Rhodostomin inhibits thrombin-enhanced adhesion of ROS 17/2.8 cells through the blockade of alphavbeta3 integrin.

Osteosarcoma is a very malignant bone tumor which has a high metastatic potential and usually lead to poor prognosis. The adhesion of tumor cells to the endothelium or extracellular matrix (ECM) is an essential step in the metastatic cascade. We investigated the effect of thrombin on the adhesion activity of the osteosarcoma cell line, ROS 17/2.8. Incubation with the low concentrations of thrombin (0.01-5 U/ml, 5 min to 24 h) elevated the adhesion activity of ROS 17/2.8 to both human umbilical vein endothelial cells (HUVEC) and extracellular matrix, with the peak effect at the concentration of 0.5 U/ml for 30 min at 37 degrees C. The ROS 17/2.8 cells responded to thrombin by a peak effect of increased adhesion to HUVEC (5.5 folds vs. control) and fibronectin (4.8 folds) after thrombin pretreatment (0.5 U/ml, 30 min, 37 degrees C). Pretreatment with monoclonal antibodies against beta3 integrins, including anti-alphavbeta3, 10E5 and 7E3, effectively antagonized the thrombin-enhanced cell adhesion activity, whereas anti-alpha3beta1 and anti-alpha5beta1 did not antagonize the enhanced cell adhesion. Rhodostomin, an Arg-Gly-Asp (RGD)-containing snake venom peptide, and synthetic peptide RGDS also blocked the thrombin-enhanced ROS 17/2.8 cell adhesion. This study demonstrated that thrombin enhanced the cell adhesion of ROS 17/2.8 cells to HUVEC or ECM through an upregulation of beta3 integrins, and rhodostomin was a strong inhibitor on thrombin-enhanced cell adhesion, either to HUVEC or fibronectin substratum.     

丝裂霉素C预防浅表性膀胱癌等离子电切术后复发

目的探讨丝裂霉素C（MMC）预防浅表性膀胱癌等离子电切术（PKRBT）后复发的有效性。方法73例浅袁性膀胱癌病人行PKBRT后即MMC 40mg膀胱内灌注，常规MMC膀胱灌注12月。结果术后6月复发3例（4．1％），12月复发11例（15．1％），20月复发15例（20．5％）。结论MMC膀胱内灌注在PKRBT术后预防复发疗效良好。     

A comparison of glutathione S-transferase mutant frequencies in healthy Han and Uygur Chinese.

OBJECTIVE: This study was to compare the frequencies of genetic polymorphisms of GSTM1, GSTT1, and GSTP1 in Uygur Chinese with those in Han Chinese. METHODS: GSTM1 and GSTT1 polymorphisms were analyzed by a PCR-Multiplex procedure, whereas GSTP1 polymorphism was analyzed by PCR-RFLP. RESULTS: The frequency of GSTM1 null genotype in Han Chinese (56.1%) was similar to that in Uygur Chinese (53.2%) (P = 0.592), whilst the frequency of GSTT1 null genotype in Han Chinese (50.0%) was significantly (P < 0.05) higher than that of Uygur Chinese (26.6%). GSTP1 had a genotype distribution of 60.7% I/I, 35.2% I/V and 4.1% V/V in Han Chinese, and 51.3% I/I, 40.2% I/V and 8.4% V/V in Uygur Chinese. CONCLUSION: There is marked ethnic difference in the mutant frequencies of GSTT1 and GSTP1, but not GSTM1, between Uygur and Han Chinese.     

Association of serotonin 5-HT2A receptor binding and the T102C polymorphism in depressed and healthy Caucasian subjects.

Serotonin 5-HT2A receptor (5-HT2A) binding is reported to be altered in individuals with suicidal behavior, mood disorders, and aggressive-impulsive traits. Genetic association with major depression, suicidal behavior, and aggressive-impulsive traits has not been established. This study examines the possible association of the 5-HT2A gene C102T polymorphism with the receptor binding kinetics, and clinical overt phenotypes. The study population included 63 healthy volunteers and 152 subjects with mood disorders, 56 of whom had a history of suicide attempts. All were Caucasian. Platelet 5-HT2A binding kinetics (Bmax and KD) were assayed and adjusted for seasonal variation. All subjects were genotyped for the T102C polymorphism. Clinical phenotype was determined by structured clinical interview. The TT genotype was associated with higher Bmax in all subjects (F=3.53, df=2,211; p=0.03), controlling for diagnosis. Bonferroni-adjusted post hoc testing showed higher binding in the TT compared with TC genotype in the control group (F=7.56, df=2,60, p=0.001), but not in the mood-disordered subjects. No difference was found in genotype and allele distribution between the mood-disordered subjects, with and without suicide attempt history, and controls. Bmax was not related to a diagnosis of mood disorders. The TT genotype appears associated with higher platelet 5-HT2A Bmax in the healthy population, but this genotypic effect appears absent in mood disorders and unrelated to psychopathology.     

N-desmethylclozapine, a major metabolite of clozapine, increases cortical acetylcholine and dopamine release in vivo via stimulation of M1 muscarinic receptors.

