Tritiated-naloxone binding to brainstem opioid receptors in the sudden infant death syndrome

The sudden infant death syndrome (SIDS) is defined as the sudden death of an infant under 1 year of age that remains unexplained after a thorough case investigation, including a complete autopsy. We hypothesized that SIDS is associated with altered 3H - naloxone binding to opioid receptors in brainstem nuclei related to respiratory and autonomic control. We analyzed 3H - naloxone binding in 21 regions in SIDS and control brainstems using quantitative tissue receptor autoradiography. Three groups were analyzed: SIDS (n = 45); acute controls (n = 14); and a chronic group with oxygenation disorders (n = 15). Opioid binding was heavily concentrated in the caudal nucleus of the solitary tract, nucleus parabrachialis medialis, spinal trigeminal nucleus, inferior olive, and interpeduncular nucleus in all cases analyzed (n = 74). The arcuate nucleus on the ventral medullary surface contained negligible binding in all cases (n = 74), and therefore binding was not measurable at this site. We found no significant differences among the three groups in the age-adjusted mean 3H - naloxone binding in 21 brainstem sites analyzed. The only differences we have found to date between SIDS and acute controls are decreases in 3H - quinuclidinyl benzilate binding to muscarinic cholinergic receptors and in 3H - kainate binding to kainate receptors in the arcuate nucleus in alternate sections of this same data set. The present study suggests that there is not a defect in opioid receptor binding in cardiorespiratory nuclei in SIDS brainstems.     

Relationship of passive cigarette-smoking to sudden infant death syndrome

The smoking habits of 56 families who lost babies to the sudden infant death syndrome (SIDS) were compared to those of 86 control families. A higher proportion of SIDS mothers smoked both during pregnancy (61% vs. 42%) and after their babies were born (59% vs. 37%). SIDS mother also smoked a significantly greater number of cigarettes than controls. Exposure to cigarette smoke ("passive smoking") appears to enhance the risk of SIDS for reasons not known.     

Dose-dependent induction of IL-12 but not IL-10 from human keratinocytes after exposure to ultraviolet light A

OBJECTIVE: Our purpose was to assess the risk of ectopic pregnancy among women who smoke cigarettes. STUDY DESIGN: We used data from a case-control study of ectopic pregnancy conducted from October 1988 to August 1990 at an inner-city hospital in Georgia. Cases were 196 non-Hispanic black women with a surgically confirmed ectopic pregnancy. Controls were non-Hispanic black women who had delivered either a live or a stillborn infant weighing at least 500 gm (n = 882) or who were pregnant and seeking an induced abortion (n = 237). RESULTS: After we adjusted for parity, douching history, history of infertility, and age, the odds ratio for ectopic pregnancy was 1.9 (95% confidence interval 1.4 to 2.7) for women who smoked during the periconception period compared with women who did not smoke at that time. After stratification by the amount of daily smoking during the periconception period, the odds ratio rose from 1.6 (95% confidence interval 0.9 to 2.9) for women who smoked 1 to 5 cigarettes to 1.7 (95% confidence interval 1.1 to 2.8) for women who smoked 6 to 10 cigarettes to 2.3 (95% confidence interval 1.3 to 4.0) for women who smoked 11 to 20 cigarettes, and to 3.5 (95% confidence interval 1.4 to 8.6) for women who smoked >20 cigarettes per day. CONCLUSION: In this inner-city population, cigarette smoking was an independent, dose-related risk factor for ectopic pregnancy among black women. The public health and medical care communities should inform the public of this additional risk associated with cigarette smoking and intensify intervention strategies to reduce cigarette smoking among women of reproductive age.     

