Protective Effects of Hyperpolarizing Cardioplegia with Pinacidil on Myocardium in Rats

Whether the ATP-sensitive potassium channel opener pinacidil can provide myocardial protective effects in prolonged isolated global ischemic rat heart was investigated. On modified isolated rat working heart model, 40 hearts were divided into four groups randomly: Hyperpolarized arrest H-K solution containing pinacidil (50 tmol/L) (P1 and P2) and depolarized arrest St. Thomas‘ solution (S1 and S2) subjected to 15 C hypothermia, 60 min (P1 and S1) or 120 min (P1 and S2) of ischemia and 30 min reperfusion. The experimental indices included cardioplegic efficiency, cardiac function, coronary blood flow, myocardial enzyme release, myocardial water and ATP content. Hyperpolarized arrest provided significantly better recovery of cardiac function than depolarized arrest.Postischemic coronary flow and myocardial ATP content were higher. The arrest time of electro-mechanical activities were longer than depolarized arrest. There were no differences among the groups in myocardial water contents. The hyperpolarized arrest solution containing pinacidil can provide a marked myocardial protective effect during prolonged hypothermic myocardial ischemia.     

TAXUS支架治疗急性冠状动脉综合症的疗效评价

目的评价紫杉醇洗脱冠状动脉支架(TAXUStmBoston公司产品)应用于急性冠状动脉综合症病人的临床疗效及安全性。方法自2003年5月至2004年12月接受TAXUS支架治疗的94例急性冠状动脉综合症患者,观察术后即刻效果、术后6个月心脏性死亡、心肌梗塞、再次血管重建及冠状动脉造影复查情况。病例中包括ST段抬高的急性心肌梗塞27例,非ST段抬高的急性心肌梗死8例,不稳定心绞痛59例。结果支架植入成功率为99%,术中和随访期间无死亡,术后1例出现亚急性血栓,1例晚期血栓致心肌梗塞,另有5例随访中进行了血管重建术,6个月主要心脏不良事件(MACE)发生率7.4%。术后6～7个月23例的冠状动脉造影复查再狭窄率为13.0%(支架内为8.6%),靶病变重建率为2.7%。结论应用TAXUS支架治疗急性冠状动脉综合症是安全和有效的,支架内再狭窄率明显低于普通金属支架。     

大剂量尿激酶静脉溶栓治疗急性心肌梗塞25例临床分析

目的 了解大剂量尿激酶静脉溶栓治疗急性心肌梗塞疗效.方法 对符合溶栓条件急性心肌梗塞25例病人,在常规治疗基础上,给予100万单位尿激酶静脉输注.结果 治愈23例,有效率92%.结论 使用大剂量尿激酶静脉溶栓治疗急性心肌梗塞,临床效果确切.     

他莫昔芬与γ-干扰素联合抗人乳腺癌细胞株的作用及其机制研究

目的: 探讨他莫昔芬(TAM)与 γ-干扰素(γ-IFN)联合抗乳腺癌细胞株的作用及其机制。方法:在体外培养条件下，分别或联合应用γ-IFN,TAM或雌二醇（E2）作用于ER阳性的MCF-7人乳腺癌细胞株，用MTT比色法分析细胞生长抑制作用;用流式细胞仪（FCM）检测细胞周期分布、凋亡率及用药前后Bcl-2,Bax,Fas,FasL及Caspase-8蛋白的变化;荧光分光光度仪检测Caspase-3活性。结果:TAM能抑制ER阳性乳腺癌细胞的生长，阻滞细胞周期于G0/G1期，并可诱导细胞凋亡;同时，TAM能拮抗外源性雌激素对MCF-7细胞的促生长作用。γ-IFN预处理细胞24h后，TAM抗乳腺癌细胞的作用增强。联用γ-IFN与TAM后，细胞Bcl-2蛋白表达下调，Caspase-8表达上调;但药物处理前后，细胞Bax，Fas，FasL蛋白表达水平及Caspase-3活性未见明显变化。结论:体外条件下，TAM通过影响细胞周期、诱导细胞凋亡而发挥抗ER阳性乳腺癌细胞作用;γ-IFN能加强TAM的抗乳腺癌作用。两者作用机制可能系通过下调Bcl-2表达和上调Caspase-8的表达。     

昆虫色氨酸羟化酶的研究进展

色氨酸羟化酶（tryptophan hydroxylase、TPH）为5-羟色胺（5-hydroxytryptamine，5-HT）合成的限速酶，具有专一性，在组织中含量较低，且具有不稳定性。TPH的活性是5-HT合成的唯一前提，因此它可以作为5-HT能神经元的特异标志，也可以作为5-HT能神经元的一个分化特征。它的存在，住区分神经细胞特征方面比5-HT本身的含苗更有价值。因而近年来TPH迅速成为国际研究的热点和难点之一。本文主要就TPH在昆虫中的存在形式、调节机制及进化地位等方面已取得的研究进展作一简述。     

Elimination of malignant clonogenic cells from human bone marrow using multiple myeloid cell-specific monoclonal antibodies and complement.

