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)

Lodoxamid is an antiallergic drug, which stabilizes the mast cells' membrane blocking the release of the type I hypersensitivity reaction chemical mediators. A number of 25 patients with ocular allergic diseases (allergic conjunctivitis, vernal and atopic keratoconjunctivitis, giant papillary conjunctivitis), were included in this study. Lodoxamid, solution 0.1% (Alomide), was given 4 times daily for 6 weeks. The study's aim was to assess the lodoxamid's efficiency, on the ocular signs and symptoms. The study's results showed a significant improvement, or the disappearance of the ocular allergic disease. It is debated upon the lodoxamid's way and place of action, in blocking the type I hypersensitivity reaction. The lodoxamid's efficiency is due to its pharmacological features, by means of which it is effective on many links of the pathogenic chain: mast cells, eosinophils, lymphocytes, neutrophils, antigen presenting cells. Due to its action lodoxamid stabilizes the mast cell's membrane, and inhibits the release of histamine, prostaglandins, leukotrienes, triptase, interleukines -4, -8 and TNF-. During therapy with lodoxamid recruitment and activation of eosinophils is decreased, causing a significant reduction of the basic major protein, cationic eosinophilic protein, eosinophilic derived neurotoxin, eosinophilic peroxidase. Lodoxamid reduces the expression of ICAM-1 on the surface of the antigen presenting cells, and decreases the number of the TH2 cells, from the tears of the allergic patients.
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PMID:[An efficacy study of lodoxamide treatment in allergic eye lesions]. 1102 Nov 10

Histamine remains the main mediator released by both specific allergic and non-specific mast cell activation. Histamine is the classic mediator of itching, flare and redness. The effects of histamine in allergic conjunctivitis are mediated by H1-receptor activation on blood vessels and nociceptive nerves. Histamine effects may be prolonged and exaggerated since a defect in the histaminase enzymes has been recently demonstrated in VKC. The effects of histamine on conjunctival tissues may be more complex than those manifested by the simple symptom of itching. In fact, proinflammatory effects of histamine on conjunctival epithelial cells and fibroblasts have been demonstrated. Preliminary results showed that the H1 antagonist, emedastine, reduces significantly cytokine production from histamine-stimulated fibroblasts.
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PMID:Role of histamine in allergic conjunctivitis. 1105 44

Ophthalmic allergoses belong to highly prevalent ocular diseases. According to the records of the first center of allergic diseases of the eye set up in 1971 at Helmholtz Institute of Ocular Diseases in Moscow, the most prevalent clinical forms are seasonal pollenosis conjunctivitis, drug allergies, spring keratoconjunctivitis, large-papillary conjunctivitis, chronic allergic conjunctivitis, allergy associated with the "dry eye" syndrome, atopic keratoconjunctivitis, and ocular involvement in systemic immune diseases. Therapy of ocular allergies is based on the three main principles: removal of the allergen responsible for disease, immunotherapy, and symptomatic drug therapy. The main agents used in local antiallergic therapy are antihistaminic drugs (antasoline and acelastin), drugs inhibiting mast cell degranulation (chromoglycates and lodoxamide), and accessory drugs: corticosteroids (dexamethasone and deosonide), nonsteroid antiinflammatory agents (diclofenak), immunosuppressants (cyclosporin), and vasoconstrictors (tetrisoline). Antiallergic drugs can be used as monotherapy or in combinations, as they differ by the mechanism of action. Antiallergic drugs are used with good results in combined therapy of infectious conjunctivitis and keratitis.
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PMID:[New aspects in drug therapy of ocular allergies]. 1122 68

