Structural and functional alterations caused at the extraneuronal level by sympathetic denervation of blood vessels

Summary The lateral saphenous vein of the dog and the rabbit ear artery were surgically denervated, by clamping the vessel or by removal of the superior cervical ganglion, respectively. Both procedures resulted in denervation of the vessels.The denervated, lateral saphenous vein was supersensitive to exogenous noradrenaline and inactivation of the amine (in oil immersion experiments) was slower in denervated vein strips than in control strips treated with cocaine. Incubation experiments with ³H-noradrenaline confirmed that denervated strips formed considerably fewer metabolites than control ones (in the absence or presence of cocaine) and that O-methylation of noradrenaline was reduced by about 50%. When the strips were incubated with ³H-isoprenaline, the denervated ones accumulated and metabolized isoprenaline to a lesser degree than control strips. Hydrocortisone did not reduce the accumulation of isoprenaline in the denervated vein and had only minor effects on O-methylation. The metabolism of noradrenaline and isoprenaline gradually recovered with time.In the ear artery, denervation was accompanied by a marked reduction in O-methylation, but not in accumulation, of isoprenaline. In both vessels there was a highly significant positive correlation between noradrenaline content and O-methylating capacity; in the saphenous vein accumulation of isoprenaline was also positively correlated to noradrenaline content.Morphological changes observed in the denervated vessels consisted essentially in dedifferentiation of smooth muscle cells (which attained larger dimensions, had an indented, large nucleus, augmented euchromatin and an increased amount of ribosomes), abundance of extracellular material and fibroblasts. Mast cells were present in denervated veins (but not in controls) and the histamine content was increased in the former. Structural alterations were homogeneously distributed in the saphenous vein but restricted to the adventitio-medial area in the rabbit ear artery. Depletion of endogenous noradrenaline by reserpine pretreatment did not cause the alterations seen after denervation. On the other hand, continuous intravenous infusion of noradrenaline during 5 days did not prevent, and even worsened, the alterations caused by denervation. It was concluded that noradrenaline does not appear to be the factor the lack of which is exclusively responsible for the impairment of the extraneuronal system, in the denervated tissue.Taken together, the data show that the sympathetic innervation of blood vessels exerts a regulatory function on extraneuronal events; the disappearance of innervation results in marked impairment of the corticosteroid-sensitive O-methylating system and in morphological changes of both smooth muscle cells and fibroblasts.Part of the results were presented at 3rd Joint Meeting of the French and Spanish Pharmacological Societies in Toulouse, 1981 (Branco et al. 1982)     

Toxicological overview of cigarette smoking on angiogenesis

Angiogenesis is the process of generating new capillary blood vessels. It occurs under tight regulation in the female reproductive system, during wound healing and during embryogenesis. Angiogenesis also plays an important role in the pregnancy-associated changes in the reproductive tract. Cigarette smoke inhibits processes that may hinder normal process of angiogenesis resulting in abnormal blood supply to tissues, decreased repair and remodeling. This report summarizes the evidences of the causal association between tobacco smoking and disruption of angiogenesis. Application of small amount of nicotine on day 5 old chorioallantoic membranes (CAMs) did not disrupt the process of angiogenesis, while application of mainstream smokes (MSS) solutions to CAMs caused varying levels of disruption on normal process of angiogenesis and adversely affect capillary plexus formation, diameters of secondary and tertiary vessels. We have also observed that at equivalent doses, sidestream smoke (SSS) can significantly be more potent than MSS and can alter the normal process of angiogenesis more drastically than MSS. It suggests that SSS either contains a toxicant(s) not present in MSS or that the toxicant(s) that produces these effects is present in higher concentration in SSS than in MSS. Therefore, it is undisputed that smoking can interfere the normal process of angiogenesis, which is a vital process to maintain pregnancy and development of fetus. Smoking during pregnancy is harmful to fetal development and is associated with an increased risk of miscarriage, perinatal death and sudden infant death syndrome. Smoking-cessation programs remain a crucial strategy for preventing poor birth outcomes and decreasing the social and financial costs of smoking during pregnancy.     

