Comparative evaluation of the effect of carbidine and levamisole on the E-rosette-forming activity of the lymphocytes in alcoholic intoxication

The E-rosette formation activity of lymphocytes in human alcoholics treated with carbidine was studied. In experimental alcohol intoxication in animals the effect of carbidine on the E-rosette formation was compared with that of levamisole. The effects of the both drugs in the in vitro experiments were studied as well. The use of carbidine for treating alcoholism was shown to produce changes in the E-rosette formation indicating possible immunodulating properties of the drug. In experimental conditions of the immune response to ram erythrocytes during alcoholic intoxication the inhibitory effect of carbidine on the E-rosette formation was more pronounced. In the in vitro conditions carbidine changes the E-rosette formation in alcoholics similarly to levamisole suggesting the immunomodulating properties of carbidine.     

Monoamine content of the blood in the experimental pharmacotherapy of alcoholic intoxication

Experiments on rabbits have shown that caffeine (10 mg/kg), ethimizol (10 mg/kg) and particularly bemegride (5 mg/kg) increase the blood adrenaline and noradrenaline content up to the level characteristic for intact animals under acute ethanol poisoning (2.5 g/kg per os). This effect has been found to be more remarkable on repeated administration. The shifts in the serotonin content are inconsistent in this case.     

Effect of acute alcoholic intoxication on lipogenesis in the liver of rats

Thirty minutes after a single ethanol injection (4 g/kg bw, i.p.) the activity of rat liver acetyl-CoA-synthetase and ATP-citralyase was decreased. Cholesterol synthesis estimated by label incorporation from 3H2O was increased whereas the synthesis of fatty acids remained at the control level. The possibility of alternative ways of acetyl-CoA production under the conditions of acute alcoholic intoxication is discussed.     

Effect of chronic alcoholic intoxication on the body of rats]

Experiments involving chronic introduction of ethanol (36 per cent of caloric value) as a part of a specially devised liquid ration demonstrated the trainability of rats to sharply decrease, their antistress resistance to significantly decline, especially in rats kept on a low-protein diet. A general tendency toward a reduced activity of acetylcholinesterase in different sectors of the brain was revealed both in animals receiving alcohol against the background of a normal protein allowance and in those kept on a low-protein diet (when compared with the enzyme activity in animals maintained on a ration with a normal of protein).     

Effect of type of dietary fat and ethanol on hepatic leukotriene level in experimental alcoholic liver disease]

The purpose of our study is to determine if a relationship exists between the severity of injury in experimental alcoholic liver disease and hepatic levels of leukotriene B4, leukotriene C4 and lipid peroxide. Splague-Dawley rats were fed ethanol (46% of calories) with either safflower oil (SE) or beef oil (BE) (20% of calories) for 12 weeks. Control animals were fed isocaloric amounts of dextrose instead of ethanol with the same diets. The followings were evaluated in each group: hepatic levels of leukotriene B4, C4, lipid peroxide, and collagen-bound hydroxyl-proline, hepatic fatty acid composition, incorporation of 14C-L-proline into hydroxyproline of collagen protein by liver slice. Rats fed SE showed the most abundant accumulation of hepatic hydroxyproline and lipid peroxide. Hepatic leukotriene B4 and C4, hepatic levels of linoleic acid and arachidonic acid were also greater in rat livers from animals fed the SE diet. A strong positive correlation was seen between hepatic levels of leukotrien B4 as well as C4 and lipid peroxide. The hepatic level of lipid peroxide also correlated positively with hepatic levels of linoleic acid and arachidonic acid. Our study shows the importance of leukotriene derived from arachidonic acid cascade in the pathogenesis of experimental alcoholic liver disease.     

Pharmacological modulation of nitrogen oxide system in experimental chronic alcoholic intoxication in rats

The modeling of chronic alcohol intoxication for 30 days in rats leads to an increase in the level of free metabolites of nitrogen oxide and NO-synthase with simultaneous decrease in the levels of L-arginine, catalase, and superoxide dismutase. The subsequent 14-day treatment with neuropeptide cerebroprotectors cerebrocurin, cortexin, and cerebrolysin led to normalization of the parameters of nitrogen oxide system. The maximum therapeutic activity was shown by cerebrocurin, which can be recommended for inclusion as component of alcoholic encephalopathy treatment.     