Prostaglandin (PG) D2, the major cyclooxygenase metabolite generated from immunologically stimulated mast cells, is thought to contribute to the pathogenesis of allergic diseases due to its various inflammatory effects. However, since no DP receptor antagonist has been developed as an antiallergic drug, the role of PGD2 in the pathogenesis of allergic diseases remains uncertain. Here, we report the in vivo efficacy of our newly established DP receptor antagonist, S-5751 [((Z)-7-[(1R,2R,3S,5S)-2-(5-hydroxy benzo[b]thiophen-3-ylcarbonylamino)-10-norpinan-3-yl]hept-5- enoic acid)], using various allergic inflammation guinea pig models. In allergic rhinitis models, oral administration of S-5751 dramatically inhibited not only early nasal responses, as assessed by sneezing, mucosal plasma exudation, and nasal blockage, but also late responses such as mucosal plasma exudation and eosinophil infiltration. Even when S-5751 was administered after recovery from the early responses, these late phase responses were almost completely suppressed. In addition, S-5751 alleviated allergen-induced plasma exudation in the conjunctiva in an allergic conjunctivitis model and antigen-induced eosinophil infiltration into the lung in an asthma model. These findings provide evidence for the crucial role of PGD2 as a mediator of allergic inflammation in guinea pigs and suggest that DP receptor antagonists may be useful in the treatment of allergic diseases triggered by mast cell activation.
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PMID:Prevention of allergic inflammation by a novel prostaglandin receptor antagonist, S-5751. 1145 1

The clinical presentation of the various forms of allergic conjunctivitis varies greatly from mild symptoms to severe disease with vision-threatening complications. Although an IgE-mediated type-1 hypersensitivity reaction has been demonstrated or postulated in many types of allergic eye disease, the pathophysiology underlying the allergic conjunctivitides is not fully understood. The variety of currently available treatment options underscores the complexity of the chemical reactions associated with mast cell degranulation and mediator release causing the onset of allergic signs and symptoms. Many of these treatments are merely palliative and do not eliminate the complex immune response initiating the symptoms, so there is a recurrence of disease as soon as the therapy is discontinued. Models of allergic eye disease have significantly aided the discovery of new anti-allergic and anti-inflammatory compounds that can be used safely in the eye.
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PMID:The pathogenesis of allergic conjunctivitis. 1189 84

Ocular allergy presents unsolved mysteries in molecular and cellular mechanisms, and at the same time continues to challenge ophthalmologists daily in a wide array of disease forms. The recent understanding of the key role of the T helper type 2 cytokines, adhesion molecules and chemokines may provide future avenues for pharmacological targeting of releasable inflammatory mediators. More potent topical mast cell stabilizers and H1 receptor antagonists have become commercially available for the management of the prevalent and benign forms of allergic conjunctivitis. Immunostimulatory DNA sequences present an innovative and promising route for the treatment of ocular allergy, but clinical studies are needed to demonstrate their efficacy in humans. Surgical methods are suggested to reconstruct the ocular surface in the sight-threatening diseases vernal keratoconjunctivitis and atopic keratoconjunctivitis. This review presents an update of the major advances in both the basic mechanisms and clinical and therapeutic aspects of ocular allergic diseases that were reported during the past year.
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PMID:Advances in ocular allergy: basic mechanisms, clinical patterns and new therapies. 1196 30

The treatment of ocular allergy requires a better understanding of the spectrum of clinical disorders involving various components of the immune system, and of interactions at the conjunctival surface. The immune response focuses primarily on the different levels of activity of Th2 lymphocytes and various other immune cells associated with allergic disorders, including mast cells, eosinophils, fibroblasts, and epithelial and endothelial cells. Ocular allergic disorders include seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC), giant papillary conjunctivitis (GPC) and atopic keratoconjunctivitis (AKC), which, through immunopathological and molecular immunological techniques, can all be better appreciated as being part of a larger spectrum of an atopic disease state. In SAC, pathological changes, such as increased mast-cell activation, the presence of migratory inflammatory cells, and early signs of cellular activation at the molecular level, are minimal. In PAC, these changes are more pronounced in line with the increased duration of allergenic stimulation. In more chronic forms of allergic conjunctivitis, such as VKC in children and AKC in adults, the following changes are evident: a persistent state of mast cell, eosinophil and lymphocyte activation; noted switching from connective-tissue to mucosal-type mast cells; increased involvement of corneal pathology; and follicular development and fibrosis. The treatment of acute and more chronic forms of allergic conjunctivitis has focused in the past on symptomatic relief of symptoms, but with a better understanding of the mechanisms involved we can now provide interventional therapeutic strategies and symptomatic relief. Our advances in the basic understanding of these conditions are providing the foundation for guidelines that improve the ocular health of patients with ocular allergies.
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PMID:Ocular allergy guidelines: a practical treatment algorithm. 1210 24

