院外纳曲酮治疗酒精依赖的疗效观察

目的 :评估纳曲酮院外治疗酒依赖的临床疗效。方法 :采用随机对照的方法 ,分别对纳曲酮组和安慰剂组各 2 3例和 2 2例 ,作总疗程 12周的临床观察。结果 :纳曲酮显著降低病人对酒精的渴求程度 ,其疗后 4、 8、 12周的保持率分别为 91 3 %、 77 9%、 73 3 % ,明显高于安慰剂。纳曲酮的副作用与安慰剂相当 ,其主要副作用为轻度的恶心、厌食、头晕。结论 :纳曲酮是一种安全有效的治疗酒依赖的药物     

Seven generations of genetic selection for ethanol dependence in mice

An animal model of alcohol dependence is being produced by selecting mice for differences in severity of ethanol withdrawal seizures. Replicate lines of high-dependence (HA), low-dependence (LA), and control (CA) mice are being developed by within-family selection. After seven generations both (replicate) HA and LA lines have separated significantly. Some of the difference between the replicate pairs of HA and LA in the early generations was due to differences in ethanol consumption. This difference in consumption may be attributable to a difference in metabolic rate or activity level rather than to a difference in ethanol preference. Females are more susceptible to seizures than males; this appears to be due partly to their higher consumption of ethanol during treatment.This research was supported in part by Grant AA-03527 from the National Institute of Alcohol Abuse and Alcoholism to the University of Colorado Alcohol Research Center.     

Identification of a voltage- and calcium-dependent non-selective cation channel in cultured adult and fetal human nasal epithelial cells

The apical membranes of cultured human nasal epithelial cells from adults and fetuses were investigated with the patch-clamp technique. Amiloride-insensitive, calcium- and voltage-dependent, non-selective cation channels were found in 4% of the cell-attached, and 18% of the inside-out and outside-out patches (n=412). Multiple functional channels were present in more than 90% of these patches, with a mean of 3.9 channels per patch (n=55). The current-voltage relationship can be described by the Goldman equations and the single channel conductance was 20.1±0.3 pS (n=29) in adult and 20.7±0.4 pS (n=44) in fetal cells in symmetrical 150mM NaCl solutions. The channels were highly selective for cations: P_Na/P_Cl was 30 in adult and 45 in fetal experiments. They were equally permeable for K⁺ and Na⁺, somewhat less for Cs⁺, and impermeable for choline⁺ and tetraethylammonium⁺. The open probability was voltage dependent: it increased approximately 2-fold with 30mV depolarization in the potential range from −60mV to +60mV. The channels were activated by Ca²⁺ concentrations of about 10⁻⁴M at the cytoplasmic side, but were insensitive to extracellular Ca²⁺ and amiloride (10⁻⁴M). The non-selective cation channels found in apical membranes of cultured fetal nasal epithelial cells were not different from the adult ones.     

An Assessment of the Genetic Relationship Between Alcohol Metabolism and Alcoholism Risk in Australian Twins of European Ancestry

The present analyses examined genetic influences on alcohol metabolism and their possible relationship to risk of alcohol dependence. Subjects were 206 Australian twin pairs who participated in an alcohol challenge protocol in 1979–1981, in which they were given a 0.75 g/kg dose of alcohol; blood alcohol concentrations (BACs) measured at five times over a 3-hr period after alcohol ingestion were examined. Structural equation modeling, fitting a combined autoregressive and common factor model, indicated significant heritabilities for both men and women (h ² range = 0.19–0.71), with significant parameter heterogeneity as a function of gender. In 1992–1993, both twins from 159 of the alcohol challenge pairs completed a telephone-administered psychiatric diagnostic interview. Repeated-measures MANOVAs were used to examine whether respondent's or cotwin's DSM-III-R alcohol dependence status, or parental history of alcohol problems, was associated with variation in alcohol metabolism. There was some evidence that individuals at increased genetic risk of alcohol dependence [with either a paternal history of alcohol problems (women) or an MZ male cotwin who reported a history of alcohol dependence by 1992–1993] showed lower initial BACs than other groups. However, this effect was not seen in those who themselves had a history of alcohol dependence by interview follow-up, perhaps because this relationship was already masked by a history of excessive drinking at baseline.     

