Increase in Cerebral Blood Flow as a Predictor of Hyperbaric Oxygen-Induced Convulsion in Artificially Ventilated Rats

In spontaneously breathing rats, a transient increase in cerebral blood flow (CBF) has been shown to be a predictor of hyperbaric oxygen (HBO)-induced convulsion. In the present study, we evaluated whether artificially ventilated animals also show an increase in CBF prior to the onset of HBO-induced convulsion. Rats were ventilated with 100% oxygen in 5 atmospheres. CBF, blood pressure, and an electroencephalogram were monitored continuously. Convulsion was observed at 41 +/- 12 min after the initiation of HBO treatment. A single abrupt increase in CBF, reaching 223 +/- 39% of the control level, was observed at 29 +/- 13 min after the initiation of HBO exposure and lasted until the onset of convulsion 12 +/- 2 min later. The time of the increase in CBF correlated strongly with the onset of convulsion (r = 0.99, P < 0.001). Further, the logistic regression curve demonstrated a close relationship between the duration of increased CBF and percentage of epileptiform electrical-discharge incidence (r = 0.92, P < 0.006). The durations of increased CBF causing convulsion in 10%, 50%, and 90% of the rats were 8.4 min, 11.7 min, and 15.1 min, respectively. These results indicate that an increase in CBF is a predictor of HBO-induced convulsion in artificially ventilated rats. The increase in CBF may be involved in the pathogenesis of HBO-induced convulsion

Endolymphatic Hydrops After Sac Surgery

Meniere’s disease is a common disease, that presents with recurrent vertigo and cochlear symptoms. The pathology of Meniere’s disease was first reported to involve endolymphatic hydrops in 1938. The endolymphatic sac is thought to have a role to keep the hydrostatic pressure and endolymph homeostasis for the inner ear. As a surgery for intractable Meniere’s disease, endolymphatic sac drainage with intraendolymphatic sac application of large doses of steroids is performed to control the endolymphatic hydrops and preserve or improve inner ear function. In the present study, to observe the effect of this surgery, we calculated the endolymphatic space size using 3-Teslamagnetic resonance imaging (MRI) 4 h after intravenous injection of gadolinium enhancement at two time points: just before surgery and 2 years after. To reveal the condition of the endolymphatic space, we constructed three-dimensional MR images semi-automatically and fused the three-dimensional images of the total fluid space of inner ear and the endolymphatic space. After fusing the images, we calculated the volume of the total fluid space and endolymphatic space. Two years after surgery, 16 of 20 patients (80.0%) showed relief from vertigo/dizziness and reductions in the ratio of the volume of the endolymphatic size to the total fluid space of inner ear. Endolymphatic sac drainage with intraendolymphatic sac application of large doses of steroids could control vertigo/dizziness and decrease the endolymphatic hydrops. These results indicate that endolymphatic sac drainage is a good treatment option for patients with intractable Meniere’s disease. In addition, volumetric measurement of inner ear volume could be useful for confirming the effect of treatments on Meniere’s disease

Vestibular Compensation after Vestibular Dysfunction Induced by Arsanilic Acid in Mice

When vestibular function is lost, vestibular compensation works for the reacquisition of body balance. For the study of vestibular dysfunction and vestibular compensation, surgical or chemical labyrinthectomy has been performed in various animal species. In the present study, we performed chemical labyrinthectomy using arsanilic acid in mice and investigated the time course of vestibular compensation through behavioral observations and histological studies. The surgical procedures required only paracentesis and storage of 50 μL of p-arsanilic acid sodium salt solution in the tympanic cavity for 5 min. From behavioral observations, vestibular functions were worst at 2 days and recovered by 7 days after surgery. Spontaneous nystagmus appeared at 1 day after surgery with arsanilic acid and disappeared by 2 days. Histological studies revealed specific damage to the vestibular endorgans. In the ipsilateral spinal vestibular nucleus, the medial vestibular nucleus, and the contralateral prepositus hypoglossal nucleus, a substantial number of c-Fos-immunoreactive cells appeared by 1 day after surgery with arsanilic acid, with a maximum increase in number by 2 days and complete disappearance by 7 days. Taken together, these findings indicate that chemical labyrinthectomy with arsanilic acid and the subsequent observation of vestibular compensation is a useful strategy for elucidation of the molecular mechanisms underlying vestibular pathophysiologies

アルサニル酸を用いたマウス内耳破壊後の前庭代償過程

When vestibular function is lost, vestibular compensation works for the reacquisition of body balance. For the study of vestibular dysfunction and vestibular compensation, surgical or chemical labyrinthectomy has been performed in various animal species. In the present study, we performed chemical labyrinthectomy using arsanilic acid in mice and investigated the time course of vestibular compensation through behavioral observations and histological studies. The surgical procedures required only paracentesis and storage of 50 µL of p-arsanilic acid sodium salt solution in the tympanic cavity for 5 min. From behavioral observations, vestibular functions were worst at 2 days and recovered by 7 days after surgery. Spontaneous nystagmus appeared at 1 day after surgery with arsanilic acid and disappeared by 2 days. Histological studies revealed specific damage to the vestibular endorgans. In the ipsilateral spinal vestibular nucleus, the medial vestibular nucleus, and the contralateral prepositus hypoglossal nucleus, a substantial number of c-Fos-immunoreactive cells appeared by 1 day after surgery with arsanilic acid, with a maximum increase in number by 2 days and complete disappearance by 7 days. Taken together, these findings indicate that chemical labyrinthectomy with arsanilic acid and the subsequent observation of vestibular compensation is a useful strategy for elucidation of the molecular mechanisms underlying vestibular pathophysiologies.博士（医学）・甲第742号・令和2年3月16日© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

