骨髓间充质干细胞静脉移植脊髓损伤大鼠肿瘤坏死因子α及 白细胞介素1β的表达

背景：研究认为间充质干细胞的营养支持在脊髓损伤治疗中起了主要作用,其同损伤宿主神经组织间的相互作用可导致一些不利于损伤修复的炎症因子表达减少。 目的：观察大鼠骨髓间充质干细胞静脉注射移植对脊髓损伤后肿瘤坏死因子α、白细胞介素1β 表达的影响。 方法：运用改良Allen法制备大鼠T10脊髓外伤性截瘫模型,随机分为对照组和骨髓间充质干细胞移植组,设未损伤脊髓的假手术组做对照。骨髓间充质干细胞移植组、假手术组均接受大鼠骨髓间充质干细胞静脉注射移植,对照组静脉注射等量PBS。 结果与结论：对照组和骨髓间充质干细胞移植组损伤脊髓肿瘤坏死因子α、白细胞介素1β蛋白表达较假手术组有明显增加(P < 0.05);骨髓间充质干细胞移植组与对照组比较, 肿瘤坏死因子α、白细胞介素1β蛋白表达受到明显抑制(P < 0.05)。提示大鼠骨髓间充质干细胞静脉移植后能使损伤脊髓局部的肿瘤坏死因子α、白细胞介素1β表达程度降低。这可能是改变脊髓损伤区的微环境,减少脊髓继发性损伤,促进损伤大鼠运动功能恢复的机制之一。     

骨髓间充质干细胞移植抑制肺气肿炎症反应及细胞凋亡

背景:骨髓间充质干细胞移植可以通过旁分泌机制改变周围区微环境,通过促进血管新生、抑制细胞凋亡和维护自主神经功能稳定等作用,可用于治疗肺功能严重损害。目的:通过骨髓间充质干细胞移植,观察其对实验性肺气肿炎症反应及细胞凋亡的抑制作用。方法:24只Wistar雌性大鼠随机分健康对照组、模型组及实验组,后两组烟熏加气管内滴注猪胰弹性蛋白酶法建立肺气肿模型。建模后大鼠尾静脉注射骨髓间充质干细胞,观察细胞移植后大鼠肺组织的病理学变化、检测支气管肺泡灌洗液中细胞数及肿瘤坏死因子水平、肺泡壁细胞凋亡指数。结果与结论:模型组、实验组大鼠的肺组织都存在不同程度的肺气肿病理改变,实验组较轻,差异有显著性意义(P0.01);实验组肿瘤坏死因子水平及肺组织细胞凋亡指数均低于模型组,差异有显著性意义(P0.01)。提示骨髓间充质干细胞通过抑制实验性肺气肿炎症反应及细胞凋亡,改善了肺气肿病理学,对肺气肿有明显的治疗作用。     

促红细胞生成素基因修饰骨髓间充质干细胞移植治疗大鼠脑梗死

背景：促红细胞生成素具有神经元的保护及促进神经再生的作用。目的：观察促红细胞生成素修饰的骨髓间充质干细胞尾静脉移植对大鼠脑梗死的治疗效果。方法：用Western blot鉴定外源人促红细胞生成素基因在骨髓间充质干细胞中的表达。采用线栓法建立大鼠大脑中动脉阻塞模型,模型组尾静脉注射PBS、骨髓间充质干细胞组注射骨髓间充质干细胞悬液,促红细胞生成素-骨髓间充质干细胞组注射转染了促红细胞生成素的骨髓间充质干细胞悬液。移植后3 d及移植后1,2,3,4 周行改良神经功能评分,检测神经功能的损伤情况。移植后4 周将大鼠麻醉后断头取脑,RT-PCR检测脑组织中bcl-2/bax基因表达变化,用原位末端标记法测定细胞凋亡情况、苏木精-伊红染色及荧光显微镜观察PKH26标记的骨髓间充质干细胞的存活和分布情况。结果与结论：Western blot结果显示,转染人促红细胞生成素基因的骨髓间充质干细胞体外能表达促红细胞生成素蛋白。移植后1-4周,骨髓间充质干细胞组和促红细胞生成素-骨髓间充质干细胞组神经缺损评分明显低于模型组(P < 0.05,P < 0.01)。与骨髓间充质干细胞组及模型组相比,大鼠脑梗死区组织促红细胞生成素-骨髓间充质干细胞组bcl-2基因的表达明显增高(P < 0.05),bax基因的表达明显降低(P < 0.05),凋亡细胞明显减少,PKH26阳性细胞数明显增多(P < 0.05)。结果证实,促红细胞生成素修饰的骨髓间充质干细胞尾静脉移植对脑梗死大鼠脑梗死疗效较好。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

