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H F Simmons

Publications and source records attributed to H F Simmons.

8 recordsLinked to original sources
PubMed1995

Investigation of arsenic exposure from soil at a superfund site.

The purpose of this study was to determine if significant arsenic exposure was occurring at a Superfund site with elevated surface soil arsenic concentrations. A second objective was to determine the statistical relationship between the various methods of measuring arsenic exposure in humans. Random urine, 24-hr urine, hair, and fingernail samples were collected at the end of the workweek from 40 employees at an active pesticide manufacturing facility which had formerly produced arsenical pesticides. There was no indication of adverse health effects among the employees attributable to arsenic exposure. Mean urinary, hair, and fingernail concentrations of arsenic were well within normal values and indicated that significant arsenic exposure was not occurring among the employees. Random and 24-hr urine measurements were significantly correlated. Hair and fingernail results also were significantly correlated. Urine results did not correlate well with hair or fingernail results. Results of this study suggest that although there may be some individual variation, random and 24-hr urine arsenic results are not substantially different. For the purpose of screening for arsenic exposure, random urine samples may be an adequate and preferable test for those populations in equilibrium with their environment.

Arsenic↗
PubMed1994

2,6-Dimethylaniline--hemoglobin adducts from lidocaine in humans.

Lidocaine (xylocaine) is utilized for the treatment of ventricular arrhythmias which occur during cardiac surgery or myocardial infarction and as a local anesthetic. Recent data from the National Toxicology Program reported that a principal metabolite in man, 2,6-dimethylaniline, is carcinogenic in rats. In addition, the putative metabolite N-hydroxy-2,6-dimethylaniline has been reported to be mutagenic in Salmonella typhimurium TA100. N-Hydroxy metabolites of aromatic amines may be oxidized by hemoglobin to the corresponding nitroso metabolites and the nitroso may covalently bind to cysteine groups in hemoglobin as the corresponding sulfinic acid amide. Since hemoglobin binding is an indirect measure of the formation of the N-hydroxy metabolite, we have examined the possibility that lidocaine or a metabolite may similarly covalently bind to hemoglobin in rats and humans. Using a previously developed gas chromatographic-mas spectrometric assay, hemoglobin adducts of 2,6-dimethylaniline were detected covalently bound to rat hemoglobin after administration of either 2,6-dimethylaniline or lidocaine. Consistent with previously reported observations, low levels of 2,6-dimethylaniline-hemoglobin adducts were also observed in human subjects before lidocaine administration. Following administration of lidocaine, all patients had much higher levels of 2,6-dimethylaniline-hemoglobin adducts. Differences in adduct levels in patients treated with lidocaine (70-3760 mg) ranged from 93 to 636 ng/g hemoglobin. These data indicate that N-hydroxy-2,6-dimethylaniline is a metabolite of lidocaine in man.

Aniline Compounds↗
PubMed1991

Examination of the role of catecholamines in hepatic glutathione suppression by cold-restraint in mice.

Cold-restraint stress was found to produce a depression in hepatic glutathione content and to elevate circulating catecholamine levels in four mouse strains--ICR, NIH, B6C3F1, and ND/4. Serum norepinephrine concentrations were significantly elevated after cold-restraint (2--3 h) in all strains, and serum epinephrine levels were increased in the B6C3F1 and ND/4 strains. In time-course studies conducted using ND/4 mice, the decline in hepatic glutathione concentrations was found to slightly precede increases in serum epinephrine and norepinephrine concentrations. Also, pretreatment with phentolamine, an alpha-adrenoreceptor antagonist compound shown in previous studies to block epinephrine-induced hepatic glutathione suppression, had no effect on glutathione losses from cold-restraint. These observations are inconsistent with catecholamines as sole mediators of cold-restraint induced hepatic glutathione depression. Two other endogenous substances elevated during stress, corticosteroids and glucagon, were found to diminish glutathione concentrations in the liver in ND/4 mice when administered exogenously. The effects of catecholamines (epinephrine), corticosteroids (hydrocortisone) and glucagon were not additive, i.e. the depression in glutathione when these agents were administered in combination was generally no greater than that induced when the most effective agent was administered alone. It is postulated that during cold-restraint stress multiple endogenous agents are released which are independently capable of causing a depression in hepatic glutathione content.

Animals↗
PubMed1990

Depression of glutathione by cold-restraint in mice.

The effects of cold-restraint as a physiological stressor on the glutathione (GSH) content of the liver and other tissues were examined in male mice. Mice of the ICR, NIH, ND/4, and B6C3F1 strains subjected to cold-restraint for 2 or 3 h experienced a loss of hepatic GSH concentrations ranging from approximately 15 to 50%. Though 3 of these strains (ICR, NIH, and B6C3F1) experienced hypothermia as result of the cold-restraint treatment, with average decreases in core body temperature ranging from 3.3 to 9.8 degrees C, hepatic GSH levels were depressed in the ND/4 mouse in the absence of changes in core body temperature. The ability of cold-restraint as a stressor to diminish hepatic GSH therefore could not be attributed simply to hypothermia. The decrease in hepatic GSH from cold-restraint in ND/4 mice was paralleled by a decrease in non-protein sulfhydryl (NPSH) content of the liver. In addition to its effects on liver GSH and NPSH concentrations, 1.5 h of cold-restraint stress significantly depressed plasma, heart, kidney, and lung NPSH concentrations. The extent of NPSH depression was equivalent to the GSH depression in the liver, heart, and kidney, despite the observation that the normal contribution of GSH to total NPSH content in these tissues ranged from a high of 89% (liver) to a low of 49% (heart). These results with cold-restraint in the ND/4 mouse suggest that other stressors may significantly depress cellular concentrations of GSH and other thiols, and may thereby render the affected tissues more susceptible to the toxicity of free radicals, electrophilic xenobiotic metabolites, or reactive oxygen species.

Animals↗