ACOS患者血清Hs-CRP、MPO的检测意义

目的:对ACOS稳定期及急性加重期患者血清中的Hs-CRP、MPO水平进行检测,探讨二因子在ACOS病情活动中的变化,进而分析其在临床中的应用价值。方法:采用乳胶增强免疫比浊法检测血清Hs-CRP,采用酶联免疫吸附测定MPO浓度值。结果:ACOS急性加重期组血清Hs-CRP值为(64.96±12.89)mg/L,血清MPO的值为(41.10±17.44)ng/ml;ACOS稳定期组此二因子分别为(14.71±6.26)mg/L、(88.76±14.52)ng/ml;健康对照组此二因子分别为(6.18±3.98)mg/L、(70.49±11.04)ng/ml。     

Stable dry powder inhaler formulation of tranilast attenuated antigen-evoked airway inflammation in rats

Tranilast (TL) has been clinically used for the treatment of airway inflammatory diseases, although the clinical use of TL is limited because of its poor solubility and systemic side effects. To overcome these drawbacks, a novel respirable powder of TL (CSD/TL-RP) for inhalation therapy was developed using nanocrystal solid dispersion of TL (CSD/TL). Stability study on CSD/TL-RP was carried out with a focus on inhalation performance. Even after 6 months of storage at room temperature, there were no significant morphological changes in micronized particles on the surface of carrier particles as compared with that before storage. Cascade impactor analyses on CSD/TL-RP demonstrated high inhalation performance with emitted dose and fine particle fraction (FPF) of ca. 98% and 60%, respectively. Long-term storage of CSD/TL-RP resulted in only a slight decrease in FPF value (ca. 54%). Inhaled CSD/TL-RP could attenuate antigen-induced inflammatory events in rats, as evidenced by marked reduction of granulocytes in bronchoalveolar lavage fluid and inflammatory biomarkers such as eosinophil peroxidase, myeloperoxidase, and lactate dehydrogenase. These findings were consistent with decreased expression levels of mRNAs for nuclear factor-kappa B and cyclooxygenase-2, typical inflammatory mediators. Given these findings, inhalable TL formulation might be an interesting alternative to oral therapy for the treatment of asthma and other airway inflammatory diseases with sufficient dispersing stability.     

Neutrophils do not contribute to infarction,oxidative stress,and NO synthase activity in severe brain ischemia

Polymorphonuclear leukocytes (PMNs) were reported to contribute to ischemia-reperfusion-induced brain damage. The present work examined whether PMN infiltration is deleterious in a severe model of transient focal cerebral ischemia and in which part PMNs contribute to oxidative stress and nitric oxide (NO) production. A 20-min occlusion of the left middle cerebral artery and both common carotid arteries was performed in rats. Infarction was maximal 24 h after reperfusion, while accumulation of PMNs in infarcted tissue was not significant before 48 h. Moreover, neutropenia induced by vinblastine (0.5 mg/kg iv) significantly decreased by 60-80% PMN infiltration 48 h after reperfusion but did not reduce the infarct volume. Thus PMNs do not contribute to cerebral injury in our model. Furthermore, decreased PMN infiltration modified neither oxidative stress evaluated by glutathione concentrations nor NO synthase activities 48 h after reperfusion. In conclusion, our results suggest that PMNs are not involved in severe cerebral ischemia and that anti-PMN strategies may be inefficient in some pathological conditions.     

Resveratrol, a polyphenol found in grapes, suppresses oxidative damage and stimulates apoptosis during early colonic inflammation in rats

Oxidative stress, neutrophil infiltration, proinflammatory cytokines and eicosanoid generation are clearly involved in the pathogenesis of intestinal bowel disease. Resveratrol, a polyphenolic compound found in grapes and wine, has been shown to have anti-inflammatory, antioxidant, antitumour and immunomodulatory activities, however, its effects on experimental colitis remain unknown. We have investigated the effects of resveratrol on the colon injury caused by intracolonic instillation of trinitrobenzenesulphonic acid (TNBS) in rats. We determined the production of prostaglandin (PG)E(2) and PGD(2) in colon mucosa and the expression of cyclo-oxygenases (COX)-1 and -2 immunohistochemically. The inflammatory response was assessed by histology and myeloperoxidase activity, as an index of neutrophil infiltration. Interleukin-1 beta production, histological and histochemical analysis of the lesions were also carried out. Finally, since resveratrol has been found to modulate apoptosis we intended to elucidate its effects on colonic mucosa under early acute inflammatory conditions. Resveratrol (5-10mg/kg/day) significantly reduced the degree of colonic injury, the index of neutrophil infiltration and the levels of the cytokine. Resveratrol did not revert the increased PGE(2) levels but produced a significant fall in the PGD(2) concentration. Compared with inflamed colon, no changes in staining for COX-1 were observed in colon of resveratrol and TNBS-treated rats. In contrast, COX-2 expression was decreased. Furthermore, resveratrol enhanced apoptosis compared with already high level induced by TNBS. In conclusion, resveratrol reduces the damage in experimentally induced colitis, alleviates the oxidative events and stimulates apoptosis.     

