Increased cerebrospinal fluid interleukin-6 levels in patients with schizophrenia and those with major depressive disorder

信州大学博士（医学）・学位論文・平成25年3月31日授与（甲第944号）・篠山 大明Elevated peripheral levels of interleukin-6 (IL-6) are common findings in schizophrenia and depression. However, previous studies that measured cerebrospinal fluid (CSF) IL-6 levels in these disorders reported controversial results. The present study examined whether CSF IL-6 levels are altered in patients with schizophrenia and those with depression. Lumbar punctures were performed in 32 patients with schizophrenia, 30 with major depressive disorder (MDD), and 35 healthy controls. Serum samples were simultaneously collected from all subjects in the patient groups and from 32 of the control group. CSF and serum IL-6 levels were determined by enzyme-linked immunosorbent assay. Both the patients with schizophrenia and MDD had significantly higher CSF IL-6 levels compared to the controls (schizophrenia: P = 0.0027; MDD: P = 0.012). IL-6 levels were significantly higher in the CSF than in the serum. No significant correlation was observed between CSF and serum IL-6 levels. The present findings suggest that IL-6 of central origin is associated with the pathophysiology of schizophrenia and MDD, although confounding effect of smoking status can not be entirely excluded. (C) 2012 Elsevier Ltd. All rights reserved.ArticleJOURNAL OF PSYCHIATRIC RESEARCH. 47(3):401-406 (2013)journal articl

Large Right Pulmonary Vein Is a Predictor of Atrial Fibrillation Recurrence after Pulmonary Vein Isolation in Patients with Persistent Atrial Fibrillation

Pulmonary vein isolation（PVI）is an effective treatment for atrial fibrillation（AF）. However, outcomes differ between paroxysmal AF and persistent AF. We analyzed the predictors of recurrence by examining the recurrence group after ablation. Of 372 consecutive patients with AF who underwent PVI between June 2016 and December 2018, we evaluated 250 patients（age, 67±12y, 65％ men）whose left atrium（LA）was constructed using the PENTARAY catheter（BioSense Webster, Los Angeles, CA）, a multipolar electrode catheter with a novel shape and excellent mapping capability. We measured the LA total volume（LATV）, right pulmonary vein＋antrum volume（RPAV）, left PV＋antrum volume（LPAV）, LA central volume（LACV）, and LA bipolar voltage. Of the 250 patients, 78 had persistent AF（recurrence, 20）and 172 had paroxysmal AF（recurrence, 16）. In all patients, LATV, LACV, RPAV, and LPAV were significantly larger in patients with persistent AF than those with paroxysmal AF. The mean LA bipolar voltage in patients with persistent AF was significantly lower than those with paroxysmal AF. In cases of persistent AF, RPAV was significantly larger in the recurrence group than that in the non-recurrence group（15.9±4.8 vs 13.4±5.4ml; P＜0.05）. In cases of paroxysmal AF, there were no differences in any volume between the recurrence and non-recurrence groups. In conclusion, larger right PV is a predictor of AF recurrence after PVI in patients with persistent AF. The right PV is close to the atrial septum and the septopulmonary bundle, and the expansion of RPAV reflects the disruption of these structures, which may be involved in this result

Possible involvement of Interleukin‐17A in the deterioration of prepulse inhibition on acoustic startle response in mice

Abstract Aim Proinflammatory cytokines such as interleukin‐6 (IL‐6) and IL‐17A have been implicated in the pathophysiology of schizophrenia which often shows sensorimotor gating abnormalities. This study aimed to examine whether a proinflammatory cytokine, IL‐17A, induces impairment in sensorimotor gating in mice. We also examined whether IL‐17A administration affects GSK3α/β protein level or phosphorylation in the striatum. Methods Recombinant mouse IL‐17A (low‐dose: 0.5 ng/mL and high‐dose: 50 ng/mL with 10 μL/g mouse body weight, respectively) or vehicle was intraperitoneally administered into C57BL/6 male mice 10 times in 3 weeks (sub‐chronic administration). Prepulse inhibition test using acoustic startle stimulus was conducted 4 weeks after the final IL‐17A administration. We evaluated the effect of IL‐17A administration on protein level or phosphorylation of GSK3α/β in the striatum by using Western blot analysis. Results Administration of IL‐17A induced significant PPI deterioration. Low‐dose of IL‐17A administration significantly decreased both GSK3α (Ser21) and GSK3β (Ser9) phosphorylation in mouse striatum. There was no significant alteration of GSK3α/β protein levels except for GSK3α in low‐dose IL‐17A administration group. Conclusion We demonstrated for the first time that sub‐chronic IL‐17A administration induced PPI disruption and that IL‐17A administration resulted in decreased phosphorylation of GSKα/β at the striatum. These results suggest that IL‐17A could be a target molecule in the prevention and treatment of sensorimotor gating abnormalities observed in schizophrenia

The Curriculum for Early Childhood Education and Care Centers : Current Situation and Future Hopes <Original work paper>

The aim of the present research is to clarify the current curriculum used by early childhood education and care centers. To achieve this objective, questionnaire surveys were carried out at the early childhood education and care centers in Japan. The results revealed that (1) about 10% of all centers still do not have a curriculum, (2) only 30% of childcare workers are involved in the creation of a curriculum, and (3) over 10% of childcare workers participate in childcare activities without awareness of the curriculum. To ensure and enhance the quality of early childhood education and care, in addition to having a thorough awareness of the curriculum, childcare workers should be encouraged to participate in creating the curriculum.本研究は平成19-21年度科学研究費補助金（種目：基盤研究（C），研究課題番号：19530493，研究題目：乳幼児の発達における児童福祉施設の役割と保育カリキュラムに関する研究，代表者：山崎晃）による助成を受けて行ったものの一部である。なお，本稿の一部は日本保育学会第62回大会及び日本教育心理学会第51回総会において発表した

Concept of "Educare," and Perspectives and Problems of Approved Child Institutions' Curriculum

The conditions of approved child institutions are decided mainly from a management perspective, rather than from the need to think about childcare from the parent's, caregiver's, or children's perspectives. In the field of childcare, enriching the curriculums of approved child institutions has been an important topic. In closely examining the desirable curriculum for approved child institutions, we have introduced the concept of "educare," that combines education with care. We have discussed the theoretical background and the curriculum based on "educare." It is necessary to gather caregiver's opinions and different case studies to buildup a bottom-up curriculum that corresponds to "educare.