Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For the symptomatic treatment of allergic rhinitis the following groups of drugs are available: decongestants (sympathicomimetics), stabilizers of the mast cell membrane (DNCG, nedocromil), corticosteroids (aerosols), antihistamines, ketotifen, anticholinergics. The world wide use (and abuse) of decongestants (sympathicomimetics) is limited by the so-called rhinopathia medicamentosa, when the necessary treatment exceeds 3 or 4 weeks. The antiallergic preparations like sodiumcromoglycat and nedocromil prevent sneezing, rhinorrhea and eye irritations. Their reported effect is "stabilisation" of the mast cell membrane. They have practical no side effects, but the patients compliance is limited by the short, prophylactic effect, necessitating frequent topical applications up to 6 times daily. As the overall symptom scores are only reduced between 30% to 50%, they are not suited for severe cases of allergic rhinitis. Nedocromil should have a significantly better efficiency than DNCG. The development of efficient topical glucocorticosteroid aerosols was a great progress in the treatment of allergic rhinitis. With daily doses of 100 micrograms to 800 micrograms they are very effective against hypersecretion, sneezing, itching and also blocking of the nose. Because of the so-called "first pass" effect after resorption through the nasal mucosa they have minimal general side effects, especially on the balance of the endocrine system. Their rate local side effects on the nasal respiratory mucosa include local irritations, crusting, dryness and seldom nose bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The symptomatic therapy of allergic rhinitis]. 196 61

Nedocromil is a new non-bronchodilator substance with mast cell stabilizing properties. In an acute placebo-controlled randomized double blind study, the protective effect of nedocromil on the bronchoconstrictor action of nebulised hypo-(distilled water) and hyperosmolar (4% saline) solutions was investigated in 12 patients with allergic asthma. Inhalations of distilled water and hypertonic saline had similar bronchoconstrictor effects. The effect of both solutions was significantly (p less than 0.01) attenuated by pretreatment with nedocromil, as compared with placebo. Thus, nedocromil could be useful in the treatment of allergic asthma.
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PMID:[Protective effect of nedocromil on hypo- and hypertonic solution-induced airway obstruction in exogenous allergic bronchial asthma]. 254 35

1. Nedocromil 2% iontophoresed into human skin had no effect on wealing produced by intradermal histamine, 48/80 or house dust mite antigen. 2. Iontophoresis of 0.002-2% nedocromil itself resulted in dose-related wealing. 3. This wealing was reduced by 62 +/- 8% s.e. mean by the H1-receptor antagonist terfenadine which decreased histamine wealing by 68 +/- 2% s.e. mean. 4. Nedocromil may therefore act as a weak agonist on a skin mast cell receptor concerned with histamine release.
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PMID:The effect of nedocromil on weal reactions in human skin. 289 67

Nedocromil, the disodium salt of a pyranoquinoline dicarboxylic acid, has a similar profile of activity to disodium cromoglycate (DSCG) but appears to be more active in stabilizing mucosal-type mast cells. In a double-blind placebo-controlled trial nedocromil (2 mg) was given by inhalation to eight asthmatic patients prior to a treadmill exercise task. There was a significant reduction in the fall in FEV1 (P less than 0.01) and FVC (P less than 0.05) after nedocromil when compared to placebo. This study indicates that nedocromil might be an effective anti-asthma agent and in addition may help define the role of the mucosal mast cell.
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PMID:Nedocromil, a mucosal and connective tissue mast cell stabilizer, inhibits exercise-induced asthma. 299 80

We tested the hypothesis that mast cells contribute to platelet-activating factor (PAF)-induced airways hyperreactivity and hyperpermeability in mice. Airways reactivity to acetylcholine (ACh) and lung permeability to Evans blue (EB) dye were measured before and after PAF challenge in genetically mast cell-deficient (WBB6F1 W/Wv) and normal congenic (WBB6F1 +/+) mice, as well as mast cell-reconstituted (BMT W/Wv) mice. In addition, prostaglandin D2 (PGD2), a mast cell-specific mediator, was measured in the bronchoalveolar lavage (BAL) from +/+ and W/Wv mice to determine if lung mast cell activation was a consequence of PAF challenge. Genetically PAF-sensitive AKR/J mice were also treated with the mast cell stabilizer nedocromil prior to assessment of PAF effects on ACh reactivity. Intravenous PAF (10 micrograms/kg) induced a significant (P < 0.05) increase in airways reactivity to ACh (25 micrograms/kg) in both +/+ (371 +/- 52%) and W/Wv (122 +/- 24%) mice. There was a significantly greater increase in +/+ compared with W/Wv mice. PAF-induced hyperreactivity to ACh in BMT W/Wv mice (191 +/- 44%) was significantly (P < 0.05) greater than age-matched W/Wv mice (80 +/- 16%), but not significantly different from age-matched +/+ mice (153 +/- 44%). PAF (10 micrograms/kg) also significantly (P < 0.5) increased lung permeability in +/+ and W/Wv mice, but there was no significant difference between groups. BAL PGD2 increased significantly in +/+ mice following PAF challenge (559 +/- 24 ng/ml) compared with vehicle controls (152 +/- 8 pg/ml). There was no significant increase in BAL PGD2 from W/Wv mice. Nedocromil pretreatment significantly (P < 0.05) decreased PAF-induced hyperreactivity in AKR/J mice but not in W/Wv mice (P > 0.05). We conclude that mast cells contribute significantly to PAF-induced hyperreactivity but not hyperpermeability in mice.
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PMID:PAF-induced airways hyperreactivity is modulated by mast cells in mice. 862 51

