海洛因成瘾者唾液表皮生长因子含量及相关舌苔的观察

目的测定海洛因成瘾者脱瘾后唾液表皮生长因子(EGF)含量,观察相应的舌苔变化,探讨成瘾者EGF与舌苔的关系及脾虚的本质.方法92例海洛因成瘾者脱毒后15～30d,对照组85例,测定唾液EGF并同时观察舌苔.结果成瘾者唾液EGF含量比对照组显著低下(P＜0.01).成瘾者舌苔厚腻者明显多于对照组.结论海洛因成瘾者脱瘾后EGF低下是其舌苔厚腻和脾虚的原因之一.     

Genetic studies of neuropeptide Y and neuropeptide Y receptors Y1 and Y5 regions in morbid obesity

Summary Synthesis and release of neuropeptide Y (NPY) are both regulated by leptin binding to its hypothalamic receptor mediating some of the effects of leptin on food intake. Moreover, NPY administration is a powerful stimulant of feeding behaviour. Thus, we investigated the potential implication of NPY, NPY-Y1 and -Y5 subtype receptors [rNPY-Y1/-Y5] in the development of human obesity. Two complementary genetic approaches were used: 1) linkage analyses between obesity and polymorphic markers located nearby NPY and rNPY-Y1/-Y5 genes (respectively on chromosomes 7p15.1 and 4q[31.3–32]) in 93 French Caucasian morbidly obese families; 2) single strand conformation polymorphism (SSCP) scanning of the coding region of the NPY and rNPY-Y1 genes performed in 50 unrelated obese patients ascertained on the basis of a body mass index of 27 kg/m² or more and a family history of obesity. No evidence of linkage between morbid obesity or obesity-related quantitative traits and NPY and rNPY-Y1/Y5 regions was found in this population. Moreover, SSCP scanning revealed no mutation in the coding region of NPY and rNPY-Y1 genes among obese subjects. These results suggest that NPY and NPY-Y1/Y5 receptors are unlikely to be implicated in the development of human morbid obesity, at least in the French Caucasian population. [Diabetologia (1997) 40: 671–675] Received: 27 December 1996 and in revised form: 26 February 1997     

Validation of the cocaine versions of the Obsessive Compulsive Drug Use Scale and the Desires for Drug Questionnaire

Background: The Obsessive Compulsive Drug Use Scale (OCDUS) and the Desires for Drug Questionnaire (DDQ) are two frequently used drug craving questionnaires. Although both heroin and cocaine versions of the questionnaires exist, only the heroin versions have been psychometrically evaluated. The present study was conducted to evaluate the psychometric qualities of the cocaine versions of the OCDUS (OCDUS-C) and DDQ (DDQ-C). Methods: Cocaine-dependent inpatients (n?=?101) completed both scales as well as a Visual Analogue Craving Scale (VACS), an alternative, one-item index for assessing momentary craving. We examined the reliability (internal consistency), construct validity (factor structure), and concurrent validity (correlations among both questionnaires, the VACS, and indicators of severity of dependence). A subsample also completed the OCDUS-C and DDQ-C for a second time, one week after the initial administration to obtain a preliminary investigation of the test-retest reliability. Results: In general, both questionnaires displayed good internal consistency, test-retest reliability, and concurrent validity. Further, the construct validity of both the DDQ and OCDUS was demonstrated by means of confirmatory factor analyses showing the expected three-factor models. Conclusion: Our results indicate that the OCDUS and DDQ for cocaine are both easy to administer and reliable instruments to assist the clinical practitioner or researcher to measure craving in cocaine dependent subjects. Moreover, the factor structure for the cocaine versions were similar to the heroin versions, indicating the OCDUS and the DDQ can be reliably used to measure craving for both substances, enabling a direct comparison between heroin and cocaine craving.     

