Simvastatin attenuates acute lung injury by activation of A2B adenosine receptor.

To explore the protective mechanism of simvastatin in acute lung injury (ALI), the lipopolysaccharide (LPS) induced (5 mg/kg) ALI rat model was used to examine the effects of simvastatin. Following simvastatin treatment, the histopathological evaluation of lung tissues was made using hematoxylin and eosin (H&E) staining. Also, myeloperoxidase (MPO) activity and the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and IL-10 were determined by ELISA. Blood gas analyses of arterial blood samples were performed to assess the pulmonary gas exchange. Moreover, the neutrophil count and total protein content were determined in the bronchoalveolar lavage (BAL) fluid. The ratio of wet lung to dry lung (W/D) and the alveolar fluid clearance (AFC) were calculated to estimate the severity of edema. Lastly, the levels of A2BAR, CFTR, claudin4, and claudin18 were also measured by qRT-PCR and Western blotting. Simvastatin treatment, in a dose-related manner, markedly improved the lung histological injury and decreased the levels of TNF-α, IL-1ß, and increased IL-10 in LPS induced ALI. Also, pulmonary neutrophil count was alleviated. Besides, a decreased ratio of W/D lung also confirmed the simvastatin intervention. Notably, simvastatin reduced the levels of A2BAR, CFTR, and claudin18 but upregulated claudin4 in lung tissues. Additionally, treatment with PSB1115, an antagonist of A2BAR, countered the protective effect of simvastatin in ALI. Our study demonstrates that simvastatin has a protective effect against LPS-induced ALI by activating A2BAR and should be exploited as a novel therapeutic target for the treatment of ALI.

Ferulic acid attenuates adhesion molecule expression in gamma-radiated human umbilical vascular endothelial cells.

Radiation induces an important inflammatory response in the irradiated organs, characterized by leukocyte infiltration and vascular changes. Since adhesion molecules play an important role in facilitating the immune response at the inflammation sites, interfering with the expression of these molecules may be an important therapeutic target of radiation induced inflammation. Many adhesion molecules such as intercellular cell adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) have been identified in radiation. Ferulic acid (FA), an effective radioprotector during radiotherapy, is widely used in endothelium protection. The present study examined the effect of FA on the induction of adhesion molecules by gamma-radiation and the mechanisms of its effect in gamma-irradiated human umbilical vein endothelial cells (HUVECs). HUVECs were pretreated for 18 h with FA and then exposed to 10 Gy radiation. The result of cell adhesion assay showed FA inhibited radiation-induced U937 adhesion to HUVECs. FA prevented induction of ICAM-1 and VCAM-1 expression in a concentration-dependent manner after stimulation with radiation at the level of mRNA and protein. Inhibitors of the extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways were used to determine which pathway was involved in FA action; the result showed that the inhibitory effect of FA on adhesion molecule expression was mediated by the blockade of JNK. FA appears to be a potential therapeutic agent for treating various inflammatory disorders including radiation induced inflammation.

[Value of blinded sampling methods in the pathogenic diagnosis of ventilator-associated pneumonia].

OBJECTIVE: To evaluate the diagnostic value of blinded protected specimen brush and quantitative culture (BPSB-QC) in the pathogenic diagnosis of ventilator-associated pneumonia (VAP). METHODS: A prospective, self-controlled clinical trial was conducted during a 36-month period. QC of paired samples of BPSB and PSB via a fiberoptic bronchoscopy (FOB- PSB) in a total of 54 patients during 125 suspected episodes of VAP was compared. The sensitivity and accuracy, as well as the concordance between BPSB-QC and FOB-PSB-QC result in 48 patients with 106 episodes of VAP were assessed. Both BPSB-QC and FOB-PSB-QC greater than 103 cfu/ml (positive cutoff) was considered diagnostic of VAP. RESULTS: Forty-eight patients with 106 episodes were considered to have VAP (84.8%). The accuracy of BPSB-QC and FOB-PSB-QC were 80.8% (101/125) and 83.2% (104/125), respectively. The rate of complete concordant results was high (75.2%) for BPSB-QC and FOB-PSB-QC. The pathogenic diagnostic agreement between the two techniques was 84.8% (106/125). There were no significant differences with regard to site of pneumonia and positive diagnostic rate between the two techniques. CONCLUSION: BPSB-QC has similar accuracy and same feasibility compared with FOB-PSB-QC which was commonly primarily used in the pathogenic diagnosis of VAP, and that its use is substantially simpler, safe and cost saving, especially when FOB technique is not available.