reproductive-age women and five postmenopausal women undergoing oophorectomy for nonovarian diseases and seven women having controlled ovarian hyperstimulation for IVF. Intervention(s): Ovarian tissue was obtained from the reproductive-age women and postmenopausal women undergoing oophorectomy for nonovarian diseases. Follicular fluid (FF) samples were obtained from the women having controlled ovarian hyperstimulation for IVF. Main Outcome Measure(s): Localization of Ang-(1-7) and Mas by immunohistochemistry; measurement of Ang-(1-7) in ovarian FF by RIA; detection of messenger RNAs encoding Mas and ACE2 with use of real-time polymerase chain reaction; assessment of 125I-labeled Ang-(1-7) binding to ovarian sections with use of autoradiographic binding assay. Result(s): Angiotensin-(1-7) and the receptor Mas were localized to primordial, primary, secondary, and antral follicles, stroma, and corpora lutea of reproductive-age ovaries. Postmenopausal women expressed both the peptide and its receptor in the ovarian stroma. Angiotensin-(1-7) was detectable in FF (mean ± SE: 191 ± 54 pg/mL). Both Mas and ACE2 messenger RNAs were expressed in ovarian tissue, as revealed by real-time polymerase chain reaction, and ovarian binding sites for 125I-labeled Ang-(1-7) were identified by autoradiography. Conclusion(s): Angiotensin-(1-7), its receptor Mas, and ACE2 are expressed in the human ovary. The peptide is present in several ovarian compartments and can be quantified in FF. © 2011 American Society for Reproductive Medicine, Published by Elsevier Inc.

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