摘要:

The cardiovascular effects of ethanol ingestion after pretreatment with a new antialcohol drug, nitrefazole (2‐methy1‐4‐nrlro‐1‐(4‐nitro‐pfienyl)tmidazote, AMmol) were studied. Left ventricular function was examined by echocardiography and systolic time intervals in six healthy Finnish male volunteers who ingested 0.15‐0.25 g of ethanol/ kg, 24 hr after an 800 or 1600‐mg peroral dose of nitrefazole. After ethanol ingestion, accumulation of acetaldehyde in blood (25–150 /IM) was accompanied by a 1.5‐2‐foW increase in plasma noradrenaline, a 3–10‐foM increase in plasma adrenaline, and a 0.5‐2.0oC rise hi skin temperature. Heart rate increased by 70% and cardiac output by 107%. Diastolic blood pressure decreased by 30% and peripheral vascular resistance by 54%. Election fraction and maximum circumferential fiber‐shortening velocity increased by 26 and 71%, respectively; the pre‐ejection period/ejection time ratio decreased by 46%. An apparent vasovagal collapse was noticed in two nrirefazoietreated subjects after ethanol ingestion, and a third subject experienced a fainting attack shortly after the experiment Thus, in subjects pretreated with nitrefazole, ingestion of rather small amounts of ethanol results in marked accumulation of acetaldehyde apparently due to aldehyde dehydrogenase inhibition. This causes elevation of plasma catecholamines and intense enhancement of cardiac performance. The marked cardiovascular changes demonstrate the potency of nitrefazole, suggesting that, particularly with alcoholics with occult myocardial diseases, its interaction with ethanol may be even more hazardous than that pr

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1985.tb05739.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

In order to relate the catalytic properties of alcohol dehydrogenase (ADH), the rate‐limiting enzyme for alcohol metabolism, with the pharmacokinetics of ethanol elimination in vivo, the multiple molecular forms of dog Hver ADH were purified and their steady state kinetics investigated. Two different classes of ADH forms were identified by starch gel electrophoresis: the class I isoenzymes migrate to the cathode and the class II forms migrate to the anode. Three different patterns of the cathodic class I isoenzymes were identified in different liver specimens. Three molecular forms were observed for patterns A and C, and five for B. The two classes of isoenzymes were separated by affinity chromatography and purified by column chromatography. The three predominant class I isoenzymes, A1, B2, and C1, in type A, B, and C livers, respectively, were isolated by high performance cation‐exchange chromatography. The steady state kinetic constants of the A1, B2, and C1 isoenzymes are similar, but differ substantially from those of the class II enzyme. The class II enzyme is much less sensitive to pyrazole inhibition,Ki= 2 nw, than the class I forms,Ki= 0.6μM.Methanol is not a substrate for the class II enzyme, whereas it is oxidized by the class I isoenzymes. The class I isoenzymes exhibit a lower K., and substrate inhibition K, for ethanol, 0.4 and 160 nw, respectively, than values for the class II enzyme, 10 and 610 mi, respectively. The properties of class I and II dog liver ADH are similar to those of the respective isoenzymes purified from human and monkey liver. Based on kinetic data for the two classes of dog liver alcohol dehydrogenase, we suggest that the pharmacokinetics of ethanol elimination should obey a two term Michaeiis‐Menten model with substrate inhibition at high alcohol concent

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1985.tb05740.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1985.tb05741.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Acute alcohol consumption has no effect on the levels of enzymes in serum. Regardless of the amount consumed, no significant changes in serum enzymes were observed. Age‐related differences in γ‐glutamyltransferase were not apparent Peak blood alcohol concentration and consumption are not related to the body mass. Screening of drunk drivers for detecting problem drinkers could be undertaken by performing biochemical measurements of serum enzymes, especially γ‐glutamyftran

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1985.tb05742.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Twenty male alcoholics with alcohol withdrawal syndrome were randomized to receive either oral clonidine (3–600 μg, six hourty)ororal chlormethiazole (500–1000 mg, six hourty) for 4 days. All subjects were also given oral caroamazepine (200 mg, 12 hourly) throughout the study. Nine subjects given clonidine and eight given chlormethiazole completed the study. Clonidine was as effective as chlormethiazole in suppressing the symptoms and signs of alcohol withdrawal. However, plasma catecholamines, blood pressure, and pulse rate feH more rapidly and to a greater extent during clonidine than following chlormethiazole, findings which could have therapeutic implications, tt is suggested that activation of brain noradrenergic neurons constitutes a common denominator in the pathophysiology of several withdrawal syndr

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1985.tb05743.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

During the first year after treatment, 44% of a sample of alcohol abusers reported relapse to alcohol use. Relapse rate Increased to a peak at 6 months after treatment and then decined. Depressed or anxious mood was the reason most frequently given (31%) for relapse. Of subjects who relapsed, almost half (42%) reported a subsequent return to abstinence which was then maintained for the remainder of the foNowup period. Of these subjects, half (51%) reported the duration of the drinking period to be less than 2 weeks. Of subjects showing a daily drinking pattern prior to treatment, 20% showed a dairy drinking pattern after relapse, 46% showed bouts of drinking and abstinence, and 33% showed abstinence with no further drinking. Of subjects snowing bouts of drinking prior to treatment, none showed a deify drinking pattern after relapse, 44% showed bouts of drinking and abstinence, and 56% showed abstinence with no further drinking. There was no significant effect of sex or age on relapse rate, time to relapse, or reasons for relapse.

