Topical application of glycyrrhizin preparation ameliorates experimentally induced colitis in rats

AIM:To examine the efficacy of glycyrrhizin preparation(GL-p) in the treatment of a rat model of ulcerative colitis(UC).METHODS:Experimental colitis was induced by oral administration of dextran sodium sulfate.Rats with colitis were intrarectally administered GL-p or saline.The extent of colitis was evaluated based on body weight gain,colon wet weight,and macroscopic damage score.The expression levels of pro-inflammatory cytokines and chemokines in the inflamed mucosa were measured by cytokine antibody arra...     

Regional citrate anticoagulation reduces polymorphonuclear cell degranulation in critically ill patients treated with continuous venovenous hemofiltration

Citrate which chelates ionized calcium can be used as regional anticoagulation in continuous venovenous hemofiltration (CVVH). This is the first study conducted to examine the potentially additive benefit effect of regional citrate anticoagulation (RCA) on polymorphonuclear (PMN) cell degranulation of myeloperoxidase (MPO) and cytokines production in patients with critically acute kidney injury (AKI) undergoing CVVH treatment. This prospective randomized controlled trial was conducted in 20 critically ill patients with AKI who underwent CVVH. The patients were randomized into regional citrate group (n=10) and heparin group (n=10). The pre-dilution CVVH with polyethersulfone dialyzers were utilized in both groups. The levels of pre-filter and post-filter MPO as well as inflammatory and anti-inflammatory cytokines were measured at baseline, 6h, and 24 h after initiating CVVH. In the heparin group, the post-filter serum MPO levels were significantly higher than the pre-filter (median 49.0 vs. 60.5 ng/mL, P<0.05) at 6 h. There were no significant differences between pre- and post-dialyzer MPO levels in the citrate group. Citrate could significantly decrease systemic pre-filter serum MPO levels from baseline at 6 h (median 43.5 vs. 17.3 ng/mL, P<0.01) as well as IL-8 levels (P<0.05) whereas heparin provided only significant TNF-α reduction (P<0.05). The CVVH circuit survival in the citrate group was longer than the heparin group. In conclusion, citrate, utilized as a regional anticoagulant in CVVH, can reduce both membrane bioincompatibility-induced and systemic oxidative stress and inflammation, and can prolong CVVH circuit survival time.     

Fucoidin, a neutrophil rolling inhibitor, reduces damage in a rat electrical burn injury model

Background

Electrical injuries induce progressive tissue loss caused by free oxygen radicals released from neutrophil aggregates. Fucoidin, a potent inhibitor of L-selectin function, reduces the aggregation of neutrophils. The aim of this study was to evaluate the effect of fucoidin on tissue damage in rat electrical burn injury model.

Methods

Forty-two male Wistar albino rats (250–300 g) were divided into 3 groups (Group A (n = 6), control group without electrical burn injury; Groups B (n = 18) and C (n = 18), electrical burn injury groups without and with fucoidin therapy, respectively). Three separate analyses were performed at different time points on 6 out of 18 mice from Group B and C at each time point. Biochemistry (myeloperoxidase and malondialdehyde levels) and histopathology (number of neutrophils) of the skin and muscle biopsies at 1st hour; tissue edema (ratio of wet weight/dry weight of extremities) at 24th hour; and necrotic areas at 7th day after electrical injury were evaluated. The electrical burn was induced by exposing rats to 220 V AC between their left upper extremity and right lower extremity for 10 s. Fucoidin was administered as 25 mg/kg intravenous bolus injection at 15 min after electrical burn injury.

Results

Myeloperoxidase and malondialdehyde levels, number of neutrophils, tissue edema, and necrotic area were significantly less in fucoidin-applied rats than the group without fucoidin therapy.

Conclusions

Fucoidin inhibits tissue damage induced by electrical burn injury in rats by reducing necrotic area, edema and number of neutrophils.     

Modified HDL: biological and physiopathological consequences

Epidemiological and clinical studies have demonstrated the inverse association between HDL cholesterol levels (HDL-C) and the risk of coronary heart disease (CHD). This correlation is believed to relate to the ability of HDL to promote reverse cholesterol transport. Remodeling of HDL due to chemical/physical modifications can dramatically affect its functions, leading to dysfunctional HDL that could promote atherogenesis. HDL modification can be achieved by different means: (i) non-enzymatic modifications, owing to the presence of free metal ions in the atherosclerotic plaques; (ii) cell-associated enzymes, which can degrade the apoproteins without significant changes in the lipid moiety, or can alternatively induce apoprotein cross-linking and lipid oxidation; (iii) association with acute phase proteins, whose circulating levels are significantly increased during inflammation which may modify HDL structure and functions; and (iv) metabolic modifications, such as glycation that occurs under hyperglycaemic conditions. Available data suggest that HDL can easily be modified losing their anti-atherogenic activities. These observation results mainly from in vitro studies, while few in vivo data, are available. Furthermore the in vivo mechanisms involved in HDL modification are ill understood. A better knowledge of these pathways may provide possible therapeutic target aimed at reducing HDL modification.     

