康妇消炎栓联合甲磺酸帕珠沙星治疗盆腔炎性疾病后遗症314例临床分析

目的探讨康妇消炎栓联合甲磺酸帕珠沙星治疗盆腔炎性疾病后遗症的临床效果。方法将618例盆腔炎性疾病后遗症患者随机分为治疗组和对照组,治疗组使用康妇消炎栓直肠给药连用3个月,同时静滴甲磺酸帕珠沙星,对照组单独使用甲磺酸帕珠沙星静滴,0.3g,每日2次,经期用药,7d为1个疗程,1个月经期为1个疗程,连用2～3个疗程,治疗组与对照组都加用甲硝唑,比较疗效。结果治疗组总有效率为98.4%,对照组为76.1%,两组比较,差异有显著性(P<0.05)。结论康妇消炎栓联合甲磺酸帕珠沙星治疗盆腔炎性疾病后遗症效果显著,值得临床推广。     

HPLC法测定甲磺酸帕珠沙星原料及其制剂含量

目的:采用高效液相色谱法测定甲磺酸帕珠沙星原料及其制剂含量.方法:Hypersil C18(5 μm,4.6 mm×250 mm)色谱柱,0.1%磷酸溶液(加磷酸氢二钾80.5 mg)-乙腈(85:15)为流动相,流速1.0ml·min-1,柱温30℃,检测波长243 nm.结果:甲磺酸帕珠沙星在5～500μg·ml-1内与峰面积呈良好的线性关系.甲磺酸帕珠沙星原料(3批)加样回收率99.2%甲磺酸帕珠沙星注射液加样回收率均值为100.1%;甲磺酸帕珠沙星氯化钠注射液加样回收率均值为99.7%.结论:采用HPLC测定原料及其制剂中甲磺酸帕珠沙星含量方法简便,结果可靠.     

中国健康志愿者单剂静脉滴注甲磺酸帕珠沙星氯化钠注射液的药动学研究

目的对中国健康成年志愿者单剂静脉滴注甲磺酸帕珠沙星氯化钠注射液的药动学研究。方法按GcP指导原则设计试验方案,选择10名健康受试者分别在30min内空腹静脉滴注甲磺酸帕珠沙星氯化钠注射液300和500mg,用HPLC-荧光法测定血浆、尿液中帕珠沙星的浓度,并采用3P97软件进行试验数据统计处理,求出药动学参数。结果帕珠沙星的血药浓度经时变化符合二房室模型,300和500mg的主要药动学参数如下：峰浓度Cmax分别为(7．716±1．373)和(11．652±2．197)μg／ml；半衰期t1/2分别为(2．00±0．26)h和(2．13±0．22)h；药时曲线下面积AUCo-∞分别为(14．170±3．244)和(25．370±3．234)μg·h／ml；表观分布容积Vc分别为(28．83±12．92)L和(31．62±8．91)L。尿药浓度测定结果表明,帕珠沙星0-24 h累积排出量分别为(261．82±30．92)mg和(452．27±32．35)mg,0-24 h累积排出百分比分别为(87．27±10．31)％和(90．45±6．47)％。结论帕珠沙星单次给药在中国健康人体耐受性良好,药时曲线符合二房室模型,帕珠沙星在300-500mg剂量范围内药物体内过程呈线性动力学特征,药物主要经肾脏排泄。     

甲磺酸帕珠沙星与其它抗生素联用于大鼠模型的药动学研究

目的:对甲磺酸帕珠沙星与其它抗生素联合应用的大鼠药代动力学进行对比研究,评价药物间的相互作用及联合用药的合理性.方法:采用一个剂量组,3种用药方案分别单次给药.用药方案:帕珠沙星45 mg/kg;帕珠沙星45 mg/kg加头孢哌酮/舒巴坦180 mg/kg;帕珠沙星45 mg/kg加阿奇霉素45 mg/kg.采用反相HPLC-UV法测定大鼠血药浓度,用DAS软件估算药动学参数,进行统计学分析及临床药效评价.结果:甲磺酸帕珠沙星单用及与头孢哌酮/舒巴坦或阿奇霉素联用的主要药动学参数t1/2、Cmax、tmax、AUC无显著性差异,但帕珠沙星与阿奇霉素联用后清除率(CL)降低及体内驻留时间(MRT)延长,具有统计学意义.结论:帕珠沙星与头孢哌酮/舒巴坦,帕珠沙星与阿奇霉素联用是可行的用药方案.     