Smoking and preterm labor: effect of a cigarette smoke extract on the secretion of platelet-activating factor-acetylhydrolase by human decidual macrophages

OBJECTIVE: Maternal smoking in pregnancy is associated with a significant increase in the incidence of preterm labor, premature rupture of membranes, and premature delivery. Our aim was to clarify the cause underlying this association. STUDY DESIGN: The effect of cigarette smoke extract on the secretion of platelet-activating factor-acetylhydrolase by both decidual macrophages and peripheral blood monocytes and macrophages was investigated. RESULTS: The cigarette smoke extract inhibited the platelet-activating factor-acetylhydrolase secretion by these cells. The inhibitory effect of cigarette smoke extract on the secretion was a hundred times more potent compared with its direct effect on the plasma enzyme. Glutathione and dithiothreitol blocked the inhibition, whereas catalase or superoxide dismutase did not. Nicotine and cotinine have no effect on the secretion. CONCLUSION: The presence in cigarette smoke extract of a potent inhibitor(s) of platelet-activating factor-acetylhydrolase secretion by decidual macrophages may provide an insight into the pathogenesis of preterm labor, premature rupture of membranes, and premature delivery in women who smoke during pregnancy.     

Involvement of free radicals and histamine in the potentiating action of cigarette smoke exposure on ethanol-induced gastric mucosal damage in rats

Cigarette smoking has been associated with peptic ulcer diseases. We studied the effects of cigarette smoke exposure on ethanol-induced gastric mucosal damage and its relationship with vascular integrity and the possible role of free radicals and histamine. Male Sprague-Dawley rats were exposed to cigarette smoke followed by ethanol administration (70% v/v). Smoke exposure alone dose-dependently reduced basal blood flow and increased xanthine oxidase (XO) activity but superoxide dismutase (SOD) activity remained unaffected in gastric mucosa. Cigarette smoking followed by ethanol administration significantly potentiated mucosal lesion formation along with augmentation of the mucosal blood flow, vascular permeability and myeloperoxidase (MPO) activity. The potentiating effect of smoking on ethanol-induced gastric mucosal lesion and MPO activity was abolished by pretreatment with allopurinol, terfenadine or ranitidine. Terfenadine and ranitidine also reduced the increased mucosal blood flow and vascular permeability induced by smoking and ethanol combined. These findings suggested that cigarette smoke adversely affected the defense mechanisms of the gastric mucosa by reducing the mucosal blood flow which in turn led to ischemia and increased XO activity. Activation of XO together with histamine H1 and H2 receptors stimulation could lead to neutrophil aggregation and vascular damage. However, the potentiating action of cigarette smoke on ethanol ulceration is unlikely through reduction of SOD activity in gastric mucosa.     

Mechanisms underlying cerebrovascular effects of cigarette smoking in rats in vivo

BACKGROUND AND PURPOSE: The effects of acute smoking on cerebral circulation are controversial. This study was designed (1) to clarify any differences between the effects of cigarette smoking and nicotine infusion and between the effects of single- and multiple-cigarette smoking on cerebral vessels and (2) to probe the mechanism(s) underlying the vascular responses. METHODS: In pentobarbital-anesthetized, mechanically ventilated Sprague-Dawley rats, pial vessel diameters were measured with the use of a cranial window preparation. We studied the effects of (1) 60 puffs per minute of mainstream cigarette smoke from cigarettes having 2 nicotine levels (0.1 and 1 mg per cigarette), (2) administration of nicotine (0.05 mg per body IV), and (3) repeated smoking (four 1 mg nicotine-containing cigarettes at 30-minute intervals) (n=6 each). RESULTS: Inhalation of smoke from a 0.1 or 1 mg nicotine-containing cigarette for 1 minute caused pial arterioles to constrict at 30 seconds (7.2% and 7.3%, respectively) and then to dilate (peak at 5 to 10 minutes; 4.6% and 17.9%, respectively). Nicotine infusion caused pial vasodilation (35.7%) without an initial vasoconstriction. Repeated smoking suppressed the pial vasodilation but not the initial vasoconstriction. The vasodilation induced by a single cigarette was greatly inhibited by pretreatment with mecamylamine or glibenclamide and attenuated by propranolol or Nomega-nitro-L-arginine methyl ester; the initial vasoconstriction was inhibited by seratrodast, a thromboxane A2 receptor antagonist (n=6 in each case). CONCLUSIONS: Single-cigarette smoking had a significant biphasic effect on cerebral arteriolar tone. The vasodilation was attenuated by repeated smoking. The vasodilation is most likely an effect of nicotine, at least in part mediated via sympathetic activation, NO production, and K+ channel activation. The vasoconstriction is partially due to thromboxane A2 induced by cigarette smoke.     

