曲美他嗪对大鼠放射性心肌损伤后TNF-α表达的影响

目的:放射性心肌损伤是纵膈及胸腔等部位恶性肿瘤放射治疗后发生的严重并发症,目前尚无有效防治方法,而本实验拟探索曲美他嗪对放射性心肌损伤的保护作用。方法:将45只SD大鼠随机分为正常对照组(C组)、单纯照射组(X组)、曲美他嗪治疗组(T组),每组15只,其中X组、T组予以10 Gy/d,共3天。大鼠照射完毕处死后测定血清cTnI浓度,心肌组织TNF-αmRNA及蛋白的表达。结果:1.X组与C组相比,血清cTnI浓度,心肌组织TNF-αmRNA及蛋白的表达均明显升高(P0.05);2.T组与C组相比,血清cTnI浓度,心肌组织TNF-αmRNA及蛋白的表达均明显升高(P0.05);3.T组与X组相比,血清cTnI浓度,心肌组织TNF-αmRNA及蛋白的表达均明显降低(P0.05)。结论:曲美他嗪能够通过减少心肌组织TNF-αmRNA及蛋白的表达,从而有效减轻大鼠放射后心脏炎症反应,以减轻心肌损伤。     

麝香保心丸与曲美他嗪联合治疗老年冠心病心绞痛的疗效及对血浆BNP水平的影响

目的:分析麝香保心丸联合曲美他嗪治疗老年冠心病心绞痛的疗效及对血浆B型脑钠肽(BNP)水平的影响。方法:选取2010年1月-2015年1月我院收治的老年冠心病心绞痛患者128例作为研究对象,采用随机数字表法将其分为实验组(64例)和对照组(64例),单纯使用曲美他嗪对对照组患者进行治疗,联合使用麝香保心丸和曲美他嗪对实验组患者进行治疗,观察两组患者的临床疗效,比较治疗前后两组血浆BNP水平、左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)以及左室射血分数(LVEF),统计两组的不良反应。结果:实验组的治疗总有效率为92.19%,明显高于对照组的62.50%,差异具有统计学意义(P0.05);治疗后,实验组与对照组血浆BNP、LVEDD、LVESD、LVEF均得到改善,但是实验组改善更明显,差异具有统计学意义(P0.05);两组不良反应率比较,无统计学差异(P0.05)。结论:应用麝香保心丸联合曲美他嗪治疗老年冠心病心绞痛的临床疗效显著,且明显降低血浆BNP水平,值得在临床上推广应用。     

尼可地尔联合盐酸曲美他嗪治疗微血管性心绞痛的临床效果和安全性分析

目的:分析尼可地尔联合盐酸曲美他嗪治疗微血管性心绞痛的临床效果和安全性。方法:选择陕西省人民医院2013年1月-2017年1月收治的微血管性心绞痛患者518例为研究对象,根据入院顺序经随机数字表法分为对照组和研究组,对照组260例患者采用盐酸曲美他嗪进行治疗,研究组258例在对照组基础上联合尼可地尔进行治疗,对比两组患者的临床总有效率、内皮血管功能和不良反应发生率。结果:治疗后,研究组的总有效率[88.76%(229/258)]显著高于对照组[62.69%(163/260)](P0.05);治疗前,两组患者的一氧化氮(NO)、内皮素(ET-1)和C-反应蛋白(CRP)水平均无差异(P0.05);治疗后,两组患者的CRP、ET-1水平均低于治疗前,且研究组低于对照组(P0.05);NO水平均高于治疗前,且研究组高于对照组(P0.05);对照组患者在治疗后的总不良反应发生率为9.23%(24/260),与研究组[10.85%(28/258)]相比差异无统计学意义(P0.05)。结论:尼可地尔联合盐酸曲美他嗪较单用盐酸曲美他嗪治疗微血管性心绞痛的效果更好,其可显著改善患者内皮血管功能,且安全性与单用盐酸曲美他嗪相当。     

