145 resultados para Pharmacological sites


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In the karyotypes of the bat species Molossus ater and M molossus, spontaneous and bromodeoxyuridine (BrdU)- or aphidicolin (APC)-sensitive fragile sites were located. Four chromosome regions harbored APC-sensitive fragile sites: 1q9 and 8q4 in both M ater and M molossus, 3q3 in M ater, and 1p7 in M molossus. The fragile sites in 1q9 and 8q4 were also observed without induction in M molossus. BrdU-sensitive fragile sites were not detected. Despite observations in several other species, the fragile sites detected in Molossus are not coincident with the breakpoints involved in the chromosome rearrangements occurring in the evolution of 7 species of the Molossidae family.

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Mutants of each of the four divalent cation binding sites of chicken skeletal muscle troponin C (TnC) were constructed using site directed mutagenesis to convert Asp to Ala at the first coordinating position in each site. With a view to evaluating the importance of site-site interactions both within and between the N- and C-terminal domains, in this study the mutants are examined for their ability to associate with other components of the troponin-tropomyosin regulatory complex and to regulate thin filaments. The functional effects of each mutation in reconstitution assays are largely confined to the domain in which it occurs, where the unmutated site is unable to compensate for the defect, Thus the mutants of sites I and II bind to the regulatory complex but are impaired in ability to regulate tension and actomyosin ATPase activity, whereas the mutants of sites III and IV regulate activity but are unable to remain bound to thin filaments unless Ca2+ is present. When all four sites are intact, free Mg2+ causes a 50-60-fold increase in TnC's affinity for the other components of the regulatory complex, allowing it to attach firmly to thin filaments. Calcium can replace Mg2+ at a concentration ratio of 1:5000, and at this ratio the Ca2 . TnC complex is more tightly bound to the filaments than the Mg2 . TnC form, In the C-terminal mutants, higher concentrations of Ca2+ (above tension threshold) are required to effect this transformation than in the recombinant wild-type protein, suggesting that the mutants reveal an attachment mediated by Ca2+ in the N-domain sites.

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The influence of subacute and chronic lead intoxication on the responsiveness of the rat vas deferens was investigated by determining pD2 and relative responsiveness ratio (p) values for noradrenaline and for acetylcholine. Thus, the pD2 values of noradrenaline and acetylcholine from vas deferens of lead-treated rats were greater than those from normal rats, indicating that lead, in the dose and periods of treatment utilized, provoked a rise in vas deferens sensibility to noradrenaline and acetylcholine. Since it is known that the cirurgical or chemical denervation of the sexual ducts also provokes hypersensitivity, it may be suggested that this would be a possible mechanism for the observed alterations. A local lead toxic effect on the smooth muscle or at the level of androgen receptors should also be considered.

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To explore three possible binding sites of trypanothione and glutathione reductase, namely, the active, the dimer interface and the coenzyme NADPH binding site, a series of eight compounds, nitrofurans and nitrothiophenes derivatives, were docked, using their crystallographic and modeled conformations. Docking results showed that, for both families and both enzymes, compounds are more likely to bind in the interface site, even though there is some probability of binding in the active site. These studies are in agreement with experimental data, which suggest that these class of compounds can act either as uncompetitive or mixed type inhibitors, and also with the finding that there is an alpha-helix which connects the active with the interface site, thus allowing charge transference between them. (c) 2005 Elsevier B.V. All rights reserved.

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Methane and carbon dioxide seasonal cycles during years 1998 and 1999 at two Brazilian urban and inland sites are presented. The mixing ratio averages over the studied period of time were 1.80 ppm CH4 and 384.7 ppm CO2. A comparison is made between continental averages and the averages of the three nearest global network background sites of NOAA-CMDL comprising Ascension Island, Namibia and Easter Island. Inland sites had 0.08 ppm or 4.9% more CH4 and 19.0 ppm or 4.9% more CO2 than background over the same time span. The CH4 summer minimum observed in remote sites was also detected inland. During the month of October 98 and 99 inland mixing ratios were frequently similar to background.

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Few are studies on P elements that have addressed the saltans group. These studies had shown that species from the cordata and elliptica subgroups were devoid of any discernible P homologous sequences, while species from the parasaltans, sturtevanti, and saltans subgroups all contain P element sequences. Our analyses showed the presence of one to 15 P element insertion sites in species of the saltans group, including Drosophila neocordata and Drosophila emarginata (cordata and elliptica subgroups, respectively). From these species, only those from the parasaltans, sturtevanti, and saltans subgroups harbor canonical P elements and, only those of the last two subgroups seem to harbor putative full-sized elements. Due to the low similarity of the sequences found in D. neocordata and D. emarginata to those earlier described, we suggest that these sequences might be rudimental P element derivatives that were present in the ancestral of the subgenus Sophophora. (C) 2004 Elsevier B.V. All rights reserved.