The active moiety of clozapine, the prototypical antipsychotic drug, consists of clozapine and its major metabolite, N-desmethylclozapine (NDMC). Previous studies have suggested that NDMC may be more important than the patent compound itself for the improvement in cognition in patients with schizophrenia treated with clozapine. While the pharmacology of clozapine and NDMC are similar in most respects, NDMC has been shown to be an M1 muscarinic receptor partial agonist whereas clozapine is an M1 antagonist in vitro and in vivo. We hypothesized that NDMC may improve cognition by increasing dopamine (DA) and acetylcholine (ACh) release in medial prefrontal cortex (mPFC) via direct stimulation of M1 receptors, whereas both NDMC and clozapine itself would do so by other mechanisms as well, and that clozapine would inhibit the M1 agonist effect of NDMC. In the present study, using microdialysis in awake, freely moving rats, we found that NDMC at doses of 10 and 20, but not 5 mg/kg, significantly increased DA and ACh release in the mPFC and HIP, but not in the nucleus accumbens (NAC). The M1-preferring antagonist, telenzepine (3 mg/kg), completely blocked NDMC (10 mg/kg)-induced increases in cortical DA and ACh release. Clozapine (1.25 mg/kg), which by itself had no effect on DA or ACh release in the cortex, blocked NDMC (10 mg/kg)-induced ACh, but not DA, release in the mPFC. The 5-HT1A receptor antagonist, WAY100635 (0.2 mg/kg) blocked NDMC (20 mg/kg)-induced cortical DA but not ACh release. These findings suggest that: (1) NDMC is an M1 agonist while clozapine is an M1 antagonist in vivo; (2) M1 agonism of NDMC can contribute to the release of cortical ACh and DA release; (3) NDMC, because of its M1 agonism, may more effectively treat the cognitive impairments observed in schizophrenia than clozapine itself; and (4) M1 receptor agonism may be a valuable target for the development of drugs that can improve cognitive deficit in schizophrenia, and perhaps other neuropsychiatric disorders as well.     

Dynamic contrast-enhanced subtraction and delayed MRI of gastric tumors: radiologic-pathologic correlation

PURPOSE: Our goal was to determine whether dynamic MR subtraction images could be used to detect and stage gastric tumors. METHOD: Dynamic MR subtraction images were prospectively performed in 20 patients without gastric lesions and in 39 patients with gastric tumors. The flat- or depressed-type early gastric cancers were excluded. The MR findings were assessed for layered pattern of the normal gastric wall, detectability of tumors, enhanced pattern of tumor, and depth of the tumor invasion. Surgical specimens were obtained from 30 of the patients with tumors, and histopathologic sections were made in the dynamic MR scanning direction. RESULTS: The three-layered structure of the normal gastric wall was apparent in more of the dynamic MR subtraction images (60%) than of the nonsubtraction images (30%) in the control group. All 39 gastric tumors were detected by MRI. The intact inner layers overlying stromal tumors and outer layers interrupted by advanced gastric cancers were clear on the subtracted images. MRI accurately T-staged 88% of the gastric cancers. CONCLUSION: Dynamic MR subtraction images can be used to identify gastric tumors and to stage gastric cancers.     

复方魔芋葡甘聚糖对大鼠高脂血症的影响

目的:研究复方魔芋葡甘聚糖对大鼠高脂血症的影响.方法:建立高脂血症大鼠模型,将魔芋葡甘聚糖复配黄酮化合物,并喂饲大鼠,分别检测复方魔芋葡甘聚糖以及魔芋葡甘聚糖对大鼠血脂水平和肝脏组织形态的影响.结果:复方魔芋葡甘聚糖能显著降低大鼠血清总胆固醇的低密度脂蛋白-胆固醇(LDL-C)和载脂蛋白B(ApoB)浓度,显著增加高密度脂蛋白-胆固醇(HDL-C)和载脂蛋白A1(ApoAl)浓度,显著改善TG代谢,调节脂质代谢紊乱,降低血糖水平.肝组织形态学观察显示,复方魔芋葡甘聚糖对实验大鼠肝脏组织有保护作用.结论:复方魔芋葡甘聚糖能改善对实验大鼠高脂血症脂质代谢紊乱的调节作用.     

聚髌器与改良张力带治疗髌骨粉碎性骨折疗效比较

为比较两种不同内固定方式在治疗髌骨粉碎性骨折中的临床疗效,将60例病人采用随机分组方法分成两组,分别采用镍钛记忆合金聚髌器(Niti-Patellar Concentrator NT-PC)(A组)和改良张力带钢丝内固定(B组)治疗,并对手术时间、术后骨折复位情况、骨折愈合时间、术后功能锻炼开始时间、膝关节屈曲达到90°的时间、手术后膝关节功能完全恢复时间及术后的并发症等结果进行比较.结果显示A组在手术时间、术后膝关节功能锻炼开始时间、膝关节屈曲达到90°和完全恢复的时间及骨折愈合的时间均早于B组,术后骨折复位比B组好(P＜0.05),手术后无并发症.表明治疗髌骨粉碎性骨折NT-PC比改良张力带钢丝内固定有更广泛的适应症与更理想的效果.     

以主药溶解性能筛选体外经皮渗透试验中的接收液

目的:筛选舒心贴剂中CVD体外经皮渗透试验的接收液.方法:采用异氰酸苯酯柱前衍生化RP-HPLC法,测定CVD在不同接收液中的饱和浓度,根据溶解性能筛选体外经皮渗透接收液.结果:七种接收液中以30%乙醇/生理盐水中CVD的浓度最高.结论:以主药溶解性能筛选体外经皮渗透试验的接收液,方法可靠、简便.     

舒心平胶囊对大鼠实验性心律失常的作用

目的:观察舒心平胶囊对心律失常的影响.方法:舒心平连续给药7天,乌头碱静注诱发大鼠心律失常,记录各组动物发生室性早搏(VP)、室性心动过速(VT)时乌头碱用量;乌头碱侧脑室给药观察各组动物心律失常的持续时间;氯化钡静脉给药,观察各组动物出现心律失常时氯化钡用量.结果:舒心平可明显提高乌头碱致大鼠发生VP、VT的用量;明显缩短大鼠中枢性心律失常的持续时间,并可提高氯化钡诱发大鼠心律失常的剂量.结论:舒心平胶囊对模型动物诱发的室性早搏、室性心动过速具有拮抗作用.