Active assistance technology reduces glycosylated hemoglobin and weight in individuals with type 2 diabetes: results of a theory-based randomized trial.

BACKGROUND: Type 2 diabetes is an individual health challenge requiring ongoing self-management. Remote patient reporting of relevant health parameters and linked automated feedback via mobile telephone have potential to strengthen self-management and improve outcomes. This research involved development and evaluation of a mobile telephone-based remote patient reporting and automated telephone feedback system, guided by health behavior change theory, aimed at improving self-management and health status in individuals with type 2 diabetes. SUBJECTS AND METHODS: This research comprised a randomized controlled trial. Inclusion criteria were diagnosis of type 2 diabetes, elevated glycosylated hemoglobin (HbA1c) levels (range, 6.5-11%) or use of oral diabetes medication, and 30-70 years of age. Intervention subjects (n=24) participated in remote patient reporting of health status parameters and linked health behavior change feedback. Control participants (n=24) received standard of care including diabetes education and healthcare provider counseling. Patients were followed for approximately 10 months. RESULTS: Intervention participants achieved, compared with controls and controlling for baseline, a significantly greater mean reduction in HbA1c of -0.40% (95% confidence interval [CI] -0.67% to -0.14%) versus 0.036% (95% CI -0.23% to 0.30%) (P<0.03) and significantly greater weight reduction of -2.1 kg (95% CI -3.6 to -0.6 kg) versus 0.4 kg (95% CI -1.1 to 1.9 kg). Nonsignificant trends for greater intervention compared with control improvement in systolic and diastolic blood pressure were observed. CONCLUSIONS: 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.

Formulation and in-vivo evaluation of L-cysteine chewing gums for binding carcinogenic acetaldehyde in the saliva during smoking.

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).

Pharmacological treatments and strategies for reducing oral and intestinal acetaldehyde.

Strong epidemiological, genetic and biochemical evidence indicates that local acetaldehyde exposure is a major factor behind gastrointestinal cancers especially associated with alcohol drinking and smoking. Thus, reducing the exposure to carcinogenic acetaldehyde either by decreasing the production or by eliminating acetaldehyde locally might offer a preventive strategy against acetaldehyde-induced gastrointestinal cancers. Thiol products, such as the amino acid cysteine, are known to be able to protect against acetaldehyde toxicity. Cysteine is able to bind acetaldehyde efficiently by forming a stable thiazolidine-carboxylic acid compound. Special cysteine preparations (such as lozenge and chewing gum) have already been developed to bind smoking and alcohol drinking derived acetaldehyde from the oral cavity. Most importantly, these type of drug formulations offer a novel method for intervention studies aimed to resolve the eventual role of acetaldehyde in the pathogenesis of upper digestive tract cancers. Acetaldehyde exposure could also be influenced by modifying the acetaldehyde producing microbiota. With regard to the upper digestive tract, acetaldehyde production from ingested ethanol could be significantly reduced by using an antiseptic mouthwash, chlorhexidine. In the large intestine acetaldehyde production could be markedly decreased either by reducing the Gram-negative microbes by ciprofloxacin antibiotic or by lowering the intraluminal pH by lactulose.

Acetaldehyde production from ethanol by oral streptococci.

Alcohol is a well documented risk factor for upper digestive tract cancers. It has been shown that acetaldehyde, the first metabolite of ethanol is carcinogenic. The role of microbes in the production of acetaldehyde to the oral cavity has previously been described in several studies. In the present study, the aim was to investigate the capability of viridans group streptococci of normal oral flora to produce acetaldehyde in vitro during ethanol incubation. Furthermore, the aim was to measure the alcohol dehydrogenase (ADH) activity of the bacteria. Eight clinical strains and eight American Type Culture Collection (ATCC) strains of viridans group streptococci were selected for the study. Bacterial suspensions were incubated in two different ethanol concentrations, 11 mM and 1100 mM and the acetaldehyde was measured by gas chromatography. ADH-activity was measured by using a sensitive spectroscopy. The results show significant differences between the bacterial strains regarding acetaldehyde production capability and the detected ADH-activity. In particular, clinical strain of Streptococcus salivarius, both clinical and culture collection strains of Streptococcus intermedius and culture collection strain of Streptococcus mitis produced high amounts of acetaldehyde in 11 mM and 1100 mM ethanol incubation. All these four bacterial strains also showed significant ADH-enzyme activity. Twelve other strains were found to be low acetaldehyde producers. Consequently, our study shows that viridans group streptococci may play a role in metabolizing ethanol to carcinogenic acetaldehyde in the mouth. The observation supports the concept of a novel mechanism in the pathogenesis of oral cancer.

Eliminating carcinogenic acetaldehyde by cysteine from saliva during smoking.

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+/-115 micromol/L, 85+/-42 micromol/L (P=0.007), 9+/-7 micromol/L, 0.09+/- 0.2 micromol/L, 0+/- 0 micromol/L (P<0.001), respectively. In 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 smokers.

Blockade of vascular adhesion protein-1 inhibits lymphocyte infiltration in rat liver allograft rejection.

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.

Synergistic effect of alcohol drinking and smoking on in vivo acetaldehyde concentration in saliva.

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 114.8 +/- 11.5 vs. 54.2 +/- 8.7 microM x hr, respectively; p = 0.002). Secondly, smokers with active smoking during ethanol challenge had 7 times higher in vivo salivary acetaldehyde levels than nonsmokers (AUC 369.5 +/- 12.2 vs. 54.2 +/- 8.7 microM x hr, respectively; p < 0.001). We conclude that this markedly increased exposure of upper digestive tract mucosa to carcinogenic salivary acetaldehyde of smoking and drinking subjects may explain the synergistic and multiplicative risk effect of alcohol drinking and tobacco smoking on upper gastrointestinal tract carcinogenesis.

Removal of acetaldehyde from saliva by a slow-release buccal tablet of L-cysteine.

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 microM x hr and 162 +/- 34.2 microM x 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.