Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
Inflammation of the large airways in the lung including any part of the BRONCHI, from the PRIMARY BRONCHI to the TERTIARY BRONCHI.
A subcategory of CHRONIC OBSTRUCTIVE PULMONARY DISEASE. The disease is characterized by hypersecretion of mucus accompanied by a chronic (more than 3 months in 2 consecutive years) productive cough. Infectious agents are a major cause of chronic bronchitis.
Material coughed up from the lungs and expectorated via the mouth. It contains MUCUS, cellular debris, and microorganisms. It may also contain blood or pus.
Derivatives of propionic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxyethane structure.
Substances that reduce or suppress INFLAMMATION.
The application of drug preparations to the surfaces of the body, especially the skin (ADMINISTRATION, CUTANEOUS) or mucous membranes. This method of treatment is used to avoid systemic side effects when high doses are required at a localized area or as an alternative systemic administration route, to avoid hepatic processing for example.
This intrgrin is a key component of HEMIDESMOSOMES and is required for their formation and maintenance in epithelial cells. Integrin alpha6beta4 is also found on thymocytes, fibroblasts, and Schwann cells, where it functions as a laminin receptor (RECEPTORS, LAMININ) and is involved in wound healing, cell migration, and tumor invasiveness.
Ability of neoplasms to infiltrate and actively destroy surrounding tissue.
An anchoring junction of the cell to a non-cellular substrate, similar in morphology to halves of DESMOSOMES. They are composed of specialized areas of the plasma membrane where INTERMEDIATE FILAMENTS bind on the cytoplasmic face to the transmembrane linkers, INTEGRINS, via intracellular attachment proteins, while the extracellular domain of the integrins binds to EXTRACELLULAR MATRIX PROTEINS.
A cell line derived from cultured tumor cells.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for "cancer." (From Dorland, 27th ed)
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A malignant kidney tumor, caused by the uncontrolled multiplication of renal stem (blastemal), stromal (STROMAL CELLS), and epithelial (EPITHELIAL CELLS) elements. However, not all three are present in every case. Several genes or chromosomal areas have been associated with Wilms tumor which is usually found in childhood as a firm lump in a child's side or ABDOMEN.
Software used to locate data or information stored in machine-readable form locally or at a distance such as an INTERNET site.
The thin serous membrane enveloping the lungs (LUNG) and lining the THORACIC CAVITY. Pleura consist of two layers, the inner visceral pleura lying next to the pulmonary parenchyma and the outer parietal pleura. Between the two layers is the PLEURAL CAVITY which contains a thin film of liquid.
A member of the c-ets family of transcription factors that is preferentially expressed in cells of hematopoietic lineages and vascular endothelial cells. It was originally identified as a protein that provides a retroviral integration site for integration of FRIEND MURINE LEUKEMIA VIRUS.
Genes at loci that are involved in the development of WILMS TUMOR. Included are human WT1 at 11p13 and human WT2 (MTACR1) at 11p15.
An intermediate filament protein found predominantly in smooth, skeletal, and cardiac muscle cells. Localized at the Z line. MW 50,000 to 55,000 is species dependent.
Isoforms encoded by the WT1 Wilms tumor suppressor gene (GENES, WILMS TUMOR) and produced by alternative splicings. They are zinc finger-containing transcription factors involved in both transactivation and repression, and are critical for normal development and function of the urogenital tract.
A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.
A publication issued at stated, more or less regular, intervals.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
"The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.
The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).
Publications in any medium issued in successive parts bearing numerical or chronological designations and intended to be continued indefinitely. (ALA Glossary of Library and Information Science, 1983, p203)
All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.
Enzymes that catalyze the joining of glutamine-derived ammonia and another molecule. The linkage is in the form of a carbon-nitrogen bond. EC 6.3.5.
The sum or the stock of words used by a language, a group, or an individual. (From Webster, 3d ed)
Any woven or knit material of open texture used in surgery for the repair, reconstruction, or substitution of tissue. The mesh is usually a synthetic fabric made of various polymers. It is occasionally made of metal.
A superfamily of nematodes of the order RHABDITIDA. Characteristics include an open tube stoma and an excretory system with lateral canals.
A specified list of terms with a fixed and unalterable meaning, and from which a selection is made when CATALOGING; ABSTRACTING AND INDEXING; or searching BOOKS; JOURNALS AS TOPIC; and other documents. The control is intended to avoid the scattering of related subjects under different headings (SUBJECT HEADINGS). The list may be altered or extended only by the publisher or issuing agency. (From Harrod's Librarians' Glossary, 7th ed, p163)
Sequential operating programs and data which instruct the functioning of a digital computer.
A contagious disease caused by canine adenovirus (ADENOVIRUSES, CANINE) infecting the LIVER, the EYE, the KIDNEY, and other organs in dogs, other canids, and bears. Symptoms include FEVER; EDEMA; VOMITING; and DIARRHEA.
A diffuse parenchymal lung disease caused by inhalation of dust and by tissue reaction to their presence. These inorganic, organic, particulate, or vaporized matters usually are inhaled by workers in their occupational environment, leading to the various forms (ASBESTOSIS; BYSSINOSIS; and others). Similar air pollution can also have deleterious effects on the general population.
Infections with nontuberculous mycobacteria (atypical mycobacteria): M. kansasii, M. marinum, M. scrofulaceum, M. flavescens, M. gordonae, M. obuense, M. gilvum, M. duvali, M. szulgai, M. intracellulare (see MYCOBACTERIUM AVIUM COMPLEX;), M. xenopi (littorale), M. ulcerans, M. buruli, M. terrae, M. fortuitum (minetti, giae), M. chelonae.
Infections with bacteria of the genus MYCOBACTERIUM.
Persistent abnormal dilatation of the bronchi.
So-called atypical species of the genus MYCOBACTERIUM that do not cause tuberculosis. They are also called tuberculoid bacilli, i.e.: M. buruli, M. chelonae, M. duvalii, M. flavescens, M. fortuitum, M. gilvum, M. gordonae, M. intracellulare (see MYCOBACTERIUM AVIUM COMPLEX;), M. kansasii, M. marinum, M. obuense, M. scrofulaceum, M. szulgai, M. terrae, M. ulcerans, M. xenopi.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A member of the P450 superfamily, this enzyme catalyzes the first oxidative step of the phenylpropanoid pathway in higher PLANTS by transforming trans-cinnamate into p-coumarate.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (AEROSOLS) and other colloidal systems; water-insoluble drugs may be given as suspensions.

Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor-2. (1/2714)

Interaction between integrin alphavbeta3 and extracellular matrix is crucial for endothelial cells sprouting from capillaries and for angiogenesis. Furthermore, integrin-mediated outside-in signals co-operate with growth factor receptors to promote cell proliferation and motility. To determine a potential regulation of angiogenic inducer receptors by the integrin system, we investigated the interaction between alphavbeta3 integrin and tyrosine kinase vascular endothelial growth factor receptor-2 (VEGFR-2) in human endothelial cells. We report that tyrosine-phosphorylated VEGFR-2 co-immunoprecipitated with beta3 integrin subunit, but not with beta1 or beta5, from cells stimulated with VEGF-A165. VEGFR-2 phosphorylation and mitogenicity induced by VEGF-A165 were enhanced in cells plated on the alphavbeta3 ligand, vitronectin, compared with cells plated on the alpha5beta1 ligand, fibronectin or the alpha2beta1 ligand, collagen. BV4 anti-beta3 integrin mAb, which does not interfere with endothelial cell adhesion to vitronectin, reduced (i) the tyrosine phosphorylation of VEGFR-2; (ii) the activation of downstream transductor phosphoinositide 3-OH kinase; and (iii) biological effects triggered by VEGF-A165. These results indicate a new role for alphavbeta3 integrin in the activation of an in vitro angiogenic program in endothelial cells. Besides being the most important survival system for nascent vessels by regulating cell adhesion to matrix, alphavbeta3 integrin participates in the full activation of VEGFR-2 triggered by VEGF-A, which is an important angiogenic inducer in tumors, inflammation and tissue regeneration.  (+info)

Activation of c-Jun N-terminal kinase 1 by UV irradiation is inhibited by wortmannin without affecting c-iun expression. (2/2714)

Activation of c-Jun N-terminal kinases (JNKs)/stress-activated protein kinases is an early response of cells upon exposure to DNA-damaging agents. JNK-mediated phosphorylation of c-Jun is currently understood to stimulate the transactivating potency of AP-1 (e.g., c-Jun/c-Fos; c-Jun/ATF-2), thereby increasing the expression of AP-1 target genes. Here we show that stimulation of JNK1 activity is not a general early response of cells exposed to genotoxic agents. Treatment of NIH 3T3 cells with UV light (UV-C) as well as with methyl methanesulfonate (MMS) caused activation of JNK1 and an increase in c-Jun protein and AP-1 binding activity, whereas antineoplastic drugs such as mafosfamide, mitomycin C, N-hydroxyethyl-N-chloroethylnitrosourea, and treosulfan did not elicit this response. The phosphatidylinositol 3-kinase inhibitor wortmannin specifically blocked the UV-stimulated activation of JNK1 but did not affect UV-driven activation of extracellular regulated kinase 2 (ERK2). To investigate the significance of JNK1 for transactivation of c-jun, we analyzed the effect of UV irradiation on c-jun expression under conditions of wortmannin-mediated inhibition of UV-induced stimulation of JNK1. Neither the UV-induced increase in c-jun mRNA, c-Jun protein, and AP-1 binding nor the activation of the collagenase and c-jun promoters was affected by wortmannin. In contrast, the mitogen-activated protein kinase/ERK kinase inhibitor PD98056, which blocked ERK2 but not JNK1 activation by UV irradiation, impaired UV-driven c-Jun protein induction and AP-1 binding. Based on the data, we suggest that JNK1 stimulation is not essential for transactivation of c-jun after UV exposure, whereas activation of ERK2 is required for UV-induced signaling leading to elevated c-jun expression.  (+info)

