Sophisticated information technology platforms for remote patient reporting linked with theory-based health behavior change automated feedback have potential to improve patient outcomes in type 2 diabetes and merit scaled-up research efforts.

Alcohol drinking and smoking are independent risk factors for upper digestive tract cancers. Furthermore, their combined use interacts in a multiplicative way on cancer risk. There is convincing evidence that acetaldehyde, the first metabolite of ethanol and a constituent of tobacco smoke, is a local carcinogen in humans. Therefore, we examined the combined effect of alcohol drinking and tobacco smoking on in vivo acetaldehyde concentration in saliva. Seven smokers and 6 nonsmokers participated in the study. First, to measure the effect of alcohol on salivary acetaldehyde, all volunteers ingested 0.8 g/kg body weight of ethanol and saliva samples were collected every 20 min for 160 min thereafter. After a 3-day washout period, smokers ingested again the same amount of ethanol and smoked one cigarette every 20 min and saliva samples were collected at 10 min intervals for 160 min. Acetaldehyde and ethanol concentrations were analyzed by headspace gas chromatograph. Firstly, smokers without concomitant smoking during ethanol challenge had 2 times higher in vivo salivary acetaldehyde concentrations than nonsmokers after ethanol ingestion (AUC 114. The main causes of upper digestive tract cancers are smoking and alcohol drinking. It has been estimated, for the United States, that up to 80% of these cancers can be avoided by abstaining from alcohol drinking and smoking. 1-3 Both alcohol and tobacco are independent risk factors for upper digestive tract cancers. Additionally, several epidemiologic studies have confirmed that alcohol and tobacco interact in a multiplicative way on cancer risk. 4 -8 The combined tumor-promoting effect of alcohol and tobacco smoking is poorly understood. Ethanol per se is not carcinogenic. 9 However, acetaldehyde, the first metabolite of ethanol, is carcinogenic in animals. 10,11 There is convincing evidence for acetaldehyde being the ultimate carcinogenic compound behind alcohol intake also in humans. 12,13 After alcohol intake, acetaldehyde is locally formed in the oral cavity by oral mucosal alcohol dehydrogenases (ADHs) and by the oral microflora, both of which are able to oxidize ethanol to acetaldehyde. 14 -16 Also, tobacco smoke contains high levels of acetaldehyde, which is one of the most toxic compounds in cigarette smoke condensate. 17 Acetaldehyde is highly toxic and mutagenic under various experimental conditions. 18 -21 Epidemiologic and biochemical studies on Asian heavy drinkers with aldehyde dehydrogenase-2 (ALDH2) deficiency strongly suggest that acetaldehyde is a local and topical carcinogen also in humans. 13 This deficiency results in the accumulation of acetaldehyde in saliva 22 and in markedly increased risk for upper gastrointestinal (GI) tract cancers. [23][24][25] Also, most studies concerning Caucasian individuals who are homozygous for the fast alcohol metabolizing alcohol dehydrogenase (ADH3*1) enzyme show increased salivary acetaldehyde levels related to increased risk of alcohol-related upper digestive tract cancers. 26 Our earlier studies indicate that he...

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Tobacco smoking is one of the strongest risk factors not only for lung cancer but also for cancers of the upper gastrointestinal tract. Acetaldehyde has been shown to dissolve into the saliva during smoking and to be a local carcinogen in the human upper digestive tract. Cysteine can bind to acetaldehyde and eliminate its toxicity. We developed a tablet that releases cysteine into the oral cavity during smoking and could therefore be a potential chemopreventive agent against toxicity of tobacco smoke. In this study, the efficacy of L-cysteine -containing tablets to reduce the carcinogenic acetaldehyde in the saliva during tobacco smoking was examined. Seven volunteers smoked five cigarettes. During every smoking period, each volunteer sucked a blinded tablet containing 0, 1.25, 2.5, 5, or 10 mg of L-cysteine. Acetaldehyde was analyzed from salivary samples gas chromatographically at 0, 5, and 10 minutes from the beginning of the smoking. All tablets containing L-cysteine reduced highly significantly the salivary acetaldehyde; 5 mg of L-cysteine was the minimum concentration to totally eliminate the acetaldehyde from saliva. The mean salivary acetaldehyde concentrations in samples collected immediately after smoking with 0, 1.25, 2.5, 5, or 10 mg of L-cysteine were 228 F 115In conclusion, carcinogenic acetaldehyde could be totally inactivated in the saliva during smoking by sucking tablet containing 5 mg of L-cysteine. Even a small reduction of the carcinogenicity of cigarette smoke could gain benefit at the population level. Hence, this finding warrants for further clinical trials for L-cysteine tablet in the prevention of upper digestive tract cancers in

