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

T-Bar clasp-retained removable partial denture as an alternative to implant-based prosthetic treatment

This article reports the case of a 55-year-old female patient who presented with unsatisfactory temporary crowns in the right mandibular premolars and molars, and a premolar-to-molar fixed partial denture in the left side. The clinical and radiographic examinations revealed a fracture of the left first premolar that was a retainer of the fixed partial denture and required extraction. Initially, the acrylic resin crowns were replaced by new ones, and a provisional RPD was made using acrylic resin and orthodontic wire clasps to resolve the problem arising from the loss of the fixed partial denture. Considering the patient's high esthetic demands, the treatment options for the definitive prosthetic treatment were discussed with her and rehabilitation with implant-supported dentures was proposed because the clinical conditions of the residual alveolar ridge were suitable for implant installation, and the patient's general health was excellent. However, the patient did not agree because she knew of a failed case of implant-retained denture in a diabetic individual and was concerned. The patient was fully informed that implant installation was the best indication for her case, but the arguments were not sufficient to change her decision. The treatment possibilities were presented and the patient opted for a clasp-retained removable partial denture (RPD) associated with the placement of crowns in the pillar teeth. The temporary RPD was replaced by the definitive RPD constructed subsequently. Although RPD was not the first choice, satisfactory esthetic and functional outcomes were achieved, overcaming the patient's expectations. This case report illustrates that the dentist must be prepared to deal with situations where, for reasons that cannot be managed, the patient does not accept the treatment considered as the most indicated for his/her case. Alternatives must be proposed and the functional and esthetic requirements must be fulfilled in the best possible manner.

Retention force of T-bar clasps for titanium and cobalt-chromium removable partial dentures

The objective of this study was to evaluate the retention force of T-bar clasps made from commercially pure titanium (CP Ti) and cobalt-chromium (Co-Cr) alloy by the insertion/removal test simulating 5 years use. Thirty-six frameworks were cast from CP Ti (n=18) and Co-Cr alloy (n=18) with identical prefabricated patterns on refractory casts from a distal extension mandibular hemi-arch segment. The castings were made on a vacuum-pressure machine, under vacuum and argon atmosphere. Each group was subdivided in three, corresponding to 0.25 mm, 0.50 mm and 0.75 mm undercuts, respectively. No polishing procedures were performed to ensure uniformity. The specimens were subjected to an insertion/removal test and data was analyzed statistically to compare CP Ti and Co-Cr alloy in the same undercut (Student's t-test for independent samples) and each material in different undercuts (one-way ANOVA) (p=0.05). Comparisons between materials revealed significant differences (p=0.017) only for the 0.50-mm undercut. No significant differences (p>0.05) were found when comparing the same material for the undercuts. It may be concluded that for different undercuts, both Co-Cr alloy and CP Ti had no significant differences for T-bar clasps; CP Ti showed the lowest retention force values when compared to Co-Cr alloy in each undercut, but with significant difference only for the 0.50-mm undercut; and both materials maintained the retentive capacity during the simulation test.

Surface and subsurface erosion of primary enamel by acid beverages over time

This study evaluated the influence of a cola-type soft drink and a soy-based orange juice on the surface and subsurface erosion of primary enamel, as a function of the exposure time. Seventy-five primary incisors were divided for microhardness test (n=45) or scanning electron microscopy (SEM) analysis (n=30). The specimens were randomly assigned to 3 groups: 1 - artificial saliva (control); 2 - cola-type soft drink; and 3 - soy-based orange juice. Immersion cycles in the beverages were undertaken under agitation for 5 min, 3 times a day, during 60 days. Surface microhardness was measured at 7, 15, 30, 45 and 60 days. After 60 days, specimens were bisected and subsurface microhardness was measured at 30, 60, 90, 120, 150 and 200 µm from the surface exposed. Data were analyzed by ANOVA and Tukey’s test (a=0.05). Groups 2 and 3 presented similar decrease of surface microhardness. Regarding subsurface microhardness, group 2 presented the lowest values. SEM images revealed that after 60 days the surfaces clearly exhibited structural loss, unlike those immersed in artificial saliva. It may be concluded that erosion of the surfaces exposed to the cola-type soft drink was more accentuated and directly proportional to the exposure time.

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, 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.

An Eulerian Immersed Boundary Method for flow simulations over stationary and moving rigid bodies

The fluid flow over bodies with complex geometry has been the subject of research of many scientists and widely explored experimentally and numerically. The present study proposes an Eulerian Immersed Boundary Method for flows simulations over stationary or moving rigid bodies. The proposed method allows the use of Cartesians Meshes. Here, two-dimensional simulations of fluid flow over stationary and oscillating circular cylinders were used for verification and validation. Four different cases were explored: the flow over a stationary cylinder, the flow over a cylinder oscillating in the flow direction, the flow over a cylinder oscillating in the normal flow direction, and a cylinder with angular oscillation. The time integration was carried out by a classical 4th order Runge-Kutta scheme, with a time step of the same order of distance between two consecutive points in x direction. High-order compact finite difference schemes were used to calculate spatial derivatives. The drag and lift coefficients, the lock-in phenomenon and vorticity contour plots were used for the verification and validation of the proposed method. The extension of the current method allowing the study of a body with different geometry and three-dimensional simulations is straightforward. The results obtained show a good agreement with both numerical and experimental results, encouraging the use of the proposed method.

A hybrid heuristic for the multi-plant capacitated lot sizing problem with setup carry-over

This paper addresses the capacitated lot sizing problem (CLSP) with a single stage composed of multiple plants, items and periods with setup carry-over among the periods. The CLSP is well studied and many heuristics have been proposed to solve it. Nevertheless, few researches explored the multi-plant capacitated lot sizing problem (MPCLSP), which means that few solution methods were proposed to solve it. Furthermore, to our knowledge, no study of the MPCLSP with setup carry-over was found in the literature. This paper presents a mathematical model and a GRASP (Greedy Randomized Adaptive Search Procedure) with path relinking to the MPCLSP with setup carry-over. This solution method is an extension and adaptation of a previously adopted methodology without the setup carry-over. Computational tests showed that the improvement of the setup carry-over is significant in terms of the solution value with a low increase in computational time.