多西紫杉醇联合卡培他滨治疗晚期蒽环类耐药三阴乳腺癌的临床观察

目的观察多西紫杉醇联合卡培他滨治疗晚期蒽环类耐药三阴乳腺癌的疗效、影响因素和不良反应。方法采用多西紫杉醇联合卡培他滨治疗24例蒽环类耐药晚期三阴性乳腺癌患者。多西他赛3周给药剂量为75 mg/m2,静脉滴注,第1天,卡培他滨2000 mg/m2,分早、晚2次口服,d1~14。化疗以21 d为1个周期,至少应用2个周期。结果本组患者治疗有效率为50.0%,中位疾病进展时问为7.9个月,无化疗相关死亡病例,主要不良反应为骨髓抑制、手足综合征及胃肠道反应,Ⅲ~Ⅳ级白细胞下降为16.6%。结论多西紫杉醇联合卡培他滨治疗晚期蒽环类耐药三阴乳腺癌仍有较好的近期疗效,不良反应可耐受,是有效的治疗方案。     

多西紫杉醇联合卡培他滨新辅助化疗13例局部晚期乳腺癌的观察

目的探讨多西紫杉醇联合卡培他滨新辅助化疗方案治疗局部晚期乳腺癌的疗效及安全性。方法 13例局部晚期乳腺癌初治患者,卡培他滨药2500 mg/(m2?d),分早晚2次,餐后30 min口服。连续服用2周,休息1周为1个周期。多西紫杉醇75 mg/m2,静脉输注1 h滴完。21 d为1个周期,2周期后评价疗效。结果 13例局部晚期乳腺癌中治疗后完全缓解4例,部分缓解6例,稳定2例,进展1例,有效率76.92%(10/13),主要不良反应为白细胞减少,发生率为82.33%,其中Ⅲ度占29.61%,没有发现有Ⅳ度。结论多西紫杉醇联合卡培他滨新辅助化疗方案治疗局部晚期乳腺癌疗效确切,不良反应可耐受。     

多西紫杉醇联合顺铂治疗晚期乳腺癌31例临床观察

目的 观察多西紫杉醇联合顺铂方案治疗晚期乳腺癌的临床疗效和不良反应.方法 晚期乳腺癌31例,其中包括既往应用蒽环类药物治疗18例,非蒽环类药物化疗13例.用多西紫杉醇75mg/m2,第1天静滴,顺铂25mg/m2,第1～3天静滴,21天为1周期,2周期后评价疗效.结果 31例中CR3例,PR 14例,总有效率为54.84%.主要不良反应为骨髓抑制.恶心呕吐和脱发,但均可耐受.结论 多西紫杉醇联合顺铂治疗晚期乳腺癌疗效确切,副作用较轻可耐受.     

多西紫杉醇联合卡培他滨治疗晚期乳腺癌临床观察

目的观察多西紫杉醇联合卡培他滨治疗晚期乳腺癌疗效和不良反应。方法多西紫杉醇75mg／m^2,静脉滴注,第1天;卡培他滨900mg／m^2,口服,2次／d,第1～14天,每21天为1个周期,每2个周期评价疗效。结果共计28例入组。其中完全缓解3例（10．7％）、部分缓解10例（35．7％）、稳定10例（35．7％）、PD5例（17．9％）,总有效率为46．4％。中位疾病进展时间6．9个月,中位生存期14．1个月。主要不良反应为骨髓抑制、手足综合征、恶心呕吐、脱发。结论多西紫杉醇联合卡培他滨方案治疗晚期乳腺癌疗效肯定,不良反应较轻,患者耐受性好。     

多西紫杉醇联合顺铂治疗晚期乳腺癌31例临床观察

目的观察多西紫杉醇联合顺铂方案治疗晚期乳腺癌的临床疗效和不良反应。方法晚期乳腺癌31例,其中包括既往应用蒽环类药物治疗18例,非蒽环类药物化疗13例。用多西紫杉醇75mg／m^2,第1天静滴,顺铂25mg／m^2。第1～3天静滴,21天为1周期,2周期后评价疗效。结果31例中CR3例,PR14例,总有效率为54．84％。主要不良反应为骨髓抑制、恶心呕吐和脱发,但均可耐受。结论多西紫杉醇联合顺铂治疗晚期乳腺癌疗效确切,副作用较轻可耐受。     

多西他赛联合卡培他滨治疗转移性乳腺癌的疗效观察

目的分析评价多西他赛联合卡培他滨治疗转移性乳腺癌（MBC,Metastatic Breast Cancer）的短期疗效和不良反应。方法对53例经病理证实的转移性乳腺癌患者均给予多西他赛75mg/m^2,静滴第一天;卡培他滨1250mg/m2口服,1日2次,餐后服用,连续服用14d,治疗周期为21d,每治疗2个周期后评估疗效及副反应。结果本组53例患者中完全缓解（CR）7例（13.2%）,部分缓解（PR）26例（49.1%）,稳定（SD）12例（22.6%）,疾病进展（PD）8例（15.1%）,总有效率（CR＋PR）为62.3%,肿瘤控制率（CR＋PR＋SD）为84.9%。主要不良反应为胃肠道反应、脱发、骨髓抑制、手足综合征等,予临床处理后均可耐受。结论多西他赛联合卡培他滨治疗晚期转移性乳腺癌疗效肯定,毒副反应可耐受,可以作为蒽环类药物治疗失败的晚期乳腺癌的解救方案。     

