Bioreductive activation of quinones: A mixed blessing

Quinones can be metabolized by various routes: substitution or reductive addition with nucleophilic compounds (mainly glutathione and protein thiol groups), one-electron reduction (mainly by NADPH: cytochrome P-450 reductase) and two-electron reduction (by D,T-diaphorase). During reduction semiquinone radicals and hydroquinones are formed, which can transfer electrons to molecular oxygen, resulting in the formation of reactive oxygen intermediates and back-formation of the parent quinone (redox cycling). Reaction of semiquinones and reactive oxygen intermediates with DNA and other macromolecules can lead to acute cytotoxicity and/or to mutagenicity and carcinogenicity. The enhanced DNA-alkylating properties of certain hydroquinones are exploited in the bioreductive alkylating quinones. Acute cytotoxicity of quinones appears to be related to glutathione depletion and to interaction with mitochondria and subsequent disturbance of cellular energy homoeostasis and calcium homoeostasis. These effects can to a certain extent be predicted from the electron-withdrawing and electron-donating effects of the substituents on the quinone nucleus of the molecule. Prediction of cytostatic potential remains much more complicated, because reduction of the quinones and the reactivity of the reduction products with DNA are modulated by the prevailing oxygen tension and by the prevalence of reducing enzymes in tumour cells.This article is based on a lecture given at the 16th LOF Symposium, 27 October 1989, Utrecht, the Netherlands.     

水面长航舰载保存血液生化指标的实验研究

目的探讨和观察经水面长航舰载保存血液出海前后对生化指标的影响与变化。方法随机采集和制备WB、AS-RBC和LP-RBC各18人份(200ml)。每份血液各等分为4袋,配对设计为实验组(A区、B区和C区)与对照组。分别于长航前和长航后进行血液生化指标检测。结果①K+和P3+浓度在三种血液制品的实验组与对照组各观察点的结果均随保存血液时间的延长而增高(P<0.05或P<0.01);Na+浓度由长航前的水平而逐步降低(P<0.01);P3+、Mg2+实验组和对照组较长航前增高,Cl-、Ca2+的含量与长航前没有显著变化;②LDH、AST、CKP和HBDH结果实验组和对照组均呈递增趋势,AKP结果实验组和对照组均呈下降表现,ALT与GGT结果在长航前后变化不明显;③Glu指标减低,UA呈上升趋势。结论长航对血液保存有一定的影响,但总的变化趋势与常规(4±2)℃血库冰箱保存相似。此项研究对于我们进一步探索海上血液保障与运输以及血液海上救护均具有十分重要的实用和军事价值。     

海南文昌汉族人群中两种葡萄糖-6-磷酸脱氢酶基因突变的研究

目的:分析海南文昌人群中葡萄糖-6-磷酸脱氢酶基因1376G→T、95A→G突变。方法:应用硝基四氮唑蓝定量法进行G6PD缺乏症的筛查,用等位基因特异PCR检测1376G→T、95A→G突变。结果:在358位海南文昌汉族人中,发现G6PD缺乏症患者20例,其中9例患者有1376G→T突变,3例患者有95A→G突变。结论:1376G→T、95A→G突变是文昌人群中常见的突变。     

高职高专院校生物化学教学体会

生物化学这门课程理论性强，内容复杂、抽象、难学难记，教学过程中如果采用灵活多样的教学手段，注意调动学生学习的主动性和积极性，即可克服学生的畏难情绪，从而提高学习效率。     

羊心淋巴流阻断后血清生化指标的改变

为给临床心脏术后监测心淋巴管损伤程度及可能出现的并发症提供参考指标，以手术方法阻断羊心淋巴流并对其血清相关成份进行了测定。实验发现，实验组术后谷草转氨酶（ＳＧＯＴ）、谷丙转氨酶（ＳＧＰＴ）、碱性磷酸酶（ＡＫＰ）、乳酸脱氢酶（ＬＤＨ）均有不同程度的增高，以ＳＧＯＴ增高最为明显，术前均值为４７．５３Ｕ，术后２天增至１０４．２０Ｕ，高峰出现时间最早，多在术后２４小时。血清离子改变中低钾最为突出，血钾在术后２天明显降低（Ｐ＜０．０１），术后７天逐渐恢复，术后１４天恢复至术前水平。血清蛋白改变以球蛋白降低、白蛋白／球蛋白比值升高为主。提示心淋巴循环郁滞可导致心肌细胞损伤、毛细血管通透性和结构的改变。不同酶活性的变化对郁滞的敏感度存在着差异。     

