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1.
Plasma and lipoprotein lipid composition and endogenous hepatic antioxidant status were investigated in hypertensive, 14-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats fed a standard commercial rat chow. Total plasma calcium and magnesium concentrations were similar between both rat strains; however, systolic blood pressure in SHR was greater than in WKY at 13 weeks of age (197 +/- 12 vs. 132 +/- 14 mmHg; p < or = 0.05), confirming hypertension in SHR. Total plasma cholesterol and triacylglycerol concentrations were lower (p < or = 0.05) in SHR compared with WKY. A lower (p < 0.05) HDL cholesterol level in SHR plasma resulted in a higher LDL to HDL cholesterol ratio compared with WKY counterparts. No significant differences in the relative proportion of HDL apolipoprotein A-I fraction were observed between SHR and WKY. Both SHR VLDL and HDL triacylglycerol fractions were lower (p < 0.05) in SHR than WKY. Analysis of liver antioxidant enzyme activities showed no differences in rat liver superoxide dismutase (SOD), but lower (p < 0.05) liver glutathione peroxidase (GSH-Px) activity in SHR. However, liver glutathione (GSH) levels were similar in SHR and WKY counterparts. A possible compensatory effect to the oxidative status of SHR was suggested by the significant (p < 0.05) increase in both liver catalase (CAT) and glutathione reductase (GSSG-Red) activities. Despite these results, in vitro oxidative challenge studies with H2O2 demonstrated a greater susceptibility of liver to GSH depletion in the SHR, although no parallel change in thiobarbituric acid reactive substances (TBARS) production was observed. The comparatively lower plasma cholesterol observed in hypertensive SHR paralleled specific differences in liver catalase and glutathione redox antioxidant enzyme activities.  相似文献   

2.
OBJECTIVES: Variations among states in household exposure to firearms, loaded firearms, and handguns were examined. METHODS: Data from the Behavioral Risk Factor Surveillance System in 22 states were used to estimate the prevalence of adults and children exposed to household firearms. RESULTS: The prevalence of adults living in households with firearms ranged from 12% to 57%; the corresponding ranges were 1% to 23% for loaded firearms and 5% to 36% for handguns. The prevalence of children less than 18 years of age living in households with loaded firearms ranged from 2% to 12%. CONCLUSIONS: Important variations among states exist in the prevalence of adults and children living in households with firearms, loaded firearms, and handguns.  相似文献   

3.
The influence of the 1,4-dihydropyridines (DHPs), water-soluble glutapyrone available as sodium, potassium and ammonium salts of 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-DHP-4-carboxamide)glutaric acid, from one side, and a lipophylic cerebrocrast, 2-propoxyethyl 2,6-dimethyl-4-(2-difluoromethoxyphenyl)-1,4-DHP-3,5-dicarboxylate, from the other side, on partially damaged mitochondria of the Wistar rat hindlimb muscle was also studied. The following tests were made: (1) rates of endogenous respiration and substrate (succinate) oxidation and oxidative phosphorylation; (2) rates and amplitudes of high-amplitude swelling and contraction after the addition of ATP, ADP and succinate to the previously swollen mitochondria and (3) rate of reversible self-aggregation of mitochondria isolated in salt media after ATP-induced contraction without and in the presence of azidothymidine (AZT). Cerebrocrast (10-100 microM) partially normalized the endogenous respiration rate and slightly augmented the respiration rate after the addition of succinate and to lesser extent ADP. Cerebrocrast in a concentration-dependent manner (2.5-50 microM) increased (two-fold at 20-50 microM) the active contraction amplitude of swollen mitochondria, induced by single or repeated additions of ATP. The influence of cerebrocrast on the ADP- and succinate-induced contractions was less obvious. Unlike cerebrocrast glutapyrone caused a reduction of the ATP-induced contraction amplitude (two-fold at 0.5-5.0 mM), not impairing the mitochondrial contraction ability in response to ATP or succinate. Pre-exposure to 2.5 mM glutapyrone resulted in at least a 10-fold inhibition of the reversible aggregation rate in the presence of 99 and 198 microM AZT. The results suggest the usefulness of further study of cerebrocrast and glutapyrone in preventing AZT-induced and some other mitochondrial myopathies.  相似文献   

