Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042109 (urticaria)
 6,569 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the majority of itching skin diseases are inflammatory or allergic, it has been assumed that release or activation of inflammatory mediators, stimulating the itch receptors, play an essential role in the pathophysiology of itch. In this review some of the possible mediators are discussed. Histamine induces itch upon intradermal injection, but urticaria is the only itching dermatosis which is significantly relieved by antihistamines. Serotonin is much weaker than histamine in provoking itch upon intradermal injection. Serotonin acting in synergism with prostaglandins may cause itch in polycythaemia vera. Neuropeptides release histamine from skin mast cells, but it remains to be determined whether neurogenic peptides are responsible for clinical pruritus. Prostaglandins enhance pruritus induced by intradermal histamine (and serotonin) but are weak pruritogens per se. Lymphocytes are present in many itching skin diseases and it could be assumed that lymphokines are involved in the pathogenesis of itch. Supporting this theory is the finding that ciclosporin A, an inhibitor of lymphokine production, reduces itch in atopic dermatitis. Central mechanisms are essentially unknown, but there are indications that opioid peptides might be involved in the central transmission of itch.
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PMID:Peripheral and central mediators of itch. 157 79

The effect of treatment with a monoclonal antibody against the CD4 antigen present on T helper cells was studied in 10 patients with severe intractable rheumatoid arthritis. In an open trial, monoclonal antibody 16H5 was infused at a dosage of 0.3 mg/kg of body weight on 7 consecutive days. Studies of the kinetics demonstrated a drastic depletion of CD4+ cells, to as low as 25 cells/microliters, 1 hour after the first infusion. The subsequent recovery of the CD4+ cell numbers 24 hours after infusion did not reach initial levels, and after the full 7-day treatment cycle there was a significant reduction of the number of CD4+ cells (mean +/- SD 51 +/- 28%; P less than 0.02). There was a reduced or even inverse CD4:CD8 ratio, which generally persisted 3-4 weeks. Lymphocyte transformation assays demonstrated significantly reduced reactivity in 5 of the 9 patients who completed the 7-day course, whereas 4 individuals exhibited an unexpected elevation in the T cell response to mitogens and common antigens. Parallel laboratory studies showed a significant decrease in the erythrocyte sedimentation rate (P less than 0.05), rheumatoid factor titer (P less than 0.04), and total immunoglobulin values (P less than 0.01), as well as a reduction in C-reactive protein levels, in 7 of the 9 patients. Clinically, there was a significant reduction in the Ritchie articular index (P less than 0.05) and in the number of swollen joints (P less than 0.04). Adverse effects were urticaria in 2 patients, which led to withdrawal of therapy in 1 of them, and chills with fever, suggestive of a lymphokine release syndrome, in another 2 patients. Only low levels of human anti-mouse immunoglobulin antibodies developed (not exceeding 1.7 mg/liter). It was therefore possible to repeat the treatment cycle, achieving still better efficacy, in 4 of the patients (reductions in the Ritchie index and the number of swollen joints P less than 0.02). Our findings indicate that treatment with monoclonal antibodies against the CD4 antigen leads to immunomodulation which results in clinical benefits, at least during initial observation periods (up to 6 months postinfusion). However, it remains to be determined whether long-term remission can be induced with this therapeutic approach. The use of immunosuppressive therapies or repeated antibody treatments will have to be considered.
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PMID:Treatment of rheumatoid arthritis with an anti-CD4 monoclonal antibody. 199 9

Food allergy (FA) and food intolerance (FI) are complex syndromes caused by adverse reactions to foods. Since mucosal permeability of the digestive tract is often increased during this pathology, we evaluated the clinical efficacy of two different cytoprotective drugs in patients with urticaria-angioedema due to FA and FI. These drugs were pirenzepine, an anti-muscarinic (anti-MI) receptor antagonist, and rosaprostol, a synthetic prostaglandin. Further, the results obtained by these schedules of treatment were compared with those achieved by the previously described polyantihistaminic treatment (ie, the association of anti-H1 plus anti-H2 receptor blockers). The present investigation suggests that the cytoprotective drugs are more effective than the antisecretive ones (ie, the anti-H2). Recently, anti-H2 drugs and ketotifen were shown to be in vitro inhibitors of the immune response and cromolyn was demonstrated capable of exerting an enhancing effect on T cell proliferation. In the present study we tested the effect of pirenzepine on several immunologic parameters, such as lymphocyte proliferation (through different activation pathways) and lymphokine (interleukin-2 and interferon-gamma) production. Since we found that pirenzepine does not affect the immune response and in consideration of its clinical efficacy, we consider this cytoprotective drug a valuable tool in the treatment of adverse reactions to foods.
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PMID:Cytoprotective drugs: a new perspective in the treatment of adverse reactions to foods. 296 61

In some cases of chronic urticaria it is suspected that food additives such as tartrazine and sodium benzoate or salicylates may play a role in the pathogenesis of the condition. Since, at times, chronic urticaria may appear histologically similar to a mild cell-mediated immune response, the release of the T cell-derived lymphokine leucocyte inhibitory factor (LIF), in response to incubation with these additives and with acetylsalicylic acid (ASA), was measured in vitro using cells from normal controls, from patients with chronic urticaria with or without clinically associated additive sensitivity and from patients with asthma with or without associated ASA sensitivity. It was found that significant production of LIF occurred in response to tartrazine and sodium benzoate in those individuals with chronic additive induced urticaria. In addition, tartrazine caused LIF release from mononuclear cells of ASA-sensitive asthmatics. These results may indicate a possible role for additive-induced cell-mediated immune responses in the pathogenesis of some cases of chronic urticaria and suggest a potential diagnostic test for this condition.
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PMID:Cell-mediated immune responses to artificial food additives in chronic urticaria. 353 8

The therapeutic and biologic effects of murine monoclonal antibodies in patients with malignancies have been widely investigated. Attempts to enhance results by combining these agents with cytotoxic drugs are now under study. A Phase I trial was performed to assess the toxicity and biologic effects of escalating doses of R24 (0-40 mg/m2/day 1-5, 8-12), an antibody that binds to the ganglioside GD3 present on melanoma cells, administered in combination with cisplatin (120 mg/m2) and WR-2721 (740 mg/m2) on day 1. Twenty-three patients with metastatic malignant melanoma were treated and are evaluable. The true maximum tolerated dose of R24 given as part of this combination was not reached. The toxicity of the regimen was moderate and included fever and urticaria, which were attributed to R24. Severe but reversible renal failure was noted in six patients in subsequent (two or more) treatment cycles, but when cisplatin was administered in 3% saline, this toxicity was not seen. Responses were seen in 2 of 19 patients receiving all three agents and in 1 of 4 patients receiving only cisplatin and WR-2721. No significant enhancement of natural killer, lymphokine-activated killer, and antibody-dependent cellular cytotoxicity lytic activity or significant changes from baseline in lymphocyte subsets secondary to R24 were seen. In 4 of 10 patients tumor localization of mouse monoclonal antibody was found and appeared greatest at higher R24 doses and during week 1 of therapy. Human anti-mouse antibody responses developed by day 22 in 17 of 19 patients treated with R24, and the coadministration of cisplatin did not appear to abrogate this response. Finally, the half-life and Cmax of cisplatin were not affected by R24. In summary, the combination was well tolerated, responses were few, and significant biologic interactions or immunomodulation were not observed.
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PMID:Phase I trial of cisplatin, WR-2721, and the murine monoclonal antibody R24 in patients with metastatic melanoma: clinical and biologic effects. 806