肿瘤坏死因子α刺激骨髓间充质干细胞表达及分泌肝细胞生长因子

背景：有研究表明,肿瘤坏死因子α可以刺激骨髓间充质干细胞发挥免疫抑制功能,并促进骨髓间充质干细胞表达肝细胞生长因子。 目的：观察肿瘤坏死因子α刺激大鼠骨髓间充质干细胞是否可以促进肝细胞生长因子的表达及分泌。 方法：全骨髓贴壁法分离、纯化SD大鼠骨髓间充质干细胞,传代至第三四代使用。以100 µg/L肿瘤坏死因子α预刺激骨髓间充质干细胞 5 h后弃去培养基,换上新鲜培养基作为实验组,以正常培养的骨髓间充质干细胞为空白组。采用倒置相差显微镜观察细胞形态;流式细胞仪鉴定骨髓间充质干细胞表面标记物CD29、CD34、CD44、CD45的表达;RT-PCR 、Western blot检测细胞肝细胞生长因子mRNA及蛋白表达;ELISA测定细胞上清液中肝细胞生长因子水平。 结果与结论：获得的骨髓间充质干细胞形态均一,呈典型的旋涡样生长。骨髓间充质干细胞表达CD29⁺99.45%,CD34^-97.91%、CD44⁺99.52%、CD45^-98.42%;骨髓间充质干细胞中肝细胞生长因子 mRNA及蛋白与上清液中肝细胞生长因子表达量呈时间依赖性增加,实验组肝细胞生长因子 mRNA及蛋白与上清液中肝细胞生长因子的表达量明显高于空白组(P < 0.01)。说明肿瘤坏死因子α刺激骨髓间充质干细胞可以有效促进肝细胞生长因子的表达及分泌。     

骨髓间充质干细胞治疗肾缺血再灌注损伤的旁分泌机制

背景：骨髓间充质干细胞已用于肾缺血再灌注损伤修复的实验动物研究。 目的：探讨骨髓间充质干细胞治疗肾缺血再灌注损伤的旁分泌机制。 方法：体外培养、纯化并体外DAPI标记大鼠骨髓间充质干细胞,经下腔静脉移植入肾缺血再灌注损伤模型大鼠体内,观察骨髓间充质干细胞对肾缺血再灌注损伤肾功能的保护作用以及在受体鼠体内的迁移情况,并应用免疫组织化学法检测骨髓间充质干细胞治疗后第2天缺血肾脏组织中血管内皮生长因子、肿瘤坏死因子α细胞因子的表达。 结果与结论：与注射生理盐水的对照组比较,细胞移植组大鼠血清肌酐和尿素氮水平在移植后第1、2天明显降低(P < 0.05),但细胞移植组移植后第1、2天肾组织中均未见DAPI阳性细胞;第3、4天则逐渐可见DAPI阳性细胞。免疫组织化学染色结果显示,与对照组相比,移植后第2天肾组织中可见较多血管内皮生长因子阳性细胞,而肾组织中肿瘤坏死因子α阳性细胞明显减少。结果显示旁分泌机制参与了骨髓间充质干细胞治疗肾缺血再灌注损伤。     

