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Biomedical subjects

R Snyder

Publications and source records attributed to R Snyder.

161 records · Page 9Linked to original sources

Dimethyl sulfoxide: interactions with aromatic hydrocarbons.

Dimethyl sulfoxide (DMSO) enhanced the hypertaurinuria produced by benzene, chlorobenzene, and toluene in rats. Undiluted DMSO was more effective than DMSO diluted with water in potentiating the toxicity of benzene in both rats and mice. Supernatants (9000g) prepared from livers of rats treated with DMSO 24 hours earlier metabolized more benzene than those from control rats.

Animals↗

Investigation of hepatic cytochrome P-450 enzyme induction and DNA adduct formation in male CD/1 mice following oral administration of toxaphene.

Exposure of experimental animals to toxaphene induces hepatic cytochrome P-450 (CYP). Although chronic administration of toxaphene to mice was found to cause an increased incidence of liver tumors, a mechanism for its carcinogenicity has yet to be elucidated. We investigated two potential mechanisms of toxaphene-induced carcinogenicity: peroxisomal proliferation and DNA binding. Peroxisomal proliferation was evaluated by measuring the level of immunodetectable CYP 4A1, an isozyme of CYP that is specifically induced by peroxisomal proliferators, in hepatic microsomes from CD1 mice that were treated by oral gavage for seven consecutive days with corn oil vehicle or 10, 25, 50 or 100 mg kg(-1) toxaphene. In comparison to control mice, toxaphene-treated mice had increased liver weight, increased liver/body weight ratios and increased levels of total hepatic CYP and cytochrome b5. No increase in the level of immunodetectable levels of CYP 4A1 was found in hepatic microsomes from toxaphene-treated mice when compared to controls. In contrast, increases in immunodetectable CYP 4A1 were detected in hepatic microsomes from mice treated with the peroxisomal proliferator clofibrate. These findings suggest that toxaphene-induced induction of CYP may not involve CYP 4A1 and that peroxisomal proliferation may not be involved in toxicity. Significant increases in immunodetectable levels of CYP 2B were, however, detected in toxaphene-treated mice, and are consistent with earlier reports demonstrating that toxaphene, like many other pesticides, induces the phenobarbital-inducible subfamily of CYP. Analysis of DNA adduct levels in the livers of toxaphene-treated mice by DNA 32P-post-labeling showed no evidence of DNA adduct formation.

Animals↗

Oxidative modifications produced in HL-60 cells on exposure to benzene metabolites.

We have studied the effects of the benzene metabolites hydroquinone, p-benzoquinone or 1,2,4-benzenetriol on cytotoxicity, active oxygen formation, hydrogen peroxide (i.e. hydroperoxide) production and nitric oxide formation in HL-60 cells. We also examined the effects of these compounds on antioxidant enzymes and intracellular antioxidants in these cells. The cytotoxicity of benzene metabolites to HL-60 cells was found to be of the order of p-benzoquinone>hydroquinone>benzenetriol. No appreciable changes in the basal levels of either superoxide anion production or nitric oxide formation were observed following exposures to the benzene metabolites, but significant increases in superoxide were seen on stimulation with TPA for each metabolite, whereas hydroquinone and p-benzoquinone, but not 1,2,4-benzenetriol, increased nitric oxide production under these conditions. Following exposure to the benzene metabolites, HL-60 cells showed significant rises in hydrogen peroxide formation compared to controls. The study of antioxidant enzymes and intracellular antioxidants suggested that the benzene metabolites inhibit or reduce the levels of different antioxidant mechanisms and, thereby, cause the accumulation of free radicals in these cells predisposing them for oxidative damage.

Ascorbic Acid↗

Validation of cold chain procedures suitable for distribution of vaccines by public health programs in the USA.

To enhance quality assurance of vaccine distribution by public health programs in the US, various methods for packing vaccines were validated. Validation involved both tests in an environmental chamber and actual shipping of packages by commercial overnight delivery service. Dry ice was used with vaccines needing to be kept at temperatures lower than -14 degrees C, and water-based cold packs with other vaccines. The latter could be used in two ways. When frozen, and placed over two or three faces of well-insulated boxes, assortments of vaccines were kept cold but not frozen for 2 days or more. However, packages with -15 degrees C cold packs may reach < 0 degree C. When cold packs at refrigerator temperature cover four to six faces of well insulated boxes, vaccine freezing in winter conditions or warming in temperate conditions was slowed considerably. These approaches, which require materials costing less than approximately 1% of the cost of the vaccines they protect, provide examples of packaging suitable for overnight delivery of vaccines in the US in different seasons.

Cold Temperature↗

Fluoride stimulation of microsomal benzene metabolism.

Benzene metabolism was examined in hepatic microsomes from male Sprague-Dawley rats. In addition to phenol, a highly polar unidentified component was formed. Fluoride, but not other halides, stimulated in vitro formation of both metabolites. Fluoride did not affect covalent binding of benzene metabolites to protein. Other mixed-function-oxidase reactions, and codeine and ethylmorphine demethylation and benzo[a]pyrene hydroxylation, were not affected by fluoride. The polar metabolite(s) was not retained on either a C-18 reverse-phase or a DEAE-Sephadex anion-exchange column. Thus, although highly polar, this component does not appear to be anionic. These results suggest that an enzyme with high specificity for benzene is responsible for microsomal benzene metabolism. Both phenol and the polar metabolite(s) appear to be formed through a common initial step, which is stimulated by fluoride.

