弥散型左旋多巴-苄丝肼治疗帕金森病204例的多中心研究

目的 :观察弥散型左旋多巴 苄丝肼 (DM )治疗帕金森病的疗效和安全性。方法 :采用全国多中心、开放性试验 ,给原用标准片左旋多巴 苄丝肼的 2 0 4例帕金森病病人 ,根据伴随症状的不同 ,选用不同的弥散型左旋多巴 苄丝肼治疗共 8wk。通过Webster评分、病人日记和实验室检查评价药物疗效和安全性。结果 :由标准片左旋多巴 苄丝肼改用或加用弥散型左旋多巴 苄丝肼后 ,“开”期潜伏期缩短 37min ,“开”期持续时间增加 4 7min ,“关”期减少 11min ,Webster评分改善 2 5% ,P <0 .0 1。不良反应少。结论 :弥散型左旋多巴 苄丝肼是一种快速有效和安全的抗帕金森病药物新剂型 ,尤适用于晨僵、“开”期延迟、午后“关闭”、吞咽困难等帕金森病病人     

培高利特、司来吉兰和左旋多巴-苄丝肼治疗帕金森病疗效比较

目的 :比较培高利特、司来吉兰、左旋多巴 苄丝肼治疗帕金森病 (PD)的疗效并观察其神经保护作用 ,筛选安全、有效、适合早期PD治疗的药物。方法 :4 4例早期PD病人 (HY分级I～II级 )随机分为 4组 (均n =11) ,平行地接受左旋多巴 苄丝肼、培高利特、司来吉兰和苯海索治疗 13mo ,观察治疗前后纹状体多巴胺运载体99mTc TRODAT 1特异性 /非特异性摄取、校正帕金森评分量表 (UP DRS)分值的变化。结果 :(1)起病肢体对侧、同侧纹状体99mTc TRODAT 1特异性摄取下降值 ,各组之间未见显著差异 (均P >0 .0 5 )。 (2 )UPDRS量表评分减少 :左旋多巴 苄丝肼治疗组最明显 ,培高利特组、司来吉兰组次之。结论 :3种药物均不增加纹状体多巴胺能神经元的凋亡。培高利特、司来吉兰适合作为早期PD的治疗选择。     

普拉克索联合左旋多巴／苄丝肼治疗晚期帕金森病的疗效观察

目的 评估盐酸普拉克索联合左旋多巴/苄丝肼治疗晚期帕金森病的临床疗效.方法 50例患者随机分为治疗组25例、对照组25例.对照组给予左旋多巴/苄丝肼片和安慰剂,疗程16周;治疗组给予盐酸普拉克索片、左旋多巴/苄丝肼片,疗程16周.观察两组临床疗效.结果 与对照组比较,治疗组帕金森病评定量表评分显著下降,临床疗效明显提高（P＜0.05）,治疗组显效率（84.0%）高于对照组（36.0%）（χ^2=10.08,P＜0.01）.结论 盐酸普拉克索联合左旋多巴/苄丝肼治疗晚期帕金森病效果满意,值得推广应用.     

多巴丝肼联合司来吉兰治疗帕金森病的临床探讨

目的:分析帕金森病运用多巴丝肼联合司来吉兰的临床治疗效果。方法:研究对象选取我院2015.12-2017.1月接诊的帕金森病患者,随机分为对照组和观察组,对照组患者仅服用多巴丝肼,观察组患者服用多巴丝肼联合司来吉兰,观察并比较两组患者的整体治疗效果,不良反应发生率、症状改善情况。结果:观察组患者治疗后的总有效率明显高于对照组患者(P0.05)。观察组治疗后不良反应发生率明显比对照组低,差异有统计学意义(P0.05)。两组患者治疗前症状评分比较(P0.05),两组患者治疗后症状评分明显优于治疗前(P0.05),观察组治疗后改善水平对对照组明显要好,差异有统计学意义(P0.05)。结论:多巴丝肼联合司来吉兰在帕金森病治疗上获得了较好的临床临床疗效,可被临床推广使用。     

