Traditional Japanese medicine Kamikihito ameliorates sucrose preference, chronic inflammation and obesity induced by a high fat diet in middle-aged mice

The high prevalence of obesity has become a pressing global public health problem and there exists a strong association between increased BMI and mortality at a BMI of 25 kg/m2 or higher. The prevalence of obesity is higher among middle-aged adults than among younger groups and the combination of aging and obesity exacerbate systemic inflammation. Increased inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha (TNFα) are hallmarks of obesity, and promote the secretion of hepatic C-reactive protein (CRP) which further induces systematic inflammation. The neuropeptide oxytocin has been shown to have anti-obesity and anti-inflammation effects, and also suppress sweet-tasting carbohydrate consumption in mammals. Previously, we have shown that the Japanese herbal medicine Kamikihito (KKT), which is used to treat neuropsychological stress disorders in Japan, functions as an oxytocin receptors agonist. In the present study, we further investigated the effect of KKT on body weight (BW), food intake, inflammation, and sweet preferences in middle-aged obese mice. KKT oral administration for 12 days decreased the expression of pro-inflammatory cytokines in the liver, and the plasma CRP and TNFα levels in obese mice. The effect of KKT administration was found to be different between male and female mice. In the absence of sucrose, KKT administration decreased food intake only in male mice. However, while having access to a 30% sucrose solution, both BW and food intake was decreased by KKT administration in male and female mice; but sucrose intake was decreased in female mice alone. In addition, KKT administration decreased sucrose intake in oxytocin deficient lean mice, but not in the WT lean mice. The present study demonstrates that KKT ameliorates chronic inflammation, which is strongly associated with aging and obesity, and decreases food intake in male mice as well as sucrose intake in female mice; in an oxytocin receptor dependent manner

Brain structure alterations in girls with central precocious puberty

PurposeCentral precocious puberty (CPP) is puberty that occurs at an unusually early age with several negative psychological outcomes. There is a paucity of data on the morphological characteristics of the brain in CPP. This study aimed to determine the structural differences in the brain of patients with CPP.MethodsWe performed voxel- and surface-based morphometric analyses of 1.5 T T1-weighted brain images scanned from 15 girls with CPP and 13 age-matched non-CPP controls (NC). All patients with CPP were diagnosed by gonadotropin-releasing hormone (GnRH) stimulation test. The magnetic resonance imaging (MRI) data were evaluated using Levene’s test for equality of variances and a two-tailed unpaired t-test for equality of means. False discovery rate correction for multiple comparisons was applied using the Benjamini–Hochberg procedure.ResultsMorphometric analyses of the brain scans identified 33 candidate measurements. Subsequently, increased thickness of the right precuneus was identified in the patients with CPP using general linear models and visualizations of cortical thickness with a t-statistical map and a random field theory map.ConclusionThe brain scans of the patients with CPP showed specific morphological differences to those of the control. The features of brain morphology in CPP identified in this study could contribute to further understanding the association between CPP and detrimental psychological outcomes

CD39 deficiency in murine liver allografts promotes inflammatory injury and immune-mediated rejection

Adenosine triphosphate (ATP), an essential metabolic energy source, is released following cell apoptosis or necrosis. It acts as a damage-associated molecule pattern to stimulate innate immune cells. The ectonucleotidase CD39 regulates immune activation by hydrolysis of extracellular ATP. We have shown previously that CD39 expression by donor livers helps protect syngeneic grafts with extended (24 hr) cold preservation time from ischemia reperfusion injury. Given its immune regulatory properties, we hypothesized that CD39 expression in donor livers might modulate transplant tolerance that occurs following mouse allogeneic liver transplantation (LTx). Livers from C57BL/6 (B6) wild-type (WT) or CD39 KO mice were transplanted into normal C3H recipients with minimal (approximately 1 hr) cold ischemia. Serum alanine aminotransferase levels at day 4 post LTx were significantly higher in animals given CD39KO compared with WT livers. Moreover, IFN-γ production by liver-infiltrating CD8+ T cells at day 4 was significantly higher in CD39KO than in WT grafts. Furthermore, splenic T cells from CD39KO liver recipients exhibited greater proliferative responses to donor alloantigens than those from mice given WT grafts. By contrast, there was a concomitant significant reduction in the frequency of regulatory T cells (Treg) in CD39KO than in WT livers. Whereas WT liver allografts survived > 100 days, no CD39KO grafts survived beyond 40 days (median survival time [MST]: WT: >100 days vs CD39KO: 8 days; p<0.01). In addition, soluble CD39 administration significantly prolonged CD39KO liver allograft survival (MST: 27.5 days). These novel data suggest that CD39 expression in liver allografts modulates tissue injury, inflammation, anti-donor effector T cell responses and Treg infiltration and can suppress transplant rejection

