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Biomedical subjects

J D Adams

Publications and source records attributed to J D Adams.

At least 109 records · Page 6Linked to original sources
PubMed1984

Tobacco sidestream smoke: uptake by nonsmokers.

Some epidemiological studies indicate an association between passive smoking and an increased risk for cancer, especially for cancer of the lung. Other reports, however, have failed to confirm these findings. Biochemical analyses of the physiological fluids for markers of exposure to tobacco smoke are needed as measurements of the uptake of smoke components by nonsmokers and for the estimation of relative cancer risk to passively exposed persons compared with that to active cigarette smokers. This communication reports the uptake of carbon monoxide, hydrogen cyanide, and nicotine after passive smoke exposure under controlled conditions. The results indicate that salivary nicotine values reflect the level of recent passive smoke exposure within an hour and that urinary cotinine values indicate the level of passive smoke exposure in the preceding hours. N-Nitrosoproline has been shown to serve as an indicator of endogenous N-nitrosamine formation in cigarette smokers: yet, preliminary studies do not indicate that urinary excretion of N-nitrosoproline is increased following short-term passive smoke exposure. In infants, first field studies suggest a correlation between exposure to tobacco-smoke-polluted environments and levels of cotinine in both serum and urine.

Carboxyhemoglobin↗
PubMed1984

Carcinogenic agents in cigarette smoke and the influence of nitrate on their formation.

The nitrate level of a nonfilter reference cigarette was elevated from 0.52% to 1.2, 1.8, 2.4 and 3.05%, respectively, by addition of sodium nitrate. Data from the mainstream smoke analyses of these cigarettes were compared. Yields of carbon monoxide and carbon dioxide were not significantly altered as a result of nitrate elevation. Tar, nicotine, benzo[a]pyrene (BaP) and catechol in mainstream smoke were reduced while yields of nitrogen oxides (NOx), volatile N-nitrosamines (VNA) and tobacco-specific N-nitrosamines (TSNA) were significantly increased. On the basis of previous bioassays with smoke condensates from high-nitrate cigarettes, it was expected that the cutaneous tumorigenicity of these tars would be reduced due to lower levels of BaP (and other carcinogenic PAH) and catechol. However, the total carcinogenic potential of whole smoke from high nitrate cigarettes is considered by us to be significantly increased due to the elevated yields of Nox, VNA and TSNA. The nitrosamines are regarded as a major group of carcinogens in tobacco smoke; the nitrogen oxides are the most important precursors for the endogenous formation of N-nitrosamines upon smoke inhalation. The findings of this model study support the recommendation that the nitrate content of tobacco products should be reduced.

Carcinogens↗
PubMed1984

Ambulatory use of high-dose intravenous morphine for severe pain.

A case is presented that describes the use of an intravenous morphine infusion to treat severe pain in an outpatient setting. The patient had severe pain secondary to tumor involvement of the brachial plexus. Morphine was administered as a concentrated solution (50 mg/ml), using an autosyringe (model AS-2F) via a Hickman catheter. The dose was titrated to pain relief. A dose of 200-250 mg/h was required.

Aged↗
PubMed1984

Plasma glutathione disulfide as an index of oxidant stress in vivo: effects of carbon tetrachloride, dimethylnitrosamine, nitrofurantoin, metronidazole, doxorubicin and diquat.

The plasma concentrations of glutathione and glutathione disulfide were measured in rats following the administration of diquat, metronidazole, nitrofurantoin, doxorubicin, dimethylnitrosamine or carbon tetrachloride. None of these agents significantly influenced the plasma concentrations of glutathione. Diquat, metronidazole and nitrofurantoin acutely increased plasma glutathione disulfide by 4 to 13 fold from 0.3 +/- 0.1 microM to 3.8 +/- 1.1 microM, 2.0 +/- 0.5 microM and 1.2 +/- 0.3 microM, respectively. Carbon tetrachloride, doxorubicin and dimethylnitrosamine did not affect plasma glutathione disulfide. The determination of plasma glutathione disulfide identifies compounds that generate potentially toxic amounts of reactive oxygen species during their metabolism and helps to distinguish these compounds from xenobiotics which generate organic free radicals and electrophilic metabolites under toxicologically relevant conditions.

