Dextromethorphan Protect the Valproic Acid Induced Downregulation of Neutrophils in Patients with Bipolar Disorder

Ru-Band Lu,Yun-Hsuan Chang,Sheng-Yu Lee,Tzu-Yun Wang,Shu-Li Cheng,Po See Chen,Yen Kuang Yang,Jau-Shyong Hong,Shiou-Lan Chen 대한정신약물학회 2020 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.18 No.1

Objective: Valproic acid (VPA) is an anticonvulsant and commonly long term used as a mood stabilizer for patients with mood disorders. However its chronic effects on the hematological changes were noticed and need to be further evaluated. In this study, we evaluated, in Taiwanese Han Chinese patients with bipolar disorders (BD), the chronic effects of VPA or VPA plus dextromethorphan (DM) on the hematological molecules (white blood cell [WBCs], red blood cells [RBCs], hemoglobin, hematocrit, and platelets). Methods: In a 12-week, randomized, double-blind study, we randomly assigned BD patients to one of three groups: VPA plus either placebo (VPA+P, n = 57) or DM (30 mg/day, VPA+DM30, n = 56) or 60 mg/day (VPA+DM60, n = 53). The Young Mania Rating Scale and Hamilton Depression Rating Scale were used to evaluate symptom severity, and the hematological molecules were checked. Results: Paired t test showed that the WBC, neutrophils, platelets and RBCs were significantly lowered after 12 weeks of VPA+P or VPA+DM30 treatment. VPA+DM60 represented the protective effects in the WBCs, neutrophils, and RBCs but not in the platelets. We further calculated the changes of each hematological molecules after 12 weeks treatment. We found that combination use of DM60 significantly improved the decline in neutrophils induced by the long-term VPA treatment. Conclusion: Hematological molecule levels were lower after long-term treatment with VPA. VPA+DM60, which yielded the protective effect in hematological change, especially in the neutrophil counts. Thus, DM might be adjunct therapy for maintaining hematological molecules in VPA treatment.

Elucidating the role of ApxI in hemolysis and cellular damage by using a novel apxIA mutant of Actinobacillus pleuropneumoniae serotype 10

Nai-Yun Chang,Zeng-Weng Chen,Ter-Hsin Chen,Jiunn-Wang Liao,Cheng-Chung Lin,Maw-Sheng Chien,Wei-Cheng Lee,Jiunn-Horng Lin,Shih-Ling Hsuan 대한수의학회 2014 Journal of Veterinary Science Vol.15 No.1

Exotoxins produced by Actinobacillus (A.) pleuropneumoniae(Apx) play major roles in the pathogenesis of pleuropneumoniain swine. This study investigated the role of ApxI in hemolysisand cellular damage using a novel apxIA mutant, ApxIA336,which was developed from the parental strain A. pleuropneumoniae serotype 10 that produces only ApxI in vitro. The genotype of ApxIA336 was confirmed by PCR, Southernblotting, and gene sequencing. Exotoxin preparation derivedfrom ApxIA336 was analyzed for its bioactivity towardsporcine erythrocytes and alveolar macrophages. Analysisresults indicated that ApxIA336 contained a kanamycinresistantcassette inserted immediately after 1005 bp of theapxIA gene. Phenotype analysis of ApxIA336 revealed nodifference in the growth rate as compared to the parentalstrain. Meanwhile, ApxI production was abolished in thebacterial culture supernatant, i.e. exotoxin preparation. Theinability of ApxIA336 to produce ApxI corresponded to the lossof hemolytic and cytotoxic bioactivity in exotoxin preparation,as demonstrated by hemolysis, lactate dehydrogenase release,mitochondrial activity, and apoptosis assays. Additionally, thevirulence of ApxIA336 appeared to be attenuated by 15-fold inBALB/c mice. Collectively, ApxI, but not other components inthe exotoxin preparation of A. pleuropneumoniae serotype 10,was responsible for the hemolytic and cytotoxic effects onporcine erythrocytes and alveolar macrophages.

