缺血修饰白蛋白对急性冠脉综合征的早期诊断价值

目的 分析缺血修饰白蛋白(IMA)对急性冠脉综合征的早期诊断价值.方法 选取我院2015年06月～2016年10月收治的82例急性冠脉综合征患者为研究对象,根据急性冠脉综合征不同类型,将其分为两组,即41例不稳定心绞痛患者(UA组),41例急性心肌梗死(AMI组),并选择同期进行健康检查且检查结果为健康的41例患者(对照组).对比三组患者的缺血修饰白蛋白水平.同时给予上述急性冠脉综合征患者心电图、肌钙蛋白Ⅰ联合检测以及缺血修饰白蛋白检测,对比两种检测方法早期诊断的敏感性.结果 不稳定心绞痛组、急性心肌梗死组、对照组的IMA水平相比,差异具有统计学意义(P ＜0.05);IMA检测的敏感性与联合检测相比明显升高,差异具有统计学意义(P＜0.05).结论 缺血修饰白蛋白(IMA)诊断急性冠脉综合征的敏感性较高,在临床上具有重要的早期诊断价值.     

心脏型脂肪酸结合蛋白、缺血修饰白蛋白联合检测在急性冠脉综合征早期诊断和危险分层中的临床价值

目的:探讨心脏型脂肪酸结合蛋白(H-FABP)、缺血修饰白蛋白(IMA)联合检测在急性冠脉综合征(ACS)早期诊断和危险分层中的临床价值。方法:97例ACS患者根据疾病类型分为UA组(n=52例)和AMI组(n=45例),按院内死亡风险分为低危组(n=21例)、中危组(n=39例)和高危组(n=37例),同期选择50例门诊健康体检者作为对照组。比较各组H-FABP、IMA、c Tn I、CK-MB阳性率及血清H-FABP、IMA表达水平。结果:UA组和AMI组H-FABP、IMA诊断阳性率均明显高于c Tn I、CK-MB(P<0.05),且AMI组H-FABP诊断阳性率均明显高于UA组(P<0.05),而UA组和AMI组IMA诊断阳性率比较无显著差异性(P>0.05);ACS患者血清H-FABP、IMA表达水平均高于对照组(P<0.05),且随着危险程度加重,血清H-FABP、IMA表达水平均明显升高(P<0.05)。结论:H-FABP、IMA联合检测在ACS早期诊断和危险分层中均具有较高的临床价值。     

血清缺血修饰白蛋白和肌酸激酶同工酶联合检测在急性冠脉综合征(ACS)早期诊断中的价值

目的 探讨血清缺血修饰白蛋白和肌酸激酶同工酶联合检测在急性冠脉综合征(ACS)早期诊断中的价值.方法 测定82例ACS患者和80例健康对照者血清IMA及CK-MB浓度.结果 联合IMA和CK-MB诊断ACS,敏感度提高至92.9%,此时特异度为67.0%,联合诊断的PPV和NPV分别为76.4%,89.0%.结论联合检测IMA和CK-MB可提高联合诊断敏感度,提高ACS的诊断效能.     

血清缺血修饰白蛋白在急性冠脉综合征患者中的诊断价值探讨

目的分析血清缺血修饰白蛋白在急性冠脉综合征与急性脑梗死（ACI）患者中的变化，以探讨IMA对ACS的诊断价值。方法检测非冠心患者群及发病12小时内ACI、不稳定心绞痛（UA）、急性心肌梗死（AMI）患者血清IMA、CK～MB、cTnT值。结果①uA及AMI组患者血清IMA均显著高于非冠心病组（均P〈0．01），UA组crrnT及CK—MB与非冠心病组无显著差异（P均〉0．05）；②ACI患者血清IMA值显著高于非冠心病组（P均〈0．01），但均显著低于UA及AMI组。结论①UA及AMI患者血清IMA均显著升高。因心肌坏死标志物cTnT及CK—MB均无显著升高的uA组患者其IMA显著升高，提示IMA形成可能与心肌缺血有关。②IMA可作为诊断ACS的标记物，但因ACI患者IMA也升高，故IMA诊断ACS缺乏特异性。     

