Humans ; Pulmonary Embolism ; Pyrazoles ; Pyridones ; Venous Thrombosis

The concept on idiopathic pulmonary fibrosis (IPF) pathogenesis has progressed from chronic inflammation to aberrant wounding healing and even more to the current paradigms of a multifactorial and heterogeneous disease process. Despite the growth of clinical trials for IPF, most of the results, including N-acetylcysteine combination, warfarin, and bosentan, were disappointing. On the other hand, there have been a number of important developments; the foremost is the licensing of pirfenidone in Europe and Asia. In this article, we briefly review the recent knowledge of pathogenesis of IPF. We also summarize the recent clinical trials regarding the management of IPF.
Acetylcysteine ; Asia ; Europe ; Hand ; Idiopathic Pulmonary Fibrosis ; Inflammation ; Licensure ; Pyridones ; Sulfonamides ; Warfarin

BACKGROUND: Iron overload is a predictable and life-threatening complication in patients dependent on the regular transfusion of RBCs. The aims of this study were to investigate the efficacy and safety of deferiprone in a variety of pediatric hematologic and/or oncologic patients with a high iron overload. METHODS: Seventeen patients (age: 1.1-20.4 years; median: 10.6 years) from 7 hospitals who were treated with deferiprone from 2006 to 2009 were enrolled in this study. Medical records of enrolled patients were reviewed retrospectively. RESULTS: Serum ferritin levels were 4,677.8+/-1,130.9 microgram/L at baseline compared to 3,363.9+/-1,149.7 microgram/L at the end of deferiprone treatment (P=0.033). Only 1 patient developed neutropenia as a complication. CONCLUSION: Deferiprone treatment is relatively safe for pediatric patients suffering from various hematologic and oncologic diseases that require RBC transfusions as part of treatment. However, the potential development of critical complications such as agranulocytosis and/or neutropenia remains a concern.
Agranulocytosis ; Ferritins ; Humans ; Iron ; Iron Overload ; Medical Records ; Neutropenia ; Pyridones ; Stress, Psychological

Fibrosis can occur in different organs with high incidence rate and great danger. It still lacks effective drugs for prevention of fibrosis. Fluorofenidone is a newly developed drug with anti-fibrotic activity, which provides a new hope for treating the progressive fibrotic diseases. Recent studies have shown that fluorofenidone is a multifunctional small molecule with anti-inflammatory, antioxidative and anti-apoptotic eff ects. It can inhibit the activation and proliferation of myofibroblasts, promote the degradation of extracellular matrix and regulate the cellular signal transmission. Fluorofenidone can be applied to attenuate the progression of renal, hepatic and pulmonary fibrosis.
Apoptosis ; Extracellular Matrix ; Fibrosis ; Humans ; Kidney ; pathology ; Liver Cirrhosis ; Pulmonary Fibrosis ; Pyridones ; pharmacology ; Signal Transduction

N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity is one of the major causes for neuronal cell death during cerebral ischemic insult. Previously, we reported that the final product of lipid membrane peroxidation 4-hydroxy-2E-nonenal (HNE) synergistically increased NMDA receptor-mediated excitotoxicity (J Neurochem., 2006). In this study, we investigated the mechanism involved in the synergistic neuronal cell death induced by co-treatment with HNE and NMDA. Although neither HNE (1 microM) nor NMDA (2 microM) alone induced the death of cortical neurons, simultaneous treatment of neuronal cells with HNE and NMDA synergistically evoked the death of the cells. However, the synergistic effect on neuronal death was observed only in the presence of calcium. HNE neither increased the cytosolic calcium level ([Ca2+]i) nor altered the NMDA-induced intracellular calcium influx. However, HNE together with NMDA elevated the mitochondrial calcium level and depolarized the mitochondrial transmembrane potential. Furthermore, HNE evoked damage of isolated mitochondria at the cytosolic calcium level (200 nM), which is maximally induced by 2 microM NMDA. Consistently, ATP was depleted in neurons when treated with both HNE and NMDA together. Ciclopirox, a potent inhibitor of mitochondrial permeability transition pore opening (Br. J. Pharmacol., 2005), largely prevented the synergistic damage of mitochondria and death of cortical neurons. Therefore, although low concentrations of HNE and NMDA cannot individually induce neuronal cell death, they can evoke the neuronal cell death by synergistically accelerating mitochondrial dysfunction.
Adenosine Triphosphate ; Calcium ; Cell Death ; Cytosol ; Membrane Potentials ; Membranes ; Mitochondria ; Mitochondrial Membrane Transport Proteins ; N-Methylaspartate ; Neurons ; Permeability ; Pyridones

The most important and widely-prescribed drug for anticoagulation is a vitamin K antagonist such as warfarin although it has several limitations in clinical use. New oral anticoagulants (NOACs) have been developed to overcome these problems. The clinical efficacy and safety of dabigatran, rivaroxaban, and apixaban have been shown to be superior to warfarin through large-scale clinical trials. These NOACs can replace warfarin in significant proportions of patients with non-valvular atrial fibrillation to prevent stroke. Recent management guidelines for atrial fibrillation have already recommended NOACs for stroke prevention instead of warfarin. Future clinical studies should resolve the limitations of NOACs and try to extend their clinical indications.
Anticoagulants ; Atrial Fibrillation ; Benzimidazoles ; beta-Alanine ; Dabigatran ; Humans ; Morpholines ; Pyrazoles ; Pyridones ; Rivaroxaban ; Stroke ; Thiophenes ; Vitamin K ; Warfarin

OBJECTIVETo develop a LC-MS/MS method for determination of deferiprone in cell lysate and to study the potential interaction between deferiprone and hOCTs or hOAT1 transporters in vitro.

