盐酸氨溴索佐治小儿毛细支气管炎临床观察

目的：观察盐酸氨溴索注射液辅助治疗小儿毛细支气管炎的临床疗效。方法：135例毛细支气管炎患儿分为治疗组75例和对照组60例。两组均给予常规抗感染及对症支持治疗,治疗组另辅以盐酸氨溴索注射液,15mg,ivd,qd,疗程3—5d。结果：治疗组和对照组总有效率分别为97．3％和86．6％（P〈0．05）;治疗组咳嗽、肺部哆音消失时间及住院天数较对照组明显缩短（P〈0．01）,未见明显不良反应。结论：盐酸氨溴索注射液佐治小儿毛细支气管炎安全、有效。     

氨麻美敏分散片的人体相对生物利用度和生物等效性

目的：研究氨麻美敏分散片受试制剂与参比制剂中盐酸伪黄碱、马来酸氯苯那敏、氢溴酸右美沙芬、对乙酰氨基酚的人体相对生物利用度及生物等效性。方法：18名健康受试者采用随机分组自身交叉对照实验设计，口服氨麻美敏分散片受试制剂和参比制剂各2片（相当于对乙酰氨基酚650mg，盐酸伪麻黄碱60mg，氢溴酸右美沙芬30mg，马来酸氯苯那敏4mg），定时取血，用LC-MS／MS法测定血药浓度，以DAS软件计算人体相对生物利用度，评价生物等效性。结果：口服氨麻美敏分散片受试制剂和参比制剂，盐酸伪麻黄碱的消除半衰期分别为（4．3±1．6）h和（4．0±1．5）h，达峰时间分别为（1．8±1．3）h和（1．9±1．0）h，达峰浓度分别为（463．3±149．7）和（462．6±193．6）μg·L^-1。，相对生物利用度为（105．7±44．6）％；马来酸氯苯那敏的消除半衰期分别为（20．0±8．2）h和（18．2±8．5）h，达峰时间分别为（3．0±1．3）h和（3．2±1．6）h，达峰浓度分别为（8．8±3．8）μg·L^-1和（9．3±4．5）μg·L^-1相对生物利用度为（104．0±38．3）％；氢溴酸右美沙芬的消除半衰期分别为（4．0±1．4）h和（3．8±1．7）h，达峰时间分别为（2．6±1．2）h和（2．9±2．1）h，达峰浓度分别为（5．8±6．8）μg·L^-1。和（5．8±6．8）μg·L^-1，相对生物利用度为（93．7±25．3）％；对乙酰氨基酚的消除半衰期分别为（3．1±1．4）h和（3．2±1．6）h，达峰时间分别为（1．2±0．8）h和（1．2±0．6）h，达峰浓度分别为（9924．5±4419．6）μg·L^-1和（10131．1±5320．3）μg·L^-1，相对生物利用度为（112．3±57．9）％。结论：受试制剂与参比制剂具有生物等效性。     

依沙吖啶湿敷对肾病综合征患儿阴囊水肿的作用

目的：回顾性分析依沙吖啶湿敷对肾病综合征患儿阴囊水肿的疗效。方法：对1998年－2008年120例肾病综合征阴囊水肿的患儿分为治疗组和对照组各60例,两组患儿均按肾病常规治疗,对照组患儿阴囊水肿未作处理,治疗组用0．1％依沙吖啶湿敷阴囊。结果：治疗组和对照组阴囊水肿消退时间分别为（5．28±0．65）d和（13．88±3．62）d,治愈时间分别为（5．62±0．73）d和（14．30±4．36）d,两组比较差异均有统计学意义（P〈0．01）。结论：对肾病综合征患儿采用0．1％依沙吖啶湿敷,能防止阴囊水肿的感染,加快阴囊水肿消退,是一种有效的辅助治疗方法和护理手段。     