胸痛患者缺血修饰白蛋白的表达及其临床意义

目的：探讨缺血修饰白蛋白（IMA）对急性冠脉综合征（ACS）的诊断价值。方法：选本院心内科住院患者90例,男53例,女37例,平均年龄52.1岁,根据出院诊断分成3组,即急性心肌梗死（AMI）组、不稳定性心绞痛（UAP）组和非缺血性胸痛（NICP）组,另选同期来本院健康体检人群30例,其中,男18例,女12例,平均年龄46.00岁,作为健康对照组。分别检测各组IMA浓度,对比其对急性冠脉综合征的诊断效能。结果：ACS组的IMA值为（50.10±28.35）μg/L,明显高于NICP组（23.53±21.34）μg/L和健康对照组（20.30±11.05）μg/L,其差异有统计学意义（均P〈0.05）。结论：IMA可用于疑似ACS的急性胸痛患者的早期诊断。     

IMA、BNP和hsCRP在急性冠状动脉综合征早期诊断中的应用

目的探讨缺血修饰白蛋白(IMA)、B型尿钠肽(BNP)、超敏C反应蛋白(hs CRP)在急性冠脉综合征(ACS)早期诊断中的作用。方法来自青岛市立医院96例ACS患者作为治疗组,其中急性心肌梗死(AMI)42例,不稳定型心绞痛(UAP)54例,分别于胸痛发作2、4、6、12、18及24 h抽血,另选50名健康体检者作为对照组,两组均检测其IMA、BNP、hs CRP含量,评价这三项指标在ACS早期的应用价值。结果在急性冠状动脉综合征患者中IMA水平于胸痛发作2 h已明显增高,4 h仍持续增高,明显高于正常对照组(P<0.05),6 h降至正常。BNP、hs CRP水平于胸痛发作2 h显著升高,于12 h达到峰值。结论 IMA、BNP、hs CRP的表达与ACS密切相关,在ACS早期诊断中具有很高的应用价值。     

缺血修饰蛋白在老年急性冠脉综合征患者中的早期诊断价值研究

目的研究缺血修饰蛋白在老年急性冠脉综合征患者早期诊断价值。方法选取141例老年均以胸痛为首发症状患者为研究对象,根据肌钙蛋白结果分为两个观察组,分别测量不同时间段的IMA值,同时选取53例健康年龄在60岁以上患者为对照组,测量IMA及CTnI。结果观察组1的IMA值为(125.38±7.49)U/ml,胸痛2组为(96.44±6.96)U/ml。两观察组之间在年龄、性别、吸烟史、血糖等方面差异无统计学意义,而IMA值在两组之间差异有统计学意义(P=0.001)。IMA值用于诊断健康者与老年急性冠脉综合征患者的ROC曲线下面积为0.95,95%可信区间为(0.87、0.96)。结论 IMA可能是老年急性冠脉综合征患者早期诊断指标。     

青年急性胸痛患者血清缺血修饰白蛋白对诊断心源性疾病的意义

目的:探讨血清缺血修饰白蛋白对于诊断心源性疾病引起青年人(年龄≤40)急性胸痛的临床意义,从而做到早发现,早治疗。方法:研究对象为急性胸痛发作12小时内就诊于某院急诊科的46名青年患者,分别于入院后即刻、2～12小时、超过12小时这3个时段采血分离血清,检测肌酸激酶同工酶MB(CK-MB)、肌钙蛋白I(cTnI)和缺血修饰白蛋白(IMA)。入院后动态心电图监测,根据最终诊断结果,将患者分为非缺血性胸痛(NICP)组和缺血性胸痛(ICP)组,ICP组进一步分为急性心肌梗死(AMI)组和不稳定型心绞痛(UA)组。比较两组的IMA、cTnI、CK-MB在不同时段的检测结果和心电图表现,分析急性胸痛患者IMA水平对ICP的诊断价值。结果:46例入选患者中,诊断为UA20例,AMI4例,NICP22例。ICP组IMA水平于发病小于2小时、2～12小时明显升高,与NICP组存在明显差异,ICP组发病超过12小时的IMA水平与NICP组比较无明显差异。UA组和AMI组IMA水平在各时间段比较差异无统计学意义。结论:IMA是早期区分ICP和NICP的敏感生化指标,对于发病12小时内的ICP诊断具有较高的敏感性,与其它指标相结合可以进一步提高对ICP的诊断。但是IMA不能作为区分AMI和UA的生化指标。     

缺血修饰性白蛋白检测在急性冠脉综合征诊断中的应用(附33例报告)

目的将缺血修饰白蛋白应用于急性心肌缺血的早期诊断,排除急性冠脉综合征(ACS)。方法采用白蛋白钴结合试验检测血浆中的缺血修饰性白蛋白,结果以吸光度单位(ABSU)报告。结果缺血修饰白蛋白正常对照组为x=0.228±0.078、心肌缺血组为x=0.481±0.111,(P<0.01)阳性率(25/33)为75.8%。结论缺血修饰性白蛋白可作为诊断早期心肌缺血的生化指标。     

