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81.
Padmaja Yalamanchili Eric Wexler Megan Hayes Ming Yu Jody Bozek Mikhail Kagan Heike S. Radeke Michael Azure Ajay Purohit David S. Casebier Simon P. Robinson 《Journal of nuclear cardiology》2007,14(6):782-788
Background
BMS-747158-02 is a novel fluorine 18-labeled pyridazinone derivative designed for cardiac imaging. The uptake and retention
mechanisms of F-18 BMS-747158-02 in cardiac myocytes were studied in vitro, and the biodistribution of F-18 BMS-747158-02
was studied in vivo in mice.
Methods and Results
Fluorine 19 BMS-747158-01 inhibited mitochondrial complex I (MC-I) in bovine heart submitochondrial particles with an IC50 of 16.6±3 nmol/L that was comparable to the reference inhibitors of MC-1, rotenone, pyridaben, and deguelin (IC50 of 18.2±6.7 nmol/L, 19.8±2.6 nmol/L, and 23.1±1.5 nmol/L, respectively). F-18 BMS-747158-02 had high uptake in monolayers
of neonatal rat cardiomyocytes (10.3%±0.7% of incubated drug at 60 minutes) that was inhibited by 200 nmol/L of rotenone (91%±2%)
and deguelin (89%±3%). In contrast, an inactive pyridaben analog, P-0 (IC50 value>4 μmol/L in MC-1 assay), did not inhibit the binding of F-18 BMS-747158-02 in cardiomyocytes. Uptake and washout kinetics
for F-18 BMS-747158-02 in rat cardiomyocytes indicated that the time to half-maximal (t1/2) uptake was very rapid (approximately 35 seconds), and washout t1/2 for efflux of F-18 BMS-747158-02 was greater than 120 minutes. In vivo biodistribution studies in mice showed that F-18 BMS-747158-02
had substatial myocardial uptake (9.5%±0.5% of injected dose per gram) at 60 minutes and heart-to-lung and heart-to-liver
ratios of 14.1±2.5 and 8.3±0.5, respectively. Positron emission tomography imaging in the mouse allowed clear cardiac visualization
and demonstrated sustained myocardial uptake through 55 minutes.
Conclusions
F-18 BMS-747158-02 is a novel positron emission tomography cardiac tracer targeting MC-I in cardiomyocytes with rapid uptake
and slow washout. These characteristics allow fast and sustained accumulation in the heart. 相似文献
82.
The Hemodynamic Mechanisms of Lung Injury and Systemic Inflammatory Response Following Brain Death in the Transplant Donor 总被引:7,自引:2,他引:5
Vassilios S. Avlonitis Christopher H. Wigfield John A. Kirby John H. Dark 《American journal of transplantation》2005,5(4):684-693
Brain-dead donors are the major source of lungs for transplantation. Brain death is characterized by two hemodynamic phases. Initially, massive sympathetic discharge results in a hypertensive crisis. This is followed by neurogenic hypotension. Up-regulation of pro-inflammatory mediators occurs in all organs and lung injury develops; this can adversely affect graft function post-transplantation. The mechanisms of the systemic and lung inflammation are unknown. We hypothesized that the hemodynamic changes are responsible for these inflammatory phenomena. Brain death was induced by intra-cranial balloon inflation in rats. This resulted in hypertensive crisis, followed by hypotension. There was a significant increase in blood neutrophil CD11b/CD18 expression and pro-inflammatory cytokine levels in serum and bronchoalveolar lavage, compared with control animals. Rupture of the capillary-alveolar membrane was demonstrated by electron microscopy. Elimination of the hypertensive response by α-adrenergic antagonist pre-treatment prevented inflammatory lung injury, reduced the systemic inflammatory markers and preserved capillary-alveolar membrane integrity. Correction of the neurogenic hypotension with noradrenaline ameliorated the systemic inflammatory response and improved oxygenation. We conclude that the sympathetic discharge triggers systemic and lung inflammation, which can be further enhanced by neurogenic hypotension. Management of the brain-dead donor with early anti-inflammatory treatment and vasoconstrictors is warranted. 相似文献
83.
