三氧化二砷肾毒性及其防治研究进展

三氧化二砷(ATO,As₂O₃)能够有效治疗急性早幼粒细胞白血病(acute promyelocytic leukemia,APL)及其他恶性肿瘤。但在治疗过程中发现ATO具有肾毒性作用,从而限制了ATO的临床应用。研究表明,使用ATO后,会干扰机体的氧化而引起氧化应激反应,损伤DNA修复途径,诱导DNA突变,从而导致细胞癌变,这是目前产生ATO肾毒性的重要机制之一。ATO所引起的细胞凋亡、DNA甲基化也是产生肾毒性的原因。该文就ATO肾毒性机制研究及防治综述。     

苯丙胺类精神活性物质依赖机制的研究进展

新型毒品冰毒、麻谷的主要成分是苯丙胺类精神活性物质(以下简称苯丙胺类物质)的一种-甲基苯丙胺(methamphetamine,MA).甲基苯丙胺是联合国精神药品公约明令管制的精神活性物质,其毒性不仅损伤神经系统,对心血管系统的损害也比较明显,表现为滥用者的心电图异常[1].长期以来,关于苯丙胺类物质的生理依赖问题观点不一,但随着研究的深入,许多学者认为甲基苯丙胺存在着生理依赖.本文就苯丙胺类物质的依赖机制予以综述.     

青少年大麻滥用与认知功能的损伤

受部分西方国家大麻合法化影响,以及合成大麻滥用的日益增加,青少年有更多风险接触并使用大麻类物质。作为世界范围内被广泛使用的精神活性物质之一,大麻类物质不仅具有不可忽视的成瘾性,同时可造成认知损伤及更高的精神疾病发病风险。本文简要介绍了大麻类物质的使用历史、青少年滥用现状和成瘾风险,并系统回顾了关于青少年滥用对认知损伤及精神分裂症发病风险影响的研究成果。目前,大麻滥用产生的远期影响,尤其是在神经发育期使用对成年期认知功能的影响及其潜在神经机制仍缺乏统一结论,值得进一步探索。     

DNA甲基化在肿瘤发生作用中的研究进展

表遗传学现象广泛地存在于各种生物中,表遗传现象形成的重要机制之一是DNA甲基化作用引起基因转录沉默。鉴于该重要机制,研究DNA甲基化水平的改变对肿瘤的发生、发展有重要的作用。经研究发现DNA甲基化改变可以引起细胞中C→T突变、抑癌基因的高甲基化、癌基因的低甲基化、错配修复基因异常以及诱导染色体不稳定导致肿瘤的发生。因此,通过探索肿瘤发生时DNA甲基化的变化特征,可为肿瘤治疗提供理论依据。     

非靶受体在精神活性物质依赖中的作用

当前精神活性物质滥用和成瘾呈上升趋势,它既是一个严重的社会问题,又是一个非常重要的生物学问题。在我国导致精神依赖的活性物质主要是阿片类。精神活性物质作用的靶受体为阿片受体,非靶受体主要包括多巴胺受体、N-甲基-D-门冬氨酸(NMDA)受体和组胺等。本文主要论述NMDA受体和组胺受体等非靶受体在精神活性物质依赖发生发展过程中功能和结构上的变化,探讨精神活性药物成瘾的机制,研究和开发以NMDA和组胺受体为靶标的新药,为阿片类药物成瘾的防治开辟新的研究领域。     

去甲基化药物地西他滨治疗血液系统恶性肿瘤的研究进展

随着对恶性血液肿瘤发生机制的表观遗传学研究的不断深入,发现DNA异常甲基化在恶性血液肿瘤的发生、发展中起着重要的作用。地西他滨是一种去甲基化药物,具有抑制甲基化转移酶的作用,对血液性恶性癌变及实体瘤具有广谱抗肿瘤活性,在上述肿瘤的治疗中取得了良好的疗效。     

简要干预技术在精神活性物质滥用领域的应用

1精神活性物质滥用现状 精神活性物质（psychoactive substance）是指能够影响人类情绪、行为,改变意识状态,并有致依赖作用的一类化学物质,人们使用这些物质的目的在于取得或保持某些特殊的心理、生理状态[1]。精神活性物质的使用不仅能引起令人愉悦欣快的感觉,而且还会引起对欣快感的强烈渴求,并迫使人们无止境地用药,导致非医疗目的的自行反复、大量地使用,即通常所说的＂物质滥用＂[1]。     