骨髓间充质干细胞移植修复慢性阻塞性肺病气道损伤

背景：间充质干细胞能够分化为肺实质细胞并参与肺部损伤的修复,为间充质干细胞在慢性阻塞性肺病中的应用提供了新的方法。 目的：观察骨髓间充质干细胞移植对大鼠慢性阻塞性肺病气道损伤的修复作用。 方法：将24只雌性大鼠随机分为4组：①骨髓间充质干细胞移植组(12只)：采用熏烟+脂多糖法建立慢性阻塞性肺病大鼠模型,于造模后第1天经尾静脉输注1 mL CM-Dil标记的骨髓间充质干细胞。②骨髓间充质干细胞对照组(4只)：在第1天和第14天经气管注入生理盐水300 μL,经尾静脉输注1 mL CM-Dil标记的骨髓间充质干细胞。③慢性阻塞性肺病模型组(4只)：采用熏烟+脂多糖法建立慢性阻塞性肺病大鼠模型,于造模后第1天经尾静脉输注1 mL PBS。④健康对照组(4只)：在第1天和第14天经气管注入生理盐水300 μL,经尾静脉输注1 mL PBS。在各组大鼠注射骨髓间充质干细胞后的第1,7,15,30天,进行病理学和血清学检测。 结果与结论：①苏木精-伊红染色结果显示：骨髓间充质干细胞移植组大鼠肺气肿和气道病变较慢性阻塞性肺病模型组轻,但较骨髓间充质干细胞对照组和健康对照组严重。②移植后第1天,骨髓间充质干细胞移植组外周血白细胞总数和中性粒细胞比例高于骨髓间充质干细胞对照组和健康对照组(P < 0.05),随着时间延长,骨髓间充质干细胞移植组白细胞总数和中性粒细胞比例不断降低。③移植后第1天,骨髓间充质干细胞移植组外周血白细胞介素10水平低于骨髓间充质干细胞对照组和健康对照组(P < 0.05),肿瘤坏死因子α和粒细胞集落刺激因子水平高于骨髓间充质干细胞对照组和健康对照组(P < 0.05)。随着移植时间的延长,骨髓间充质干细胞移植组外周血肿瘤坏死因子α水平不断降低,白细胞介素10水平不断升高,粒细胞集落刺激因子水平先升高再降低,其中第7天水平最高。④CM-Dil染色联合免疫组化检测提示,部分 CM-Dil阳性细胞同时CC16表达阳性。结果显示经尾静脉注射骨髓间充质干细胞能够改善慢性阻塞性肺病大鼠的肺部病理损伤,通过分化为气管黏膜上皮细胞以及参与免疫调节对气道进行修复。 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

骨髓间充质干细胞移植后颈动脉损伤球囊核转录因子κBp65和增殖细胞核抗原的表达

背景：炎症反应在经皮腔内冠状动脉支架置入后再狭窄的发生中起了重要作用。近年的研究发现,骨髓间充质干细胞具有较强的免疫调节特性。然而骨髓间充质干细胞对损伤血管炎症反应影响的报道较少。 目的：观察骨髓间充质干细胞移植对兔颈动脉球囊损伤后核转录因子κBp65和增殖细胞核抗原表达的影响,分析其与内膜增殖作用的相关性。 方法：制作颈动脉粥样硬化狭窄兔模型36只,随机分成2组,骨髓间充质干细胞移植组球囊损伤后接受4’,6-二脒基-2-苯基吲哚标记的骨髓间充质干细胞移植,对照组球囊损伤后接受等量的PBS液注射。造模前和细胞移植后7,14,28 d分别抽取外周血,ELIAS法检测血清肿瘤坏死因子α和白细胞介素6的质量浓度;细胞移植后14 d取血管组织,采用免疫组织化学分析法测定局部组织核转录因子κBp65和增殖细胞核抗原的表达,细胞移植后28 d对血管组织行苏木精-伊红染色检测血管形态学变化。 结果与结论：细胞移植后14 d 骨髓间充质干细胞移植组损伤血管局部核转录因子κBp65和增殖细胞核抗原的表达均较对照组明显减少(P < 0.05)。细胞移植后7,14,28 d骨髓间充质干细胞移植组血清肿瘤坏死因子α和白细胞介素6质量浓度均较对照组显著降低(P < 0.05)。细胞移植后28 d 骨髓间充质干细胞移植组新生内膜面积、新生内膜/中膜面积及血管狭窄率均较对照组显著降低(P < 0.05)。提示骨髓间充质干细胞可能通过抑制损伤血管核转录因子κBp65活性,减轻炎症反应进而下调增殖细胞核抗原的表达,对抑制损伤血管新生内膜的增殖可能发挥有益作用。     

