抗心肌缺血药3-{4-[(2-羟基-3-烷氨基)丙氧基]苯基(苄基)}-取代4(3H)-喹唑酮的合成

β-受体阻断药在心血管病的治疗中占有相当重要的地位,对缺血性心脏病有肯定的疗效。但也存有不良反应或禁忌症,其中有的是由于其选择性不高所致。因此,寻找特异性的β_1受体阻断药是目前研究抗心肌缺血药的一个重要方面。据报道,在β-受体阻断药的基本有效结构的苯环的对位与4(3H)-喹唑酮环的2位     

3-甲基芬太尼衍生物构效关系及受体结合特征研究

对3-甲基芬太尼的1-苯乙基、4-N-丙酰基进行了结构改造、测定了所合成化合物的镇痛活性及部分化合物的镇痛作用持续时间、阿片受体亲和力和对阿片受体亚型的选择性。结果表明,大部分化合物均有较强的吗啡样镇痛活性,强度约为吗啡的2～180倍。所试化合物的镇痛作用持续时间比芬太尼延长6～10倍。化合物1～4的受体亲和力(IC₅₀)约为10^-7～10^-3mol。化合物13对阿片μ-受体有较高的选择性,对大鼠脑膜的λ/δ比值大于700,对小鼠脑膜的μ/δ比值为1000。     

云谷霉素的抗肿瘤作用

来自云南省关坪自然保护区土壤的一株链霉菌产生的抗生素云谷霉素经鉴别确定为谷氏菌素。本研究通过口服给药,证明云谷霉素对小鼠结肠癌26和肉瘤180(实体型)有显著疗效;用小鼠可耐受剂量,对小鼠结肠癌26和肉瘤180的抑瘤率分别达85%和83%。提示云谷霉素用于治疗肿瘤的可能性。     

Raised bile acid concentrations in SIDS lungs at necropsy

Previous studies of the abnormal physical properties of lung surfactant derived from infants experiencing prolonged expiratory apnoea, or who have died of sudden infant death syndrome (SIDS), have led to a search for the agent responsible. Bronchoalveolar lavage (BAL) has been performed upon 12 infants under 12 months at necropsy and the rinsings analysed for up to 26 bile acids using high performance liquid chromatography, which requires nanomolar quantities. They were also analysed for simultaneously retrieved phospholipid and proteolipid-a minor component of lung surfactant-as markers of lavage efficiency. Total bile acid (TBA) was found to be higher in six SIDS cases, reaching a mean (SE) 8.54 (2.24) mumol/l in the BAL fluid compared with 4.66 (1.47) mumol/l in the six controls of similar age. When related to the concomitant surfactant yield, the TBA/ proteolipid and TBA/phospholipid ratios both showed highly significant differences between index lungs and controls, providing another postmortem marker of SIDS with potential for development as a test of risk. Since the bile:phospholipid ratio determines whether phospholipase A2 synthesises or hydrolyses phospholipid, the raised TBA/phospholipid ratio could be highly significant, causing this enzyme to function more like its role in the gut than in the lung.     

Distinct time courses of increase in cytochromes P450 1A2, 2A5 and glutathione S-transferases during the progressive hepatitis associated with Helicobacter hepaticus

