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

The effects of an amino acid L-glutamine on aspirin-induced gastric lesions as well as on the mast cell population were studied in rats. L-glutamine had a pronounced inhibitory effect on gastric lesions produced by oral aspirin administration. Aspirin-induced increase in the mast cell population of the stomach was also prevented. Parenteral administration of aspirain did not produce any significant damage to the gastric mucosa.
 ...
PMID:Inhibition of mast cell population by L-glutamine in aspirin-induced ulceration in rat stomach. 61 89

The effect of immunosuppressive drugs, 4-aminosalicylic acid (4-ASA), acetyl 5-aminosalicylic acid (5-ASA), and ketotifen on human colonic eicosanoid accumulation was evaluated in view of enhanced accumulation in patients with active ulcerative colitis. Azathioprine (100 micrograms/ml), cyclosporin (100 micrograms/ml), and methotrexate (100 micrograms/ml) significantly inhibited, by 25-35%, prostaglandin E2 (PGE2) accumulation by organ-cultured colonic mucosa of ulcerative colitis patients. Methotrexate was the only immunosuppressive drug that inhibited leukotriene B4 (LTB4) accumulation (50%), whereas azathioprine inhibited the accumulation of leukotriene C4 (LTC4) (25%). 5-ASA and its metabolite, acetyl 5-ASA, inhibited by 20-70% PGE2, LTB4, and LTC4 accumulation in the culture, supporting the contention that acetyl 5-ASA is as active as 5-ASA in these respects. 4-ASA had no effect on any of the eicosanoids. Ketotifen, a mast cell stabilizer, significantly inhibited the accumulation of PGE2, LTB4, and LTC4 by 33-60%. These results suggest a potential, new, unrecognized mode by which the immunomodulators induce part of their therapeutic effects in inflammatory bowel disease and support the contention that acetyl 5-ASA is as active as 5-ASA. The results obtained also indicate that ketotifen, used effectively in the prevention of bronchial asthma, inhibits the accumulation of colonic eicosanoids and, thus, may be of value in the treatment of inflammatory bowel disease.
 ...
PMID:Effect of drugs on colonic eicosanoid accumulation in active ulcerative colitis. 145 96

The involvement of mast cells in the pathogenesis of aspirin (ASA)-induced respiratory reactions was investigated by measuring serum levels of tryptase, a neutral protease that is a specific marker of mast cell activation. ASA challenges were performed in 17 ASA-sensitive patients with asthma and rhinosinusitis, and tryptase and histamine levels were measured in their venous blood samples. In three subjects who experienced moderate to severe respiratory reactions extending to the skin and/or gastrointestinal tract, marked elevations of tryptase levels in postreaction serum samples (peak levels, 51.9 and 40.0 ng/ml) were discovered in two of these three subjects, and a small elevation of tryptase occurred in the serum of the third subject (3.1 ng/ml peak). Plasma histamine levels in postreaction samples were significantly elevated over baseline values in all three subjects (delta mean plasma histamine, 238 pg/ml versus 56 pg/ml for the remaining 14 subjects; p less than 0.04). In the remaining 14 subjects, who experienced similar respiratory reactions without extrapulmonary symptoms during aspirin challenge, changes in tryptase and histamine levels were not observed.
 ...
PMID:Tryptase and histamine release during aspirin-induced respiratory reactions. 172 Jul 95

The effects of sulphasalazine and of its major constituents, sulphapyridine and 5-aminosalicylic acid (5-ASA), on gastric ulceration as well as on changes in mast cell counts and mucus levels in the glandular mucosa were examined in restrained rats exposed to 4 degrees C (stress) for 2 h. Sulphasalazine (50, 100, 200 mg/kg), sulphapyridine (31.25, 62.5, 125 mg/kg) or 5-ASA (18.75, 37.5, 75 mg/kg) was injected subcutaneously 0.5 h before stress induction. Cold-restraint stress produced gastric glandular mucosal ulcers which were significantly reduced by all three doses of sulphasalazine and the higher doses of sulphapyridine and 5-ASA. Sulphasalazine prevented mast cell degranulation and increased the amount of mucus adhering to the mucosa. In contrast, the higher doses of sulphapyridine significantly increased only the mucus levels, whereas those of 5-ASA effectively prevented mast cell degranulation. The results show that the total effect of sulphasalazine is approximately equivalent to the summation of the actions of its component doses of sulphapyridine and 5-ASA. It is notable that sulphapyridine itself appears to be biologically active in reducing ulcer severity.
 ...
PMID:Inhibition of stress-induced gastric ulcers by sulphasalazine and its constituents (sulphapyridine and 5-aminosalicylic acid) in rats. 197 55

