阿立哌唑治疗老年期精神分裂症的疗效观察

目的:比较阿立哌唑和利培酮治疗老年期精神分裂症的疗效和安全性.方法:将60例老年期精神分裂症患者随机分为阿立哌唑组和利培酮组,分别给予阿立哌唑和利培酮治疗8周,采用简明精神病评定量表(BPRS),不良反应量表(TESS)分别评定疗效和不良反应.结果:两组疗效差异无显著性(P＞0.05),但阿立哌唑的不良反应较利培酮少而轻微.结论:阿立哌唑治疗老年期精神分裂症疗效好,起效快,不良反应少.     

精神分裂症应用利培酮与阿立哌唑治疗的临床疗效对比研究

目的 探讨阿立哌唑与利培酮治疗精神分裂症的疗效和安全性。方法 64例精神分裂症患者随机分为阿立哌唑组和利培酮组,各32例,阿立哌唑组给予阿立哌唑治疗,利培酮组给予利培酮治疗,8周为1个疗程。在治疗前及治疗后第2、4、8周来采用阳性阴性症状量表(PANSS)及不良反应量表(TESS)评定其疗效及药物不良反应。结果 阿立哌唑组有效率78.13%(25/32),利培酮组有效率81.25%(26/32),两组疗效比较差异无统计学意义(P>0.05),两药均无严重不良反应,但阿立哌唑组震颤、静坐不能、乳汁分泌、体质量改变及月经周期改变发生率明显低于利培酮组,差异有统计学意义(P<0.05)。结论 阿立哌唑与利培酮治疗精神分裂症均有较好疗效,前者不良反应更少、更安全。     

阿立哌唑与利培酮治疗精神分裂症对照研究

目的:探讨阿立哌唑治疗精神分裂症的疗效及不良反应。方法:以阿立哌唑与利培酮治疗精神分裂症各30例作对照研究,采用阳性症状与阴性症状量表(PANSS)、不良反应症状量表(TESS)评定疗效及不良反应。结果:两组RANSS总分在治疗后与治疗前比较有显著性差异(P<0.01),阿立哌唑组有效率93%,显效率83%,利培酮组有效率90%,显效率80%;两组间疗效无显著性差异(P>0.05),利培酮组副作用比阿立哌唑组多。结论:阿立哌唑治疗精神分裂症疗效确切,且安全性高。     

阿立哌唑与利培酮治疗首发精神分裂症对照研究

目的:评估阿立哌唑治疗首发精神分裂症的疗效和不良反应。方法:将60例门诊首发精神分裂症患者随机分为两组,分别给予阿立哌唑和利培酮治疗6周,采用简明精神病量表(BPRS)和不良反应量表(TESS)评定疗效与不良反应。结果:两组疗效和不良反应发生率比较差异无显著性,但阿立哌唑的锥体外系反应和内分泌改变发生率显著低于利培酮。结论:阿立哌唑治疗首发精神分裂症安全有效。     

利培酮片与阿立哌唑片对慢性精神分裂症维持治疗的对照研究

目的比较利培酮片与阿立哌唑片对慢性精神分裂症疗效及不良反应的影响。方法按照入院顺序随机分配法,将100例慢性精神分裂症患者随机分配为研究组(利培酮)和对照组(阿立哌唑),在治疗前,治疗后1月末、6月末、1年末、3年末分别用BPRS(简明精神病评定量表)CGI(临床疗效总评量表)TESS(不良反应量表)评定疗效和不良反应。结果两组总分和各因子分在治疗前和治疗后比较有显著性差异(P<0.01),研究组总有效率86%。对照组总有效率92%。两组间总分及各因子分在治疗前和治疗后比较无显著性差异(P>0.05),两组间不良反应比较阿立哌唑少于利培酮。结论利培酮与阿立哌唑治疗慢性精神分裂症均有效,不良反应阿立哌唑少于利培酮     

