94 resultados para inhibitory effects


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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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

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Anthocyanins are the largest group of water-soluble pigments in the plant kingdom. A number of studies have demonstrated that anthocyanins present antioxidant capacity and show inhibitory effects on the growth of some cancer cells. Thus, the goal of this study was to evaluate both the antimutagenicity/antigenotoxicity and mutagenicity/genotoxicity of aqueous extract obtained from the Solanum melanogena, a possible novel source of anthocyanin, and its main purified anthocyanin extract (delphinidin), using the single cell (comet) assay and micronucleus test. Pretreatment with higher doses of the purified anthocyanin (10 and 20 mg/kg b.w.) led to a statistically significant reduction (p < 0.05) in the frequency of micronuclei in polychromatic erythrocytes induced by cyclophosphamide. The pattern of reduction ranged from 48% to 57% independent of concentration. No apparent: genotoxicity and mutagenicity was found for either the anthocyanin or delphinidin extracts. Taken together, these results suggest that mice pre-treated with specific compounds present in anthocyanins (delphinidin) displayed a lower incidence of mutations induced by cyclophosphamide. This finding emphasizes the potential of natural colorants to prevent mutations and also the applicability of genotoxic evaluation for improving health. Furthermore, the results presented here could be an additional argument to support the use of anthocyanins in the diet. (c) 2006 Published by Elsevier Ltd.

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Avaliaram-se os efeitos da progesterona (P4) sobre o crescimento folicular e na endocrinologia reprodutiva em ovelhas Bergamácia. Quatorze ovelhas sincronizadas com prostaglandinas (PGF2alfa ) foram distribuídas em dois grupos (n=7/grupo): grupo-controle e grupo tratado com progesterona (CIDR) depois da ovulação (dia zero). Desde o dia anterior à aplicação de PG até o dia 10, realizaram-se monitoramentos ultra-sonográficos para estabelecer o crescimento folicular. Amostras de sangue foram colhidas para a determinação de P4 desde o dia anterior à aplicação de PG até o dia 10 depois da ovulação. Para o perfil dos pulsos de hormônio luteinizante (LH), as colheitas de sangue ocorreram em intervalos de 30 minutos por um período de oito horas, nos dias um e seis. As taxas de crescimento diferiram (P<0,001) entre os grupos, 0,91±0,15 e 0,70±0,16mm/dia para os grupos controle e tratado, respectivamente. Os dias do platô dos animais controle e tratados foram de 1,9±0,72 e 2,9±0,45 (P<0,05), respectivamente. As concentrações médias de progesterona (P<0,001) foram diferentes entre os tratamentos. A freqüência dos pulsos diferiu no primeiro dia do ciclo (P<0,01), com valores de 2,55±0,09 pulsos/8 horas no grupo-controle e de 1,49±0,11 pulsos/8 horas no grupo tratado. No sexto dia, o grupo-controle 2,20±0,09 pulsos/8 horas apresentou maior número de pulsos (P<0,05) que o grupo tratado, 1,22±0,11 pulsos/8 horas. Os efeitos inibitórios da progesterona exógena no diâmetro do folículo dominante foram mediados pela redução na freqüência dos pulsos de LH.

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The circumventricular structures and the lateral hypothalamus (LH) have been shown to be important for the central action of angiotensin II (ANGII) on water and electrolyte regulation. Several anatomical findings have demonstrated neural connection between circumventricular structures and the LH, the present experiments were conducted to investigate the role of the alpha-adrenergic antagonists and agonistic injected into the LH on the water intake, sodium and potassium excretion elicited by injections of ANGII into the lateral ventricle (LV), the water intake was measured every 30 min over a period of 120 min. The sodium, potassium and urinary volume were measured over a period of 120 min in water-loaded rats. The injection of ANGII into the LV increased the water intake, which was reduced by previous injection of clonidine (an alpha-2-adrenergic agonist) into the LH. The injection of yohimbine (an alpha-2-adrenergic antagonist) and prazosin (an alpha-l-adrenergic antagonist) into the LH, which was done before injecting ANGII into the LV, also reduced the water intake induced by ANGII. The injection of ANGII into the LV reduced the sodium, potassium and urinary volume. Previous treatment with clonidine attenuated the action of ANGII in reducing the sodium, potassium and urinary volume, whereas previous treatment with yohimbine attenuated the effects of ANGII but with less intensity than that caused by clonidine. Previous treatment with prazosin increased the inhibitory effects of ANGII in those parameters. The injection of yohimbine and prazosin, which was done before the injection of clonidine, attenuated the effect of clonidine on the ANGII mechanism. The results of this study led us to postulate that when alpha-2-adrenergic receptors are blocked, the clonidine may act on the imidazoline receptors to produce its effects on the ANGII mechanism. We may also conclude that the LH is involved with circumventricular structures, which present excitatory and inhibitory mechanisms. Such mechanisms are responsible for regulating the renal excretion of sodium, potassium and water, (C) 2000 Elsevier B.V.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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The anti-allergic active fractionation of hexane extracts of the leaves and stems of Anchietia salutaris,ar. martiana (family Violaceae) nas performed by monitoring their activities with an in vitro bioassay system measuring the inhibitory effects on induced histamine release from guinea pig lung cells. Three known pentacyclic triterpenes (friedelin, alpha-amyrin, beta-amyrin) were isolated, but these compounds were inactive. Aliphatic hydrocarbons and methyl esters of fatty acids (palmitic, oleic, linoleic, linolenic acids) were detected in active fractions. All compounds isolated were detected for the first time in this medicinal plant.