Animals↗
PubMed1984

Pharmacokinetics of tobacco-specific N-nitrosamines.

Methods were developed to determine the biological half-life of N'-nitrosonornicotine (NNN) and 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) in Syrian golden hamsters and Fischer rats. The formation and elimination of 4-(N-nitrosomethylamino)-1-(-3-pyridyl)-1-butanol (NNA1), the major metabolite of NNK, was determined in the context of this study. The method consisted of extraction of the nitrosamine with ethyl acetate, elution through a Clin-Elut column, and concentration of the sample, followed by gas chromatography-thermal energy analysis. Biological half-lives of NNN, NNK and NNA1 in hamsters were found to be 0.77, 0.25 and 1.78 h, respectively; in rats they were 5.78, 1.78 and 3.56 h. These findings clearly indicate species differences in the pharmacokinetics associated with the distribution and elimination of the tobacco-specific N-nitrosamines.

Animals↗
PubMed1983

On the formation of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone during smoking.

Tobacco-specific N-nitrosamines (TSNA) are the most abundant carcinogens identified in tobacco and its smoke. Reducing their levels in tobacco products and especially in cigarette smoke is, therefore, a primary goal towards minimizing the carcinogenic burden of the tobacco consumer. This study delineates the mechanisms of formation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), the most powerful of the carcinogenic TSNA during cigarette smoking. It demonstrates, by means of radiolabeled tracer compounds that 6.9-11.0% of the NNK formed in tobacco during the curing process transfers into the mainstream smoke. This constitutes 26-37% of the NNK present in the smoke. Addition of [methyl-14C]-nicotine to cigarettes, prior to smoking, led to the finding that 0.001% of nicotine in the cigarette column appears in the smoke as NNK. Thus, 63-74% of NNK in smoke is formed during smoking. NNK yield in the smoke was independent of nitrate content of the tobacco. These data serve to devise methods of reducing TSNA in smoke.

Carbon Radioisotopes↗
PubMed1983

Induction of respiratory tract tumors in Syrian golden hamsters by a single dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and the effect of smoke inhalation.

Four groups of 10 male and 10 female Syrian golden hamsters were given single s.c. injections of either 0.3 ml of trioctanoin or of 0.3 ml of trioctanoin containing either 1.0 mg, 3.3 mg, or 10.0 mg of the tobacco specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These hamsters were then exposed to cigarette smoke for the next 72 weeks. Four control groups received the same injections of NNK or trioctanoin but were treated by sham smoking. All groups treated with NNK had tumors of either the lung, nasal mucosa, and/or trachea. These tumors were not observed in hamsters injected with trioctanoin. These results demonstrate that even a single dose of NNK can induce respiratory tract tumors in Syrian golden hamsters. Smoke inhalation did not result in an increase in respiratory tract tumor incidence in most of the NNK treated groups.

Animals↗
PubMed1983

Reported cigarette smoke values: a closer look.

Effects of mechanical compression of the filter tips and of blocking the air channels of a special filter design on the smoke yields of seven brands of commercial filter cigarettes were investigated. In addition, the influence of these variables on actual uptake of smoke constituents by smokers was studied with four subjects. Compression of filter tips produced major increases in smoke yields for the cigarette which features a filter tip with four longitudinal air channels at its periphery. Blocking of these air channels increased tar yields by 51 per cent, nicotine by 69 per cent, and carbon monoxide by 147 per cent. Subjects who smoked the cigarette with this special filter design tended to smoke fewer cigarettes per day than when they smoked cigarettes with perforated filter tips, yet their plasma cotinine levels were significantly higher. Blood pressure and pulse rate were markedly elevated after first exposure to smoke from the special filter cigarette, as were plasma nicotine levels. These results point out that individuals inhale different quantities of smoke constituents from cigarettes with reportedly similar smoke yields according to Federal Trade Commission methods. A redefinition of "average" smoking parameters readjustment of standard laboratory methodology are suggested.

