周剂量多烯紫杉醇联合顺铂治疗老年晚期非小细胞肺癌疗效观察

目的:观察周剂量多烯紫杉醇联合顺铂治疗老年晚期非小细胞肺癌(NSCLC)的疗效。方法:40例Ⅲ～Ⅳ期老年晚期NSCLC患者随机分为常规组(多烯紫杉醇70mg·m-2静脉滴注,第1天;顺铂90mg·m-2静脉滴注,第1天)与周剂量组(多烯紫杉醇35mg·m-2静脉滴注,第1天、第8天;顺铂30mg·m-2静脉滴注,第2～4天)。4wk为1个周期,共2个周期。结果:常规组有效率45%,Ⅲ～Ⅳ度呕吐发生率55%,Ⅲ～Ⅳ度白细胞下降率5%;周剂量组有效率45%,Ⅲ～Ⅳ度呕吐发生率10%,Ⅲ～Ⅳ度白细胞下降率25%。结论:周剂量多烯紫杉醇不影响疗效,能明显减少毒性反应。     

紫杉醇联合卡铂治疗24例晚期非小细胞肺癌疗效观察

目的:观察紫杉醇联合卡铂治疗晚期非小细胞肺癌的疗效、不良反应.方法:24例晚期非小细胞肺癌患者给予紫杉醇135mg/m2第一天+卡铂300 mg/m2第一天,4周为1个周期,治疗2个周期以上.结果:总有效率45.9%,KPS评分增加者占62.5%,不良反应主要为骨髓抑制,Ⅲ度以上白细胞下降率37.5%,其他不良反应轻微.结论:紫杉醇联合卡铂治疗晚期非小细胞肺癌有较高的疗效.     

周剂量多西紫杉醇联合低剂量顺铂治疗晚期非小细胞肺癌的临床研究

目的探讨周剂量多西紫杉醇联合低剂量顺铂治疗晚期非小细胞肺癌（NSCLC）的疗效及不良反应。方法对50例晚期NSCLC患者使用多西紫杉醇30mg／m^2,静脉滴注,第1、8、15天给药;顺铂14mg／m^2,静脉滴注,第1—5天给药;以上化疗方案每4周重复1次,每例进行2周期化疗。结果全组50例,有效率36．0％（18／50）,病情稳定率54．0％（27／50）,其中PR18例,SD27例,PD5例,无CR病例,中位生存时间11．6个月。ⅠⅡ度的中性粒细胞减少发生率为44．0％（22／50）,Ⅲ度中性粒细胞减少发生率为4．0％（2／50）,无Ⅳ度中性粒细胞减少发生。非血液学毒性发生率较低且较轻微。结论周剂量多西紫杉醇联合低剂量顺铂是治疗晚期非小细胞肺癌（NSCLC）较好的化疗方案。     

老年晚期非小细胞肺癌DP方案化疗的疗效分析

目的评价国产多西他赛(多帕菲)联合顺铂(DDP)方案(简称DP方案)在治疗老年人晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)中的近期疗效、不良反应的多因素分析。方法对病理证实的78例晚期NSCLC患者,采用DP方案化疗,多帕菲30mg/m2。第1、8d给药,DDP 20mg/m2第1～4d给药,21d为1周期。至少化疗2周期后复查评价疗效。结果本组研究总有效率35.90%,其中Ⅲ期总有效率41.03%,Ⅳ期有效率20.00%。不良反应Ⅲ、Ⅳ度粒细胞减少发生率20.51%.Ⅲ、Ⅳ度血小板减少发生率5.13%,恶心、呕吐的Ⅲ、Ⅳ度发生率为17.95%。结论多帕菲联合DDP方案治疗老年性非小细胞肺癌疗效高且不良反应低,是治疗老年性NSCLC较好的方案,值得进一步推广。     

紫杉醇脂质体、奥沙利铂和氟尿嘧啶联合治疗晚期胃癌47例临床观察

目的 观察紫杉醇脂质体、奥沙利铂和氟尿嘧啶三药联合治疗晚期胃癌的近期疗效和毒副作用.方法 对初治和复治的晚期胃癌患者47例,应用紫杉醇脂质体、奥沙利铂和氟尿嘧啶联合化疗,每14 d为1个周期,每2个周期后评价疗效及毒副作用.结果 可评价疗效者41例,部分缓解占34.15%,临床受益率为82.9%.可评价毒副作用的患者47例,主要为Ⅲ～Ⅳ度不良反应,其中,白细胞减少9例(占19.15%),周围神经毒性8例(占17.02%),恶心呕吐9例(占19.15%).结论 紫杉醇脂质体、奥沙利铂和氟尿嘧啶三药联合可有效治疗晚期胃癌,且安全可耐受.     

