复方葡萄籽提取物对乙醇及四氯化碳肝损伤的影响

目的：探讨复方葡萄籽提取物（GSE）对化学性肝损伤的预防和治疗作用。方法：用小鼠建造四氯化碳肝损伤和乙醇肝损伤模型，观察乙醇灌胃前预先给予复方GSE及乙醇或四氯化碳灌胃后再给予复方GSE后小鼠血清谷丙转氨酶（ALT），肝细胞超氧化物歧化酶（SOD）、谷光甘肽（GSH）、丙二醛（MDA）。结果：预先给予GSE可增强SOD活性，防止乙醇导致的肝GSH减少，有效降低小鼠血清ALT和肝细胞MDA上升程度，在乙醇或四氯化碳灌胃后再给予复方GSE，也可降低小鼠血清中ALT和肝细胞脂质过氧化产物。结论：复方GSE对乙醇肝损伤有预防和治疗作用。对四氯化碳肝损伤也有一定治疗作用。     

Flavor preference conditioning by oral self-administration of ethanol

 Oral self-administration and operant tasks have been used successfully to confirm ethanol′s positive reinforcing effects in rats. However, in flavor conditioning tasks, ethanol is typically found to have aversive effects. The present studies explored this apparent paradox by examining the change in value of a flavor paired with orally self-administered ethanol in two different limited-access procedures. Rats were food-deprived and trained to drink (experiment 1) or to barpress for (experiment 2) 10% (v/v) ethanol during daily 30-min sessions using prandial initiation techniques. All rats were then exposed to a differential flavor conditioning procedure in which banana or almond extract was added to the drinking solution. One flavor (counterbalanced) was always mixed with ethanol (CS+), whereas the other flavor was mixed with water (CS–). By the end of conditioning, rats in both experiments drank more flavored ethanol than flavored water, confirming ethanol’s efficacy as a reinforcer. Moreover, barpress rates for CS+ exceeded those for CS– in the operant task. Ethanol doses self-administered in final sessions averaged about 1 g/kg. The effect of the flavor-ethanol contingency was assessed in preference tests that offered a choice between the two flavor solutions without ethanol. In both experiments, subjects developed a preference for the flavor that had been paired with ethanol. Thus, the outcome of flavor conditioning was consistent with that of the oral self-administration tasks in providing evidence of ethanol’s rewarding effects. These experiments confirm and extend previous studies showing that flavor aversion is not the inevitable result of flavor-ethanol association in rats. It seems likely that ethanol’s nutrient and pharmacological effects both contributed to the development of conditioned flavor preference. Received: 15 February 1997 / Final version: 11 June 1997     

Naltrexone Blocks Acquisition of Voluntary Ethanol Intake in Rats

The effects of naltrexone (NTX) on the acquisition of ethanol drinking was assessed in rats. NTX (0, 2.5, 5.0, or 10.0 mg/kg) was administered to rats presented with an ascending series of ethanol concentrations (2%, 4%, 6%, and 8% v/v) and water. The 2.5 and 10 mg/kg doses of NTX attenuated the acquisition of voluntary drinking of 8% ethanol, but the 5.0 mg/kg dose of NTX had no effect on ethanol intake. The acquisition paradigm was repeated in experiment 2 with naïve animals that received 0, 5.0, or 7.5 mg/kg of NTX. Neither dose of NTX affected ethanol intake, preference for alcohol, or water intake. Total fluid intake was suppressed in the NTX groups, but only on the second presentations of the 2% and 6% concentrations of ethanol. We suggest that the 2.5 and 10 mg/kg doses of NTX may have attenuated the acquisition of ethanol drinking by at least two different behavioral mechanisms.     

乙醇摄入对小鼠肝功能及磺胺嘧啶代谢动力学的影响

动态观察了乙醇摄入对小鼠肝功能及磺胺嘧啶（ＳＤ）代谢动力学的影响。结果表明，每天以２５ｇ／ｋｇ乙醇摄入２周，ＳＧＳＴ活性明显升高，随着摄入时间的延长，在一定时间范围内呈进行性增高，同时，ＳＡＬＴ活性也与乙醇摄入时间呈明显正相关，提示长期乙醇摄入对肝脏的不利影响。乙醇对肝匀浆中ＧＳＴ和苯胺羟化酶活性呈双重作用，早期具有诱导酶活性的作用，但诱导的时间和强度不同，后期则可抑制酶的活性。ＳＤ在小鼠体内的代谢符合二房室模型，乙醇对ＳＤ的代谢具有双相作用，早期使ＳＤ代谢加速，后期则使代谢延缓，表明乙醇对代谢ＳＤ的Ｎ乙酰化酶可能具有酶促酶抑双重作用。     

Alcohol and Platelet Function

Epidemiological studies have shown that moderate consumption of alcoholic beverages is inversely related to the incidence of the complications of coronary artery disease. The protective effect of ethanol may be partially attributable to an inhibitory effect of ethanol on platelets. This article summarizes the experimental observations that ethanol inhibits platelet responses to specific physiological agonists. In alcoholics, various platelet defects have been observed, but these may be influenced by metabolic factors rather than the presence of ethanol alone. The acute effects of ethanol on platelet functions both in vivo and ex vivo will be reviewed. Evidence will be presented demonstrating that ethanol added acutely in vitro inhibits phospholipase A₂ in stimulated platelets. The interaction of ethanol with other signal transduction pathways will also be discussed.     

