Kinetics of mouse jejunum radiosensitization by 2',2'-difluorodeoxycytidine (gemcitabine) and its relationship with pharmacodynamics of DNA synthesis inhibition and cell cycle redistribution in crypt cells.

Gemcitabine (dFdC), a deoxycitidine nucleoside analogue, inhibits DNA synthesis and repair of radiation-induced chromosome breaks in vitro, radiosensitizes various human and mouse cells in vitro and shows clinical activity in several tumours. Limited data are however available on the effect of dFdC on normal tissue radiotolerance and on factors associated with dFdC's radiosensitization in vivo. The purpose of this study was to determine the effect of dFdC on mouse jejunum radiosensitization and to investigate the kinetics of DNA synthesis inhibition and cell cycle redistribution in the jejunal crypts as surrogates of radiosensitization in vivo. For assessment of jejunum tolerance, the mice were irradiated on the whole body with 60Co gamma rays (3.5-18 Gy single dose) with or without prior administration of dFdC (150 mg kg-1). Jejunum tolerance was evaluated by the number of regenerated crypts per circumference at 86 h after irradiation. For pharmacodynamic studies, dFdC (150 or 600 mg kg-1) was given i.p. and jejunum was harvested at various times (0-48 h), preceded by a pulse BrdUrd labelling. Labelled cells were detected by immunohistochemistry on paraffin-embedded sections. DNA synthesis was inhibited within 3 h after dFdC administration. After an early wave of apoptosis (3-6 h), DNA synthesis recovered by 6 h, and crypt cells became synchronized. At 48 h, the labelling index returned almost to background level. At a level of 40 regenerated crypts, radiosensitization was observed for a 3 h time interval (dose modification factor of 1.3) and was associated with DNA synthesis inhibition, whereas a slight radioprotection was observed for a 48-h time interval (dose modification factor of 0.9) when DNA synthesis has reinitiated. In conclusion, dFdC altered the radioresponse of the mouse jejunum in a schedule-dependent fashion. Our data tend to support the hypothesis that DNA synthesis inhibition and cell cycle redistribution are surrogates for radiosensitization. More data points are however required before a definite conclusion can be drawn

The genetics of nicotine addiction liability: Ethical and social policy implications

Aim To assess the promise and risks of technological applications of genetic research on liability to develop nicotine dependence. Methods We reviewed (i) the evidence on the genetics of nicotine dependence; (ii) the technical feasibility of using genetic information to reduce smoking uptake and increase cessation; and (iii) policy and ethical issues raised by the uses of genetic information on addiction liability. Results (i) Despite evidence from twin studies that genes contribute to addiction susceptibility, research to date has not identified commonly occurring alleles that are strongly predictive of developing nicotine addiction. Nicotine addiction is likely to involve multiple alleles of small effect that interact with each other and with the environment. (ii) Population screening for susceptibility alleles is unlikely to be effective or cost-effective. Tailoring of smoking cessation treatments with genetic information is more plausible but results to date have been disappointing. Population health strategies such as increased taxation and reduced opportunities to smoke are more efficient in reducing cigarette smoking. Tobacco harm reduction policies applied to populations may also play a role in reducing tobacco-related harm. (iii) Future uses of genomic information on addiction risk will need to assess the risks of medicalising addiction (e.g. pessimism about capacity to quit) and community concerns about genetic privacy. Conclusions Nicotine genomics is a very new and underdeveloped field. On the evidence to date, its advocates would be wise to avoid extravagant claims about its preventive applications

Recent Contributions of Air- and Biomarkers to the Control of Secondhand Smoke (SHS): A Review

Since the publication of the US Surgeon General Reports in 1996 and 2006 and the report of the California Environmental Protection Agency in 1999, many reports have appeared on the contribution of air and biomarkers to different facets of the secondhand smoke (SHS) issue, which are the targets of this review. These recent studies have allowed earlier epidemiological surveys to be biologically validated, and their plausibility demonstrated, quantified the levels of exposure to SHS before the bans in various environments, showed the deficiencies of mechanical control methods and of partial bans and the frequently correct implementation of the efficient total bans. More stringent regulation remains necessary in the public domain (workplaces, hospitality venues, transport sector, etc.) in many countries. Personal voluntary protection efforts against SHS are also needed in the private domain (homes, private cars). The effects of SHS on the cardiovascular, respiratory and neuropsychic systems, on pregnancy and fertility, on cancers and on SHS genotoxicity are confirmed through experimental human studies and through the relationship between markers and prevalence of disease or of markers of disease risk

