GUSTAVO ARANTES ROSA MACIEL
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
11 resultados
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- Association of glucocorticoid receptor polymorphisms with clinical and metabolic profiles in polycystic ovary syndrome(2014) MACIEL, Gustavo A.Rosa; MOREIRA, Ricardo P.P.; BUGANO, Diogo D.G.; HAYASHIDA, Sylvia A.Y.; MARCONDES, Jose A.M.; GOMES, Larissa G.; MENDONCA, Berenice B.; BACHEGA, Tania A.S.S.; BARACAT, Edmund C.OBJECTIVES: We aimed to investigate whether glucocorticoid receptor gene polymorphisms are associated with clinical and metabolic profiles in patients with polycystic ovary syndrome. Polycystic ovary syndrome is a complex endocrine disease that affects 5-8% of women and may be associated with metabolic syndrome, which is a risk factor for cardiovascular disease. Cortisol action and dysregulation account for metabolic syndrome development in the general population. As glucocorticoid receptor gene (NR3C1) polymorphisms regulate cortisol sensitivity, we hypothesized that variants of this gene may be involved in the adverse metabolic profiles of patients with polycystic ovary syndrome. METHOD: Clinical, metabolic and hormonal profiles were evaluated in 97 patients with polycystic ovary syndrome who were diagnosed according to the Rotterdam criteria. The alleles of the glucocorticoid gene were genotyped. Association analyses were performed using the appropriate statistical tests. RESULTS: Obesity and metabolic syndrome were observed in 42.3% and 26.8% of patients, respectively. Body mass index was positively correlated with blood pressure, triglyceride, LDL-c, total cholesterol, glucose and insulin levels as well as HOMA-IR values and inversely correlated with HDL-c and SHBG levels. The BclI and A3669G variants were found in 24.7% and 13.4% of alleles, respectively. BclI carriers presented a lower frequency of insulin resistance compared with wild-type subjects. CONCLUSION: The BclI variant is associated with a lower frequency of insulin resistance in women with polycystic ovary syndrome. Glucocorticoid gene polymorphism screening during treatment of the syndrome may be useful for identifying subgroups of at-risk patients who would benefit the most from personalized treatment.
bookPart Sarcoma uterino(2014) CARVALHO, Kátia Candido; GARCIA, Natália; JúNIOR, José Maria Soares; MACIEL, Gustavo Arantes Rosa; BARACAT, Edmund ChadaconferenceObject The Influence of Insulin on the Degree of Hirsutism of Patients with Polycystic Ovary Syndrome(2014) HAYASHIDA, Sylvia Yamashita; SOARES JR., Jose Maria; MIRALDI, Priscila Dias; MARCONDES, Jose Antonio; BARCELLOS, Cristiano Roberto; ANZAI, Alvaro; MACIEL, Gustavo Arantes R.; BARACAT, Edmund ChadabookPart Esteroides sexuais: androgênios(2014) SIMõES, Ricardo dos Santos; DAMáSIO, Lia Cruz Vaz da Costa; MACIEL, Gustavo Arantes Rosa; JúNIOR, José Maria Soares; BARACAT, Edmund Chada- Trp28Arg/Ile35Thr LHB gene variants are associated with elevated testosterone levels in women with polycystic ovary syndrome(2014) BATISTA, Mariani Carla Prudente; DUARTE, Eliane de Fatima; BORBA, Michele Delarmelina dos Reis; ZINGLER, Emilie; MANGUSSI-GOMES, Joao; SANTOS, Beatriz Taynara Araujo dos; MORAES, Olivia Laquis de; HAYASHIDA, Sylvia Asaka Yamashita; BARACAT, Edmund C.; NEVES, Francisco de Assis da Rocha; MACIEL, Gustavo Arantes Rosa; BACHEGA, Tania Aparecida Sartori Sanchez; BARRA, Gustavo Barcelos; LOFRANO-PORTO, AdrianaIntroduction: Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder, of multifactorial etiology, which affects 6-10% of women of reproductive age. It is considered the leading cause of anovulatory infertility, menstrual disorders and hyperandrogenism in this population. The genetic basis of PCOS is still largely unknown despite significant family clustering; determining its mode of inheritance is particularly difficult given the heterogenic presentation of the disease. Materials and methods: 130 Brazilian women, aged 14-42 years, who met the 2003 Rotterdam criteria for PCOS diagnosis, were included, and 96 healthy women constituted the control group. Presence of hirsutism was classified using the modified Ferriman-Gallwey score (F-G score) as absent (<= 7), mild (8-14), and severe (>= 15). Blood levels of luteinizing hormone (LH), total testosterone (TT), dehydroepiandrosterone sulfate (DHEA-S) and androstenedione were determined. The coding region of the luteinizing hormone beta-subunit (LHB) gene was amplified and sequenced. Differences in allelic and genotypic frequency distribution of each polymorphism across controls and cases were estimated by the Mantel-Haenszel chi-square or Fisher's exact test (p < 0.05), and the probability of an association between the detection of a polymorphism and presence of a diagnosis of PCOS, by logistic regression. Result(s): Sequencing detected 8 polymorphisms in the LHB gene coding region. Two polymorphisms in linkage disequilibrium were significantly more prevalent in the presence of hyperandrogenemia: rsl 800447/rs34349826 (Trp28Arg/Ile35Thr) (p = 0.02). Conclusion(s): In this series, a modulatory effect of LHB polymorphisms on hyperandrogenemia phenotype of PCOS was observed; however, this finding needs to be replicated in other populations.
bookPart Aspectos moleculares da síndrome dos ovários policísticos(2014) MACIEL, Gustavo Arantes Rosa; BARACAT, Maria Cândida Pinheiro; MARCONDES, Rodrigo Rodrigues; JúNIOR, José Maria Soares; BARACAT, Edmund Chada- Evaluation of macroprolactinemia in 259 women under investigation for polycystic ovary syndrome(2014) HAYASHIDA, Sylvia A. Y.; MARCONDES, Jose A. M.; SOARES JR., Jose M.; ROCHA, Michelle P.; BARCELLOS, Cristiano R. G.; KOBAYASHI, Nelly K. A.; BARACAT, Edmund C.; MACIEL, Gustavo A. R.
