Effect of dipyridamole with or without aspirin on urine protein excretion in patients with membranous glomerulonephritis

Summary The antiproteinuric effect of the antiplatelet agent dipyridamole has been assessed after inhibiton of thromboxane B₂ (TxB₂) synthesis in 8 patients with confirmed membranous glomerulonephritis. There were three study periods, each of 30 days, and 45 days apart, namely a washout period, treatment with dipyridamole 300 mg/d, and dipyridamole 225 mg/d plus aspirin 150 mg/d. On Days 1 and 30 of each study period serum and urine creatinine, 24-h excretion of protein, creatinine clearance, platelet aggregometry on whole blood and serum TxB₂ were measured. Treatment with dipyridamole alone or with aspirin produced significant inhibition of platelet aggregation and a fall in 24-h protein excretion; the latter amounted to 54% with dipyridamole alone and 56 % with dipyridamole plus aspirin (NS). Dipyridamole plus aspirin caused an 82 % reduction in serum TxB₂.     

凝血酶受体结构与功能的研究现状

凝血酶（ｔｈｒｏｍｉｂｉｎ，Ⅱａ）是一种生成于损伤处血管内皮细胞多功能蛋白酶，它是参与凝血过程各个环节反应中的关键酶。在发挥止血作用的同时，还可能诱导炎症、增生及修复等反应。最近发现的凝血酶受体（ｔｈｒｏｍｂｉｎ ｒｅｃｅｐｔｏｒ，ＴＲ）分子可能为解释上述现象提供了一个理论框架。同时，ＴＲＮ端被Ⅱａ切下的４１个氨基酸片段是否具有特殊功效，值得研究探讨。     

Chronic isolated macrothrombocytopenia with autosomal dominant transmission: a morphological and qualitative platelet disorder

Abstract: We studied 47 subjects belonging to 13 unrelated families with a history of mild haemorrhagic diathesis and chronic thrombocytopenia. 36 patients presented some degree of thrombocytopenia: 7/36 (19%) had slight thrombocytopenia (100–150×10⁹/L); 26/36 (72%) had mild thrombocytopenia (50–100×10⁹/L) and 3/36 (8%) had severe thrombocytopenia (<50×10⁹/L). No correlation was observed between platelet count and the degree of haemorrhagic diathesis, which was mild in the majority of patients. Transmission was autosomal dominant. Platelet anisocytosis, increased percentage of large platelets and absence of leukocyte inclusions were observed in 26/30 (87%) of the examined blood smears. The ultrastructural appearance of platelets was normal. Megakaryocytes appeared normal in number in 10/10 patients, but showed asynchronous nuclear-cytoplasm maturation and mainly nonlobulated nuclei. Platelet aggregation was studied in 26 patients and either increased or decreased curves were variably observed in response to different aggregating agents. Platelet-associated IgG (PAIgG) was increased in 18/31 (58%) patients, while serum autoantibodies against platelet glycoproteins Ib/IX or IIb/IIIa were demonstrable in only 1 case. An increased expression of platelet surface glycoproteins Ib and IIb/IIIa, as studied by murine monoclonal antibodies binding in 17 cases, was observed. Platelet survival performed by 111In-oxine-labelled autologous platelets was normal in the 3 studied patients. Congenital macrothrombocytopenia confirms to be a distinct clinical disorder for which the name of “chronic isolated hereditary macrothrombocytopenia” is proposed.     

Blood platelets in severely injured burned patients

Unbelievable decrease of blood-platelet in the severely burned patients during the treatment of skingrafting caused two patients to unexpected death. From the records of changes of platelet number, a certain ‘platelet curve’ was made. By observing the curve, our treatments of skingrafting were carried out during the stable period and from then on we had no death cases.     

Comparison of the effect of intravenous ketoprofen, ketorolac and diclofenac on platelet function in volunteers

Background : Nonsteroidal anti–inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis which may result in impaired platelet function. Because NSAIDs have different abilities to inhibit cyclo–oxygenases we compared the effect of intravenous ketoprofen, ketorolac and diclofenac on platelet function in volunteers. Methods : Ten healthy male volunteers were given ketoprofen 1.4 mg kg^-1, ketorolac 0.4 mg kg^-1 and diclofenac 1.1 mg kg^-1 in saline i.v. on three different occasions, at more than one–week intervals, in a randomized double–blind crossover study. Platelet function was evaluated before (sample 0), 2 (sample 2) and 24 h (sample 3) after the beginning of the infusion. Results : Two of the volunteers had no secondary platelet aggregation in their aggregation curves before the experiment (sample 0, studied three times) and their results were excluded from the final analysis. Diclofenac inhibited adrenaline (0.9 μg–ml^-1) induced platelet aggregation less (median maximal aggregation 22.5%) than ketoprofen (18.3%) and ketorolac (15.7%) (P<0.05) in sample 2. In the ketorolac group in sample 3 an impairment of adrenaline (0.9 ng ml^-1) induced platelet aggregation was still seen (26.7%) (P<0.05) but not in the other groups. Diclofenac did not affect adenosine diphosphate (ADP) induced platelet aggregation. However, ketorolac caused an impairment in ADP (3 μM and 6 μM) induced platelet aggregation and ketoprofen in ADP (6 μM) induced platelet aggregation in sample 2. Bleeding time was prolonged (P<0.05) after ketoprofen and ketorolac (sample 2) but not after diclofenac. Platelet retention on glass beads was unaffected by the tested drugs. Conclusion : Ketoprofen, ketorolac and diclofenac caused a reversible platelet dysfunction. Diclofenac had the mildest effect, while platelet dysfunction was still seen 24 h after the beginning of ketorolac.     

