Acquired dyschromatopsia in combined exposure to solvents and alcohol

Hypothesis: Does occupational exposure to solvents in combination with alcohol intake give rise to acquired color vision defects? Method: A total of 138 individuals exposed to solvents (toluene, xylene, trichloroethylene, tetrachloroethylene) were examined using Lanthony’s D-15 test and compared with 100 nonexposed controls. The extent of color vision loss was quantitatively assessed based on Bowman’s color confusion index (CCI). A cumulative exposure index was calculated from the hours of exposure per day and the years of exposure. In 30 persons who were exposed to trichloroethylene and tetrachloroethylene, urinary trichloroacetic acid was assessed as a parameter of exposure. Alcohol intake was calculated as based on interviews of patients in grams of ethyl alcohol per week. Results: Individuals who consumed more than 250 g alcohol/week and were simultaneously exposed to solvents showed a significantly elevated CCI (P = 0.0044). No significant correlation emerged between trichloroacetid acid excretion in the urine or the cumulative exposure index and the CCI. Conclusion: The combination of alcohol intake and occupational exposure to solvents discloses the risk of acquired subclinical color vision defects.     

Ginkgo biloba Extract (EGb 761) Pretreatment Limits Free Radical Oxidative Stress in Patients Undergoing Coronary Bypass Surgery

A growing body of evidence supports the trigger role of free radicals in the delayed functional and metabolic myocardial recovery following cardiopulmonary bypass (CPB) in humans, thus opening the field to specific therapies. This clinical study was designed to evaluate, in 15 patients undergoing aortic valve replacement, whether the extent of CPB- and reperfusion-induced lipid peroxidation, ascorbate depletion, tissue necrosis, and cardiac dysfunction is reduced by orally administered EGb 761, a Ginkgo biloba extract withpotent in vitro antiradical properties. Patients received either EGb 761 (Tanakan, 320 mg/day, n = 8) or a matching placebo (n = 7) for 5 days before surgical intervention. Plasma samples were obtained from the peripheral circulation and the coronary sinus at crucial stages of the operation (i.e., before incision, during ischemia, and within the first 30 minutes post-unclamping), and up to 8 days postoperatively. Upon aortic unclamping, EGb 761 inhibited the transcardiac release of thiobarbituric acid species (p ` 0.05), as assessed by high-performance liquid chromatography, and attenuated the early (5–10 minute) decrease in dimethylsulfoxide/ascorbyl free radical levels, an electron spin resonance index of the plasma ascorbate pool (p ` 0.05). EGb 761 also significantly reduced the more delayed leakage of myoglobin (p = 0.007) and had an almost significant effect on ventricular myosin leakage (p = 0.053, 6 days postoperatively). The clinical outcome of recovery of treated patients was improved, but not significantly, compared with untreated patients. Our results demonstrate the usefulness of adjuvant EGb 761 therapy in limiting oxidative stress in cardiovascular surgery and suggest the possible role of highly bioavailable terpene constituents of the drug.     

Brain dysfunction in social drinkers

Thirty-four social drinkers who had referred themselves to the Regional Brain Damage Unit for assessment of the effects of drinking alcohol were compared with 42 volunteer control subjects of equivalent age but with low alcohol intake, using two 'learning' tests — the Rey Auditory Verbal Learning Test (RAVLT) and the Austin Button Maze. The Maze Test gave no evidence of disorder, but the two groups were significantly different on the RAVLT. No abnormalities in standard cognitive tests were apparent. These results suggest that a deficit in learning ability may be an early feature of the brain dysfunction associated with excessive alcohol consumption.     

Alcohol and drug use following traumatic brain injury: A prospective study

Primary objectives: To establish pre-morbid alcohol and drug use in persons with TBI, relative to controls, investigate how patterns of substance use change over time following TBI and identify factors associated with heavy post-injury substance use.

Methods and procedures: The Alcohol Use Disorders Identification test (AUDIT) and Drug Abuse Screening Test (DAST) was completed by 121 hospital inpatients with TBI, documenting pre-injury alcohol and drug use, and 133 demographically similar controls. Participants with TBI completed these measures and the Hospital Anxiety and Depression Scale (HADS) again 1 and 2 years post-injury and 76 also completed them at 3 years.

