losartan-potassium and Asthma

Theophylline, a drug that has been used for several decades, has several different actions at a cellular level, including inhibition of phosphodiesterase isoenzymes, antagonism of adenosine, enhancement of catecholamine secretion, and modulation of calcium fluxes. Recently, theophylline was found to have several immunomodulatory and anti-inflammatory properties, and thus interest in its use in patients with asthma has been renewed. The use of theophylline in the treatment of asthma and chronic obstructive pulmonary disease has diminished with the advent of new medications, but theophylline remains beneficial, especially in the patient with difficult refractory symptoms. In the future, theophylline may be used as treatment for bradyarrhythmias after cardiac transplantation, prophylactic medication to reduce the severity of nephropathy associated with intravenous administration of contrast material, therapy for breathing problems during sleep, and treatment for leukemias.

Topics: Apnea; Apoptosis; Asthma; Calcium Channels; Capillary Leak Syndrome; Catecholamines; Erythropoietin; Humans; Immunity; Kidney; Leukemia, Lymphocytic, Chronic, B-Cell; Lung Diseases, Obstructive; Phosphoric Diester Hydrolases; Receptors, Purinergic P1; Theophylline

Topics: Anemia, Hemolytic, Autoimmune; Asthma; beta-Globins; Cell Differentiation; Cell Proliferation; Cells, Cultured; Child; Erythrocytes; Erythropoiesis; Erythropoietin; Exome Sequencing; Gene Expression Regulation; Germ-Line Mutation; Humans; Iron Chelating Agents; Receptors, Erythropoietin; Severity of Illness Index; Signal Transduction; STAT3 Transcription Factor; STAT5 Transcription Factor

There was no effective measures can be obtained at present to reverse or prevent airway remodeling. We investigated the therapeutic effect of Erythropoietin (EPO) gene modified mesenchymal stem cells (MSCs) on asthmatic airway remodeling and the possible underlied molecular mechanisms. EPO gene was transfected into MSCs via lentivirus vector. The transfected cells (EPO-MSCs) were identified by flow cytometry and the EPO secreting function was detected by PCR and Western blot. MSCs or EPO-MSCs were administrated to albumin (OVA)-induced chronic asthmatic mouse model via tail veins. The asthmatic phenotype was analyzed. Number of cells in bronchoalveolar lavage fluid (BALF) was counted using a hemocytometer. Histological findings of airways were evaluated by microscopic examination. The concentrations of interleukin 4(IL-4), interleukin 5(IL-5), and interleukin 13(IL-13) in lung homogenate were determined by ELISA. The activation state of transforming growth factor-β 1 (TGF-β1), Transforming growth factor beta-activated kinase 1 (TAK1), and p38 Mitogen Activated Protein Kinase (p38MAPK) signaling was detected by Real-Time PCR and Western blotting. EPO-MSCs were successfully constructed. EPO-MSCs showed a more potently suppressive effect on local asthmatic airway inflammation and the level of IL-4, IL-5, and IL-13 in lung tissue than MSCs. Moreover, the numbers of goblet cells, the thicknesses of smooth muscle layer, collagen density, percentage of proliferating cell nuclear antigen positive (PCNA

Topics: Airway Remodeling; Animals; Asthma; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Erythropoietin; Gene Expression Regulation; Genetic Therapy; Interleukins; Lentivirus; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Mice, Inbred BALB C

Proteomic approaches identifying biomarkers have been applied to asthma to only a very limited extent.. With an antibody array (RayBiotech, Norcross, GA, USA), the relative intensity and rank differences of 444 proteins were compared in 24 plasma samples obtained at age 3, 11 from children with and 12 without asthma diagnoses at ages 5 and 9. Protein candidates identified by antibody array were quantitated by ELISA in an enlarged sample. Proteins found to differentiate children with and without asthma were also examined for association with known Year 1 asthma risk factors, eczema, and wheeze.. In the antibody array, four proteins had rank differences between asthma and non-asthma groups (FDR <0.1). By ELISA, mean log (±s.e.m.) erythropoietin (EPO) level (IU/l) was lower (0.750 ± 0.048 vs. 0.898 ± 0.035; p = 0.006) and mean (±s.e.m.) soluble GP130 (sGP130) level (ng/ml) was higher in the asthma vs. the non-asthma group (302 ± 13 vs. 270 ± 8; p = 0.041). The other 2 array proteins (galactin-3 and eotaxin-3) did not differ by ELISA by asthma. EPO related to the asthma risk factor, first year eczema, whereas sGP130 related to first year wheeze.. Through two independent assessments, age 3 plasma levels of EPO and sGP130 were found related to childhood asthma.