Uncoupling of sympathetic nervous system and hypothalamic-pituitary-adrenal axis in cirrhosis

Background and Aim: The hypothalamic‐autonomic nervous system (HANS) axis and the hypothalamic‐pituitary‐adrenal (HPA) axis are stimulated in parallel in response to stress factors under healthy conditions. This physiological synergism of the axes aims at optimizing anti‐inflammatory actions. Therefore, we investigated whether this synergism is altered in patients with liver cirrhosis. Methods: As a typical marker of the HANS axis neuropeptide Y (NPY is a neurotransmitter of the sympathetic nerve terminal) and of the HPA axis, cortisol together with adrenocorticotropic hormone (ACTH) and cortisol‐binding globulin (CBG), were measured in samples from control subjects and patients with liver cirrhosis. Results: Plasma NPY was found to be increased in cirrhotic patients compared to control subjects (P < 0.01). This increase was observed to be independent of the severity of liver disease (Child class). Serum cortisol was decreased in cirrhotics, particularly in patients with Child A cirrhosis. Plasma NPY was positively correlated with serum cortisol in control subjects (r = 0.32, P < 0.05) reflecting the parallel activation of both axes under the normal condition. However, serum cortisol was not correlated with plasma NPY in cirrhotic patients. For the subgroup of Child A patients, even a negative correlation between NPY and cortisol was observed (r = ?0.43, P < 0.05). No significant change in serum levels of ACTH and its positive correlation with serum cortisol was observed in cirrhotic patients. Conclusions: The present study demonstrates that the two stress axes seem to act in parallel fashion in control subjects but are uncoupled in liver cirrhosis. We discuss how uncoupling of the two anti‐inflammatory axes can occur and may contribute to the increased susceptibility for infections and lethal complications in cirrhotic patients.     

阻塞性睡眠呼吸暂停低通气综合征血浆β内啡肽 神经肽Y及人生长激素释放多肽的变化及其与情绪相关性研究

阻塞性睡眠呼吸暂停低通气综合征(OSAHS)可导致白天嗜睡及精神、心理障碍。β内啡肽(β-EP)、神经肽Y(NPY)、人生长激素释放多肽(Ghre-lin)参与机体能量平衡及心理调节等,生物学作用广泛。本研究通过检测OSAHS患者血浆β-EP、NPY、Ghrelin浓度,分析其与焦虑抑郁情绪的相关性,以探讨3者与OSAHS患者情绪的关系。     

Resisting the Urge to Smoke and Craving during a Smoking Quit Attempt on Varenicline: Results from a Pilot FMRI Study

Background: Varenicline has been shown to reduce cigarette craving during a quit attempt. Objectives: Use BOLD fMRI to explore differences in smoking cue reactivity at baseline and after five weeks of varenicline smoking cessation treatment. Methods: Treatment-seeking nicotine-dependent adult smokers underwent BOLD fMRI scans with block presentation of visual smoking, neutral, and rest cues under two conditions: craving or resisting the urge to smoke at baseline and following 5 weeks of standard varenicline therapy. Data were analyzed using FMRI Expert Analysis Tool, version 5.98 of Functional Magnetic Imaging of the Brain Software Library focused on the smoking vs. neutral cue contrast at the individual and group level, Z>2.3 with cluster threshold p=0.05. Results: Twenty-one participants were scanned at baseline and 16 completed the study; 10 were abstinent at the 2^nd session, confirmed with urinary cotinine. In the Crave Condition no significant differences were found between the abstinent and non-abstinent groups at either time point. During the baseline Resist Condition, the abstinent group compared to the non-abstinent group demonstrated activation in a distributed network involved in alertness, learning and memory. Additionally, within the abstinent group, increased activation of the superior frontal gyrus was found at baseline compared to week 5. Conclusion: Successful smoking cessation with varenicline is associated with increased activation, prior to a quit attempt, in brain areas related to attentiveness and memory while resisting the urge to smoke Scientific Significance: Varenicline may exert effects by both reducing craving and enhancing resistance to smoking urges during cue-elicited craving.     

