A prospective randomised trial on the effect of monitoring plasma anticonvulsant levels in epilepsy

Summary To evaluate whether knowledge of plasma levels of anti-epileptic drugs has an effect on therapeutic outcome, 127 epileptic outpatients were randomly assigned to two groups (A and B). Plasma levels of group A were reported to the treating physician who attempted to keep the plasma levels within the therapeutic range. The treating physician was not informed of the results of plasma lavel determinations of group B. Data from 105 patients were available for assessment at the end of the study year. Therapeutic results of groups A and B were not significantly different. The reduction in seizure frequency was associated with an increase in plasma concentrations of the anti-epileptic drugs. Thus, under the conditions of the study, knowledge of plasma levels of anti-epileptic drugs did not further improve therapeutic results.

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Zusammenfassung Um festzustellen, ob die Kenntnis des Plasmaspiegels der Antiepileptika das Therapieergebnis verbessern kann, wurden 127 ambulant behandelte Patienten mit Epilepsie in randomisierter Reihenfolge in zwei Gruppen eingeteilt (A und B). Die Plasmaspiegel der Antiepileptika in Gruppe A wurden dem behandelnden Arzt mitgeteilt, der versuchen sollte, die Plasmaspiegel in den Therapeutischen Bereich zu bringen. Die Ergebnisse der Plasmaspiegelbestimmung in Gruppe B (Kontrollgruppe) wurden dem behandelnden Arzt nicht mitgeteilt. Am Ende des Untersuchungsjahres konnten die Daten von 105 Patienten ausgewertet werden. Das Behandlungsergebnis von Gruppe A und von Gruppe B war am Ende des Beobachtungsjahres nicht signifikant verschieden. Die Abnahme der Anfallshäufigkeit ging mit einem Anstieg der Plasmakonzentration der Antiepileptika einher. Somit konnte unter den Bedingungen dieser Studie das Therapieergebnis durch die Kenntnis der Plasmaspiegel der Antiepileptika nicht weiter verbessert werden.

     

Alcohol and recreational drug use by HIV-seropositive homosexual men

The objectives of this study were to describe the patterns of alcohol and recreational drug use of HIV-seropositive homosexual men and to determine the effect of alcohol use on HIV risk-taking behaviour. Of particular interest was the effect of knowledge of HIV status on these behaviours. Information on alcohol and drug use was obtained from 485 HIV-seropositive homosexual and bisexual men presenting to a HIV-antibody testing and medical management clinic. Heavy alcohol use was common, with 46.2% reporting consumption of six or more standard drinks on one day recently. Men who knew that they were HIV infected drank significantly more than those men who had yet to learn of their HIV status at the time of interview. There was clear evidence in this study for a role of alcohol use in HIV risk-taking behaviour. Almost one-third (27%) of the HIV-seropositive men reported unprotected anal intercourse during the previous 3 months with approximately one-third of these (27/76, 35·5%) nominating alcohol as contributing to their high HIV-risk behaviour.     

Pharmacology of antimigraine drugs

The drugs used in migraine therapy can be divided into two groups: agents that abort an established migraine attack and agents used prophylactically to reduce the number of migraine attacks. Both groups have drugs that are specific for migrainous headaches and that are non-specific, and are used to treat the accompanying headache (analgesics), vomiting (anti-emetics), anxiety (sedatives and anxiolytics), or depression (antidepressants). The main drugs with specific action on migraine include ergot alkaloids (ergotamine, dihydroergotamine), agonists (sumatriptan) or partial agonists (methysergide) at a specific subtype of 5-HT₁-like receptors, -adrenoceptor antagonists (propranolol, metoprolol), calcium antagonists (flunarizine) and anti-inflammatory agents (indomethacin). The pharmacological basis of therapeutic action of several of these drugs is not well understood. In the case of the ergot alkaloids and 5-HT₁-like receptor agonists, however, it is likely that the antimigraine effect is related to the potent and rather selective constriction of the large arteries and arteriovenous anastomoses in the scalp and dural regions. In addition, these drugs inhibit plasma extravasation into the dura in response to trigeminal ganglion stimulation, but it is possible that this effect is related to the selective vasoconstriction in the extracerebral vascular bed. The selectivity of the pharmacological effects of these antimigraine drugs (constriction of the extracerebral arteries and arteriovenous anastomoses, poor penetration into the central nervous system and the absence of an antinociceptive effect even after intrathecal administration) strongly suggests that excessive dilatation in the extracerebral cranial vasculature, probably initiated by a neuronal event, is an integral part of the pathophysiology of migraine.     