川芎嗪对局灶性脑缺血后MPO活性及白细胞介素-6含量的影响

目的探讨川芎嗪对大鼠局灶性脑缺血后脑组织髓过氧化物酶（MPO）活性及IL-6含量的影响。方法采用线栓法制备大鼠局灶性脑缺血模型。将SD大鼠随机分为假手术组、模型组、川芎嗪组,并施以相应处理。分光光度法检测各组大鼠脑组织MPO活性,酶联免疫吸附法检测各组大鼠脑组织IL-6含量的变化。结果与假手术组相比,模型组脑组织MPO活性显著升高;与模型组相比,川芎嗪组脑组织MPO活性降低。假手术组脑组织中未检测出IL-6;模型组IL-6含量升高明显;川芎嗪组IL-6含量较模型组升高。结论川芎嗪可增加抗炎症细胞因子IL-6的含量,从而降低脑组织MPO活性,减轻局灶性脑缺血后的炎症反应,这可能是川芎嗪治疗缺血性脑血管病的机理之一。     

CYP2E1和MPO基因单核苷酸多态性对慢性苯中毒危险性的影响

[目的 ]本文旨在探讨CYP2E1(cytochromeP45 0 2E1)和MPO(myeloperoxidase)基因单核苷酸多态性与苯中毒易感性的关系。 [方法 ]以 15 6名慢性苯中毒工人作为病例组 ,以 15 2名接触苯而未中毒的工人作为对照组。用PCR、测序和DHPLC等分子生物学技术检测CYP2E1和MPO基因上的SNP ,比较病例组、对照组间的差别。 [结果 ]在男性苯中毒者中 ,MPO基因的c . 463G/A基因型的比例为 2 2 95 % ,高于对照组的 7 14 % (OR =3 87,95 %CI :1 0 8～ 15 0 9,P <0 0 5 )。在经常吸烟的研究对象中 ,携带CYP2E1基因c . 12 93G/C或C/C基因型的个体发生苯中毒的危险性是G/G基因型的 3 3 0倍 (95 %CI :0 88～ 12 71,P <0 0 5 )。 [结论 ]具有CYP2E1基因c . 12 93C/C或C/G基因型而又经常吸烟的个体可能对苯中毒性较易感。男性苯中毒者MPO基因c . 463G/A基因型高频率与理论推断不符 ,提示苯中毒的发生可能是多基因、多因素 (如生活方式等 )相互作用的结果     

Systemic inflammation and COPD: the Framingham Heart Study

BACKGROUND: The current paradigm for the pathogenesis of COPD includes an ultimately maladaptive local inflammatory response to environmental stimuli. We examined the hypothesis that systemic inflammatory biomarkers are associated with impaired lung function, particularly among those with extensive cigarette smoking. METHODS: Using data from the Framingham Heart Study, we examined cross-sectional associations of systemic inflammatory biomarkers (CD40 ligand [CD40L], intercellular adhesion molecule [ICAM]-1, interleukin [IL]-6, monocyte chemoattractant protein-1, P-selectin, and myeloperoxidase, in addition to C-reactive protein) to impaired lung function. RESULTS: IL-6 was consistently associated with impaired lung function; a 1-SD higher concentration of IL-6 was associated with a 41-mL lower FEV(1) (95% confidence interval [CI], - 61 to - 20) and a borderline 15% higher odds of COPD (odds ratio, 1.15; 95% CI, 0.99 to 1.34). Additionally, P-selectin was associated with lower FEV(1) levels; after adjusting for the other biomarkers, a 1-SD higher concentration of P-selectin predicted an FEV(1) that was on average 19 mL lower (95% CI, - 37 to 0). Including the biomarkers individually as sole exposures in the models generally strengthened the impaired lung function/biomarker association; the relations of ICAM-1 to FEV(1), and ICAM and CD40L to COPD became significant. The observed associations did not vary significantly with smoking history, except that the association between CD40L and COPD appeared greater in individuals with more extensive smoking histories. CONCLUSIONS: Among participants in the Framingham Heart Study, systemic inflammation was associated with lower levels of pulmonary function. Further research into the role of systemic inflammation in the development of pulmonary dysfunction is merited.