急性心肌梗死患者动员和采集外周血干细胞的安全性观察

目的　观察急性心肌梗死 (AMI)患者外周血干细胞分离与采集的可行性与安全性。方法　我院自 2 0 0 3年 11月至 2 0 0 4年 1月收治的 2 7例AMI患者 ,入院后在常规急性心肌梗死治疗 (药物与介入治疗 )基础上随机给予包涵体型粒细胞集落刺激因子 (包涵体型G CSF ,商品名 :惠尔血 )或分泌型G CSF(商品名 :金磊赛强 ) ,30 0～ 6 0 0 μg d皮下注射连续 5d ,第 6天分离外周血干细胞 ,进行经皮经腔冠状动脉内移植自体外周血干细胞。观察外周血干细胞动员和采集过程中的不良反应。结果　AMI患者在外周血干细胞的动员期间不良反应发生率为 4 4 4 % (12 2 7) ,在外周血干细胞采集过程中的不良反应发生率约为 2 5 9% (7 2 7) ,未见其他不良反应。结论　AMI患者经G CSF动员后 ,分离与采集外周血干细胞是安全的。     

自体外周血干细胞经冠状动脉移植治疗急性心肌梗死的近期临床疗效观察

目的观察经皮经腔冠状动脉内移植外周血干细胞(PBSC)治疗急性心肌梗死(AMI)的可行性与近期临床疗效.方法自2003年11月至2004年8月共入选AMI患者45例,AMI患者入院后在常规急性心肌梗死治疗(药物与介入治疗)基础上给予包涵体型G-CSF或分泌型G-CSF(商品名惠尔血,金磊赛强),300～6μg/d皮下注射,连用5天.第6日经美国Baxter公司生产的CS3000 PLUS血细胞分离机,分离外周血干细胞悬液57毫升,采集后的干细胞悬液未做任何处理,常规经皮经腔导管技术建立梗死相关动脉(IRA)通道,利用OVERTHEWIRE球囊封闭IRA,并将分离的PBSC经PBSC经over the wire导管中心腔注入IRA.术前、术后6月应用超声心动图评价全心动能及局部心肌节段运动评分.结果术后6个月随访病例13例显示移植前后左室射血分数(LVEFD)分别为0.44、0.60,(P=0.008);移植前后室壁运动积分指数(WISM)分别为1.23、1.11,(P=0.100);移植前后左室舒张末期容积(LVDD)分别为52.42、52.00,(P=0.591)结论经皮经腔冠状动脉内移植外周血干细胞治疗急性心肌梗死安全可行,能显著改善左室射血分数.     

自体外周血干细胞移植治疗急性心肌梗死安全性的观察

目的　观察经皮经腔冠状动脉内移植自体外周血干细胞 (PBSC)治疗急性心肌梗死 (AMI)的可行性与安全性。方法　患者入院后在常规急性心肌梗死治疗 (药物与介入治疗 )基础上给予包涵体型G CSF(商品名惠尔血 ) 30 0～ 6 0 0 μg/d皮下注射 ,连续 5d ;或分泌型G CSF(商品名金磊赛强 ) ,6 0 0 μg/d皮下注射 ,连用 5d。第 6d经美国Baxter公司生产的CS30 0 0PLUS血细胞分离机 ,分离外周血干细胞悬液 5 0mL ,采集后干细胞未做任何处理 ,常规经皮经腔导管技术建立梗死相关动脉 (IRA)通道 ,利用over the Wire球囊封闭IRA ,并将分离的PBSC经Over the Wire导管中心腔注入IRA。在外周血干细胞动员时观察有无骨痛 ,乏力 ,皮疹 ,发热 ,胃肠道反应 (恶心、呕吐、便秘 ) ,心绞痛或心衰加重及一些少见的并发症 :自发性脾破裂、严重化脓性感染、高凝状态、自身免疫性疾病等发生 ;在外周血干细胞分离及采集过程中观察有无低钙性口周麻木、抽搐 ,迷走神经反应性面色苍白、晕厥 ,低血容量性面色苍白、晕厥 ,心绞痛发作 ,心衰加重等 ;在自体外周血干细胞经冠状动脉内回输过程中可出现心律失常 ,如 :窦性心动过缓 (球囊封堵所致 )、窦性停搏 (窦停 )或三度房室传导阻滞 (AVB) (球囊刺激支架近端引起严重的冠脉痉挛所致 )、室颤     