DNA 甲基化在肿瘤发生中的作用

在肿瘤形成过程中,表观遗传学机制越来越受到重视。即DNA突变时核苷酸序列不变,通过碱基修饰的改变导致基因表达水平的变化。其中,一个重要机制就是DNA甲基化。 DNA甲基化就是在DNA复制后,DNA在甲基转移酶催化下将 S-腺苷甲硫氨酸（ SAM）上的甲基连接到DNA分子的腺嘌呤碱基或胞嘧啶碱基上,进行DNA修复的过程。负责DNA甲基化作用的酶称为 DNA 甲基化转移酶（ DNA Methyl-transferases, DNMTs ）。 DNA 甲基化主要发生在 CpG二核苷酸中的胞嘧啶［1］,它对于维持染色体结构的稳定性,保障基因组表观遗传信息在亲代细胞间的正确传递起着重要作用。除此之外,DNMTs还直接参与基因的转录抑制和DNA复制的正确起始等。人类DNA甲基化系统的功能异常将会导致胚胎发育异常,亦可诱发恶性疾病甚至肿瘤的发生。近年来,国内外开展了许多有关DNA甲基化的分子生物学及其作用机制的研究,本文就相关研究现状予以综述。     

新精神活性物质药理作用研究进展

新精神活性物质是近几年开始流行的新型滥用物质,比起传统毒品来说其种类更丰富、化学结构更复杂。新精神活性物质按照药理学作用可分为七大类,除了效果未知的类别,其余的兴奋剂类、合成大麻素受体激动剂类、经典致幻剂类、合成阿片类、身心分离剂类和镇静催眠类都可通过与特异性受体结合从而发挥作用。该文对新精神活性物质的药理作用及其机制进行综述,以期为新精神活性物质的研究提供参考。     

电针灸暗示治疗对精神活性物质所致躯体症状的临床观察

<正>随着社会进步,经济的加速发展,人们在社会、生活、工作中的压力也急剧增加,如不能得到有效的排解,则易导致不良情绪的增加,甚至出现对精神活性物质,如:麻古、冰毒、K粉、摇头丸等新型毒品的滥用。精神活性物质滥用后会使滥用者出现很多的躯体不适,     

Toxicological investigation of drug-related cases in Greece: interpretation of analytical findings

The process of toxicological analysis of postmortem specimens can reveal some special difficulty compared to the clinically derived specimens. Many drugs are not stable and the chemical changes that occur in the specimens, due to the hydrolysis processing, the time passed, the drug metabolism, and matrix effect, even when the postmortem interval is short, may affect the interpretation of the toxicological results. This interpretation may be critical, not only to the thorough investigation of different kind of forensic cases, but also to clinical or other cases as it provides very significant challenges to the scientists. This article reviews (a) particular toxicological issues associated with some toxic substances responsible for common lethal or nonlethal poisonings, such as opiates, cannabis, and cocaine and the vast number of factors that affect drug concentration; and (b) focuses on toxicological issues associated with the analytical findings of certain postmortem specimens. The toxic substances cited in the present paper are the most commonly found in forensic cases in Greece. The investigation of these drug-related deaths has revealed that heroin, alone or in combination with other psychoactive substances, such as cannabis and cocaine, is the main drug involved in these deaths.     

Intoxication cases associated with the novel designer drug 3′,4′‐methylenedioxy‐α‐pyrrolidinohexanophenone and studies on its human metabolism using high‐resolution mass spectrometry

Among the increasing number of new psychoactive substances, 3′,4′‐methylenedioxy‐α‐pyrrolidinohexanophenone (MDPHP) belongs to the group of synthetic cathinones, which are the derivatives of the naturally occurring compound cathinone, the main psychoactive ingredient in the khat plant. Currently, only limited data are available for MDPHP, and no information is available on its human metabolism. We describe the toxicological investigation of nine cases associated with the use of MDPHP during the period February–June 2019. Serum MDPHP concentrations showed a high variability ranging from 3.3 to 140 ng/mL (mean 30.3 ng/mL and median 16 ng/mL). Intoxication symptoms of the described cases could not be explained by the abuse of MDPHP alone because in all cases the co‐consumption of other psychotropic drugs with frequent occurrence of opiates and benzodiazepines could be verified. Therefore, the patients showed different clinical symptoms, including aggressive behaviour, delayed physical response, loss of consciousness and coma. Liquid chromatography–high‐resolution mass spectrometry was successfully used to investigate the human in vivo metabolism of MDPHP using authentic human urine samples. The metabolism data for MDPHP were further substantiated by the analysis of human urine using gas chromatography–mass spectrometry (GC–MS, a widely used systematic toxicological analysis method appropriate for the toxicological detection of MDPHP intake), which revealed the presence of seven phase I metabolites and three phase II metabolites as glucuronides. GC‐MS spectral data for MDPHP and metabolites are provided. The identified metabolite pattern corroborates the principal metabolic pathways of α‐pyrrolidinophenones in humans.     