复方丹参滴丸联合曲美他嗪对冠心病合并高脂血症患者血液流变学及血脂的影响

目的:探讨复方丹参滴丸联合曲美他嗪治疗冠心病合并高脂血症患者的效果。方法:选取2016年1月-2017年12月我院收治的冠心病合并高脂血症患者81例,按照治疗方法的不同分为观察组、对照组、,分别41例、40例。对照组实施常规联合曲美他嗪进行治疗,观察组在对照组的基础上联合应用复方丹参滴丸进行治疗。比较两组临床疗效、治疗前后血脂、血液流变学相关指标、不良反应的发生情况。结果:观察组总有效率显著高于对照组(P0.05)。两组治疗前血清HDL-C、TC、LDL-C、TG水平间差异不显著(P0.05);观察组治疗后血清TC、LDL-C、TG水平均显著比对照组低(P0.05),血清HDL-C水平显著比对照组高(P0.05)。两组治疗前PV、WBC比较差异不显著(P0.05);两组治疗后PV、WBC均显著降低(P0.05),且观察组以上指标下降更明显(P0.05)。两组患者在治疗期间都没发生严重的不良反应。结论:与单用曲美他嗪治疗相比,复方丹参滴丸联合曲美他嗪治疗冠心病合并高脂血症效果更优,可明显改善患者血脂水平和血液流变学,且安全性较高。     

平衡透析法考察豆腐果苷血浆蛋白结合率:种属差异研究（英文）

糖苷类化合物豆腐果苷在人与大鼠体内处置过程存在种属差异。药物血浆蛋白结合率是决定药物整体分布、排泄、活性及毒性的重要决定过程。本文旨在应用平衡透析法评价蛋白结合率差异在豆腐果苷种属差异中的作用。研究采用HPLC-ESI-MS方法进行检测,并对试验中的一些影响因素进行了优化。在试验中的四个浓度下,大鼠血浆蛋白结合率在10.33%~11.03%,人血浆蛋白结合率在10.60%~10.98%。结果表明人与大鼠药代动力学参数的差异不是由蛋白结合率的差异所导致。这是有关豆腐果苷蛋白结合率相关研究的首次报道。     

异育银鲫体内盐酸双氟沙星血浆蛋白结合率的变化与其药代动力学研究

为了研究盐酸双氟沙星(difloxacin, DIF)在异育银鲫体内血浆蛋白结合率的变化及其与药代动力学之间的关系, 实验采用超滤法测定了DIF在异育银鲫体内血浆蛋白结合率, 运用HPLC测定其对应时间点药物浓度, 并分析了血浆蛋白结合率变化对DIF体内处置的影响。实验以感染嗜水气单胞菌的异育银鲫为感染组, 健康异育银鲫为对照组。结果显示: 感染组各时间点DIF血浆蛋白结合率均高于对照组, 感染组与对照组DIF血浆蛋白结合率与总药物浓度呈对数关系: y=-9.01ln x+74.34和y=-4.81ln x+65.15, DIF血浆蛋白结合率与游离药物浓度的对数关系式分别为: y=-6.36ln x+64.91和y=-4.36ln x+ 60.63; 感染组和对照组血浆药时曲线均可使用开放性二室模型描述; 感染组DIF的吸收和消除慢于对照组, 其表观分布容积和曲线下面积大于对照组。结果显示异育银鲫体内感染嗜水气单胞菌促使DIF血浆蛋白结合率升高; 血浆蛋白结合率升高导致药物以结合药物的形式储存于血液中可能是导致药物组织分布受限、消除缓慢、长时间滞留于血液原因之一。     

曲美他嗪与稳心颗粒联合治疗不稳定性心绞痛疗效观察

目的:探讨曲美他嗪与稳心颗粒联合治疗不稳定性心绞痛临床疗效。方法:选取我院2011年6月-2012年6月不稳定性心绞痛患者150例,随机分为治疗组和对照组。对照组仅给予曲美他嗪治疗;治疗组给予曲美他嗪与稳心颗粒联合治疗。观察两组临床疗效、治疗前后心绞痛持续时间及发作次数、心电图改善情况及不良反应。结果:治疗组总有效率为86.8%,对照组总有效率为49.3%,两组疗效比较,差异具有统计学意义(P0.05);治疗组心电图总有效率为89.33%,对照组总有效率为72.00%,两组疗效比较,差异具有统计学意义(P0.05);治疗组心绞痛发作次数、持续时间、血液流变学指标较治疗前有显著下降(P0.05),较对照组有明显差异(P0.05)。两组患者治疗期间尿常规、血常规、肾功能、肝功能及电解质均未见明显变化,且两组患者不良反应差异无统计学意义(P0.05)。结论:曲美他嗪与稳心颗粒联合治疗不稳定性心绞痛临床疗效确切,具有很大临床意义。     

