Hypothermia alleviated LPS-induced acute lung injury in Rat models through TLR2/MyD88 pathway.

Acute lung injury (ALI) is a common clinical syndrome in ICU departments with high mortality. The pathology of ALI is still not clear and there is no specific and efficient treatment against ALI. In this study, we established ALI rat model through lipopolysaccharide administration. We found that hypothermia therapy led to significant improvement in oxygenation index, edema formation and pathological score, demonstrating that hypothermia is beneficial to the recovery of lung function and alleviation of lung injury. Besides, hypothermia resulted in a decrease in plasminogen activator inhibitor-1(PAI-1) concentration, showing the inflammation was partially inhibited. This was also confirmed by a decrease in TNF-α mRNA and protein level in hypothermia group. The effect of hypothermia was mediated by TLR2/MyD88 signaling, which led to the alteration in NF-κB p65 level. Collectively, this study indicated that hypothermia therapy was potentially an efficient therapy against ALI.

Effect of mild hypothermia on the expression of toll-like receptor 2 in lung tissues with experimental acute lung injury.

OBJECTIVE AND DESIGN: Our study aimed to determine the effect of mild hypothermia (MHT) on the expression of toll-like receptor 2 (TLR2) in lung tissue with acute lung injury. The animals were randomly divided into control, model and mild hypothermia groups. METHODS: A total of 40 rats was used in the study. Acute lung injury was induced by lipopolysaccharide and MHT was maintained at 32.5∼33.0 °C using body surface ice-bag placement combined with animal thermostat system. The ratio of PaO2/FiO2 was recorded. The mRNA and protein expressions of TLR2 were measured by real-time polymerase chain reaction and western blotting respectively. Moreover, enzyme linked immunosorbent assay were used for the quantification of TNF-α. RESULTS: The ratio of PaO2/FiO2 was increased by MHT. TLR2 and TNF-α were increased in the rat lung 1h and 8h in the rats with acute lung injury while they were significantly decreased by MHT. Histological examination revealed that MHT alleviated the degree of inflammation. CONCLUSION: Our study suggested that MHT might improve the lung function by inhibiting the inflammation via down-regulating the expressions of TLR2 in the acute injury lung tissues.

[Value of creatinine clearance rate estimated based on serum cystatin C in patients with acute kidney injury].

OBJECTIVE: To investigate diagnostic value of creatinine clearance rate (CCr) based on serum cystatin C (SCys C) in acute kidney injury (AKI), and whether it could predict the need for renal replacement therapy (RRT). METHODS: The patients enrolled with the length of intensive care unit (ICU) stay over 3 days were collected from August 2010 to May 2011. According to the diagnosis of AKI during the ICU stay, patients were divided into the AKI group (n=21) and non-AKI group (n=30). After patients were admitted, the level of SCys C and creatinine (SCr) were measured so as to count CCr based on SCys C (SCys C-CCr) or on SCr (SCr-CCr) respectively, meanwhile urine volume and acute physiology and chronic health evaluation II (APACHE II) score were monitored. The value of CCr counted by SCys C and SCr on predict AKI and the correlations between RRT were compared. RESULTS: SCr-CCr and SCys C-CCr in AKI group both were significantly lower than non-AKI group all the way through on admission, and 2 days and 1 day before AKI diagnosed and the day AKI diagnosed. The level of SCys C-CCr on 2 days prior to AKI diagnosed was significantly lower than the day admitted (70.6±8.4 ml×min(-1)×1.73 m(-2) vs. 114.8±15.8 ml×min(-1)×1.73 m(-2), P<0.01), whereas the level of SCr-CCr were not significantly changed (76.4±19.3 ml×min(-1)×1.73 m(-2) vs. 78.7±22.1 ml×min(-1)×1.73 m(-2), P>0.05). Receptor operative curve (ROC) analysis indicated that SCys C-CCr could predict AKI earlier than SCr-CCr, as the area under curve (AUC) of SCys C-CCr and SCr-CCr on 2 days prior to AKI diagnosed were 0.859 and 0.664, respectively, and the sensitivity were 90.5% and 47.6%, the specificity were 76.2% and 81.0%. In AKI group 6 patients were treated with RRT, the AKI patients receiving RRT had significantly higher APACHE II score on admission (29.6±4.5 vs. 17.0±5.6, P<0.05) and less urine volume within 24 hours (740±465 ml vs. 1780±1230 ml, P<0.05) than patients not received RRT, however, SCys C-CCr has no significant difference between the sub-group (50.4±11.2 ml×min(-1)×1.73 m(-2) vs. 53.0±8.4 ml×min(-1)×1.73 m(-2), P>0.05). SCys C-CCr did not predict the need of RRT on the day to diagnose AKI (AUC=0.65). CONCLUSIONS: The sensitivity of SCys C-CCr were high, but its specificity not. The SCys C-CCr may be helpful for excluding diagnose of AKI in high risk patients. However, it could not predict the need for renal replacement therapy on the day AKI diagnosed.

