盐酸美金刚片联合天智颗粒治疗血管性痴呆的临床观察

目的:探讨盐酸美金刚片联合天智颗粒治疗血管性痴呆的临床疗效及安全性。方法:选取2014年6月-2016年6月我院收治的血管性痴呆患者94例作为研究对象,按照随机数字表法分为观察组和对照组,各47例。除基础药物治疗外,对照组患者给予天智颗粒5 g,po,tid;观察组患者在对照组基础上给予盐酸美金刚片起始剂量5 mg,每周增加5 mg,至治疗第4周时达维持剂量20 mg/d,po,qd。两组患者均连续治疗4周。观察两组患者的临床疗效以及治疗前后的简易智能状态检查量表(MMSE)、蒙特利尔认知评估量表(MoCA)、日常生活能力量表(ADL)评分,检测血清脑源性神经营养因子(BDNF)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平,并记录不良反应发生情况。结果:观察组患者的临床总有效率(80.85%)显著高于对照组(61.70%),差异有统计学意义(P<0.05)。治疗前,两组患者MMSE、MoCA、ADL评分和BDNF、MDA、SOD水平比较,差异均无统计学意义(P>0.05);治疗后,两组患者MMSE、MoCA、ADL评分以及BDNF、SOD水平均显著增加,MDA水平显著降低,且观察组显著优于对照组,差异均有统计学意义(P<0.05)。两组患者均未见明显不良反应发生。结论:盐酸美金刚片联合天智颗粒治疗血管性痴呆的临床疗效显著,可提高患者的认知功能和日常活动能力,改善其BDNF、MDA和SOD水平,且安全性较高。     

丁苯酞联合尼莫地平治疗血管性认知障碍的临床观察

目的探讨丁苯酞联合尼莫地平治疗血管性认知障碍的临床效果。方法选取2011年6月—2015年5月陕西省第二人民医院收治的血管性认知障碍患者72例,随机分为对照组和治疗组,每组各36例。对照组口服尼莫地平片,30 mg/次,3次/d。治疗组在对照组基础上口服丁苯酞软胶囊,0.2 g/次,4次/d。两组均治疗8周。观察两组的临床疗效,比较治疗前后双侧大脑前动脉(ACA)、双侧大脑中动脉(MCA)、双侧大脑后动脉(PCA)、双侧椎动脉(VA)和基底动脉(BA)平均血流速度、蒙特利尔认知评估量表(MOCA)评分、简易智力状态检查量表(MMSE)评分、神经元特异性烯醇化酶(NSE)、血栓素B2(TXB2)的变化。结果治疗后,对照组和治疗组的总有效率分别为72.22%、91.67%,两组比较差异有统计学意义(P0.05)。治疗后,两组双侧ACA、双侧MCA、双侧PCA、双侧VA和BA平均血流速度均上升,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标的上升程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组MMSE和MOCA评分均上升,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标的上升程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组TXB2和NSE水平均降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标的下降程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。结论丁苯酞联合尼莫地平治疗血管性认知障碍具有较好的临床疗效,可改善认知功能和脑血液循环,降低炎症因子水平,安全性较好,具有一定的临床推广应用价值。     

丁苯酞联合尼莫地平对脑梗死后血管性认知障碍患者ACA、MCA、PCA的影响

目的:探究丁苯酞联合尼莫地平对脑梗死后血管性认知障碍患者双侧大脑前动脉(ACA)、双侧大脑中动脉(MCA)、双侧大脑后动脉(PCA)的影响。方法:选取2018年2月～2020年2月收治的68例脑梗死后血管性认知障碍患者作为研究对象,按照随机数字表法将患者均分为对照组和研究组,对照组给予丁苯酞治疗,研究组在对照组基础上联合尼莫地平治疗,对比两组患者的ACA、MCA、PCA水平。结果:研究组两侧大脑前动脉、后动脉、中动脉搏动指数与对照组相比,差异显著有统计学意义(P0.05)。结论:脑梗死后血管性认知障碍患者联合丁苯酞与尼莫地平治疗,对患者脑血管功能的恢复有积极的促进作用。     

美金刚片联合奥拉西坦注射液治疗血管性痴呆的疗效分析

目的分析美金刚片联合奥拉西坦注射液治疗血管性痴呆的临床疗效。方法 52例血管性痴呆患者,按照随机数字表法分为对照组和观察组,各26例。对照组单纯给予美金刚片治疗,观察组给予美金刚片联合奥拉西坦注射液治疗。比较两组患者临床疗效、不良反应发生率及简明精神状态量表(MMSE)、日常生活能力量表(ADL)、蒙特利尔认知评估量表(MoCA)评分。结果观察组MMSE评分(22.36±3.45)分及MoCA评分(65.43±1.14)分均显著高于对照组的(18.47±2.68)、(58.28±2.12)分,ADL评分(17.19±2.32)分明显低于对照组的(18.84±2.57)分,差异具统计学意义(P<0.05)。观察组临床总有效率为96.15%,高于对照组的73.08%,差异具统计学意义(P<0.05)。两组不良反应发生率比较差异无统计学意义(χ^2=1.083, P>0.05)。结论对血管性痴呆患者应用美金刚片联合奥拉西坦注射液治疗,可有效增强其临床疗效,安全性较高。     