卡培他滨联合多西他赛治疗晚期乳腺癌的临床观察

目的观察卡培他滨联合多西他赛治疗晚期乳腺癌的有效性和安全性。方法晚期乳腺癌49例,应用卡培他滨1250 mg/m2,2次/d间歇治疗(2周治疗后停止治疗1周)至少6周,每3周疗程的第1天使用多西他赛75 mg/m2静脉注射。2周期后评价近期疗效和毒副反应。结果 49例晚期乳腺癌总有效率为38.7%,其中CR2例,PR17例。结论卡培他滨联合多西他赛治疗晚期乳腺癌有较好的确切疗效,并且毒性反应小。     

多西紫杉醇联合奥沙利铂、卡培他滨治疗晚期胃癌临床观察

目的探讨多西紫杉醇联合奥沙利铂、卡培他滨治疗晚期胃癌的疗效和毒副作用。方法晚期胃癌30例,化疗方案多西紫杉醇60mg/(m2·d)静脉滴注,第1、8d;奥沙利铂85mg/(m2·d)静脉滴注,第1、8d;卡培他滨800mg/(m2·d)分两次口服,第1～14d,每3周为1个周期,连用2个周期,治疗结束2周后评价疗效。结果 30例患者中CR3例,PR16例,总有效率63.3%;主要毒副作用为骨髓抑制和胃肠道反应,均可耐受。结论多西紫杉醇联合奥沙利铂、卡培他滨治疗晚期胃癌疗效肯定、毒副作用可耐受。     

曲妥单抗联合多西紫杉醇和卡培他滨治疗晚期转移性乳腺癌

目的观察曲妥单抗(Trastuzumab)联合多西紫杉醇(Docetaxel)和卡培他滨(Capecitabine)方案治疗人类表皮生长因子受体2(Her-2)阳性晚期转移乳腺癌的临床疗效与毒副作用。方法将我院2004年1月至2009年1月收治的Her-2阳性晚期转移乳腺癌患者96例,随机分成两组,曲妥单抗联合多西紫杉醇治疗(TD)组48例,曲妥单抗联合多西紫杉醇和卡培他滨治疗(TDC)组48例。TD组用曲妥单抗6mg/kg,多西紫杉醇75 mg/m2,静滴,第1天,21d为1周期;TDC组用曲妥单抗6mg/kg,多西紫杉醇75 mg/m2,静滴,第1天,卡培他滨950 mg/m2,静滴,第1天至第14天,21d为1周期。两组中位化疗周期数均为6周期,检测指标为疗效、无进展生存期(progressionfree survival,PFS)和毒副作用。结果 TD组和TDC组的中位无进展生存期分别为(11.47±0.73)个月与(18.61±0.85)个月,两者比较具有显著性差异(P<0.05)。TD组疗效为总有效率(CR+PR)为(45.3±6.5)%。TDC组总有效率(CR+PR)为(68.3±7.7)%,两者比较具有显著性差异(P<0.05)。两组的主要毒副作用为胃肠道反应和骨髓抑制反应。结论曲妥单抗联合多西紫杉醇和卡培他滨化疗方案治疗Her-2阳性晚期转移乳腺癌疗效好,无交叉耐药性,不良反应轻,是Her-2阳性晚期转移乳腺癌的有效解救治疗方案。     

卡培他滨联合多西紫杉醇治疗晚期胃癌疗效观察

目的观察卡培他滨联合多西紫杉醇方案治疗晚期胃癌的临床疗效。方法 62例胃癌患者随机分为治疗组32例和对照组30例。治疗组给予多西紫杉醇75mg/m2静脉滴注,分为第1天和第8天,卡培他滨每天2500mg/m2,分2次口服,连用14d,21d为1个周期;对照组给予多西紫杉醇75mg/m2静脉滴注,第1天;顺铂20mg/m2静脉滴注第1～4天,氟尿嘧啶每天500mg/m2持续静脉滴注24h,第1～5天。观察2组临床疗效。结果治疗组有效率（RR）为62.5%,中位疾病进展时间（TTP）为7.0个月,中位生存期（MST）12.8个月;对照组RR为50.0%,中位TTP5.1个月,MST11.8个月。2组有效率比较差异有统计学意义（P〈0.05）。治疗组血液毒性主要表现为白细胞减少,其中Ⅲ～Ⅳ度白细胞减少占15.6%,手足综合征发生率为18.8%;对照组血液毒性偏重,其中Ⅲ～Ⅳ度白细胞减少达86.0%。结论卡培他滨联合多西紫杉醇治疗晚期胃癌有较好的疗效,不良反应轻微,应是将来有前景的治疗晚期胃癌的有效方案。     

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.