他克林的合成研究

目的：合成抗早老性痴呆药他克林。方法：以邻氨基苯甲酸为原料,经缩合,氯化,氨化反应,制得他克林,结果：每步反庆均经改进,总收率达40．7％,所得产品熔点,IR,^1HNMR光谱数据,与文献报道值一致。结论：本工艺路线方法简单,原料易得,易工业化生产。     

Radioimmunotherapy of relapsed B-cell lymphoma with yttrium 90 anti- idiotype monoclonal antibodies

Tumor-specific anti-idiotype (anti-Id) monoclonal antibodies (MoAbs) to B-cell lymphomas have been administered to patients, resulting in significant clinical responses. However, clinical responses have been limited by the emergence of Id-negative lymphoma. To overcome the problem of tumor heterogeneity, we conducted a pilot evaluation of the safety and effectiveness of yttrium 90 (90Y)-labeled anti-Id and shared Id (sId) MoAbs in non-Hodgkin's B-cell lymphoma. Nine patients with relapsed B-cell lymphoma in whom tumor was successfully targeted with 111In-labeled anti-Id MoAb were treated with 90Y-labeled anti-Id MoAb. A total of 19 courses (one to four per patient) were administered using 1,000 to 2,320 mg unlabeled clearing MoAb and 10 to 54 mCi 90Y MoAb per patient. Two of nine patients had a complete response, one a partial response, three stable disease, and three disease progression. Time to progression varied from 1 to 12 months. Toxicities were predominately hematologic, and only one patient developed infection and required transfusion. At progression, three of five assessable patients had Id- positive lymphoma and two had Id-negative lymphoma. Human antimouse antibodies (HAMA) did not develop in the patients after treatment. 90Y anti-Id MoAbs demonstrated excellent in vivo stability, produced significantly tumor regression in three of nine patients, exhibited acceptable toxicities, and elicited no HAMA formation. Further investigation of repetitive, low-dose 90Y anti-Id and MoAb therapy is warranted; however, the advantages of a pan B MoAb may prove the latter to be the agent of choice for the radio immunotherapy of B-cell lymphoma.     

Reduction of angiocidin contributes to decreased HepG2 cell proliferation

Background

Angiocidin plays a key role in angiogenesis and tumor progression. High angiocidin expression is detected in some kind of solid tumors and tumor vascular endothelial cells. Several reports have shown the inhibition of angiogenesis and tumor growth caused by angiocidin. However, the role of angiocidin in liver cancers growth is still unclear.

Objectives

To examine angiocidin expression in SMMC-7221 and HepG2 cells and the role of angiocidin in liver cancer cell growth.

Methods

RT-PCR and western blot are used in this study to detect angiocidin expression. SiRNA and MTT experiments are used in exploring the role of angiocidin in tumor cell growth.

Results

Our study showed high angiocidin expression in two kinds of liver cancer cells. Angiocidin protein production in HepG2 cells were reduced significantly by siRNA. When HepG2 cells were transfected with siRNA-angiocidin, these cells showed very low proliferation activity compared with control cells. Our study suggests that reduction of angiocidin may contribute to decreased proliferation activity in liver cancer cells.

Conclusion

Angiocidin is highly expressed in liver cancer cells, and it may play a key role in tumor growth of liver cancers.     

Presentation of Primary Open Angle Glaucoma (POAG) at Lions Sight First Eye Hospital in Blantyre,Malawi

Objective

Primary open angle glaucoma (POAG) is the most common type of glaucoma in Africa. We carried out a study to determine the clinical presentation pattern of patients with primary open angle glaucoma (POAG) at a tertiary hospital in Malawi.

Design

A cross-sectional study

Setting

Lions Sight First Eye Hospital—a major referral and teaching state eye hospital in Blantyre, Malawi

Subjects

Study participants were newly diagnosed POAG patients at specialist eye clinic during study period.

Results

A total of 60 POAG patients were recruited into the study. The mean age was 58.7 years (SD= 16.6, range 18 - 86). There were more male (44, 73.3%) than female (16, 27.7%) patients. The majority of patients (73%) presented one year after onset of visual symptoms. Twenty-six patients (43%) had unilateral blindness (visual acuity < 3/60; WHO classification), while nine patients (15%) presented with bilateral blindness. A vertical cup-to-disc ratio (CDR) of 0.8 or worse was seen in 92 eyes (79%). The mean intraocular pressure (IOP) reading was 35.5 mmHg (SD 13.30). Of the thirty-three eyes that successfully underwent visual field analysis, very advanced defects were recorded in 12 eyes (36%).

