Metal-dependent neutral proteoglycanase activity from monolayer-cultured lapine articular chondrocytes.

Neutral proteoglycanase and other protease activity from cellular and CM fractions of monolayer-cultured rabbit articular chondrocytes were studied. The cellular fraction comprising soluble cytoplasmic enzymes possessed concentration-dependent elastase-like esterase activity and activity against trypsin and chymotrypsin synthetic substrates but had little caseinase activity. The 20% ammonium sulfate precipitate of CM possessed more neutral caseinase activity than the 60% ammonium sulfate precipitate and the bulk of activity against the synthetic substrates. Activity against bovine nasal septum PG was present in these fractions. Both the 20% and 60% ammonium sulfate fractions reduced the viscosity and the S of the PG substrate. This activity was incompletely inhibited by preincubation with either 5 mM o-phenanthroline or 10 mM EDTA, indicating that it was paritally metal-dependent. The activity in the cellular fraction was also partially inhibited by o-phenanthroline but more so by EDTA. These data indicate that chondrocytes synthesize and secrete into the culture medium neutral proteoglycanase(s) capable of initiating degradation of PG derived from the neutral pH cartilage matrix. The inhibitory profiles, together with recent evidence of enzymes with similar activity extracted from cartilage suggested that the proteoglycanase enzyme(s) may occur in multiple forms.     

急性缺血再灌注肾损伤过程中Mg2+及K+协同胰岛素的对抗效应

目的:在肾移植术后可能发生急性缺血再灌注性肾损伤.作者前期实验表明在肾缺血再灌注期间注射胰岛素可减轻缺血再灌注肾损伤,在此基础上,在胰岛素溶液中加入天冬氨酸钾镁,观察Mg2 ,K 协同胰岛素对家兔急性肾缺血再灌注损伤的影响,并分析其可能机制.方法:实验于2002-02/04在泸州医学院生理实验室完成,动物实验方法符合动物伦理学要求.①实验材料及方法:选用健康成年日本大耳白兔27只,按随机数字表法分为3组(n=9),即缺血再灌注组、缺血再灌注胰岛素处理组及对照组,前两组采用钳夹肾动脉法建立急性肾缺血再灌注肾损伤模型,缺血再灌注胰岛素处理组再灌注的同时给予胰岛素溶液,含胰岛素3 U/kg,葡萄糖1.5 g/kg,K 4 mg/kg,Mg2 1.7 mg/kg.②实验评估:分别观察3组动物缺血再灌注2 h,48 h后,血清尿素氮、血糖、血清及肾组织中丙二醛含量以及肾组织超微结构变化.结果:23只动物进入结果分析.①肾缺血再灌注48 h后,缺血再灌注组血清尿素氮含量显著高于对照组(P＜0.01),缺血再灌注胰岛素处理组与对照组差异无显著性意义(P＞0.05).②缺血再灌注组血清及肾组织中丙二醛含量显著高于对照组(P＜0.05),缺血再灌注胰岛素处理组丙二醛含量显著低于缺血再灌注组(P＜0.05).③缺血再灌注2 h后,3组动物血糖均较术前增高,但以缺血再灌注组增高更为显著,与对照组比较差异具有显著性意义(P＜0.05),缺血再灌注胰岛素处理组与对照组差异无显著性意义(P＞0.05).④对照组肾组织超微结构正常,缺血再灌注组肾组织呈变性和坏死改变,缺血再灌注胰岛素处理组肾组织轻度变性.结论:Mg2 ,K 可协同胰岛素减轻家兔急性缺血再灌注性肾损伤,其作用途径可能和降低血糖、抗自由基损伤、改善能量代谢、减轻钙超载、防止低血钾等因素有关.     

Training in endoscopic submucosal dissection

Endoscopic submucosal dissection (ESD) represents an important advancement in the therapy of early neoplastic gastrointestinal lesions by providing higher en-bloc curative resection rate with lower recurrence compared to endoscopic mucosal resection (EMR) and by sparing the involved organ and protecting patient’ s quality of life. Despite these advantages ESD is associated with long procedure times and a higher rate of complications, making ESD a challenging procedure which requires advanced endoscopic skills. Thus, there has been a recognized need for structured training system for ESD to enhance trainee experience and, to reduce the risks of complications and inadequate treatment. ESD has a very flat learning curve. However, we do not have uniformly accepted benchmarks for competency. Nevertheless, it appears that, in Japan, more than 30 supervised gastric ESD procedures are required to achieve technical proficiency and minimize complications. A number of training algorithms have been pro-posed in Japan with the aim to standardize ESD training. These algorithms cannot be directly applied in the West due to substantial differences including the availability of highly qualified mentors, the type of pathology seen, choice of devices, and trainee’s background. We propose a training algorithm for Western physicians which integrates both hands-on training courses, animal model work as well as visits to expert centers. No specific preceptor training programs have been yet developed but there is a consensus that these programs are important for permeation of ESD worldwide.     

