公徳会研究室の日常

社会医療法人 公徳会 佐藤病院・若宮病院は、精神神経学会の精神科専門医制度の研修施設に認定されており、専門資格の取得を目指す後期研修医を受け入れています。スーパー救急(精神科救急病棟)を擁することで、多くの症例を経験できることが特長です。さらに、東北大学敷地内に研究室を持ち、博士号を取得したい医師が活用できる体制を整えるなど、「臨床、教育、研究」の三本柱の充実に努めています。

著作権





西野です。




今回のお話は、ビデオアブストラクトについてです。


(以前のお話はこちら




著作権は、


一度出版してしまうと自分たちのものでは


なくなってしまいます。


アメリカは例外のようですが・・・

(さすがアメリカです。)


その場合、自分の論文であっても、


その図を使用する際には、


許諾と使用料金を雑誌社へ支払う必要があります。





時代は進み、


掲載料を著者が負担するオープンアクセスジャーナルになると


経費を負担しているのは、雑誌社ではありません。


許諾は、必要ないとおもっていました。


多くのオープンアクセスの場合、


クレジットを入れればOKということが多いのです。


しかし、ビデオアブストラクトの担当者から言われたのは、



『許諾を取るか、図を削除しなさい』


1つの図については、他の雑誌社だったので、


丁寧に説明し、ご理解頂けました。



もう1つの図については、『許諾必要』との回答、


許諾が必要なのは、その雑誌社なんですが・・・


何とも事務的な・・・










無事、許諾を得ることができました!!!













ちなみにこういったブログの記事は、


著作権で保護されるのものなのでしょうか?????







さて本日、珍客が研究室参りました。



IMG_4476




















スズメバチさんです。


手は、カブトムシのような手をしています。


ガラスもスイスイです。


早々にご帰宅頂きました。









双極性障害のswitchingに関する総説を出しました

栗田です

福島県立医大精神科の医局に在籍していた若かりし頃、双極性障害のswitchingは謎であると教えられていました。
双極性障害のswitchingとは躁状態からうつ状態になったり、逆にうつ状態から躁状態になることです。
今回の総説で最も伝えたいのは双極性障害のswitchingの原因として、ノルアドレナリン(ノルエピネフリン)が重要な役割を果たしているとすると言うことです。
そして、双極性障害うつ状態治療における抗うつ薬の使い分けについても表にしました。
双極性障害うつ状態にたいする抗うつ薬の是非論が戦わされて来ました。
「ありかなしか」ではなく、個々の抗うつ薬について検討しました。
新しい考えだと自分では思っています。

そして、今回、初めて英語でのこの総説を紹介するビデオを作成しました。
私が、拙いですが、一生懸命英語で申し上げています。

論文と共に是非、ご覧下さい。

Noradrenaline plays a critical role in the switch to a manic episode and treatment of a depressive episode

【急告】平成28年10月の予定

栗田です。

公徳会研究室5周年記念研究会についての再度のお知らせです。
今まで何度かこのブログでも取り上げて、また、5周年記念研究会専用ホームページを作って告知をしています。

日時;平成28年10月15日(土)10:00〜17:00
場所:山形テルサ(山形県山形市双葉町1丁目2-3)大会議室
参加対象:医師、薬剤師、臨床検査技師、看護師など医療従事者
     製薬メーカー、検査会社等に企業に所属している方
     大学・研究機関の研究職
     理系の学生、大学院生
パンフレット(1)




































内容は東北大学で行った基礎研究のみならず、公徳会 佐藤病院で得られた臨床データと血液中のバイオマーカーとの関係など臨床基礎研究になります。
臨床基礎研究は実臨床の場から得られた”リアルワールド”のデータを論文にしたものをまとめて発表します。

午前は基礎研究のセッションで、当研究室の西野敏研究員や東北大学大学院薬学研究科の守屋孝洋准教授が発表します
午後は臨床基礎研究のセッションで、私栗田征武が気分障害、認知症の分野について全ての内容を発表します

発表内容を元に発表者と参加者、参加者間で活発なディスカッションがなされ、研究会の名に相応しい時間と空間を共有できたらと思っています。
パンフレット(2)




































既に5周年記念研究会専用ホームページより、参加登録をいただいていますが、100名を収容する大会議室を会場とするために、席に余裕があります。

私が院長をさせてもらっている公徳会 若宮病院担当の某製薬メーカーMRさんにこの研究会の紹介をしたところ、「メーカーごときが参加して良いのでしょうか」と言われました。
謙遜してそうおっしゃっているのかどうか…。
生化学、薬理学のベースにした発表なので製薬メーカーのMRのみならず、研究・開発担当者の方にも興味を持っていただける内容かと思います。

