白花丹参化学成分的研究

从白花丹参(Salvia miltiorrhiza f.alba)中分离出14个二萜醌类化合物,其中2个为新化合物,由光谱分析推定为1,2,15,16-四氢丹参醌(Ⅰ)和丹参醛(Ⅱ);另一个化合物Ⅲ与R₀-090680的结构相同。化合物Ⅰ和Ⅲ对淋巴白血病细胞P₃₈₈均有较强的抑制作用。     

Aged venous thrombi: radioimmunoimaging with fibrin-specific monoclonal antibody

Radioimmunoimaging of fresh canine venous thrombi with a murine monoclonal antibody specific for human and dog fibrin has been reported. Successful imaging of canine deep venous thrombi 1, 3, and 5 days old at the time of antibody injection is reported. Images were positive in all dogs, and the uptake of fibrin-specific antibody was equivalent to that of fresh thrombi.     

Mortality among United States Coast Guard marine inspectors

Work history records and fitness reports were obtained for 1,767 marine inspectors of the U.S. Coast Guard between 1942 and 1970 and for a comparison group of 1,914 officers who had never been marine inspectors. Potential exposure to chemicals was assessed by one of the authors (RP), who is knowledgeable about marine inspection duties. Marine inspectors and noninspectors had a deficit in overall mortality compared to that expected from the general U.S. population (standardized mortality ratios [SMRs = 79 and 63, respectively]). Deficits occurred for most major causes of death, including infectious and parasitic diseases, digestive and urinary systems, and accidents. Marine inspectors had excesses of cirrhosis of the liver (SMR = 136) and motor vehicle accidents (SMR = 107), and cancers of the lymphatic and hematopoietic system (SMR = 157), whereas noninspectors had deficits for these causes of death. Comparison of mortality rates directly adjusted to the age distribution of the inspectors and noninspectors combined also demonstrated that mortality for these causes of death was greater among inspectors than noninspectors (directly adjusted ratio ratios of 190, 145, and 198) for cirrhosis of the liver, motor vehicle accidents, and lymphatic and hematopoietic system cancer, respectively. The SMRs rose with increasing probability of exposure to chemicals for motor vehicle accidents, cirrhosis of the liver, liver cancer, and leukemia, which suggests that contact with chemicals during inspection of merchant vessels may be involved in the development of these diseases among marine inspectors.     

Pharmacokinetics of 18F-labeled fleroxacin in rabbits with Escherichia coli infections, studied with positron emission tomography.

18F-labeled fleroxacin was used to measure the pharmacokinetics of fleroxacin in healthy and infected animals by positron emission tomography (PET) and tissue radioactivity measurements. In all experiments, a pharmacological dose of unlabeled drug (10 mg/kg) was coinjected with the tracer. The pharmacokinetics of [18F]fleroxacin was measured in groups of healthy mice (n = six per group) at 10, 30, 60, and 120 min after injection and in groups of rats with Escherichia coli thigh infections (n = six per group) at 60 and 120 min after injection by radioactivity measurements in excised tissues. In healthy rabbits (n = 4) and in rabbits with E. coli thigh infections (n = 4), tissue concentrations of drug were determined by serial PET imaging over 2 h; after the final image was acquired, animals were sacrificed and concentrations measured by PET were compared with the results of tissue radioactivity measurements. In all three species, there was rapid equilibration of [18F]fleroxacin to significant concentrations in most peripheral organs; low concentrations of drug were detected in the brain. Accumulations of radiolabeled drug in infected and healthy thigh muscles were similar. Peak concentrations of drug of more than three times the MIC for 90% of members of the family Enterobacteriaceae (greater than 100-fold for most organisms) were achieved in all tissues except brain and remained above this level for more than 2 h. Especially high peak concentrations were achieved in the kidney (greater than 75 micrograms/g), liver (greater than 50 micrograms/g), blood (greater than 25 micrograms/g), and bone and lung (greater than 10 micrograms/g).Since the MICs for 90% of all Enterobacteriaceae are <2 micrograms/ml, fleroxacin should be particularly useful in treating gram-negative infections affecting these tissues. In contrast, the low concentration of drug delivered to the brain should limit the toxicity of the drug for the central nervous system.     