Reducing craving for cigarettes while decreasing smoke intake using capsaicin-enhanced low tar cigarettes.

The effects on smoking behavior and subjective evaluation of adding capsaicin (a pungent principle of chili pepper) to a low tar and nicotine cigarette were studied in 12 cigarette smokers. In a 4-hr session, Ss inhaled smoke from 3 types of cigarettes: low tar and nicotine with capsaicin added; low tar and nicotine without capsaicin (control); and commercial high tar and nicotine. Ss puffed significantly less on the capsaicin cigarettes than on the other 2 types of cigarettes and reported greater reduction in cigarette craving after smoking capsaicin cigarettes than after smoking control low nicotine cigarettes. Estimated nicotine intake and respiratory tract sensations for the capsaicin cigarettes were also significantly higher than for the control cigarettes. Results support the view that respiratory tract sensations are important in reducing smokers' craving for cigarettes and in modulating smoking behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of alcohol on cigarette craving in heavy smokers and tobacco chippers.

The authors examined the effects of alcohol consumption on cigarette craving in heavy smokers and tobacco chippers (n = 138) who were instructed not to smoke for 12 hr. Participants were exposed to both smoking cues (a lit cigarette) and control cues. Half received a moderate dose of alcohol, adjusted for gender, and half received a placebo. Results indicated that alcohol consumption produced an increase in urge-to-smoke ratings before smoking cue exposure. Moreover, during cue exposure, alcohol consumption produced a sharper increase in urge ratings than did the placebo. In addition, during smoking cue exposure, alcohol increased the likelihood of displaying facial expressions associated with positive affect. These findings suggest that alcohol consumption influences both the magnitude and the emotional valence of cigarette cravings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The smoking of psychology.

Studied cigarette smoking and its correlates among 344 academic psychologists. Results show that males were less likely to smoke than unselected US adult males but were similar to most professional comparison groups. Females were more likely to smoke than the men because relatively fewer had stopped. Most smokers reported the expectation of reducing or stopping smoking in the future. Substantial proportions of both sexes who had ever smoked and who had reached middle age had in fact stopped. Among those of advanced academic rank, smokers were significantly higher in book and article authorship. The sex differences are interpreted in terms of sex roles and role stress. The productivity data are interpreted relative to personality differences, work roles, and the arousal effect of nicotine. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cigarette mentholation increases smokers' exhaled carbon monoxide levels.

12 male smokers participated in 3 controlled-dose smoking sessions spaced 1 wk apart. In each session, Ss inhaled 1,200 cc of cigarette smoke. Menthol dosage varied across sessions, such that Ss smoked experimental cigarettes that had been injected with 0, 4, or 8 mg of menthol. Exhaled CO levels increased concomitantly with menthol dosage. There were no differences in smoking topography across the 3 conditions. The ability of menthol to increase the toxicity of cigarette smoke by raising CO levels is discussed. Results suggest that menthol cigarette preference may account for some of the racial differences in smoking behavior and smoking-related outcomes found in past literature. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Smoking and nicotine addiction: a pediatric epidemic with sequelae in adulthood

Pediatric addiction to nicotine from cigarette smoking is a major public health problem, extracting a tremendous societal toll in terms of human suffering, a loss of future productivity, and the consumption of scarce health care resources. Teenagers smoke 1.1 billion packs of cigarettes yearly and will account for more than $200 billion in future health care costs. Recent behavioral studies confirm nicotine's ability to induce in adolescents both the tolerance and abstinence phenomena typical of other addicting substances. A range of adverse health effects, first detectable in adolescent cigarette smokers, extend into adulthood. Through the effects of environmental smoke or smoking during pregnancy, adolescent smokers affect not only their own health, but that of friends, family members, and even their own fetuses and children. Additional research into effective prevention and smoking cessation programs is urgently needed to forestall the ravaging of yet another generation by this preventable and deadly habit.     