Serum myeloperoxidase level predicts reperfusion in patients with myocardial infarction receiving thrombolytic therapy

Polymorphonuclear leukocytes play a central role in all stages of the atherothrombotic inflammatory process. The atherothrombotic activity of polymorphonuclear leukocytes is exerted by mediators such as myeloperoxidase (MPO). Although the role of MPO has been studied with respect to the development of adverse cardiac events in acute coronary syndromes (ACS), the association of this molecule with effectiveness of reperfusion in patients receiving thrombolysis is not yet known. The study population consisted of a total of 158 patients with acute coronary syndromes. Final diagnosis was ST-segment elevation myocardial infarction in 86 patients, 80 of whom received thrombolysis. Blood samples were drawn at presentation of the patients and serum myeloperoxidase levels were measured. Reperfusion was defined in terms of electrocardiographic ST-segment resolution. The serum levels of MPO were found to be correlated with rates of in-hospital adverse events including death (P < 0.001), reinfarction (P < 0.001), recurrent ischemia (P < 0.001), arrhythmias (P < 0.001), clinical heart failure (P < 0.001), and cardiogenic shock (P < 0.001). There was a significant difference in serum MPO levels between subjects with three-vessel disease and two- or one-vessel disease (P < 0.001). Pre-lytic serum high-sensitivity C-reactive protein levels in patients with successful reperfusion were lower than in patients with failed reperfusion (P < 0.001). Analysis of patients with ST segment elevation myocardial infarction receiving thrombolytic therapy revealed that pre-lytic serum MPO levels in patients with successful reperfusion were significantly lower than those of patients with failed reperfusion (P < 0.001). In the present study, serum MPO levels were found to be a strong predictor of response to thrombolytic treatment in patients with ST-segment elevation myocardial infarction. Therefore the level of inflammatory activity in acute coronary syndromes seems to influence the effectiveness of fibrinolysis.     

急性冠脉综合征PCI术后血清sCD40L,MPO水平的变化以及阿托伐他汀对二者的影响

目的:探讨ACS患者PCI术后血小板CD40L表达及血浆MPO水平的变化以及阿托伐他汀对二者的影响.方法:126例急性冠脉综合征患者随机分40 mg治疗组、20 mg对照组,分别于术前、术后第1天、7天、1个月空腹检测血清中MPO和sCD40L的水平.结果:(1)ACS发生后血液中sCD40L、MPO会迅速升高,在PCI的影响下,两者继续升高,然后逐渐下降.(2)治疗组PCI术后血清sCD40L、MPO水平的水平明显低于对照组,有统计学差异(P＜0.05).(2).sCD40L与MPO的变化趋势的相关性分析无相关性(P=0.58,r=0.153),结论:PCI术后患者血清炎性因子sCD40L、MPO进一步升高;阿托伐他汀对ACS患者PCI后血清sCD40L、MPO有明显的抑制作用.     

脓毒症小鼠心肌P-选择素基因的表达及意义

目的:探讨脓毒症时小鼠心肌P-选择素表达的改变及其意义.方法:雌性昆明小鼠72只,随机分为对照组(12只)、假手术组(12只)、盲肠结扎穿孔(CLP)组(48只),CLP法制备脓毒症模型,CLP后2、4、8和12 h处死动物分别留取血和心脏组织,采用双抗夹心酶联免疫法(ELISA)检测血清肌钙蛋白Ⅰ(cTnI),测心肌组织髓过氧化物酶(MPO)活性,采用实时荧光定量逆转录多聚酶链反应(RT-PCR)法检测心肌组织P-选择素mRNA表达.结果:CLP组2、4、8和12 h心肌组织P-选择素mRNA表达进行性升高,与对照组和假手术组相比,差异有统计学意义(P＜0.05).而且CLP后心肌组织p-选择素mRNA表达水平与心肌组织MPO活性及血清肌钙蛋白Ⅰ浓度均呈显著正相关.结论:脓毒症时小鼠心肌损伤时,心肌组织P-选择素表达显著升高,可能与心肌组织中性粒细胞浸润及心肌损伤密切相关.     

颈动脉粥样硬化斑块与血浆髓过氧化物酶预测冠状动脉狭窄程度

目的 探讨以颈动脉内-中膜厚度(IMT)、粥样斑块Crouse积分联合血浆髓过氧化物酶(MPO)浓度预测冠状动脉粥样硬化性心脏病患者冠状动脉狭窄程度的价值.方法 收集131例疑似急性冠脉综合征患者,均于入院第2天接受血浆MPO浓度检测,入院1周内接受冠状动脉造影(CAG)及颈动脉超声检查.根据CAG结果将其分为冠心病组和对照组,计算颈动脉斑块的IMT积分及粥样斑块Crouse积分,应用ROC分析分别比较颈动脉IMT积分、粥样斑块Crouse积分、血浆MPO浓度及三者联合检测冠心病的价值.结果 冠心病组血浆MPO浓度、颈动脉IMT和粥样斑块Crouse积分均明显高于对照组(P均＜0.01),IMT积分、Crouse积分及血浆MPO浓度均与冠状动脉狭窄程度呈正相关.IMT积分、Crouse积分、MPO及三者联合检测冠心病的ROC曲线下面积分别为0.657、0.792、0.785及0.814,提示三者联合预测冠状动脉狭窄程度明显优于单个指标.结论 联合应用彩色多普勒超声检测颈动脉IMT及粥样斑块Crouse积分与血浆MPO浓度检测可作为评估冠状动脉粥样硬化性心脏病患者血管狭窄程度的有效辅助方法.