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Biomedical subjects

H Van Vunakis

Publications and source records attributed to H Van Vunakis.

At least 37 records · Page 2Linked to original sources
PubMed1987

Production of antibodies to palytoxin: neutralization of several biological properties of palytoxin.

Palytoxin stimulated arachidonic acid metabolism (in bovine aorta endothelial and smooth muscle cells, rat keratinocytes, porcine aorta endothelial cells and rat liver cells), hemolyzed rat erythrocytes and was lethal to mice when administered intraperitoneally. Serum from rabbits immunized with a conjugate in which palytoxin was covalently bound to bovine albumin through its free amino group neutralized these biologic activities of palytoxin. Ninety-nine per cent of the neutralizing activity of the immunized rabbit serum was removed after precipitation of the rabbit IgG with a goat anti-rabbit IgG.

Acrylamides↗
PubMed1986

Stereospecific monoclonal antibodies to nicotine and cotinine and their use in enzyme-linked immunosorbent assays.

Stereospecific monoclonal antibodies (McAb) have been prepared against the tobacco alkaloid (S)-(-)-nicotine and its major metabolite (S)-(-)-cotinine. Nine anti-nicotine and 4 anti-cotinine hybridomas, selected by a screening procedure that utilized immunoprecipitation of the 3H-labeled natural isomers of nicotine or continine, were grown in the ascites fluid of pristane-primed syngeneic BALB/c mice. Antibodies in concentrations up to 7.5 mg/ml ascites and with binding affinities that generally exceeded 10(8) M-1 were obtained. Enzyme-linked immunosorbent assays (ELISAs) were developed in which nicotine or cotinine derivatives bound covalently to poly-L-lysine were coated onto wells of polyvinyl chloride microtiter plates. Coated wells were incubated sequentially with McAb in the presence or absence of inhibitor, rabbit anti-mouse immunoglobulin, then horseradish peroxidase-labeled protein A (HRP-SpA) before addition of substrate. The antibodies are highly specific and show minimal cross-reactivity with several nicotine metabolites and other structurally related compounds. In the respective assays, only 0.25 ng (S)-(-)-nicotine and 0.12 ng (S)-(-)-cotinine are required to give 50% inhibition of antibody binding, and as little as 0.05 ng nicotine and 0.02 ng cotinine give 15% inhibition. These assays are 5-10 times more sensitive than analogous ELISAs developed with rabbit antisera and HRP-SpA or conventional radioimmunoassays (RIAs) that utilize the rabbit antisera and 3H-labeled ligands. There was good correlation between the levels of nicotine (r = 0.967) and cotinine (r = 0.981) found in saliva samples from smokers and non-smokers assayed by McAb-based ELISAs and conventional RIAs.

Antibodies, Monoclonal↗
PubMed1985

Uterine blood flow and catecholamine response to repetitive nicotine exposure in the pregnant ewe.

In order to simulate human smoking, experiments were designed to determine what dose of nicotine in the pregnant sheep would produce those plasma nicotine concentrations observed in human smokers and to measure uterine blood flow and plasma catecholamines in response to repetitive exposure (every 30 minutes) to that nicotine dose. Utilizing seven chronically catheterized pregnant sheep equipped with electromagnetic flow probes around both uterine arteries, we observed that a nicotine dose of 0.2 mg/min for 5 minutes results in mean plasma nicotine concentrations of 23.1 +/- 1.1 ng/ml SEM (n = 17) immediately following infusion. This dose of nicotine was then infused every 30 minutes for 4 hours, and aliquots of blood were drawn immediately before and after nicotine infusion for determination of plasma catecholamines. No significant alterations in plasma epinephrine and norepinephrine were observed throughout the experiments (n = 8), and no significant changes in uterine blood flow occurred at any time during the experiment (n = 30). We conclude that there is a species difference between sheep and man with respect to the nicotinic threshold for catecholamine release.

Animals↗
PubMed1984

Controlled trial of three different antismoking interventions in general practice.