沙库巴曲缬沙坦联合曲美他嗪治疗老年慢性心力衰竭的疗效及相关炎症因子影响

目的:探究沙库巴曲缬沙坦联合曲美他嗪治疗老年慢性心力衰竭竭的疗效及相关炎症因子影响。方法:随机选取2018年1月～2019年10月期间在本院接受治疗的60例慢性心力衰竭老年患者,将其随机平分为对照组和研究组,每组各30例,其中对照组在常规治疗的基础上给予沙库巴曲缬沙坦进行治疗,研究组在对照组的基础上给予曲美他嗪进行治疗,两组患者均连续治疗3个月,对比两组治疗总有效率,两组治疗前后的心功能指标,两组治疗前后的炎性因子水平,两组治疗期间的不良反应发生率。结果:研究组的治疗总有效率显著高于对照组(93.33%vs.76.67%,P0.05)。治疗前,两组的左心室收缩末期内径(left ventricular end-systolic diameter, LVESD)、左心室舒张末期内径(left ventricular end-diastolic diameter,LVEDD)、左心室射血分数(left ventricular ejection fraction, LVEF)、血浆N-末端脑钠素前体(N-terminal pro-brain natriuretic peptide,NT-pro BNP)等心功能指标对比均无统计学差异(P0.05);治疗后,两组的LVEDD、LVESD、NT-pro BNP指标均比治疗前显著降低,LVEF水平均比治疗前显著升高(P0.05),且研究组更优(P0.05);治疗前,两组的超敏C反应蛋白(high-sensitivity C-reactive protein, hs-CRP)、白介素6(interleukin 6, IL-6)、IL-1、肿瘤坏死因子α(tumor necrosis factorα, TNF-α)等炎性因子水平对比均无统计学差异(P0.05);治疗后,两组的上述指标均比治疗前显著降低(P0.05),且研究组更低(P0.05);治疗期间,对照组的不良反应发生率10.0%(3/30)与研究组13.3%(4/30)之间无显著性差异(P0.05)。结论:沙库巴曲缬沙坦联合曲美他嗪治疗老年慢性心力衰竭的效果显著,该方法可有效改善患者的心功能和炎症因子水平,且不良反应未增加,值得临床推广使用。     

探讨美托洛尔联合曲美他嗪治疗冠心病心力衰竭患者临床疗效

目的:研究美托洛尔联合曲美他嗪治疗冠心病心力衰竭患者的临床治疗效果。方法:选取冠心病心力衰竭患者160例作为研究对象,应用随机分组的方法将其分为研究组与对照组,对照组患者给予常规治疗,研究组患者在对照组治疗的基础上给予美托洛尔与曲美他嗪进行治疗,对比两组患者的心功能改善情况与临床疗效。结果:研究组患者的治疗有效率与心功能改善情况明显优于对照组,(p0.05)差异具有统计学意义。结论:应用美托洛尔联合曲美他嗪治疗冠心病心力衰竭患者能够明显的改善患者的心功能,提高临床治疗效果,应在临床治疗中进行推广应用。     

参仙升脉口服液联合曲美他嗪对缓慢性心律失常患者外周血单个核细胞中cAMP/PKA信号通路相关蛋白水平的影响

摘要 目的：观察缓慢性心律失常（BA）经参仙升脉口服液联合曲美他嗪治疗4周后的临床疗效及对外周血单个核细胞中环磷酸腺苷( cAMP) /蛋白激酶A（PKA）信号通路相关蛋白水平的影响。方法：将2017年8月~2020年8月期间我院收治的126例BA患者随机分为两组,对照组和观察组,各63例。对照组接受曲美他嗪治疗,观察组接受参仙升脉口服液联合曲美他嗪治疗,观察并对比两组24 h动态心电图指标（最慢心率、静息状态下心率、24 h平均心率）、心功能指标[左室射血分数(LVEF)、心输出量(CO)、心脏指数(CI)]、疗效、外周血单个核细胞中cAMP/PKA信号通路相关蛋白（cAMP蛋白、PKA蛋白）水平及不良反应。结果：观察组的临床总有效率90.48%（57/63）高于对照组的71.43%（45/63）,差异有统计学意义（P<0.05）。治疗4周后,与对照组比较,观察组静息状态下心率、24 h平均心率、最慢心率均较高（P<0.05）。治疗4周后,观察组LVEF、CO、CI高于对照组（P<0.05）。治疗4周后,观察组外周血单个核细胞中cAMP蛋白、PKA蛋白水平高于对照组（P<0.05）。两组不良反应发生率组间对比无差异（P>0.05）。结论：参仙升脉口服液联合曲美他嗪治疗BA患者,可改善治疗效果,促进24h动态心电图、心功能指标改善,其主要作用机制可能与调节cAMP/PKA信号通路相关蛋白表达有关。     

