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M Salaspuro

Publications and source records attributed to M Salaspuro.

At least 55 records · Page 3Linked to original sources
PubMed1996

Formation of tetrahydroharman (1-methyl-1,2,3,4-tetrahydro-beta-carboline) by Helicobacter pylori in the presence of ethanol and tryptamine.

Helicobacter pylori contains alcohol dehydrogenase which oxidizes ethanol to acetaldehyde. In the present study, H. pylori cytosol was incubated in a buffered media at pH 6.0 and 7.4 in the presence of ethanol and tryptamine. Under these conditions, tetrahydroharman (1-methyl-tetrahydro-beta-carboline) was produced as a condensation product of tryptamine and acetaldehyde. At pH 6.0, 20.60 +/- 5.00% of the added tryptamine was converted to tetrahydroharman, while 27.00 +/- 4.80% (mean +/-SD) was converted at pH 7.4. Similar reactions between acetaldehyde and other dietary amines seem likely. Such biogenic alkaloids, if formed in vivo, might contribute to the dysphoric effects of alcohol.

Acetaldehyde↗
PubMed1996

Citalopram in the treatment of alcoholism: a double-blind placebo-controlled study.

The effect of citalopram and placebo in the treatment of alcoholism was studied in a sample of 62 patients with a follow-up period of four months. The results imply that the new 5-HT re-uptake inhibitor citalopram is significantly more effective than placebo in the treatment of alcoholism. The present study indicates that even severe alcoholism may be treated effectively with a generally available psychopharmacological agent.

Adult↗
PubMed1996

Aldehyde dehydrogenase activity and acetate production by aerobic bacteria representing the normal flora of human large intestine.

We have recently proposed the existence of a bacteriological pathway for ethanol oxidation, i.e. ethanol is oxidized by alcohol dehydrogenase of intestinal bacteria resulting in high intracolonic levels of reactive and toxic acetaldehyde. This study was aimed to examine aldehyde dehydrogenase (ALDH) activity, acetaldehyde consumption and production of acetate by aerobic bacteria (n = 27), representing the normal human colonic flora. Most bacterial strains did not show any membrane-associated aldehyde dehydrogenase, but possessed marked cytosolic NADP(+) - and NAD(+) - dependent aldehyde dehydrogenase activity, ranging from 155 nmol of NAD(P)H produced/min/mg of protein to zero with acetaldehyde as substrate. NADP(+)-linked ALDH activity was significantly higher than NAD(+)-linked activity in most of the tested bacteria. In addition, aerobic bacteria metabolized acetaldehyde effectively in vitro and this could be inhibited by cyanamide in nearly half of the tested strains. Production of acetate from acetaldehyde ranged from 2420 nmol/10(9) colony-forming units to almost negligible. In conclusion, many human aerobic colonic bacteria possess significant aldehyde dehydrogenase activity and can, consequently, produce acetate from acetaldehyde in vitro at least under the partially aerobic conditions proposed to prevail on the colonic mucosal surface. Individual variation in the capability of colonic flora to remove toxic acetaldehyde may be one factor regulating intracolonic acetaldehyde levels, as well as the rate of bacteriocolonic pathway for ethanol oxidation.

Acetaldehyde↗
PubMed1996

Aldehyde dehydrogenases of the rat colon: comparison with other tissues of the alimentary tract and the liver.