粒细胞集落刺激因子动员自体外周血干细胞移植治疗急性心肌梗死的临床研究

目的观察经皮经腔冠状动脉内移植自体外周血干细胞(PBSC)治疗急性心肌梗死(AMI)的疗效。方法自2003年11月至2005年1月共入选AMI患者70例,随机分为干细胞移植组和对照组,两组均为35例。干细胞治疗组在常规AMI治疗(药物与介入治疗)基础上应用粒细胞集落刺激因子(GCSF)皮下注射动员自体骨髄干细胞,连用5天,第6天分离外周血干细胞悬液,将采集后的干细胞悬液经OVERTHEWIRE球囊导管中心腔注入梗死相关动脉(IRA),进行外周血干细胞移植;对照组经AMI常规方法(药物与介入)治疗。在外周血干细胞动员、采集及经冠状动脉回输过程中观察其不良反应。两组患者在移植前及移植后6个月应用超声心动图评价左室形态及心功能变化,室壁节段性运动积分;比较两组患者生存率及心脏事件发生率。结果6个月时干细胞移植组心脏收缩末容积(ESV)明显减小[(63.8±23.9)ML比(52.6±20.3)ML,P=0.01],舒张末容积(EDV)无显著性变化[(134.2±36.7)ML比(119.2±30.3)ML,P=0.07];左室射血分数(LVEF)显著增高[(50.0±8.2)%比(57.1±7.8)%,P<0.001];左室壁节段性运动积分指数(WMSI)明显减低[(1.219±0.190)比(1.101±0.118),P<0.001]。对照组介入术前及术后6个月随访ESV、EDV、LVEF及WMSI均无统计学差异(P=0.490、0.259、0.117、0.395)。两组术后6个月生存率及心脏事件发生率无统计学差异。不良反应:在PBSC动员、分离、采集及回输中总的不良反应共25例次,其中动员时不良反应占37.1%(13/35),分离和采集中的不良反应占14.3%(5/35),经冠状动脉回输过程中出现的不良反应占20.0%(7/35)。结论经皮经腔冠状动脉内移植自体PBSC治疗AMI可以在近期有效地减少心肌梗死缺血面积,减轻左室重构,改善心功能。     

急性心肌梗塞患者外周血干细胞动员效率及安全性观察

目的:观察急性心肌梗塞(AMI)患者使用粒细胞集落刺激因子(G-CSF)行自体外周血干细胞动员的效率与安全性。方法:我院2003年11月至2004年8月收治的45例AMI患者,入院后在常规急性心肌梗塞 (AMI)药物与介入治疗的基础上给予包涵体型G-CSF(商品名:惠尔血)或分泌型G-CSF(商品名:金磊赛强),300～600μg／d皮下注射,连续5 d,第6 d经美国Baxter公司生产的CS3000PLUS血细胞分离机,分离外周血干细胞,然后进行经皮经腔冠状动脉内移植,进一步治疗AMI。外周血干细胞动员前及动员后第3、 4、5、6、7 d行外周血白细胞(WBC)计数检查,经流式细胞仪测定CD34 的细胞数量。并在外周血干细胞同时观察其副作用。结果:在外周血干细胞动员前及动员后第3、4、5、6、7 d外周血中WBC数量分别为 (8．42±2．59)×109／L、(31．28±8．34)×109／L、(35．24±9．38)×109／L、(37．03±13．07)×109／L、(35．34 ±14．68)×109／L、(20．35±9．22)×109／L;CD34 量分别为(14．89±11．46)×106、(67．78±50．88)× 106、(124．79±136．13)×106、(208．92±206．97)×106、(206．10±164．57)×106、(66．63±56．56)×106; 在动员前及动员后第3、4、5、6、7 d外周血中WBC,CD34 量与动员时间变化曲线均显示曲线高峰在动员后第5 d;患者外周血中CD34 细胞数量与WBC数量变化呈正相关(r=0．835),外周血干细胞动员时不良反应占37．8%(17／45),其中骨痛发生率为15．6％(7／45),低热约6．7%(3／45),乏力约4．4％(2／45),皮疹约4．4％(2／45),心衰加重约4．4％(2／45),自发性脾栓塞约2．2％(1／45);无死亡等严重并发症发生。结论:AMI患者应用G-CSF行外周血干细胞动员安全可行;外周血中CD34 细胞数量与WBC变化曲线高峰均出现在第5 d,且WBC与CD34 细胞数量之间具有正相关,与体重、年龄、性别、AMI时间,无明显相关性。     

