冠状动脉病变与2型糖尿病及髓过氧化物酶关系的探讨

目的:探讨冠状动脉病变与2型糖尿病和髓过氧化酶的关系.方法:对2006年9月至2007年9月在我院就诊的210例胸痛临床怀疑患冠心病的患者进行冠状动脉造影.将其中冠状动脉狭窄大于50%的160例患者按照2003中国糖尿病指南的标准分为糖尿病组和非糖尿病组.对两组同时进行髓过氧化物酶水平的测定.结果:不同髓过氧化物酶水平下冠状动脉病变类型的比较说明,随着髓过氧化物酶水平的升高,糖尿病组的冠状动脉病变严重程度增加,差异有统计学意义,特别是在髓过氧化物酶大于65.2Auu/L,这种差异更为明显.结论:髓过氧化物酶可以作为预测糖尿病合并冠状动脉粥样硬化性心脏病患者冠状动脉病变严重程度的预测指标.     

Juvenile polyarteritis: results of a multicenter survey of 110 children

OBJECTIVE: To characterize pediatric patients who had been diagnosed with polyarteritis nodosa (PAN) through necrotizing vasculitis of the small and mid-size arteries or those with characteristic findings on angiograms data were collected. STUDY DESIGN: Pediatricians were asked to classify their patients into one of the four suggested groups for juvenile PAN. Twenty-one pediatric centers worldwide participated with 110 patients. RESULTS: The girl:boy ratio was 56:54, with a mean age of 9.05 +/- 3.57 years. The cases were classified as: 33 (30%) cutaneous PAN; 5 (4.6%) classic PAN associated with hepatitis B surface antigen (HBs Ag); 9 (8.1%) microscopic polyarteritis of adults associated with antineutrophil cytoplasmic antibodies (ANCA); and 63 (57.2%) systemic PAN. Cutaneous PAN was disease confined to the skin and musculoskeletal system. All patients with HBs Ag-associated classic PAN were diagnosed with renal angiograms. Antiviral treatment was administered in most cases. Microscopic PAN patients had pulmonary-renal disease, in combination or separately. ANCA was present in 87%, and 2 patients progressed to end-stage renal failure. Patients classified with systemic PAN had multiple system involvement, almost all had constitutional symptoms, and all had elevated acute phase reactants. Corticosteroids and cyclophosphamide were the first choices of immunosuppressive treatment. The overall mortality was 1.1%. CONCLUSIONS: There were remarkable differences among pediatric patients with PAN, with different clinical manifestations and overall better survival and lower relapse rates when compared with adults.     

Genetic variants in SOD2, MPO, and NQO1, and risk of ovarian cancer

OBJECTIVE: One way in which parity and use of oral contraceptives may protect against ovarian cancer is by preventing inflammation and oxidative stress associated with ovulation. Since the genes superoxide dismutase (SOD2), myeloperoxidase (MPO), and NAD(P)H:quinone oxidoreductase 1 (NQO1) are involved in inflammation and oxidative stress, we investigated whether variants of these genes are associated with risk of ovarian cancer. METHODS: In a hospital-based case-control study, we compared 125 cases and 193 controls with respect to prevalence of (1) the T-->C (val-->ala) substitution at the -9 position in the signal sequence of SOD2; (2) the G-->A substitution at the -463 position in the promoter region of MPO; and (3) the C-->T (pro-->ser) change in exon 6 of NQO1. Genotyping was done using PCR and gel electrophoresis for MPO and NQO1 and using MALDI-TOF mass spectrometry for SOD2. RESULTS: For SOD2, women with the TC (val/ala) or CC (ala/ala) genotypes were at increased risk [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-4.0]. Results for MPO and NQO1 were in the hypothesized directions but were not statistically significant. For MPO, there was a small inverse association among women with GA or AA genotypes (OR = 0.72, 95% CI 0.43-1.2). For NQO1, the TT (ser/ser) genotype was associated with somewhat increased risk (OR = 2.3, 95% CI 0.69-7.6). CONCLUSIONS: While these results need to be confirmed in other studies, they point to a possible role for genes involved in oxidative stress in the development of ovarian cancer.     

