苦豆子生物碱衍生物施普睿达对小鼠肝癌H22的抑制作用

目的 观察苦豆子生物碱衍生物施普睿达体内对小鼠肝癌H22的抑制作用及量效关系. 方法 将75只昆明种小鼠移植肝癌H22细胞后,随机分为5组,每组15只. 空白对照组给予纯化水10 mL•kg^-1•d^-1,低、中、高剂量给药组分别给予施普睿达150,300,600 mg•kg^-1•d^-1,阳性对照组每2 d给予顺铂（4 mg•kg^-1）,各组均连续给予相应药物10 d. 观察施普睿达对实体瘤的抑瘤率,通过体重变化,肝重,脾、胸腺指数等多项指标综合考察施普睿达对荷瘤动物免疫机能的影响. 结果 低、中和高剂量药物组对小鼠肝癌H22抑瘤率分别为33.44%,41.90%,48.25%,各组对小鼠的肝、脾指数和胸腺指数几乎无影响;而阳性对照组小鼠的肝、脾指数和胸腺指数明显下降. 结论 施普睿达对小鼠肝癌H22有较好的治疗作用,而且不影响荷瘤动物免疫功能,属于低毒的抗肿瘤新药.     

甲磺酸伊马替尼缓解小鼠肾组织纤维化作用研究

目的 研究甲磺酸伊马替尼（STI571）对单侧输尿管梗阻（UUO）小鼠肾间质纤维化的防治作用.方法 40只雄性清洁级昆明种小鼠随机分为4组：假手术组、模型组、小剂量治疗组（80 mg•kg^-1•d^-1）、大剂量治疗组（160 mg•kg^-1•d^-1）.治疗组在手术后分别以STI571 80,160 mg•kg^-1•d^-1灌胃.各组小鼠均于术后第8天处死.观察肾间质病理学改变;用酸水解-比色法测定肾组织胶原的含量,免疫组化技术检测α-SMA、PCNA、FN的表达.结果 与模型组相比, 治疗组肾间质纤维化程度明显减轻,肾间质α-SMA、PCNA、FN的表达也明显减少.结论 STI571能够下调肾组织α-SMA表达水平,抑制肾间质细胞增殖活化,减少肾间质细胞外基质的沉积,对UUO小鼠早期肾间质纤维化有一定防治作用.     

槲皮素对去卵巢大鼠股骨OPG与RANKL表达的影响

目的观察槲皮素对去卵巢大鼠股骨骨保护素（osteoprotegerin, OPG）及核因子κB受体活化子配体（ligand of receptor activator of NF κB,RANKL）表达的影响。方法健康雌性SD大鼠48只,按体质量随机分为6组：假手术组（SHAM组）、单纯去卵巢组（OVX组）、17β-雌二醇组（ERT组,0.1 mg•kg^-1•d^-1）、高剂量槲皮素组（QH组,300 mg•kg^-1•d^-1）、中剂量槲皮素组（QM组,150 mg•kg^-1•d^-1）、低剂量槲皮素组（QL组,75 mg•kg^-1•d^-1）。除假手术组外其余各组均切除双侧卵巢,术后1周开始给药,给药 16周后处死所有大鼠,测定腰椎及股骨骨生物力学性能：弹性模量（ELASTIC） 、刚度（STIFFNESS）、最大应力（M STRESS）及最大承载力（M LORD）,用免疫组织化学染色方法观察股骨OPG、RANKL表达情况。结果 槲皮素高、中剂量均能上调股骨OPG、下调RANKL表达,部分改善股骨、腰椎生物力学性能。结论 槲皮素可通过调节骨组织中OPG、RANKL的相对含量而抑制骨吸收,防止骨质疏松。     

