Empagliflozin treatment rescues abnormally reduced Na currents in ventricular cardiomyocytes from dystrophin-deficient mice.

Cardiac arrhythmias significantly contribute to mortality in Duchenne muscular dystrophy (DMD), a severe muscle illness caused by mutations in the gene encoding for the intracellular protein dystrophin. A major source for arrhythmia vulnerability in patients with DMD is impaired ventricular impulse conduction, which predisposes for ventricular asynchrony, decreased cardiac output, and the development of reentrant circuits. Using the dystrophin-deficient mouse model for human DMD, we previously reported that the lack of dystrophin causes a significant loss of peak Na current () in ventricular cardiomyocytes.

X-Ray fluorescence as a method of characterizing inorganic pigment patterns in the work of Julian Onderdonk.

This study utilized portable X-Ray fluorescence to analyze pigment patterns in 33 paintings by Julian Onderdonk, a 19th-20th century Texas impressionist. This analysis led to the identification of distinctive pigment preferences for Onderdonk at different periods of his career. Using the pigment preference patterns identified in the paintings that were dated by the artist, undated works were analyzed and assigned to different periods in the artists career based on their pigment patterns.

Inflammasome Activity in the Skeletal Muscle and Heart of Rodent Models for Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is characterized by wasting of muscles that leads to difficulty moving and premature death, mainly from heart failure. Glucocorticoids are applied in the management of the disease, supporting the hypothesis that inflammation may be driver as well as target. However, the inflammatory mechanisms during progression of cardiac and skeletal muscle dysfunction are still not well characterized.

Ivabradine acutely improves cardiac Ca handling and function in a rat model of Duchenne muscular dystrophy.

The muscular dystrophies caused by dystrophin deficiency, the so-called dystrophinopathies, are associated with impaired cardiac contractility and arrhythmias, which considerably contribute to disease morbidity and mortality. Impaired Ca handling in ventricular cardiomyocytes has been identified as a causative factor for complications in the dystrophic heart, and restoration of normal Ca handling in myocytes has emerged as a promising new therapeutic strategy. In the present study, we explored the hypothesis that ivabradine, a drug clinically approved for the treatment of heart failure and stable angina pectoris, improves Ca handling in dystrophic cardiomyocytes and thereby enhances contractile performance in the dystrophic heart.

Alterations in Coronary Resistance Artery Network Geometry in Diabetes and the Role of Tenascin C.

Background: Geometrical alterations in the coronary resistance artery network and the potential involvement of Tenascin C (TNC) extracellular matrix protein were investigated in diabetic and control mice.

Methods: Diabetes was induced by streptozotocin (STZ) injections (n = 7-11 animals in each group) in Tenascin C KO (TNC KO) mice and their Wild type (A/J) littermates. After 16-18 weeks the heart was removed and the whole subsurface network of the left coronary artery was prepared (down to branches of 40 m outer diameter), pressure-perfused and studied using video-microscopy.

Specific Graft Treatment Solution Enhances Vascular Endothelial Function.

Background: Saline is still the most widely used storage and rinsing solution for vessel grafts during cardiac surgery despite knowing evidence of its negative influence on the human endothelial cell function. Aim of this study was to assess the effect of DuraGraft©, an intraoperative graft treatment solution, on human saphenous vein segments and further elaborate the vasoprotective effect on rat aortic segments in comparison to saline.

Methods: Human Saphenous vein (HSV) graft segments from patients undergoing aortocoronary bypass surgery (n = 15), were randomized to DuraGraft© (n = 15) or saline (n = 15) solution before intraoperative storage.

Remote Ischemic Perconditioning Ameliorates Myocardial Ischemia and Reperfusion-Induced Coronary Endothelial Dysfunction and Aortic Stiffness in Rats.

Background: Vascular stiffness and endothelial dysfunction are accelerated by acute myocardial infarction (AMI) and subsequently increase the risk for recurrent coronary events.

Aim: To explore whether remote ischemic perconditioning (RIPerc) protects against coronary and aorta endothelial dysfunction as well as aortic stiffness following AMI.

Methods: Male OFA-1 rats were subjected to 30 min of occlusion of the left anterior descending artery (LAD) followed by reperfusion either 3 or 28 days with or without RIPerc.

Glial and tissue-specific regulation of dioxygenases by acute stress of mice.

Stressors activate the hypothalamic-pituitary-adrenal (HPA) axis and immune system eliciting changes in cognitive function, mood and anxiety. An important link between stress and altered behavior is stimulation of the which generates neuroactive and immunomodulatory kynurenines. Tryptophan entry into this pathway is controlled by rate-limiting indoleamine/tryptophan 2,3-dioxygenases (DOs: Ido1, Ido2, Tdo2).

Glia- and tissue-specific changes in the Kynurenine Pathway after treatment of mice with lipopolysaccharide and dexamethasone.

Behavioral symptoms associated with mood disorders have been intimately linked with immunological and psychological stress. Induction of immune and stress pathways is accompanied by increased tryptophan entry into the Kynurenine (Kyn) Pathway as governed by the rate-limiting enzymes indoleamine/tryptophan 2,3-dioxygenases (DO's: Ido1, Ido2, Tdo2). Indeed, elevated DO expression is associated with inflammation- and stress-related depression symptoms.