Effect of methanol intoxication on free-radical induced protein oxidation

Oxygen free radicals are generated during methanol-induced liver injury, as was shown for ethanol. The effect of methanol intoxication (6 g kg(-1) body wt.) on protein modification in the liver of rats was investigated. Electron spin resonance determination indicated an increase in the free radical signal 6 and 12 h after intoxication. After 7 days of treatment, the contents of malondialdehyde and carbonyl groups in proteins were significantly increased. The level of amino groups and sulphydryl groups and the amount of tryptophan in proteins were decreased, whereas the amount of bi-tyrosine was increased significantly. Changes in protein structure resulted both from free radical action and formaldehyde generation during methanol intoxication.     

Effect of alcoholic intoxication on the phospholipid composition of human myocardial mitochondria

Mitochondrial phospholipids of the myocardium of persons consuming alcohol are characterized by an appreciable increase in the concentration of lysophospholipids (lysophosphatidylserines, lysophosphatidylcholines, lysophosphatidylethanolamines), which occurs in the presence of a reduction in the quantity of phosphatidylcholines and phosphatidylethanolamines.     

Misattribution of ethanol intoxication

Although studies indicate that cognitive variables are sufficient to influence intoxication experiences, the potential for interplay between physiological and cognitive influences remains intuitively appealing. To test the hypothesis that the interoceptive events caused by alcohol consumption can be attributed to nonalcoholic stimuli, subjects were given a placebo medication. Instructions led subjects to believe that the placebo had effects either similar or dissimilar to alcohol or no effects. Low or moderate doses of ethanol were used. Attribution of physiological sensations to the placebo, perceptions of impairment and mood state were assessed 20, 40, and 60 minutes after completion of the drink. Forthy-eight nonalcoholic male students participated in the study.Misattribution to the placebo was greatest at the lower dose and with increasing time. The manipulation of instructions did not affect the degree of misattribution. However, individuals instructed to expect side effects from the placebo perceived significantly less impairment than participants who did not expect side effects. Both similar and dissimilar side effects affected perceptions of impairment. The implications of these data for cognitive and cognitive- pharmacological theories of intoxication are examined.     

Renin-aldosterone axis in ethanol intoxication

The effect of acute moderate ethanol intoxication on renin-aldosterone axis was studied in four healthy humans in normal sodium and water balance. The subjects drank ethanol 1.2 g/kg body weight during 90 minutes. A dissociation between plasma renin activity (PRA) and plasma aldosterone took place; PRA increased (p less than 0.001) and aldosterone showed a decreasing trend, which was not significant. Serum Na+/K+-ratio increased (p less than 0.001). We observed no significant change in serum osmolality, blood pressure nor heart rate. The increase (p less than 0.001). We observed no significant change in serum osmolality, blood pressure nor heart rate. The increase in PRA was probably caused primarily by dehydration due to ethanol diuresis. The dissociation between plasma aldosterone and PRA may be associated with increasing serum Na+/K+-ratio or an inhibitory action of ethanol on aldosterone secretion.     

Effects of ethanol intoxication on LH receptors and glucose oxidation in Leydig cells of adult albino rats

The present study was designed to assess the dose-dependent effects of ethanol on Leydig cells of adult albino rats of the Wistar strain. Ethanol was given orally through gastric intubation at three different dose levels (0.5, 1 and 3 g/kg body weight) twice daily as 25% (v/v) aqueous solution for 15 days. Ethanol treatment reduced body and testes weights. Serum testosterone registered a decrease while estradiol levels became elevated. Activities of the steroidogenic enzymes 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17-ketosteroid reductase (17-KSR) decreased significantly. The glucose oxidative capacity of Leydig cells was impaired by ethanol treatment in a dose-dependent manner. Similarly, ethanol treatment caused significant reduction in LH receptors on the Leydig cell membrane at higher doses (1 and 3 g/kg) whereas no significant change was observed with the lower dose (0.5 g/kg) as compared to controls. The present findings suggest that the decrease in Leydig cellular LH receptors, glucose oxidation and the activities of 3β-HSD and 17-KSR are possible mechanisms by which ethanol treatment perturbs Leydig cell steroidogenesis.     

