DMT1在小肠吸收细胞的摄铁机制

铁是生物体最丰富的微量金属元素之一,小肠是机体铁吸收和铁稳态调节最关键结构,小肠吸收细胞对非血红素铁的吸收摄取主要由二价金属离子转运体(divalent metal transporter1,DMT1)介导的。DMT1对铁的吸收转运主要通过囊泡运输和载体运输实现的。囊泡运输主要包括DMT1形成吸收铁的囊泡、与apo-Tf囊泡融合、分离、分选转运完成的;载体运输则是在肠表面H+电化学梯度的驱动下将铁转入细胞内的。本文着重介绍了最近国内外关于DMT1在小肠非血红素铁吸收转运中的作用机制的最新研究进展。     

革兰氏阳性细菌铁摄取机制的研究进展

铁是大多数细菌生长存活的基本营养物质,细菌能否从宿主体内摄取足够的铁对于其毒力和致病起着关键的作用.铁在宿主体内主要以游离铁、含铁蛋白和血红素三种形式存在.细菌可以通过复杂的铁摄取机制来获得宿主体内的铁进而感染宿主.因此,探究细菌的铁摄取机制有助更好的了解细菌的生长和致病过程.     

铁过载与糖尿病关系的研究进展

铁是生物体必不可少的微量元素,铁缺乏或铁过载均会导致铁代谢相关疾病。铁缺乏会导致缺铁性贫血,铁过载主要表现为遗传性血色素沉着症(HH)。研究发现HH与二型糖尿病(typeⅡ diabetes mellitus,T2DM)之间存在某种关联。大量的临床、流行病学和基础实验研究均表明组织铁沉积可能与T2DM的发生及其并发症有关。血清铁蛋白(ferritin)已经成为T2DM患者的重要检测指标之一。然而铁在T2DM发病过程中的作用机制研究较少。最新研究表明缺氧诱导因子1α(hypoxia-inducible factor 1α,HIF-1α)是连接铁代谢与糖代谢的关键因子。通过减少饮食中血红素铁的摄取、放血以及用铁螯合剂处理可以起到对HH诱导的T2DM的预防和治疗作用。     

不同强度游泳运动对大鼠不同组织铁分布及血清铁状态的影响

目的观察不同负荷的游泳运动对大鼠血清铁状态及不同组织铁含量的影响. 方法将30只雌性SD大鼠随机分为对照组、适度运动组和过度运动组,运动训练10周后,测定血清铁、血清未饱和铁结合力、总铁结合力、转铁蛋白饱和度及心、肝、脾、十二指肠、腓肠肌和骨髓非血红素铁含量的变化.结果1.过度运动组血清铁和转铁蛋白饱和度显著降低,适度运动组血清铁升高;2.过度运动组和适度运动组腓肠肌非血红素铁含量显著增加,而骨髓铁含量均有不同程度的降低,其中过度运动组降低最多. 结论适度的运动可以促进机体铁的动员,而过度运动则会破坏机体铁代谢的动态平衡,引起非贫血性铁缺乏.     

铁超载在肝脏疾病中的研究进展

铁是生物体必需的微量元素，含铁蛋白质在细胞功能中起关键作用。铁超载可通过电子传递产生活性氧，引起DNA损伤、氧化应激，造成机体代谢紊乱、组织器官功能障碍。肝脏是机体铁存储的主要脏器，可调节铁的代谢、利用和排出，维持机体铁稳态平衡，铁超载与肝脏疾病的发生发展密切相关。     

铁摄入过量对人体健康的影响

铁摄入过量会造成大量铁在机体内蓄积。当正常的铁储存机制不能容纳总的机体铁时,过量的铁会导致组织炎症、多器官的损伤和纤维化,因为铁是自由基反应的催化剂,可将超氧化物和氢氧化物转变为极其活跃的自由基,从而引起氧化反应导致细胞老化和死亡。本文就铁摄入过量与癌症、肝脏疾病、神经变性性疾病、心血管疾病、免疫系统疾病等对人体健康的影响作一综述。     

