Search PubMed⌕ Search

Biomedical subjects

Mikko Salaspuro

Publications and source records attributed to Mikko Salaspuro.

18 recordsLinked to original sources
PubMed2006

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.

Acetaldehyde↗
PubMed2006

[Not Available].

Explore the source record for details and available documents.

Journal Article↗
PubMed2005

From alcohol toxicity to treatment.

This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism in Mannheim, Germany, in October 2004. This symposium was dedicated to Charles S. Lieber in recognition of his contribution in alcohol research over the last 50 years. It was divided into two parts, namely effects of alcohol on the gastrointestinal tract and effects of alcohol on the liver. Major emphasis was given to recent discoveries elucidating mechanisms of alcohol-associated carcinogenesis. M. Salaspuro (Finland) discussed the role of acetaldehyde in the saliva and in the large intestine with respect to its role in the pathogenesis of alcohol-associated cancer, and H. K. Seitz (Germany) presented new data identifying individuals homozygous for the ADH1C&1 allele as high on risk for alcohol-associated upper aerodigestive tract cancer. M. Savolainen (Finland) discussed the role phosphatidylethanol as a bioactive lipid that can mediate beneficial and harmful effects of alcohol drinking. In the second part of the symposium, alcoholic liver disease was discussed. P. Haber (Australia) presented new data on hepatic transcriptome in alcoholic liver disease with the identification of new genes possibly involved in alcohol-initiated fibrogenesis of the liver, and H. Moshage (The Netherlands) described survival mechanisms of the cholestatic hepatocytes with implications for therapy in cholestatic liver disease. The role of the hepatic microsomal ethanol oxidizing system in the metabolism of alcohol in alcoholic liver disease was summarized by R. Teschke (Germany). H. Ishii (Japan) discussed the current status and treatment of alcoholic hepatitis in Japan. Finally, in a state-of-the-art lecture, Charles S. Lieber (USA) discussed the development of the understanding of the pathophysiology of alcoholic liver disease in the last 50 years. He emphasized the role of pathophysiology as an important prerequisite for better treatment strategies.

Acetaldehyde↗
PubMed2004

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.

Acetaldehyde↗
PubMed2003

Lactulose reduces intracolonic acetaldehyde concentration and ethanol elimination rate in rats.

BACKGROUND: Normal colonic bacteria possessing alcohol dehydrogenase activity can oxidize ethanol to acetaldehyde. Acetaldehyde recently has been shown to be a local carcinogen in humans. The aim of the study was to examine the effect of lactulose feeding on fecal and cecal pH, intracolonic acetaldehyde concentration, and total ethanol elimination rate in rats. METHODS: Sixty Wistar rats were divided into four groups. Groups 2 and 4 received lactulose daily (11 g/kg body weight for 14 days). On days 7 and 14, groups 1 and 2 received ethanol (1.5 g/kg body weight) intraperitoneally, whereas groups 3 and 4 received saline. RESULTS: Fecal and cecal pH values decreased significantly after lactulose treatment compared with the controls. Lactulose feeding reduced the total ethanol elimination rate by 13.8% (257 +/- 0.008 mg/kg/hr vs. 298 +/- 0.003 mg/kg/hr, p < 0.001) and the intracecal acetaldehyde concentration by 66.2% after ethanol (49 +/- 29 microM vs. 145 +/- 47 microM, p = 0.03) compared with the controls. CONCLUSION: Lactulose feeding to rats significantly reduces ethanol elimination rate and intraluminal acetaldehyde concentration in the colon after ethanol administration. This prebiotic thus could be used as an effective agent to block the microbial production of carcinogenic acetaldehyde in the large intestine.

Acetaldehyde↗
PubMed2003

Treatment of alcohol abuse: an evidence-based review.

This article represents the proceedings of a symposium at the 2002 annual meeting of the Research Society on Alcoholism in San Francisco, CA, organized and cochaired by Mats Berglund and Sten Thelander. The presentations were (1) Preventive interventions against hazardous consumption of alcohol, by Mikko Salaspuro; (2) Treatment of alcohol withdrawal, by Johan Franck; (3) Psychosocial treatment for alcohol problems, by Sven Andréasson and Agneta Ojehagen; and (4) Pharmacological treatment of alcohol dependence, by Mats Berglund.

