Long-term treatment of l-3-n-butylphthalide attenuated neurodegenerative changes in aged rats

It is shown that l-3-n-butylphthalide (l-NBP), the isomer of dl-NBP (racemic 3-n-butylphthalide, a new anti-cerebral ischemic agent) significantly attenuated cerebral hypoperfusion-induced learning dysfunction and brain damage in rats. In the present study, l-NBP (10 and 30 mg/kg) long-term (3-month) treatment of aged rat (21-month-old) significantly improved the learning and memory capability measured by the Morris water maze test. Hematoxylin–eosin-stained slices showed that both l-NBP at 30 mg/kg, and memantine as control at 20 mg/kg, attenuated the neurodegenerative changes in aged rats. l-NBP treatment significantly increased the choline acetyltransferase activity and dose-dependently decreased the acetylcholinesterases activity in the hippocampus of aged rats. The immunohistological study demonstrated that expressions of β-secretase and hyperphosphorylated tau protein were significantly increased in the hippocampus CA1 subfield and parietal cortex in aged rats. However, they were decreased significantly by treatment of l-NBP and memantine for 3 months. Our results indicated that long-term treatment with l-NBP might prevent age-related neurodegenerative changes by modulation of cholinergic system, reduction of phosphorylated tau and maintain structure and morphology of neurons. Therefore, l-NBP might be a potential drug for treatment of senile dementia.     

The effects of systemic treatment with aminobisphosphonates and statins on circulating Vγ9Vδ2-T cells in patients with advanced cancer

Aminobisphosphonates (NBP) are used for treatment of metastatic bone disease. Frequently, patients undergoing NBP-treatment experience side-effects, known as acute phase response (APR), resulting from cytokine production by Vγ9Vδ2-T cells. As opposed to NBP, statins reduce intracellular phosphoantigen levels and prevent NBP-induced Vγ9Vδ2-T cell activation in vitro. We conducted a pilot study in patients with (bone-)metastasized malignancies receiving NBP-treatment and evaluated the phenotype and function of circulating Vγ9Vδ2-T cells in vivo and the effects of statins on Vγ9Vδ2-T cell responses and the associated APR. We observed reduced expression of perforin, granzyme B and HLA-DR on Vγ9Vδ2-T cells in patients treated with NBP and statins. However, statins could not prevent NBP-induced changes in circulating Vγ9Vδ2-T cell numbers or production of IFNγ and TNFα. Consistent with this, simvastatin could not prevent the occurrence of APR upon NBP-infusion. These observations call for the exploration of alternative strategies to prevent collateral APR upon NBP treatment.     

Effect of adjuvant disease in rats on cyclophosphamide and isophosphamide metabolism

After the injection of a variety of arthritogenic adjuvants into male Wistar rats, hepatic activation of cyclophosphamide and isophosphamide is rapidly and profoundly depressed. This selective injury is largely reversible with phenobarbital and principally restricted to the liver microsomal protein fraction, which demethylates aminopyrine and N, N-dimethylaniline and generates “alkylating metabolites” from cyclophosphamide in vitro. Evidence is presented, based upon both metabolite excretion studies and the duration of hexabarbital-induced hypnosis, that this phenomenon is not an artifact in vitro and must be seriously considered in evaluating both the efficacy of potential anti-arthritic drugs against the rat adjuvant arthritis and their toxicity in these arthritic animals. A quantitative separation of two pathological responses to the same adjuvant may be obtained: (1) in Buffalo rats, whose liver metabolism may be profoundly impaired while they suffer minimal (or no) arthritis after being inoculated with adjuvants which are truly arthritogenic in other rat strains; (2) with Mycobacterium tuberculosis dispersed in methyl oleate, which induces minimal arthritis in Wistar rats, but nevertheless impairs their liver metabolism over a prolonged period (14 days or more). Drug metabolism appeared to be normal in rats with two other immunologically mediated “inflammatory diseases” (graft vs host disease and allergic encephalomyelitis) and in other rodents examined after adjuvant inoculations. A novel bioassay for cyclophosphamide and isophosphamide metabolites is described which utilizes their ability to prevent grafted rat lymphocytes from initiating a graft vs host reaction in tolerant recipient rats. At least four alkylating metabolites of cyclophosphamide were found in rat bile and tentatively identified by thin-layer chromatography. The possible error in relying on changes in urinary excretion (rather than biliary excretion) of drug metabolites as a guide to changes in hepatic xenobiotic metabolism is discussed.     

