阿托伐他汀对急性脑梗死调脂及MMP-9影响的观察

目的观察阿托伐他汀对急性脑梗死患者调脂及人单核细胞基质金属蛋白酶-9（MMP-9）的影响。方法60例急性脑梗死患者给予阿托伐他汀20mg,口服,1次/d,疗程4周。观察治疗前后血脂和血清MMP-9的变化。结果经阿托伐他汀治疗4周后,TC、LDL—C较治疗前均明显降低,HDL—C较治疗前明显升高,且明显优于对照组（P〈0．05和0．01）,血清MMP-9水平显著降低（P〈0．01）。结论阿托伐他汀不仅具有调脂作用,还明显降低MMP-9的作用。     

阿托伐他汀治疗急性冠状动脉综合症的疗效分析

目的探讨不同剂量的阿托伐他汀治疗急性冠状动脉综合症的疗效．方法90例急性冠脉综合征患者随机分为3组：A组为常规治疗组（30例）予以常规治疗但不用降脂药物;B组（30例）为20mg阿托伐他汀治疗组;C组为40mg阿托伐他汀治疗组（30例）;30例稳定性心绞痛患者为对照组。90例急性冠脉综合征患者在治疗2周前后分别测定血清高敏C反应蛋白（hs—CRP）及血脂水平。结果90例急性冠脉综合征患者就诊时的血清高敏CRP水平明显高于对照组稳定性心绞痛患者（P〈0．05）,B、C组治疗2周后血清高敏CRP较前有明显下降（P〈0．05）,而以C组作用更明显。结论急性冠脉综合征患者血清高敏CRP水平增高,早期他汀类药物强化治疗可使急性冠脉综合征患者获益更大。     

早期阿托伐他汀强化治疗对急性冠脉综合征患者疗效机制探讨

目的研究阿托伐他汀对急性冠脉综合征早期的作用机制和治疗价值。方法急性冠脉综合征患者196例随机分组，小剂量治疗组101例，口服阿托伐他汀10mg，每日1次，共30d；大剂量治疗组95例，口服阿托伐他汀80mg，每日1次，共30d，治疗前和治疗30d时测定血脂，MMP-1、MMP-9和hs-CRP，并进行活动平板检查，患者每周接受门诊或电话随访。结果30d后，两治疗组血脂水平有所好转，但差异无统计学意义，血清MMP-1、MMP-9、hs-CRP水平均有降低，两组下降程度差异有统计学意义（P〈0．05），胸痛发作次数减少，硝酸甘油用量减少和运动平板运动持续时间增加，两组相比差异有统计学意义（P〈0．05）。结论阿托伐他汀治疗可减少急性冠脉综合征患者斑块基质成分降解和炎性反应，改善患者生活质量，大剂量阿托伐他汀应用获益更多。     

阿托伐他汀对急性冠脉综合征患者血浆纤维蛋白原的影响

目的：研究阿托伐他汀对急性冠脉综合征（ACS）患者血浆纤维蛋白原（Fib）的影响。方法：急性冠脉综合征患者112例，随机单盲分为阿托伐他汀组56例，常规治疗组56例，另外随机选择40例正常人做对照组。采用血凝仪法测定Fib含量。结果：急性冠脉综合征患者血浆Fib水平明显升高，明显高于正常对照组（P〈0．01）；阿托伐他汀组和常规治疗组两组治疗前Fib水平比较无显著性差异（P〉0．05）。阿托伐他汀组治疗后Fib水平较前明显降低，而常规治疗组治疗后Fib水平无明显变化，两组比较有显著性差异（P〈0．01）。结论：阿托伐他汀可通过降低Fib水平改善急性冠脉综合征患者血液流变学状态，从而改善心肌供血，抑制冠心病的发生发展过程。     

阿托伐他汀对急性冠脉综合征患者血清基质金属蛋白酶-9及其组织抑制因子-1的影响

目的 探讨阿托伐他汀对急性冠脉综合征（ACS）患者基质金属蛋白酶-9（MMP-9）及其组织抑制因子1（TIMP-1）表达的影响.方法 ACS患者124例按治疗方法不同分组：常规治疗为对照组,在常规治疗基础上加用阿托伐他汀为治疗组.观察两组治疗前后MMP-9、TIMP-1的变化.结果 治疗3周后治疗组血清MMP-9水平与对照组治疗后相比明显下降,血清TIMP-1水平明显升高,MMP-9/TIMP-1值明显降低（均P〈0.05）.结论 阿托伐他汀可明显降低MMP-9/TIMP-1值,从而减少炎性反应,稳定斑块,改善预后,值得临床推广使用.     

早期应用阿托伐他汀对急性冠脉综合征患者远期疗效的影响

目的观察阿托伐他汀对急性冠状动脉综合征（ACS）患者早期炎症因子和心脑血管事件的干预效果。方法将53例ACS患者随机分为阿托伐他汀治疗组（n=29）和常规对照组（n=24）。阿托伐他汀治疗组在对照组常规治疗基础上加用阿托伐他汀20mg,每晚1次顿服。所有患者分别于入院24h内和治疗后1个月清晨空腹采血1次,测定血脂、hs-CRP、MMP-9。同时观察6个月随访期内主要心脑血管终点事件的发生。结果治疗4周后,阿托伐他汀治疗组与对照组相比,患者TC、TG、hs-CRP及MMP-9浓度显著降低（均P〈0.01）,而对照组治疗前后差异无统计学意义（P〉0.05）。阿托伐他汀治疗组6个月随访期内复发性心绞痛、心律失常、心力衰竭及非致命性心肌梗塞等均较常规对照组明显降低（P〈0.05）。结论阿托伐他汀早期治疗ACS能够抑制炎症因子并降低半年随访期间主要心血管事件的发生率。     