Pharmacokinetics of [18F]fleroxacin in healthy human subjects studied by using positron emission tomography.

Positron emission tomography (PET) with [18F]fleroxacin was used to study the pharmacokinetics of fleroxacin, a new broad-spectrum fluoroquinolone, in 12 healthy volunteers (9 men and 3 women). The subjects were infused with a standard therapeutic dose of fleroxacin (400 mg) supplemented with approximately 20 mCi of [18F]fleroxacin. Serial PET images were made and blood samples were collected for 8 h, starting at the initiation of the infusion. The subjects were then treated with unlabeled drug for 3 days (400 mg/day). On the fifth day, infusion of radiolabeled drug, PET imaging, and blood collection were repeated. In most organs, there was rapid accumulation of radiolabeled drug, with stable levels achieved within 1 h after completion of the infusion. Especially high peak concentrations (in micrograms per gram) were achieved in the kidney (> 34), liver (> 25), lung (> 20), myocardium (> 19), and spleen (> 18). Peak concentrations of drug more than two times the MIC for 90% of Enterobacteriaceae strains tested (> 10-fold for most organisms) were achieved in all tissues except the brain and remained above this level for more than 6 to 8 h. The plateau concentrations in tissues (2 to 8 h, in micrograms per gram +/- standard error of the mean) of drug were as follows: brain, 0.83 +/- 0.032; myocardium, 4.53 +/- 0.24; lung, 5.80 +/- 0.48; liver, 7.31 +/- 0.33; spleen, 6.00 +/- 0.47; bowel, 3.53 +/- 0.74; kidney, 8.85 +/- 0.64; bone, 2.87 +/- 0.29; muscle, 4.60 +/- 0.33; prostate, 4.65 +/- 0.48; uterus, 3.87 +/- 0.39; breast, 2.68 +/- 0.11; and blood, 2.35 +/- 0.09. Concentrations of fleroxacin in tissue were similar in males and females, before and after pretreatment with unlabeled drug.     

福建省高校贫困大学生心理健康水平与人格特征

目的:了解贫困生的心理健康现状和人格特征。方法:于2005-09/11随机抽取福州大学、福建师范大学、福建农林大学、福建中医学院、闽江学院2002-2004级学生2400名。男1478名,女922名,平均(20±1)岁。根据2004-11-04福建省福州市政府办公厅正式下发的《福州市人民政府关于提高城区城镇及农村居民最低生活保障标准的通知》中的规定,即城镇多人户每人每个月210元、单人户230元;农村多人户每人每月155元、单人户175元,本文把家庭人均月收入较少,有一定数额债务,只能缴纳部分学杂费,基本生活费接近于当地居民最低生活保障线(如上规定,本文以230元为基准)的学生定为“贫困生”。采用精神症状自评量表和16种人格因素问卷对高校贫困生的心理健康和人格特征进行调查。结果:发放问卷2400份,收回有效问卷2111份。其中贫困生539份。①贫困生精神症状自评量表的躯体化、强迫、人际敏感、抑郁、焦虑、敌对、恐怖、偏执、精神病性、其他、总症状指数得分均高于非贫困生(贫困生:1.61±0.56,2.02±0.64,1.92±0.63,1.71±0.56,1.65±0.58,1.73±0.68,1.57±0.62,1.81±0.65,1.67±0.54,1.76±0.63,1.74±0.49;非贫困生:1.48±0.45,1.89±0.56,1.79±0.57,1.61±0.51,1.54±0.50,1.61±0.56,1.44±0.49,1.66±0.54,1.54±0.46,1.61±0.53,1.62±0.41,P<0.01)。男女贫困生之间各因子分差异均不显著(P>0.05)。②福建省高校贫困大学生的心理问题检出率为24.5%,其中轻度心理问题(2≤因子分<3)为22.6%;中度心理问题(3≤因子分<4)为1.7%;重度心理问题(4≤因子分<5)为0.2%。心理问题以强迫、人际敏感、偏执、忧郁、敌对、焦虑等心理问题最为突出。③16种人格因素问卷中,贫困生乐群性、聪慧性、兴奋性、敏感性、怀疑性上得分低于非贫困生,有恒性、忧虑性、独立性得分高于非贫困生(贫困生:5.20±1.77,4.70±1.93,5.49±1.87,6.46±1.79,4.29±1.71,4.60±1.63,6.64±1.82,5.07±1.82;非贫困生:5.39±1.74,4.95±1.99,5.82±1.91,6.66±1.75,4.55±1.77,4.36±1.69,6.43±1.94,4.89±1.77,P<0.05～0.01)。④影响贫困生心理健康水平的主要人格因素按其影响作用从大到小有怀疑性、忧虑性、稳定性、兴奋性、自律性。结论:福建省高校贫困大学生的心理健康状况令人担忧,其人格特征对心理健康水平有重要影响。     