The continuous and simultaneous blood flow velocity measurement of four cerebral vessels and a peripheral vessel during cigarette smoking

There has been no consensus about the acute effect of cigarette smoking on cerebral blood flow, and the continuous change of flow in four cerebral vessel flow with peripheral flow during different kinds of cigarette smoking has not been reported until now. Our results indicate smoking increases the flow of four cerebral vessels almost at the same time and with the same pattern. Many cerebral vessels began to show increases about 10 s after commencement. In most cases, cerebral blood velocity began to decrease between 10 and 20 s after cessation. Blood flow in peripheral vessels decreases after commencement, which is thought to be the effect of nicotine. The effect of high nicotine cigarettes is greater than that of low nicotine cigarettes. Continuous and simultaneous measurement of cerebral vessels by ultrasonic Doppler is thought to be the only way to establish the detailed blood flow changes during smoking. Received: 4 February 1996/Final version: 8 January 1997     

Imitation of cigarette smoking: an experimental study on smoking in a naturalistic setting

AIMS: Examine whether smokers imitate smoking behaviour of strangers and to what extent this is moderated by the nature of social interactions. DESIGN AND PARTICIPANTS: An experiment with a three (heavy smoking, light smoking, or no smoking condition) by two (warm versus cold social interaction condition) factorial design. Daily smoking young adults were exposed to same-gender confederates and were observed in a bar laboratory. MEASUREMENTS: Smoking and social behaviour were observed and coded during a 30-min break between two tasks, consisting of rating television advertisements. FINDINGS: Participants imitated the smoking behaviour of confederates. After controlling for young people's craving, confederate's smoking explains 35% of the variance in the number of cigarettes smoked. Participants are more likely to smoke and to continue smoking in the warm social interaction condition. Lighting up the first cigarette was affected by confederate's smoking and participant's urges to smoke. Lighting up a second was affected by the heavy smoking condition and warm social interaction condition. Lighting up a third cigarette was affected only by the heavy smoking condition. CONCLUSION: Imitation largely explains why individuals light up a cigarette and continue to smoke.     

Effects of ventilated cigarette holders on cigarette smoking by humans

Heavy cigarette smokers individually attended daily 3-h test sessions which were run in specially designed cigarette smoking evaluation rooms. Subjects were required to use the cigarette holder provided, and were required to extinguish each cigarette 4 min after the first puff on the cigarette. Other than these restrictions, subjects were allowed to smoke ad libitum. The concentration of delivered tobacco product was varied from 100 to 10% across sessions by using graded commercially available ventilated cigarette holders. As concentration of tobacco product was decreased, rate of puffing and total number of puffs showed robust compensatory increases. Number of cigarettes increased only moderately in response to decreases in tobacco product concentration. There was little change in subjective ratings of strength on smoking satisfaction. Finally, expired air carbon monoxide (CO) values and cigarette butt weights were relatively stable across the four ventilation conditions. These later findings suggest that a significant degree of compensation had occurred in response to the concentration manipulations.     

Coffee drinking and cigarette smoking: I. coffee,caffeine and cigarette smoking behavior

Two experiments designed to assess the relationship between coffee intake and smoking are reported. In Experiment I, coffee drinking smokers were randomly assigned to four groups in which they received 0, 1, 2, or 3 cups of coffee during two one-hour sessions while they worked on crossword puzzles. Results showed that subjects receiving coffee in any amount smoked more than subjects who were not provided coffee. Moderate and low rate smokers were then randomly assigned to one of five groups in Experiment II, in which they were provided no drink, water, Postum^® (a coffee substitute), caffeinated, or decaffeinated coffee. These groups were selected to assess the characteristics of coffee that may have influenced increased smoking. Results for number of cigarettes smoked and puff rate generally showed that subjects receiving caffeinated or decaffeinated coffee smoked more than subjects in the no drink or water control groups. The results of this study provide experimental evidence of the role of coffee in setting the occasion for smoking, as well as ruling out the presence of a liquid or caffeine as the important characteristics of coffee in influencing smoking.     

