The Lipoprotein Profile Evaluated by 1H-NMR Improves the Performance of Genetic Testing in Familial Hypercholesterolemia.

Background: The familial hypercholesterolemia (FH) diagnosis is based on clinical and genetic criteria. A relevant proportion of FH patients fulfilling the criteria for definite FH have negative genetic testing. Increasing the identification of true genetic-based FH is a clinical challenge.

Engineering and utilization of reporter cell lines for cell-based assays of transmembrane receptors.

Transmembrane receptors, a subset of integral membrane proteins, are the receivers that transduce an extracellular chemical message into an intracellular response. Accordingly, these proteins are of particular interest in the scientific community and are probably best studied as part of a cellular system. Herein, we detail the engineering of a fluorescent and bioluminescent reporter cell line for a transmembrane receptor and how to employ it in a directed evolution screen that identifies peptide regulators of receptor activity.

Protein engineering methods applied to membrane protein targets.

Genes encoding membrane proteins have been estimated to comprise as much as 30% of the human genome. Among these membrane, proteins are a large number of signaling receptors, transporters, ion channels and enzymes that are vital to cellular regulation, metabolism and homeostasis. While many membrane proteins are considered high-priority targets for drug design, there is a dearth of structural and biochemical information on them.

Evaluation of myocyte proliferation in alcoholic cardiomyopathy: telomerase enzyme activity (TERT) compared with Ki-67 expression.

Aims: Although the human heart was classically considered a terminal organ, recent studies have reported a myocyte proliferation response versus some aggressions. Excessive ethanol consumption induces development of cardiomyopathy (CMP) through myocyte apoptosis. We evaluated myocyte proliferation response in the heart of chronic alcoholic donors with telomerase activity (telomerase reverse transcriptase (TERT)) compared with Ki-67 nuclear expression.

Increased myostatin activity and decreased myocyte proliferation in chronic alcoholic cardiomyopathy.

Background: Apoptosis mediates in alcohol-induced heart damage leading to cardiomyopathy (CMP). Myocyte proliferation may compensate for myocyte loss. Myostatin is upregulated after cardiac damage and by alcohol consumption thereby decreasing myocyte renewal.

Characterization of C-alkyl amidines as bioavailable covalent reversible inhibitors of human DDAH-1.

C-Alkyl amidine analogues of asymmetric N(ω),N(ω)-dimethyl-L-arginine are dual-targeted inhibitors of both human DDAH-1 and nitric oxide (NO) synthase, and provide a promising scaffold for the development of therapeutics to control NO overproduction in a variety of pathologies including septic shock and some cancers. Using a two-part click-chemistry-mediated activity probe, a homologated series of C-alkyl amidines were ranked for their ability to inhibit DDAH-1 within cultured HEK 293T cells. N⁵-(1-Iminopentyl)-L-ornithine was determined to be the most potent compound in vitro (K(d)=7 μM) as well as in cultured cells, and the binding conformation and covalent reversible mode of inhibition was investigated by comparison of interactions made with DDAH-1 and a catalytically inactive C274S variant, as gauged by X-ray crystallography and isothermal titration calorimetry.

Analysis of nucleic acid binding by a recombinant translin-trax complex.

Translin is a highly conserved mammalian RNA and DNA-binding protein involved in DNA recombination and RNA trafficking. Crystal structures of mouse and human translin have been solved, but do not provide information about nucleic acid binding or recognition. Translin has a partner protein, translin-associated factor x (trax), which is believed to regulate translin's subcellular locale and affinity for certain RNA and DNA sequences.

Severe acute poisoning due to a glufosinate containing preparation without mitochondrial involvement.

Glufosinate is a non-selective herbicide widely used in domestic gardens and agriculture. Few cases of glufosinate poisoning have been reported although there has been an increase in recent years, particularly in Japan. Glufosinate toxicity is related to its capacity to inhibit glutamine synthetase and glutamate decarboxylase, which may lead to a potentially fatal multiorgan failure.

Diphenhydramine overdose and Brugada sign.

We report a case of electrocardiographic signature of the Brugada syndrome in a 39-year-old patient with an overdose of diphenhydramine. He was found unconscious and hypotensive. His serum potassium concentration was 8.

Myocardial antioxidant status in chronic alcoholism.

Background: Excessive ethanol intake is one of the most frequent causes of acquired dilated cardiomyopathy in developed countries. The pathogenesis is multifactorial, with the antioxidant imbalance of cardiac muscle being a potential factor. The current study evaluates myocardial antioxidant status in ethanol consumers and its relation to cardiac damage.