研究会への参加は無料で、日本製薬工業協会(製薬協)の医療用医薬品製造販売業公正競争規約に則り、飲食を伴わない会合です。
研究会終了後の交流会を、会の終了後の17時から19時にかけて会場のテルサ建物内のレストランシロー絵夢で行います。交流会については、「会場・金額・全ての参加者が同額である旨」の記述がある案内状を参加者に送ります。
われわれの手作りの研究会なので、至らぬ点が多々ありますが、異なる立場の皆様が安心して参加出来る研究会と交流会です。

秋真っ盛りの山形で研究会に参加して勉強をして、交流会で新しい繋がりを持ってみませんか。
5周年記念研究会専用ホームページより多数の参加登録を待っています。



第1部(基礎編)3題

10:0012:00

 

Prog Neuropsychopharmacol Biol Psychiatry. 2012 Oct 1;39(1):17-22. doi: 10.1016/j.pnpbp.2011.07.008. Epub 2011 Jul 22.

Divergent effects of lithium and sodium valproate on brain-derived neurotrophic factor (BDNF) production in human astrocytoma cells at therapeutic concentrations.

Nishino S, Ohtomo K, Numata Y, Sato T, Nakahata N, Kurita M.

 

Abstract

Mood stabilizers such as lithium (Li) or valproic acid (VPA) are used in the therapy of bipolar disorders, but the mechanisms by which these medicines work is unclear. Recently, neuroprotection has attracted attention as a potential action for VPA and Li. The close spatial relationship of the pre- and post-synapse with an astrocyte process within a 'tripartite synapse' suggests that mood stabilizer actions on astrocytes may be important. Therefore, we examined the effect of Li and VPA, at therapeutic concentrations, on brain-derived neurotrophic factor (BDNF) production in cultured human astrocytoma cells over an extended period of exposure. Released (extracellular) and intracellular BDNF was measured with sandwich-ELISA. Intracellular BDNF mRNA was also quantified using RT-PCR. VPA treatment potentiated the level of extracellular BDNF, whereas Li reduced it. Furthermore, VPA caused increased intracellular levels of BDNF protein and mRNA, while exposure to Li led to no significant differences compared to control cells. We suggest the possibility that VPA and Li have divergent effects on astrocyte BDNF production. Mood stabilizers play an essential role in regulating BDNF not only in neurons, but also in astrocytes. These findings could form the basis of a new astrocyte-targeted approach towards developing effective medications to treat bipolar disorders.

Copyright © 2011 Elsevier Inc. All rights reserved.


体内時計機能の脆弱化による気分障害発症と海馬ニューロン新生亢進機序

 

Takouda J, Sawauchi M, Mogi A, Nishino S, Kurita M, Shibata S, Moriya T

 

 

Nihon Rinsho. 2010 Jul;68 Suppl 7:131-3.

[Brain-derived neurotrophic factor (BDNF)]

[Article in Japanese]

Kurita M, Nishino S, Nakahata N.

 

PMID: 20960761


第2部(気分障害編)3題

13:0015:00

 

PLoS One. 2014 Jun 27;9(6):e100634. doi: 10.1371/journal.pone.0100634. eCollection 2014.

The noradrenaline metabolite MHPG is a candidate biomarker from the manic to the remission state in bipolar disorder I: a clinical naturalistic study.

Kurita M, Nishino S, Numata Y, Okubo Y, Sato T.

 

Abstract

Remission is the primary goal of treatment for bipolar disorder I (BDI). Metabolites of noradrenaline and dopamine, 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA), respectively, are reduced by treatment with antipsychotics, but whether these phenomena are caused by antipsychotics or by the pathophysiology of BDI is not known. Interactions between brain-derived neurotrophic factor (BDNF) and mood disorders have also been suggested. We conducted a multifaceted study in BDI patients to ascertain if biological markers are associated with the manic state. Patients with Young Mania Rating Scale (YMRS) scores >20 participated in the study. Final analyses involved 24 BDI patients (13 men and 11 women). We used YMRS scores to identify mania stages in individual BDI patients (i.e., manic syndrome, response and remission stages). Statistical analyses were done using one-way repeated-measures analyses of variance (rep-ANOVA) throughout manic syndrome, response and remission stages. Plasma concentrations of MHPG and HVA were analyzed by high-performance liquid chromatography with electrochemical detection. Plasma levels of BDNF were measured by sandwich enzyme-linked immunosorbent assay. BDI patients had significantly reduced plasma levels of MHPG throughout manic syndrome, response and remission stages (rep-ANOVA, p=0.002). Without a case of response state, there was a significant positive correlation between YMRS scores and plasma levels of MHPG (ρ=0.33, p=0.033, n=48). Plasma levels of HVA and BDNF were not significantly altered throughout manic syndrome, response and remission stages. These data suggest that the peripheral level of MHPG (which is associated with noradrenaline levels in the brain) could be used as a biomarker for the manic state in BDI. The MHPG level is likely to reflect the clinical characteristics of the manic syndrome in BDI, and noradrenaline may reflect the pathophysiology from manic to remission states.