骨髓间充质干细胞向胰岛素分泌细胞诱导分化的动态观察

目的:探讨体外诱导骨髓间充质干细胞向胰岛素分泌细胞分化的可能性,并观察其动态变化。方法:实验于2005-09/2007-03在山东大学齐鲁医院完成。①标本来源:骨髓标本15例来自山东大学齐鲁医院成人骨髓检查结果正常者,均签署捐献同意书。②实验方法:无菌条件下取骨髓2.0～5.0mL,采用percoll分离液和贴壁法获得纯化的成人骨髓间充质干细胞。③实验评估:流式细胞仪行细胞表面抗原检测,在适当的条件下诱导其分化为成骨细胞和脂肪细胞。采用两步法向胰岛素分泌细胞诱导,观察其在碱性成纤维细胞生长因子、活化素A、胰岛素样生长因子、尼克酰胺等因子刺激下向胰岛素分泌细胞分化的动态变化。双硫踪染色鉴定胰岛样细胞团,酶联免疫吸附试验检测细胞分泌胰岛素的情况,RT-PCR检测胰岛细胞特异基因的表达。结果:①骨髓间充质干细胞的生长特性及免疫表型:分离培养获得的贴壁细胞,呈形态均一的梭形,流式细胞仪检测CD34、CD45表达阴性,CD29、CD44表达阳性。②向成骨细胞和脂肪细胞的诱导分化:此类细胞经茜素红染色、油红O染色均呈阳性,可诱导分化为成骨细胞和脂肪细胞。③向胰岛素分泌细胞的诱导分化:第1步诱导后出现细胞簇,双硫腙染色不着色,胰岛素分泌量少,仅检测到PDX-1基因的表达,证实其为胰岛前体细胞。第2步诱导后细胞簇数目逐渐上升,至诱导14d大部分细胞簇经双硫腙染色都呈红色。④诱导后培养上清中胰岛素含量:诱导第3,7,14,21天的胰岛素分泌量分别为(15.3±4.9),(34.1±5.6),(40.4±5.3),(39.8±5.1)mU/L。⑤胰岛细胞特异基因的表达:诱导7d仅检测到PDX-1基因的表达,insulin1、insulin2和Glut2基因均不表达。诱导14,21d检测到insulin2、PDX-1基因表达,insulin1基因弱表达,Glut2基因不表达。结论:体外分离、纯化得到的骨髓间充质干细胞诱导7d可分化出胰岛前体细胞,不具功能性;诱导14d后可成功地分化出成熟的具有功能性的胰岛素分泌细胞。