伊马替尼治疗Ph阳性进展期慢性粒细胞白血病

目的:观察伊马替尼治疗Ph阳性进展期慢性粒细胞白血病(CML)的疗效和耐药情况,研究改善伊马替尼耐药的方法。方法:32例Ph阳性进展期CML病人,其中加速期12例,急变期20例,每日口服伊马替尼600或800mg,持续3～9mo。结果:CML加速期病人血液学完全缓解率和总有效率分别为42%和83%,主要细胞遗传学缓解率25%,持续完全血液学缓解病例占25%。CML急变期各类型病人血液学完全缓解率和总有效率分别为20%和55%,主要细胞遗传学缓解率15%,持续完全血液学缓解病例占10%。CML急变期原发耐药和继发耐药分别为45%和20%,联合化疗与暂停伊马替尼对继发耐药可暂时改善其耐药性,但药物有效时间明显缩短。结论:伊马替尼对初治或复治的CML加速期和急变期病人均有效,可作为非移植CML治疗的标准一线方案,伊马替尼治疗CML急变期的原发耐药和继发耐药率较高,联合化疗和暂停伊马替尼可暂时改善其耐药性。     

干扰素-α联合小剂量阿糖胞苷治疗慢性髓细胞白血病的疗效观察

目的：探讨干扰素-α联合小剂量阿糖胞苷治疗CML的疗效。方法：所有患者均短程给予羟基脲降低白细胞总数，继而给予干扰素-α和小剂量阿糖胞苷联合治疗12个疗程。结果：血液学完全缓解率86％，有细胞遗传学反应80％，其中2例完全反应，造血组织及粒红细胞比例分别下降至7914％及4．0：1，网状纤维含量增高，而CD41细胞数量无明显改变。结论：干扰素-α联合小剂量阿糖胞苷治疗CML在血液学缓解率、细胞遗传学反应率及骨髓组织学改变上均取得良好疗效，可作为治疗CML（慢性期）的一线治疗方案。     

甲磺酸伊马替尼(格列卫)治疗晚期慢性粒细胞性白血病的临床疗效观察

目的:探讨甲磺酸伊马替尼(格列卫)治疗晚期慢性粒细胞白血病的临床疗效及不良反应情况。方法:对我院近年来应用甲磺酸伊马替尼治疗的29例晚期慢性粒细胞白血病患者的临床资料进行回顾性分析,并记录治疗过程中各时间点血常规、骨髓细胞形态学检查、细胞遗传学检查情况,对临床疗效及不良反应进行评价。结果:急变期CML患者血液学缓解率为28.6%,完全细胞遗传学缓解率为0,均明显低于加速期CML患者的73.3%和26.7%,差异均有统计学意义。治疗过程中血液学不良反应主要以白细胞,血小板减少多主,非血液学不良反应可有恶心、呕吐、水肿、骨骼肌酸痛、乏力、头昏、头痛、皮疹等。结论:甲磺酸伊马替尼治疗慢性粒细胞白血病加速期急变期患者疗效好,不良反应少,可耐受且加速期疗效优于急变期。     

国产甲磺酸伊马替尼片治疗慢性粒细胞白血病的临床观察

目的:观察国产甲磺酸伊马替尼片治疗慢性粒细胞白血病(CML)患者的疗效及安全性。方法:选取CML患者16例,其中初诊CML即给予甲磺酸IM治疗者7例,诊断CML超过12个月后再给予甲磺酸IM治疗者9例,所有患者均长期口服甲磺酸伊马替尼片400 mg,qd。治疗后3个月通过检测所有患者血常规、骨髓细胞学、费城染色体(Ph染色体)评估疗效,并观察外周血Bcr-Abl/Abl融合基因突变及不良反应发生情况。结果:治疗后,16例患者均达到完全血液学缓解(CHR);12例患者获得部分细胞遗传学缓解(PCy R),2例患者获得完全细胞遗传学缓解(CCy R),2例患者无细胞遗传学缓解;15例患者Bcr-Abl/Abl转录水平<10%,仅1例>10%。16例患者均未出现难以耐受的不良反应。结论:国产甲磺酸伊马替尼片早期疗效确切,安全性高。     

急性巨核细胞白血病变为首发的慢性粒细胞白血病1例观察并文献复习

目的探讨提高对急性巨核细胞白血病变为首发的慢性粒细胞白血病患者的细胞遗传学、免疫表型和临床特点认识的措施。方法对患者进行骨髓形态学、免疫学和细胞遗传学检查,并对其治疗效果进行分析。结果该患者经常规化疗未获缓解,建议口服格列卫治疗,因经济条件拒绝。结论急性巨核细胞白血病变为首发的慢性粒细胞白血病比较少见,伊马替尼能够使部分慢性粒细胞急变,使Philadelphia染色体阳性的急性巨核细胞白血病取得完全血液学缓解和细胞遗传学缓解。但目前伊马替尼仍较昂贵,限制了其在临床上广泛及长期的应用,若联合化疗方案,可能减少伊马替尼用量,并延长缓解期。     