人骨髓间充质干细胞对肝癌细胞的生物学效应

背景：肝癌的转移特性是影响预后的关键因素,观察人骨髓间充质干细胞对肝癌转移行为的影响,对于提高肝癌患者的生存期具有重要意义。 目的：探讨人骨髓间充质干细胞对不同转移潜能肝癌细胞生物学特性的影响。 方法：Transwell下室加入人骨髓间充质干细胞,上室加入高、低转移潜能肝癌细胞悬液,共培养36 h酶标仪检测吸光度值及细胞计数法观察肝癌细胞侵袭能力的变化。CCK-8 法检测人骨髓间充质干细胞对高低转移潜能肝癌细胞增殖能力的影响。PCR检测人骨髓间充质干细胞与高低转移潜能肝癌细胞共培养前后转移相关因子骨桥蛋白、唾液酸蛋白、整合(α-V)以及增殖相关基因转化生长因子β1和程序化凋亡因子的表达。 结果与结论：①共培养组的肝癌细胞迁移数量显著少于单独培养组,经酶标仪半定量检测肝癌细胞侵袭性显示,共培养组吸光度值明显低于单独培养组,差异有显著性意义(P < 0.05)。②高转移潜能肝癌细胞与人骨髓间充质干细胞共培养组转移相关因子骨桥蛋白和骨唾液酸蛋白表达显著下降(P < 0.05),但整合(α-V)基因表达未出现明显改变(P > 0.05)。低转移潜能肝癌细胞与人骨髓间充质干细胞共培养组转移相关因子骨桥蛋白、骨唾液酸蛋白以及整合(α-V)基因表达显著下降(P < 0.05)。③经酶标仪半定量检测肝癌细胞增殖能力显示,共培养组吸光度值明显高于单独培养组,差异有显著性意义(P < 0.05)。④高转移潜能肝癌细胞与人骨髓间充质干细胞共培养组的转化生长因子β1基因表达显著上调(P < 0.05);但程序化凋亡因子基因表达无明显改变(P > 0.05)。低转移潜能肝癌细胞与人骨髓间充质干细胞共培养组的转化生长因子β1、程序化凋亡因子基因表达均显著上调(P < 0.05)。以上结果提示人骨髓间充质干细胞与肝癌细胞共培养后,肝癌细胞侵袭能力明显下调,增殖能力明显提高。 中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程全文链接：     

干细胞生长因子和粒细胞集落刺激因子与心肌梗死大鼠体内骨髓间充质干细胞的迁移

背景：外周静脉移植间充质干细胞只有1%~5%的移植细胞能归巢到心肌梗死区域。 目的：观察干细胞生长因子、粒细胞集落刺激因子对骨髓间充质干细胞归巢的影响。 方法：采用贴壁培养法分离培养SD大鼠骨髓间充质干细胞,取传至3~5代细胞。建立SD大鼠急性心肌梗死模型,干细胞生长因子组、粒细胞集落刺激因子组、干细胞生长因子+粒细胞集落刺激因子组在骨髓间充质干细胞移植前3 d和移植后3 d单独或混合皮下注射干细胞生长因子、粒细胞集落刺激因子,骨髓间充质干细胞组不注射细胞因子。 结果与结论：荧光显微镜下观察,骨髓间充质干细胞迁移至心肌梗死组织,骨髓间充质干细胞组、干细胞生长因子组、粒细胞集落刺激因子组迁移至心肌梗死区的骨髓间充质干细胞数量没有明显的区别(P > 0.05),干细胞生长因子+粒细胞集落刺激因子组的骨髓间充质干细胞数量明显高于其他3组(P < 0.05)。免疫荧光组织化学显示,植入的部分骨髓间充质干细胞表达心肌特异蛋白cTnI。结果说明干细胞生长因子和粒细胞集落刺激因子两种细胞因子联合应用可以促进骨髓间充质干细胞归巢至心肌梗死区域,在体内微环境的诱导下,骨髓间充质干细胞能够转化为心肌样细胞。     