盐酸伊托必利缓释片在犬体内的药动学

目的：对盐酸伊托必利缓释片和分散片在家犬体内进行药动学研究。方法：6只家犬按照单剂量双周期实验设计方案给药，建立一个测定狗血中的伊托必利的高效液相色谱法。结果：2种制剂在体内均符合单隔室一级吸收模型，缓释片和分散片Cmax分别为（548．6±54．2）μg·L^-1和（798．1±42.5）μg·L^-1。tmax分别为（6．7±1．2）h和（1．83±0．25）h，应用3P97药动学程序进行计算，t1/2（Ke）分别为（6．0±0．6）h和（5．72±0．26）h，AUC0→∞分别为（6．6±0．5）mg·L^-1·h和（7．0±0．6）mg·L^-1·h。结论：盐酸伊托必利缓释片具有显著缓释作用。     

普伐他汀钠片和胶囊的人体生物等效性

目的：评价健康受试者单剂量口服受试普伐他汀钠片剂、胶囊剂及参比普伐他汀钠片剂在人体内的生物等效性。方法：采用3周期的二重3×3拉丁方交叉试验设计，24名健康男性受试者随机交叉口服40mg的3种普伐他汀钠制剂。用HPLC法测定受试者体内普伐他汀钠的血药浓度变化，并进行生物等效性评价。结果：普伐他汀钠片剂、胶囊剂与参比制剂普伐他汀钠片的AUG0→∞分别为（234．3±45．0），（229．7±50．3），（243．0±40．9）μg·h·L^-1；AUG0→T分别为（205．4±38．3），（202．8±40．1），（211．4±36．7）μg·h·L^-1；tmax分别为（1．4±0．4），（1．4±0．3），（1．5±0．3）h；Cmax分别为（48．3±9．7），（49．0±12．5），（49．2±11．3）μg·L^-1。普伐他汀钠片与胶囊的相对生物利用度分别为（97．5±10．7）％和（96．2±10．2）％。结论：经统计学分析，2种受试制剂均与参比制剂生物等效。     

布地奈德吸入联合氨溴索静脉点滴辅治毛细支气管炎疗效分析

目的探讨布地奈德雾化吸入联合盐酸氨溴索静脉点滴辅治毛细支气管炎的临床疗效。方法将112例毛细支气管炎患儿随机分人对照组与观察组,给予52例对照组患儿抗感染、平喘等常规治疗,60例观察组患者接受布地奈德雾化吸人联合盐酸氨溴索静脉点滴治疗。比较两组临床疗效、临床症状体征消失时间、缺氧症状评分的差别。结果观察组与对照组治疗总有效率分别为98．3％和78．9％,差别具有统计学意义（P〈0．I）5）;观察组咳嗽、气促、肺部体征及X线征象消失时间均显著早于对照组（P〈0．05）;观察组治疗1d、3d和5d缺氧症状评分显著低于对照组（P〈0．05）。结论布地奈德雾化吸人联合盐酸氨溴索静脉点滴辅治毛细支气管炎临床疗效更为理想,更有利于患儿病情恢复。     

液-质联用法考察单硝酸异山梨酯片的人体生物等效性

目的：建立液-质联用法（LC-MS／MS）的检测方法，评价受试与参比的单硝酸异山梨酯片在健康人体的生物等效性。方法：健康志愿者20名，随机交叉试验设计，单剂量口服受试或参比制剂，给药剂量均为20mg，应用LC-MS／MS法测定各受试者给药后不同时间点的血药浓度，计算药动学参数，应用BAPP 2．0软件进行生物等效性评价。结果：受试与参比制剂的药动学参数如下，AUC0-24分别为（3．4±0．6）mg·h·L^-1、（3．3±0．7）mg·h·L^-1，AUC0-∞分别为（3．6±0．7）mg·h·L^-1、（3．5±0．7）mg·h·L^-1；tmax分别为（1．2±0．9）h、（1．0±0．6）h；Cmax分别为（464．9±108．2）μg·L^-1、（433．6±115．3）μg·L^-1；t1／2分别为（5．4±0．7）h、（5．5±0．9）h。单硝酸异山梨酯片的相对生物利用度为（106．0±16．0）％，主要药动学参数经统计学分析无显著性差异。结论：受试与参比制剂具有生物等效性。     