缺血修饰白蛋白检测对急性冠脉综合征的诊断价值

目的：探讨血清缺血修饰白蛋白（ IMA）检测对急性冠脉综合征（ ACS）的早期诊断意义。方法采用白蛋白钴结合试验检测97例疑似ACS 患者（观察组）3 h内血清标本,间接测定白蛋白与钴离子的结合能力（ ACB）来测定IMA,采用免疫抑制法检测肌酸激酶、肌酸激酶同功酶,化学发光法检测肌红蛋白、肌钙蛋白Ⅰ,观察它们的变化水平,同时对59例健康体检者（对照组）检测IMA水平。结果观察组ACB （53.55±8．23）U/mL,明显低于对照组的（78．00±6．35） U/mL（ t＝34．51,P＜0．01）;观察组IMA 阳性率84.8％,均明显高于其他四种心肌标志物（肌酸激酶、肌酸激酶同功酶、肌红蛋白、肌钙蛋白Ⅰ）（χ^2＝17．34、15.21、13．34、13．38,均P＜0．01）。结论对ACS患者进行IMA检测,可做到早期诊断,值得临床推广应用。     

The silatecans,a novel class of lipophilic camptothecins

Camptothecin, a potent cytotoxic agent that inhibits topoisomerase I, was identified in 1966 as a cytotoxic component in extracts of the Chinese tree Camptotheca acuminata. Initial clinical trials with this agent showed promising antitumour activity but due to unacceptable toxicity the trials were halted. The underlying cause of the toxicity was soon determined to be instability of the δ-lactone present in the structure. As a result, analogues were prepared that overcame the lactone instability, leading eventually to the chemotherapeutic drugs irinotecan and topotecan. Although these drugs proved successful in the clinic, side effects and a narrow spectrum of activity have limited their utility. In the decade since the development of these agents, continued research has greatly improved our understanding of camptothecin stability and pharmacology. From this has emerged several new series of analogues that will produce the next generation camptothecin. Silatecans are novel third generation camptothecin analogues that contain lipophilic silane groups. The incorporation of lipophilic substituents into the camptothecin structure provides enhanced blood stability, increased cell penetration and improved pharmacokinetics. This review will first examine the various mechanisms involved and approaches taken to develop new camptothecin-based drugs followed by an analysis of silatecan patents, example compounds and biological data.     

Toxicities of aristolochic acid I and aristololactam I in cultured renal epithelial cells

Aristolochic acid nephropathy, a progressive tubulointerstitial renal disease, is primarily caused by aristolochic acid I (AA-I) intoxication. Aristololactam I (AL-I), the main metabolite of AA-I, may also participate in the processes that lead to renal damage. To investigate the role and mechanism of the AL-I-mediated cytotoxicity, we determined and compared the cytotoxic effects of AA-I and AL-I on cells of the human proximal tubular epithelial (HK-2) cell line. To this end, we treated HK-2 cells with AA-I and AL-I and assessed the cytotoxicity of these agents by using the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, flow cytometry, and an assay to determine the activity of caspase 3. The proliferation of HK-2 cells was inhibited in a concentration- and time-dependent manner. Cell-cycle analysis revealed that the cells were arrested in the S-phase. Apoptosis was evidenced by the results of the annexin V/propidium iodide (PI) assay and the occurrence of a sub-G1 peak. In addition, AA-I and AL-I increased caspase 3-like activity in a concentration-dependent manner. These results also suggested that the cytotoxic potency of AL-I is higher than that of AA-I and that the cytotoxic effects of these molecules are mediated through the induction of apoptosis in a caspase 3-dependent pathway.     

Chloric acid(I) affects antioxidant defense of lung epitelial cells

Generation of chloric acid(I) and reactive oxygen and nitrogen species by activated phagocytes is associated with the course of many inflammatory-related lung diseases. Thus, we studied the effects of HOCl on the redox state of A549 cells as well as on the activity of enzymes involved in cell protection against oxidants. Additionally, we determined the ability of plasma antioxidants to prevent the HOCl-induced cytotoxicity to lung epithelial A549 cells. Cell treatment with HOCl at concentrations above 50 μM for 1 h resulted in the loss of cell viability. The decrease of GSH concentration and antioxidant capacity of cell extracts was accompanied by an increase of the level of GSSG and the rate of generation of ROS and peroxyl radicals. Hyperpolarization of the mitochondrial membrane was also observed. HOCl at concentrations of 50 μM significantly decreased the activity of all antioxidant enzymes studied in A549 cells. All antioxidants employed protected cells against the action of HOCl, with the efficiency decreasing as follows: albumin > GSH > uric acid > ascorbate > Trolox. HOCl was found to affect the redox state of A549 by oxidation of GSH, inactivation of antioxidant enzymes and increase of ROS generation.     