Role of fat amount and type in ameliorating diet-induced obesity: insights at the level of hypothalamic arcuate nucleus leptin receptor, neuropeptide Y and pro-opiomelanocortin mRNA expression

Aims: Dietary fatty acid profile, independent of caloric percent of fat, is a major regulator of body adiposity. This study examined the effects of dietary fat amount and types on fat storage and hypothalamic gene expression in the mouse model of chronic diet‐induced obesity. Methods: The dietary interventions were in twofold: (1) the obesity was induced by a 13‐week obesogenic fat diet compared with a low‐fat (LF) diet, and (2) the reversibility was tested by using high n‐3 polyunsaturated fat (PUFA) and LF diets. Fifty‐four C57Bl/6 mice were fed a high‐fat (59% in kcal) diet for 13 weeks and then classified as diet‐induced obese (DIO) or diet‐resistant (DR) mice according to upper and lower tertiles of body weight gain. The DIO mice were then subdivided into three groups for a 6‐week secondary dietary intervention. Two of the groups were switched to either a high n‐3 PUFA (DIO‐n3) or a low‐fat (10% in kcal, DIO‐LF) diet, whereas the third (controls) and DR mice continued on the initial high‐fat diet. Food efficiency was calculated as weekly body weight gain per gram of food intake. Results: After switching the DIO mice to the n‐3 PUFA or LF diet, their body weights were reduced to the level of the DR and LF mice. The food efficiencies were, from the highest to lowest, in the order: DIO > LF > DR > DIO‐LF > DIO‐n3. Using quantitative in situ hybridization, we found that the DIO mice had higher levels of leptin receptor (LR, +290%, p < 0.005) and neuropeptide Y (NPY, +25%, p < 0.05) mRNA expression in the hypothalamic arcuate nucleus (Arc) than the DR mice, whereas the level of pro‐opiomelanocortin (POMC) mRNA expression was significantly reduced (?45%, p < 0.01). All effects that were essentially returned to DR levels by the change to the n‐3 PUFA diet and, with the exception of a failure to normalize Arc NPY mRNA levels, by the change to LF diet. Conclusions: Taken together, the present results show that both change in level and quality of dietary fat can potently alter hypothalamic neuropeptide expression and result in effective amelioration of diet‐induced obesity. Interestingly, the n‐3 PUFA diet when fed to already obese mice produced a pattern of hypothalamic gene expression similar to that in obesity resistant (DR) mice. It remains to be determined if the effects of n‐3 fatty acids on brain neuropeptide gene expression are direct or indirect.     

脑出血大鼠血浆神经肽Y及血清肌酸磷酸激酶MB型的变化

目的　观察实验性脑出血条件下血浆神经肽Y(NPY)及肌酸磷酸激酶MB型 (CK MB)含量的动态变化 ,以探讨脑心综合征的发生机制。方法　采用胶原酶和肝素联合注入尾状核方法建立大鼠脑出血模型 ,测定出血前、出血后 30min、6、12、2 4、4 8及 72h血浆NPY活性及血清CK MB变化。采用放射免疫法测定血浆NPY的变化 ,采用酶反应速率法测定血清CK MB的变化。结果　大鼠脑内血肿开始形成的 6h血浆NPY活性、血清CK MB均较术前水平及对照组显著升高 (P <0 .0 5 ) ,并以脑出血 2 4h血肿高峰期时最为显著 (P <0 .0 1) ,随后逐渐下降 ,72h仍高于术前水平及对照组 (P <0 .0 5 )。结论　脑出血时常伴有血清CK MB改变 ,外周NPY含量升高可能参与脑心综合征的发生发展。     

Development of neuropeptide Y-related peptides in the digestive organs during the larval stage of Japanese flounder, Paralichthys olivaceus

cDNAs encoding three neuropeptide Y (NPY)-related peptides were identified from the Japanese flounder. One peptide corresponds to NPY, and its mRNA was expressed in the brain and retina. The second peptide corresponds to peptide YY (PYY), and its mRNA was expressed in the brain but surprisingly not in the digestive organs. This suggests that PYY lacks function as a digestive hormone in flounder. The third peptide corresponds to peptide Y (PY), and its mRNA occupied the brain and the endocrine cells of the intestine and the pancreatic accessory islets, but not of the principal islet. This suggests that PY has a dual role as a neuropeptide and a digestive hormone. In flounder larvae, PY cells appear in the intestinal epithelia at 3 days posthatching (dph), when larvae start feeding, in contrast to the endocrine pancreas at 30 dph. Therefore, the endocrine system of PY, which probably regulates the pancreatic enzyme secretion, develops synchronously with the start of feeding in the intestine but about 1 month later in the endocrine pancreas in flounder.     