Increased vascular contractility in isolated vessels from cigarette smoking rats is mediated by basal endothelin release

The effect of chronic cigarette smoking on endothelin modulation of vascular contraction, and CYP enzyme levels was studied in 20 male Sprague-Dawley rats. The animals were divided equally into smoking and non-smoking groups. The smoking group was exposed to 6 research cigarettes per rat per day 5 days a week for 16 weeks. The control group was sham smoked. Functional contractile studies were performed in aortas and carotid arteries to determine the regulation of vascular tone by basal release of endothelin. Liver samples were analyzed for CYP1A1 and CYP1A2 gene expression by RT-PCR. Plasma samples were assessed for endothelin-1 (ET-1) level by enzyme immuno assay (EIA). Treatment of aortas and carotid arteries with bosentan, the dual endothelin receptor antagonist, caused a significant reduction in constrictor responses of smoking rats, indicating, increase greater regulation of tone by endothelin in smoker rats compared to controls. There was a greater expression of the cytochrome P450-liver enzymes (CYP1A1 and CYP1A2) in smoker rats. Body weight gain was also significantly decreased in smoker rats. We conclude that increased endothelin release in smoker rats significantly contributes to increased arterial tone and so contribute to the cardiovascular pathophysiology associated with cigarette smoking, such as increased vascular muscularization, increased contraction, decreased dilation and possibly vasospasm.     

Coffee drinking and cigarette smoking: II. coffee, urinary pH and cigarette smoking behavior

Two experiments designed to assess the relationship between coffee intake and smoking are reported. In Experiment I, coffee drinking smokers were randomly assigned to four groups in which they received 0, 1, 2, or 3 cups of coffee during two one-hour sessions while they worked on crossword puzzles. Results showed that subjects receiving coffee in any amount smoked more than subjects who were not provided coffee. Moderate and low rate smokers were then randomly assigned to one of five groups in Experiment II, in which they were provided no drink, water, Postum^® (a coffee substitute), caffeinated, or decaffeinated coffee. These groups were selected to assess the characteristics of coffee that may have influenced increased smoking. Results for number of cigarettes smoked and puff rate generally showed that subjects receiving caffeinated or decaffeinated coffee smoked more than subjects in the no drink or water control groups. The results of this study provide experimental evidence of the role of coffee in setting the occasion for smoking, as well as ruling out the presence of a liquid or caffeine as the important characteristics of coffee in influencing smoking.     

吸烟对血液过氧化与抗氧化平衡的影响

比较吸烟与不吸烟人静脉血血浆及红细胞脂质过氧化物-丙二醛（MDA）含量，血浆及红细胞超氧化物歧化酶（SOD）活力、全血谷胱甘肽过氧化物酶（GSH－Px）活力及血浆总抗氧化能力（AOA）．结果表明：吸烟组血浆及红细胞MDA的含量高于不吸烟组（P＜0．01），红细胞SOD含量高于不吸烟组（P＜0．01），血浆SOD、全血GSH－Px活力．血浆AOA均低0于不吸烟组（P＜0．01，P＜0．05，P＜0.05）．提示长期吸烟可使血中氧化与抗氧化失去平衡。     

Acute effects of electronic and tobacco cigarette smoking on complete blood count

The World Health Organisation called for research assessing the safety of electronic cigarette (e-cigarette). We evaluated the acute effect of active and passive e-cigarette and tobacco cigarette smoking on complete blood count (CBC) markers in 15 smokers and 15 never-smokers, respectively. Smokers underwent a control session, an active tobacco cigarette smoking session, and an active e-cigarette smoking session. Never-smokers underwent a control session, a passive tobacco cigarette smoking session, and a passive e-cigarette smoking session.The results demonstrated that CBC indices remained unchanged during the control sessionand the active and passive e-cigarette smoking sessions (P > 0.05). Active and passive tobacco cigarette smoking increased white blood cell, lymphocyte, and granulocyte counts for at least one hour in smokers and never smokers (P < 0.05).It is concluded that acute active and passive smoking using the e-cigarettes tested in the current study does not influence CBC indices in smokers and never smokers, respectively. In contrast, acute active and passive tobacco cigarette smoking increase the secondary proteins of acute inflammatory load for at least one hour. More research is needed to evaluate chemical safety issues and other areas of consumer product safety of e-cigarettes, because the nicotine content in the liquids used may vary considerably.     