Anti-ischemic effects of nimesulide, a cyclooxygenase-2 inhibitor on the ischemic model of rabbit induced by isoproterenol

The objective was to devise an animal model of myocardial infarction (MI) against which cardioprotective drugs might be tested. We describe the effects of nimesulide, a COX experience with development and validation of such a model. The rabbit was chosen in preference to rodents because its heart and cardiac circulation more closely resemble those of human. Thus, the cardiovascular system of anaesthetized male rabbits, 1 to 1.5 kg (n=11), was stressed by a single bolus intravenous injection of isoprenaline (ISP), 65 mg/kg. The effects of the injection were followed for sixteen days and were evaluated in four ways: 1) measurements of creatinine kinase isozyme and troponin-I (TPI) in serum 2) Electrocardiographic (ECG) changes (ST elevation and Q wave development) 3) Cardiac histopathology observed in tissue sections of the isolated of the heart. The histopathological analysis showed that rabbit heart on 2nd day after ISP injection showed changes of coagulation necrosis. Day 4 total coagulation with the loss of nuclear and striation associated with heavy interstitial infiltrate of neutrophils was found. Day 8 after infarction showed collagen deposition with capillary channels in between the remaining islands of myocytes in the infarcted area. On the 16th day scarring was complete. Coronary perfusion rates (CPR) and heart rate (HR) of the infarcted and nimesulide (a COX-2 inhibitor) treated rabbits displayed significant improvement (n=11) on each corresponding day after infarction as compared to the infarcted and saline treated rabbits (P<0.05). All four indices revealed similarities with effects commonly associated with MI in humans.     

益母草对产后子宫内膜炎大鼠内膜止血修复的实验研究

目的建立产后大鼠子宫炎症模型,从分子生物学角度探讨益母草对产后子宫复旧的内在机制。方法将大鼠随机分为4组:空白对照组、模型组、益母草组、三七总皂苷组。建立产后子宫炎症模型,用三七总皂苷作阳性对照,采用ELISA法对各组大鼠血清肿瘤坏死因子-α(TNF-α)的量进行测定,对各组大鼠的子宫组织进行HE染色观察,同时用免疫组化法检测子宫组织中基质金属蛋白酶-13(MMP-13)、金属蛋白酶组织抑制因子-1(TIMP-1)、I型胶原(collagen I)的表达。结果模型组血清TNF-α水平明显高于空白对照组;与模型组比较,益母草组血清TNF-α水平显著降低。模型组与空白对照组比较,MMP-13、TIMP-1明显升高,collagen I表达上调;与模型组比较,益母草组MMP-13无明显变化,TIMP-1明显降低,collagen I表达下降。结论益母草可能使产后炎症子宫的TNF-α水平下降,下调TIMP-1的表达,启动止血修复机制,并加快细胞外基质(ECM)降解,从而加速产后子宫复旧。     

肌钙蛋白Ⅰ与肌红蛋白联合应用评价异丙肾上腺素诱导的心肌缺血损伤及凋亡发生

目的:探讨肌钙蛋白Ⅰ与肌红蛋白在异丙肾上腺素诱导的心肌缺血中,对心肌损伤评价的价值。方法:将32只大鼠随机分成4组,用异丙肾上腺素建立不同程度的心肌缺血模型,分别为对照组和低、中、高剂量组,用ELISA方法检测不同程度心肌缺血大鼠血清中肌钙蛋白I含量与外周血肌红蛋白表达水平,同时结合心肌酶CK、CK-MB结果,分析血清中肌钙蛋白I检测的灵敏性,分析大鼠心肌缺血后外周血肌红蛋白与心肌缺血严重程度之间的关系。取大鼠心肌组织制成石蜡切片,采用末端标记法对其进行免疫组化染色,镜下观察心肌细胞是否凋亡及凋亡的程度与心肌缺血的关系,以凋亡细胞占细胞总数的平均百分比表示。结果:(1)大鼠模型建立成功,大鼠血清中肌钙蛋白Ⅰ含量明显升高,与CK、CK-MB的升高程度相比有显著差异(P<0.05),其升高的倍数均大于CK、CK-MB,且随着程度的加重,血清中肌钙蛋白Ⅰ蛋白的含量越高。(2)肌红蛋白在缺血早期升高较早且幅度较大,随缺血程度的进一步加重,其升高程度也随之增加。(3)心肌细胞凋亡检测可见,对照组未见明显凋亡细胞,低剂量组和中剂量组相继出现数量不等的棕黄色颗粒,而高剂量组出现大量棕黄色颗粒。结论:肌钙蛋白Ⅰ与肌红蛋白都可作为缺血心肌损伤程度评价的指标,肌钙蛋白Ⅰ具有较高的灵敏性并随缺血程度加深而升高。肌红蛋白在缺血发生的早期即可大幅升高,但对于缺血程度的评价价值不及肌钙蛋白Ⅰ。随着缺血程度的加深,心肌细胞除缺血坏死外还可出现凋亡,说明凋亡也是加重缺血表现的一个因素。     

