942 resultados para Glycogen storage disease type II
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Recently, it has been proposed that there are two type Ia supernova progenitors: short-lived and long-lived. On the basis of this idea, we develop a theory of a unified mechanism for the formation of the bimodal radial distribution of iron and oxygen in the Galactic disc. The underlying cause for the formation of the fine structure of the radial abundance pattern is the influence of the spiral arms, specifically the combined effect of the corotation resonance and turbulent diffusion. From our modelling, we conclude that in order to explain the bimodal radial distributions simultaneously for oxygen and iron and to obtain approximately equal total iron output from different types of supernovae, the mean ejected iron mass per supernova event should be the same as quoted in the literature if the maximum mass of stars, which eject heavy elements, is 50 M(circle dot). For the upper mass limit of 70 M(circle dot), the production of iron by a type II supernova explosion should increase by about 1.5 times.
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Mu hiding resistance associated protein 2 (Mrp2) is a canalicular transporter responsible for organic anion secretion into bile. Mrp2 activity is regulated by insertion into the plasma membrane; however, the factors that control this are not understood. Calcium (Ca(2+)) signaling regulates exocytosis of vesicles in most cell types, and the type II inositol 1,4,5-triphosphate receptor (InsP(3)R2) regulates Ca(2+) release in the canalicular region of hepatocytes. However, the role of InsP(3)R2 and of Ca(2+) signals in canalicular insertion and function of Mrp2 is not known. The aim of this study was to determine the role of InsP(3)R2-mediated Ca(2+) signals in targeting Mrp2 to the canalicular membrane. Livers, isolated hepatocytes, and hepatocytes in collagen sandwich culture from wild-type (WT) and InsP(3)R2 knockout (KO) mice were used for western blots, confocal immunofluorescence, and time-lapse imaging of Ca(2+) signals and of secretion of a fluorescent organic anion. Plasma membrane insertion of green fluorescent protein (GFP)-Mrp2 expressed in HepG2 cells was monitored by total internal reflection microscopy. InsP(3)R2 was concentrated in the canalicular region of WT mice but absent in InsP(3)R2 KO livers, whereas expression and localization of InsP(3)R1 was preserved, and InsP(3)R3 was absent from both WT and KO livers. Ca(2+) signals induced by either adenosine triphosphate (ATP) or vasopressin were impaired in hepatocytes lacking InsP(3)R2. Canalicular secretion of the organic anion 5-chloromethylfluorescein diacetate (CMFDA) was reduced in KO hepatocytes, as well as in WT hepatocytes treated with 1,2-bis(o-aminophenoxy)ethane-N,N,N`,N`-tetra-acetic acid (BAPTA). Moreover, the choleretic effect of tauroursodeoxycholic acid (TUDCA) was impaired in InsP(3)R2 KO mice. Finally, ATP increased GFP-Mrp2 fluorescence in the plasma membrane of HepG2 cells, and this also was reduced by BAPTA. Conclusion: InsP(3)R2-mediated Ca(2+) signals enhance organic anion secretion into bile by targeting Mrp2 to the canalicular membrane. (HEPATOLOGY 2010;52:327-337)
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The objective of this study was to investigate the catalytic activity of basic aminopeptidase (APB) and its association with periarticular edema and circulating tumor necrosis factor (TNF)-alpha and type II collagen (CII) antibodies (AACII) in a rat model of rheumatoid arthritis (RA) induced by CII (CIA). Edema does not occur in part of CH-treated, even when AACII is higher than in control. TNF-alpha is detectable only in edematous CII-treated. APB in synovial membrane is predominantly a membrane-bound activity also present in soluble form and with higher activity in edematous than in non-edematous CH-treated or control. Synovial fluid and blood plasma have lower APB in non-edematous than in edematous CII-treated or control. In peripheral blood mononuclear cells (PBMCs) the highest levels of APB are found in soluble form in control and in membrane-bound form in non-edematous CII-treated. CII treatment distinguishes two categories of rats: one with arthritic edema, high AACII, detectable TNF-alpha, high soluble and membrane-bound APB in synovial membrane and low APB in the soluble fraction of PBMCs, and another without edema and with high AACII, undetectable TNF-alpha, low APB in the synovial fluid and blood plasma and high APB in the membrane-bound fraction of PBMCs. Data suggest that APB and CIA are strongly related. (C) 2011 Elsevier B.V. All rights reserved.