The effect of immobilization, gentle handling and decapitation on the level of plasma histamine in Wistar rats was investigated. Mast cell deficient (Ws/Ws) rats were used to characterize the source of elevated histamine in plasma by stress, and the effect of nedocromil, a mast cell stabilizer, on histamine release was assessed in these models in vivo. The plasma histamine concentration of freely moving rats was 93.0+/-2.3 pmol/ml. Gentle handling produced a transient increase in plasma histamine level by 1.9-fold, whereas immobilization resulted in a longer-lasting elevation by 2.6-fold compared to that in the freely moving rats. Decapitation increased the plasma histamine level by 10- to 16-fold compared with that in the freely moving rats. No increase in plasma histamine was found in Ws/Ws rats exposed to stress. Nedocromil inhibited the increase in plasma histamine level induced by stress in a dose-dependent manner. These findings suggest that stress induces histamine release from mast cells in Wistar rats and the extent of this histamine release increases with the severity of stress. Nedocromil proved to be a good pharmacological tool to inhibit stress-induced release of mediators from mast cells.
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PMID:Histamine release induced by immobilization, gentle handling and decapitation from mast cells and its inhibition by nedocromil in rats. 1046 71

Activation of mast cells, the key cells of allergic inflammation, causes typical morphological changes associated with an increase in volume, that is a function of area and perimeter. The purpose of this study was to evaluate the effect of mast cell activation to degranulate, carried out by the secretagogue Compound 48/80, and of inhibition of this activation carried out by Nedocromil sodium, a mast cell stabilizing drug, on mast cell area, perimeter and shape factor by a computerized image analyzer. Mast cells were isolated and purified by peritoneal lavage of rats (purity >98%) and co-cultured with mouse 3T3 fibroblasts to which they adhere. Cultures were incubated for 10 min at 37 degrees C with culture medium alone (Enriched Medium) or Enriched Medium containing either Nedocromil (10(-4) M) or Compound 48/80 (0.3 microg/ml) or Compound 48/80 and Nedocromil (0.3 microg/ml and 10(-4) M respectively). Supernatants were then assessed for histamine release, as a marker of mast cell activation and the cell monolayers were fixed and stained with an alcoholic-acidic toluidine blue solution and examined with a computerized image analyzer connected with a light microscope. Mast cells incubated in Enriched Medium or Nedocromil possessed similar morphometric parameters. Mast cells activated with Compound 48/80 (70% histamine release) had a significant increase in area and perimeter and a decrease in shape factor in comparison to mast cells in Enriched Medium alone. Simultaneous incubation of mast cells with Compound 48/80 and Nedocromil significantly inhibited their histamine release (36% histamine release) and the increase in area and perimeter, but did not affect significantly their shape factor, in comparison with mast cells incubated with Compound 48/80 alone. These data clearly show that there is a relationship between mast cell activation, consequent histamine release and changes in cell area, perimeter and shape factor and that Nedocromil not only inhibits mast cell histamine release but also the activation induced morphometric changes in mast cells.
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PMID:Activation and inhibition of mast cells degranulation affect their morphometric parameters. 1082 51