进口与国产培高利特治疗帕金森病的疗效比较

目的 :比较进口与国产培高利特治疗帕金森病的疗效。方法 :在并用 (进口组有 6例不并用 )左旋多巴 苄丝肼下 ,进口组帕金森病 68例 ,男性 35例 ,女性 33例 ,年龄 64a±s 12a ,给进口培高利特从 0 .0 2 5mg·d- 1开始 ;国产组 70例 ,男性 37例 ,女性 33例 ,年龄 64a± 9a ,给国产培高利特从 0 .0 5mg·d- 1开始 ,均逐渐增至 0 .5～ 0 .75mg·d- 1,于 3mo后评定疗效。结果 :进口组总有效率 91% ,运动波动总有效率 94 % ,平均每例左旋多巴 苄丝肼剂量减少 2 8% ,国产组分别为 4 6% ,35% ,8%。差异有非常显著意义 (P <0 .0 1)。进口组副作用略多于国产组。结论 :进口培高利特治疗帕金森病效果优于国产品 ,副作用较国产培高利特略明显。     

左旋多巴/苄丝肼治疗帕金森病39例临床疗效观察

目的探讨左旋多巴/苄丝肼（美多巴）治疗帕金森病的临床疗效。方法选择我院73例帕金森病患者,随机分为2组,治疗组39和对照组34。对照组给予常规药物治疗。治疗组在对照组基础上给予美多巴和司来吉兰治疗。疗程均为3个月,对2组患者治疗前后进行帕金森病症状评分量表（UPDRS）评分,并且评定2组的治疗效果。结果治疗组治疗后UPDRS评分改善情况显著优于对照组,差异有统计学意义（P〈0.01）;治疗组总有效率为89.7%,高于对照组的70.5%,差异有统计学意义（P〈0.01）。结论在常规治疗基础上口服美多巴治疗帕金森病,临床治疗效果显著,值得临床借鉴。     

左旋多巴联合司来吉兰或普拉克索治疗帕金森病的药物剂量多中心研究

目的:分析左旋多巴联合司来吉兰或普拉克索治疗帕金森病的真实世界临床给药剂量情况，为合理用药提供参考。方法:基于全国30个三甲医院随机抽取的2014-2019年的帕金森患者用药真实世界处方数据，筛选帕金森病治疗药物，根据实际用药情况分为单用左旋多巴、左旋多巴+司来吉兰、左旋多巴+普拉克索3组的处方数据，分析不同方案中左旋多巴的给药剂量，以及小剂量左旋多巴(≤400.00 mg·d^-1)处方占比。结果:左旋多巴+司来吉兰组的左旋多巴等效日剂量与左旋多巴+普拉克索组(P<0.01)、左旋多巴组(P<0.01)差异均有统计学意义，左旋多巴+普拉克索组与左旋多巴组的左旋多巴等效日剂量差异并无统计学意义(P=0.76)。不同年龄段、年份和地区的左旋多巴等效日剂量有一定差异，小剂量左旋多巴处方占比呈逐年增加。结论:帕金森患者联合使用司来吉兰时可能需要减少左旋多巴用药剂量，而普拉克索的联合使用不需要调整左旋多巴的应用剂量。     

