Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0220723 (PCA)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

RU 31156, the tris-(hydroxymethyl)-aminomethane salt of 7-(S-methylsulphonimidoyl)-5-(n-hexyl)-xanthen-9-one-2-carboxylic acid has been found to be a potent inhibitor of experimental immediate hypersensitivity reactions in vivo. In the IgE-mediated rat PCA test, RU 31156 had an ED50 of 0.0046 (00037--0.0057) mg/kg which compared to a figure of 1.21 (1.04--1.42) mg/kg for disocium cromoglycate (DSCG), both compounds being administered intravenously. RU 31156 was also active when administered orally, having an ED50 of 0.19 (0.07--0.30) mg/kg when given 10 min before antigen. RU 31156 partially inhibited an IgG-mediated PCA reaction in the rat. Both RU 31156 and DSCG inhibited anaphylactic bronchoconstriction in the rat, giving bell-shaped dose-response curves. From the upward part of the curves, approximate ED30 values of 0.02 and 2.0 mg/kg were obtained for RU 31156 AND DSCG respectively. Anaphylactic bronchoconstriction in the guinea-pig was not affected by RU 31156 and pinnal anaphylaxis was inhibited at only relatively high doses of 1--10 mg/kg i.v. The effects of both histamine and 5-hydroxytryptamine in the mouse pinna were not affected by RU 31156. In PCA experiments, RU 31156 showed self-tachyphylaxis following both intravenous and oral administration. It also showed cross-tachyphylaxis with DSCG, indicating that these compounds are likely to share a similar mode of action.
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PMID:Inhibition of experimental immediate hypersensitivity reactions by a novel xanthone, RU 31156. 2 34

Five non-steroidal anti-inflammatory drugs (indomethacin, naproxen, meclofenamic acid, feprazone and phenylbutazone: NSAIDs) and three glucocorticosteroids (dexamethasone, hydrocortisone and prednisolone) have been tested as local inhibitors of increased vascular permeability in guinea-pig skin. Lesions were induced by histamine or by antigen to evoke type I (passive cutaneous anaphylaxis), type III (reverse passive Arthus) and type IV (delayed hypersensitivity) allergic reactions. NSAIDs and glucocorticosteroids caused either weak, inconsistent inhibition or slight, high-dose inhibition of the response to histamine. None of the drugs tested showed significant inhibition of the type IV response. The NSAIDs caused dose-related inhibition of both type I and type III responses whereas glucocorticosteroids were ineffective. Maximum inhibition with the NSAIDs was never greater than 50--60% Feprazone, meclofenamic acid and indomethacin were the most potent inhibitors of histamine, PCA and Arthus responses respectively. The possible significance of the effects of these anti-inflammatory agents on vascular permeability is discussed.
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PMID:Anti-inflammatory drug actions on allergic responses in guinea-pig skin. 3 Oct 78

A newly synthesized compound, 6-ethyl-3-(1H-tetrazol-5-yl)chromone (AA-344) given intravenously or orally inhibited considerably the 72-hr passive cutaneous anaphylaxis (72-hr PCA) induced by IgE in rats. The antiallergic action of AA-344 was neither due to the antihistamine or antiserotonin effect nor was it mediated via adrenergic mechanisms. The results obtained in a double sensitization with two IgE antibodies suggest that AA-344 may not impair antigen-antibody combination but probably prevents the release of chemical mediators including histamine. This assumption was supported by observation that AA-344 inhibited a reduction in the skin histamine content caused by the 72-hr PCA, without effect on the compound 48/80-induced histamine reduction. AA-344 also partially inhibited the IgGa-mediated 3-hr PCA in rats. These results indicate that the inhibitory action of AA-344 on the immediate hypersensitivity reactions is due to prevention of the release of chemical mediators from the mast cells, by acting on some process in sequential events leading to the mediator release following antigen-antibody combination.
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PMID:Antiallergic action of 6-ethyl-3-(1h-tetrazol-5-YL) chromone (AA-344) on immediate hypersensitivity reaction in rats. 4 12

