Isoproterenol mechanisms in inducing myocardial fibrosis and its application as an experimental model for the evaluation of therapeutic potential of phytochemicals and pharmaceuticals

Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extracellular matrix proteins,mainly collagen in the cardiac interstitium.Many experimental studies have demonstrated that fibrotic injury in the heart is reversible;therefore,it is vital to understand differ-ent molecular mechanisms that are involved in the initiation,progression,and resolu-tion of cardiac fibrosis to enable the development of antifibrotic agents.Of the many experimental models,one of the recent models that has gained renewed interest is isoproterenol(ISP)-induced cardiac fibrosis.ISP is a synthetic catecholamine,sympa-thomimetic,and nonselectiveβ-adrenergic receptor agonist.The overstimulated and sustained activation ofβ-adrenergic receptors has been reported to induce biochemi-cal and physiological alterations and ultimately result in cardiac remodeling.ISP has been used for decades to induce acute myocardial infarction.However,the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis;this practice has increased in recent years.Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy.The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is consid-ered the initiating mechanism of myocardial fibrosis.ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals.In recent years,numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis.The present review exclusively provides a comprehensive summary of the pathological biochemical,histological,and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy.It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as syn-thetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.

探索中药材质量优化:GAP、HACCP和ISO体系的综合运用

中医药在世界范围内的应用增加,但我国中医药产品进入国际市场仍面临东西方文化差异、中药质量标准不完善、全球针对植物药的政策壁垒、中药材质量不达标等问题。2022年《中药材生产质量管理规范》引入危害分析与关键控制点理念,对中药材生产中的危害因素进行控制;同时,国际标准化组织中医药技术委员会ISO/TC249成立后,建立中医药国际标准,中医药企业开展GAP和ISO双认证,从源头上控制中医药的质量,是我国中医药扩大国际市场份额的根本途径。本文通过GAP、HACCP和ISO体系在中药材质量控制应用现状的对比研究,提出我国的中药材生产规范要充分借鉴国际上其他质量管理体系的优点,在降低生产风险和成本的同时,使GAP更具有操作性。

Betulin protects against isoproterenol-induced myocardial injury by inhibiting NF-κB signaling and attenuating cardiac inflammation and oxidative stress in rats

Objective:To investigate the cardioprotective potential of betulin in isoproterenol(ISO)-induced myocardial injury in rats.Methods:Wistar rats were divided into five groups(n=10):normal,ISO,nebivolol 5 mg/kg,and betulin(20&40 mg/kg).Nebivolol and betulin were administered orally for 29 days.ISO(85 mg/kg)was administered subcutaneously on day 27 and day 28 to induce myocardial injury.On day 29,blood was collected for determination of cardiac markers,and hemodynamic parameters were investigated.The levels of oxidative stress markers and the gene expressions of apoptotic markers and inflammatory mediators were evaluated.Moreover,2,3,5-triphenyltetrazolium chloride staining and histopathological analysis were also performed.Results:Betulin reduced the size of myocardial infarction,decreased elevated levels of cardiac enzymes,and maintained hemodynamic functions.It also inhibited ISO-induced upregulation of Bax,caspase-3,NF-κB,and IL-6,enhanced endogenous antioxidant enzymes,and reduced lipid peroxidation.Additionally,pretreatment with betulin alleviated myocardial ischemic damage,as reflected by reduced myonecrosis,edema,and inflammatory changes.Conclusions:Betulin exhibits strong cardioprotective activity against ISO-induced myocardial injury by anti-inflammatory,anti-apoptotic,and antioxidant activities.

基于ISO 9001的设备管理创新与实践经验

中铝山东有限公司自2020年探索实践在设备全员生产维护管理(TPM)基础上,基于ISO 9001《质量管理体系要求》,融合设备全生命周期管理,创建更加综合、全面、安全、高效、独具自身特色的设备管理体系,助推企业设备管理水平从合规走向优秀和卓越。

国际标准化组织(ISO)管理模式和运行机制初探

本文简要回顾了国际标准化组织(ISO)的历史和发展,概述了ISO的管理模式,强调了ISO的核心价值观及其作用与重要性。从灵活、多样的办公模式,人性化的人力资源培养与储备模式,以及营造工作—生活平衡的整体运行环境等三个方面,阐述了ISO的运行机制。为我国深入了解ISO内部管理和运行机制,更好地理解ISO决策和思维模式,进而更好地履行我国作为ISO常任理事国职责,更高效地参与其活动并开展工作提供借鉴与参考。