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1985.tb05744.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

The effects of alcohol abuse on cellular immune functions were measured by various levels of alcohol use in adult men. Total lifelong abstainers were used as controls. Previous abusers, current abusers, and patients with alcoholic cirrhosis or pancreatitis were age‐matched to controls. T‐lymphocyte mitogenesis stimulated by phy‐tohemagglutmin and concanavaNn A was generally reduced in peripheral blood lymphocytes of current and previous alcohol consumers, although the decrease was not statistically significant B‐cefl mitogenesis stimulated by pokeweed mitogen was not changed by previous alcohol consumption. The number of T‐ceHs was not changed by either previous or current alcohol abuse. T‐helper cells were signiftcantty increased and T‐suppressor cefls increased only in the patients with alcoholic cirrhosis or pancreatitis. The percentage of T‐lymphocytes with T‐suppressor characteristics in controls was 27% while in alcoholic cirrhosis or pancreatitis subjects it was 16%. Plasma corticosteroid levels were significantly increased in people currently consuming alcohol (12.1 ± 1.1 mg/dl) compared to controls (7.7 ± 1.1). The corticosteroid levels were also higher in previous alcohol abusers although not statistically significant. Plasma endorphin levels were increased by severe alcohol abuse in the patients with cirrhosis or pancreatitis to 25.03 ± 6.74 from 11.85 ± 2

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1985.tb05745.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Canine liver aldehyde dehydrogenases (ALDH) (aldehyde:NAO oxi‐doreductase; EC 1.2.1.3)tmanalogous to enzymes identified in human and other mammalian liver tissue in regard to subcellular localization, affinity for substrates, inhibition by disutfiram, and effects of magnesium ions on enzyme activity. Aldehyde dehydrogenase activity is distributed in the mitochondrial, microsomal, and cytosolic fractions of the cell. Four isoenzymes designated ALDH IA, IB, HA, and IIB have been isolated from canine Kver via ammonium sulfate fractionation, ion‐exchange chromatography, and affinity chromatography. Based on cell fractionation followed by enzyme isolation, ALDH IA and IB appear to be extramitochondrial whereas ALDH HA and IIB appear to be mitochondrial in origin. ALDH IA has ‐a highKmfor acetaldehyde (3 mM) and propionaldehyde (4 mM). ALDH IB and IIA haveKmvalues for acetaldehyde and propionalde hyde in the range of 4–60 μM. ALDH IIB has the lowestKmof the four isoenzymes for acetaldehyde and propionaldehyde (1–3 μM). All four isoenzymes haveKmvalues for NAD in the range of 4–70 MM. ALDH IB and IIAansensitive to inhibition by disulfiram whereas ALDH IA and IIB are resistant Magnesium ions inhibit ALDH IA, IB, and IIA whereas ALDH IIB activity is stimulated approximately 2‐fold. Magnesium ions do not affect molecular weight estimates of the isoen zymes as determined by gel filtration

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1985.tb05746.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

Isoelectric focusing and electrophoresis were used to identify the various isozymes of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), aldehyde oxidase (AOX), and xanthine oxidase (XOX). ADH types I, II, and III were located primarily in the cytosol fraction of liver, but some activity was found also in the small granule fraction. The ALDH‐I and ‐IV isozymes were found in the large granule fraction, while ALDH‐II and ‐III were present in the cytosol and ALDH‐V in the small granule fraction. AOX and XOX each appeared as a single cytosolic form with some small granule activity. The tissue distribution of these isozymes is presented and the physiological role of each enzyme is

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1985.tb05747.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY

摘要:

A rise in Mood acetaldehyde concentration* foftowmg alcohol ingestion was significantly inhibited when healthy nonflushing sutojecti were administered a clinical dose of pantethine oraty. However, similar findings were not observed in flushing (alcohol‐sensitive) subjects lacking hepatic lowKmaldehyde dehydrogenase (ALOH). The blood ethanol concentrations were not altered by this treatment in either flushing or nonflushing subjects. Acetaldehyde (45 μM) added in vitro to whole blood and plasma obtained 1 hr after pantethine administration disappeared as the incubation continued similarly as with blood and plasma obtained prior to pantethine treatment Pantethine‐related metabolites, such as taurine, pantetheine, coenzyme A, and pantothenate, activated ALOH in vitro. Hepatic acetaldehyde levels following ethanol loading of rats treated with pantethine were much lower than in untreated rats. The pantethine action observed only in nonflushing subjects might be due to an accelerated oxidation of acetaldehyde by the activation of lowKmALOH by pantethine‐related metabolites formed in the

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1985.tb05748.x

出版商:Blackwell Publishing Ltd    

年代:1985

数据来源: WILEY