美沙拉嗪联合双歧杆菌四联活菌片对溃疡性结肠炎患者脂质过氧化损伤保护作用的观察

摘 要 目的:探讨美沙拉嗪联合双歧杆菌四联活菌片对溃疡性结肠炎（UC）患者脂质过氧化损伤的保护作用。方法：72例轻中度活动期UC患者随机分为试验组和对照组各36例。对照组患者予美沙拉嗪肠溶片1.0 g,po  qid。试验组患者在对照组基础上加用双歧杆菌四联活菌片1.5 g,po tid。两组均连用6周后,比较两组治疗前后血清丙二醛(MDA)、氧化低密度脂蛋白(ox-LDL)、过氧化脂质(LPO)和超氧化物歧化酶(SOD)水平变化,评估其临床疗效及药物不良反应。结果：治疗6周后,两组患者的血清MDA、ox LDL和LPO水平均较前明显下降,SOD水平较前明显上升(P<0.05或P<0.01),且试验组明显优于对照组(P<0.05)。试验组临床总有效率为93.75%,明显高于对照组的73.53%(P<0.05);两组药物不良反应发生率比较,差异无统计学意义(P>0.05)。结论：美沙拉嗪联合双歧杆菌四联活菌片治疗UC疗效较显著,其作用机制与其降低血清MDA、ox LDL和LPO水平,升高SOD水平,保护脂质过氧化损伤的作用密切相关。     

丁苯酞联合较高剂量阿托伐他汀治疗急性脑梗死临床观察

摘 要 目的：观察丁苯酞联合较高剂量阿托伐他汀治疗急性脑梗死的疗效,及对患者炎性反应、氧化应激和动脉粥样斑块的影响。 方法: 146例急性脑梗死患者随机分为观察组和对照组各73例。对照组给予丁苯酞联合常规剂量阿托伐他汀治疗,观察组给予丁苯酞联合较高剂量阿托伐他汀治疗。评价两组治疗总有效率,比较两组患者治疗前后血浆同型半胱氨酸(Hcy)、C 反应蛋白(CRP)、丙二醛（MDA）、超氧化物歧化酶(SOD)、总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇(LDL C)、 氧化修饰低密度脂蛋白 （oxLDL）、基质金属蛋白酶 9(MMP 9)水平,和颈动脉内膜中层厚度(cIMT)、颈动脉粥样斑块面积、不稳定斑块数量变化情况。对Hey、MDA、斑块面积、不稳定斑块变化幅度与年龄、入院NHSS评分、脑梗死体积及丁苯酞联合降脂、联合一般降脂、联合强化降脂等指标的相关性进行分析。出院后进行3个月的预后随访。结果: 治疗后观察组总有效率为81.2%,明显高于对照组的61.4%（P＜0.05）。治疗后两组患者的Hcy、CRP、MDA、TC、TG、LDL、oxLDL、MMP 9、cIMT及颈动脉斑块面积、不稳定斑块数量等指标均较治疗前明显降低(P＜0.05),SOD则较治疗前升高(P＜0.05),且观察组各项指标均优于对照组(P＜0.05)。Hcy、MDA、斑块面积、不稳定斑块变化值与丁苯酞联合降脂呈正相关,而与强化降脂的相关性更高（P＜0.05）。观察组预后良好率明显优于对照组（P＜0.05）。结论: 丁苯酞联合阿托伐他汀强化降脂治疗急性脑梗死的效果明显,可有效改善患者炎性反应和氧化应激状态,有利于促进神经功能恢复和抑制动脉斑块形成。     

