阿片类毒品对HIV-1感染者PBMCs中TLR9基因表达的影响

探讨滥用阿片类毒品(Opiates)对Ⅰ型艾滋病病毒(Human immunodeficiency virus,HIV-1)感染者外周血单个核细胞(PBMCs)中TLR9基因表达水平的影响,为阐明阿片类毒品促进HIV-1复制的作用机制奠定基础。首先在南宁、柳州、钦州市地区的美沙酮、艾滋病自愿咨询检测门诊招募对象,经研究对象知情同意,分为4组,即阿片类毒品滥用的HIV-1感染组(Opiates HIV(+)组)、阿片类毒品滥用非HIV-1感染组(Opiates HIV(-)组)、非阿片类毒品滥用的HIV感染组(Non-opiates HIV(+)组)和健康对照组(Control组),每组随机招募50人。其次,以问卷形式调查对象的人口学特征,并采集其外周静脉血,分离出PBMCs后提取RNA。最后采用qPCR、蛋白质印迹法(Western blot,WB)法检测4组人群PBMCs中TLR9的mRNA、蛋白表达水平。经调查发现4组人群在年龄、性别、民族、户籍所在地、婚姻状况、文化程度和吸毒年限等人口学特征方面差异均无统计学意义(P0.05)。Opiates HIV(+)与Non-Opiates HIV(+)组病毒载量中位数分别为4.450×103和3.977×103 cp/mL,差异有统计学意义(P0.05)。TLR9 mRNA相对表达量在Opiates HIV(+)、Non-Opiates HIV(+)、Opiates HIV(-)和Control组中分别为(2.13±1.59)×10-3、(3.66±2.22)×10-3、(1.96±1.42)×10-3和(7.66±4.87)×10-3。阿片类毒品滥用和HIV感染对TLR9的表达存在交互作用(F=25.91,P=0.000)。经单独效应分析,HIV阳性与阴性人群中,阿片类毒品滥用者TLR9相对表达量均明显低于非毒品滥用者(P0.05);在吸毒人群中,HIV阳性者与HIV阴性者两组间差异没有统计学意义(P0.05);在不吸毒人群中,HIV阳性者低于正常组,两组间差异有统计学意义(P0.05)。WB的结果显示,Opiates HIV(+)、Non-Opiates HIV(+)、Opiates HIV(-)三组TLR9蛋白的表达量均低于Control组。上述结果表明阿片类毒品能够下调HIV-1感染者PBMCs中TLR9的表达水平,提示阿片类毒品可能通过影响TLR9所介导的机体免疫效应,进而促进HIV-1的感染复制。     

氯胺酮在体内的分布与代谢

目前,氯胺酮(ketamine,俗称K粉)的滥用现象日益严重,并有愈演愈烈之势,特别流行于舞厅等娱乐场所,对社会治安和经济建设造成极大危害。滥用毒品倾向呈现年轻化、男女平均化且女性滥用者的比例上升和用药多元化的趋势,由滥用鸦片类药物发展到多种药物的滥用。调查发现,毒品滥用中K粉比例达20%以上,短期可使语言迷糊,引起幻觉,长期可使人记忆力衰退及认知能力障碍,导致心功能损害。因吸食氯胺酮或服用含有氯胺酮的摇头丸、迷奸药而中毒死亡的案件逐年上升。本文综述了对氯胺酮在体内各个部分的分布与代谢,更多、更快、更好的为氯胺酮相关案件的检材选取,分析检测及体内过程的评价提供科学依据。     

毒品成瘾与脑组织基因表达谱的研究进展

毒品成瘾是由滥用毒品外在因素与遗传易感性等内在因素共同作用而导致的一种慢性脑疾病; 毒品成瘾的机制目前还不十分清楚。毒品成瘾研究的一个主要目标是鉴别和分离毒品导致脑功能障碍的分子机制; 采用高通量的基因表达谱技术研究毒品成瘾者在不同状态下脑基因表达全貌, 对深入认识毒品成瘾的机制具有重要的意义。文章综述了毒品成瘾的遗传机制及高通量脑组织基因组表达技术——SAGE和微阵列(Microarry)在毒品成瘾研究中的进展。     

