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991.
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993.
Oral toxicity of bis(2-ethylhexyl) phthalate during pregnancy and suckling in the Long-Evans rat 总被引:3,自引:0,他引:3
FA Arcadi C Costa C Imperatore A Marchese A Rapisarda M Salemi GR Trimarchi G Costa 《Canadian Metallurgical Quarterly》1998,36(11):963-970
Bis(2-ethylhexyl) phthalate (DEHP) is a compound widely used in plastics technology to impart flexibility to rigid polymers. We sought to determine whether the oral exposure of female rats to DEHP during gestation and suckling produces alterations in the litter. Female rats were exposed to different concentrations of DEHP suspended in drinking water (32.5 and 325 microl/litre) from day 1 of pregnancy to day 21 after delivery. Pup body weight gain and kidney, liver and testes weight was measured at different times (21, 28, 35, 42 and 56 days) after birth. Plasma concentrations of DEHP and histopathological alterations in kidneys, liver and testes were also studied. In addition, the ability of female pups (1 month of age) to perform a learned avoidance test, the 'beam walking' test, was evaluated. Perinatal exposure to DEHP produced no statistically significant changes in the body weight gain of offspring. Conversely, it produced a significant decrease in kidney and testes relative weight (organ/body weight) with a significant increase in relative liver weight. Signs of histological damage in kidneys, liver, and particularly testes, were observed. Pups exposed perinatally to the highest concentration of DEHP elicited a significant increase in the time necessary to perform the beam walking test. 相似文献
994.
MJ Tolentino JW Miller ES Gragoudas FA Jakobiec E Flynn K Chatzistefanou N Ferrara AP Adamis 《Canadian Metallurgical Quarterly》1996,103(11):1820-1828
PURPOSE: The purpose of the study is to determine the effect of exogenous vascular endothelial growth factor (VEGF) on the primate retina and its vasculature. METHODS: Ten eyes of five animals were studied. Physiologically relevant amounts of the 165 amino acid isoform of human recombinant VEGF were injected into the vitreous of six healthy cynomolgus monkey eyes. Inactivated human recombinant VEGF or vehicle was injected into four contralateral control subject eyes. Eyes were assessed by slit-lamp biomicroscopy, tonometry, fundus color photography, fundus fluorescein angiography, light microscopy, and immunostaining with antibodies against proliferating cell nuclear antigen and factor VIII antigen. RESULTS: All six bioactive VEGF-injected eyes developed dilated, tortuous retinal vessels that leaked fluorescein. Eyes receiving multiple injections of VEGF developed progressively dilated and tortuous vessels, venous beading, edema, microaneurysms, intraretinal hemorrhages and capillary closure with ischemia. The severity of the retinopathy correlated with the number of VEGF injections. None of the four control eyes exhibited any abnormal retinal vascular changes. The endothelial cells of retinal blood vessels were proliferating cell nuclear antigen positive only in the bioactive VEGF-injected eyes. CONCLUSION: Vascular endothelial growth factor is sufficient to produce many of the vascular abnormalities common to diabetic retinopathy and other ischemic retinopathies, such as hemorrhage, edema, venous beading, capillary occlusion with ischemia, microaneurysm formation, and intraretinal vascular proliferation. 相似文献
995.
Neonatal treatment with monosodium glutamate (MSG) decreases proopiomelanocortin (POMC) peptides and results in obesity. The yellow mouse is a model of obesity induced by the viable yellow (Avy) gene at the agouti locus on Chromosome 2, which results in overproduction of a POMC receptor antagonist. Thus we hypothesized that MSG, when imposed on the genetically susceptible model, would alter the development of obesity. Both yellow obese (Avy) and black lean (alpha/alpha) males were injected on Postnatal Days 1, 3, 5, 7, and 9 with 2.0 mg/g body weight MSG or saline SC. Their food intake, growth parameters, and neurochemical status were examined. Paradoxically, MSG interacted with the yellow phenotype to delay the rapid rate of weight gain characteristic of this model (p < 0.05). Food intake was decreased (p < 0.05) in both phenotypes treated with MSG, as was hypothalamic content of dopamine (p < 0.05) and of the POMC peptide, beta-endorphin (p < 0.001). The yellow obese phenotype was more sensitive than the black lean phenotype to the neurochemical effect of early postnatal MSG administration. Recent reports suggest the agouti locus protein is an antagonist of the receptor for another POMC peptide, melanocyte-stimulating hormone (MSH). Therefore, the balance of functional activity between various POMC peptides appears to be an important factor in the development of both acquired and genetic obesity. 相似文献
996.