免疫金标记法研究血小板功能缺陷性疾病

本文利用国产抗血小板膜糖蛋白单克隆抗体分别制备出抗人血小板膜糖蛋白（GPIb、GPⅡb及GPⅢa）的免疫金探针。以此探针检测了9例“刺参诱聚缺陷症”患者及2例血小板无力症患者血小板膜糖蛋白。结果表明“剌参诱聚缺陷症患者”其静息状态下血小板GPIb、GPⅡb正常，GPⅢa低于正常时照组（P＜0．01）。经“剌参”刺激后，GPⅢa仍低于正常（P＜O．01），而经ADP刺激后GPⅢa可恢复正常。血小板无力症患者其静息状态下GPIb正常，GPⅡb、GPⅢa、均低于正常（P＜0.01）。经“刺参”、ADP刺激后GPⅢa、GPⅡb仍低于正常，（P＜O．01）。     

Efficient RT-PCR on platelet mRNA after long-term storage

We have developed a procedure permitting RT-PCR from mRNA even after a long-term storage (1 year) of platelet samples in ethanol (EtOH-platelets) at −80°C. To validate our method, we have analysed the human platelet alloantigen system (HPA-1) which is coded by β₃ mRNA. We have also demonstrated the efficiency of amplification of part of the coding region for (i) α_IIb subunit mRNA, (ii) α_v subunit mRNA, and (iii) the seven transmembrane domain thrombin receptor mRNA.     

粉防己碱与牛磺酸合用对血小板聚集与血栓形成的影响

粉防己碱（Ｔｅｔ）和牛磺酸（Ｔａｕ）均能抑制ＡＤＰ、胶原和凝血酶诱导的大鼠血小板聚集及血栓形成。Ｔｅｔ抑制ＡＤＰ诱导聚集较强，Ｔａｕ则对胶原作用最明显，二药减半量合并应用时，较各药单用强     

Triflavin, an Arg-Gly-Asp containing snake venom peptide, inhibits aggregation of human platelets induced by human hepatoma cell line

Triflavin, an Arg-Gly-Asp (RGD)-containing peptide, purified from snake venom of Trimeresurus flavoviridis, inhibits human platelet aggregation through the blockade of fibrinogen binding to fibrinogen receptors associated with glycoprotein IIb/IIIa complex. In this report, we examined the effect of triflavin on tumor cells (human hepatoma J-5)-induced platelet aggregation (TCIPA) of heparinized platelet-rich plasma (PRP). ADP-scavenger agents, apyrase (10 U/ml) and creatine phosphate (5 mM)/creatine phosphokinase (5 U/ml) did not inhibit TCIPA while hirudin (5u/ml) completely inhibited it. J-5 cells initially induced platelet aggregation, then blood coagulation occurred. J-5 cells concentration-dependently shortened the recalcification time of normal as well as Factor VIII, IX-deficient human plasmas, while it was inactive at shortening the recalcification time of Factor VII-deficient plasma, suggesting J-5 cells induced platelet aggregation through activation of extrinsic pathway, leading to thrombin formation as evidenced by the amidolytic activity on S-2238 by expressing tissue factor-like activity. Triflavin inhibited TCIPA in a dose-dependent manner (IC₅₀, 0.02 μM). When compared on molar ratio, triflavin was approximately 30,000 times more potent than GRGDS (IC₅₀,0.58 mM). On the other hand, GRGES showed no significant effect on TCIPA, even its concentration was raised to 4 mM. Additionally, the monoclonal antibodies, raised against glycoprotein IIb/IIIa complex (i.e., 7E₃ and 10 E₅) inhibited J-5 TCIPA. In conclusion, we suggest the inhibitory effect of triflavin on J-5 TCIPA may be chiefly mediated by the binding of triflavin to the fibrinogen receptor associated with glycoprotein IIb/IIIa complex on platelet surface membrane.