Association between polymorphism SLC6A3 3 UTR VNTR and response to treatment of nicotine dependence

Objective: To evaluate the association between response to treatment of nicotine dependence with bupropion and the presence of the polymorphism SLC6A3 3 UTR VNTR, in the gene that codifies the dopaminergic transporter. Method: A hundred patients were treated in the Nicotine Dependence Outpatient Clinic of the Institute of Psychiatry, University of São Paulo Medical School. All patients were male, diagnosed as nicotine dependents and had no other diseases. All received bupropion until 300 mg a day for 12 weeks, combined with cognitive-behavioral group therapy. The Fagerström Scale was applied at the beginning and at the end of treatment. Cigarette cessation was evaluated in the last week of treatment and one month later. Patients had 10 ml blood extracted and genotiped for SLC6A3 3 UTR VNTR polymorphism. Results: There was no association between cigarettes cessation and the presence of polymorphism. Conclusion: More studies are needed to assess whether the presence of polymorphism SLC6A3 3 UTR VNTR could be associated with a better response to treatment of nicotine dependence.Objetivo: Avaliar a associação entre a resposta ao tratamento da dependência de nicotina com bupropiona e a presença do polimorfismo SLC6A3 3 UTR VNTR, localizado no gene que codifica o transportador dopaminérgico. Método: Foram acompanhados no Ambulatório de Tabagismo do Instituto de Psiquiatria da Faculdade de Medicina da USP 100 pacientes do sexo masculino com diagnóstico de dependência de nicotina, sem outras patologias. Todos receberam bupropiona até 300 mg ao dia por 12 semanas, associada à terapia cognitivo-comportamental em grupo. A Escala de Fagerström foi aplicada no início e no final do tratamento, e avaliou-se a parada do uso de cigarros na última semana de tratamento e um mês após. Os pacientes tiveram 10 ml de sangue colhidos e genotipados para a existência do polimorfismo SLC6A3 3 UTR VNTR. Resultados: Não foi encontrada associação entre cessação do uso de cigarro e presença do polimorfismo. Conclusão: São necessários mais estudos para avaliar se a presença do polimorfismo SLC6A3 3 UTR VNTR estaria relacionada à melhor resposta ao tratamento da dependência de nicotina.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade de São Paulo Faculdade de Medicina Instituto de PsiquiatriaUniversidade Federal de São Paulo (UNIFESP) Faculdade de Medicina Departamento de GinecologiaUSP Faculdade de Medicina Departamento de PsiquiatriaUNIFESP, Faculdade de Medicina Depto. de GinecologiaSciEL

O espectro das falências ovarianas ligadas ao cromossomo X

Clinically ovarian failure is presented by primary or secondary amenorrhea and high levels of pituitary gonadotropins mainly FSH. Monossomy or X-chromosome rearrangements are among a variable number of suggested etiopathogenic factors of ovarian failure in young women. Besides in Turner syndrome (X-monossomy or mosaicism), where the short stature and sexual infantilism point to the diagnosis, X-chromosome long arm (Xq) rearrangements, or genetic mutations of genes mapped at this segment are related with ovarian failure presented in prepubertal girls and in young women without other clinical signal. The present revision focuses these chromosomal abnormalities, some of them disclosed by conventional cytogenetic methods and other only disclosed by means of molecular biological toolsA falência ovariana manifesta-se clinicamente por amenorréia primária ou secundária, e do ponto de vista hormonal caracteriza-se pelos níveis elevados de gonadotrofinas hipofisárias, principalmente FSH, cuja etiologia pode ser atribuída a varias causas, como redução numérica ou rearranjos do cromossomo X, entre outras. Além da síndrome de Turner (monossomia do cromossomo X, com ou sem mosaicismo cromossômico), cujo principal estigma - a baixa estatura - e o infantilismo sexual apontam o diagnóstico, rearranjos do braço longo de X (Xq), ou mutações instaladas em genes mapeados neste cromossomo estão relacionados com a falência ovariana em meninas pré-púberes e em mulheres adultas jovens, sem outros sinais clínicos. Neste cromossomo, nos segmentos da falência ovariana precoce (FOP1 e FOP2) situam-se genes já relacionados à insuficiência ovariana de instalação precoce. Esta revisão trata destas alterações, algumas detectadas pelas técnicas citogenéticas convencionais, outras somente por meio de recursos de biologia molecularUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de Endocrinologia e MetabologiaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de GinecologiaUNIFESP, EPM, Disciplina de Endocrinologia e MetabologiaUNIFESP, EPM, Depto. de GinecologiaSciEL