自体外周血干细胞移植治疗急性心肌梗死对左心室功能的影响研究

目的探讨自体外周血干细胞(PBSCs)移植治疗急性心肌梗死(AMI)对左心室功能的影响。方法选择2003年11月至2005年9月辽宁省人民医院收治的69例AMI患者,分成干细胞移植组35例和对照组34例,两组均接受药物和冠状动脉内介入治疗,干细胞移植组在此基础上动员自体骨髓干细胞,进行外周血干细胞移植。两组均于治疗前、治疗后6个月进行超声心动图检查。结果6个月时干细胞移植组心脏收缩末容积(ESV)明显减小(P<0·05);舒张末容积(EDV)无显著性变化(P>0·05);左室射血分数(LVEF)显著增高(P<0·05);左室壁节段性运动积分指数(WMSI)明显减低(P<0·001);对照组于介入术前及术后6个月随访ESV、EDV、LVEF及WMSI差异均无显著性意义;术后6个月随访移植组与对照组比较ESV下降,LVEF升高,WMSI降低(P<0·05)。结论自体外周血干细胞治疗AMI可以在近期有效地缩小缺血梗死面积,减轻左室重构,改善心功能。     

急性心肌梗死患者外周血干细胞动员的安全性

目的观察急性心肌梗死(AMI)患者在外周血干细胞动员过程中出现的不良反应,探讨其安全性。方法对44例AMI患者在药物治疗与介入治疗的基础上,给予包涵体型粒细胞集落刺激因子(GCSF)300～600μg/d,皮下注射,连续5d;或分泌型GCSF600μg/d,皮下注射,连续5d,观察出现的不良反应。结果在外周血干细胞的动员过程中共发生不良反应16例(36.4%),骨痛6例(13.6%),低热3例(6.8%),皮疹、乏力、心力衰竭或心绞痛加重各2例(4.5%),脾栓塞1例(2.3%)。结论GCSF动员过程中近期最常见的不良反应为骨痛,外周血干细胞移植治疗AMI已成为一种新的治疗途径。     

