新缩瞳剂包公藤甲素人工合成研究

包公藤甲素是从包公藤(Erycibe obtusifolia Benth.)茎中提得的一个新莨菪烷生物碱,具有强烈的缩瞳作用,临床用于治疗青光眼。本文报道用合成的6β-乙酰氧基托品酮为原料,经卤代、水解、还原和N-去甲基化等反应合成包甲素(8)。经光谱测定证实8与天然包甲素的结构完全一致。合成品系外消旋体,其作用机理与天然品相同,而强度则减半。     

Peroxisome proliferator-activated receptor delta agonists attenuated the C-reactive protein-induced pro-inflammation in cardiomyocytes and H9c2 cardiomyoblasts

C-reactive protein (CRP) has emerged as a new marker for cardiovascular diseases. Activation of peroxisome proliferator-activated receptor δ (PPARδ) plays beneficial roles in cardiac disorders. However, the relationship between CRP and PPARδ in cardiac cells remains unclear. This study focused on the underlying molecular mechanisms of CRP and PPARδagonists. Cardiomyocytes and cardiomyoblast cell line (H9c2) were used in different groups: Untreated; 15 μg/ml CRP with or without 1 μM PPARδ agonists (L-165041). CRP increased PPARδ and interleukin-6 expression in cardiomyocytes and H9c2 cardiomyoblasts. NF-κB inducing kinase (NIK) and NF-κB pathway also activated by CRP stimulation. These changes could be inhibited by L-165041 through p38MAPK and c-JNK pathways. However, transfection with siRNA of CD32 CRP receptor did not decrease CRP signaling or reverse the effects of L-165041 in CRP-treated cardiomyocytes and H9c2. Pretreatment with L-165041 attenuated apoptosis induced by hypoxia with or without CRP in H9c2 cardiomyoblasts. CRP up-regulated PPARδ expression in cardiomyocytes and H9c2. L-165041 attenuated CRP-induced pro-inflammatory signaling through p38MAPK and c-JNK in H9c2 cardiomyoblasts. However, PPARδ activation attenuated CRP-induced NF-κB pathway may be independent of CD32. These results may provide new evidence of PPARδ beneficial effects for inflammatory cardiomyopathy.     

Effects of Insulin-Like Growth Factor-1 and Donor Age on Transplantation of Porcine Neonatal Pancreatic Cell Clusters

Porcine neonatal pancreatic cell clusters (NPCCs) isolated from 1- to 3-day-old pigs cured diabetic nude mice more than 14 weeks after transplantation. To shorten the latent period between transplantation and reversal of hyperglycemia, we investigated the effects of insulin-like growth factor-1 (IGF-1) and NPCCs isolated from 1-month-old pigs after transplantation. Pig pancreata were cut into fragments, collagenase digested, and then cultured. Three hundred and 2000 NPCCs were transplanted under the kidney capsule of nondiabetic and diabetic nude mice, respectively. After transplantation, the graft-bearing kidneys were removed to measure insulin content. NPCCs isolated from 1- to 3-day-old pigs were cultured with or without IGF-1 for 6 days. The stimulation index was not significantly different between the 2 groups at 1, 2, or 4 weeks. Moreover, at 4 weeks after transplantation of 300 NPCCs to nondiabetic nude mice yielded comparable graft insulin content as the recipients of NPCCs precultured with or without IGF-1. Two thousand cultured NPCCs isolated from 1-to 3-day-old pigs or 1-month-old pigs were transplanted into diabetic nude mice. The blood glucose levels of diabetic recipients in both groups decreased at the same rate after transplantation, achieving normoglycemia at 8 weeks. The graft insulin content at 12 weeks was not different between the 2 groups. Our data indicated that isolated NPCCs cultured with IGF-1 showed no beneficial effects on insulin secretion and transplantation; NPCCs isolated from 1-to 3-day-old and 1-month-old pigs displayed similar effects on transplantation.     

Intravenous digital subtraction renal angiography: use in screening for renovascular hypertension

Intravenous digital subtraction renal angiography (DSRA) has been compared with conventional angiography only in small, selected series of hypertensive patients. The authors prospectively examined with intravenous DSRA 94 patients at increased risk for renovascular hypertension and compared these studies with conventional angiography. A stenosis of at least one main renal artery was identified with intravenous DSRA in 22 patients and confirmed in 20 patients. No significant stenoses were seen with conventional angiography in any of the 64 patients in whom lesions were not seen with intravenous DSRA. Since inadequate DSRA studies were considered positive for renal artery stenosis, the sensitivity of intravenous DSRA was 100% (25 of 25); specificity, 93% (64 of 69); positive predictive value, 83% (25 of 30); and negative predictive value, 100% (64 of 64). The authors conclude that intravenous DSRA is a sensitive test for identifying stenosis of the main renal arteries and is appropriate to use as a screening test among patients at increased risk for renovascular hypertension.     

MR imaging of facial nerve enhancement in Bell palsy or after temporal bone surgery

The authors evaluated magnetic resonance (MR) images obtained with intravenously administered gadolinium in ten patients who had facial paralysis and no facial nerve tumor. In patients with either Bell palsy (four patients) or facial paralysis after temporal bone surgery (six patients), intratemporal facial nerve enhancement was seen. Facial nerve enhancement on MR images proved to be a nonspecific finding.     