多巴丝肼片联合左旋多巴治疗帕金森病的临床研究

目的探讨多巴丝肼片联合左旋多巴治疗帕金森病的临床效果。方法回顾性分析110例帕金森病患者作为研究对象,随机分为实验组和对照组,各55例。两组患者均进行常规的康复及认知功能训练。对照组单纯口服多巴丝肼片治疗,实验组患者口服多巴丝肼片联合左旋多巴治疗。比较两组治疗前后帕金森病综合评分量表(UPDRS)评分及治疗后蒙特利尔认知评估量表(MoCA)评分、临床疗效。结果治疗后,实验组患者的UPDRSⅠ、UPDRSⅡ、UPDRSⅢ、UPDRSⅣ评分均明显低于对照组,差异均具有统计学意义(P<0.05)。治疗后,实验组患者的MoCA评分(29.67±1.29)分明显高于对照组的(20.18±1.73)分,差异具有统计学意义(P<0.05)。实验组患者的总有效率96.36%明显高于对照组的63.64%,差异具有统计学意义(P<0.05)。结论在帕金森病的治疗过程中,与单一应用左旋多巴相比,多巴丝肼片与左旋多巴联合应用,能够提高患者的治疗效果,改善预后生活质量,患者依从性好。     

司来吉兰联合左旋多巴治疗帕金森病的Meta分析

目的 系统评价司来吉兰联用左旋多巴治疗帕金森病(Parkinson’s disease,PD)的有效性与安全性。方法 检索英文数据库：Cochrane library、PubMed和中文数据库：CNKI、WanFang、VIP,检索时间从建库至2014年11月,收集司来吉兰联用左旋多巴治疗PD的随机对照试验。由2名研究者严格按照纳入与排除标准独立筛选文献、提取资料并评价质量后,使用RevMan5.3软件进行Meta分析。结果 最终纳入5个随机对照试验,共计1 158例PD患者。Meta分析结果显示：司来吉兰联合左旋多巴在改善帕金森病综合评分量表(unified Parkinson’s disease rating scale,UPDRS)总评分、UPDRS运动评分、Webster评分方面优于单用左旋多巴,且有显著性差异[UPDRS总评分：MD=-5.29,95%CI(-7.65,-2.94),P<0.000 1;UPDRS运动评分：MD=-3.57,95%CI(-5.32,-1.82),P<0.000 1;Webster评分：MD=-4.99,95%CI(-7.15,-2.83),P<0.000 01];在死亡率、不良反应发生率方面相当,其差异无统计学意义[死亡率：OR=1.23,95%CI(0.89,1.69),P=0.22;不良反应：OR=1.10,95%CI(0.77,1.57),P=0.60]。 结论 本研究结果表明,司来吉兰联用左旋多巴治疗PD,可显著改善UPDRS总评分、UPDRS运动评分和Webster评分,且安全可靠。     

司来吉兰联合左旋多巴治疗帕金森病 51例

目的 观察司来吉兰联合左旋多巴治疗帕金森病(PD)的临床疗效及其对PD病人帕金森病评分量表(UPDRS)评分、血清β淀粉样蛋白1-42(Aβ1-42)水平及平衡能力的影响.方法 选取2018年6月至2019年8月在重庆医科大学附属遂宁市中心医院就诊的PD病人102例,采用随机数字表法分为观察组和对照组各51例,对照组予以左旋多巴治疗,观察组予以司来吉兰联合左旋多巴治疗,治疗2个月后进行疗效评价,并比较两组病人治疗前后血清Aβ1-42水平、UPDRS评分、Berg平衡量表(BBS)评分、跌倒效能量表(MFES)评分、害怕跌倒(FOF)例数及生活质量综合评价量表(SF-36)评分变化情况.结果 治疗后,观察组总有效率显著高于对照组(94.12％比76.47％,P<0.05);治疗后观察组血清Aβ1-42水平[(1.32±0.42)μg/L比(1.27±0.45)μg/L]、BBS评分[(47.05±4.16)分比(45.31±4.01)分]、MFES评分[(97.22±10.46)分比(89.52±10.75)分]及SF-36评分[(68.54±7.22)分比(61.37±7.46)分]均高于对照组,UPDRS评分[(25.36±1.54)分比(31.33±1.62)分]及FOF例数[8例比18例]均低于对照组(P<0.05).结论 司来吉兰联合左旋多巴治疗PD效果显著,可有效缓解病人病情,改善临床症状.     

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.