Neutrophil kinetics in O2-exposed rabbits

Hyperoxic injury results in an influx of polymorphonuclear leukocytes (PMN) into the lung. To better understand the role of the PMN in this injury, kinetic studies were used to assess the survival of PMNs in the circulation. The rate of deposition of PMNs in the lungs of rabbits exposed to hyperoxia was also examined. The half-lives (T1/2) of [3H]thymidine-labeled PMNs in the circulation in rabbits exposed to air or to 95% O2 for less than or equal to 48 h varied between 3.9 and 4.5 h. After 72 h of hyperoxic exposure, T1/2 fell to 2.2 h, the marginal and circulating PMN pool increased and 3H deposition in the lung increased 10-fold. Autoradiographs confirmed that [3H]thymidine was initially nuclear- and cellular-associated but, with time, [3H]thymidine dispersed throughout the lung, suggesting PMN disintegration. These PMN events seem to occur in the later phases of O2 toxicity, and because PMNs are an additional source of oxyradicals, they may further amplify oxidant injury.     

Malignant hypertension and cigarette smoking.

The smoking habits of 48 patients with malignant hypertension were compared with those of 92 consecutive patients with non-malignant hypertension. Thirty-three of the patients with malignant and 34 of the patients with non-malignant hypertension were smokers when first diagnosed. This difference was significant, and remained so when only men or black and white patients were considered separately. Results suggest that malignant hypertension is yet another disease related to cigarette smoking.     

Metabolic effects of cigarette smoking.

The inverse relationship between cigarette smoking and body weight, a potent obstacle to stopping smoking, may be due in part to effects of smoking on increasing whole body metabolism. Studies examining chronic and acute metabolic effects of smoking, as well as its constituent nicotine, are reviewed. Evidence suggests the absence of a chronic effect; most studies indicate that smokers and nonsmokers have similar resting metabolic rates (RMR) and that RMR declines very little after smoking cessation. Although an acute effect due to smoking is apparent, its magnitude is inconsistent across studies, possibly because of variability in smoke exposure or nicotine intake. In smokers at rest, the acute effect of smoking (and nicotine intake) appears to be significant but small (less than 10% of RMR) and transient (less than or equal to 30 min). However, the specific situations in which smokers tend to smoke may mediate the magnitude of this effect, inasmuch as smoking during casual physical activity may enhance it while smoking after eating may reduce it. Sympathoadrenal activation by nicotine appears to be primarily responsible for the metabolic effect of smoking, but possible contributions from nonnicotine constituents of tobacco smoke and behavioral effects of inhaling may also be important. Improved understanding of these metabolic effects may lead to better prediction and control of weight gain after smoking cessation, thus increasing the likelihood of maintaining abstinence.     

Variation in size at birth and cigarette smoking during pregnancy

The influence of cigarette smoking during pregnancy and other familial factors on size at birth and gestation length is investigated among 458 births to 227 mothers living in a suburban community in the U.S. In this sample, 56% of the births were to mothers who reported not smoking during the pregnancy and 35% were to mothers who reported smoking 20 cigarettes or less. Multiple stepwise regression analysis was employed to examine the influence of cigarette smoking after statistical adjustment for such social and biological characteristics of the family as parents' sizes, education, income, and aspects of mother's reproductive history. After correction for significant social and biological characteristics, smoking status was a significant contributor to birth weight variation. In fact, cigarette smoking had the next-largest partial correlation coefficient (r = -0.26) second to gestation length. Birth length is also negatively associated with cigarette smoking, though not so strongly as is birth weight. The reduction in birth lengths can be attributed to the reduction in birth weights. Gestation length was not associated with cigarette smoking in this sample. The analysis of collinearity between smoking status and the other independent variables indicates that the effect of smoking appears to be independent of interrelationships among the independent variables.     

Maternal cigarette smoking during pregnancy and offspring DNA methylation in midlife

Maternal smoking in pregnancy (MSP) has been associated with DNA methylation in specific CpG sites (CpGs) in infants and children. We investigated whether MSP, independent of own personal active smoking, was associated with midlife DNA methylation in CpGs that were previously identified in studies of MSP-DNA methylation in children. We used data on MSP collected from pregnant mothers of 89 adult women born in 1959–1964 and measured DNA methylation in blood (granulocytes) collected in 2001–2007 (mean age: 43 years). Seventeen CpGs were differentially methylated by MSP, with multiple CpGs mapping to CYP1A1, MYO1G, AHRR, and GFI1. These associations were consistent in direction with prior studies (e.g., MSP associated with more and less methylation in AHRR and CYP1A1, respectively) and, with the exception of AHRR CpGs, were not substantially altered by adjustment for active smoking. These preliminary results confirm prior prospective reports that MSP influences the offspring DNA methylation, and extends the timeframe to midlife, and suggest that these effects may persist into adulthood, independently of active smoking.     