Intracolonic bacteria have previously been shown to produce substantial amounts of acetaldehyde during ethanol oxidation, and it has been suggested that this acetaldehyde might be associated with alcohol-related colonic disorders, as well as other alcohol-induced organ injuries. The capacity of colonic mucosa to remove this bacterial acetaldehyde by aldehyde dehydrogenase (ALDH) is, however, poorly known. We therefore measured ALDH activities and determined ALDH isoenzyme profiles from different subcellular fractions of rat colonic mucosa. For comparison, hepatic, gastric, and small intestinal samples were studied similarly. Alcohol dehydrogenase (ADH) activities were also measured from all of these tissues. Rat colonic mucosa was found to possess detectable amounts of ALDH activity with both micromolar and millimolar acetaldehyde concentrations and in all subcellular fractions. The ALDH activities of colonic mucosa were, however, generally low when compared with the liver and stomach, and they also tended to be lower than in small intestine. Mitochondrial low K(m) ALDH2 and cytosolic ALDH with low K(m) for acetaldehyde were expressed in the colonic mucosa, whereas some cytosolic high K(m) isoenzymes found in the small intestine and stomach were not detectable in colonic samples. Cytosolic ADH activity corresponded well to ALDH activity in different tissues: in colonic mucosa, it was approximately 6 times lower than in the liver and about one-half of gastric ADH activity. ALDH activity of the colonic mucosa should, thus, be sufficient for the removal of acetaldehyde produced by colonic mucosal ADH during ethanol oxidation. It may, however, be insufficient for the removal of the acetaldehyde produced by intracolonic bacteria. This may lead to the accumulation of acetaldehyde in the colon and colonic mucosa after ingestion of ethanol that might, at least after chronic heavy alcohol consumption, contribute to the development of alcohol-related colonic morbidity, diarrhea, and cancer.

Acetaldehyde↗
PubMed1996

Increased acetaldehyde production by mouthwashings from patients with oral cavity, laryngeal, or pharyngeal cancer.

Excessive ethanol consumption is associated with an increased risk of oral cavity, laryngeal, and pharyngeal cancer. Ethanol has been shown to be oxidized to acetaldehyde by microflora of the upper respiratory tract. As a highly toxic and reactive compound, acetaldehyde of microbial origin has been incriminated as a possible carcinogenic factor behind alcohol-associated malignancies of the upper respiratory tract. The aim of the present in vitro study was to compare the acetaldehyde producing capacity of mouthwashings obtained from patients with oral cavity, laryngeal, or pharyngeal cancer to that of mouthwashings from controls. The ability of mouthwashings to produce acetaldehyde from ethanol in vitro was determined by incubating them in closed vials containing various concentrations of ethanol (0-44 mM) at 37 degrees C for 1 hr. Acetaldehyde formed during the incubation was then analyzed by head space gas chromatography. Acetaldehyde production by mouthwashings increased with raising ethanol concentration in both groups. Acetaldehyde production by mouthwashings from patients with oral cavity, laryngeal, or pharyngeal cancer was significantly (p < 0.01) higher than that of the controls. Increased acetaldehyde formation from ethanol in the upper respiratory tract could thus contribute to the pathogenesis of alcohol-associated oral cavity, laryngeal, and pharyngeal cancers.

Acetaldehyde↗
PubMed1996

The combined effect of alcohol and physical exercise on serum testosterone, luteinizing hormone, and cortisol in males.

The combined effect of alcohol and physical exercise on the serum levels of testosterone, luteinizing hormone, and cortisol was studied in healthy male volunteers by performing an exhaustive ergometer exercise (1) followed by alcohol intoxication (induced by 1.5 g of alcohol/kg body weight), (2) during alcohol intoxication (induced by 0.8 g of alcohol/kg body weight), and (3) during hangover (13 hr after a dose of 1.5 g of alcohol/kg body weight). Physical stress immediately before alcohol administration prolonged the depressant effect of alcohol on testosterone secretion. This seemed to be mainly a consequence of direct inhibition at the testicular level, even though the role of luteinizing hormone as a contributory regulatory factor cannot be totally ruled out. Cortisol response to exercise was not modified by alcohol under any of the experimental conditions.

Adult↗
PubMed1996

In vitro alcohol dehydrogenase-mediated acetaldehyde production by aerobic bacteria representing the normal colonic flora in man.

