Bleeding in renal failure: a possible role of vascular prostacyclin (PGI2).

Specimens of venous tissues from a group of 25 patients with chronic uremia and 7 patients with acute renal failure generated significantly higher PGI2-like (platelet aggregation inhibiting) activity than venous tissues from 30 normal subjects. After repeated washings, when this activity could barely be detected in the controls, pronounced inhibitory activity was still evident in samples containing venous tissues from uremic patients. Both prolonged bleeding times and increased PGI2-like activity returned to normal in 4 acute uremic patients on restoration of their renal function. These findings may be relevant to the pathogenesis of bleeding in renal failure.     

Inhibition of human platelet aggregation by parathyroid hormone. Is cyclic AMP implicated?

Parathyroid hormone (PTH) is a polypeptide which in different in vitro systems raises intracellular cyclic AMP (cAMP) levels via adenyl cyclase activation and stimulates Ca2+ transport across cell membranes. We tested whether, on the basis of this mechanism, PTH would inhibit human platelet aggregation. The latter was tested in vitro by a photometric technique. Platelet aggregation induced by the calcium ionophore A 23187 was inhibited by PTH at concentrations (0.5-3 USP U/ml) similar to those effective in other in vitro systems. Higher concentrations of PTH were required to prevent aggregation initiated by adenosine-5'-diphosphate, arachidonic acid, or platelet-aggregating factor. The terminal synthetic fragment 1-34 b PTH was ineffective against all aggregation stimuli. The antiaggregating effect of PTH was potentiated by verapamil and theophylline and was additive to that of PGI2. However, PTH did not appear to increase platelet cAMP levels and was not counteracted by an inhibitor of platelet adenyl cyclase. It is therefore unlikely that PTH inhibits platelet aggregation through an adenyl cyclase stimulated increase of cAMP. Since PTH levels are markedly increased in uremic plasma, it might contribute to the defective platelet function and the bleeding tendency frequently occurring in uremic patients.     

注射用头孢曲松钠无菌检查方法验证

目的建立注射用头孢曲松钠无菌检查标准方法。方法按《中国药典》2005年版的有关要求,通过接种代表性的阳性菌株,采用薄膜过滤进行方法学验证。结果每筒冲洗300mL(分3次),可以消除样品对5株实验菌:金黄色葡萄球菌、铜绿假单胞菌、生孢梭菌、白色念珠菌、黑曲霉菌的抗菌活性,使其正常生长;每筒冲洗400mL(分3次),可以消除样品对2株实验菌:枯草杆菌、大肠杆菌的抗菌活性。结论本样品可以采用薄膜过滤法总冲洗量1200mL(冲洗液为400mL/筒)测定。     

荜茇宁降血脂和急性毒性实验研究

目的:研究荜茇宁对动物血脂的影响及急性毒性作用。方法:以大鼠食饵性高脂血症为模型,给予高脂饲料的同时灌服荜茇宁,连续14d,测定血清中总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-c)、低密度脂蛋白胆固醇(LDL-c)含量;采用高脂饲料喂养建立家兔高脂血症模型,观察荜茇宁对血脂、肝脏脂质和动脉粥样硬化的改善情况.通过小鼠急性毒性实验观察其对小鼠产生的毒性反应。结果:荜茇宁显著降低大鼠血清TC、TG、LDL-c和动脉硬化指数(AI),升高HDL-c的含量;能降低家兔血清TC、TG、LDL-c和肝脏TC、TG,并且显著改善动脉粥样硬化。小鼠急性限量毒性实验显示,给药后小鼠未出现死亡及毒性反应。结论:荜茇宁具有明显地降血脂和改善动脉粥样硬化作用,而且毒性极低。     

Less hypoglycemia with insulin glargine in intensive insulin therapy for type 1 diabetes. U.S. Study Group of Insulin Glargine in Type 1 Diabetes

OBJECTIVE: Insulin glargine (21A-Gly-30Ba-L-Arg-30Bb-L-Arg-human insulin) is a biosynthetic insulin analog with a prolonged duration of action compared with NPH human insulin. This study compared insulin glargine with NPH human insulin in subjects with type 1 diabetes who had been previously treated with multiple daily injections of NPH insulin and regular insulin. RESEARCH DESIGN AND METHODS: This study was a multicenter randomized parallel-group study in which subjects were randomized to receive premeal regular insulin and either insulin glargine (at bedtime) or NPH insulin (at bedtime for patients on once-daily therapy and at bedtime and in the morning for patients on twice-daily therapy) for up to 28 weeks. Dose titration of both basal insulins was based on capillary fasting whole blood glucose (FBG) levels; the goal was a premeal blood glucose concentration of 4.4-6.7 mmol/l. RESULTS: A total of 534 well-controlled type 1 diabetic subjects (mean GHb 7.7%, mean fasting plasma glucose [FPG] 11.8 mmo/l) were treated. A small decrease in GHb levels was noted with both insulin glargine (-0.16%) and NPH insulin (-0.21%; P > 0.05). Significant reductions in median FPG levels from baseline (-1.67 vs. -0.33 mmol/l with NPH insulin, P = 0.0145) and a trend for a reduction in capillary FBG levels were achieved with insulin glargine. After the 1-month titration phase, significantly fewer subjects receiving insulin glargine experienced symptomatic hypoglycemia (39.9 vs. 49.2%, P = 0.0219) or nocturnal hypoglycemia (18.2 vs. 27.1%, P = 0.0116) with a blood glucose level <2.0 mmol/l compared with subjects receiving NPH insulin. CONCLUSIONS: Lower FPG levels with fewer episodes of hypoglycemia were achieved with insulin glargine compared with once- or twice-daily NPH insulin as part of a basal-bolus regimen in patients with type 1 diabetes.     

Comparison of cytopathic changes in oral hairy leukoplakia with in situ hybridization for EBV DNA

OBJECTIVE: It has been observed that the cytopathic changes in hairy leukoplakia (HL) correlate with ultra-structural evidence of intra-keratinocyte herpes-type viral particles. In situ hybridization is considered to be the definitive confirmation of Epstein-Barr virus (EBV)-induced HL. This study evaluated the consistency of histopathological findings, which many believe to be diagnostic, with in situ hybridization for EBV-DNA in 60 patients with lesions clinically suggestive of HL.
MATERIALS AND METHODS: Hematoxylin and eosin (H&E)-stained sections were reviewed independently by three oral pathologists who did not know the hybridization results. The presence in keratinocytes of nuclear inclusions and/or homogenization, believed to be specific for EBV in these lesions, was used as an indicator for infection. Cytoplasmic changes were evaluated separately.
RESULTS: With in situ hybridization, 48 cases were positive and 12 were negative. When the two methods were compared, pathologist concurrence ranged from 83% to 92%. False negatives ranged from 6% to 19%, and false positives ranged from 8% to 25%. Cytoplasmic ballooning, homogenization, and perinuclear clearing were evident in all cases of hybridization-confirmed HL; however, these changes were also noted in 75% (9/12) of the cases with negative hybridization results. Most confirmed HL cases exhibited both nuclear homogenization and inclusions, although the former was more consistently seen.
CONCLUSION: Cytoplasmic changes did not agree well with EBV-DNA hybridization results, whereas nuclear changes demonstrated good, but not complete, agreement. In appropriate clinical settings, the finding of nuclear inclusions and/or homogenization may be of diagnostic value. However, because the potential for false positives and negatives is high, H&E cytopathology should not be used as a substitute for in situ hybridization in the definitive diagnosis of oral hairy leukoplakia.