Association between cigarette smoking and FHIT gene alterations in lung cancer

Epidemiologic data have strongly indicated that cigarette smoking is linked to the development of lung cancer. However, little is known of the molecular targets of carcinogens contained in tobacco smoke. To identify genetic lesions characteristic of tobacco damage, we undertook a molecular analysis of microsatellite alterations within the FHIT gene and FRA3B, as well as at an independent locus on chromosome 10, D10S197, in lung tumors from heavy smokers and in tumors from never smokers. Loss of heterozygosity affecting at least one locus of the FHIT gene was observed in 41 of 51 tumors in the smokers group (80%) but in only 9 of 40 tumors in nonsmokers (22%). The comparison between the frequency of losses in FHIT in smokers and nonsmokers was statistically significant (P = 0.0001), whereas no difference in loss of heterozygosity rate was observed at D10S197 locus. These findings suggest that FHIT is a candidate molecular target of carcinogens contained in tobacco smoke.     

The association between cigarette smoking and ocular diseases

Tobacco smoke is composed of as many as 4,000 active compounds, most of them toxic on either acute or long-term exposure. Many of them are also poisonous to ocular tissues, affecting the eye mainly through ischemic or oxidative mechanisms. The list of ophthalmologic disorders associated with cigarette smoking continues to grow. Most chronic ocular diseases, with the possible exception of diabetic retinopathy and primary open-angle glaucoma, appear to be associated with smoking. Both cataract development and age-related macular degeneration, the leading causes of severe visual impairment and blindness, are directly accelerated by smoking. Other common ocular disorders, such as retinal ischemia, anterior ischemic optic neuropathy, and Graves ophthalmopathy, are also significantly linked to this harmful habit. Tobacco smoking is the direct cause of tobacco-alcohol amblyopia, a once common but now rare disease characterized by severe visual loss, which is probably a result of toxic optic nerve damage. Cigarette smoking is highly irritating to the conjunctival mucosa, also affecting the eyes of nonsmokers by passive exposure (secondhand smoking). The dangerous effects of smoking are transmitted through the placenta, and offspring of smoking mothers are prone to develop strabismus. Efforts should be directed toward augmenting the campaign against tobacco smoking by adding the increased risk of blindness to the better-known arguments against smoking. We should urge our patients to quit smoking, and we must make them keenly aware of the afflictions that can develop when smoke gets in our eyes.     

The relationship between body mass and cigarette smoking using a biochemical index of smoking exposure

This study evaluated the relationship between smoking and body mass using objective indices of both smoking exposure (COHb) and body mass. The subjects were 4240 adults who participated in the Second National Health and Nutrition Examination Survey (NHANES II). Measurements of dietary intake, physical activity, demographics, body mass index (BMI) and blood carboxy-haemoglobin (COHb) were used in these analyses. After controlling for covariables of body mass, the results indicated that smokers displayed a significantly lower mass compared with non-smokers. Smokers with higher levels of COHb had lower BMIs than smokers at lower COHb levels. White smokers had lower BMIs with increasing COHb exposure whereas black smokers had BMIs at high COHb exposure similar to those of non-smokers. Results indicated that smokers weighed less than non-smokers and that the weight control 'benefits' of smoking were most pronounced in white subjects who were heavy smokers.     

Evidence that suggests a negative association between cigarette smoking and learning performance

The results of this study indicate that tobacco smoking may have a deleterious effect on the learning process. One hundred and fifteen male volunteers were assessed on four learning tasks. Those Ss who smoked in excess of 12 cigarettes per day did significantly less well, as a group, than nonsmokers and light smokers on three of the four learning tests.     

Association of coffee drinking with cigarette smoking in the natural environment.

Coffee drinking may serve as a cue for cigarette smoking. The association of coffee drinking and cigarette smoking in the natural environment was studied in 6 participants who recorded every instance of ad lib cigarette smoking and coffee drinking for 4 consecutive days. The rate of cigarette smoking was higher during intervals associated with coffee drinking (2.4 cigarettes/hr) than at other times of the day (1.0 cigarettes/hr). However, diary records revealed that on average only 14% of cigarettes were smoked while drinking coffee, and only 55% of coffee-drinking events were accompanied by cigarettes. These results suggest that coffee drinking may exert some stimulus control over smoking in the natural environment. However, given the limited number of coffee-drinking episodes compared with cigarettes consumed in a day, the contributions of coffee drinking to maintaining smoking behavior are probably minimal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Passive cigarette smoking and reduced HDL cholesterol levels in children with high-risk lipid profiles

