fumarates and Lung-Diseases

Methicillin-resistant

Topics: Acetylglucosamine; Adult; Animals; Biofilms; Bronchi; Bronchoalveolar Lavage Fluid; Cystic Fibrosis; Cytokines; Female; Fumarates; Gentamicins; Glucose; Humans; Lung Diseases; Malates; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred C57BL; Middle Aged; Phylogeny; Pneumonia, Staphylococcal; Pyruvic Acid; Staphylococcal Infections; Transcription, Genetic; Tricarboxylic Acids; Whole Genome Sequencing

The renin-angiotensin system (RAS), which plays an important role in the progression of heart failure, is efficiently blocked by the inhibition of renin, the rate-limiting enzyme in the RAS cascade. In the present study, we investigated the cardioprotective effects of TAK-272 (SCO-272, imarikiren), a novel, orally effective direct renin inhibitor (DRI), and compared its efficacy with that of aliskiren, a DRI that is already available in the market. TAK-272 was administered to calsequestrin transgenic (CSQ-tg) heart failure mouse model that show severe symptoms and high mortality. The CSQ-tg mice treated with 300 mg/kg, the highest dose tested, of TAK-272 showed significantly reduced plasma renin activity (PRA), cardiac hypertrophy, and lung congestion. Further, TAK-272 reduced cardiomyocyte injury accompanied by an attenuation of the increase in NADPH oxidase 4 and nitric oxide synthase 3 expressions. TAK-272 also prolonged the survival of CSQ-tg mice in a dose-dependent manner (30 mg/kg: P = 0.42, 100 mg/kg: P = 0.12, 300 mg/kg: P < 0.01). Additionally, when compared at the same dose level (300 mg/kg), TAK-272 showed strong and sustained PRA inhibition and reduced the heart weight and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration, a heart failure biomarker, while aliskiren showed a significant weaker PRA inhibition and failed to demonstrate any cardioprotective effects. Our results showed that TAK-272 is an orally active and persistent renin inhibitor, which reduced the mortality of CSQ-tg mice and conferred protection against cardiac hypertrophy and injury. Thus, TAK-272 treatment could provide a new therapeutic approach for heart failure.

Topics: Amides; Animals; Benzimidazoles; Cardiovascular Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Fumarates; Heart; Heart Failure; Hypertrophy; Lung Diseases; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Transgenic; Morpholines; Piperidines; Protective Agents; Random Allocation; Renin

  We present the case of a 49-year old male who presented with dyspnoea, cough, weight loss, night sweats and general malaise. He had been on treatment with oral fumaric acid esters (FAE, Fumaderm®; Biogen Idec GmbH, Ismaning, Germany) for 6 months..   Report of a case..   His chest X-ray showed patchy infiltrates in the left upper lobe which failed to resolve under empiric antibiotic therapy. A computed tomography of thorax revealed bilateral, mostly peripheral foci of consolidation with air bronchograms. Transbronchial biopsies showed a pattern of organising pneumonia (OP)..   Therapy with oral prednisolone (40 mg/day) resulted in a rapid clinical and radiological improvement. An association of FAE and OP has not previously been reported. Please cite this paper as: Deegan AP, Kirby B, Rogers S, Crotty TB and McDonnell TJ. Organising pneumonia associated with fumaric acid ester treatment for psoriasis.

Topics: Administration, Oral; Biopsy; Cryptogenic Organizing Pneumonia; Fumarates; Glucocorticoids; Humans; Lung Diseases; Male; Middle Aged; Prednisolone; Psoriasis; Tomography, X-Ray Computed

Superoxide dismutase and catalase, which catalytically remove O-2 and H2O2, respectively, each separately protected cultured pulmonary artery endothelial cells from loss of membrane integrity after exposure to oxygen radicals generated either cellularly (polymorphonuclear leukocytes) or chemically (dihydroxyfumarate). Nicotinamide, a precursor of nicotinamide-adenine dinucleotide (NAD) and an inhibitor of ADP-ribose synthetase, also protected cultured endothelial cells from loss of membrane integrity in a concentration-dependent manner after exposure to DHF.

Topics: Animals; Catalase; Cattle; Drug Interactions; Endothelium; Fumarates; In Vitro Techniques; L-Lactate Dehydrogenase; Lung Diseases; Niacinamide; Pulmonary Artery; Superoxide Dismutase