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Biomedical subjects

J D Adams

Publications and source records attributed to J D Adams.

At least 19 recordsLinked to original sources
PubMed1992

Relative potency estimates of acceptable residues and reentry intervals after nerve agent release.

In the event of an unplanned release of a chemical warfare agent during any stage of the Chemical Stockpile Disposal Program, the potential exists for off-post contamination of drinking water, forage crops, grains, garden produce, and livestock. The more persistent agents, such as the organophosphate nerve agent VX, pose the greatest human health concern for reentry. A relative potency approach comparing the toxicity of VX to organophosphate insecticide analogues is developed and used to estimate allowable residues for VX in agricultural products and reentry intervals for public access to contaminated areas. Analysis of mammalian LD50 data by all exposure routes indicates that VX is 10(3) to 10(4) times more toxic than most commercially available organophosphate insecticides. Thus, allowable residues of VX could be considered at concentration levels 10(3) to 10(4) lower than those established for certain insecticides by the U.S. EPA. Evaluation of reentry intervals developed for these organophosphate analogues indicate that, if environmental monitoring cannot reliably demonstrate acceptable levels of VX, restricted access to suspect or contaminated areas may be on the order of weeks to months following agent release. Planning for relocation, mass care centers, and quarantine should take this time period into account.

Chemical Warfare Agents↗
PubMed1992

The acute retinal histopathology of MPTP.

The effects of MPTP on the retina have been examined with emphasis on the effects that are apparent within a few hours of administration. Histopathologic changes were found within one day after MPTP administration. These changes were most prominent in the Muller cells, which demonstrated edematous changes in the cellular processes and occasionally pyknotic nuclei in the inner nuclear layer. Capillary endothelial cells also were damaged by MPTP administration as evidenced by disruption of the cellular cytoplasms. This damage may have caused pooling of blood in the blood vessels of the retina. Finally, mitochondria in some retinal layers may have been altered by MPTP administration with swelling and possible rupture seen in some cells. These acute effects of MPTP may be involved in the formation of lesions to dopaminergic amacrine cells found in the retina following MPTP exposure.

Animals↗
PubMed1991

Alzheimer's and Parkinson's disease. Brain levels of glutathione, glutathione disulfide, and vitamin E.

Human brain levels of glutathione (GSH), glutathione disulfide (GSSG), and vitamin E were measured in neurologically normal control patients and two groups of patients with neurodegeneration: those with Alzheimer's disease (AD), and AD with some features of Parkinson's disease (AD-PD). Control brain samples contained GSH levels more than 50 times higher than GSSG. The levels of GSH were highest in the caudate nucleus and lowest in the medulla. In patients with AD or AD-PD, hippocampal levels of GSH were significantly higher than controls. Patients with AD also demonstrated high GSH levels in the midbrain compared to normal. In contrast, patients with AD-PD did not have significantly elevated GSH levels in this site. GSSG levels were not significantly different in any brain region between controls and diseased patients. In control brains, the medulla had higher levels of vitamin E than any other brain region. The caudate nucleus had the lowest levels, which were about half the levels in the medulla. Control levels of vitamin E in the midbrain were about 18.8 micrograms/g. In AD patients the midbrain levels of vitamin E doubled to 42.3 micrograms/g. This doubling also occurred in AD-PD patients where midbrain vitamin E levels increased to 44.0 micrograms/g. These results may indicate that compensatory increases in GSH and vitamin E levels occur following damage to specific brain regions in patients with AD or AD-PD.

Aged↗
PubMed1991

Effects of MPTP on the cerebrovasculature.

The neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, has been shown to cause pooling of blood in the brain microvasculature and decrease the permeability of the blood-brain barrier. All areas of the brain examined in this study were affected. This study points out the possibility that reduced nutrient uptake, hypoxia and ensuring free radical damage are involved in the mechanism of toxicity of this neurotoxin.

Animals↗
PubMed1991

Oxygen free radicals and Parkinson's disease.

The involvement of oxygen radicals in the pathogenesis of Parkinson's disease has been suggested for some time. This article reviews the evidence supporting the involvement of oxygen radicals in the disease process in the brain. This includes a discussion of iron, lipid peroxidation, peroxidase, catalase, superoxide dismutase, and glutathione levels in the brain. In addition, various theories of induction of Parkinson's disease are discussed in relation to the possible involvement of oxygen radicals. These theories include the environmental toxin theory, the dopamine turnover theory, and the cerebral blood flow theory.

Brain↗
PubMed1990

MPTP toxicity in the mouse brain and vitamin E.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused transient alterations in vitamin E levels in every brain region examined. However, vitamin E returned to normal levels within a few hours in all brain regions but the substantia nigra, where at 2 days vitamin E levels first rose above normal levels. Vitamin E deficient mice were much more susceptible to MPTP toxicity than controls, in terms of lethality and DOPAC depletion in the substantia nigra. However, in the same vitamin E deficient mice, the striatum was partially protected from neurotransmitter and metabolite depletion by MPTP. The mechanism of toxicity of MPTP may differ in the striatum and the midbrain.

Animals↗
PubMed1989

Perturbations in cerebral oxygen radical formation and membrane order following vitamin E deficiency.

