Interaction between anti-Alzheimer and antipsychotic drugs in modulating extrapyramidal motor disorders in mice

AbstractAntipsychotics are often used in conjunction with anti-Alzheimer drugs to treat the behavioral and psychological symptoms of dementia (BPSD). Here, we examined the effects of cholinesterase inhibitors (ChEIs), donepezil and galantamine, on antipsychotic-induced extrapyramidal side effects (EPS) in mice. The effects of serotonergic agents on the EPS drug interaction were also evaluated. Donepezil (0.3–3 mg/kg) did not induce EPS signs by itself; however, it significantly potentiated bradykinesia induction with a low dose of haloperidol (0.5 mg/kg) in dose-dependent and synergistic manners. Galantamine (0.3–3 mg/kg) elicited mild bradykinesia at a high dose and dose-dependently augmented haloperidol-induced bradykinesia. The EPS potentiation by galantamine was blocked by trihexyphenidyl (a muscarinic antagonist), but not by mecamylamine (a nicotinic antagonist). In addition, the bradykinesia potentiation by galantamine was significantly reduced by (±)-8-hydroxy-2-(di-n-propylamino)-tetralin (a 5-HT1A agonist), ritanserin (a 5-HT2 antagonist), and SB-258585 (a 5-HT6 antagonist). The present results give us a caution for the antipsychotics and ChEIs interaction in inducing EPS in the treatment of BPSD. In addition, second generation antipsychotics, which can stimulate 5-HT1A receptors or antagonize 5-HT2 and 5-HT6 receptors, seem to be favorable as an adjunctive therapy for BPSD

Decline in Left Ventricular Ejection Fraction during Follow-up in Patients with Severe Aortic Stenosis

Objectives: The aim of this study was to investigate the prognostic impact of the decline in left ventricular ejection fraction (LVEF) at 1-year follow-up in patients with severe aortic stenosis (AS) managed conservatively. Background: No previous study has explored the association between LVEF decline during follow-up and clinical outcomes in patients with severe AS. Methods: Among 3, 815 patients with severe AS enrolled in the multicenter CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry in Japan, 839 conservatively managed patients who underwent echocardiography at 1-year follow-up were analyzed. The primary outcome measure was a composite of AS-related deaths and hospitalization for heart failure. Results: There were 91 patients (10.8%) with >10% declines in LVEF and 748 patients (89.2%) without declines. Left ventricular dimensions and the prevalence of valve regurgitation and atrial fibrillation or flutter significantly increased in the group with declines in LVEF. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the group with declines in LVEF than in the group with no decline (39.5% vs. 26.5%; p 10% declines in LVEF at 1 year after diagnosis had worse AS-related clinical outcomes than those without declines in LVEF under conservative management. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140

Granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α in combination is a useful diagnostic biomarker to distinguish familial Mediterranean fever from sepsis

Objective: To identify potential biomarkers to distinguish familial Mediterranean fever (FMF) from sepsis.Method: We recruited 28 patients diagnosed with typical FMF (according to the Tel Hashomer criteria), 22 patients with sepsis, and 118 age-matched controls. Serum levels of 40 cytokines were analyzed using multi-suspension cytokine array. We performed a cluster analysis of each cytokine in the FMF and sepsis groups in order to identify specific molecular networks. Multivariate classification (random forest analysis) and logistic regression analysis were used to rank the cytokines by importance and determine specific biomarkers for distinguishing FMF from sepsis.Results: Fifteen of the 40 cytokines were found to be suitable for further analysis. Levels of serum granulocyte-macrophage colony-stimulating factor (GM-CSF), fibroblast growth factor 2, vascular endothelial growth factor, macrophage inflammatory protein-1b, and interleukin-17 were significantly elevated, whereas tumor necrosis factor-α (TNF-α) was significantly lower in patients with FMF compared with those with sepsis. Cytokine clustering patterns differed between the two groups. Multivariate classification followed by logistic regression analysis revealed that measurement of both GM-CSF and TNF-α could distinguish FMF from sepsis with high accuracy (cut-off values for GM-CSF = 8.3 pg/mL; TNF-α = 16.3 pg/mL; sensitivity, 92.9%; specificity, 94.4%; accuracy, 93.4%).Conclusion: Determination of GM-CSF and TNF-α levels in combination may represent a biomarker for the differential diagnosis of FMF from sepsis, based on measurement of multiple cytokines

