Gleevec与慢性髓细胞性白血病疗效监测

Gleevec是抑制致癌的融合蛋白BCR-ABL的一种分子靶向治疗药物,BCR-ABL是一种与慢性髓细胞性白血病(CML)有关的酪氨酸激酶抑制剂。用Gleevec选择性抑制BCR-ABL活性,在治疗CML中有很好的效果,特别是在CMl的慢性期。因此,监测治疗的疗效非常重要。现就Gleevec的研究进展及如何监测它在CML中的治疗效果作一综述。     

多酚类化合物对饼干中羧甲基赖氨酸的抑制作用

羧甲基赖氨酸(CML)是晚期糖基化终产物(AGEs)中最具代表性,研究最多的一种化合物。由于CML在人体内的积累与多种疾病相关,因而控制食源性CML的摄入具有重要的意义。本文研究多种多酚类化合物对饼干和模拟体系中CML的抑制效果,通过活性羰基的捕获试验对其抑制机理进行探讨。以含水量、硬度、颜色、感官评分以及CML的含量为优化指标,优化饼干的烘烤条件。结果表明,饼干最优的烘烤条件为烘烤温度190℃,烘烤时间8 min。在最优烘烤条件下对油脂和糖种类进行优化,结果表明,以菜籽油作为油脂来源,蔗糖作为糖来源制备的饼干中CML含量达到最大值【984.23 mg/(kg蛋白)】。按照饼干中各原料的配比构建模拟体系,其中葡萄糖(Glu)∶赖氨酸(Lys)∶亚油酸(Lin)=15∶14∶4(质量比)。向饼干和模拟体系中加入6种多酚类化合物,结果表明都对CML有一定的抑制作用,且6种多酚类化合物都能不同程度地清除甲基乙二醛(MGO)——形成AGEs的一种重要中间产物,推测6种多酚类物质可能是通过捕获MGO来达到抑制CML的效果,其中白藜芦醇的添加量为0.2 g/(kg面团)时对CML的抑制率最大,可达83%。     

慢性髓性白血病急变期基因机制及治疗进展

研究发现,慢性随行白血病患者其发病加速期及急变期基因的染色体突变远高于慢性期。尽管CML即便患者可以合并多种基因突变,但是经过研究发现,并未有一种特定的基因突变在CML急变中发挥出关键行作用,这样就可以认为,CML急变是在多种基因突变综合作用下产生的,并且具有一定的复杂性。基于此,本文对慢性髓性白血病急变期基因机制及治疗进展进行了综述。     

麻花加工与贮藏过程中晚期糖基化末端产物（AGEs）的形成及抑制研究

油炸食品加工与贮藏过程中易发生美拉德反应、脂肪氧化反应而形成晚期糖基化产物(advanced glycation end products,AGEs)。AGEs与人类诸多慢性疾病的发生密切相关。本文研究了油炸麻花加工与贮藏过程中荧光性AGEs和羧甲基赖氨酸(Nε-(Carboxymethyl)lysine,CML)的变化规律及AGEs抑制剂(槲皮素、阿魏酸和硫胺素)对荧光性AGEs和CML的抑制特性。结果表明,荧光性AGEs和CML均随着油炸温度升高和油炸时间的延长呈上升趋势,荧光性AGEs含量为258.34~1068.90 AU/g样品,CML为1036.56~1603.72 mg/kg蛋白质;较高贮藏温度和氧气对荧光性AGEs的变化有显著(P0.05)影响,光照对荧光性AGEs的影响较小。随着温度升高和贮藏时间延长CML显著(P0.05)升高,氧气和光照对CML的形成无影响;AGEs抑制剂(槲皮素、阿魏酸和硫胺素)能够有效的抑制麻花加工过程中荧光性AGEs和CML的形成,硫胺素的抑制效果最好。因此,在麻花的加工和贮藏过程中,通过部分条件的改变如油炸温度、油炸时间、贮藏条件和加入适量的AGEs抑制剂,在一定程度上调控AGEs的形成是可行的。     

