Bangle (Zingiber purpureum) Improves Spatial Learning, Reduces Deficits in Memory, and Promotes Neurogenesis in the Dentate Gyrus of Senescence-Accelerated Mouse P8

Megumi Nakai,Michiro Iizuka,Nobuaki Matsui,Kazuko Hosogi,Akiko Imai,Noriaki Abe,Hisashi Shiraishi,Ayumu Hirata,Yusuke Yagi,Kohei Jobu,Junko Yokota,Eishin Kato,Shinya Hosoda,Saburo Yoshioka,Kenichi Har 한국식품영양과학회 2016 Journal of medicinal food Vol.19 No.5

Bangle (Zingiber purpureum) is a tropical ginger that is used as a spice in Southeast Asia. Phenylbutenoid dimers isolated from Bangle have exhibited neurotrophic effects in primary cultured rat cortical neurons and PC12 cells. Furthermore, chronic treatment with phenylbutenoid dimers enhances hippocampal neurogenesis in olfactory bulbectomized mice. In this study, we investigated the effects of Bangle extract on behavior and hippocampal neurogenesis in vivo. SAMP8 mice, which are an established model for accelerated aging, with age-related learning and memory impairments, were given a Bangle-containing diet for 1 month, and subsequent behavioral tests and immunohistochemistry for Ki67, a proliferating cellmarker, were performed. We found that the Bangle-containing diet improved spatial learning and memory deficits in the Morris water maze and significantly increased the numbers of Ki67-positive cells in the dentate gyrus of the SAMP8 mice. In addition, the Bangle extract exhibited a neurotrophin-like activity as indicated by the induction of neurite sprouting in PC12 cells. Our results suggest that Bangle is beneficial for the prevention of age-related progression of cognitive impairment.

Early Improvement and Marriage Are Determinants of the 12-Month Treatment Outcome of Paroxetine in Outpatients with Panic Disorder

Takashi Watanabe,Mikito Ueda,Shin Ishiguro,Yuki Hayashi,Akiko Aoki,Masataka Shinozaki,Kazuko Kato,Kazufumi Akiyama,Kazutaka Shimoda 대한정신약물학회 2017 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.15 No.4

Objective: In this study, we investigated the determinants of remission and discontinuation of paroxetine pharmacotherapy in outpatients with panic disorder (PD). Methods: Subjects were 79 outpatients diagnosed with PD who took 10-40 mg/day of paroxetine for 12 months. The candidate therapeutic determinants included the serotonin transporter gene-linked polymorphic region and the −1019C/G promoter polymorphism of the serotonin receptor 1A as genetic factors, educational background and marital status as environmental factors, and early improvement (EI) at 2 weeks as a clinical factor were assessed. The Clinical Global Impression scale was used to assess the therapeutic effects of the pharmacotherapy. Results: Cox proportional hazards regression was performed to investigate the significant predictive factors of remission and discontinuation. EI was only a significant predictive factor of remission. EI was a significant predictive factor of remission (hazard ratio [HR], 2.709; 95% confidence interval [CI], 1.177-6.235). Otherwise, EI and marital status were significant predictive factors of the discontinuation. EI (HR, 0.266; 95% CI, 0.115-0.617) and being married (HR, 0.437; 95% CI, 0.204-0.939) were considered to reduce the risk of treatment discontinuation. In married subjects, EI was a significant predictive factor of the discontinuation (HR, 0.160; 95% CI, 0.045-0.565). However, in unmarried subjects, EI was not a significantly predictive factor for the discontinuation. Conclusion: EI achievement appears to be a determinant of PD remission in paroxetine treatment. In married PD patients, EI achievement also appears to reduce a risk of discontinuation of paroxetine treatment

Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase ‘Synoviolin’

Yamasaki, Satoshi,Yagishita, Naoko,Sasaki, Takeshi,Nakazawa, Minako,Kato, Yukihiro,Yamadera, Tadayuki,Bae, Eunkyung,Toriyama, Sayumi,Ikeda, Rie,Zhang, Lei,Fujitani, Kazuko,Yoo, Eunkyung,Tsuchimochi, K Wiley (John WileySons) 2007 The EMBO journal Vol.26 No.1

<P>Synoviolin, also called HRD1, is an E3 ubiquitin ligase and is implicated in endoplasmic reticulum -associated degradation. In mammals, Synoviolin plays crucial roles in various physiological and pathological processes, including embryogenesis and the pathogenesis of arthropathy. However, little is known about the molecular mechanisms of Synoviolin in these actions. To clarify these issues, we analyzed the profile of protein expression in synoviolin-null cells. Here, we report that Synoviolin targets tumor suppressor gene p53 for ubiquitination. Synoviolin sequestrated and metabolized p53 in the cytoplasm and negatively regulated its cellular level and biological functions, including transcription, cell cycle regulation and apoptosis. Furthermore, these p53 regulatory functions of Synoviolin were irrelevant to other E3 ubiquitin ligases for p53, such as MDM2, Pirh2 and Cop1, which form autoregulatory feedback loops. Our results provide novel insights into p53 signaling mediated by Synoviolin.</P>

