Serological Biomarker Panel in Diagnosis of Atrophic Gastritis and Helicobacter pylori Infection in Gastroscopy Referral Patients: Clinical Validation of the New-Generation GastroPanel® Test.

BACKGROUND/AIM: Prompted by the increasing demand of non-invasive diagnostic tools for screening of gastric cancer (GC) risk conditions, i.e., atrophic gastritis (AG) and Helicobacter pylori (Hp) infection, the GastroPanel® test (GP: biomarker panel of PGI, PGII, G-17, Hp IgG ELISA) that was developed in the early 2000's, was recently updated to a new-generation (unified GP) test version. This clinical validation study evaluated the diagnostic accuracy of the new-generation GP test in detection of AG and Hp among gastroscopy referral patients in a University Clinic. PATIENTS AND METHODS: Altogether, 522 patients were enrolled among the patients referred for gastroscopy at the Gastro Center, Oulu University Hospital (OUH). All patients underwent gastroscopy with biopsies classified using the Updated Sydney System (USS), and blood sampling for GP testing. RESULTS: Biopsy-confirmed AG was found in 10.2% (53/511) of the patients. The overall agreement between the GP and the USS classification was 92.4% (95%CI=90.0-94.6%), with the weighted kappa (κw) of 0.861 (95%CI=0.834-0.883). In ROC analysis using moderate/severe AG of the corpus (AGC2+) as the endpoint, AUC=0.952 (95%CI=0.891-1.000) and AUC=0.998 (95%CI=0.996-1.000) for PGI and PGI/PGII, respectively. Hp IgG antibody ELISA detected biopsy-confirmed Hp-infection with AUC=0.993 (95%CI=0.987-0.999). CONCLUSION: The new generation GastroPanel® is a precise test for non-invasive diagnosis of atrophic gastritis and Hp-infection in dyspeptic patients referred for diagnostic gastroscopy.

Influence of calcium-induced workload transitions and fatty acid supply on myocardial substrate selection.

Because of differences in energy yield and oxygen demand, the selection of oxidative fuels is important in the hypoxic or ischemic heart muscle. The aim of the present study was to clarify the contradictions observed in the effects of workload and fatty acid supply on myocardial fuel preference in isolated perfused rat hearts. Nuclear magnetic resonance spectroscopy combined with the administration of substrates labeled with the stable isotope carbon 13 and isotopomer analysis of glutamate labeling offers an opportunity to simultaneously measure metabolic fluxes in pathways feeding into the tricarboxylic acid (TCA) cycle. The work output was modulated by changes in extracellular calcium. In the presence of 5 mmol/L glucose, 0.5 mmol/L octanoate in the perfusate dominated the oxidative metabolism, and workload had little effect on the ratio of glucose to fatty acid utilization. This was the case even when the octanoate concentration was lowered to 50 micromol/L. The relative rate of replenishment of the TCA cycle intermediates was higher at a low workload. The redox state of flavoproteins in the intact heart was monitored fluorometrically to obtain an estimate of the mitochondrial reduced/oxidized nicotinamide-adenine dinucleotide ratio (NADH/NAD ratio) for assessment of the dominant level of regulation of cell respiration, and the myoglobin spectrum was simultaneously monitored to evaluate the oxygenation status of the myocardium. Commencement of octanoate infusion (50 micromol/L or 0.5 mmol/L) caused a large but transient reduction of mitochondrial NAD and, conversely, its cessation elicited NADH oxidation and rebound reduction. During glucose oxidation, an increase in workload led to oxidation of the mitochondrial NADH, but this effect was much smaller in the presence of 50 micromol/L octanoate and absent in the presence of 0.5 mmol/L. This indicates that strong control of oxygen consumption during glucose oxidation is exerted in the mitochondrial respiratory chain, whereas equal control during fatty acid oxidation is exerted within the metabolic pathway upstream from the respiratory chain. It is concluded that when a medium-chain fatty acid is available, myocardial workload and energy consumption have little influence on fuel preference and glucose oxidation remains suppressed.

Ischaemic preconditioning and a mitochondrial KATP channel opener both produce cardioprotection accompanied by F1F0-ATPase inhibition in early ischaemia.

Ischaemic preconditioning gives powerful protection against prolonged ischaemia affecting several intracellular regulatory and messenger pathways, although their mutual importance is far from established. Protective, preconditioning-like effects have been reported for K(ATP) channel openers, and most of the evidence points to the mitochondrial K(ATP) channels. We show here that the K(ATP) channel opener diazoxide, which acts selectively on the mitochondrial channel, causes potentiation of ischaemic inhibition of mitochondrial ATP synthase (F(1)F(0)-ATPase) along with cardioprotection. These effects are comparable with that of ischaemic preconditioning. The administration of diazoxide did not affect the cellular energy state as monitored with (31)P NMR. The actions of both diazoxide and ischaemic preconditioning were prevented by 5-hydroxydecanoate, a specific inhibitor of the mitochondrial K(ATP) channel. Thus mitochondrial K(ATP) channel opening and ischaemic preconditioning must share common mechanisms of action involving mitochondrial F(1)F(0)-ATPase, although involvement of the energy state in protection could not be proved.