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.

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

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.

Fitossociologia de um Cerrado denso em área de influência de torre de fluxo de carbono, P��-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 P��-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 esp��cies que comp��em 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 P��-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 esp��cies, 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 esp��cies (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 esp��cie 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 esp��cie 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.

Time resolved emission spectroscopy of poly(2,5-dicyano-p-phenylene-vinylene) films

Films of poly (2,5-dicyano-p-phenylene vinylene), DCNPPV, were obtained by electrochemical synthesis over gold thin layer (20 nm) transparent electrode deposited on a glass plate. The DCNPPV films of 4 µm thickness were produced by electropolymerization process of α,α,α',α'-tetrabromo-2-5-dicyano-p-xilene at different applied potentials (-0.15, -0.25, -0.40, -0.60, -0.80, and -1.0 V) using 0.1 mol L-1 of tetraethylammonium bromide in acetonitrile as the supporting electrolyte. The emission decays have three exponential components: a fast component in the picosecond range (200-400 ps), and two other of about one and five nanoseconds at 293 K. The fluorescence quenching process seems to occur by exciton trapping in a low-energy site and quenching by residual bromine monomer attached at the end of the polymer chain. However, the electrochemical synthesis generates entrapped bromide or ion pairs during the growth step of the film which also contributes to the deactivation. The change of the electrolyte from bromide to perchlorate reduces significantly this additional quenching effect by allowing ion exchange of formed bromide with the nonquenching perchloride anion.

Estudo da eletrocristalização de Ni e Ni-P sobre ultramicroeletrodo de platina

This work describes a comparative study of the electrocrystallization of Ni and Ni-P on Pt ultramicroelectrodes using chronoamperometric measurements. It was possible to confirm that in all cases a progressive nucleation was the predominant mechanism. Moreover, the application of the Atomistic Theory to the experimental rate of nuclei formation showed that the number of atoms in the critical nucleus was zero, except for Ni-P on Pt at low overpotentials were a value of one was observed. Furthermore, the physical characterisation of the different deposits on Pt by atomic force microscopy allowed observing the coalescence of the hemispherical nuclei of Ni and Ni-P at t max thus confirming the results obtained from the current-time analysis.

Recovery of p-TBC from a butadiene washing stream in a pilot plant

Results obtained in a pilot-scale unit designed for COD removal and p-TBC (p-tert-butylcatechol) recovery from a butadiene washing stream (pH 14, 200,000 mg COD L-1, highly toxic) at a petrochemical industry are presented. By adding H3PO4, phase separation is achieved and p-TBC is successfully recovered (88 g L-1 of washing stream). Information (time for phase separation and organic phase characterization) was gathered for designing a future industrial unit. The estimated heat generation rate was 990 kJ min-1 and 15 min were enough to promote phase separation for a liquid column of approximately 1.15 m.

Cerambycidae (Coleoptera) do Estado do Maranhão, Brasil. II

Nesta segunda contribuição à fauna dos Cerambycidae do Estado do Maranhão arrolam-se 123 esp��cies das quais 114 constituem novos registros. Novas esp��cies descritas em Cerambycinae: Ophtalmoplon similis (Hexoplonini), Gorybia bispinosa (Piezocerini), Aneuthetochorus punctatus, Minibidion bicolor (Ibidionini), Piezophidion thoracicum (Elaphidionini), Temnopis rubricollis (Oemini); em Lamiinae: Anobrium minimum (Pteropliini), Cacostola bimaculata, C. parafusca, Trestonia rugosicollis (Onciderini), Eupromerella maculosa, E. picturata, Nesozineus unicolor (Acanthoderini), Piruana pulchra (Desmiphorini), Pachypeza ferruginea (Hippopsini).

Estudo clínico da aplicação de matriz inorgânica de osso associado a peptídeo sintético de adesão celular (MIO/P-15), PepGen P-15®, em lesões periodontais avançadas de cães

Os mecanismos biológicos desenvolvidos para aumentar a qualidade da regeneração óssea e da reparação tecidual de sítios periodontais específicos continuam a ser um desafio e têm sido complementado pela capacidade de adesão celular do colágeno do tipo I, promovida por um peptídeo sintético de adesão celular (P-15), associado a uma matriz inorgânica de osso (MIO) para formar MIO/P-15. O objetivo deste estudo foi avaliar a perda do nível clínico de inserção e a resposta da bolsa periodontal em dentes ap��s 3 e 6 meses da aplicação de enxerto com MIO/P-15. Vinte e um cães do Hospital Veterinário da Universidade de São Paulo foram anestesiados para realização de tratamento periodontal e 132 faces dentais com perda de nível clínico de inserção foram tratadas, sendo que 36,4% (48 faces) receberam o peptídeo de adesão celular e 63,6% (84 faces) compuseram o grupo controle que recebeu tratamento convencional (retalho muco-gengival e aplainamento radicular). O procedimento foi documentado através de radiografia intra-oral e todas as sondagens de bolsas periodontais foram fotografadas. Depois de 3 e de 6 meses, os animais foram re-anestesiados a fim de se obter novas avaliações, radiografias, fotografias e sondagens periodontais. As 48 faces com perda de nível clínico de inserção que receberam material de enxertia apresentaram taxa de 40% de recuperação do nível clínico de inserção ap��s 6 meses. O grupo controle de faces dentais não apresentou alteração do nível clínico de inserção. A face palatina foi a que apresentou melhor taxa de regeneração (40%) e os dentes caninos e molares mostraram as melhores respostas (57,14% e 65%, respectivamente). Não houve sinais de infecção p��s-cirúrgica relacionadas à falta de higienização oral dos animais. Pode-se concluir que o MIO/P-15 auxilia na regeneração e re-aderência das estruturas periodontais, incluindo osso alveolar. Sua aplicação mostrou-se fácil e prática e a incidência de complicações p��s-cirúrgicas foi baixa. Ainda assim, mais estudos e pesquisas são necessários para que se avalie a quantidade e a qualidade do osso e do ligamento periodontal formados.