自体外周血干细胞经冠状动脉移植治疗冠心病心衰的安全性观察

目的：观察经皮经腔冠状动脉内移植外周血干细胞(PBSC)治疗冠心病心力衰竭(CHF)的可行性与安全性。方法：自2003年11月至2004年8月共入选CHF患者14例,CHF 患者入院后在常规心力衰竭治疗 (药物与介入f台疗)基础上给予包涵体型粒细胞集落刺激因子(G—CSF)(商品名：惠尔血),300～600 μg/d, 皮下注射,连用5 d。第6日经美国 Baxter 公司生产的 CS3000PLUS 血细胞分离机,分离 PBSC 悬液57 ml,采集后的干细胞悬液未做任何处理,常规经皮经腔导管技术建立一支或多支狭窄动脉通道,利用 OVER THE WIRE球囊封闭缺血相关动脉,并将分离的 PBSC 经 OVER THE WIRE 导管中心腔注入缺血相关动脉远端。在PBSC动员时观察有无骨痛、乏力、皮疹、发热、胃肠道反应(恶心、呕吐、便秘),心绞痛或心哀加重,及一些少见的并发症：自发性脾破裂、严重化脓性感染、高凝状态、自身免疫性疾病等发生；在外周血干细胞分离及采集过程中观察有无低钙性口唇麻木、抽搐、迷走神经反射性面色苍白、晕厥、心绞痛发作、心衰加重等；在自体 PBSC 经冠状动脉回输过程中可出现心律失常,如：窦性心动过缓、窦停或Ⅲ度房室传导阻滞、室颤,低血压等。结果：在 PBSC 的动员、分离、采集及回输中总的不良反应11例,其中PBSC动员时不良反应占28.5%(4/14),骨痛占21.4%(3/14),发热占7.1(1/14)；PBSC分离时的不良反应占28.5%(4/ 14),低钙性口唇麻木占21.4%(3/14),心绞痛发作占7.1%(1/14)：PBSC经冠状动脉回输过程中出现的不良反应占21.4%(3/14),频发室早占14.1%(2/14),血压下降占7.1%(1/14)。结论：经皮经腔冠状动脉内移植外周血干细胞治疗充血性心力衰竭安全可行。     

儿童难治性自身免疫性疾病自体外周血干细胞动员采集和分选的临床研究

目的 探讨儿童难治性自身免疫性疾病进行自体外周血干细胞动员采集的安全性和CD34+细胞分选纯化的可行性及其临床意义.方法 8例儿童难治性自身免疫性疾病,包括4例系统性红斑狼疮、2例皮肌炎,1例幼年型类风湿关节炎和1例多发性硬化,予行CD34+细胞纯化的自体外周血干细胞移植.首先采用环磷酰胺(CTX)联合粒细胞集落刺激因子(G-CSF)方案动员外周血干细胞,然后采用CS-3000血细胞分离机采集外周血,通过CliniMACS细胞分选仪分选自体外周血CD34+细胞,将其用保养液配置冻存于-80℃冰箱.采用非清髓内去除T的预处理方案,即卡氮芥+足叶乙苷+阿糖胞苷+马法兰+抗胸腺球蛋白(ATG)或CTX+ATG或CTX+马法兰+ATG,于第0天回输自体外周血CD34+细胞.结果 儿童能够耐受自体外周血干细胞动员采集过程,无动员相关死亡,动员后获得的单个核细胞数和CD34+细胞数的平均值分别为8.35×108/kg和7.92×106/kg,纯化后的白体外周血CD34+和CD3+细胞数的平均值分别为6.28×106/kg和0.71×105/kg.回输后中性粒细胞和血小板的植入中位时间分别为+11d和+15 d.结论 经CTX联合G-CSF方案可动员出足量的外周血干细胞,经CS-3000血细胞分离机采集可获得足够的单个核细胞,在动员过程中原发病无明显进展恶化,患儿能耐受动员方案,采集过程顺利安全;经CliniMACS细胞分选仪分选的自体外周血CD34+细胞纯度高,移植后造血恢复;采用CD34+细胞纯化的自体外周血移植治疗是常规治疗无效的儿童难治性自身免疫性疾病的可选择治疗措施之一.     