4.
All-female vertebrates are excellent model systems for studying many evolutionary problems. One of these is the Amazon molly. In this review, three aspects of its biology are discussed: (1) An important question is how dispensable genes, such as all male coding genes, evolve in this species. A number of studies found that most of these genes remain remarkably stable and functional. (2) The gynogenetic Amazon mollies have to live in sympatry with males of a gonochoristic species, because sperm are needed to trigger embryogenesis. Yet, Amazon mollies cannot replace their sexual competitors, because this would lead to their own extinction. Studies on the behavior of Amazon mollies and their sperm-donor species indicate that a number of behavior patterns stabilize the mating system by providing Amazon mollies with the copulations they need to reproduce. (3) The age of Amazon mollies has been estimated to be approximately 100,000 years. This is older than predicted by some theoretical models. In Amazon mollies two ways to occasionally incorporate fresh genetic material have evolved. One way is to add one complete set of paternal chromosomes, which, in nature, leads to stable triploid lineages. The second way is the incorporation of minute, centromere-containing microchromosomes. The evolutionary impact of these phenomena, however, is not resolved so far and needs further study.  相似文献   

5.
The ubiquitous nature of mercury in the environment, its global atmospheric cycling, and its toxicity to humans at levels that are uncomfortably close to exposures experienced by a proportion of the population are some of the current concerns associated with this pollutant. The purpose of this review is to critically evaluate the scientific quality of published reports involving human exposures to mercury and associated health outcomes as an aid in the risk evaluation of this chemical. A comprehensive review of the scientific literature involving human exposures to mercury was performed and each publication evaluated using a defined set of criteria that are considered standards in epidemiologic and toxicologic research. Severe, sometimes fatal, effects of mercury exposure at high levels were primarily reported as case studies. The disasters in Minamata, Japan, in the 1950s and in Iraq in 1971-1972 clearly demonstrated neurologic effects associated with ingestion of methylmercury both in adults and in infants exposed in utero. The effects were convincingly associated with methylmercury ingestion, despite limitations of the study design. Several well-conducted studies have investigated the effects of methylmercury at levels below those in the Iraq incident but have not provided clear evidence of an effect. The lower end of the dose-response curve constructed from the Iraq data therefore still needs to be confirmed. The studies of mercury exposure in the workplace were mainly of elemental or inorganic mercury, and effects that were observed at relatively low exposure levels were primarily neurologic and renal. Several studies have investigated effects associated with dental amalgam but have been rated as inconclusive because of methodologic deficiencies. In our overall evaluation, 29 of 110 occupational studies and 20 of 54 studies where exposure occurred in the natural environment provided at least suggestive evidence of an exposure-related effect.  相似文献   

6.
7.
HSV-1 mutants in the RL-1 gene encoding the ICP34.5 protein have been demonstrated to have diminished neurovirulence in brain yet replicate as efficiently as parental virus in transformed tissue culture cells. Thus they have been proposed as candidates viruses for human brain tumor therapies. Evaluation of their replicative properties and pathogenesis within the nervous system has been limited. As most patients undergoing therapies for brain tumors are likely to be immunocompromised, it will be important to understand the pathogenesis of these viruses in immunocompromised hosts. To this end, the lateral ventricle of nude mice was injected with high (2.5 x 10(7) PFU), medium (10(5) PFU), or low dose (10(3) PFU) HSV-1 variant-1716, which has a deletion in the RL-1 gene. Ten of 10 mice died within 2-3 days following the high titer infection. Six of 19 animals with medium titer infection died within 9 days, and viral antigens were seen in ependymal cells as well as neurons within the brainstem and thalamus. Although only two of 19 animals became moribund 18 days after medium titer viral infection, many neocortical and hippocampal neurons were positive for HSV-1 antigens. However, plaque-purified viral isolates recovered from brain homogenates of these animals demonstrated no increase in pathogenicity. Nine of 20 animals died following low dose infection; six of these animals, from which tissue was analyzed, all had many HSV antigen-positive neurons in the neocortex and hippocampus. These data imply that if this type of virus is used for human brain tumor therapy immunosuppressed patients may suffer from significant viral pathogenesis outside the tumor.  相似文献   