PMID: 24971450 PMCID: PMC4074114 DOI: 10.1371/journal.pone.0100634

 

 

Neuropsychiatr Dis Treat. 2015 Feb 11;11:353-8. doi: 10.2147/NDT.S74550. eCollection 2015.

The noradrenaline metabolite MHPG is a candidate biomarker between the depressive, remission, and manic states in bipolar disorder I: two long-term naturalistic case reports.

Kurita M, Nishino S, Numata Y, Okubo Y, Sato T.

 

Abstract

BACKGROUND:

Treatment of the depressive and manic states in bipolar disorder I (BDI) is a challenge for psychiatrists. Despite the recognized importance of the switch phenomenon, the precise mechanisms underlying this process are yet to be shown. We conducted a naturalistic study in two BDI patients to determine whether biological markers (monoamine metabolites and brain-derived neurotrophic factor [BDNF]) are associated with the switch between depressive and manic states.

CASE PRESENTATION AND METHODS:

Blood sampling and mood assessments were performed at 2-week intervals over a period of 2 (Case 1, n=72) and 6 (Case 2, n=183) years. Plasma concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were analyzed by high-performance liquid chromatography with electrochemical detection. Plasma BDNF was assayed by sandwich ELISA (enzyme-linked immunosorbent assay).

RESULTS:

MHPG had the highest standardized coefficient (β) in the multiple regression analysis. We found a significant positive correlation between Young Mania Rating Scale scores and plasma MHPG levels (Case 1: ρ=0.429; Case 2: ρ=0.488), and a significant negative correlation between Montgomery-Asberg Depression Rating Scale scores and MHPG levels (Case 1: ρ=-0.542; Case 2: ρ=-0.465). Conversely, no significant correlation was found between the level of BDNF and the presence of a manic or depressive state, and although HVA had a slightly stronger correlation than MHPG, the levels of neither of these were found to significantly correlate with the symptoms.

CONCLUSION:

These data suggest that peripheral MHPG levels (which is related to noradrenaline levels in the brain) could be used as a biomarker of mood states in BDI. The noradrenaline level in the brain is likely to reflect the clinical characteristics of the switch process in BDI, and has prognostic significance for the treatment of both manic and depressive states.

PMID: 25709459 PMCID: PMC4334324 DOI: 10.2147/NDT.S74550

 

 

PLoS One. 2012;7(6):e39212. doi: 10.1371/journal.pone.0039212. Epub 2012 Jun 27.

Plasma brain-derived neurotrophic factor levels predict the clinical outcome of depression treatment in a naturalistic study.

Kurita M, Nishino S, Kato M, Numata Y, Sato T.

 

Abstract

Remission is the primary goal of treatment for major depressive disorder (MDD). However, some patients do not respond to treatment. The main purpose of this study was to determine whether brain-derived neurotrophic factor (BDNF) levels are correlated with treatment outcomes. In a naturalistic study, we assessed whether plasma BDNF levels were correlated with clinical outcomes by measuring plasma BDNF in patients with depressive syndrome (MADRS score ≥ 18), and subsequently comparing levels between the subgroup of patients who underwent remission (MADRS score ≤ 8) and the subgroup who were refractory to treatment (non-responders). Patients with depressive syndrome who underwent remission had significantly higher plasma BDNF levels (p<0.001), regardless of age or sex. We also found a significant negative correlation between MADRS scores and plasma BDNF levels within this group (ρ = -0.287, p = 0.003). In contrast, non-responders had significantly lower plasma BDNF levels (p = 0.029). Interestingly, plasma BDNF levels in the non-responder group were significantly higher than those in the remission group in the initial stage of depressive syndrome (p = 0.002). Our results show that plasma BDNF levels are associated with clinical outcomes during the treatment of depression. We suggest that plasma BDNF could potentially serve as a prognostic biomarker for depression, predicting clinical outcome.

