Vitamin C is a natural nutrient with antioxidant properties and is used as a health supplement. In this study, we examined the effects of intraperitoneal administration of high-dose vitamin C (4 ...g/kg) on dextran sodium sulfate (DSS)-induced ulcerative colitis. We prepared a mouse ulcerative colitis model by administering DSS for 7 d along with high-dose vitamin C each day during DSS treatment. Ulcerative colitis induced by DSS was ameliorated by high-dose vitamin C administration. Blood levels of interleukin-6, tumor necrosis factor-α, hydrogen peroxide (H2O2), and iron were elevated in DSS-treated mice but lowered by high-dose vitamin C administration. Contrarily, the levels of H2O2 and iron and the numbers of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells in the colon were further increased by high-dose vitamin C administration. The expression levels of fibroblasts, collagen type I, and collagen type III decreased in the DSS-treated mice but increased in mice administered high-dose vitamin C. These results suggest that high-dose vitamin C administration can improve ulcerative colitis.
High-dose vitamin C administration has been reported to exhibit antitumor effect in various mouse models of cancer. However, the underlying mechanism of antitumor effect against colorectal cancer ...remains to be elucidated. In this study, we investigated the antitumor effect of high-dose vitamin C in a mouse model of chronic inflammation-associated colorectal cancer induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). After cancer induction, the mice were administered vitamin C and/or irinotecan. Because irinotecan is a key drug in colorectal cancer treatment, it was used for comparison in this study. We examined reactive oxygen species (ROS) and interleukin-6 (IL-6) levels in the plasma of mice, as well as collagen type I and caspase-1 expression and neutrophil and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cell counts in the colon tissue. Vitamin C and/or irinotecan administration decreased the plasma level of ROS and IL-6 and increased the expression of collagen type I and caspase-1. Furthermore, it increased neutrophil and TUNEL-positive cell counts. The most significant changes in the parameters analyzed were observed when both vitamin C and irinotecan were administered.
Forkhead box protein O1 (FoxO1) is a transcription factor and a critical regulator of angiogenesis. Various environmental stimuli, including growth factors, nutrients, shear stress, oxidative stress ...and hypoxia, affect FoxO1 subcellular localization and strongly influence its transcriptional activity; however, FoxO1-localization patterns in endothelial cells (ECs) during development have not been clarified in vivo. Here, we reported that FoxO1 expression was observed in three layers of angiogenic vessels in developing mouse retinas and that among these layers, the front layer showed high levels of FoxO1 expression in the nuclei of most tip ECs. Because tip ECs migrate toward the avascular hypoxic area, we focused on hypoxia as a major stimulus regulating FoxO1 subcellular localization in tip cells. In cultured ECs, FoxO1 accumulated into the nucleus under hypoxic conditions, with hypoxia also inducing expression of tip-cell-specific genes, including endothelial-specific molecule 1 (ESM1), which was suppressed by FoxO1 knockdown. Additionally, in murine models, EC-specific FoxO1 deletion resulted in reduced ESM1 expression and suppressed tip-cell migration during angiogenesis. These findings indicated roles for FoxO1 in tip-cell migration and that its transcriptional activity is regulated by hypoxia.
Congenitally deaf children with a cochlear implant (CI) improve their speech production intelligibility, but their prosody, including stress and intonation produced by voice pitch and loudness ...changes, often differs from normal hearing people, which affects their fluent oral communication. This study is aimed to clarify abnormal characteristics of voice pitch and loudness control in CI recipients using a newly developed visually guided pitch change task.
We included 13 normal hearing volunteers (NH group) and 17 congenitally deaf CI users who showed good speech intelligibility. The 17 CI users were divided into Early-CI and Late-CI groups, based on their age at implantation of 2.5 years. Using the visually guided pitch change task and acoustic voice analysis of sustained vowels, we assessed their vocal skills to maintain constant pitch and loudness and intentionally change the voice pitch independent from loudness. At the time of examination, the mean age was 24.1, 12.7, and 18.9 years in the NH, Early-CI, and Late-CI groups.