Results: Participants with TBI showed similar levels of drug and alcohol use to controls pre-injury, with 31.4% of the TBI group and 29.3% of controls drinking at hazardous levels. Alcohol and drug use declined in the first year post-injury, but increased by 2 years post-injury, with only 21.4% of participants with TBI reporting abstinence from alcohol and 25.4% drinking at hazardous levels. Only 9% showed a drug problem, but 24% had returned to some drug use. Those showing heavy alcohol use post-injury were young, male and heavy drinkers pre-injury. Drug and alcohol use was similar at 3 years post-injury.

Conclusions: More active intervention is needed to reduce alcohol and drug use following TBI.     

焦痂提取液中丙二醛含量对线粒体呼吸及内膜能化作用的影响

大鼠背部20％光辐射Ⅲ度烧伤7天后的焦痂提取液及1:4、1:8稀释液能对正常大鼠肝线粒体呼吸产生明显的抑制作用,相同方法制成的正常皮提取液只呈轻度抑制,1:4稀释液已无抑制作用,两者丙二醛含量相差悬殊,丙二醛含量与抑制率呈相关,但进一步分析表明这种相关为共存现象,丙二醛含量增高不是呼吸率下降的直接原因。丙二醛增高与膜脂双层的破坏有关,内膜能化作用实验表明,当膜脂受到一定程度破坏时,能化作用受到抑制。然而在能化作用未表现异常时,呼吸率已呈一定程度抑制,故呼吸率抑制还受到提取液其他组分的影响。     

The development of addiction to d-amphetamine in an animal model: same principles as for alcohol and opiate

We have established a rat model that reflects the course of development of alcohol and opiate addiction. The present study with d-amphetamine aimed to define general principles in the development of an addiction. Male rats had a continuous free choice between d-amphetamine solutions (100, 200 and 400 mg/l) and water for 47 weeks. An initial intake of high doses of d-amphetamine during the first weeks of drug choice was followed by an individually stable pattern of drug consumption of moderate drug doses. During this period of controlled consumption (from week 10 to week 40), the voluntary intake of d-amphetamine depended on individual factors (dominant rats: 0.37 ± 0.02 mg/kg per day, subordinate rats: 0.57 ± 0.05 mg/kg per day) and environmental variables (group housing: 0.21 ± 0.02 mg/kg per day, single housing: 0.41 ± 0.03 mg/kg per day). Beginning with week 41, voluntary d-amphetamine consumption progressively increased (1.9 ± 0.2 mg/kg per day in week 47), although the experimental conditions remained unchanged. Drug intake during a retest (free choice as before) after 6 months of drug deprivation revealed that the rats had persistently lost their control over drug intake and were no longer able to adjust drug taking to internal and external conditions. These addicted rats took very high drug doses, even when all d-amphetamine solutions but not water were adulterated with bitter tasting quinine (6.6 ± 0.6 mg/kg per day; age-matched controls: 0.37 ± 0.04 mg/kg per day). Forced intake of d-amphetamine for 47 weeks (7.1 ± 0.3 mg/kg per day) via the drinking fluid caused physical dependence (hyperreactivity during withdrawal) but did not lead to drug addiction (voluntary intake in the retest with adulteration: 0.42 ± 0.04 mg/kg per day). Both the temporal development and the prerequisites of psychostimulant addiction were in principle the same as for alcohol and opiates. Received: 3 April 1998/Final version: 26 August 1998     

Triazolam-induced changes in alcoholic thought processes

 This study was designed to examine and contrast cognitive effects (explicit memory and access to semantic knowledge) of the benzodiazepine Halcion (triazolam) in ten normal volunteers and ten cognitively unimpaired detoxified alcoholics. The two groups were indistinguishable from one another under placebo conditions on all measures of cognitive functioning. Under Halcion test conditions (0.375 mg PO), both groups were about equally impaired in their recall of to-be-remembered information. However, alcoholics, were more likely to recall information that they were not asked to remember (intrusion errors) on all measures of explicit remembering. Alcoholics also generated relatively uncommon (low frequency) responses from semantic memory, rather than common, categorically related associations in response to stimuli such as types of vegetables, flowers, and fruit following the administration of Halcion, but were not different from normal volunteers in the types of responses generated under placebo conditions. These findings suggest that a drug challenge that simulates many of the effects of acute alcohol administration induces alcoholics to think and remember differently (qualitatively) from normal volunteers. Received: 7 July 1997 / Final version: 22 September 1997     