BACKGROUND: HDL cholesterol levels are known to be lower in smokers than in nonsmokers. Previous studies have demonstrated an association of decreased HDL cholesterol with passive smoking in children but have not adjusted for potential confounding factors. METHODS AND RESULTS: In a cross-sectional, pilot-scale study, we examined the relationship of HDL cholesterol levels to passive smoking in children and adolescents referred to a tertiary hyperlipidemia clinic. Eligibility criteria included (1) first visit to a lipid clinic, (2) LDL cholesterol >95th percentile for age or HDL cholesterol <5th percentile, (3) age between 2 and 18 years, and (4) absence of secondary causes of hyperlipidemia. Sociodemographic information, diet record, medical history, and fasting lipid profiles were obtained. Of 109 eligible patients, 103 (94%) were studied. Twenty-seven percent came from households with cigarette smokers. HDL cholesterol levels were 38.7+/-1.2 mg/dL (mean+/-SEM) in passive smokers versus 43.6+/-1.2 mg/dL in children without smoke exposure (P=.005). Smoking exposure was not significantly associated with other lipid values. The effect of smoking on HDL cholesterol was minimally affected by potential confounders. In multivariate regression adjusting for body mass index, age, sex, exercise, and dietary fat intake, passive smoking remained a significant risk factor for decreased HDL cholesterol (P=.012). CONCLUSIONS: Mean HDL cholesterol levels are lower in dyslipidemic children from households with smokers than in those without household smoke exposure. Passive smoking may worsen the risk profile for later atherosclerosis among high-risk young persons.     

The relationship between religious activities and cigarette smoking in older adults

BACKGROUND: The objective of this study was to examine the relationship between religious activities and cigarette smoking in community-dwelling older adults. METHODS: Cigarette smoking and religious activities were assessed in a probability sample of 3968 persons age 65 years or older participating in the Duke Populations for Epidemiologic Studies of the Elderly (EPESE) survey. Participants were asked if they currently smoked, if they ever smoked, and how many cigarettes per day they smoked. Attendance at religious services, participation in private religious activities (prayer or Bible study), and use of religious media (religious TV or radio) were also assessed. Data were available for Waves I-III of the survey (1986, 1989, and 1992). Analyses were controlled for age, race, sex, education, alcohol use, physical health, and in the longitudinal analyses, smoking status at prior waves. RESULTS: Cross-sectional analyses revealed that participants who frequently attended religious services were significantly less likely to smoke cigarettes at all three waves. Likewise, elders frequently involved in private religious activity were less likely to smoke (Waves II and III). Total number of pack-years smoked was also inversely related to both attendance at religious services and private religious activities. Watching religious TV or listening to religious radio, on the other hand, was not related to smoking at Waves I and II nor to total pack-years smoked, but was positively related to current smoking at Wave III. Among those who smoked, number of cigarettes smoked was inversely related to frequency of attendance at religious services (Wave I), private religious activities (Wave III), and religious TV/radio (Waves II and III). Retrospective and prospective analyses revealed that religiously active persons were less likely to ever start smoking, not more likely to quit smoking. CONCLUSIONS: Religiously active persons are less likely to smoke cigarettes, and if they do smoke, smoke fewer cigarettes. Given the association between smoking and disease, and the widespread prevalence of both smoking and religious activity, this finding has implications for public health.     

The association between cigarette smoking and selected HIV-related medical conditions

OBJECTIVE: To clarify the effect of cigarette smoking on the development of conditions associated with HIV infection. DESIGN: Prospective and retrospective cohort study, with interview and examination twice a year since 1988. METHODS: Data on 516 HIV-infected men from cohorts of homosexual and bisexual men in San Francisco, Denver and Chicago, who were repeatedly interviewed and examined between 1988 and 1992, were analysed. After excluding men who did not have well-defined dates of seroconversion and those who were classified as ex- or intermittent smokers, 232 men remained for analysis: 106 were smokers and 126 were non-smokers. Univariate and Kaplan-Meier survival analyses were performed to assess the relationship between cigarette smoking and loss of CD4+ T-lymphocytes, diagnosis of any AIDS-defining illness, and specific diagnosis of Kaposi's sarcoma, Pneumocystis carinii pneumonia (PCP), oral candidiasis, hairy leukoplakia, and community-acquired pneumonia. RESULTS: By univariate analyses, cigarette smoking was not associated with clinical AIDS, loss of CD4+ cells, Kaposi's sarcoma or PCP, but was significantly associated with oral candidiasis [relative risk (RR), 1.32; 95% confidence interval (CI), 1.02-1.70], hairy leukoplakia (RR, 1.51; 95% CI, 1.15-1.99), and community-acquired pneumonia (RR, 2.62; 95% CI, 1.30-5.27). Dose-response effect was also evident for these three conditions (all P < 0.01). Kaplan-Meier survival analysis indicated no association between cigarette smoking and time of progression to clinical AIDS, Kaposi's sarcoma (KS), or PCP (P = 0.62, 0.54 and 0.11, respectively) but showed that cigarette smokers developed oral candidiasis, hairy leukoplakia, and pneumonia more quickly than non-smokers (P = 0.031, 0.006 and 0.009, respectively). CONCLUSIONS: Cigarette smoking was not associated with an increased likelihood or rate of developing KS, PCP or AIDS, but was associated with developing community-acquired pneumonia, oral candidiasis, and hairy leukoplakia in these HIV-infected men.     