Chewing tobacco use by adolescents: Prevalence and relation to cigarette smoking

The prevalence of teenage smokeless tobacco use and its relation to cigarette smoking was studied. Nine percent of 7th grade boys and 20% of 9th and 10th grade boys reported daily use. There was very little regular chewing among girls although about 20% reported having tried it. There was a strong association between smoking and chewing among 7th graders but only a weak association among 9th and 10th graders. Boys who chew tended to have friends who chew and/or smoke. The data suggested that chewing is affected by peer social influence processes in a manner similar to smoking.     

Comparison of environmental tobacco smoke (ETS) concentrations generated by an electrically heated cigarette smoking system and a conventional cigarette

Smoking conventional lit-end cigarettes results in exposure of nonsmokers to potentially harmful cigarette smoke constituents present in environmental tobacco smoke (ETS) generated by sidestream smoke emissions and exhaled mainstream smoke. ETS constituent concentrations generated by a conventional lit-end cigarette and a newly developed electrically heated cigarette smoking system (EHCSS) that produces only mainstream smoke and no sidestream smoke emissions were investigated in simulated "office" and "hospitality" environments with different levels of baseline indoor air quality. Smoking the EHCSS (International Organisation for Standardization yields: 5 mg tar, 0.3 mg nicotine, and 0.6 mg carbon monoxide) in simulated indoor environments resulted in significant reductions in ETS constituent concentrations compared to when smoking a representative lit-end cigarette (Marlboro: 6 mg tar, 0.5 mg nicotine, and 7 mg carbon monoxide). In direct comparisons, 24 of 29 measured smoke constituents (83%) showed mean reductions of greater than 90%, and 5 smoke constituents (17%) showed mean reductions between 80% and 90%. Gas-vapor phase ETS markers (nicotine and 3-ethenylpyridine) were reduced by an average of 97% (range 94-99%). Total respirable suspended particles, determined by online particle measurements and as gravimetric respirable suspended particles, were reduced by 90% (range 82-100%). The mean and standard deviation of the reduction of all constituents was 94 +/- 4%, indicating that smoking the new EHCSS in simulated "office" and "hospitality" indoor environments resulted in substantial reductions of ETS constituents in indoor air.     

Changes in muscle blood flow after smoking a cigarette determined by a new noninvasive method

Summary The pharmacokinetics of the H₂-receptor antagonist famotidine, after oral administration of a 20 mg tablet, has been studied in 10 elderly patients with normal renal function (CL_CR59 ml·min^–1, Mean=80 ml·min^–1), 5 elderly patients with renal insufficiency (CL_CR38 ml·min^–1, Mean=15 ml·min^–1), and 6 healthy young volunteers.Elimination half-life in the elderly patients with renal insufficiency was significantly prolonged compared to the elderly patients with normal renal function and the young volunteers. The correlation coefficient between creatinine clearance and the elimination rate constant of famotidine was 0.672. Mean urinary recovery of unchanged drug up to 24 h in the young volunteers was 44%. The mean renal clearance of famotidine in the young volunteers (270 ml·min^–1) was substantially greater than the creatinine clearance, 128 ml·min^–1, which suggests the possibility of tubular secretion of famotidine.     

脑损伤过程中血脑屏障通透性的变化及其调节机制

血脑屏障是由脑微血管内皮细胞、星形神经胶质细胞、外膜细胞、血管周围巨噬细胞和基底膜组成的一个复杂系统,对维持中枢神经系统的正常功能非常重要。脑损伤如脑缺血、脑缺氧、脑外伤和蛛网膜下腔出血过程中伴随血脑屏障通透性的变化。脑缺血及其再灌注后可通过花生四烯酸代谢途径、嘌呤核苷酸代谢途径及一氧化氮途径产生自由基,可能是血脑屏障通透性增加的重要机制。血脑屏障的破坏可加重脑损伤程度;脑血管疾病时,保护血脑屏障的完整性可能是减轻脑损伤的重要措施。     

The economics of smoking: an overview of the international and New Zealand literature

