托伐普坦与呋塞米治疗老年心力衰竭患者的疗效对比观察

目的对比分析托伐普坦与呋塞米治疗老年心力衰竭患者的临床疗效。方法随机将2017年3月至2018年3月本院收治的160例老年心力衰竭患者分到观察组(n=80例)和对照组(n=80例),两组患者均采取强心、利尿、抗血小板聚集等常规抗心衰治疗。观察组患者在常规治疗基础上采取托伐普坦治疗,对照组患者在常规治疗基础上采取呋塞米治疗,两组患者的治疗周期均为4周。对比分析两组患者治疗前后24 h尿量、心脏射血分数(LVEF)。结果治疗前,观察组及对照组患者的24 h尿量、LVEF比较,均有P> 0.05。治疗后,观察组患者的24 h尿量明显高于对照组,LVEF明显高于对照组,均有P <0.05。结论与呋塞米治疗相比,采用托伐普坦治疗老年心力衰竭患者,其对24 h尿量及心功能的改善疗效更佳。     

托伐普坦与补肾清利活血汤在治疗慢性肾功能衰竭中的临床防治应用效果及对患者尿量、血钾血钠的影响

目的:观察托伐普坦与补肾清利活血汤在治疗慢性肾功能衰竭(CRF)中的临床防治应用效果,同时分析对患者尿量、血钾、血钠的影响。方法:于某院2019年3月~2021年3月期间治疗的CRF患者中遴选与本研究要求相符的102例为主体实施分析,保证全部患者诊疗资料完整且应用数字双盲法分组,分为参照组和实验组各51例,参照组采取托伐普坦治疗,实验组采取托伐普坦+补肾清利活血汤治疗,评价两组疗效、肾功能及尿量、电解质指标、中医证候积分。结果:组间电解质指标、肾功能与中医证候积分均有改善,实验组血钾、血钠、血钙水平均显著较参照组高,BUN、Scr水平均明显较参照组低,24h尿量显著大于参照组,各项中医证候积分均明显较参照组低(P<0.05);实验组临床总有效率为94.12%,相比较参照组高(P<0.05)。结论:在CRF患者的治疗中,托伐普坦+补肾清利活血汤治疗具有理想的效果,可明显改善电解质水平与24h尿量,促进中医证候积分改善,同时还可促进肾功能提高,对减轻疾病损害,改善预后具有重要作用,值得应用。     

托伐普坦联合特利加压素与人血白蛋白治疗乙型肝炎肝硬化并发肝肾综合征—急性肾损伤的疗效

目的 观察托伐普坦联合特利加压素与人血白蛋白治疗乙型肝炎肝硬化并发肝肾综合征—急性肾损伤的疗效。方法 选取2021年6月—2023年2月龙岩市第二医院收治的乙型肝炎肝硬化并发肝肾综合征—急性肾损伤患者70例,根据系统随机法分为特利加压素组(n=35)和联合治疗组(n=35)。特利加压素组予以注射用特利加压素联合人血白蛋白治疗,联合治疗组在特利加压素组基础上加用托伐普坦片,2组均连续治疗14 d。比较2组临床疗效,用药前及用药14 d后临床指标(24 h尿量、体质量以及腰围)、肝功能指标[天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)以及总胆红素(TBil)]、肾功能指标[血肌酐(SCr)、血尿素氮(BUN)、血钠(Na⁺)、胱抑素C(CysC)],不良反应。结果 联合治疗组与特利加压素组治疗总有效率比较,差异无统计学意义(68.57%vs. 51.43%,χ²=2.143,P=0.143)。用药14 d后,2组24 h尿量较用药前升高,体质量、腰围较用药前降低,且联合治疗组升高/降低幅度大于特利加压素组(P<0.01);2组A...     