Excessive ethanol consumption has been related with the development of liver cirrhosis, as well as with rapid intestinal transit time and diarrhea. Moreover, heavy drinking is associated with an increased incidence of cancer of the oropharynx, larynx, esophagus, and colorectum. Acetaldehyde of microbial origin has recently been suggested as a possible pathogenic factor behind this alcohol-associated gastrointestinal morbidity. The present in vitro study was aimed to investigate alcohol dehydrogenase activity and acetaldehyde formation capacity of some major aerobic bacteria representing the normal colonic flora in man. Cytosolic alcohol dehydrogenase activity and cytosolic protein concentration were determined spectrophotometrically. Alcohol dehydrogenase activity was then calculated as nmoles of reduced substrate produced by milligrams of protein per minute. The ability of different bacteria to produce acetaldehyde was determined by incubating the intact bacterial suspension in closed vials containing ethanol (final concentration 22 mM) for 1 hr at 37 degrees C. The acetaldehyde formed during the incubation was analyzed by headspace gas chromatography. Marked differences in the alcohol dehydrogenase activity and acetaldehyde forming capacity were found among the strains tested. The alcohol dehydrogenase activity varied from 606 +/- 91 nmol/min/mg protein (Escherichia coli IH 50546) to 1 +/- 0.2 nmol/min/mg protein (E. coli IH 50817), and acetaldehyde formation varied from 1,717 +/- 2 nmol acetaldehyde/10(9) colony-forming units (Klebsiella oxytoca IH 35403) to 5 +/- 2 nmol acetaldehyde/10(9) colony-forming units (Pseudomonas aeruginosa ATCC 27853). There was a statistically significant correlation (r = 0.77; p < 0.001) between alcohol dehydrogenase activity and acetaldehyde production from ethanol, strongly suggesting the catalytic role of bacterial alcohol dehydrogenase in this reaction.

Acetaldehyde↗
PubMed1996

Role of catalase in rat gastric mucosal ethanol metabolism in vitro.

To evaluate the possible role of catalase in gastric ethanol metabolism in rats, we studied acetaldehyde formation from ethanol by gastric mucosal homogenate under various in vitro conditions. Homogenized rat gastric mucosa produced significant amounts of acetaldehyde in a time and ethanol concentration-dependent manner, even in the absence of added NAD. Both acetaldehyde formation and catalase activity peaked around the physiological pH, whereas alcohol dehydrogenase (ADH) activity was in that pH range low and reached peak values only at a higher pH of 9 to 10. Catalase inhibitors sodium azide (SA) and 3-amino-1,2,4-triazole (3-AT) had little effect on ADH activity but markedly decreased catalase activity and acetaldehyde formation (1 mM of SA to 56 +/- 13% of control, 5 mM of 3-AT to 67 +/- 3% of control; mean +/- SE). 4-Methylpyrazole decreased ADH activity significantly, but did not affect acetaldehyde formation. Heating of the homogenate at 60 degrees C for 5 min decreased ADH activity only slightly, but totally abolished catalase activity and reduced acetaldehyde formation to 39 +/- 3% of control. Addition of a H2O2 generating system (beta-D(+)-glucose + glucose oxidase] increased acetaldehyde formation in a concentration-dependent manner up to 8-fold of the control value. Our results strongly suggest that, in addition to ADH, catalase may play a significant role in gastric ethanol metabolism in rats.

Acetaldehyde↗
PubMed1996

Biological markers of alcohol consumption and effect of calcitonin in nonalcoholic men: a prospective, double-blind study.