ISO 15189全面质量管理体系下临床生化领域比对方案应用

目的基于ISO 15189建立的全面质量管理体系,探讨临床生化实验室涉及的多种比对方案,为日常检验工作正确使用比对方案提供参考。方法参照医学实验室认可相关文件、国家相关卫生行业标准、CLSI系列相关文件、结合工作实践经验,对临床生化领域比对活动中多种质量评估方案的应用进行分析,梳理总结其中涉及的比对方案。结果本研究针对临床生化领域中涉及的11种比对实验进行了列举总结,比对结果分别满足不同情况的要求。结论通过对不同比对方案的梳理及案例分析,能够指导日常检验工作比对方案的正确选择,提高实验室检验质量和能力。

将ISO15189质量管理体系融入医学检验技术专业本科实习的教学模式探讨

通过让医学检验专业的临床实习生模拟整个ISO15189认可过程,有助于实习生全面、深入的了解质量管理体系的各个环节,有助于其就业后能尽快投入到单位的质量管理工作中去。经过ISO15189实战培训的实习生,理论学习和实践操作能力均得到提高。该教学方法为培养高水平的医学检验人才提供临床实习带教新模式,并为用人单位定向培养指定岗位人才开辟新的教学途径。

ISO 11798:2023《信息与文献纸张上书写、打印和复印图像的耐久性和耐用性要求与测试方法》标准解读

ISO11798:2023规定了长期保存在图书馆、档案馆等可控环境中纸质文献的书写、打印、复印图像的耐久性和耐用性的要求与测试方法,不仅为图书馆、档案馆等单位更好地开展纸质文献保护工作提供助力,同时也为出版印刷行业提高印刷质量提供了重要参考。本文详细介绍了最新版ISO11798标准的修订背景、修订过程以及主要修订内容,希望能为相关从业人员研究新标准文本及制定相应国家标准提供帮助。

ISO针灸国际标准建设概况与特点分析

目的:分析国际标准化组织(international organization for standardization,ISO)针灸国际标准建设的概况与特点,为进一步推进针灸国际标准化建设提供依据,以促进针灸疗法的推广、应用与国际交流。方法:对ISO官网中针灸相关标准进行检索,并分析其特点。结果:目前ISO已发布的针灸相关标准共19项,包括器具标准13项、术语标准5项、安全标准1项;正在研制中的针灸相关标准共6项,包括器具标准3项、术语标准1项、安全标准2项。结论:ISO针灸国际标准制定快速增长,涉及的领域逐步扩大;ISO针灸相关标准以器具标准为主,安全标准仅涉及器具安全;ISO针灸相关国际标准的推广和应用有待提高。

Tomato lycopene attenuates myocardial infarction induced by isoproterenol:Electrocardiographic,biochemical and anti-apoptotic study

Objective:To assess the protective effects of lycopene on electrocardiographic,hemodynamic, biochemical and apoptotic changes in isoproterenol induced myocardial infarction.Methods: Myocardial infarction was induced in rats by subcutaneous injection of isoproterenol(200 mg/kg) for two consecutive days at an interval of 24 h.Rats were treated with lycopene(10 mg/kg/day, p.o.) for a period of 30 days and isoproterenol(ISO) was injected on the 29th and 30th day.At the end of experiment i.e.on the 31st day electrocardiographic,hemodynamic,biochemical and apoptotic changes were monitored from control and experimental groups.Results:ISO injected ruts showed a significant alteration in electrocardiograph pattern and hemodynamic changes(i.e. systolic,diastolic and mean arterial pressure).It also showed significant increase in C-reactive protein,myeloperoxidase,nitrite levels and Caspase-3 protease activity.In addition,it also exhibited alteration in the levels of electrolytes(Na^+,K^+ and Ca^(2+),vitamin E,uric acid and serum protein.Cel electrophoresis of ISO injected rats showed increase in DNA fragmentation.Triphenyl tetrazolium chloride staining of the heart section shows increase area of infarction in ISO injected rats.Pre-co-treatment with lycopene significantly prevented the ISO induced ullerution in ECC, haemodynamic,biochemical and apoptotic changes.Conclusions:The present result shows that treatment of lycopene in ISO injected rats significantly attenuates induced myocardial infarction.