Comparative evaluations of lignocellulose reactivity and usability in transgenic rice plants with altered lignin composition

The aromatic composition of lignins is considered an important trait that affects the physico-chemical properties of lignocellulosic biomass. However, our knowledge of the relationship between lignin structure and biomass utilization properties remains limited, especially in monocotyledonous grass species, despite their potential as biomass feedstocks. In this study, we used recently produced rice transgenic lines with distinct lignin monomer compositions, i.e., guaiacyl (G)/syringyl (S)/p-hydroxyphenyl (H) aromatic unit ratios, to study the impact of lignin composition on the chemical reactivity, enzymatic saccharification efficiency and calorific value of rice lignocellulose. The H-lignin-enriched rice transgenic line showed significantly enhanced biomass saccharification efficiency after alkali and acid pretreatments and even without any pretreatment, whereas the S-lignin-enriched rice transgenic line displayed enhanced saccharification efficiency after liquid hot water pretreatment. While we detected no significant differences in biomass heating values between the transgenic rice materials tested, analysis of synthetic lignins comprising only G, S or H units suggested that increased ratios of G or H units could increase the heating value of lignin-based solid biofuels

新規な磁気共鳴イメージングを用いたメニエール病の高精度診断法

Background: Pathologically, Meniere's disease symptoms are considered to be associated with endolymphatic hydrops. Examinations revealing endolymphatic hydrops can be useful for accurate Meniere's disease diagnosis. We previously reported a quantitative method for evaluating endolymphatic hydrops, i.e., by measuring the volume of the endolymphatic space using three-dimensional magnetic resonance imaging (MRI) of the inner ear. This study aimed to confirm the usefulness of our methods for diagnosing Meniere's disease. Here, we extracted new explanatory factors for diagnosing Meniere's disease by comparing the volume of the endolymphatic space between healthy volunteers and patients with Meniere's disease. Additionally, we validated our method by comparing its diagnostic accuracy with that of the conventional method. Methods and Findings: This is a prospective diagnostic accuracy study performed at vertigo/dizziness centre of our university hospital, a tertiary hospital. Eighty-six patients with definite unilateral Meniere's disease and 47 healthy volunteers (25 and 33 males, and 22 and 53 females in the control and patient groups, respectively) were enrolled. All participants underwent 3-Tesla MRI 4 h after intravenous injection of gadolinium to reveal the endolymphatic space. The volume of the endolymphatic space was measured and a model for Meniere's disease diagnosis was constructed and compared with models using conventional criteria to confirm the effectiveness of the methods used. The area under the receiver operating characteristic curve of the method proposed in this study was excellent (0.924), and significantly higher than that derived using the conventional criteria (0.877). The four indices, sensitivity, specificity, positive predictive value, and negative predictive value, were given at the threshold; all of these indices achieved higher scores for the 3D model compared to the 2D model. Cross-validation of the models revealed that the improvement was due to the incorporation of the semi-circular canals. Conclusions: Our method showed high diagnostic accuracy for Meniere's disease. Additionally, we revealed the importance of observing the semi-circular canals for Meniere's disease diagnosis. The proposed method can contribute toward providing effective symptomatic relief in Meniere's disease.博士（医学）・甲第807号・令和3年12月21日Copyright © 2021 Ito, Inoue, Inui, Miyasaka, Yamanaka, Kichikawa, Takeda, Kasahara, Kitahara and Naganawa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

Incidence of Serious Upper Gastrointestinal Bleeding in Patients Taking Non-steroidal Anti-infl ammatory Drugs in Japan

Upper gastrointestinal bleeding is a major adverse event of non-steroidal anti-inflammatory drugs (NSAIDs), and co-administration of proton pump inhibitors and H2 receptor antagonists has been established as a means of preventing such an eff ect. However, the incidence of bleeding associated with NSAID-induced ulcers under conditions where such strong anti-acid agents are used for prevention has yet to be clarified. We aimed to determine the annual incidence of serious upper gastrointestinal ulcer bleeding among Japanese patients in whom NSAIDs were used in our hospital. Before commencing the study, we recommended to all the physicians in our hospital the best method for caring for NSAID users, focusing on the concomitant use of proton pump inhibitors or H2 receptor antagonists. We conducted a cohort study involving 17,270 patients for whom NSAIDs had been newly prescribed. Bleeding from gastric ulcers was observed in 8 of the 17,270 patients using NSAIDs (0.05%). The pooled incidence rate for bleeding was calculated as 2.65 (95% confidence interval, 2.56-2.74) and 1.29 (1.27-1.31) per 1,000 patient years for low-dose aspirin and non-aspirin NSAID users, respectively. None of the bleeding ulcer patients required blood transfusion or were in serious condition. In conclusion, gastric ulcer bleeding occurred in low-dose aspirin or non-aspirin NSAID users, but its incidence was low and outcomes were not serious when adequate preventive measures were taken.</p