西洛他唑与银杏叶提取物治疗糖尿病周围神经病变对比临床观察

[目的]对比西洛他唑(培达)与银杏叶提取物治疗糖尿病周围神经病变(DNP)的临床疗效。[方法]将46例DNP患者随机分为培达组23例,银杏叶组23例。两组均经糖尿病教育、饮食控制、合理运动、降糖药物及胰岛素强化治疗,血糖基本平稳后,两组均予甲钴胺注射液500μg肌肉注射,每日1次,银杏叶组加用银杏叶提取物87.5mg加入生理盐水250mL内静滴每日1次;培达组加用西洛他唑0.2g加入生理盐水250mL内静滴每日1次,分别治疗15天。观察治疗后两组症状、体征并监测感觉神经和运动神经传导速度。[结果]治疗后两组症状均有改善,但培达组的效果更明显,两组间比较差异有显著性(P<0.05)。[结论]培达与银杏叶提取物治疗糖尿病周围神经病变均有临床疗效,但培达组优于银杏叶提取物组。     

Trends of Antiplatelet Therapy for the Management of Moyamoya Disease in Japan: Results of a Nationwide Survey

Background

The efficacy and safety of antiplatelet drugs in the treatment of moyamoya disease remain unclear. This study reports results of a nationwide survey conducted in 2016 on the trends of antiplatelet therapy for moyamoya disease in Japan.

Cilostazol enhances neovascularization in the mouse hippocampus after transient forebrain ischemia

Cilostazol is known to be a specific type III phosphodiesterase inhibitor, which promotes increased intracellular cAMP levels. We assessed the effect of cilostazol on production of angioneurins and chemokines and recruitment of new endothelial cells for vasculogenesis in a mouse model of transient forebrain ischemia. Pyramidal cell loss was prominently evident 3–28 days postischemia, which was markedly ameliorated by cilostazol treatment. Expression of angioneurins, including endothelial nitric oxide synthase, vascular endothelial growth factor, and brain‐derived neurotrophic factor, was up‐regulated by cilostazol treatment in the postischemic hippocampus. Cilostazol also increased Sca‐1/vascular endothelial growth factor receptor‐2 positive cells in the bone marrow and circulating peripheral blood and the number of stromal cell‐derived factor‐1α‐positive cells in the molecular layer of the hippocampus, which colocalized with CD31. CXCR4 chemokine receptors were up‐regulated by cilostazol in mouse bone marrow‐derived endothelial progenitor cells, suggesting that cilostazol may be important in targeting or homing in of bone marrow‐derived stem cells to areas of injured tissues. CD31‐positive cells were colocalized with almost all bromodeoxyuridine‐positive cells in the molecular layer, indicating stimulation of endothelial cell proliferation by cilostazol. These data suggest that cilostazol markedly enhances neovascularization in the hippocampus CA1 area in a mouse model of transient forebrain ischemia, providing a beneficial interface in which both bone marrow‐derived endothelial progenitor cells and angioneurins influence neurogenesis in injured tissue. © 2010 Wiley‐Liss, Inc.     

基因多态性对急性脑梗死患者抗血小板聚集药物个体化用药的临床价值

目的研究阿司匹林、氯吡格雷、西洛他唑的药物基因多态性特点及其在脑梗死患者个体化给药中的临床应用价值。方法选取2018年12月-2019年6月就诊中国人民解放军联勤保障部队第九〇〇医院神经内科的139例急性脑梗死患者,所有患者入院后均口服硫酸氢氯吡格雷片75mg,1次/d,用药后均行阿司匹林、氯吡格雷、西洛他唑的药物基因检测,结合患者的一般信息对3种药物基因检测结果进行统计分析,依据基因检测结果和循证医学证据选择个体化抗血小板聚集药物治疗方案,记录患者住院期间和出院后90d使用抗血小板聚集药物出现的不良反应和临床疗效。结果在139例患者中,氯吡格雷中代谢、慢代谢的患者有83例,阿司匹林高抵抗的患者有52例,西洛他唑弱代谢型的患者有9例,其中对氯吡格雷抵抗的患者比例最高,达59.71%。合并基础疾病的患者中,糖尿病为氯吡格雷抵抗的独立危险因素之一,差异具有统计学意义(P<0.05),而对于阿司匹林、西洛他唑则无统计学差异。对于氯吡格雷抵抗的患者均按基因检测的结果调整抗血小板聚集药物治疗方案,所有患者随访90d均未出现新发的脑血管事件。结论抗血小板聚集药物基因多态性在急性脑梗死患者的治疗中具有重要的参考价值。     