The objective of this study was to study the ability of biological markers of alcohol consumption in differentiating subjects below weekly consumption of 400 or 600 g of absolute ethanol from those above, and to study the effect of intranasal calcitonin on alcohol drinking. A prospective 12-week double-blind study that used anonymous data collection with drinking diaries was done. The drug that was studied (calcitonin or placebo) was used during study weeks 5-8. This study was performed at the research unit of a university hospital. The subjects consisted of 59-nine men aged 26 to 57 years who considered themselves as regular but modest drinkers and were recruited by advertisements. The measurements were obtained from monthly questionnaires and daily anonymous diaries for alcohol drinking data, and biological markers of alcohol consumption (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, beta hexosaminidase, and carbohydrate deficient transferrin). The results indicated intranasal calcitonin with a dose of 200 IU three times a week had no effect on alcohol use. All biological markers studied had only a modest ability to differentiate those with weekly alcohol consumption of 400 or 600 g or over from those below these limits. The areas under receiver operating characteristic (ROC) curve with the limit 400 g/week were 0.71 for aspartate aminotransferase, 0.61 for alanine aminotransferase, 0.74 for gamma-glutamyl transpeptidase, 0.68 for beta-hexosaminidase, and 0.78 for carbohydrate deficient transferrin. Respective numbers for the 600-g limit were more uniform. As evaluated by ROC analysis, carbohydrate deficient transferrin was the best biological marker to find men with weekly alcohol consumption over 400 g. Intranasal salmon calcitonin had no affect on alcohol drinking.

Administration, Intranasal↗
PubMed1996

High intracolonic acetaldehyde values produced by a bacteriocolonic pathway for ethanol oxidation in piglets.

BACKGROUND: Human colonic contents and many colonic microbes produce considerable amounts of acetaldehyde from ethanol in vitro. AIMS: To examine in piglets if acetaldehyde is produced in the colon also in vivo, and if so, what is the fate of intracolonically formed acetaldehyde. ANIMALS: Seventeen native, non-fasted female piglets (20-25 kg) were used. METHODS: Six piglets received either 1.5 g/kg bw or 2.5 g/kg bw of ethanol intravenously. In seven piglets, 0.7 g or 1.75 g of ethanol/kg bw was administered intravenously, followed by a subsequent intragastric ethanol infusion of 1.8 g/kg bw and 4.5 g/kg bw, respectively. The samples of colonic contents for the assessment of ethanol and acetaldehyde concentrations were obtained up to seven hours. In four additional piglets, the intracolonic values of ethanol, acetaldehyde, and acetate were observed for 60 minutes after an intracolonic infusion of acetaldehyde solution. RESULTS: A raised intracolonic, endogenous acetaldehyde concentration (mean (SEM); 36 (9) microM) was found in all piglets before ethanol infusion. After the infusion of ethanol, intracolonic ethanol and acetaldehyde values increased in parallel, reaching the peak values 57 (4) mM of ethanol and 271 (20) microM of acetaldehyde in the group that received the highest dose of ethanol. A positive correlation (r = 0.45; p < 0.001) was found between intracolonic ethanol and acetaldehyde values. Acetaldehyde administered intracolonically was mainly metabolised to acetate but also to ethanol in the colon. CONCLUSIONS: Significant endogenous intracolonic acetaldehyde values can be found in the normal porcine colon. Furthermore, our results suggest the existence of a bacteriocolonic pathway for ethanol oxidation. Increased amounts of acetaldehyde are formed intracolonically from ingested ethanol by this pathway.

Acetaldehyde↗
PubMed1996

The Helicobacter felis mouse model in assessing anti-Helicobacter therapies and gastric mucosal prostaglandin E2 levels.

BACKGROUND: The aims of the present study were to assess the usefulness of the Helicobacter felis mouse model in the evaluation of antimicrobial therapies and the effect of Helicobacter infection on gastric mucosal prostaglandin E2 release. METHODS: Barrier-maintained BALB/c mice were infected with H. felis and treated with different antibacterial therapies. H. felis status was determined by bacterial culture, urease test, and bacterial and histologic stainings. Release of prostaglandin E2 from the gastric mucosa was measured by radioimmunoassay. RESULTS: All triple-treated mice were cleared of bacteria both 24 h and 1 month after treatment. However, tinidazole alone also resulted in 100% eradication. Monotherapies with erythromycin acistrate, tetracycline, colloidal bismuth subcitrate, and nitecapone failed to eradicate the bacteria. The release of gastric prostaglandin E2 was doubled in the infected mice (554 +/- 39, mean +/- SE) compared with the noninfected mice (270 +/- 35) (p < 0.01). CONCLUSIONS: The H. felis mouse model proved satisfactory for assessing both anti-Helicobacter therapies and the prostaglandin E2 release. The reliability of this method was improved when several methods to assess the H. felis status were used in parallel.