神经节苷脂联合骨髓间充质干细胞移植治疗颅脑创伤

背景：骨髓间充质干细胞可以在体内外诱导下分泌神经营养因子,还可向神经元方向转化,从而促进创伤脑组织再生修复,但骨髓间充质干细胞又存在生存周期短的问题而影响其发挥对损伤脑组织的保护作用。目的：观察骨髓间充质干细胞移植联合神经节苷脂治疗大鼠颅脑创伤的效果。方法：60只Wistar大鼠采用液压颅脑损伤仪制备大鼠重型颅脑创伤模型,建模24 h后按照随机表法随机分为3组：模型组经尾静脉注入1 mL DMEM培养液,移植组经尾静脉注入1 mL(1×10¹⁰ L^-1)骨髓间充质干细胞悬液,联合组经尾静脉注入1 mL(1×10¹⁰ L^-1)骨髓间充质干细胞悬液以及经腹腔注射神经节苷脂水溶液(30 mg/kg),1次/d,共3 d。伤后24 h,细胞移植后3 d及1,2,3,4 周依据Longa 5分法进行神经功能行为学评分;移植后3 d应用RT-PCR、Western blot检测创伤脑组织中水通道蛋白4基因和蛋白的表达;移植后1周,行苏木精-伊红染色观察创伤脑组织病理变化。结果与结论：移植后3 d及1,2,3,4 周,联合组神经行为学功能评分低于移植组(P < 0.05),移植组低于模型组(P < 0.05);移植后3 d,模型组创伤脑周围组织水通道蛋白4蛋白及mRNA的表达高于移植组(P < 0.05),移植组高于联合组(P < 0.05);苏木精-伊红染色观察到联合组脑组织恢复明显优于模型组和移植组(P < 0.05)。结果提示骨髓间充质干细胞移植联合神经节苷脂可以明显改善颅脑创伤大鼠的神经行为学功能。中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程      

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

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.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

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.     

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.     

Class II HLA in Georgia Caucasus Tbilisi Georgians and their Mediterranean ancestry: The Usko Mediterranean languages

Georgia (or Sakartvelo in its own language) is a South Caucasus Mts. country with its easternmost part is enigmatically named Iberia, like the Iberian Peninsula, which may refer to rivers “Kura” and “Ebro” or their valleys respectively. Most of their inhabitants speak Georgian which is included within Dene-Caucasian group and Usko-Mediterranean subgroup of languages. The latter includes Basque, Berber, ancient Iberian-Tartessian, Etruscan, Hittite, Minoan Lineal A and others. In the present paper, HLA class II -DRB1 and -DQB1 alleles has been studied and extended haplotypes calculated. Most frequent haplotypes are also of Mediterranean origin (i. e.: (A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*51)-DRB1*13:01-DQB1*06:03, or (A*24-B*35)-DRB1*01:01-DQB1*05:01) and DA genetic distances show that closest world populations to Georgians are Mediterraneans. Georgians also show common extended haplotypes ((A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*13)-DRB1*07:01-DQB1*02:01 and (A*03-B*35)-DRB1*11:01-DQB1*03:01) with Svan people, a secluded population in North Georgia mountains. We can conclude that Georgians belong to a very old Mediterranean substratum according to both linguistics (Usko Mediterranean languages) and HLA genetics.     

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.     

État de l’art : nouveaux anticoagulants et transfusion

Direct oral anticoagulants (DOAC) are indicated for stroke prevention in atrial fibrillation and for the prevention and treatment of venous thromboembolism. As any anticoagulant, they are associated with a bleeding risk. Management of DOAC-induced bleeding is challenging. Idarucizumab, antidote for dabigatran, is currently available and is part of the therapeutic strategy, whereas antidotes for anti-Xa agents are under development. Activated or non-activated prothrombin concentrates are proposed, although their efficacy to reverse DOAC is uncertain. We propose an update on DOAC-associated bleeding management, integrating the availability of idarucizumab and the critical place of DOAC concentration measurements.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.