Extracellular purines in lung endothelial permeability and pulmonary diseases.

The purinergic signaling system is an evolutionarily conserved and critical regulatory circuit that maintains homeostatic balance across various organ systems and cell types by providing compensatory responses to diverse pathologies. Despite cardiovascular diseases taking a leading position in human morbidity and mortality worldwide, pulmonary diseases represent significant health concerns as well. The endothelium of both pulmonary and systemic circulation (bronchial vessels) plays a pivotal role in maintaining lung tissue homeostasis by providing an active barrier and modulating adhesion and infiltration of inflammatory cells.

The long term effects of uncoupling interventions as a therapy for dementia in humans.

In this paper we use simulation methods to study a hypothetical uncoupling agent as a therapy for dementia. We simulate the proliferation of mitochondrial deletion mutants amongst a population of wild-type in human neurons. Mitochondria play a key role in ATP generation.

The prevalence of dementia in humans could be the result of a functional adaptation.

In this paper we propose that high copy number of the mitochondrial genome in neurons is a functional adaptation. We simulated the proliferation of deletion mutants of the human mitochondrial genome in a virtual mitochondrion and recorded the cell loss rates due to deletions overwhelming the wild-type. Our results showed that cell loss increased with mtDNA copy number.

A comparison of mtDNA deletion mutant proliferation mechanisms.

In this paper we use simulation methods to investigate the proliferation of deletion mutations of mitochondrial DNA in neurons. We simulate three mtDNA proliferation mechanisms, namely, random drift, replicative advantage and vicious cycle. For each mechanism, we investigated the effect mutation rates have on neuron loss within a human host.

The Effect of Mitochondrial DNA Half-Life on Deletion Mutation Proliferation in Long Lived Cells.

The proliferation of mitochondrial DNA (mtDNA) with deletion mutations has been linked to aging and age related neurodegenerative conditions. In this study we model the effect of mtDNA half-life on mtDNA competition and selection. It has been proposed that mutation deletions ([Formula: see text]) have a replicative advantage over wild-type ([Formula: see text]) and that this is detrimental to the host cell, especially in post-mitotic cells.

Metabolism and pharmacokinetics of naronapride (ATI-7505), a serotonin 5-HT(4) receptor agonist for gastrointestinal motility disorders.

The absorption and disposition of the serotonin 5-HT(4) receptor agonist, naronapride (6-[(3S,4R)-4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-1-yl]-hexanoic acid 1-aza-bicyclo[2,2,2]oct-(R)-3-yl ester dihydrochloride; ATI-7505), were evaluated in healthy males given a single 120-mg oral dose of (14)C-labeled compound. Serial blood samples and complete urine and feces were collected up to 552 h postdose. Naronapride was extensively metabolized, undergoing rapid hydrolysis to 6-[(3S,4R)-4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-1-yl]-hexanoic acid (ATI-7500) with stoichiometric loss of quinuclidinol.

Impact of catheter sizes and intracoronary glyceryl trinitrate on the TIMI frame count when digital angiograms are acquired at lower frame rates during elective angiography and PCI.

Unlabelled: The TIMI frame count (TFC) is a useful measure of coronary flow. To be widely applicable, the effect of different catheter sizes and the use of intracoronary glyceryl trinitrate (ICGTN) must be determined when films are acquired at lower acquisition rates (12.5 frames/s, f/s).

Early invasive versus conservative treatment in patients with failed fibrinolysis--no late survival benefit: the final analysis of the Middlesbrough Early Revascularisation to Limit Infarction (MERLIN) randomized trial.

Background: Early (30 days) and midterm (6 months) clinical outcomes in trials comparing rescue angioplasty (rescue percutaneous coronary intervention [rPCI]) with conservative treatment of failed fibrinolysis complicating ST-segment elevation myocardial infarction have shown variable results. Whether early rPCI confers late (up to 3 years) clinical benefits is not known.

Methods: The MERLIN trial compared rPCI and a conservative strategy in patients with failed fibrinolysis complicating ST-segment elevation myocardial infarction.

A prospective randomised controlled trial to determine the early and late reactions after the use of iopamidol 340 (Niopam) and iomeprol 350 (Iomeron) in cardiac catheterisation.

Unlabelled: A new generation of intravascular contrast agents, the non-ionic monomers have safety profiles that are superior to those of older ionic compounds. There are, however, significant differences between these agents.

Aim: The aim of this study was to determine the incidence of early (<24h) and late (>24h to 7 days) reactions to two non-ionic contrast agents currently used during cardiac catheterisation: iopamidol 340 (Niopam Bracco UK Ltd.

A randomized trial of prophylactic antiarrhythmic agents (amiodarone and sotalol) in patients with atrial fibrillation for whom direct current cardioversion is planned.