Salmonella typhimurium and lipopolysaccharide stimulate extracellularly regulated kinase activation in macrophages by a mechanism involving phosphatidylinositol 3-kinase and phospholipase D as novel intermediates. (3/2714)

Activation of the extracellularly regulated kinase (ERK) pathway is part of the early biochemical events that follow lipopolysaccharide (LPS) treatment of macrophages or their infection by virulent and attenuated Salmonella strains. Phagocytosis as well as the secretion of invasion-associated proteins is dispensable for ERK activation by the pathogen. Furthermore, the pathways used by Salmonella and LPS to stimulate ERK are identical, suggesting that kinase activation might be solely mediated by LPS. Both stimuli activate ERK by a mechanism involving herbimycin-dependent tyrosine kinase(s) and phosphatidylinositol 3-kinase. Phospholipase D activation and stimulation of protein kinase C appear to be intermediates in this novel pathway of MEK/ERK activation.  (+info)

Phosphatidylinositol 3-kinase and protein kinase C are required for the inhibition of caspase activity by epidermal growth factor. (4/2714)

The mechanism by which growth factors exert an anti-apoptotic function on many cell types is not well understood. This issue is addressed in relation to epidermal growth factor (EGF) which inhibits apoptosis induced by staurosporine or wortmannin in an epithelial tumour cell line (CNE-2). The presence of EGF substantially reduced the in vitro Ac-DEVD-AMC hydrolytic activity and almost completely suppressed the intracellular cleavage of poly(ADP-ribose) polymerase in staurosporine- or wortmannin-treated cells. Staurosporine but not wortmannin caused the intracellular proteolytic processing of pro-caspase-3 and this event was transiently inhibited by EGF. Staurosporine-induced apoptosis was not inhibited by EGF in the presence of wortmannin or LY294002. Similarly, EGF failed to inhibit wortmannin-induced apoptosis in the presence of staurosporine, chelerythrine chloride or Go6850. These results suggest that phosphatidylinositol 3-kinase and protein kinase C play a role in the survival function of EGF but the reduction of cellular caspase activity cannot be satisfactorily explained by a lack of pro-caspase-3 activation.  (+info)

Nerve growth factor induces zif268 gene expression via MAPK-dependent and -independent pathways in PC12D cells. (5/2714)

In this study we examined the contribution of MAPK1 and 2 [also known as extracellular signal-regulated kinases (ERK)-1 and 2] to the induction of zif268 mRNA in PC12D cells by using two methods to block the activation of these kinases. In one set of experiments, we inhibited the activation of MAPK by pretreating cells with PD098059, a specific inhibitor of MEK (MAPKK), the immediate upstream activator of MAPK. In the second set of experiments, we blocked the activation of MAPK by overexpressing N17Ras, a dominant-negative form of Ha-Ras. These two approaches yielded similar results and showed that inhibition of MAPK blocks less than half of the induction of zif268 mRNA by NGF. Much of the residual induction of zif268 mRNA is blocked by low concentrations of wortmannin, an inhibitor of phosphatidylinositol (PI) 3-kinase. Since PI 3-kinase was previously shown to function upstream in epidermal growth factor (EGF)-mediated activation of c-Jun N-terminal kinase (JNK), and JNK is known to phosphorylate and activate transcription factors that regulate the expression of zif268, we investigated the role of JNK in the induction of zif268 mRNA by NGF. Stimulation of PC12D cells with NGF weakly activates JNK, but this activation is enhanced rather than inhibited by pretreatment with wortmannin, suggesting that JNK does not function downstream of PI 3-kinase in the induction of zif268 mRNA. A role for JNK in the induction of the zif268 gene is indicated, however, by the fact that cotransfection of expression vectors encoding JIP-1 or the JNK binding domain of JIP-1, which act as dominant-negative inhibitors of JNK, partially blocks the NGF-mediated induction of a luciferase reporter gene linked to the zif268 promoter. Together, these results suggest that MAPK, PI-3 kinase and JNK each play a role in the induction of zif268 gene expression by NGF in PC12D cells.  (+info)

Autophosphorylation of p110delta phosphoinositide 3-kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo. (6/2714)

