卡培他滨联合长春瑞宾治疗晚期乳腺癌

目的:观察卡培他滨联合长春瑞宾对紫杉醇类和／或蒽环类耐药的晚期转移性乳腺癌的疗效及安全性。方法:对24例紫杉类和／或蒽环类耐药的、具有可测量病灶的晚期乳腺癌患者采用卡培他滨联合长春瑞宾进行治疗,21 d为1个周期,治疗2-6个周期。所有患者以往均接受过1种以上包括紫杉醇和／或多柔比星化疗方案的化疗。结果:24例患者中4例接受了2个周期化疗,5例完成3个周期化疗,12例完成4个周期的化疗,3例完成6个周期化疗。有效率(RR)为45．8％。不良反应14例。结论:卡培他滨联合长春瑞宾治疗晚期转移性乳腺癌的疗效确切且不良反应轻,有望成为紫杉醇类和／或蒽环类药物治疗失败的晚期转移性乳腺癌的理想方案。     

泰索帝联合顺铂治疗蒽环类耐药性晚期乳腺癌疗效分析

目的 探讨分析泰索帝联合顺铂方案治疗蒽环类耐药性晚期乳腺癌的疗效与毒副作用。方法 应用泰索帝联合顺铂对24例蒽环类耐药性晚期乳腺癌患者进行治疗,化疗结束后评价其疗效及毒副作用。结果 CR 2例(8.33%),PR 12例(50.00%),SD 6例(25.00%),PD 4例(16.67%),总有效率为CR+PR14例(58.33%)。本组毒副作用以胃肠道反应和骨髓抑制为主。结论 泰索帝联合顺铂治疗蒽环类耐药性晚期乳腺癌疗效显著,毒副作用少,是治疗蒽环类耐药性晚期乳腺癌的理想化疗方案,值得在临床上推广。     

多西紫杉醇联合顺铂治疗晚期乳腺癌35例分析

目的观察多西紫杉醇联合顺铂治疗晚期乳腺癌的疗效及不良反应。方法晚期乳腺癌患者35例,予多西紫杉醇联合顺铂方案化疗,2周期后评价疗效。结果35例中总有效率为54．3％,不良反应主要为骨髓抑制、脱发、消化道反应,但均可耐受,无化疗相关死亡。结论多西紫杉醇为主的联合化疗方案治疗晚期乳腺癌疗效较好,不良反应可耐受。     

泰索帝联合顺铂治疗蒽环类耐药性晚期乳腺癌疗效分析

目的 探讨分析泰索帝联合顺铂方案治疗蒽环类耐药性晚期乳腺癌的疗效与毒副作用。方法 应用泰索帝联合顺铂对24例蒽环类耐药性晚期乳腺癌患者进行治疗,化疗结束后评价其疗效及毒副作用。结果 CR 2例(8.33%),PR 12例(50.00%),SD 6例(25.00%),PD 4例(16.67%),总有效率为CR+PR14例(58.33%)。本组毒副作用以胃肠道反应和骨髓抑制为主。结论 泰索帝联合顺铂治疗蒽环类耐药性晚期乳腺癌疗效显著,毒副作用少,是治疗蒽环类耐药性晚期乳腺癌的理想化疗方案,值得在临床上推广。     

吡柔比星为主的联合化疗方案治疗晚期乳腺癌临床疗效分析

目的观察吡柔比星为主的联合化疗方案治疗晚期乳腺癌近期疗效、毒副反应。方法40例晚期乳腺癌患者,接受以吡柔比星为主的联合化疗方案治疗,按WHO疗效及毒副反应评价标准,完成两个周期以上治疗的患者进行临床疗效及不良反应评估。结果40例化疗患者总有效率(RR)达57.5%,稳定(NC)占25%,进展(PD)占17.5%。中位缓解期为6(4～1 3)个月,中位生存期11(6～18)个,一年生存率为58.9%。主要毒副反应为骨髓抑制,非血液毒性反应较轻,主要为Ⅰ-Ⅱ度胃肠道反应。结论吡柔比星为主的联合化疗方案治疗晚期乳腺癌患者临床疗效明显,不良反应轻,能提高生存率。     

低剂量多西紫杉醇每周用药联合顺铂治疗蒽环类耐药晚期乳腺癌的近期疗效及临床价值

目的观察多西紫杉醇、顺铂联合方案在对蒽环类耐药晚期乳腺癌治疗中的疗效、不良反应及临床价值。方法蒽环类耐药性晚期乳腺癌患者37例,采用多西紫杉醇、顺铂方案联合化疗,多西紫杉醇30mg/m2静脉滴注,第1,8,15天;顺铂25mg/m^2静脉滴注,第2～4天,每3周为1个周期。每个周期化疗结束后复查CT或MRI评价疗效,记录不良反应。结果完全缓解1例,部分缓解18例,稳定10例,疾病进展8例,总有效率为51.3%。不良反应主要有过敏反应、骨髓抑制、消化道反应等,均可耐受。结论低剂量多西紫杉醇联合顺铂治疗蒽环类耐药的晚期乳腺癌有较好的疗效,不良反应可以耐受。     