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Aim: Glimepiride, a low-potency insulin secretagogue, is as efficient on glycaemic control as other sulphonylureas, suggesting an additional insulin-sensitizer role. The aim of the present study was to confirm the insulin-sensitizer role of glimepiride and to show extra-pancreatic effects of the drug. Methods: Three-month-old monosodium glutamate (MSG)-induced obese insulin-resistant rats were treated (OG) or not treated (O) with glimepiride for 4 weeks and compared with age-matched non-obese rats (C). Insulin sensitivity in whole body, glucose transporter 4 (GLUT4) protein content, glucose uptake and glycogen synthesis in oxidative skeletal muscle and phospho-glycogen synthase kinase (p-GSK3) and glycogen content in liver were analysed. Results: Insulin sensitivity, analysed by the insulin tolerance test, was 30% lower in O than in C rats (p < 0.05), and OG rats recovered this parameter (p < 0.05). In oxidative muscle, glimepiride increased the GLUT4 protein content (50%, p < 0.001) and recovered the obesity-induced reduction (similar to 20%) of the in vitro insulin-stimulated glucose uptake and incorporation into glycogen. In liver, glimepiride increased p-GSK3 (p < 0.01) and glycogen (p < 0.05) contents. Conclusion: The increased GLUT4 protein expression and glucose utilization in oxidative muscle and the increased insulin sensitivity and glycogen storage in liver evidence the insulin-sensitizer effect of glimepiride, which must be important to enable the glimepiride drug to promote an efficient glycaemic control.
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BACKGROUND Oxidized lipoproteins and antioxidized low-density lipoprotein (anti-oxLDL) antibodies (Abs) have been detected in plasma in response to blood pressure (BP) elevation, suggesting the participation of the adaptive immune system. Therefore, treatment of hypertension may act on the immune response by decreasing oxidation stimuli. However, this issue has not been addressed. Thus, we have here analyzed anti-oxLDL Abs in untreated (naive) hypertensive patients shortly after initiation of anti hypertensive therapeutic regimens. METHODS Titers of anti-oxLDL Abs were measured in subjects with recently diagnosed hypertension on stage 1 (n = 94), in primary prevention of coronary disease, with no other risk factors, and naive of anti hypertensive medication at entry. Subjects were randomly assigned to receive perindopril, hydrochlorothiazide (HCTZ), or indapamide (INDA) for 12 weeks, with additional perindopril if necessary to achieve BP control. Abs against copper-oxidized LDL were measured by enzyme-linked immunosorbent assay. RESULTS Twelve-week antihypertensive treatment reduced both office-based and 24-h ambulatory BP measurements (P < 0.0005). The decrease in BP was accompanied by reduction in thiobarbituric acid-reactive substances (TBARS) (P < 0.05), increase in anti-oxLDL Ab titers (P < 0.005), and improvement in flow-mediated dilation (FMD) (P < 0.0005), independently of treatment. Although BP was reduced, we observed favorable changes in anti-oxLDL titers and FMD. CONCLUSIONS We observed that anti-oxLDL Ab titers increase after antihypertensive therapy in primary prevention when achieving BP targets. Our results are in agreement with the concept that propensity to oxidation is increased by essential hypertension and anti-oxLDL Abs may be protective and potential biomarkers for the follow-up of hypertension treatment.
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In this work we use magnetic resonant x-ray diffraction to study the magnetic properties of a 1.5 mu m EuTe film and an EuTe/PbTe superlattice (SL). The samples were grown by molecular beam epitaxy on (111) oriented BaF(2) substrates. The measurements were made at the Eu L(2) absorption edge, taking profit of the resonant enhancement of more than two orders in the magnetically diffracted intensity. At resonance, high counting rates above 11000 cps were obtained for the 1.5 gm EuTe film, allowing to check for the type II antiferromagnetic order of EuTe. An equal population of the three possible in-plane magnetic domains was found. The EuTe/PbTe SL magnetic peak showed a satellite structure, indicating the presence of magnetic correlations among the 5 ML (monolayers) EuTe layers across the 15 ML PbTe non-magnetic spacers. The temperature dependence of the integrated intensities of the film and the SL yielded different Neel temperatures T(N). The lower T(N) for the SL is explained considering the higher influence of the surface atoms, with partial bonds lost.
