放射性心脏损伤机制及其防治研究进展

放疗是胸部恶性肿瘤的主要治疗手段之一,乳腺癌、肺癌、食管癌、纵隔淋巴瘤、胸腺瘤等胸部恶性肿瘤接受放射治疗时,肿瘤组织在受到放射线照射的同时,纵隔处的心脏亦不可避免受到不同体积、不同剂量的照射,引起不同程度的放射性心脏损伤(Radiation-Induced Heart Disease,RIHD)。由其所致的放射性损伤严重地影响了患者的生存质量,重者死亡,抵消放疗带来的生存受益。若能及早发现急性放射性心脏损伤、及时治疗、降低放射后并发症的发生,可大幅度提高患者生存质量,因此研究放射性心脏损伤的发生条件、发生机制、临床特点、影像学及实验室检查以及防治措施,具有重要的临床意义。     

放疗导致心脏损伤的发生机制及防治进展

摘要：放疗作为恶性肿瘤的主要治疗方法之一，广泛应用于乳腺癌、食管癌、肺癌、纵隔肿瘤和淋巴瘤等疾病。 接受放疗患者长时间在X线照射下很容易导致心脏损伤，引起不同程度的放射性心脏病（RIHD），RIHD可以破坏心 脏的任何结构，因此心脏损伤在癌症幸存者中成为危及生命的疾病，而有效的临床管理及防治仍然具有很大的挑战 性。本文对放疗后心脏损伤的表现、发生机制、心脏相关指标监测及防治进展等方面作一综述。     

淋巴瘤放疗术后致放射性心脏损伤1例

放射性治疗可明显改善肿瘤患者的预后,但同时因放射线的照射带来纵隔器官的损害。近年放射性心脏损害日渐增多,应该受到临床医生和放射科医生的重视。进一步改善放疗方法,减少放射性心脏损害,关注放射性心脏损害,改善患者预后及生活质量。     

胸部肿瘤放射治疗对心脏损伤的研究进展

<正>放射治疗是肿瘤治疗的三大重要手段之一。WHO于1998年公布有45%的恶性肿瘤可以治愈,其中手术治疗占22%,放射治疗占18%,化学治疗占5%,可见放射治疗占有极其重要的地位。胸部放射治疗是食管癌、肺癌、乳腺癌、纵隔肿瘤等恶性肿瘤的主要治疗措施,而邻近纵隔的心脏在放疗时不可避免地受到照射影响。以往认为心脏对放射线具有较高的抵抗力和耐受性,但近年来的临床实践和研究证明心脏的抗辐射能力并非如此,胸部放疗可引起不同程度的心     

miRNAs与放射性心脏损伤的相关性研究进展

放射治疗（简称“放疗”）作为多种恶性肿瘤综合治疗的重要手段,在胸部肿瘤的诊疗中居于重要地位。随着放疗技术的不断发展,恶性肿瘤患者整体生存率和放射性相关损伤的发生率均不断上升。放射性心脏损伤（RIHD）逐渐成为影响肿瘤放疗患者生存质量和预后的重要原因。目前RIHD的发病机制逐渐被阐明,并提出了一些预防和治疗RIHD的潜在手段。微小RNAs(miRNAs)是一种大小约为22个核苷酸的非编码小分子RNA,在基因的调控中发挥重要的作用,miRNAs可以调节多种心脏功能,具有发育、病理生理和临床意义。现有越来越多的证据表明,miRNAs的表达与RIHD密切相关。本文结合RIHD的现状,对miRNAs在放射性心脏损伤发生发展过程中的作用进行综述,为RIHD的防治提供新思路。     

