Exercise Training and Caloric Restriction Prevent Reduction in Cardiac Ca2+-Handling Protein Profile in Obese Rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Interfacial surface charge and free accessibility to the PLA(2)-active site-like region are essential requirements for the activity of Lys49 PLA(2) homologues

Lys49 phospholipase A(2) homologues are highly myotoxic and cause extensive tissue damage but do not display hydrolytic activity towards natural phospholipids. The binding of heparin, heparin derivatives and polyanionic compounds such as suramin result in partial inhibition (up to 60%) of the myotoxic effects due to a change in the overall charge of the interfacial surface. In vivo experiments demonstrate that polyethylene glycol inhibits more than 90% of the myotoxic effects without exhibiting secondary toxic effects. The crystal structure of bothropstoxin-I complexed with polyethylene glycol reveals that this inhibition is due to steric hindrance of the access to the PLA(2)-active site-like region. These two inhibitory pathways indicate the roles of the overall surface charge and free accessibility to the PLA2-active site-like region in the functioning of Lys49 phospholipases A(2) homologues. Molecular dynamics simulations, small angle X-ray scattering and structural analysis indicate that the oligomeric states both in solution and in the crystalline states of Lys49 phospholipases A2 are principally mediated by hydrophobic contacts formed between the interfacial surfaces. These results provide the framework for the potential application of both clinically approved drugs for the treatment of Viperidae snakebites. (c) 2006 Elsevier Ltd. All rights reserved.

Occurrence and geochemistry of metamafic rocks from the Forquilha Eclogite Zone, central Ceara (NE Brazil): geodynamic implications

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Geranylation of benzoic acid derivatives by enzymatic extracts from Piper crassinervium (Piperaceae)

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

Neurohormonal, hemodynamic, and electrocardiographic evaluations of healthy dogs receiving long-term administration of doxorubicin

Objective - To evaluate diagnostic testing that could be used to establish an early diagnosis of cardiotoxicosis induced by long-term administration of doxorubicin. Animals - 13 adult mixed-breed dogs. Procedures - 7 dogs were administered doxorubicin chloride (30 mg/m2, IV, q 21 d for 168 days [cumulative dose, 240 mg/m2]), and 6 dogs received saline (0.9% NaCl) solution (5 mL, IV, q 21 d for 168 days; control group). Echocardiography, ECG, arterial blood pressure, plasma renin activity (PRA), and plasma concentrations of norepinephrine and brain natriuretic peptide (BNP) were assessed before each subsequent administration of doxorubicin and saline solution. Results - Dogs that received doxorubicin had a significant decrease in R-wave amplitude, compared with values for the control group, from 30 to 210 mg/m2. Doxorubicin-treated dogs had decreases in fractional shortening and left ventricular ejection fraction evident as early as 30 mg/m2, but significant differences between groups were not detected until 90 mg/m2 was reached. There was also a significant increase in PRA (≥ 120 mg/m2) and left ventricular end-systolic and end-diastolic dimensions (≥ 60 and ≥ 180 mg/m2, respectively). Systemic arterial pressure, remaining echocardiographic variables, and concentrations of norepinephrine and BNP had significant variations, but of no clinical importance, during doxorubicin administration. Conclusions and clinical relevance - Doxorubicin-induced cardiotoxicosis developed at 120 mg/m2, but there were no clinical signs of dilated cardiomyopathy or congestive heart failure. Echocardiography and determination of PRA were able to detect early cardiac alterations during the development of dilated cardiomyopathy, despite apparently differing degrees of sensitivity to development of doxorubicin-induced cardiotoxicosis.

Modulatory effect of Byrsonima basiloba extracts on the mutagenicity of certain direct and indirect-acting mutagens in Salmonella typhimurium assays

Byrsonima basiloba A. Juss. species is a native arboreal type from the Brazilian cerrado (tropical American savanna), and the local population uses it to treat diseases, such as diarrhea and gastric ulcer. It belongs to the Malpighiaceae family, and it is commonly known as murici. Considering the popular use of B. basiloba derivatives and the lack of pharmacological potential studies regarding this vegetal species, the mutagenic and antimutagenic effect of methanol (MeOH) and chloroform extracts were evaluated by the Ames test, using strains TA97a, TA98, TA100, and TA102 of Salmonella typhimurium. No mutagenic activity was observed in any of the extracts. To evaluate the antimutagenic potential, direct and indirect mutagenic agents were used: 4 nitro-o-phenylenediamine, sodium azide, mitomycin C, aflatoxin B1, benzo[a]pyrene, and hydrogen peroxide. Both the extracts evaluated showed antimutagenic activity, but the highest value of inhibition level (89%) was obtained with the MeOH extract and strain TA100 in the presence of aflatoxin B1. Phytochemical analysis of the extracts revealed the presence of n-alkanes, lupeol, ursolic and oleanolic acid, (+)-catechin, quercetin-3-O-α-L-arabinopyranoside, gallic acid, methyl gallate, amentoflavone, quercetin, quercetin-3-O-(2″-O-galloyl)-β-D- galactopyranoside, and quercetin-3-O-(2″-O-galloyl)-α-L- arabinopyranoside. © 2008 Mary Ann Liebert, Inc.