Reinstatement of alcohol-seeking by priming injections of alcohol and exposure to stress in rats

 Previous studies using a reinstatement procedure have found that acute reexposure to the self-administered drug and exposure to footshock stress reinstate heroin and cocaine seeking after prolonged drug-free periods. Here we tested whether these findings generalize to alcohol-taking behavior. Male rats were initially allowed to consume alcohol in a two-bottle choice procedure (water versus alcohol) for 30 min/day for 36 days. Rats were then trained for 60 min/day in operant chambers to press a lever for the drug (0.13 ml of 12% w/v of an alcohol solution) for up to 55 days. After stable drug-taking on a fixed-ratio-3 schedule of reinforcement was obtained, lever pressing for alcohol was extinguished by terminating drug delivery for 4–9 days. Reinstatement of drug seeking was then determined after non-contingent priming injections of alcohol (0.24 and 0.48 g/kg; given IP and orally) or exposure to intermittent footshock stress (5 and 15 min; 0.8 mA). Priming injections of alcohol produced a modest dose-dependent reinstatement of drug seeking, whereas footshock stress potently reinstated extinguished alcohol seeking. In contrast, similar parameters of footshock failed to reinstate extinguished sucrose-taking behavior in rats previously trained to lever press for sucrose pellets. These findings extend previous reports on reinstatement of cocaine and heroin seeking by a footshock stressor and by priming drug injections. It also appears that the reinstatement procedure provides an appropriate methodology to study relapse to alcohol-taking behavior in the drug-free state. Received: 9 April 1997 / Final version: 1 August 1997     

Percutaneous aspiration and ethanol sclerotherapy of symptomatic hepatic cysts

Nineteen patients with 49 symptomatic non-neoplastic non-parasitic simple hepatic cysts were subjected to ultrasonographically guided percutaneous aspiration and temporary injection of 99% ethanol into the cyst. Small cysts were treated twice, the large ones three times at the same sitting. The volume of alcohol per injection varied from 20 to 100 ml, depending on the size of the cyst. A cure was usually achieved with one ethanol sclerotherapy treatment. Only minor side effects such as transient pain and temperature elevation occurred. Forty-seven of the 49 cysts could be treated adequately, and did not recur during a follow-up period af 12–40 months. The results indicate that aspiration an and ethanol sclerotherapy is the treatment of choice in patients with symptomatic non-neoplastic simple hepatic cysts or polycystic liver disease. Correspondence to: A. Leinonen     

Substitution of the 5-HT1 agonist trifluoromethylphenylpiperazine (TFMPP) for the discriminative stimulus effects of ethanol: effect of training dose

The role of the ethanol training dose on the ability of the selective 5-HT¹ agonist TFMPP (m-trifluoromethylphenylpiperazine) to produce ethanol-like discriminative stimulus effects was evaluated in three groups of rats trained to discriminate 1.0 g/kg (n=5), 1.5 g/kg (n=6) or 2.0 g/kg (n=7) ethanol (IG) from water using a two-lever procedure with food reinforcement available under a fixed ratio 20 (FR 20) schedule. Ethanol generalization gradients were comparable in the three groups, indicating few potency differences in the ethanol stimulus across training dose. However, the ability of TFMPP (0.1–1.7 mg/kg; IP) to substitute for ethanol was dependent on the training dose. TFMPP resulted in partial substitution in the 1.0 g/kg group, complete substitution for 1.5 g/kg group and no substitution in the 2.0 g/kg ethanol training group. The results indicate a serotonergic component to the discriminative stimulus effects of an intermediate dose of ethanol that is not prominent as the dose of ethanol is raised. These data add further support for the hypothesis that ethanol produces a mixed discriminative cue, the components of which are not uniformly amplified when the dose of ethanol is increased.