Elevation of plasma neuropeptide Y-like immunoreactivity and noradrenaline during myocardial ischaemia in man

Plasma levels of neuropeptide Y-like immunoreactivity (NPY-LI) and noradrenaline were studied for 25 h in 22 patients with acute ischaemic heart disease. On admission, NPY-LI levels were above normal in 16 patients, and 20 patients had increased noradrenaline levels. The initial plasma NPY-LI did not differ between patients with acute myocardial infarction (AMI) and angina pectoris. Initial plasma noradrenaline levels were higher in patients with AMI than in those with angina pectoris. Plasma levels of noradrenaline remained elevated in AMI patients, but decreased towards normal values in patients with angina pectoris. Levels of NPY-LI returned to normal within 25 h in all patients. Tachycardia and left ventricular failure were related to high NPY-LI and noradrenaline levels. A positive correlation was found between noradrenaline and NPY-LI in plasma. It is suggested that neuropeptide Y (NPY), an endogenous vasoconstrictor peptide, should be considered as one of the mediators involved in the cardiovascular response to sympathetic activation induced by myocardial ischaemia.     

瘦素受体及神经肽Y mRNA在肥胖大鼠下丘脑弓状核的表达

以高脂饮食制备肥胖大鼠模型和用寡核苷酸探针在下丘脑弓状核进行原位杂交检测，结果显示肥胖大鼠下丘脑弓状核瘦素受体mRNA和神经肽Y mRNA表达明显增加，提示可能为瘦素受体抵抗所致。     

祛风药与活血药对实验性脑缺血大鼠血液流变学的影响

目的观察祛风药、活血药及祛风活血药对实验性脑缺血大鼠血液流变学的影响。方法采用线拴法阻塞大鼠大脑中动脉造成局灶性脑缺血(MCAO)模型,各组使用相应药物灌胃10d后测定MCAO大鼠血液流变学各参数指标。结果祛风活血组、祛风组、活血组可不同程度地降低大鼠全血黏度、血浆黏度及全血还原黏度(P<0.05或P<0.01)。与假手术组比较,祛风活血组可降低红细胞比容至0.37±0.04(P<0.01)及高切状态下的全血黏度为(5.56±0.99)mPa·s(P<0.05),活血组可明显降低低切状态下的全血黏度至(14.89±3.52)mPa·s(P<0.01),祛风活血组、活血组、祛风组组间比较无统计学意义(P>0.05)。结论祛风活血药、祛风药、活血药均对实验性脑缺血大鼠血液流变的异常变化有明显的改善作用。     

Tamoxifen is an estrogen antagonist on gonadotropin secretion and responsiveness of the hypothalamic-pituitary- adrenal axis in female monkeys