Amoxicillin↗
PubMed1996

Bacteriocolonic pathway for ethanol oxidation: characteristics and implications.

Alcohol ingested orally is transported to the colon by blood circulation, and after the distribution phase, intracolonic ethanol levels are equal to those in the blood. Recent studies in our laboratory suggest that in the large bowel ethanol is oxidized by a bacteriocolonic pathway. In this pathway intracolonic ethanol is at first oxidized by bacterial alcohol dehydrogenase to acetaldehyde. Then acetaldehyde is oxidized either by colonic mucosal or bacterial aldehyde dehydrogenase to acetate. Part of intracolonic acetaldehyde may also be absorbed to portal vein and be metabolized in the liver. The bacteriocolonic pathway offers a new explanation for the disappearance of a part of ethanol calories. Due to the low aldehyde dehydrogenase activity of colonic mucosa, acetaldehyde accumulates in the colon. Accordingly during ethanol oxidation highest acetaldehyde levels of the body are found in the colon and not in the liver. High intracolonic acetaldehyde may contribute to the pathogenesis of alcohol-induced diarrhoea. Because acetaldehyde is a carcinogen in experimental animals, it may also contribute to the increased risk of colon polyps and colon cancer, which have been found to be associated with heavy alcohol consumption. Intracolonic acetaldehyde may also be an important determinant of the blood acetaldehyde level and a possible hepatotoxin. In addition to acetaldehyde, gut-derived endotoxin is another potential candidate in the pathogenesis of alcohol-related liver injury. Experimental alcoholic liver injury has recently been prevented by antibiotics, and this effect was related to the prevention of endotoxin-induced activation of Kupffer's cells.

Aldehyde Dehydrogenase↗
PubMed1995

Inhibition of gastric cell proliferation by acetaldehyde.

Helicobacter pylori possesses alcohol dehydrogenase activity and is capable of producing acetaldehyde from ethanol in vitro. Acetaldehyde is a toxic and reactive compound and has been shown to inhibit the proliferation of many different cell lines in vitro. To study the effects of acetaldehyde on the proliferation of gastric epithelial cells in vivo, we employed an immunohistochemical method after labelling proliferating cells with 5'-bromo-2'-deoxyuridine in rats receiving acetaldehyde intragastrically. Chronic (16 weeks) exposure of gastric mucosa to acetaldehyde given to rats in their drinking water in concentrations of 10 or 20 mM resulted in significant (P < 0.05) inhibition of gastric epithelial cell proliferation, expressed as 332 +/- 36, 348 +/- 8, and 695 +/- 15 proliferating cells per ten high-power (x 400) fields in the groups drinking 10 mM acetaldehyde, 20 mM acetaldehyde, and in controls respectively. In an acute study, significant inhibition of proliferation was observed after as few as 4 days of exposure to acetaldehyde, but only when a higher dose (50 mM) of acetaldehyde was given (438 +/- 44 versus 615 +/- 19 in controls, P < 0.05). The inhibition of gastric cell renewal by acetaldehyde may play a role in the pathogenesis of ethanol- and/or H. pylori-associated gastric diseases by inhibiting normal gastric mucosal protection and repair.

Acetaldehyde↗
PubMed1995

Alcohol metabolism in Helicobacter pylori-infected stomach.