Alcoholism↗
PubMed2002

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.

Acetaldehyde↗
PubMed2002

Long-term effects of and physiological responses to nitrous oxide gas treatment during alcohol withdrawal: a double-blind, placebo-controlled trial.

BACKGROUND: Nitrous oxide gas (N2O) has been proposed to be effective in the treatment of the alcohol withdrawal syndrome (AWS). This has not been proved, however, in studies performed according to good clinical practice guidelines. Moreover, previous studies have not measured end tidal N2O concentrations or physiologic responses during N2O treatment. We have recently reported that in a double-blind, randomized, controlled setting, N2O was not superior to placebo in relieving AWS symptoms. In this previous study, we did not find significant differences between the treatments either in the Clinical Institute Withdrawal Assessment of Alcohol scores or in the total use of benzodiazepines (diazepam and temazepam). The aim of the present study was to characterize other effects and side effects of the N2O treatment using several objective measures and to study the possible long-term efficacy of the treatment. METHODS: A total of 105 inpatients who had AWS and were admitted to the A-Clinic detoxification center were included in the study. The subjects were randomly assigned to one of the following three treatments: (1) N2O/oxygen (from 30 to 70% in oxygen), (2) air/oxygen (30%/70%), and (3) medical (normal) air. During the single 45-min treatment period, end-tidal N2O, carbon dioxide, and oxygen concentrations were measured. The physiologic responses were studied by measuring heart rate, blood pressure, pulse oximetric saturation, frontal muscle electromyographic activity, and plethysmographic pulse amplitude. Long-term effects were studied by measuring craving with the Obsessive-Compulsive Drinking Scale; severity of dependency with Severity of Alcohol Dependence Data; and liver enzymes with aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase 3 and 6 months after the treatment. RESULTS: Patients in the N2O group demonstrated significantly higher facial muscle electromyographic activity and higher pulse amplitude than the air-treated subjects. Self-reported side effects between the gas treatments, however, did not differ between the groups. Regarding long-term effects of the treatments, there were no differences between the groups. CONCLUSIONS: Contrary to previously published data, N2O treatment did not decrease craving or liver enzymes during the 6-month follow-up. At the concentration used, N2O treatment produced signs of arousal instead of strong sedation.

Alcoholism↗
PubMedDate not supplied

Microbes and mucosa in the regulation of intracolonic acetaldehyde concentration during ethanol challenge.

AIMS: The bacteriocolonic pathway for ethanol oxidation leads to high intracolonic levels of carcinogenic acetaldehyde. The respective roles of colonic mucosal cells and gut flora in the regulation of intracolonic acetaldehyde concentration are not known. Disulfiram inhibits hepatic acetaldehyde oxidation and may have an effect on colonic mucosal cells. On the other hand, metronidazole treatment leads to overgrowth of acetaldehyde-producing aerobic flora in the large intestine. The aim of this study was to characterize by means of disulfiram and metronidazole the contribution of colonic mucosal cells and intracolonic microbes to the regulation of intracolonic acetaldehyde concentration during ethanol oxidation in rats. METHODS: Forty male Wistar rats were used. Three groups of 10 rats each received metronidazole, disulfiram, or both for 5 days, and a fourth group of 10 rats served as controls and did not receive any premedication. Faecal samples were taken for the ALDH (aldehyde dehydrogenase) determination before the injection of ethanol, after which all rats received ethanol (1.5 g/kg) 2 h prior to taking samples from blood, liver, colonic mucosa and colonic contents. RESULTS: Disulfiram decreased significantly hepatic and colonic mucosal ALDH activities, and resulted in increased blood and intracolonic acetaldehyde levels. In disulfiram-treated rats, mean intracolonic acetaldehyde level was 8-fold higher than that in the blood. Metronidazole inhibited only colonic mucosal high K(M) ALDH and increased intracolonic, but not blood, acetaldehyde levels. Faecal ALDH activity was not detectable in any of the groups. CONCLUSIONS: This study demonstrates that during ethanol challenge, intracolonic acetaldehyde level is regulated not only by intracolonic microbes, but also by colonic mucosal cells.

Acetaldehyde↗