胞磷胆碱联合美金刚治疗血管性痴呆的临床研究

目的探讨胞磷胆碱钠联合美金刚治疗血管性痴呆的临床疗效。方法选取2015年1月—2018年2月在南京医科大学第二附属医院治疗血管性痴呆患者84例,随机分为对照组(42例)和治疗组(42例)。对照组口服盐酸美金刚片,第1周5 mg/次,1次/d,第2周5 mg/次,2次/d,第3周早晨10 mg/次,下午5 mg/次,维持剂量10 mg/次,2次/d;治疗组在对照组基础上口服胞磷胆碱钠片,0.2 g/次,3次/d。两组患者均经过4周治疗。观察两组患者临床疗效,同时比较治疗前后两组患者简易智力状态检查量表(MMSE)、长谷川痴呆量表(HDS)、蒙特利尔认知评估量表(Mo CA)和日常生活能力(ADL)评分及血清学指标。结果治疗后,对照组和治疗组临床总有效率分别为80.95%和95.24%,两组比较差异具有统计学意义(P0.05)。治疗后,两组MMSE量表评分、HDS量表评分、Mo CA量表评分、ADL量表评分均明显升高(P0.05),且治疗组上述评分明显高于对照组(P0.05)。治疗后,两组血清同型半胱氨酸(Hcy)、白细胞介素-6(IL-6)水平均显著降低(P0.05),降钙素基因相关肽(CGRP)和脑源性神经营养因子(BDNF)水平显著升高(P0.05),且治疗组血清学指标改善程度明显优于对照组(P0.05)。结论胞磷胆碱钠联合美金刚治疗血管性痴呆可有效改善患者认知和行为功能,提高日常生活能力,具有一定的临床推广应用价值。     

谷红注射液治疗血管性痴呆的效果及对患者相关指标的影响分析

目的探讨谷红注射液治疗血管性痴呆患者的临床效果及对其相关指标的影响。方法74例血管性痴呆患者,依据随机数字表法分为观察组与对照组,各37例。对照组患者应用脑复康(通用名:吡拉西坦片)治疗,观察组则应用谷红注射液治疗。对比两组治疗前后的蒙特利尔认知评估量表(MoCA)评分、简明精神状态量表(MMSE)评分、日常生活活动能力量表(ADL)评分、大脑动脉血流速度,药物不良反应发生率。结果治疗后,观察组的MoCA评分(22.03±3.62)分、MMSE评分(20.96±3.97)分、ADL评分(69.79±10.15)分高于对照组的(19.53±3.01)、(17.82±2.36)、(53.26±5.19)分,差异有统计学意义(P<0.05)。治疗后,观察组的大脑前动脉、大脑中动脉、大脑后动脉血流速度均高于对照组,差异有统计学意义(P<0.05)。观察组的药物不良反应率为2.70%,与对照组的为5.41%比较,差异无统计学意义(P>0.05)。结论对于血管性痴呆患者通过给予谷红注射液治疗可获得满意疗效,有利于改善患者的认知功能并提升日常生活自理能力,且有利于提高患者大脑动脉血流速度,同时药物安全性良好。     

盐酸美金刚治疗老年帕金森病痴呆的临床疗效分析

目的:探讨盐酸美金刚治疗老年帕金森痴呆患者的临床疗效及安全性。方法:64例老年帕金森痴呆患者随机分为治疗组和对照组,每组各32例。对照组采用盐酸多奈哌齐联合多巴丝肼片进行治疗,治疗组采用盐酸美金刚联合多巴丝肼片治疗,16周后对两种不同方案的临床疗效、患者日常生活能力及不良反应进行比较分析。结果:采用不同方案进行治疗后,两组患者的治疗效果均有一定提高,即MoCA和MMSE评分均有所上升,且治疗组MoCA和MMSE评分显著高于对照组(P0.05);在患者日常生活能力方面,治疗组也优于对照组(P0.05)。结论:盐酸美金刚在治疗老年帕金森痴呆中疗效显著,能显著提高患者日常生活能力,且服药期间不良反应轻微安全,有一定的临床推广价值。     

