Reduction of adiposity with prolonged growth hormone treatment in old obese rats: effects on glucose handling and early insulin signaling.

OBJECTIVES: Growth Hormone (GH) promotes loss of body fat and causes insulin resistance. It is debated whether reduction of body fat mass during long term growth hormone (GH) administration improves carbohydrate metabolism. To answer this question we assessed carbohydrate handling and tissue specific function of the insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) during prolonged GH treatment of obese rats. METHODS: Body fat % estimated by DEXA scanning, plasma IGF-I, glucose and insulin were studied in 17 months old dietary induced obese rats treated for 4, 21 or 41 days (GH: 4 mg/kg/d or saline total n=90). Adipose tissue, muscle and liver samples were obtained after 21 days and expression and tyrosine phosphorylation of IR and IRS-1 proteins and the degree of IRS-1-Janus Kinase-2 (JAK2) interaction were analyzed by immunoprecipitation and immunoblotting. RESULTS: Forty-one days GH treatment caused the body fat to decline significantly to 20+/-3% (Mean+/-SEM), whereas it remained steady on 51+/-4% in the pair fed group. Insulin levels in response to OGTT were significantly elevated throughout the experiment. IR amount was elevated in adipose tissue but decreased in liver after GH treatment while IR phosphorylation was increased in muscle only. IRS-1 amount was elevated in adipose tissue and muscle while IRS-1 phosphorylation was increased only in liver. The association of IRS-1 with JAK-2 was increased in liver and muscle. CONCLUSIONS: An extensive reduction of fat mass did not improved signs of insulin resistance in GH treated old obese rats. The molecular events associated with GH treatment included tissue specific changes in the function of IR and IRS-1 suggesting the liver to be the primary site of insulin resistance. Furthermore, the association of IRS-1with JAK-2 in the course of GH signaling could present a mechanism for GH to directly induce insulin resistance.     

Preventable fatal injury during rally race: a multidisciplinary approach

International Journal of Legal Medicine - The motor vehicle crash (MVC) constitutes an important challenge for forensic pathology in order to identify the manner and cause of death. Our study...     

Three differentiation states risk-stratify bladder cancer into distinct subtypes

Current clinical judgment in bladder cancer (BC) relies primarily on pathological stage and grade. We investigated whether a molecular classification of tumor cell differentiation, based on a developmental biology approach, can provide additional prognostic information. Exploiting large preexisting gene-expression databases, we developed a biologically supervised computational model to predict markers that correspond with BC differentiation. To provide mechanistic insight, we assessed relative tumorigenicity and differentiation potential via xenotransplantation. We then correlated the prognostic utility of the identified markers to outcomes within gene expression and formalin-fixed paraffin-embedded (FFPE) tissue datasets. Our data indicate that BC can be subclassified into three subtypes, on the basis of their differentiation states: basal, intermediate, and differentiated, where only the most primitive tumor cell subpopulation within each subtype is capable of generating xenograft tumors and recapitulating downstream populations. We found that keratin 14 (KRT14) marks the most primitive differentiation state that precedes KRT5 and KRT20 expression. Furthermore, KRT14 expression is consistently associated with worse prognosis in both univariate and multivariate analyses. We identify here three distinct BC subtypes on the basis of their differentiation states, each harboring a unique tumor-initiating population.     

Prediction of incident type 2 diabetes mellitus based on a twenty-year follow-up of the Ventimiglia heart study

