Specific mediator inhibition by the NO donors SNP and NCX 2057 in the peripheral lung: implications for allergen-induced bronchoconstriction

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine potential therapeutic effect of the two NO donors NCX 2057 (3-(4-hydroxy-3-methoxyphenyl)-2-propenoic acid) 4-(nitrooxy)butyl ester) and SNP (sodium nitroprusside) on the early allergic airway response in the peripheral lung.</p> <p>Methods</p> <p>The experiments were performed in guinea pig lung parenchyma (GPLP) derived from ovalbumin (OVA) sensitized guinea pigs. The effects of NCX 2057 and SNP were evaluated by contractile responses and mediator release during OVA challenge. The generation of nitrite and nitrate was assessed by chemiluminescence. Statistical analysis was evaluated by ANOVA.</p> <p>Results</p> <p>Cumulatively increasing concentrations of OVA (1–10,000 ng/ml) induced concentration-dependent contractions of the GPLP that were reduced by NCX 2057 (100 μM, p < 0.001) and SNP (100 μM, p < 0.05). Antigen-induced eicosanoid release was decreased by NCX 2057 (100 μM, p < 0.001) but not by SNP (100 μM), whereas the release of histamine was reduced by SNP (100 μM, p < 0.001) but not by NCX 2057 (100 μM). In addition, NCX 2057 (0.1–100 μM), but not SNP (0.1–100 μM), relaxed leukotriene D₄(10 nM) precontracted GPLP (p < 0.01). The guanylyl cyclase inhibitor ODQ had no effect on the NCX 2057 mediated relaxation. SNP released significantly less nitrite than NCX 2057.</p> <p>Conclusion</p> <p>Although both SNP and NCX 2057 reduced the release of pro-inflammatory mediators, their profiles were distinctly different. Furthermore, NCX 2057 also induced smooth muscle dilation in the GPLP. The findings point to specific anti-inflammatory effects of different NO donors in the peripheral lung tissue.</p

The thrombotic potential of oral pathogens

In recent times the concept of infectious agents playing a role in cardiovascular disease has attracted much attention. Chronic oral disease such as periodontitis, provides a plausible route for entry of bacteria to the circulation. Upon entry to the circulation, the oral bacteria interact with platelets. It has been proposed that their ability to induce platelet aggregation and support platelet adhesion is a critical step in the pathogenesis of the infection process. Many published studies have demonstrated multiple mechanisms through which oral bacteria are able to bind to and activate platelets. This paper will review the various mechanisms oral bacteria use to interact with platelets

Crosstalk between reactive oxygen species and pro-inflammatory markers in developing various chronic diseases: a review

The inflammation process in the human body plays a central role in the pathogenesis of many chronic diseases. In addition, reactive oxygen species (ROS) exert potentially a decisive role in human body, particularly in physiological and pathological process. The chronic inflammation state could generate several types of diseases such as cancer, atherosclerosis, diabetes mellitus and arthritis, especially if it is concomitant with high levels of pro-inflammatory markers and ROS. The respiratory burst of inflammatory cells during inflammation increases the production and accumulation of ROS. However, ROS regulate various types of kinases and transcription factors such nuclear factor-kappa B which is related to the activation of pro-inflammatory genes. The exact crosstalk between pro-inflammatory markers and ROS in terms of pathogenesis and development of serious diseases is still ambitious. Many studies have been attempting to determine the mechanistic mutual relationship between ROS and pro-inflammatory markers. Therefore hereby, we review the hypothetical relationship between ROS and pro-inflammatory markers in which they have been proposed to initiate cancer, atherosclerosis, diabetes mellitus and arthritis