Immediate Antecedents of Cigarette Smoking: An Analysis of Unrestricted Smoking Patterns.

Theory suggests that cigarette smoking is under stimulus control and that affect is a key trigger for smoking. A previous study (S. Shiftman et al., 2002) showed little relationship between affect and smoking, but this relationship could have been suppressed by the impact of smoking restrictions. The study evaluated these associations in a 1988 sample that was subject to few smoking restrictions. Smokers (N = 28) not seeking treatment used palmtop computers to record context and affect prior to smoking (n = 2,217 observations) and also at random times when not smoking (n = 2,380). Comparisons showed little relationship between smoking and affect. Smoking was associated with particular activities and locations. Urge to smoke was the strongest predictor of smoking. The results replicated the findings of S. Shiffman et al. (2002). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neural mechanisms underlying nicotine dependence

There is little doubt that many habitual smokers find it difficult to quit the habit because they have become addicted to the nicotine present in the smoke. This paper addresses some of the pharmacological mechanisms underlying this addiction and discusses how an understanding of these mechanisms may contribute to the more effective use of nicotine replacement therapy during smoking cessation. It considers critically the evidence that the "rewarding" properties of nicotine, which serve to reinforce drug-seeking behaviour, are related to stimulation of the mesolimbic dopamine system of the brain. The critique focuses specifically on the evidence that many central nicotinic receptors, including those which mediate the effects of the drug on dopamine secretion, are readily desensitized by chronic exposure to agonist and that hypotheses which assume that nicotine inhaled from tobacco smoke invariably results in stimulation of the receptors must be treated with caution. Nicotinic receptors in the brain are, however, heterogeneous in nature with different molecular structures and pharmacologies. It is concluded that the reinforcing properties of nicotine sought by smokers may reflect both stimulation and desensitization of the different nicotinic receptor populations, and that smokers may adjust their smoking habits to achieve the balance of receptor stimulation and desensitization which they find most reinforcing. It seems likely that the efficacy of the different nicotine formulations during the treatment of smoking cessation may also reflect their ability to stimulate or desensitize brain nicotinic receptors.     

Leaving work to smoke

Work-place smoking bans have not only reduced work-day cigarette consumption but also been associated with going outside to smoke during working hours. We examined the extent of "exiled smoking", estimated how much work-day cigarette consumption can be attributed to it, and examined proximal predictors of both these two variables. Some 794 smokers from 42 medium-sized work-places were surveyed as the baseline for an intervention study. A self-completed questionnaire assessed smoking behaviour on work and non-working days, leaving work to smoke, and beliefs and opinions about smoking and smoking bans. Multiple regressions were used to examine predictors of leaving work to smoke, and of the amount smoked when doing so. Smokers reported consuming an average of 5.4 cigarettes during work breaks, 3.5 of which were associated with deliberately seeking opportunities to smoke; 39% reported leaving work to smoke one or more times per day during non-break periods. Indices of addiction were significant predictors of both leaving work to smoke and of cigarette consumption while doing so. Leaving work to smoke is in part an activity of addicted smokers, presumably to maintain blood nicotine levels. There is the potential to further reduce rates of cigarette consumption associated with work-place smoking bans if this "exiled smoking" can be reduced. This may be easier to achieve in light smokers.     