What products are considered psychoactive under New Zealand's legal market for new psychoactive substances (NPS, ‘legal highs’)? Implications for law enforcement and penalties

The problem of defining what psychoactive products and substances should be covered by legislation aimed at controlling new psychoactive substances (NPS; ‘legal highs’) is central to the current debate on designing new legislative responses to NPS. In New Zealand, implementation of the Psychoactive Substances Act 2013 (PSA) revealed uncertainties about which psychoactive products are covered by the new regime, with important implications for legal penalties. We reviewed five pieces of legislation which can cover substances with psychoactive properties: PSA, Misuse of Drugs Act (MODA), Food Act, Dietary Supplements Regulations and Medicines Act. Our analysis revealed that a number of psychoactive substances which are not MODA‐scheduled may potentially fall under more than one regulatory regime, including kava, Salvia divinorum, nitrous oxide, 25I‐NBOMe, and 1,3‐dimethylbutylamine (DMBA). For example, kava may be classified as a food, a dietary supplement, a herbal remedy, or a psychoactive substance, depending on how it is presented (including advertising and labelling). There are considerable differences in penalties and regulatory requirements between the different legislative regimes and these may result in unnecessary prosecutions or ‘gaming’ of the system. We discuss a number of ways to more clearly categorize products, including a public schedule of psychoactive substances and products, demarcation criteria based on the quantity of the active ingredient, and demarcation based on ‘discernible intoxication’. Routine use of forensic testing is essential to ensure appropriate prosecutions and penalties. Robust safety standards are also required in legislative regimes exempted from psychoactive substances regime to prevent ‘creative compliance’. Copyright © 2016 John Wiley & Sons, Ltd.     

Aminoindanes--the next wave of 'legal highs'?

Due to its closed ring system, 2-aminoindane is a conformationally rigid analogue of amphetamine. Internet websites offering synthetic compounds as 'research chemicals' have recently been advertising 5,6-methylenedioxy-2-aminoindane (MDAI), 5, 6-methylenedioxy-N-methyl-2-aminoindane (MDMAI), 5-iodo-2-aminoindane (5-IAI), and 5-methoxy-6-methyl-2-aminoindane (MMAI). The chemistry, pharmacology, and toxicological aspects of this new class of psychoactive substances are reviewed, as these could become the next wave of 'legal highs'.     

Psychoactive properties of !Kung Bushmen medicine plants

This article addresses some of the recent controversy over the role of psychoactive substances in the !Kung Bushmen healing ceremonies and trance induction. Although some contemporary works on the !Kung and their healing ceremonies give no evidence of the use of psychoactive plants, an examination of the available biochemical and pharmacological literature on the properties of these plants indicates that most contain psychoactive or toxic substances that are likely to have trance-inducing properties. Almost half of the !Kung medicine plants contain psychoactive substances or have toxic properties, and a similarly large group of these plants has psychoactive or toxic properties in related species. Although recent reports have shown little concern with the use of psychoactive substances, the earlier literature illustrated a major concern with their use in !Kung Bushmen trance and healing. This contrast with more recent research suggests a decline in the use of psychoactive plants in the recent past. This decline is examined with respect to changes in the !Kung Bushmen society and how attitudes in the United States regarding drug use may have influenced investigators and their research reports.     

