Preserved Fertility In A Patient With Gynecomastia Associated With The P.pro695ser Mutation In The Androgen Receptor.

The androgen insensitivity syndrome (AIS) is described as a dysfunction of the androgen receptor (AR) in 46,XY individuals, which can be associated with mutations in the AR gene or can be due to unknown mechanisms. Different mutations in AIS generally cause variable phenotypes that range from a complete hormone resistance to a mild form usually associated with male infertility. The purpose of this study was to search for mutations in the AR gene in a fertile man with gynecomastia and to evaluate the influence of the mutation on the AR transactivation ability. Sequencing of the AR gene revealed the p.Pro695Ser mutation. It is located within the AR ligand-binding domain. Bioinformatics analysis indicated a deleterious role, which was verified after testing transactivation activity and N-/C-terminal (N/C) interaction by in vitro expression of a reporter gene and 2-hybrid assays. p.Pro695Ser showed low levels of both transactivation activity and N/C interaction at low dihydrotestosterone (DHT) conditions. As the ligand concentration increased, both transactivation activity and N/C interaction also increased and reached normal levels. Therefore, this study provides functional insights for the p.Pro695Ser mutation described here for the first time in a patient with mild AIS. The expression profile of p.Pro695Ser not only correlates to the patient's phenotype, but also suggests that a high-dose DHT therapy may overcome the functional deficit of the mutant AR.

Glicoproteína-P, resistência a múltiplas drogas (MDR) e relação estrutura-atividade de moduladores

Multidrug resistance, MDR is a major obstacle for cancer chemotherapy. MDR can be reversed by drugs that vary in their chemical structure and main biological activity. Many efforts have been done to overcome MDR based on studies of structure-activity relationships and in this review we summarize some aspects of MDR mediated by P-glycoprotein (P-gp), as the most experimentally and clinically tested form of drug resistance. The most significant MDR mechanisms revealed until now are shortly discussed. Physicochemical and structural properties of MDR modulators, measures of the MDR reversal, and QSAR studies are included.

O papel da interação no processo de ensino-aprendizagem de português para alunos surdos em uma escola inclusiva

In this article, it is discussed the role of interaction in the process of teaching and learning Portuguese of deaf students at an inclusive school. In the context where the research took place, the hearing teacher does not understand sign language, and there are, in her classroom, hearing students and four deaf students, being three of them sign language users. As the communication between the hearing teacher and the deaf students occurred in different codes - Portuguese and Brazilian sign language - and having a social-interactional approach of language (MOITA LOPES, 1986; FREIRE, 1999), we observed if the interaction among the subjects enabled the deaf students to understand what was being taught. The results showed that the fact of having four deaf students in the same classroom allowed them to work in a cooperative way. Besides, the sign language became more visible in this institution. On the other hand, the interaction between the teacher and her deaf students revealed to be of little significance to the learning process of this small group.

Phenotypic variability in a family with x-linked adrenoleukodystrophy caused by the p.Trp132Ter mutation

X-linked adrenoleukodystrophy (X-ALD) is an inherited disease with clinical heterogeneity varying from presymptomatic individuals to rapidly progressive cerebral ALD forms. This disease is characterized by increased concentration of very long chain fatty acids (VLCFAs) in plasma and in adrenal, testicular and nervous tissues. Affected individuals can be classified in different clinical settings, according to phenotypic expression and age at onset of initial symptoms. Molecular defects in X-ALD individuals usually result from ABCD1 gene mutations. In the present report we describe clinical data and the ABCD1 gene study in two boys affected with the childhood cerebral form that presented with different symptomatic manifestations at diagnosis. In addition, their maternal grandfather had been diagnosed with Addison's disease indicating phenotypic variation for X-ALD within this family. The mutation p.Trp132Ter was identified in both male patients; additionally, three females, out of eleven family members, were found to be heterozygous after screening for this mutation. In the present report, the molecular analysis was especially important since one of the heterozygous females was in first stages of pregnancy. Therefore, depending on the fetus outcome, if male and p.Trp132Ter carrier, storage of the umbilical cord blood should be recommended as hematopoietic stem cell transplantation could be considered as an option for treatment in the future.

Structural aspects of the p.P222Q homozygous mutation of HSD3B2 gene in a patient with congenital adrenal hyperplasia

Type II 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase (3β-HSD2), encoded by the HSD3B2 gene, is a key enzyme involved in the biosynthesis of all the classes of steroid hormones. Deleterious mutations in the HSD3B2 gene cause the classical deficiency of 3β-HSD2, which is a rare autosomal recessive disease that leads to congenital adrenal hyperplasia (CAH). CAH is the most frequent cause of ambiguous genitalia and adrenal insufficiency in newborn infants with variable degrees of salt losing. Here we report the molecular and structural analysis of the HSD3B2 gene in a 46,XY child, who was born from consanguineous parents, and presented with ambiguous genitalia and salt losing. The patient carries a homozygous nucleotide c.665C>A change in exon 4 that putatively substitutes the proline at codon 222 for glutamine. Molecular homology modeling of normal and mutant 3β-HSD2 enzymes emphasizes codon 222 as an important residue for the folding pattern of the enzyme and validates a suitable model for analysis of new mutations.