胃切除術後患者の食の変化と生活満足感への影響

　本研究は，胃切除術後患者の食の変化の影響について主観的な生活満足感の視点から明らかにすることを目的とした．大学病院と一般総合病院の2 施設で胃がんの手術を受け術後１ケ月以内の患者25名を対象に，退院後初回の外来受診日に自記式の質問紙による調査を行った．調査には，古谷野らが作成した生活満足度尺度Kを使用した．分析では，対象者を生活満足度尺度のスケール中央値で2群に分け5.0点以上を高群，5.0 点未満を低群とし群間比較を行った．統計解析ソフトPASW　Ver.18 for Win. を用いて，χ2 検定，Mann‐Whitney U検定を行った．その結果，対象者の性別は男性21名（84.0%），女性4名（16.0%），平均年齢は62.2 ± 10.3歳（SD）で対象者全員に同居者があり，16名が職業をもっていた．術式は，13名が胃全摘出術であった．生活満足度尺度は9項目で構成され｢人生全体についての満足感｣4項目，｢心理的安定｣3項目，｢老いについての評価｣2項目の3因子構造である．対象の｢人生全体についての満足感｣は平均1.9 ± 0.9点，｢心理的安定｣は平均1.8± 0.9点，｢老いについての評価｣は平均0.8 ± 0.7点で，生活満足度総得点は平均4.4 ± 1.6点であった．生活満足度得点の高群は14名で生活満足度総得点平均5.8 ± 0.8点，低群は11 名で3.0 ± 1.0点であった．高群･低群の2群間比較では，因子｢人生全体についての満足感｣，｢心理的安定｣は高群の方が低群に比べ有意に得点が高く，「老いについての評価」では有意差は認められなかった．生活満足度総得点では，高群の方が低群に比べ有意に高かった．以上のことから，胃切除術後患者の生活満足度は，健康に生活している人々と比較しても得点に大きな違いはなく，術後1ヶ月の人々では食の変化のおよぼす主観的な生活満足度への影響は少ないことが明らかになった．　The aim of the present study was to clarify subjective life satisfaction in patients aftergastrectomy with respect to the effects of changes in patients’ diets. The subjects were 25 patients　who had undergone operation for stomach cancer within the preceding month at 2　hospitals, a university hospital and a general hospital. A survey was conducted by self-administered questionnaire on patients’ first outpatient visit since leaving the hospital following the operation. The Life Satisfaction Index K developed by Koyano et al. was used in the investigation. The subjects were divided into 2 groups using the median value for life satisfaction as the cutoff point. The groups were a high group with a score of ≥ 5 and a low group with a score of <5. The groups were then compared using the χ 2 test and Mann-Whitney U test with statistical analysis software PASW Ver. 18 for Windows. The subjects were 21 men （84.0%） and 4 woman （16.0%）, with a mean age of 62.2 ± 10.3 years（SD）. All subjects lived with family members. There were none who lived alone. Sixteen were employed and 9 were not. The surgical procedure was distal gastrectomy in 12 patients and total gastric resection in 13 patients. There were 3 factors for life satisfaction,“ satisfaction with entire life,”“ psychological stability,” and “assessment on aging,” for which the mean scores were 1.9 ± 0.9, 1.8 ± 0.9, and 0.8 ± 0.7, respectively. The mean total score for life satisfaction was 4.4 ± 1.6. The 14 patients of the high life satisfaction score group had a mean total score for life satisfaction of 5.8±0.8. The mean total score for the 11 patients of the low group was 3.0 ± 1.0. A comparison of the 2 groups revealed that the life satisfaction score was significantly higher in the high group than in the low group. There was not a large difference in a comparison between the life satisfaction of patients following gastrectomy and that of healthy people. This demonstrates that changes in diet do not have a large effect on subjective life satisfaction of patients 1 month after gastrectomy

Combination Therapy of Cyclosporin A and Plasma Exchange for Infants with Immunoglobulin-resistant Kawasaki Disease

Article信州医学雑誌 70(4) : 225-231(2022)departmental bulletin pape

Group cognitive remediation therapy for younger adolescents with anorexia nervosa:A feasibility study in a Japanese sample

Abstract Objective Cognitive remediation therapy (CRT) aims to increase patients’ cognitive flexibility by practicing new ways of thinking as well as facilitating bigger picture thinking, supporting patients with relevant tasks and encouraging an awareness of their own thinking styles. CRT has been applied in the treatment of adult anorexia nervosa (AN), and has been shown to be effective and acceptable. In adolescents, CRT has been piloted on both individual and group format. However, no studies are published in CRT for adolescents with AN in a Japanese sample. The objectives of this study were to assess the feasibility, to estimate effect sizes for the purpose of designing a larger study, and to assess the acceptability of a CRT group for younger adolescents with AN in a Japanese sample. Methods Group CRT interventions were carried out with a total of seven adolescents with AN. Neuropsychological and psychological assessments (motivation, self-efficacy and depression) were administered before and after the group intervention. The participants completed worksheets (documents of participants’ thinking about their thinking style and the relation of the skills that they learnt through each session to real-life) and questionnaires after the group. Results There were small effect sizes differences between the part of the pre and post neuropsychological tests and the pre and post ability to change (motivation). There were medium effect sizes differences between the pre and post depressive symptoms and importance to change (motivation). There was a large effect size shown between the pre and post weights. All participants were able to reflect on their own thinking styles, such as having difficulty with changing feelings and the tendency to focus on details in real-life. Adolescents’ feedback was positive, and the rate of dropout was low. Conclusion CRT groups could be feasible and acceptable for younger adolescents with AN in a Japanese sample. Trial registration UMIN No. 000020623. Registered 18 January 201