Endometrial biopsy with uretral plastic No. 12 sonde

The authors demonstrate technique for obtaining endometrial fragments in 25 patients sent to Gynecological Cancer Preventive Service of the Arnaldo Vieira de Carvalho Cancer Institute, during the period of September 1991 through January 1992, presenting abnormal uterine hemorrhage. Technique consists in vacuum aspiration with the support of a No. 12 uretral sonde , provided with one lateral opening only. Correlation with curettage was positive in 88% of the patients; biopsy with sonde did not result in confirmation in three patients only. No complications at all were observed (infection, hemorrhage or uterus perforation). Authors understand that this method is in conformity with a correct diagnostic performance, being a low cost procedure, almost painless, easy to be done and furnishing sufficient material for the histopathologic diagnosis, in 88% of the cases studied.INTRODUÇÃO : Os autores demonstram a técnica de obtenção de fragmentos endometriais em 25 pacientes encaminhadas ao Serviço de Prevenção do Câncer Ginecológico do Instituto do Câncer Arnaldo Vieira de Carvalho por quadro de sangramento uterino anormal no período de setembro de 1991 a janeiro de 1992. MATERIAL E MÉTODOS: A técnica consistiu na vácuo aspiração do endométrio com auxílio de sonda uretral n° 12 de orifício lateral único. RESULTADOS: A correlação com curetagem foi positiva em 88% dos casos; a biópsia com sonda não mostrou confirmação em apenas três pacientes. Não foram observadas complicações de qualquer espécie (infecção, hemorragia ou perfuração uterina). CONCLUSÃO: Os autores concluem que o método está adequado a uma correta abordagem diagnóstica, trata-se de procedimento de baixo custo, pouco doloroso, de fácil execução e que possibilitou material suficiente para o diagnóstico histopatológico em 88% dos casos estudadosEscola Paulista de Medicina Instituto de Câncer Antonio Vieira de Carvalho Gynecological Oncology DepartmentUNIFESP, EPM, Instituto de Câncer Antonio Vieira de Carvalho Gynecological Oncology DepartmentSciEL

Polymorphism in CYP17, GSTM1 and the progesterone receptor genes and its relationship with mammographic density

Radiologic breast density is one of the predictive factors for breast cancer and the extent of the density is directly related to postmenopause. However, some patients have dense breasts even during postmenopause. This condition may be explained by the genes that codify for the proteins involved in the biosynthesis, as well as the activity and metabolism of steroid hormones. They are polymorphic, which could explain the variations of individual hormones and, consequently, breast density. The constant need to find markers that may assist in the primary prevention of breast cancer as well as in selecting high risk patients motived this study. We determined the influence of genetic polymorphism of CYP17 (cytochrome P450c17, the gene involved in steroid hormone biosynthesis), GSTM1 (glutathione S-transferase M1, an enzyme involved in estrogen metabolism) and PROGINS (progesterone receptor), for association with high breast density. One hundred and twenty-three postmenopausal patients who were not on hormone therapy and had no clinical or mammographic breast alterations were included in the present study. The results of this study reveal that there was no association between dense breasts and CYP17 or GSTM1. There was a trend, which was not statistically significant (P = 0.084), towards the association between PROGINS polymorphism and dense breasts. However, multivariate logistic regression showed that wild-type PROGINS and mutated CYP17, taken together, resulted in a 4.87 times higher chance of having dense breasts (P = 0.030). In conclusion, in the present study, we were able to identify an association among polymorphisms, involved in estradiol biosyntheses as well as progesterone response, and radiological mammary density.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de MastologiaUNIFESP, EPM, Disciplina de MastologiaSciEL

Polymorphism of Interleukin-6 is not associated with the presence or absence of high HPV E6/E7

The present study evaluated the frequency of the polymorphism of Interleukin-6 (IL6) in women positive for E6/E7 Human Papillomavirus (HPV) (n=152) and women negative for HPV (n=238), 390 women in total. Material for analysis was obtained at the Federal University of São Paulo. Interleukin-6 polymorphism was detected by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and analyzed in 3% agarose gel. RESULTS: No significant associations between the frequency of the polymorphism of IL6 in patients expressing E6 and E7 with HPV-positive and -negative reactions were found. There was no statistically significant difference between the case and control group for genotype distribution (p=0.280). CONCLUSION: Genotypic analysis showed a striking similarity of IL6 polymorphisms in both cases and controls. The allelic distribution in cases and controls for G and C of IL6 were very similar (p=0.186), which could point to similar IL6 functionality for both groups

