Evaluation of treatment pattern and symptom control in patients with gastroesophageal reflux disease: multihospital questionnaire survey on the current situation in Korea.

Proton pump inhibitors (PPIs) are the most effective treatment for gastroesophageal reflux disease (GERD); however, a considerable number of patients fail to respond to PPI therapy and complain of nocturnal heartburn and sleep disturbance. The aims of this study are to evaluate the treatment pattern of GERD-related medications and their efficacy in relieving nocturnal heartburn. A total of 334 patients with GERD receiving PPI therapy within 6 months were enrolled in a multihospital questionnaire survey from January, 2014 to March, 2015. GERD symptoms and patients' satisfaction were assessed by patient questionnaires, and treatment patterns of GERD-related medications were assessed by investigators. Among the 334 patients, 95.8% used PPI once daily and 58.6% used a half-dose of PPI. The PPI treatment pattern was changed in 26.6% of all patients, of those, 54% of the patients doubled the PPI dose, and 29.2% of the patients switched to another PPI. Approximately 60.3% of all patients were prescribed more than three GERD-related medications. The overall satisfaction rate was 61.8%, and 32.2% of patients experienced nocturnal heartburn and sleep disturbance. In the extended-release PPI group, there were fewer nocturnal symptoms compared with the conventional PPI group (10% vs. 33.7%, respectively, P = 0.027). The use of more than three medications was inversely associated with patients' satisfaction (OR = 0.355, 95% CI; 0.197-0.642, P = 0.001). Most patients were prescribed adjunctive medications other than PPIs; however, patients' satisfaction was inversely associated with multiple drugs. Patients' satisfaction was superior in extended-release PPIs than conventional PPIs for the relief of nocturnal heartburn in Korean patients.

AMP-activated protein kinase-α1 as an activating kinase of TGF-ß-activated kinase 1 has a key role in inflammatory signals.

Although previous studies have proposed plausible mechanisms of the activation of transforming growth factor-ß-activated kinase 1 (TAK1) in inflammatory signals, including Toll-like receptors (TLRs), its activating kinase still remains to be unclear. In the present study, we have provided evidences that AMP-activated protein kinase (AMPK)-α1 has a pivotal role for activating TAK1, and thereby regulate NF-κB-dependent gene expressions in inflammatory signaling mediated by TLR4 and TNF-α stimulation. AMPK-α1 specifically interacts with TAK1 and reciprocally regulates their kinase activities. Upon the stimulation of lipopolysaccharide, AMPK-α1-knockdown (AMPK-α1(KD)) or TAK1-knockdown human monocytic THP-1 cells exhibit a dramatic reduction in the TAK1 or AMPK-α1 kinase activity, respectively, and subsequent suppressions of its downstream signaling cascades, which further leads to inhibitions of NF-κB and thereby productions of proinflammatory cytokines, such as TNF-α, IL-1ß, and IL-6. Importantly, the microarray analysis of AMPK-α1(KD) cells revealed a dramatic reduction in the NF-κB-dependent genes induced by TLR4 and TNF-α stimulation, and the observation was in significant correlation with the results of quantitative real-time PCR. Moreover, AMPK-α1(KD) cells are highly sensitive to the TNF-α-induced apoptosis, which is accompanied with dramatic reductions in the NF-κB-dependent and anti-apoptotic genes. As a result, our data demonstrate that AMPK-α1 as an activating kinase of TAK1 has a key role in mediating inflammatory signals triggered by TLR4 and TNF-α.

Effects of restricted feeding, low-energy diet, and implantation of trenbolone acetate plus estradiol on growth, carcass traits, and circulating concentrations of insulin-like growth factor (IGF)-I and IGF-binding protein-3 in finishing barrows.

Effects of restricted feeding (80% ad libitum), feeding a low-energy diet containing 84% DE (2.95 Mcal/kg) of the control diet, and implantation of Revalor H (140 mg trenbolone acetate plus 14 mg estradiol-17beta) on growth, carcass traits, and serum concentrations of insulin-like growth factor (IGF)-I and IGFbinding protein-3 (IGFBP-3) were studied in crossbred finishing barrows beginning from 59 +/- 0.9 kg of body weight. Blood samples were taken every 3 wk and the animals were slaughtered at approximately 105 kg body weight. Restricted feeding caused a decrease (P < 0.01) in ADG; feeding the low-energy diet was effective in reducing backfat thickness but decreased gain:feed; the implantation caused a decrease in ADG, feed intake, and backfat thickness and increased gain:feed. Overall pork quality based on pH, drip loss, and the lightness in color of longissimus muscle was not affected by any of the treatments. Serum IGF-I concentration increased following the implantation but did not change (P > 0.05) due to other treatments. Immunoreactive IGFBP-3 concentration was not changed by any of the treatments. Overall ADG was positively correlated with early-stage (d 21) IGF-I and IGFBP-3 concentrations only in unimplanted barrows, whereas backfat thickness was negatively correlated with d-42 IGF-I concentration in all but unimplanted barrows with ad libitum intake. A strong positive correlation (P < 0.01) between IGF-I and IGFBP-3 concentrations was apparent with increasing age of the animals. Results suggest that growth rate and backfat thickness are decreased by a moderate restriction of feed or energy intake with no accompanying changes in circulating IGF-I and IGFBP-3 concentrations and that the beneficial effect of Revalor H implantation on feed efficiency may be mediated, in part, by IGF-I. Moreover, both IGF-I and IGFBP-3 concentrations may be useful as growth indices in pigs.