恩必普治疗急性缺血性脑卒中的疗效及其对患者血清hs-CRP水平的影响

目的 观察恩必普治疗急性缺血性脑卒中的疗效,探讨其对患者血清超敏C反应蛋白(hs-CRP)水平的影响.方法 选择我院内科于2015年8月至2016年8月期间收治的56例急性缺血性脑卒中患者为研究对象,根据随机数表法随机分为观察组(n=28)和对照组(n=28),对照组予抗血小板等常规治疗,观察组联合应用口服恩必普(丁苯酞软胶囊),14 d为一个疗程.采用美国国立卫生研究院卒中量表(NIHSS)评价两组患者治疗前后的神经功能缺损情况,并比较其血清hs-CRP水平.结果 观察组与对照组治疗后NIHSS评分分别为(5.81±1.94)分和(7.33±2.38)分,血清hs-CRP分别为(6.69±1.54)mg/L和(8.96±1.98)mg/L,均明显低于治疗前的(12.78±3.51)分、(12.64±4.86)分和(12.69±3.94)mg/L、(12.84±3.58)mg/L,差异均有统计学意义(P<0.05).结论 恩必普治疗急性缺血性脑卒中可以有效降低患者血清hs-CRP水平,改善患者的神经功能缺损,提高临床疗效.     

丁苯酞软胶囊治疗合并糖尿病的急性脑梗死70例

目的 观察丁苯酞软胶囊治疗合并糖尿病的急性脑梗死的临床疗效及安全性.方法 141 例急性脑梗死患者随机分为对照组和丁苯酞治疗组,对照组给予拜阿司匹林、依达拉奉、银杏叶等治疗,丁苯酞治疗组在对照组的基础上加用丁苯酞软胶囊.在入院时和治疗后第1 天、第7 天、第14 天、第2 1 天进行NIHSS 评分及日常生活能力评分,在第1 天第14 天及第21 天检测肝功、肾功,血凝常规.结果 2 组第14 天、2 1 天的NIHSS 评分、Barthel 指数评分均较治疗前明显好转,观察组优于对照组,差异有显著性(P ＜0.01);而2 组的血凝常规比较差异无显著性.结论 丁苯酞治疗合并糖尿病的急性脑梗死能有效改善神经功能缺损.而相对安全,对肝、肾功、凝血功能无明显影响.可作为糖尿病并发急性期脑梗死治疗安全有效的选择.     

Efficacy of sequential N-butylphthalide therapy on psychiatric and behavioral functions in acute ischemic stroke

Background:Stroke can cause physical and mental problems. This study examined how the sequential therapy of N-butylphthalide (NBP) could effectively improve physical movement, life activities, and psychological disorders in stroke patients.Methods:This double-blind, randomized controlled trial included middle-aged or elderly patients with acute ischemic stroke that had commenced within 48 hours before enrolment in the study. The experimental group was administered 100 mL NBP injections twice a day in the first 14 days, and a sequential 200 mg NBP soft capsule 3 times a day for the next 76 days. The control group was administered 100 mL NBP placebo injections twice a day in the first 14 days and 200 mg sequential NBP placebo soft capsule 3 times a day for the next 76 days. Primary outcomes were the National Institutes of Health Stroke Scale, the Barthel Index of activities of daily living, and Modified Rankin Scale which were evaluated at day 0, day 14, and month 1 or at day 14, month 3, and month 6. Secondary outcomes included the Hamilton Anxiety Scale and the Hamilton Depression Scale, all were evaluated on day 0, month 3, and month 6. Moreover, the adverse reaction of NBP or other serious adverse events were evaluated at each time.Results:Our therapy significantly increased the Barthel Index of activities of daily living scores, decreased the National Institutes of Health Stroke Scale and Modified Rankin Scale scores, and the incidence of the Hamilton Anxiety Scale and the Hamilton Depression Scale of ischemic stroke patients (P < .05).Conclusion:Our results indicated that 90 days’ sequential therapy with NBP as an additional therapy in the treatment of ischemic stroke can better improve patients’ psychological and behavioral functions without significant side effects.     