Acute mesenteric ischemia. CT and plain radiographic analysis of 26 cases

GABA acts as a trophic signal for cultured embryonic rat monoamine neurons by activating GABA(A) receptors. These effects are blocked by the organochlorine insecticide dieldrin and the classic GABA(A) antagonist bicuculline. Both dieldrin and another organochlorine insecticide, lindane, block the effects of GABA on the GABA(A) receptor by binding directly to the Cl- channel. Therefore, prenatal exposure to these chemicals could lead to disturbances in the trophic actions of GABA on monoamine neurotransmitter systems in the embryonic brain and produce alterations in GABA(A) receptor expression and function. Effects of daily prenatal exposure to organochlorine insecticide (dieldrin or lindane) or bicuculline from embryonic day (E)12-17 were determined in brains of E17 fetal rats using t-[35S]butyl-bicyclophosphorothionate ([35S]TBPS) binding. This radioligand was chosen because, like organochlorine insecticides, it binds directly to GABA(A) receptor/Cl- channels. [35S]TBPS binding was analyzed in extensively washed membranes from E17 brainstem and whole brain with the brainstem removed ('rest of brain') at a TBPS concentration that approximated the KD determined in [35S]TBPS saturation binding experiments performed on normal E17 rat brainstem. In utero exposure to dieldrin, lindane, or bicuculline from E12-E17 caused a significant reduction in the amount of [35S]TBPS binding in E17 brainstem compared to vehicle-injected controls, but had no significant effect on 'rest of brain'. These data suggest that in utero exposure to organochlorine insecticides that act as GABA(A) antagonists negatively regulate expression of GABAA receptors in fetal brainstem. If these effects persist, they could lead to disturbances in postnatal functions of the ascending GABAergic system, possibly with behavioral consequences.     

Primary aromatic amines from side-stream cigarette smoke are common contaminants of indoor air

A very sensitive mass-spectrometry method has been developed for the analysis of aromatic amines in tobacco smoke and in indoor air. Cigarettes were smoked with a smoking machine; the amines from the smoke were trapped in a 5% HCl water solution containing internal standards and detected by gas chromatography/mass spectrometry in the selected-ion-monitoring (SIM) mode. The amines measured were the following: aniline, 2-toluidine, 3-toluidine, 4-toluidine, 2-ethylaniline, 3-ethylaniline, 4-ethylaniline, 2,3-dimethylaniline, 2,4-dimethylaniline, 2,5-dimethylaniline, 2,6-dimethylaniline, 1-naphthylamine, 2-naphthylamine, 2-methyl-1-naphthylamine, 2-aminobiphenyl, 3-aminobiphenyl and 4-aminobiphenyl. We analyzed nine brands of cigarettes sold commercially in Italy (Gauloise, Nazionali, Marlboro, Camel, MS, MS mild and MS lights), with and without filter. Main-stream smoke contained a lower amount of aromatic amines than side-stream smoke: the total level of these amines in main-stream smoke ranged from 200 to 1300 ng/cigarette, whereas the level of aromatic amines in side-stream smoke varied from 20,000 to 30,000 ng/cigarette. The smoke of black-tobacco cigarettes had higher levels of aromatic amines compared to light-tobacco cigarettes and the filters significantly reduced aromatic amines in main-stream smoke. We also determined the levels of aromatic amines in ambient air, offices and houses. Some aromatic amines (aniline and toluidine) were detected in ambient air, as well as in rooms of non-smokers. Most measurements showed a considerable contamination of aromatic amines derived from side-stream smoke, which was detected also in parts of the buildings in which smoking was not allowed.     

Effect of dietary protein and environmental temperature on growth performance and water consumption of male broiler chickens

The purpose of this study was to investigate whether smokers outside buildings with work-place smoking bans smoke "harder" than those smoking in social settings. An unobtrusive random observational study of smokers followed by structured interview was used, with 143 smokers taking smoking breaks outside their office buildings and 113 smokers in social settings. The main outcome measurements were number of puffs per cigarette and cigarette smoking duration. The mean number of puffs per cigarette for the office building group was 18.7% greater than that for the social settings group (10.7 +/- 3.2 vs. 8.7 +/- 2.7, t = 5.58, df = 253, p < 0.001); 74.8% of smokers outside offices took more than the mean number of puffs for the group compared to 42.5% of smokers in social settings (chi 2 df 1 = 26.31, p < 0.0001). Mean cigarette smoking duration was 30.4% shorter for the work-place group than the social settings group (3.9 +/- 1.2 minutes vs. 5.6 +/- 2.6 minutes). Of smokers outside offices, 55.2% had a cigarette smoking duration between 3 and 4.59 minutes, while 53.1% of smokers in social settings took > or = 5 minutes to smoke the observed cigarette (chi 2 df 2 = 31.55, p < 0.0001). Smokers who scored at the 75th percentile on the Fagerstrom Tolerance Scale took a mean 9.5 +/- 2.6 puffs per cigarette compared to 9.3 +/- 2.7 puffs by those who scored in the 25th percentile on the scale (t = 0.34, df = 145, p = 0.73). Regardless of degree of nicotine dependency, smokers leaving work-stations to smoke outside buildings smoked their cigarettes nearly 19% "harder" than cigarettes smoked in social settings. The individual and public health benefits of reduced smoking frequency engendered by work-place smoking bans may be lessened by policies which allow smokers to take smoking breaks.     