Of 6052 adult patients who consulted their doctors in six Oxfordshire general practices between October 1980 and February 1981, 2110 (35%) were smokers. The smokers were allocated to one of four study groups--a control (non-intervention) group; a group that received verbal and written antismoking advice from the general practitioner; a group that received this advice and also a demonstration of exhaled carbon monoxide; and a group that received the advice plus the offer of further help from a health visitor. After one year 72% of smokers replied to a postal follow up questionnaire: 11% of the control group claimed to have stopped smoking compared with 15% in the group that received advice alone, 17% in the exhaled carbon monoxide group, and 13% in the health visitor group. Validation of these findings by assays of urinary concentrations of cotinine showed that between 24% and 40% of subjects may have misreported their smoking habits, but there was no indication that the rate of misreporting was higher in the intervention groups than in the control group. Giving advice routinely against smoking has a useful effect, and showing an immediate, personal, and potentially harmful consequence of smoking using a CO-oximeter may improve this, particularly in lower socioeconomic groups.

Carbon Monoxide↗
PubMed1984

Urinary nicotine concentrations in cigarette and pipe smokers.

Urinary concentrations of nicotine were studied in men who did not smoke (27) and in men who smoked cigarettes only (145) or pipes only (48). The median urinary nicotine concentrations were less than 50 ng/ml (the detection limit of the assay for urine tests) in the non-smokers, 1393 ng/ml in the cigarette smokers, and 1048 ng/ml in the pipe smokers. These values were standardised for urinary pH and creatinine concentration to allow for the fact that nicotine excretion is influenced by the acidity of the urine and by urinary flow rate. The high urinary nicotine concentrations in the pipe and cigarette smokers indicated that both types of smoker have relatively high systemic nicotine concentrations. This observation, together with the fact that large prospective studies have shown that pipe smokers have no material excess risk of coronary heart disease whereas cigarette smokers do, provides evidence that nicotine is unlikely to be the major cause of the excess deaths from coronary heart disease in cigarette smokers. This conclusion is consistent with earlier observations based on serum cotinine concentrations in smokers and non-smokers.

Creatinine↗
PubMed1982

Nicotine from cigarette smoking increases circulating levels of cortisol, growth hormone, and prolactin in male chronic smokers.

Results of this study indicate that nicotine from cigarette smoking increases circulating levels of cortisol, growth hormone, and prolactin in male chronic smokers. Previous studies have not addressed the question of whether the stimulus for smoking-related hormone release is the 'stress' of smoking or a pharmacologic action of nicotine and other tobacco substrates. Nicotine exposure is controlled in this study by allowing each subject to smoke only two 2.0 mg nicotine cigarettes during one experimental session and two 0.2 mg nicotine cigarettes in another session. Plasma levels of cortisol, growth hormone, and prolactin for the higher nicotine session were found to be significantly elevated over those for the low-nicotine session, indicating that nicotine itself plays a predominate role in smoking-induced hormone increases. All hormone levels for the 2.0 mg nicotine session had not returned to baseline 60 min after smoking.

Adult↗
PubMed1981

The effect of phenothiazines and their metabolites on prostaglandin production by rat basophilic leukemia cells in culture.

Seven clinically important phenothiazine drugs (chlorpromazine, promazine, triflupromazine, thioridazine, fluphenazine, trifluoperazine and perphenazine) stimulated synthesis of PGE2 and PGF2alpha in RBL-1 cells in culture. Structural differences in the side chain at N10 had little effect on their activities. Some of the metabolites also were active, in keeping with the clinical observation that phenothiazines may have antipsychotic effects long after the parent compound has been eliminated from the circulation. Among the chlorpromazine metabolites, methoxy substituents on the phenothiazine nucleus did not strikingly affect stimulating activity. Monohydroxy derivatives were slightly more effective than the parent compound; there was little difference between hydroxy substitution at 7 or 8 position. The 7,8 dioxo, the N-oxido, the sulfoxide, and the 7-OH glucuronide derivatives were inactive.

Animals↗
PubMed1981

Plasma nicotine and cotinine concentrations in habitual smokeless tobacco users.

