ABSTRACT Background: Insulin resistance is common in septic patients. The level at which the serum glucose should be maintained using insulin infusions for optimal utilization by skeletal muscles is not yet established. Objective: The objective of the present study was to compare glucose transporter 4 (GLUT4) mRNA and GLUT4 expression and glucose utilization at the recommended glucose levels of 6–8 mmol/L (110-140 mg/dL) and 8–10 mmol/L (140–180 mg/dL) in septic rats. Subjects and Methods: This was a prospective randomized study using 44 Sprague-Dawley rats (260–330 g). Rats were anaesthetized with gaseous diethyl ether. Catheters were implanted into the jugular vein and artery. Following a laparotomy, rats in the experimental group (n = 36) were rendered septic by standard caecal ligation and puncture (CLP) and intraperitoneal lipopolysaccharide (LPS) infusion (O111:[B4], 1 mg/kg). Control animals (n = 8) underwent laparotomy, but no caecal ligation or puncture and no LPS injection. Four experimental groups were studied: sham-operated control, sepsis treated with fluid maintenance only, sepsis treated with fluid and insulin infusion controlling blood glucose concentration at 6–8 mmol/L and sepsis treated with fluid and insulin infusion controlling blood glucose concentration at 8–10 mmol/L. Hyperinsulinaemic-euglycaemic clamp experiment was done before fluid maintenance and insulin treatment to calculate average glucose infusion rate. Results: All septic rats were markedly hyperglycaemic compared with sham-operated controls two hours after operation. Glucose infusion rate during hyperinsulinaemic-euglycaemic clamp experiment was slower in septic rats, suggesting that they were insulin resistant. At the 12th and 24th hour, skeletal muscle was taken to observe pathological change and analyse the GLUT4 mRNA and GLUT4 levels. There were more inflammatory cells, less GLUT4 mRNA and GLUT4 expression in the skeletal muscles of septic rats. Insulin increased the expression of GLUT4 mRNA and GLUT4 in the skeletal muscle of septic rats. Among all septic rats, the expression of GLUT4 mRNA and GLUT4 was more in the 8–10 mmol/L group. Conclusion: Blood glucose concentration of 8–10 mmol/L results in more glucose utilization than 6–8 mmol/L in the skeletal muscle of septic rats during insulin therapy.

RESUMEN: Antecedentes: La resistencia a la insulina es común en pacientes sépticos. Todavía no se ha determinado el nivel al que la glucosa sérica debe mantenerse mediante infusiones de insulina para su utilización óptima por los músculos esqueléticos. Objetivo: El objetivo del presente estudio fue comparar el transportador de glucosa 4 (GLUT4) mRNA y la utilización de la glucosa y la expresión de GLUT4 en los niveles recomendados de glucosa de 6–8 mmol/L (110-140 mg/dL) y 8–10 mmol/L (140–180 mg/dL) en ratas sépticas. Sujetos y método: Se trató de un estudio prospectivo aleatorio con 44 ratas Sprague-Dawley (260–330 g). Las ratas fueron anestesiadas con éter dietílico gaseoso. Se les implantaron catéteres en la vena yugular y la arteria. Luego de una laparotomía, las ratas en el grupo experimental (n = 36) fueron reducidas a condición séptica mediante el método estándar de ligadura y punción cecal e infusión intraperitoneal de lipopolisacárido (LPS) (O111: [B4], 1 mg/kg). A los animales de control (n = 8) se les practicó la laparotomía, pero no se les hizo ligadura cecal o punción, ni se les administró inyección de LPS. Se estudiaron cuatro grupos experimentales: control de simulación, sepsis tratada con mantenimiento de fluidos solamente, sepsis tratada con infusión de fluídos e infusión de insulina para el control de la concentración de glucosa sanguínea en 6 – 8 mmol/L, sepsis tratada con infusión de fluídos e infusión de insulina para el control de la concentración de glucosa sanguínea en 8–10 mmol/L. Se realizó un experimento de pinzamiento euglucémico hiperinsulinémico antes del mantenimiento del fluido y el tratamiento con insulina a fin de calcular la velocidad media de infusión de glucosa (VIG). Resultados: Todas las ratas sépticas fueron ostensiblemente hiperglicémicas en comparación con los controles de simulación dos horas después de la operación. La velocidad de infusión de glucosa durante el experimento de pinzamiento euglucémico hiperinsulinémico fue más lenta en ratas sépticas, sugiriendo que eran resistentes a la insulina. A las 12 y a las 24 horas, el músculo esquelético fue llevado para observar los cambios patológicos, y para analizar los niveles de GLUT4 mRNA y GLUT4. Había más células inflamatorias, y menos expresión de GLUT4 mRNA y GLUT4 en los músculos esqueléticos de las ratas sépticas. La insulina aumenta la expresión de mRNA de GLUT4 y GLUT4 en el músculo esquelético de ratas sépticas. Entre todas las ratas sépticas, la expresión de GLUT4 mRNA y GLUT4 fue mayor en el grupo de 8 – 10 mmol/L. Conclusión: La concentración de glucosa sanguínea de 8–10 mmol/L trae como resultado más utilización de glucosa que la de 6–8 mmol/L en el músculo esquelético de ratas sépticas durante la terapia con insulina.

