非清髓异基因外周造血干细胞移植治疗白血病疗效观察

目的 探讨非清髓性异基因外周血造血干细胞移植(NAPBSCT)治疗年龄较大的白血病患者安全性和疗效.方法 采用NAPBSCT治疗6例45～65 岁白血病患者,其中急性淋巴细胞白血病1例,淋巴瘤细胞白血病2例,急性粒细胞白血病1例,慢性粒白血病2例.以FAC为预处理方案,氟拉达宾(Flud)50mg/d(-6d～-2d)(以造血干细胞输注当日为0d,输注前为"-",输注后为" "),抗淋巴细胞免疫球蛋白(ALG)15mg/(kg·d)(-6～-2d),环磷酰胺(CTX)30mg/(kg·d)(-4～-3d).于 30 d进行第1次供者淋巴细胞输注,每4周1次,共6次.输注的供体淋巴细胞数由5×104 /kg逐渐增加至1.5×108 /kg.结果 1例患者于移植后56天死于急性移植物抗宿主病(aGVHD),1例患者于移植后81天死于肺部真菌感染,其余4例患者目前均存活,最长的1例已存活达35个月.6例患者在移植早期均形成混合性嵌合体和血液学部分缓解,供体淋巴细胞输注后有3例患者形成供体型完全嵌合体,并达到血液学完全缓解.结论 非清髓性外周血造血干细胞移植治疗年龄较大的白血病患者较为安全且疗效较好.     

自体骨髓间充质干细胞联合造血干细胞移植治疗系统性红斑狼疮

目的 探讨间充质干细胞(MSC)联合自体造血干细胞移植(HSCT)治疗系统性红斑狼疮(SLE)的安全性、疗效和对造血重建的影响.方法 采用无血清体系培养扩增骨髓MSC,联合APBSCT治疗1例SLE.干细胞动员应用异环磷酰胺(IF0)7g/m2,分两天应用和粒细胞集落刺激因子(G-CSF)5～10 μ g/kg·d-1;预处理方案包括氟达拉滨(30 mg/m2·d-1,-6、-5、-4、-3、-2d),抗胸腺细胞球蛋白(ATG 15 mg/kg·d-1,-3、-2、-1、0、 1d).结果 患者获得造血重建,中性粒细胞＞0.5×109/L的时间是 4d,血小板未＜20 × 109/L;SLE的临床表现明显减轻,尿蛋白消失,自身抗体转阴,泼尼松用量＜10mg/d.结论 MSC联合APBSCT治疗SLE近期疗效显著,造血重建恢复迅速,安全有效,远期疗效尚需进一步观察.     

异基因造血干细胞-间充质干细胞协同移植治疗急性粒细胞白血病(附2例报道)

目的探讨急性粒细胞白血病异基因造血干细胞—间充质干细胞协同移植的效果。方法培养扩增供者骨髓间充质细胞,经形态学及细胞表面分子加以鉴定,并与外周血造血干细胞协同移植给患者。结果输注供者的MSC总数分别为2×106/kg和7.7×106/kg,中性粒细胞>0.5×109/L以及血小板>20×109/L的中位时间分别是12d和14d。例1出现了Ⅰ度aGVHD,Ⅱ度cGVHD,已存活11个月;例2未出现急、慢性GVHD,现已存活6个月余。结论异基因造血干细胞-间充质干细胞协同移植可加速造血功能恢复,对GVHD的发生及严重程度有一定抑制作用,但还需加大病例数进一步观察。     

白血病异基因造血干细胞移植并发真菌性前色素膜炎1例

男性,42岁.1年前因患慢性粒细胞白血病2年,在我院干细胞移植中心行血缘相关性异基因造血干细胞移植,供者系其胞姐,45岁,血型为AB型,患者血型为B型,HLA配型主要A、B、DR位点全相合,经Bu-CY方案,Bu4 mg/公斤体质量×4 d,CY60 mg/公斤体质量×2 d.预处理后第2天回输CD34+造血干细胞5.6×106/L公斤体质量,回输后第17天,患者外周血中性粒细胞达1.0×109/L之上.     

单倍体移植时急性移植物抗宿主病的预防策略

目的探讨单倍体移植时急性移植物抗宿主病（aGVHD）的预防策略。方法采用环磷酰胺于预处理时静脉滴注,重组人粒细胞集落刺激因子（rhG—csr）动员后含有较大剂量CD34‘细胞的供者造血干细胞输注给受者,-7d（回输干细胞前为“-”,回输干细胞后为“＋”）始环孢素A静脉滴注后改为口服维持,-7d始麦考酚酸酯口服;-5d- -2d予抗胸腺细胞球蛋白静脉滴注;-6d～＋10d予白细胞介素-11皮下注射;＋1d、＋3d、＋6d及＋11d予甲氨蝶呤静脉滴注。结果6例患者完全植入,Ⅱ～Ⅳ度aGVHD的发生率50．0％,III～IV度aGVHD的发生率16．7％,随访中位时间为34．7（13—63）个月,无一例复发,至今仍无病存活。结论采用含有环磷酰胺、重组人粒细胞集落刺激因子、环孢素A、麦考酚酸酯、抗胸腺细胞球蛋白、自细胞介素-11及甲氨蝶呤预防急性移植物抗宿主病的方案疗效可值得进一步的探讨及推广。     