阿立哌唑与利培酮治疗精神分裂症对照研究

目的:探讨阿立哌唑与利培酮治疗精神分裂症的疗效和不良反应。方法:应用阿立哌唑与利培酮分别治疗精神分裂症各34例,疗程8周。用阳性与阴性症状量表(PANSS)评定疗效,用治疗中出现的症状量表(TESS)评定药物不良反应。结果:两组PNSS总评分治疗前后差异有显著性。阿立哌唑组总有效率82.3%,利培酮组为82.3%,两者相同(P>0.05)。不良反应发生率:阿立哌唑组为19.82%,利培酮组为25.32%,阿立哌唑组低于利培酮组,差异有显著性(P<0.05)。结论:阿立哌唑与利培酮对精神分裂症有疗效好,且疗效相同。但不良反应少,是一种安全、有效的抗精神药。     

阿立哌唑与利培酮治疗精神分裂症68例的疗效观察

目的:比较阿立哌唑与利培酮治疗精神分裂症的疗效及安全性.方法:将68例符合CCMD-3诊断标准的精神分裂症患者随机分为阿立哌唑组34例和利培酮组34例,观察8周.以阳性和阴性症状量表(PANSS)评估疗效,治疗时出现的症状量表(TESS)评估不良反应.结果:有效率阿立哌唑组82.35％、利培酮组79.41％,疗效相似(P＞0.05).均无严重不良反应.结论:阿立哌唑与利培酮治疗精神分裂症疗效确切,安全、有效、疗效相似.     

阿立哌唑与利培酮治疗女性精神分裂症患者的临床对照研究

目的比较阿立哌唑与利培酮治疗女性精神分裂症患者的疗效和安全性。方法采用随机、单盲对照的方法,将80例女性精神分裂症患者分为2组,分别使用阿立哌唑与利培酮对照治疗8周。采用阳性症状与阴性症状量表(PANSS)评定疗效,副反应量表%(TESS)评定副反应。结果治疗8周后阿立哌唑组显效率87.5%;利培酮组显效率为82.5%,两组差异无显著性(P>0.05),阿立哌唑组总不良反应发生率为40%,利培酮组总不良反应发生率为45%,两组差异无显著性(P>0.05)。结论阿立哌唑适用女性精神分裂症患者的临床治疗,疗效好、安全性高、依从性好、不良反应轻(且有同有异)、锥体外系反应少、对体重和月经影响小,无溢乳的抗精神病药。     

阿立哌唑与利培酮治疗精神分裂症的对照研究

目的:以利培酮为对照,验证阿立哌唑治疗精神分裂症的疗效及安全性.方法:将100例符合CCMD-3诊断标准的精神分裂症患者随机分为两组,阿立哌唑组50例,利培酮组50例.分别给予阿立哌唑和利培酮治疗8周.采用阳性和阴性症状量表(PANSS)及副反应量表(TESS)评定疗效及不良反应.结果:两组治疗8周的疗效相当,有效率差异无显著性(P>0.05).阿屯哌唑组的锥体外系反应(EPS)发生明显低于利培酮组(P<0.05).结论:阿立哌唑与利培酮治疗精神分裂症疗效相当,不良反应较利培酮少,是一种安全有效的抗精神病药.     

阿立哌唑与利培酮治疗精神分裂症的双盲双模拟多中心研究

目的:研究阿立哌唑与利培酮治疗精神分裂症的疗效与安全性。方法:采用CCMD-3精神分裂症的诊断标准,223例精神分裂症患者随机分为阿立哌唑组(109例)和利培酮组(114例),治疗6周。治疗前后用阳性症状和阴性症状量表(PANSS)、临床疗效总评量表(CGI)和副反应量表(TESS)、锥体外系副反应量表(ESRS)评定疗效和安全性。结果:经6周治疗,223例患者完成研究。阿立哌唑组治愈率31.8%,有效率83.3%;利培酮组治愈率39.1%,有效率87.5%(P>0.05)。两组治疗前后PANSS总分、阳性症状、阴性症状、一般精神病理症状评分比较有显著差异(P<0.01)。阿立哌唑组阴性症状分治疗6周末下降较利培酮组明显,有显著差异(P<0.05)。治疗4周末、6周末阿立哌唑组反应缺乏分下降,和利培酮组比较有显著差异(P<0.05)。治疗4,6周末TESS评定阿立哌唑不良反应发生率低于利培酮(P<0.05)。阿立哌唑组主要不良反应是锥体外系副反应、失眠、头昏等。结论:阿立哌唑对精神分裂症患者安全有效。     

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.