依达拉奉联合常规治疗对急性脑梗死患者神经功能的影响

摘 要 目的:观察依达拉奉联合常规治疗对急性脑梗死患者神经功能的影响。方法：144例急性脑梗死患者随机分为观察组(n=72)和对照组(n=72),对照组给予常规治疗,观察组在常规治疗基础上加用依达拉奉,疗程2周。比较两组患者治疗前后的血清超氧化物歧化酶(SOD)、血清丙二醛(MDA)和神经元特异性烯醇化酶(NSE)水平变化,根据美国国立卫生研究院卒中量表(NIHSS)评定两组神经功能缺损。结果：治疗后两组的NIHSS评分均较治疗前明显降低(P<0.05),观察组治疗后评分明显低于对照组(P<0.05)。治疗后两组患者血清SOD水平均较治疗前明显升高,MDA和NSE水平则明显降低(P<0.05);且治疗后两组患者SOD、MDA和NSE水平比较,差异有统计学意义(P<0.05)。两组药品不良反应发生率比较,差异无统计学意义(P>0.05)。结论：依达拉奉能明显改善急性脑梗死患者的神经功能,其作用机制与清除自由基、降低神经元特异性烯醇化酶有关。     

氨氯地平阿托伐他汀对高血压合并冠心病患者血压、血脂的影响观察

摘 要 目的： 探讨氨氯地平阿托伐他汀对高血压合并冠心病患者血压、血脂的影响。方法: 高血压合并冠心病门诊患者80例随机分为观察组40例与对照组40例。对照组患者给予氨氯地平片10 mg,po,qn;观察组患者给予氨氯地平阿托伐他汀片20 mg,po,qn。两组疗程均为6周。观察两组治疗前后血压、血脂变化,比较两组临床疗效及药品不良反应。结果: 两组患者治疗后收缩压、舒张压及血脂各项指标均较治疗前明显改善（P＜0.05）;且观察组患者各项指标均明显优于对照组（P＜0.05）。治疗后,观察组临床总有效率为92.5%,高于对照组的80.0%（P＜0.05）。两组药品不良反应发生率比较,差异无统计学意义（P＞0.05）。结论:氨氯地平阿托伐他汀片治疗高血压合并冠心病,能明显改善患者血压、血脂水平,临床疗效确切,不良反应少,值得临床推广应用。     

阿托伐他汀联合法舒地尔治疗慢性肺源性心脏病心力衰竭的临床观察

摘 要 目的：探讨阿托伐他汀联合法舒地尔治疗慢性肺源性心脏病心力衰竭的疗效,为临床治疗提供理论依据。方法: 130例慢性肺源性心脏病合并心力衰竭患者随机分为对照组和他汀组,每组65例。对照组实施常规对症治疗,并给予法舒地尔注射液30 mg,ivd,bid。他汀组在对照组基础上加用阿托伐他汀片20 mg·d-1。两组均连续治疗12周。观察两组临床疗效和药品不良反应,比较两组治疗前后动脉血氧分压（PaO2）、二氧化碳分压（PaCO2）、血氧饱和度(SaO2)、肺动脉收缩压(SPAP)、右心室射血分数（RVEF）、右心室 Tei 指数及血浆内皮素 1（ET 1）、一氧化氮（NO）、脑钠肽（BNP）水平变化。结果: 他汀组治疗后总有效率为89.23％,明显高于对照组的75.38％（P＜0.05）。治疗后,他汀组PaO2、SaO2、RVEF、NO较治疗前明显增高（P＜0.05）,PaCO2、BNP、SPAP、Tei指数、ET 1则较治疗前明显下降（P＜0.05）,且以上指标均明显优于对照组（P＜0.05）。两组药品不良反应发生率差异无统计学意义（P＞0.05）。结论: 阿托伐他汀联合法舒地尔治疗慢性肺源性心脏病心力衰竭的疗效肯定,可有效降低患者的肺动脉压、改善右心功能。     