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BjussuMP-II is an acidic low molecular weight metalloprotease (Mr similar to 24,000 and pI similar to 6.5), isolated from Bothrops jararacussu snake venom. The chromatographic profile in RP-HPLC and its N-terminal sequence confirmed its high purity level. Its complete cDNA was obtained by RT-PCR and the 615 bp codified for a mature protein of 205 amino acid residues. The multiple alignment of its deduced amino acid sequence and those of other snake venom metalloproteases showed a high structural similarity, mainly among class P-I proteases. The molecular modeling analysis of BjussuMP-II showed also conserved structural features with other SVMPs. BjussuMP-II did not induce hemorrhage, myotoxicity and lethality, but displayed dose-dependent proteolytic activity on fibrinogen, collagen, fibrin, casein and gelatin, keeping stable at different pHs, temperatures and presence of several divalent ions. BjussuMP-II did not show any clotting or anticoagulant activity on human citrated plasma, in contrast to its inhibitory effects on platelet aggregation. The aspects broached, in this work, provide data on the relationship between structure and function, in order to better understand the effects elicited by snake venom metalloproteases. (c) 2007 Elsevier B.V. All rights reserved.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Propolis has been used empirically for centuries and it was always mentioned as an immunomodulatory agent. In recent years, in vitro and in vivo assays provided new information concerning its mechanisms of action, thus a review dealing with propolis and the immune system became imperative. This review compiles data from our laboratory as well as from other researchers, focusing on its chemical composition and botanical sources, the seasonal effect on its composition and biological properties, its immunomodulatory and antitumor properties, considering its effects on antibody production and on different cells of the immune system, involving the innate and adaptive immune response. In vitro and in vivo assays demonstrated the modulatory action of propolis on murine peritoneal macrophages, increasing their microbicidal activity. Its stimulant action on the lytic activity of natural killer cells against tumor cells, and on antibody production was demonstrated. Propolis inhibitory effects on lymphoproliferation may be associated to its anti-inflammatory property. In immunological assays, the best results were observed when propolis was administered over a short-term to animals. Propolis antitumor property and its anticarcinogenic and antimutagenic potential are discussed. Since humans have used propolis for different purposes and propolis-containing products have been marketed, the knowledge of its properties with scientific basis is not only of academic interest but also of those who use propolis as well. This review opens a new perspective on the investigation of propolis biological properties, mainly with respect to the immune system. (c) 2007 Elsevier B.V.. All rights reserved.

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

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The present investigation was undertaken to identify and characterize trophozoite proteases of five axenic strains of Giardia duodenalis isolated in Brazil and the reference strain Portland 1 isolated in the United States. Trophozoite cell lysates of each strain were analysed for the pattern of proteins and for proteolytic activity. Samples were tested in SDS-polyacrylamide gel electrophoresis for the protein profiles, and the detection of proteases in cell lysates was performed using substrate gel electrophoresis [gelatin, collagen, bovine serum albumin (BSA) and haemoglobin] and azocasein assays. Indeed, synthetic inhibitors were included in the assays to characterize the protease classes. Differences on the hydrolysis patterns of protein substrates were observed in relation to the substrate composition as much as the Giardia trophozoite strain. The substrate-containing gels revealed hydrolysis bands with molecular masses ranging from > 97 to 20-15 kDa, and most zones were common to the five strains. However, some pronounced differences could be detected in the BTU-11 pattern. Azocasein was also degraded; however, depending on the lysate assayed, the degree of substrate degradation was variable. It was observed that inhibitory effects are substrate-dependent since the activity was predominantly due to cysteine proteases against gelatin, collagen, BSA and azocasein substrates and due to serine against haemoglobin. The presence of aspartic protease and aminopeptidase activity in the lysates was also indicated.

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

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A myeloperoxidase inhibitory kaempferol derivative, namely pterogynoside (1), was isolated from fruits of Pterogyne nitens, along with six known flavonols, kaempferol, afzelin, kaempferitrin, quercetin, isoquercetrin and rutin. The structures of all compounds were elucidated primarily from 1D and 2D NMR spectroscopic analyses, as well as by high resolution mass spectrometry. All flavonols were screened to identify secondary metabolites as potential myeloperoxidase (MPO) inhibitors, and at concentrations of 0.50-50 nM, quercetin (5), isoquercitrin (6) and rutin (7) exhibited strong inhibitory effects with IC(50) values of 1.22 +/- 0.01, 3.75 +/- 0.02 and 3.60 +/- 0.02, respectively. The MPO activity detected for the new derivative 1 was markedly decreased (IC(50) 10.3 +/- 0.03) when compared with known flavonols 5-7, and interestingly increased when tested against ABTS scavenging activity. (C) 2008 Published by Elsevier Ltd.

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