基于蛋白沉淀法超高效液相色谱-串联质谱法检测面包中两种蛋白结合型晚期糖基化终末产物

目的 建立面包中两种典型晚期糖基化终末产物（AGEs）的超高效液相色谱-串联质谱检测方法。方法以结合型羧甲基赖氨酸（CML）和羧乙基赖氨酸（CEL）为检测对象，面包样品经还原孵育、蛋白沉淀、加同位素内标、酸水解、氮吹、九氟戊酸水溶液复溶后，多反应监测定性及定量分析。结果 方法的检出限CML为4.5 ng/g,CEL为0.5 ng/g；定量限CML为20 ng/g,CEL为2 ng/g;CML加标回收率为89.62%～95.65%,CEL的加标回收率为86.38%～97.17%；标准曲线线性范围为CML2.5～800 ng/mL和CEL0.25～80 ng/mL，决定系数均大于0.999。结论 该方法准确且灵敏，能够满足面包中AGEs的检测需求。     

多酚黄酮物质对晚期糖基化终产物的抑制研究

研究多酚黄酮类化合物对食品加工模拟体系中晚期糖基化终产物(Advanced glycation end products,AGEs)的抑制影响。构建了牛血清白蛋白-葡萄糖模拟体系,研究多酚黄酮类化合物对AGEs的荧光产物和非荧光产物羧甲基赖氨酸(N~ε-carboxymethyllysine,CML)的抑制效果。通过研究不同的多酚黄酮类化合物对甲基乙二醛(methylglyoxal,MGO)的加合试验进一步探究抑制机理。结果表明,除阳性对照组氨基胍外,茶多酚和木犀草素对AGEs的荧光产物和CML的抑制较其他抑制剂的效果好,茶多酚和木犀草素对AGEs的荧光产物的抑制率为68.52%和61.19%,对非荧光产物CML的抑制率为13.67%、16.52%。通过多酚黄酮类化合物对活性二羰基化合物MGO的捕获试验,推测出可以与MGO发生加和反应的结构通式,初步阐述多酚黄酮类化合物对AGEs的抑制机理。     

食品中羧甲基赖氨酸的危害和检测方法的研究进展

食品中的N~ε-(1-羧甲基)-L-赖氨酸(N~ε-(1-Carboxymethyl)-L-lysine,简称羧甲基赖氨酸或CML)是还原糖的羰基与蛋白质、氨基酸的氨基等通过美拉德反应产生的晚期糖基化终末产物中的一种主要成分。CML具有较高的酸稳定性,可以作为评价食品体系美拉德反应中蛋白质化学修饰、羰基应激和脂质氧化的一个重要指标。CML通过食品介质进入人体后,可积聚于多个不同的组织器官中。达到一定数量后,会直接影响组织器官的功能,导致机体的病理变化。CML与人体许多疾病的发生密切相关,能促进糖尿病、肾病、动脉粥样硬化等疾病的发展和人体器官的快速衰老。CML的定量检测对指导人们减少CML的摄入,进而降低相关疾病的患病风险有重要的意义。本文就CML的危害和检测方法进行综述,以期为寻找具有高灵敏度、高选择性和快速高效的CML含量的检测方法提供依据。     

青稞全谷及麸皮对饼干品质的影响

饼干是颇受消费者喜欢的休闲食品,提高其品质对人们的生活有着重要的影响。本文通过在饼干的制作过程中添加0%、5%、10%、15%不同比例的青稞全谷物和青稞麸皮,测定了其蛋白质含量、质构、颜色变化并对饼干进行感官评价,结合对CML含量的抑制效果来确认最优添加量。结果表明:青稞全谷物及青稞麸皮添加量均为15%时,此时蛋白质含量最高,分别为6.83%±0.03%和6.78%±0.14%;且质构指标硬度、内聚性、弹性、咀嚼性均在消费者可以接受的范围;饼干呈现棕褐色,深受消费者喜爱;感官得分分别为15.8分和15.1分;对晚期糖基化终产物CML的抑制率分别为27.46%和22.54%,抑制效果最佳。因此在杂粮饼干的加工中,选择青稞全谷物和麸皮添加量均为15%,既能保证饼干具有较好的感官,又能最大限度的抑制CML的生成。     