Mice naturally infected by Helicobacter hepaticus develop a chronic active hepatitis leading to hepatocellular carcinoma. This mouse model of liver cancer was used to examine the impact of bacterial infection on the hepatic expression and activity of enzymes involved in carcinogen bioactivation (phase I enzymes) and detoxification (phase II enzymes). No major differences in total cytochrome P450 (CYP) content were found between control and infected mice during the course of the study. The most striking modulations of individual isoenzymes were the increases in immunohistochemical staining observed for CYP1A and CYP2A5 in relation to increasing age and liver lesions. The increase in CYP2A5 in mice aged over 12 months was confirmed by the observed increases in coumarin 7-hydroxylation (CYP2A5 substrate) in vitro and CYP2A5 mRNA levels by Northern blot analysis. Immunoblotting confirmed the specific induction of CYP1A2 in infected mice 12 and 18 months of age. Perfusion of liver with nitroblue tetrazolium, an indicator for superoxide formation, demonstrated that in livers of infected mice, hepatocytes often co-expressed CYP2A5 and formazan deposition. Concerning phase II enzymes, an enhancement of glutathione S-transferase (GST) activities, related to the disease process, was observed in infected mice. An age- specific increase of GSTpi and A4.4 (early stage of disease) and GST YaYa (>9 months) expression was also demonstrated by immunohistochemical staining. In contrast, catalase and glutathione- peroxidase activities, as well as reduced glutathione content were decreased in the early stages of disease (3-9 months) in infected mice compared to age-matched control mice. Overall, these results suggest that alterations in CYP and GST expression may contribute to the aetiology of tumour incidence due to H. hepaticus infection via production of reactive oxygen species.      

Partial thickness supraspinatus tears: Diagnosis by magnetic resonance arthrography

Two patients, with clinical symptoms of advanced impingement syndrome, presented for radiologic evaluation. The magnetic resonance (MR) images of each patient were interpreted as representing a full thickness tear of the supraspinatus tendon. Magnetic resonance arthrography was performed on both patients to further determine the extent of the tear. Using this technique, both patients were diagnosed correctly as having partial thickness tears; one on the articular surface and the other on the bursal surface of the tendon. This information is useful in surgical planning and in patient outeome.     

低氧、运动与免疫研究

目的:高原训练通过低氧、低压刺激能有效的提高机体心血管系统和呼吸系统的功能,对提高体育成绩有明显的作用,然而高原训练可能使机体出现免疫功能变化。通过文献资料法,综述了低氧、运动对集体免疫功能的影响,使人们对低氧、运动情况下免疫功能的变化有一个全面的了解。资料来源:检索中国期刊网1989-01/2004-12和维普中文期刊数据库1994-01/2004-12与低氧、运动和免疫研究相关的文章,检索词“低氧、免疫、运动、高原”并限定文章语言种类为中文。同时检索Spinger Link数据库、EBSCO期刊数据库和www.ncbi.nlm.nih.gov/pubmed网站相关低氧、运动与免疫研究的文章,检索时间没有限定,从有文献记载开始检索。检索词“immune function,exercise,hypoxia,immune”检索时一个或几个结合进行,文章语言种类限定为English。资料选择:对资料进行初审,选取包括与低氧、运动、免疫研究相关的文献,开始查找全文。纳入标准:低氧运动情况下免疫功能变化以及低氧实验情况下、居住高原或移居高原情况下免疫功能变化的文献,且查找的文献包括人体实验和动物实验两方面的资料。排除仅运动对免疫功能影响的文章。资料提炼:共检索到关于低氧、运动与免疫研究的相关文献120篇,40篇文献符合纳入标准,排除不符合标准文献80篇。资料综合:多数研究观察到低氧暴露可能出现机体免疫抑制现象;当海拔超过某一高度时,居住居民免疫功能可能随着居住海拔高度的增加而降低;由平原进驻高海拔地区,机体可能出现免疫抑制现象,且免疫抑制随着进驻高原高度的增加而增加,随着进驻时间的延长而降低;自主神经系统可能参与低氧条件下的免疫调节,交感神经系统及去甲肾上腺素有免疫抑制作用,副交感神经及乙酰胆碱起免疫增强作用。在低氧情况下,β-内啡肽可能通过交感神经系统而发挥免疫抑制作用。结论:一般研究认为适度的运动可使机体免疫功能增强,适度的运动结合低氧同样可使机体的免疫功能增强,但高强度的运动结合低氧的共同作用,机体将易产生免疫抑制,且低氧对免疫抑制起重要的作用。     