托拉塞米的利尿作用和安全性

目的 观察健康受试者口服托拉塞米的利尿作用和安全性。方法 19名健康男性受试者单次口服不同剂量托拉塞米5,10和20 mg(n=9)或连续7天每日口服托拉塞米10 mg(n=10)。观察血压,尿量,24 h尿钾、钠、氯和血钾、钠、氯,心率,呼吸,心电图和心电监测,血常规,尿常规,血生化等指标。 结果 5,10,20mg 3组单次服药后24 h总尿量分别为2.24,2.60和3.17 L(P<0.05),24 h尿钾、钠、氯的排泄随托拉塞米剂量增加而略增加(P>0.05)。连续服药,首次药后的24h尿量及尿钾、钠、氯的量最多。单次和连续给药后血钾、钠、氯均未见下降,甘油三脂增加0.1~0.4 mmol.L-1(P<0.05)。4例受试者出现药物不良反应。 结论 在5~20 mg,托拉塞米利尿作用随剂量增加而增加,国人对托拉塞米耐受性良好。     

托伐普坦对肝硬化失代偿期患者稀释性低钠血症的临床疗效评价

目的:评价托伐普坦对肝硬化失代偿期患者稀释性低钠血症的临床疗效。方法:选取2013年6月—2014年12月间收治的肝硬化失代偿期稀释性低钠血症患者76例,将其随机分成对照组和治疗组,每组38例;对照组患者均给予常规治疗,观察组患者在对照组治疗的基础上加用托伐普坦治疗,比较两组患者治疗4 d和7 d后的血Na+浓度正常率,以及治疗后24 h内的总排尿量情况。结果:治疗组患者治疗4 d和7 d后的血Na+浓度正常率分别为60.53%和65.79%,明显高于对照组为21.05%和26.32%(P<0.05);治疗组患者在治疗后24 h内总尿量大于3 500 m L的百分率明显高于对照组(P<0.05)。结论:托伐普坦与常规治疗肝硬化失代偿期稀释性低钠血症患者治疗4 d和7 d后的血Na+浓度正常率高于常规治疗,且患者在治疗后24 h内总尿量明显增多。     

托伐普坦治疗恶性腹腔积液合并低钠血症的临床观察

目的： 观察托伐普坦治疗恶性腹腔积液合并低钠血症患者后的血钠及24 h尿量等指标变化。方法： 38例恶性腹腔积液合并低钠血症患者随机分为观察组和对照组,对照组给予常规利尿处理,观察组在常规治疗基础上联用托伐普坦片,治疗7 d后,比较两组患者治疗前后血钠、24 h尿量、腹围及体重等指标的变化,并观察治疗期间两组不良反应发生情况。结果： 治疗后观察组的血钠水平较治疗前显著升高（P<0.01）,治疗后两组24 h尿量均较治疗前增多（P<0.01）,且治疗后观察组24 h尿量明显高于对照组（P<0.01）。观察组4例患者出现口干不适,两组间差异无统计学意义,治疗期间两组患者均未出现严重不良反应。结论： 托伐普坦治疗恶性腹腔积液合并低钠血症患者的疗效确切,可以改善患者的生存质量,且安全可靠。     

托伐普坦片在中国健康人体的生物等效性研究

目的：评价试验制剂托伐普坦片与参比制剂托伐普坦片在中国健康人体中的生物等效性。方法：采用双周期随机交叉试验设计,入选24名男性健康受试者单次口服参比制剂和试验制剂30mg,采用高效液相色谱-串联质谱法（HPLC—MS／MS）测定血浆中托伐普坦的浓度,经DAS2．1软件处理参数,并进行双单侧t检验确定是否等效。结果：试验制剂和参比制剂的主要药代动力学参数分别为：cmax为（179±97）和（189±86）μg／L;tmax为（2．5±1．1）和（2．5±1．0）h;AUC0-t为（1153±488）和（1225±528）μg·h·L-1;AUC0。。为（1161±492）和（1232±528）μg·h·L-1;t1／2为（5．6±2．0）和（5．6±2．0）h。试验制剂对参比制剂的相对生物利用度F为（95．8±18．7）％。结论：试验制剂托伐普坦片与参比制剂托伐普坦片生物等效。     