漫谈毒品植物

对世界三大毒品海洛因、大麻和可卡因的原植物罂粟、大麻、古柯的形态特征以及产生毒品后的危害进行了介绍,同时也对能够制造新型毒品冰毒的原植物麻黄属中的草麻黄形态特征和药理作用也作了介绍,指出了该植物与中麻黄和木贼麻黄在形态上的差异。     

云南沾益中度退化天坑草地植物群落水平空间分布特征

规模最为宏大的地表负地形——喀斯特天坑不仅是世界罕见的地质奇观,圈闭化地形而形成的独特生境更是探索植物物种多样性及其空间分布特征最为理想的地域。以云南沾益天坑群中的中度退化天坑——"巴家陷塘"坑底草地植物群落为研究对象,通过α多样性指数与β相似性系数的应用,对"巴家陷塘"中度退化天坑坑底草地植物群落物种多样性的水平空间分布特征展开探讨,并对其近邻退化漏斗和"大毛寺"原生天坑坑外草地植物群落的相似性进行对比分析,研究结果发现:(1)中度退化天坑坑底草地植物群落物种丰富度和多样性从中心到边缘呈现出"中心高边缘低"的"逆洼地效应"特征;(2)相较于土壤资源,喀斯特天坑植物群落的生长与空间分布对光照资源的响应更为明显,且四周坑壁高度差异造成的坑内光照资源的空间异质性,也使坑底草地植物物种多样性存在一定的"圈层效应";(3)喀斯特天坑独特的圈闭化地形对植物群落的"隔离"、庇护作用即使在退化天坑中也有明显体现,且对喜阴、耐湿的物种更具庇护性。因而在全球气候变化下,即使是退化天坑,也应成为区域小尺度生态避难所的重要保护对象。     

浑善达克沙地黄柳雌雄群体年龄结构及动态特征

植物种群年龄结构和动态对于揭示其生活史特征和发展趋势具有重要意义,但针对雌雄异株植物两性群体的研究却鲜有报道。黄柳是浑善达克沙地常见的一种雌雄异株植物,也是该地区最重要的固沙先锋植物,该研究通过对浑善达克沙地黄柳天然种群的实地调查,采用年龄结构图、静态生命表、存活曲线、生存分析以及时间序列分析等方法对黄柳雌雄群体现状和未来变化趋势进行研究。结果表明:(1)浑善达克沙地黄柳雌雄群体在年龄结构及发展趋势方面均存在差异,雌株群体的年龄结构表现为稳定型,雄株群体的年龄结构表现为衰退型。(2)浑善达克沙地黄柳种群中雌株个体数量约占总数的70%,雄株约占30%,性比偏雌现象明显。(3)动态变化指数表明,研究区黄柳雌株群体呈现"前期缺乏、中后期稳定"的变化特征,雄株群体呈现"前期缺乏、中后期波动"的变化特征。(4)研究区黄柳雌雄群体的存活曲线都趋近Deevey-Ⅱ型,且与生存分析结果共同显示雌株群体比雄株群体进入衰退期的时间早。(5)时间序列分析表明,随着时间的推移研究区黄柳的老龄个体数量逐渐增多,幼龄个体缺乏是导致雌雄群体衰退的重要原因;建议通过人工扦插补充雌雄幼龄个体以及平茬复壮中、老龄个体的方法以保证该地区黄柳天然种群的正常繁衍。     

