摘要:

Lipopolysaccharide is a component of the gram-negative bacterial cell wall that is responsible for 25,000-50,000 deaths in the United States each year. The sequelae of gram-negative infection and septicemia leading to death include fever, hypotension with inadequate tissue perfusion, and disseminated intravascular coagulation. It is clear that different cell types respond differently to lipopolysaccharide. Furthermore, various autacoids and cytokines are released that can affect cellular function even in cell types that do not recognize lipopolysaccharide. Despite advances made in the etiology of septic shock and organ failure, therapy is still for the most part supportive and largely ineffective. The aim of this review is to summarize the current understanding of the role of lipopolysaccharide in the development of septicemia by examining signal transduction and therapeutic approaches.

ISSN:0098-4108    

DOI:10.1080/00984109708984034

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

Nineteen workers exposed to low levels of selenium (0.047-0.202 mg/m3air) along with 15 control subjects were studied for clinical, hematological, radiological, and neurobehav-ioral variables in relation to selenium concentration in hair. The levels of selenium in the hair of exposed subjects (1.44±0.37 µg/g) were significantly higher than those of control subjects (0.78±0.18 µg/g). The levels of selenium in the hair of 22 nonvegetarian subjects were found to be significantly higher as compared to 12 vegetarian subjects. Complaints of weakness and/or fatigue were found to be more prevalent in the exposed subjects. The study holds promise that hair selenium may be used as a monitoring tool for low-level occupational exposure to selenium.

ISSN:0098-4108    

DOI:10.1080/00984109708984035

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

The in vitro penetration of [14NC]benzene through freshly prepared human skin was examined under a variety of skin conditions associated with swimming and bathing. The experimental system utilized a recirculating donor solution and a flow-through receiver solution, and was modified to accommodate the analysis of volatiles. The permeability coeffficient of 0.14 cm/h under standard conditions at 26°C was found to increase to 0.26 cm/h at 50°C and decrease to 0.10 cm/h at 15°C. Storage of the skin at −20°C did not affect the penetration of benzene. Application of baby oil, moisturizer, or insect repellant to the skin before exposure under standard conditions did not affect the flux of benzene, but a significant increase was observed when the skin was pretreated with sunscreen (permeability coefficient 0.24 cm/h). These results suggest that risk assessment or exposure modeling for benzene and other environmental contaminants should account for appropriate changes in the environmental conditions when considering the dermal route of exposure.

ISSN:0098-4108    

DOI:10.1080/00984109708984036

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

There are conflicting results in the literature concerning the effect of gavage vehicle, corn oil (CO) versus aqueous suspension, on the toxicity of haloalkanes. The purpose of our study was to assess the influence of oral dosing vehicle on the acute hepatotoxicity of CCl4and nephrotoxicity ofCHCl3. Male Sprague-Dawley rats, fed ad libitum, were treated (po) with single doses of CCl4or CHCl3using corn oil (CO), or an aqueous preparation (5%) of Emulphor (EL620) or Tween-85 (Tw-85) as vehicle (10 ml/kg). Rats were killed 48 h after treatment. Blood was collected for plasma alanine aminotransferase (ALT) determination and renal cortical slices were prepared for p-aminohippuric acid (PAH) incorporation. The comparison, between gavage vehicles, of the slopes and ED50 of the dose-response curves, although not significantly different, indicated clear trends for enhanced potency with CO for CHCl3nephrotoxicity but not for CCl4hepatotoxicity. However, ALT values, a measure of the severity of effect for CCl4also indicated that CO, when compared to EL620 and Tw-85, tended to enhance CCl4hepatotoxicity at low toxicity incidence. Furthermore, CO clearly enhanced the severity of effect for CHCl3nephrotoxicity, as measured by the slice-to-medium PAH ratios, at high dosage. The greater severity of the lesion produced by exposure to these chemicals, when administered in CO, is consistent with the trends observed for their potency (dose-response curves). Our results agree with an increased toxicity of haloalkanes by the gavage vehicle CO reported in the literature. Thus, CO should be considered a potential confounder in hepato- and nephrotoxicity assays.

