基质金属蛋白酶-9／基质金属蛋白酶抑制物-1比值与急性冠脉综合征

目的：检测基质金属蛋白酶-9（ MMP-9）／基质金属蛋白酶抑制物-1（ TIMP-1）比值在急性冠脉综合征（ ACS）中的变化。方法26例非冠心病患者作为对照组;22例稳定性心绞痛（ SA组）;ACS组40例[包括不稳定性心绞痛（UA）20例,急性心肌梗死（AMI）20例]。通过ELISA方法定量检测外周血基质金属蛋白酶-9（MMP-9）,基质金属蛋白酶抑制物-1（ TIMP-1） ,比较MMP-9／TIMP-1比值与冠脉病变的相关性。结果 MMP-9／TIMP-1比值在ACS （3.31±0．72）中显著高于SA（1．97±0．54 P＜0．01）及对照组（1．67±0．10 P＜0．01）。结论 MMP-9／TIMP-1比值可能成为ACS的新的生物学标记物;MMP-9／TIMP-1比值的增高可能反应了斑块的不稳定性,对不稳定斑块的检出、冠心病的危险度分层有一定的意义。     

普伐他汀对急性冠状动脉综合征患者血清组织抑制因子-1及基质金属蛋白酶-9水平的影响

目的观察普伐他汀对急性冠状动脉综合征（ACS）患者血清基质金属蛋白酶-9（MMP-9）及组织抑制因子-1（TIMP-1）水平的影响。方法选择ACS患者30例，稳定性心绞痛（SAP）患者30例，正常健康体检者28例，采用ELISA法测定其血清可溶性TIMP-1及MMP-9浓度，经普伐他汀治疗后复查TIMP-1及MMP-9的变化。结果ACS组血清MMP-9显著高于SAP组及对照组（均P〈0．05），而TIMP-1显著低于SAP组及对照组（均P〈0．05）．SAP组MMP-9显著高于对照组（P〈0．05），SAP组TIMP-1与对照组之间无差异（P〉0．05）；普伐他汀治疗4周后ACS患者血清MMP-9水平下降，TIMP-1水平上升，与治疗前比较差异有统计学意义（P〈0．01，P〈0．05），SAP组MMP-9与治疗前比较差异有统计学意义（P〈0．05），而TIMP-1无明显改变（P〉0．05）。结论ACS患者MMP-9升高及TIMP-1下降，可能与其发病机制相关．普伐他汀能降低ACS患者MMP-9并升高TIMP-1，对于ACS的临床治疗有着重要的意义。     

慢性心力衰竭患者血清基质金属蛋白酶的变化及其临床意义

目的 探讨慢性心力衰竭（CCF）患者血清基质金属蛋白酶-2、9（MMP-2、MMP-9）的变化及其临床意义。方法 测定60例CCF患者及50名正常对照者MMP-2、MMP-9水平、用超声心动仪测定两组患者心脏结构和功能指标，分析血清MMP-2、MMP．9与CCF的关系。结果 CCF患者血清MMP-2、MMP-9水平明显高于对照者（P〈0．05）；左室收缩末内径、左室舒张末内径、左室收缩末期容积和舒张末期容积随着CCF病情加重而增大（P〈0．05），左心室射血分数随着CCF病情加重而降低（P〈0．05）。结论 MMP-2,MMP-9共同参与了CCF的发生、发展．可作为反映心室重塑和心功能恶化的有效指标。     

心肌梗死后心脏胶原重塑与血清基质金属蛋白酶及其抑制因子的变化

目的探讨心肌梗死（M1）后患者心脏胶原重塑与血清基质金属蛋白酶-1（MMP-1）及其抑制因子（TIMP-1）水平的变化。方法测定首次发病的MI住院患者（MI组）发病后1周、3个月、6个月的血清I型前胶原羧基端肽（PICP）和Ⅲ型前胶原（PCⅢ）、MMP-1、TIMP-1的水平，并计算PICP／PCⅢ比值。以48例健康体检者作为正常对照组。结果与对照组比较，MI组PICP水平在MI后3个月、6个月组明显高于对照组（P〈0．05），血清PCⅢ水平在MI后各时间点均明显升高（P〈0．05），MI后各时间点的PICP／PCⅢ比值和血清MMP-1、TIMP-1水平均明显降低（P〈0．05）。结论MI后心脏胶原合成代谢旺盛，MMP-1／TIMP-1参与MI后心脏胶原重塑的病理生理进程。     

缺血性心脏病患者血浆基质金属蛋白酶2和基质金属蛋白酶9与心脏重塑关系

目的探测缺血性心脏病（IHD）患者血浆基质金属蛋白酶2（MMP-2）、MMP-9活性水平与心脏重塑指标左心室质量指数（LVMI）之间的关系。方法选取2007年5月至2010年9月北京安贞医院住院的IHD患者254例,根据LVMI不同分为心脏重塑组（128例）和非心脏重塑组（126例）。对照组为214例门诊健康体检心脏功能正常的健康人。利用明胶酶谱方法测定各组受试者血浆MMP．2、MMP-9的活性水平,分析两者与心脏重塑指标的关系。结果心脏重塑组患者血浆MMP-2、MMP-9的活性高于对照组和非心脏重塑组[MMP-2：（13．0±2．9）m2／（g·L^-1）比（8．9±2．3）、（10．9±2．9）m2／（g·L^-1）;MMP-9：（2．6±1．0）m2／（g·L^-1）比（1．4±0．4）、（2．1±0．7）m2／（g·L^-1）,均P〈0．05],非心脏重塑组患者的MMP-2、MMP-9活性水平高于对照组（P〈0．05）。血浆MMP-2、MMP-9活性水平与LVMI明显相关（r=0．464、0．516,均P〈0．05）。结论MMP-2、MMP-9在IHD患者心脏重塑的发生和发展过程中起着一定作用,有可能用来预测IHD患者发生心脏重塑的进展及预后。     