白蛋白结合型紫杉醇治疗晚期非小细胞肺癌的疗效及安全性

目的观察白蛋白结合型紫杉醇治疗晚期非小细胞肺癌(NSCLC)的疗效及安全性。方法 46例晚期NSCLC患者均予静脉滴注白蛋白结合型紫杉醇130 mg/m²,第1天和第8天给药,3周为1个化疗周期。其中,单药治疗10例,联合卡铂治疗23例,联合顺铂治疗13例。每2个周期按实体瘤疗效评价标准1.1评价疗效,每个周期按照常见不良反应事件评价标准4.0评价不良反应发生情况。结果白蛋白结合型紫杉醇治疗晚期NSCLC的客观缓解率(ORR)为26.09%,疾病控制率(DCR)为67.39%,无进展生存期(PFS)为4.80个月。其对鳞癌的ORR为27.78%,DCR为69.44%,PFS为5.30个月。在二线及二线以上化疗方案的患者中,其ORR和DCR可达到23.81%和61.90%,PFS为4.30个月。主要不良反应为血液毒性,但可控制,无超敏反应发生。结论白蛋白结合型紫杉醇治疗晚期NSCLC具有较好的疗效和安全性,对鳞癌的疗效更好。     

多西紫杉醇联合奥沙利铂治疗晚期非小细胞肺癌临床分析

肺癌是最常见的恶性肿瘤,每年肺癌的新病例以约0.5%的速率增长,目前已成为严重危害人民生命和健康的常见病[1].其中非小细胞肺癌(NSCLC)占肺癌发病率的75%～80%,预后差,而化疗是晚期非小细胞肺癌的主要治疗方法[2].以铂类为基础的联合化疗能改善晚期非小细胞肺癌患者的症状、生存期和生活质量[3].笔者进行了一项随机对照临床研究,观察多西紫杉醇联合奥沙利铂与多西紫杉醇联合卡铂治疗Ⅲb、Ⅳ期初治NSCLC的临床疗效和不良反应,报告如下.     

奈达铂联合紫杉醇与顺铂联合紫杉醇治疗晚期非小细胞肺癌的随机对照研究

目的:比较奈达铂联合紫杉醇(TN)与顺铂联合紫杉醇(TP)方案治疗晚期非小细胞肺癌(NSCLC)的疗效和不良反应。方法:将68例晚期非小细胞肺癌患者随机分为TN组和TP组,全组至少接受2个周期的化疗。观察其近期有效率,1年、2年生存率及不良反应。结果:TN组与TP组客观反应率分别为26.5%和32.3%,疾病控制率分别为70.6%和79.4%,中位生存时间分别为14个月和13个月,1年生存率分别为59%和53%,2年生存分别为9%和15%,两组比较差异无统计学意义。TN组恶心、呕吐明显少于TP组(P<0.05)。结论:奈达铂联合紫杉醇治疗晚期非小细胞肺癌与顺铂联合紫杉醇疗效相当,且消化道反应更低。     

吉西他滨联合顺铂治疗晚期非小细胞肺癌的临床观察

目的观察吉西他滨联合顺铂治疗晚期非小细胞肺癌（NSCLC）的疗效和毒副反应。方法 42例晚期非小细胞肺癌,吉西他滨1000mg/m2第1、8天静脉滴注,顺铂80mg/m2第1天或20mg/m2第2～5天静脉滴注,3周为1个治疗周期,2个周期后评价疗效和毒副作用,随访缓解期和生存期。结果 42例均化疗2周期以上,其中完全缓解（CR）1例,部分缓解（PR）17例,稳定（SD）20例,进展（PD）4例,缓解率（CR＋PR）42.9%。主要不良反应为骨髓抑制和胃肠道反应,Ⅲ～Ⅳ度白细胞减少发生率占35.7%（15例）,Ⅲ～Ⅳ度血小板减少发生率占19%（8例）;Ⅲ～Ⅳ度恶心、呕吐占16.7%（7例）。结论吉西他滨联合顺铂治疗晚期非小细胞肺癌具有较高的疗效,且不良反应较轻,患者可以耐受。     

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。     

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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.     

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.