Animals↗

Effects of enzyme induction on microsomal benzene metabolism.

The effect of induction by phenobarbital (PB), beta-naphthoflavone (BNF), and benzene on benzene metabolism was studied in hepatic microsomes from male Sprague-Dawley rats. Two distinct forms of mixed-function oxidase activity appeared to metabolize benzene. One form was active at all substrate concentrations in microsomes from control, benzene-treated, and BNF-treated animals, and at benzene concentrations of 0.8 mM and below in microsomes from PB-treated animals. It was saturated at benzene concentrations above 0.4 mM, had a pH optimum of approximately 6.6, and was stimulated by fluoride. Pretreatment with benzene, but not BNF, increased benzene metabolism in these preparations. Benzene metabolism in microsomes from PB-induced rats was less active than in controls at benzene concentrations below 0.8 mM, but increased rapidly at higher benzene concentrations. Further characteristics of the PB-induced enzyme activity were that saturation was not observed at benzene concentrations as high as 4 mM, the pH optimum for benzene metabolism in these preparations was 7.1, metabolism was not stimulated by fluoride, and metabolism was inhibited by metyrapone. Both phenol and an unidentified polar component were formed from benzene in all microsomal preparations. Formation of the polar component was increased by PB pretreatment and inhibited by metyrapone, suggesting that formation of the polar component involves a step requiring cytochrome P-450.

Animals↗

From chaos to excellence: preparing for a successful Joint Commission survey.

The new joint Commission on Accreditation of Healthcare Organizations survey requirements make the preparation process more challenging than ever before. In today's competitive healthcare environment, a successful survey is imperative. The authors discuss multiple and innovative ways to prepare for a survey under the 1996 guidelines. Specific examples of processes and forms are included.

Accreditation↗

Updated feasibility trial experience with the Viaderm percutaneous access device.

The percutaneous access device (PAD) is used to connect an external drive unit to the Kantrowitz CardioVad (KCV), a cardiac assist device for the treatment of chronic heart failure. The PAD conveys pneumatic power from a drive unit to the implanted blood pump and an electrocardiogram signal from the myocardium to the drive unit. The device-tissue interface of the PAD is precoated with autologous fibroblasts cultured from a skin sample of the intended recipient. This preparation demonstrated long-term stability in animals and was adopted for use in patients receiving the KCV. The KCV is activated intermittently, and the drive unit may be connected and disconnected by the patient, which subjects the PAD to frequent manipulation. To date, the PAD has been implanted in nine patients ranging in age from 41 to 74 years. Implant times ranged from 2 to 458 days, for a total of 1082 days, of which 557 days were in an outpatient setting. Two patients experienced episodes of infection that did not originate from the PAD-tissue interface. This feasibility study demonstrated that (1) the PAD is stable and infection resistant in long-term ambulatory patients, (2) the PAD withstood the challenge of daily manipulation (the KCV is turned on and off electively), and (3) PADs can be replaced, if necessary.

Adult↗

Should Medicare HMO benefits be standardized?

Legislation enacted in 1990 standardized Medigap benefits but not the benefits of health maintenance organizations (HMOs) that serve Medicare beneficiaries. An examination of marketing materials in two large counties reveals the potential for enormous confusion among beneficiaries because of differences in wording to describe the same benefit, health plans' failure to list Medicare-covered services, and the differences in the benefits themselves. To date, the Health Care Financing Administration (HCFA) has not been able to overcome this confusion through the comparative material distributed on its Web site; indeed, significant errors were found, reflecting to some extent the underlying difficulties in characterizing benefits. Ways of ameliorating the situation are discussed.

Health Maintenance Organizations↗

Percutaneous transluminal coronary angioplasty with hemoperfusion.

Balloon inflation time during percutaneous transluminal coronary angioplasty (PTCA) is limited by the patient's tolerance to ischemia. A nonpulsatile, variable flow rate syringe pump that develops pressures up to 200 psi has been developed, along with PTCA catheters capable of delivering 0-70 cc/min of blood across a lesion at these pressures. Using this system, 110 patients have been treated with active hemoperfusion during routine PTCA. In eight cases, no preperfusion tolerated inflation time was obtained. In 96 of 102 cases, the tolerated inflation time was increased by at least 50%, for a success rate of 94%. This study demonstrated that active hemoperfusion during PTCA prolongs tolerated inflation time. The catheters and pump are capable of performing routine PTCA, supported when necessary by active hemoperfusion.

Angina Pectoris↗

Mortality patterns among the youth of a northeastern American Indian cohort.

Mortality patterns prevalent among American Indian youth have not been well documented. This investigation reports on mortality patterns among the Seneca Nation of Indians from January 1, 1955, through December 31, 1989. The study cohort consisted of 3,033 Seneca tribal members born during the study period. Deaths occurring among cohort members younger than age 25 were identified through a computer match against New York State vital record files. Sex-specific standardized mortality ratios were calculated on the basis of mortality patterns exhibited by the general population of New York State, exclusive of New York City. Males exhibited significantly elevated mortality for all causes combined, for deaths due to all accidents combined, for motor vehicle accidents, and for suicide. Females demonstrated significantly elevated mortality from all accidents combined, for motor vehicle accidents, and for all other types of accidents. Age-specific mortality patterns also varied both by sex and by calendar time. These findings are important to consider in the design of programs aimed at reducing premature mortality among American Indian populations from preventable causes of death.

Accidents↗