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Biomedical subjects

N J Haley

Publications and source records attributed to N J Haley.

At least 73 records · Page 4Linked to original sources

Analysis for nicotine and cotinine in hair to determine cigarette smoker status.

Noninvasive validation of cigarette smoking behavior is necessary for large population studies, especially with adolescents, where peer pressures can compromise self-report. Saliva and urine samples provide biological material for confirmation of recent nicotine intake by analysis for cotinine, the major metabolite of nicotine. However, detection of infrequent use of cigarettes can be missed in a single annual screen when participants have not smoked in the preceding week. We analyzed scalp hair from smokers and controls, to see whether hair could provide reliable samples for determining nicotine uptake. The amounts of nicotine and cotinine we detected in these samples correlated with individual smoking habits and exposures.

Cotinine↗

Measuring the exposure of infants to tobacco smoke. Nicotine and cotinine in urine and saliva.

The effect of parental smoking on the well-being of infants and children is an important public health concern. It is necessary, however, to validate the existence of such exposure objectively before an evaluation of the effects of parental smoking behavior on the child's health can be made. We measured the concentration of nicotine and its major metabolite, cotinine, in the saliva and urine of 32 infants with household exposure to tobacco smoke, and 19 unexposed infants. The concentrations were significantly higher in the exposed group than in the unexposed group, with the best indicator of chronic exposure being the urinary cotinine:creatinine ratio; median in the exposed group, 351 ng per milligram (225.3 nmol per millimole); median in the unexposed group, 4 ng per milligram (2.6 nmol per millimole) (P less than 0.0001). There was a direct relation between cotinine excretion by the infants and the self-reported smoking behavior of the mothers during the previous 24 hours (r = 0.67, P = 0.0001). Our results indicate that infants who were exposed to tobacco smoke absorbed its constituents and that urinary excretion of cotinine is a reliable measure of such exposure in infants.

Cotinine↗

Cigarette smoking as a risk for cardiovascular disease V: Biochemical parameters with increased and decreased nicotine content cigarettes.

Cigarette smokers were assessed for customary smoking behavior and then were assigned a cigarette which was 0.4 mg higher or lower in nicotine and after 4 weeks, were returned to their customary brand. Biochemical indices of smoking behavior including blood carboxyhemoglobin (COHb), plasma nicotine, cotinine and thiocyanate (-SCN) were measured every 2 weeks. When nicotine availability was increased, smokers received an increased nicotine bolus per puff as determined by plasma nicotine and did not alter smoking topography or cigarettes per day. Over the 4 weeks, plasma cotinine increased without corresponding increases in COHb and -SCN. The return to standard brand resulted in declining cotinine levels but increasing COHb and -SCN, suggesting altered inhalation patterns. In smokers switched to a low yield cigarette, there was a decrease in the nicotine obtained per cigarette followed by a steady rise in plasma cotinine, -SCN and blood COHb over the 4-week period. A positive correlation was observed between cotinine and the gas phase constituents during the change to lower yield and back to standard brand cigarettes. These results indicate that cigarette smokers compensate for decreased nicotine yield with concomitant increases in gas phase components. In addition, increased nicotine availability results in an increased body burden of nicotine and "tar," but not gas phase constituents. The relative risks of cardiovascular disease under these two situations, which increase exposure to nicotine or gas phase components, deserve careful consideration.

Adult↗

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↗

Thyroid hormone concentrations in rats after chronic nicotine metabolite administration.

In an attempt to evaluate the observed relationship of chronic cigarette smoking and reduced thyroid hormone activity, the major urinary metabolites of nicotine were administered to rats for 78 weeks. The animals were divided equally into one control (n = 33) and three treatment groups. Treatment group 1 received 0.1% (w/v continine, group 2 received 0.02% pure trans-nicotine-N'-oxide, and group 3 received 0.02% of a trans/cis mixture (64/36%) of nicotine-N'-oxide. Plasma and urinary nicotine and cotinine concentrations were determined as well as a variety of thyroid hormone parameters. Pure trans-nicotine-N'-oxide was more extensively metabolized to its cotinine end product, relative to the diasteromeric N'-oxides, mixture. Serum triiodothyronine (T3) was markedly reduced in animals receiving nicotine-N'-oxides, but was not different in the cotinine treatment group when compared to control values. A reduction in serum thyroxine (T4) values was noted only among those rats receiving the pure trans-nicotine-N'-oxide. The T3/T4 ratio, free T3 index, T3 uptake, and rT3 were altered in animals receiving nicotine-N'-oxides. These findings indicate that specific nicotine metabolites alter thyroid hormone concentrations after chronic low-dose administration and possibly do so through back conversion to the parent compound, nicotine.