[Effects of hypothermia on the concentration of surfactant protein A during endotoxin induced acute lung injury in rats].

OBJECTIVE: To investigate the effect of hypothermia (HT) on the concentration of surfactant protein A (SP-A) during lipopolysaccharide (LPS) induced acute lung injury (ALI) in rats. METHODS: Forty male Wistar rats were randomly divided into three groups. The ALI model was reproduced by LPS intratracheal instillation; only saline was instilled intratracheally for control group. Rats in both model group and control group were sacrificed respectively at 1 hour and 8 hours (each n=8). In HT group the body temperature was lowered to 32.5-33.0 centigrade 1 hour after LPS instillation, and 8 rats were sacrificed at 8 hours. The arterial blood gas was determined in all the groups before and 1 hour and 8 hours after instillation of saline or LPS, and the oxygenation index (PaO(2)/FiO(2)) was calculated. The concentration of SP-A in bronchoalveolar lavage fluid (BALF) was determined by enzyme linked immunosorbent assay. The morphological changes in lung tissue of rats were observed under light microscope. RESULTS: At 1 hour after intratracheal instillation of LPS, the PaO(2)/FiO(2) of each group reached the diagnostic criterion of ALI. Compared with control 1 hour group, the SP-A (µg/L) in BALF of model 1 hour group was decreased (53.27±1.95 vs. 74.81±6.55, P<0.01); the SP-A in model 8 hour group and HT 8 hour group (4.35±2.76 and 51.36±2.33) was both obviously decreased compared with control 8 hour group (70.81±5.01, both P<0.01). Compared with model 8 hour group, the SP-A of HT 8 hour group was obviously increased (P<0.01). Results of light microscopic examination, it was revealed that the alveolar structure of control 1 hour group and control 8 hour group was almost normal. Inflammatory response in lung tissues in model 8 hour group was found to be most serious; compared with model 8 hour group, inflammatory response in lung tissues in model 1 hour group and HT 8 hour group was reduced in certain degree. CONCLUSION: A certain extent of HT may reduce lung injury of early endotoxin induced ALI rats by delaying lowering of alveolar SP-A levels.

The safety and efficacy of daptomycin versus other antibiotics for skin and soft-tissue infections: a meta-analysis of randomised controlled trials.

OBJECTIVE: Daptomycin, a cyclic lipopeptide that exhibits rapid, concentration-dependent bactericidal activity in vitro against a broad spectrum of Gram-positive pathogens, has now, since 2003, been approved in more than 70 countries and regions to treat skin and soft-tissue infections (SSTIs). The purpose of this meta-analysis was to compare the safety and efficacy of daptomycin with other antibiotics, especially with vancomycin which has long been considered the standard therapy for complicated SSTIs. DESIGN: Meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: We thoroughly searched PubMed, EMBASE, Cochrane Central to identify relevant RCTs. Six RCTs with a total of 1710 patients were included in this meta-analysis. RESULTS: The results demonstrated that the efficacy of daptomycin was at par with or maybe better than other first-line antibiotics for treating SSTIs as shown by the OR for clinical success (OR=1.05, 95% CI 0.84 to 1.31, p=0.65, I(2)=0%); daptomycin versus vancomycin subgroup (OR=1.19, 95% CI 0.77 to 1.83, p=0.43, I(2)=0%); overall microbiological success (OR=1.05, 95% CI 0.61 to 1.79, p=0.86, I(2)=42%); microbiological success of daptomycin versus comparators for Staphylococcus aureus (SA, OR=1.05, 95% CI 0.61 to 2.60, p=0.53, I(2)=47%), for methicillin-resistant S. aureus (OR=0.90, 95% CI 0.77 to 1.06, p=0.20, I(2)=56%). However, daptomycin tended to have a similar treatment-related adverse events (AEs) incidence in comparison with other antibiotics (OR=1.06, 95% CI 0.71 to 1.59, p=0.76, I(2)=41%). The trend showed that daptomycin might cause less discontinuation due to AEs and death compared with other first-line antibiotics (OR=0.71, 95% CI 0.46 to 1.10, p=0.12, I(2)=11%). Significantly more patients in the daptomyicn group had creatine phosphokinase elevation than those in the control group; however, it could be reversed when the therapy ended (OR=1.95, 95% CI 1.04 to 3.65, p=0.04, I(2)=0). CONCLUSIONS: This meta-analysis demonstrated that the safety and efficacy of daptomycin was not inferior to that of other first-line drugs, and daptomycin tended to exhibit superior efficacy when compared with vancomycin or with comparators for SA infections; nevertheless, more high-quality RCTs are needed to draw a more credible conclusion.