8.
The purpose of this study is to assess by age, race, ethnicity, and income the effects of air pollution control measures and population growth on human exposure to ozone in the South Coast Air Basin of California (SoCAB). A methodology to study human exposure to air pollutants from a socioeconomic perspective has been developed. Specifically, the Regional Human Exposure model (REHEX-II) has been applied to estimate historical (1980-1982) and recent (1990-1992) human exposure to ozone. The model accounts for time spent in different microenvironments for different age groups and incorporates long-term air quality data with high spatial resolution. The simulation results, expressed as per capita hours of exposure to ozone above various concentration thresholds, are associated with population race, ethnicity, and per capita income. The results indicate that ozone exposure differences by race and ethnicity have diminished over time. However, the study suggests that on average, low income areas may be experiencing higher ozone exposure than high income areas, suggesting that environmental health risks (e.g., respiratory diseases) may be systematically higher for low income groups in the SoCAB.  相似文献   

9.
A thrombin-like enzyme, balterobin, was purified from the venom of Bothrops alternatus. The purification steps included Sephadex G-75, heparin-sepharose and reverse phase HPLC C-18 column. Balterobin showed an apparent molecular weight of 30,000 in non-reduced conditions and displays a specific coagulant activity of 32.8 NIH units/mg over bovine fibrinogen. It also exhibits arginine amidase activity on DL-BAPNA. Like thrombin-like enzymes from other snakes, balterobin possesses valine as N-terminal residue, and is inhibited by PMSF.  相似文献   

10.
Effects of chronic (45 days) treatment with different doses of cadmium chloride (0.25 and 1.0 mg/kg/day), methylmercury chloride (0.4 and 4.0 mg/kg/day) and lead acetate (0.2 and 1.0 mg/kg/day) and of 28-day withdrawal of treatment on the levels of acetylcholine (ACh) and activity of acetylcholinesterase (AChE) in cerebral cortex, and concentration of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) in brain-stem were examined in rats. Exposure to both cadmium and methylmercury produced significant decreases in cortical ACh and brain-stem 5-HT levels. In addition, brain-stem NE concentration was increased in methylmercury-treated rats. In contrast, chronic treatment with lead resulted in enhanced cerebrocortical ACh levels but a decreased brain-stem NE concentration. Treatment with cadmium also produced a transient enhancement of striatal dopamine levels. Cadmium-induced decrease in brain-stem 5-HT and lead-induced accumulation of cortical ACh persisted even after 28 day withdrawal of treatment. The data indicate that chronic exposure to low doses of heavy metals produces differential changes in regional levels of various brain biogenic amines. These changes may represent the early signs of adverse effects on CNS function since they occur before any overt symptoms of neurotoxic effects of heavy metals become apparent.  相似文献   

11.
ADP-ribosylation is an essential process in the metabolism of brain neuronal proteins, including the regulation of assembly and disassembly of biological polymers. Here, we examine the effect of HgCl2 exposure on the ADP-ribosylation of tubulin and actin, both cytoskeletal proteins also found in neurons, and B-50/43-kDa growth-associated protein (B-50/GAP-43), a neuronal tissue-specific phosphoprotein. In rats we demonstrate, with both in vitro and in vivo experiments, that HgCl2 markedly inhibits the ADP-ribosylation of tubulin and actin. This is direct quantitative evidence that HgCl2, a toxic xenobiotic, alters specific neurochemical reactions involved in maintaining brain neuron structure.  相似文献   