异基因外周血造血干细胞移植治疗骨髓增生异常综合征转化的急性髓细胞白血病1例及文献复习

目的探讨异基因外周血造血干细胞移植(强行移植)治疗原发耐药的急性髓细胞白血病(由骨髓增生异常综合征转化)的可行性。方法患者,女,16岁,供者为其胞弟,HLA配型全相合。预处理方案:改良BuCy。移植单个核细胞(MNC)6.22×108/kg(受者),CD34+占6.1%。结果移植后+14d粒系植入,+21巨核系植入。+30d染色体转为46,XY。移植后合并肺炎克雷伯杆菌败血症。无急慢性移植物抗宿主病发生。随访14个月,患者获得无病生存,生活质量良好。结论对于原发耐药的急性髓细胞白血病(由骨髓增生异常综合征转化),如有合适供者,宜尽早行造血干细胞移植。     

MAG动员/BEAM预处理治疗恶性淋巴瘤的长期随访

目的探讨恶性淋巴瘤(ML)用MAG方案动员、BEAM方案预处理、自体外周血干细胞移植(APBSCT)的疗效和毒性。方法8 年采用APBSCT 治疗ML14 例[9 例非霍奇金淋巴瘤(NHL),5例霍奇金病(HD)],外周血干细胞动员采用MAG方案(Ara C 2g/m2 q12 h,d1~2,MTZ10 mg·m2d2~3,rhG CSF 300μg/d),为预处理采用BEAM方案(BCNU 250 mg/m2d1,VP 16 200mg2d2~5,Ara C 400 mg/m 2d2~5,Mel 140 mg/m2 d6)。化疗结束后36~48 h回输自体造血干细胞。结果13/14例一次采集即获足量干/祖细胞。回输单个核细胞(MNC)3 91(1 21~6 61)×108/kg、粒单核系祖细胞( CFU GM) 4 40 (2 33 ~ 6 47)×105/kg 和CD34 细胞17 79 (4 79 ~30 69)×106/kg。所有患者移植后均获造血重建,中性粒细胞(ANC)≥0 5×109/L时间为10(8~13) d,血小板(Plt)≥20×109/L为13(9~22) d。中位随访时间46(4~100)个月,12 例存活,总生存率85 7%,无病生存率78 5%。结论MAG方案动员/BEAM方案预处理APBSCT治疗ML安全有效。     

马法兰用于多发性骨髓瘤造血干细胞移植预处理的研究进展

目的:跟踪马法兰用于多发性骨髓瘤(MM)造血干细胞移植(HSCT)预处理的研究进展。方法:查阅近年来国内外相关文献,将马法兰200、140 mg/m2作为HSCT预处理方案并比较两种方案治疗MM的疗效,以及马法兰其他治疗方案的研究进展进行综述。结果与结论:马法兰200 mg/m2联合自体造血干细胞移植(ASCT)疗效好、并发症少,临床上可作为初诊年龄小于65岁MM患者的标准一线治疗方案;马法兰140 mg/m2在ASCT中作为预处理方案治疗MM的作用是肯定的,但在HSCT中的临床作用尚需进一步论证。马法兰200 mg/m2与140 mg/m2作为预处理方案在HSCT中均有不可替代的作用,但两者之间的优劣性尚无明确一致的临床证据。     

异基因骨髓移植和非清髓性干细胞移植嵌合形成过程的比较

目的 研究异基因骨髓移植（allo-BMT）和非清髓性干细胞移植（NST）两种移植方式在供体细胞嵌合状态的形成及转归上的差异,探讨早期供体细胞植入的关键因素。方法 对20例接受allo-BMT和18例NST的患者进行回顾性比较,研究两组患者疾病类型、干细胞来源、预处理方案和移植物抗宿主病预防方案。用复合扩增荧光标记STR-PCR结合毛细管电泳方法对移植后＋7、＋14、＋21d,＋1、＋3、＋6、＋9、＋12个月的嵌合体进行动态检测。结果 （1）NST组在受体年龄、单个核细胞（MNC）、CD34^＋及T细胞数量上均明显高于BMT组,造血重建方面,中性粒细胞绝对值恢复时间与BMT组无差别,但血小板恢复明显早于BMT组。（2）NST组患者供体细胞完全嵌合状态（FDC）的建立比BMT组早（1个月vs 3个月）,移植后早期（＋1个月）FDC比例亦明显高于BMT组（38．9％vs 20%）,而混合嵌合状态（MC）的发生率明显低于BMT组（61．2％ vs 80％）,移植1个月后各时间段两组在嵌合体形成上均无显著性差别。（3）氟达拉滨为基础的NST预处理方案与标准预处理方案相比并未延迟供体细胞的植入。（4）NST组慢性移植物抗宿主病的发生率明显高于BMT组（80％vs 50%,P〈0．01）,与NST组输入高剂量的CD34^＋细胞相关。结论 在供体细胞早期植入和嵌合体形成的过程中,移植物中造血干细胞和T细胞数量至关重要,并可能起决定性作用。     

非清髓异基因外周血造血干细胞移植治疗一例慢性粒细胞白血病

异基因造血干细胞移植仍是目前唯一公认能够治愈慢性粒细胞白血病(CML)的方法,在慢性期移植效果最佳,50%～60%患者可获得长期存活和长期缓解。我们采用非清髓性HLA相合同胞供者外周血造血干细胞移植成功治疗CML 1例,现报告如下。     

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.