Using our animal model of synovial mast cell-mediated arthritis in rats, we tested the effects of 3 nonsteroidal antiinflammatory drugs (NSAIDs) (aspirin, indomethacin, and ketoprofen) and an H1 and an H2 histamine receptor antagonist (diphenhydramine and cimetidine, respectively) on synovial and dermal mast cell-induced vasopermeability. Drug effects were assessed by quantifying the leakage of radiolabeled albumin into tissues following specific antigen-initiated activation of passively sensitized dermal and synovial mast cells. The 3 NSAIDs tested had different effects on synovial and dermal mast cell-induced vasopermeability. Aspirin and indomethacin significantly increased dermal and synovial plasma exudation (P less than or equal to 0.008). Ketoprofen decreased dermal (P = 0.015), but had no effect on synovial, vascular exudation. Complete histamine H1 and H2 receptor blockade with diphenhydramine and cimetidine, respectively, substantially decreased (P less than or equal to 0.0008), but did not completely inhibit, dermal and synovial mast cell-induced vasopermeability. However, the addition of indomethacin to the combined antihistamine regimen resulted in an increase in the leakage of the radiolabel into skin and synovium (back to control levels), despite the complete blockade of H1 and H2 receptors. Results of experiments with antihistamines and indomethacin suggest that mediators other than histamine are involved in synovial mast cell-induced inflammation. Furthermore, the differential response to ketoprofen indicates that the specific antigen-stimulated mediator release profiles of dermal and synovial mast cells are different. Our finding of enhanced synovial vascular leakage in animals treated with some NSAIDs, and no such effect by other NSAIDs, perhaps explains in part the diverse effects of these agents in humans with arthritis.
 ...
PMID:In vivo effects of nonsteroidal antiinflammatory drugs on rat skin and synovial mast cell-induced vasopermeability. 199 13

The way nasal polyps arise and why they tend to recur is still unknown. Quite frequently they are found in association with asthma, rhinitis and ASA-intolerance, thus suggesting a multifactorial etiopathogenesis. The incidence of atopy in patients affected with nasal polyposis is quite low (16.8%). Recent studies stress the involvement of mast cell mediators due to various degranulating stimuli other than those mediated by IgE. The finding of the interleukin-2 receptor (IL2-R) on murine mast cells and on human peripheral blood basophils, together with the possibility of inducing basophil degranulation through IL2 stimulation, have led the authors to seek IL2R on human nasal polyp mast cells and to study subpopulations of nasal polyp lymphoid infiltrates. Nasal polyps obtained from 4 patients, admitted to the E.N.T. Department of the Catholic University of Rome in 1988, were snap frozen soon after their surgical removal through transmaxillary ethmoidectomy. In this study the following monoclonal antibodies (MoAb) were used: Leu-2a (CD8), Leu-3a/3b (CD4), Leu-4 (CD3), anti-HLA-DR and anti-IL2-R (CD25), OKM1 (CD11), OKB2 (CD24) and 1HT4-4H3 (CD 25). In no patient was there evidence of atopy, asthma or ASA-intolerance. Several mast cells (MC) were observed, chiefly in the connective axis and perivascular areas. These cells were characterized by a large number of cytoplasmatic monomorphic granules. The MC displayed the IL2-R and they were very often close to T-lymphocytes. T-cell subpopulations were predominantly composed of CD4-positive cells (about 75% of all lymphocytes) often associated in clusters and located both in the submucosa and in the connective axis. CD8-positive cells (10-15% of the lymphoid cells) were located most often just under the epithelium. They were hardly ever scattered within the CD4-positive cell clusters. Almost all T cells were activated, above all those surrounding the MC. These results would appear to suggest the presence of a cell-mediated immune response in nasal polyp pathogenesis where MC degranulation, determined by activated T-cell cytokines, plays an important role.
 ...
PMID:[Recent advances concerning etiopathogenesis of nasal polyposis]. 265 69

