vitamin-k-semiquinone-radical and Lung-Diseases

A 75-year-old man was admitted to our clinic with the complaints of palpitation, fever, severe dyspnea, dizziness and bloody sputum associated with coughing. Chest radiographs revealed that the lungs were bilaterally infiltrated. A high resolution computed tomographic study of the thorax disclosed diffuse alveolar hemorrhage, of which presence was proved by histopathological study of bronchoalveolar lavage material. The hemorrhage occured at 8th day of 5 mg daily warfarin therapy, which was given for frequent atrial fibrillation attacks was controlled by fresh frozen plasma and vitamin K. Alveolar hemorrhage is difficult to diagnose and has high mortality if the treatment was not started as soon as possible. This is the first report of alveolar hemorrhage caused by 5 mg daily warfarin therapy. We propose that the patient's age, nutritional status, used drugs should be taken into consideration for true management of patients with atrial fibrillation.

Topics: Aged; Anticoagulants; Antifibrinolytic Agents; Atrial Fibrillation; Hemorrhage; Humans; International Normalized Ratio; Lung Diseases; Male; Pulmonary Alveoli; Tomography, X-Ray Computed; Vitamin K; Warfarin

Topics: Hemorrhage; Humans; Lung Diseases; Vitamin K

Elastin is a unique protein providing deformability and resilience to dynamic tissues, such as arteries and lungs. It is an absolute basic requirement for circulation and respiration. Elastin can be degraded by elastases and has a high calcium affinity. Elastin calcification and elastin degradation are two pathological processes that impair elastin's functioning. Furthermore, elastin degradation can be associated to elastin calcification. Matrix Gla Protein (MGP) is probably the most potent natural inhibitor of elastin calcification and requires vitamin K for its activation. Measuring circulating levels of inactive MGP (dp-ucMGP) is a frequently used method to assess vitamin K status. Dp-ucMGP reflects the burden of vitamin K-dependent proteins that have not been activated by vitamin K and could therefore best be regarded as a biomarker of a vitamin K deficit. Dp-ucMGP levels decrease after vitamin K supplementation. Since the amino acids desmosine and isodesmosine (DES) are unique to crosslinked elastin fibers, systemic elastin degradation can be assessed with the plasma DES assay. Recently, we discovered a strong correlation between plasma dp-ucMGP and plasma DES levels in both patients with chronic obstructive pulmonary disease (COPD) and controls. The 'Vitamin K deficit and elastolysis theory' posits that elastin degradation causes a rise in the vitamin K deficit and implies that vitamin K supplementation could be preventing elastin degradation. If this hypothesis holds true and is universally found in every state and condition, it will have an unprecedented impact on the management of every single pulmonary disease characterized by accelerated elastin degradation, such as alpha-1 antitrypsin deficiency, bronchiectasis, COPD and cystic fibrosis. Theoretically, a plasma dp-ucMGP concentration of zero would be associated with a near-complete standstill of elastin degradation and disease progression in patients with any of these debilitating conditions.

Topics: alpha 1-Antitrypsin; Biomarkers; Calcium; Calcium-Binding Proteins; Desmosine; Elasticity; Elastin; Extracellular Matrix Proteins; Humans; Isodesmosine; Lung Diseases; Matrix Gla Protein; Models, Biological; Vitamin K; Vitamin K Deficiency

Patients with cystic fibrosis (CF) often experience low bone mineral density (BMD) pre- and post-lung transplantation (LTX). The study purpose was to describe BMD and micronutrient status in adults with CF pre- and post-LTX.. Twelve patients with CF (29 ± 8 years) were recruited from the CF clinic at the University of Alberta Lung Transplant Program. BMD and vitamins A, D, E, K status, and parathyroid hormone were measured pre- and post-LTX.. No significant differences pre- and post-LTX were observed at the different bone sites measured (lumber-spine, femoral-neck (FN), hip, and femoral-trochlea) (P > 0.05). BMD T-scores (<-2) was present in lumbar-spine, FN, hip, and femoral-trochlea in 33%, 17%, 17%, and 25% of individuals pre-LTX and 58%, 33%, 58%, and 33% of individuals post-LTX, respectively. More than 50% of patients had suboptimal vitamin K levels (PIVKA-II values >3 ng/mL) pre- and post-LTX.. Adults with CF pre- and post-LTX had reduced BMD and suboptimal vitamin K status.

