Correlation between pulmonary vascular permeability index and calcitonin in acute respiratory distress syndrome associated with septic shock / 上海交通大学学报（医学版）

Objective · To analyze the assessment value of pulmonary vascular permeability index (PVPI) and procalcitonin (PCT) levels to the severity and prognosis of acute respiratory distress syndrome (ARDS) associated with septic shock.Methods·Clinic data of 100 ARDS patients admitted to Affiliated Hospital of Nantong University was analyzed retrospectively.The clinical data was collected as follows:gender,age,infection site,acute physiology,chronic health evaluation Ⅱ (APACHE Ⅱ),sequential organ failure (SOFA) score,serum PCT level,and hemodynamic parameters which were monitored by pulse indicator continuous cardiac output (PiCCO).Patients with septic shock associated with ARDS patients were divided into mild,moderate and severe groups.The patients were divided into survival group and death group according to the 28-day prognosis,and the differences in the parameters between two groups were analyzed,to evaluate PVPI and PCT in predicting the severity and prognosis of septic shock associated ARDS.Results · There were significant differences in PVPI and PCT between ARDS group associated with septic shock and not (P=0.000).PVPI and PCT increased with the severity of ARDS,and there was a statistically significant difference between the ARDS groups in different degrees of PVPI (P=0.000).Pearson correlation analysis showed that PVPI was positively correlated with APACHE Ⅱ score and SOFA score (r=0.554,P=0.000;r=0.431,P=0.000),and PCT was positively correlated with APACHE Ⅱ score and SOFA score (r=0.313,P=0.004;r=0.320,P=0.004).Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curve of the prognosis of ARDS patients with sepsis was significantly higher than those of the two groups.Conclusion · PVPI can assess the severity of ARDS in patients with septic shock,and PVPI and PCT are predictive factors of prognosis.The combination of PVPI and PCT contributes to early stage diagnosis of ARDS associated with septic shock.

mTOR partly mediates insulin resistance by phosphorylation of insulin receptor substrate-1 on serine(307) residues after burn.

Mammalian target of rapamycin (mTOR) is an important mediator for cross talk between nutritional signals and metabolic signals of insulin by downregulating insulin receptor substrate proteins. Therefore, mTOR inhibition could become a therapeutic strategy in insulin-resistant states, including insulin resistance induced by burn. We tested this hypothesis in the rat model of 30% TBSA full thickness burn, using the mTOR inhibitor rapamycin. Rapamycin (0.4 mg/kg, i.p.) was injected 2 h before euglycemic-hyperinsulinemic glucose clamps at 4 days after burn. IRS-1, phospho-serine³°7, phospho-tyrosine of IRS-1 and phospho-mTOR in muscle tissue were determined by immunoprecipitation and Western blot analysis or immunohistochemistry. Plasma TNF-α, insulin and C-peptide were determined before and after euglycemic-hyperinsulinemic glucose clamps. Our data showed that TNF-α, insulin and C-peptide significantly increased in the early stage after burn (P < 0.01). The infused rates of total 10% glucose (GIR, mg/kg min) significantly decreased at 4 days after burn. The level of IRS-1 serine³°7 phosphorylation in muscle in vivo significantly increased after burn (P < 0.01), while insulin-induced tyrosine phosphorylation of IRS-1 significantly decreased (P < 0.01). Inhibition of mTOR by rapamycin inhibited the phosphorylation of mTOR, reduced serine³°7 phosphorylation, elevated tyrosine phosphorylation and partly prevented the decrease of GIR after burn. However, TNF-α, insulin and C-peptide were not decreased by rapamycin treatment postburn. Taken together, these results indicate that the mTOR pathway is an important modulator of the signals involved in the acute regulation of insulin-stimulated glucose metabolism, and at least, partly contributes to burn-induced insulin resistance. mTOR inhibition may become a therapeutic strategy in insulin-resistant states after burn.

Insulin resistance following thermal injury: an animal study.

UNLABELLED: The aim of this study was to investigate the changes of glucose tolerance, insulin sensitivity, and euglycemic-hyperinsulinemic glucose clamps following a 30% TBSA full thickness third degree burn in rats. Sprague-Dawley rats weighing 160-170g received 30% TBSA full thickness third degree burn by immersing the back of trunk for 12s in a boiling water bath under anesthesia. Weight- and time-matched sham burn group (control) was treated in the same manner as the trauma group, except that they were immersed in a room-temperature water bath. After 12h overnight fasting, plasma insulin concentration was determined by ELISA using rat-insulin enzyme immunoassay kit (SPI-BIO) and blood glucose was assayed by glucose analyzer at 3 days after burn. Insulin sensitivity index was calculated by using slightly modified formula. The rat was injected with 5% glucose (2g/kg body weight, intraperitoneally) to observe the change of glucose tolerance at 3 days after burn. Euglycemic-hyperinsulinemic glucose clamps were performed at 4 days after burn. Insulin sensitivity index of burn group was significantly reduced compared with control group at 3 days after burn (0.58+/-0.23 versus 1.23+/-0.16, P<0.01). The significant difference of glucose tolerance was observed between the two groups and the glucose infused rate measured in burned rats was significantly decreased compared with that in control at 4 days after injury (7.23+/-1.35 versus 12.31+/-0.54, P<0.01). CONCLUSION: Burn causes the significant change of glucose metabolism and results in insulin resistance in rats.