干扰素联合小剂量阿糖胞苷治疗慢性粒细胞白血病的疗效观察

目的：观察α-干扰素(α-IFN)和小剂量阿糖胞苷(LD-Ara-c)联合治疗慢性粒细胞白血病(CML)的血液学和细胞遗传学缓解率。方法：19例CML患者均于诊断6个月内，有用α-IFN：3MU／次，皮下注射，隔天1次，当血象和骨髓完全缓解后改为每周2次：Ara-C：20mg／d，缓慢静滴，每月使用10天，检测治疗后血液学和Ph染色体阳性细胞下降情况。结果：在治疗6个月时间点，CHR为84．2％，在12个月时间点，细胞遗传学反应(CCR PCR)为57．8％。结论：对CML慢性期，尤其早期患者采用α-IFN和：LD-Ara-C联合治疗，可显著提高慢性期CML患者的血液学和细胞遗传学缓解率，延长无病生存期。急变率较低，复发率低，不良反应轻。     

羟基脲联合高三尖杉酯碱α-干扰素治疗慢性粒细胞白血病

目的 探讨羟基脲(HU)联合高三尖杉酯碱(HHT)、α-干扰素(α-IFN)治疗慢性粒细胞白血病(CML)的临床疗效.方法 40例患者随即分为实验组和对照组,实验组18例采用羟基脲联合高三尖杉酯碱、α-干扰素治疗,对照组12例用羟基脲治疗,6个月后检测其疗效.结果 实验组6个月完全血液学缓解(CHR)和完全细胞遗传学缓解(CCR)分别为77.8%和44.4%.对照组CHR和CCR分别25.0%和8.33%.结论 CML慢性期患者采用羟基脲联合高三尖杉酯碱、α-干扰素治疗可显著提高CML患者的CHR率及CCR率,延长生存期.     

达沙替尼治疗伊马替尼耐药的 BCR／ABL阳性白血病

目的评价达沙替尼治疗伊马替尼耐药的BCR/ABL阳性白血病的疗效和安全性。方法对9例伊马替尼耐药的慢性髓系白血病（CML）或Ph阳性急性淋巴细胞白血病（Ph＋ALL）患者,给予达沙替尼100～140 mg·d-1口服治疗,评估疗效和耐受情况。结果 9例伊马替尼耐药的BCR/ABL阳性白血病,2例CML-CP患者均获得CHR,1例达CCyR;5例CML-BC患者中4例获得CHR和PCyR,1例NR;2例Ph＋ALL患者中1例检测到E255V突变,采用达沙替尼治疗达CHR和PCyR,1例诱导缓解时,同时行VDP方案化疗,继发严重感染死亡。结论达沙替尼治疗伊马替尼耐药的BCR/ABL阳性白血病患者可获得血液学甚至细胞遗传学缓解,且耐受性好。     

伊马替尼与干扰素联合治疗慢性粒细胞白血病的疗效分析

目的:探讨伊马替尼与干扰素联合化疗治疗慢性粒细胞白血病(CM L)的疗效。方法:2004年6月—2009年7月新诊断的58例Ph染色体阳性CM L慢性期患者,随机分为伊马替尼组和干扰素联合化疗组,比较两组临床疗效。结果:两组总有效率差异无统计学意义(P>0.05);伊马替尼组完全血液学缓解率,完全细胞遗传学缓解率、完全分子学效应率、5年总生存率均明显高于干扰素联合化疗组(P<0.05)。结论:伊马替尼和干扰素联合化疗都可作为CM L慢性期的有效治疗方法,应依据不同情况实施个体化治疗。     

干扰素α-2b联合羟基脲治疗慢性粒细胞白血病的临床观察

目的探讨慢性粒细胞白血病(chronic myelogenous leukemia,CML)患者使用干扰素α-2b(IFNα-2b),联合羟基脲(Hu)治疗,达血液学缓解的有效方法.方法采用IFNα-2b(300万u·d-1)联合应用Hu治疗CML慢性期(CP)13例.结果IFNα-2b+Hu治疗4～6个月完全血液缓解(CHR),减少了CML加速期和急变期,生存率明显提高.结论CML(CP)患者采用IFNα-2b+Hu治疗显著提高CML患者的CHR率,延长CML生存期.     

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.