Naloxone reduces cigarette smoking

In a double-blind drug-placebo cross-over design, naloxone hydrochloride reduced the amount of cigarettes smoked by chronic smokers over a 3 hr period. The number of puffs was reduced by 32%, the weight of the amount smoked by 33%, and the number of trials in which cigarettes were smoked by 30%. The extent of the decreases in smoking was related to the amount of the decrease in the desire to smoke. There were no physiological differences or in side effects between the two conditions, and neither subjects nor experimenters were able to distinguish between the two. These findings are similar to the suppressive effects of naloxone on food, water and ethanol intake in animals and suggest that the endorphins are implicated. A heuristic theory of addiction is presented to explain these diverse effects.Naloxone hydrochloride (NAL) reduces the intake of nonintoxicating positive reinforcers, such as food and water, in animals (1–5), as well as ethanol (6). The reduction does not appear to be part of an abstinence syndrome (3), or of a general suppression of behavior (7), unless massive doses (i.e. 5 mg/kg or more) of the opiate antagonist are used (8). The mechanism for these effects is obscure, although it has been demonstrated that higher levels of Beta endorphin are associated with greater food intake, and that NAL suppresses food intake to a greater extent in genetically obese animals which have higher levels of Beta endorphin than their litter-mates of normal weight (4).Cigarette smoking has often been found to increase corticosteroid levels (9–12), which is considered presumptive evidence that there is an increase in ACTH production. Elevated levels of ACTH are associated with elevated levels of Beta endorphin in man (13–16). Assuming that smoking is another example of a nonintoxicating positive reinforcer, which also releases Beta endorphin because of ACTH release, we administered NAL to chronic smokers, with the expectation that the amount smoked, as well as the desire to do so, would be reduced. However, because of the possible addictive nature of nicotine (17–19), we were not sure whether these effects would be the result of a precipitated abstinence syndrome.     

Regional deposition of particles in the lung during cigarette smoking in humans

Studies were carried out on 11 habitual cigarette smokers to ascertain whether there was a difference in the regional deposition of particles during cigarette smoking compared with tidal breathing and also to investigate whether the ventilatory maneuvers associated with smoking influence the deposition site. A cigarette holder was constructed that permitted cigarette smoke to mix with a radioaerosol. An added resistance simulated the airflow resistance present in a filter-tipped cigarette. Respiratory patterns for the control period of tidal breathing and during smoking were monitored with a respiratory inductance plethysmograph. Smoking resulted in greater apical and central deposition than expected from the distribution of resting ventilation. The changes in the site of deposition during smoking are probably influenced mainly by the properties of the particles concerned, namely, its size, reactivity, and hygroscopicity. Changes in respiratory patterns that occur during inhalation of cigarette smoke may also have an effect but are difficult to quantify and show marked intersubject variation. In selected subjects smoking caused apical deposition to exceed that of the lower zones.     

Effect of cigarette smoking on gastric emptying.

Gastric emptying after a test meal was studied in 17 normal volunteers--10 habitual smokers and seven non-smokers. The solid component of the test meal was labelled with technetium and the liquid component with indium. After one meal the habitual smokers smoked two cigarettes. Emptying curves were produced for both technetium and indium, and the differences between curves for meals with and without cigarettes were analysed. Cigarette smoking accelerated the rate at which the liquid component of a meal left the stomach. This may be important in the pathogenesis of duodneal ulcer and the delay in healing caused by cigarette smoking.     

'Normal' cigarette smoking increases free cortisol in habitual smokers.

In habitual smokers salivary cortisol responses to cigarette smoking were investigated. In the first study, 31 adults assigned to two experimental groups smoked either one or two cigarettes of their preferred brand. Mean salivary cortisol levels were significantly elevated after smoking of two cigarettes. In the second study, 10 smokers and 10 nonsmokers provided saliva samples at 20 min intervals over a 12-hr period. While environmental stimuli were paralleled in both groups overall cortisol output was significantly elevated in the smokers. These data suggest that 'normal' cigarette smoking can increase free cortisol levels.