CHENG Yu-tong YANG Yue-jin ZHANG Hai-tao QIAN Hai-yan ZHAO Jing-lin MENG Xian-min LUO Fu-liang WU Yi-ling 《中华医学杂志(英文版)》2005,122(1):1529-1538
Background The traditional Chinese medicine Tongxinluo can protect myocardium against ischaemia/reperfusion injury, but the mechanism of its action is not well documented. We examined the involvement of nitric oxide in the protective role of Tongxinluo. Methods Miniswine were randomized to four groups of seven: sham, control, Tongxinluo and Tongxinluo coadministration with a nitric oxide synthase inhibitor Nω-nitro-L-arginine (L-NNA, 10 mg/kg i.v.). Three hours after administration of Tongxinluo, the animals were anaesthetised and the left anterior descending coronary artery ligated and maintained in situ for 90 minutes followed by 3 hours of reperfusion before death. Area of no reflow and necrosis and risk region were determined pathologically by planimetry. The degree of neutrophil accumulation in myocardium was obtained by measuring myeloperoxidase activity and histological analysis. Myocardial endothelial nitric oxide synthase activity and vascular endothelial cadherin content were measured by colorimetric method and immunoblotting analysis respectively.Results Tongxinluo significantly increased the local blood flow and limited the infarct and size of no reflow. Tongxinluo also attenuated myeloperoxidase activity and neutrophil accumulation in histological sections and maintained the level of vascular endothelial cadherin and endothelial nitric oxide synthase activity in the reflow region when compared with control group. The protection of Tongxinluo was counteracted by coadministration with L-NNA. Conclusions Tongxinluo may limit myocardial ischaemia and protect the heart against reperfusion injury. Tongxinluo regulates synthesis of nitric oxide by altering activity of endothelial nitric oxide synthase. 相似文献
84.
临床护士锐器伤调查与预防 总被引:46,自引:11,他引:35
目的探讨护士预防锐器伤的对策。方法对某所综合性医院193名护士在2004年1月~2005年6月发生的锐器伤进行问卷调查。结果46.1%护士发生锐器伤,人均1.6次;发生锐器伤的锐器主要是注射器针头(36.7%),其次是玻璃(32.4%);护士主要在掰安瓿(29.5%)、使用后处理锐器(22.3%)、安装调整针头(15.8%)、医护配合传递锐器(10.1%)等环节容易发生锐器伤;有79.1%护士发生锐器伤时未戴手套。结论护士面临锐器伤职业危险,各方应当采取对策,预防和控制锐器伤。 相似文献
85.
岛状皮瓣静脉淤血再通后对大鼠全身情况的影响 总被引:4,自引:0,他引:4
目的:探讨岛状皮瓣静脉淤血再通后对全身多脏器的影响。方法:按静脉淤血时间的不同将大鼠分为4组。观察耳部微循环的改变,测量术后肿瘤坏死因子α(TNFα),白细胞介素10(IL-10)的动态变化,观察心,肺,肝,肾,小肠及耳部血管等组织结构及中性粒细胞浸润数目。结果:皮瓣原位缝合组及静脉淤血2h组,耳部微循环、TNFα、IL-10浓度基本保持不变,各脏器结构改变较轻,中性粒细胞浸润数目少。静脉淤血6、10h组,微循环,肺,小肠,血管则有明显组织学改变,大量中性粒细胞浸润其中,但心,肝,肾组织学改变较轻。TNFα浓度再灌注1h达到高峰,其后逐渐下降,IL-10浓度3h达到最低,然后逐渐上升。结论:皮瓣静脉淤血再通后可造成肺、小肠及血管器官损伤,静脉淤血时间越长,再通后则损伤程度越重。全身微循环的改变,中性粒细胞在肺、小肠中的浸润,与血管内皮细胞的粘附及细胞因子TNFα与IL-10的浓度失衡是重要的操作原因。 相似文献
86.