加味当归四逆汤治疗糖尿病足临床研究

目的观察加味当归四逆汤治疗0级糖尿病足（DF）的临床疗效及其对血清糖基化终末产物（AGEs）水平的影响。方法将72例0级糖尿病足患者随机分为治疗组及对照组,每组36例。治疗组予加味当归四逆汤口服,对照组予西洛他唑口服。14d为1个疗程,两组均连续治疗3个疗程。观察两组治疗前后临床症状、踝肱指数（ABI）、腓总神经传导速度、下肢动脉超声多普勒血流动力学指标、空腹血糖（FBG）、糖化血红蛋白（HbA1C）、纤维蛋白原（FIB）、血清AGEs水平变化。结果治疗组总有效率为88.9%,对照组为63.9%,两组治疗差异有统计学意义（P〈0.05）;治疗组ABI、下肢动脉超声多普勒血流动力学指标、腓总神经运动传导速度和感觉传导速度改善均优于对照组（P〈0.05,P〈0.01）;治疗后两组血清AGEs均明显下降,治疗组低于对照组（P〈0.01）。结论加味当归四逆汤能改善0级DF患者临床症状,并能改善糖尿病足动脉供血。     

Cilostazol exerts antiplatelet and anti‐inflammatory effects through AMPK activation and NF‐kB inhibition on hypercholesterolemic rats

This work presents a model of rats fed a high‐cholesterol diet, receiving a long‐term oral administration of cilostazol, a PDE3‐inhibitor. The aim of this study was to evaluate the molecular mechanisms by which cilostazol interferes with platelets signaling pathways to avoid atherosclerosis early development. Male Wistar rats were divided into 3 groups: Control group received standard rat chow (C), hypercholesterolemic group (HCD), and HCD+CIL (cilostazol group) received hypercholesterolemic diet for 45 days. HCD+CIL group received cilostazol (30 mg/kg/p.o.) once daily in the last 15 days. Platelet aggregation, lipid profile, lipid peroxidation, and cytokine serum levels were assessed. Expression of P‐selectin, CD40L, PKC‐α, IkB‐α, and iNOS and activation of AMPK, NF‐κB, and eNOS in the platelets were assessed using Western blot analysis. Cilostazol reduced the levels of total cholesterol (361.0 ± 12.8 vs. 111.5 ± 1.6 mg/dL), triglycerides (186.9 ± 17.7 vs. 55.4 ±3.1 mg/dL), cLDL (330.9 ± 9.7 vs. 61.5 ± 3.5 mg/dL), cVLDL (45.0 ± 4.6 vs. 11.1 ± 0.6 mg/dL), and malondialdehyde (9.4 ± 0.5 vs. 3.2 ± 0.3 nmol/mL) compared to the HCD group. Cilostazol presented antiplatelet properties and decreased inflammatory markers levels. These effects seem to be related to AMPK activation, NF‐kB inhibition, and eNOS activation.     

贝前列腺素钠联合西洛他唑治疗高龄糖尿病患者下肢动脉病变疗效观察

目的观察贝前列腺素钠联合西洛他唑对高龄2型糖尿病(T2DM)患者合并下肢动脉病变(PAD)的疗效。方法将48例高龄2型糖尿病合并下肢血管病变患者随机分为2组(每周24例):实验组患者服用贝前列腺素钠20μg每日三次及西洛他唑口服(第一周50 mg bid,第二周开始100 mg bid);对照组仅给予均给予口服西洛他唑(第一周50 mg bid,第二周开始100 mgbid);两组受试者均据病情予降糖、降压、调脂等基础治疗,总疗程24周。观察比较用药前后两组患者症状改善情况及踝肱指数(ABI)、经皮氧分压、足背动脉内径、峰值流速、血流量变化。结果两组患者下肢间隙性跛行、疼痛、麻木感及溃疡倾向均有不同程度改善,实验组较对照组改善更为明显(P0.05);2组患者治疗后踝肱指数、经皮氧分压、足背动脉内径、峰值流速、血流量较治疗前均有明显改善(P0.05或0.01),其中实验组前述指标改善较对照组更明显(P0.05)。结论与单独使用西洛他唑相比,贝前列腺素钠联合西洛他唑治疗高龄2型糖尿病患者下肢动脉病变有效且安全性较好。     

