As a part of our studies of selectin blockers, we prepared 1-(2-tetradecylhexadecyl)-3'-O-sulfo Le(X) 1 and 1-(2-tetradecylhexadecyl) sLe(X) 2 and examined their inhibitory activities against natural ligand (sLe(X)) binding to E-, P-, and L-selectins. Compounds 1 and 2 were 2 times more potent than the sLe(X) tetrasaccharide toward E-selectin binding and up to 4 times more potent than sLe(X) toward P- and L-selectin binding. Interestingly, compound 1 provided dose-dependent protective effects against an immunoglobulin E-mediated skin reaction in mouse ears. This protective effect was associated with diminished tissue accumulation of neutrophils in the ear (as assessed by myeloperoxidase). These findings indicate that the modification of sLe(X) or 3'-O-sulfo Le(X) with a "branched anchor", a 2-tetradecylhexadecyl group, is useful in the design of a more potent selectin blocker, which has broad inhibitory activities toward all selectins.
ABSTRACT-The inhibitory effects of emedastine difumarate on histamine release were studied in rat peritoneal mast cells. Emedastine significantly inhibited substance P (SP)-induced histamine release at con centrations above 10-9 M in the presence of extracellular Ca2+ and at concentrations above 10-" M in its absence. At concentrations of 10-8 M or higher, emedastine significantly inhibited SP-induced Ca" release from intracellular Ca stores and SP-induced 45Ca uptake into mast cells. Emedastine also inhibited passive peritoneal anaphylaxis in rats and guinea pigs. We conclude that the clinical antiallergic effects of emedastine involve the inhibition of histamine release and that this inhibition is mediated by the inhibition of Ca" release from intracellular Ca stores and the inhibition of Ca" influx into mast cells.
Abstract. Severe stomatitis may lead to the need to interrupt or discontinue cancer therapy and, thus, may affect control of the primary disease. Stomatitis may also increase the risk of local and systemic infection and significantly affects the quality of life and the cost of care. The present study was conducted to evaluate the efficacy of two traditional herbal medicines in controlling treatment-induced stomatitis in a small cohort of lung cancer patients treated with afatinib. All patients who were treated with afatinib for epidermal growth factor receptor (EGFR) mutated nonsmallcell lung cancer (NSCLC) between January, 2015 and March, 2016, were included in this study. During the study period, a total of 14 NSCLC patients were treated with afatinib, an EGFR-tyrosine kinase inhibitor (TKI). Two patients already had stomatitis at the time of initiation of afatinib therapy; among the remaining 12 NSCLC patients, 2 (16.7%) developed stomatitis. All the lesions in the 4 patients who developed stomatitis were completely alleviated after 2 weeks of therapy with Aznol mouthwash, a chamomile extract with anti-inflammatory effects, and Hangeshashinto, a traditional herbal (Kampo) medicine. Afatinib therapy was re-initiated, but none of the patients developed stomatitis thereafter. To the best of our knowledge, this is the first report evaluating oral care and management of stomatitis. This type of care and treatment may reduce the incidence of complications associated with EGFR-TKI therapy.
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