多西他赛联合奥沙利铂治疗晚期食管癌的临床观察

目的观察多西他赛联合奥沙利铂治疗晚期食管癌的临床疗效和不良反应。方法晚期食管癌患者55例,多西他赛75mg/m2与奥沙利铂130mg/m2联合化疗,21d为1个周期,连用2个周期后评价疗效。结果全组55例可评价疗效,总有效率63.6%(35/55),完全缓解3例5.5%(3/55),部分缓解32例58.2%(32/55),中位生存期为8.9个月(4.1~21个月),中位疾病进展时间5.5个月,中位缓解时间4.4个月(3~7个月)。主要不良反应为骨髓抑制、消化道反应、肝肾功能损害等。结论多西他赛联合奥沙利铂治疗晚期食管癌近期疗效高,安全性较好,患者可耐受,值得临床观察应用。     

多西他赛联合顺铂治疗晚期乳腺癌30例近期疗效分析

目的观察多西他赛联合顺铂治疗晚期乳腺癌疗效及不良反应。方法30例患者均采用多西他赛75mg/m2,静滴1小时,第1天,化疗前一天予地塞米松10mg,连用3天;顺铂30mg/m2,第1～3天。28天为一周期,至少应用两周期后评价疗效。结果30例患者中完全缓解(CR)1例(3.3%),部分缓解(PR)11例(36.7%),稳定(SD)14例(46.7%),进展(PD)4例(13.3%)。总有效率(CR PR)40%。主要不良反应为骨髓抑制,胃肠道反应。结论多西他赛联合顺铂治疗晚期乳腺癌疗效确切,不良反应可以耐受,为治疗晚期乳腺癌的有效方案。     

多西他赛联合顺铂治疗晚期非小细胞肺癌57例

目的观察多西他赛联合顺铂二线治疗晚期非小细胞肺癌的疗效与不良反应。方法对57例晚期非小细胞肺癌患者采用二线化疗,第1天给予多西他赛75 mg.(m2)-1,顺铂100 mg.(m2)-1,均静脉滴注,21 d为1个周期。化疗2个周期后评价疗效及不良反应。结果所有患者均可评价,总共进行162周期的化疗。完全缓解0例,部分缓解16例,稳定18例,进展23例,总有效率28.1%。中位缓解时间5.6个月,中位生存时间8.6个月。主要不良反应为血液学毒性。Ⅲ/Ⅳ度中性粒细胞下降、血小板下降和血红蛋白下降的发生率分别为18.5%,11.1%和8.6%。其次为消化系统反应,Ⅲ/Ⅳ度食欲下降和恶心呕吐发生率分别为13.6%和11.1%。结论多西他赛联合顺铂对复治晚期非小细胞肺癌有较好疗效,不良反应可以耐受。     

多西他赛联合顺铂治疗晚期乳腺癌30例

目的观察多西他赛联合顺铂方案治疗晚期乳腺癌患者的临床疗效及引起的不良反应。方法对郑州市消防支队卫生队收治的30例经病理组织学确诊的晚期乳腺癌患者进行多西他赛35mg/m2,静脉滴注1h,第1、8、15d,化疗前1d给予地塞米松每次7.5mg,每日2次,连用3d。顺铂20mg/m2,静脉滴注第1～5d。21d为1个周期,至少应用2个周期后按照WHO标准进行疗效评价。结果晚期乳腺癌30例中完全缓解(CR)4例,部分缓解(PR)15例,稳定(SD)7例,进展(PD)4例,总有效率(PR+CR)为63%,无严重不良反应。结论多西他赛联合顺铂治疗晚期乳腺癌疗效确切,不良反应可以耐受,临床可广泛推广。     

多西他赛联合顺铂和5-氟脲嘧啶治疗晚期食管癌的疗效观察

目的：观察多西他赛联合顺铂和5-氟脲嘧啶治疗晚期食管癌的近期疗效和不良反应。方法：多西他赛75mg／m^2，静脉滴注1小时，第1天；顺铂20mg，静脉滴洼，第1～5天；5-氟脲嘧啶500mg／m^2，静脉滴注，第1～5天；21天为1周期，至少应用2周期。结果：共治疗19例患者，其中CR 1例，PR 10例，总有效率为57．89％。主要不良反应是骨髓抑制，非血液学毒性轻微。结论：多西他赛联合顺铂和5-氟脲嘧啶治疗晚期食管癌可获得较高的疗效，不良反应可以耐受，是一种较好的化疗方案，值得临床进一步研究。     

