Smoking
Life Style

Author: Gianpiero Pescarmona
Date: 06/02/2009

Description

Drinking and smoking association: a bad habit?

Alcohol addiction
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[Article in Polish]

Strauss E, Waliszewski K, Pawlak AL.

Instytut Genetyki Człowieka Polskiej Akademii Nauk w Poznaniu. strauss@icpnet.pl

In abdominal aortic aneurysm (AAA) both the etiology and the pathogenesis are of the multifactorial character. The genetic component in the determination of this disease is proven by its familial occurrence. Smoking represents the best recognized risk factor of the AAA development. Increased concentrations of homocysteine (Hcy) in plasma are the common finding in these patients. It is assumed that the Hcy thiolactone, the most reactive metabolite of Hcy, may participate in the aortic wall destruction in AAA. The polymorphic variants of the methylenetetrahydrofolate reductase (MTHFR 677C>T and 1298A>C) influence tissue concentrations of the Hcy. Paraoxonase (PON1), the enzyme associated in plasma with the HDL fraction, as lactonase detoxicates the Hcy thiolactone. The promotor polymorphism of PON1 - 108C>T gene may determine the lower activity of this enzyme. In the case-control study of 106 patients with AAA and 97 healthy persons, the effects of selected genetic and nongenetic risk factors on development of AAA were assessed, considering the possibilities of interaction between them. It was found, that the arterial hypertension, cigarette smoking and the lower HDL fraction are independent risk factors of AAA. The arterial hypertension was a risk factor both in the smoking and the nonsmoking males, whereas the lower HDL fraction has been the risk factor only for the smoking men. By the multivariate analysis in the nonsmoking males the MTHFR 1298 AC and CC genotypes increased the risk of AAA development 4,8-fold in relation to the MTHFR 1298 AA nonsmoking males. In reference to the genotypes of the expected high impact on the metabolism of Hcy and of Hcy thiolactone, the genotypes of MTHFR 677TT and PON1 -108CT and TT were more frequent in smoking ones, but the difference was not significant. This observation fits with the assumption that the influence of smoking on the occurrence of AAA prevails over that of genetic variability. When the patients age was considered in the analysis, the PON1 -108CT and TT genotypes were identified as the significant risk factors for the development of AAA in the older smokers.

Am J Obstet Gynecol. 2002 Sep;187(3):620-5.
Folate levels in pregnant women who smoke: an important gene/environment interaction.

McDonald SD, Perkins SL, Jodouin CA, Walker MC.

University of Ottawa, Ottawa Hospital, Ontario, Canada. sarahmcdonald999@hotmail.com

OBJECTIVE: The objective of this study was to determine whether serum and red blood cell folate levels were decreased in pregnant women who smoke and whether total plasma homocysteine levels were elevated. STUDY DESIGN: In this cross-sectional study, serum folate, red blood cell folate, and homocysteine were measured in pregnant first- and early second-trimester pregnant women who smoked (case subjects) and pregnant women who did not smoke (control subjects). In addition, vitamin B(12), albumin, creatinine, cotinine, and hematocrit levels and methylenetetrahydrofolate reductase status were determined and compared between groups. RESULTS: Pregnant women who smoked had significantly lower concentrations of serum folate (22.7 vs 29.4 nmol/L; P =.001) and lower concentrations of red blood cell folate (766 vs 900 nmol/L; P =.038 [not significant]) than pregnant women who did not smoke. Dietary folate intake was not significantly different between pregnant women who smoked and pregnant women who did not smoke. Homocysteine levels were also not significantly different between the groups. For each genotype of methylenetetrahydrofolate reductase, lower levels of serum folate were observed in pregnant women who smoked, with the lowest folate levels seen in homozygous mutant methylenetetrahydrofolate reductase 677TT (18.6 nmol/L in pregnant women who smoked vs 24.2 nmol/L in pregnant women who did not smoke). CONCLUSION: Both serum folate and red blood cell folate are lower in pregnant women who smoked than in pregnant women who did not smoke, although homocysteine levels are not significantly different. There is an important gene environment interaction between methylenetetrahydrofolate reductase gene activity and tobacco exposure on serum folate levels. Lower levels of serum folate may account for the higher rate of miscarriage, stillbirth, abruptio placentae, and fetal anomalies that are observed in pregnant women who smoke. Pregnant women who smoke may benefit from higher doses of folic acid periconceptionally.