骨关节炎大鼠关节软骨修复与橄榄叶提取物的干预效应

目的:观察橄榄叶提取物对白陶土及鹿角菜胶诱导的大鼠骨关节炎组织炎症的预防作用及对关节软骨的修复作用。方法:试验于2005-11/12在大连医科大学中日合作医药科学研究所进行。实验动物:选择健康雄性SD大鼠80只。实验材料:受试物橄榄叶提取物[由日本国Eisai食品与化学有限公司(日本国东京市)提供]。实验分组及给药:按体质量将大鼠随机分为5组,每组16只。模型对照组,灌胃给予蒸馏水,消炎痛组,灌胃给予消炎痛2mg/kg体质量,其余3组为橄榄叶提取物组,分别给予橄榄叶提取物(活性成分为以羟基酪醇为主的多酚)25,50,100mg/kg体质量灌胃,连续5d。第1天给药后1h,采用白陶土与鹿角菜胶诱发大鼠单发亚急性关节炎。实验评估:①诱发关节炎后1,3,5d,用容积测量法测定每组8只大鼠的左右后肢足跖体积,计算肿胀度,并同时用游标卡尺测定其胫跗骨关节最大径。②诱发关节炎后第5天,测定大鼠足跖伊文思蓝含量。每组的另8只大鼠,在诱发关节炎第5天麻醉后处死,剪下右足跖做组织病理学检查,观察橄榄叶提取物对大鼠骨关节炎中组织炎症的预防作用及对关节软骨的修复作用。结果:80只大鼠全部进入结果分析。①足跖肿胀度及胫跗骨关节径:诱发关节炎后1,3,5d,橄榄叶提取物50mg/kg组和100mg/kg组大鼠的右后足跖肿胀度均明显小于模型对照组大鼠[1d:(46.7±4.2)%,(44.8±6.8)%,(52.5±4.0)%;3d:(40.4±4.8)%,(37.4±5.7)%,(45.0±2.9)%;5d:(34.5±4.8),(31.7±5.3)%,(40.4±4.0)%,P<0.05],橄榄叶提取物25mg/kg体质量组,50mg/kg体质量组,100mg/kg体质量组大鼠的右后胫跗骨关节径与模型对照组大鼠比较差异无显著性(P>0.05)。②足跖伊文思蓝含量:诱发关节炎后第5天,橄榄叶提取物50mg/kg,100mg/kg组大鼠的右后足跖伊文思蓝含量均明显小于模型对照组大鼠(P<0.05)。③组织病理学检查及评分:组织病理学检查可见,与模型对照组比较,橄榄叶提取物50mg/kg组,100mg/kg组大鼠骨关节炎中组织炎症浸润明显减少,软骨组织无破坏,且组织病理学评分也明显小于模型对照组(P<0.05)。结论:橄榄叶提取物在50mg/kg体质量及以上剂量能有效地预防白陶土与鹿角菜胶诱发的大鼠骨关节炎中组织炎症,且对软骨有修复作用。     

Recovery of autologous erythrocytes in transfused patients

A microcapillary method utilizing phthalate esters or an ultracentrifuge method are both capable of separating autologous from homologous erythrocytes in polytransfused patients. The microcapillary technique which is readily adaptable to blood bank laboratories provides a previously unavailable method for defining blood group antigen typings in transfused patients. Such typings are of vital importance in the laboratory evaluation of transfused patients with multiple or weak blood group antibodies.     

亲体肾及造血干细胞联合移植治疗多发性骨髓瘤并发慢性肾功能衰竭

目的:肾功能不全是多发性骨髓瘤并发肾脏疾病的主要表现且决定其预后,探讨1例多发性骨髓瘤并发慢性肾功能衰竭患者行肾及造血干细胞联合移植的治疗体会。方法:南京中医药大学附属医院于2005-04采用肾及造血干细胞联合移植治疗多发性骨髓瘤并发慢性肾功能衰竭患者1例,男性,46岁,经严格的配型及常规检查,发现其胞兄为适合的亲体供者,经供、受者双方同意,结合病情资料并复习文献,先制订出详细治疗方案,然后行亲体肾及造血干细胞联合移植。结果:①供者术后恢复顺利,术后第7天拆线出院,肾功能正常。②受者肾移植术后第3天,血肌酐降至98.2μmol/L,肌酐清除率为45.7mL/min,肾功能恢复正常;干细胞移植术后第13天,查血红蛋白为54g/L、白细胞为4.0×109L-1、中性粒细胞为1.92×109L-1、血小板为30×109L-1,受者造血功能逐步重建,同时抽血行短片段串联重复的嵌合体监测证实受者造血干细胞基因型为完全供者型,说明受者造血功能和免疫功能重建。结论:肾及造血干细胞联合移植治疗多发性骨髓瘤并发慢性肾功能衰竭是一种可行、有效的方法;供、受者的良好配型是移植进行的必备基本条件;另外,术后初期患者处于完全性免疫缺陷状态,故手术后的消毒、隔离措施和抗感染治疗是移植成功的关键。