富马酸卢帕他定胶囊的人体生物等效性

目的：研究国产富马酸卢帕他定胶囊和普通片的人体生物等效性。方法：20名健康男性志愿者按2×2交叉试验方案设计，分别口服受试制剂和参比制剂各10mg，并采集24h内动态血标本；用HPLC／MS法测定血浆中卢帕他定浓度，计算药动学参数，并判定两种制剂的生物等效性。结果：受试制剂和参比制剂的主要药动学参数Cmax分别为（3．6±1．6）ug·L^-1和（3．7±1．9）ug·L^-1,tmax分别为（0．8±0．1）h和（0．8±0．1）h，AUC0-24分别为（12．3±7．1）ug·L^-1·h和（13．1±9．5）ug·L^-1·h，AUC0-∞分别为（13．1±7．5）ug·L^-1·h和（13．9±10．0）ug·L^-1·h，t1/2（ke）分别为（5．9±2．4）和（5．4±1．7）h，两制剂主要药动学参数经对数转换后进行方差分析及双单侧t检验，并计算90％置信区间，表明两种制剂生物等效，受试制剂的人体生物利用度为（100．4±19．3）％。结论：两种制剂生物等效。     

单次口服法罗培南钠片的人体药动学

目的：研究中国健康受试者单次口服不同剂量法罗培南钠片后的药动学。方法：30名健康受试者（男、女各15名）按性别随机分为3组（每组男女各5名），分别口服低、中、高（150，300，600mg）3个剂量的法罗培南钠片，于不同时间分别测定血浆中法罗培南浓度。结果：法罗培南的体内经时过程符合有滞后时间的一室模型，3个剂量组的tmax分别为（1．0±0．5），（0．8±0．5），（0．88±0．27）h；Cmax分别为（2．2±0．8），（4．8±1．8），（9．7±2．9）mg·L^-1；AUC0-t分别为（4．1±2．0），（7．8±4．5），（18．7±6．5）mg·h·L^-1；AUC0-∞分别为（4．2±2．0），（7．8±4．6），（18．9±6．6）mg·h·L^-1；t1，2分别为（1．11±0．28），（0．97±0．21），（1．1±0．4）h；CLz/F分别为（46．8±27．5），（48．8±21．4），（34．8±9．9）L·h^-1。结论：健康人单剂量口服法罗培南钠片的体内药动学符合有滞后时间的一房室模型。Cmax与AUC与服药剂量呈正相关，不同性别受试者单剂量口服法罗培南钠片后的药动学参数在性别受中无明显差异，单剂量口服法罗培南钠片在健康人体的代谢特征基本与文献报道参数一致．     

反相高效液相色谱-荧光检测法测定大鼠血浆中延胡索乙素的浓度

目的：建立大鼠血浆中延胡索乙素浓度的高效液相色谱-荧光检测法。方法：色谱柱为Phenomenex C18色谱柱（250mm×4．6mm,5μm）;流动相为乙腈-0．1％磷酸（用三乙胺调至pH6．15）（60：40）;柱温：30℃;流速：1．0mL·min^-1;荧光检测器：激发波长：231nm,发射波长：324nm：进样量：60μL.结果：标准曲线的线性范围为5～1000ng·mL^-1（r=0．9989,n=8）,低、中、高3种浓度的绝对回收率分别为（90．1±2．4）％、（94．1±2．7）％、（93．6±3．0）％;方法回收率分别为（93．4±1．2）％、（96．1±2．7）％、（95．8±1．5）％;日内精密度RSD≤2．3％,日间精密度RSD≤4．0％。本方法的检测限0．5ng·mL^-1。结论：本方法快速、简便、灵敏、准确.     

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.