脂康颗粒联合不同剂量阿托伐他汀用于脑梗死二级预防效果观察及析因分析

摘 要 目的：评估脂康颗粒联合阿托伐他汀在动脉粥样硬化脑梗死二级预防中的效果。方法：180例患者随机分为对照组和观察组各90例,2组再随机分为三个亚组。对照组3个亚组分别每日顿服阿托伐他汀片10,20,40 mg;观察组3个亚组在对照组基础上加用脂康颗粒。两组均连续治疗6个月。测定治疗前、治疗3个月、治疗6个月时各组患者的血脂指标（TG、TC、LDL C）和ALT、动脉内 中膜厚度（IMT）;使用析因分析比较用药种类、阿托伐他汀剂量、治疗时间对上述指标的影响。结果：治疗3个月后,两组及各亚组TG、TC、LDL C等血脂指标均较治疗前明显下降（P<0.05）,ALT较前明显升高（P<0.05）;观察组及各亚组TG、TC、LDL C水平明显低于对照组及各相应亚组（P<0.05）;两组40 mg亚组、20 mg亚组的TC、LDL C水平均明显低于本组10 mg亚组（P<0.05）。治疗6个月后,两组及各亚组TG、TC、LDL C等血脂指标均较治疗前进一步明显下降（P<0.05）,ALT也进一步明显升高（P<0.05）,两组IMT较治疗前明显降低（P<0.05）;观察组及各亚组TG、TC、LDL C水平明显低于对照组及各相应亚组（P<0.05）;两组40 mg亚组的TG、TC、LDL C水平明显低于本组10 mg亚组（P<0.05）,20 mg亚组的TC、LDL C水平明显低于本组10 mg亚组（P<0.05）。析因分析结果：增加阿托伐他汀剂量显著降低TG、TC、LDL C和升高ALT（P<0.05）。延长治疗时间显著降低TG、TC、LDL C、IMT和升高ALT（P<0.05）。用药种类和治疗时间对降低TC、LDL C有交互作用,阿托伐他汀剂量和治疗时间对降低TC、LDL C和升高ALT有交互作用（P<0.05）。结论：联用脂康颗粒提高了阿托伐他汀在动脉粥样硬化所致脑梗死二级预防中的效果。     

不同剂量瑞舒伐他汀钙联合基础治疗老年不稳定型心绞痛患者临床观察

摘 要 目的：观察不同剂量瑞舒伐他汀钙联合基础治疗老年不稳定型心绞痛（UAP）患者的临床疗效,及对患者血清炎症因子的影响。方法: 老年UAP患者82例随机分为低剂量组（n=40）和高剂量组（n=42）。在基础治疗外,低剂量组给予瑞舒伐他汀钙片10 mg,po,qn;高剂量组给予瑞舒伐他汀钙片20 mg,po,qn。比较两组患者治疗前及治疗3个月后血清炎症因子及血脂水平变化,观察两组疗效,心绞痛发作频率、发作时间,以及相关不良事件发生情况。结果:治疗后,两组患者总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白（LDL-C）水平均较治疗前明显下降,高密度脂蛋白（HDL-C）水平则较前升高（P<0.05）,且高剂量组各项血脂指标均优于低剂量组（P<0.05）,两组患者肿瘤坏死因子（TNF-α）、白细胞介素6（IL-6）及转化生长因子β1（TGF-β1）水平均较治疗前明显下降（P<0.05）,且高剂量组明显低于低剂量组（P<0.05）。高剂量组治疗总有效率为95.43%,明显优于低剂量组的77.50%（P<0.05）;且高剂量组患者的心绞痛发作频率及发作时间均少于低剂量组患者（P<0.05）。两组相关不良事件发生率差异无统计学意义（P＞0.05）。结论:大剂量瑞舒伐他汀钙联合基础治疗可有效改善老年UAP患者的血脂和血清炎症因子水平,具有较好的临床疗效。     

