Localization of Xenobiotic Transporter OCTN1/SLC22A4 in Hepatic Stellate Cells and Its Protective Role in Liver Fibrosis

Xenobiotic transporters play key roles in disposition of certain therapeutic agents, although limited information is available on their roles other than pharmacokinetic issues. Here, suppressive effect of multispecific organic cation transporter OCTN1/SLC22A4 on liver fibrosis was proposed in liver injury models. After injection of hepatotoxins such as dimethylnitrosamine (DMN) or concanavalin A, hepatic fibrosis, and oxidative stress, evaluated in terms of Sirius red and 4-hydroxy-2-nonenal staining, respectively, were more severe in liver of octn1/slc22a4 gene knockout (octn1-/-) mice than that in wild-type mice. DMN treatment markedly increased α-smooth muscle actin and F4/80, markers of activated stellate and Kupffer cells, respectively, in liver of octn1-/-, but had less effect in wild-type mice. Thus, octn1/slc22a4 gene deletion results in more severe hepatic fibrosis, oxidative stress, and inflammation. DMN-treated wild-type mice showed increased Octn1 staining and hepatic concentration of its food-derived antioxidant ergothioneine (ERGO). The upregulated Octn1 was co-localized with α-smooth muscle actin. Functional expression of Octn1 was demonstrated in activated human hepatic stellate cell lines, LI90 and LX-2. Provision of ERGO-rich feed ameliorated DMN-induced liver fibrosis and oxidative stress. Overall, Octn1 is upregulated in activated stellate cells, resulting in increased delivery of its substrate antioxidant ERGO and a protective effect against liver fibrosis. © 2016 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.Embargo Period 12 month

The Device of Ethylene Vinyl Acetate Sheet for Trismus Caused by Bilateral Mandible Fractures

Trismus is commonly caused by temporomandibular joint disorders and maxillofacial fractures. We report the case of a 62-year-old woman with trismus and difficulty in mastication caused by bilateral mandibular fractures. She had a maximal interincisal opening distance (MID) of 22 mm. Mouth-opening training was administered using a novel dental mouth-training device custom-made using ethylene vinyl acetate sheets and according to the dentition and extent of mouth-opening of the patient. After 2 months of training, the MID increased to 42 mm. With adequate training, this device is effective in treating trismus due to scarring

Identifying the Timing of Swallowing Sounds Using Videoendoscopy Findings in Healthy Adults

Cervical auscultation is a useful tool for detecting dysphagia; however, the sites where swallowing sounds are produced are unknown. In this study, we investigated the relationship between swallowing sounds and videoendoscopy (VE) images in healthy adults to identify the timing of swallowing sounds. Fifteen healthy young adults participated in the study. Each participant was seated in an upright position while a stethoscope probe with an inserted microphone was placed at the center of his or her lower neck to detect swallowing sounds during the VE. The detected sounds were recorded simultaneously with the VE images while the subjects swallowed 4g of liquid or jelly. Swallowing duration, swallowing sound duration, and VE findings at the beginning and end of swallowing sounds were analyzed. One hundred and thirty-four sound samples produced by a single swallowed bolus were obtained and analyzed. The mean swallowing duration for each material ranged from 1.25 to 2.39s. Swallowing duration was significantly longer for jelly compared with liquids (p<0.01). Swallowing sound duration was approximately 0.5s in all samples, and there were no significant differences between materials. Most swallowing sounds started during velopharyngeal closure (109/134, 81.3%), and most swallowing sounds ended during velopharyngeal closure (98/134, 73.1%). For all materials, swallowing sounds did not start when the materials flowed into the pyriform sinuses, and very few sounds corresponded with epiglottic movements. These results show that many movements associated with physiologic events―including hyoid bone and laryngeal excursion, and opening of the upper esophageal sphincter―may be involved in the production of swallowing sounds