Search PubMed⌕ Search

Biomedical subjects

J D Adams

Publications and source records attributed to J D Adams.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1989

Optimal performance health. Making sure employees run on all cylinders without rustout or burnout.

To promote and sustain high level performance, which also promotes and sustains high level health, there are a few low cost and easy-to-implement factors available to the manager. One is to encourage and even reward positive self management habits such as regular exercise, regular relaxation, good nutrition, not smoking, very limited alcohol use, and management of blood pressure and cholesterol levels. The second is to develop and enhance the four C's--challenge, control, commitment, and clarity t--through conscious and dedicated management practice. When these factors are fully in place, the department will realize unprecedented levels of sustained performance plus sharply reduced costs due to absenteeism, turnover, and health benefits payments.

Burnout, Professional↗
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

3-Methylindole inhibits lipid peroxidation.

The mechanism of pneumotoxicity of 3-methylindole has been postulated to occur via protein alkylation or lipid peroxidation. This report describes the effects of the addition of 3-methylindole to goat lung microsomes to evaluate the possibility that this xenobiotic may increase NADPH-supported lipid peroxidation. Concentrations of malondialdehyde were measured as an index of lipid peroxidation. Instead of a stimulation of lipid peroxidation by 3-methylindole, a complete inhibition of lipid peroxidation was produced by concentrations of 3-methylindole as low as 10 microM. The addition of 3-methylindole to actively peroxidizing microsomes (NADPH-supported) caused an immediate cessation of malondialdehyde production. These results demonstrate that 3-methylindole pneumotoxicity does not proceed by a mechanism of lipid peroxidation, but in fact, this molecule may act as an effective antioxidant to prevent lipid peroxidation in pulmonary tissue.

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

Tumorigenic activity of the tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanol (iso-NNAL) and N'-nitrosonornicotine (NNN) on topical application to Sencar mice.

The tumor-initiating activities of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanol (iso-NNAL) and N'-nitrosonornicotine (NNN) were evaluated on the skin of female SENCAR mice. A total initiator dose of 28 mumol/mouse of each nitrosamine was applied in 10 subdoses administered every second day. Promotion commenced 10 days after the last initiator dose and consisted of twice weekly application of 2.0 micrograms of tetradecanoylphorbol acetate for 20 weeks. NNK induced a 79% incidence of skin tumors with an average of 1.6 tumors/mouse and a 59% incidence of lung adenomas. In contrast, iso-NNAL and NNN were not active as tumor initiators in either the skin or lung of mice. The tumorigenic activity of NNK on SENCAR mouse skin was evaluated at several doses. At a total initiator dose of 28 and 5.6 mumol/mouse, NNK exhibited significant activity (P less than 0.005) inducing a 59% and 24% incidence of skin tumors, respectively. In this dose response bioassay, NNK at a total initiator dose of 28 mumol induced a 63% incidence (P less than 0.005) of lung adenomas. The numbers of lung adenomas induced at the lower doses employed were not significant. NNK, at a total initiation dose of 1.4 mumol, did not exhibit significant tumorigenic activity (P greater than 0.05). Analysis of DNA from the skin of mice treated with NNK using HPLC with fluorescence detection failed to detect O6- and N-methylguanine (O6-MG and N7-MG) adducts. These data indicate that NNK can exert a contact carcinogenic effect and suggest that mechanisms other than DNA methylation may be involved in its activation to a tumorigenic agent in mouse skin.

Administration, Topical↗
PubMed1987

A critical look at N-nitrosamines in environmental tobacco smoke.

The amounts of cigarette smoke carcinogens released into the environment as sidestream smoke (SS) constituents are generally twice as high as the levels of the carcinogens that are inhaled as mainstream smoke (MS). However, certain carcinogens in undiluted SS, such as nitrosamines, exceed MS levels up to 50 times. Regardless of the fact that SS is usually substantially diluted before being inhaled, its constituents can be determined in environmental tobacco smoke (ETS) by modern analytical methods and levels of exposure of involuntary smokers can be assessed by the use of specific markers. Currently, the uptake of ETS by nonsmokers is determined by measuring nicotine and its metabolite cotinine in saliva, serum and/or urine. In on-going studies, we are now exploring the determination of the two highly carcinogenic nicotine-derived nitrosamines N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), respectively of their metabolites, in physiological fluids of smokers and nonsmokers.

Animals↗
PubMed1987

Uptake of sidestream smoke by Syrian golden hamsters.