Synthesis and evaluation of diethylethylamine-chitosan for gene delivery: Composition effects on the in vitro transfection efficiency

Chitosan has been indicated as a safe and promising polycation vector for gene delivery. However its low transfection efficiency has been a challenging obstacle for its application. To address this limitation, we synthesized chitosan derivatives which had increasing amounts of diethylethylamine groups (DEAE) attached to the chitosan main chain. The plasmid DNA VR1412 (pDNA), encoding the ß-galactosidase (ß-gal) reporter gene was used to prepare nanoparticles with the chitosan derivatives, and the transfection studies were performed with HeLa cells. By means of dynamic light scattering and zeta potential measurements, it was shown that diethylethylamine-chitosan derivatives (DEAEx-CH) were able to condense DNA into small particles having a surface charge depending on the polymer/DNA ratio (N/P ratio). Nanoparticles prepared with derivatives containing 15 and 25% of DEAE groups (DEAE15-CH and DEAE25-CH) exhibited transfection efficiencies ten times higher than that observed with deacetylated chitosan (CH). For derivatives with higher degrees of substitution (DS), transfection efficiency decreased. The most effective carriers showed low cytotoxicity and good transfection activities at low charge ratios (N/P). Vectors with low DS were easily degraded in the presence of lysozyme at physiological conditions in vitro and the nontoxicity displayed by these vectors opens up new opportunities in the design of DEAE-chitosan-based nanoparticles for gene delivery. © 2013 IOP Publishing Ltd.

Characterization and Quantification of Compounds in the Hydroalcoholic Extract of the Leaves from Terminalia catappa Linn. (Combretaceae) and Their Mutagenic Activity

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

Das transformadas integrais ao cálculo fracionário aplicado à equação logística

Pós-graduação em Biometria - IBB

In Vitro Antibacterial Activity of Prenylated Guanidine Alkaloids from Pterogyne nitens and Synthetic Analogues

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

Synthesis of Quinoline Derivatives by Multicomponent Reaction Using Niobium Pentachloride as Lewis Acid

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

Determination of the mercury fraction linked to protein of muscle and liver tissue of Tucunaré (Cichla spp.) from the Amazon Region of Brazil

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

Avaliação da função renal de cães sob dois protocolos para administração da cisplatina

OBJETIVO: Avaliar a função renal de cães sadios, sob dois protocolos para administração de cisplatina. MÉTODOS: Todos os animais foram submetidos a três sessões de quimioterapia com cisplatina (60mg/m², iv) a intervalos de 21 dias. Foi realizada fluidoterapia com solução de cloreto de sódio a 0,9%, (25mL/kg/hora,iv), durante duas horas e, após administração de cisplatina, por mais uma hora. Os animais do grupo 2 receberam furosemida (2mg/kg, iv) 20 minutos antes da administração da cisplatina. A avaliação da função renal foi feita por exame clinico, urinálise, concentrações séricas de uréia e creatinina, clearance de creatinina, excreção fracionada de sódio e de potássio e razão proteína: creatinina urinária. As avaliações foram feitas imediatamente antes e 1, 2, 5, e 21 dias após cada uma das três sessões de quimioterapia. RESULTADOS: Mantiveram-se dentro da normalidade, não sendo detectados sinais de lesões ou insuficiência renal. Os animais que não receberam furosemida sofreram aumento gradativo nas concentrações séricas de creatinina e diminuição no clearance da mesma. CONCLUSÃO: O regime de fluidoterapia empregado mostra ser efetivo em minimizar a ação nefrotóxica da cisplatina e benefício adicional importante é obtido pela administração de furosemida.

Antimycobacterial activity of lichen substances

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

Duality of parity doublets of helicity +/- 2 in D=2+1 dimensions

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)