ISO9000融入中医类别医师资格实践技能考试考务质量管理的设计与实践

考务质量管理是中医类别医师资格实践技能考试质量管理的重要内容。本研究以ISO9000族质量管理体系要求为基准,借助服务蓝图技术将ISO9000标准理念引入中医类别医师资格实践技能考试基地考务管理,分析中医类别医师资格实践技能考试考务质量管理过程、剖析质量管理过程要素、识别考务组织潜在风险,并开展了考务质量管理实践,为规范中医类别医师资格实践技能考试基地考务管理、提升考试质量、防范考试风险、强化考试的公平公正性提供借鉴和帮助。

Nigella sativa protects against isoproterenol-induced myocardial infarction by alleviating oxidative stress,biochemical alterations and histological damage

Objective: To evaluate the cardioprotective effect of Nigella sativa L.(N.sativa) in isoproterenol-induced myocardial infarction(MI).Methods: Groups were treated with different doses of ethanol extract of N.sativa(EENS)and N.sativa oil alone and along with enalapril for 28 days.MI was induced by subcutaneous administration of isoproterenol(85 mg/kg) in two consecutive doses.Levels of cardiac biomarkers and antioxidant enzymes such as creatine kinase–N-acetyl-L-cysteine, lactate dehydrogenase, aspartate aminotransferase, malondialdehyde, superoxide dismutase, reduced glutathione and catalase were evaluated along with gross histopathological examination.Results: Isoproterenol(85 mg/kg) induced MI by causing the significant(P < 0.01)reduction in the activity of cardiac biomarkers(creatine kinase–N-acetyl-L-cysteine,lactate dehydrogenase, aspartate aminotransferase) and antioxidant markers(superoxide dismutase, catalase, glutathione) along with significant(P < 0.01) increase in the level of malondialdehyde.Furthermore, histopathological evaluation also confirmed the isoproterenol-induced MI.Pretreatment with EENS(800 mg/kg) and combination of EENS(800 mg/kg) with enalapril(1 mg/kg) significantly(P < 0.01) prevented the development of these alteration and restored activity of cardiac biomarkers as well as antioxidant markers almost near to normal levels.Histopathological evaluation of cardiac tissue further confirmed the restoration of biochemical activity.Conclusions: Experimental findings thus indicate that EENS(800 mg/kg) demonstrated cardioprotective effect against isoproterenol-induced MI by restoring cardiac biomarkers and antioxidant status.

Synthesis,isolation,identification and characterization of new process-related impurity in isoproterenol hydrochloride by HPLC,LC/ESI-MS and NMR

One unknown impurity （Imp-II） during the analysis of laboratory batches of isoproterenol hydrochloride was detected in the level ranging from 0.04% to 0.12% by high performance liquid chromatography with UV detection. The unknown impurity structure was proposed as 4-[2-（propan-2oylamino）ethyl]benzene-l,2-diol （Imp-II） using the liquid chromatography-mass spectrophotometry （LC-MS） analysis. Imp-II was isolated by semi-preparative liquid chromatography from the impurity-enriched reaction crude sample. Its proposed structure was confirmed by nuclear magnetic spectroscopy such as 1H, 13C, DEPT （1D NMR）, HSQC （2D NMR） and infrared spectroscopy （IR）, and retention time and purity with HPLC followed by the chemical synthesis. Due to less removable nature of Imp-II during the purification, the synthetic process was optimized proficiently to control the formation of Imp-II below to the limit 〈 0.12% in the course of reaction. The new chemical route was developed for the preparation of this impurity in required quantity with purity to use as reference standard. The most probable mechanism for the formation of Imp-II was discussed in details.

ISO 15489-1:2016《信息与文献文件(档案)管理概念与原则》的修订预研进展

ISO 15489-1的基本介绍I SO 15489-1由国际标准化组织信息与文献标准化技术委员会档案(文件)管理分技术委员会(以下简称“ISO TC46/S C11”)最早发布于2001年,是全球第一个关于文件管理的国际标准,综合了世界各国文件管理的先进经验,吸收了国际公认的最优化文件管理方法,具有较强的先进性、前瞻性和实用性。该标准是ISOT C46/SC11所制定系列标准的基础标准,现已被全球50多个国家采用,并先后被翻译超过22余种语言。经过10余年的应用、持续研究与改进、审核与咨询,2016年,ISO发布了15489-1:2001的修订版。

Raman and UV-Vis Spectroscopy Applied to the Analysis of Liver Tissues from Rats with Myocardial Ischemia Induced by Isoproterenol

The application of the laser Raman spectroscopic（LRS） technique for the analysis of liver tissues from rats with myocardial ischemia induced by isoproterenol（ISO） was described.Animal model of myocardial ischemia was established for rats induced by ISO.Rats were randomly divided into four groups as normal group and myocardial ischemia groups.We observed the successful myocardial ischemia model via serum enzymes levels and hematoxylin-eosin（HE） staining,and detected the liver tissue of the rats from normal group and liver tissue of the rats from myocardial ischemia groups via UV-Vis spectroscopy（UV-Vis） and LRS,and the changes of the absorbance spectra were compared in the above four different groups.The results show that ISO can induce rat myocardial ischemia successfully.The spectrum of normal liver tissue supernatant exhibits a strong absorption band at 968 nm,but no absorption band appears in the spectra of liver tissue supernatant solutions from the rats with myocardial ischemia induction after 2,12 and 72 h presented at 968 nm.LRS results show that Raman intensities of the precipitates suffered from ISO-treatment after 2,12 and 72 h were obviously increased compared with that of the precipitate of the liver tissue of the normal rats suffered from 0.9 g/L normal saline（NS） treatment.These results indicate that LRS and UV-Vis can be harmless,nondestructive,rapid and effective methods for analyzing different pathological specimens of liver tissue from myocardial ischemia rats.