Keratinocyte growth factor, tumor necrosis factor-alpha and interleukin-1 beta gene expression in cultured fibroblasts and keratinocytes from burned patients

PURPOSE: To evaluate the gene expression of KGF, TNF-alpha and IL-1 beta in skin fibroblasts and keratinocytes cultured from burned patients. METHODS: Three patients with large burns and three patients with small burns, as well as two controls, were included. The cell culture was initiated by the enzymatic method. After extraction and purification of mRNA, qPCR was used to assess the gene expression of KGF, TNF-alpha and IL-1 beta. RESULTS: The expression of KGF was increased on average 220-fold in large burns and 33.33-fold in small burns in fibroblasts, and 11.2-fold in large burns and 3.45-fold in small burns in keratinocytes compared to healthy patients (p<0.05). Expression of TNF-alpha was not observed. IL-1 beta is down-regulated in fibroblasts of burned patients, and much more repressed in small burns (687-fold, p<0.05). In keratinocytes, the repression of IL-1 beta expression occurs in patients with small burns (28-fold), while patients with large burns express this gene intensively (15-fold). CONCLUSIONS: The study showed a quantitative pattern in the expression of KGF gene, which is more expressed according to the size of the burn. TNF-alpha was not expressed. A qualitative pattern in the expression of IL-1 beta gene was demonstrated.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)UNIFESP-EPM Department of SurgeryUNIFESP-EPMUNIFESP-EPM Department of GynecologyUNIFESP, EPM, Department of SurgeryUNIFESP-EPMUNIFESP, EPM Department of GynecologySciEL

Prevalence of codon 72 P53 polymorphism in Brazilian women with cervix cancer

The p53 codon 72 polymorphism seems to be associated with HPV-carcinogenesis, although controversial data have been reported. A series of Brazilian women with cervix carcinomas were analyzed. Ninety-nine (67%) of 148 women were found to be homozygous (arg/arg) for the arginine polymorphism, and 49 (33%) were heterozygous (arg/pro). This polymorphism may be an important determinant of the risk for cervix cancer, but does not seem to be sufficient for carcinogenesis.Hospital Maternidade Leonor Mendes de Barros Oncologia GinecológicaUniversidade Federal de São Paulo (UNIFESP) Laboratório de Ginecologia MolecularUniversidade Estadual de Campinas Faculdade de Medicina Oncologia GinecológicaUniversidade de São Paulo Departamento de Medicina Social Faculdade de Medicina de Ribeirão PretoIstituto Superiore di Sanità Laboratory of Epidemiology and Biostatistics Cytopathology UnitUNIFESP, Laboratório de Ginecologia MolecularSciEL

Polymorphism in genes of the progesterone receptor (PROGINS) in women with breast cancer: a case-control study

