Activation Of The Low Molecular Weight Protein Tyrosine Phosphatase In Keratinocytes Exposed To Hyperosmotic Stress.

Herein, we provide new contribution to the mechanisms involved in keratinocytes response to hyperosmotic shock showing, for the first time, the participation of Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP) activity in this event. We reported that sorbitol-induced osmotic stress mediates alterations in the phosphorylation of pivotal cytoskeletal proteins, particularly Src and cofilin. Furthermore, an increase in the expression of the phosphorylated form of LMWPTP, which was followed by an augment in its catalytic activity, was observed. Of particular importance, these responses occurred in an intracellular milieu characterized by elevated levels of reduced glutathione (GSH) and increased expression of the antioxidant enzymes glutathione peroxidase and glutathione reductase. Altogether, our results suggest that hyperosmostic stress provides a favorable cellular environment to the activation of LMWPTP, which is associated with increased expression of antioxidant enzymes, high levels of GSH and inhibition of Src kinase. Finally, the real contribution of LMWPTP in the hyperosmotic stress response of keratinocytes was demonstrated through analysis of the effects of ACP1 gene knockdown in stressed and non-stressed cells. LMWPTP knockdown attenuates the effects of sorbitol induced-stress in HaCaT cells, mainly in the status of Src kinase, Rac and STAT5 phosphorylation and activity. These results describe for the first time the participation of LMWPTP in the dynamics of cytoskeleton rearrangement during exposure of human keratinocytes to hyperosmotic shock, which may contribute to cell death.

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.

Repeated exposure of adolescent rats to oral methylphenidate does not induce behavioral sensitization or cross-sensitization to nicotine

Several lines of evidence indicate that the use of stimulant drugs, including methylphenidate (MPD), increases tobacco smoking. This has raised concerns that MPD use during adolescence could facilitate nicotine abuse. Preclinical studies have shown that repeated treatment with an addictive drug produces sensitization to that drug and usually cross-sensitization to other drugs. Behavioral sensitization has been implicated in the development of drug addiction. We examined whether repeated oral MPD administration during adolescence could induce behavioral sensitization to MPD and long-lasting cross-sensitization to nicotine. Adolescent male Wistar rats were treated orally with 10 mg/kg MPD or saline (SAL) from postnatal day (PND) 27 to 33. To evaluate behavioral sensitization to MPD in adolescent rats (PND 39), the SAL pretreated group was subdivided into two groups that received intragastric SAL (1.0 mL/kg) or MPD (10 mg/kg); MPD pretreated rats received MPD (10 mg/kg). Cross-sensitization was evaluated on PND 39 or PND 70 (adulthood). To this end, SAL- and MPD-pretreated groups received subcutaneous injections of SAL (1.0 mL/kg) or nicotine (0.4 mg/kg). All groups had 8 animals. Immediately after injections, locomotor activity was determined. The locomotor response to MPD challenge of MPD-pretreated rats was not significantly different from that of the SAL-pretreated group. Moreover, the locomotor response of MPD-pretreated rats to nicotine challenge was not significantly different from that of the SAL-pretreated group. This lack of sensitization and cross-sensitization suggests that MPD treatment during adolescence does not induce short- or long-term neuroadaptation in rats that could increase sensitivity to MPD or nicotine.

A medição da grandeza practical peak voltage na prática radiológica

OBJETIVO: O objetivo deste trabalho foi estudar a grandeza practical peak voltage (PPV), determinada a partir da forma de onda de tensão aplicada a tubos radiológicos, e compará-la com algumas definições de kVp para diferentes tipos de geradores: monofásico (onda completa, clínico), trifásico (seis pulsos, clínico) e potencial constante (industrial). MATERIAIS E MÉTODOS: O trabalho envolveu a comparação do PPV medido invasivamente (utilizando um divisor de tensão) com a resposta de dois medidores comerciais não invasivos, além dos valores de outras grandezas usadas para medição da tensão de pico aplicada ao tubo de raios X, e a análise da variação do PPV com a ondulação percentual da tensão (ripple). RESULTADOS: Verificou-se que a diferença entre o PPV e as definições mais comuns de tensão de pico aumenta com o ripple. Os valores de PPV variaram em até 3% e 5%, respectivamente, na comparação entre medições invasivas e não invasivas feitas com os equipamentos trifásico e monofásico. CONCLUSÃO: Os resultados demonstraram que a principal grandeza de influência que afeta o PPV é o ripple da tensão. Adicionalmente, valores de PPV obtidos com medidores não invasivos devem ser avaliados considerando que eles dependem da taxa de aquisição e da forma de onda adquirida pelo instrumento.

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.