基于ISO标准的颜色便捷控制与体系化交流模式

印刷技术的发展与颜色的控制息息相关,借用数字化模式降低颜色再现时主观判断的难度,是印刷行业一直坚持探求的目标。ISO/TC 130为印刷行业奠定了系统化的颜色交流模式与体系,本文探讨了基于ISO标准的颜色便捷控制与体系化交流模式。

基于ISO标准下达芬奇机器人手术医用耗材的精细化管理实践

目的基于ISO标准实施达芬奇机器人手术医用耗材精细化管理,规范管理流程,做好人员、质量监管保障,实施成本效益分析及绩效考核,引入电子订单和智能柜信息化管理,提高管理效率。方法制定精细化管理流程,对达芬奇机器人手术医用耗材实施精细化管理,通过比较精细化管理实施前后的手术成本及不良事件发生率,评估精细化管理的效果。结果实施精细化管理后,达芬奇机器人手术单台成本由1.98万元减少至1.76万元,差异具有统计学意义(P<0.001);医用耗材不良事件发生率由3.78%降低至0.74%,差异具有统计学意义(P<0.05)。结论达芬奇机器人手术医用耗材的精细化管理可以降低手术成本,减少不良事件的发生,推动医用耗材管理的标准化,促进医院高质量发展。

ISO汉信码Unicode模式详解

2021年8月27日,国际标准化组织(ISO)和国际电工委员会(IEC)正式发布ISO/IEC 20830:2021《信息技术自动识别与数据采集技术汉信码条码符号规范》(Information technology-Automatic identification and data capture techniques-HanXin Code bar code symbology specification)。为帮助我国条码与自动识别技术产业界深入理解该标准中Unicode模式的技术实现方法,解决应用该模式进行信息编码的问题,本文详细介绍了汉信码Unicode模式的设计思路与编解码技术方案,并给出了编码实例进行解释和说明。

基于ISO方法论下的5G电力行业标准化效益评估

本文运用ISO方法论2.0,评估5G技术与标准应用对电力行业所产生的影响。以深圳供电局为评价对象,通过分析深圳供电局的价值链,总结关键价值驱动因素,选定价值链上的工程、输电管理、变电管理、配电管理和电力调度等环节作为评估范围,分析评估范围内所使用到的标准,整理出衡量标准影响的营运指标。评估结果显示,5G标准与技术应用后,在深圳供电局的电力管理中产生了显著的经济效益、社会效益和环境效益,且对不同业务环节产生的效益也有所差异。

L-carvone attenuates myocardial injury and dyslipidemia in rats with isoproterenol-induced cardiac hypertrophy

Objective:To explore the therapeutic efficacy of L-carvone from Mentha spicata L.leaf extracts against isoproterenol-induced cardiac hypertrophy in rats.Methods:Isoproterenol(5 mg/kg)was injected intraperitoneally into rats for one month to induce cardiac hypertrophy.L-carvone(25 and 100 mg/kg)was administered orally to treat cardiac hypertrophy.The cardioprotective activity of L-carvone was evaluated by electrocardiogram,histopathological analysis as well as determination of biochemical parameters and enzymatic markers.Results:L-carvone from Mentha spicata L.at 25 and 100 mg/kg ameliorated isoproterenol-induced cardiac hypertrophy,as evidenced by reduced QRS interval on electrocardiogram,and decreased heart weight and heart index.In addition,both doses of L-carvone markedly lowered the levels of glucose,total protein,low-density lipoprotein cholesterol,aspartate transaminase,alanine transaminase,lactate dehydrogenase,creatine kinase MB,troponin-Ⅰ,N-terminal pro-B type natriuretic peptide and triglycerides while increasing high-density lipoprotein cholesterol and lipase level(P<0.05).Moreover,L-carvone alleviated contraction band necrosis,and reorganized the myofibrils with normal striations and myocytes as well as normal nuclei in cardiac histoarchitecture of rats with isoproterenol-induced cardiac hypertrophy.Conclusions:L-carvone from Mentha spicata L.leaf extract can restore abnormal cardiac function and may be further explored as a therapeutic agent against the deleterious effects of cardiac hypertrophy after further evaluation.