Determination of ticarcillin epimers in plasma and urine with high-performance liquid chromatography

A high-performance liquid chromatogaphic method was developed for determining the concentrations of ticarcillin (TIPC) epimers in human plasma and urine. Samples were prepared for HPLC analysis with a solid-phase extraction method and the concentrations of TIPC epimers were determined using reversed-phase HPLC. The mobile phase was a mixture of 0.005 M phosphate buffer (pH 7.0) and methanol (12:1, v/v) with a flow-rate of 1.0 ml/min. TIPC epimers were detected at 254 nm. Baseline separation of the two epimers was observed for both plasma and urine samples with a detection limit of ca. 1 μg/ml with a S/N ratio of 3. No peaks interfering with either of the TIPC epimers were observed on the HPLC chromatograms for blank plasma and urine. The recovery was more than 80% for both plasma and urine samples. C.V. values for intra- and inter-day variabilities were 0.9–2.1 and 1.1–6.4%, respectively, at concentrations ranging between 5 and 200 μg/ml. The present method was used to determine the concentrations of TIPC epimers in plasma and urine following intravenous injection of TIPC to a human volunteer. It was found that both epimers were actively secreted into urine and that the secretion of TIPC was not stereoselective. Plasma protein binding was also measured, which revealed stereoselective binding of TIPC in human plasma.     

Automated analysis of free and total concentrations of three antiepileptic drugs in plasma with on-line dialysis and high-performance liquid chromatography

A fully automated method for determination of the free and total concentration of drugs with a varying degree of protein binding is described. The antiepileptic drugs phenytoin, carbamazepine and phenobarbitone were chosen to demonstrate the utility of this technique. The method was based on the ASTED system and combined on-line equilibrium dialysis at 37°C with concentration of the dialysate on a trace enrichment column and HPLC determination with UV detection. The dialysis cell was a modification of the ASTED dialysis cell and 22% of the free concentration of the drugs were recovered in the recipient channel of the dialyser after 10 min of dialysis at 37°C. The free concentration, the total concentration as well as the drugs protein binding could be determined. The method was shown to be well suited for routine monitoring of the free and the total concentrations of the drugs in plasma from epileptic patients.     

Highly sensitive method for the determination of tamsulosin hydrochloride in human plasma dialysate, plasma and urine by high-performance liquid chromatography–electrospray tandem mass spectrometry

A highly sensitive method for the determination of tamsulosin hydrochloride, a structurally new type of sulphamoile derivative, in human plasma dialysate, plasma and urine has been developed by using liquid chromatography–electrospray tandem mass spectrometry (LC–MS–MS). Plasma dialysate, plasma and urine samples were extracted by brief liquid-phase extraction and analyzed using an HPLC system coupled to a mass spectrometer via an electrospray ionization interface. Selected reaction monitoring was used for the detection of tamsulosin and its internal standard. This method was validated in the concentration range 10–1000 pg/ml in plasma dialysate, 0.5–50 ng/ml in plasma, and 1–100 ng/ml in urine with sufficient specificity, accuracy and precision. The in vivo protein binding study demonstrated that the unbound tamsulosin in human plasma obtained by the equilibrium dialysis after 0.4-mg oral dosing was measurable. In addition, the percentage of unbound tamsulosin in an in vitro study (0.71–0.91%) obtained by using spiked ¹⁴C-labelled tamsulosin was slightly larger than that of the in vivo study (0.68–0.86%), indicating that the unbound concentration calculated by the product of the plasma concentration and the in vitro unbound fraction (fu) was unfavorably overestimated. These results suggest that the combination of LC–MS–MS and equilibrium dialysis method has enough sensitivity to determine the unbound concentration in clinical use and gives the concentration more exactly than the in vitro fu.     