Understanding the risks associated with the use of new psychoactive substances (NPS): High variability of active ingredients concentration,mislabelled preparations,multiple psychoactive substances in single products

New psychoactive substances (NPS), are now a large group of substances of abuse not yet completely controlled by international drug conventions, which may pose a public health threat. Anxiety, paranoia, hallucinations, seizures, hyperthermia and cardiotoxicity are some of the common adverse effects associated with these compounds. In this paper, three case reports taken from the archive of processed cases of the authors' laboratory are presented and discussed to stress the risks of possible adverse consequences for NPS users: in particular, (i) the risk deriving from the difficulty of predicting the actual consumed dose, due to variability of active ingredients concentration in consumed products, (ii) the risk deriving from the difficulty of predicting the actual active ingredients present in consumed products, as opposed to those claimed by the manufacturer, and (iii) the risk deriving from the difficulty of predicting the actual pharmacological and toxicological effects related to the simultaneous consumption of different psychoactive ingredients contained in single products, whose interactions are mostly unknown. Each of them individually provide a source of concern for possible serious health related consequences. However, they should be considered in conjunction with each others, with the worldwide availability of NPS through the web and also with the incessantly growing business derived from the manipulation and synthesis of new substances. The resulting scenario is that of a cultural challenge which demands a global approach from different fields of knowledge.     

Novel psychoactive substances: how to understand the acute toxicity associated with the use of these substances

Since the turn of the 21st century, there has been an increase in the availability and use of novel psychoactive substances (also known as "legal highs") across Europe. Currently, there is limited information available on the potential acute toxicity (harms) associated with the use of these novel psychoactive substances. There are a number of potential data sources that can provide information on the acute toxicity associated with their use: (1) user reports on Internet discussion fora; (2) subpopulation level surveys of self-reported harms/unwanted effects (3) regional or national poisons information service accesses for support on presentations to healthcare facilities relating to acute toxicity; (4) case reports/series based on self-reported use or analytically confirmed use; and (5) human volunteer studies assessing potential acute toxicological effects. Each of these data sources has its own limitations, particularly those that are based on self-reported use because there are a number of European studies that show that there is inconsistency in the substance(s) in the "drug" that an individual uses. However, by using a multilayered approach of combining different sources, it is possible to reduce the overall impact of the limitations of any one individual data source. In this review article, we will combine information from these different data sources to describe the pattern of acute toxicity associated with 4 novel psychoactive substances: 1-benzylpiperazine, mephedrone (4-methylmethcathinone), synthetic cannabinoid receptor agonists, and methoxetamine.     

4,4′‐DMAR: Chemistry,Pharmacology and Toxicology of a New Synthetic Stimulant of Abuse

In recent years, the spread of new psychoactive substances has dramatically increased in term of availability of both number of compounds and chemical families. In November 2012, 4,4′‐Dimethylaminorex (4,4′‐DMAR), a novel synthetic stimulant, was first detected in the Netherlands. Between June 2013 and June 2014, thirty‐one deaths associated with the consumption of this new drug have been registered across Europe. In this MiniReview, we have summarized the chemical, pharmacological and toxicological information about this new legal high.     

Impact of physical activity and doping on epigenetic gene regulation

To achieve success in sports, many athletes consume doping substances, such as anabolic androgenic steroids and growth hormones, and ignore the negative influence of these drugs on their health. Apart from the unethical aspect of doping in sports, it is essential to consider the tremendous risk it represents to their physical condition. The abuse of pharmaceuticals which improve athletic performance may alter the expression of specific genes involved in muscle and bone metabolism by epigenetic mechanisms, such as DNA methylation and histone modifications. Moreover, excessive and relentless training to increase the muscle mass, may also have an influence on the health of the athletes. This stress releases neurotransmitters and growth factors, and may affect the expression of endogenous genes by DNA methylation, too. This paper focuses on the relationship between epigenetic mechanisms and sports, highlights the potential consequences of abuse of doping drugs on gene expression, and describes methods to molecularly detect epigenetic changes of gene markers reflecting the physiological or metabolic effects of doping agents.     

The Effects of Food on Mood and Behavior: Implications for the Addictions Model of Obesity and Eating Disorders

SUMMARY

The addictions model of obesity claims that individuals gain excess weight due to their dependence on and inability to control the intake of certain food substances. The dependence and lack of control over these food substances is undergirded by, according to the addictions model, the psychoactive properties of foods. The article reviews the literature on the purported psychoactive effects of foods and concludes that although, under certain circumstances, some food substances may have subtle effects on mood and behavior, the effects of food are quite different from that of psychoactive drugs such as nicotine and alcohol. Therefore, the food addictions model is unlikely to provide a fruitful paradigm for understanding the complex problem of obesity.