Smoking Behavior and the C677T Allele of the MethylenetetrahydrofolateReductase(MTHFR)Gene 2001

Local fullText

Genetics of smoking

Genome-wide meta-analyses identify multiple loci associated with smoking behavior 2010
Sequence variants at CHRNB3–CHRNA6 and CYP2A6 affect smoking behavior 2010
Meta-analysis and imputation refines the association of 15q25 with smoking quantity 2010

more from the press

Fumo materno riduce flusso ematico al feto

Il fumo in gravidanza riduce la produzione di ossido nitrico nel letto vascolare fetale, riducendo pertanto anche il flusso ematico al feto, e ritardando pertanto anche la crescita. Si tratta di una delle prime occasioni in cui viene mostrato un parametro biochimico di ciò che accade alla base dell'insorgenza del basso peso neonatale: è noto da 50 anni che i bambini delle madri che fumano sono esposti al rischio di basso peso neonatale, ma oggi è stata indicata una possibile spiegazione del fatto che vi sia una restrizione del flusso ematico al feto. Sono in progetto nuovi studi atti a determinare se la compromissione della funzionalità vascolare nel feto si traduca o meno in arteriosclerosi nelle fasi successive della vita. (Circulation online 2009, pubblicato il 3/2)

e all'adulto?

Tabagismo (Prevenzione Oncologica)

Il Fumo e' la Principale Causa di Malattia e Morte nella Societa' Attuale. Vari Tipi di
Tumore, Malattie Cardiovascolari e Respiratorie, Complicazioni della Gravidanza
Nonche' Altre Patologie sia dell'Adulto sia del Bambino sono Associati all' Esposizione
a Fumo, Attivo o Passivo. Nonostante Queste Conoscenze siano per la Gran Parte
Ormai Disponibili da Molti Anni e vi sia una Consapevolezza Diffusa, anche al di
Fuori del Mondo Scientifico e Sanitario, degi Effetti Dannosi sulla Salute del Fumo
del Tabacco si fa Ancora Molto Uso.
Questo Documento Offre, agli Operatori Sociosanitari, agli Amministratori del Sistema
Sanitario e a Tutti Coloro che sono Interessati all' Argomento, una Sintesi Condivisa
piu' che dello Stato delle Conoscenze sui Danni Oncologici da Fumo, Ormai ben Noti
degli Interventi per Contrastare la Diffusione del Tabagismo e l' Esposizione a Fumo
Passivo (Dimensione Del File PDF = 2.2 MB - Pagine = 64)

Roma, 26 apr. (Adnkronos Salute) - Il 'vizio' del fumo è scritto nel Dna. Alcune varianti genetiche, infatti, influiscono sulla decisione di iniziare con le 'bionde', sul numero di sigarette accese e sulla capacità di smettere. A identificare e pubblicare su 'Nature Genetics' i nuovi marcatori genetici associati all'attitudine al fumo sono stati gli scienziati del Tabacco and Genetics (Tag) Consortium, una collaborazione di 19 gruppi di ricerca internazionali, nato proprio per studiare linfluenza genetica sulla predisposizione a iniziare e smettere di fumare."In tutto il mondo ogni giorno si fumano più di 15 miliardi di sigarette e i fumatori sono stimati in 1,2 miliardi", spiega all'Adnkronos Salute il cardiologo Diego Ardissino, dellAzienda Ospedaliero-Universitaria di Parma. Nel Tag Consortium è stato fondamentale il contributo dei ricercatori italiani del gruppo Ateroscerosi, trombosi e biologia vascolare coordinato da Ardissino. "Abbiamo infatti arruolato una grossa coorte di pazienti italiani, assistiti presso 125 unità coronariche, per eseguire un'analisi genetica completa". E scovare così i 'tasselli' del Dna legati al vizio del fumo.I dati ottenuti dai ricercatori nello studio coordinato da Helena Furberg dell'University of North Carolina (Usa), dimostrano che non solo la decisione di iniziare a fumare, ma anche quella di smettere e il numero di sigarette accese ogni giorno - misura della dipendenza dal tabacco - sono geneticamente determinati. Inoltre i dati ottenuti dal gruppo sono stati confermati da altri due studi indipendenti, pubblicati sullo stesso numero di 'Nature Genetics'. Si tratta di lavori che hanno coinvolto complessivamente oltre 140 mila persone. I tre studi, coordinati rispettivamente dalla Furberg, componente del Tag Consortium, da Kari Stefansson della deCode di Reykjavik (Islanda) e da Clyde Francks dell'Oxford University (GB), hanno portato i ricercatori a confrontare il Dna di un vasto gruppo di fumatori e non, per identificare le varianti genetiche che influenzano lattitudine al fumo. "In questo modo - prosegue Ardissino - è stato possibile individuare le varianti genetiche associate alla decisione di iniziare a fumare (nel cromosoma 11), smettere di fumare (cromosoma 9) e al numero di sigarette fumate ogni giorno (cromosoma 15, 10, 9)". La forza di questo lavoro sta nell'avere documentato per la prima volta in maniera chiara ed inequivocabile lesistenza di un preciso legame tra specifiche varianti genetiche e labitudine al fumo. I ricercatori, infatti, mediante una nuova metodica di analisi coinvolgente lintero genoma umano, hanno dimostrato nei fumatori la presenza di modificazioni genetiche nei cromosomi 11, 9, 10 e 15. Al momento non si sa quale sia la funzione di queste varianti genetiche, spiega ancora l'esperto italiano, e come si estrinsechi la loro influenza sullattitudine al fumo. "Lunico dato noto è che le varianti genetiche sul cromosoma 15 sono localizzate in una regione che contiene i geni dei recettori della nicotina precedentemente associati alla dipendenza da questa sostanza e al cancro del polmone", conclude.