Anti-oxidant enzymes, gamma-glutamyl transpeptidase and lipid peroxidation in kidney of rats exposed to cigarette smoke

Glutathione reductase (GR), glutathione peroxidase (GSH Px) and catalase (Cat) were determined in the kidneys of rats exposed to cigarette smoke for 3 months. Activity of the brush-border enzyme gamma-glutamyl transpeptidase (GGT), glutathione (GSH) and lipid peroxide levels (LPX) were also estimated in both, kidney homogenates and urine. Activities of GR, Cat, GGT and the levels of GSH were decreased in the kidney. However, the activities of GSH Px and LPX levels were increased. Urinary excretion of GGT, GSH and LPX were also higher. Fall in the activity of GR and rise in the activity of GSH Px, may perturb the reduced glutathione/oxidised glutathione ratio, which in turn could lead to increased LPX seen in chronic cigarette smoke exposure.     

Respiratory response to cigarette smoking among adolescent smokers: a pilot study

BACKGROUND: Because cigarette smoking affects the respiratory system earlier than many other systems of the human body, an attempt was made to identify objective and subjective respiratory problems among adolescent smokers. METHODS: Two studies based on a pulmonary function test (PFT), respiratory symptom assessment, and other smoking-related variables were undertaken. Study 1 involved cigarette smokers (N = 18, 22% males, mean age 18.7 years) from a freshman college class who participated in an acute smoking experiment that involved performing a PFT before and after smoking a single cigarette. Study 2 was performed on a combined group of vocational-technical high school students and freshman college students (N = 44, 48% males, mean age 17.8 years) where PFT parameters, respiratory symptoms, and smoking-related health vulnerability were assessed among smokers vs nonsmokers. RESULTS: In Study 1, the average reduction across PFT parameters was 4.4% and the mean estimated lung age increased from 27.15 to 29.84 years. In Study 2, a consistent trend toward reduction of PFT values among smokers vs nonsmokers was observed; the mean forced expiratory volume in 1 sec/forced vital capacity ratio (90.51% vs 94.59%), peak expiratory flow rate (80.32% vs 92.06%), and flow rate of 50% of forced vital capacity (88.39% vs 102.81%) differed significantly. Significant differences in respiratory symptoms were also observed among smokers vs nonsmokers. CONCLUSIONS: The beginning of respiratory health disorders can be identified among adolescent smokers. These findings might provide important clues on how to improve outcomes from health care provider-based adolescent smoking cessation counseling.     

The relationship between lipid peroxidation and life span in Drosophila melanogaster

Using Drosophila lines pre-selected for adaptive characters, studies have been made on the relationship between the intensity of lipid peroxidation and life span in flies of different genotype, age and physiological condition. It was shown that the intensity of lipid peroxidation depends mainly on different factors (sex, age, virginity) in different lines. No expected negative correlation was found between the level of lipid peroxidation and life span in hybrids between two inbred lines. The intensity of lipid peroxidation was inherited like a dominant character, the dynamics of aging--like a codominant one in females and superdominant in males. Both the level of lipid peroxidation and life span appeared to be sex-dependent characters.     

Dupuytren''s contracture and cigarette smoking

Neisseria lactamica was isolated from the blood of a pediatric patient who had signs of septicemia and otitis media. Organisms morphologically resembling Neisseria, as well as gram-positive cocci, were seen on a Gram stain of fluid from the middle ear. It is hypothesized that the N. lactamica septicemia was secondary to infection of the middle ear by this organism.     

The relationship between cigarette smoking and the risk of endometrial neoplasms

A series of therapeutic and educational workshops were conducted with women nursing home residents with the twin goals of improving self-esteem and self-reliance, and facilitating community building and networking. Alongside these workshops were nursing home staff trainings whereby staff were encouraged to articulate their needs and those of resident women in productive ways.     

Genetic damage in exfoliated cells of the uterine cervix. Association and interaction between cigarette smoking and progression to malignant transformation?