Utility of a simplified ultrasonography scoring system among patients with rheumatoid arthritis: A multicenter cohort study

ABSTRACT: We aimed to evaluate the utility of a simplified ultrasonography (US) scoring system, which is desired in daily clinical practice, among patients with rheumatoid arthritis (RA) receiving biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs).A total of 289 Japanese patients with RA who were started on tumor necrosis factor inhibitors, abatacept, tocilizumab, or Janus kinase inhibitors between June 2013 and April 2019 at one of the 15 participating rheumatology centers were reviewed. We performed US assessment of articular synovia over 22 joints among bilateral wrist and finger joints, and the 22-joint (22j)-GS and 22-joint (22j)-PD scores were evaluated as an indicator of US activity using the sum of the GS and PD scores, respectively.The top 6 most affected joints included the bilateral wrist and second/third metacarpophalangeal joints. Therefore, 6-joint (6j)-GS and -PD scores were defined as the sum of the GS and PD scores from the 6 synovial sites over the aforementioned 6 joints, respectively. Although the 22j- or 6j-US scores were significantly correlated with DAS28-ESR or -CRP scores, the correlations were weak. Conversely, 6j-US scores were significantly and strongly correlated with 22j-US scores not only at baseline but also after therapy initiation.Using a multicenter cohort data, our results indicated that a simplified US scoring system could be adequately tolerated during any disease course among patients with RA receiving biological/targeted synthetic DMARDs

コガタ クライオサンプラー ヲ モチイタ ショウワキチ デノ セイソウケン タイキ サイシュ ジッケン ダイ49ジタイ ジッケン ホウコク

第49次南極地域観測隊(第49次隊)夏期間に昭和基地において,新たに開発した小型クライオサンプラーを用いた成層圏大気採取実験を実施した.小型クライオサンプラーは高圧ネオンガスを断熱膨張させて液体ネオンを製造し,希薄な成層圏大気を固化・液化採取するものであり,既存の大型サンプラーが必要とした液体ヘリウムが不要であること,小型軽量であるために満膨張時容積1000-2000 m3の小型プラスチック気球を用いて成層圏まで飛揚させることが可能であるという特徴がある.2007年12月30日と2008年1月4日に計4機の小型サンプラーを放球し,すべて回収に成功した.そのうち,2機は高度18 km及び25kmの成層圏大気の採取に成功した.採取された大気試料は国内に持ち帰られた後,各種温室効果気体濃度と同位体比の分析が行われた.As a part of summer observations of the 49th Japanese Antarctic Research Expedition, stratospheric whole air sampling experiments were conducted at Syowa Station using newly developed compact cryogenic air samplers. The compact sampler uses liquefied neon (produced in-situ) as a refrigerant to solidify or liquefy atmospheric constituents. Because of its reduced size and weight, the sampler can be launched using small-size balloons (1000–2000 m3 in volume). On December 30, 2007 and January 4, 2008, a total of 4 samplers were launched from Syowa Station and recovered on the same day as their launches. Two of them functioned as designed and collected stratospheric air samples at altitudes of 18 and 25 km. The air samples were analyzed for greenhouse gas concentrations and stable isotopes after return to Japan

Unilateral rotation in baseball fielder causes low back pain contralateral to the hitting side

Low back pain (LBP) often occurs in baseball players ; however, the characteristics of the location of their LBP with respect to their throwing and hitting sides have not been clarified. In order to clarify the left-right asymmetry of LBP that occurs in baseball players, we surveyed 247 university baseball players using an LBP questionnaire. The main investigational items were : throwing and hitting side, position at the time of LBP experience, and LBP location. Based upon the indication of their throwing and hitting side, subjects were classified into unilateral rotational (UR) or bilateral rotational (BR) types. Subjects were also classified into categories of LBP location as described by ipsilateral or contralateral to dominant side of throwing or hitting. Chi-square test or Fisher exact test were used to compare LBP location side by rotational type (UR/BR) in all subjects and by position (pitcher/fielder). We found that among fielders, LBP occurring contralateral to the hitting side in UR was significantly more frequent than that in BR. We conclude that LBP occurred in baseball fielders with a left-right asymmetry, which suggests that high frequency unilateral rotation causes the lumbar region contralateral to the dominant hitting side to be subject to a high load