12.
Cholera returned to South America in January 1991, after almost a century of absence. The hygienic status of the countries affected, aggravated by economic and political difficulties, allowed the disease to spread rapidly. In Peru, fishery products were incriminated from the outset, although without conclusive evidence. However, epidemiological and laboratory findings in other countries have confirmed the transmission of the disease by these products. The authors discuss the effects of the recent cholera epidemic on the trade and consumption of fishery products in countries of South America. The actual risk of cholera transmission by food and in particular by the consumption of fishery products is discussed, and a basis for conducting an accurate evaluation of these risks is proposed. Finally, the authors summarise the measures recommended to prevent the transmission of cholera by fishery products.  相似文献   

13.
RhoA/B/C and CDC42/Rac, which form two subgroups of the rho guanosine triphosphatase (GTPase) family, regulate various aspects of actin cytoskeleton organisation. In cytosol, guanosine diphosphate (GDP) dissociation inhibitor (GDI) interacts with and maintains rho GTPases in their inactive GDP-bound form. RhoGDI is a ubiquitously expressed GDI, whereas D4/LyGDI is hematopoietic cell-specific and 10-fold less potent than RhoGDI in binding to and regulating rho GTPases. We have combined microanalytical liquid chromatography with the use of specific antibodies in order to separate D4/LyGDI and RhoDGI-complexes from the cytosol of U937 cells and to demonstrate that the two GDIs associate with different rho protein partners. RhoGDI can form a complex with CDC42Hs, RhoA, Rac1 and Rac2, while none of these GTPases was found to interact with D4/LyGDI. In addition, we found that stimulation of U937 cells with phorbol ester leads to phosphorylation of D4/LyGDI. Our results suggest that LyGDI forms complexes with specific rho GTPases expressed in hematopoietic cells where it may regulate specific pathways.  相似文献   

14.
BACKGROUND: Hepatocyte growth factor (HGF) plays a key role in the regulation of liver regeneration after hepatocyte damage. Changes in HGF production reflect the status of the regeneration process. METHODS: Serum concentrations of HGF and energy substrates were measured during and after liver transplantation in 30 recipients. RESULTS: In the patients with compromised grafts (group A) HGF concentrations were persistently high after reperfusion, whereas in the patients with well-functioning grafts (group B), HGF concentrations decreased rapidly and remained low 4 hours after reperfusion. The patients in group A who died had persistently high concentrations of HGF. The surviving patients with reversible primary graft dysfunction in group A exhibited low concentrations 48 hours after reperfusion. The decrease in HGF concentration preceded the decrease in aspartate aminotransferase concentration. The metabolic parameters that reflect carbohydrate metabolism by the graft paralleled the changes in HGF. CONCLUSIONS: HGF may be more sensitive and specific in predicting early graft function than prothrombin time, ratio, aspartate aminotransferase, or arterial ketone body ratio. The determination of HGF levels after liver transplantation may yield valuable information for evaluating early graft function and making an early decision to repeat a graft procedure in an acutely ill patient.  相似文献   

15.
Risk adjustment and/or equalization has become a central issue in the health care reform initiatives of many countries, including Germany, Switzerland, the Netherlands, Israel, the U.K. and the U.S. Risk adjustment is widely seen as essential to prevent cream skimming and to promote fair competition. In this vein, the 1993 German health reforms require implementation of a risk-based contribution rate equalization scheme by 1996. This paper provides a preliminary assessment of the risk equalization methodology currently proposed for Germany. Recent research in the U.S. and the Netherlands is used to examine whether the sociodemographic factors being used in Germany are likely to be effective. Research findings from both countries indicate that risk formulas based only on socio-demographic factors predict only one-tenth to one-fourth of the maximum possible explainable variance. If the current formula is used, sickness funds with higher concentrations of high risk groups are likely to be substantially under compensated, and to face serious enrollment and financial problems. The authors conclude that improvements in the formula through measures based on diagnosis and prior hospitalization, disability status, and regional variations in utilization and cost are urgently needed before the system is implemented. The German experience is also relevant to other countries that have relied to date on socio-demographic measures for risk adjustment.  相似文献   

