Insulin-degrading enzyme higher in subjects with metabolic syndrome.

Metabolic syndrome (MS) is comprised of a cluster of abnormalities in glucose, lipid, and vascular homeostasis, which is most commonly linked to abdominal obesity. MS heralds increased risk for development of diabetes and is linked to impairment in insulin signaling. Insulin-degrading enzyme (IDE) is one of the mechanisms through which insulin blood levels are maintained. It has been previously suggested that controlling IDE levels could provide yet another potential therapeutic approach in diabetes. Here we aim to investigate whether changes in serum IDE levels correlate with the severity of MS. Using a highly sensitive ELISA assay of active IDE in human serum, we found a strong correlation between circulating IDE levels and circulating levels of triglycerides, insulin, and c-peptide and an inverse correlation with HDL cholesterol (HDLc). Serum IDE levels were higher in MS subjects than in control subjects. Hence, circulating IDE may serve as a tool to identify subjects with abnormal insulin metabolism, possibly those with MS that are at risk to develop diabetes.

Non-fermentative Gram-negative rods bacteremia in children with cancer: a 14-year single-center experience.

PURPOSE: Data on non-fermentative Gram-negative rods (NFGNR) bacteremia in children with malignancies are limited. The aim of this study was to present clinical picture, antimicrobial susceptibility pattern, risk factors for resistance and outcome in NFGNR bacteremia in children with cancer. METHODS: All episodes of NFGNR bacteremia occurring during 2001-2014 in children with cancer in a tertiary-care hospital were retrospectively analyzed. Pseudomonas and Acinetobacter spp. resistant to three or more antibiotic classes and all Stenotrophomonas maltophilia (SM) were defined as multidrug-resistant bacteria (MDR). RESULTS: A total of 80 children (44 males, 0.8-18 years, median 5 years) developed 107 episodes (116 pathogens) of NFGNR bacteremia; Pseudomonas aeruginosa (PA) (51; 43.9%), Acinetobacter baumannii (AB) (21, 18.1%), SM (18, 15.5%); and others (27, 25.2%). The rate of NFGNR bacteremia in children with certain solid tumors (e.g. sarcoma, 12/134 (9.0%)) was comparable to that of hematological malignancies (52/429 (12.2%). Focal infection and septic shock occurred in 16 (14.9%) and four (3.7%) episodes, respectively. Thirty (25.8%) of 116 NFGNR were MDR. The most significant predictors of bacteremia with MDR PA or AB were severe neutropenia (<100 cells/mm3; OR 7.8, p = 0.002), hospital-acquired (OR 16.9, p < 0.0001) and breakthrough (OR 11.2, p < 0.0001) infection. Infection with MDR bacteria was associated with inappropriate empirical therapy. The 30-day mortality was 3/107 (2.8%), all in neutropenic patients with hematological malignancies. CONCLUSIONS: NFGNR bacteremia can present with nonspecific signs or symptoms. MDR NFGNRs are common and compromise treatment options, but mortality is relatively low. Knowledge of local epidemiology, pattern and risk factors for resistance is important to guide empirical therapy.

Low protective PON1 lactonase activity in an Arab population with high rates of coronary heart disease and diabetes.

BACKGROUND: Recent studies showing that high density lipoproteins (HDL) can effect plaque regression indicate that recent trial failures do not exclude an atheroprotective role of HDL. Instead, they highlight differences between HDL function and measured HDL-cholesterol (HDL-C). PON1 is one key functional activity of HDL. Urban Palestinians have lower HDL-C and a higher incidence and mortality of coronary heart disease than those of Israelis. We hypothesized that the cardioprotective PON1 lactonase and arylesterase activities and PON1 functional genotype may differ between Palestinians and Israelis. METHODS: We measured PON1 activities in a cross-sectional population-based study of Palestinian (n=960) and Israeli (n=694) residents in Jerusalem, 1654 participants in all. RESULTS: Palestinians had high prevalences of obesity and diabetes and low mean concentrations of HDL-cholesterol (0.97 mmol/l in men and 1.19 mmol/l in women). Lactonase and arylesterase activities were lower by 10.8% (p=1.2∗10(-14)) and 2.7% (p<0.0005), respectively, in Palestinians as compared to Israelis. The functional genotype distribution, demonstrated by plotting paraoxonase vs lactonase activities, showed a modest between-group difference (p=0.024), with 12.1% RR in Palestinian Arabs vs 8.4% in Israeli Jews, but no overall difference in allele frequencies. Lactonase correlated inversely with age (Spearman's rho=-.156), weakly with BMI (-.059), positively with HDL-C (.173) and non-HDL-C (.103), but was not associated with triglycerides or fasting glucose. Palestinians showed consistently lower lactonase activity in logistic regression models adjusted for multiple covariates and for functional genotype (odds ratios of 1.81 and 1.98, respectively, for the lower fifth vs the upper 4 fifths of lactonase activity p<0.0001). CONCLUSION: We showed a lower physiologically-significant lactonase PON1 activity in an Arab population, a finding consistent with the high cardiovascular and diabetes risk of Palestinians.