Idiosyncratic Drug-Induced Liver Injury: Mechanistic and Clinical Challenges

Idiosyncratic drug-induced liver injury (IDILI) remains a significant problem for patients and drug development. The idiosyncratic nature of IDILI makes mechanistic studies difficult, and little is known of its pathogenesis for certain. Circumstantial evidence suggests that most, but not all, IDILI is caused by reactive metabolites of drugs that are bioactivated by cytochromes P450 and other enzymes in the liver. Additionally, there is overwhelming evidence that most IDILI is mediated by the adaptive immune system; one example being the association of IDILI caused by specific drugs with specific human leukocyte antigen (HLA) haplotypes, and this may in part explain the idiosyncratic nature of these reactions. The T cell receptor repertoire likely also contributes to the idiosyncratic nature. Although most of the liver injury is likely mediated by the adaptive immune system, specifically cytotoxic CD8+ T cells, adaptive immune activation first requires an innate immune response to activate antigen presenting cells and produce cytokines required for T cell proliferation. This innate response is likely caused by either a reactive metabolite or some form of cell stress that is clinically silent but not idiosyncratic. If this is true it would make it possible to study the early steps in the immune response that in some patients can lead to IDILI. Other hypotheses have been proposed, such as mitochondrial injury, inhibition of the bile salt export pump, unfolded protein response, and oxidative stress although, in most cases, it is likely that they are also involved in the initiation of an immune response rather than representing a completely separate mechanism. Using the clinical manifestations of liver injury from a number of examples of IDILI-associated drugs, this review aims to summarize and illustrate these mechanistic hypotheses.     

市售西班牙自然发酵香肠的食用品质特征分析

以销量较高的市售西班牙自然发酵香肠为研究对象，通过感官评价筛选出喜好度较高的发酵香肠，测定香肠水分含量、pH值、色泽、质地等指标，采用顶空固相微萃取-气相色谱-质谱联用（headspace-solid phase microextraction-gas chromatography-mass spectrometry，HS-SPME-GC-MS）法分析香肠挥发性风味成分。结果表明，总体可接受性较高的自然发酵香肠具有以下特征：光泽度高、色泽暗红（亮度值16.028～31.399，红度值13.80～16.31），组织紧密、质地均一、硬度（4 721.859 0～6 360.352 0 g）适中，pH值（5.68～5.89）、水分含量（20.12%～28.09%）较低，咀嚼感好、干燥度适中，果香味、清香味、甜味、乳香味、鲜味明显，咸味、酸味适中，胡椒味较淡。总体接受性最高的香肠（1号香肠）中检出81 种挥发性风味成分，其中乙醛、异戊醛、2,3-丁二酮、月桂烯、3-甲基丁酸乙酯、顺-4-羟基-6-十二烯酸内酯、乙酸为主要风味成分（香气活力值＞50）。     

植物基蛋白模拟肉研制技术与发展前景展望

基于营养健康需求差异化、个性化及简约化消费模式特点,分析植物基蛋白模拟肉发展趋势。从研究角度以植物蛋白功能特性为切入点,分析蛋白组织纤维化加工技术研发进展及其对模拟肉制品质构、口感的影响,并进一步分析外源风味与模拟肉制品的协同关系,以提升消费者对模拟肉的认知及对其风味口感的接受度。文章着重总结了模拟肉制品的口感形成原理以及风味改善的方法,为模拟肉生产工艺的优化提供依据和支持。     

气相色谱-三重四极杆质谱法快速测定糙米中氟虫腈及其代谢物残留

目的建立气相色谱-三重四极杆质谱(gas chromatography-triple quadrupole mass spectrometry,GC-MS/MS)测定糙米中氟虫腈及其代谢产物氟甲腈、氟虫腈砜、氟虫腈硫醚残留的的分析方法。方法糙米加水涡旋混匀后乙腈提取,通过N-丙基乙二胺(primary secondary amine,PSA)、C_(18)粉末、石墨化炭黑(graphitized carbon black,GCB)粉末净化提取液,气相色谱-三重四极杆质谱多重反应离子监测模式(multiple reaction monitoring,MRM)检测,以外标法定量。结果在1～50μg/L范围下,氟虫腈及其代谢物具有良好的线性关系,相关系数(r)均大于0.99,在2、10、20μg/kg 3个添加水平下,氟虫腈及其代谢物的平均回收率为91.6%～109.9%,相对标准偏差(relative standard deviation,RSD)为4.3%～6.3%。氟虫腈及其代谢物在糙米中的定量限为0.2～0.5μg/kg,定量限添加回收率在85.0%～108.0%,RSD为5.9%～6.9%。结论该方法操作简单快速、试剂耗材消耗少、灵敏度高,适用于快速处理大批量糙米中氟虫腈及其代谢产物的残留量检测。     

一种浓香型白酒大曲培曲架及其翻曲装置的设计与应用

大曲是浓香型白酒酿造过程中必不可少的糖化发酵剂,以小麦或多种粮食为主要原料,人工踩制或机械压制成砖状曲块,自然开放的条件下培育而成的粗酶制剂,对大曲酒的风格、产量和质量都有重要的影响。传统制曲生产的人工翻曲操作,其劳动强度大,工人操作环境差;因此,发展架子曲是白酒企业技术改造的重要课题。设计了一种浓香型白酒大曲培曲架及其翻曲装置,并分析探讨了该装置在浓香型白酒大曲生产过程中应用。该装置主要包括机座、培曲架及其配套装置等。该装置的配套装置主要构成材质为不锈钢,并经防腐处理,适用于曲房特殊的温度、湿度等环境;满足了浓香型白酒中高温大曲的培曲、翻曲等生产工艺要求,符合设备安全操作的需要,结构简单,减轻了劳动强度,应用该装置培养的成品架子曲质量稳定。     

基于聚类分析的浓缩苹果汁风味品质分析与评价

通过对浓缩苹果汁主要风味物质进行分析,建立其风味品质的客观评价方法,为生产者合理调整工艺提供参考。分别选取风味较好和风味较差的浓缩苹果汁样品,对其挥发性风味物质、有机酸、氨基酸、糖类等主要风味物质进行分析,采用主成分分析、因子分析综合打分、聚类分析等方法筛选出能够有效区分不同风味品质浓缩苹果汁样品的主要风味化合物。选取12批次浓缩苹果汁样品,检测样品中39种主要挥发性风味物质、14种主要氨基酸、6种主要有机酸以及4种主要的糖类等风味物质。根据因子分析综合打分结果,从29种组合中,筛选出能够区分浓缩苹果汁风味的5种主要风味物质,分别为天冬氨酸、丝氨酸、蛋氨酸、果糖和葡萄糖。利用不同年份的8个批次浓缩苹果汁样品对该结果进行了验证,结果表明,这5种风味物质能够有效区分A、B两类浓缩苹果汁。利用筛选出的5种主要风味物质,能够对浓缩苹果汁风味品质进行客观、准确的判别。