906 resultados para Web content adaptation


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The disposition kinetics of six cationic drugs in perfused diseased and normal rat livers were determined by multiple indicator dilution and related to the drug physicochemical properties and liver histopathology. A carbon tetrachloride (CCl4)induced acute hepatocellular injury model had a higher fibrosis index (FI), determined by computer-assisted image analysis, than did an alcohol-induced chronic hepatocellular injury model. The alcohol-treated group had the highest hepatic alpha(1)- acid glycoprotein, microsomal protein (MP), and cytochrome P450 (P450) concentrations. Various pharmacokinetic parameters could be related to the octanol-water partition coefficient (log P-app) of the drug as a surrogate for plasma membrane partition coefficient and affinity for MP or P450, the dependence being lower in the CCl4-treated group and higher in the alcohol-treated group relative to controls. Stepwise regression analysis showed that hepatic extraction ratio, permeability-surface area product, tissue-binding constant, intrinsic clearance, partition ratio of influx (k(in)) and efflux rate constant (k(out)), and k(in)/k(out) were related to physicochemical properties of drug (log P-app or pK(a)) and liver histopathology (FI, MP, or P450). In addition, hepatocyte organelle ion trapping of cationic drugs was evident in all groups. It is concluded that fibrosis-inducing hepatic disease effects on cationic drug disposition in the liver may be predicted from drug properties and liver histopathology.

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Australian funnel-web spiders are recognized as one of the most venomous spiders to humans world-wide. Funnel-web spider antivenom (FWS AV) reverses clinical effects of envenomation from the bite of Atrax robustus and a small number of related Hadronyche species. This study assessed the in vitro efficacy of FWS AV in neutralization of the effects of funnel-web spider venoms, collected from various locations along the eastern seaboard of Australia, in an isolated chick biventer cervicis nerve-muscle preparation. Venoms were separated by SDS-PAGE electrophoresis to compare protein composition and transblotted for Western blotting and incubation with FWS AV. SDS-PAGE of venoms revealed similar low and high molecular weight protein bands. Western blotting with FWS AV showed similar antivenom binding with protein bands in all the venoms tested. Male funnel-web spider venoms (7/7) and female venoms (5110) produced muscle contracture and fasciculation when applied to the nerve-muscle preparation. Venom effects were reversed by subsequent application of FWS AV or prevented by pretreatment of the preparation with antivenom. FWS AV appears to reverse the in vitro toxicity of a number of funnel-web spider venoms from the eastern seaboard of Australia. FWS AV should be effective in the treatment of envenomation from most, if not all, species of Australian funnel-web spiders. (C) 2001 Elsevier Science Ltd. All rights reserved.

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Experiments involving 14 accessions of Panicum miliaceum L. (Proso millet) and 11 accessions of Setaria italica L. (Foxtail millet) have demonstrated variability in the degree of osmoregulative capacity among these accessions. Birdseed millet is generally claimed to be sensitive to drought stress, apparently because of a shallow root system. Accessions with high osmoregulative capacity demonstrate at least some drought tolerance. Osmoregulative capacity was measured on flag leaves of headed millet plants in pots undergoing water stress in a controlled environment chamber. Osmoregulative capacity was determined from the relationship between osmotic potential and leaf water potential; and the logarithmic relationship between osmotic potential and relative water content. The group of accessions of S. italica showed an overall level of osmoregulative capacity which was greater than that observed for the group of P. miliaceum accessions. Four accessions of S. italica (108042, 108463, 108541 and 108564) and one accession of P. miliaceum (108104) demonstrated high osmoregulative capacity. Differences of 1.05 MPa or more between observed and estimated osmotic potential were found at relative water contents of 80 % among these accessions. The extent of osmoregulative capacity was associated with osmotic potential at full turgor and the rate of decline in osmotic potential as leaf water potentail declined.

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This present study was undertaken to assess potential effects of cadmium on CYP4A11 apoprotein in human liver and kidney as detected by Western blotting using a highly specific anti-peptide antibody. Liver and kidney cortex samples were autopsy specimens of 37 individuals (26 mates and I I females) whose ages ranged from 3 to 89 years. All were Caucasians who had not been exposed to cadmium in the workplace. Reduced CYP4A11 apoprotein levels were found in chronic hepatitis samples and in liver samples showing fatty changes. In contrast, increased CYP4A11 apoprotein levels were found in liver samples having higher cadmium content compared to the lower cadmium content samples. Increased CYP4A11 levels were also found in liver samples from female donors, compared to male donors; the difference being attributable to higher female liver cadmium burden. In distinction to liver, lowered CYP4A11 levels were seen in the kidney cortex samples which have high cadmium content, It is proposed here that the difference between the absolute cadmium burden of the liver and kidney samples may be responsible for the different patterns of expression of CYP4A11 in these two tissues. Further, since cadmium exposure may be associated with derangement in blood pressure control, it is interesting to note the possible relationship between altered CYP4A11-dependent production of arachidonic acid hydroxy and epoxy metabolites in kidney cortex and altered control of blood pressure. Our findings provide a possible link between these observations. (C) 2002 Elsevier Science Inc. All rights reserved.

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The aim of this study was to review the published literature values for the selenium content of Australian foods. A secondary aim was to compare the results for Australian foods with food composition data from international sources to investigate the extent of geographical variation. Published food composition data sources for the selenium content in Australian foods were identified and assessed for data quality using established criteria. The selenium content is available for 148 individual food items. The highest values found are for fish (12.0-63.2 mug/100 g), meats (4.75-37.9 mug/100 g) and eggs (9.00-41.4 mug/100 g), followed by cereals (1.00-20.3 mug/100 g). Moderate levels are seen in dairy products (2.00-7.89 mug/100 g) while most fruits and vegetables have low levels (trace-3.27 mug/100 g). High selenium foods show the greatest level of geographical variation, with foods from the United States generally having higher selenium levels than Australian foods and foods from the United Kingdom and New Zealand having lower levels. This is the first attempt to review the available literature for selenium composition of Australian foods. These data serve as an interim measure for the assessment of selenium intake for use in epidemiological studies of diet-disease relationships. (C) 2002 Published by Elsevier Science Ltd.

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