Topics: Antibodies; Asthma; Biomarkers; Child; Child, Preschool; Cohort Studies; Cytokine Receptor gp130; Eczema; Erythropoietin; Female; Follow-Up Studies; Humans; Male; Protein Array Analysis; Proteomics; Respiratory Sounds; Risk Factors

In this study, we attempt to determine whether lycopene regulates inflammatory mediators in the ovalbumin (OVA)-induced murine asthma model. To address this, mice were sensitized and challenged with OVA, and then treated with lycopene before the last OVA challenge. Administration of lycopene significantly alleviated the OVA-induced airway hyperresponsiveness to inhaled methacholine. Administration of lycopene also resulted in a significant inhibition of the infiltration of inflammatory immunocytes into the bronchoalveolar lavage, and attenuated the gelatinolytic activity of matrix metalloproteinase-9 and the expression of eosinophil peroxidase. Additionally, lycopene reduced the increased levels of GATA-3 mRNA level and IL-4 expression in OVA-challenged mice. However, it increased T-bet mRNA level and IFN-gamma expression in lycopene-challenged mice. These findings provide new insight into the immunopharmacological role of lycopene in terms of its effects in a murine model of asthma.

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Carotenoids; Disease Models, Animal; Eosinophils; Erythropoietin; Female; GATA3 Transcription Factor; Inflammation Mediators; Interleukin-4; Lycopene; Lymphocytes; Macrophages; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Mice; Mice, Inbred BALB C; Neutrophils; Ovalbumin; RNA, Messenger

The tetraspanin CD63 (also known as LAMP-3) has been implicated in phagocytic and intracellular lysosome-phagosome fusion events. It is also present in eosinophils, with predominant expression on crystalloid granule membrane. However, its role in eosinophil function is obscure. We hypothesized that CD63 is associated with intracellular events involved in eosinophil activation and mediator release. We used a combination of confocal immunofluorescence microscopy, flow cytometry, and secretion assays, including beta-hexosaminidase, eosinophil peroxidase, and RANTES, to examine CD63 expression, intracellular localization, and its association with cell activation and mediator release. In resting eosinophils, CD63 immunoreactivity was localized to plasma and crystalloid granule membranes. In interferon-gamma (IFN-gamma)- or C5a/CB-stimulated cells (10 minutes), intracellular CD63 appeared to shift to the cell periphery and plasma membrane, while stimulation with a cocktail of interleukin-3 (IL-3)/IL-5/granulocyte-macrophage colony-stimulating factor induced the appearance of discrete intracellular clusters of CD63 immunoreactivity. IFN-gamma induced mobilization of CD63 to the cell periphery, which coincided with selective mobilization of RANTES prior to its release, implying CD63 association with piecemeal degranulation. Agonist-induced CD63 mobilization and cell surface up-regulation was associated with beta-hexosaminidase, eosinophil peroxidase, and RANTES release. Dexamethasone as well as genistein (a broad-spectrum inhibitor of tyrosine kinases) inhibited agonist-induced intracellular mobilization of CD63 and RANTES together with cell surface up-regulation of CD63 and mediator release. This is the first report of an association between CD63 mobilization and agonist-induced selective mediator release, which may imply the involvement of CD63 in eosinophil activation and piecemeal degranulation.

Topics: Antigens, CD; Asthma; beta-N-Acetylhexosaminidases; Cell Adhesion Molecules; Chemokine CCL5; Dexamethasone; Enzyme Inhibitors; Eosinophils; Erythropoietin; Humans; Microscopy, Confocal; Microscopy, Fluorescence; Platelet Membrane Glycoproteins; Protein Transport; Protein-Tyrosine Kinases; Tetraspanin 30

Topics: Aged; Asthma; Bicarbonates; Bloodletting; Carbon Dioxide; Carotid Body; Erythrocyte Count; Erythropoiesis; Erythropoietin; Hematocrit; Humans; Hydrogen-Ion Concentration; Lung Diseases, Obstructive; Male; Middle Aged; Oxygen; Respiration; Reticulocytes; Time Factors