Preclinical and clinical activity of the topoisomerase I inhibitor,karenitecin, in melanoma

Introduction: This review covers the preclinical and clinical activity of the novel camptothecin analog, karenitecin, in melanoma.

Areas covered: While the camptothecins are widely used antitumor agents that inhibit topoisomerase I, their utility is limited by instability, high interpatient variability and the development of drug resistance. Karenitecin was rationally designed to overcome these limitations. The authors review the data on karenitecin in preclinical models and in clinical trials in melanoma using studies published in Medline and reports presented at AACR and ASCO.

Expert opinion: Karenitecin shows activity in melanoma, both as a single agent and in combination. In adverse prognostic factor melanoma, karenitecin showed prolonged disease stabilization in 34% of patients. Because preclinical studies suggested a synergistic interaction between karenitecin and HDAC inhibitors, a schedule-specific combination Phase I–II trial of valproic acid and karenitecin was carried out in heavily pretreated melanoma patients which showed a benefit rate in 47% patients with acceptable toxicity. The treatment for melanoma is in rapid transition and genomic profiling is now an integral part, and hence the optimal use of karenitecin in melanoma should be re-evaluated with regard to specific mutational status.     

肌钙蛋白Ⅰ在急性心肌梗死诊断中的应用价值

目的 通过肌钙蛋白Ⅰ(cTnI)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)在急性心肌梗死(AMI)诊断中的比较研究,探讨各指标对于在心肌梗死诊断中的应用价值.方法 将63例AMI患者分成未溶栓组和溶栓再通组,采用Access全自动微粒子化学发光免疫分析系统,检测两组患者血清cTnI、CK、CK-MB的检出时间、达到高峰时间及恢复时间,进行统计学处理及分析比较.结果 cTnI升高对急性心肌梗死诊断的灵敏度高于CK、CK-MB;在心肌梗死后cTnI的增高和峰值出现时间均先于CK和CK-MB,且增高持续时间长.结论 cTnI的检测有助于早期诊断AMI,对延迟入院的AMI患者检测cTnI也有重要意义.     

Synthesis and evaluation of tritium labelled 10‐methylgalanthamine iodide: a novel compound to examine the mechanism of interaction of galanthamine derivatives with the nicotinic acetylcholine receptors

A new promising galanthamine derivative, 10‐[³H]methylgalanthamine iodide, was synthesized for binding studies to nicotinic acetylcholine receptors expressed in Torpedo electric ray electroplaques. Galanthamine was reacted with [³H]methyl iodide to yield 10‐[³H]methylgalanthamine iodide with a radiochemical yield of >70% and a specific activity of 32 Ci/mmol after purification via solid phase extraction. To test the ligand properties of the radioligand, calcium imaging and electrophysiology of the non‐radioactive analogue were performed to obtain an EC₅₀ of 270 nM, a Hill coefficient of 1.9 and the induced cell current. Copyright © 2003 John Wiley & Sons, Ltd.     

自动溶出仪对硝苯地平缓释片(I)释放度测定的干扰

目的探讨自动过滤取样模式对硝苯地平缓释片(I)释放度测定的干扰。方法采用溶出度测定法第二法装置,分别手工取样滤膜过滤和自动取样器滤芯过滤,测定硝苯地平缓释片(I)的释放度。结果通过两种过滤模式及回收率的测定显示,自动过滤取样装置对硝苯地平(I)有吸附作用。结论药品测定溶出度或释放度时,应先考察溶出度测定仪的自动取样装置对其是否有吸附作用,否则影响测定结果。