Rosuvastatin in diabetic hemodialysis patients

A randomized, placebo-controlled trial in diabetic patients receiving hemodialysis showed no effect of atorvastatin on a composite cardiovascular endpoint, but analysis of the component cardiac endpoints suggested that atorvastatin may significantly reduce risk. Because the AURORA (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events) trial included patients with and without diabetes, we conducted a post hoc analysis to determine whether rosuvastatin might reduce the risk of cardiac events in diabetic patients receiving hemodialysis. Among the 731 participants with diabetes, traditional risk factors such as LDL-C, smoking, and BP did not associate with cardiac events (cardiac death and nonfatal myocardial infarction). At baseline, only age and high-sensitivity C-reactive protein were independent risk factors for cardiac events. Assignment to rosuvastatin associated with a nonsignificant 16.2% reduction in risk for the AURORA trial's composite primary endpoint of cardiac death, nonfatal MI, or fatal or nonfatal stroke (HR 0.84; 95% CI 0.65 to 1.07). There was no difference in overall stroke, but the rosuvastatin group had more hemorrhagic strokes than the placebo group (12 versus two strokes, respectively; HR, 5.21; 95% CI 1.17 to 23.27). Rosuvastatin treatment significantly reduced the rates of cardiac events by 32% among patients with diabetes (HR 0.68; 95% CI 0.51 to 0.90). In conclusion, among hemodialysis patients with diabetes mellitus, rosuvastatin might reduce the risk of fatal and nonfatal cardiac events.     

Influence of prenatal ethanol exposure on vascular contractile response in rat thoracic aorta.

Fetal alcohol syndrome is associated with cardiovascular malformation. However, the impact of prenatal ethanol exposure on vascular function is not clear. The purpose of this study was to examine the influence of prenatal ethanol exposure on vascular response in adulthood. Timed-pregnancy, female rats were fed an ethanol-containing liquid diet (36% calorically or 6.36% [vol./vol.]) or control diet from gestation day 2 until labor. The pups continued to receive a standard rat chow through adulthood, and the force-generating capacity of aortic ring segments was examined. Prenatal ethanol exposure did not significantly affect postnatal growth, but it did lead to elevated blood pressure in adulthood. The contractile response to potassium chloride was similar in vessels with intact endothelium, although the median effective concentration (EC(50)) was significantly reduced by prenatal ethanol exposure in rings with denuded endothelium. The response to norepinephrine was attenuated by prenatal ethanol exposure in rings with either intact or denuded endothelium. The endothelium-dependent relaxation to carbamylcholine chloride was significantly attenuated by prenatal ethanol exposure. Vasorelaxant response to the nitric oxide donor sodium nitroprusside or beta-adrenergic agonist isoproterenol was similar between control and prenatal-ethanol-exposed groups with either intact or denuded endothelium. Ethanol elicited a dose-dependent endothelium-dependent vasorelaxation, which was comparable between the two animal groups. The ethanol-induced endothelium-dependent vasorelaxation was attenuated by the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester. These findings seem to indicate that prenatal ethanol exposure contributes to alterations of both endothelium-dependent and endothelium-independent vascular contractile responses.     

Bone marrow transplantation for refractory acute leukemia in 34 patients with identical twins

Thirty-four patients aged 4-67 yr (median 17) with acute lymphocytic leukemia (ALL) (18 patients) or acute nonlymphocytic leukemia (ANL) (16 patients) who failed to enter complete remission (CR) or relapsed on conventional chemotherapy were treated with cyclophosphamide (CY), 60 mg/kg/day for 2 days, 1000 rad total body irradiation, and a marrow transplant from a genotypically identical normal twin. Sixteen of the patients received additional chemotherapy within the week before CY. After the transplant, 23 patients received immunotherapy consisting of killed autologous leukemic cells and/or normal twin peripheral blood lymphocytes, 16 as part of a prospectively randomized study. One moribund patient died before engraftment. Nine patients (6 ALL, 3 ANL) continued to have detectable leukemic cells. Twenty-four patients (70%) achieved CR. One of them died of viral hepatitis at 1 mo and another of viral interstitial pneumonitis at 4 mo in CR. Fourteen patients (7 ALL, 7 ANL) relapsed 2-16 mo (median 4) after transplantation. However, 8 patients (24%) (3 ALL, 5 ANL) remain in CR without any maintenance chemotherapy at 29-103 mo (median 80) after the transplant. The end results were not signficantly influenced by the type of leukemia, the immediated pre-CY chemotherapy, or the immunotherapy. The results show that this approach, even when applied to endstage patients with acute leukemia in relapse, causes tolerable morbidity, rare nonleukemic deaths, and frequent remissions, some of which represent cures.