The selective estrogen receptor modulator, tamoxifen, effectively slows the progression of estrogen-positive breast cancer and reduces the possibility of this cancer developing in women at high risk. Despite the widespread acceptance of tamoxifen as a therapeutic agent for this disease, its effects on other estrogen-dependent pathways, particularly on neural circuits regulating brain function and peripheral hormone secretion, are poorly understood. The present study, using previously ovariectomized rhesus monkeys, examined the effects of tamoxifen, in both the presence and absence of estradiol replacement, on the reproductive and hypo-thalamic-pituitary-adrenal (HPA) axes. In Experiment 1, monkeys randomly assigned to three groups (n=8 each) were treated with placebo and either two doses of estradiol, two doses of tamoxifen alone, or two doses of tamoxifen plus high-dose estradiol to assess the effects on negative feedback suppression of luteinizing hormone (LH). Both doses of tamoxifen effectively antag-onized the negative feedback efficacy of estradiol on LH secretion. In contrast, neither the low- or high-dose tamoxifen alone had any effect on LH secretion, as con-centrations during tamoxifen treatments were indistinguishable from those during placebo. In Experiment 2, females were randomly assigned to one of four treatment groups (placebo, n=6; estradiol, n=5; tamoxifen only, n=5; or tamoxifen plus estradiol, n=6) to assess the effects on glucocorticoid negative feedback and pituitary and adrenal responsiveness to exogenous corticotropin-releasing hormone (CRH). Tamoxifen also antagonized the facilitating effects of estradiol on basal and CRH-induced ACTH and cortisol secretion. However, this antagonism produced basal and CRH-stimulated cortisol and ACTH concentrations that were lower than placebo-treated females. Interestingly, tamoxifen in the absence of estradiol produced a similar diminution in ACTH and cortisol response. These data suggest that, in the presence of estradiol, tamoxifen not only antagonized estrogenic facilitation of HPA responsivity but also actually attenuated the response compared with the placebo-treatment condition. Taken together, these data indicate that tamoxifen acts as an estrogen antagonist on the neural circuits controlling the neuroendocrine regulation of the hypothalamic-pituitary-ovarian and adrenal axes in ovariectomized macaque females.     

The impact of illicit drug supply reduction on health and social outcomes: the heroin shortage in the Australian Capital Territory

Aims We seek to establish whether a substantial decline in the supply of heroin, as measured by indicators such as drug purity, is related to changes in drug‐related health indicators such as ambulance callouts to heroin overdoses and numbers participating in methadone treatment programmes, and to changes in levels of property crime. The guiding hypothesis is that reduced supply will result in positive health and social outcomes. Design Standard time‐series methods are employed to analyse official data from local law‐enforcement and heroin supply indicators and several health and social outcome indicators within the Australian Capital Territory (ACT), spanning the late 1990s to early 2002. Autoregressive moving average (ARMA) models are estimated to remove autocorrelation from these series. Cross‐correlation and autoregression models are then employed to identify the best predictive models. Findings When autocorrelation has been removed, a reduction in heroin purity predicts a large decline in heroin‐related ambulance callouts and an increase in methadone treatment programme enrolments. There is little evidence of an increase in negative outcomes due to heroin users switching to other drugs. A reduction in purity also predicts declines in robbery and burglary but not in theft. Conclusion The overall evidence indicates modest links between the declines in heroin supply and increases in positive health outcomes and decreases in crime, as predicted by a simple economic model. Due to the shortness of some of the series and consequent limitations in statistical power, these conclusions should be regarded as tentative.     

老年人心血管病药物治疗及其不良反应

本文观察１００例老年心血管病患者的用药情况及药物不良反应，其心血管病药物不良反应总发生率为１４％，地高辛为１３％、硝苯地平为１１％、维拉帕米为２５％、莫雷西嗪为２０％、消心痛为９．２％、β受体阻滞剂为７．６％、利尿剂为５．８％。为此，并讨论了老年人合理用药措施。     

Monetary-Based Consequences for Drug Abstinence: Methods of Implementation and Some Considerations about the Allocation of Finances in Substance Abusers

Conceptualizing drug abuse within the framework of behavioral theories of choice highlights the relevance of environmental variables in shifting behavior away from drug-related purchases. Choosing to use drugs results in immediate and certain consequences (e.g., drug high and relief from withdrawal), whereas choosing abstinence typically results in delayed, and often uncertain, consequences (e.g., improved health, interpersonal relationships, money). Methods: This is a selective review of the literature on Contingency management (CM). Results: We highlight a variety of methods to deliver CM in practical, effective, and sustainable ways. We consider a number of parameters that are critical to the success of monetary-based CM, and the role of the context in influencing CM’s effects. To illustrate the broad range of applications of CM, we also review different methods for arranging contingencies to promote abstinence and other relevant behavior. Finally, we discuss some considerations about how drug-dependent individuals allocate their finances in the context of CM interventions. Conclusions: Contingency management (CM) increases choice for drug abstinence via the availability of immediate, financial-based gains, contingent on objective evidence of abstinence.