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ABSTRACT-The ability of IPD-1151T to suppress the induction of human IgE synthesis was investigated with an in vitro model of IgE production mediated by an allergen-specific helper T cell line (SN-4) from a patient allergic to Japanese cedar pollen. IPD-1151T induced a concentration-dependent suppression of purified allergen (Cry j 1)-dependent IgE synthesis in autologous B cell cultures mediated by SN-4, without significantly affecting the IgG synthesis. In addition, the production of interleukin 4 (IL-4) by Cry j 1-ac tivated SN-4 as well as that by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) of normal donors was inhibited in a concentration-dependent manner by the agent. Interestingly, IPD-1151T clearly depressed PHA-induced expression of IL-4 mRNA in normal PBMC, indicating that this agent inhibits IL-4 gene transcription. However, IPD-1151T had no antagonistic action on IL-4, since neither IL-4-induced expression of low-affinity IgE receptor (Fc e RII/CD23) on normal B cells nor soluble Fc e RII release from IL-4-stimulated B cells was affected by the agent. On the other hand, IPD-1151T had no effect on the production of interferon-y by both Cry j 1-stimulated SN-4 and anti-CD3 monoclonal anti body-activated T cells of normal donors. These results suggest that the selective suppression of IgE syn thesis by IPD-1151T results from the inhibition of IL-4 production by T cells at the gene level.

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These results suggest that excessive portal flow is attributed to post transplant liver dysfunction after extreme small-for-size liver transplantation caused by sinusoidal microcirculatory injury.

Background and objectivesBilastine is a novel second-generation antihistamine for the symptomatic treatment of allergic rhinitis and urticaria. The objective of this study was to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of bilastine following single and multiple oral doses in healthy Japanese subjects. The pharmacokinetic and pharmacodynamic profiles were compared with those reported in Caucasian subjects.MethodsIn a single-blind, randomized, placebo-controlled, parallel-group, single- and multiple-ascending dose study, bilastine tablets were administered at single doses of 10, 20, and 50 mg (Part I), and once daily for 14 days at 20 and 50 mg (Part II).ResultsAfter single oral doses, maximum plasma concentrations (C max) were reached at 1.0–1.5 h postdose. Plasma exposure [C max and area under the plasma concentration-time curve (AUC)] increased dose-proportionally at single doses of 10–50 mg. In repeated-dose administration, no remarkable differences were observed between Day 1 and Day 14 for C max or AUC. For inhibitory effects on wheal and flare response, bilastine 20 and 50 mg showed significant inhibition from 1.5 h after administration as compared with placebo, and the significant effect persisted for 24 h after administration. The rates of adverse events (AEs) were comparable between bilastine and placebo in both Part I and Part II. In addition, no dose- or administration period-dependent tendency of increase in rate of AEs or worsening of severity was observed.ConclusionBilastine exhibits similar single- and multiple-dose pharmacokinetic and pharmacodynamic characteristics in healthy Japanese subjects compared with those observed in Caucasian subjects in previous studies.Electronic supplementary materialThe online version of this article (doi:10.1007/s40261-016-0447-2) contains supplementary material, which is available to authorized users.

It is suggested that murine cutaneous LPR against OVA is a type 2 inflammatory response in which both IgE antibodies and CD4 T cells play an obligatory role.

The combination of nab-paclitaxel (100 mg/m(2)) administered weekly and carboplatin at an AUC of 6 every 3 weeks was well tolerated in Japanese patients with advanced NSCLC. This combination therapy also showed promising antitumor activity and was not associated with relevant pharmacokinetic interactions.

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