Conclusion

This study demonstrates delayed presentation and male predominance among POAG patients at a tertiary eye hospital in Malawi. Glaucoma intervention programmes should aim at identifying patients with treatable glaucoma with particular attention to women.     

Decrease in serum matrix metalloproteinase-9 and matrix metalloproteinase-3 levels in Zucker fa/fa obese rats after treatment with swertiamarin

Diabetes mellitus encompasses a group of chronic metabolic conditions associated with cardiovascular complications such as atherosclerosis, cardiomyopathy and nephropathy. In the present study, the authors investigated the beneficial effects of swertiamarin in diabetes and its associated cardiovascular complications in Zucker fa/fa rats. Six male Zucker fa/fa rats in each group were treated for 28 days with swertiamarin (75 mg/kg/day, intraperitoneally) or pioglitazone (30 mg/kg orally). Blood samples were collected and evaluated for several parameters. Elevated serum glucose, triglyceride, nonesterified free-fatty acid and cholesterol levels were found in untreated Zucker fa/fa rats. Serum matrix metalloproteinase (MMP)-9 and MMP-3 levels were also found to be significantly higher in untreated Zucker fa/fa rats. Treatment with swertiamarin significantly (P<0.05) reduced serum glucose, triglyceride, nonesterified free-fatty acid and cholesterol levels, and also reduced serum MMP-9 and MMP-3 levels compared with untreated rats. Swertiamarin also significantly (P<0.05) decreased serum levels of urea compared with untreated Zucker fa/fa rats. Overall, the data suggest that swertiamarin produced beneficial effects with respect to diabetes-induced cardiovascular complications such as atherosclerosis and nephropathy. A swertiamarin-induced decrease in serum MMP-9 and MMP-3 levels is one of the possible mechanisms responsible for improvement of these complications.     

异戊塞平和克塞平对大鼠脑内各受体亲和力的比较及慢性给药后的受体下调作用

用放射配体受体结合法测定表明:克塞平对多巴胺D₁受体的亲和力较异戊塞平高近20倍。两药对其它各受体的亲和力差別不大。慢性给药后,异戊塞平和克塞平均能使大鼠脑皮层5-HT₂受体的密度显著下降,而亲和力变化不明显。这种下调5-HT₂受体的作用发生在给异戊塞平后1～2周之间,给克塞平后的2～3周之间。慢性给药3周,异戊塞平和克塞平均未使大鼠脑皮层的β受体密度及亲和力产生显著变化。     

Development of a high affinity and stereoselective photoaffinity label for the D-1 dopamine receptor: synthesis and resolution of 7-[125I]iodo-8-hydroxy-3-methyl-1-(4'-azidophenyl)-2,3,4,5-tetrahydro- 1H-3-benzazepine

In an earlier paper, we reported the development of (+-)-7-iodo-8-hydroxy-3-methyl-1-(4'-azidophenyl)-2,3,4,5-tetrahydro- 1H-3-benzazepine (I-MAB) and its 125I analogue ([125I]I-MAB) as selective, high affinity photoaffinity labels for the D-1 dopamine receptor. In this report, we now describe the complete synthesis and resolution of I-MAB and the pharmacological characterization of the stereoisomers in canine striatal membranes. R-(+)-I-MAB showed highly specific dopamine D-1 receptor binding (KD = 0.28 nM) and binds selectively and stereoselectively to the D-1 receptor. These results further confirm the previous suggestion that, in the benzazepine series of DA agonists and antagonists, the activity principally resides in the R-(+) enantiomer, the S-(-) enantiomer being considerably less potent or inactive. Moreover, R-(+)-[125I]I-MAB, upon photolysis, identifies the ligand-binding subunits of the neuronal D-1 receptor, with an apparent Mr of 74,000, 62,000, and 51,000 as assessed by autoradiography following sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Photoincorporation of R-(+)-[125I]I-MAB into these polypeptides was stereoselectively blocked by D-1 dopaminergic ligands with an appropriate pharmacologic profile for the receptor. R-(+)-[125I]I-MAB should thus prove to be a useful stereoselective photoaffinity label for the further characterization of the D-1 receptors.     

雷公藤内酯醇的结构修饰

为降低雷公藤内酯醇的毒性,寻找高效低毒的抗炎免疫化合物,对雷公藤内酯醇(trip-tolide,1)的结构进行了修饰,合成了九个雷公藤内酯醇衍生物。初步活性测定显示雷公藤氯内酯(tri-pchlorolide,2)和雷公藤溴内酯醇(tripbromolide,3)的免疫抑制活性与雷公藤内酯醇近似,但毒性有所降低。其他化合物的活性大大低于雷公藤内酯醇。