An inhalation bioassay with Syrian golden hamsters is being conducted to evaluate the toxic and carcinogenic potential of cigarette sidestream smoke (SS) relative to mainstream smoke (MS). A Hamburg II smoking machine is used to deliver MS by nose-only exposure to hamsters and a modification allows for the simultaneous collection of SS for whole-body delivery to a different rack of animals. The tolerated dose of SS was determined by varying the air/smoke dilutions drawn through the animal restrainers. Preliminary data indicated that 20% carboxyhemoglobin (COHb) could be obtained in SS-exposed animals without fatality. Optimum exposure levels were determined. Monthly measurements of COHb, nicotine and cotinine indicate that the SS-exposed animals are absorbing slightly higher amounts of these smoke constituents than the MS-exposed hamsters. Tumor incidence and carcinogenicity data are being collected through complete necropsy and histology protocols and uptake data continue to be collected. These studies should help elucidate the carcinogenic potential of SS which has been suggested from its composition and from recent epidemiological data of cancer incidence in non-smokers.

Animals↗
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

Transfer of the tobacco-specific carcinogens N'-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene into the milk of lactating rats.

The extent to which some of the more prevalent and potent carcinogens in cigarette smoke could be transferred from circulating blood into the milk of lactating rats was determined. One hour after i.v. administration of benzo[a]pyrene (BaP), N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to the dams, the levels of these carcinogens were determined in both blood and milk specimens. The average amount of radioactivity detected 1 h after administration of 14C-labeled BaP was 0.21% of the administered dose per ml of milk as compared with 0.17% per ml of blood. The amount of NNN in milk ranged from 0.20 to 0.36% of the administered dose per ml which closely paralleled the levels detected in blood. NNK is readily converted in vivo to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). The sum of NNK and NNAL was similar in the blood and milk of treated dams. There was, however, a major difference in the ratio of NNAL/NNK as detected in milk and blood. The ratio of NNAL/NNK in blood ranged from 1.3:1 to 1.9:1 while the ratio in milk ranged from 2.4:1 to 3.3:1. In a comparative study of the levels of NNN in the blood and milk of lactating rats at less than 1.0, 20, 60, 120 and 240 min after administration, it was confirmed that similar concentrations of NNN are present in blood and milk 1 h after administration. These data indicate that these carcinogens, which are present in both cigarette smoke and tobacco, can be transferred into the milk of lactating rats.

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↗
PubMed1987

Biotransformation of ketamine, (Z)-6-hydroxyketamine, and (E)-6-hydroxyketamine by rat, rabbit, and human liver microsomal preparations.

1. (Z)- and (E)-6-Hydroxyketamine have been synthesized and their metabolism by hepatic microsomal preparations studied to elucidate the metabolism of ketamine. 2. Both 6-hydroxyketamines are exclusively converted to 6-hydroxy-norketamines by N-demethylation. The g.l.c. retention properties and mass spectral characteristics of these 6-hydroxy-norketamines were used to confirm the structures of ketamine metabolites. 3. Ketamine is converted to norketamine, 4-, 5- and 6-hydroxynorketamines and possibly 4- and 6-hydroxyketamines in hepatic microsomal preparations from rats, rabbits and man. Norketamine is the major metabolite in all species tested. 4. 6-Hydroxynorketamine is the major hydroxylated metabolite and is found only in the (Z)-form in the species examined. 5. The metabolism of ketamine and the 6-hydroxy-ketamines is greatly increased after phenobarbital pretreatment of rats and rabbits.

Animals↗
PubMed1987

Selenium in mainstream and sidestream smoke of cigarettes containing fly ash-grown tobacco.

The quantities of selenium, tar and nicotine present in mainstream (MS) and sidestream (SS) smoke of machine-smoked cigarettes was studied. The cigarettes were prepared from tobacco purposely cultured on fly ash-amended soil so as to increase its selenium concentration. Selenium concentration was found to be the same in the gaseous phase of both MS and SS smoke, but its concentration was significantly higher (p less than 0.05) in the particulate matter of the MS smoke. Tar was higher in MS smoke and nicotine in SS smoke. Factors affecting selenium concentrations in tobacco and its possible environmental significance are discussed.

Carbon↗
PubMed1987

Effectiveness of cigarette filter tips for reducing cadmium in relation to other mainstream smoke constituents.

The effectiveness of filter tips for reducing cadmium, tar, nicotine, carbon monoxide and carbon dioxide in cigarettes was studied. The cigarettes were made from tobacco grown on municipal sewage sludge-amended soil and were therefore high in cadmium. When machine-smoked, filter tips did not result in a significant reduction of cadmium deposited on Cambridge filters. This may indicate that a considerable fraction of cadmium is present in the vapor phase of the smoke and therefore not reduced to the same extent as the tar by certain filters. Nicotine and carbon monoxide were reduced to a lesser extent than tar. This indicates that the filter tip has influenced the combustion of the tobacco column during smoking.

Cadmium↗