BackgroundClinically used antidepressants suffer from various side effects. Therefore, we searched for a safe antidepressant with minimal side effects among food ingredients that are distributed to the brain. Here, we focused on ERGO (ergothioneine), which is a hydrophilic antioxidant and contained at high levels in edible golden oyster mushrooms. ERGO is a typical substrate of carnitine/organic cation transporter OCTN1/SLC22A4, which is expressed in the brain and neuronal stem cells, although little is known about its permeation through the BBB (blood–brain barrier) or its neurological activity.MethodsTo clarify the exposure of ERGO to brain and the possible antidepressant‐like effect after oral ingestion, ERGO or GOME (golden oyster mushroom extract) which contains 1.2% (w/w) ERGO was mixed with feed and provided to mice for 2 weeks, and then ERGO concentration and antidepressant‐like effect were evaluated by LC‐MS/MS and FST (forced swimming test) or TST (tail suspension test), respectively.ResultsDiet containing ERGO or GOME greatly increased the ERGO concentrations in plasma and brain, and significantly decreased the immobility time in both FST and TST. The required amount of GOME (~37 mg/day) to show the antidepressant‐like effect corresponds to at most 8 g/day in humans. In mice receiving GOME‐containing diet, doublecortin‐positive cells showed a significant increase from the basal level, suggesting promotion of neuronal differentiation.ConclusionThus, orally ingested ERGO is transported across the BBB into the brain, where it may promote neuronal differentiation and alleviate symptoms of depression at plausibly achieved level of daily ingestion.

BackgroundWe developed, and examined the reliability and validity of, a Japanese version of the Dysphagia Handicap Index (DHI; DHI-J), which is a self-reported measure to assess the quality of life (QOL) of individuals with dysphagia.Participants and methodsThe DHI-J was developed via the back-translation method: the DHI was translated into Japanese and then translated back into English by a native English speaker. The back translation was discussed with and approved by the DHI’s lead author. A total of 229 patients (119 males, 110 females; median age: 66 years) who underwent videofluorography at our hospital between January and December 2013 and 65 controls (23 males, 42 females; median age: 44 years) were included in the study. All the subjects completed the DHI-J and self-reported their dysphagia severity. Twenty-three patients repeated the procedure 1 week later. Patients’ swallowing function was classified as “normal”, “moderately impaired”, or “severely impaired”, and the DHI-J total scores were compared between the severity groups.ResultsThe internal consistency of the DHI-J was high (Cronbach’s α=0.95), as was the test–retest reliability of the 23 patients who answered the questionnaire twice (intraclass correlation coefficient =0.98, P<0.01). The DHI-J total score and its three subscale scores were significantly higher among the patients than among controls. A significant correlation (ρ=0.85) was observed between the DHI-J total score and self-reported dysphagia severity score. Regarding the comparison of DHI-J scores by severity groups, the DHI-J total scores significantly differed between the normal and moderately impaired groups, and the normal and severely impaired groups. However, the moderately and severely impaired groups showed no significant difference in scores.ConclusionThe DHI-J is a reliable and valid questionnaire for assessing the QOL of patients with dysphagia. However, we did not survey patients with cerebrovascular diseases; thus, the questionnaire must be validated for that patient group.

Background. Lee Silverman Voice Treatment® LOUD (LSVT®) is an intensive program devised in the United States to train patients with Parkinson’s disease (PD) to speak louder, at normal intensity, while keeping a good voice quality. Four weeks of LSVT® has been shown to increase vocal loudness and improve intelligibility among Japanese-speaking PD patients. However, the long-term effects of LSVT® have not been examined in these patients. Objective. This study aimed to investigate the long-term effects of LSVT® on Japanese-speaking PD patients. Methods. Twenty-one Japanese PD patients underwent a standardized course (four sessions over four consecutive days, for four weeks) of LSVT® at our hospital. Vocal loudness and intelligibility were assessed at the following three time-points: pretreatment (baseline), immediately after treatment, and at the end of the 12 month follow-up (12FU). Sound pressure levels (dB SPL) were measured during the following tasks: sustained phonation of /a/, reading a standardized text, and delivery of a monologue. Three experienced speech-language pathologists, who were blinded to patients’ identities and assessment points, assessed speech intelligibility based on recorded audio samples of each participant during the reading and monologue tasks. Results. Fourteen patients were evaluated at 12FU. Changes in dB SPL from baseline to immediately after treatment were +6.5 dB, +4.2 dB, and +2.8 dB, and those from baseline until 12FU were +4.7 dB, +3.5 dB, and +2.5 dB in sustained phonation of /a/, reading a passage, and delivery of a monologue, respectively. These changes were significant (p < 0.025) in both the baseline-to-immediately-after-treatment and baseline-to-12FU intervals. Intelligibility relative to baseline was significantly improved immediately after treatment, but not at 12FU. Conclusions. LSVT® had a long-term effect on the vocal loudness of Japanese-speaking PD patients. A short-term effect was seen in intelligibility, however, there was no significant long-term effect.

In this study, total body clearance (CL), volume of distribution at steady state (V) and plasma concentration-time profiles in humans of model compounds were predicted using chimeric mice with humanized livers. On the basis of assumption that unbound intrinsic clearance (CL) per liver weight in chimeric mice was equal to those in humans, CL were predicted by substituting human liver blood flow and liver weights in well-stirred model. V were predicted by Rodgers equation using scaling factors of tissue-plasma concentration ratios (SF) in chimeric mice estimated from a difference between the observed and predicted V. These physiological approaches showed high prediction accuracy for CL and V values in humans. We compared the predictability of CL and V determined by the physiologically based predictive approach using chimeric mice with those from predictive methods reported by Pharmaceutical Research Manufacturers of America. The physiological approach using chimeric mice indicated the best prediction accuracy in each predictive method. Simulation of human plasma concentration-time profiles were generally successful with physiologically based pharmacokinetic (PBPK) model incorporating CL and SF obtained from chimeric mice. Combined application of chimeric mice and PBPK modeling is effective for prediction of human PK in various compounds.