During constant vowel production, Early-CI and Late-CI groups showed more significant fluctuations in pitch and loudness than the NH group. However, when focusing on intentionally changing only the pitch of the voice, the Early-CI group was significantly better than the Late-CI group and comparable to the NH group in terms of their ability to change vocal pitch independently from loudness.
Among congenitally deaf patients, age at implantation was associated with the development of voice skills to control voice pitch and loudness separately, which may influence their fluent prosody production.
Fructose may play a crucial role in the pathogenesis of metabolic syndrome (MetS). However, the pathogenic mechanism of the fructose-induced MetS has not yet been investigated fully. Recently, ...several reports have investigated the association between mitochondrial DNA (mtDNA) and MetS. We examined the effect of fructose-rich diets on mtDNA content, transcription, and epigenetic changes.
Four-week-old male Sprague-Dawley rats were offered a 20% fructose solution for 14weeks. We quantified mRNAs for hepatic mitochondrial genes and analyzed the mtDNA methylation (5-mC and 5-hmC) levels using ELISA kits.
Histological analysis revealed non-alcoholic fatty liver disease (NAFLD) in fructose-fed rats. Hepatic mtDNA content and transcription were higher in fructose-fed rats than in the control group. Global hypomethylation of mtDNA was also observed in fructose-fed rats.
We showed that fructose consumption stimulates hepatic mtDNA-encoded gene expression. This phenomenon might be due to epigenetic changes in mtDNA. Fructose-induced mitochondrial epigenetic changes appear to be a novel mechanism underlying the pathology of MetS and NAFLD.
The high-sensitivity analytical method for the determination of N-nitroso duloxetine (NDXT), which can be carcinogenic and harmful in duloxetine drug products, was successfully developed utilizing ...liquid chromatography-tandem mass spectrometry (LC-MS/MS). Tandem mass spectrometric detection at positive electrospray ionization in multiple reaction monitoring (MRM) mode was then employed for the determination of NDXT. The quantitative range for NDXT was found in 0.075–3.75 ng/mL in terms of concentration in the dilution solvent for duloxetine active pharmaceutical ingredient (API) and capsules and 0.075–1.875 ng/mL for duloxetine tablets, and the recovery rates were in the range of 82.5–91.6% for the API, 91.0–113.4% for capsules, and 70.6–109.1% for tablets, respectively. The repeatability was 6.9% with a %RSD of n = 9 for the API, 10.9% with a %RSD of n = 9 for capsules, and 21.6% with a %RSD of n = 9 for tablets, respectively. For reproducibility, the %RSD of the n = 6 measurements between the two sites was 3.5%. The calibration curve of NDXT in the concentration range of 0.075–3.75 ng/mL was carried out, and the correlation coefficient (R) was found to be 1.000. The sample solution was stable for 7 days. The applicability of the determination of the content of NDXT in a variety of duloxetine drug products was demonstrated. This manuscript seeks to aid the risk assessment process of NDXT in duloxetine drug products through providing a fast and reliable quantitative LC-MS/MS analytical method.
Purpose: Auditory-perceptual evaluation is essential for the assessment of voice quality. The Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) provides a standardized protocol and ...assessment form for clinicians to analyze the voice quality and has been adapted into several different languages. The aims of this study were to develop the Japanese version of the CAPE-V and to investigate its reliability and validity. Method: The Japanese CAPE-V consisted of the same three speech contexts (vowels, sentences, and conversation) as developed in the original English version. The sentences were designed according to the concepts of the original version and reviewed by Japanese phoneticians. To validate the usefulness of the Japanese CAPE-V, voices of 173 Japanese-speaking subjects (76 subjects with dysphonia and 97 without voice complaints) were evaluated by five experienced judges, according to the Japanese CAPE-V as well as the GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) scale. Results: The Japanese CAPE-V provided a high interrater reliability (intraclass correlation coefficients ICCs > 0.85 for all the parameters) as well as a high intrarater reliability (ICCs > 0.85 for all the parameters). In addition, overall severity, roughness, and breathiness in the Japanese CAPE-V were highly correlated with the corresponding dimensions in the GRBAS scale, having Spearman correlation coefficients greater than 0.8. Conclusion: This study demonstrated the reliability and validity of the newly developed Japanese CAPE-V as an auditory-perceptual evaluation instrument.