The majority of work to date on the costs of smoking has focused on the enumeration of direct medical care costs. Published estimates of excess medical care expenditure attributable to smoking range from $US54 to $US1058 per smoker per year (1990 prices). Most of these studies used a cross-sectional approach to costing, however consensus increasingly favours the 'life cycle' approach to estimating the costs of cigarette smoking. The life cycle approach to costing consists of tracking all expenditures associated with smoking over the individual's lifetime. The purpose of taking this approach is to separate out the opposite impacts on medical care expenditures of higher utilisation and higher mortality. Thus, in a cross-sectional costing approach, smokers always appear to incur higher medical care costs. Using the 'life cycle' methodology, however, some of the higher medical care costs of smokers are offset by their shorter life expectancy. The policy question is whether smoking is associated with higher healthcare expenditures over the lifetime. The conclusion from studies that have adopted the 'life cycle' approach have been inconsistent. One of the earliest studies, based on Swiss data, concluded that the lifetime medical care costs for a cohort of nonsmokers was equivalent to the costs of providing care for a society of smokers. This conclusion was based on the finding that nonsmokers lived longer than smokers and used medical services more heavily during the last years of their lives.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of response requirement and the availability of an alternative reinforcer on cigarette smoking by schizophrenics

Cigarette smoking and other forms of drug abuse are more prevalent among schizophrenics than the general population. Despite the clinical importance of this problem, there has been relatively little experimental study of schizophrenic drug use. We examined under controlled laboratory conditions the effects of response requirement and the availability of an alternative (monetary) reinforcer on cigarette smoking by schizophrenics. Subjects were six heavy smokers with diagnoses of schizophrenia or schizoaffective disorder. Before each session, subjects provided carbon monoxide samples indicating recent smoking abstinence. During 3-h sessions, subjects obtained opportunities to smoke (2 puffs/opportunity) under a fixed ratio (FR) schedule of reinforcement, which varied across sessions from FR50 to FR6400. In half of the sessions, subjects also were able to earn a small amount of money ($0.25/ratio completed) under an FR400 schedule. Increasing the response requirement for smoking decreased smoking and increased smoking-maintained responding. The availability of the monetary reinforcer decreased smoking and smoking-maintained responding by approximately half. These results are consistent with those seen previously in community volunteers without major mental illness studied under the same experimental conditions, suggesting that smoking by these two populations is controlled, at least in part, by a common set of determinants. Received: 20 April 1998/Final version: 20 January 1999     

Youth crowds and cigarette smoking: A prospective study

This study examined the prospective relationship between crowd affiliation and smoking behavior among a national sample of 16–22 year old Danes (N = 952). Self-reported data were collected by means of a postal questionnaire at baseline and at 18 months follow-up. The sample included participants, who at baseline reported to identify with a crowd with either a low-smoking norm (n = 705) or a high-smoking norm (n = 247). The results showed that participants, who at baseline identified with a crowd with a high-smoking norm were compared to those, who identified with a low-smoking norm crowd, more likely to have started smoking at time of the follow-up (OR = 2.15). Further, discordance between one's behavior and the norm of the crowd resulted more often in a change in smoking behavior (OR = 2.00) and crowd identification (OR = 2.15) than the absence of such discordance. The results confirm the importance of crowds in smoking initiation and call for more attention to this issue in smoking prevention.     

Manipulation of cigarette craving through rapid smoking: efficacy and effects on smoking behavior

Craving is thought to play an important role in maintaining regular smoking patterns in current smokers, and in leading to relapse in smokers attempting to quit. Within the scientific community however, the concept is surrounded by controversy. In an effort to 1) identify interventions that can reliably influence cigarette cravings, and 2) assess the relationship between cigarette craving and smoking behavior, effects of aversive rapid smoking (up to nine cigarettes with puffs taken every 6 s) on self-reported craving and subsequent smoking behavior were compared to effects of self-paced smoking or no smoking. Subjects (n = 14) engaged in a rapid, self-paced or no smoking procedure at the start of three separate sessions. Craving levels, measured repeatedly during the next 3 h of no smoking, were significantly lower after rapid smoking than after either self-paced or no smoking. Measures of subsequent smoking behavior (latency to first cigarette, number of cigarettes, number of puffs) did not differ systematically across conditions. Thus, craving was reliably suppressed by aversive rapid smoking, but craving scores did not predict actual smoking behavior. Received: 2 April 1998/Final version: 7 August 1998