6-(4-酰基-1-哌嗪乙酰氨基)-3,4-二氢-2(1H)-喹啉酮类化合物的合成及正肌力活性初探

目的 :寻找具有正性肌力活性的化合物。方法 :根据文献报道的二氢喹啉酮类正性肌力药物的结构特点 ,设计、合成了其类似物。以苯胺为起始原料经多步合成 ,对所得化合物用离体豚鼠心脏与主动脉观察了心肌收缩力、扩血管作用及心率。结果 :合成了 1 0个 6 ( 4 酰基 1 哌嗪乙酰氨基 ) 3 ,4 二氢 2 ( 1H) 喹啉酮类化合物 ( 4a～ 4j) ,均为未见文献报道的化合物。结论 :初步药理试验表明 ,化合物 ( 4h)显示了正性肌力及扩血管活性。     

Postamputation neuromas and other symptomatic stump abnormalities: detection with CT

One of the potentially troublesome sequelae of limb amputations is the development of stump neuromas at the severed ends of major nerves. The ability to define them and to distinguish them from other causes of stump pain is of considerable clinical significance. Computed tomography was performed on ten lower limb amputees with stump pain. Five patients had neuromas that were manifest as focal or generalized alteration in the caliber, size, or contour of the nerve trunk in the affected stump. The remaining five patients each had an abnormality detected; these abnormalities included heterotopic bone formation, popliteal artery aneurysm, lipoma, scar tissue, and abscess in the contralateral limb.     

普通教师与特殊教育教师职业倦怠和教学效能感的比较

目的:比较普通教育教师和特殊教育教师的职业倦怠与教学效能感特点,分析其影响因素。对象:①采用Maslach教师职业倦怠问卷和教师教学效能感量表于2006-06/09根据年龄、性别、教龄及是否担任班主任等对重庆市200名普通教育教师、100名特殊教育教师的职业倦怠和教学效能感的现状进行调查。Maslach教师职业倦怠问卷包括22个条目共3个维度:情绪衰竭、去人性化、低成就感。教师教学效能感量表共27个条目,包括一般教育效能感和个人教学效能感,各个维度总分相加形成总效能感。两个量表/问卷各题项均采用5点计分,分数越高,表示职业倦怠感越严重,教学效能感越强。②计量差异比较采用t检验和方差分析,并应用相关分析以及逐步回归分析统计学方法。结果:普通中小学共发放200份问卷,收回有效问卷176份,有效率占91.7%;特殊教育学校共发放100份问卷,收回有效问卷76份,有效率为80%。①职业倦怠和教学效能评分差异:普教与特教教师之间的职业倦怠感存在着显著的差异(t=2.837,P<0.01),普教教师与特教教师职业倦怠感的差异主要体现在情感衰竭维度上[普教:(3.16±0.71)分,特教:(2.63±0.65)分,t=5.535,P<0.01];去人性化和低成就感维度上无显著差异。普教教师的一般教育效能感得分显著低于特教教师[(3.40±0.66),(3.70±.57)分,t=-3.391,P<0.01]。②职业倦怠感和教学效能的人口学差异:除5年及以下教龄的教师外,普教与特教教师在性别、教龄及是否班主任等方面存在着情感衰竭方面的显著差异(P<0.05～0.01)。除6～10年教龄的教师之间外,普教与特教之间的一般教育效能感也存在明显差异(P<0.05～0.01),普教低于特教。同时,女教师之间的个人教学效能感存在着显著差异,普教女教师高于特教女教师。③相关性:普教与特教教师的教学效能感与职业倦怠都呈明显负相关(r=-0.515,-0.502,P<0.01),但特教在情感衰竭维度上的相关性不如普教强(r=-0.320,-0.240,P<0.01,0.05)。④逐步回归分析结果:一般教育效能感对普教的情感衰竭和去人性化程度、对特教教师的低成就感预测性较强(Beta=-0.321,-0.274,-0.404,P<0.01);个人教学效能感同时预测着普教和特教的去人性化和低成就感(普教:Beta=-0.286,-0.360,P<0.01;特教:Beta=-0.480,-0.585,P<0.01)。是否班主任因素对普教教师的情感衰竭和去人性化预测作用明显(Beta=-0.283,-0.179,P<0.01,0.05),而教龄对特教教师的去人性化和低成就感的预测作用明显(Beta=0.258,0.212,P<0.05)。结论:①普教与特教教师的职业倦怠感中的情感衰竭维度和教学效能感中的一般教育效能感有明显差别。②普教与特教教师的职业倦怠感和教学效能感存在性别、教龄及是否班主任的差别。③教学效能感在普教与特教教师中对职业倦怠各因素的预测作用不尽相同。是否班主任因素对普教教师的情感衰竭和去人性化预测作用明显,而教龄对特教教师的去人性化和低成就感的预测作用明显。     