前列疏胶囊治疗前列腺炎药理学研究Ⅱ——对试验性非细菌性前列腺炎、炎症、疼痛及利尿动物模型的作用

目的:研究前列疏胶囊治疗前列腺炎的药理作用。方法:通过试验性非细菌性前列腺炎模型、抗炎、镇痛和利尿等试验,研究其药理作用。结果:前列疏胶囊可明显抑制非细菌性前列腺炎模型大鼠病理生理改变;明显减轻二甲苯所致小鼠耳肿胀和降低毛细血管通透性的增高;抑制大鼠肉芽肿;明显减少冰醋酸诱发小鼠疼痛性扭体次数,延长热板刺激性疼痛反应痛阈值;增加大鼠排尿量。结论:前列疏胶囊具有明显对抗非细菌性前列腺炎、抗炎、镇痛和利尿作用。     

丁苯酞对Aβ1-42致阿尔茨海默病模型大鼠记忆的影响作用和可能机制

目的 探讨丁苯酞(3-n-Butylphthalide,NBP)对Aβ142致阿尔茨海默病模型大鼠记忆的影响作用与可能机理.方法 将Aβ1-42制备的AD大鼠随机分为五组,对照组,AD模型组、NBP 40 mg/kg组、NBP 80 mg/kg组和NBP 160 mg/kg组,20只/组,对照与模型组给予蒸馏水,给药30 d.结果 对照组大鼠状态良好,AD模型组大鼠精神萎靡,活动迟缓,进食量少,体质量增高不明显,NBP组大鼠的状态介于模型和对照组间.与对照组比,AD模型组逃避潜伏期延长,SOD和OH-降低,胆碱酯酶增高(P＜0.05).NBP组可明显降低AD大鼠逃避潜伏期,增高SOD和OH,降低胆碱酯酶(P＜0.05),与NBP低剂量组比,NBP中、高剂量可明显降低逃避潜伏期时间、增高OH、降低胆碱酯酶(P＜0.05).与对照组比,AD模型组的Tau表达明显增高(P＜0.05),AKT表达明显降低(P＜0.05),与AD模型组比,NBP组的Tau表达明显降低(P＜0.05),AKT表达明显增高(P＜0.05).结论 NBP可明显改善AD大鼠的记忆能力,可增高脑内SOD和OH,降低胆碱酯酶,改善脑内Tau和AKT表达.     

Periodontal health during orthodontic treatment with clear aligners and fixed appliances: A meta-analysis

Background

Clear aligners have become increasingly popular because of their esthetics and comfort. The authors’ aim in this systematic review was to compare periodontal health in patients undergoing orthodontic treatment with clear aligners with that of those undergoing orthodontic treatment with fixed appliances.

丁基苯酞对帕金森病细胞模型保护作用的初步研究

目的探讨丁基苯酞(dl-3-n-Butylphthalide,NBP)对鱼藤酮诱导的帕金森病细胞模型的保护作用及其机制。方法分别使用终浓度为0.1、1、10、100μM NBP和溶剂二甲基亚砜(DMSO)预处理SH-SY5Y细胞24h后,加入终浓度为200nM的鱼藤酮处理24h建立多巴胺能细胞损伤模型,观察各组细胞形态,采用四甲基偶氮唑盐(MTT)比色法检测细胞活性,流式细胞术检测细胞凋亡率(Annexin V-FITC/PI)、线粒体膜电位(JC-1)、细胞内活性氧水平(DCFH-DA)。结果200nmol/L鱼藤酮处理SH-SY5Y细胞24h能够诱导细胞活性下降和细胞凋亡,NBP预处理后SH-SY5Y细胞存活率明显升高,细胞凋亡率降低,线粒体膜电位显著升高(P0.05),细胞内活性氧水平显著降低(P0.05),且随NBP浓度的增加对SH-SY5Y细胞的保护作用增强。结论NBP对鱼藤酮诱导的SH-SY5Y细胞损伤具有良好的保护作用,线粒体保护可能是其作用机制之一。