Synthesis and Properties of Haptens for the Development of Radioimmunoassays for Thioridazine,Mesoridazine, and Sulforidazine

For the separate development of radioimmunoassay procedures for thioridazine and its two major active metabolites, mesoridazine and sulforidazine, three haptens, respectively, 2-methylthio-, 2-methylsulfinyl-, and 2-methylsulfonyl-substituted 10-[2-[l-(2-carboxyethyl)-2-piperidinyl]ethyl]-10H-phenothiazine, were synthesized and characterized. Thioridazine hapten was coupled to bovine serum albumin, whereas the haptens for mesoridazine and sulforidazine were coupled to porcine thyroglobulin. The number of hapten residues per mole of carrier protein was determined in each case by an ultraviolet spectrophotometric method. Polyclonal antibodies to each hapten–protein conjugate were obtained in rabbits, and titers of the antisera were checked by evaluating their binding characteristics to the appropriate tritiated analyte. A hapten for the ring sulfoxide metabolite of thioridazine was also synthesized.     

Radiation dose reduction during hysterosalpingography: an application of scanning-beam digital radiography

Hysterosalpingography was performed in 31 patients by means of a low-dose scanning-beam digital radiographic system. The technique permits adequate evaluation of gynecologic abnormalities while allowing significant reduction in radiation: 2.4-mR (6.1 X 10(-7) C/kg) exposure to the skin and 0.7-mrad (7 X 10(-6) Gy) mean dose to the ovaries per image obtained. Sixteen patients demonstrated readily recognizable and documented abnormalities, corroborated by laparoscopy, laparotomy, or other supportive evidence.     

Elevated levels of acute phase plasma proteins in major depression.

Levels of acute phase and other plasma proteins were measured in 21 men with major depression, 28 men with alcohol dependence, and 12 men who acted as controls. The depressed men had significantly elevated levels of the acute phase proteins, haptoglobin and alpha-1-antichymotrypsin, and of immunoglobulin G. The elevations in haptoglobin and alpha-1-antichymotrypsin were highly correlated with each other, and were correlated with the severity of depression and negatively correlated with the thyroid stimulating hormone response to thyrotropin. The alcoholic men had elevated haptoglobin levels, but significantly decreased levels of immunoglobulin G. These findings provide further evidence for an inflammatory response during depression.     

F-19 MR imaging of glucose metabolism in the rabbit

Noninvasive metabolic magnetic resonance (MR) imaging reflecting glucose metabolism in the aldose-reductase-sorbitol (ARS) pathway was performed in the rabbit head; after administration of the fluorinated glucose analogue 3-fluoro-3-deoxy-D-glucose (3FD-glucose), fluorine-19 images were generated. Images of 3FD-glucose showed significant 3FD-glucose uptake by adipose tissue, indicating its buffering effects in case of excess loads of glucose. Images of 3-fluoro-3-deoxy-D-sorbitol (3FD-sorbitol) demonstrated the spatial distribution of aldose reductase activities and significant sorbitol accumulation in the lens. Images of 3-fluoro-3-deoxy-D-fructose (3FD-fructose) showed preferential uptake of fructose by muscle tissue. The extremely low toxicity of 3FD-glucose indicates promise for its clinical application in metabolic imaging.     

大鼠移植心脏组织中血小板衍生生长因子A mRNA表达及雷帕霉素的干预效应

目的:血小板衍生生长因子在平滑肌细胞的表型转化过程中起重要作用。观察大鼠移植心脏组织中血小板衍生生长因子AmRNA表达的变化及雷帕霉素的干预效应。方法:实验于2005-10/2006-01在中南大学湘雅二医院胸心外科实验室完成。将60只SD大鼠、24只Wistar大鼠按随机数字表法分为3组:①同系移植组:供、受体各12只,均为SD大鼠。②异系移植组:供体为Wistar大鼠(n=24),受体为SD大鼠(n=24),受体大鼠随机分为雷帕霉素组(n=12)和环孢霉素组(n=12),术后分别给予雷帕霉素1.25mg/(kg·d)灌胃及环孢霉素A10mg/(kg·d)皮下注射,给药60d,给药结束后留取移植心脏待检。③另12只SD大鼠直接取心脏组织作为正常对照组。指标检测:①对移植心脏组织行VanGieson染色后采用Miassystem4.1医学图像分析管理系统分析血管狭窄程度。②应用反转录-聚合酶链反应检测血小板衍生生长因子AmRNA在移植心脏组织中的表达情况。结果:36只受体SD大鼠及12只正常SD大鼠全部进入结果分析,无脱失。①同系移植组、环孢霉素组及雷帕霉素组大鼠的冠状动脉狭窄指数均显著高于正常对照组[(13.12±0.72)%,(62.45±8.12)%,(28.91±3.24)%,(0.09±0.02)%(P<0.01)],环孢霉素组及雷帕霉素组高于同系移植组(P<0.05),环孢霉素组高于雷帕霉素组(P<0.01)。②正常对照组、同系移植组、环孢霉素组及雷帕霉素组大鼠的血小板衍生生长因子AmRNA相对含量分别为0.19±0.06,0.21±0.08,1.12±0.22及0.47±0.11,环孢霉素组、雷帕霉素组显著高于同系移植组(P<0.01),环孢霉素组高于雷帕霉素组(P<0.05)。结论:血小板衍生生长因子AmRNA的高表达与移植心脏的血管硬化有关;雷帕霉素具有预防大鼠心脏移植物血管病变的作用,其作用可能与抑制心脏组织中血小板衍生生长因子AmRNA的表达有关。     

Intersubject variation in the pharmacokinetics of chlorpromazine in healthy men

Interpatient variation in response to therapy with antipsychotic drugs is a major problem. This study was designed to assess the extent of variation in disease-free subjects in whom known sources of variance were controlled as much as possible. The subjects were 32 healthy, nonsmoking males of European origin, aged 18-25 years, and weighing no more than +/- 15% from the ideal weight for height. After an overnight fast, each subject ingested 50 mg of chlorpromazine. Plasma samples were harvested over a 24-hour period during which the subjects were on a standardized, caffeine-free diet. Plasma levels of chlorpromazine were measured by gas-liquid chromatography-mass spectrometry. The results showed wide intersubject variation in all pharmacokinetic parameters including maximum concentration, area under the curve, and oral clearance. Furthermore, none of the data were normally distributed. For each pharmacokinetic parameter, the distribution was leptokurtotic and skewed. As a consequence, the geometric means provided better estimates of central tendency than the arithmetic means. It seems that a major proportion of intersubject variation is an inherent problem that cannot be accounted for by differences in race, diet, smoking habits, or concomitant drug ingestion.