Genetic Polymorphism of 1019C/G (rs6295) Promoter of Serotonin 1A Receptor and Catechol-O-Methyltransferase in Panic Disorder

Takashi Watanabe,Shin Ishiguro,Akiko Aoki,Mikito Ueda,Yuki Hayashi,Kazufumi Akiyama,Kazuko Kato,Kazutaka Shimoda1 대한신경정신의학회 2017 PSYCHIATRY INVESTIGATION Vol.14 No.1

Objective-Family and twin studies have suggested genetic liability for panic disorder (PD) and therefore we sought to determine the role of noradrenergic and serotonergic candidate genes for susceptibility for PD in a Japanese population. Methods-In this age-and gender-matched case-control study involving 119 PD patients and 119 healthy controls, we examined the genotype distributions and allele frequencies of the serotonin transporter gene linked polymorphic region (5-HTTLPR), -1019C/G (rs6295) promoter polymorphism of the serotonin receptor 1A (5-HT1A), and catechol-O-methyltransferase (COMT) gene polymorphism (rs4680) and their association with PD. Results-No significant differences were evident in the allele frequencies or genotype distributions of the COMT (rs4680), 5-HTTLPR polymorphisms or the -1019C/G (rs6295) promoter polymorphism of 5-HT1A between PD patients and controls. Although there were no significant associations of these polymorphisms with in subgroups of PD patients differentiated by gender or in subgroup comorbid with agoraphobia (AP), significant difference was observed in genotype distributions of the -1019C/G (rs6295) promoter polymorphism of 5-HT1A between PD patients without AP and controls (p=0.047). Conclusion-In this association study, the 1019C/G (rs6295) promoter polymorphism of the 5-HT1A receptor G/G genotype was associated with PD without AP in a Japanese population.

Evaluation of 131I (monoiodide) BSP for Clinical Studies

Ueda, Hideo,Iro, Masahiro,Kurata, Kunio,Yamada, Hideo,Iwase, Tohru,Migita, Tohru,Kameda, Haruo,Kato, Sadatake,Sato, Noboru,Ide, Kazuko,Wakebayashi, Takao 대한핵의학회 1971 핵의학 분자영상 Vol.5 No.1

"In 1925 Rosenthal and White introduced a bromosulfophthalein (BSP) dye retention test as a sensitive indicator of liver function. Even now it is regared as one of the most sensitive agents for the detection of non-icteric liver disease (liver cirrhosis, early stage of acute-hepatitis and hepatic tumor). BSP accumulates in the liver cells, conjugates with glutathione and is excreted into the bile. Therefore, a disorder in its excretion is due to a disturbance of one of these processes. Since bilirubin and BSP compete for uptake by the liver and increased serum bilirubin interferes with the colorimetric determination of BSP, it has been considered that BSP test is inappropriate for the differential diagnosis of jaundice conditions. It has been generally said that when jaundice is present, the BSP test is useless and should not be performed. In 1955, Taplin et al. labeled rose bengal, a dye similarly metabolized in the liver as BSP, with 131I and measured the hepatic excretion of this dye by external monitoring. Laster, Blahd et al. applied this method to the determination of the peripheral pool, succeeding in the diagnosis of chronic and subacute hepatic diseases without colorimetry. In 1968, Yamada, Taplin et al. suggested the possibility of differentiating so-called medical jaundice from surgical jaundice by scanning the subjects during 24 to 48 hours following intravenous injection of 131I-labeled rose bengal. As mentioned before, many authorities hold the opinion that BSP is not proper for the differential diagnosis of jaundice states. Some have tried to diagnose biliary tract obstruction by a malignant tumor by measuring BSP excretion into duodenal fluid and others by quantitating changes in serum levels of conjugated and free BSP. Furthermore, Burton et al. reported that in patients with extrahepatic obstructive jaundice, BSP retention was observed for 24 days after its administration. From a consideration of all these finding we came to a conclusion that the differential diagnosis of various jaundice states, (medical, surgical and constitutional) is possible by sequential scanning with radioisotope-labeled BSP, as with rose bengal, in accordance with procedures described by Yamada, Taplin et al. The evidence suggested that labeled BSP might make a more important contribution than rose bengal. "