血清基质金属蛋白酶-9和C反应蛋白与急性冠脉综合征的相关性

目的 研究血清基质金属蛋白酶-9（MMP-9）和C反应蛋白（CRP）与急性冠脉综合征（ACS）的关系。方法选择42例ACS患者、27例SAP患者及25例健康对照,用ELISA法检测血清MMP-9浓度,免疫散射比浊法测定CRP浓度。结果ACS组MMP-9、CRP浓度为（50．64±7．68）ng／ml和（10．24±3．47）mg／L,明显高于SAP组和正常组,差异有统计学意义（P〈0．05）,而SAP组与正常组MMP-9、CRP浓度相比差异无统计学意义（P〉0．05）。结论急性冠脉综合征患者血清基质金属蛋白酶-9（MMP-9）和C反应蛋白（CRP）明显升高。     

哮喘患者检测痰中基质金属蛋白酶的临床意义

目的探讨支气管哮喘（简称哮喘）患者诱导痰中基质金属蛋白酶9（MMP-9）和基质金属蛋白酶抑制剂1（TIMP-1）的浓度比值与气道炎症和气流受限的关系。方法选择缓解期哮喘患者（哮喘组）和健康对照者（健康对照组）进行肺功能测定;用诱导痰检查方法对痰炎性细胞进行分类计数,并用酶联免疫吸附试验（ELISA）法测定诱导痰上清液中MMP-9和TIMP-1浓度。结果哮喘组和健康对照组诱导痰中MMP-9、TIMP-1浓度比较差异和MMP-9／TIMP-1比值比较差异有统计学意义。结论哮喘组患者诱导痰中MMP-9／TIMP-1比值的失衡与气道炎症有关,从而造成气道重塑和气流受限,导致肺功能下降。     

氟伐他汀对慢性心力衰竭患者血清基质金属蛋白酶的影响

目的 探讨慢性心力衰竭患者应用氟伐他汀治疗对血清基质金属蛋白酶-9（MMP-9）的影响。方法235例患者分为2组,对照组118例,应用利尿剂、血管紧张素转换酶抑制剂、β-受体阻滞剂、螺内酯、硝酸酯类药物等常规治疗;他汀组117例,在常规治疗基础上,加用氟伐他汀治疗。2组均于治疗前及治疗6个月后测血清MMP-9浓度,评价其心功能变化,分析2纽治疗前后MMP-9的差异。结果治疗6个月后2组MMP-9浓度均明显下降（P均〈0．01）,他汀组下降更明显（P〈0．01）;6个月后他汀组总有效率高于对照组（P〈0．05）。结论慢性心力衰竭患者在常规治疗同时加用氟伐他汀治疗,可明显降低血清MMP-9浓度,改善心功能。     

基质金属蛋白酶-9及其组织抑制物-1与子宫内膜异位症的相关性研究

目的研究基质金属蛋白酶-9（MMP-9）及其组织抑制物-1（TIMP-1）是否与子宫内膜异位症（EMs）有关。方法将11例EMs轻度和32例重度患者分别作为观察组1和2,41例卵巢畸胎瘤患者作为对照组。通过ELISA法测定腹水中MMP-9及TIMP-1值,比较各组两者及其比值的差异。结果与对照组比较,EMs轻度组MMP-9、TIMP-1差异无统计学意义（P〉0.05）,EMs重度组MMP-9、TIMP-1差异有统计学意义（P〈0.05）;3组的MMP-9/TIMP-1差异均有统计学意义（P〈0.05）;EMs轻度组与重度组相比较,MMP-9差异有统计学意义（P〈0.05）,TIMP-1差异无统计学意义（P〉0.05）。结论随着疾病的加重,MMP-9升高、TIMP-1降低、MMP-9/TIMP-1比值升高,MMP-9、TIMP-1与子宫内膜异位症发生、发展有相关性,特别是两者的比值,具有重要诊断价值。     

急性冠脉综合征患者基质金属蛋白酶-9和妊娠相关血浆蛋白-A的变化及相关性

目的探讨急性冠脉综合征患者血浆基质金属蛋白酶-9（MMP-9）和妊娠相关血浆蛋白-A（PAPP—A）水平的变化及其之间的相关性。方法选择73例急性冠脉综合征患者和28例稳定型心绞痛患者,采用酶联免疫吸附法（ELISA）双抗体夹心法检测血浆MMP-9和PAPP．A水平。采用冠状动脉造影（CAG）对冠脉狭窄程度进行评分。结果急性冠脉综合征组MMP-9和PAPP—A的浓度显著高于稳性型心绞痛组（P〈0．05）,而且MMP-9和PAPP—A之间存在直线正相关关系（r=0．407,P〈0．01）。Jenkins评分与MMP-9水平（r=0．267,P〈0．05）及PAPP—A（r=0．308,P〈0．05）均呈正相关。结论急性冠脉综合征患者血浆MMP-9和PAPP—A升高可能提示冠状动脉粥样斑块的不稳定。     

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.

     

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.     

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.     

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.