Effects of acute ethanol intoxication,chronic ethanol intoxication,and ethanol withdrawal on magnesium and calcium metabolism in the rat

Effects of ethanol intoxication and withdrawal on magnesium and calcium metabolism were studied in rats. During acute ethanol intoxication, plasma [Mg²⁺] was increased and plasma [Ca²⁺] decreased. During chronic intoxication, plasma [Mg²⁺] was normalized whereas plasma [Ca²⁺] was persistently subnormal. Ethanol withdrawal was followed by a decrease in plasma [Mg²⁺] and a normalization of plasma [Ca²⁺]. These various changes are probably related to changes in systemic pH and to the biochemical effects of ethanol and ethanol withdrawal on intermediary metabolism. Cerebrospinal fluid [Mg²⁺] was unchanged during intoxication and withdrawal and it was concluded that no etiological role can presently be ascribed to the magnesium ion as far as cerebral signs of ethanol intoxication and withdrawal in the rat are concerned. No consistent changes in erythrocyte [Mg²⁺] were encountered during ethanol intoxication and withdrawal in rats.     

Effect of chronic acetaldehyde intoxication on ethanol tolerance and membrane fatty acids

Recent studies have suggested that acetaldehyde participates directly in the pathogenesis of alcoholism. Its action has been attributed mainly to its physico-chemical properties. Results of direct intoxication of laboratory animals with acetaldehyde have been reported, but only for short periods of exposure and at high doses. These are probably not representative of the conditions found during alcohol intoxication. The pulmonary route of administration described here enables long term intoxication with acetaldehyde, at levels corresponding to values measured during chronic ethanol intoxication. Chronic administration of acetaldehyde during 3 weeks induced a metabolic tolerance to ethanol as tested by the sleeping time after a challenge dose of ethanol; behavioural tolerance (measured by blood alcohol levels on waking) was not observed. At the end of the intoxication, phospholipid fatty acids of erythrocyte and synaptosome membranes were also analysed. Small changes in levels of the shorter fatty acids were observed in the phosphatidyl-choline fraction. By comparison with the effects of ethanol on the same membrane preparations, only a small part of this effect can be attributed to acetaldehyde. The first metabolite of ethanol has, however, a sure effect on the pattern of fatty acid phospholipids.     

Effect of carbidine on dopamine turnover in the rat corpus striatum

It has been shown that carbidine increases the level of homovanillic acid (HVA) in the corpus striatum of the rat brain. The changes in HVA level allowed forming a judgement on dopamine turnover. By the intensity of this effect, carbidine proved inferior to typical neuroleptics--triphtazine and ftorfenazin. The antidepressant ftoracizin did not alter HVA level. Carbidine ranks between neuroleptics and antidepressants in terms of the effect on dopamine turnover.     

醒脑静对急性酒精中毒患者炎性因子含量的影响

目的 探讨急性酒精中毒患者血浆炎性因子含量的变化及醒脑静对其影响.方法 选取甘肃省兰州市第一人民医院严重急性酒精中毒患者50例,采用随机数字表法分为常规治疗组（对照组）和醒脑静＋常规治疗组（观察组）,各25例.分别检测2组患者治疗前后内皮素1、一氧化氮、肿瘤坏死因子α（TNF-α）和白细胞介素6（IL-6）含量的变化,并与20名体检者健康（正常组）进行对比分析.结果 对照组和观察组治疗前后的内皮素1、一氧化氮、TNF-α和IL-6[对照组：治疗前（77±7）ng/L、（34±10）μmol/L、（2.6±0.1）ng/L、（31.3±3.2）ng/L,治疗后（68±6）ng/L、（48±10）μmol/L、（2.2±0.2）ng/L、（26.3±3.1）ng/L;观察组：治疗前（78±7）ng/L、（35±11）μmol/L、（2.6±0.2）ng/ml、（32.4±3.1）ng/L,治疗后（62±7）ng/L、（57±9）μmol/L、（2.0±0.3）ng/ml、（22.6±3.2）ng/L]与正常组[（55±9）ng/L、（57±14）μmol/L、（2.0±0.4）ng/ml、（16.6±2.8）ng/L]相比,差异均有统计学意义（均P〈0.01）.观察组、对照组治疗后血浆内皮素1、一氧化氮、TNF-α、IL-6与治疗前比较,差异均有统计学意义（均P〈0.05）.观察组治疗后血浆内皮素1、TNF-α及IL-6显著低于对照组（P〈0.01）,一氧化氮明显高于对照组（P〈0.01）.结论 急性酒精中毒患者血中内皮素1、TNF-α和IL-6明显升高,一氧化氮水平降低,醒脑静治疗后可降低内皮素1、TNF-α和IL-6,提高一氧化氮水平,具有改善急性酒精中毒病理损害的作用.