Topics: Adult; Anthropometry; Biomarkers; Bone Density; Cystic Fibrosis; Female; Humans; Lumbar Vertebrae; Lung Diseases; Lung Transplantation; Male; Middle Aged; Osteoporosis; Parathyroid Hormone; Pilot Projects; Protein Precursors; Prothrombin; Vitamin A; Vitamin D; Vitamin E; Vitamin K; Vitamins; Young Adult

Fibronectin (Fn) and tenascin (Tn) are two major extracellular matrix (ECM) glycoproteins that may have important roles both in fibrotic lung diseases and in lung tumors. The significance of Fn and Tn in human pleural mesothelial cells and pleural diseases is unclear. Transformed human pleural mesothelial cells (Met5A), primary cultures of mesothelial cells, and cultured mesothelioma cell lines were investigated for Fn and Tn immunoreactivity. Mesothelial cells were exposed for 48 to 96 h to transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), amosite asbestos fibers, or oxidants (H2O2 and menadione, a compound that auto-oxidizes to produce superoxide). Immunofluorescence and Western blotting with monoclonal anti-Fn and anti-Tn antibodies, and Northern blotting with a complementary DNA (cDNA) probe for Tn showed that mesothelial cells are capable of producing Fn and Tn. The mRNA level and immunoreactivity of Tn was enhanced by TGF-beta and TNF-alpha, whereas Fn was intensified only by TGF-beta. A wide range of amosite, H2O2, or menadione concentrations had no clear effect on Fn or Tn reactivity. Fn and Tn were present at low or undetectable concentrations in five of six mesothelioma cell lines, whereas the organization of Fn immunoreactivity in these cell lines was variable. Furthermore, results obtained with the tumor tissue of these same mesothelioma patients suggested that Fn and Tn expressions do not necessarily parallel either each other or results obtained with the cultured cells.

Topics: Asbestos, Amosite; Fibronectins; Gene Expression Regulation; Humans; Hydrogen Peroxide; Immunohistochemistry; Lung Diseases; Pleural Neoplasms; RNA, Messenger; Tenascin; Transforming Growth Factor beta; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha; Vitamin K

The abilities of paraquat, diquat, and nitrofurantoin to undergo cyclic oxidation and reduction with rat microsomal systems have been assessed and compared to that of the potent redox cycler, menadione. Diquat and menadione were found to be potent redox cyclers with comparable abilities to elicit a nonstoichiometric increase in both the consumption of O2 and the oxidation of NADPH, compared to the amounts of substrate added. In contrast, paraquat and nitrofurantoin redox cycled poorly, being an order of magnitude less potent than either diquat or menadione. This was reflected in kinetic studies using lung and liver microsomes, which showed that NADPH-cytochrome P-450 reductase had a lower affinity (Km) for paraquat and nitrofurantoin than for menadione and diquat, although values of Vmax were comparable for all the substrates except nitrofurantoin, which was lower. In order to assess redox cycling of the substrates in an intact lung system, the O2 consumption of rat lung slices was measured in the presence of all four compounds. A small increase in lung slice O2 uptake was observed with paraquat (10(-5) M) in the first 2.5 hr of incubation, possibly because of redox cycling of a high intracellular concentration of paraquat resulting from active accumulation into target cells. This stimulation in O2 uptake was no longer observed when slices were incubated for a longer period or with higher paraquat concentrations (10(-4) M), possibly because of toxic effects in target cells. High concentrations of diquat (10(-5) M) had no effect on O2 consumption of lung slices.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Diquat; Lung Diseases; Male; Microsomes; Nitrofurantoin; Oxidation-Reduction; Oxygen Consumption; Paraquat; Pyridinium Compounds; Rats; Rats, Inbred Strains; Vitamin K

Topics: Anticoagulants; Hemorrhage; Humans; Lung Diseases; Male; Middle Aged; Vitamin K

A 1,760-G MALE INFANT SURVIVED MASSIVE PUlmonary hemorrhage. The literature is reviewed and the pathophysiologic changes and pathologic findings of this usually lethal complication of prematurity are discussed. Aggressive pulmonary toilet and ventilation seems warranted for these infants.

Topics: Asphyxia; Atropine; Blood Transfusion; Furosemide; Heart Failure; Hemorrhage; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lung Diseases; Male; Respiration, Artificial; Vitamin K

Topics: Anticoagulants; Hematuria; Hemoptysis; Humans; Lung Diseases; Male; Middle Aged; Radiography, Thoracic; Vitamin K

Topics: Anti-Glomerular Basement Membrane Disease; Cerebrospinal Fluid Rhinorrhea; Diagnosis, Differential; Glomerulonephritis; Hematuria; Hemoptysis; Hemorrhage; Humans; Hydrocortisone; Lung Diseases; Prednisone; Vitamin K

Topics: Acrolein; Ascorbic Acid; Humans; Inositol; Lung Diseases; Poisoning; Vitamin A; Vitamin E; Vitamin K; Vitamins