Chronic treatment with desipramine caused a sustained decrease of 3,4-dihydroxyphenylglycol-sulphate and total 3-methoxy-4-hydroxyphenylglycol in the rat brain

Summary The 2 major metabolites of norepinephrine (NE), 3,4-dihydroxyphenylglycol-sulphate (DOPEG-SO₄) and free plus conjugated 3-methoxy-4-hydroxyphenylglycol (total-MOPEG), both their endogenous concentrations and their accumulation from the NE-precursors ³H-tyrosine or ³H-dopamine, were determined in the whole rat brain to assess the effect of chronic treatment with desipramine (DMI), imipramine and amitriptyline. DOPEG-SO₄ was decreased 2 h and 24 h after the last administration of DMI (10 mg/kg twice daily for 4, 10 or 20 days) or imipramine (10 mg/kg twice daily for 10 days). When measured within 24 h after the last dose of DMI or imipramine, several schedules resulted in reduced accumulation of total-³H-MOPEG and ³H-NE, while ³H-NE and MOPEG were unchanged in the remaining schedules. These results indicate that DMI retains its ability to decrease NE-turnover over a period of 20 days of treatment. Forty-eight hours or 72 h after the last administration of desipramine and imipramine an overshoot was observed in NE-metabolism, consisting of increased levels of total-³H-MOPEG and endogenous total-MOPEG; DOPEG-SO₄ was some-times concomitantly increased. The overshoot was more consistent after 20 or 10 days of treatment than after 4 days of treatment. This finding, together with a tendency to partial tolerance to the metabolite decreasing effects of DMI, indicate that adaptive changes occur in the NE system after treatment for 10–20 days with DMI or imipramine.Abbreviations Used NE norepinephrine - DOPEG 3,4-dihydroxyphenylglycol - DOPEG-SO₄ DOPEG sulphate ester - MOPEG 3-methoxy-4-hydroxyphenylglycol - total-MOPEG free plus conjugated MOPEG - DOPAC 3,4-dihydroxyphenylacetic acid - HVA homovanillic acid - NM normetanephrine - DA dopamine - DMI desipramine     

Effects of antipsychotic drugs on cytokine networks

It has been known since the 1950s that phenothiazines have immunomodulatory effects. This review summarizes recent evidence suggesting that antipsychotic drugs, in particular chlorpromazine and the atypical compound clozapine, influence the production of cytokines. Cytokines, organized in networks of related peptides with pleiotropic functions, are pivotal humoral mediators of infection and inflammation, and they play an important role in hematopoiesis and autoimmunity. Therefore, the effects of antipsychotic drugs on cytokine networks are important for the understanding of immune-mediated side effects of these drugs, e.g. agranulocytosis. In addition, modulation of cytokine production by antipsychotic agents suggests that these drugs might be useful for the treatment of diseases which primarily involve the immune system. Moreover, because cytokines are known to have numerous effects on the CNS, they may mediate effects of antipsychotic drugs on brain functions. Finally, the influence of antipsychotic drugs on cytokine networks is an important confounding factor in studies investigating disease-related immunopathology in psychiatric disorders. This review provides a synopsis of the data published on these topics and outlines future research perspectives.     