Phosphoinositide 3-kinases (PI3Ks) are lipid kinases which also possess an in vitro protein kinase activity towards themselves or their adaptor proteins. The physiological relevance of these phosphorylations is unclear at present. Here, the protein kinase activity of the tyrosine kinase-linked PI3K, p110delta, is characterized and its functional impact assessed. In vitro autophosphorylation of p110delta completely down-regulates its lipid kinase activity. The single site of autophosphorylation was mapped to Ser1039 at the C-terminus of p110delta. Antisera specific for phospho-Ser1039 revealed a very low level of phosphorylation of this residue in cell lines. However, p110delta that is recruited to activated receptors (such as CD28 in T cells) shows a time-dependent increase in Ser1039 phosphorylation and a concomitant decrease in associated lipid kinase activity. Treatment of cells with okadaic acid, an inhibitor of Ser/Thr phosphatases, also dramatically increases the level of Ser1039-phosphorylated p110delta. LY294002 and wortmannin blocked these in vivo increases in Ser1039 phosphorylation, consistent with the notion that PI3Ks, and possibly p110delta itself, are involved in the in vivo phosphorylation of p110delta. In summary, we show that PI3Ks are subject to regulatory phosphorylations in vivo similar to those identified under in vitro conditions, identifying a new level of control of these signalling molecules.  (+info)

Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes. (7/2714)

Replication protein A (RPA) is a DNA single-strand binding protein essential for DNA replication, recombination and repair. In human cells treated with the topoisomerase inhibitors camptothecin or etoposide (VP-16), we find that RPA2, the middle-sized subunit of RPA, becomes rapidly phosphorylated. This response appears to be due to DNA-dependent protein kinase (DNA-PK) and to be independent of p53 or the ataxia telangiectasia mutated (ATM) protein. RPA2 phosphorylation in response to camptothecin required ongoing DNA replication. Camptothecin itself partially inhibited DNA synthesis, and this inhibition followed the same kinetics as DNA-PK activation and RPA2 phosphorylation. DNA-PK activation and RPA2 phosphorylation were prevented by the cell-cycle checkpoint abrogator 7-hydroxystaurosporine (UCN-01), which markedly potentiates camptothecin cytotoxicity. The DNA-PK catalytic subunit (DNA-PKcs) was found to bind RPA which was replaced by the Ku autoantigen upon camptothecin treatment. DNA-PKcs interacted directly with RPA1 in vitro. We propose that the encounter of a replication fork with a topoisomerase-DNA cleavage complex could lead to a juxtaposition of replication fork-associated RPA and DNA double-strand end-associated DNA-PK, leading to RPA2 phosphorylation which may signal the presence of DNA damage to an S-phase checkpoint mechanism. KEYWORDS: camptothecin/DNA damage/DNA-dependent protein kinase/RPA2 phosphorylation  (+info)

A phosphatidylinositol 3-kinase-dependent pathway that differentially regulates c-Raf and A-Raf. (8/2714)

Cytokines trigger the rapid assembly of multimolecular signaling complexes that direct the activation of downstream protein kinase cascades. Two protein kinases that have been linked to growth factor-regulated proliferation and survival are mitogen-activated protein/ERK kinase (MEK) and its downstream target Erk, a member of the mitogen-activated protein kinase family. Using complementary pharmacological and genetic approaches, we demonstrate that MEK and Erk activation requires a phosphatidylinositol 3-kinase (PI3-K)-generated signal in an interleukin (IL)-3-dependent myeloid progenitor cell line. Analysis of the upstream pathway leading to MEK activation revealed that inhibition of PI3-K did not block c-Raf activation, whereas MEK activation was effectively blocked under these conditions. Furthermore, agents that elevated cAMP suppressed IL-3-induced c-Raf activation but did not inhibit MEK activation. Because c-Raf activation and MEK activation were inversely affected by PI3-K- and cAMP-dependent pathways, we examined whether IL-3 activated the alternative Raf isoforms A-Raf and B-Raf. Although IL-3 did not activate B-Raf, A-Raf was activated by the cytokine. Moreover, A-Raf activation, like MEK activation, was blocked by inhibition of PI3-K but was insensitive to cAMP. Experiments with dominant negative mutants of the Raf isoforms showed that overexpression of dominant negative c-Raf did not prevent MEK activation. However, dominant negative A-Raf effectively blocked MEK activation, suggesting that activation of the MEK-Erk signaling cascade is mediated through A-Raf. Taken together, these results suggest that IL-3 receptors engage and activate both c-Raf and A-Raf in hemopoietic cells. However, these intermediates are differentially regulated by upstream signaling cascades and selectively coupled to downstream signaling pathways.  (+info)