50例正常生育力男子精液和血液激素的一年动态观察

作者对南京市50名正常男子,每月1次、连续12个月测定了精液常规、某些精液生化和血清激素水平。结果表明:精子密度每次之间波动范围较大,冬季数值比夏季显著为高(P<0.01)。其它指标包括正常形态精子、活动精子、前向运动级别、精液果糖、硷性磷酸酶、酸性磷酸酶及血清,FSH LH T 则变动不显著。精液常规中除精子密度和各参数关系不明显外,所有其它参数之间呈正相关;但精液常规、精液生化和血清激素三者互不相关。从本组研究结果,作者提出了南京市正常男子这些指标的参考正常值。     

生物化学与细胞生物学课程整合的探讨

为了适应新世纪教学内容和课程体系改革的要求,我校借鉴美国哈佛大学医学院的经验,将生物化学与细胞生物学两门课程整合为“细胞的化学与生物学”。整合后在减少两个学科间重复内容、增加学科间联系、减少学时、早期接触临床、培养学生分析解决问题的能力、创新能力等方面有了很大改进,为这两门课程的改革开辟了新途径。     

将素质教育理念贯穿在生化课教学中的探索

为适应知识经济时代对医学人才培养的要求,应将素质教育引入生化教学中。本文从提高教师综合素质,生化课堂教学、第二课堂教育,多媒体应用等方面入手,探索在生化课教学中提高学生素质的有效途径,以全面提高教学质量,实现对医学人才的培养目标。     

5-HT1A receptor agonists: recent developments and controversial issues

During the last decade, serotonin (5-HT)_1A receptors have been a major target for neurobiological research and drug development. 5-HT_1A receptors have been cloned and a variety of selective agonists, such as the aminotetraline 8-OH-DPAT and the pyrimidinylpiperazine ipsapirone, have become available. Demonstrations of apparent intrinsic activity of these ligands at 5-HT_1A receptors, however, depend highly on the particular assay system. This may be due to the possible existence of receptor subtypes and to assay (or brain region)-dependent differences in receptor reserve and the nature of receptor-effector coupling. Nevertheless, the apparent intrinsic activity of 8-OH-DPAT seems to be higher (although possibly not yet maximal) than that of the pyrimidinylpiperazines. In the brain, 5-HT_1A receptors are located presynaptically as somatodendritic receptors on 5-HT neurons and postsynaptically in particular limbic and cortical regions. Although it is generally accepted that presynaptic 5-HT_1A receptors control 5-HT neuronal activity, recent evidence suggests an additional role of postsynaptic 5-HT_1A receptors in cortex as part of a negative feedback loop. Anxiolytic and antidepressive properties of selective 5-HT_1A receptor agonists have now been confirmed by clinical studies. Although it is well established that the latter properties depend on theagonistic activity of these compounds, theoptimal level of intrinsic activity is still a matter of debate and may be dependent on the clinical indication. Such compounds may also have antiaggressive effects, and possibly anticraving effects (manifested by their alcohol intake-reducing effects in dependent animals), but the specificity of these so-called anti-impulsivity effects is still controversial and not yet tested clinically. Anticataleptic, antiemetic and neuroprotective properties have been demonstrated in different species. Behavioral studies on the mechanisms underlying the anxiolytic and antidepressive effects have examined the relative contribution of pre-and postsynaptic 5-HT_1A receptors by means of local cerebral application and lesion techniques. Most evidence points towards a critical involvement of presynaptic receptors in the anxiolytic effects of 5-HT_1A receptor agonists (although a possible contribution of postsynaptic receptors cannot be excluded). With regard to the antidepressive properties, a case can be made for the reverse; i.e., a strong involvement of postsynaptic receptors and a questionable contribution of presynaptic receptors. However, as the therapeutic effects of those 5-HT_1A receptor (partial) agonists which have been tested clinically require repeated administration, attention has been directed increasingly towards chronic studies. These studies have shown that a number of electrophysiological, biochemical, behavioral and endocrinological 5-HT_1A receptor-related events adapt differentially to repeated or sustained administration. Thus, several hypotheses accounting for the delayed onset of action have been advanced. Among these, time-dependent downregulation /desensitization of eitherpre- orpostsynaptic 5-HT_1A receptors, or cortical 5-HT₂ receptors have received much attention. However, these hypotheses have their weaknesses, and it is argued thatfunctional sensitization of particular postsynaptic 5-HT_1A receptor-mediated events remains a valuable alternate hypothesis. Basic research on the role of 5-HT_1A receptors in psychopathology and in the therapeutic effects of clinically effective therapeutics, as well as on the mechanism of action of 5-HT_1A receptor ligands, will enable rational design of ligands with particular profiles of intrinsic activity at different 5-HT_1A receptor populations, and may contribute to a more efficient treatment of a multiplicity of brain disorders.