重组人粒细胞-巨噬细胞集落刺激因子乳酸链球菌表达载体的构建

目的:构建重组人粒细胞-巨噬细胞集落刺激因子乳酸链球菌表达载体,为进一步研究人粒细胞-巨噬细胞集落刺激因子在乳链菌的表达及其治疗价值奠定基础。方法:实验于2005-04/2006-03在南方医科大学南方医院消化病研究所完成。①载体pNCSF的构建:将质粒集落刺激因子及含有P59启动子、USP45蛋白信号肽的pNBC1000质粒分别加入BamH Ⅰ和Pst Ⅰ进行双酶切,并用Apa Ⅰ、Sac Ⅰ进行双酶切鉴定,重组质粒命名为pNCSF。②SDGFP的TA克隆及载体pNCSFGFP的构建:将经过优化适合在乳链菌表达的人粒细胞-巨噬细胞集落刺激因子基因克隆于含有P59启动子、USP45蛋白信号肽的pNBC1000载体,得到重组质粒pNCSF;同时设计上下游引物经PCR扩增增强荧光表达蛋白(EGFP),TA克隆后经测序验证,再连接于pNCSF获得重组质粒pNCSFGFP。③载体pTRCSF、pTRCSFGFP的建立:将获得的pNCSF和pNCSFGFP进一步克隆于穿梭载体pTR1001c,以获得人粒细胞-巨噬细胞集落刺激因子乳链菌表达载体pTRCSF及pTRCSFGFP。结果:①载体pNCSF构建结果:酶切鉴定产物经1.0%的琼脂糖凝胶电泳后,发现有(含启动子P59、信号肽USP45、人粒细胞-巨噬细胞集落刺激因子)720bp的目的片段。②SDGFP的TA克隆及载体pNCSFEGFP的构建结果:SDGFP阳性克隆产物经EcoRⅠ酶切鉴定得到775bp目的片段。pNCSFEGFP酶切鉴定产物经1.0%的琼脂糖凝胶电泳后,发现有(含启动子P59、信号肽USP45、人粒细胞-巨噬细胞集落刺激因子、SDGFP)1495bp的目的片段。③穿梭质粒pTRCSF、pTRCSFGFP酶切鉴定结果:经Xba Ⅰ、Sac Ⅰ进行双酶切鉴定,分别得到约717bp、1492bp大小目的片段。结论:获得了人粒细胞-巨噬细胞集落刺激因子乳链菌表达载体pTRCSF及pTRCSFGFP,并经酶切鉴定和测序证实。     

Altered activity of 11beta-hydroxysteroid dehydrogenase types 1 and 2 in skeletal muscle confers metabolic protection in subjects with type 2 diabetes

CONTEXT: There is little information regarding the regulation of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes in skeletal muscle in the setting of type 2 diabetes. OBJECTIVE: Our objective was to investigate whether there is differential mRNA expression and enzyme activity of 11beta-HSD1 and 11beta-HSD2 in the skeletal muscle of diabetic subjects compared with controls at baseline and in response to dexamethasone. DESIGN: Participants underwent muscle biopsy of vastus lateralis at baseline and after dexamethasone. SETTING: The study took place at a university teaching hospital. PARTICIPANTS: Twelve subjects with type 2 diabetes and 12 age- and sex-matched controls participated. INTERVENTION: Subjects were given oral dexamethasone, 4 mg/d for 4 d. MAIN OUTCOME MEASURES: We assessed 11beta-HSD1, 11beta-HSD2, and H6PDH mRNA levels by quantitative RT-PCR and enzyme activity by percent conversion of [(3)H]cortisone and [(3)H]cortisol, respectively. RESULTS: At baseline, mRNA levels were similar in diabetic and control subjects for 11beta-HSD1, 11beta-HSD2, and H6PDH. 11beta-HSD1 activity was reduced in diabetic subjects (percent conversion of [(3)H]cortisone to [(3)H]cortisol was 11.4 +/- 2.5% vs. 18.5 +/- 2.2%; P = 0.041), and 11beta-HSD2 enzyme activity was higher in diabetic subjects (percent conversion of [(3)H]cortisone to [(3)H]cortisol was 17.2 +/- 2.6% vs. 9.2 +/- 1.3%; P = 0.012). After dexamethasone, 11beta-HSD1 mRNA increased in both groups (P < 0.001), whereas 11beta-HSD2 mRNA decreased (P = 0.002). 11beta-HSD1 activity increased in diabetic subjects (P = 0.021) but not in controls, whereas 11beta-HSD2 activity did not change in either group. At baseline, there was a significant negative correlation between 11beta-HSD1 and 11beta-HSD2 enzyme activity (r = -0.463; P = 0.026). CONCLUSIONS: The activities of skeletal muscle 11beta-HSD1 and 11beta-HSD2 are altered in diabetes, which together may reduce intracellular cortisol generation, potentially conferring metabolic protection.     

