Two indole-2-carboxamide derivatives attenuate lipopolysaccharide-induced acute lung injury by inhibiting inflammatory response.

Acute lung injury (ALI) is the leading cause of mortality in the intensive care unit. Currently, there is no effective pharmacological treatment for ALI. In our previous study, we reported that Lg25 and Lg26, two indole-2-carboxamide derivatives, inhibited the lipopolysaccharide (LPS)-induced inflammatory cytokines in vitro and attenuated LPS-induced sepsis in vivo. In the present study, we confirmed data from previous studies that LPS significantly induced pulmonary edema and pathological changes in lung tissue, increased protein concentration and number of inflammatory cells in bronchoalveolar lavage fluids (BALF), and increased inflammatory cytokine TNF-α expression in serum and BALF, pro-inflammatory genes expression, and macrophages infiltration in lung tissue. However, pretreatment with Lg25 and Lg26 significantly attenuated the LPS-induced changes in mice. Taken together, these data indicate that the newly discovered indole-2-carboxamide derivatives could be particularly useful in the treatment of inflammatory diseases such as ALI.

The role of HDAC2 in cigarette smoke-induced airway inflammation in a murine model of asthma and the effect of intervention with roxithromycin.

BACKGROUND: Cigarette smoke is well known to worsen asthma symptoms in asthmatic patients and to make them refractory to treatment, but the underling molecular mechanism is unclear. We hypothesized that cigarette smoke can reduce the expression of HDAC2 in asthma and the process was achieved by activating the PI3K-δ/Akt signaling pathway. We further hypothesized that roxithromycin (RXM) can alleviate the impacts by cigarette smoke. METHODS: A murine model of asthma induced by ovalbumin (OVA) and cigarette smoke has been established. The infiltration of inflammatory cells and inflammatory factors was examined in this model. Finally, we evaluated the expression of HDAC2, Akt phosphorylation levels, and the effects of RXM treatment on the model described earlier. RESULTS: Cigarette smoke exposure reduced HDAC2 protein expression by enhancing the phosphorylation of Akt in PI3K-δ/Akt signaling pathway. Furthermore, RMX reduced the airway inflammation and improved the level of expression of HDAC2 in the cigarette smoke-exposed asthma mice. CONCLUSIONS: This study provides a novel insight into the mechanism of cigarette smoke exposure in asthma and the effects of RXM treatment on this condition. These results may be helpful for treating refractory asthma and emphasizing the need for a smoke-free environment for asthmatic patients.

[Prognostic value of extra-vascular lung water index and pulmonary vascular permeability index in patients with ARDS].

OBJECTIVE: To investigate the correlation of the extra-vascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) with disease severity and their prognostic value in patients with acute respiratory distress syndrome (ARDS). METHODS: A total of 44 patients with ARDS from October 2012 to June 2014 admitted in the Second Affiliated Hospital of Wenzhou Medical University were recruited in this study. According to the severity, patients were divided into three groups (Mild group, Moderate group and Severe group); the acute physiology and chronic health evaluation system II score (APACHE II), the lung injury score (LIS), the pulse contour curve continuous cardiac output (PiCCO) and other clinical indicators were respectively monitored in the period of 24, 48, 72 hrs after admission; then the correlation of EVLWI, PVPI and oxygenation index (OI) among groups were analyzed; According to the prognosis, patients were divided into the survival group and the death group, both given the univariate and multivariate Logistic regression analysis; EVLWI, PVPI, APACHE II score, LIS and lactic acid were admitted into the receiver operating characteristic (ROC) curve analysis, and the prognosis was evaluated respectively. RESULTS: With the increase of disease severity, LIS and lactic acid gradually increased, the difference was significant among the three groups of Mild, Moderate and Severe (P<0.05). And the APACHE II score also increased gradually with the severity, but the difference was statistically significant only between the Mild group and the Severe group (P<0.01). And likewise, mild, moderate, severe ARDS patients had 1, 6, 9 cases of death, respectively. The 28-day mortality rate increased gradually after admission, with a significant difference between the Mild group and the Severe group (P<0.05). When all the 44 patients of three severities (during the 24 hrs period and during the 72 hrs period) were compared, the OI gradually decreased with the increase of severity of ARDS, while EVLWI and PVPI ascended, and differences between any two groups were statistically significant (P<0.05). In addition, there was a significant negative correlation between EVLWI and OI or between PVPI and OI (r=-0.666, -0.763, all P<0.01), and a significant positive correlation between EVLWI and PVPI, the APACHE II score or LIS (r=0.929, 0.895, 0.661, all P<0.01). Besides, OI was a predictive protection factor of ARDS, whereas lactic acid, EVLWI and PVPI were risk factors. Multivariate Logistic regression analysis showed that EVLWI and lactic acid were risk factors for ARDS death (all P<0.05). ROC curve analysis results suggested EVLWI and lactic acid were risk factors, (odd ratio (OR)> 1, and 95%CI: 1.071-5.201, 5.201-99.852, all P<0.05). CONCLUSION: EVLWI, PVPI were positively correlated with the severity of ARDS illness; EVLWI can be used as an independent risk factor for forecasting ARDS death, jointing EVLWI with PVPI could improve the accuracy of ARDS death forecasting.