Carbon Monoxide↗
PubMed1983

Plasma glutathione and glutathione disulfide in the rat: regulation and response to oxidative stress.

Plasma GSH and GSSG concentrations were examined after the administration of compounds that deplete intracellular GSH either by adduct formation or by production of oxidative stress. A modified assay based on the GSSG reductase method was developed that minimizes the artifactual auto-oxidation of GSH to GSSG and mixed disulfides by rapid addition of bis(3-carboxy-4-nitrophenyl)disulfide or N-ethylmaleimide directly to whole blood or tissue samples. Control arterial plasma GSH and GSSG concentrations were found to be 16.5 +/- 0.7 and 0.3 +/- 0.1 microM, respectively. Depletion of GSH by fasting or by the administration of acetaminophen or diethyl maleate was associated with a proportional decrease in the arterial plasma GSH concentrations (r = 0.94) consistent with the hypothesis that the liver in vivo is a major source of plasma GSH. Diquat and t-butyl hydroperoxide, but not acetaminophen or diethyl maleate, elicited large increases in arterial plasma GSSG concentrations (17- and 115-fold, respectively) and several-fold increases in biliary GSSG levels without markedly increasing hepatic GSSG levels (2.7- and 1.2-fold, respectively). In contrast, treatment with paraquat produced substantial increases in arterial plasma GSSG levels (22-fold) without large increases in the bile (3-fold). Assessment of the arteriovenous difference for GSSG across the lungs after paraquat administration demonstrated that the lung may be a significant source of plasma GSSG. In conclusion, plasma GSH concentrations appear to reflect mainly intrahepatic GSH concentration, whereas plasma GSSG appears to arise from both hepatic and extrahepatic sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1983

Effects of route of administration and dose on the carcinogenicity of N-nitrosodiethanolamine in the Syrian golden hamster.

N-Nitrosodiethanolamine was assayed for carcinogenicity in Syrian golden hamsters by s.c. injection, topical application, and oral cavity swabbing. Three groups of 30 hamsters each received 27 weekly s.c. injections of either 500, 170, or 58 mg of N-nitrosodiethanolamine per kg in 0.9% NaCl solution. In the group treated with 500 mg/kg, 19 of 30 animals developed nasal cavity tumors, 7 of 30 had tracheal tumors, and 2 of 30 had tumors of the larynx. Among the animals treated with 170 mg/kg, 7 of 29 presented with nasal cavity tumors and 4 of 29 presented with tracheal tumors. In the group treated with 58 mg/kg, only two tracheal tumors were observed. Acetone solutions of N-nitrosodiethanolamine were applied to the shaved backs of three groups of 30 hamsters, each three times weekly for 36 weeks, at doses of 25, 8, or 2.5 mg; the total doses were the same as in the groups treated by s.c. injection. At the 25-mg dose level, 5 of 30 animals developed nasal cavity tumors and 4 of 30 animals had tumors of the trachea. No skin tumors were observed. The incidence of respiratory tract tumors in the groups treated with 8 or 2.5 mg was not significant compared to controls. The oral cavities of 40 hamsters were swabbed three times weekly for 45 weeks with 20 mg of N-nitrosodiethanolamine; the total dose was the same as the highest doses given by s.c. or topical administration. Seventeen of 38 hamsters had nasal cavity tumors, 6 of 38 developed tracheal tumors, and 1 of 38 presented with a tumor of the larynx. No tumors were observed in the oral cavity. The results of this study demonstrate that N-nitrosodiethanolamine is organospecific for the Syrian golden hamster nasal cavity and trachea and that it induces tumors in these sites at doses lower than previously reported.

Administration, Oral↗