Animals↗

Endogenous formation of N-nitrosoproline upon cigarette smoke inhalation.

It was the goal of this study to assay the potential of inhaled cigarette smoke for endogenous N-nitrosation of amines in smokers by measuring urinary excretion of N-nitrosoproline (NPRO). Nonsmoking and smoking men were placed on a controlled diet which was low in proline and in ascorbic acid. On days 1-3, the volunteers received the controlled diet alone (Group I); on days 4-6, the diet was supplemented by a single daily dose of 300 mg proline (Group II); on days 7-9, the diet was supplemented by a single daily dose of 1 g ascorbic acid followed by 300 mg proline (Group III); and for the last three days, a single daily dose of 1 g ascorbic acid was given (Group IV). Collections of 24-h urine were made on days 3, 6, 9 and 12 of the study. The urine was analysed for NPRO, creatinine and cotinine. The mean 24-h NPRO excretion for 13 nonsmokers in Group I was 3.6 micrograms, whereas the NPRO excretion in 13 smokers was 5.9 micrograms/24 h, significantly higher than that of the nonsmokers (p less than 0.05). Urinary NPRO in 14 nonsmokers of Group II was significantly lower than that of the 14 smoking volunteers (p less than 0.05). In Group III smokers had reduced urinary levels of NPRO as a consequence of ascorbic acid intake. Differences in NPRO excretion by smokers and nonsmokers in Group IV were insignificant. These findings suggest that the documented endogenous N-nitrosation of proline which occurs as a result of cigarette smoke inhalation may also apply to other N-nitrosatable amines, including nicotine, and thus lead to in-vivo formation of carcinogenic N-nitrosamines. Four nonsmokers exposed to passive smoke for 80 min three times per day did not exhibit elevated NPRO levels in their 24-h urine.

Adult↗

Thyroid activity in cigarette smokers.

Recent studies have shown a possible relationship between cigarette smoking and endocrine function. Since changes in thyroid hormone concentrations can have a profound effect on overall metabolism as well as influencing both androgenic and estrogenic steroid activity, we investigated the relationship between cigarette smoking and thyroid function. Volunteers were divided into four groups according to self-reported and biochemical data, including blood carboxyhemoglobin, plasma cotinine, and thiocyanate, and were described as nonsmokers, light, moderate, and heavy smokers. Substantial decreases were found in serum thyroxine (T4) and triiodothyronine (T3) concentrations in heavy smokers compared with nonsmokers. Reduced serum thyroid hormone levels were not accompanied by a substantial change in serum thyrotropin concentrations. The free T4 index, free T3 index, and T4-T3 ratio were not substantially different for either group.

Adult↗

Cigarette smoking: carboxyhemoglobin, plasma nicotine, cotinine and thiocyanate vs self-reported smoking data and cardiovascular disease.

Measurement of the absorption of cigarette smoke constituents were compared with self-reported daily consumption from 450 smokers to determine the most reliable dose dependent indicator of smoke inhalation and risk for coronary heart disease. A plateau of plasma nicotine and cotinine concentration at levels above 20 cigarettes per day with a continued increase of carboxyhemoglobin and thiocyanate with increasing consumption of cigarettes occurred. Classification of smokers into groups smoking cigarettes yielding more or less than 1 mg nicotine showed that smokers of low yield brands had lower plasma levels of nicotine and cotinine, but comparable levels of carboxyhemoglobin and thiocyanate. Plasma nicotine bore no relationship to smoke inhalation, while the number of cigarettes consumed per day showed a weak correlation to smoke inhalation. Despite the lower nicotine yield of cigarettes, modification in smoking behaviour enabled the smoker to derive as much carbon monoxide and thiocyanate constituents from low and high yield cigarettes; thus counteracting the advantage of low nicotine yield brands. The relationship of these parameters to the risk of coronary heart disease is discussed.

Carbon Monoxide↗

Cigarette smoking as a risk for cardiovascular disease III: Biochemical effects with higher nicotine yield cigarettes.