奥拉西坦胶囊和脑肽胶囊治疗老年血管性痴呆的疗效比较

目的探讨奥拉西坦胶囊和脑肽胶囊治疗血管性痴呆的疗效对比。方法选取2017年5月—2018年5月在河南省人民医院省直第一医院治疗血管性痴呆患者86例,根据入院的先后分为对照组(43例)和治疗组(43例)。对照组口服脑肽胶囊,3粒/次,2次/d;治疗组口服奥拉西坦胶囊,2粒/次,3次/d。两组患者均治疗4周。观察两组患者临床疗效,同时比较治疗前后两组患者MMSE评分、MoCA评分、BDAE评分、ADL评分以及血清同型半胱氨酸(Hcy)、白细胞介素-1β(IL-1β)、血管紧张素Ⅱ(AngⅡ)、脂蛋白磷脂酶A2(Lp-PLA2)和胰岛素样生长因子-1(IGF-1)水平。结果治疗后,对照组临床有效率为81.40%,显著低于治疗组的97.67%,两组比较差异具有统计学意义(P0.05)。治疗后,两组MMSE评分、MoCA评分、BDAE评分、ADL评分均显著升高(P0.05),且治疗组上述评分明显高于对照组(P0.05)。治疗后,两组患者血清Hcy、IL-1β、AngⅡ、Lp-PLA2、IGF-1水平均显著降低(P0.05),且治疗组上述血清学指标明显低于对照组(P0.05)。结论奥拉西坦胶囊治疗血管性痴呆可有效改善认知功能,有利于语言功能和行为功能改善,提高日常生活能力,具有一定的临床推广应用价值。     

六经头痛片联合氟桂利嗪治疗偏头痛的临床研究

目的观察六经头痛片联合盐酸氟桂利嗪治疗偏头痛的临床效果。方法选择2017年1月—2018年11月郑州煤炭工业(集团)有限责任公司米村煤矿职工医院收治的偏头痛患者123例,随机分为对照组(62例)和治疗组(61例)。对照组患者睡前口服盐酸氟桂利嗪胶囊,2粒/次,1次/d。治疗组在对照组用药基础上口服六经头痛片,3片/次,3次/d。两组患者连续治疗3个月。观察两组患者临床疗效,同时比较治疗前后两组患者同型半胱氨酸(Hcy)、降钙素基因相关肽(CGRP)、5-羟色胺(5-HT)水平,大脑后动脉(PCA)、大脑前动脉(ACA)和大脑中动脉(MCA)血流速度,以及视觉模拟评分法(VAS)评分和头痛发作频率。结果治疗后,对照组和治疗组临床有效率分别为77.42%和93.44%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者Hcy和CGRP水平显著降低(P0.05),而5-HT水平显著升高(P0.05);且治疗组患者Hcy、CGRP和5-HT水平改善效果明显优于对照组(P0.05)。治疗后,两组患者PCA、ACA和MCA血流速度水平,以及VAS评分和头痛发作频率均明显降低(P0.05),且治疗组患者明显比对照组低(P0.05)。结论六经头痛片联合盐酸氟桂利嗪治疗偏头痛可降低患者疼痛次数,降低脑血流速度,安全可靠,具有一定的临床推广应用价值。     

盐酸丁咯地尔治疗血管性痴呆及对血流动力学的影响

目的评价盐酸丁咯地尔对血管性痴呆患者血流动力学的影响及临床疗效。方法将64例血管性痴呆患者随机分为2组,治疗组(33例)给予盐酸丁咯地尔150~200mg,每日1次静脉滴注,对照组(31例)给予胞二磷胆碱750mg,每日1次静脉滴注;4周为1个疗程。应用简易智能状态检查量表(MMSE)、长谷川痴呆量表(HDS)、痴呆严重程度临床评定量表(WMS)评定认知功能、采用Barthel指数(BI)评价日常生活活动能力(ADL)以判定疗效,治疗前后采用经颅多普勒(TCD)检测大脑中动脉(VMCA)、大脑前动脉(VACA)、大脑后动脉(VPCA)、椎动脉(VVA)、基底动脉(VBA)的血管平均血流速度(VM)及搏动指数(PI)的变化。结果治疗组用药后认知功能明显改善(P<0.05和P<0.01),大脑中动脉、大脑前动脉、大脑后动脉、椎动脉、基底动脉的血管平均血流速度及搏动指数改善,与对照组比较差异有显著性(P<0.05和P<0.01)。结论盐酸丁咯地尔可提高血管性痴呆患者的脑血流量,降低血管阻力,明显改善血管性痴呆的认知功能、智能状态及提高生活质量。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

2-(Acetoxyphenyl)-(Z)-styryl sulfides as cyclooxygenase inhibitors

2-(Acetoxyphenyl)-(Z)-styryl sulfides are described as selective cyclooxygenase-2 (COX-2) inhibitors, useful for treating inflammation and COX-2-mediated disorders including neoplasia. 2-(Acetoxyphenyl)-(Z)-styryl sulfide is claimed to be the most potent COX inhibitor in the series with a COX-2 selectivity ratio of 33. This compound is also claimed to be superior to celecoxib (Celebrex^®, Pfizer) in inhibiting cell growth of colorectal carcinoma cells. In this evaluation, the COX inhibitory activity of this compound is compared to that previously disclosed for diarylheterocycles and 2-(acetoxyphenyl)alkyl sulfides. The validity of the DLD-1 cell line in the growth inhibition studies is questioned based on recent literature reports indicating the lack of COX-2 expression in this cell line.     

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ～ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.     

Drug targets for cognitive enhancement in neuropsychiatric disorders

The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA_A α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.