Unlabelled: Antiarrhythmic agents enhance maintenance of sinus rhythm (SR) after direct current cardioversion (DCC) for atrial fibrillation but there are few comparative trials.

Background: The aims of the study were (1) to establish whether patients successfully cardioverted to SR are more likely to stay in SR over 6 months if taking amiodarone or sotalol, and if so, to establish whether one agent is better than the other; (2) to establish whether taking amiodarone or sotalol is better at achieving chemical cardioversion within the 6 weeks before DCC; and (3) to establish whether DCC is more likely to be successful on a drug.

Methods: Randomized, prospective, nonblinded, controlled study of treatment with either amiodarone (n = 27), sotalol (n = 36), or no antiarrhythmic agent (n = 31).

Ethanol feeding enhances age-related deterioration of the rat hepatic mitochondrion.

Chronic ethanol feeding damages the hepatic mitochondrion by increasing mitochondrial DNA (mtDNA) oxidation, lowering mtDNA yields and impairing mitochondrial respiration. These effects are also seen during aging. By employing a 21-day chronic feeding regimen, we investigated the effects of ethanol consumption on mtDNA content and mitochondrial respiration in 2-, 12-, and 24-mo-old male rats.

A prospective, randomized trial to determine the early and late reactions after the use of iopamidol 340 (Niopam) and iobitridol 350 (Xenetix) in cardiac catheterization.

Background: Intravascular contrast agents presently used in modern digital catheter laboratories during cardiac catheterization are superior to older agents as regards patient tolerance. There are, however, significant differences between these agents.

Purpose: The aim of this study was to determine the incidence of early (< 24 hours) and late (> 24 hours to 7 days) reactions to 2 contrast agents currently used during cardiac catheterization: iopamidol 340 (Niopam) and iobitridol 350 (Xenetix).

Corrected TIMI frame count: applicability in modern digital catheter laboratories when different frame acquisition rates are used.

The original description of the TIMI frame count (TFC) method was based on angiograms acquired at 30 f/sec. Modern digital angiograms are acquired at lower frame rates (between 12.5 and 25 f/sec).

A randomized trial of rescue angioplasty versus a conservative approach for failed fibrinolysis in ST-segment elevation myocardial infarction: the Middlesbrough Early Revascularization to Limit INfarction (MERLIN) trial.

Objectives: We sought to compare emergency coronary angiography with or without rescue percutaneous coronary intervention (PCI) with conservative treatment in patients with failed fibrinolysis complicating ST-segment elevation myocardial infarction (STEMI).

Background: Most patients with STEMI receive fibrinolytic therapy and aspirin. The management of failed fibrinolysis is unclear.

Infection-induced expansion of a MHC Class Ib-dependent intestinal intraepithelial gammadelta T cell subset.

Salmonella species invade the host via the intestinal epithelium. Hence, intestinal intraepithelial lymphocytes (iIELs) are potentially the first element of the immune system to encounter Salmonella during infection. In this study, we demonstrate, in a mouse model, the expansion of a CD8alphabeta(+)CD94(-)TCRgammadelta(+) T cell subset within the iIEL population in response to oral infection with virulent or avirulent Salmonella.

A peptide from heat shock protein 60 is the dominant peptide bound to Qa-1 in the absence of the MHC class Ia leader sequence peptide Qdm.

The MHC class Ib molecule Qa-1 binds specifically and predominantly to a single 9-aa peptide (AMAPRTLLL) derived from the leader sequence of many MHC class Ia proteins. This peptide is referred to as Qdm. In this study, we report the isolation and sequencing of a heat shock protein 60-derived peptide (GMKFDRGYI) from Qa-1.

A Ca2+-induced mitochondrial permeability transition causes complete release of rat liver endonuclease G activity from its exclusive location within the mitochondrial intermembrane space. Identification of a novel endo-exonuclease activity residing within the mitochondrial matrix.

Endonuclease G, a protein historically thought to be involved in mitochondrial DNA (mtDNA) replication, repair, recombination and degradation, has recently been reported to be involved in nuclear DNA degradation during the apoptotic process. As a result, its involvement in mtDNA homeostasis has been called into question and has necessitated detailed analyses of its precise location within the mitochondrion. Data is presented localizing rat liver endonuclease G activity exclusively to the mitochondrial intermembrane space with no activity associated with either the interior face of the inner mitochondrial membrane or with the mitochondrial matrix.

Effects of alcohol and oxidative stress on liver pathology: the role of the mitochondrion.

This article represents the proceedings of a symposium at the 2001 Research Society on Alcoholism meeting in Montreal, Canada. The chairs were Alan Cahill and Carol C. Cunningham.