High alcohol intake is an independent risk factor for upper gastrointestinal (GI)-tract cancers. There is increasing evidence that acetaldehyde, the first metabolite of ethanol, might be responsible for ethanol-associated carcinogenesis. Especially among Asian heavy drinkers with the ALDH2-deficiency gene, i.e., a genetic inability to remove acetaldehyde, the risk of digestive tract cancers is markedly increased. Local acetaldehyde production from ethanol either by oral microbes, mucosal cells or salivary glands is a plausible carcinogenic agent in the saliva. The aim of our study was to examine whether is it possible to bind carcinogenic acetaldehyde from saliva with L-cysteine, which is slowly released from a special buccal tablet. Nine healthy male volunteers took part in our study, and each subject served as his own control. A placebo or L-cysteine-containing tablet was fastened under the upper lip. Thereafter the volunteers ingested 0.8 g/kg of body weight of 10% (v/v) ethanol, and saliva samples were collected at 20 min intervals for 320 min. Salivary acetaldehyde and ethanol levels were analysed by headspace gas chromatography. The mean reduction of acetaldehyde concentration of the saliva with the L-cysteine tablet compared to placebo was 59% (CL 95% 43%, 76%). Area under the curve (AUC 0 -320min ) with the L-cysteine and placebo tablet were 54.3 ؎ 11 M ؋ hr and 162 ؎ 34.2 M ؋ hr (mean ؎ SEM), respectively (p ‫؍‬ 0.003). After alcohol intake, up to two-thirds of carcinogenic acetaldehyde can be removed from saliva with a slow-releasing buccal L-cysteine drug formulation. Thus, a buccal cysteine tablet could potentially be used to prevent upper GI-tract cancers, especially among high-risk individuals. © 2002 Wiley-Liss, Inc. Key words: acetaldehyde; L-cysteine; upper digestive tract; carcinogenesisAlcohol intake and tobacco smoking are the most important independent risk factors for upper digestive tract cancers. [1][2][3][4][5] Many of the compounds in the tobacco smoke are carcinogenic, but, in contrast, the tumour-promoting effects of alcohol drinking has so far been less well defined. Acetaldehyde, the first metabolite of ethanol, has been shown to be carcinogenic in animals and there exists strong evidence of its carcinogenic action also in man. 6,7 Asian heavy drinkers with a genetically deficient aldehyde dehydrogenase (ALDH2) enzyme do show a markedly increased risk for GI-tract cancers. 8 Our recent findings demonstrate that Asians with this mutant ALDH2 have 2-3 times higher salivary acetaldehyde levels after a moderate dose of ethanol than Asians with the normal ALDH2 enzyme. 7 When this observation is combined with the earlier epidemiologic data, our results provide strong evidence for the local carcinogenic action of acetaldehyde produced from alcohol in the saliva by either oral microbes or in the salivary glands.After absorption, ethanol is evenly distributed to the waterphase of the body, and ethanol concentration in the saliva equals that of the blood. 9 In addition to the tissue alcohol ...

Vascular adhesion protein-1 (VAP-1) has been shown to mediate lymphocyte adhesion to endothelia at sites of inflammation, but its functional role in vivo has not been tested in any rodent model. Here we report the effects of VAP-1 blockade on rat liver allograft rejection. BN recipients of PVG liver allografts (known to develop acute rejection by day 7) were treated with 2 mg/kg anti-VAP-1 (a new anti-rat VAP-1 mAb 174-5) or isotype-matched irrelevant antibody (NS1) every other day (n = 6/group) and one group with anti-VAP-1 2 mg/kg daily (n = 7). On day 7, samples were collected for transplant aspiration cytology, histology, and immunohistochemistry. Lymphocyte infiltration to the graft was clearly affected by VAP-blockade. The total inflammation, mainly the number of active lymphoid cells, in transplant aspiration cytology was significantly decreased in animals treated with anti-VAP-1 (4.7 +/- 1.0 and 2.4 +/- 1.0 corrected increment units, respectively) compared to control (6.6 +/- 1.0) (P < 0.05). In histology, the intensity of portal inflammation was significantly decreased (P < 0.05). The amount of T cells expressing activation markers diminished. This is the first demonstration in any prolonged in vivo model that VAP-1 plays an important role in lymphocyte infiltration to sites of inflammation, and, in particular, liver allograft rejection.

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Cigarette smoke contains toxic amounts of acetaldehyde that dissolves in saliva, posing a significant risk of developing oral, laryngeal and pharyngeal carcinomas. L-cysteine, a non-essential amino acid, can react covalently with carcinogenic acetaldehyde to form a stable, non-toxic 2-methylthiazolidine-4-carboxylic acid. The main aim of this study was to find out whether it is possible to develop a chewing gum formulation that would contain cysteine in amounts sufficient to bind all the acetaldehyde dissolved in saliva during the smoking of one cigarette. The main variables in the development process were: (1) chemical form of cysteine (L-cysteine or L-cysteine hydrochloride), (2) the amount of the active ingredient in a gum and (3) manufacturing procedure (traditional or novel compression method). Saliva samples were taken over 2.5 minutes before smoking and since smoking was started for 2.5 minutes periods for 10 minutes. During a five minutes smoking period with a placebo chewing gum, acetaldehyde levels increased from 0 to 150-185 microM. Once smoking was stopped, the acetaldehyde levels quickly fell to levels clearly below the in-vitro mutagenic level of 50 microM. All chewing gums containing cysteine could bind almost the whole of the acetaldehyde in the saliva during smoking. However, elimination of saliva acetaldehyde during smoking does not make smoking completely harmless. Cysteine as a free base would be somewhat better than cysteine hydrochloride due to its slower dissolution rate. Both traditional and direct compression methods to prepare chewing gums can be utilized and the dose of L-cysteine required is very low (5 mg).