多西紫杉醇联合顺铂治疗蒽环类耐药的晚期乳腺癌的临床疗效观察

目的观察多西紫杉醇联合顺铂治疗蒽环类耐药的晚期乳腺癌的疗效与不良反应。方法 2003年6月至2007年6月,我科以多西紫杉醇联合顺铂治疗蒽环类耐药的晚期乳腺癌36例。多西紫杉醇75mg/m2,静脉点滴,第1天;顺铂30mg/（m2.d）,静脉点滴,第1天至第3天;每21d为一周期,至少两个周期后评价疗效。本组中位化疗周期数为4（2-6）周期。结果 36例均可评价疗效。完全缓解（CR）2例（5.6%）,部分缓解（PR）18例（50%）,稳定（SD）9例（25%）,进展（PD）7例（19.4%）,总有效率（CR＋PR）55.6%,中位肿瘤进展时间6个月,一年生存率71%,中为生存时间16个月。主要的不良反应为胃肠道反应和骨髓抑制。结论多西紫杉醇联合顺铂治疗蒽环类耐药的晚期乳腺癌疗效较好,不良反应可以耐受,是蒽环类耐药的晚期乳腺癌的有效解救方案。     

吉西他滨联合顺铂治疗紫杉类联合蒽环类耐药性晚期乳腺癌62例疗效分析

目的 观察吉西他滨联合顺铂方案治疗紫杉类联合蒽环类耐药性晚期乳腺癌的疗效与安全性.方法 选择62例紫杉类联合蒽环类耐药性晚期乳腺癌患者.给予吉西他滨1250 mg/m2,静滴,第1、8天;顺铂75 mg/m2,静滴,第1天加水化、利尿、止呕等治疗,第8天止呕等治疗;21 d为1个周期.一般至少用2周期.如果肿瘤完全缓解(CR)部分缓解(RR)或稳定,则继续用药,可用至6～8个周期.然后评价疗效和不良反应.结果 6例均可评价疗效.完全缓解(CR)4例(6.5%),部分缓解(RR)30例(48.4%),稳定(SD)14例(22.6%),进展(PD)14例(22.6%),总有效率(CR+RR)54.9%,中位肿瘤进展时间(TTP)6个月.1年生存率66.7%.主要不良反应为恶心、呕吐和骨髓抑制.结论 吉西他滨联合顺铂方案治疗紫杉类联合蒽环类耐药性晚期乳腺癌疗效较好,不良反应轻,多数患者能耐受,是紫杉联合葸环类耐药性晚期乳腺癌的有效解救治疗方案之一.     

吉西他滨联合顺铂治疗晚期乳腺癌内脏转移的疗效观察

目的探讨吉西他滨联合顺铂治疗晚期乳腺癌的近期疗效和不良反应。方法选择51例已用紫杉类和(或)蒽环类化疗后出现内脏转移的晚期乳腺癌患者。采用吉西他滨:1000 mg/m2,静脉滴注,第1、8天;顺铂:25 mg/m2,静脉滴注,第1³天,21 d为1个周期,至少2周期后评价疗效。结果 CR 4例(7.8%),PR 21例(41.2%),SD 15例(29.4%),PD 11例(21.6%),总有效率为45.1%。中位生存期12.5个月,中位疾病进展时间5.8个月。主要不良反应为骨髓抑制及胃肠道反应。结论吉西他滨联合顺铂治疗晚期乳腺癌具有较好的近期疗效,不良反应可耐受,是有效的解救方案。     

多西他赛联合替吉奥治疗蒽环类耐药晚期乳腺癌

目的：观察多西他赛联合替吉奥治疗蒽环类耐药晚期乳腺癌的疗效及不良反应.方法：多西他赛75 mg·m-2,第1天;替吉奥40 mg·m-2餐后口服,bid,连用14 d,21 d为1周期,每结束2周期评价疗效及不良反应.结果：40例蒽环类耐药晚期乳腺癌患者总有效率57.5%,肿瘤控制率80%,中位生存期420 d,中位疾病进展时间221 d,1年生存率67.5%.主要不良反应为骨髓抑制,其次为手足综合征、恶心、呕吐、腹泻、纳差等不良反应,经对症处理均可耐受,无治疗相关死亡患者.结论：多西他赛联合替吉奥治疗蒽环类耐药乳腺癌的疗效好,不良反应可耐受,值得临床推广使用.     

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.

     

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.     

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.     

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.     

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.