Positive Symptoms in Antipsychotic-naïve Schizophrenia are Associated with Increased Body Mass Index after Treatment

Shih-Hsien Lin,Huai-Hsuan Tseng,Hsin Chun Tsai,Mei Hung Chi,I Hui Lee,Po See Chen,Kao Chin Chen,Yen Kuang Yang 대한정신약물학회 2021 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.19 No.1

Objective: Weight gain is an important risk factor for morbidity and mortality among patients with schizophrenia. We speculated that positive symptoms, related to dopaminergic hyperactivity and altered mesolimbic function, are associated with weight gain. Methods: Twenty-two antipsychotic-naïve, first-episode patients with schizophrenia were enrolled. The Positive and Negative Syndrome Scale was completed at enrollment and follow-up. Body mass index (BMI) was also measured. Results: The increase in BMI, after 6.04 ± 2.16 years of follow-up, was associated with positive symptoms, but not negative symptoms, before treatment with antipsychotics in antipsychotic-naïve patients with schizophrenia. Conclusion: This finding implied that dopaminergic hyperactivity could be an important factor to predict the treatment outcome. Body weight control is important for the health management of patients with schizophrenia with more severe positive symptoms.

Life Science : Inula japonica extract inhibits mast cell-mediated allergic reaction and mast cell activation

( Yue Lu ),( Ying Li ),( Mei Hua Jin ),( Ju Hye Yang ),( Xian Li ),( Guang Hsuan Chao ),( Hyo Hyun Park ),( Young Na Park ),( Jong Keun Son ),( Eun Kyung Lee ),( Hyeun Wook Chang ) 영남대학교 약품개발연구소 2012 영남대학교 약품개발연구소 연구업적집 Vol.22 No.0

ETHNOPHARMACOLOGICAL RELEVANCE: The flowers of Inula japonica (Inulae Flos) have long been used in traditional medicine for the treatment of bronchitis, digestive disorders, and inflammation. However, the mechanisms underlying its anti-inflammatory effects remain yet to be elucidated. The objectives of this study were 1) to assess the anti-allergic activity of the ethanol extract of flowers of Inula japonica extract (IFE) in vivo, 2) to investigate the mechanism of its action on mast cells in vitro, and 3) to identify its major phytochemical compositions. MATERIALS AND METHODS: The anti-allergic activity of IFE was evaluated using mouse bone marrow-derived mast cells (BMMCs) in vitro and a passive cutaneous anaphylaxis (PCA) animal model in vivo. The effects of IFE on mast cell activation were evaluated in terms of degranulation, eicosanoid generation, Ca(2+) influx, and immunoblotting of various signaling molecules. RESULTS: IFE inhibited degranulation and the generation of eicosanoids (PGD(2) and LTC(4)) in stem cell factor (SCF)-stimulated BMMCs. Biochemical analysis of the SCF-mediated signaling pathways demonstrated that IFE inhibited the activation of multiple downstream signaling processes including mobilization of intracellular Ca(2+) and phosphorylation of the mitogen-activated protein kinases (MAPKs), PLCγ1, and cPLA(2) pathways. When administered orally, IFE attenuated themast cell-mediated PCA reaction in IgE-sensitized mice. Its major phytochemical composition included three sesquiterpenes, 1-O-acetylbritannilactone, britanin and tomentosin. CONCLUSIONS: This study suggests that IFE modulates eicosanoids generation and degranulation through the suppression of SCF-mediated signaling pathways that would be beneficial for the prevention of allergic inflammatory diseases. Anti-allergic activity of IFE may be in part attributed particularly to the presence of britanin and tomentosin as major components evidenced by a HPLC analysis. Crown Copyright ⓒ2012 Published by Elsevier lreland Ltd. All rights reserved.