Absorption:Fluticasone Propionate:Healthy Subjects: Fluticasone propionate acts locally in the lung; therefore, plasma levels do not predict therapeutic effect. Studies using oral dosing of labeled and unlabeled drug have demonstrated that the oral systemic bioavailability of fluticasone propionate is negligible (,1%), primarily due to incomplete absorption and presystemic metabolism in the gut and liver. In contrast, the majority of the fluticasone propionate delivered to the lung is systemically absorbed.. Following administration of ADVAIR DISKUS to healthy adult subjects, peak plasma concentrations of fluticasone propionate were achieved in 1 to 2 hours. In a single-dose crossover study, a higher-than-recommended dose of ADVAIR DISKUS was administered to 14 healthy adult subjects. Two (2) inhalations of the following treatments were administered: ADVAIR DISKUS 500/50, fluticasone propionate powder 500 mcg and salmeterol powder 50 mcg given concurrently, and fluticasone propionate powder 500 ...
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Evaluation of Fluticasone Propionate and Fluticasone Propionate/Salmeterol Combination on Exercise in Pediatric and Adolescent Patients with Asthma
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Absorption Fluticasone Propionate: Healthy Subjects: Fluticasone propionate acts locally in the lung; therefore, plasma levels do not predict therapeutic effect. Trials using oral dosing of labeled and unlabeled drug have demonstrated that the oral systemic bioavailability of fluticasone propionate is negligible (,1%), primarily due to incomplete absorption and presystemic metabolism in the gut and liver. In contrast, the majority of the fluticasone propionate delivered to the lung is systemically absorbed.. Three (3) single-dose, placebo-controlled, crossover trials were conducted in healthy subjects: (1) a trial using 4 inhalations of ADVAIR HFA 230/21, salmeterol CFC inhalation aerosol 21 mcg, or fluticasone propionate CFC inhalation aerosol 220 mcg, (2) a trial using 8 inhalations of ADVAIR HFA 45/21, ADVAIR HFA 115/21, or ADVAIR HFA 230/21, and (3) a trial using 4 inhalations of ADVAIR HFA 230/21; 2 inhalations of ADVAIR DISKUS 500/50; 4 inhalations of fluticasone propionate CFC inhalation ...
Long-term use of fluticasone propionate/salmeterol fixed-dose combination and incidence of cataracts and glaucoma among chronic obstructive pulmonary disease patients in the UK General Practice Research Database David P Miller, Stephanie E Watkins, Tim Sampson, Kourtney J Davis WorldWide Epidemiology, GlaxoSmithKline, Durham, NC, USA Objectives: Some large population-based studies have reported a dose-related increased risk of cataracts and glaucoma associated with use of inhaled corticosteroids (ICS) in patients with asthma or chronic obstructive pulmonary disease (COPD). We evaluated the association between use of ICS-containing products, specifically fluticasone propionate/salmeterol fixed-dose combination (FSC), and incidence of cataracts and glaucoma among patients with COPD in a large electronic medical record database in the United Kingdom. Methods: We identified a cohort of patients aged 45 years and over with COPD in the General Practice Research Database (GPRD) between 2003 and 2006. Cases of
Chronic-obstructive pulmonary disease (COPD) is a global public health problem and its impact is increasing. Although only smoking cessation has been shown to alter the natural history of the disease, current treatment guidelines recommend the use of inhaled bronchodilators to decrease symptoms, improve lung function and quality of life and to prevent exacerbations. For a subset of patients with more severe disease, inhaled corticosteroids may also have a role in achieving these goals. Fluticasone propionate/salmeterol (Advair) or Seretide), GlaxoSmithKline) is a combination inhaled steroid and long-acting bronchodilator that is delivered by a dry-powder inhaler and was recently approved for use in COPD in the US. Fluticasone propionate/salmeterol is a potent bronchodilator and also appears to have important effects on the frequency of exacerbations and overall quality of life for some patients with COPD. Issues of patient selection as well as the pharmacology, efficacy and safety of the drug ...
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A prescription event monitoring study to assess safety and health outcomes of Airtec SF® (salmeterol fluticasone propionate combination) in Indian population
Anti-inflammatory effects of salmeterol/fluticasone propionate 50/250 mcg combination therapy in Japanese patients with chronic obstructive pulmonary disease Kazuhisa Asai,1 Akihiro Kobayashi,2 Yukio Makihara,3 Malcolm Johnson4 1Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan; 2Biomedical Data Sciences, 3Medical Affairs Respiratory Department, GlaxoSmithKline, Tokyo, Japan; 4Respiratory Global Franchise, GlaxoSmithKline, Uxbridge, UK Purpose: Using sputum neutrophils as the primary measure, and other inflammation biomarkers, this study evaluated the anti-inflammatory effects of the combination salmeterol 50 mcg and fluticasone propionate 250 mcg (SFC 250) in Japanese patients with chronic obstructive pulmonary disease (COPD). Patients and methods: Patients were treated in a randomized, double-blind, parallel group, placebo-controlled trial with SFC 250 twice daily (n=26) or placebo (n=26) for 12 weeks. At the start and end of treatment, inflammation
