多西他赛联合奥沙利铂同步化放疗治疗局部晚期非小细胞肺癌临床观察

目的 观察多西他赛联合奥沙利铂同步化、放疗治疗局部晚期非小细胞肺癌（NSCLC）的临床疗效和不良反应.方法 72例Ⅲ期NSCLC患者采用抽签法分为2组：治疗组35例进行同期放化疗,化疗在放疗开始时同期进行,用药多西他赛75 mg/m2第1天静脉滴注;奥沙利铂130 mg/m2第2天静脉滴注.21 d为1个周期,共2个周期.放疗采用X线三维适形放疗,2 Gy/次,5 次/周,总剂量60～70 Gy/30～50次,6～7周内完成.对照组37例只行三维适形放疗,具体剂量、分割方式同治疗组.治疗完成后评价疗效和不良反应.结果 治疗组总有效率80.0%,完全缓解率22.9%;对照组总有效率56.8%,完全缓解率10.8%,2组间总有效率差异有统计学意义（x2=5.77,P＜0.05）.治疗组1、2年生存率分别为68.6%、42.9%,对照组分别为40.5%、18.9%.治疗组肿瘤进展时间平均为10.2个月,单纯放疗组为4.5个月（x2=6.34,P＜0.05）.经对症治疗后均顺利完成,治疗过程无治疗相关死亡.结论 多西他赛联合奥沙利铂同期放疗可以提高晚期非小细胞肺癌的近期疗效和远期生存率,是一种安全有效的综合治疗手段.     

多西他赛联合奥沙利铂或卡铂治疗晚期非小细胞肺癌的近期疗效观察

目的比较多西他赛分别与奥沙利铂和卡铂联合治疗晚期非小细胞肺癌的疗效和不良反应,为安全用药提供参考。方法 52例晚期非小细胞肺癌患者随机分为2组。多西他赛/奥沙利铂组:多西他赛75mg/m2,静脉滴注,d1;奥沙利铂120mg/m2,静脉滴注,持续2h,d1。多西他赛/卡铂组:多西他赛用法同前,卡铂AUC=5 mg/(mL min),静脉滴注,d1。两种方案均21d为一周期,2~4周期后评价疗效。结果多西他赛/奥沙利铂组中8例达到部分缓解,有效率为30.77%,临床获益率84.62%;多西他赛/卡铂组7例达到PR,有效率为30.43%,临床获益率86.96%。两组疗效比较差异无统计学意义(P>0.05),Ⅲ、Ⅳ度毒副反应发生率,多西他赛/奥沙利铂组组低于多西他赛/卡铂组,差异有统计学意义(P<0.05)。结论多西他赛联合奥沙利铂方案治疗晚期非小细胞肺癌是一个疗效较好、毒性较低的方案,值得推广应用。     

多西紫杉醇联合奥沙利铂治疗晚期非小细胞肺癌的临床观察

目的:观察多西紫杉醇联合奥沙利铂治疗晚期非小细胞肺癌的近期疗效、不良反应及神经毒性。方法:61例晚期非小细胞肺癌随机分两组。治疗组33例:多西紫杉醇75 mg/m2,静脉滴入,d1;奥沙利铂130 mg/m2,静脉滴入,d2;每3周重复疗程。对照组28例:多西紫杉醇用法及用量同治疗组,顺铂25 mg/m2,静滴,d2～d4,每3周重复疗程,分别评价近期疗效、KPS评分、1年生存率、不良反应和神经毒性。结果:治疗组与对照组近期有效率分别为39.39%和35.71%(P>0.05),KPS评分改善率为48.4%和32.14%(P>0.05),1年生存率分别为45.16%和45.83%(P>0.05),神经毒性发生率分别为21.21%和25.10%(P>0.05),其他不良反应包括中性粒细胞减少、恶心、呕吐及疲劳等,治疗组明显低于对照组(P<0.01)。结论:多西紫杉醇联合奥沙利铂治疗晚期非小细胞肺癌相比多西紫杉醇联合顺铂方案疗效相似,但不良反应减少,多西紫杉醇可明显减少奥沙利铂的神经毒性。     