The kynurenine to tryptophan ratio as a prognostic tool for glioblastoma patients enrolling in immunotherapy.

We hypothesized that peripheral tryptophan (Trp) and/or kynurenine (Kyn) levels would provide prognostic value for physicians planning to enroll glioblastoma multiforme (GBM) patients in immunotherapy. GBM is the most common form of malignant glioma in adults. Despite aggressive surgical resection, irradiation and chemotherapy, patients with GBM have a median survival of only 14.

Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study.

Intravenous cyclophosphamide is considered to be the standard of care for the treatment of proliferative lupus nephritis. However, its use is limited by potentially severe toxic effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative to cyclophosphamide.

HLA-Cw*06 class I region rather than MICA is associated with psoriatic arthritis in Czech population.

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease which affects patients suffering from psoriasis. The genetic background especially the susceptibility loci on the short arm of the chromosome six contribute to PsA development. In our study, we looked for the role of the MICA and HLA-Cw genes polymorphisms in PsA pathogenesis.

Magnetic resonance volumetry of pathological brain foci in patients with systemic lupus erythematosus.

Objective: The aim of our study was to determine the volume of pathological foci in the brain tissue of patients suffering from systemic lupus erythematosus (SLE) with or without neuropsychiatric manifestations (NP), and also to find out if that volume depends on the study subjects' data and clinical records. Magnetic resonance (MR) scans of patients with SLE and, in particular, signs of neuropsychiatric involvement, show pathological foci in the cerebral white matter.

Methods: A total of 53 SLE patients, 29 with signs of neuropsychiatric syndromes (NPSLE), 24 without, and 16 healthy controls underwent prospective volumetric magnetic resonance imaging in a flow attenuated inversion recovery (FLAIR) sequence.

EULAR points to consider for conducting clinical trials in systemic lupus erythematosus: literature based evidence for the selection of endpoints.

Objective: To assess available evidence on the use of end-points (outcome measures) in clinical trials in systemic lupus erythematosus (SLE), as a part of the development of evidence-based recommendations for points to consider in clinical trials in SLE.

Methods: The European League Against Rheumatism (EULAR) Task Force on SLE comprised 19 specialists, a clinical epidemiologist and a research fellow. Key questions addressing the evidence for clinical trial end-points in SLE were compiled using the Delphi technique.

EULAR points to consider for conducting clinical trials in systemic lupus erythematosus.

Objective: Systemic lupus erythematosus (SLE) is a complex multi-organ disease, characterised by relapses and remissions.

Design: ng a high-quality randomised controlled trial poses many challenges. We have developed evidenced-based recommendations for points to consider in conducting clinical trials in patients with SLE.

[Prolactin response to stress in patients with systemic lupus erythematodes (SLE), rheumatoid arthritis (RA) and in healthy controls].

Prolactin is a one of the stress hormones, like the growth hormone, ACTH, cortisol and catecholamins. Among its wide range of functions is the important role of controlling the immune response which is, unlike in the case of cortisol, of stimulatory nature. For this activity, it is monitored as a factor influencing the progress and course of autoimmune diseases.

Prevalence of antinucleosome antibodies by enzyme-linked immunosorbent assays in patients with systemic lupus erythematosus and other autoimmune systemic diseases.

The objective was to report our experience with the detection of antinucleosome antibodies (anti-Ncs Ab) in a series of systemic lupus erythematosus (SLE) patients, and to compare these results with those of antihistone and anti-double-stranded (ds) DNA antibodies. For this we selected 128 patients (106 females, 22 males, mean age 40 years) including 52 patients with SLE without organ involvement, 14 with lupus nephritis, 8 with neuropsychiatric lupus (NPSLE), 39 with systemic sclerosis (SSc), 15 with Sjögren syndrome (SS), and 51 healthy controls (38 females, 13 males, mean age 42 years). The sera were assayed for the levels of anti-ds DNA (ELISA), antihistone (INNO LIA ANA Update), anti-Ncs Ab (ELISA) and antinuclear antibodies (ANA-indirect immunofluorescence (IIF) on Hep-2 cells).

Opposed independent effects and epistasis in the complex association of IRF5 to SLE.

Genetic variation in the interferon regulatory factor 5 (IRF5) gene affects systemic lupus erythematosus (SLE) susceptibility. However, association is complex and incompletely defined. We obtained fourteen European sample collections with a total of 1383 SLE patients and 1614 controls to better define the role of the different IRF5 variants.

EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics.

Objective: Systemic lupus erythematosus (SLE) is a complex disease with variable presentations, course and prognosis. We sought to develop evidence-based recommendations addressing the major issues in the management of SLE.

Methods: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist.

Treatment of lupus nephritis with cyclosporine - an outcome analysis.

Background: The optimal therapy for lupus nephritis (LN), including the role of cyclosporine (CsA), still lacks scientifically valid clinical experience. We evaluated the efficacy of CsA in the induction and maintenance treatment of patients with biopsy-proven LN.

Patients And Methods: A total of 31 patients (25 women, 6 men, mean age 29.