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• W1978496711 endingPage "1786" @default.
• W1978496711 startingPage "1778" @default.
• W1978496711 abstract "1. Initiation of a peritoneal Arthus reaction by deposition of immune-complexes results in vascular leakage, polymorphonuclear leukocyte (PMN) infiltration, and tumour necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) production. We now demonstrate in rats that oral administration of the C5a receptor antagonist AcPhe[Orn-Pro-D-Cyclohexylalanine-Trp-Arg] (AcF-[OPdChaWR]; 1 - 10 mg kg(-1) 30 min prior to immune-complex deposition) inhibits these inflammatory markers in the peritoneal Arthus reaction. 2. Initiation of a dermal Arthus reaction resulted in a significant increase in vascular leakage, PMN infiltration, systemic production of TNFalpha and pathological changes in the dermis. 3. Pretreatment of rats with AcF-[OPdChaWR] either intravenously (1 mg kg(-1) 10 min prior to immune-complex deposition) or orally (1 - 10 mg kg(-1) 30 min prior to immune-complex deposition) significantly inhibited immune-complex mediated dermal vascular leakage and systemic cytokine production. Topical pretreatment with AcF-[OPdChaWR] (400 microg site(-1) in 10% dimethyl sulphoxide 10 min prior to immune-complex deposition) also inhibited vascular leakage, as well as histopathological changes associated with a dermal Arthus reaction. 4. Oral administration of 3 mg kg(-1) AcF-[OPdChaWR] resulted in the appearance of the drug in plasma within 5 min, with peak blood levels approximately 0.3 microM reached within 20 min. The plasma elimination half-life was approximately 70 min. The oral activity and bioavailability of AcF-[OPdChaWR], its activity when applied topically to the skin, suggest that small molecule C5a receptor antagonists may have therapeutic utility in dermal inflammatory disorders involving complement activation. 5. This is the first demonstration for either an orally or topically active C5a receptor antagonist, and suggests that small molecule C5a antagonists may have therapeutic utility when given by multiple routes of application." @default.
• W1978496711 created "2016-06-24" @default.
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• W1978496711 date "2001-12-01" @default.
• W1978496711 modified "2023-10-18" @default.
• W1978496711 title "Inhibition of immune-complex mediated dermal inflammation in rats following either oral or topical administration of a small molecule C5a receptor antagonist" @default.
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• W1978496711 doi "https://doi.org/10.1038/sj.bjp.0704417" @default.
• W1978496711 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1573161" @default.
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