Heart Metabolism in Sepsis-Induced Cardiomyopathy-Unusual Metabolic Dysfunction of the Heart.

Due to the need for continuous work, the heart uses up to 8% of the total energy expenditure. Due to the relatively low adenosine triphosphate (ATP) storage capacity, the heart's work is dependent on its production. This is possible due to the metabolic flexibility of the heart, which allows it to use numerous substrates as a source of energy. Under normal conditions, a healthy heart obtains approximately 95% of its ATP by oxidative phosphorylation in the mitochondria. The primary source of energy is fatty acid oxidation, the rest of the energy comes from the oxidation of pyruvate. A failed heart is characterised by a disturbance in these proportions, with the contribution of individual components as a source of energy depending on the aetiology and stage of heart failure. A unique form of cardiac dysfunction is sepsis-induced cardiomyopathy, characterised by a significant reduction in energy production and impairment of cardiac oxidation of both fatty acids and glucose. Metabolic disorders appear to contribute to the pathogenesis of cardiac dysfunction and therefore are a promising target for future therapies. However, as many aspects of the metabolism of the failing heart remain unexplained, this issue requires further research.

Quinaldic acid in synovial fluid of patients with rheumatoid arthritis and osteoarthritis and its effect on synoviocytes in vitro.

BACKGROUND: Previously, we have demonstrated that kynurenic acid (KYNA), an endogenous metabolite of tryptophan formed along kynurenine pathway, is present in synovial fluid of rheumatoid arthritis (RA) and osteoarthritis (OA) patients. In this study, the goal was to investigate the presence of quinaldic acid (QUDA), a putative metabolite of KYNA, in synovial fluid of RA and OA patients. METHODS: The effect of QUDA on proliferation and motility of synovial fibroblasts and its interaction with KYNA were determined in vitro. The study was conducted on synovial fluid obtained from 38 patients with RA and 15 patients with OA. QUDA was identified and quantified using the gas chromatography-mass spectrometry (GC-MS) method. In vitro experiments were conducted on rabbit synoviocyte cell line HIG-82. RESULTS: Presence of QUDA was detected in all 53 samples of synovial fluid. The concentration of QUDA in synovial fluid obtained from patients with RA was 28.6 ±â€¯14.9 pmol/ml, which was lower in comparison with OA 42.3 ±â€¯10.0 pmol/ml. QUDA content positively correlated with the number of tender joints and negatively with the total cell counts determined in synovial fluid of RA patients. It did not correlate with KYNA content. QUDA reduced both proliferation and motility of synoviocytes in a dose-dependent manner. The enhancement of antiproliferative action of QUDA by KYNA was evidenced. CONCLUSIONS: Data show a local deficit of QUDA in RA patients and suggest its potential role as an endogenous substance controlling synoviocyte viability.

Plasma kynurenic acid concentration in patients undergoing cardiac surgery: effect of anaesthesia.

Increases in plasma kynurenic acid (KYNA) concentration relate to the severity of inflammation. The aim of this study was to analyse changes in plasma KYNA concentration and neutrophil/lymphocyte ratio (NLR) in cardiac surgery patients. Additionally, the effect of anaesthesia was analysed. Adult cardiac surgery patients under intravenous general anaesthesia were studied. Additionally, some patients received sevoflurane (SEV) prior to cardiopulmonary bypass. Plasma KYNA concentration and NLR were measured before anaesthesia, just after surgery and on postoperative days 1, 2 and 3. Patients were assigned to two groups: patients who did not receive SEV (NonSEV group) and patients who received SEV (SEV group). Forty-three patients were studied. Twenty-four of them received SEV. KYNA increased immediately after surgery and remained elevated through postoperative day 3 in the NonSEV group, whereas it was similar to the preoperative concentration in the SEV group. NLR increased immediately after surgery in both groups, and higher values were noted in the NonSEV group than in the SEV group at postoperative days 2 and 3. Plasma KYNA concentration correlated with NLR in the NonSEV group. Cardiac surgery caused an increase in NLR. Plasma KYNA increased in the NonSEV group and correlated with NLR. Administration of SEV inhibited the increase in KYNA, most likely due to its anti-inflammatory properties.

Anti-epileptic drugs inhibit viability of synoviocytes in vitro.

INTRODUCTION AND OBJECTIVE: The hyperplasia of synovial fibroblasts is considered to be essential for the evolution of joint destruction in rheumatoid arthritis (RA). Previously, we reported that anti-rheumatic drugs, both COX inhibitors and disease-modifying anti-rheumatic drugs inhibit proliferation of synoviocytes in vitro. The presented study investigates the effect of anti-epileptic drugs on the viability and proliferation of synovial fibroblasts in vitro. METHODS: Experiments were conducted on human synoviocytes derived from an RA patient and rabbit synoviocytes cell line HIG-82. Cell proliferation and viability were assessed by means of BrdU assay and MTT assay, respectively. The IC50 value (the concentration of drug necessary to induce 50% inhibition) together with confidence limits was calculated. RESULTS: Carbamazepine inhibited proliferation of human fibroblasts and viability of HIG-82 with IC 50 values of 86 µM and 82 µM, respectively. Diphenylhydantoin, valproate and phenobarbital inhibited viability of HIG-82 cells with the IC50 values of 110, 500 and 1031 µM, respectively. CONCLUSION: Based on these findings, it can be suggested that anti-epileptic drugs may have a disease-modifying effect on rheumatoid synovial proliferation.

[Kynurenic acid--a new tool in the treatment of hiperhomocysteinemia and its consequences?]. / Kwas kynureninowy--nowy orez w walce z hiperhomocysteinemia i jej nastepstwami?

Atherosclerosis together with its cardiovascular consequences is the most common and significant cause of death, particularly in highly developed countries. The process of atherogenesis begins as soon as in childhood and depends on classical risk factors. Atherosclerosis also results from a chronic inflammatory-immune process which takes place in the vascular walls. Furthermore, it has been known for a number of years that the development of atherosclerotic lesions is closely connected with the concentration of homocysteine in serum. Homocysteine is a sulfur amino acid originating from methionine. An increased concentration of homocysteine in blood harmfully influences blood vessels, leading to a higher risk of ischemic heart disease and stroke. Since tackling classical atherosclerosis risk factors is not efficient enough when it comes to protecting the cardiovascular system from diseases, new substances possessing anti-atherogenic properties, especially endogenous ones, are sought. Recently, researchers have paid attention to a connection between homocysteine and an endogenous tryptophan derivative, kynurenic acid. Recently, it was revealed that kynurenic acid counteracts the harmful effects of homocysteine on endothelium cells in vitro. The hypothesis assuming homocysteine-kynurenate interplay suggests the existence of a new mechanism of atherogenesis and gives us an opportunity to use this knowledge in both prevention and treatment of cardiovascular diseases.