The objective of the present study was to explore the factors related to the prognosis of colorectal cancer (CRC) and to establish a prognostic model for the selection of patients who might benefit from hepatic resection for metastatic CRC. A total of 293 patients undergoing liver resection for metastatic CRC (172 males and 80 females ranging in age from 26 to 80 years) were selected and clinical, pathological and outcome data were examined in this retrospective study. The prognostic index (PI) of the patients was calculated on the basis of results of multivariate analysis. Patients were stratified into different groups, with survival curves projected according to PI. The 1-, 3-, and 5-year overall survival rates were 58.3, 26.4, and 11.3%, respectively. Univariate analysis indicated that degree of primary tumor differentiation, resection margin, preoperative carcinoembryonic antigen (CEA) level, number of liver metastases, and resection of liver metastases were associated with prognosis (P < 0.05). In multivariate analysis, the last three factors were found to be independent prognostic factors. The resection of liver metastases was a favorable factor. Patients were classified into three groups according to PI, which differed significantly in survival rate (P < 0.05). The individual survival rate was evaluated based on PI. Resection of hepatic colorectal metastases may produce long-term survival and cure. The proposed PI was easy to use, was highly predictive of patient outcome, and permitted categorization of patients into treatment groups.

Angiotensin II (Ang II) plays a crucial role in the pathogenesis of renal diseases. The objective of the present study was to investigate the possible inflammatory effect of Ang II on glomerular endothelial cells and the underlying mechanism. We isolated and characterized primary cultures of rat glomerular endothelial cells (GECs) and observed that Ang II induced the synthesis of monocyte chemoattractant protein-1 (MCP-1) in GECs as demonstrated by Western blot. Ang II stimulation, at concentrations ranging from 0.1 to 10 µm, of rat GECs induced a rapid increase in the generation of reactive oxygen species as indicated by laser fluoroscopy. The level of p47phox protein, an NAD(P)H oxidase subunit, was also increased by Ang II treatment. These effects of Ang II on GECs were all reduced by diphenyleneiodonium (1.0 µm), an NAD(P)H oxidase inhibitor. Ang II stimulation also promoted the activation of nuclear factor-kappa B (NF-κB). Telmisartan (1.0 µm), an AT1 receptor blocker, blocked all the effects of Ang II on rat GECs. These data suggest that the inhibition of NAD(P)H oxidase-dependent NF-κB signaling reduces the increase in MCP-1 production by GECs induced by Ang II. This may provide a mechanistic basis for the benefits of selective AT1 blockade in dealing with chronic renal disease.