Biomedical subjects

B T Culpepper

Publications and source records attributed to B T Culpepper.

6 recordsLinked to original sources

PubMed1990

The determination of the repeated oral toxicity of halocarbon oil, series 27-S.

Halocarbon 27-S (HC 27-S), a polymer of chlorotrifluoroethylene (CTFE), is used as a lubricating oil for pumps in hyperbaric chambers. Although monomeric CTFE has been shown to produce renal lesions in rats, the toxicity of CTFE polymers have not been investigated. To assess the toxicity of repeated exposure to HC 27-S, three groups (N = 6/group) of male and female Fischer-344 rats were dosed with 2.5 g HC 27-S/kg for 7 or 21 consecutive days. Groups were sacrificed at 7, 21, and 35 days (14 days after the 21-day dosing). Corresponding control groups (N = 6) were dosed with deionized water. Decreased water consumption and urine output were apparent in all test groups. Statistically significant increases in fluoride excretion were noted in 24-hr urine samples assessed periodically during the study. Neurotoxic signs were observed in female rats but not in male rats. Significant increases in liver and kidney weights were seen in all rats, regardless of number of dosing days. The increased fluoride burden in treated animals appeared sufficient to alter bone calcium/phosphate ratios in male rats but not female rats. Gross liver enlargement and hepatocellular cytomegaly indicated that the liver was probably the primary target organ following repeated administration of HC 27-S.

Animals↗

PubMed1988

Prostacyclin and thromboxane formation following chronic exposure to cigarette smoke condensate administered via osmotic pumps in rats. A method for chronic administration of particulates of whole smoke.

Chronic cigarette smoke exposure in vivo causes decreased conversion of [14C]arachidonic acid (AA) to prostacyclin (PGI2) by isolated aortic tissue and increased conversion to thromboxane (TXA2) by isolated platelets from rats. Alterations in the PGL2/TXA2 balance may be part of the mechanism by which smoking increases the risk of cardiovascular disease. In order to ascertain whether the particulate phase of whole smoke alone could cause these changes, rats were administered smoke condensate in propylene glycol for 56 days via two Alzet (2ML4) osmotic pumps. Pumps containing vehicle, low dose (150 micrograms/hr) or high dose (300 micrograms/hr) condensate were implanted s.c. dorsal to the thoracic vertebrae in male Sprague-Dawley rats. Three-quarters of the condensate-treated rats developed fibrin cysts encapsulating the pumps. Cysts were not seen in vehicle-treated rats. Residual pump contents were weighed and analyzed by GLC to ensure condensate delivery. No significant difference in weight gain patterns between sham-operated and treatment groups were observed. Vehicle had no effect on aortic PGI2 or platelet TXA2 formation compared to sham. Low-dose condensate was without effect on PGI2/TXA2 formation. In high-dose condensate-treated rats, PGI2 and TXA2 formation were 84% and 136%, respectively, of the vehicle control (n.s.). Pump encapsulation may be a limiting factor in the administration of complex particulate suspensions.

Animals↗

PubMed1988

Relative participation of the gas phase and total particulate matter in the imbalance in prostacyclin and thromboxane formation seen following chronic cigarette smoke exposure.

Chronic exposure to cigarette smoke causes an imbalance in the ratio of PGI2 and TXA2 production and is believed to favor the development of atherosclerosis. Components of the particulate phase of smoke (especially nicotine) as well as the gas phase of smoke have been shown to adversely alter arachidonic acid metabolism. To determine the relative participation of nicotine, particulate and gas phases in eliciting an imbalance in TXA2 formation, male Sprague-Dawley rats were chronically exposed (7 days/wk/mo.) to freshly generated whole smoke or gas phase from University of Kentucky Reference cigarettes and allowed access to regular drinking water or to water supplemented with nicotine (10 micrograms/ml). COHb levels were monitored to confirm smoke or gas phase inhalation. All treatment groups had lower body weights than shams. No differences in body weights were observed between smoke (+/- oral nicotine) and gas phase (+/- oral nicotine) treatment groups but all were significantly lower than oral nicotine treated animals. Platelet TXA2 production was elevated in all treatment groups compared to shams. No differences in TXA2 production were observed between smoke (+/- oral nicotine), gas phase and oral nicotine treated animals. Animals receiving gas phase/oral nicotine exhibited significantly higher platelet TXA2 production compared to the other treatments. Constituents of the gas phase as well as the particulate phase of whole smoke were both shown to elevate platelet TXA2 formation. Components of the particulate matter appear to modulate the effects of nicotine and the gas phase in the perturbation of TXA2 production in the rat smoking model.