杂交马褂木叶片发育过程中资源利用效率的变化格局

对一年生杂交马褂木( Liriodendron chinense Sarg.× L. tulipifera L.)叶片展开过程中光能转换效率、水分利用效率和光合碳同化的变化规律及栽植密度对中下部叶片资源利用效率的影响进行了研究,结果表明(1) 叶片展开过程中,净光合速率(Pn)、气孔导度(Gs)、蒸腾速率(E)、气孔限制值(Ls)、总光合速率(Pm)、净光合比率(Pn/Pm)、PSⅡ的原初光能转化效率(Fv/Fm)和PSⅡ的光量子产率(φPSⅡ) 、羧化效率(CE) 和水分利用效率(WUE)显著上升,而胞间CO2浓度(Ci)和呼吸速率(R)显著下降;(2) 叶片展开过程中,光合碳同化"暗系统"的完善远远慢于能量转换的"光系统";(3) 叶片展开过程中,影响净光合速率增长的主导因素不是气孔导度,而是"暗系统"完善程度, "光系统"的影响远小于"暗系统"的影响; (4) 郁闭的高密度群体中,中下部叶片的Pn、Gs、E、Ls、Pm、Fv/Fm、φPSⅡ、CE和WUE显著低于上部完全展开叶,Ci显著高于上部完全展开叶,Pn/Pm和上部完全展开叶没有显著差异,而未郁闭的低密度群体中,中下部叶片的上述所有参数与上部完全展开叶无显著差异;(5) 导致高密度群体叶片Pn大幅度下降的主导因素是CE的大幅下降,而不是"光系统"和气孔导度;(6) 密度过大加速了中下部叶片光合功能的下降.     

人类群体遗传结构的协方差阵主成分分析方法

目的:探讨基因频率矩阵的中心化(或均值化)协方差阵主成分分析方法在人类群体遗传结构研究中的适用性和合理性。方法:从基因频率矩阵的结构特征入手,分析中心化、均值化协方差阵主成分分析与标准化相关阵主成分分析在特征根、特征向量以及降维效果等方面的差异,并通过实例比较不同方法在解释群体遗传结构特征上合理性。结果:中心化(或均值化)协方差阵的主成分不仅反映了基因变异程度的“方差信息量权”,而且反映了基因间相互影响程度的“相关信息量权”;标准化相关阵的主成分反映的仅是“相关信息量权”,不包括“方差信息量权”。通过比较中国26个汉族人群HLA-A基因座中心化协方差阵和标准化相关阵2种主成分分析结果,证实中心化协方差阵主成分分析方法在特征根与特征向量、保留主成分的个数和对主成分的群体遗传学解释的合理性等方面均优于标准化相关阵主成分分析方法。结论:在对群体遗传结构进行主成分分析时,应使用中心化(或均值化)变换消除基因频率矩阵中量级的影响,然后在用其协方差阵提取主成分。     

毒品的种类及危害

毒品犯罪已成为严重危害社会的一大毒瘤,青少年又是毒品传播的高危人群。从毒品的概念入手,介绍了毒品的种类、特征及对人体造成的危害,分析了我国的毒品形势,意在教育青少年拒绝毒品,珍爱生命。     

本刊举办"毒品预防教育讲座

为落实国家禁毒委、国家教委"关于对大中小学生开展毒品预防教育的通知"精神,本刊编委会、北京市教育科学院基础教育研究中心和北京师范大学党委宣传部在北京师范大学英东学术会议厅举办了"毒品预防教育讲座",北京市19个区县的中学生物学教师、北京师范大学从事宣传、学生工作的教师共300多人到会听课。中国药物依赖性研究所副所长郑继旺教授做了"毒品危害与对策"报告,中国药物依赖性研究所刘志民副教授介绍了毒品在我国流行的情况。他们首先指出毒品在我国蔓延的严峻形势。在中国近代史L,毒品祸国殃民,对中华民族造成了严重的危害。…     

Human immunodeficiency virus and drug misuse: the Edinburgh experience.

During 1985 many drug abusers who lived in Edinburgh were found to be infected with the human immunodeficiency virus (HIV). As a result an alternative counselling and screening clinic for testing for antibodies to HIV was established for use by drug abusers. Four hundred and forty one patients were counselled in the first year, and over 60% were either drug abusers or their sexual contacts. One hundred and fourteen (26%) patients were positive for HIV antibody, and 100 (88%) of these were current or former drug abusers. The HIV seropositivity rate in drug abusers was 52% but was only 7% in their sexual contacts. Services were provided for these people as well as counselling before and after the test. The cost of this counselling service for the first year was 27,000 pounds or 61.22 pounds per patient. The unexpected mobility of 23% of the Edinburgh drug abusers, particularly to other areas of Britain, suggests that similar services need to be set up elsewhere.     