ISSN:0098-4108    

DOI:10.1080/00984109708984037

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

Styrene is both hepatotoxic and pneumotoxic in mice, with non-Swiss albino (NSA) mice being more sensitive than Swiss (CD-1) mice. The toxicity of styrene is potentiated by treatment with phenobarbital, β-naphthoflavone, or pyridine. Since the toxicity of styrene is generally associated with its metabolism to styrene oxide (SO), the formation of SO by hepatic and pulmonary microsomes of NSA and CD-I mice was measured to examine correlations with toxicity. Both enantiomers of SO were quantified since the R-SO enantiomer is more toxic than the S-SO enantiomer. No strain differences in rates of styrene metabolism or enantiomeric ratio were observed in control mice or mice treated with inducers. Pyridine, an inducer of CYP2E I, increased S-SO but not R-SO formation in liver. Phenobarbital, an inducer of CYP2B, increased the production of both enantiomers. β-Naphthoflavone, an inducer of CYP1A, had no effect. None of the inducers had any effect in lung. Addition of the CYP2E1 inhibitor diethyldithiocarbamate decreased the formation of both enantiomers in both tissues from control mice, whereas 5-phenyl-l-pen-tyne (an inhibitor of CYP2F2) inhibited metabolism primarily in lung. In both control and phenobarbital-treated mice, SKF525A inhibited both R-SO and S-SO in liver but only S-SO in lung. Thus there are tissue differences in metabolism and susceptibility to induction and inhibition but no strain differences in metabolism to explain differences in susceptibility to styrene-induced toxicity.

ISSN:0098-4108    

DOI:10.1080/00984109708984038

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

A study of dimethyl hydrogen phosphite (DMHP) by the National Toxicology Program (NTP) indicated that chronic administration by oral gavage resulted in an increased incidence of neoplastic lesions in the lungs and forestomachs of Fischer 344 rats but not in B6C3F1 mice. The current study was designed to evaluate the metabolic basis, if any, of this species selectivity by studying the metabolism and disposition of [14C]DMHP in the respective strains of rats and mice. Results of this study indicate that DMHP administered at a range of dose of 10–200 mg/kg was readily and near completely absorbed from the gastrointestinal tracts of rats and mice. DMHP-derived radioactivity was eliminated primarily as C02in the expired air, 44–57%, and urine, 28–49%, and very little was collected in feces, 1–2%, or as volatile organics, 2–3%. DMHP-derived radioactivity was widely distributed in tissues of rats and mice, with the highest concentrations observed in the liver, kidneys, spleen, lungs, and forestomach, and the lowest in brain, skeletal muscle, and adipose tissue. The disappearance of radioactivity from mouse tissues was approximately twice as rapid as from rat tissues. In vitro, DMHP was metabolized to formaldehyde by the microsomal fractions of liver, lungs, kidneys, forestomach, and glandular stomach. In vivo, DMHP was metabolized to the product of demethylation, monomethyl hydrogen phosphite (MMHP), which was excreted in urine. Results of this study indicate that the NTP carcinogenicity study with DMHP was carried out within the dose range in which the absorption, metabolism, and disposition of DMHP are linear in both species. Apparent species-dependent differences in the metabolism and disposition of DMHP are limited to the more rapid metabolism and elimination by the mouse. Therefore, the species-dependent variations in the carcinogenicity of DMHP are most likely attributable to factors other than metabolism and disposition.

ISSN:0098-4108    

DOI:10.1080/00984109708984039

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

Weanling female Sprague-Dawley rats were given either 2 or 5 consecutive daily doses of 30 mg/kg 2,2′,4,4′-tetrachlorobiphenyl (CB 47) or a total dose of 120 mg/kg Aroclor 1242 divided into 2, 3, or 5 daily doses by intraperitoneal injection. One day after the final dose, serum total thyroxine (T4) was determined and thyroid glands were collected and prepared for morphometry analysis. Serum T4increased between 20 and 25 d of age, but declined to 35–52% of controls by d 25 in PCB-treated rats. In rats receiving only 2 doses of CB 47, the declines in serum T4were more modest but the thyroid follicular epithelial cell height increased from 9 µm to 10–12 µm and the colloid area decreased from 1100 µm2to 800–900 µm2. In Aroclor 1242-treated rats, follicular cell height increases and colloid area decreases were somewhat greater; serum T4was higher (partially restored) in the rats having received earlier doses. The rapid response of the thyroid gland to moderate decreases in serum T4attenuates the observed decrease in T4and may mask effects on T4metabolism in short-term structure-activity studies. Morphometric measurements may be helpful in characterizing early and/or transient responses to toxicants such as PCBs that have multiple endocrine disrupting effects.

ISSN:0098-4108    

DOI:10.1080/00984109708984040

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/00984109708984041

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor