The goal of this study was to develop a sensitive in vitro bioassay for quantification of the total esterase inhibiting potency of low concentrations of organophosphate and carbamate insecticides in ...relatively small rainwater samples. Purified acetylcholinesterase (AChE) from electric eel (Electrophorus electricus) and carboxylesterases from a homogenate of honeybee heads (Apis mellifera) were used as esterases, each having different affinities for the substrates S-acetylthiocholine-iodide (ATC) and N-methylindoxylacetate (MIA). MIA hydrolysis by honeybee homogenate was more sensitive to inhibition by organophosphate insecticides than ATC hydrolysis by purified AChE, although the latter parameter is often used for in vitro monitoring of esterase inhibitors. The higher sensitivity of carboxylesterases is attributed to the instant formation of a reversible Michaelis-Menten complex with the inhibitor, which competes with MIA for the active sites of the free enzymes. This dose-dependent instant inhibition can be quantified with kinetics for competitive inhibition at dichlorvos concentrations < 16 nM. At similar concentrations, purified AChE was not instantly inhibited, whereas both AChE and carboxylesterases were irreversibly and progressively inhibited at higher dichlorvos concentrations (IC50(10min) >/= 0.1 microM). Honeybee homogenate mediated MIA hydrolysis was applied as the most sensitive enzyme-substrate combination for experiments with fractionated extracts of 4 rainwater samples collected in a natural conservation area. Most esterase inhibiting potency was found in the polar methanol fraction, with recalculated concentrations equivalent to 12-125 ng dichlorvos per liter rainwater.
A scientific evaluation was made of the mechanisms of action of polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls. Distinction is made between the aryl-hydrocarbon (Ah) receptor-mediated ...and non-Ah receptor-mediated toxic responses. Special attention is paid to the applicability of the toxic equivalency factor (TEF) concept.
A subchronic toxicity/reproduction study was performed in Japanese quails that were fed a diet containing 0, 24, 60, and 150 mg tri-n-butyltin oxide (TBTO) per kg basal diet for 6 weeks. Eggs ...produced during the 6 weeks of treatment were incubated and hatched, and chicks hatched from eggs collected in weeks 5 and 6 of exposure were reared for 2 weeks. In parent quail, neither diminished food consumption nor any overt toxic or histopathologic signs were observed following exposure to TBTO. A statistically significant decrease in hatch-ability and increase in percent of chicks found dead in the shell were observed following TBTO exposure at concentrations of 60 and 150 mg/kg food. However, no significant, adverse effects were recorded on total egg production, eggshell thickness and cracked eggs. Blood chemistry parameters of birds measured at the last day of TBTO treatment revealed a statistically significant decrease in serum aspartate aminotransferase (ASAT) enzyme activity among both sexes in all treatment groups. In addition, a statistically significant dose-related decrease in serum calcium level was observed in females only, while serum follicle stimulating hormone (FSH) levels were statistically significantly reduced in male birds in all treatment groups (approximately 50% of the controls). Moreover, a significant decrease in hepatic microsomal 7-ethoxyresorufin (EROD) activity was recorded in females fed 24 and 60 mg TBTO/kg diet and males fed 60 and 150 mg TBTO/kg diet, whereas pentoxyresorufin-o-deetylase (PROD) activity was only significantly decreased in males fed 150 mg TBTO/kg diet.
By using a small example, an analogy to photographic compression, and a simple visualization using heatmaps, we show that latent semantic analysis (LSA) is able to extract what appears to be semantic ...meaning of words from a set of documents by blurring the distinctions between the words.
A Macaque Model for Hantavirus Infection Groen, Jan; Gerding, Martin; Koeman, Jan P. ...
The Journal of infectious diseases,
07/1995, Letnik:
172, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Cynomolgus macaques (Macaca fascicularis) were experimentally infected with Puumala virus (strain Hällnäs), which causes nephropathia epidemica in humans in western Europe. During the first week ...after intratracheal inoculation, the monkeys exhibited signs of lethargy followed by mild proteinuria and microhematuria. Histopathologic changes during the first 7 weeks after infection were largely confined to abnormalities in medullary tubular cells of the kidneys, which coincided with the demonstration of viral antigen and viral RNA. The development of different classes of virus-specific plasma antibodies to the respective viral antigens were similar to those observed in humans with nephropathia epidemica. This first description of a nonhuman primate model for hantavirus infection shows that the cynomolgus macaque provides a suitable model with which to study the pathogenesis of Puumala virus infections and to evaluate new diagnostic methods, immunization strategies, and therapies.
Bile acids and fatty acids may promote colon cancer by inducing colonic hyperproliferation. Dietary calcium inhibits the promoting effects of bile acids and fatty acids, possibly by precipitating ...these surfactants and lowering their cytolytic activity. Because bile acids and fatty acids are products of fat digestion, their effects may be dependent on the type of dietary fat. The effects of the type of dietary fat (energy percentage, 40) and of CaHPO4 supplementation (25 versus 225 mumol/g diet) on the luminal solubility of surfactants, cytolytic activity, epitheliolysis, and in vivo colonic proliferation were studied in rats using Western high-risk diets. The different types of commercially available fats were butter, saturated margarine, and polyunsaturated margarine. Supplemental calcium drastically increased fecal fatty acid excretion, the effect being dependent on the type of fat, and slightly stimulated fecal bile acid excretion. Soluble surfactant concentrations were drastically decreased by calcium supplementation with all three types of dietary fat. Consequently, cytolytic activity of fecal water was decreased by supplemental calcium. These luminal effects of calcium resulted in a lower intestinal epitheliolysis. The compensatory proliferation of the colonic epithelium was decreased by supplemental CaHPO4 for the butter and saturated margarine diets. Despite CaHPO4-dependent decreases in luminal effects and epitheliolysis, no significant decrease in proliferation on the polyunsaturated margarine diet was observed. Multiple regression analysis of soluble surfactants with cytolytic activity (R = 0.76), epitheliolysis (R = 0.74), and colonic proliferation (R = 0.84) showed highly significant associations. Cytolytic activity and epitheliolysis as well as epitheliolysis and proliferation were highly correlated (r = 0.97 and r = 0.88, respectively; n = 36) for control and CaHPO4-supplemented diets, suggesting cause-and-effect relationships. It is concluded that the antiproliferative effect of dietary calcium is mediated by the precipitation of luminal surfactants and is dependent on the type of dietary fat.
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