美金刚、阿托伐他汀联合多奈哌齐治疗老年血管性痴呆疗效观察

摘 要 目的：探讨美金刚、阿托伐他汀和多奈哌齐联合治疗老年血管性痴呆的临床疗效、安全性及作用机制。方法：老年血管性痴呆患者140例随机分为观察组和对照组,每组70例。对照组在常规治疗基础上给予多奈哌齐片治疗,观察组在对照组基础上再加用美金刚片和阿托伐他汀片治疗。两组均治疗6个月。治疗前后采用简易精神认知量表(MMSE)、Blessed 痴呆量表(BDS)、日常生活能力量表(ADL)评定及精神科问卷(NPI)评估两组疗效,采用药物副反应量表(TESS)评估安全性。同时比较治疗前后两组患者血清学指标脑源性神经营养因子（BDNF）、内皮素(ET)、一氧化氮（NO）含量及血脂水平变化。结果：治疗后,两组MMSE、BDS、ADL、NPI评分均较前显著改善（P<0.05）,且观察组各项评分均优于对照组（P<0.05）。两组TESS各项评分比较,差异无统计学意义（P>0.05）。治疗后,观察组各项血脂指标均较治疗前显著改善（P<0.05）,且均显著优于对照组（P<0.05）;两组BDNF含量均较治疗前增加,ET、NO含量均较治疗前降低（P<0.05）,且观察组BDNF、ET、NO含量均优于对照组（P<0.05）。结论：美金刚、阿托伐他汀和多奈哌齐可改善老年血管性痴呆行为能力、日常生活能力、精神认知能力,临床疗效好,可能与联合用药可降低血液 ET 、NO 的含量,升高BDNF含量有关。     

瑞舒伐他汀与阿托伐他汀对高脂血症患者血糖影响的Meta分析

摘 要 目的：利用 Meta 分析方法评价瑞舒伐他汀与阿托伐他汀在降脂同时对非糖尿病高脂血症患者血糖的影响。方法：检索PubMed、ISI Web of Knowledge、中国知网、万方数据、维普数据库中有关瑞舒伐他汀与阿托伐他汀治疗高脂血症患者的随机对照试验（RCT）,文献检索年限为各数据库建库至2014年12月31日,对符合标准的RCT采用RevMan5.2软件进行Meta分析。结果：共纳入4个RCT,累计484例非糖尿病高脂血症患者。Meta分析结果显示,与阿托伐他汀相比,瑞舒伐他汀对空腹血糖的影响差异无统计意义（MD=-1.02, 95%CI:-2.10~0.06, P=0.07）,对糖化血红蛋白影响的差异有统计学意义（MD=-0.06, 95%CI:-0.10~-0.01, P=0.01）。结论：现有证据表明瑞舒伐他汀对高脂血症患者的血糖影响可能会比阿托伐他汀更加稳定,但是这个差别较小。     

鼠神经生长因子对新生儿缺氧缺血性脑病患儿血清神经肽Y和神经元特异性烯醇化酶水平的影响及疗效观察

摘 要 目的： 探讨鼠神经生长因子对新生儿缺氧缺血性脑病(HIE)患儿血清神经肽Y(NPY)和神经元特异性烯醇化酶(NSE)水平的影响及疗效观察。方法: 采用随机数字表法将70例新生儿HIE患儿分成观察组和对照组。两组患儿均予以吸氧、控制颅内压、血压和血糖,抗惊厥、保持水电解质平衡等常规治疗。观察组患儿加用鼠神经生长因子20 μg, im,qd。对照组患儿加用胞磷胆碱注射液100 mg,ivd,qd,均连用10～14 d。观察两组患儿治疗前后血清NPY 和NSE水平变化,比较两组疗效及药品不良反应,随访1年内神经系统后遗症的发生率。结果: 治疗2周后,两组血清NPY和NSE水平较前均明显下降(P<0.05和P<0.01),且观察组下降幅度明显大于对照组(P<0.05);观察组临床总有效率为94.28%,明显高于对照组的68.57%(P<0.01),两组患儿治疗中未出现明显药品不良反应。随访观察1年,观察组后遗症的发生率明显低于对照组(P<0.05)。结论: 鼠神经生长因子治疗新生儿HIE的疗效肯定,安全性好,可促进受损神经元细胞的修复,减少神经系统后遗症的发生率,其作用与降低血清NPY和NSE水平密切相关。     

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.