2,2-双取代-4,6-二氨基-1,2-二氢-1-羟基-s-三嗪类化合物的合成研究

目的 对三嗪类化合物进行合成研究。方法 以盐酸羟胺和苯甲酰氯为原料，经酰化、烃化、水解、缩合、环合及脱苄反应合成目的物。结果和结论 共合成了9个2，2-双取代-4，6-二氨基-l，2-二氢-l-羟基-s-三嗪类化合物(11-i)，结构经元素分析、红外吸收光谱、核磁共振氢谱及质谱确证。     

中药复方对实验性2型糖尿病肾病肾组织内皮素及其受体基因表达的影响

目的:观察中药复方、苯那普利对2型实验性糖尿病肾病(DN)肾组织内皮素及其受体基因表达的影响。揭示中药复方治疗2型DN机理。方法:建立2型链脲菌素DN模型,以中药复方、苯那普利干预。比较Upro,Glu,HbAlC变化,检测(RT-PCR)肾皮质ET-1,ETA-R的mRNA表达水平,分析肾组织病理学特征。结果:对Up-ro,Glu,HbAlC改善作用,中药复方、苯那普利与生理盐水差异有显著性;对Glu,HbAlC改善作用,中药复方与苯那普利差异有显著性;DN模型鼠肾皮质ET-1,ETA-R的mRNA表达水平增加,经中药复方、苯那普利干预,其表达过高水平下调,但仍高于正常对照。对肾小球系膜、系膜细胞增殖的影响,中药复方优于苯那普利。结论:ET参与DN发病机制;中药复方、苯那普利都能从ET及其受体基因转录水平上影响其表达量;中药复方不仅能减少DN尿白蛋白,而且还能改善血糖、糖化血红蛋白,抑制蛋白非酶糖化,抑制肾小球系膜、系膜细胞增殖。     

多种中药成分诱导大鼠骨髓间质干细胞转变为神经元样细胞

目的　体外定向诱导大鼠骨髓间质干细胞 (MSCs)分化为神经元样细胞。方法　通过贴壁法分离大鼠MSCs,体外扩增培养 ,流式细胞仪检测其表面抗原表达 ,中药成分定向诱导MSCs分化为神经元样细胞。光镜下观察细胞形态 ,免疫细胞化学法检测神经细胞特异性抗原标志。结果　大鼠MSCs可通过贴壁法成功分离并可在体外大量扩增。流式细胞仪检测结果显示CD1 4、CD1 1α、CD34、CD38、CD45、CD80、CD86为阴性 ,CD2 9、CD44、CD90、CD1 0 5、CD1 66呈阳性。黄芪、天麻、人参、当归、脑新舒、人参蜂王浆等多种中药诱导 1～ 3h后大部分MSCs转变为神经元样细胞 ,出现胞体和突起 ,免疫细胞化学染色神经元特异性烯醇酶 (NSE)、巢蛋白 (nestin)呈阳性 ,胶质纤维酸性蛋白 (GFAP)阴性。结论　多种传统中药成分及中药制剂体外能诱导大鼠MSCs分化为神经元样细胞     

通天口服液治疗不同类型紧张型头痛的疗效比较

目的 :观察通天口服液治疗不同类型紧张型头痛的临床疗效。方法 :紧张型头痛病人 1 2 1例 ,分为发作性紧张型头痛组 44例和慢性紧张型头痛组 77例 ,口服通天口服液 1mo,治疗后 2mo内动态观察头痛程度、发作频率、持续时间的变化。结果 :治疗 1mo后 1 2 1例病人临床总有效率为90 .9% ,发作性紧张型头痛组临床有效率为 98% ,慢性紧张型头痛组为 87% (P <0 .0 1 )。停药 1mo后全组临床总有效率为 83 .5 % ,发作性紧张型头痛组临床有效率为 93 % ,慢性紧张型头痛组为 78%(P <0 .0 1 )。无效的 2 0例多为慢性紧张型头痛组病人。 2组病人未见不良反应发生。结论 :通天口服液治疗紧张型头痛安全、有效 ,对发作性紧张型头痛的疗效优于慢性紧张型头痛