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This paper presents the results of a new investigation of the Guarani Aquifer System (SAG) in Sao Paulo state. New data were acquired about sedimentary framework, flow pattern, and hydrogeochemistry. The flow direction in the north of the state is towards the southwest and not towards the west as expected previously. This is linked to the absence of SAG outcrop in the northeast of Sao Paulo state. Both the underlying Piramboia Formation and the overlying Botucatu Formation possess high porosity (18.9% and 19.5%, respectively), which was not modified significantly by diagenetic changes. Investigation of sediments confirmed a zone of chalcedony cement close to the SAG outcrop and a zone of calcite cement in the deep confined zone. The main events in the SAG post-sedimentary history were: (1) adhesion of ferrugineous coatings on grains, (2) infiltration of clays in eodiagenetic stage, (3) regeneration of coatings with formation of smectites, (4) authigenic overgrowth of quartz and K-feldspar in advanced eodiagenetic stage, (5) bitumen cementation of Piramboia Formation in mesodiagenetic stage, (6) cementation by calcite in mesodiagenetic and telodiagenetic stages in Piramboia Formation, (7) formation of secondary porosity by dissolution of unstable minerals after appearance of hydraulic gradient and penetration of the meteoric water caused by the uplift of the Serra do Mar coastal range in the Late Cretaceous, (8) authigenesis of kaolinite and amorphous silica in unconfined zone of the SAG and cation exchange coupled with the dissolution of calcite at the transition between unconfined and confined zone, and (9) authigenesis of analcime in the confined SAG zone. The last two processes are still under operation. The deep zone of the SAG comprises an alkaline pH, Na-HCO(3) groundwater type with old water and enriched delta(13)C values (<-3.9), which evolved from a neutral pH, Ca-HCO(3) groundwater type with young water and depleted delta(13)C values (>-18.8) close to the SAG outcrop. This is consistent with a conceptual geochemical model of the SAG, suggesting dissolution of calcite driven by cation exchange, which occurs at a relatively narrow front recently moving downgradient at much slower rate compared to groundwater flow. More depleted values of delta(18)O in the deep confined zone close to the Parana River compared to values of relative recent recharged water indicate recharge occur during a period of cold climate. The SAG is a ""storage-dominated"" type of aquifer which has to be managed properly to avoid its overexploitation. (C) 2011 Elsevier Ltd. All rights reserved.
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We present a study on whether and to what extent subcellular localization may compete favorably with photosensitization efficiency with respect to the overall efficiency of photoinduced cell death. We have compared the efficiency with which two cationic photosensitizers, namely methylene blue (MB) and crystal violet (CV), induce the photoinduced death of human cervical adenocarcinoma (HeLa) cells. Whereas MB is well known to generate singlet oxygen and related triplet excited species with high quantum yields in a variety of biological and chemical environments (i.e., acting as a typical type II photosensitizer), the highly mitochondria-specific CV produces triplet species and singlet oxygen with low yields, acting mostly via the classical type I mechanism (e.g., via free radicals). The findings described here indicate that the presumably more phototoxic type II photosensitizer (MB) does not lead to higher degrees of cell death compared to the type I (CV) photosensitizer. In fact, CV kills cells with the same efficiency as MB, generating at least 10 times fewer photoinduced reactive species. Therefore, subcellular localization is indeed more important than photochemical reactivity in terms of overall cell killing, with mitochondrial localization representing a highly desirable property for the development of more specific/efficient photosensitizers for photodynamic therapy applications. (C) 2011 Elsevier Inc. All rights reserved.
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Herein, we report on the synthesis of photosensitizing nanoparticles in which the generation of different oxidizing species, i.e., singlet oxygen ((1)O(2)) or radicals, was modulated. Sol gel and surface chemistry were used to obtain nanoparticles with specific ratios of dimer to monomer species of phenothiazine photosensitizers (PSs). Due to competition between the reactions involving electron transfer within dimer species and energy transfer from monomer triplets to oxygen, the efficiency of (1)O(2) generation could be controlled. Nanoparticles with an excess of dimer have an (1)O(2) generation efficiency (S(Delta)) of 0.01 while those without dimer have a S, value of 0.4. Furthermore, we demonstrate that the PS properties of the nanoparticles are not subjected to interference from the external medium as is commonly the case for free PSs, i.e., PS ground and triplet states are not reduced by NADH and ascorbate, respectively, and singlet excited states are less suppressed by bromide. The modulated (1)O(2) generation and the PS protection from external interferences make this nanoparticle platform a promising tool to aid in performing mechanistic studies in biological systems. Also, it offers potential application in technological areas in which photo-induced processes take place.