Single or combined monoclonal antibodies (McAbs) Zh53, Zh820, and Zh2-1 have been used to eliminate malignant clonogenic cells from human bone marrow. The test of cytotoxicity showed that all of these McAbs could express high specific cytotoxic action against HL-60 cells and were selectively complement-dependent cytotoxic to various types of fresh leukemic cells. Clonogenic assay detected that single treatment with antibody and rabbit complement (RC) could reduce clonogenic units of HL-60 cells by more than 2 logs and two treatments reduced clonogenic units by more than 4 logs. However, combination of 2 McAbs could reduce clonogenic units by 4-5 logs. The data suggest that multiple treatments with McAbs and RC or a combination of 2 McAbs are more effective than a single treatment in eliminating clonogenic tumor cells. Treatment of normal human bone marrow with Zh53, Zh2-1 and RC did not produce a loss of normal CFU-GM, but treatment with Zh820 reduced the clonic units of normal CFU-GM by 24%.

     

Studies on Toxicity of Nitroquine-Dapsone Compound and Therapeutic Effects of Folic or Folinic Acid on Toxicated Animals

The toxic effects of nitroquine-dapsone compound(NQD)in mice and dogs were studied.The therapeutic index of NQDin mice is 1911,the greatest among the 6 antimalarials tested.Thetoxic effects of NQD(50 mg/kg/day for 3 days per os)and nitro-quine in dogs were manifested by injuries on the adrenal cortexand intestinal epithelium.When folic acid(4 mg/kg/day for 4 days)or calcium leucovorinum(0.3 mg/kg/day for 4 days)were usedconcomitantly with NQD,the death rate and the incidence of dia-rrhea in the toxicated dogs were greatly reduced,the injury on theintestinal epithelium was much milder,and the goblet cells weremuch more numerous than those without treatment.The results suggestthat folic acid and calcium leucovorinum can protect the undifferen-tiated cells in the intestinal crypts from being injured by NQD.     

浅谈医院人性化管理

文章从医院人性化管理的定义,僵硬制度化管理的弊端,医院人性化管理的作用,怎样人性化管理职工和患者,阐明了如何实现医院人性化管理的问题。     

NEUROTROPIN IMMUNOSTIMULATING ACTION ON IMMUNOCOMPETENT CELLS

Neurotropin (NSP) is an extract isolated from the skin of rabbits inoculated with vaccinia virus. The present study examines the possible action of NSP on the number and function of immunocompe tent cells in mice. The experiment showed that NSP had no effect on both T and B lymphocytes of nor- malimmunized mouse spleen. The degree of plaque forming cell reaction and titre of specific antibody showed no significant differences when the NSP treated group and controls were compared. How- ever, NSP exhibited promotive effect on specific antigen binding cells in the early stage of immune responses. It was also noted that the rosette forming capacity of human T lymphocytes in vitro was restor- ed markedly by NSP. These results suggest that NSP possesses certain immunostimulating activity, particularly on the specific antigen binding cells and human T lymphocytes.     

Computational modeling to predict effect of treatment schedule on drug delivery to prostate in humans.

PURPOSE: To evaluate a computational approach that incorporates experimental data in preclinical models to depict doxorubicin human tissue pharmacokinetics. EXPERIMENTAL DESIGN: Beagle dogs were given 2 mg/kg doxorubicin as i.v. bolus, 4-h infusion, or 96-h infusion. Concentrations in plasma, prostate (target tissue), heart (toxicity), and major tissues for disposition were determined and modeled. Model parameters were obtained after the bolus injection with model validation based on the 4-h and 96-h infusion data. Clinical pharmacokinetic data and scale-up gave doxorubicin profiles in human prostate and heart. RESULTS: In agreement with in vitro results, tissues were best modeled with two compartments, one rapidly and one slowly equilibrating. The developed tissue distribution model predicted concentrations for all three administration regimens well, with an average deviation of 34% (median, 29%). Interspecies scale-up to humans showed that the change from a bolus injection to a slow, 96-h infusion (a) had different effects on the drug partition and accumulation in heart and prostate, and (b) lowered the peak concentration in the plasma by approximately 100-fold but had relatively little effect on maximal heart concentration ( approximately 33% lower). The simulated drug exposure in a human prostate was above the exposure required to inhibit tumor proliferation but was 30 to 50 times below that needed for cell death. CONCLUSION: The present study shows a computation-based paradigm for translating in vitro and in vivo preclinical data and to estimate and compare the drug delivery and pharmacokinetics in target tissues after different treatment schedules.