由于心肌细胞的增殖能力很低,细胞移植作为一种新的治疗方法用于改善心功能及心肌活力已受到广泛的关注。目前已有胚胎干细胞、骨髓间充质干细胞和内皮干细胞在体外诱导分化为心肌细胞;动物实验中用于心肌移植的细胞有胚胎心肌细胞、造血干细胞、骨髓间充质干细胞、骨骼肌成肌细胞、内皮干细胞、肝干细胞和神经干细胞。其中成肌细胞移植用来改善心肌梗死后的心脏功能,已有临床报道,并取得成功。 相似文献
87.
情绪波动对急性心肌梗死后心律失常和心力衰竭的影响 总被引:2,自引:0,他引:2
目的回顾性探讨情绪波动对急性心肌梗死后心律失常、休克和心力衰竭的影响 ,为针对性地护理提供理论依据。方法将 2 4 1例急性心肌梗死病人有情绪波动 15 6例为观察组 ,无情绪波动 85例为对照组 ,比较情绪波动与心律失常、休克和心力衰竭的关系。结果观察组心律失常的发病率比对照组明显增高 (P <0 .0 1) ,差异有显著性意义。并得出相对危险度 (RR) =1.6 3,归因危险度 (AR) =2 9.12 % ,归因危险比数 (ARP) =38.83% ;室性期前收缩发病率比对照组明显增高 (P <0 .0 1) ,差异有显著性意义 ,并得出RR =2 .2 9,AR =2 6 .5 0 % ,ARP =5 6 .37%。结论情绪波动可使急性心肌梗死后心律失常 ,特别是室性期前收缩的发病率增高。 相似文献
88.
中国急性心肌梗塞的疾病经济负担 总被引:8,自引:1,他引:7
主要通过对急性心肌梗塞疾病经济负担的研究,总体描述进行二线预防的重要性。资料主要来源于中文文献检索、政府统计报表。主要利用直接医疗费用来计算疾病经济负担,而未考虑直接非医疗费用和间接费用。中日急性心肌梗塞的发病率约为45/10万。55/10万。城市高于农村,男性高于女性。在2000年,急性心肌梗塞的死亡率在城市为32.39/10万,农村为17.99/10万,其死亡率随年龄增长而相应增长。与发病率一样,城市高于农村,男性高于女性。25岁以上人群因急性心肌梗塞而损失的DALY在2000年为3.57DALYs/千人口。怎性心肌梗塞的直接医疗费用在国家卫生部部属医院为28257元/例,省级医院为8663元/例,县级医院为5447无/例。测算2000年急性心肌梗塞的疾病经济负担为13亿元。19亿元。但由于只有10.6%的急性心肌梗塞病人得到临床床治疗,因此,本测算结果可能低估了在中国实际发生的疾病经济负担。 相似文献
89.
大鼠骨髓间充质干细胞静脉移植对脊髓损伤的修复作用 总被引:9,自引:1,他引:8
目的初步探讨骨髓间充质干细胞(BMSCs)静脉移植对脊髓损伤后神经功能恢复和神经修复的影响。方法体外培养BMSCs,改良Allen法制备大鼠脊髓损伤模型,经尾静脉移植Brdu标记的BMSCs,损伤后24h、移植后1、3、5周评价实验动物的神经功能状况,并检测BMSCs在体内迁移、存活以及分化情况,电子显微镜观察组织形态学变化。结果移植的BMSCs在宿主损伤脊髓中聚集并存活,3~5周后有部分移植细胞表达神经元特异性烯醇化酶(NSE)、神经丝蛋白(NF)、微管相关蛋白(MAP2);BMSCs静脉移植组大鼠运动功能改善,BBB评分高于对照组(P〈0.05);5周后组织学观察,与对照组相比移植组损伤区脊髓结构较完整。结论BMSCs经静脉移植后可向脊髓损伤处聚集并存活分化,促进神经修复及神经功能的恢复。 相似文献
90.