Anaphylactic release of slow-reacting substance of anaphylaxis (SRS-A) from chopped guinea pig lung was studied. The antibodies mediating the anaphylactic reaction were classified as IgG antibodies by PCA technique. Isoprenaline was found to inhibit the release of SRS-A in the concentration range 10-8-10-6M, while the beta2-selective agonist terbutaline showed inhibition in the concentration range 10-6-10-5M. The beta1-selective beta-agonist tazolol was ineffective when tested in the concentration range 10-7-10-5M. The rank order of inhibitory potency of the compounds on SRS-A release agree with that for histamine release.
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PMID:Release of slow-reacting substance from anaphylactic lung tissue and its modification by beta-sympathomimetics. 43 10

Relationship between delayed-in-onset erythema and infiltrating leucocytes in the skin reaction site of Jones-Mote type hypersensitivity was observed in guinea-pigs. Guinea-pigs were immunized with formalin-fixed (F-SRBC) or native form (N-SRBC) of sheep red blood cells in incomplete Freund's adjuvant (IFA). Elicitation was carried out with intradermal injection of F-SRBC or N-SRBC in saline 1 or 3 weeks after immunization. One week after immunization with F-SRBC or N-SRBC in IFA, erythema accompanied by basophil infiltration was detected, but antibody production was negative. Erythema reached a peak at 24 h, but basophil infiltration reached a peak at 48 h or later. In the skin reaction site elicited with N-SRBC, high levels of basophil infiltration were detected persistently even after erythema had disappeared. Three weeks after immunization, low titres of PCA (passive cutaneous anaphylaxis) were detected in guinea-pigs immunized with F-SRBC in IFA. At that time erythematous skin reaction was detected, but the level of basophil infiltration was lower than that of 1 week after immunization. In guinea-pigs immunized with N-SRBC in IFA, skin reaction of the Arthus type accompanied by haemorrhage was observed at the site elicited with N-SRBC.
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PMID:Dissociation of erythema and basophil accumulation in Jones-Mote type hypersensitivity in the guinea-pig. 54 Jan 1

Biologic properties of antibodies are known to be mediated by the Fc portion of the H chains. In the present study such properties as complement fixation, cutaneous anaphylaxis, and macrophage cytophilia were examined in relation to the CH2 and CH3 domains of rabbit IgG. Fragments containing but one of these domains were prepared from plasmin and papain digests. Facb fragments of anti-DNP antibodies, together with the antigen DNP-BSA, were able to fix complement by the classical pathway, a result which implicates the CH2 domain; however, guinea pig Fab fragments directed to regions of the rabbit antibody molecule other than CH2 were able to inhibit complement fixation. Facb fragments were unable to mediate PCA or reverse PCA reactions in guinea pigs, nor were CH3 fragments active in tests of reverse PCA or inhibition of PCA. These results suggest that the entire Fc region is needed for cutaneous anaphylaxis. The ability to bind to guinea pig lung macrophages was studied with a rosette technique. Facb fragments were active whereas CH3 fragments failed to inhibit. It is suggested that although some effector functions of antibodies can be assigned to individual domains, others require the entire Fc region.
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PMID:Biologic activities of rabbit immunoglobulin G in relation to domains of the Fc region. 81 12

The heterologous adoptive cutaneous anaphylaxis system was used to determine the kinetics of appearance of IgE-producing cells in various lymphoid tissues of mice following intratracheal (i.t.), intraperitoneal (i.p.), or subcutaneous (s.c.) immunization with tetanus toxoid and Bordetella pertussis organisms. Immunization, i.t. and i.p., produced similar patterns of response with the bronchial lymph nodes quantitatively exceeding the responses in other lymphoid tissues. In both cases the splenic lymphocyte response was second only to the bronchial and both appeared to parallel the serum PCA antibody. It is suggested that both responses represent draining lymph node responses since the bronchial lymph node drains both sites of immunization. After s.c. immunization a primary response of low order was found in the draining popliteal lymph node but not elsewhere. Although a dissociation was seen between responses obtained in various lymphoid tissues following s.c. and i.p. or i.t. immunization, no real evidence for a local mucosal response, such as has been reported for IgA, was obtained. These results lend experimental support to the observations that intratracheal and intraperitoneal immunization routes are most effective in production of IgE antibodies.
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PMID:Kinetics and localization of IgE tetanus antibody response in mice immunized by the intratracheal, intraperitoneal and subcutaneous routes. 99 17

