Induction pegylated interferon Alfa-2a and high dose ribavirin do not increase SVR in heavy patients with HCV genotype 1 and high viral loads

Background & Aims Patients infected with hepatitis C virus (HCV) genotype 1, body weight <85 kg, and high baseline viral load respond poorly to standard doses of pegylated interferon (peginterferon) and ribavirin. We evaluated intensified therapy with peginterferon alfa-2a plus ribavirin. Methods This double-blind randomized trial included HCV genotype 1-infected outpatients from hepatology clinics with body weight <85 kg and HCV RNA titer <400,000 IU/mL. Patients were randomized to 180 μg/wk peginterferon alfa-2a for 48 weeks plus 1200 mg/day ribavirin (standard of care) (group A, n = 191) or 1400/1600 mg/day ribavirin (group B, n = 189). Additional groups included 360 μg/wk peginterferon alfa-2a for 12 weeks then 180 μg/wk peginterferon alfa-2a for 36 weeks plus 1200 mg/day ribavirin (group C, n = 382) or 1400/1600 mg/day ribavirin (group D, n = 383). Follow-up lasted 24 weeks after treatment. Results Sustained virologic response rates (HCV RNA level <15 IU/mL at end of follow-up) in groups A, B, C, and D were 38%, 43%, 44%, and 41%, respectively. There were no significant differences among the 4 groups or between pooled peginterferon alfa-2a regimens (A + B vs C + D: odds ratio [OR], 1.08; 95% confidence interval [CI], 0.831.39; P = .584) or pooled ribavirin regimens (A + C vs B + D: OR, 1.00; 95% CI, 0.791.28; P = .974). Conclusions In patients infected with HCV genotype 1 who are difficult to treat (high viral load, body weight <85 kg), a 12-week induction regimen of peginterferon alfa-2a and/or higher-dose ribavirin is not more effective than the standard regimen. © 2010 AGA Institute.

O papel das argininas alfa-92 e alfa-141 na regulação das propriedades funcionais de hemoglobinas por íons cloreto

The oxygenation of human Hb (HbA) demands a three state model: two deoxy states To and Tx, free and complexed with anions respectively, and an oxy R state. The regulation between these states is modulated by the presence of anions, such as chloride, that binds to T state. The b inding if chloride, however, remains controversial. The aim of this work is the study of arginines 92a (a1ß2 interface) and 141a (C-terminal) as chloride binding sites. To investigate that, we have studied 92 and 141 site directed mutant species: natural mutants Hb J-Cape-Town (R92Q), desArg (R141Δ), Chesapeake (R92L), and the constructed Chesapeake desArg (R92L,141Δ). We expressed Hbs in Escherichia coli and purified. Through oxygen binding curves we measured affinity and cooperativity, in function of water effect and Bohr effect in presence and absence of chloride. Structural features were obtained through 1H NMR spectroscopy Oxygen binding properties and Bohr effect measured indicated a higher affinity and lower cooperativity in absence and presence of chloride for all mutants. Structural changes represent functional aspects of mutant Hbs, such as a significant rise in affinity or a change in cooperativity. Water activity studies conducted as a function of chloride concentration showed that the only Hb desArg follows the thre state model. The other mutant Hbs do not exhibit the Tx state, a fact confirmed by the number of water molecules bound to each Hb during the deoxy-oxy transition. This behavior suggests that the Arginine 92 site could be responsible for chloride binding to Hb, since oxygenation of 92 mutant Hbs cannot be adjusted by the three state model. However, Bohr effect showed that all mutant Hbs released~1 proton in chloride presence, different from HbA that releases ~2, suggesting a role for 141 arginine in the tertiary and quaternary Bohr effect.

Participação da via alfa-2 adrenérgica no controle da secreção do hormônio do crescimento no período prépúbere em novilhas da raça Nelore

This study investigated GH secretion after clonidine (alpha-2 adrenergic agonist) treatment in pre-pubertal Nelore heifers. Clonidine (10 mg/kg, IV, 15 min samples for 4 h) was administrated in the same Nelore heifers at eight (n = 4), 12 (n = 5) and 15 (n = 4) months of age. The GH concentration was measured by radioimmunoassay (sensivity = 0.25 ng/mL, CV = 16%). At eight months, clonidine increased GH average concentration, total area of peaks, the total area of GH secretion and increased peak amplitude and reduced time to onset of peak (P < 0.05). At 15 months, the administration of clonidine increased the GH average concentration and at 12 months the increased occurred only in restricted intervals (P < 0.05). Clonidine injection stimulated GH secretion in prepubertal heifers and this effect was more evident in Nelore heifers at eight months compared to 12 and 15 months of age.