OBJECTIVE: To determine, through the micronucleus (MN) test, the cytogenetic effects of cigarette smoking on exfoliated cells from the uterine cervix in women with normal smears and women with inflammatory atypia, squamous intraepithelial lesion (SIL) (cervical intraepithelial neoplasia [CIN] 1-3) and cervical cancer. STUDY DESIGN: The study group consisted of 200 women divided into three subgroups: group 1 (n = 116), women periodically undergoing cervical cytology and residents of Salvador-Bahia; group II (n = 57), women residing in S?o Paulo and previously selected because of a possible cytopathologic test positive for such conditions as human papillomavirus infections or malignant or premalignant cervical lesions (CIN 1-3); group III (n = 27), inmates of the Tatuapé Penal Institution, S?o Paulo. All the women underwent cytologic and colposcopic examination, and biopsies were performed on 68 of them. RESULTS: Considering the samples as a whole and using the chi(2) test for rare events, the number of MNs in smokers was significantly greater than in nonsmokers. It was also greater in women with larger exposure to smoking. The occurrence of MN was significantly lower in women with normal smears (smokers and nonsmokers) than in those showing any kind of pathologic alteration. In nonsmokers the occurrence of MN was similar between those with inflammatory atypia (IA) or low grade (L) SIL (CIN 1) and significantly higher in women with more severe lesions or high grade (H) SIL (CIN 2 and 3). Smokers with LSIL (CIN 1) showed a higher number of MNs than nonsmokers with a comparable diagnosis and smokers with IA. No differences were observed when compared with smokers with HSIL (CIN 2 and 3). MN occurrence was not associated with other risk factors for SIL or cancer development, such as age at first coitus, number of sexual partners, multiparity and use of hormonal contraceptives. CONCLUSION: These results suggest that the mutagenic effect of cigarette smoking occurs in cervical cells and that the progression of SIL is associated with increased frequency of chromosomal damage. Moreover, the data suggest that cigarette smoking introduces an additional risk to the progression of low grade LSIL (CIN 1). MN testing would be helpful in monitoring smokers with this kind of lesion.     

Gamma-irradiation and UV-C light-induced lipid peroxidation: a Fourier transform-infrared absorption spectroscopic study

Metabolism of most drugs influences their pharmacological and toxicological effects. Drugs particularly affected are those with a narrow therapeutic window and that are subjected to considerable first-pass metabolism. Much of the interindividual and interethnic differences in effects of drugs is now attributable to genetic differences in their metabolism. Genetic polymorphisms have been described for many drug-metabolising enzymes in Caucasian and Oriental populations, the most well-characterised being those for cytochrome P450 2D6, cytochrome P450 2C19, glutathione S-transferases, and N-acetyl transferase 2. African populations have been studied to a lesser extent, but it is apparent that populations within Africa are heterogeneous with respect to these polymorphisms. In addition, although some allelic variants are common to all populations throughout the world (e.g., CYP2D6*5), some allelic variants are specific for an African population (e.g., CYP2D6*17). The polymorphisms give rise to enzymes with changed or no activity towards drug substrates. Two of the most important enzymes for metabolism of neuroleptics and other psychoactive drugs are CYP2D6 and CYP2C19. This article compares the current information on polymorphisms of these two enzymes in African and other populations and discusses the implications of these polymorphisms for neuropharmacotherapy.     

A longitudinal study predicting patterns of cigarette smoking in late childhood

Early initiation of cigarette smoking so strongly predicts future smoking that several investigators have advocated delaying the age of initiation as a prevention strategy. To complement retrospective studies of early initiation, this study assessed prospectively patterns of smoking behavior in a sample of 401 children who were surveyed in the fifth, sixth, and seventh grades. The principal findings were (1) modeling of smoking by parents and friends is sufficient to influence children to initiate smoking, particularly when children also have low behavioral self-control, and (2) when modeling occurs in combination with poor adjustment to school, low parental monitoring, easy access to cigarettes, and other risk attributes, early initiators are significantly more likely to continue smoking. The results suggest that delaying initiation of smoking without also modifying child attributes and socialization factors that predict early initiation and persistent smoking is unlikely to reduce the proportion of children who become habitual smokers.     