Cocaine abusers show a blunted response to alcohol intoxication in limbic brain regions

Cocaine and alcohol are frequently used simultaneously and this combination is associated with enhanced toxicity. We recently showed that active cocaine abusers have a markedly enhanced sensitivity to benzodiazepines. Because both benzodiazepines and alcohol facilitate GABAergic neurotransmission we questioned whether cocaine abusers would also have an enhanced sensitivity to alcohol that could contribute to the toxicity. In this study we compared the effects of alcohol (0.75 g/kg) on regional brain glucose metabolism between cocaine abusers (n = 9) and controls (n = 10) using PET and FDG. Alcohol significantly decreased whole brain metabolism and this effect was greater in controls (26+/-6%) than in abusers (17+/-10%) even though they had equivalent levels of alcohol in plasma. Analysis of the regional measures showed that cocaine abusers had a blunted response to alcohol in limbic regions, cingulate gyrus, medial frontal and orbitofrontal cortices. CONCLUSIONS: The blunted response to alcohol in cocaine abusers contrasts with their enhanced sensitivity to benzodiazepines suggesting that targets other than GABA-benzodiazepine receptors are involved in the blunted sensitivity to alcohol and that the toxicity from combined cocaine-alcohol use is not due to an enhanced sensitivity to alcohol in cocaine abusers. The blunted response to alcohol in limbic regions and in cortical regions connected to limbic areas could result from a decreased sensitivity of reward circuits in cocaine abusers.     

Multi-task learning for cross-platform siRNA efficacy prediction: an in-silico study

Background  

Gene silencing using exogenous small interfering RNAs (siRNAs) is now a widespread molecular tool for gene functional study and new-drug target identification. The key mechanism in this technique is to design efficient siRNAs that incorporated into the RNA-induced silencing complexes (RISC) to bind and interact with the mRNA targets to repress their translations to proteins. Although considerable progress has been made in the computational analysis of siRNA binding efficacy, few joint analysis of different RNAi experiments conducted under different experimental scenarios has been done in research so far, while the joint analysis is an important issue in cross-platform siRNA efficacy prediction. A collective analysis of RNAi mechanisms for different datasets and experimental conditions can often provide new clues on the design of potent siRNAs.     

Reduction in the concentration and activity of plasma cholesteryl ester transfer protein by alcohol.

Plasma cholesteryl esters, synthesized within high density lipoproteins (HDL), may be transferred from HDL particles to other lipoproteins by plasma cholesteryl ester transfer protein (CETP). Alcohol consumption is associated with increased HDL cholesterol concentration and reduced plasma CETP activity. The alcohol-induced decrease in CETP activity may be due to a low concentration of CETP in plasma or the inhibition of CETP by specific inhibitor proteins or alterations in the composition of plasma lipoproteins. The first two possibilities are studied further in this paper using data on 47 alcohol abusers and 31 control subjects. The activity of CETP was measured as the rate of cholesteryl ester transfer between radio-labeled low density lipoproteins and unlabeled HDL using an in vitro method independent of endogenous plasma lipoproteins. Plasma CETP concentration was determined by a Triton-based radioimmunoassay. The alcohol abusers consuming alcohol (on average 154 g/day) had 28% higher HDL cholesterol (P less than 0.01), 27% lower plasma CETP concentration (P less than 0.001), and 22% lower plasma CETP activity (P less than 0.001) than the controls. Plasma CETP concentration showed a negative correlation with HDL cholesterol among all the subjects (r = -0.317, P less than 0.01) but not among the alcohol abusers alone (r = -0.102, N. S.). During 2 weeks of alcohol withdrawal, plasma CETP concentration and activity of 8 subjects increased, whereas HDL cholesterol decreased by 42% (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Abnormal brain activation to visual stimulation in cocaine abusers