酱油生产过程中游离态羧甲基赖氨酸和5-羟甲基糠醛的同步检测

为快速检测酱油生产过程中2种危害物羧甲基赖氨酸(CML)和5-羟甲基糠醛(5-HMF)的含量变化,采用高效液相色谱质谱联用(HPLC-MS/MS)技术建立了一种同步检测游离态CML和5-HMF的方法。通过质谱参数、色谱条件和前处理的优化,CML和5-HMF的回收率可达98%以上,样品中CML和5-HMF的检测限(LOD)分别为0.3 ng/mL和6.0 ng/mL,定量限(LOQ)分别为1.0 ng/mL和20.0 ng/mL。对酱油生产过程中各工艺工段的样品进行检测,发现发酵原料大曲中CML含量较高,而豆粕的蒸煮过程和老抽酱油的调配是使5-HMF含量增高的关键生产环节。     

羧甲基赖氨酸在方便面中含量及其对雄性生殖和胚胎发育毒性的研究

采用酶联免疫吸附测定法(ELISA)对市售20个品牌方便面中游离态和结合态羧甲基赖氨酸(CML)含量进行了定量分析,并以体外细胞培养评价了CML的雄性生殖毒性和胚胎发育毒性。市售方便面中,游离态CML质量分数为0.39~0.80 mg/kg,结合态CML质量分数为19.42~34.99 mg/kg。CML作用于睾丸间质细胞R2C细胞24 h,浓度在1 mmol/L以下对细胞存活率没有显著抑制作用,浓度在2 mmol/L以下对孕酮分泌量没有显著的抑制作用;CML作用于胚胎干(ES)细胞D3和成纤维细胞3T3 10 d,浓度在4 mmol/L以下对3T3细胞存活率没有显著影响,浓度在0.5 mmol/L以下对D3细胞存活率没有显著影响。根据市售方便面中的CML浓度评估CML的摄入量,常规食用方便面摄入的CML不会对这几种细胞的存活率和R2C细胞的孕酮分泌量产生显著抑制作用,可认为不会产生雄性生殖和胚胎发育毒性。     

Dietary N-epsilon-carboxymethyllysine as for a major glycotoxin in foods: A review

N-epsilon-carboxymethyllysine (CML), as a potential glycotoxin and general marker for dietary advanced glycation end products (dAGEs), exists in raw food and is formed via various formation routes in food processing such as Maillard reaction between the reducing sugars and amino acids. Although comprehensive cause-effect proof is not available yet, current research suggests a potential risk of chronic diseases such as diabetes is associated with exogenous CML. Thus, CML is causing public health concerns regarding its dietary exposure, but there is a lack of explicit guidance for understanding if it is detrimental to human health. In this review, inconsistent results of dietary CML contributed to chronic disease are discussed, available concentrations of CML in consumed foods are evaluated, measurements for dietary CML and relevant analytic procedures are listed, and the possible mitigation strategies for protecting against CML formation are presented. Finally, the main challenges and future efforts are highlighted. Further studies are needed to extend the dietary CML database in a wide category of foods, apply new identifying methods, elucidate the pathogenic mechanisms, assess its detrimental role in human health, and propose standard guidelines for processed food.     

Modelluntersuchungen zu Bedingungen der Bildung vonN ε-Carboxymethyllysin in Lebensmitteln

In model experiments with equimolar mixtures of lysinemonohydrochloride and glucose [88% (w/v) water content, 100° C heating temperature] the influence of several conditions (hydrolysis, pH) and ingredients (iron, phosphate, and nitrite) on the formation ofN ^ε-carboxymethyllysine (CML) were evaluated. CML was analysed using a reversed-phase HPLC-method after derivatisation witho-phthaldialdehyde. CML, which is an oxidative derivative of fructoselysine, is also formed during the acid hydrolysis applied for amino acid determination in food products. In model mixtures without hydrolysis only 8–21% CML compared to that in hydrolysed samples was found. Therefore, in food products all hydrolyses for CML must be performed after borohydride reduction in order to destroy fructoselysine. This can be controlled by the determination of furosine. The pH of the model mixtures considerably influenced the formation of CML. At pH 4.0 only 70 mg, at pH 7.0 370 mg, and at pH 9.0 3170 mg CML/kg lysine were determined. The CML concentration also clearly increased with higher concentrations of iron, phosphate, and nitrite. This is explained by a promoting effect on the oxidation of fructoselysine to CML.     