Items

E-Cigarette, Menthol and Smoking Dependence, Smoker's Face, Smoking Addiction, Smoking Cessation, Smoking Effects

Comments

2012-09-07T09:53:39 - Enrico Leonardi

ASSOCIATION BETWEEN CIGARETTE SMOKING AND ERECTILE DISFUNCTION

Erectile dysfunction (ED) is a widely spread problem among aging men. A large number of risk factors are associated with ED, including obesity, hypertension (and other chronic illnesses), unfavorable lipid levels, alcohol or drug abuse, scanty physical activity and cigarette smoking.

Penile erection phisiology

Penile erection is determined by changes in blood pressure in cavernal sinuses. This mechanism take advantage of the differences between the vasculature of erectile tissue from the most of the vascular beds. It is composed of arterioles and hollow blood-filled sinuses, both of which are covered by smooth muscle and endothelial cells.
In the absence of arousal stimuli, cavernosal vasoconstriction maintains the penis in the nonerect state. Contraction of the cavernosal smooth muscle, mainly in response to norepinephrine released from the sympathetic innervation of the penis restricts the arteriolar lumen and sinusoidal cavities, reducing blood flow to maintain low intracavernosal pressure
Sexual arousal produces the release of nitric oxide (NO), stimulating smooth muscle relaxation with a dilation of the cavernosal arterioles and sinuses: this events result in increased blood flow and a subsequent rise in intracavernosal pressure. This initial rise activates a reflected venous constriction mechanism to avoid the outflow of blood and preserve the pressure inside the cavernosum.
Although various vasodilators, such as acetylcholine and vasoactive intestinal peptide, are implicated in the erectile response, NO is thought to be the principal stimulator of cavernosal vasodilatation and penile erection. NO is formed from the precursor amino acid, L-arginine, by enzymatic action of NOS, which exists as three main isoforms: neuronal NOS (nNOS), inducible (iNOS), and endothelial NOS (eNOS). nNOS and eNOS are the main constitutively active NOS enzymes expressed in penile tissues. After its release, NO diffuses locally into smooth muscle cells of the corpus cavernosum and activates guanylyl cyclase leading to increased levels of cGMP that causes a decay in cytosolic Ca2+ concentration. Then occurs a relaxation of vascular and smooth muscles cells, a dilation of arterial vessels, increased blood flow into the sinuses of the corpora cavernosa, and penile erection.

The role of NO deficiency/lack in ED

While it is clear that ED is multifactorial, it is well documented that cigarette smoking has direct negative effects on erectile function. Several epidemiological studies demonstrated that smoke not only increases the risk of ED, but also amplifies the risk of ED associated with other risk factors (e.g., hypertension, diabetes, and dyslipidaemia) or with aging.

As NO is thought to be the principal stimulator of cavernosal relaxation and penile erection, smoking-induced decreases in the synthesis of NO may lead to ED. An insufficient synthesis of NO, leading to inadequate corporal smooth muscle relaxation, occurs in either of two ways:
- An endothelial damage leading to reduced activity of eNOS;
- Decrease in the activity or levels of the penile nNOS. Accordingly, studies from several laboratories and clinical trials have demonstrated that both acute and chronic smoking cause impairment of NO production.
It is irrefutable that tobacco smoke has direct effects on endothelial cells, causing architectural and functional changes. These changes include a decreased eNOS activity, impaired endothelium-dependent vasorelaxation, increased expression of cell adhesion molecules and transendothelial migration of monocyte-like cells, reduced response to vascular endothelial growth factor, and upset regulation of important thrombotic factors. Furthermore, chronic smoking modifies the viscoelastic properties of the extracellular matrix and induces calcification of the medial elastic fibers.