托伐普坦治疗肝硬化腹水伴低钠血症疗效与安全性的Meta分析

目的:系统评价托伐普坦治疗肝硬化腹水伴低钠血症的疗效和安全性,为临床用药提供参考。方法:计算机检索Cochrane图书馆、PubMed、中国知网(CNKI)以及万方数据库等,收集托伐普坦联合常规治疗方案(试验组)对比单纯常规方案加或不加安慰剂(对照组)治疗肝硬化腹水伴低钠血症的随机对照试验(RCT),提取相关资料并按照改良的Jadad评分量表评价纳入研究质量,采用RevMan 5.3统计软件对数据进行Meta分析。结果:共纳入16项RCT,合计1 271例患者。Meta分析结果显示,试验组患者血钠浓度[MD=6.51,95%CI(4.64,8.39),P<0.001]、24 h尿量[MD=1.36,95%CI(1.01,1.70),P<0.001]、腹水及水肿治疗总有效率[RD=0.27,95%CI(0.20,0.35),P<0.001]、体质量改善[MD=-1.11,95%CI(-1.31,-0.91),P<0.001]和腹围改善[MD=-2.13,95%CI(-2.96,-1.31),P<0.001]均显著优于对照组,差异均有统计学意义。两组患者治疗前后及组间比较,血钾、血压、心率、总胆红素、血肌酐和尿素氮水平,差异均无统计学意义(P>0.05);试验组患者丙氨酸转氨酶水平显著低于对照组,差异有统计学意义(P=0.003)。亚组分析显示,仅对照组使用传统利尿药或两组均未使用传统利尿药时,两组24 h尿量比较差异无统计学意义(P>0.05),其余亚组试验组患者血钠浓度和24 h尿量均显著高于对照组,差异有统计学意义(P<0.001)。试验组患者口渴、口干、尿频和失眠等不良反应发生率显著高于对照组,差异均有统计学意义(P<0.05);总不良反应发生率较对照组稍高,但差异无统计学意义(P>0.05)。结论:托伐普坦治疗肝硬化腹水伴低钠血症疗效较好,可以显著改善患者血钠浓度、24 h尿量、腹水及水肿、体质量及腹围,且几乎不影响血钾、心率、血压和肝肾功能,但应注意口渴等不良反应的发生。     

奈西立肽联合托伐普坦治疗难治性心力衰竭的疗效观察

目的 探讨奈西立肽联合托伐普坦治疗难治性心力衰竭疗效及安全性.方法 难治性心力衰竭患者60例随机分为对照组和观察组,每组30例.对照组采用托伐普坦治疗,观察组在对照组此基础上给予奈西立肽治疗.比较2组治疗后临床症状评分,各项实验室指标包括24 h尿量,肌酐、血钾、血钠、NT-pro-BNP,以及心功能(收缩压、舒张压、心率),评定2组治疗效果.结果 观察组肺部啰音、下肢水肿、呼吸困难情况评分明显优于对照组,差异有统计学意义(P<0.05).观察组24 h尿量,肌酐、血钾、血钠、NT-pro-BNP水平改善程度也显著优于对照组(P<0.05);观察组收缩压、舒张压、心率明显低于对照组,差异有统计学意义(P<0.05).观察组总有效率低于对照组,不良反应低于对照组,差异有统计学意义(P<0.05).结论 奈西立肽联合托伐普坦治疗难治性心力衰竭具有较好的临床疗效,并且安全性好.     

高脂饮食及性别差异对托伐普坦在健康人体内药动学的影响

目的探究高脂饮食及性别差异对托伐普坦在人体内药动学的影响,指导临床合理用药。方法采用随机、双周期交叉自身对照设计,将30名健康志愿者(男∶女=1∶1)随机分成2组,分别于高脂或空腹口服托伐普坦片30 mg,采集血样并采用LC-MS/MS法测定血浆中托伐普坦的浓度。用SAS 9.3药动学软件进行药动学参数计算及统计学分析。结果高脂组与空腹组给药的主要药动学参数相比,ρmax和t1/2具有显著差异(P<0.05),而tmax、AUC无统计学差异(P>0.05);男女性别之间无论在高脂组还是空腹组相比,其主要药动学参数AUC、t1/2、ρmax、tmax在性别间均无统计学差异(P>0.05)。结论高脂饮食可显著提高托伐普坦的峰质量浓度(ρmax)并显著缩短其消除期的半衰期(t1/2);而无论是高脂或空腹口服托伐普坦片,性别差异均不影响其药动学参数。     

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.