Synthesis and Purine P2X Receptor Antagonist Activity of Thiazole Derivatives

The ability of 12 new thiazole derivatives to influence the muscle contractility mediated by purine P2X receptors has been studied in vitro using isolated tissues of rats and guinea pigs. Most of the synthesized compounds did not cause significant effects, but two compounds exhibited pronounced antagonism with respect to P2X-mediated contractility response. These compounds offer a good starting point for the synthesis of new effective antagonists of P2 receptors. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 6, pp. 22 – 25, June, 2005.     

Effect of kanamycin on the cochleas in guinea pigs

Kanamycin (400 mg/kg) was injected daily for 5 days in guinea pigs, the changes in CM and AP responses were recorded. The CM threshold was elevated in 34.5% of the animals and the CM amplitude was reduced when compared with normal animals (P less than 0.005). The AP threshold was elevated in 13.8%. The latency of N1 was increased (P less than 0.001) and the amplitude of N1 reduced at 80 dB (S-L) (P less than 0.001).cAMP and cGMP levels in the organ of Corti and stria vascularis spiral ligament decreased, and the decrease correlated with the changes in auditory function. We consider the reduction of cyclic nucleotides in the cochlea may be important in kanamycin ototoxicity.     

Design of a bifunctional fusion protein for ovarian cancer drug delivery: single-chain anti-CA125 core-streptavidin fusion protein.

We have developed a universal ovarian cancer cell targeting vehicle that can deliver biotinylated therapeutic drugs. A single-chain antibody variable domain (scFv) that recognizes the CA125 antigen of ovarian cancer cells was fused with a core-streptavidin domain (core-streptavidin-VL-VH and VL-VH-core-streptavidin orientations) using recombinant DNA technology and then expressed in Escherichia coli using the T7 expression system. The bifunctional fusion protein (bfFp) was expressed in a shaker flask culture, extracted from the periplasmic soluble protein, and affinity purified using an IMAC column. The two distinct activities (biotin binding and anti-CA125) of the bfFp were demonstrated using ELISA, Western blot and confocal laser-scanning microscopy (CLSM). The ELISA method utilized human NIH OVCAR-3 cells along with biotinylated bovine serum albumin (B-BSA) or biotinylated liposomes, whereas, the Western blot involved probing with B-BSA. The CLSM study has shown specificity in binding to the OVCAR-3 cell-line. ELISA and Western blot studies have confirmed the bifunctional activity and specificity. In the presence of bfFp, there was enhanced binding of biotinylated antigen and liposome to OVCAR-3 cells. In contrast, the control EMT6 cells, which do not express the CA125 antigen, showed minimal binding of the bfFp. Consequently, bfFp based targeting of biotinylated therapeutic drugs, proteins, liposomes, or nanoparticles could be an alternative, convenient method to deliver effective therapy to ovarian cancer patients. Peritoneal infusion of the bfFp-therapeutic complex could also be effective in locally targeting the most common site of metastatic spread.     

Development and optimization of an indirect enzyme-linked immunosorbent assay for the determination of Hexoestrol

An indirect enzyme-linked immunosorbent assay (ELISA) for the detection of hexoestrol (HES) was developed, optimized and validated for the analysis of HES in pork. Many parameters, such as the volume ratio of solution A and solution B, colour developing time, pH value, incubation time, the volume ratio of the standard solution and diluted antiserum, blocking solution, blocking condition, coating solution and coating condition were studied and optimized in the paper. The regression equation of the final inhibition curve is y = - 0.3345x + 1.4955, R²=0.9913. The linear range is 0.1-8.1 ng/ml, and the IC₅₀ is 0.671 ng/ml. The specificity of the assay was evaluated by the cross-reactivity rates of six compounds, of which two structurally related compounds had a relatively higher cross-reactivity rate of 25% and 6%. HES was added into a pork sample at 5 ng/g level and then the sample was extracted. The recovery is between 49.6% and 79.2%, and the variation coefficient is 0.164.     