Animals↗

PubMed1987

Alterations in prostacyclin and thromboxane formation following chronic exposure to high and low nicotine cigarettes in rats.

Chronic exposure to cigarette smoke causes an imbalance in both PGI2 and TXA2 production which is believed to favor the development of atherosclerosis. Nicotine, a major constituent of smoke, has been shown to adversely alter arachidonic acid metabolism. To determine whether varying doses of nicotine in cigarettes would influence the extent of PGI2/TXA2 alterations, male Sprague-Dawley rats were chronically exposed (7 days/wk/6 mo.) to smoke from University of Kentucky Reference cigarettes containing "low" nicotine (3A1), "high" nicotine (2R1) and "low" nicotine cigarettes spiked with enough nicotine to deliver amounts equivalent to the 2R1. COHb levels were monitored to confirm smoke inhalation. No differences in body weights were observed between treatment groups, but all were significantly lower than sham. Aortic PGI2 formation was not significantly depressed by any of the treatment groups compared to shams. Platelet TXA2 production was elevated in all treatment groups compared to shams, irrespective of nicotine content. In the rat smoking model, low nicotine cigarettes do not appear to be an advantage over higher nicotine cigarettes.

Animals↗

PubMed1986

Alterations in prostacyclin and thromboxane formation by chronic cigarette smoke exposure: temporal relationships and whole smoke vs. gas phase.

Chronic cigarette smoke exposure in vivo causes decreased conversion of [14C]arachidonic acid (AA) to prostacyclin (PGI2) by isolated aortic tissue and increased conversion to thromboxane (TXA2) by isolated platelets from rats. Alterations in the PGI2/TXA2 balance may be part of the mechanism through which smoking increases the risk of cardiovascular disease. To study the influence of smoke exposure duration on this response, male rats were exposed daily to 10 puffs of freshly generated cigarette smoke. Animals were killed after 1, 4, 14, 28 and 57 days of smoke exposure and 3, 7, 14 and 28 days after cessation of the 57-day of smoke-exposure regimen. Elevated carboxyhemoglobin levels during the smoke-exposure sessions verified smoke (gas phase) inhalation. Statistically significant alterations in prostacyclin synthesis preceded those of thromboxane. A decrease of 20-25% (P less than 0.05) in PGI2 production from [14C]AA in isolated aortic tissue was found beginning 28 days after smoke was initiated and quickly rebounded when smoke exposure was terminated. Increased production of TXA2 from [14C]AA by isolated platelets became statistically significant (P less than 0.05) on the 57th day and returned to normal 7-14 days after cessation of smoke exposure. To determine the effect of gas phase constituents on the PGI2/TXA2 balance a second series of experiments divided male and female Sprague-Dawley rats into sham, whole smoke and gas phase groups. Gas phase was produced by passing whole smoke through a Cambridge filter to remove particulate matter. Per cent COHb averaged 1.4 for sham, 7.8 for whole smoke and 9.4 for gas phase groups.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

PubMedDate not supplied

Research integrity: a government perspective.

What is research integrity? At the United States Environmental Protection Agency (U.S. EPA) research integrity can be defined as conducting and fostering research to define, anticipate, and understand environmental problems; and generating sound, appropriate, credible, and effective solutions to those problems. Whether in government, academia, or industry, integrity is required at all stages of research--from data generation to data analysis. What constitutes research integrity? Simply put, Did we do the right thing? Did we do it the right way? Did we honestly document what we did? This is especially important if the research is used as a basis for public policy. The extensive and intensive use of the results of science in EPA's standard setting, regulatory, and enforcement responsibilities means that scientific misconduct can lead to costly and inappropriate actions through unnecessary expenditure or inadequate protection. The soundness, effectiveness, and credibility of EPA's regulations ultimately rest on the scientific and technical bases for these actions. Careful attention to research record keeping can help ensure data quality and integrity. The U.S. Environmental Protection Agency, its research requirements, and the work of the National Health and Environmental Effects Research Laboratory are discussed below.

Environmental Monitoring↗