自体骨骼肌成肌细胞和骨髓间充质干细胞移植对心肌梗死兔心室重构和心功能的影响

目的：观察经冠状动脉途径移植自体骨骼肌成肌细胞（SMs）和骨髓间充质干细胞（BM—MSCs）到兔急性心肌梗死（AMI）区后对心室重构和心脏功能的影响。方法：取日本大耳白兔60只,随机分为经冠状动脉注射SMs移植组、BM—MSCs移植组、对照组和假手术组,各15只。结扎兔左冠状动脉前降支,建立AMI模型：再灌注后,SMs移植组经冠状动脉注射自体SMs悬液1ml（5×10^6个细胞）;BM—MSCs移植组经冠脉注射自体BM—MSCs悬液1ml（5×10^6个细胞）;对照组注入等量的无血清培养液;假手术组除不结扎左前降支外,其余操作均同对照组。术后4周,以超声心动图仪测量各组左心室舒张末期内径（LVEDd）和左心室射血分数（LVEF）。测定各组兔左心室质量及左心室质量指数并以免疫组织化学法检测各组兔新生血管数目。结果：术后4周,与对照组比较,SMs和BM—MSCs移植组的I。VEF明显提高[（53．21±2．32）％比（61．93±4．11）％比（62．41±2．58）％,P〈0．01],LVEDd明显减小[（12．48±0．84）mm比（11．23±0．44）mm比（11．34±0．36）mm,P〈0．01],左心室质量、左心室质量指数明显减低（P〈0．01）,新生血管数目明显增多[（4．08±1．8）个／HP比（13．6±1．6）个／HP比（12．5±1．7）个／HP,P〈0．05]。两移植组间各指标比较均无显著性（P〉0．05）。结论：经冠状动脉途径自体骨骼肌成肌细胞和骨髓间充质干细胞移植可促进血管新生,改善心肌梗死后心室重构,从而增强心脏收缩功能。     

Advances in Retinal Tissue Engineering

Retinal degenerations cause permanent visual loss and affect millions world-wide. Current treatment strategies, such as gene therapy and anti-angiogenic drugs, merely delay disease progression. Research is underway which aims to regenerate the diseased retina by transplanting a variety of cell types, including embryonic stem cells, fetal cells, progenitor cells and induced pluripotent stem cells. Initial retinal transplantation studies injected stem and progenitor cells into the vitreous or subretinal space with the hope that these donor cells would migrate to the site of retinal degeneration, integrate within the host retina and restore functional vision. Despite promising outcomes, these studies showed that the bolus injection technique gave rise to poorly localized tissue grafts. Subsequently, retinal tissue engineers have drawn upon the success of bone, cartilage and vasculature tissue engineering by employing a polymeric tissue engineering approach. This review will describe the evolution of retinal tissue engineering to date, with particular emphasis on the types of polymers that have routinely been used in recent investigations. Further, this review will show that the field of retinal tissue engineering will require new types of materials and fabrication techniques that optimize the survival, differentiation and delivery of retinal transplant cells.     

International Hemoglobin Information Center Policies - Ihic

Abstract

The levels of the inactive hemoglobin (Hb) pigments [such as methemoglobin (metHb), carboxyhemoglobin (HbCO) and sulfohemoglobin (SHb)] and the active Hb [in the oxyhemoglobin (oxyHb) form] as well as the blood Hb concentration in healthy non pregnant female volunteers were determined using a newly developed multi-component spectrophotometric method. The results of this method revealed values of SHb% in the range (0.0727–0.370%), metHb% (0.43–1.0%), HbCO% (0.4–1.52%) and oxyHb% (97.06–98.62%). Furthermore, the results of this method revealed values of blood Hb concentration in the range (12.608–15.777?g/dL). The method is highly sensitive, accurate and reproducible.     

同型半胱氨酸对血管内皮细胞合成蛋白聚糖的影响

为探讨同型半胱氨酸对血管内皮细胞合成蛋白聚糖的影响，采用400umol／L同型半胱氨酸作用于培养的人脐静脉内皮细胞，以^35S-Na2SO4为示踪物标记细胞合成的蛋白聚糖，通过离子交换层析，凝胶过滤层析分离蛋白聚糖。结果发现，实验组培养液中总蛋白聚糖降低，硫酸乙酰肝素蛋白聚糖及硫酸软骨素-硫酸皮肤素蛋白聚糖含量也降低，但其百分含量未见改变。细胞层中蛋白聚糖未见明显变化。     

