T cell stimulation via glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related protein (GITR) elicits antitumor activity in various tumor models; however, the underlying mechanism of action remains unclear. Here we demonstrate a crucial role for interleukin (IL)-9 in antitumor immunity generated by the GITR agonistic antibody DTA-1. IL-4 receptor knockout (Il4ra(-/-)) mice, which have reduced expression of IL-9, were resistant to tumor growth inhibition by DTA-1. Notably, neutralization of IL-9 considerably impaired tumor rejection induced by DTA-1. In particular, DTA-1-induced IL-9 promoted tumor-specific cytotoxic T lymphocyte (CTL) responses by enhancing the function of dendritic cells in vivo. Furthermore, GITR signaling enhanced the differentiation of IL-9-producing CD4(+) T-helper (TH9) cells in a TNFR-associated factor 6 (TRAF6)- and NF-κB-dependent manner and inhibited the generation of induced regulatory T cells in vitro. Our findings demonstrate that GITR co-stimulation mediates antitumor immunity by promoting TH9 cell differentiation and enhancing CTL responses and thus provide a mechanism of action for GITR agonist-mediated cancer immunotherapies.

Introduction In Korea, although male sexual problems have been relatively well addressed, few surveys have been conducted on female sexual dysfunction (FSD) in the general population. In the present study, we investigated the prevalence and identified the risk factors of sexual dysfunction in young Korean women. Aim To evaluate the prevalence and to identify the risk factors of FSD in young Korean women. Methods A total of 47,000 women were initially approached. All received an e-mail requesting that they participate in a Web-based survey. The participants were asked to complete a questionnaire requesting detailed medical and sexual histories, which included the questions contained in the Korean version of the Female Sexual Function Index questionnaire. Main Outcome Measures The prevalence of FSD in young Korean women in the different age groups and risk factors for developing FSD. Results A total of 504 women of average age 28.5 years (18–52 years) were evaluated during this survey. Setting the cutoff score for FSD using a receiver operating characteristic curve of our data as 25.0 points, 43.1% of women under 40 years old reported FSD. FSD was detected as a desire problem in 44.0% of women, an arousal problem in 49.0%, a lubrication problem in 37.0%, an orgasm problem in 32.0%, a satisfaction problem in 37.0%, and a pain problem in 34.6%. Risk factors for FSD as determined by logistic regression analysis were increasing age, a low frequency of sex, depression, a sexually abused history, and voiding dysfunction. Conclusions The prevalence of FSD in Korean young women was common and comparable to those reported worldwide.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Atenolol is an antihypertensive drug, of which negligible amounts are metabolized. • Fruit juices may decrease the oral absorption of drugs by inhibiting intestinal drug transporters, as demonstrated in vitro and in vivo. WHAT THIS STUDY ADDS • The pharmacokinetic characteristics of atenolol were determined according to the SLCO2B1 genotype after apple juice administration in healthy Korean volunteers. • Apple juice ingestion markedly reduced the systemic exposure to atenolol, but genetic variations in SLCO2B1 were unlikely to contribute substantial variability to the pharmacokinetics of atenolol. AIM Fruit juice reduces the plasma concentrations of several β‐adrenoceptor blockers, likely by inhibiting OATP2B1‐mediated intestinal absorption. The aim of this study was to investigate the effects of apple juice on the pharmacokinetics of atenolol. METHODS Twelve healthy Korean volunteers with genotypes of SLCO2B1 c.1457C> T (*1/*1 (n= 6) and *3/*3 (n= 6)) were enrolled in this study. In a three‐phase, one‐sequence crossover study, the pharmacokinetics (PK) of atenolol was evaluated after administration of 50 mg atenolol. Subjects received atenolol with either 300 ml water, 1200 ml apple juice or 600 ml apple juice. RESULTS Apple juice markedly reduced the systemic exposure to atenolol. The geometric mean ratios (95% confidence intervals) of apple juice : water were 0.18 (0.13, 0.25, 1200 ml) and 0.42 (0.30, 0.59, 600 ml) for the AUC(0,tlast). In this study, the PK parameters of atenolol responded in a dose‐dependent manner to apple juice. CONCLUSIONS Apple juice markedly reduced systemic exposure to atenolol. The genetic variation of SLCO2B1 c.1457C>T had a minimal effect on the pharmacokinetics of atenolol when the drug was administered with water or apple juice.

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Tolvaptan is a selective arginine vasopressin V2-receptor antagonist that is used as an aquaretic agent. This trial investigated the pharmacokinetics and pharmacodynamics of 15- to 60-mg single oral doses of tolvaptan in healthy Korean men. A dose block-randomized, placebo-controlled, double-blind, single ascending dose trial was conducted with 46 subjects receiving tolvaptan (15, 30, or 60 mg) or placebo. To determine pharmacokinetics and pharmacodynamics, blood and urine samples were collected at baseline and up to 48 hours after drug administration. Urine volume and fluid intake were measured for 24 hours starting the day before dosing (day -1) as baseline, and on the day of drug administration (day 1). Tolvaptan showed dose-linear pharmacokinetic characteristics regarding area under the concentration-time curve. Changes from baseline in 24-hour urine volume and 24-hour fluid balance correlated significantly with area under the concentration-time curve from time 0 to the last measurable time. Dose-dependent increases were observed in serum osmolality, serum sodium concentration, and free water clearance in the 4- to 8-hour interval after dosing, and these increases were maintained for at least 24 hours. Single 15- to 60-mg doses of tolvaptan exhibited linear pharmacokinetics and resulted in substantial, dose-dependent aquaresis in healthy Korean men.

DA-3031 showed non-linear pharmacodynamic and pharmacokinetic profiles and an extended duration of action compared with non-modified filgrastim, without unexpected toxicities in healthy subjects.

Fimasartan administered alone or in combination with HCTZ was well tolerated at the described dosages. Coadministration of fimasartan increased the urinary excretion of HCTZ and urine volume, but these observations are unlikely to have any clinical relevance.

[Purpose] We examined the effects of an abdominal drawing-in bridge exercise using a pressure biofeedback unit on different bases on the thickness of trunk and abdominal muscles, and lumbar stability. [Subjects] Thirty healthy young adults (2 males, 28 females) took part in this study. The subjects were randomly and equally assigned to a stable bridge exercise group and an unstable bridge exercise group. [Methods] The subjects performed bridge exercises using an abdominal drawing-in method on a stable base and on an unstable base, and changes in their abdominal muscle thickness and on the stable and on unstable bases lumbar stability were evaluated. [Results] After the intervention, the stable bridge exercise group showed a statistically significantly increased muscle thickness in the transversus abdominis, and the unstable bridge exercise group showed significantly increased muscle thicknesses of the transversus abdominis and internal obliques in static and dynamic lumbar stability. The unstable bridge exercise group showed significant increase after performing the exercise. [Conclusion] Lumbar stability exercise, with the compensation of the lumbar spine minimized, using an abdominal drawing-in method on an unstable support of base is effective and efforts to prevent the compensation may induce a greater exercise effect.