Plasma nicotine and cotinine levels were measured in habitual users of smokeless tobacco. The subjects were 12 male college students who regularly used smokeless tobacco (11 dipped snuff and one chewed tobacco) and did not smoke cigarettes. Subjects abstained from tobacco use overnight and blood was drawn at 8 A.M. and again after a single day of ad libitum consumption of their own tobacco product. Subjects recorded the times at which tobacco was used and the remainder product was weighed. Plasma samples were analyzed by both gas-liquid chromatography (GLC) and radioimmunoassay (RIA) techniques. Subjects consumed about one third of a can of moist ground snuff (10.8 gm) in eight dips spaced throughout the day. Nicotine absorption was observed and an increase in mean plasma concentration fro 2.9 ng/ml after overnight abstinence to 21.6 ng/ml after 6 to 8 hr ad libitum consumption was recorded. Plasma cotinine concentrations rose from a morning mean of 137.3 ng/ml to an afternoon mean of 197.2 ng/ml, concentrations that are typical of those reached in regular cigarette smokers. Subjects fell into two subgroups by post hoc analysis: two-thirds absorbed substantial amounts of nicotine and one-third appeared to have almost no absorption. Subjective effects of tobacco use were not marked; there was little perception of physiologic changes, stimulation, or feelings of relaxation/satisfaction. Results are discussed in terms of pharmacologic effects, comparison of results from GLC and RIA methodologies, and implications for health behaviors.

Absorption↗
PubMed1981

Determination of fluphenazine, related phenothiazine drugs and metabolites by combined high-performance liquid chromatography and radioimmunoassay.

Antibodies have been produced in rabbits immunized with a fluphenazine succinate-human serum albumin conjugate. By radioimmunoassay it is possible to quantify fluphenazine (FPZ), related phenothiazine drugs and several of their metabolites at the femtomole level. As little as 370 fmol (160 pg) of FPZ can be detected and up to 0.4 ml of plasma can be added to the incubation mixture (final volume = 1.1 ml). The phenothiazine heterocyclic nucleus is immunodominant and determines the specificity of the antiserum. When a parent drug cross-reacts significantly with antibody, its 7-hydroxide, N-oxide and N-10 side chain altered metabolites can also be determined by the assay. The 8-hydroxide, sulfoxide and 7-hydroxyglucuronide metabolites are not detectable unless present in large amounts. High-performance liquid chromatography was used to separate phenothiazine drugs and metabolites. Since the antiserum has broad specificity, a combined high-performance liquid chromatography and radioimmunoassay procedure permits the identification and quantification of a phenothiazine drug and its serologically reactive metabolites. Patterns of high-performance liquid chromatographic elution and extent of immunologic cross-reaction are characteristic for metabolites relative to the parent drug. This procedure offers distinct advantages in the analysis of this complex family of compounds. FPZ was quantitatively extracted from plasma samples obtained from patients receiving FPZ per os. Although large amounts of serological activity were present in the samples 2 to 6 hr after FPZ ingestion, only 2 to 23% was extractable. The major contributors to the serological activity at times greater than 6 hr were FPZ metabolites. In a preliminary application of the combined techniques, FPZ and a metabolite identified as N-[alpha-(trifluoromethylphenothiazinyl-10)propyl]perazine were quantified in the organic extract of one plasma sample.

Antibody Specificity↗
PubMed1979

Radioimmunoassay for phencyclidine.

A sensitive and specific radioimmunoassay has been developed for the drug phencyclidine (PCP). Levels as low as 50 pg (200 femto-moles) of PCP can be detected. The specificity of the antisera has been investigated by inhibiting the [3H]PCP-anti PCP reaction with the parent drug, metabolites, and other related compounds. Three urinary metabolites, 4-phenyl-4-piperidinocyclohexanol, 1-(1-phenylcyclohexyl)-4-hydroxypiperidine and 1-phenylcyclohexylamine inhibit 2,5, and 0.002% as effectively as PCP respectively. Plasma samples supplemented with PCP (1.2 to 10,000 ng/ml) can be analyzed directly by this procedure.

Animals↗