阿托伐他汀对急性冠脉综合征C-反应蛋白及血脂的影响

目的应用阿托伐他汀治疗急性冠脉综合征（ACS），以观察其对患者超敏C-反应蛋白（CRP）及血脂水平的影响。方法选择83例急性冠脉综合征患者于治疗前后分别检测超敏CRP和血脂水平，进行对比分析，以及与健康对照组36例超敏CRP进行对比。结果ACS患者血清超敏CRP较健康对照组明显高（P〈0．01）。经4周治疗后较治疗前超敏CRP、总胆固醇、低密度胆固醇、甘油三脂均有明显下降（P〈0．01），高密度胆固醇有明显升高（P〈0．01）。结论阿托伐他汀不仅能有效改善ACS患者血脂水平．而且可明显降低血清超敏CRP，抑制斑块内炎症反应。     

高龄老年急性冠状动脉综合征患者早期应用大剂量阿托伐他汀的临床研究

目的 研究高龄老年（80岁以上）急性冠状动脉综合征（ACS）患者服用40mg阿托伐他汀强化调脂对炎症因子、调脂疗效的影响,同时观察不良反应。方法将87例高龄老年ACS患者随机分为两组,实验组41例给予阿托伐他汀40mg／d,对照组46例给予阿托伐他汀10mg／d。用药后2周、12周抽取外周血,测定血浆总胆固醇（TC）及低密度脂蛋白胆固醇（LDL—C）、血清高敏C-反应蛋白（hs—CRP）、基质金属蛋白酶-9（MMP-9）水平,并观察药物不良反应。结果（11药物治疗前,两组ACS患者TC、LDL—C水平以及hs—CRP和MMP-9水平差异无统计学意义（P〉0．05）（2）药物治疗2周后Tc和LDL—C水平：与用药前比较,对照组和实验组均无明显改变（P〉0．05）。（3）治疗12周后TC和LDL—C水平：与用药前比较,两组均明显降低（P〈0．01）,实验组较对照组降低更为显著（P〈0．05）。（4）药物治疗2周后hs—CRP及MMP-9水平：与用药前比较,两组均明显降低（P〈0．01）,且实验组较对照组降低更明显（P〈0．05）。（5）治疗12周后hs—CRP及MMP～9水平：两组hs—CRP及MMP-9水平进一步下降,且实验组较对照组降低更明显（P〈0．05）。（6）两组患者服药后不良反应轻微。结论高龄老年ACS患者服用40mg阿托伐他汀,不但调脂效果更加显著,还可明显抑制冠脉内炎症反应及稳定斑块,且药物副作用小。     

应用不同剂量阿托伐他汀治疗急性冠脉综合征临床疗效比较

目的：探讨不同剂量阿托伐他汀治疗急性冠脉综合征的临床疗效。方法：选择本院急性冠脉综合征患者82例,将上述患者随机分为观察组和对照组。两组患者均给予急性冠脉综合征常规治疗外,对照组患者给予阿托伐他汀每天10mg口服,观察组患者给予阿托伐他汀每天40mg口服。两组患者均连续服用6个月。对两组患者治疗前后血脂进行检测;观察两组患者出院后主要心脑血管事件。结果：观察组患者治疗后TG、TC、LDL-C水平与对照组治疗后比较,差异有统计意义（P〈0.05）;观察组复发性心绞痛、心力衰竭、心律失常发生率显著低于对照组,差异有统计学意义（P〈0.05）。结论：较大剂量阿托伐他汀（每天40mg）能够显著改善急性冠脉综合征患者血脂及减少心脑血管事件,临床效果显著。     

阿托伐他汀强化降脂对急性冠脉综合征患者血清炎症标志物水平的影响

目的：探讨阿托伐他汀强化降脂对急性冠脉综合征患者血清炎症标志物水平的影响及疗效。方法选择急性冠脉综合征患者70例,采用随机数字表将纳入患者分为强化组和对照组。两组患者均予以阿司匹林、肝素、硝酸酯类、β-受体阻滞剂和血管紧张素转换酶抑制剂等常规治疗。强化组患者在此基础上加用阿托伐他汀20 mg,每晚1次,连用8周。对照组患者在此基础上加用阿托伐他汀10 mg,每晚1次,连用8周。观察并比较两组患者治疗前及治疗8周后血清hs-CRP、IL-10和MMP-9水平的变化,并进行疗效观察。结果治疗8周后,两组血清hs-CRP和MMP-9水平均较前明显下降,血清IL-10水平较前明显上升（ t＝2.44、2．27、2．45、3．05、2．90、2．93,P＜0．05或P＜0．01）,且强化组下降或上升值较对照组更明显（t＝2．31、2．37、2．24,P＜0．05）;强化组临床总有效率（91．4％）明显优于对照组（68．6％）（χ2＝5．71,P＜0．05）。结论阿托伐他汀强化降脂治疗急性冠脉综合征具有较好的效果,能降低血清hs-CRP和MMP-9水平,提高血清IL-10水平,从而抑制斑块局部炎性反应,提高动脉粥样硬化斑块的稳定性。     

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.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

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.