997.
JM Cheverud EJ Routman FA Duarte B van Swinderen K Cothran C Perel 《Canadian Metallurgical Quarterly》1996,142(4):1305-1319
Body size is an archetypal quantitative trait with variation due to the segregation of many gene loci, each of relatively minor effect, and the environment. We examine the effects of quantitative trait loci (QTLs) on age-specific body weights and growth in the F2 intercross of the LG/J and SM/J strains of inbred mice. Weekly weights (1-10 wk) and 75 microsatellite genotypes were obtained for 535 mice. Interval mapping was used to locate and measure the genotypic effects of QTLs on body weight and growth. QTL effects were detected on 16 of the 19 autosomes with several chromosomes carrying more than one QTL. The number of QTLs for age-specific weights varied from seven at 1 week to 17 at 10 wk. The QTLs were each of relatively minor, subequal effect. QTLs affecting early and late growth were generally distinct, mapping to different chromosomal locations indicating separate genetic and physiological systems for early and later murine growth. 相似文献
998.
FA Chervenak RM Greenlee L Lewenstein HM Tovell 《Canadian Metallurgical Quarterly》1981,57(3):379-381
Massive ascites associated with pelvic endometriosis is an unusual occurrence. Two cases recently encountered by the authors are presented, and 7 additional cases from the literature are reviewed. Clinical courses and operative findings are described, and the management of the cases is presented. The etiology of ascites is explored and the possibility of conservative surgery and hormonal control with danazol is discussed. 相似文献
999.
Leukotriene-A4 hydrolase (EC 3.3.2.6) cleaved the NH2-terminal amino acid from several tripeptides, typified by arginyl-glycyl-aspartic acid, arginyl-glycyl-glycine, and arginyl-histidyl-phenylalanine, with catalytic efficiencies (kcat/Km) > or = 1 x 10(6) M-1 s-1. This exceeds by 10-fold the kcat/Km for its lipid substrate leukotriene A4. Catalytic efficiency declined for dipeptides which had kcat/Km ratios 10-100-fold lower than tripeptides. Tetrapeptides and pentapeptides were even poorer substrates with catalytic efficiencies below 10(3) M-1 s-1. The enzyme preferentially hydrolyzed tripeptide substrates and single amino acid p-nitroanilides with L-arginine at the NH2 terminus. Peptides with proline at the second position were not hydrolyzed, suggesting a requirement for an N-hydrogen at the peptide bond cleaved. Peptides with a blocked NH2 terminus were not hydrolyzed. The specificity constant (kcat/Km) was optimal at pH 7.2 with pK values at 6.8 and 7.9; binding was maximal at pH 8.0. Serum albumins activated the peptidase, increasing tripeptide affinities (Km) by 3-10-fold and specificities (kcat/Km) by 4-13-fold. Two known inhibitors of arginine peptidases, arphamenine A and B, inhibited hydrolysis of L-arginine p-nitroanilide with dissociation constants = 2.0 and 2.5 microM, respectively. Although the primary role of LTA4 hydrolase is widely regarded as the conversion of the lipid substrate leukotriene A4 into the inflammatory lipid mediator leukotriene B4, our data are the first showing that tripeptides are "better" substrates. This is compatible with a biological role for the peptidase activity of the enzyme and may be relevant to the distribution of the enzyme in organs like the ileum, liver, lung, and brain. We present a model which accommodates the available data on the interaction of substrates and inhibitors with the enzyme. This model can account for overlap in the active site for hydrolysis of leukotriene A4 and peptide or p-nitroanilide substrates. 相似文献
1000.