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Drimys angustifolia Miers. (Winteraceae) is a Brazilian medicinal plant used as analgesic, antiulcer and anti-inflammatory without studies to assure its efficacy and safety Leaf and stem bark extracts were evaluated to determine the antiulcer, analgesic, antiinflammatory and antioxidant activities. Preliminary toxic effects and qualitative phytochemical profile were also performed. The antiulcer activity was detected in both extracts. Administration of the leaf extract at 250 mg/kg inhibited total lesion area by 76.50% (p < 0.01 in ethanol/HCl method), while carbenoxolone at 250 mg/kg reduced lesions by 69.48%. Stem bark extract (250 mg/kg) inhibited lesion by 81.42%, while carbenoxolone by 74.10%. Similar effects were observed in the ethanol-induced ulcer method, but no activity was observed in piroxican model. The effects involve nitric oxide in gastric protection, since the L-NAME treatment reversed the protection given by the extracts. Antioxidant effects suggest an involvement against oxidative stress. In the pain (writhing, tail-flick and hot-plate tests) and inflammation (carrageenan-induced paw edema) models, the extracts did not present any effect. The phytochemical studies demonstrated that both extracts contain flavonoids, saponins, glycosilated triterpenoids, fixed acids, cyanogenic glycosides, quinones, tannins, xanthone and steroidal aglycones. Toxicological studies showed that the extracts are safe at the effective antiulcer doses. (c) 2006 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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Patterns of nest construction and nest site selection of two murid rodents of the Brazilian Atlantic rainforest were described. The animals were captured in an area of about 1.5 ha of primary forest, marked, equipped with a spool-and-line device and released at the capture point. The next day we followed the thread to find their nests. In total 11 nests of Nectomys squamipes (Brants, 1827) and 13 of Oryzomys intermedius (Leche, 1886) were found. They were all egg-shaped, about 15 cm long and 10 cm wide, without any apparent entrance and consisted of dry leaves and grass. The two species differed in the selection of nest sites. The nests of N. squamipes were close to streams and built inside decomposed fallen logs or using natural entrances between the soil and tangled roots or rocky crevices. Nests of O. intermedius were built under or inside fallen logs and inside aerial root systems of palms. The spool-and-line technique used here is useful to provide detailed information on several aspects of the ecology and natural history of small mammals.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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This study shows for the first time that terrestrial tank bromeliads from Brazilian restinga can act as natural traps for dispersed palm Euterpe edulis seeds. Such bromeliads, which are shade intolerant, gain benefits by limiting palm recruitment since they hinder canopy formation and, consequently, increase luminosity over its aggregates.

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Snake venoms are an extremely rich source of pharmacologically active proteins with a considerable clinical and medical potential. To date, this potential has not been fully explored, mainly because of our incomplete knowledge of the venom proteome and the pharmacological properties of its components, in particular those devoid of enzymatic activity. This review summarizes the latest achievements in the determination of snake venom proteome, based primarily on the development of new strategies and techniques. Detailed knowledge of the venom toxin composition and biological properties of the protein constituents should provide the scaffold for the design of new more effective drugs for the treatment of the hemostatic system and heart disorders, inflammation, cancer and consequences of snake bites, as well as new tools for clinical diagnostic and assays of hemostatic parameters.

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Based on the Johnson-Mehl-Avrami-Kolmogorov (JMAK) theory, we propose two new models to describe the crystallisation kinetics of glass particles and use them to determine the density of nucleation sites, N(s), on glass powders. We tested these models with sintered compacts of diopside glass particles using sinter-crystallisation treatments at 825 degrees C (T(g)similar to 727 degrees C), that covered from null to almost 100% crystallised volume time fraction. We measured and compared the evolution of the crystallised volume fractions by optical microscopy and x-ray diffraction. Then we fit our expressions to experimental data using Ns and R (the average particle radius) as adjustable parameters. For comparison, we also fit to our data existing expressions that describe the crystallised volume fraction in glass powders. We demonstrate that all the methods allow one to estimate N(s) with reasonable accuracy. For our ground and water washed diopside glass powder, N(s) is between 10(10)-10(11) sites.m(-2). The reasonable agreement between experimental and adjusted R confirms the consistency of all five models tested. However, one of our equations does not require taking into account the change of crystallisation mode from 3-dimensional to 1-dimensional, and this is advantageous.

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P>The reactivity of sera collected from guinea pigs after three infestations with Amblyomma triste nymphs on histological sections of the same tick species was investigated through immunohistochemistry to identify potential target cells and tissues. Six guinea pigs were infested thrice, at 30 day intervals, with 30 nymphs of A. triste per animal per infestation. Blood samples were collected from the guinea pigs 15 days after each infestation for serum separation; normal serum was obtained before the first infestation as control. Unfed A. triste nymphs' histological sections were submitted to indirect immunohistochemistry technique by using normal or hyperimmune guinea pig serum as primary antibody and a goat IgG-alkaline phosphatase-APase conjugate as secondary antibody. A weak to moderate APase activity was observed in cells of salivary glands, midgut and haemolymph of unfed nymphs incubated with hyperimmune serum.