Key clinical point: Patients with chronic obstructive pulmonary disease (COPD) fared better on an inhaled fixed-dose long-acting muscarinic antagonist/long-acting β2-agonist vs. an inhaled corticosteroid.Major finding: Patients who began umeclidinium/vilanterol (62.5/25 msg) therapy were less likely to progress to multiple-inhaler triple therapy (hazard ratio = 0.65; 95% CI, 0.47-0.89; P = .008) vs. fluticasone propionate/salmeterol (250/50 msg).
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Allergic rhinitis is an inflammation of the nasal airways due to allergens, such as dust, animal dander and pollen. Overall, those with allergic rhinitis have a sensitized immune system. The allergen produces the antibody immunoglobulin E and typically causes symptoms like rashes, flu, watery eyes, itching and sneezing. Fluticasone propionate nasal spray is an intranasal corticosteroid to treat those with allergic rhinitis.. When the nasal passages are exposed to allergens, the cells in the nose begin to release chemicals that produce an allergic response. When the fluticasone propionate nasal spray is used, the fluticasone is absorbed directly by the cells. It prevents these cells from triggering the chemicals that cause an allergic response. However, fluticasone propionate doesnt work right away; it can take up to four days to get the full effect. This is why doctors recommend using it prior to the allergy season, such as spring pollen. It also needs to be used on a regular basis to keep ...
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TY - JOUR. T1 - Asthma exacerbations in African Americans treated for 1 year with combination fluticasone propionate and salmeterol or fluticasone propionate alone. AU - Bailey, William. AU - Castro, Mario. AU - Matz, Jonathan. AU - White, Martha. AU - Dransfield, Mark. AU - Yancey, Steve. AU - Ortega, Hector. PY - 2008/6/1. Y1 - 2008/6/1. N2 - Objective: This long-term prospective study was conducted in African Americans with persistent asthma to examine the safety and effectiveness of the combination of the inhaled corticosteroid, fluticasone propionate (FP), and the long-acting beta-agonist, salmeterol, compared with FP alone. Research and design methods: This was a randomized, double-blind, parallel group, multi-center trial in adolescent and adult subjects ≥12 years of age symptomatic on a low dose of an inhaled corticosteroid (ICS). The study consisted of a 2-week screening period on low dose ICS; a 4-week open-label FP 250 mcg twice daily (BID) run-in; a 52-week double-blind period ...
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The effects of fluticasone propionate (FP) on sputum chemotactic activity, elastase inhibitory potential, albumin concentrations, and peripheral neutrophil function were studied in a group of patients with clinically stable, smoking-related chronic bronchitis and emphysema. Seventeen patients (50 to …
The combination of salmeterol and fluticasone propionate has a broad spectrum of antiinflammatory effects in both current and former smokers with chronic obstructive pulmonary disease, which may contribute to clinical efficacy.
Australia. Adverse Drug Reactions Advisory Committee (ADRAC) in Australia has received 10 reports of inhaled corticosteroid-associated adrenal crisis. Eight cases involved children aged 3 10 years who had received fluticasone propionate (Flixotide) 250 1500 µg/day; in six cases, the daily dose was , 500µg, the upper limit recommended by The Thoracic Society of Australia and New Zealand and by The National Asthma Council in Australia, before referral to a respiratory physician. The committee notes that higher fluticasone propionate doses may not confer greater efficacy and prescribers are reminded that inhaled corticosteroids should be given at the lowest effective dose and reviewed regularly.. Reports in WHO-file: Adrenal insufficiency 100. Reference: ...
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Aims: To investigate whether aerosol-type fluticasone propionate/formoterol combination (FFC) controls residual eosinophilic inflammation in the distal airways of well-controlled asthmatic patients more effectively than salmeterol/fluticasone propionate combination (SFC).. Methods: Subjects comprised 32 outpatients (61.9±17.0 years) with well-controlled moderate asthma who had used SFC for more than 4 weeks. Evidence of eosinophilic cationic protein (ECP) in 10% hypertonic saline-induced sputum was assessed, together with pulmonary function tests, respiratory resistance, exhaled nitric oxide (FeNO) and an Asthma Control Questionnaire (ACQ-5).. Results: ECP levels in late-phase sputum (117.6±144.7 mg/L at study entry) were significantly decreased 65.7±89.5 (p=0.019) at 4 weeks in the FFC group, but not in the SFC group. FeNo levels (44.8±23.5 ppb at study entry) were also significantly decreased to 37.8±23.5 (p=0.025) at 4 weeks in the FFC group. None of the indexes of pulmonary function ...
