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101.
102.
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
103.
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
104.
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
105.
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
106.
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
107.
Nobuyuki Oka Teruaki Kawasaki Kotaro Mizutani Hiroshi Sugiyama Ichiro Akiguchi 《Neuropathology》2007,27(6):509-515
Neuromuscular biopsy is still an essential method for diagnosing vasculitic neuropathy, although its diagnostic sensitivity is at most 60%. Our objective was to examine the expression of hypoxia‐inducible factor 1α (HIF‐1α) in peripheral nerves and to evaluate its usefulness in diagnosing vasculitic neuropathy, especially for discrimination from other axonal neuropathies. Forty‐one patients with vasculitic neuropathy consisting of 20 definite, 14 probable and seven possible diagnoses, 15 patients with metabolic neuropathy, five with motor neuron disease and six with chronic inflammatory demyelinating polyneuropathy were included. Nerve biopsy specimens were immunohistochemically examined for HIF‐1α and various cell markers. Distinct immunoreactivity (IR) was observed in nuclei of endoneurial cells in 54% (22/41) of vasculitic patients, while specimens from metabolic neuropathies showed less nuclear IR and the difference of mean density of HIF‐1α‐positive nuclei was significant. Two patients with possible vasculitis who showed HIF‐1α‐positive nuclei in endoneurium, were later confirmed to have vasculitis by skin biopsies. Most of the cells expressing HIF were demonstrated to be Schwann cells. There was a trend in the vasculitic patients with early phase nerve damage to display higher endoneurial HIF‐1α‐IR. HIF‐1α may be an immunohistochemical marker for vasculitic neuropathy, especially when the observed section contains no vasculitic lesions. 相似文献
108.
尿激酶溶栓对大鼠局灶性脑缺血基质金属蛋白酶-9表达的影响 总被引:1,自引:1,他引:0
目的研究大鼠局灶性脑缺血后应用尿激酶(urokinase,UK)溶栓对基质金属蛋白酶-9(Matrix metalloproteinase-9,MMP-9)表达的影响,探讨MMP-9在UK溶栓引起的再灌注损伤及出血性转化中的作用。方法将实验动物随机分成3组进行研究(1)UK溶栓组;(2)缺血对照组;(3)假手术组。分别用免疫组织化学方法分析3组缺血后24hMMP-9的表达,对比研究两组MMP-9表达的差异性。结果缺血后24h前两组均有MMP-9的表达,但是UK溶栓组表达的程度明显高于缺血对照组;假手术组无MMP-9的表达。结论(1)缺血能导致MMP- 9的表达。(2)UK溶栓引起MMP-9表达的上调。 相似文献
109.
110.
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