PubMed · 15520153
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James Clark, N Theodorou. 2004. Appendicitis after appendicectomy.. https://doi.org/10.1177/014107680409701111
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Novel transient receptor potential vanilloid 1 (TRPV1) receptor antagonists with various bicyclic heteroaromatic pharmacophores were synthesized, and their in vitro activity in blocking capsaicin activation of TRPV1 was assessed. On the basis of the contribution of these pharmacophores to the in vitro potency, they were ranked in the order of 5-isoquinoline > 8-quinoline = 8-quinazoline > 8-isoquinoline > or = cinnoline approximately phthalazine approximately quinoxaline approximately 5-quinoline. The 5-isoquinoline-containing compound 14a (hTRPV1 IC50 = 4 nM) exhibited 46% oral bioavailability and in vivo activity in animal models of visceral and inflammatory pain. Pharmacokinetic and pharmacological properties of 14a are substantial improvements over the profile of the high-throughput screening hit 1 (hTRPV1 IC50 = 22 nM), which was not efficacious in animal pain models and was not orally bioavailable.
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INTRODUCTION: Strongyloidiasis can result in severe forms in immunodepressed patients or those treated with prolonged corticosteroids. OBSERVATION: A 59 year-old woman suffering from chronic kidney failure, treated for the past year by haemodialysis, was hospitalized for alteration in her general status of health and severe digestive problems. Three parasitological examinations of the faeces revealed the presence of Strongyloides stercoralis larvae, although she had never spent time in the Tropics. The outcome was rapidly good following treatment with thiabendazole. DISCUSSION: Some severe forms of strongyloidiasis occurring in immunodepressed or chronic dialysed patients can be fatal in the absence of early management.