原发性高血压患者醛固酮合酶基因-344C／T多态性与左室结构及功能的关系

目的:分析醛固酮合酶(CYP11B2)基因-344C/T多态性与左室结构和功能的关系。方法:选择2004-10/2005-12于湖北省新华医院高血压专科就诊的68例原发性高血压患者,均符合1999年世界卫生组织/国际高血压联盟高血压诊断标准,男39例,女29例,年龄30￣60岁,平均(43±8)岁,所有患者均对检测项目知情同意。①应用PCR-RELP技术对68例原发性高血压患者的CYP11B2基因-344C/T多态性进行分析。②通过M-型及多普勒超声心动图测定左心室舒张末期内径、左室收缩末期内径、舒张末期室间隔厚度、舒张末期左室后壁厚度、二尖瓣血流舒张早期最大流速以及二尖瓣血流心房收缩期最大流速。③根据左室质量指数判定患者是否存在左室肥厚,左室肥厚的标准:左室质量指数>134g/m2(男性)>110g/m2(女性)。④以性别、年龄、体质量指数、体表面积、血压状况、血脂水平、血浆醛固酮浓度以及醛固酮合酶基因型为自变量,分别以左室舒张末期内径、左室质量为应变量进行分析。⑤以性别、年龄、体质量指数、体表面积、血压状况、血脂水平、血浆醛固酮浓度以及醛固酮合酶基因型为自变量,以左室肥厚发生与否为应变量,进行Logistic回归分析。结果:纳入患者68例全部进入结果分析。①在68例原发性高血压患者中,36例为TT基因型,28例为CT基因型,CC基因型仅为4例。为便于进行统计学分析,将其与CT基因型合并为1组,即根据基因型的不同分为TT基因型组和CT CC基因型组。②CT CC基因型高血压患者的左室舒张期内径、左室质量、左室质量指数分别为(50.2±3.2)mm,(220.8±34.4)g,(123.4±21.5)g/m2,高于TT基因型高血压患者[(48.1±3.2)mm,(197.4±35.5)g,(107.2±15.9)g/m2,t=2.73,2.74,3.54,P<0.01],CT CC基因型的二尖瓣血流舒张早期最大流速/二尖瓣血流心房收缩期最大流速值低于TT基因型高血压患者(0.85±0.20,0.98±0.20,t=2.75,P<0.01)。③在68例高血压患者中,共有23例发生左室肥厚,其中8例为TT基因型、15例为CT CC基因型。④左室肥厚的发生率在2组之间存在显著性差异(χ2=4.60,P=0.03)。CYP11B2基因型与左室舒张末期内径(β=0.290,P=0.007)及左室质量(β=0.294,P=0.006)呈显著性相关。⑤CT CC基因型是未经治疗的原发性高血压患者发生左室肥厚的危险因素(OR值=5.11,P=0.02)。结论:CYP11B2基因-344C/T多态性能影响原发性高血压患者的左室结构及功能,CT CC基因型是未经治疗的原发性高血压患者发生左室肥厚的危险因素。     

Polycystic ovary syndrome in patients on antiepileptic drugs

Objective:This study aims to discuss the prevalence of polycystic ovary (PCO) and Polycystic ovary syndrome (PCOS) in women with epilepsy (WWE) on valproate (VPA), carbamazepine (CBZ), or phenobarbitone (PB), drug naive WWE and women with bipolar affective disorder (BPAD) on VPA.Results:Fifty-two women (52/190; 27.4%) had menstrual disturbances, in which oligomenorrhea was the most common (55.8%). There was a significant difference in the occurrence of PCOS in patients on VPA versus normal population (P = 0.05) and patients on other antiepileptic drugs (AEDs) (P = 0.02). There was, however, no significant difference in the occurrence of PCO between patients on VPA and the untreated epileptic women. VPA group (Epilepsy + BPAD) had a significantly higher occurrence of obesity than other treatment groups (P = 0.043, OR = 2.11).Conclusions:The study observed significantly higher occurrence of PCO in patients on VPA compared to other AEDs and the normal population. The importance of proper clinical evaluation before initiating VPA is highlighted.