铁代谢及铁蛋白与心血管疾病关系的现状分析

铁是一种双面元素,铁稳态的紊乱对部分组织有害。研究表明心脏是受铁代谢紊乱影响的主要器官之一。铁代谢障碍无论是缺乏还是超载,都与心血管疾病的发生率和死亡率增加有关。铁蛋白是研究铁状态的唯一指标,被认为是诊断铁状态的最佳单一测定。就目前研究结果来看,多种心血管疾病与铁代谢紊乱有关,如冠心病、心力衰竭、心肌病、阿霉素导致的心肌损伤及心肌缺血再灌注。明确铁代谢紊乱引起细胞损伤的机制,并进一步研究铁蛋白与铁代谢紊乱所引起的心血管疾病的相关性,可以为临床上提供便捷、准确的检测方法,并可指导临床治疗。     

hepcidin:连接免疫和铁代谢的桥梁

铁是人体必需的金属元素。铁在机体内参与很多反应，如电子传递、氧化磷酸化、三羧酸循环，以及在血色素和肌血球素中参与氧的转运等。所以铁缺乏会引起一系列疾病，如缺铁性贫血、神经功能紊乱、机体防御能力降低、含铁氧化酶（细胞色素类、过氧化氢酶、脂质过氧化酶等）功能下降、能量代谢障碍等。因此，人体存在着严格的铁代谢调节机制，确保体内铁始终处于正常生理水平。[第一段]     

铁抑素-1抑制血红素诱导的小鼠海马神经元铁死亡

目的:研究铁抑素-1(Fer-1)对血红素诱导的小鼠海马神经元铁死亡的影响。方法:小鼠海马神经元细胞系HT22细胞分为对照组(control)、血红素处理组(hemin)以及血红素和铁抑素-1联合处理组(hemin+Fer-1)。利用CCK-8试剂盒检测各组细胞的活性,利用活性氧荧光探针(DCFH-DA)法检测各组细胞中反应性活性氧(ROS)的含量,利用商品化试剂盒检测谷胱甘肽(GSH)的含量,利用JC-1试剂盒检测线粒体膜电位(MMP)变化,利用Western Blot和real time RT-PCR检测细胞中谷胱甘肽过氧化物酶4(GPX4)的表达。结果:血红素处理可降低HT22细胞活性,诱发氧化应激,破坏线粒体膜电位(MMP),并下调GPX4表达而诱导铁死亡。相反,Fer-1可以使细胞活性恢复,降低氧化应激反应,从而抑制HT22细胞铁死亡。结论:血红素中诱发了HT22细胞内脂质过氧化反应,引起线粒体损伤及铁死亡;铁死亡抑制剂Fer-1可以阻断血红素这种细胞毒性。     

肥胖及减肥手术对铁代谢的影响

铁是人体内含量最丰富的微量元素,对于维持人体正常生理活动非常重要.最近的研究发现炎症可上调铁调素水平,减少铁的吸收.肥胖与慢性炎症反应相关,肥胖的患者常存在缺铁.传统治疗肥胖的方法主要包括控制饮食、运动及药物,白减肥手术开始用于治疗病态肥胖,患者体质量能显著地减轻,但术后由于解剖结构等改变,可以引起铁的变化,缺铁性贫血在胃旁路术后较常见.     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