Role of c-Jun NH (2)-terminal kinase in insulin resistance after burn / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the role of c-Jun NH (2)-terminal kinase (JNk) in insulin resistance after burn and its mechanism.</p><p><b>METHODS</b>Twenty-four Sprague-Dawley rats were randomized to control, burn and burn + anisomycin groups. The rats in control group received sham burn trauma, and burn and burn + anisomycin groups received 30% total body surface area (TBSA) full thickness burn injury. Anisomycin (5 mg/kg) together with 250 microl dimethyl sulfoxide (DMSO) was injected to the rats in anisomycin group intravenously, and only 250 microl DMSO in the other two groups. Euglycemic-hyperinsulinemic glucose clamps was performed 2 hours after the injection. The changes of phospho-serine 307, phospho-tyrosine of insulin receptor substrate (IRS)-1 and phospho-JNK in muscle tissues were determined and compared using immunoprecipitation and Western blot analysis or immunohistochemistry in the three groups.</p><p><b>RESULTS</b>The infusing rates of total 10% glucose (mg x kg(-1) x min(-1)) in control, burn and burn + anisomycin group were 12.3 +/- 0.4, 6.6 +/- 0.3, 6.5 +/- 0.4, respectively. The level of IRS-1 Serine 307 phosphorylation and phospho-JNK in muscle increased significantly, while insulin-induced tyrosine phosphorylation of IRS-1 decreased markedly after burn.</p><p><b>CONCLUSIONS</b>The activation of JNK elevates the level of IRS-1 phospho-serine 307 and might play a role in insulin resistance after burn in rats.</p>

Amelioration of insulin resistance after scald by c-Jun N-terminal kinase inhibitor in rat / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the role and mechanism of c-Jun N-terminal kinase (JNk) inhibitor (SP600125) in amelioration of insulin resistance after scald.</p><p><b>METHODS</b>Twenty-four Sprague-Dawley rats were randomized into sham (the process of scald was mimicked by water at room temperature) , scald, scald and SP600125 groups. The rats were inflicted with 30% TBSA full-thickness scald in the latter two groups. Euglycemic-hyperinsulinemic glucose clamp experiment was carried out 4 days after scald. SP600125 was administered to the rats in scald and SP600125 2 hrs before Euglycemic-hyperinsulinemic glucose clamp was performed. Changes in the phospho-Serine307 and phospho-tyrosine of IRS-1 activity, as well as expression of phospho-JNK in muscles were determined.</p><p><b>RESULTS</b>Euglycemic-Hyperinsulinemic Glucose Clamps experiment showed that the infusion rate of 100 g/L glucose in sham, scald, scald and SP600125 groups were (12. 33 +/-0. 42) , (6. 61 +/-0. 27) , (11. 11 +/-0. 68) mgx kg(-1) x min(-1) , respectively ( P <0.01). The level of IRS-1 Serine307 phosphorylation and JNK activity in muscles were significantly increased, while insulin-induced tyrosine phosphorylation of IRS-1 decreased markedly after scald. Compared with scald group, the level of IRS-1 Serine307 phosphorylation and JNK activity in scald and SP600125 group were decreased but tyrosine phosphorylation was elevated.</p><p><b>CONCLUSION</b>SP600125 can partially ameliorate insulin resistance after scald by inhibition of JNK activation, and decrease the level of IRS-1 phospho-serine307.</p>

Clinical study on the changes in plasma sodium level and blood erythrocyte after resuscitation with different fluid regimes at early postburn stage / 中华烧伤杂志

<p><b>OBJECTIVE</b>To study the changes in plasma sodium level and blood erythrocyte after resuscitation with different fluid regimes at early postburn stage.</p><p><b>METHODS</b>One hundred and fifty burn patients admitted to our burn ward were randomly divided into three groups based on the different regimes of fluid resuscitation, i.e. A (n = 50, resuscitation with balanced salt solution for to the patients with middle and small burn area, Na(+) = 130 mmol/L); B (n = 50, with the same regime as in group A for those with large burn area), and C (n = 50, with hypertonic saline resuscitation for those with large burn area, Na(+) = 174 mmol/L) groups. The fluid supplementation, and changes in plasma sodium level and blood erythrocyte count, and the mean corpuscular volume (MCV) were observed during 1st to 3rd post burn day (PBD).</p><p><b>RESULTS</b>The average volume of fluid supplementation in C group was lower than that in A and B groups (P < 0.01), though the average sodium supplementation in C group was higher than that in B group within 3 PBDs (P < 0.01). The average plasma level of sodium in B group was obviously lower than that in C group within 3 PBDs (P < 0.05). Negative correlation between the plasma sodium level and burn index (BI) was observed in A and B group on 1 PBD (r = -0.84, P < 0.01). The plasma sodium level was in the lower margin of normal range (137.4 +/- 3.9) mmol/L in B group, while that in C group was in the higher margin of normal range with obvious difference compared with B and C groups (P < 0.05 or 0.01). The MCV in group was lower than that in B group on the 1st and 2nd PBD, i.e. (92.1 +/- 4.5) fl vs (95.5 +/- 5.5) fl on the 1st PBD, and (90.9 +/- 5.4) fl vs (93.2 +/- 6.4) fl on the 2nd PBD, P > 0.05).</p><p><b>CONCLUSION</b>The plasma sodium level was stable with milder degree of swelling of the erythrocytes when hypertonic saline resuscitation was given to patients with large burn area during early postburn stage.</p>