Estudo das lesões agudas da ginastica artistica feminina na infancia, a partir da população em treinamento em Campinas, S.P

Universidade Estadual de Campinas. Faculdade de Educação Física

Treinamento fisico militar e aptidão fisica relacionada a saude : estudo a partir de conscritos do Tiro-de-Guerra 02-40 Sorocaba, S.P

Universidade Estadual de Campinas. Faculdade de Educação Física

Oral health conditions among the elderly in Southeastern São Paulo State

OBJECTIVE: This study aimed to asses oral health conditions in a population aged 60 years and over living in Botucatu, Southeastern Brazil. A cross-sectional population-based study was carried out using a random sample (N=372) of the urban population aged 60 years and over from the city of Botucatu, in 2005. World Health Organization criteria and codes for oral health epidemiological surveys were used. Re-examination was carried out in 10% of individuals aiming to evaluate intra-examiner agreement. Statistical analysis was performed by one-way ANOVA or Kruskal-Wallis ANOVA, as applicable. Also, the t-test was used in the absence of homoscedasticity. Fisher's exact test was used for situations where the categories with less than five units were observed. Adjusted residuals and multiple-comparison analysis were conducted to identify associations between variable categories and subgroups. The intra-examiner agreement was 98% and Kappa statistics result was 0.95. Loss component represented 90.68% of DMF-T index, which was 29.85. The prevalence of edentulism was 63.17%. Upper and lower dentures were found in 80% and 58% respectively, with complete denture as the most commonly used. In those studied, 15% required upper and 38% lower dentures. There was more need for complete denture in both jaws. Approximately 20% had soft tissue alterations. For periodontal conditions, most sextants were excluded (81.81%). Periodontal pockets (4 - 5 mm) were seen in 11.29% of the examined individuals. The oral health status of the elderly population in Botucatu is poor, as well as in other Brazilian cities. The results of this study may help planning collective health actions, giving an accurate description of the oral problems among the elderly.

Bone response to a Ca- and P-enriched titanium surface obtained by anodization

This study evaluated bone response to a Ca- and P- enriched titanium (Ti) surface treated by a multiphase anodic spark deposition coating (BSP-AK). Two mongrel dogs received bilateral implantation of 3 Ti cylinders (4.1 x 12 mm) in the humerus, being either BSP-AK treated or untreated (machined - control). At 8 weeks postimplantation, bone fragments containing the implants were harvested and processed for histologic and histomorphometric analyses. Bone formation was observed in cortical area and towards the medullary canal associated to approximately 1/3 of implant extension. In most cases, in the medullary area, collagen fiber bundles were detected adjacent and oriented parallel to Ti surfaces. Such connective tissue formation exhibited focal areas of mineralized matrix lined by active osteoblasts. The mean percentages of bone-to-implant contact were 2.3 (0.0-7.2 range) for BSP-AK and 0.4 (0.0-1.3 range) for control. Although the Mann-Whitney test did not detect statistically significant differences between groups, these results indicate a trend of BSP-AK treated surfaces to support contact osteogenesis in an experimental model that produces low bone-to-implant contact values.

Uso da Classificação Internacional de Doenças na análise do absenteísmo odontológico

OBJETIVO: Comparar o uso das codificações da classificação de doenças e agravos em solicitações de afastamento do trabalho por motivo odontológico. MÉTODOS: Foram analisadas 240 solicitações emitidas em um serviço público federal entre janeiro de 2008 e dezembro de 2009. O uso da Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde - Décima Revisão (CID-10) foi comparado ao sistema de Classificação Internacional de Doenças em Odontologia e Estomatologia (CID-OE). Foi determinada a especificidade da codificação nas solicitações de afastamento, bem como da codificação atribuída por peritos oficiais em inspeções indiretas, perícias e juntas odontológicas. RESULTADOS: Do total de atestados, 22,9% não apresentaram a CID, 7,1% apresentaram a CID-9, 3,3% a CID-OE e 66,7% a CID-10. A maioria das codificações foi concordante (55,1%), com maior especificidade nas codificações atribuídas após avaliação dos cirurgiões-dentistas peritos oficiais. CONCLUSÕES: É necessário aperfeiçoar a utilização da CID-10 entre os profissionais de Odontologia e perícia odontológica no trabalho. Sugere-se a incorporação do uso da CID-OE e da Classificação Internacional de Funcionamento, Incapacidade e Saúde para a análise dos afastamentos do trabalho, fornecendo dados relevantes para o monitoramento do absenteísmo por motivo odontológico.