High Therapeutic Efficiency of LDV/SOF in Asian Patients with CHC Genotype 1 Infection

( Young-suk Lim ),( Henry Lik Yuen Chan ),( Yock Young Dan ),( Mei Hsuan Lee ),( Ming-lung Yu ),( Marta Silva ),( Jorge Felix ),( Zobair M. Younossi ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Current Asian treatment practices for Chronic Hepatitis C (CHC) Genotype (GT) 1 patients use regimens containing pegylated inferferon and ribavirin (PR). As interferon-free regimens become the standard of care in most Western countries, it is necessary to understand the potential impact of an all-oral, PR-free single-tablet regimen of Ledipasvir/Sofosbuvir (LDV/SOF) on Asian CHC patients. The aim of this study was to estimate long-term health outcomes of LDV/SOF therapy in 4 Asian countries: Taiwan, South Korea, Singapore, Hong Kong. Methods: A hypothetical cohort of 10,000 adult patients/country was modeled with a hybrid decision tree and Markov state-transition model capturing the natural history of CHC and treatment implications over a lifetime. Efficacy was based on randomized controlled trials; country-specific demographics, HCV-related epidemiology and treatment data were retrieved from literature. Therapeutic efficiency was defined as the number of advanced liver disease (ALD) cases averted (decompensated cirrhosis, hepatocellular carcinoma, liver transplants, HCV-related deaths) with LDV/SOF relative to PR or no treatment (NT) in treatment-naive patients. The differing immunomodulatory and anti-tumor effects of the therapies were not modeled. Results: A 12 week regimen of LDV/SOF compared to PR/NT is estimated to substantially impact CHC disease burden by reducing the incidence of ALD (Table 1): -90.6% / -94.2% vs. PR/NT (Taiwan), -92.5% / -95.7% (South Korea), -93.3% / -96.2% (Singapore), -93.4% / -96.3% (Hong Kong). Conclusions: LDV/SOF is a highly effective treatment associated with potentially more favorable health outcomes when compared with current treatment practices or no treatment for GT1 CHC Asian patients.

PE-164: Impact of Ledipasvir/Sofosbuvir on the Work Productivity of Chronic Hepatitis C Patients in Asia

( Young-suk Lim ),( Henry Lik Yuen Chan ),( Yock Young Dan ),( Mei Hsuan Lee ),( Eliza Kruger ),( Seng Tan5,Zobair M. Younossi ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: To estimate the work productivity gains associated with LDV/SOF treatment for CHC in Hong Kong, Singapore, South Korea and Taiwan. Methods: The model captures anticipated impact of LDV/SOF on productivity loss over a one-year time horizon from a societal perspective for each country. A literature review was performed to identify country- specific inputs and expert advice was solicited to verify key variables. Patients enter the model post-treatment, having achieved SVR12, or not. Absenteeism and presenteeism rates were estimated based on the Work Productivity and Activity Index-Specific Health Problem (WPAI-SHP) data collected from the Phase III ION trials (US participants only) at baseline and at 12 weeks with rates assumed to remain unchanged from baseline for patients not achieving SVR. Sensitivity analyses were performed on key variables. Results: Total Work productivity loss due to not treating CHC was highest in Taiwan at US$349M ($355 per capita) given high prevalence of HCV, followed by US$146M ($358) in Korea, US$17M ($914) in Singapore and US$11M ($351) in Hong Kong. Treatment with LDV/SOF resulted in estimated productivity gains of $138 million, $58.7 million, $6.8 million and $4.5 million in Taiwan, Korea, Singapore and Hong Kong respectively. Conclusions: CHC imposes a significant indirect economic burden. Our model demonstrates that treatment of HCV GT1 patients with LDV/SOF is likely to result in significant cost savings due to an improvement in presenteeism versus no treatment across 4 Asian countries. This indirect economic gain should be considered when assessing the benefits of treating CHC.