- Females transplanted with ovaries subjected to hypoxic preconditioning show impair of ovarian function(2014) DAMOUS, Luciana Lamarao; NAKAMUTA, Juliana Sanajotti; SOARES- JR., Jose Maria; MACIEL, Gustavo Arantes Rosa; SIMOES, Ricardo dos Santos; MONTERO, Edna Frasson de Souza; KRIEGER, Jose Eduardo; BARACAT, Edmund ChadaBackground: Cryopreservation of the ovarian tissue has shown promising results. However, there remain controversial issues such as the short half-life of grafts. In this aspect, there are some evidences that preconditioning the ovarian tissue before transplantation is beneficial. Objective: To determine the effect of hypoxic preconditioning in vitro on ovarian tissue prior to transplantation. Methods: Eighteen female adult Wistar rats, were sorted into three experimental groups. Ovaries were maintained in DMEM low glucose serum free at 37 degrees C with 5% CO2, at atmospheric oxigen concentration (normoxia) or 1% O-2 (hypoxia) for 16 hours. Oxigen concentration was determined by injection of nitrogen in the incubator. Animals submitted to ovarian transplantation immediately after oophorectomy were the Control Group (C). After this, the ovaries were implanted in the retroperitoneum with nonabsorbable suture and animals evaluated for thirty days after transplantation. Beginning on postoperative (PO) day 11, a daily collection of vaginal smear was carried out. Analyses comprised morphological, morphometric (counting ovarian follicles and corpora lutea) and immunohistochemistry for cleaved caspase-3 (apoptosis). Results: In normoxia and control groups all animals recovered their estrous cycles, while in the hypoxia group, two animals did not ovulate but, among those which did, resumption took longer than in the other groups (p < 0.05). The number of ovarian follicles and corpora lutea decreased significantly in the hypoxia group when compared to the other two groups (p < 0.001) and apoptosis was increased in the few ovarian follicles which remained viable (p < 0.001). Conclusion: The hypoxic preconditioning in vitro was not beneficial to the graft and worsened their viability, compromising its functionality or delaying the return of this.
conferenceObject Transcriptional Expression of Genes Related to Histone Modification in the Hypothalamus of Female Rats Submitted to Neonatal Exposure to Sex Steroids(2014) MARCONDES, Rodrigo Rodrigues; CARVALHO, Katia Candido; GARCIA, Natalia; DUARTE, Daniele Coelho; SOARES JR., Jose Maria; COSTA, Leonardo Tomiatti; AMARAL, Vinicius Cestari; GIANNOCCO, Gisele; BARACAT, Edmund Chada; MACIEL, Gustavo Arantes R.- Triple-negative and luminal A breast tumors: differential expression of miR-18a-5p, miR-17-5p, and miR-20a-5p(2014) CALVANO FILHO, Carlos Marino Cabral; CALVANO-MENDES, Daniele Carvalho; CARVALHO, Katia Candido; MACIEL, Gustavo Arantes; RICCI, Marcos Desiderio; TORRES, Ana Paula; FILASSI, Jose Roberto; BARACAT, Edmund ChadaNew concepts in epigenetics, microRNAs, and gene expression analysis have significantly enhanced knowledge of cancer pathogenesis over the last decade. MicroRNAs (miRNAs) are a class of non-coding RNAs that regulate gene expression by base pairing with target messenger RNAs (mRNAs), resulting in the repression of translation or the degradation of mRNA. To compare the carcinogenic process in tumors with different prognoses, we used real-time RT-PCR to evaluate the miRNA expression profiles of 24 triple-negative breast invasive ductal carcinoma, 20 luminal A breast invasive ductal carcinoma, and 13 normal breast parenchyma controls. We extracted total RNA from tissues fixed in formol and embedded in paraffin (FFPE). Results revealed the upregulation of miR-96-5p (9.35-fold; p = 0.000115), miR-182-5p (7.75-fold; p = 0.000033), miR-7-5p (6.71-fold; p = 0.015626), and miR-21-5p (6.10-fold; p = 0.000000) in tumors group. In addition, the expression of miR-125b-5p (4.49-fold; p = 0.000000) and miR-205-5p (4.36-fold; p = 0.006098) was downregulated. When the expression profiles of triple-negative and luminal A tumors were compared, there was enhanced expression of miR-17-5p (4.27-fold; p = 0.000664), miR-18a-5p (9.68-fold; p = 0.000545), and miR-20a-5 (4.07-fold; p = 0.001487) in the triple-negative tumors compared with luminal A. These data suggest that there is a similar regulation of certain miRNAs in triple-negative and luminal A tumors. However, it is possible that differences in the expression of miR-17-92 cluster will explain the phenotypic differences between these molecular tumor subtypes.