艾司西酞普兰与文拉法辛治疗难治性抑郁症的对照研究

目的 探讨艾司西酞普兰对难治性抑郁症患者的疗效和安全性. 方法 68例难治性抑郁症的住院患者随机分为治疗组和对照组各34例, 治疗组给予艾司西酞普兰,起始剂量10 mg•d^-1,早餐后服,根据病情调整10～20 mg•d^-1,平均剂量（16.62±3.65） mg•d^-1. 对照组给予文拉法辛缓释剂,起始剂量75 mg•d^-1,早餐后服用,7～10 d加至治疗量150～225 mg•d^-1,平均剂量（175.54±20.50） mg•d^-1. 两组疗程均6周. 采用汉密尔顿抑郁量表（HAMD）评定疗效,不良反应和安全性采用不良反应量表（TESS）及实验室检查评定. 结果 有效率和痊愈率治疗组分别为58.8%,20.6%;对照组分别为61.8%,23.5%;两组比较差异无显著性（P＞0.05）. TESS评定显示,两组不良反应发生率差异无显著性（P＞0.05）. 结论 艾司西酞普兰治疗难治性抑郁症的疗效与文拉法辛相似,起效快,不良反应较轻.     

奥卡西平单药和添加治疗儿童癫痫的疗效与安全性

目的 观察奥卡西平治疗儿童部分性发作（PS）和全面性强直-阵挛发作（ GTCS）癫痫患者的疗效、耐受性和副作用. 方法 73例癫痫患儿, 其中56例新诊断者进入单治组, 17例应用过其他抗癫痫药物治疗者进入加治组. 奥卡西平起始剂量5～10 mg•kg^-1•d^-1, 最大剂量30～40 mg•kg^-1•d^-1, 维持剂量中位值20 mg•kg^-1•d^-1, bid. 加治组其他抗癫痫药物的使用不变. 通过自身对比开放性观察, 分析单治组与加治组52周的疗效、不良反应、耐受性和安全性. 结果 全部患者总有效率84.9%、控制率54.8%、累积退出率11.0%, 其中3例（4.1%）失访, 不良反应或其他原因退出者5例（6.8%）, 其中因皮疹退出2例（2.7% ）. 常见不良反应：乏力8例、烦躁7例, 困倦和皮疹各2例. 单治组临床控制率（62.5%）显著高于加治组（29.4%）. 结论 奥卡西平是治疗儿童部分性发作和全面性强直-阵挛发作癫痫相对理想的药物选择.     

喹硫平治疗精神分裂症30例

目的 考察喹硫平治疗精神分裂症的有效性及安全性. 方法 将60例精神分裂症患者分为治疗组和对照组, 每组30例.治疗组给予喹硫平, 初始剂量100 mg&#8226;d^-1, 2周内加至400~800 mg&#8226;d^-1, 以后3周内视病情及不良反应调整剂量, 最大剂量1 200 mg&#8226;d^-1, 平均（728.3±199.9） mg&#8226;d^-1.对照组给予利培酮, 起始剂量1 mg&#8226;d^-1, 2周后加至治疗量3~6 mg&#8226;d^-1, 平均（4.9±0.9） mg&#8226;d^-1.疗程均为8周.两组根据情况给予苯海索、氮类药或普萘洛尔等对症处理, 以阴性和阳性症状量表（PANSS）、不良反应量表（TESS）分别评定疗效、病情严重程度和不良反应. 结果 治疗组与对照组的显效率均为70.0%, 有效率分别为90.0%和86.7%.两组在治疗前PANSS评分差异无显著性, 在治疗8周末, 两组PANSS评分较治疗前显著下降, 均差异有极显著性（均P< 0.01）.两组比较差异无显著性（P＞0.05）.治疗组的不良反应较对照组少而轻.结论 喹硫平可显著改善精神分裂症症状, 且不良反应发生率低, 是一种安全有效的抗精神病药物.     

枳实消痞丸对大鼠血液中胃泌素和胃动素含量的影响

目的 研究不同剂量枳实消痞丸对大鼠血液中胃泌素及胃动素含量的影响. 方法 50只大鼠分为正常对照组、阳性对照组及低、中和高剂量药物组,每组10只. 正常对照组灌胃纯化水,低、中和高剂量药物组分别给予枳实消痞丸,相当于生药7.5,15.0 和30.0 g&#8226;kg^-1,阳性对照组给予多潘立酮 2.7 mg&#8226;kg^-1,容量均为10 mL&#8226;kg^-1. 连续给药4周后用放免法测定血清胃泌素及血浆胃动素的含量. 结果 中、高剂量枳实消痞丸能显著提高血清胃泌素及血浆胃动素的含量. 结论 枳实消痞丸对胃肠动力的影响可能与其增加血清胃泌素及血浆胃动素的含量有关.     

