Search results for "PEPTIDE"

Neddylation inhibition ameliorates steatosis in NAFLD by boosting hepatic fatty acid oxidation via the DEPTOR-mTOR axis

2021

Objective Neddylation is a druggable and reversible ubiquitin-like post-translational modification upregulated in many diseases, including liver fibrosis, hepatocellular carcinoma, and more recently, non-alcoholic fatty liver disease (NAFLD). Herein, we propose to address the effects of neddylation inhibition and the underlying mechanisms in pre-clinical models of NAFLD. Methods Hepatic neddylation measured by immunohistochemical analysis and NEDD8 serum levels measured by ELISA assay were evaluated in NAFLD clinical and pre-clinical samples. The effects of neddylation inhibition by using a pharmacological small inhibitor, MLN4924, or molecular approaches were assessed in isolated mouse hep…

Effects of Intravenous Corticotropin-Releasing Hormone upon Sleep-Related Growth Hormone Surge and Sleep EEG in Man

1988

Corticotropin-releasing hormone (CRH) plays a key role in coordinating neuroendocrine, metabolic and behavioral responses in stress and affective disorders. To further investigate the effects of enhanced pituitary-adrenocortical activity upon sleep-related phenomena we administered four intravenous injections of 50 micrograms human (h)-CRH or saline to 11 normal males at 10 p.m., 11 p.m., 12 p.m. and 1 a.m. and measured plasma levels of cortisol and growth hormone (GH) as well as sleep EEG recordings throughout the night. Treatment with h-CRH resulted in a significant increase of mean (+/- SEM) cortisol secretion between 11 p.m. and 3 a.m. (h-CRH: 100.6 +/- 9.5 ng/ml; saline: 39.0 +/- 1.5 n…

Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk population: The ESCARVAL-RISK study

2018

Introduction The potential impact of targeting different components of an adverse lipid profile in populations with multiple cardiovascular risk factors is not completely clear. This study aims to assess the association between different components of the standard lipid profile with all-cause mortality and hospitalization due to cardiovascular events in a high-risk population. Methods This prospective registry included high risk adults over 30 years old free of cardiovascular disease (2008–2012). Diagnosis of hypertension, dyslipidemia or diabetes mellitus was inclusion criterion. Lipid biomarkers were evaluated. Primary endpoints were all-cause mortality and hospital admission due to coron…

Development of a Rapid LC-MS/MS Method for the Determination of Emerging Fusarium mycotoxins Enniatins and Beauvericin in Human Biological Fluids

2015

A novel method for the simultaneous determination of enniatins A, A1, B and B1 and beauvericin, both in human urine and plasma samples, was developed and validated. The method consisted of a simple and easy pretreatment, specific for each matrix, followed by solid phase extraction (SPE) and detection by high performance liquid chromatography-tandem mass spectrometry with an electrospray ion source. The optimized SPE method was performed on graphitized carbon black cartridges after suitable dilution of the extracts, which allowed high mycotoxin absolute recoveries (76%–103%) and the removal of the major interferences from the matrix. The method was extensively evaluated for plasma and urine …

Red cell enzyme polymorphisms in Bulgaria.

1972

7 human red cell enzyme polymophisms have been typed on a sample of n=138 unrelated adults from Bulgaria, which revealed the following gene frequencies: ADA1=0.8623. ADA2=0.1376; AK1=0.9637, AK2=0.0362; 6-PGDA=0.9891, 6-PGDC=0.0108; PGM11=0.8346, PGM12=0.1653; PA=0.1596, PB=0.7983, PC=0.0420. In the LDH-system one B-subunit variant was found, whilst no Peptidase A or B variant could be observed. The anthropological significance of these findings is discussed.

Urinary levels of enniatin B and its phase I metabolites: First human pilot biomonitoring study

2018

Abstract Enniatins (Enns) are mycotoxins produced by Fusarium spp. and are widely distributed contaminants of cereals and derivate products. Among the different identified enniatins, Enn B is the most relevant analogue in cereals in Europe. Therefore, the aim of this study was to investigate for the first time the occurrence of Enn B and Enn B phase I metabolites in 300 human urine samples throughout an ultrahigh-performance liquid chromatography-high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) methodology. Three different sample preparation procedures were evaluated and salting-out liquid-liquid extraction showed satisfactory validation results. Enn B was quantified in 83.7% of sa…

Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial

2022

AbstractThe STEP 5 trial assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo (both plus behavioral intervention) for long-term treatment of adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes. The co-primary endpoints were the percentage change in body weight and achievement of weight loss of ≥5% at week 104. Efficacy was assessed among all randomized participants regardless of treatment discontinuation or rescue intervention. From 5 October 2018 to 1 February 2019, 304 participants were randomly assigned to semaglutide 2.4 mg (n = 152) or placebo (n = 152), 92.8% of whom completed the trial (attended t…

Rare NLRP12 variants associated with the NLRP12-autoinflammatory disorder phenotype: an Italian case series.

2013

Influence of genetic variation at the apo A-I gene locus on lipid levels and response to diet in familial hypercholesterolemia

1998

We have examined the apo AI - 75 (G/A) and apo AI + 83(MspI +/-) polymorphisms at the APOA1 gene locus for associations with plasma lipid levels and response to an NCEP-I diet in 69 (44 women, 25 men) heterozygotes for familial hypercholesterolemia (FH). Subjects were studied at baseline (after consuming for one month a diet with 35%, fat, 10% saturated, and 300 mg/day cholesterol) and after 3 months of an NCEP-I diet. No gender-related differences for any of the lipid variables examined were found and the data were analyzed for men and women combined. For the apo AI - 75 (G/A) polymorphism, there were 51 G/G and 18 G/A subjects. At baseline, G/A subjects showed significantly lower total ch…

Evaluation of clinical diagnosis criteria of familial ligand defective apoB 100 and lipoprotein phenotype comparison between LDL receptor gene mutati…

2007

Familial hypercholesterolemia (FH) and familial defective apoB 100 (FDB) are characterized by increased plasma low-density lipoprotein cholesterol (LDLc) levels and risk of coronary heart disease (CHD). FDB is clinically indistinguishable from FH. The aims of this study were to evaluate clinical diagnosis criteria for FDB and to compare the lipoprotein phenotype between carriers of LDL receptor (LDLR) gene mutations that affect the ligand-binding domain and subjects with the R3500Q mutation in apoB gene. We studied 213 subjects (113 probands) with FH and 19 heterozygous FDB subjects. Genetic diagnosis was determined by following a protocol based on Southern blot and polymerase chain reactio…