A novel algorithm to predict incident type 2 diabetes mellitus (iT2DM) is presented considering data from a 20-year prospective study in a Southern Italy population. Eight hundred and fifty-eight out of 1,351 subjects (24?C85?years range of age) were selected. Incident type 2 diabetes was diagnosed in 103 patients in a 20-year follow-up. The Finnish Diabetes Risk Score (FINDRISC) and the Framingham Offspring Study simple clinical model (FOS) have been used as reference algorithms. Two custom algorithms have been created using Cox parametric hazard models followed by PROBIT analyses: the first one (VHSRISK) includes all the study subjects and the second one (VHS95RISK) evaluates separately subjects with baseline fasting blood glucose (FBG) above/below 5.2?mmol/L (95?mg/dL). The 44 iT2DM cases below 5.2?mmol/L of baseline FBG were predicted by high LDL cholesterol, metabolic syndrome (ATPIII criteria), BMI?>?30?kg/m², and high factor VII activity. The 59 cases above the FBG threshold were predicted by FBG classes, hypertension, and age. ROC areas for iT2DM prediction were: FINDRISC?=?0.759, FOS?=?0.762, VHSRISK?=?0.789, and VHS95RISK?=?0.803. In a Mediterranean population, the use of a custom generated algorithm evaluating separately low/high FBG subjects improves the prediction of iT2DM in subjects classified at lower risk by common estimation algorithms.     

Current Concept in the Pathophysiology of Hepatitis Delta Infection

Hepatitis delta virus (HDV) is a unique human virus, showing similarities with plant viroids. Although impressive knowledge on virus structure and replication has been achieved, several questions like HBV/HDV interaction and post translational modifications of HD antigens remain to be answered. Potential targets for therapeutic strategies are now emerging. To date, eight major genotypes of the HDV have been identified. The HDV-1 is the prevailing genotype in Europe, but migration phenomena may change this profile. Immune response is likely to play an important role in the pathogenesis of HDV-induced liver disease; few data are available on T cells response either during infection and therapy. HDV usually suppresses HBV replication; recent studies show as viral dominances may change over time. Delta infection leads to severe liver disease, with different patterns of progression to liver fibrosis and decompensation. Beside the association between HDV/HBV and HCC is demonstrated a risk specifically related to HDV remains controversial.     

Efficacy and safety of prostate vaporesection using a 120-W 2-μm continuous-wave Tm:YAG laser (RevoLix 2) in patients on continuous oral anticoagulant or antiplatelet therapy

The aim of our current study was to demonstrate the efficacy and safety of vaporesection using a 120-W Tm:YAG laser (Revolix Duo) in patients with BPH receiving systemic anticoagulation or antiplatelet therapy. Between April 2010 and November 2011, a total of 76 patients using oral antiplatelet or anticoagulant (OA) agents affected by LUTS for BPH were underwent thulium vaporesection of the prostate (ThuVARP) using a 120-W 2-μm CW Tm:YAG laser and evaluated at 3- and 6-month follow-up. Of these, in 41 patients (group A) was performed vaporesection while receiving OA therapy. In 35 patients (group B), OA agents were discontinued 10 days before surgery. There were no significant differences in average vaporesection times, catheterization time, or hospital stay. There was no significant change in serum sodium level before and immediately after vaporesection in either group. Significant improvements compared to baseline were observed at each postoperative assessment in both groups for Qmax, PVR, IPSS, and QoL. More specifically, the IPSS score improved from 21.7 at baseline to 5.2 at 6 months in group A and from 20.7 to 4.5 in group B. At 6 months, Qmax increased 226 and 190 % for the 2 groups, respectively. The PVR decreased from 119 at baseline to 11 mL at 6 months in group A and from 125 to 11 mL in group B. ThuVARP is a safe and efficient procedure for patients with BPH, refractory to pharmacotherapy, who require active antiplatelet or anticoagulant therapy.     

Case-control association study of 36 single-nucleotide polymorphisms within 10 candidate genes for major depression and bipolar disorder

In this study we investigated 36 single nucleotide polymorphisms within 10 genes previously associated with major depression and bipolar disorder, as well as with the response to their treatment (ABCB1, ABCB4, TAP2, CLOCK, CPLX1, CPLX2, SYN2, NRG1, 5HTR1A and GPRIN2). No association with mood disorders and clinical outcomes was observed.     

Comment to the article titled: “Autonomic nervous system function in women with anorexia nervosa” by Jenkins and coll

Clinical Autonomic Research -