放射治疗导致心脏并发症的研究进展

随着癌症治疗的改进,癌症患者的生存期也随之延长。因此,癌症治疗所致的并发症也日益显著。本文将介绍目前所知胸部放疗对心血管系统的副作用,并对其病理改变、影响其发病及预后的危险因素、发病机制及防治进行论述。胸部放疗导致的心脏损伤多种多样,包括冠状动脉粥样硬化、心包炎、心肌病及心脏瓣膜疾病等。研究表明放疗所致心脏损伤与放射剂量、受照射心脏的范围、患者年龄以及放射技术等因素相关。随着一些新技术应用于胸部放射治疗中,使其所致心血管疾病的发病率随之降低。然而,放射性心脏损伤的发病机制及其防治仍有待进一步研究。     

食管癌适形放疗对急性放射性心脏损伤的影响

目的总结近年来我院食管癌患者行三维适形及调强适形放疗时对心脏放射性损伤的监测、观察其影响。方法对2011年8月~2014年2月在我院行食管癌放射治疗的102例患者,分为普通放疗组和适形放疗组,在放疗前后及放射治疗后3个月内分别检查患者心电图、心肌酶谱、心肌肌钙蛋白、超声心动图和胸部CT等,进行统计学分析。结果普通放疗组患者49例出现急性放射性损伤39例,占79.6%,适形放疗组患者53例出现急性放射性心脏损伤32例,占60.4%,x2=3.938,P0.05,差异有统计学意义。结论食管癌患者适形放疗对累及心脏照射剂量及体积予以适当限制,可以减轻急性放射性心脏损伤。     

胸部恶性肿瘤放化疗致放射性心包炎及肺纤维化的预防及治疗

目的 分析胸部恶性肿瘤放化疗致放射性心包炎及肺纤维化的预防及治疗措施。方法 43例经胸部恶性肿瘤放化疗后出现放射性心包炎及肺纤维化患者为研究对象,分析其预防措施与治疗方法。结果 放射性心包炎需要应用适量抗生素与大量激素治疗,并同时进行吸氧、参麦、卧床休养等治疗措施;若患者心包积液量较大,则上述治疗方法疗效不明显,需要进行心包穿刺抽液。另外严格控制心脏照射体积,保持心脏照射体积<60%,剂量<50 Gy为有效预防措施;肺纤维化患者需应用抗生素与大剂量糖皮质激素治疗,减少对肺组织的照射剂量,缩小照射面积为主要预防措施。结论 胸部恶性肿瘤放化疗致放射性心包炎及肺纤维化均可治疗与预防。     

白英汤防治放射性肺损伤及对TGF-β1表达的影响研究

目的观察中药白英汤预防胸部恶性肿瘤放射性肺损伤和对生活质量的临床疗效及对血浆转化生长因子-β1(TGF-β1)表达的影响。方法 60例胸部恶性肿瘤放疗患者随机分为两组:治疗组和对照组各30例。对照组常规放疗,治疗组采用放疗的同时同步服用中药白英汤水剂。放疗结束后3个月测定血浆TGF-β1水平,并观察两组的急性放射性肺损伤、晚期放射性肺损伤发生率和患者的生活质量情况。结果放疗结束时和放疗后3个月,治疗组3-4级急性放射性肺损伤、晚期放射性肺损伤发生率和血浆TGF-β1水平均低于对照组;生活质量优于对照组;差异均有统计学意义。结论中药白英汤能降低胸部恶性肿瘤放射治疗患者血浆TGF-β1的过度表达,减少3-4级急性放射性肺损伤和晚期放射性肺损伤发生,改善患者生活质量。     

胸部肿瘤放疗放射性食管炎发生的相关因素分析

<正>胸部肿瘤为包括肺部肿瘤、食管肿瘤、纵隔肿瘤在内的多种发生于胸部的恶性肿瘤。对于胸部肿瘤而言,不仅肿瘤本身可严重威胁患者的生命安全,而且因发病后所导致临近器官功能显著降低,也同样是引起患者死亡的重要原因[1,2]。放疗与手术治疗及化疗一样,在胸部肿瘤的治疗中扮演着极为重要的角色[3-6]。但是在患者接受放射治疗过程中,往往导致并发放射性食管炎,在降低患者临床治疗效果的同时,也可进一步影响患者的预后[7,8]。放射性食管炎是指照射野内正     

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.