给药系统

近年来，伴随着药物治疗的快速发展．以药理活性非常强的药物为代表，开发出许多用药时必须给予足够关注的药物，“用药最适化”这一概念逐渐成为人们非常关注的问题。这主要是为了实现用药时的最佳形式。尽可能地根据选择或者需要控制药物的浓度．时间模式。输送到药物的作用表达部位。实现治疗用药的安全性。但是，历来的方法却很难实现这一点，通过利用新的技术和方法调控药物在体内的动态变化，以获得最好治疗效果为中心的药物使用方法和药剂正在开发之中。这就是给药系统，使用可以表达自身概念的语言来命名。虽然都是以各种药物在体内的动态过程作为调控对象，但是还分为①controlled release（调控释放给药）；②开发新的给药途径、克服药物吸收障碍；③靶向给药（targeting）等三个途径。     

Study on hemostatic mechanism of fully soluble hemostatic fiber.

Fully soluble hemostatic fiber (FHF) is made from cotton yarn through a series of chemical reactions with NaOH and chloroacetic acid. The major component of FHF is carboxymethylcellulose. FHF is a kind of biodegradation macromolecule material that can disassociate into a low-molecular-weight compound or a simple substance by hydrolytic and enzymatic courses. The purpose of the present study is to investigate the hemostatic mechanism of FHF. The study indicated that FHF can stop bleeding by physical, chemical and physiological routes. In the physical route, expansion of carboxymethylcellulose in FHF stops bleeding by forming a mechanical clog after contacting with the blood. In the chemical route, the platelets can quickly aggregate around FHF and stimulate releasing and disaggregating reactions, after contacting with the rough surface of FHF, producing thrombus and hemostasis. In the physiological route, gluey particles with negative charges can activate intrinsic coagulation systems by activating the blood coagulation factor XII after FHF dissolution.     

Low HDL‐cholesterol is common in European Type 2 diabetic patients receiving treatment for dyslipidaemia: data from a pan‐European survey

Aims To measure the prevalence of low high‐density lipoprotein (HDL)‐cholesterol (men < 1.03 mmol/l; women < 1.29 mmol/l) in European Type 2 diabetic patients receiving treatment for dyslipidaemia. Methods The pan‐European Survey of HDL‐cholesterol measured lipids and other cardiovascular risk factors in 3866 patients with Type 2 diabetes and 4436 non‐diabetic patients undergoing treatment for dyslipidaemia in 11 European countries. Results Diabetic patients were more likely to be obese or hypertensive than non‐diabetic patients. Most patients received lifestyle interventions (87%) and/or a statin (89%); treatment patterns were similar between groups. Diabetic patients had [means (SD)] lower HDL‐cholesterol [1.22 (0.37) vs. 1.35 mmol/l (0.44) vs. non‐diabetic patients, P < 0.001] and higher triglycerides [2.32 (2.10) vs. 1.85 mmol/l (1.60), P < 0.001]. More diabetic vs. non‐diabetic patients had low HDL‐cholesterol (45% vs. 30%), high triglycerides (≥ 1.7 mmol/l; 57% vs. 42%) or both (32% vs. 19%). HDL‐cholesterol < 0.9 mmol/l was observed in 18% of diabetic and 12% of non‐diabetic subjects. Differences between diabetic and non‐diabetic groups were slightly greater for women. LDL‐ and total cholesterol were lower in the diabetic group [3.02 (1.05) vs. 3.30 mmol/l (1.14) and 5.12 (1.32) vs. 5.38 mmol/l (1.34), respectively, P < 0.001 for each]. Conclusions Low HDL‐cholesterol is common in diabetes: one in two diabetic women has low HDL‐cholesterol and one diabetic man in four has very low HDL‐cholesterol. Management strategies should include correction of low HDL‐cholesterol to optimize cardiovascular risk in diabetes.