N-Acetylcysteine for Preventing Pump-Induced Oxidoinflammatory Response During Cardiopulmonary Bypass

Purpose To investigate the effect of N-acetylcysteine on preventing pump-induced oxidoinflammatory response during cardiopulmonary bypass (CPB).Methods Forty patients undergoing coronary artery bypass grafting (CABG) were randomly divided into a study group (n = 20), given 50mgkg^–1 N-acetylcysteine intravenously for 3 days, and a control group (n = 20) given saline. Serum samples were collected for measurement of myeloperoxidase (MPO), malondialdehyde (MDA), interleukin-6, ₁-acid glycoprotein (AAGP), and C-reactive protein (CRP) during surgery and postoperatively.Results The MPO and MDA values showed a similar pattern during and after CPB in the study group, with significantly less variance than in the control group. Interleukin-6 showed similar patterns in the two groups, but the data from 30min after the start of CPB and from 6h post-CPB were significantly different. The AAGP and CRP values were both elevated during CPB in the two groups without a significant difference, but 6 and 24h post-CPB, the values were significantly higher in the control group than in the study group.Conclusions N-Acetylcysteine decreased pump-induced oxidoinflammatory response during CPB, suggesting that it could be a novel therapy for assisting in the prevention of CBP-induced oxidoinflammatory damage.     

Fluconazole attenuates lung injury and mortality in a rat peritonitis model

Objective Acute lung injury following peritonitis constitutes an enigmatic clinical problem with no specific therapy. Recently, immunomodulators such as azole compounds have been shown to attenuate shock-related tissue injury. The present investigation was undertaken to study the effect of fluconazole on acute lung injury and survival following faecal peritonitis in rats.Subjects Male Wistar rats weighing 225–235 g.Design and setting Faecal peritonitis (Fp) was produced in four groups of adult male Wistar rats by intraperitoneal administration of non-sterile faecal suspension (1:1 w/v saline). A fifth group of rats was given sterile faecal material (SFM), which served as control.Interventions Rats in Fp groups were given fluconazole in doses of 0 mg/kg, 3 mg/kg, 10 mg/kg, and 30 mg/kg by gavage 30 min before induction of peritonitis. The control animals received an equal volume of distilled water.Measurements and results Survival over a period of 72 h, oxidative stress, neutrophil activity, and lung injury were measured. This study showed a 90% survival in the fluconazole-treated group compared to only 20% survival in untreated rats (P<0.008 log-rank test). The lungs of animals with Fp showed massive pathological changes including intraalveolar oedema, fibrosis, and mixed inflammatory cell infiltrate. These changes were dose-dependently attenuated by fluconazole. Enhanced oxidative stress (P<0.001) and neutrophil activity in the peritoneal fluid and lung (P<0.001) in Fp animals was dose-dependently reduced by fluconazole.Conclusion This study clearly suggests the role of neutrophils in Fp-induced tissue injury/mortality, which may be dose-dependently, attenuated by fluconazole.     

IL-10在大鼠心肌缺血再灌注中的变化及意义

目的探讨大鼠心肌缺血再灌注过程中血清IL-10浓度及意义,为临床诊断IRI提供实验依据。方法将大鼠随机分成假手术组(对照组,n=21),缺血/再灌注(模型组)和甲基强的松龙治疗组(药物组,n=21)3组,每组内再随机分成缺血0.5h(n=7)、再灌注0.5h(n=7)再灌注2h(n=7)三个亚组。在心肌缺血前用甲基强的松龙(30mg/kg)对药物组大鼠预处理。分别测定缺血0.5h、再灌注0.5h及2h血清中IL-10的含量和心肌组织中MPO含量。结果①对照组IL-10无明显变化,模型组与药物组自缺血0.5h、再灌注0.5h至2hIL-10呈逐渐升高趋势,差异具有显著性意义(模型组:F=26.075,P<0.01;药物组:F=39.263,P<0.01),两两比较差异具有显著性意义(P<0.05);各时段内,自对照组、模型组、药物组IL-10明显升高,差异具有显著性意义(缺血0.5h:F=85.383,P<0.05;再灌注0.5h:F=64.923,P<0.01;再灌注2h:F=131.727,P<0.01),两两比较差异具有显著性意义(P<0.05)②对照组心肌组织MPO活性无明显变化;模型组和药物组中,心肌组织MPO含量随着再灌注时间延长而升高,并随着再灌注时间进一步延长而略有降低,差异具有显著性意义;模型组F=4.153,P<0.05;药物组F=8.725,P<0.01);相应时段内,对照组、药物组、模型组差异具有显著性意义(缺血0.5h:F=403.785,P<0.01;再灌注0.5h:F=119.8     

Myeloperoxidase Activity Imaging Using <Superscript>67</Superscript>Ga Labeled Substrate