Antiplatelet treatment with cilostazol after stent implantation

Objectives—To evaluate the efficacy of cilostazol, a new synthetic inhibitor of phosphodiesterase, in preventing stent thrombosis after successful implantation.
Design—Preliminary prospective study.
Setting—A single coronary care unit in Japan.
Patients—Elective, bailout, or primary stents were implanted in 85 consecutive patients with 93 lesions. Primary stent implantation was performed in 18 patients with acute myocardial infarction. Patients received 200 mg cilostazol and 243 mg aspirin after stenting.
Main outcome measures—Stent thrombosis, major and minor complications, and side effects were assessed in the six months after stenting.
Results—Gianturco-Roubin stents were implanted in 37 lesions, Wiktor stents in 55, and Palmaz-Schatz stents in 27. Multiple stents were used in 26 lesions. There was no mortality, stent thrombosis related Q wave myocardial infarction, emergency bypass surgery, repeat intervention, or vascular complications in the six months of follow up. Acute or subacute closure did not occur after stenting. There were no serious side effects such as leucopenia and/or abnormal liver function for three months. Cilostazol was withdrawn in one patient because of skin rash. Patients who underwent primary stenting had no clinical events, such as acute or subacute thrombosis, or side effects.
Conclusions—Cilostazol is an effective antiplatelet agent with minimum side effects after elective, bailout, or primary stent implantation.

Keywords: antiplatelet treatment; stents; stent thrombosis; cilostazol     

Effect of cilostazol on experimental diabetic neuropathy in the rat

Summary Two proposed mechanisms of diabetic neuropathy are microvascular ischaemia and a reduction in Na,K-ATPase activity. We evaluated the effect of cilostazol, a drug that is both a potent phosphodiesterase inhibitor that normalizes nerve Na,K-AT-Pase and a vasodilator, on nerve blood flow (NBF) to determine whether it would improve experimental diabetic neuropathy. We examined whether epineurally applied cilostazol acted as a vasodilator on the peripheral nerve of normal and diabetic rats, and whether feeding the rats a cilostazol-supplemented diet could improve diabetic neuropathy. Cilostazol increased nerve blood flow (NBF) in a dose-dependent fashion with an EC₅₀ of 10^–5.74 mol/l. Cilostazol also normalized NBF in experimental diabetic neuropathy with a 10^–4 mol/l local application on the sciatic nerve. In diabetic neuropathy, a cilostazol-supplemented diet improved both NBF and nerve conduction in a dose- and time-dependent fashion. Potential mechanisms of action of cilostazol on the nerve include its effect on NBF, Na, K-ATPase, and restoration of the thromboxane:prostacyclin ratio. Cilostazol may have potential in the treatment of diabetic neuropathy.Abbreviations EDN Experimental diabetic neuropathy - NBF nerve blood flow - STZ streptozotocin - NRC control rats receiving normal diet - NRH control rats receiving a high (0.1%) cilostazol diet - CSH STZ rats receiving high (0.1%) cilostazol diet - CSL STZ rats receiving low (0.03%) cilostazol diet - CV conduction velocity     

Effect of cilostazol on cerebral arteries in secondary prevention of ischemic stroke

Objective

To compare the effects of cilostazol on cerebral arteries and cerebrovascular blood flow in secondary prevention of ischemic stroke, with those of aspirin.

Methods

Sixty-eight patients who had ischemic stroke during the recent 1–6 months were recruited and randomized into cilostazol or aspirin group. Cerebrovascular condition was assessed by magnetic resonance angiography (MRA) and transcranial doppler ultrasonography (TCD) at the beginning of the study and after 12-month medication.

Results

During the clinical follow-up, ischemic stroke recurred in 2 patients in cilostazol group, while in aspirin group, one case of ischemic stroke recurrence and one case of acute myocardial infarction were found. MRA revealed that in aspirin group, the percentages of patients experiencing aggravation and attenuation of cerebrovascular condition were 3.3% and 6.7%, respectively, while in aspirin group, they were 3.3% and 10%, respectively. Moreover, TCD revealed that 26.9% of the patients in aspirin group and 14.3% of the patients in cilostazol group experienced aggravation of cerebrovascular condition. However, the systolic peak flow velocity of the previously abnormal arteries increased by 42.9% after 12-month medication of cilostazol, which was significantly higher than that after aspirin medication (27.5%) (P = 0.04). Furthermore, as a major side effect of antiplatelet therapy, the frequrency of bleeding was much less in cilostazol group (0 case in cilostazol group vs 5 in aspirin, P < 0.05).

Conclusion

Cilostazol is as effective as aspirin in preventing the aggravation of cerebral arteries in secondary prevention of ischemic stroke. Besides, it is more safe. Cilostazol can increase the systolic peak flow velocity of cerebral arteries, which may improve the blood supply of focal ischemia.