Resolution of chlorpromazine-induced cutaneous pigmentation following substitution with levomepromazine or other neuroleptics

Eleven chronic schizophrenic patients with abnormal skin pigmentation associated with neuroleptic treatment were withdrawn from chlorpromazine (CPZ), which was replaced by levomepromazine (n= 4), trifluoperazine (n= 1) or thioproperazine (n= 1) as the sole neuroleptic, by a combination of these phenothiazines (n= 4) or with haloperidol plus pipotiazine (n= 1). Seven patients showed complete resolution of abnormal skin pigmentation over a period of 1–5 years and 4 markedly improved over 2.0–2.6 years of follow-up. Our observations suggest that neuroleptic-induced abnormal skin pigmentation is (i) predominantly, if not exclusively, a side effect of CPZ and (ii) reversible, providing that CPZ is withdrawn and sufficient time is allowed to elapse.     

4－甲基－5－取代苯氧基－伯氨喹类似物的合成及抗疟活性的初步评价

以2-硝基-4-甲氧基-5-溴乙酰苯胺为原料，经6步反应，合成了7个4-甲基-5-取代苯氧基伯氨喹类似物(Ⅱ_2～8)。抗疟活性的初步评价结果表明，这类化合物对鼠疟 Plasmodium yoelii 的病因性预防作用明显优于伯氨喹．可达伯氨唪的4～8倍；同时，Ⅱ_2～8还有较强的杀血液裂殖体作用．Ⅱ_2,5,6,8在0.781 mg·kg^-1 的剂量对原虫的抑制率为100％。     

小檗碱对培养大鼠神经细胞内游离Ca^2＋的影响

以Ｆｕｒａ２／ＡＭ为细胞内钙离子的荧光指示剂，用ＡＲＣＭＭＩＣ阳离子测定系统，直接测定了体外培养的新生大鼠神经细胞内游离钙（［Ｃａ２＋］ｉ）值，并观察了小檗碱（Ｂｅｒ）的影响。结果表明，Ｂｅｒ对神经细胞静息［Ｃａ２＋］ｉ无明显影响，Ｂｅｒ１～１００μｍｏｌ·Ｌ－１能剂量依赖地抑制去甲肾上腺素和Ｈ２Ｏ２引起的［Ｃａ２＋］ｉ升高，其ＩＣ５０分别为３９．９和１７．９μｍｏｌ·Ｌ－１。高剂量Ｂｅｒ（１０～１００μｍｏｌ·Ｌ－１）能抑制高Ｋ＋引起的［Ｃａ２＋］ｉ升高。姐果提示，Ｂｅｒ对去甲肾上腺素，高Ｋ＋及Ｈ２Ｏ２引起的［Ｃａ２＋］ｉ升高的抑制作用可能是其抗脑缺血作用机制之一。     

硫酸沙丁胺醇控释小丸胶囊的人体相对生物利用度研究

目的：研究硫酸沙丁胺醇控释小丸胶囊和进口控释片及普通片在健康志愿者体内单剂量和多剂量给药后的药代动力学和生物利用度。方法：８名健康男性志愿者自身随机交叉先后ｐｏ ８ｍｇ受试硫酸沙丁胺醇控释小丸胶囊、沙丁胺醇控释片（Ｖｏｌｍａｘ）或沙丁胺醇普通片（Ｖｅｎｔｏｌｉｎ）,观察其药代动力学和相对生物利用度。另２０名受试者自身随机交叉ｐｏ受试胶囊（８ｍｇｍ,ｂｉｄ）和Ｖｏｌｍａｘ（８ｍｇ,ｂｉｂ）,连服５ｄ     

三氧化二砷对小鼠肾组织RNA的损伤

目的:通过检测活性氮族引起的核酸损伤标志物8-硝基鸟嘌呤在砷暴露小鼠肾脏组织中的表达情况,分析三氧化二砷对肾组织RNA损伤的作用途径。方法:实验于2005-11/2006-01在大连医科大学毒理学实验室完成。选用昆明种健康小鼠40只,按体质量随机分为4组,即正常对照组、5μmol/L、10μmol/L和20μmol/L三氧化二砷染毒组,每组10只。各染砷组小鼠通过饮用含不同剂量三氧化二砷自来水的方式使小鼠暴露砷,连续染砷60d。正常对照组每天摄入相同剂量的生理盐水。染砷60d后处死各组小鼠,立即取肾脏皮质,应用苏木精-伊红染色法进行肾皮质组织病理学观察;应用免疫组织化学及图像分析的方法检测肾组织内8-硝基鸟嘌呤的表达,根据8-硝基鸟嘌呤表达的吸光度值进行定量分析。结果:40只小鼠全部进入结果分析,无脱失。①各染砷组小鼠肾脏皮质区肾小管细胞出现肿胀,胞质内有空泡变性,核固缩、溶解等明显的病理学变化;而正常对照组小鼠的肾脏细胞未见上述病理变化。②5μmol/L、10μmol/L和20μmol/L三氧化二砷染毒组小鼠肾组织细胞的抗8-硝基鸟嘌呤免疫染色平均吸光度显著大于正常对照组(0.027±0.014,0.039±0.015,0.043±0.014,0.004±0.002,P<0.05),20μmol/L三氧化二砷染毒组与5μmol/L三氧化二砷染毒组相比,吸光度明显增加(P<0.05)。结论:活性氮族可能参与了砷对肾脏细胞核酸的损伤作用,8-硝基鸟嘌呤可能是砷致肾损伤的标志物。     

Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups

Linkage disequilibrium (association) analysis was used to evaluate a candidate region near the CTLA4/CD28 genes using a multi-ethnic collection of families with one or more children affected by IDDM. In the data set unique to this study (Spanish, French, Mexican-American, Chinese and Korean), the transmission/disequilibrium test (TDT) revealed a highly significant deviation for transmission of alleles at the (AT)n microsatellite marker in the 3' untranslated region (P = 0.002) and the A/G polymorphism in the first exon (P = 0.00002) of the CTLA4 gene. The overall evidence for transmission deviation of the CTLA4 A/G alleles is also highly significant (P = 0.00005) in the combined data set (669 multiplex and 357 simplex families) from this study and a previous report on families from USA, Italy, UK, Spain and Sardinia. Significant heterogeneity was observed in these data sets. The British, Sardinian and Chinese data sets did not show any deviation for the A/G polymorphism, while the Caucasian-American data set showed a weak transmission deviation. Strong deviation for transmission was seen in the three Mediterranean-European populations (Italian, Spanish and French) (P = 10(-5)), the Mexican-American population (P = 0.002) and the Korean population (P = 0.03). These results suggest that a true IDDM susceptibility locus (designated IDDM12) is located near CTLA4.      

盐酸三环哌酯在大鼠体内外的代谢

用大鼠原位灌流肝脏、整体实验和大鼠肝脏微粒体酶制备对盐酸三环哌酯(TCPN)的代谢转化进行了研究。结果经大鼠原位肝脏灌流后,灌流液经提取和HPLC分离制备,得到两个代谢产物。经MS,NMR,IR和UV鉴定,证明产物I是TCPN氮上脱甲基的产物,产物I是TCPN苯环羟化的产物。从大鼠igTCPN后的尿中及在TCPN和肝脏微粒体的温孵液中均得到产物I和产物II,提示TCPN的代谢转化主要由大鼠肝脏微粒体酶催化。以[³H]QNB为配体对TCPN及其代谢产物的受体结合活性进行了研究,结果表明产物I和产物I与M受体的亲和力分别是TCPN的1/20和1/50。     

Nicotine and behavioral markers of risk for schizophrenia: a double-blind, placebo-controlled, cross-over study.

We investigated the effect of nicotine on three behavioral markers of risk for schizophrenia: sustained attention (using the Continuous Performance Task (CPT)), antisaccade performance, and smooth pursuit. Smooth pursuit was investigated in two conditions, one in which attention was enhanced (monitoring target changes) and one in which attention was not enhanced (no monitoring). Patients with schizophrenia (n = 15) and controls (n = 14) were given a 14-mg nicotine patch in a double-blind, placebo-controlled, crossover design and plasma nicotine concentrations were monitored. Nicotine concentrations were similar in both groups. A Group x Drug interaction (p <.02) on CPT hits indicated that nicotine improved sustained attention in patients but not in controls. Nicotine significantly decreased antisaccade errors (p <.01) in both groups. A Drug x Monitoring condition interaction (p <.01) on pursuit gain indicated that nicotine significantly increased pursuit gain in the no-monitoring condition in patients and controls equally, but did not improve pursuit in the monitoring condition. Thus, improvement in pursuit may have been mediated via an effect on attention rather than by an effect on oculomotor function per se. In patients, the magnitude of improvement in attention on nicotine was correlated with the improvement on eye movement tasks. Thus, nicotine improves performance on both attention and oculomotor markers of risk for schizophrenia, possibly via common mechanisms.     

九里香抗生育活性物质——月橘烯碱的仿生合成研究

月橘烯碱是从芸香科植物九里香根中分出的双吲哚生物碱。药理实验结果表明它具有抗着床和抗早孕的活性。本文报道其仿生合成:吲哚经3位醛基化、与丙酮缩合成化合物Ⅱ;将氮原子保护后进行wittig反应,脱保护基得到β-异戊二烯吲哚(Ⅴ);经分子间Diels-Alder加成反应得消旋月橘烯碱(Ⅵ)。     

脑错构瘤致女婴真性性早熟1例

0　引言　性早熟是指性成熟开始年龄显著提早 ,医学文献具体年限尚无明确界定 ,如按第二性征或月经初潮的平均年龄加减 2个标准差 (x± 2 s)来推断 ,第二性征发育在 9岁以前 ,月经初潮在 10岁以前者被认为是性早熟 . 1999- 0 9- 0 1我们收治脑错构瘤致女婴真性性早熟 1例 ,报道如下 .1　病例报告　女 ,1998- 0 8- 2 5生 ,出生时体质量 2 .1kg,身长48cm,出生后 ,阴道便有白色分泌物流出 ,6 mo时发现与其母同一日阴道出血 ,后成为规律周期性月经 ,时间一般持续 4～ 5 d. 1999- 0 7- 0 1门诊接诊 ,B超检查显示 ,子宫 :轮廓清 ,切面大小约 2 …