Effects of CRL 41034 on the adrenergic neuroeffector interaction in the canine saphenous vein

Experiments were designed to determine the effect of CRL 41034, a buflomedil analogue, on the adrenergic responsiveness of canine veins. Rings of saphenous vein (without endothelium) were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution at 37 degrees C. CRL 41034 produced a concentration-dependent inhibition of the contractions evoked by the alpha adrenergic agonists norepinephrine, phenylephrine and UK 14304 which was insensitive to the blockade of neuronal uptake by cocaine. CRL 41034 was more potent in inhibiting the concentration-dependent contractions evoked by UK 14304 than those by phenylephrine and the antagonism it caused against the response to UK 14304 fulfilled the criteria for competitivity. CRL 41034, at 10(-5) M significantly depressed, and at 10(-4) M abolished the contractions induced by electrical stimulation of the adrenergic nerves and those evoked by the indirect sympathomimetic amine tyramine. Strips of canine saphenous vein were superfused after incubation with [3H] norepinephrine. During sympathetic nerve activation, CRL 41304 increased the stimulation-evoked overflow of [3H] norepinephrine and 3-methoxy-4-dihydroxyphenylglycol; in the presence of rauwolscine the compound only increased the stimulation-evoked overflow of 3,4-dihydroxyphenylglycol. These experiments suggest that the major vascular effects of CRL 41034 in canine veins are blockade of alpha 2-adrenoceptors on vascular smooth muscle, and inhibition of prejunctional alpha 2-adrenoceptors on adrenergic nerve endings.     

Vascular complications of prolonged intra-aortic balloon counterpulsation in cardiac surgical patients

Background. Use of intra-aortic balloon pump (IABP) is associated with certain vascular complications, which are likely to develop more frequently in patients where IABP is used for prolonged period. The present study was undertaken to analyze vascular complications after prolonged IABP use in patients undergoing various cardiac surgical procedures. Methods. Between January 1995 and February 2001, a total of 1130 patients (7.4% of all adult patients undergoing cardiac procedures) required IABP counterpulsation, out of which 220 patients required IABP for more than 4 days. The vascular complications in these patients were studied. The IABP was inserted by percutaneous technique in 211 (95.5%) patients. The mean age of the patients was 57.5±9.5 years and 15% patients were female. The prevalence of peripheral vascular disease was 11.8%. Results. The duration of IABP therapy ranged from 5 days to 21 days with mean duration of 9.71±4.29 days. A total of 41 complications developed in 38 (17.3%) patients. Acute lower limb ischemia, requiring urgent surgical intervention, was the commonest major complication, which developed in 17 patients. This required thromboembolectomy in 11 patients and femoro-femoral bypass in 3 patients. One patient developed gangrene of the leg, requiring below knee amputation. On multivariate analysis, peripheral vascular disease, preoperative serum creatinine, surgery for LV aneurysm and unstable angina and hemodynamic instability (as the indications for IABP) were found as the predictors of vascular complications. Conclusions. Prolonged use of IABP counterpulsation is associated with significant incidence of vascular complications. Proper assessment of peripheral circulation before IABP insertion and appropriate management of ischemic complications are important to avoid limb loss to the patient.     

THE HETEROGENEITY OF 11-β-HYDROXYSTEROID DEHYDROGENASE ACTIVITIES IN THE RAT HIPPOCAMPUS IMPLIES A COMPLEX REGULATION OF STEROID HORMONE ACTION

1. The rat hippocampus 11-beta-hydroxysteroid dehydrogenase (11-HSD) displays a different substrate specificity to that of other tissues. S1 nuclease analysis was used to determine whether the hippocampal messenger RNA is different from that found in other tissues. 2. S1 nuclease analysis using probes spanning the full length cDNA demonstrated that there were no differences in sequence between the hippocampal 11-HSD and the enzyme originally cloned from the liver. 3. These results suggest that there may be multiple 11-HSD isoforms in the hippocampus with different substrate specificities.     

Age-estimations of rats based on the average lateral diffusion constant of hepatocyte membrane proteins as revealed by fluorescence recovery after photobleaching

A method has been developed recently for measuring the average lateral diffusion constant of the proteins (D) in the cell membrane of hepatocytes in liver smears by fluorescence recovery after photobleaching (FRAP). A peroxide-induced autofluorescence (PIAF) of the membrane proteins was used as a fluorescent label. It has been established that D displays a significant negative linear correlation with age. The present paper describes age-estimations carried out on 12 male Fischer 344 rats (7–29 months of age) in so-called “blind experiments”: the operator knew only the sex of the rat, determined D from a small piece of the freshly removed liver, and estimated the age of the rat from the age-dependent regression line for D established previously on 16 other Fischer 344 male rats of various ages. There was a strong correlation of the estimated age with the actual one (r = 0.92), the slope of the regression line was 0.98 and its intercept differed from 0 by only 0.5 months. These results indicate that D may play a decisive role in the determination of membrane functions as predicted by the membrane hypothesis of aging.