N ϵ-(carboxymethyl)lysine: A Review on Analytical Methods,Formation, and Occurrence in Processed Food,and Health Impact

Foods are often heat processed and may contain advanced glycation end products (AGE). One of the most widely studied AGE is N ^?-(carboxymethyl)lysine (CML); nevertheless, knowledge on dietary CML is fragmentary. This study aimed to review current scientific knowledge on analytical methods to determine CML contents in food, chemical pathways of CML formation in food, occurrence of CML in food, and health implications of dietary exposure to CML. Chemical analyses of CML in food products are carried out by immunochemical assays and instrumental methods, but the former method may interfere with the food matrix. CML is formed in food through various chemical pathways, depending on food ingredients and processing conditions. The compound is present in many cooked foods, with relatively high concentrations in carbohydrate-rich foods and dairy products. Dietary CML is very likely to impair human health, but full cause-effect evidence is not available yet. More studies on metabolic effects and impact of food-derived CML on human health should be performed. Food production should be optimized to minimize CML concentrations, while maintaining acceptable microbiological safety and organoleptic properties of the final food product. To this end, more insights into effects of food composition and processing conditions on CML formation are necessary.     

低蛋白饮食在延缓慢性肾功能衰竭恶化方面的疗效、作用机理、副作用及其应有的对策

对慢性肾功能衰竭的患者而言，在现有的治疗方法中，采用低蛋白饮食是延缓慢性肾功能衰竭的有效方法，但饮食的蛋白含量也并非越低越好。本章就低蛋白饮食疗法的治疗疗效、作用机理、影响疗效的因素、依从性、副作用及应用前景等方面的研究进展予以述评。     

儿茶素及表儿茶素对老化啤酒中晚期糖基化终末产物的抑制作用

该研究利用真实啤酒体系,向啤酒中加入不同浓度的儿茶素（CC）及表儿茶素（EC）,以氨基胍（AG）作为阳性对照,在50 ℃分别老化2 d和5 d。测定了不同原花青素单体对啤酒中荧光性晚期糖基化终末产物（AGEs）、非荧光性AGEs代表物Nε-羧甲基赖氨酸（CML）及啤酒非生物稳定性的影响,同时利用分子对接解释原花青素抑制CML构效关系。结果表明,对于啤酒老化过程中产生的荧光性AGEs,抑制效果CC＞EC＞AG;对于非荧光性AGEs代表物CML,抑制效果EC＞CC,并与分子对接结果一致。CC及EC的添加,对啤酒蛋白含量无显著影响（P＞0.05）,但对啤酒总酚和色度均有显著性影响（P＜0.05）,且呈剂量依赖性。研究结果为原花青素作为老化啤酒中AGEs抑制剂提供科学依据。     

Determination of Nε-carboxymethyllysine in heated milk products by immunochemical methods

  N ^ε-Carboxymethyllysine (CML) is an important Maillard product which is formed in vivo and during food processing and heating, and which can therefore be used as a marker for heat damage of foodstuffs. A competitive enzyme-linked immunosorbent assay (ELISA) was developed to detect CML modifications on proteins. CML protein was synthesized and anti-CML antiserum was prepared, which recognized CML modifications specifically on CML proteins and proteins which were incubated with various carbohydrates. Heated milk and milk powder samples could be directly tested by ELISA without further clean-up procedures and the CML contents were determined in relation to reaction time and heating conditions. Positive results were confirmed by SDS-PAGE/immunoblotting using the same antiserum. ELISA proved to be a fast, specific, and easy-to-handle method to evaluate CML formation in heated milk products. Additionally, SDS-PAGE/immunoblotting can be helpful to detect CML also in insoluble food proteins. Received: 10 September 1998     

色氨酸抑制体外模型中晚期糖基化终末产物形成机理

食源性晚期糖基化终末产物(advanced glycation end products,AGEs)与多种慢性疾病密切相关,尤其是糖尿病和肾脏疾病.为减少AGEs对机体的健康风险,降低食品中AGEs含量,本研究从13种氨基酸中筛选出具有良好AGEs抑制效果的色氨酸(tryptophan,Trp),利用牛血清白蛋白(bo...