增塑剂DEHP的神经和行为发育毒性

增塑剂邻苯二甲酸二乙基己酯(Di-(2-ethylhexyl) phthalate,DEHP)是一种具有拟雌激素和抗雄激素活性的环境内分泌干扰物,人类和野生动物可通过不同途径终生暴露于DEHP.母体摄入的DEHP可通过胎盘和乳汁转入子代体内并进入脑组织.围生期DEHP暴露性别特异性地改变子代大鼠下丘脑视前区芳香酶活性而影响雌激素合成,并通过改变雌激素受体活性干扰雌激素对脑发育的调节作用.DEHP及其代谢产物可以影响神经细胞的增殖分化和突触形成,干扰性激素调控发育过程中的下丘脑氨基酸递质系统对促性腺激素释放激素分泌的刺激作用,影响中脑多巴胺递质系统发育而诱导自发性多动症.DEHP对脑发育的作用最终影响动物的早期行为、学习记忆和情感等行为发育.     

雷公藤多苷对肝脏的双重作用及其思考

文献研究表明,雷公藤多苷既可治疗肝脏疾病,又能引起肝脏毒性。本文对其双重作用从不同角度进行了分析,认为药物均存在治疗作用和毒副作用的双重效应,且与用药剂量、时间密切相关,并从严控剂量时间、加强监测、重视“治未病”、改进剂型等方面提出了应对措施。     

靶向药物不良反应的认识与思考

新的靶向药物出现提高了抗癌疗效,降低了毒性,使转移性恶性肿瘤患者从治疗中获益。靶向药物耐受性好,通常出现轻微或中度的毒副反应。尽管大多数不良反应是可以得到迅速处理的,但是严重的甚至危及生命的不良反应仍能够发生。因此,为更好地指导临床实践工作,该文综述了实体瘤治疗中常用靶向药物的主要不良反应和安全数据,并按照药物的作用靶...     

抗肿瘤药物心脏毒性的监测和治疗进展

许多临床常用的抗肿瘤药物均有不同程度的心脏毒性,常见的心血管并发症包括心力衰竭、心肌缺血、心律失常、高血压、低血压、血栓形成等。现就国内外近年对抗肿瘤药物心脏毒性的监测和治疗等方面的进展进行综述。     

Evaluation of drug toxicity in clinical trials

An increasing number of drugs removed from the market because of unacceptable toxicity raises concerns regarding preapproval testing of drug safety. In the present paper it is postulated that the non-inferiority type of trial should be abandoned in favor of the superiority trial with active controls and less stringent (p<0.1, both for efficacy and toxicity) statistics. This approach will increase sensitivity of detection of drug-induced adverse effects at the expense of increasing false positive results regarding the difference in efficacy between the tested and reference drug. Such a move will increase the protection of future patients. In addition, the proposed design is far more acceptable from the clinical (e.g. no need to specify the statistically expected “unimportant” number of deaths) and ethical points of view, as well as being favored by the strong incentive of involved parties. In the second part of this paper arguments are presented in favor of the hypothesis that placebo (still used in some superiority trials) does not induce adverse effects. The assertion that placebo may induce adverse effects is probably biased by the nature of the clinical experiment. Such a conclusion is supported by studies indicating that placebo-induced adverse effects are disease — and treatment — specific. The modification of clinical trials according to the proposed changes may increase the trials’ sensitivity at detecting adverse effects of drugs. A lecture on the subject of this paper was presented at the 6th International Bioethics Conference on the subject of ‘The Responsible Conduct of Basic and Clinical Research’, held in Warsaw, Poland, 3–4 June 2005.     

The impact of valence framing on response expectancies of side effects and subsequent experiences: a randomised controlled trial

Abstract

Objective: Pre-treatment side effect expectancies often influence subsequent experiences; however, expectancy-based reduction strategies are lacking. We explored whether framing information about adverse responses (in positive or negative formats) altered expectancies and experiences of a cold pressor task. We further investigated associations between expectancies and experiences, to inform potential interventions.

Design: Healthy volunteers (N?=?134), randomised to receive positively- or negatively-framed pre-cold pressor task information, self-rated 12 expectancies for cold pressor experiences, emotional state and coping style.

Main Outcome Measures: Self-reports of the same 12-experiences (recorded during and after the experiment) were assessed.

Results: Framing had minimal impact on expectancies and experiences; however, discomfort threshold (p?=?.08, d?=?0.22) showed a trend in the expected direction. Hierarchical regressions revealed expectancies uniquely, significantly predicted 6–23% of the variance for 11 subsequent experiences. Following a popular charity event (Ice Bucket Challenge), all participants showed higher ‘discomfort thresholds’ (p?=?.001, d?=?0.59), and those in the negative frame reported more overall ‘discomfort’ (p?=?.01, d?=?0.60) than participants in the positive condition.

Conclusion: Expectancies uniquely influenced subsequent cold pressor experiences. Framing had minimal impact in this ‘analogue’ medical setting, only influencing ‘discomfort threshold’. ‘Discomfort threshold’ and overall ‘discomfort’ were also impacted by a social media challenge, highlighting a potential area for intervention.     

Ethical aspects of the safety of medicines and other social chemicals

The historical background of the discovery of adverse health effects of medicines, food additives, pesticides, and other chemicals is reviewed, and the development of national and international regulations and testing procedures to protect the public against the toxic effects of these drugs and chemicals is outlined. Ethical considerations of the safety evaluation of drugs and chemicals by human experimentation and animal toxicity studies, ethical problems associated with clinical trials, with the falsification of clinical and toxicological data, and with inadequate experimental methodology, are reviewed, and the ethics of the marketing of drugs and their post-marketing surveillance, are similarly considered. These ethical problems are illustrated with many specific examples, including the drugs neoarsphenamine, chloramphenicol, thalidomide, diethyl stilboestrol and benoxaprofen.     

中药注射剂有效性及“毒性”的物质基础分析

中药注射剂的有效性得到了临床用药的广泛验证,但带来的安全性（“毒性”）问题也引起业界和社会的广泛关注。本文通过分析中药注射剂和同处方的口服剂有效性和“毒性”的特点,认为中药注射剂的有效性来自于小分子物质,而大分子物质则是导致“毒性”的主要物质基础,进而提出从严监控中药注射剂中的大分子物质是提高中药注射剂的有效策略。