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TY - JOUR. T1 - Fluticasone propionate plasma concentration and systemic effect. T2 - Effect of delivery device and duration of administration. AU - Whelan, Glenn J.. AU - Blumer, Jeffrey L.. AU - Martin, Richard J.. AU - Szefler, Stanley J.. AU - Chinchilli, Vernon. AU - Kraft, Monica. AU - Dolovich, Myrna. AU - Boushey, Homer A.. AU - Cherniack, Reuben M.. AU - Craig, Timothy. AU - Drazen, Jeffrey M.. AU - Fagan, Joanne K.. AU - Fahy, John V.. AU - Fish, James E.. AU - Ford, Jean G.. AU - Israel, Elliott. AU - Kunselman, Susan J.. AU - Lazarus, Stephen C.. AU - Lemanske, Robert F.. AU - Peters, Stephen P.. AU - Sorkness, Christine A.. AU - King, Tonya. AU - Mauger, Elizabeth. PY - 2005/9/1. Y1 - 2005/9/1. N2 - Background: Inhaled corticosteroids are the preferred therapy in persistent asthma. Dry powder inhalers (DPIs) generate a larger particle size compared with metered-dose inhalers (MDIs), which affects pulmonary deposition, bioavailability, and subsequent systemic effects of fluticasone ...
Fluticasone propionate belongs to a class of drugs known as corticosteroids, specifically glucocorticoids, which are hormones that predominantly affect the metabolism of carbohydrates and, to a lesser extent, fat and protein. It is used to treat asthma, allergic rhinitis, nasal polyps, various skin disorders and Crohns disease and ulcerative colitis. It is also used to treat eosinophilic esophagitis. Fluticasone is used by powder or aerosol inhalation for the prophylaxis of asthma, the nasal spray is used for prophylaxis and treatment of allergic rhinitis, nasal drops are used in the treatment of nasal polyps, and creams and ointments are applied topically in the treatment of various skin disorders. It can be given orally in the treatment of Crohns disease and ulcerative colitis. Some benefit was also reported in coeliac disease.[citation needed] If taken correctly, the nasal spray and oral inhaler formulation have less corticosteroid side effects than the tablet formulation because they limit ...
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Fluticasone propionate is a highly selective agonist at the glucocorticoid receptor with negligible activity at androgen , estrogen , or mineralocorticoid receptors , thereby producing anti-inflammatory and vasoconstriction effects. It has
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Fluticasone propionate is metabolized in the liver by cytochrome P450 3A4-mediated hydrolysis of the 5fluoromethyl carbothiolate grouping. This transformation occurs in 1 metabolic step to produce the inactive 17β-carboxylic acid metabolite, the
The active component of Fluticasone Propionate Nasal Spray is fluticasone propionate, a corticosteroid having the chemical name \n \n \n -(fluoromethyl)6α,9-difluoro-11β,17-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carbothioate, 17-propionate and the following chemical structure:\n \n\n Fluticasone propionate is a white powder with a molecular weight of 500
Analytical methods development and validation play important roles in the discovery, development, and manufacture of pharmaceuticals. Simple, precise and accurate UV spectroscopic method has been developed and validated for estimation of Fluticasone propionate. It is a selective agonist at the glucocorticoid receptor. UV spectroscopic method which is based on measurement of absorption of UV light, the spectra of Fluticasone propionate in methanol showed maximum wavelength at 236nm and calibration curve were plotted over the concentrations ranging from 2-22ug/ml of Fluticasone propionate with correlation coefficient 0.9812 validation was performed as per ICH Q2 (R1) guidelines for linearity, accuracy, precision and recovery. The proposed method was validated.
Changes have been made to the WARNINGS and PRECAUTIONS sections of the safety label for Advair HFA 115/21 (fluticasone propionate 115 mcg and salmeterol 21 mcg*) Inhalation Aerosol
Description Of SEROFLO 125 INHALER Seroflo 125 Inhaler Tablet is used for Asthma, Lung diseases, Treatment of asthma (oral inhalation), Management of the nasal symptoms of perennial nonallergic rhinitis (nasal), Coughing, Shortness of breath, Cough, Bron
Inclusion Criteria for Entry in Treatment Period A subject will be considered eligible for inclusion in the treatment period only if he/she has completed the run-in period and meets the following criterion.. 1. Has been able, in the investigators/subinvestigators judgment, to make entries in the asthma diary and measure PEF, as directed, during the run-in period.. Exclusion criteria:. ...
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Fluticasone Propionate,(6alpha,11beta,16alpha,17alpha)-6,9-Difluoro-11-hydroxy-16-methyl-3-oxo-17-(1-oxopropoxy)androsta-1,4-diene-17-carbothioic acid S-(fluoromethyl) ester,S-fluoromethyl 6alpha,9alpha-difluoro-11beta-hydroxy-16alpha-methyl-17alpha-propionyloxy-3-oxoandrosta-1,4-diene-17beta-carbothioate,CCI-18781,Cutivate,Flixonase,Flixotide,Flonase,Flovent,Flunase