Subjects who smoked a medium range nicotine yield cigarette were given a higher nicotine yield cigarette (an increase of 0.34 mg nicotine) to smoke ad libitum for two weeks. Plasma nicotine, cotinine, thiocyanate and blood carboxyhemoglobin levels were determined as well as various physiological parameters including heart rate and blood pressure. Increases in plasma nicotine were most directly correlated to heart rate when smokers were first challenged with a higher nicotine yield cigarette (r = 0.85); less directly correlated after a two-week acclimatization period (r = 0.42) and poorly related to their customary product (r = 0.23). Interestingly, it was noted that subjects did not compensate for higher nicotine yield by smoking fewer cigarettes per day when incremental nicotine changes were realistic. They did, however, show higher plasma nicotine, thiocyanate and an upward trend in plasma cotinine with the stronger cigarettes. These increases in cigarette constituents present in plasma, coupled with increasing correlation of heart rate and nicotine uptake, lead us to suggest that uptitration of smokers might cause them to establish new baseline levels. These findings have important health implications in light of recent suggestions to increase the nicotine yet decrease the tar of cigarettes in an attempt to overcome smoker compensation phenomena observed with low yield products.

Adult↗

Validation of self-reported smoking behavior: biochemical analyses of cotinine and thiocyanate.

Biochemical determinations of plasma and salivary cotinine and thiocyanate were used to differentiate smokers from non-smokers and to follow daily smoking patterns in smokers. Results indicate that cotinine is better suited than thiocyanate to determine smoking status in large scale epidemiologic studies and to follow alterations in smoking behavior over periods of time. Salivary cotinine is a reliable alternative to plasma for validation of smoking status and for following changes in daily smoking patterns.

Cotinine↗

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↗

Characterization of lipid-laden aortic cells from cholesterol-fed rabbits. III. Intracellular localization of cholesterol and cholesteryl ester.

The subcellular sites of accumulation of cholesterol and cholesteryl esters in rabbit atheromatous cells, were investigated by morphologic and biochemical techniques. Electron microscopy of lipid-filled cells in situ in atheromatous aortas of cholesterol-fed rabbits revealed lipid accumulation in the cytoplasm as lipid droplets and within lysosomes in the form of lipid globules, membranous whorls, and crystals. When such cells were isolated from the rabbit aortas by enzymic digestion, and then treated with Flickinger's aldehyde fixative containing 0.2 per cent digitonin, characteristic digitonide-lipid complexes ("spicules") were observed in discrete sites of the cytoplasm distinct from the cytoplasmic droplets. If these cells were first stained cytochemically for acid phosphatase and then treated with digitonin-aldehyde fixative, enzyme reaction product was found associated with the spicules indicating that the lysosomes of the atheromatous cells possess digitonin-reactive lipid. Subcellular fractionation of isolated rabbit aortic foam cells by sucrose density gradient centrifugation demonstrated the coequilibration of most of the intracellular unesterified cholesterol with low density lysosomes. Some cholesteryl ester was also associated with low density lysosomes, although most was found in a lipid droplet fraction of very low density. Together the results indicate that in rabbit atheromatous cells, lysosomes are the site of accumulation of intracellular cholesterol in excess of that structurally associated with membranes and that both cytoplasmic droplets and lysosomes are depot sites for cholesteryl esters.

Acid Phosphatase↗

Characterization of lipid-laden aortic cells from cholesterol-fed rabbits. I. Resolution of aortic cell populations by metrizamide density gradient centrifugation.

Enzymatically isolated aortic cells from control and cholesterol-fed rabbits were subjected to isopycnic density gradient centrifugation in Metrizamide. Control cells formed a single band equilibrating at a median density of 1.13 to 1.14, while cells isolated from atheromatous aortas formed two distinct bands, one equilibrating in the density range of 1.12 to 1.14 and the other occurring at a lower density of 1.03 to 1.07. Morphologically, the low density cells exhibited typical features of aortic foam cells. They were found to be greatly enriched in free and esterified cholesterol and in four lysosomal hydrolases. Further studies showed these cells to contain lipid-laden lysosomes. The high density cells from cholesterol-fed rabbits were also enriched in cholesterol and lysosomal enzymes compared to control aortic cells but not to the extent showen by the low density foam cells. While exhibiting the ultrastructural characteristics of smooth muscle cells, the cells in this fraction showed a considerable degree of morphologic and biochemical heterogeneity, suggesting the occurrence of many transition forms between normal smooth muscle cells and fully transformed foam cells.

Animals↗

The interaction of sociological and biological factors in adolescent cigarette smoking.

This article considers the interaction of social and biological factors in the context of adolescent cigarette smoking. Parent and peer smoking are the sociological variables and testosterone is the biological indicator. The subjects are 212 males and females 12-14 years of age. The findings support the interaction model, suggesting that both sociological and biological factors are necessary for understanding adolescent smoking.

Adolescent↗