Chronic cocaine abuse has been associated with cerebrovascular pathology. This is likely to reflect its vasoactive effects; cocaine produces vasoconstriction and reduces cerebral blood flow. We propose that cerebrovascular pathology in chronic cocaine abusers would result in abnormal BOLD [blood oxygenation level dependent] responses to activation stimuli. Here, we used fMRI to compared the BOLD response to photic visual stimulation in neurologically intact active cocaine abusers to that in non-drug-using healthy controls. Cocaine abusers showed a significantly enhanced positive BOLD response to photic stimulation when compared to control subjects. The enhanced activation in the cocaine abusers could result from low resting cerebral blood flow secondary to increased vasoconstriction and/or from low oxidative metabolism during activation. Alternatively, the larger signal intensity in the cocaine abusers could result from inefficient neuronal processing as has been shown to occur in other conditions of cerebral pathology. These findings provide evidence of cerebral dysfunction with chronic cocaine abuse, which could reflect cerebral blood flow or neuronal changes. Further studies are required to determine if the cerebrovascular changes we observed in the cocaine abusers recover with detoxification and to assess their functional consequences.     

Clinical evaluation and use of urine screening for drug abuse.

Urine drug screening is indicated to evaluate patients who show mental status or behavioral changes and to monitor the abstinence of drug abusers. The appropriate timing for collecting urine specimens may vary depending on the suspected drug of abuse and on laboratory factors. Laboratories use a variety of techniques to do urine screens, and these must be understood by clinicians ordering the screens to interpret results correctly. In treating drug-abusing patients, clinicians must apply structured reinforcement in conjunction with urine screen results to aid patients in achieving abstinence.     

Forensic dentistry joins DNA analysis as important tool for police work.

A Vancouver dentist who works as a teacher, researcher and administrator at the University of British Columbia has a unique extracurricular interest. Dr. David Sweet, one of four forensic odontologists in Canada, has put names to unidentified bodies and the remains of car-crash victims, helped convict child abusers and provided evidence in robbery cases.     

Interactions of the neurotoxic amine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine with monoamine oxidases.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a thermal breakdown product of a meperidine-like narcotic used by drug abusers as a heroin substitute, produces Parkinsonian symptoms in humans and primates. The nigrostriatal toxicity is not due to MPTP itself but to one or more oxidation products resulting from the action of monoamine oxidase (MAO) on this tertiary allylamine. Both MAO A and B catalyse the oxidation of MPTP to the 1-methyl-4-phenyl-2,3-dihydropyridinium species (MPDP+), which undergoes further oxidation to the fully aromatic 1-methyl-4-phenylpyridinium species (MPP+). These bio-oxidations are blocked by selective inhibitors of MAO A and B. Additionally, MPTP, MPDP+ and MPP+ are competitive inhibitors of MAO A and B. The A form of the enzyme is particularly sensitive to this type of reversible inhibition. Both MAO A and B also are irreversibly inactivated by MPTP and MPDP+, but not by MPP+. This inactivation obeys the characteristics of a mechanism-based or 'suicide' process. The inactivation, which is accompanied by the incorporation of radioactivity from methyl-labelled MPTP, is likely to result from covalent modification of the enzyme.     

Serotonin 5-HT2 receptor availability in chronic cocaine abusers

Serotonin 5-HT₂ receptor availability was evaluated in chronic cocaine abusers (n = 19) using positron emission tomography and F-18 N-methylspiperone and was compared to control subjects (n = 19). 5-HT₂ Receptor availability was measured in frontal, occipital, cingulate and orbitofrontal cortices using the ratio of the distribution volume in the region of interest to that in the cerebellum which is a function of B_max/K_d- 5-HT₂ Receptor availability was significantly higer in cingulate and orbitofrontal cortices than in other frontal regions or occipital cortex. The values were not different in normal subjects and cocaine abusers. These results did not show any changes in 5-HT₂ receptor availability in cocaine abusers as compared to the control subjects.