Purpose The aim of the study is to assess the feasibility of imaging specific activity of myeloperoxidase (MPO), a leukocyte enzyme with important roles in inflammation and atherosclerosis, by single photon emission computed tomography (SPECT) using a novel ⁶⁷Ga-labeled radiotracer obtained by conjugating desferrioxamine (DF) and hydroxyindolyl acetic acid in vivo. Materials and Methods A reducing substrate of MPO (I) was synthesized by reacting commercially available DF with 2-(5-hydroxy-1H-indol-3-yl) acetic acid in the presence of a coupling agent [dicyclohexyl carbodiimide (DCC)]. The chelating unit was labeled with ⁶⁷Ga, and its interaction with MPO was characterized using MALDI-TOF and UV–vis. Mice with Matrigel implants containing human MPO were used to model diseased tissues rich in MPO. Three hours after the injection of ⁶⁷Ga–I, SPECT/computed tomography (CT) imaging was performed on a high-resolution Gamma Medica X-SPECT system. Biodistribution studies were performed six hours after the injection of the radiotracer. Results The feasibility of compound I oligomerization in the presence of MPO and MPO-mediated cross-linking with proteins was initially confirmed in vitro. In vivo, a 2.7-fold increase in target-to-muscle ratio could be measured in MPO-containing Matrigel implants in mice. Biodistribution experiments demonstrated a 60% increase of radioactivity in MPO-containing vs. control (contralateral) Matrigel implants. Conclusion ⁶⁷Ga–I can be used to image MPO activity in a model system. The accumulation mechanism is based on a differential pharmacokinetics because of the size increase resulting from ⁶⁷Ga–I interaction with the target enzyme. M. Querol and J. W. Chen contributed equally to this work.     

二氢石蒜碱对大鼠局灶性脑缺血/再灌注损伤的治疗作用

目的:观察二氢石蒜碱(dihydrolycorine,DL)对大鼠局部脑缺血/再灌注损伤的治疗作用和可能机制。方法:线栓法制备右侧大脑中动脉局灶性脑缺血模型,缺血1 h再灌注24 h。SD大鼠随机分为假手术组、模型组和DL低、中、高剂量组,于大鼠脑缺血后即刻及复灌后11 h及23 h DL组腹腔注射DL(10,20,40 mg.kg-1)治疗,假手术组和模型组则注射生理盐水对照。观察不同剂量DL对脑缺血再灌注大鼠神经功能状态、脑梗塞面积、脑水肿程度和脑组织髓过氧化物酶(myeloperoxidase,MPO)活性的影响。结果:脑缺血后给予DL可明显降低缺血侧脑梗死及脑水肿程度,使神经病学症状得到明显改善,降低缺血再灌注损伤后脑组织内MPO的活性(P<0.05)。结论:DL对脑缺血/再灌注损伤具有治疗作用,可能与其减轻脑缺血再灌注所致脑组织的炎症反应有关。     

Anti-myeloperoxidase antibodies enhance phagocytosis,IL-8 production,and glucose uptake of polymorphonuclear neutrophils rather than anti-proteinase 3 antibodies leading to activation-induced cell death of the neutrophils

Anti-neutrophil cytoplasmic antibodies (ANCA) not only are triggered by target protein myeloperoxidase (MPO) and proteinase 3 (PR3) of polymorphonuclear neutrophil (PMN) but also react with primed PMN to exert the inflammatory process in vasculitis syndrome. To clarify the crucial role of PMN in ANCA-associated vasculitis and the related mechanism, PMN was cultured with monoclonal antibody MPO–ANCA and PR3–ANCA to determine the function of phagocytosis, Interleukin- 8 (IL-8) production, glucose uptake, and TNF-related apoptosis induced ligand (TRAIL) production. The spontaneous membrane expression of MPO and PR3 on PMN could be significantly increased by lipopolysaccharide (LPS) and TNF-α, but not by IL-8 or GRO-α. The PMN-stimulating activity of ANCA was demonstrated by enhancing phagocytosis, IL-8 production, and glucose uptake that was more prominent by MPO–ANCA. The PMN stimulation by ANCA was not through protein kinase, H₂O₂, or superoxide anion radicals as their inhibitors exerted no effect on ANCA-mediated activation. On the other hand, ANCA also accelerated PMN apoptosis and increased TRAIL production. These results demonstrate that activation-induced cell death (AICD) mechanism could be initiated in PMN with existence of ANCA. In conclusion, MPO–ANCA is more potent in stimulating PMN than PR3–ANCA. ANCA-activated PMN is not only responsible for the amplified inflammatory process in blood vessel but also initiates immune circuit via triggered macrophage/monocyte by apoptotic PMN through the mechanism of AICD elicited by ANCA.     

MPO、TGF-β1和CD15在结肠癌组织中的表达

P＜0.05),但CD15表达与二者表达无关.结论 MPO、TGF-β1及CD15在结肠癌的发生发展及淋巴结转移过程中有一定的作用,联合检测MPO、TGF-β1和CD15表达情况,可作为分析结肠癌分化程度、淋巴结转移和预后的参考指标.