多西他赛联合顺铂方案治疗晚期乳腺癌的化疗疗效观察

目的:观察多西他赛联合顺铂治疗方案对晚期乳腺癌的治疗效果及不良反应。方法:对本科收治的29例经病理组织学确诊的晚期乳腺癌患者进行多西他赛35mg/m2,静脉滴注1h,第1、8、15天,化疗前1d给予地塞米松每次7.5mg,每日2次,连用3d。顺铂20mg/m2,静脉滴注第1～5天。21d为1个周期,至少应用2个周期后按照WHO标准进行疗效评价。结果:晚期乳腺癌29例中完全缓解(CR)3例,部分缓解(PR)15例,稳定(SD)7例,进展(PD)4例,总有效率(PR+CR)为62%。无严重毒副作用。结论:多西他赛联合顺铂治疗晚期乳腺癌疗效确切,毒副作用可以耐受,临床可广泛推广。     

多西他赛联合顺铂或卡铂治疗32例晚期非小细胞肺癌疗效分析

目的观察多西他赛联合顺铂或卡铂治疗晚期非小细胞肺癌的疗效及药物不良反应。方法对32例晚期非小细胞肺癌患者给予多西他赛联合顺铂或卡铂治疗。28d为1个周期，每例患者均接受≥2个周期治疗。结果完全缓解1例，部分缓解13例，稳定16例，进展2例，总有效率43．75％。结论多西他赛联合顺铂或卡铂治疗晚期非小细胞肺癌疗效较好，药物不良反应较轻，采用每周疗法，患者耐受性较好，老年晚期患者更为适宜。     

多西他赛和顺铂联合同步放疗治疗中晚期贲门癌

目的观察多西他赛联合顺铂同步放化疗治疗晚期贲门癌的疗效。方法将73例中晚期贲门癌患者随机分为两组,放化疗同步组32例采用2Gy/次,共60Gy/6周,同时以多西他赛120mg/d静脉滴注d1,顺铂30mg/d静脉滴注d2～4,每3周一周期方案连续化疗4周期。结果同步放化疗组和单纯放疗组CR分别为6.3%、0(χ2=1.354,P=0.245),两组PR分别为78.1%3、1.7%(χ2=44.721,P=0.000),同步放化疗不良反应发生率高于单纯放疗组,其中主要为Ⅱ度白细胞计数降低,发生率分别为43.8%、0(P<0.05),Ⅰ～Ⅱ度周围神经炎发生率分别为9.4%0、(P<0.05),经对症处理后患者均耐受良好。结论多西他赛联合顺铂同步放化疗治疗中晚期贲门癌是较单纯放疗疗效好、不良反应较轻的治疗方法,值得进一步研究,甚至临床推广。     

多西他赛联合顺铂治疗晚期非小细胞肺癌40例临床观察

目的观察多西他赛联合顺铂治疗晚期非小细胞肺癌的疗效和安全性。方法40例晚期非小细胞肺癌患者应用多西他赛（75mg／m2,第1天）联合顺铂（25mg／m2,静脉滴注,第1～3天）化疗,21d为1个周期,连续应用2个周期后采用WHO标准进行化疗效果评价。结果4JD例患者中部分缓解16例（40．0％）、稳定17例（42．5％）、进展7例（17．5％）,近期有效率为40．0％（16／40）,中位生存期11．8个月。不良反应以骨髓抑制、关节肌肉疼痛和消化道反应为主,均对症治疗后缓解,未发生严重不良反应。结论多西他赛联合顺铂治疗晚期非小细胞肺癌有较好的疗效,不良反应少。     

多西他赛联合顺铂同步放化疗治疗局部晚期非小细胞肺癌

目的探讨多西他赛联合顺铂化疗同步三维适形放射治疗(3-DCRT)局部晚期非小细胞肺癌的近期疗效及近远期不良反应。方法 68例局部晚期非小细胞肺癌患者随机分为同期放化疗(同步组)与新辅助化疗加放疗(诱导组)两组。两组病例均采用3-DCRT计划。诱导组:多西他赛60mg/m2,静脉滴入,d1,顺铂30 mg/m2,静脉滴入,d1～d3,每3周1次,2个周期后行3-DCRT。同步组:多西他赛20mg/m2,静脉滴入,dl,顺铂30mg/m2,静脉滴入,dl,在放射治疗开始时同步进行,1次/周,用7～8次。结果同步组和诱导组的总有效率分别为70.6%和41.2%,差异有统计学意义(P<0.05);中位生存时间分别为22.6和18.9个月;1年总生存率分别为66.35%和51.99%。结论 3-DCRT联合周剂量多西他赛加顺铂同步治疗局部晚期非小细胞肺癌近期疗效较好,能明显提高患者的生活质量,不良反应均能耐受。     

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.