Publication date: March 2018 Source: Oral Oncology, Volume 78 Author(s): Zeno A.R. Gouw, Jan Paul de Boer, Arash Navran, Michiel W.M. va ...
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Fig. 4. Endosomal NHX antiporter activity is required for wortmannin-induced LE/MVB swelling. (A,C) Representative confocal images of root epidermal cells from plants expressing YFP-Rab5 (LE/MVB marker) (A), or a complementing p35S:NHX5-CFP line and antiporter inactive p35S:NHX6D194N-EGFP lines. Roots were mock treated (0.1% DMSO) or treated with 33 μM wortmannin (Wm) for 90 min. Wortmannin inhibits late endosome trafficking and induces homotypic fusion of MVBs into large bodies with a ring morphology in wild type (arrows), compared to smaller, dense bodies in nhx5 nhx6 (arrowheads). Plasma membrane is counterstained with FM5-95 in magenta. (B,D) Number of wortmannin bodies, and quantification of body size of wortmannin-treated seedlings from A and C. Data are the means±s.d., **P,0.01; two-tailed Students t-test. For each genotype ≥9 cells from ≥4 independent roots were analysed. (E) Response of root cap cells expressing YFP-ARA7 to treatment with 50 μM LY294002 or 1 μM wortmannin. ...
Adding an inhibitor of mammalian target of rapamycin (mTOR) to an aromatase inhibitor more than doubled the time to disease progression in patients with advanced, treatment-refractory breast cancer in the phase III BOLERO-2 trial, whose updated results were presented at the San Antonio Breast Cancer Symposium by Gabriel Hortobagyi, MD, of The University of Texas MD Anderson Cancer Center, Houston.1. We believe these results underline the fact that everolimus [Afinitor] is the first agent to significantly enhance the efficacy of hormonal therapy in patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, and could represent a paradigm shift in the management of this patient population, Dr. Hortobagyi predicted.. Virtually all patients with ER-positive advanced disease develop resistance to hormonal therapies, and finding a means of overcoming this resistance is the subject of strong research efforts. Resistance to hormonal therapy in breast cancer has been associated ...
Fluticasone medication - Please describe the medication: advair diskus (salmeterol and fluticasone)? Asthma Controller. Advair diskus (salmeterol and fluticasone) is used to treat asthma, it is an inhaled medication that has a steroid (fluticasone) which reduced lung inflammation and long acting salmeterol which relaxes airway muscles and improves breathing. Advair comes in 2 inhaler forms, hfa and diskus.
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... androstadienes MeSH D04.808.054.079.129.453 - methandrostenolone MeSH D04.808.054.079.129.782 - testolactone MeSH D04.808. ...
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... androstadienes MeSH D04.808.054.079.129.453 - methandrostenolone MeSH D04.808.054.079.129.782 - testolactone MeSH D04.808. ...
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Landt, S. G., Marinov, G. K., Kundaje, A., Kheradpour, P., Pauli, F., Batzoglou, S., Bernstein, B. E., Bickel, P., Brown, J. B., Cayting, P., Chen, Y., DeSalvo, G., Epstein, C., Fisher-Aylor, K. I., Euskirchen, G., Gerstein, M., Gertz, J., Hartemink, A. J., Hoffman, M. M., Iyer, V. R. & 27 others, Jung, Y. L., Karmakar, S., Kellis, M., Kharchenko, P. V., Li, Q., Liu, T., Liu, X. S., Ma, L., Milosavljevic, A., Myers, R. M., Park, P. J., Pazin, M. J., Perry, M. D., Raha, D., Reddy, T. E., Rozowsky, J., Shoresh, N., Sidow, A., Slattery, M., Stamatoyannopoulos, J. A., Tolstorukov, M. Y., White, K. P., Xi, S., Farnham, P. J., Lieb, J. D., Wold, B. J. & Snyder, M., Sep 1 2012, In : Genome research. 22, 9, p. 1813-1831 19 p.. Research output: Contribution to journal › Review article ...
MeSH-major] Androstadienes / therapeutic use. Antineoplastic Agents / therapeutic use. Breast Neoplasms / drug therapy. ... Chemical-registry-number] 0 / Androstadienes; 0 / Antineoplastic Agents; 0 / Biomarkers, Tumor; 0 / Carcinoembryonic Antigen; 0 ...
MeSH-major] Androstadienes / therapeutic use. Antineoplastic Agents / therapeutic use. Breast Neoplasms / drug therapy. ... Chemical-registry-number] 0 / Androstadienes; 0 / Antineoplastic Agents; 0 / Biomarkers, Tumor; 0 / Carcinoembryonic Antigen; 0 ...
Kim, B. G., Li, C., Qiao, W., Mamura, M., Kasperczak, B., Anver, M., Wolfraim, L., Hong, S., Mushinski, E., Potter, M., Kim, S. J., Fu, X. Y., Deng, C. & Letterio, J. J., Jun 22 2006, In : Nature. 441, 7096, p. 1015-1019 5 p.. Research output: Contribution to journal › Article ...
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": "Androstadienes", "type": "DefinedTerm" }, { "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", "name": "Antineoplastic ...
Androstadienes. -. dc.subject.mesh. Antineoplastic Combined Chemotherapy Protocols. -. dc.subject.mesh. Aromatase Inhibitors. - ...
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keywords = "androstadienes, tumor cell line, cell membrane, cytosol, guanine nucleotide exchange factors, guanosine diphosphate ...
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