Efficacy of combination treatment with cyclosporin A and corticosteroids for acute interstitial pneumonitis associated with dermatomyositis

Interstitial pneumonitis (IP) associated with polymyositis and dermatomyositis (PM/DM) is a serious complication that affects prognosis. We therefore undertook a retrospective multicenter study to examine the efficacy of a combination treatment with cyclosporin A (CsA) and corticosteroids. Fifty-three IP patients with PM/DM (9 PM, 44 DM) were analyzed. Thirty-two patients treated with CsA plus corticosteroids (9 PM, 23 DM) were included in the study. Four parameters, i.e., subjective symptoms, ausculatory sound, chest radiographs, and respiratory index, were serially evaluated. A general evaluation was performed 4 weeks after the start of the combination treatment. All patients with PM and chronic IP with DM, and 52% of those with acute IP with DM were graded as better than partially effective in the general evaluation. In contrast, all patients graded as progressive in the general evaluation had acute IP with DM. It is of note that in acute IP with DM, the survival rate of the group primarily treated with CsA and corticosteroids from the early stage of their disease was significantly higher than that of the group initially treated with corticosteroids alone (P = 0.049). In conclusion, a combination treatment of CsA and corticosteroids from the early stage of disease may be advantageous for patients with IP with PM/DM, especially acute IP with DM.     

Methemoglobin Forming Effect of Dimethyl Trisulfide in Mice

Abstract

Dimethyl trisulfide (DMTS) is a natural organic trisulfide that has been patented as a promising antidotal candidate against cyanide (CN). The primary mode of action of DMTS is as a sulfur donor that enables the conversion of CN to thiocyanate. Recently, it was discovered that DMTS is capable of oxidizing hemoglobin (Hb) to methemoglobin (MetHb) in vitro. The goal of these experiments was to measure the extent of DMTS-induced MetHb formation in vivo. In these experiments, intramuscular (IM) injections of formulated DMTS were administered to mice. Following the IM injection, blood was drawn and analyzed for MetHb using a rapid spectrophotometric method. Methemoglobin levels peaked in a dose-dependent manner between 20 and 30?min., and then began dropping. The highest MetHb levels measured for the 50, 100, 200 and 250?mg/kg doses of DMTS were respectively 3.28, 6.12, 9.69, and 10.76% MetHb. These experiments provide the first experimental evidence that IM administered DMTS generates MetHb in vivo and provide additional evidence for the presence of a secondary therapeutic pathway for DMTS - CN scavenging by DMTS-generated MetHb.     

Efficacy of combination treatment with cyclosporin A and corticosteroids for acute interstitial pneumonitis associated with dermatomyositis

Abstract

Interstitial pneumonitis (IP) associated with polymyositis and dermatomyositis (PM/DM) is a serious complication that affects prognosis. We therefore undertook a retrospective multicenter study to examine the efficacy of a combination treatment with cyclosporin A (CsA) and corticosteroids. Fifty-three IP patients with PM/DM (9 PM, 44 DM) were analyzed. Thirty-two patients treated with CsA plus corticosteroids (9 PM, 23 DM) were included in the study. Four parameters, i.e., subjective symptoms, ausculatory sound, chest radiographs, and respiratory index, were serially evaluated. A general evaluation was performed 4 weeks after the start of the combination treatment. All patients with PM and chronic IP with DM, and 52% of those with acute IP with DM were graded as better than “partially effective” in the general evaluation. In contrast, all patients graded as “progressive” in the general evaluation had acute IP with DM. It is of note that in acute IP with DM, the survival rate of the group primarily treated with CsA and corticosteroids from the early stage of their disease was significantly higher than that of the group initially treated with corticosteroids alone (P = 0.049). In conclusion, a combination treatment of CsA and corticosteroids from the early stage of disease may be advantageous for patients with IP with PM/DM, especially acute IP with DM.     