Hookah (Shisha, Narghile) Smoking and Environmental Tobacco Smoke (ETS). A Critical Review of the Relevant Literature and the Public Health Consequences

Hookah (narghile, shisha, “water-pipe”) smoking is now seen by public health officials as a global tobacco epidemic. Cigarette Environmental Tobacco Smoke (ETS) is classically understood as a combination of Side-Stream Smoke (SSS) and Exhaled Main-Stream Smoke (EMSS), both diluted and aged. Some of the corresponding cigarette studies have served as the scientific basis for stringent legislation on indoor smoking across the world. Interestingly, one of the distinctive traits of the hookah device is that it generates almost no SSS. Indeed, its ETS is made up almost exclusively by the smoke exhaled by the smoker (EMSS), i.e. which has been filtered by the hookah at the level of the bowl, inside the water, along the hose and then by the smoker’s respiratory tract itself. The present paper reviews the sparse and scattered scientific evidence available about hookah EMSS and the corresponding inferences that can be drawn from the composition of cigarette EMSS. The reviewed literature shows that most of hookah ETS is made up of EMSS and that the latter qualitatively differs from MSS. Keeping in mind that the first victim of passive smoking is the active smoker her/himself, the toxicity of hookah ETS for non-smokers should not be overestimated and hyped in an unscientific way

L'onde, la preuve et le militant: L'écosophie de Félix Guattari à l'épreuve de l'électrosensibilité et de la polémique sur les dangers des ondes électromagnétiques

Les ondes électromagnétiques utilisées pour la téléphonie mobile, le WiFi ou encore le Bluetooth sont-elles nocives pour la santé et l’environnement ? La polémique fait rage entre ceux qui considèrent qu’il n’y a aucune raison de s’inquiéter, et qu’il n’est donc pas nécessaire de légiférer à ce sujet, et ceux qui voient de vrais faisceaux de preuves à propos de la dangerosité de ces ondes. Les militants contre celles-ci soulèvent des risques, des doutes ou même des certitudes sur leurs dangers sanitaires, mais aussi sociaux, environnementaux et même mentaux. Au cœur de la polémique, les malades des ondes, les électrosensibles, ont une place particulière :eux souffrent déjà des ondes et sont donc une vraie preuve de ce danger, leur corps est l’inscription de ce danger. À l’aide des outils conceptuels développés par le philosophe Félix Guattari, ce travail déploie cette controverse à travers ces multiples composantes. La thèse explore l’électrosensibilité comme une maladie relative à un milieu et à une époque, en décrivant les épreuves que les malades et les militants subissent.Doctorat en PhilosophieTHPHILOinfo:eu-repo/semantics/nonPublishe

La substitution nicotinique dans l'aide au sevrage tabagique. Modes d'action, modalités et appréciation des résultats.

Failure in smoking cessation is linked with behavioural factors and with nicotine dependence, due to the psychoactive effects of the drug, mainly on locus ceruleus and on mesolimbic dopaminergic system. Nicotine substitution partially controls the withdrawal syndrome, sometimes very intense in smokers with pharmacological dependence. After transdermal nicotine administration, nicotine blood levels are relatively low but steady; nicotine chewing gum can be used alone or in combination with transdermal administration. Both methods can double biologically controlled success rates. Risks are limited in comparison with those of continued smoking. Recent data from the literature allow a better understanding of indications and limits of the pharmacological approach to cessation, that should address smokers firmly decided to stop, and be completed by behavioural support, including changes in the way of life

[Nicotine Substitution in Smoking Cessation - Modes of Action, Modalities and Evaluation of Results]

Failure in smoking cessation is linked with behavioural factors and with nicotine dependence, due to the psychoactive effects of the drug, mainly on locus ceruleus and on mesolimbic dopaminergic system. Nicotine substitution partially controls the withdrawal syndrome, sometimes very intense in smokers with pharmacological dependence. After transdermal nicotine administration, nicotine blood levels are relatively low bur steady, nicotine chewing gum can be used alone or in combination with transdermal administration Both methods can double biologically controlled success rates. Risks are limited in comparison with those of continued smoking. Recent data from the literature allow a better understanding of indications and limits of the pharmacological approach to cessation, that should address smokers firmly decided to stop, and be completed by behavioural support, including changes in the way of life