Hypo- und Hypermagnesämie aus kardiologischer Sicht

Zusammenfassung Eine Reihe pathologischer Zustände bedingen Magnesiummangel. Zustände mit Hypermagnesämie sind ebenfalls bekannt, doch wesentlich seltener. Für den Kardiologen beachtenswert ist, daß unter Therapie mit bestimmten Diuretica bei Herzinsuffizienz, bei Herzinfarkt, Kardiomyopathie, Digitalisintoxikation und bestimmten Herzrhythmusstörungen Hypomagnesämie beobachtet wurde. Leider kann in der klinischen Routine nur ein extracelluläres Magnesiumdefizit durch Serumbestimmungen gemessen werden; über Magnesiummangel einzelner Organe kann nichts ausgesagt werden. Hinweise für Magnesiummangel geben aber neben der Messung des Serumspiegels Anamnese, klinischer Befund, bestimmte EKG-Veränderungen wie auch evtl. Hypokalämie, ein Zustand, bei dem sich oft — besonders bei Aldosteronismus — parallele Veränderungen zeigten.Tierexperimente deuten darauf hin, daß infarktähnliche Läsionen unter Magnesiummangel entstehen, doch ob Herzinfarkt beim Menschen durch Magnesiummangel ausgelöst werden kann, ist noch ungeklärt. In Leichenherzen zeigte sich im Infarktgebiet neben Calciumakkumulation signifikanter Magnesiumverlust, wobei unklar blieb, ob sich Ursache oder Folge des Infarktes widerspiegelten. Falls ein ursächlicher Zusammenhang besteht, ist er im Myokardstoffwechsel selbst zu suchen, wie bei der Alkoholkardiomyopathie, wo myokardialer Magnesiummangel zumindest als pathogenetischer Teilfaktor anerkannt wird. Andererseits versucht man aber auch Beziehungen zwischen Atherosklerose, Blutgerinnung und Hypomagnesämie herzustellen, in der Meinung, daß Magnesiummangel auch über den coronaren Pathomechanismus des Herzinfarktes wirken könnte. Sicher scheint, daß gewisse EKG-Veränderungen und Herzrhythmusstörungen durch einen irritierten Magnesiumhaushalt bedingt sein können, da sie bei Gabe bzw. Entzug von Magnesium verschwinden. Daß Magnesiummangel die Glykosidtoleranz verringert, wird tierexperimentell bestätigt. Unter Hypomagnesämie bewirkt Acetylstrophanthidin eher und länger Rhythmusstörungen als ohne, außerdem lassen diese sich durch Magnesiumgaben eliminieren. Da in gewissen Fällen spontane und digitalisinduzierte Herzrythmusstörungen durch Magnesiuminjektionen beseitigt wurden, scheint Magnesium als Therapeuticum angebracht. Einsatz verschiedener Magnesiumsalze bei Angina pectoris, degenerativen Herzerkrankungen und Herzinsuffizienz ohne geprüften und offensichtlich gestörten Magnesiumhaushalt ist fragwürdig, weil keine eindeutigen klinischen Erfolgsbeweise vorliegen. Immerhin mag es aber larvierte, durch Serumbestimmungen nicht erfaßbare Mangelzustände geben. Allgemein erscheint es aus kardiologischer Sicht ratsam, den Magnesiumhaushalt zu überwachen und in entsprechenden Fällen auszugleichen, um möglichen Myokardläsionen oder fatalen Herzrhythmusstörungen entgegenzuwirken.     

Environmental risk factors and their role in the management of atopic dermatitis

Introduction: The etiology of atopic dermatitis (AD) is multifactorial with interaction between genetics, immune and environmental factors.

Areas covered: We review the role of prenatal exposures, irritants and pruritogens, pathogens, climate factors, including temperature, humidity, ultraviolet radiation, outdoor and indoor air pollutants, tobacco smoke exposure, water hardness, urban vs. rural living, diet, breastfeeding, probiotics and prebiotics on AD.

Expert commentary: The increased global prevalence of AD cannot be attributed to genetics alone, suggesting that evolving environmental exposures may trigger and/or flare disease in predisposed individuals. There is a complex interplay between different environmental factors, including individual use of personal care products and exposure to climate, pollution, food and other exogenous factors. Understanding these complex risk factors is crucial to developing targeted interventions to prevent the disease in millions. Moreover, patients require counseling on optimal regimens for minimization of exposure to irritants and pruritogens and other harmful exposures.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

HLA genes in Amerindians from Mexico San Vicente Tancuayalab Teenek/Huastecos

Huastecos or Teenek Amerindians are presently living at North East Mexico (San Luis Potosi State). They have probably one of the most ancient culture of Mexico and Central America together with Mayas and Olmec groups with which also show close relationships. Proximity to Atlantic Ocean/Mexican Gulf originated that Spaniards had very early contact with them at about 1519 CE or before. In the present paper we have aimed to study HLA gene profile which may be useful for HLA and disease epidemiology and transplant programs in Teeneks. HLA-DRB1*04:07, -DRB1*14:06 and -DRB1*04:11 have been found in high frequency like in other Amerindian groups. High frequency typical Amerindians HLA extended haplotypes have been found, such as A*02-B*35-DRB1*04:07-DQB1*03:02; A*68-B*39-DRB1*04:07-DQB1*03:02 and A*02-B*39-DRB1*04:07-DQB1*03:02; also new haplotypes have been described, like A*02-B*52-DRB1*04:11-DQB1*03:02, A*68-B*35-DRB1*14:02-DQB1*03:01 and A*68-B*40-DRB1*16:02-DQB1*03:01. Genetic proximity is observed not only to linguistically close Mayans, but also to Mazatecans, Mixtecans and Zapotecans, who speak an altogether different languages; it shows once more that genes and languages do not correlate. This population was greatly diminished after European contact between 1500 and 1600 years CE; in fact, North and South America First Inhabitants population was brought from 80 down to 8 million people because of diseases (i.e.: measles, smallpox or influenza), slavery and war.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.