BI-ALFA, estrategias y aplicación de una propuesta para el desarrollo indígena

Incluye Bibliografía

Influence of convergence angle of tooth preparation on the fracture resistance of Y-TZP-based all-ceramic restorations

Objective: To investigate the influence of the convergence angle of tooth preparation on the fracture load of Y-TZP-based ceramic (YZ-Vita YZ) substructure (SB) veneered with a feldspathic porcelain (VM9-Vita VM9). Methods: Finite element stress analysis (FEA) was performed to examine the stress distribution of the system. Eighty YZ SB were fabricated using a CAD-CAM system and divided into four groups (n = 20), according to the total occlusal convergence (TOC) angle: G6-6° TOC; G12-12° TOC; G20-20° TOC; and G20MOD-20° TOC with modified SB. All SB were veneered with VM9, cemented in a fiber reinforced epoxy resin die, and loaded to failure. Half of the specimens from each group (n = 10) were cyclic fatigued (106 cycles) before testing. Failure analysis was performed to determine the fracture origin. Data were statistically analyzed using Anova and Tukey's tests (α = 0.05). Results: The greatest mean load to fracture value was found for the G20MOD, which was predicted by the FEA. Cyclic fatigue did not significantly affect the load of fracture. Catastrophic failure originating from the internal occlusal surface of the SB was the predominant failure mode, except for G20MOD. Significance: The YZ-VM9 restorations resisted greater compression load than the usual physiological occlusal load, regardless of the TOC angle of preparations. Yet, the G20MOD design produced the best performance among the experimental conditions evaluated. © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Small-angle X-ray scattering and structural modeling of full-length: Cellobiohydrolase I from Trichoderma harzianum

Cellobiohydrolases hydrolyze cellulose releasing cellobiose units. They are very important for a number of biotechnological applications, such as, for example, production of cellulosic ethanol and cotton fiber processing. The Trichoderma cellobiohydrolase I (CBH1 or Cel7A) is an industrially important exocellulase. It exhibits a typical two domain architecture, with a small C-terminal cellulose-binding domain and a large N-terminal catalytic core domain, connected by an O-glycosylated linker peptide. The mechanism by which the linker mediates the concerted action of the two domains remains a conundrum. Here, we probe the protein shape and domain organization of the CBH1 of Trichoderma harzianum (ThCel7A) by small angle X-ray scattering (SAXS) and structural modeling. Our SAXS data shows that ThCel7A linker is partially-extended in solution. Structural modeling suggests that this linker conformation is stabilized by inter- and intra-molecular interactions involving the linker peptide and its O-glycosylations. © 2013 Springer Science+Business Media Dordrecht.

Sodium dodecyl sulfate (SDS) effect on the thermal stability of oxy-HbGp: Dynamic light scattering (DLS) and small angle X-ray scattering (SAXS) studies

Glossoscolex paulistus (HbGp) hemoglobin is an oligomeric protein, presenting a quaternary structure constituted by 144 globin and 36 non-globin chains (named linkers) with a total molecular mass of 3.6MDa. SDS effects on the oxy-HbGp thermal stability were studied, by DLS and SAXS, at pH 5.0, 7.0 and 9.0. DLS and SAXS data show that the SDS-oxy-HbGp interactions induce a significant decrease of the protein thermal stability, with the formation of larger aggregates, at pH 5.0. At pH 7.0, oxy-HbGp undergoes complete oligomeric dissociation, with increase of temperature, in the presence of SDS. Besides, oxy-HbGp 3.0mg/mL, pH 7.0, in the presence of SDS, has the oligomeric dissociation process reduced as compared to 0.5mg/mL of protein. At pH 9.0, oxy-HbGp starts to dissociate at 20°C, and the protein is totally dissociated at 50°C. The thermal dissociation kinetic data show that oxy-HbGp oligomeric dissociation at pH 7.0, in the presence of SDS, is strongly dependent on the protein concentration. At 0.5mg/mL of protein, the oligomeric dissociation is complete and fast at 40 and 42°C, with kinetic constants of (2.1±0.2)×10-4 and (5.5±0.4)×10-4s-1, respectively, at 0.6mmol/L SDS. However, at 3.0mg/mL, the oligomeric dissociation process starts at 46°C, and only partial dissociation, accompanied by aggregates formation is observed. Moreover, our data show, for the first time, that, for 3.0mg/mL of protein, the oligomeric dissociation, denaturation and aggregation phenomena occur simultaneously, in the presence of SDS. Our present results on the surfactant-HbGp interactions and the protein thermal unfolding process correspond to a step forward in the understanding of SDS effects. © 2013 Elsevier B.V.

Reação de trans-splicing in vitro utilizando extrato nuclear livre de células e sequencia parcial de alfa tubulina de Trypanosoma cruzi

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Ação antioxidante de alfa-tocoferol e extrato de alecrim em óleo de soja submetido à termoxidação

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Desenvolvimento de cosmético contendo ácido Alfa-Lipóico para prevenção de alterações da pele e do envelhecimento cutâneo

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Análise dos parâmetros clínicos periodontais e expressão genética de interferons alfa, gama e genes relacionados em indivíduos portadores de Síndrome de Down com doença periodontal

Pós-graduação em Ciências Odontológicas - FOAR

Implante de cimento de alfa-fosfato tricálcico de dupla pega munido de canais de interconexão em órbita de coelhos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Malondialdeído, troponina I cardíaca e eletrocardiografia em equinos da raça puro sangue árabe submetido ao exercício e à suplementação com vitamina E(dl-alfa-tocofenol)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Eritrograma glutationa reduzida e superóxido dismutase eritrocitários e metahemoglobina em equinos da raça Árabe submetidos a exercício em esteira: efeito da suplementação com vitamina E (dl-alfa-tocoferol)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estudo caso-controle em genes polimórficos das vias esteróide (ER-alfa e ER-beta) e da insulina (INSR, PA-1 e IGF2) na síndrome do ovário policístico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)