生血颗粒对免疫介导再生障碍性贫血模型小鼠的作用

目的观察生血颗粒对再生障碍性贫血模型小鼠的作用。方法取自DBA/2小鼠的胸腺单细胞悬液,输入经亚致死量γ-射线照射后的BALB/C小鼠体内,制作再生障碍性贫血模型,观察生血颗粒对再生障碍性贫血模型小鼠红细胞数、血红蛋白含量、骨髓有核细胞数、脾脏指数的影响。结果生血颗粒可增加免疫介导再生障碍性贫血模型小鼠的红细胞数、血红蛋白含量、骨髓有核细胞数和脾脏指数。结论生血颗粒具有生血作用。     

营养造血汤剂对再生障碍性贫血小鼠骨髓造血功能的影响

目的探讨营养造血汤剂对小鼠再生障碍性贫血造血功能的影响。方法 BALB/c小鼠90只,随机分为正常组、模型组及治疗组。苯、X射线、环磷酰胺联合应用的方法建立再生障碍性贫血小鼠模型,试验第8天开始,治疗组小鼠每天灌胃,给予19.76g(/kg·d)营养造血汤药液,直至第60天,观察试验小鼠的血象、骨髓象、造血干细胞集落形成;TUNEL及免疫组化法检测小鼠造血细胞凋亡以及相关调控蛋白Fas与Caspase-3的表达。结果治疗组的外周血象、骨髓有核细胞数、造血干细胞集落的形成明显高于模型组(P<0.05)。结论营养造血汤剂对再障小鼠疗效显著,能改善骨髓增殖。     

人参二醇组皂苷提取物对再生障碍性贫血小鼠免疫调节作用的研究

目的观察自行提取分离的中药新药人参二醇组皂苷提取物(PDS-C)对再生障碍性贫血(再障)小鼠促进造血和调节免疫的作用。方法 BALB/c小鼠经亚致死量照射后输入DBA/2小鼠的淋巴细胞,制成免疫介导型再障模型。实验分6组,正常小鼠、模型组、PDS-C低、中和高剂量治疗组及环孢素阳性药物对照组,均灌胃给药15 d。检测外周血象、骨髓病理检查造血组织增生状况、脾脏T细胞亚群比例,及T细胞分化相关T-bet、GATA-3和FOXP3转录调控蛋白的表达水平。结果 PDS-C治疗再障小鼠的疗效明显,中、高剂量组的外周血红蛋白、白细胞和血小板计数均明显高于模型组,骨髓造血组织增生状况也明显优于模型组。PDS-C升高Th2细胞和调节性T细胞(Treg)的比例,降低Th1细胞比例,并上调GATA-3和FOXP3蛋白及下调T-bet蛋白的表达。结论 PDS-C有效地促进造血,改善再障的骨髓抑制,加快造血功能恢复而升高外周血象;同时通过恢复再障小鼠失衡的Th1/Th2/Treg细胞比例而参与调节免疫,该文为PDS-C的临床应用提供实验依据。     

生血胶囊对免疫介导的再生障碍盆血小鼠骨髓增殖的影响

为了探讨生血胶囊对免疫介导的再生障碍性贫血(再障)小鼠骨髓增殖的影响,建立免疫介导的再障小鼠模型,分别胃饲生血胶囊7g生药/kg及2.3g/kg,2次/日,连续9天,并以生血丸1号为对照.于制模第10天处死动物,检测外周血白细胞数及股骨骨髓有核细胞数(BMNC),股骨中段骨髓切片HE染色行病理形态学观察.结果表明生血胶囊组白细胞数、股骨BMNC及骨髓造血组织容量均显著高于模型对照组(P＜0.05-0.01),生血胶囊大剂量组与生血丸1号组比较无显著差异(P＞0.05).说明生血胶囊能促进再障小鼠骨髓增殖.     