Chromatographically separated antigens of Mycobacterium leprae were tested for their ability to elicit skin reactions in guinea-pigs sensitised with homologous and heterologous mycobacteria. Of the three antigen-positive fractions obtained, one showed specific activity and the other two cross-reactivity, as indicated by studies of hypersensitivity and passive cutaneous anaphylaxis. The fraction exhibiting specificity contained only one antigen, which was protein in nature, whereas the other two fractions contained more than one antigen and possessed both protein and polysaccharide constituents. Because the single-antigen-containing fraction showed both positive skin and PCA reactivity, the suggestion is made that this fraction may contain either an antigen with two determinants or may contain two antigens that are not easily distinguishable by immunodiffusion methods.
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PMID:Immunological studies on leprosy: separation and evaluation of the antigens of Mycobacterium leprae. 109 49

The inhibition of the haematological alterations and prevention of death due to systemic anaphylaxis after antigen challenge were investigated in rats after various drug treatments. The i.v. injection of ovalbumin (250 micrograms/kg) into actively sensitized rats induced marked thrombocytopenia and haemoconcentration within 5 min and significant leukocytosis within 30 min, lasting for 2 h after the challenge. Pretreatment with meclizine or terfenadine (15-30 mg/kg i.p.) inhibited antigen-induced haemoconcentration, whereas WEB 2086 (2-10 mg/kg i.p.) and PCA 4248 (5-10 mg/kg p.o.), two platelet-activating factor (PAF) antagonists, interfered with thrombocytopenia only. Azelastine (1-20 mg/kg p.o.) dose dependently inhibited antigen-induced haemoconcentration and thrombocytopenia but failed to block leukocytosis. Azelastine also inhibited the thrombocytopenia observed after the i.v. administration of PAF (4 micrograms/kg). Administration of ovalbumin at a dose of 1.5 mg/kg resulted in a lethal anaphylactic reaction in about 85% of the rats. Pretreatment with WEB 2086 (10 mg/kg i.p.), meclizine (30 mg/kg i.p.) or both increased the survival rate from 15 to 57, 68 and 87%, respectively. Azelastine alone (20 mg/kg p.o.) completely blocked the lethal reaction. It was concluded that the ability of azelastine to antagonize histamine and PAF is important for its effectiveness against anaphylactic shock.
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PMID:Interference of azelastine with anaphylaxis induced by ovalbumin challenge in actively sensitized rats. 135 32

Conjunctival tissue of 12 guinea pigs (6 experimental animals, 6 controls) was sensitized with IgG1 (PCA titer 1:2,000) antisera to dinitrophenol carrier and challenged topically with hapten. Periorbital swelling, conjunctival edema and conjunctival redness were evaluated clinically at 0.5 h and hourly for 12 h, and again at 24 and 48 h. Tears were collected at each time point for cytology. Results showed an early-phase reaction (EPR) peaking at 0.5 h and a late-phase reaction (LPR) peaking at 5-7 h. Periorbital swelling was minimal 4 h after appearance of the EPR. Conjunctival edema and redness increased in both the early and late phases, but without two distinct peaks. However, individual animals in both groups did show biphasic reactions. Tear cytology showed an abnormal increase in neutrophils and eosinophils in the later time periods and was a significant way to detect ocular anaphylaxis. In conclusion, if the presence of two significant peaks of clinical inflammation after one antigen challenge is taken as the narrowest definition of a late phase in anaphylaxis, our results show an ocular LPR occurring in our animal model.
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PMID:Clinical and cytologic aspects of ocular late-phase reaction in the guinea pig. 137 86


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