帕罗西汀合并认知疗法治疗酒依赖伴发抑郁及对戒酒的影响

目的评价帕罗西汀合并认知疗法治疗酒依赖伴发抑郁的疗效及对戒酒的影响。方法将98例酒依赖伴发抑郁的患者随机分为研究组和对照组,分别用认知疗法合并帕罗西汀、单用帕罗西汀治疗4个月。用汉密顿抑郁量表(HAMD)评定疗效;用复饮率评定戒酒效果。结果治疗1个月后,研究组HAMD评分16.79±6.50与对照组相近17.88±6.59(P>0.05)。治疗4个月后HAMD评分10.76±5.32、明显低于对照组14.54±5.12(P<0.01);临床疗效(痊愈率44.44%、显效率22.22%、有效率33.34%)明显高于对照组(21.74%、21.74%、56.52%)(P<0.05);复饮率(24.44%)低于对照对照组(45.56%)(P<0.05)。结论认知疗法合并帕罗西汀治疗酒依赖伴发抑郁疗效较好,戒酒效果较好。     

Effect of Temperature on Guinea Pig Urinary Bladder Contraction Mediated via P2X-Receptors

In vitro experiments showed that P2X-receptor agonist ,-methylene-ATP and electrical field stimulation in the presence of muscarinic and -adrenoreceptors blockers induced contractile responses of isolated guinea pig bladder, which were more pronounced at 30°C than at 37°C or 42°C. P2X-receptor antagonist pyridoxal-6-phosphate-2',4'-disulfonic acid, produced a more potent inhibitory effect on contractions induced by electrical field stimulation at 30°C in comparison with that at 37°C or 42°C, while the contractions induced by ,-methylene-ATP were similarly suppressed at all examined temperatures.     

Regulation and possible physiological role of the Ca2-dependent K+ channel of cortical collecting ducts of the rat

In the luminal membrane of rat cortical collecting duct (CCD) a big Ca²⁺-dependent and a small Ca²⁺-independent K⁺ channel have been described. Whereas the latter most likely is responsible for the K⁺ secretion in this nephron segment, the function of the large-conductance K⁺ channel is unknown. The regulation of this channel and its possible physiological role were examined with the conventional cell-free and the cell-attached nystatin patch-clamp techniques. Patch-clamp recordings were obtained from the luminal membrane of isolated perfused CCD segments and from freshly isolated CCD cells. Intracellular calcium was measured using the calcium-sensitive dye fura-2. The large-conductance K⁺ channel was strongly voltage- and calcium-dependent. At 3 mol/l cytosolic Ca²⁺ activity it was half-maximally activated. At 1 mmol/l it was neither regulated by cytosolic pH nor by ATP. At 1 mol/l Ca²⁺ activity the open probability (P _o) of this channel was pH-dependent. At pH 7.0 P _o was decreased to 4±2% (n=9) and at pH 8.5 it was increased to 425±52% (n=9) of the control. At this low Ca²⁺ activity the P _o of the channel was reduced by 1 mmol/l ATP to 8±4% (n=6). Cell swelling activated the large-conductance K⁺ channel (n=14) and hyperpolarized the membrane potential of the cells by 9±1 mV (n=23). Intracellular Ca²⁺ activity increased after hypotonic stress. This increase depended on the extracellular Ca²⁺ activity. A possible physiological function of the large-conductance K⁺ channel in rat CCD cells may be the reduction of the intracellular K⁺ concentration after cell swelling. Once this channel is activated by increases in the cytosolic Ca²⁺ activity it can be regulated by changes in cellular pH and ATP.Supported by DFG Schl 277/2-3     

Temporal relationship between noradrenaline release in the central amygdala and plasma noradrenaline secretion in rats and tree shrews

In pentobarbital anesthetized Wistar rats and tree shrews (Tupaia belangeri) the hypothalamus, the hippocampus and the amygdala were simultaneously superfused through push-pull cannulae with artificial cerebrospinal fluid. Blood samples were withdrawn in order to make an attempt to correlate release rates of noradrenaline (NA), adrenaline and dopamine in the above-mentioned areas with plasma catecholamine levels. A strong, positive correlation was found between NA release in central amygdala and NA concentrations in peripheral blood suggesting a functional relationship between noradrenergic systems in discrete brain areas and the activity of the peripheral sympathetic nervous system.     

Psychiatric comorbidity of smoking and nicotine dependence

Recent epidemiologic studies have revealed that comorbidity of psychiatric disorders is far more pervasive than previously suspected. Strong associations have been reported between specific substance use disorders and between any mental disorder and any substance use disorder. This report focuses on comorbidity of nicotine dependence, a substance use disorder on which little epidemiologic information is available. Data come from an epidemiologic study of approximately 1000 young adults in southeast Michigan, in which the NIMH-DIS, revised according to DSM-III-R, was used. Lifetime prevalence of nicotine dependence was 20%. Males and females with nicotine dependence had increased odds for alcohol and illicit drug disorders, major depression, and anxiety disorders, compared with nondependent smokers and nonsmokers combined. Major depression and any anxiety disorder were associated specifically with nicotine dependence. Increased odds for alcohol or illicit drug disorders were observed also in nondependent smokers, compared to nonsmokers. History of early conduct problems increased the odds for nicotine dependence among smokers. Potential mechanisms in the comorbidity of nicotine dependence are discussed.