Although the effects of smoking on endothelial cells and eNOS are well established, we have less information about the correlation of smoking and nNOS-inhibition mediated ED.

The role Of ROS and oxidative stress In ED

It is well known that cigarette smoke contains reactive oxygen species such as superoxide, so a well accepted thesis confirm that some of the adverse effects of smoking may derive from oxidative damage to the cells involved in NO production. ROS are mainly generated by NOX enzymes (NADPH oxidases; nicotinamide adenine dinucleotide phosphate-oxidase). ROS avidly interact with a large number of molecules including small inorganic molecules as well as proteins, lipids, carbohydrates, and nucleic acids. Through such interactions, ROS may irreversibly destroy or alter the function of the target molecule. The antagonistic effect of ROS on the NO pathway could be identified with the fast reaction between superoxide and NO to produce peroxynitrite, subtracting NO to physiologic requirement.
Specific compounds of cigarette smoke increase superoxide generation by both endothelial and smooth muscle cells, inhibit acetylcholine-induced relaxation of arteries, increase pro-inflammatory cytokine’s mRNA expression. A treatment with antioxidants (NADH inhibitors) shows a efficient prevention of these effects. Furthermore eNOS disfunction because of BH4 (tetrahidrobiopterine) depletion contributes to endothelial dysfunction in chronic smokers. In addition, cigarette smoking causes increased production of cyclooxygenase.
Another biochemical effect is the activation of Rho-associated kinase (ROCK) wich is demonstrated to raise oxidative stress and vascular stiffness. Aging and accumulating smoking habit, which might induce excessive oxidative stress, are involved in ROCK activity in the vasculature: knowing the importance of ROCK in the Ca2+ sensitization (in this case in corpus cavernosum smooth muscle), we can easily understand the role of this kinase in ED trend.

Tar and gas, the two phases of cigarette smoke, contain high concentrations of ROS, NO, peroxynitrite, peroxynitrate, and free radicals of organic compounds. In addition to these short-lived, highly reactive substances, the gas phase of cigarette smoke contains varying amounts of more stable substances that are able to increase intracellular production of ROS even in areas remote from the primary site of exposure.

Smoking and testosterone

Testosterone plays a major role in men’s sexual function. Testosterone regulates not only sexual activity and libido, but also cGMP formation, through NOS stimulation, and its catabolism. Decreased hematic testosterone levels are associated with ED and studies have proven that addition of testosterone in castrated animals, and its conversion to dihydrotestosterone, restores erectile function.
Paradoxically smoking increases testosterone levels: it could deceitfully suggest a more powerful and efficient hormonal condition. Actually we have to read it as a compensatory reaction to the damage generated by smoking.

Nicotine and other compounds responsibility

A lot of the vascular effects of smoking are due to nicotine wich mainly induces endothelial dysfunction. Nicotine-induced endothelial dysfunction has been associated with increased plasma levels of asymmetric dimethylarginine (ADMA), an endogenous NOS inhibitor. The accumulation of this molecule is related to a decrease in activity of DDAH, a major hydrolase of ADMA.
In vitro analyses have shown that out of 4,800 different compounds in cigarette smoke, the mixture of metals and oxidants is crucial to produce endothelium damage. Cigarette smoke contains a number of different metals, including aluminum, cadmium, chromium, copper, lead, mercury, nickel, and zinc. The combination of metals and antioxidants leads to a chain reaction of protein oxidation, functional weakening of the microtubule system, contraction of endothelial cells, endothelial dysfunction, and the inner vascular surface impairment.
The impotency issue has the potential to subvert ages of tobacco industry characterization of smoking as a symbol of male strength. If widespread attitude came to accept the idea of a natural correlation between the cigarette and male impotency, the symbolism of smoking may change radically.

For further references:
http://www.ncbi.nlm.nih.gov/pubmed/18331273

Attachments

file	user	date
4683_smoking-drinking.gif	gp	11/01/2010
smoking-drinking.gif	gp	11/01/2010
Smoking_Behavior_and_the_C677T_MTHFR_2001.pdf	gp	20/11/2009
LG_prevenzione_Oncologica_Tabagismo.pdf	gp	09/11/2009

SmokingLife Style