PURPOSE: to analyze the correlation between PROGINS polymorphism and breast cancer. METHODS: a case-control study was carried out from April to October 2004. The genotypes of 50 women with breast cancer and 49 healthy women were analyzed. The 306-base pair Alu insertion polymorphism in the G intron of progesterone receptor gene was detected by polymerase chain reaction and analyzed on 2% agarose gel stained with ethidium bromide. The control and experimental groups were compared regarding genotypes using the statistical Epi-Info 6.0 program and for frequencies the exact Fisher test or chi2 test were used. p value smaller p than 5% was considered to be significant. RESULTS: in relation to PROGINS we found in the studied population a prevalence of 62 (62.6%) wild homozygous, 35 (35.3%) heterozygous individuals and two (2.1%) cases with the presence of the mutation. Regarding PROGINS polymorphism, significance was not evidenced when cases and controls were compared, as related to homozygosis (62 vs 65.3%), heterozygosis (36 vs 34,6%) or the mutation (2.0 vs 2.1%), with p=0.920 (OR=1.01), 0.891 (OR=1.06), and 0.988 (OR=1.10), respectively. CONCLUSIONS: the results show that single-gene PROGINS polymorphism does not confer a substantial risk of breast cancer to its carriers.OBJETIVOS: analisar a correlação entre o polimorfismo PROGINS e o câncer de mama. MÉTODOS: estudo caso-controle desenvolvido entre abril e outubro de 2004 com o pareamento de 50 mulheres com diagnóstico histopatológico de carcinoma de mama e 49 mulheres saudáveis. A inserção Alu de 306 pares de base no intron G do gene do receptor da progesterona denominada PROGINS foi detectada por meio de reação em cadeia da polimerase e analisada em gel de agarose 2% corado com brometo de etídio. Os grupos controle e experimental foram comparados, por meio de programa estatístico Epi-Info 6.0, quanto aos genótipos e às freqüências alélicas, utilizando-se o teste do chi2. RESULTADOS: em relação ao PROGINS encontramos uma prevalência na população estudada de 62 (62,6%) indivíduos homozigotos selvagens, 35 (35,3%) de heterozigotos e dois (2,1%) casos com a presença da mutação. Não foi evidenciada diferença significante em relação ao polimorfismo PROGINS, quando comparados os casos e controles, seja com relação à homozigose (62 vs 65,3%), heterozigose (36 vs 34,6%) ou à presença de mutação (2,0 vs 2,1%), com p de 0,920 (OR=1,01), 0,891 (OR=1,06) e 0,988 (OR=1,10), respectivamente. CONCLUSÕES: os resultados mostraram que o polimorfismo PROGINS não conferiu risco substancial de câncer de mama em seus portadores.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal do Ceará Faculdade de MedicinaUniversidade Federal de São Paulo (UNIFESP) Departamento de Ginecologia Laboratório de Ginecologia MolecularUniversidade Federal de São Paulo (UNIFESP) Departamento de GinecologiaHospital do Servidor Público Estadual Laboratório de ImunologiaHospital do Servidor Público Estadual Seção de MastologiaHospital do Servidor Público Estadual Serviço de Ginecologia e ObstetríciaUNIFESP, Depto. de Ginecologia Laboratório de Ginecologia MolecularUNIFESP, Depto. de GinecologiaSciEL

Pentoxifylline decreases tumor necrosis factor and interleukin-1 during high tidal volume

Tumor necrosis factor-alpha (TNF-alpha) is one of the most important proinflammatory cytokines which plays a central role in host defense and in the acute inflammatory response related to tissue injury. The major source of TNF-alpha are immune cells such as neutrophils and macrophages. We tested the hypothesis that pentoxifylline, a methylxanthine derivative, down-regulates proinflammatory cytokine expression during acute lung injury in rats. Male Wistar rats weighing 250 to 450 g were anesthetized ip with 50 mg/kg sodium thiopental and randomly divided into three groups: group 1 (N = 7): tidal volume (V T) = 7 ml/kg, respiratory rate (RR) = 50 breaths/min and normal saline infusion; group 2 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and normal saline infusion; group 3 (N = 7): V T = 42 ml/kg, RR = 9 breaths/min and pentoxifylline infusion. The animals were ventilated with an inspired oxygen fraction of 1.0, a positive end-expiratory pressure of 3 cmH2O, and normal saline or pentoxifylline injected into the left femoral vein. The mRNA of TNF-alpha rapidly increased in the lung tissue within 180 min of ventilation with a higher V T with normal saline infusion. The concentrations of inflammatory mediators were decreased in plasma and bronchoalveolar lavage (BAL) in the presence of higher V T with pentoxifylline infusion (TNF-alpha: plasma, 102.2 ± 90.9 and BAL, 118.2 ± 82.1; IL-1ß: plasma, 45.2 ± 42.7 and BAL, 50.2 ± 34.9, P < 0.05). We conclude that TNF-alpha produced by neutrophil influx may function as an alert signal in host defense to induce production of other inflammatory mediators.Universidade Federal de São Paulo (UNIFESP) Departamento de Doenças Infecciosas e Parasitárias Disciplina de PneumologiaUniversidade Federal de São Paulo (UNIFESP) Departamento de Doenças Infecciosas e Parasitárias Laboratório de Ginecologia MolecularUniversidade Federal de São Paulo (UNIFESP) Departamento de Doenças Infecciosas e Parasitárias Laboratório de ImunologiaUniversidade Estadual de Campinas Departamento de Clínica Médica Disciplina e Laboratório de Imunologia ClínicaUNIFESP, Depto. de Doenças Infecciosas e Parasitárias Disciplina de PneumologiaUNIFESP, Depto. de Doenças Infecciosas e Parasitárias Laboratório de Ginecologia MolecularUNIFESP, Depto. de Doenças Infecciosas e Parasitárias Laboratório de ImunologiaSciEL