3种药物治疗男性非淋菌性尿道炎的成本-效果分析

目的 评价3种药物治疗男性非淋菌性尿道炎的成本-效果。方法 男性非淋菌性尿道炎患者200例，随机分为3组，A、B组各67例，C组66例。A组给予交沙霉素0．4g，tid；B组给予氧氟沙星0．3g，bid；C组给予多西环素0．1g，bid；3组均连续使用7d。结果 A、B和C组总有效率分别为98．5％，85．1％和92．4％，治愈率分别为97．0％，46．3％和65．2％。假设治愈率达100％，则所需增加的成本△CE=100％分别为1．15，117．20和0．88元。A组成本-效果评价最好。结论 选择交沙霉素治疗男性非淋菌性尿道炎是比较好的方案。     

雷贝拉唑钠中有机溶剂残留量的毛细管GC测定

建立了毛细管GC法测定雷贝拉唑钠中甲醇、乙醚、丙酮、二氯甲烷、乙酸乙酯、甲苯等6种有机溶剂的残留量。采用DB-624毛细管柱，程序升温。6种有机溶剂的平均回收率分别为100．4％、98．7％、100．3％、100．4％、100．2％和99．9％，检测限分别为0．6、1、1、2．4、1、2．8ng。     

洗发水中违禁抗真菌药物的检测

建立了HPLC法同时检测洗发水中违禁氟康唑、酮康唑、特康唑和硝酸咪康唑的含量。采用C18柱，流动相为0.34％硫酸氢四丁铵-乙腈（95：5），检测波长210mn。4个组分均在1～100μg/ml浓度范围内线性关系良好。平均回收率分别为101.2％、101．8％、102．4%和101．7％，RSD分别为0．44%、0．59%、0．50％和0．61％。检测限分别为10．4、1．4、5．6和1．3ng。     

异福酰胺片的近红外光谱法测定

采用近红外光谱法快速定量分析异福酰胺片。按处方配制41个实验室样品，并收集10批市售产品，采集近红外光谱。分别对光谱进行卷积平滑、快速傅里叶变换、一阶导数和二阶导数预处理，采用偏最小二乘回归法建立样品中主药含量的定量分析模型。模型对15个预测集样品进行预测结果为：利福平、异烟肼、吡嗪酰胺模型的交互验证均方差RMSEC盼别为0．00287、0．00216和0．00435，平均回收率分别为100．7％、100．3％和99．8％，RSD）分别为1．5％、2．1％和0．7％。     

硫酸依替米星与硫酸阿米卡星治疗下呼吸道细菌性感染临床评价

目的：进一步评价硫酸依替米星治疗下呼吸道细菌感染的安全有效性。方法：采用随机对照开放试验方法。硫酸依替米星组100mg溶于生理盐水100ml中静脉滴注，每日2次。硫酸阿米卡星400mg溶于生理盐水500ml中静脉滴注，每日1次，疗程均为5－10d。结果：硫酸依替米星组和硫酸阿米卡星组各有30例评价疗效。两组有效率分别为90．0％及86．7％，细菌清除除率分别为88．5％及88．0％，两组安全性评价各为30例，耳聋性不良反应分别为3．3％和3．3％，肾毒性不良反应分别为3．3％和3．3％。两组经统计学处理差异无显著性（P＞0．05）。结论：采用硫酸依替米星治疗下呼吸道细菌性感染安全有效。     

HPLC法同时测定复方水杨酸搽剂中三组分的含量

目的：建立高效液相色谱法同时测定复方水杨酸搽剂中3组分含量的方法。方法：采用Hypersil BDS C18（4．6mm×200mm，5μm）色谱柱，0．1mol·L^-1磷酸氢二钠溶液-甲醇（60：40，用20％磷酸调节pH5．0）为流动相，流速为1．0mL·min^-1，检测波长为212nm。结果：间苯二酚、水杨酸、苯酚分别在0．0388—0．776μg（r=0．9999），0．1176～2．352μg（r=0．9999）、0．0218～0．436μg（r=0．9999）范围内线性关系良好，3个浓度组间苯二酚的平均回收率分别为99．0％（RSD=0．3％），97．2％（RSD=0．5％），98．5％（RSD=0．8％），水杨酸的平均回收率分别为100．3％（RSD=0．4％），99．5％（RSD=0．7％），97．5％（RSD=0．6％），苯酚的平均回收率分别为97．1％（RSD=1．1％），97．8％（RSD=0．7％），99．6％（RSD=0．9％）。结论：本测定方法简便、快速、准确，为复方水杨酸搽剂质量评价提供了可靠方法。     

高效液相色谱法测定布洛芬片中布洛芬含量

目的建立高效液相色谱法测定布洛芬片中布洛芬的含量。方法色谱柱为Zorbax—Extend C18柱（150mm×4．6mm，5μm），甲醇-0．01m01／L磷酸二氢钾一磷酸（700：300：0．1）为流动相，流速为1．0mL／min，检测波长为263nm。结果布洛芬质量浓度线性范围是100～800μg／mL，r=0．9999，其低、中、高3个量级的平均回收率分别为99．4％，98．8％，100．2％，RSD分别为0．8％，0．7％，1．0％。结论该法测定布洛芬中布洛芬的含量，结果可靠、简便、准确。     

气相色谱法测定岗松油中芳樟醇的含量

目的：建立芳樟醇的含量测定方法。方法：采用气相色谱外标法，以聚乙二醇（PEG）-20M和硅酮（OV-17）为固定液的混合柱，柱温为100℃，测定岗松油中芳樟醇的含量。结果：芳樟醇在6．97—34．86μg范围内呈线性关系，低、中、高浓度的平均回收率分别为100．0％，102．1％，105．2％；RSD分别为3．1％，2．0％，3．7％（n=3）。结论：该方法简便、准确，重复性、回收率好，可作为岗松油中芳樟醇的质量控制方法。     

HPLC法测定大蒜、蒜氨酸中间体及单体的蒜氨酸含量

目的：建立高效液相色谱测定大蒜、蒜氨酸中间体及单体中的蒜氨酸含量的方法。方法：采用Hypersil BDS C18（4．6mm×25cm，5μm）柱，分别以0．04％CF3 COOH水溶液和甲醇-0．02％CF3 COOH水溶液（5：95）为流动相，流速0．5mL·min^-1，检测波长214nm。结果：蒜氨酸在26．3～263．2μg·mL。呈良好线性关系，相关系数均为0．9999，方法灵敏、准确、重复性好，平均回收率（n=9）分别为99．1％和100．1％，日内精密度RSD（n=5）分别为0．56％和0．35％，日间精密度RSD（n=5）分别为0．57％和0．99％。结论：试验表明该方法简便、快速、适用性好。     

布格呋喃中有机溶剂残留量的毛细管GC法测定

建立了毛细管GC法测定布格呋喃中甲醇、乙醇、二氯甲烷、叔丁醇、正己烷、异丙醚、乙酸乙酯7种有机溶剂的残留量。采用DB-624毛细管柱，FID检测器，程序升温。平均回收率分别为100．4％、99．3％、99．7％、99．6％、97．4％、101．0％、100．6％，RSD分别为1．5％、1．5％、2．8％、1．5％、5．4％、2．7％、1．6％。     

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.