In order to assess the role of arachidonic acid metabolites in the early reaction to antigen, we challenged six allergic individuals with and without premedication with aspirin and recorded their clinical response, as indicated by number of sneezes, and measured the levels of inflammatory mediators. The early reaction to antigen was associated with increases in the levels of histamine, N-alpha-tosyl-L-arginine methyl esterase (TAME-esterase) activity, prostaglandin (PG) D2, leukotriene C4, PGE, and thromboxane. Aspirin significantly inhibited the increases in the cyclooxygenase metabolites PGE, PGD2, PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane but did not affect the amount of sneezing or the levels of histamine, TAME-esterase activity, or leukotrienes. The pattern of the metabolites and their response to pretreatment with aspirin parallel the response of purified human lung mast cells, supporting the notion that the early phase of allergic rhinitis is a mast cell-dominated event.
 ...
PMID:Arachidonic acid metabolites during nasal challenge. 309 12

Progressively increasing doses of aspirin (acetylsalicylic acid--ASA) were tolerated by 14 out of 15 patients with confirmed aspirin-sensitive urticaria and in 7 out of 9 patients with aspirin-sensitive asthma. Blood levels of histamine and prostaglandin (PG) F2 alpha were significantly raised in these patients before ASA administration. PGF2 alpha levels fell to within the normal range after challenge doses of ASA which were sufficient to cause symptoms. Skin prick testing with histamine and codeine phosphate did not show evidence of abnormal tissue reactivity or mast cell reactivity. A wider spectrum of mediators will need to be considered if the mechanism of symptom production is to be understood.
 ...
PMID:Clinical and biochemical aspects of "aspirin-sensitivity". 347 39

Sorbic acid concentrations as low as 0.1% produced transient erythema with edema and flare after open or closed application to human skin. Multiple areas of the body were tested. Reactions were most intense on the face but also could be produced on the back, forearm, and deltoid areas. Sorbic acid-induced erythema, edema, and flare were not associated with mast cell degranulation. Pretreatment of skin with topical steroids to induce vasoconstriction resulted in a diminished response to sorbic acid. Aspirin blocked the erythematous component, suggesting that prostaglandins are important mediators. Systemic steroids, antihistamines, and hydroxyzine failed to influence sorbic acid-induced erythema and edema. The anti-inflammatory effect of topical steroids was not affected by sorbic acid-induced erythema.
 ...
PMID:Sorbic acid-induced erythema and edema. 395 Jan 21

In a group of aspirin-sensitive asthmatics we studied skin weal and flare responses to intradermal injections of compound 48/80 and histamine during oral aspirin (ASA) provocation and after ASA "desensitisation". During provocation (bronchospasm accompanied by naso-ocular symptoms) the mean weal area after compound 48/80 increased to about 42.4% (P less than 0.05). Neither the threshold (provocative) doses of ASA nor 600 mg ASA, when given after ASA-desensitisation, significantly influenced the weal reactions to compound 48/80 (mean changes of area were -1.8% and -16.5% respectively). Aspirin did not change flare reactions to compound 48/80 and weal and flare reactions to histamine on any of the three study occasions. Initial (pre-aspirin) weal reactions to compound 48/80 after desensitisation to the threshold ASA doses were significantly reduced, but after desensitisation to 600 mg ASA were significantly increased as compared with the reactions before. These data suggest that ASA-"desensitisation" may influence the skin reactivity to non-specific mast cell degranulating stimulus in ASA-sensitive asthmatics.
 ...
PMID:The effect of aspirin during aspirin "desensitisation" on compound 48/80 and histamine-induced skin responses in aspirin-sensitive asthmatics. 399 67


1 2 3 4 Next >>