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Coupling a liquid core waveguide cell to a sequential injection chromatograph improved the detection limits for determination of triazine herbicides without compromising peak resolution. Separation of simazine, atrazine, and propazine was achieved in water samples by a 25mm long C18 monolithic column. Detection was made at 238nm using a type II LCW (silica capillary coated with Teflon (R) AF2400) cell with 100cm of optical path length. Detection limits for simazine, atrazine, and propazine were 2.3, 1.9, and 4.5 mu g L-1, respectively. Reduced analysis time and low solvent consumption are other remarkable features of the proposed method.
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A Gangliosidose GM1 é um Erro Inato do Metabolismo (EIM) causado pela deficiência da enzima B-galactosidase ácida. Essa doença é caracterizada pelo acúmulo de metabólitos não degradados, principalmente gangliosídeo GM1, nos lisossomos de vários tipos celulares. Baseado na idade de início e na atividade residual da enzima, a Gangliosidose GM1 é classificada em três diferentes tipos: infantil, juvenil e adulto. O gene da B-galactosidase ácida (GLB1, GeneBank M27507) está situado no cromossomo 3 e possui mais de 60 kb, contendo 16 exons. Cerca de 50 mutações associadas à doença estão descritas na literatura. No sul do Brasil, há uma alta freqüência dessa doença (1:17.000 nascidos vivos). Neste trabalho, vinte pacientes diagnosticados no Hospital de Clínicas de Porto Alegre (Brasil) tiveram o gene GLB1 investigado por SSCP (Single Strand Conformational Polymorphism) usando DNA extraído de sangue periférico. Através desta triagem foram encontradas 52 alterações de mobilidade do DNA, indicando a presença de mutações. As amostras relativas aos exons 2 e 15 foram submetidas a sequenciamento direto com seqüenciador ABI31O(Applied Biosystens) utilizado kit BigDye 3.1. Cinco novas mutações no gene GLB1 (F63Y, R38G, Y36S, Y64F e R59C) e duas mutações já descritas (R59H e 1622-1627insG) foram encontradas. Este trabalho possibilitou a genotipagem completa de 6 pacientes e parcial de 5, e direcionou a investigação de mutações, contribuindo diretamente no diagnóstico da enfermidade e permitindo a realização de estudos de correlação genótipo/fenótipo destes pacientes.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Protozoa may be an important alternative food source for Calanoida copepods in these environments. Aiming to quantify the feeding preferences of N. cearensis by ciliates in the presence of cyanobacteria, in vitro experiments were conducted, using mixed cultures in different concentrations of total food for copepod. Two ciliates species (Paramecium sp. and Cyclidium sp.) and a cyanobacteria toxic strain (Microcystis aeruginosa) were offered as food. Previous experiments were done to identify the copepod s maximum ingestion rate through the use of a type II functional response model when each prey is offered separately. High maximum ingestion rate were found when those protists were offered as prey. N. cearensis showed significant preference for protozoal prey over the cyanobacterium tested both in low (corresponding 95.15% of the diet) and in high food concentration treatments (about 91.56% of the diet), preferring the bigger ciliate in lower concentrations (67.52% of the diet). The meaningful involvement of heterotrophic organisms in the zooplankton diet emphasis the microbial loop participation in the energy transition from copepods to higher trophic levels. This data contributes to understand the stability of existing trophic interactions in reservoirs subjected to eutrophication and assists trophic cascade studies in these environments
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Morphological structures of the head of 1st and 5th instar nymphs of Triatoma circummaculata and Triatoma rubrovaria were revealed by analysis using scanning electron microscopy (SEM). Differences between Ist and 5th instar nymphs of these two species were observed in the postocular callosity, the number of ommatidia and tapered hair, the small segment between antennal segments, the rostrum third segment and slit lines. These slit lines were different only in the 5th instar. Similarities observed were the presence of tapered hairs in the joints, and the type of sensilla in the antennal segments. Only the Ist instar shows anteclypeus and gena sensilla. The antennal segments comprise the following types of sensilla: basiconica, bristles type I, bristles type II, bristles type III, campaniformia, coeloconica, chemosensilla, placodea, trichobothria and trichoidea. We describe here for the first time six (3+3) sensilla basiconica on the dorsal portion of the first segment of the rostrum. (C) 2000 Elsevier B.V. Ltd. All rights reserved.