Advanced glycation endproducts and cigarette smoking

The incidence of certain ageing sequelae such as lung and cardiovascular disease and cataract are higher in smokers than in non-smokers. We recently proposed that certain components of mainstream cigarette smoke can react with plasma and extracellular matrix proteins to form covalent adducts with many of the properties of advanced glycation endproducts (AGE). AGEs have been implicated previously in the pathogenesis of the end-organ complications of diabetes and ageing, including cataract, atherosclerosis and renal insufficiency. In these circumstances, AGEs arise in vivo from the non-enzymatic reaction of reducing sugars with amino groups. Over time the initial Schiff base and Amadori products that form gradually undergo dehydration and rearrangement to produce reactive, carbonyl containing compounds with characteristic fluorescence and covalent crosslinking properties. Recent studies indicate that in smokers, tobacco-derived AGEs accumulate on plasma low density lipoprotein (LDL), structural proteins present within the vascular wall, and the lens proteins of the eye. These data point to a new and significant source of Maillard products in the human environment, significantly broaden the role of Maillard chemistry in pathological processes, and provide new insight into the pathogenesis of atherosclerosis and other diseases associated with tobacco usage.     

Nitric oxide and lipid peroxidation

Nitric oxide (NO) is a free radical produced enzymatically in biological systems from the guanidino group of L-arginine. Its large spectrum of biological effects is achieved through chemical interactions with different targets including oxygen (O2), superoxide (O2o-) and other oxygen reactive species (ROS), transition metals and thiols. Superoxide anions and other ROS have been reported to react with NO to produce peroxynitrite anions that can decompose to form nitrogen dioxide (NO2) and hydroxyl radial (OHo). Thus, NO has been reported to have a dual effect on lipid peroxidation (prooxidant via the peroxynitrite or antioxydant via the chelation of ROS). In the present study we have investigated in different models the in vitro and in vivo action of NO on lipid peroxidation. Copper-induced LDL oxidation were used as an in vitro model. Human LDL (100 micrograms ApoB/ml) were incubated in oxygene-saturated PBS buffer in presence or absence of Cu2+ (2.5 microM) with increasing concentrations of NO donnors (sodium nitroprussiate or nitroso-glutathione). LDL oxidation was monitored continuously for conjugated diene formation (234 nm) and 4-hydroxynonenal (HNE) accumulation. Exogenous NO prevents in a dose dependent manner the progress of copper-induced oxidation. Ischaemia-reperfusion injury (I/R), characterized by an overproduction of ROS, is used as an in vivo model. Anaesthetized rats were submitted to 1 hour renal ischaemia following by 2 hours of reperfusion. Sham-operated rats (SOP) were used as control. Lipid peroxidation was evaluated by measuring the HNE accumulated in rats kidneys in presence or absence of L-arginine or D-arginine infusion. L-arginine, but not D-arginine, enhances HNE accumulation in I/R but not in SOP (< 0.050 pmol/g tissue in SOP versus 0.6 nmol/g tissue in I/R), showing that, in this experimental conditions, NO produced from L-arginine, enhances the toxicity of ROS. This study shows that the pro- or antioxydant effects of NO are different in vivo and in vitro and could be driven by environmental conditions such as pH, relative concentrations of NO and ROS, ferryl species.     

Association between marginal bone loss around osseointegrated mandibular implants and smoking habits: a 10-year follow-up study

While many factors are conceivable, occlusal loading and plaque-induced inflammation are frequently stated as the most important ones negatively affecting the prognosis of oral implants. Currently, little is known about the relative importance of such factors. The aim of this study was to analyze the influence of smoking and other possibly relevant factors on bone loss around mandibular implants. The participants were 45 edentulous patients, 21 smokers and 24 non-smokers, who were followed for 10-year period after treatment with a fixed implant-supported prosthesis in the mandible. The peri-implant bone level was measured on intraoral radiographs, information about smoking habits was based on a careful interview, and oral hygiene was evaluated from clinical registration of plaque accumulation. Besides standard statistical methods, multiple linear regression models were constructed for estimation of the relative influence of some factors on peri-implant bone loss. The long-term results of the implant treatment were good, and only three implants (1%) were lost. The mean marginal bone loss around the mandibular implants was very small, about 1 mm for the entire 10-year period. It was greater in smokers than in non-smokers and correlated to the amount of cigarette consumption. Smokers with poor oral hygiene showed greater marginal bone loss around the mandibular implants than those with good oral hygiene. Oral hygiene did not significantly affect bone loss in non-smokers. Multivariate analyses showed that smoking was the most important factor among those analyzed for association with peri-implant bone loss. The separate models for smokers and non-smokers revealed that oral hygiene had a greater impact on peri-implant bone loss among smokers than among non-smokers. This study showed that smoking was the most important factor affecting the rate of peri-implant bone loss, and that oral hygiene also had an influence, especially in smokers, while other factors, e.g., those associated with occlusal loading, were of minor importance. These results indicate that smoking habits should be included in analyses of implant survival and peri-implant bone loss.