Paced smoking in the laboratory and in the natural smoking setting: differential situation-specific effects in light and heavy smokers

The present study examined the situation-specific effects of smoking using a paced regimen of smoking to control the smoke intake. The subjects were first required to sham smoke and then actually smoke one of their cigarettes in two different test contexts: 1) in the laboratory where they had never previously smoked and 2) at home, alone in a quiet room where they regularly smoke. Light (< 10 cigarettes/day) and heavy smokers (> 15 cigarettes/day) were studied to test for a possible effect of the paced regimen itself. In the light smokers, smoking produced a larger increase in heart rate (HR) in the laboratory than in the natural smoking environment; however, in the heavy smokers the smoking had a larger effect in the normal smoking environment than in the laboratory. There were no significant group or test situation differences for baseline HR, skin conductance and finger temperature. The groups also did not differ in the intensity of drawing on the cigarette or inhaling, as indicated by a puff sensor and a respiratory belt, respectively. It was concluded that differences between the effects of a cigarette in a laboratory setting and in a natural smoking environment may reflect pharmacodynamic effects of smoking that are modified by the subjects' prior experience with smoking. The data are discussed with regard to conditioned tolerance to the effect of smoking.     

Behavioral filter vent blocking on the first cigarette of the day predicts which smokers of light cigarettes will increase smoke exposure from blocked vents.

Filter vent blocking on best-selling light cigarettes increases smoke yield during standard machine testing but not in clinical investigations of smokers. The purpose of the study was to investigate the effect of (a) manipulating cigarette filter vent blocking and (b) blocking status of first cigarette of the day on carbon monoxide (CO) boost. Participants (n = 25; Marlboro Lights nonmenthol cigarette smokers, age range 21–60 years, minimum 15 daily cigarettes, and daily smoking for a minimum 5 years) completed the laboratory-based, within-subject, double-blind, cross-over design of 2 smoking sessions, one utilizing a smoking topography device, one without. Each session consisted of smoking 4 cigarettes; 2 with filter vents blocked and 2 with filter vents unblocked. Spent first daily cigarette filters collected between sessions were scored for evidence of filter vent blocking. Smoking cigarettes with blocked filter vents significantly increased CO boost in both laboratory sessions (p     

Skeletal muscle buffering capacity and endurance performance after high-intensity interval training by well-trained cyclists

Chronic nicotine administration in animal models evokes a dose-dependent increase in brain nicotinic receptor numbers. Genetically determined variability in nicotinic receptor number in different mouse strains has also been reported, which is thought to affect sensitivity to nicotine, as well as the development of tolerance. Humans self-administer nicotine principally in the form of cigarettes and other tobacco products. The present study compared [3H]nicotine binding in human postmortem brain from thalamus and hippocampus of nonsmoking subjects, subjects who had variable life-long smoking histories and subjects who had quit smoking. A significant increase was seen in [3H]nicotine binding in both hippocampus and thalamus of subjects with life-long smoking histories. In the hippocampus, this change resulted from a change in total receptor number (Bmax), with no change in receptor affinity (Kd). There was also a positive correlation between the degree of smoking, as measured by the average reported packs smoked per day, and the number of nicotine binding sites found in both the hippocampus and thalamus, showing that humans exhibit a dose-dependent increase in brain nicotinic receptor binding. Receptor levels in these brain regions after smoking cessation were at or below those found in the control population, which indicated that smoking-induced changes are reversible after cessation of nicotine treatment. These results suggest that increases in nicotinic receptor levels in the human brain may underlie nicotine tolerance and addiction in smokers.