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、顺铂联合放疗治疗局部晚期非小细胞肺癌的疗效观察

目的 探讨多西他赛、顺铂联合放疗治疗局部晚期非小细胞肺癌的临床疗效.方法 回顾性分析120例局部晚期非小细胞肺癌患者的临床资料,依据治疗方式不同分为对照组(传统的MVP方案:丝裂霉素、长春地辛、顺铂联合治疗)30例和观察组(多西他赛、顺铂联合放疗)90例.结果 观察组局部晚期非小细胞性肺癌患者总缓解率和5年生存率均优于对照组(分别为60.0％、36.7％和43.3％、30.0％),差异均有统计学意义(x2=10.87、3.81,均P＜0.05),两组消化道反应、白细胞减少、血小板减少等不良反应发生率差异均无统计学意义(x2 =0.25.1.01、1.04,均P＞0.05).结论 多西他赛、顺铂联合放疗治疗局部晚期非小细胞肺癌近期、远期疗效明显,安全性较好,值得临床推广应用.     

多西他赛每周疗法联合精确放疗治疗老年晚期非小细胞肺癌疗效观察

目的研究多西他赛每周疗法联合精确放疗治疗老年晚期非小细胞肺癌患者的近期疗效和不良反应。方法全组122例老年晚期非小细胞肺癌患者随机自愿分为两组。治疗组：多西他赛30mg/m2静滴d1,8,15天;休息一周,28d为一周期,化疗第2天同时进行放疗,均采用三维适形放疗。对照组：单纯采用三维适形放疗。结果治疗组总有效率明显高于对照组（75.81%〉53.33%P〈0.05）平均生存期分别为22个月和14个月。骨髓抑制治疗组较对照组略有加重（P〉0.05）。结论多西他赛每周疗法联合精确放疗治疗老年晚期非小细胞肺癌患者疗效好,优于单纯放疗,不良反应可耐受,尤其适用于老年患者,值得临床推广应用。     

多西他赛和顺铂联合同步放疗治疗中晚期责门癌

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（χ^2=1.354,P=0.245）,两组PR分别为78.1%3、1.7%（χ^2=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。     

NP方案联合放疗晚期非小细胞肺癌的临床研究

目的评价NP方案(长春瑞宾加顺铂)联合放疗晚期非小细胞肺癌的疗效。方法83例晚期非小细胞肺癌患者随机分组进行比较研究,化放组42例采用NP方案联合放疗,单放组41例行单纯放疗。化放组在放疗前先接受NP方案的新辅助化疗,剂量为:长春瑞宾(NVB)25mg/m2静脉滴入d1、d8;顺铂(DDP)30mg/m2静脉滴注d1～d3,同时水化利尿。21天为一周期。放射治疗:单放组肿瘤剂量为60～70Gy/6～7周完成;化放组在接受2个周期化疗后两周行放疗,肿瘤剂量为50～60Gy/5～6周完成。结果化放组的1、3年生存率分别为52.4%、19%,单放组的1、3年生存率分别为29.3%、4.9%,两组的1、3年生存率差异有统计学意义。结论NP方案联合放疗晚期非小细胞肺癌有较好的疗效及安全性,可延长生存期,其急性毒副反应患者可耐受,是治疗晚期非小细胞肺癌的一种积极有效措施。     

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。     

多西他赛同步放疗治疗老年晚期非小细胞肺癌

目的观察多西他赛同步放疗治疗老年晚期非小细胞肺癌(NSCLC)的疗效及毒副反应。方法对病理学或细胞学证实的32例老年晚期非小细胞肺癌患者给予下列治疗:①多西他赛35mg/m2,静脉滴注,于放疗前1d开始,1次/周,共4次;②给予6-mVX-线常规体外照射,1.8～2Gy/次,5次/周,总量50～60Gy/5～6周。结果初治患者有效率86.4%,复治患者有效率40%,总有效率68.8%,中位生存期10个月。不良反应:食管炎56.4%,白细胞减少46.4%,放射性肺炎17.6%。无治疗相关的病死。结论多西他赛同步放疗治疗老年晚期NSCLC疗效满意,耐受性好。     

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.     

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.