Anaphylaxis cutaneous

Chloro-oxazolo[4,5-/i]quinoline-2-carboxylic acid methyl ester was the most active compound in tests for inhibitors of antigen-induced release of histamine in vitro from rat peritoneal mast cells (IC50 of 0.3 p,M) and as inhibitors of IgE-mediated passive cutaneous anaphylaxis in the rat (ED50 (intraperitoneal) of 0.1 mg/kg in dose 0.5 mg/kg as an inhibitor of the test)—10 times and 60 times more potent, respectively, than the disodium salt of cromoglycic acid (85JMC1255). 

Reaction of 2-aminoquinoline derivatives with BrCH2C0C02Et gave imidazoquinoline-2-carboxylate 473 which upon hydrolysis with sodium hydroxide gave the corresponding acid which had been tested against the passive cutaneous anaphylaxis (78GEP2802493, 78BEP858605) (Scheme 79). 

Although human anaphylaxis is a systemic reaction, the mouse model of passive cutaneous anaphylaxis (PGA) has been used extensively to enhance our understanding of mechanisms which also may contribute to systemic anaphylaxis. Unlike systemic anaphylaxis in the mouse, PGA appears to be entirely dependent on mast cells [4,6]. While IgE appears to be the primary antibody isotype that mediates PCA reactions in actively immunized mice, activation of FcyRIII by a fraction of IgGl antibodies (called anaphylactic IgGl) can also mediate PCA reactions in mice [4]. 

Fig. 2. IgG-mediated systemic versus local anaphylaxis, a IgG-mediated systemic anaphylaxis. When allergen-IgG immune complexes are formed in the circulation, basophils immediately capture them through IgG receptors on their surface and are activated to release PAF, that in turn act on vascular endothelial cells, leading to increased vascular permeability, b Passive cutaneous anaphylaxis. When allergen-IgG immune complexes are formed in the skin, they stimulate tissue-resident mast cells to release chemical mediators such as histamine, leading to local inflammation. 

Arimura A, Nagata M, Takeuchi M, Watanabe A, Nakamura K, Harada M Active and passive cutaneous anaphylaxis in WBB6F1 mouse, a mast cell-deficient strain. Immunol Invest 1990 19 227-233. 

They differ to some extent from signs and symptoms that occur during anaphylaxis not associated with anesthesia. Early subjective symptoms such as malaise, pruritus, sensation of heat, and dizziness are absent in the anesthetized patient. Cutaneous signs in a completely wrapped patient may escape the attention of the anesthetist. The increase in heart rate, a decrease in blood pressure and an increase in airway resistance may be initially misinterpreted as a result of a pharmacological dose-related effect of the drugs, or of excessively light anesthesia. Many differential diagnoses have to be considered (table 1). 

Initial features are mostly pulselessness, difficulty in ventilation, desaturation, and a decreased end-tidal CO2. Cutaneous symptoms are observed in 66-70% of patients in case of IgE-mediated reactions but in more than 90% in non-IgE-mediated reactions. On the contrary, cardiovascular collapse and bronchospasm are more frequent in IgE-dependent reactions (table 2). Severe anaphylaxis may be a primary cardiac arrest [9]. 

Hj-antagonists alone, such as cimetidine or ranitidine, have a modest effect on cutaneous flush reaction and maybe also on the heart [14, 52]. However, when applied they should be given together with Hj-antagonists. There are some studies showing a beneficial effect of combined H - and Hj-antagonist treatment or pretreatment in anaphylaxis [46, 53]. 

The synthetic P-o-glucopyranoside 30 was converted to the cyanoglucoside rho-diocyanoside A (38a), which was isolated from the underground part of Rhodiola quadrifida (Pall.) Fisch. et Mey. (Crassulaceae) and found to show antiallergic activity in a passive cutaneous anaphylaxis test in rat. Acetylation of 30 gave an acetate (98% yield) which was subjected to ozonolysis to afford the aldehyde 39. The Horner-Emmons reaction of 39 using diethyl (l-cyanoethyl)phosphonate furnished (Z)-40a (32% yield from 30) and ( )-40b (10% yield from 30). The physical... 

PCA Passive cutaneous anaphylaxis pCDM8 Eukaryotic expression vector PCNA Proliferating cell nuclear antigen... 

Ovary, Z., Passive cutaneous anaphylaxis in immunological methods, in Council for International Organizations of Medical Sciences Symposium, Ackroid, J.F., ed., Blackwell Scientific Publications, Oxford, 1964, 259. 

Passive cutaneous anaphylaxis (PCA)-Test for potential antigenicity of compounds Other... 

Amino-substituted naphthoquinones and heterocyclic variants have been disclosed in the patent literature as 5-LO inhibitors. Compounds represented by (80) (X = C, N) from Lilly inhibited SRS-A release from sensitized guinea-pig lung tissue [218]. Similar compounds such as (81) (R = carboxylic ester, acyl, or aryl) and related naphthalene derivatives, from American Cyanamid, gave good inhibition in guinea-pig ISN (at 10 //g/ml) and in passive cutaneous anaphylaxis in mice (25-60 /zM i.p.) [219,220]. 

Li et al. (1994) examined the effects of chloroform administered in drinking water to guinea pigs with cedar pollen-induced allergic conjunctivitis, prepared by passive cutaneous anaphylaxis. Groups of 5 male... 

Passive cutaneous anaphylaxis studies of byssinotic and nonbyssinotic sera in our laboratory and similar studies in rabbits... 

There are four subclasses of IgG IgGi, 70% IgGj, 16% IgG., 10%, and IgG, 4%. IgGi is capable of inhibiting IgE-mediated passive cutaneous anaphylaxis (PGA) reaction in baboons when injected in relatively high concentrations. 

Hypersensitivity Anaphylactoid purpura, anaphylaxis, angioneurotic edema, myocarditis, pericarditis, polyarthralgia, pulmonary infiltrates with eosinophilia, systemic lupus erythematous exacerbation, urticaria hypersensitivity syndrome (cutaneous reaction, eosinophilia, and one or more of the following Hepatitis, pneumonitis, nephritis, myocarditis, pericarditis, fever, lymphadenopathy). Muscuioskeietai - ArVr ra g a, arthritis, bone discoloration, joint stiffness and swelling, myalgia, polyarthralgia. 

Uses Severe, systemic fungal Infxns oral cutaneous candidiasis Action Binds ergosterol in the fungal membrane to alter permeability Dose Adults Peds. Test dose 1 mg IV adults or 0.1 mg/kg to 1 mg IV in children then 0.25-1.5 mg/kg/24 h IV over 2-6 h (range 25-50 mg/d or qod). Total dose varies w/ indication PO 1 mL qid Caution [B, ] Disp Inj SE -1- K /Mg from renal wasting anaphylaxis reported, HA, fever, chills, n hrotox, -1- BP, anemia, rigors Notes -1- In renal impair pre-Tx w/ APAP antihistamines (Benadryl) X SE Interactions T Nephrotoxic effects W/ antineoplastics, cyclosporine, furosemide, vancomycin, aminoglycosides, T hypokalemia W/ corticost oids, skeletal muscle relaxants EMS May cause electrolyte imbalances, monitor ECG OD May effect CV and resp Fxn symptomatic and supportive... 

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