Effects of Ethanol on the Contractile Function of the Heart: A Review

Chronic ethanol consumption leads to a number of alterations in the contractile function of the heart and is a leading cause of cardiomyopathy. Ethanol also has an acute negative inotropic effect mediated by direct interaction with cardiac muscle cells, although this action is often masked by indirect actions resulting from enhanced release of catecholamines in vivo. This article reviews the effects of ethanol on the contractile function of the heart. The specific targets affected by ethanol in cardiac muscle cells are discussed in terms of potential mechanisms underlying the depressions of contractility resulting from both acute and chronic actions of ethanol.     

Effect of ethanol on sustained attention in rats

 Acute exposure to ethanol produces deficits in sustained attention in humans, but these attentional deficits have not been modeled in animals. In this study, an operant task was used to investigate the effects of low and moderate doses of ethanol on sustained attention in rats. Performance on a two-choice reaction time task over a 1-h session was assessed immediately following administration of ethanol (0.0, 0.5, 0.75, 1.0 and 1.5 g/kg IP). Each rat was required to respond to a light stimulus of variable duration (20, 100, and 500 ms) occurring at one of two locations. Under control and saline conditions, increases in stimulus length systematically increased choice accuracy and decreased reaction time. Ethanol produced a dose-dependent decrease in choice accuracy that interacted with time, with an initial impairment that was stimulus length-dependent followed by a general vigilance decrement. The data demonstrate that ethanol impaired the ability of rats to direct and sustain attention to brief, infrequent stimuli, and provide a model for further investigations into the underlying neurobiological mechanisms for ethanol-induced attentional deficits. Received: 19 March 1996 / Final version: 30 August 1996     

Injury Type, Injury Severity, and Repeat Occurrence of Alcohol-Related Trauma in Adolescents

Injury associated with alcohol use is a significant problem among adolescents; however, routine evaluation of alcohol use in this population is not conducted. The purpose of this study was to compare injured adolescents presenting to an emergency room with a positive serum alcohol concentration (SAC+) with those injured adolescents wlth a negative serum alcohol concentration (SAC-). Data were collected retrospectively on 176 injured patients, between the ages of 13 and 18, consecutively admitted to a university hospital from January 1, 1989-December 31, 1990. Information collected included mechanism and severity of injury, outcome, SAC, length of stay, prychiatric history, prior or subsequent admission for injury, and hospital charges. Of those tested with an SAC, more than one-third had a positive SAC. Patients with positive SACs had a greater probability of having a psychiatric history and more frequently had a prior or subsequent injury. Furthermore, only 34% of SAC+ patients were referred for counseling. The results indicate that a SAC should be obtained on all adolescents admitted for trauma, that adolescents presenting with injuries and a positive SAC should be referred for alcohol and psychiatric assessment, and that injured adolescents may be at increased risk for repeat injuries in the future.     

二甲基甲酰胺与乙醇联合毒性初探

经口分别给予Wistar大鼠蒸馏水、DMF 400mg/kg、乙醇1000mg/kg及DMF400mg/kg 乙醇1000mg/kg,染毒21天。结果表明DMF组及联合染毒组大鼠血清ALT明显增高,SLDH在后者也明显升高,且两组肝组织ATP酶及SDH活性明显降低。各染毒组尿LDH活性显著上升,DMF组及联合染毒r-GT活性显著降低,此两组肾脏组织AKP、ATP、SDH活性也明显降低。上述变化联合染毒组较单独作用组明显,因此认为DMF对肝肾具有损伤作用,乙醇可加重DMF的损伤作用。     

Dietary Vitamin E Modulation of Cytokine Production by Splenocytes and Thymocytes from Alcohol-Fed Mice

As vitamin E enhances immune responses, it may reduce dietary ethanol (EtOH)-induced immune suppression, thereby favorably afffecting host disease resistance. The effects of dietary vitamin E at higher level in alcohol-fed female C57BL/6 mice was determined via in vitro cytokine production by splenocytes and thymocytes, and some other immune functions. A 15-fold increase of vitamin E (160IU/liter) in a liquid diet (National Council Research), with or without EtOH (4.5%, v/v), was fed to mice for 10 weeks. Vitamin E supplementation restored production of interleukin-2, -5, -6, -10, and inter-feron-γ by concanavalin A (Con A)-stimulated splenocytes and in terleukin-6 and tumor necrosis factor-a by lipopolysaccharide-stimulated splenocytes, which were suppressed by dietary EtOH. However, it had no effect on interleukin-4 secretion, which was also reduced by splenocytes from EtOH-fed mice. Vitamin E supplementation also restored EtOH-suppressed, mitogen-induced splenocyte proliferation, but not thymocyte proliferation, although it slightly increased production of immunoglobulin A and G by lipopolysaccha-ride-stimulated splenocytes, which were suppressed by dietary EtOH. Dietary vitamin E, furthermore, significantly increased interleu-kin-2 and -6 secretion by Con A-stimulated thymocytes, which were suppressed by dietary EtOH, although it had no effect on interleukin- 4 and interferon-γ production by Con A-stimulated thymocytes from EtOH-fed mice. These data suggest that dietary vitamin E supple-mentation can modulate dysregulation of cytokines initiated by dietary EtOH and restore immune dysfunctions induced by EtOH ingestion.