氯吡格雷治疗介入术前非ST段抬高急性冠状动脉综合征30例

目的 观察非ST段抬高型急性冠状动脉（冠脉）综合征患者行介入治疗前高剂量氯吡格雷（600 mg&#8226;d^-1）治疗的有效性及安全性. 方法 选取 90例拟行冠脉介入术的非ST段抬高急性冠脉综合征患者, 随机分为早期常规剂量组、早期高剂量组和对照组, 每组各30例.早期用药的两组患者于入院临床诊断明确后立即开始服用氯吡格雷, 早期常规剂量组首次给予负荷量 300 mg后, 维持剂量75 mg&#8226;d^-1; 早期高剂量组首次给负荷量 600 mg后, 维持剂量75 mg&#8226;d^-1.对照组患者于冠脉造影后决定行介入治疗前2 h内开始用药,首次服用氯吡格雷 300 mg后, 维持剂量75 mg&#8226;d^-1.比较3组患者在冠脉介入术后 3个月内心血管事件及药物不良反应的发生率. 结果 冠脉介入术后3个月内, 早期用药组心血管事件的发生率低于对照组（P< 0.01）, 而出血事件的发生率差异无显著性（P＞0.05）.早期高剂量组患者心血管事件的发生率低于常规剂量组（P< 0.01）, 且两组间药物不良反应的发生率差异无显著性（P＞0.05）.结论 冠脉介入术前早期使用高剂量氯吡格雷能够明显减少非ST段抬高急性冠脉综合征患者术后近期心血管事件的发生率, 且不增加药物不良反应的发生率.     

当归提取物对急性心肌梗死大鼠的保护作用

目的 观察当归提取物对大鼠急性心肌梗死的保护作用. 方法 通过结扎大鼠冠状动脉左前降支建立大鼠急性心肌梗死模型,观察当归提取物对急性心肌梗死的保护作用. 60只大鼠随机分成6组：假手术组、模型组、阳性对照组、低剂量药物组、中剂量药物组、高剂量药物组,每组10只. 低、中、高剂量药物组分别腹腔注射当归提取物0.07,0.14,0.28 g&#8226;kg^-1,qd,连续7 d;阳性对照组腹腔注射1,6二磷酸果糖注射液1.4 g&#8226;kg^-1,给药容积为10 mL&#8226;kg^-1,qd,连续7 d;模型组和假手术组分别腹腔注射等量0.9%氯化钠溶液,qd,连续7 d. 结果 当归提取物可缩小大鼠心肌梗死范围,减少心肌细胞内肌酸激酶（CK）和乳酸脱氢酶（LDH）的释放,增强心肌凋亡相关蛋白Bc1 2的表达,减少Bax表达. 结论 当归提取物对大鼠急性心肌梗死有明显的保护作用.     

齐拉西酮与利培酮治疗首发精神分裂症的对照研究

目的 探讨齐拉西酮治疗首发精神分裂症的有效性与安全性. 方法 将76例未服药的首发精神分裂症患者随机分为治疗组37例, 对照组39例. 治疗组给予齐拉西酮, 初始剂量为20～40 mg&#8226;d^-1 , bid, 餐时口服, 15 d内可视病情调整至最大剂量80～160 mg&#8226;d^-1 , 平均终末治疗剂量（90.1±10.2） mg&#8226;d^-1. 对照组给予利培酮, 初始剂量为0.5～1.0 mg&#8226;d-1 , 15 d内可视病情调整至2～6 mg&#8226;d^-1 , 平均治疗剂量（3.5 ±0.6） mg&#8226;d^-1. 疗程8周. 于治疗前和治疗第2, 4, 6, 8周末采用阳性症状与阴性症状量表（PANSS）评定临床疗效, 不良反应症状量表（TESS）评定不良反应. 结果 治疗第8周末治疗组和对照组PANSS评分均非常显著低于治疗前（P<0.01）, 但组间差异均无显著性（P>0.05）, 两组有效率分别为91.9%和89.8%, 差异无显著性（P>0.05）. 治疗组的不良反应较少, 两组差异无显著性（P>0.05）. 结论 齐拉西酮治疗首发精神分裂症的疗效与利培酮相当, 是安全、有效的新型抗精神病药物.     

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.     

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.     

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.