甲磺酸帕珠沙星治疗泌尿系感染的临床观察

目的评价国产甲磺酸帕珠沙星注射液治疗泌尿系感染的临床疗效与安全性。方法下尿路感染者予甲磺酸帕珠沙星注射液0．3 g/100 mL,2次/d静点,疗程3-5 d;急性肾盂肾炎者予甲磺酸帕珠沙星注射液0．3 g/100 mL,2次/d静点,疗程7-10 d;慢性肾盂肾炎予甲磺酸帕珠沙星注射液0．3 g/100 mL,2次/d静点, 疗程10-14 d。结果痊愈率为80％,总有效率为97．78％,细菌清除率为95．56％,不良反应发生率为3％。结论甲磺酸帕珠沙星治疗泌尿系感染疗效确切,且安全性较好。     

帕珠沙星的合成

目的:合成帕珠沙星.方法:以(S)-9,10-二氟-3-甲基-7-氧代-2,3-二氢-7H-吡啶[1,2,3-de][1,4]苯并口恶嗪-6-羧酸乙酯为起始原料,经缩合、环合、水解等反应制得帕珠沙星.结果:采用本合成工艺制得了帕珠沙星,收率为44.1%.结论:本合成工艺简单易操作,适合工业化生产.     

甲磺酸帕珠沙星乳膏的制备及质量控制

目的 制备甲磺酸帕珠沙星乳膏，建立质量控制方法。方法 采用高效液相色谱法测定甲磺酸帕珠沙星含量，并考察其稳定性。结果 甲磺酸帕珠沙星线性范围为20．0—80．0μg／ml（r=0．9999），平均回收率为98．1％，RSD=1．77％（n=6）。结论 本处方设计合理，质量控制方法准确可靠，制剂稳定性好。     

消旋甲磺酸帕珠沙星的合成

目的：合成消旋甲磺酸帕珠沙星。方法：以市售合成氧氟沙星的中间体9，10-二氟-3-甲基-7-氧-2，3-二氢-7H-吡啶[1，2，3-d，e][1，4]苯并噁嗪-6-羧酸乙酯为起始原料，经过缩合反应、水解脱羧、相转移缩-环合、腈基水解和Hofmann降解得目标化合物。结果和结论：经^1H-NMR，MS和旋光活性测定，证明所得到的产物为消旋甲磺酸帕珠沙星。     

甲磺酸帕珠沙星治疗细菌性感染的多中心临床试验

目的：评价国产新药注射用甲磺酸帕珠沙星治疗细菌性感染的临床安全性和有效性。方法：以盐酸左氧氟沙星为对照药，进行多中心随机双盲对照治疗细菌感染的试验。试验组130例，给予注射用甲磺酸帕珠沙星300mg静脉滴注，q12h；对照组128例给予注射用盐酸左氧氟沙星200mg静脉滴注，q12h。两药疗程均为7～10d。结果：甲磺酸帕珠沙星和左氧氟沙星治疗细菌性感染的临床有效率分别为86．3％和79．7％；细菌清除率分别为89．1％和81．7％；不良反应发生率分别为6．9％和11．7％。以上指标差异均无显著性（P〉0．05）。结论：注射用甲磺酸帕珠沙星治疗细菌性感染是有效和安全的，与左氧氟沙星相当。     

帕珠沙星治疗泌尿系统感染的疗效与安全性观察

帕珠沙星(pazufloxacin)是最新一代喹诺酮类广谱抗菌类药物。本品通过肾脏排泄，静滴24小时后尿中排泄率为99．7％，其中主要为原形药物(94％)，多剂量静注本品无蓄积作用。帕珠沙星抗菌谱广，尤其对难治性和对内酰胺类药物耐药的病原体具有良好的抗菌作用。左旋氧氟沙星作为一种广谱抗生素已经证实对各种感染，特别是泌尿系感染有较好的效果，本研究旨在通过与左旋氧氟沙星的对比评价帕珠沙星治疗泌尿系统感染的有效性与安全性。     

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.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

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.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.