Correlative data suggest that cardiac mast cells are a component of the inflammatory response that is important to hypertension-induced adverse myocardial remodeling. However, a causal relationship has not been established. We hypothesized that adverse myocardial remodeling would be inhibited by preventing the release of mast cell products that may interact with fibroblasts and other inflammatory cells. Eight-week-old male spontaneously hypertensive rats were treated for 12 weeks with the mast cell stabilizing compound nedocromil (30 mg/kg per day). Age-matched Wistar-Kyoto rats served as controls. Nedocromil prevented left ventricular fibrosis in the spontaneously hypertensive rat independent of hypertrophy and blood pressure, despite cardiac mast cell density being elevated. The mast cell protease tryptase was elevated in the spontaneously hypertensive rat myocardium and was normalized by nedocromil. Treatment of isolated adult spontaneously hypertensive rat cardiac fibroblasts with tryptase induced collagen synthesis and proliferation, suggesting this as a possible mechanism of mast cell-mediated fibrosis. In addition, nedocromil prevented macrophage infiltration into the ventricle. The inflammatory cytokines interferon-gamma and interleukin (IL)-4 were increased in the spontaneously hypertensive rat and normalized by nedocromil, whereas IL-6 and IL-10 were decreased in the spontaneously hypertensive rat, with nedocromil treatment normalizing IL-6 and increasing IL-10 above the control. These results demonstrate for the first time a causal relationship between mast cell activation and fibrosis in the hypertensive heart. Furthermore, these results identify several mechanisms, including tryptase, inflammatory cell recruitment, and cytokine regulation, by which mast cells may mediate hypertension-induced left ventricular fibrosis.
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PMID:Cardiac mast cells mediate left ventricular fibrosis in the hypertensive rat heart. 1939 62

Mast cells are involved in immune disorders so that many of the proinflammatory and tissue destructive mediators produced by these cells have been implicated in the pathogenesis of rheumatoid arthritis. This scenario prompted us to investigate the correlation between mast cell degranulation and neutrophil influx within the digits and knees joints of arthritic mice assessing what could be the functional role(s) of joint mast cells in the response to collagen immunization. DBA/1J mice were submitted to collagen-induced arthritis and disease was assessed on day 21, 32 and 42 post-immunization. Pharmacological treatment with the glucocorticoid prednisolone, commonly used in the clinic, and nedocromil, a mast cell stabilizer, was performed from day 21 to 30. Arthritis develop after immunization, gradually increased up to day 42. Neutrophil infiltration peaked on day 32 and 21, in the digits and knees, respectively, showing an unequal pattern of recruitment between these tissues. This difference emerged for mast cells: they peaked in the digits on day 21, but a higher degree of degranulation could be measured in the knee joints. Uneven modulation of arthritis occurred after treatment of mice with prednisolone or nedocromil. Neutrophils migration to the tissue was reduced after both therapies, but only prednisolone augmented mast cell migration to the joints. Nedocromil exerted inhibitory properties both on mast cell proliferation and migration, more effectively on the digit joints. Thus, collagen induced an inflammatory process characterized by tissue mast cells activation and degranulation, suggesting a potential driving force in propagating inflammatory circuits yielding recruitment of neutrophils. However, the different degree of affected joint involvement suggests a time-related implication of digits and knees during collagen-induced arthritis development. These results provide evidence for local alterations whereby mast cells contribute to the initiation of inflammatory arthritis and may be targeted in intervention strategies.
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PMID:An essential role for mast cells as modulators of neutrophils influx in collagen-induced arthritis in the mouse. 2071 26

Diabetic cardiomyopathy is a specific disease process distinct from coronary artery disease and hypertension. The disease features cardiac remodeling stimulated by hyperglycemia of the left ventricle wall and disrupts contractile functions. Cardiac mast cells may be activated by metabolic byproducts resulted from hyperglycermia and then participate in the remodeling process by releasing a multitude of cytokines and bioactive enzymes. Nedocromil, a pharmacologic stabilizer of mast cells, has been shown to normalize cytokine levels and attenuate cardiac remodeling. In this study, we describe the activation of cardiac mast cells by inducing diabetes in normal mice using streptozotocin (STZ). Next, we treated the diabetic mice with nedocromil for 12 weeks and then examined their hearts for signs of cardiac remodeling and quantified contractile function. We observed significantly impaired heart function in diabetic mice, as well as increased cardiac mast cell density and elevated mast cell secretions that correlated with gene expression and aberrant cytokine levels associated with cardiac remodeling. Nedocromil treatment halted contractile dysfunction in diabetic mice and reduced cardiac mast cell density, which correlated with reduced bioactive enzyme secretions, reduced expression of extracellular matrix remodeling factors and collagen synthesis, and normalized cytokine levels. However, the results showed nedocromil treatments did not return diabetic mice to a normal state. We concluded that manipulation of cardiac mast cell function is sufficient to attenuate cardiomyopathy stimulated by diabetes, but other cellular pathways also contribute to the disease process.
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PMID:Myocardial remodeling in diabetic cardiomyopathy associated with cardiac mast cell activation. 2355 5


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