This study aims to evaluate the speech perception with first, second, or bilateral cochlear implants (CI) and to reveal the effects of wearing bilateral CI in children.
After reviewing the medical ...records, a total of 19 children who underwent bilateral cochlear implantation serially between 2012 and 2015 at Kyoto University Hospital (tertiary referral center) were included in this study. All patients had no delay in language development. The study group comprised nine boys and ten girls, and their age ranged from 3 years 8 months to 12 years 5 months when they underwent the tests in this study. The mean and median ages were 8 years 6 months and 9 years 2 months, respectively.
We measured the appropriate signal/noise ratio (SNR) to test speech perception of Japanese language in noise by testing the hearing ability of unilateral CI patients with or without noise and by surveying the sound environment in a classroom of a mainstream elementary school.
Speech perception in quiet and noise and the left-right localization ability were examined using first, second, or bilateral cochlear implants in all patients.
Considering the results of hearing ability tests with noise and the SNR of the elementary school classrooms, we decided to use SNR of +10 dB to evaluate the speech perception ability in noise. The speech perception ability using the second CI was significantly worse in patients undergoing second cochlear implantation after 7 years old than in those who underwent surgery before 3.5 years old. Moreover, patients undergoing second cochlear implantation before 7 years old showed significantly better left–right localization of high-frequency sound.
Second cochlear implantation before 7 years old is a critical factor in acquiring beneficial speech perception ability with the second CI and sound localization ability with the bilateral CI.
CHARGE syndrome often accompanies sensorineural hearing loss, sometimes necessitating cochlear implantation. However, the effects of cochlear implantation are poor in patients with CHARGE syndrome ...because of inner ear malformation, cochlear nerve deficiency, and/or developmental delay. In this article, we report three children with CHARGE syndrome who underwent cochlear implantation surgery with intraoperative electrically evoked auditory brainstem response (EABR). All subjects had inner ear malformations, and two of the patients had cochlear nerve hypoplasia, which were identified by computed tomography and high-resolution magnetic resonance imaging. Intraoperative EABR waveforms were detected with a pulse width of 25 and 50 μs in two patients and one patient, respectively. The former two subjects achieved auditory recognition early, although one had a hypoplastic cochlear nerve. In contrast, the latter subject required mapping adjustments with widened pulse widths, which led to the subject achieving auditory recognition almost only a year after surgery for cochlear implantation. These results suggest that the pulse width used in intraoperative EABR precisely predicts the patient's postoperative auditory response. Moreover, preoperative imaging evaluation of the cochlear nerve does not always indicate its function, and intraoperative EABR is indispensable for accurately evaluating the cochlear nerve function in patients with CHARGE syndrome.
Sugarcane extract (Saccharum officinarum extract: SOE), a byproduct containing polyphenols obtained through the process of making raw sugar from sugarcane, exhibited an effect on the discoloration of ...salmon that suggests SOE inhibits lipid oxidation, which inhibits discoloration of carotenoid as a result. Therefore, we considered an in vitro evaluation method for inhibiting discoloration of carotenoid, and used this method to measure SOE's inhibitive effect on carotenoid discoloration. The results showed that the methylene chloride soluble portion (low-polarity fraction) had the strongest inhibitive effect. We then refined and isolated the components of the methylene chloride-soluble portion to obtain 13 known components and one new compound. Structural analysis revealed that the new compound is 3-2-(β-D-glucopyranosyloxy)-4,6-dimethoxyphenyl-1-(4-methoxyphenyl)-1-propanone, which is a glycoside of retrodihydrochalcone. The results suggest that, combined with the content and antioxidant effect of the isolated compounds, simulanol, a lignan, contributes most to inhibiting carotenoid discoloration through the methylene chloride-soluble portion in SOE.
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