补肾生髓Ⅰ号对小鼠实验性再生障碍性贫血的治疗作用

目的 :研究补肾生髓Ⅰ号治疗再生障碍性贫血的可能机制。方法 :利用补肾生髓Ⅰ号治疗 60Co-γ射线照射后所致的再生障碍性贫血小鼠 ,并观察小鼠外周血细胞计数、骨髓有核细胞数、骨髓GM -CFU -c及小鼠IL -1、IL -2和IL -6活性的变化。结果 :补肾生髓Ⅰ号治疗后 ,再生障碍性贫血小鼠的外周血细胞计数、骨髓有核细胞数及骨髓GM -CFU -c显著增高 ,小鼠IL-1和IL-6活性明显增加 ,IL -6水平增高至接近正常 ,且与IL -1呈显著正相关 (r=0.904) ;治疗组IL -2水平虽有所下降但无统计学意义。结论 :补肾生髓Ⅰ号可通过提高外周血三系及骨髓有核细胞数 ,促进骨髓GM -CFU -c的形成 ,并通过调节免疫活性因子IL -1、IL -2和IL -6的活性 ,进而促进骨髓造血重建。     

AA-PNH综合征合并门静脉血栓1例

患者,女,57岁.主因再生障碍性贫血6年,腹泻、发热2 d于2003年7月20日首次入院.患者6年前无诱因出现双下肢瘀斑,就诊于某院,查血常规:白细胞(WBC)4.0×109/L,血色素(HGB)100 g/L, 血小板(PLT)25×109/L;骨髓涂片示增生低下,活检示再生障碍性贫血.诊断为再生障碍性贫血.     

再生障碍性贫血小鼠骨髓基质细胞分泌RCAS1水平及其意义

目的研究免疫介导再生障碍性贫血(AA)小鼠骨髓基质细胞RCAS1表达及其意义。方法建立免疫介导小鼠再障模型。反转录-聚合酶链反应(RT-PCR)方法检测再障小鼠骨髓基质细胞RCAS1基因表达,流式细胞术检测再障小鼠骨髓基质细胞培养上清作用后正常小鼠骨髓单个核细胞(BMMNC)的凋亡。结果①AA小鼠骨髓基质细胞均有RCAS1的表达,表达强度为2.17±0.87,明显高于对照组0.96±0.22(P<0.01)。②AA骨髓基质细胞培养上清作用后正常小鼠BMMNC凋亡率为(8.85±1.05)%,明显高于对照组的(2.10±0.25)%(P<0.01)。结论AA骨髓基质细胞RCAS1高表达,其培养上清作用后正常小鼠BMMNC凋亡增加,提示RCAS1可能参与了再障造血功能衰竭。     

E838对再生障碍性贫血小鼠造血功能的治疗作用

目的构建再生障碍性贫血(AA)实验动物模型,研究E838对AA模型小鼠造血机能的治疗作用。方法建模BALB/C小鼠经γ射线照射后尾静脉注射DBA小鼠脾脏细胞,药物治疗组口服E838,1次/d,共14 d,无菌饲养至第15天检测与AA相关的血常规、网织红细胞、骨髓细胞计数和病理学指标,判断E838对AA的治疗作用。结果模型组小鼠外周血常规指标、骨髓病理学等造血功能相关指标与AA临床表现基本相符;E838治疗组小鼠造血功能相关指标均较AA模型组小鼠有明显改善。结论成功构建了AA实验动物模型,E838对AA模型小鼠造血功能具有改善作用,其机制有待于进一步研究。     

21例重型再生障碍性贫血患者CD34^＋细胞检测及临床意义

目的：检测重型再生障碍性贫血（SAA）患者CD34^＋细胞骨髓单个核细胞比例,了解再生障碍性贫血发病与造血干细胞、祖细胞的关系。方法：应用流式细胞仪检测21例重型再生障碍性贫血患者CD34^＋细胞表达水平。并与对照组比较。结果：再生障碍性贫血组21例患者CD34^＋细胞比例为（0．196±0．164）％,对照组10例患者CD34^＋细胞比例为（1．129±0．570）％,两组比较,差异有统计学意义（P〈0．01）。结论：再生障碍性贫血患者CD34^＋细胞表达明显减少,支持再生障碍性贫血造血干细胞内在缺陷的发病学说。此检测有助于再生障碍性贫血诊断,值得临床推广。     

复方雷公藤胶囊对再生障碍性贫血小鼠骨髓造血的影响

为研究复方雷公藤胶囊对再生障碍性贫血小鼠骨髓造血的影响，我们通过建立再生障碍性贫血小鼠模型，采用体外细胞培养技术观察复方雷公藤胶囊对骨髓造血的影响。实验结果表明：复方雷公藤胶囊对再生障碍性贫血小鼠骨髓粒—单系集落形成单位(CFU—GM)、红系集落形成单位(CFU—E)、多能造血干细胞(CFU—S)的增殖有显著促进作用，对外周血白细胞(WBC)、血红蛋白(HB)有明显升高作用。     

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.

     

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.