Health Care Utilization and Expenditures of Patients with Diabetes Comorbid with Depression Disorder: A National Population-Based Cohort Study

Chun-Jen Huang,Hui-Min Hsieh,Herng-Chia Chiu,Peng-Wei Wang,Mei-Hsuan Lee,Chih-Yi Li,Ching-Hua Lin 대한신경정신의학회 2017 PSYCHIATRY INVESTIGATION Vol.14 No.6

Objective: The study investigated to compare health care utilization and expenditures between diabetic patients with and without depression in Taiwan. Methods: Health care utilization and expenditure among diabetic patients with and without depression disorder during 2000 and 2004 were examined using Taiwan’s population-based National Health Insurance claims database. Health care utilization included outpatient visits and the use of inpatient services, and health expenditures were outpatient, inpatient, and total medical expenditures. Moreover, general estimation equation models were used for analyzing the factors associated with outpatient visits and expenditures. Multiple logistic regression analysis was applied for identifying the factors associated with hospitalization. Results: The average annual outpatient visits and annual total medical expenditures in the study period were 44.23–52.20; NT$87,496–133,077 and 30.75–32.92; NT$64,411–80,955 for diabetic patients with and without depression. After adjustment for covariates, our results revealed that gender and complication were associated with out-patient visits. Moreover, the time factor was associated with the total medical expenditure, and residential urbanization and complication factors were associated with hospitalization. Conclusion: Health care utilization and expenditures for diabetic patients with depression were significantly higher than those without depression. Sex, complications, time, and urbanization are the factors associated with health care utilization and expenditures.

A Neuroprotective Action of Quercetin and Apigenin through Inhibiting Aggregation of Aβ and Activation of TRKB Signaling in a Cellular Experiment

Chiu Ya-Jen,Teng Yu-Shan,Chen Chiung-Mei,Sun Ying-Chieh,Hsieh-Li Hsiu Mei,Chang Kuo-Hsuan,Lee-Chen Guey-Jen 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.3

Alzheimer’s disease (AD) is a neurodegenerative disease with progressive memory loss and the cognitive decline. AD is mainly caused by abnormal accumulation of misfolded amyloid β (Aβ), which leads to neurodegeneration via a number of possible mechanisms such as down-regulation of brain-derived neurotrophic factor-tropomyosin-related kinase B (BDNF-TRKB) signaling pathway. 7,8-Dihydroxyflavone (7,8-DHF), a TRKB agonist, has demonstrated potential to enhance BDNF-TRKB pathway in various neurodegenerative diseases. To expand the capacity of flavones as TRKB agonists, two natural flavones quercetin and apigenin, were evaluated. With tryptophan fluorescence quenching assay, we illustrated the direct interaction between quercetin/ apigenin and TRKB extracellular domain. Employing Aβ folding reporter SH-SY5Y cells, we showed that quercetin and apigenin reduced Aβ-aggregation, oxidative stress, caspase-1 and acetylcholinesterase activities, as well as improved the neurite outgrowth. Treatments with quercetin and apigenin increased TRKB Tyr516 and Tyr817 and downstream cAMP-response-element binding protein (CREB) Ser133 to activate transcription of BDNF and BCL2 apoptosis regulator (BCL2), as well as reduced the expression of pro-apoptotic BCL2 associated X protein (BAX). Knockdown of TRKB counteracted the improvement of neurite outgrowth by quercetin and apigenin. Our results demonstrate that quercetin and apigenin are to work likely as a direct agonist on TRKB for their neuroprotective action, strengthening the therapeutic potential of quercetin and apigenin in treating AD.

Virtual Screening and Testing of GSK-3 Inhibitors Using Human SH-SY5Y Cells Expressing Tau Folding Reporter and Mouse Hippocampal Primary Culture under Tau Cytotoxicity

Lin Chih-Hsin,Hsieh Yu-Shao,Sun Ying-Chieh,Huang Wun-Han,Chen Shu-Ling,Weng Zheng-Kui,Lin Te-Hsien,Wu Yih-Ru,Chang Kuo-Hsuan,Huang Hei-Jen,Lee Guan-Chiun,Hsieh-Li Hsiu Mei,Lee-Chen Guey-Jen 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.1

Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer’s disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine’s screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (TauRD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC50 of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 TauRD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 TauRD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.