Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats.

Insulin resistance is characteristic of the diabetic state. To define the role of hyperglycemia in generation of the insulin resistance, we examined the effect of phlorizin treatment on tissue sensitivity to insulin in partially pancreatectomized rats. Five groups were studied: group I, sham-operated controls; group II, partially pancreatectomized diabetic rats with moderate glucose intolerance; group III, diabetic rats treated with phlorizin to normalize glucose tolerance; group IV, phlorizin-treated controls; and group V, phlorizin-treated diabetic rats restudied after discontinuation of phlorizin. Insulin sensitivity was assessed with the euglyemic hyperinsulinemic clamp technique in awake, unstressed rats. Insulin-mediated glucose metabolism was reduced by approximately 30% (P less than 0.001) in diabetic rats. Phlorizin treatment of diabetic rats completely normalized insulin sensitivity but had no effect on insulin action in controls. Discontinuation of phlorizin in phlorizin-treated diabetic rats resulted in the reemergence of insulin resistance. These data demonstrate that a reduction of beta-cell mass leads to the development of insulin resistance, and correction of hyperglycemia with phlorizin, without change in insulin levels, normalizes insulin sensitivity. These results provide the first in vivo evidence that hyperglycemia per se can lead to the development of insulin resistance.     

The true value of serum elastase-1 in endoscopic retrograde cholangiopancreatography (ERCP)

BACKGROUND: The routine use of serum elastase-1 in patients, pre- and post-endoscopic retrograde cholangiopancreatography (ERCP), has been strongly supported but not sufficiently correlated with diagnosis, patient outcome/prognosis, or routine markers such as serum amylase. The value of serum elastase-1 post-ERCP, as far as clinical diagnosis and prognosis is concerned, was tested and compared with serum amylase in terms of sensitivity, specificity, positive prognostic value (PPV), and negative prognostic value (NPV). METHODS: In a prospective study of 38 consecutive patients undergoing ERCP, we assessed the following biochemical parameters 24 h before ERCP and 2 and 18 h after ERCP: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (gamma-GT), alkaline phosphatase (ALP), amylase (AMS), lactate dehydrogenase (LDH), and pancreatic elastase-1. RESULTS: Statistically significant changes were found between pre-ERCP and 18-h post-ERCP in elastase-1 (P=0.009), amylase (P=0.016), gamma-GT (P=0.04), and ALP (P=0.04). Changes between 2-h and 18-h post-ERCP in all parameters tested were not statistically significant. No statistical significance was found between any biochemical parameter and specific ERCP diagnosis. CONCLUSIONS: This study showed that 2-h post-ERCP serum elastase-1 was 100% specific for post-ERCP pancreatitis or other underlying severe pathology while, at the same time, amylase was only 50% specific. The specificity of serum elastase-1 still remained high (87.5%) 18-h post-ERCP, while amylase only had a specificity of 25% at that time. In contrast, amylase had a sensitivity of 83.3 and 90% in the 2-h and 18-h post-ERCP serum samples, while elastase-1 only had a sensitivity of 56.7 and 73.3%, respectively.     

Oseltamivir-resistant influenza A(H1N1) 2009 virus in Greece during the post-pandemic 2010-2011 season

Information on the drug susceptibility of influenza epidemic strains is important for antiviral resistance monitoring. In Greece, the 2009-2010 pandemic waves were very mild and seroprevalence rates remained low after this influenza season, resulting in exclusive detection of the pandemic strain during the 2010-2011 influenza season. In the present study during the post-pandemic 2010-2011 season, 50 consecutive influenza A(H1N1) 2009 virus-positive samples from patients hospitalised in Greek hospitals were analysed for resistance to the neuraminidase inhibitor oseltamivir. All patients were hospitalised with severe influenza complications and had previously received oseltamivir. Influenza A(H1N1) 2009 virus detection and testing for oseltamivir resistance were performed with real-time PCR amplification assays. The H275Y substitution associated with resistance to oseltamivir was identified in two immunocompetent patients who received oseltamivir treatment for 3 days and 5 days, respectively. In both cases, patients were discharged in good condition despite development of resistance to antiviral treatment.     

Obesity increases the severity of acute pancreatitis: performance of APACHE-O score and correlation with the inflammatory response.

BACKGROUND: Obese patients appear to be at risk for complications of acute pancreatitis (AP). APACHE-O score has been suggested to improve APACHE-II accuracy in predicting severe outcome in AP. AIMS: To determine if APACHE-O adds any predictive value to APACHE-II score and to test the hypothesis that obese patients are at increased risk of severe AP (SAP) because of a more intense inflammatory response to pancreatic injury. METHODS: 102 AP patients were prospectively studied. Using a body mass index (BMI) >30, 28% of the subjects were obese. Nineteen patients developed organ dysfunction and were classified as SAP. Receiver-operating curves for prediction of SAP were calculated using admission APACHE-II and APACHE-O scores. Binary logistic regression was performed to assess if obesity is a risk for SAP and to determine the clinical factors associated with severe disease. Serum levels of IL-6, MCP-1 and CRP as well as Ranson's scores were compared between obese and non-obese patients. RESULTS: Admission APACHE-O (area under the curve AUC 0.895) and APACHE-II (AUC 0.893) showed similar accuracy in predicting severe outcome. BMI was identified as a significant risk for SAP (OR 2.8, p = 0.048) and mortality (OR 11.2, p = 0.022). CRP levels were significantly higher in obese AP patients (p = 0.0001) as well as Ranson's score (p = 0.021). IL-6 and MCP-1 levels were higher in obese patients but did not reach statistical significance. CONCLUSIONS: Obesity is an independent risk for SAP. Admission APACHE-O score is not more accurate than APACHE-II. Our study results suggest that obesity increases the severity of AP by amplifying the immune response to injury.