METHODSThe determination was performed on an Agilent Eclipse Plus C18 column(3.5 μm, 2.1 mm×50 mm).The gradient mobile phase was composed of solvent A:0.1% formic acid in water, and B:0.1% formic acid in acetonitrile. The mass spectrometer with an electrospray interface was operated in positive ion mode with multiple reaction monitoring (MRM) scan mode monitored the ion pair of deferiprone at m/z 140→96, or phenacetin at m/z 180→110. The effects of deferiprone on the accumulation of typical substrates of hOCTs and hOAT1 were evaluated by MDCK-hOCTs and MDCK-hOAT1 cells respectively. The accumulation of deferiprone was also investigated in MDCK-hOCTs cells and mock cells with or without typical inhibitors.

RESULTSThe standard curve was linear over the range of 5-300 nmol/L. The assay recovery of deferiprone was above 94%, and the intra-day precision (RSD) was less than 2.0%. The accumulation of MPP(+) in MDCK-hOCTs cells with 300 μmol/L deferiprone were 73.5%, 87.1% and 70.4%, respectively. The uptake of deferiprone in MDCK-hOCTs and mock cells did not show significant difference. Deferiprone of 100 μmol/L did not significantly affect the accumulation of 6-CF in MDCK-hOAT1 cell.

CONCLUSIONThe method is sensitivity and suitable for the determination of deferiprone in cell lysate. Deferiprone can significantly inhibit hOCT1 and hOCT3, but has no effects on hOCT2 and hOAT1. hOCTs may not play a major role in the transport of deferiprone.

Animals ; Chromatography, Liquid ; Dogs ; Humans ; Madin Darby Canine Kidney Cells ; Organic Anion Transporters ; drug effects ; Pyridones ; pharmacology ; Tandem Mass Spectrometry

Adult ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use* ; COVID-19/drug therapy* ; Humans ; Pyridones/therapeutic use* ; Treatment Outcome

Pivotal clinical trials testing the efficacy of new antithrombotics for the prevention of stroke and systemic embolism in patients with atrial fibrillation have been published since the release of the first edition of Korean clinical practice guidelines for primary stroke prevention. From July 2007 to August 2012, 5 clinical studies and update of guidelines in Europe and North America were identified through systematic search. In patients with atrial fibrillation who were unsuitable for warfarin, the combination of clopidogrel and aspirin reduced the risk of stroke at the cost of increased major bleedings as compared to aspirin. In patients with nonvalvular atrial fibrillation and risk factors for stroke, new oral anticoagulants, dabigatran, rivaroxaban and apixaban, were as effective as or more effective than warfarin in preventing stroke or systemic embolism. The risks of major bleeding with novel anticoagulants were similar to or lower than that of warfarin. Particularly, the risk of intracranial bleeding was significantly lower with novel anticoagulants than with warfarin. In this report, we summarized the new evidences and updated our recommendations for primary stroke prevention in patients with atrial fibrillation.
Anticoagulants ; Aspirin ; Atrial Fibrillation ; Benzimidazoles ; beta-Alanine ; Embolism ; Europe ; Hemorrhage ; Humans ; Morpholines ; North America ; Primary Prevention ; Pyrazoles ; Pyridones ; Risk Factors ; Stroke ; Thiophenes ; Ticlopidine ; Warfarin ; Dabigatran ; Rivaroxaban

OBJECTIVES: Evaluation of a new material, high-density porous polyethylene (HDPP), which is covered with fascia lata, for experimental nasal septal perforation closure. METHODS: Twenty New Zealand albino rabbits were included and divided into study and control groups. A lateral incision was made from the lateral aspect of the left nares to the incisura nasomaxillaris. After exposure of the cavum nasi, the nasal mucoperichondrium was elevated bilaterally. A full-thickness 0.5x0.5-cm perforation was created over the septum nasi with a No. 11 surgical blade. A fascia lata graft was used for the study group. The HDPP was covered with fascia lata and placed under the elevated mucosa. HDPP without a fascial covering was used in the control group. Four months after the procedure, magnetic resonance imaging was performed to evaluate resorption of the material. The animals were sacrificed, and the nasal septum was completely removed. Macroscopic and histopathological examinations were performed on the nasal septum. RESULTS: All rabbits had survived after the 4-month period. Macroscopically, nine of 10 (90%) perforations were closed in the fascia lata-covered HDPP group. Histopathological examination of these nine rabbits revealed that the continuity of cartilage was disturbed in the perforation areas. Granulation tissue was inverted in areas in which the cartilage continuity was disturbed. The HDPP had remained intact at the edge of the perforation. In the HDPP group, six of 10 implants were still perforated (60%) and four (40%) were closed. The fascia lata-covered HDPP implant had a significantly higher perforation closure rate than that of the HDPP implant alone (P<0.05). CONCLUSION: In cases of septal perforation, it is better to cover the HDPP implant with fascia lata. This covered implant can be used for the repair of nasal septal perforations. HDPP implants are easy to work with and avoid the increased operative time and morbidity associated with harvesting autografts.
Animals ; Cartilage ; Fascia ; Fascia Lata ; Granulation Tissue ; Magnetic Resonance Imaging ; Mucous Membrane ; Nasal Septal Perforation ; Nasal Septum ; New Zealand ; Operative Time ; Polyethylene ; Polyethylenes ; Pyridones ; Rabbits ; Transplants