Studies in our laboratory have revealed that Helicobacter pylori exhibits significant cytosolic alcohol dehydrogenase activity and that the enzyme is fully active at ethanol concentrations prevailing in the stomach during alcohol consumption or after alcohol is completely absorbed from the stomach and is available through blood circulation only. Moreover, even the low levels of endogenous ethanol found in the stomach can be oxidized to acetaldehyde by H. pylori alcohol dehydrogenase. The metabolic significance of the enzyme remains as yet unresolved. Under microaerobic conditions, however, the enzyme could be of importance in the energy metabolism of the organism. In the presence of excess ethanol, H. pylori alcohol dehydrogenase produces significant amounts of acetaldehyde. Acetaldehyde is a toxic and reactive compound and could theoretically be a pathogenetic factor in H. pylori-associated gastric injury. Preliminary studies have indicated that acetaldehyde inhibits gastric mucosal regeneration and forms stable adducts with mucosal proteins. Both of these mechanisms could cause gastric injury. The role of H. pylori-related acetaldehyde formation in vivo, however, needs to be established in future studies. In antral human gastric mucosa, H. pylori infection is associated with a significant decrease in alcohol dehydrogenase activity. Similarly, in specific pathogen-free mice with a prolonged infection, gastric alcohol dehydrogenase activity is decreased; however, this is not clearly reflected in the bioavailability of ethanol or the amount of its first pass metabolism.

Acetaldehyde↗
PubMed1994

Helicobacter pylori alcohol dehydrogenase.

We have recently shown that 34 different Helicobacter pylori strains of human and three of animal origin contain alcohol dehydrogenase (ADH). Isoelectric focusing of the enzyme showed activity bands with pI at 7.1-7.3, a pattern different from that of gastric mucosal ADHs. The Km value of H. pylori ADH for ethanol oxidation ranges from 64 to 104 mM. Although H. pylori ADH was capable of utilizing both NADP and NAD as cofactors in alcohol oxidation, it showed a strong preference for NADP over NAD. At neutral pH H. pylori ADH was more effective in aldehyde reduction than in alcohol oxidation. Distinct findings suggest that H. pylori ADH could be a metabolic enzyme taking part in ethanol production by fermentation. It is a rather abundant enzyme comprising approx. 0.5% of all bacterial cytosolic proteins. Therefore, the enzyme presumably has a basic role in the functions and maintenance of H. pylori. 4-methylpyrazole inhibits H. pylori ADH, and suppresses its growth during culture. Bismuth compounds that are commonly used in the treatment of H. pylori associated gastric diseases appeared to be potent inhibitors of H. pylori ADH. Owing to its high specific activity for ethanol (14 U mg-1) under physiological conditions H. pylori ADH can also effectively produce acetaldehyde at moderate ethanol levels. This reversed function of the enzyme and the production of the toxic and reactive acetaldehyde could account for at least some of the gastrointestinal morbidity associated with H. pylori infection. H. pylori lacks aldehyde dehydrogenase activity and can therefore not remove acetaldehyde at least by this pathway.

Acetaldehyde↗
PubMed1994

Association of alcohol consumption and Helicobacter pylori infection in young adulthood and early middle age among patients with gastric complaints. A case-control study on Finnish conscripts, officers and other military personnel.

There is growing evidence that Helicobacter pylori is responsible for a variety of gastric and duodenal changes which can eventually lead to stomach cancer. Little is known about risk factors for H. pylori infection. We re-analyzed the association of alcohol with H. pylori positivity in 451 conscripts, officers and other military personnel endoscoped due to gastric complaints in the Central Military Hospital of Finland in 1987 and 1988. Serology and culture were done in all patients. Alcohol consumption histories were obtained by use of a self-administered questionnaire. We observed a high odds ratio (OR) of H. pylori infection among young adults who were heavy alcohol consumers compared to non-drinkers (OR 5.32, 95% confidence interval: 1.09-25.95). There was evidence of a dose response when heavy and moderate drinkers were compared to non-drinkers (Mantel-Haenszel chi 2 for trend, p = 0.02) in young adulthood. A subgroup of young respondents who reported drinking all classes of alcohol (including hard liquor) showed an even stronger association and more significant dose-response. Multivariate techniques revealed a qualitative interaction of alcohol with H. pylori positivity in different age groups and among old people an inverse association of H. pylori and alcohol consumption was observed. These findings, if confirmed independently, might have implications for preventing a variety of gastric and duodenal lesions, since they allow identification of high risk groups.

Adolescent↗