Fitossociologia de um Cerrado denso em área de influência de torre de fluxo de carbono, Pé-de-Gigante, Parque Estadual de Vassununga, SP

O domínio do Cerrado compreende uma área contínua nos estados centrais do Brasil e áreas disjuntas em outros estados, incluindo São Paulo. Essa vegetação ocupava originalmente 21% do território brasileiro, restando atualmente apenas 21,6% de sua extensão original. A área recoberta por essa vegetação em São Paulo cobria 14% de sua área total e seus remanescentes recobrem menos de 1% da ocorrência original dessa vegetação. Estudos recentes indicam que o valor da produtividade líquida no Cerrado Pé-de-Gigante (SP) constitui um pequeno dreno de carbono e indicou que a sazonalidade foi o fator determinante do valor observado. Os estudos dos fluxos de carbono em ecossistemas terrestres são raramente acompanhados de abordagens ecofisiológicas de modo a explorar a relação funcional das espécies que compõem o ecossistema e os valores líquidos obtidos para o mesmo. Assim, o objetivo deste trabalho foi caracterizar estruturalmente a vegetação presente na área de maior influência da torre de fluxo instalada no Cerrado Pé-de-Gigante, visando possibilitar estudos relacionados à quantificação em longo prazo da dinâmica dos fluxos de água, energia e CO2 na vegetação de Cerrado. Para isso foram levantadas 20 parcelas (10 x 10 m) em 0,2 ha de Cerrado, e amostraram-se todas as plantas com perímetro ao nível do solo >6 cm (exceto lianas e árvores mortas). A distribuição das classes de diâmetro e estrutura vertical, assim como os parâmetros fitossociológicos foram analisados. Encontramos 1451 indivíduos, distribuídos em 85 espécies, 52 gêneros e 31 famílias. A densidade absoluta e área basal foram de 7255 ind. ha-1 e de 7,9 m².ha-1, respectivamente. A família Leguminosae apresentou o maior número de espécies (13). O Índice de diversidade de Shannon (H') foi 3,27 nats.ind-1. A distribuição em classes de diâmetro mostrou uma curva de "J" invertido, estando a maioria dos indivíduos na primeira classe. Concluímos que a área deve ser classificada como Cerrado denso, devido principalmente à dominância pela espécie arbórea Anadenanthera falcata, cuja ocorrência no estado foi relatada apenas em locais com solos ricos em saturação de bases na região das Cuestas Basálticas, devido também à maior área basal dos indivíduos, comparando com outros fragmentos de Cerrado. Além da espécie citada, Myrcia lingua e Xylopia aromatica, apresentaram os maiores IVI (Valor de importância).

A novel missense mutation p.L76P in the GJB2 gene causing nonsyndromic recessive deafness in a Brazilian family

Mutations in the GJB2 gene, encoding connexin 26 (Cx26), are a major cause of nonsyndromic recessive hearing loss in many countries. We report here on a novel point mutation in GJB2, p.L76P (c.227C>T), in compound heterozygosity with a c.35delG mutation, in two Brazilian sibs, one presenting mild and the other profound nonsyndromic neurosensorial hearing impairment. Their father, who carried a wild-type allele and a p.L76P mutation, had normal hearing. The mutation leads to the substitution of leucine (L) by proline (P) at residue 76, an evolutionarily conserved position in Cx26 as well as in other connexins. This mutation is predicted to affect the first extracellular domain (EC1) or the second transmembrane domain (TM2). EC1 is important for connexon-connexon interaction and for the control of channel voltage gating. The segregation of the c.227C>T (p.L76P) mutation together with c.35delG in this family indicates a recessive mode of inheritance. The association between the p.L76P mutation and hearing impairment is further supported by its absence in a normal hearing control group of 100 individuals, 50 European-Brazilians and 50 African-Brazilians.

Medidas de audição de pais de indivíduos com deficiência auditiva de herança autossômica recessiva

TEMA: avaliação audiológica de pais de indivíduos com perda auditiva de herança autossômica recessiva. OBJETIVO: estudar o perfil audiológico de pais de indivíduos com perda auditiva, de herança autossômica recessiva, inferida pela história familial ou por testes moleculares que detectaram mutação no gene GJB2, responsável por codificar a Conexina 26. MÉTODO: 36 indivíduos entre 30 e 60 anos foram avaliados e divididos em dois grupos: grupo controle, sem queixas auditivas e sem história familiar de deficiência auditiva, e grupo de estudos composto por pais heterozigotos em relação a genes de surdez de herança autossômica recessiva inespecífica ou portadores heterozigotos de mutação no gene da Conexina 26. Todos foram submetidos à audiometria tonal liminar (0,25kHz a 8), audiometria de altas freqüências (9kHz a 20) e emissões otoacústicas produtos de distorção (EOAPD). RESULTADOS: houve diferenças significativas na amplitude das EOAPD nas freqüências 1001 e 1501Hz entre os grupos, sendo maior a amplitude no grupo controle. Não houve diferença significativa entre os grupos para os limiares tonais de 0,25 a 20KHz. CONCLUSÃO: as EOAPD foram mais eficazes, em comparação com a audiometria tonal liminar, para detectar diferenças auditivas entre os grupos. Mais pesquisas são necessárias para verificar a confiabilidade destes dados.