16.
The UK Committee on Carcinogenicity of Chemicals in Food, Consumer Products and the Environment (COC) and the related Committee on Mutagenicity provided advice on 1,3-butadiene in 1992. This followed detailed consideration of the available mutagenicity, animal carcinogenicity and epidemiology data plus information on toxicokinetics. They concluded that 1,3-butadiene was an in vivo mutagen, a potent genotoxic animal carcinogen and should be regarded as a probable human carcinogen. The Department of Health is not aware of more recent data warranting reconsideration of these conclusions. General advice on setting air quality standards for carcinogenic air pollutants was given by the COC. Although the prudent assumption of the absence of any safe level for genotoxic carcinogens was preferred, a pragmatic approach based essentially on assessment of the exposure at which no increased risk would be detected, plus a safety factor, was considered reasonable for compounds like butadiene where exposure cannot be totally avoided. This approach, plus recognition that it is unadvisable to allow ambient levels of genotoxic carcinogens to rise, is used in the UK. The procedure by which the Department of Environment's Expert Panel on Air Quality Standards recommended a value of 1 ppb for butadiene based on these principles is described.  相似文献   

17.
An issue in the assessment of toxic effects on neurobehavioural function in occupational or environmental settings is the presence and relative contribution of confounding variables. Factors such as education level and alcohol use are well-known to exert effects on the performance of neurobehavioural tests. In a prospective study of a cohort of vehicle spray painters, measures of neurobehavioural function, demographic characteristics, daily habits including alcohol-use and general health status were taken from the onset of their exposure on four occasions for three full years. This study provided the opportunity to assess the relative contribution of confounding variables and the study factor, solvent exposure, on neurobehavioural function in a study design which limits the heterogeneity of the study sample. In such a design the effects of confounding would expected to be reduced. Multiple linear regression analysis was used with three confounding variables, education level, alcohol use and occupational experience as well as solvent exposure as predictor variables of neurobehavioural test performance. Although the level of solvent exposure was considerably less than the composite threshold limit value for the solvent mixtures encountered, the results indicated that psychomotor performance deteriorated with increasing solvent exposure, but only on the hand steadiness test. The confounding variables showed even greater influences on performance. Education level affected performance on both psychomotor and cognitive tests in the expected direction. Occupational experience also influenced test performance but only for psychomotor tests. With increasing time in the trade, spray painters showed significantly superior performance on reaction time, hand steadiness and visual pursuit tests. Since training in spray painting focuses on psychomotor coordination, this result would be expected. Alcohol use was associated with mixed effects on neurobehavioural function. Painters who reported using greater amounts of alcohol showed significantly poorer performance on the visual test, critical flicker fusion, but better performance on the short term memory and learning measures of the paired associates test so supporting the findings of previous studies of facilitating effects of lower levels of alcohol on memory. These findings reinforce the importance of separating effects due to confounders from effects due to toxic exposures in studies of neurobehavioural function. They emphasise the dilemma of test selection, choosing tests that are sensitive enough to detect effects due to toxic exposure but which are not affected by confounding variables.  相似文献   

18.
The present work studies the surface evolution of cinnabar, when it is leached with HBr acid for different conditions. The dynamicin situ test has been studied by scanning electron microscopy and EDS techniques. According to the acid condition, time, and temperature, the HgS presents different mechanisms of dissolution, and the results prove that the cinnabar does not present “memory effect”, as proposed by other authors.16  相似文献   

19.
The present work studies the surface evolution of cinnabar, when it is leached with HBr acid for different conditions. The dynamicin situ test has been studied by scanning electron microscopy and EDS techniques. According to the acid condition, time, and temperature, the HgS presents different mechanisms of dissolution, and the results prove that the cinnabar does not present “memory effect”, as proposed by other authors.16  相似文献   

20.
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