PMID: 22761741 PMCID: PMC3384668 DOI: 10.1371/journal.pone.0039212

 

 


第3部(認知症編)2題

15:3017:00

 

J Clin Psychopharmacol. 2013 Oct;33(5):600-7. doi: 10.1097/JCP.0b013e31829798d5.

Efficacy and tolerability of risperidone, yokukansan, and fluvoxamine for the treatment of behavioral and psychological symptoms of dementia: a blinded, randomized trial.

Teranishi M, Kurita M, Nishino S, Takeyoshi K, Numata Y, Sato T, Tateno A, Okubo Y.

 

Abstract

The descriptive term behavioral and psychological symptoms of dementia (BPSD) is used to cover a range of noncognitive disturbances including anxiety, depression, irritability, aggression, agitation, eating disorders, and inappropriate social or sexual behaviors. Behavioral and psychological symptoms of dementia are seen in about 90% of patients with dementia. We aimed to compare the efficacy and tolerability of risperidone, yokukansan, and fluvoxamine used for BPSD in elderly patients with dementia. Ninety inpatients with dementia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria were investigated in Sato Hospital, Koutokukai. We conducted an 8-week, rater-blinded, randomized trial, administering flexibly dosed risperidone, yokukansan, or fluvoxamine. Primary outcome measures were Neuropsychiatric Inventory in Nursing Home Version total score and its items. Secondary outcome measures were cognitive function measured by Mini-Mental State Examination and daily life function measured by Functional Independence Measure (FIM). Neurological adverse effects were measured by the Drug-Induced Extra-Pyramidal Symptoms Scale. At the end of the study, we analyzed 76 patients (92.7%). Mean Neuropsychiatric Inventory in Nursing Home Version total score decreased in all 3 drug groups, with no significant between-group differences. Mini-Mental State Examination and Functional Independence Measure scores did not change significantly. Drug-Induced Extra-Pyramidal Symptoms Scale scores did not change in the yokukansan and fluvoxamine groups, but increased significantly in the risperidone group. Risperidone, yokukansan, and fluvoxamine were equally effective in the treatment of BPSD in elderly patients. However, yokukansan or fluvoxamine for BPSD showed a more favorable profile in tolerability compared with risperidone. This trial is registered at UMIN Clinical Trials Registry (identifier: UMIN000006146).

PMID: 23948783 DOI: 10.1097/JCP.0b013e31829798d5

 

 

Neuropsychiatr Dis Treat. 2016 Mar 15;12:641-9. doi: 10.2147/NDT.S99032. eCollection 2016.

Yokukansan improves behavioral and psychological symptoms of dementia by suppressing dopaminergic function.

Takeyoshi K, Kurita M, Nishino S, Teranishi M, Numata Y, Sato T, Okubo Y.

 

Abstract

Although three drugs, risperidone, yokukansan, and fluvoxamine, have shown equal efficacy in treating behavioral and psychological symptoms of dementia (BPSD) in our previous study, their mechanisms of action are different from one another. Monoamines have attracted attention for their key roles in mediating several behavioral symptoms or psychological symptoms through synaptic signaling. We aimed to clarify the monoamines changed by treatment with each drug in patients with BPSD. The main purpose of this study was to determine whether plasma levels of catecholamine metabolites are correlated with pharmacological treatments. This was an 8-week, rater-blinded, randomized, flexible-dose, triple-group trial. In total, 90 subjects were recruited and subsequently three different drugs were allocated to 82 inpatients with BPSD. We examined BPSD data from patients who completed 8 weeks of treatment. Eventually, we analyzed 42 patients (yokukansan: 17; risperidone: 9; fluvoxamine: 16). Homovanillic acid, a metabolite of dopamine, and 3-methoxy-4-hydroxyphenylglycol, a metabolite of noradrenaline, in their plasma were analyzed by high-performance liquid chromatography with electrochemical detection. All three drugs showed equal significant efficacy between baseline and study endpoint. By contrast, biomarkers showed mutually different changes. Patients in the yokukansan group had significantly decreased plasma homovanillic acid levels from baseline. Conversely, patients in the risperidone and fluvoxamine groups exhibited no significant changes in plasma homovanillic acid levels from baseline. Yokukansan contains geissoschizine methyl ether, which is known to have a partial agonist effect on dopamine D2 receptors. An improvement in BPSD condition with the intake of yokukansan is suggested to occur through a suppressed dopaminergic function, which is similar to the effect of aripiprazole.

PMID: 27042075 PMCID: PMC4801203 DOI: 10.2147/NDT.S99032

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