Ketotifen fumarate, formulated for the treatment of allergic conjunctivitis, is a histamine H1-receptor antagonist, mast cell stabilizer, and eosinophil inhibitor (decreases chemotaxis and activation of eosinophils). In this study, healthy volunteers 3 years of age or older received ketotifen fumarate .025% ophthalmic solution (n = 330) or placebo (n = 165) four times daily for 6 weeks. Ketotifen was safe and well tolerated in the adult and pediatric populations, with an incidence of ocular adverse events of 18.2%, compared with 15.2% with placebo. No ocular rebound vasodilation or itching was observed within 48 hours after treatment. Ketotifen has a favorable safety and tolerability profile, which may have a positive impact on compliance, an important aspect of effective symptomatic control of allergic conjunctivitis.
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PMID:Ocular tolerability and safety of ketotifen fumarate ophthalmic solution. 1243 Oct 41

This randomized, double-masked, active-control, parallel-group trial compared the mast cell stabilizers pemirolast potassium 0.1% and nedocromil sodium 2% in the treatment of seasonal allergic conjunctivitis. Pemirolast is currently indicated for four-times-daily administration, nedocromil, for twice-daily dosing. Both ophthalmic solutions were instilled bilaterally twice a day for 8 weeks. The study involved four office visits and two telephone contacts. Participants evaluated their symptoms daily in take-home diaries (itching was the primary efficacy variable) and completed questionnaires to assess comfort. Of a total enrollment of 80, 78 patients completed the study. No significant differences were found between pemirolast and nedocromil on any signs or symptoms of allergic conjunctivitis (redness, chemosis, itching, eyelid swelling). At each visit, pemirolast was rated significantly more comfortable than nedocromil. A significantly higher percentage of the pemirolast group experienced no signs or symptoms at work or school (58% vs 28%; P = .005). The number of adverse events did not differ significantly between groups. Twice-daily administration of pemirolast potassium was as efficacious and safe as twice-daily nedocromil sodium in the 8-week treatment of ragweed allergic conjunctivitis and was superior to nedocromil in comfort. Increased comfort with pemirolast may increase patient satisfaction and compliance with therapy.
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PMID:Two mast cell stabilizers, pemirolast potassium 0.1% and nedocromil sodium 2%, in the treatment of seasonal allergic conjunctivitis: a comparative study. 1277 16

Ocular allergic disorders can be a component of systemic or local allergies. The importance of ocular allergy results from its incidence rather than from its severity, however, some of them are vision-threatening. The majority of ocular allergies affect the conjunctiva, eyelids and sometimes cornea that is exposed to the environment and is the place of interaction between allergens and immunocompetent cells. Different types of allergic disorders in the eye may have similar signs and symptoms, but each has its own pathognomonic characteristics, which help to diagnose, differentiate and choose the most suitable therapy. Ocular allergic diseases are classified into six categories: SAC, PAC, VKC, AKC, GPC and ConBC. In 2001 EAACI suggested new classification, also of allergic conjunctivitis, into IgE-mediated and non-IgE-mediated conjunctivitis. IgE-mediated conjunctivitis may be divided into intermittent and persistent conjunctivitis. Persistent allergic conjunctivitis is classified into vernal and atopic keratoconjunctivitis. Conjunctivitis contact allergy is a non-IgE form of allergic conjunctivitis. Currently available medications provide safe and effective management of most cases of ocular allergy. Drugs used in the treatment of ocular allergic disorders include mast cell stabilizers, antihistamines, steroids, NSAID's, artificial tears and others.
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PMID:[Clinical picture, diagnosis and therapy of allergic eye diseases]. 1452 17


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