The effects of dietary vitamin E deficiency on mouse cerebral membrane order and oxygen reactive species were studied. Quantitation of vitamin E levels in several brain regions showed greatest deficiencies in striatum and cerebellum, followed by substantia nigra, and cortex. Vitamin E deficiency increased central-core membrane order in cerebral P2 fraction, but was without effect in the superficial hydrophilic membrane domain. Oxygen radical formation was studied using the probe 2',7'-dichlorofluorescein diacetate. Basal generation rates of oxygen reactive species were 2.5-fold higher when compared to control animals. While hepatic levels of vitamin E are much more reduced than brain levels, in deficient mice, the rate of oxygen radical formation in the liver was unaltered. This implies an special susceptibility of the brain to deficiency of this lipophilic antioxidant vitamin. Data demonstrate that endogenous levels of free radical scavengers, such as vitamin E, may play an important role in maintaining basal oxygen radical levels and membrane integrity. The dietary vitamin E depletion paradigm suggests that a relation exists between elevated levels of oxygen radicals and more rigid hydrophobic central-cores in cerebral membranes, effects that may play a role in mechanisms underlying the neuropathologic lesions observed following vitamin E deficiency.

Animals↗
PubMed1988

Pathology and glutathione status in 3-methylindole-treated rodents.

Light and electron microscopic studies were performed to assess the pathology induced by 3-methylindole (3MI) in Sprague-Dawley rats and Swiss-Webster mice. Rats have not been established as a susceptible species to 3MI-induced pulmonary damage, whereas mice are known to be a good model for this pneumotoxicity. Therefore, mice were used as a comparison species for pneumotoxicity studies in the rat. Rats were as susceptible to 3MI-mediated toxicity as mice. The loss of Clara cells in the bronchiolar epithelium was the major pulmonary lesion in both species. Alveolar cells in the lungs of either species were not damaged. The only other lesion in the rat was that the nasal epithelium was totally eroded in caudal areas of the sinuses. Glutathione was depleted by 3MI in pulmonary tissues of mice and rats. Maximal depletion (53% of control values) occurred in rat lung. This work demonstrates that both rodent species are susceptible to 3MI-induced pulmonary damage.

Animals↗
PubMed1987

Decreased pneumotoxicity of deuterated 3-methylindole: bioactivation requires methyl C-H bond breakage.

The bioactivation of the pulmonary toxin 3-methylindole has been postulated to proceed via the formation of an imine methide. To test this hypothesis, the toxicity in mice of 3-methylindole has been compared to the toxicity of its perdeuteromethyl analog. Deuteration of the methyl group should slow the rate of production of the corresponding imine methide and diminish the toxicity of deutero-3-methylindole, if C-H bond breakage occurs prior to or during the rate-determining step. In agreement with this hypothesis, deutero-3-methylindole was synthesized and was shown to be significantly less toxic (LD50 735 mg/kg) than 3-methylindole (LD50 578 mg/kg). Both compounds produced the same lesion at the LD50 dose, bronchiolar damage and mild alveolar edema, indicating that deuteration of 3-methylindole did not change the pathologic process. However, at a much lower dose (25 mg/kg), 3-methylindole produced a mild bronchiolar lesion whereas deutero-3-methylindole did not damage lung tissue. Additionally, administration of deutero-3-methylindole caused less pulmonary edema compared to 3-methylindole, as assessed by increased wet lung weights. Finally, the depletion of pulmonary glutathione by deutero-3-methylindole was considerably slower than depletion by 3-methylindole. The electrophilic imine methide has been postulated to be the intermediate which binds with and depletes glutathione. Therefore, the evidence presented here supports the involvement of an imine methide as the primary reactive intermediate in 3-methylindole-mediated pneumotoxicity.

Animals↗
PubMed1987

Tobacco-specific N-nitrosamines in dry snuff.

Case-control studies have shown that the oral use of dry snuff has an aetiological association with cancer of the oral cavity. This communication reports high concentrations of the powerful carcinogen N'-nitrosonornicotine (9.37-55.3 micrograms/g), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (1.98-14.4 micrograms/g) and of N'-nitrosoanatabine (18.8-40.2 micrograms/g) and N'-nitrosoanabasine (0.66-1.17 microgram/g) in three popular brands of dry snuff available in the USA.

Alkaloids↗
PubMed1987

Effect of snuff and nicotine on DNA methylation by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

In this study we assayed the effects of snuff and nicotine on the DNA methylation by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a powerful tobacco-specific N-nitrosamine. Male F344 rats were pretreated for 2 weeks with either a solution of a snuff extract or 0.002% nicotine in the drinking water. Subsequently, the rats were given a single dose of NNK and the effects of snuff and nicotine on the methylation of guanine by NNK in the DNA of target organs of this carcinogenic nitrosamine were determined. Formation of 7-methylguanine in the liver, nasal mucosae and oral cavity and of O6-methylguanine in the liver and oral cavity was much lower in the rats pretreated with snuff extract than in those not pretreated. On the other hand, pretreatment of the rats with nicotine had no significant effect on the methylation of DNA by NNK nor on the elimination constants of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridly)-1-butanol.

Animals↗
PubMed1987

Toxic and carcinogenic agents in undiluted mainstream smoke and sidestream smoke of different types of cigarettes.

The mainstream and sidestream smoke of four types of popular US cigarettes were analyzed for toxic and carcinogenic agents. The cigarettes included one without a filter tip, and one filter cigarette each with medium, low and ultra-low smoke yields. The analyses clearly demonstrated that 12 toxic agents determined in this study were significantly reduced in the mainstream smoke of filter cigarettes, as compared with smoke yields from the nonfilter cigarette. In the case of the ultra-low yield cigarette, mainstream smoke emissions were reduced by about 90%. In contrast to this finding, the emissions of the same toxic and carcinogenic components into sidestream smoke of the filter cigarettes were not greatly reduced. Sidestream smoke is the major contributor to environmental tobacco smoke, to which both smokers and non-smokers are exposed. Although the exposure of the smoker to mainstream smoke components is decreased due to proportionally greater consumption of low and ultra-low yield cigarettes, and lower rates of consumption of cigarettes with high smoke yields, the carcinogenic potential of indoor pollutants originating from tobacco products is not diminished.

Ammonia↗