Papillomavirus Infectious Pathways: A Comparison of Systems

The HPV viral lifecycle is tightly linked to the host cell differentiation, causing difficulty in growing virions in culture. A system that bypasses the need for differentiating epithelium has allowed for generation of recombinant particles, such as virus-like particles (VLPs), pseudovirions (PsV), and quasivirions (QV). Much of the research looking at the HPV life cycle, infectivity, and structure has been generated utilizing recombinant particles. While recombinant particles have proven to be invaluable, allowing for a rapid progression of the HPV field, there are some significant differences between recombinant particles and native virions and very few comparative studies using native virions to confirm results are done. This review serves to address the conflicting data in the HPV field regarding native virions and recombinant particles.     

Golimumab for moderate to severe ulcerative colitis

Introduction: Golimumab (GLM) is a subcutaneously administered human anti-tumor necrosis factor (TNF) agent that has been approved by the regulatory authorities for the treatment of moderate to severe ulcerative colitis (UC) in 2013.

Areas covered: Maintained clinical remission rates up to 50% have been shown in UC patients receiving GLM, and higher GLM serum concentrations have been associated with improved clinical outcomes. Approximately 50% of UC patients do not respond to induction therapy with GLM, and up to 40% of GLM responders will lose response over time. In most patients, loss of response is associated with low serum GLM concentrations, which suggests insufficient exposure to GLM. Low GLM serum concentrations may be avoided by therapeutic drug monitoring.

Expert commentary: So far, the therapeutic window for GLM has not yet been defined, but options to dose increase GLM based on therapeutic drug monitoring might result in improved clinical outcome and higher success rates.     

The Mitochondrial Permeability Transition: Role in Ischemia/Reperfusion Injury

The mitochondrial permeability transition (MPT) occurs when a non-specific pore opens in the inner mitochondrial membrane and converts the mitochondrion from an organelle whose ATP production sustains the normal function of the cell to an instrument of death. Conditions favouring the MPT including high [Ca2+], oxidative stress and adenine nucleotide depletion, all of which occur when a tissue is reperfused following a period of ischemia. Cyclosporin A (CsA) and low pH (<7.0) are potent inhibitors of the MPT. Methods have been devised to demonstrate directly that the MPT pores open upon reperfusion but not during ischemia. The mechanism of the MPT appears to involve binding of mitochondrial cyclophilin (CyP) to the adenine nucleotide translocase (ANT) followed by a calcium-mediated conformational change that converts the ANT into a non-specific pore. Understanding the molecular mechanism has assisted in devising strategies that can be used to protect tissues from damage caused by reperfusion injury. These might also be of benefit in the prevention of multiple organ failure for which reperfusion injury of the gut is thought to be the initial trigger. Protective regimes include the pretreatment of tissues prior to ischemia/reperfusion with CsA (binds to CyP), free radical scavengers that reduce oxidative stress (e.g., pyruvate and propofol) and agents that decrease pHi (e.g., pyruvate or amelioride derivatives). Reperfusion injury can produce both immediate cell death by necrosis or delayed apoptotic cell death and it appears that the mitochondria determine which route is taken. Prolonged opening leads to rapid cell death by necrosis, whilst transient opening leads to cytochrome c release and subsequent apoptosis hours or days later.     

An Overview of Molecular Aspects of Iron Metabolism

Iron (Fe) is an essential, but potentially noxious, metal for almost all organisms. Its precise cellular regulation is necessary to ensure synthesis of numerous iron-containing proteins required for metabolic processes yet at the same time avoiding the build-up of potentially toxic levels of iron. In humans, iron-deficiency results in anemia, while excess iron can lead to organ damage as a result of a build-up of non-transferrin-bound iron (NTBI). In recent years, the cloning of novel proteins has clarified the mechanisms of iron uptake, storage and metabolic regulation. Our current knowledge of the molecular aspects of mammalian iron metabolism and NTBI are presented in this review.