Measurement of drug-protein binding by immobilized human serum albumin-HPLC and comparison with ultrafiltration

An HPLC method employing CHIRAL-I (150 mm x 3 mm), 5 microm column from Chrom. Tech., immobilized with human serum albumin (HSA), was used to determine in vitro protein binding of several compounds. Experimentally obtained plasma protein data exhibited good correlation with the reported values. The method was compared with the conventional ultra filtration technique and both yielded similar results. Proprietary compounds that could not be analyzed by ultra filtration due to high non-specific binding to filter membrane were successfully analyzed by HSA-HPLC method. On the other hand, two proprietary compounds did not elute from HSA column due to strong binding, but were successfully analyzed by ultra filtration. This proves that both the techniques have their own merits and demerits and should be exploited judiciously as per the requirement. The plasma protein binding studies conducted on four gyrase inhibitors in rat and human plasma exhibited no interspecies difference via ultra filtration method. Further, it was also observed that the protein binding obtained for the four gyrase inhibitors by HSA-HPLC method was not only similar to that obtained by ultra filtration in human plasma but was also in accordance with ex vivo and in vitro protein binding obtained for rat plasma after ultra filtration because these compounds predominantly bind to HSA The binding of several compounds to alpha1-acid glycoprotein (AGP), another important plasma protein, was also examined using AGP immobilized column. However, the data could not be relied upon since some anti-bacterials and non-steroidal anti-inflammatory drugs (NSAIDS), which are known to predominantly bind to HSA, were also found to bind to AGP.     

Determination of the binding parameters of drug to protein by equilibrium dialysis/piezoelectric quartz crystal sensor

A novel method, equilibrium dialysis/piezoelectric quartz crystal sensor, applied to determine the binding parameters of diethyldithiocarbamate to human plasma protein is proposed. Based on the investigation of the equilibrium reaction for the binding of drug to protein, the related theoretical equations for this binding were derived. By monitoring the frequency responses of a copper-plated piezoelectric quartz crystal sensor to drug in and out of a dialysis membrane after equilibrium, the binding parameters were determined, i.e., 0.375 micromol g(-1) for beta(p), 6.496 microM for K(dp), 141.99 L mmol(-1) for K(p), and 0.043 for N. These values were in good agreement with reference values. It was found that this method may have application for studying the characteristics of the interaction between other drugs and proteins.     

Differences in the protein binding of several drugs and bilirubin in serum and heparinized plasma of rats.

The purpose of this investigation was to compare the protein binding of salicylic acid, phenytoin, warfarin and bilirubin in serum and heparinized plasma of rats. Protein binding was determined by equilibrium dialysis (drugs) or by a reaction rate method (bilirubin), using serum and plasma obtained from the same animals. The three drugs were significantly less protein bound in heparinized plasma than in serum; this difference was particularly pronounced in the case of warfarin. Addition of heparin to serum also resulted in a decrease in the protein binding of the drugs but to a lesser extent than in plasma. The protein binding of bilirubin was more extensive in plasma than in serum, irrespective of the anticoagulant used (heparin, sodium citrate, or disodium ethylenediamine-tetraacetate). It may be desirable to perform all binding studies with serum rather than plasma.     

Lipoprotein and protein binding of the calcium channel blocker diltiazem

The plasma protein binding properties of the calcium channel blocker diltiazem were studied using a three-chamber equilibrium dialysis system. Diltiazem is 81% bound to human sera with significant inter-individual variation. The relative binding of diltiazem by lipoproteins and alpha 1-acid glycoprotein was higher than by albumin. The binding to low density lipoprotein was strong and appeared not to be associated with the surface apoprotein.     

Plasma protein binding study of oxybutynin by high-performance frontal analysis

Plasma protein binding of oxybutynin (OXY) was investigated quantitatively and enantioselectively using high-performance frontal analysis (HPFA). An on-line HPLC system which consists of HPFA column, extraction column and analytical column was developed to determine the unbound concentrations of OXY enantiomers in human plasma, in human serum albumin (HSA) solutions, and in human alpha1-acid glycoprotein (AGP) solutions. OXY is bound in human plasma strongly and enantioselectively. The bound drug fraction in human plasma containing 2-10 microM (R)- or (S)-OXY was higher than 99%, and the unbound fraction of (R)-OXY was 1.56 times higher than that of (S)-isomer. AGP plays the dominant role in this strong and enantioselective plasma protein binding. The total binding affinities (nK) of (R)- and (S)-OXY to AGP were 6.86 x 10(6) and 1.53 x 10(7) M(-1), respectively, while the nK values of (R)- and (S)-OXY to HSA were 2.64 x 10(4) and 2.19 x 10(-4) M(-1), respectively. The binding affinity of OXY to AGP is much higher than that to HSA, and shows high enantioselectivity (SIR ratio of nK values is 2.2). It was found that both enantiomers are bound competitively at the same binding site on an AGP molecule. The binding property between OXY and low density lipoprotein (LDL) was investigated by using the frontal analysis method incorporated in high-performance capillary electrophoresis (HPCE/FA). It was found the binding is non-saturable and non-enantioselective.