Smek promotes corticogenesis through regulating Mbd3’s stability and Mbd3/NuRD complex recruitment to genes associated with neurogenesis

Moon, Byoung-San,Yun, Hyung-Mun,Chang, Wen-Hsuan,Steele, Bradford H.,Cai, Mingyang,Choi, Si Ho,Lu, Wange Public Library of Science 2017 PLoS biology Vol.15 No.5

<▼1><P>The fate of neural progenitor cells (NPCs) during corticogenesis is determined by a complex interplay of genetic or epigenetic components, but the underlying mechanism is incompletely understood. Here, we demonstrate that Suppressor of Mek null (Smek) interact with methyl-CpG–binding domain 3 (Mbd3) and the complex plays a critical role in self-renewal and neuronal differentiation of NPCs. We found that Smek promotes Mbd3 polyubiquitylation and degradation, blocking recruitment of the repressive Mbd3/nucleosome remodeling and deacetylase (NuRD) complex at the neurogenesis-associated gene loci, and, as a consequence, increasing acetyl histone H3 activity and cortical neurogenesis. Furthermore, overexpression of Mbd3 significantly blocked neuronal differentiation of NPCs, and Mbd3 depletion rescued neurogenesis defects seen in <I>Smek1/2</I> knockout mice. These results reveal a novel molecular mechanism underlying Smek/Mbd3/NuRD axis-mediated control of NPCs’ self-renewal and neuronal differentiation during mammalian corticogenesis.</P></▼1><▼2><P><B>Author summary</B></P><P>Neural progenitor cells are self-renewing, multipotent cells that generate major neural cell types, including neurons and glia. Their fate during development of the cerebral cortex is determined by a complex interplay of genetic and epigenetic components. It has been shown that Suppressor of Mek null (Smek) proteins—which are evolutionarily conserved—play a role during the asymmetric cell division of neuroblasts in invertebrates. Methyl-CpG–binding domain 3 (Mbd3) protein, a core component of the repressive nucleosome remodeling and deacetylase (NuRD) complex, is an important epigenetic regulator that plays an essential role in mammalian development. In this study, we discovered that Smek interacts with Mbd3 and promotes its degradation via a posttranslational modification called polyubiquitylation. Degradation of Mb3, in turn, blocks recruitment of Mbd3/NuRD complex on target gene promoters, leading to an increase in neuronal differentiation during cortical development. This study not only elucidates a distinct mechanism for Smek-mediated neuronal differentiation but also identifies Smek as a negative regulator of the Mbd3 protein during cortical brain development.</P></▼2>

ALDH2 Gene: Its Effects on the Neuropsychological Functions in Patients with Opioid Use Disorder Undergoing Methadone Maintenance Treatment

Po-Wei Lee,Tzu-Yun Wang,Yun-Hsuan Chang,Sheng-Yu Lee,Shiou-Lan Chen,Ze-Cheng Wang,Po See Chen,Chun-Hsien Chu,San-Yuan Huang,Nian-Sheng Tzeng,I Hui Lee,Kao Chin Chen,Yen Kuang Yang,Jau-Shyong Hong,Ru-B 대한정신약물학회 2020 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.18 No.1

Objective: Patients with opioid use disorder (OUD) have impaired attention, inhibition control, and memory function. The aldehyde dehydrogenase 2 (ALDH2 ) gene has been associated with OUD and ALDH2 gene polymorphisms may affect aldehyde metabolism and cognitive function in other substance use disorder. Therefore, we aimed to investigate whether ALDH2 genotypes have significant effects on neuropsychological functions in OUD patients undergoing methadone maintenance therapy (MMT). Methods: OUD patients undergoing MMT were investigated and followed-up for 12 weeks. ALDH2 gene polymorphisms were genotyped. Connors’ Continuous Performance Test (CPT) and the Wechsler Memory Scale-Revised (WMS-R) were administered at baseline and after 12 weeks of MMT. Multivariate linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between the ALDH2 genotypes and performance on the CPTs and WMS-R. Results: We enrolled 86 patients at baseline; 61 patients completed the end-of-study assessments. The GEE analysis showed that, after the 12 weeks of MMT, OUD patients with the ALDH2 *1/*2+*2/*2 (ALDH2 inactive) genotypes had significantly higher commission error T-scores (p = 0.03), significantly lower hit reaction time T-scores (p = 0.04), and significantly lower WMS-R visual memory index scores (p = 0.03) than did patients with the ALDH2 1 */*1 (ALDH2 active) genotype. Conclusion: OUD patients with the ALDH2 inactive genotypes performed worse in cognitive domains of attention, impulse control, and memory than did those with the ALDH2 active genotype. We conclude that the ALDH2 gene is important in OUD and is associated with neuropsychological performance after MMT.

A Hybrid Dynamic Stabilization and Fusion System in Multilevel Lumbar Spondylosis

Li-Yu Fay,Chih-Chang Chang,Hsuan-Kan Chang,Tsung-Hsi Tu,Tzu-Yun Tsai,Ching-Lan Wu,Wen-Cheng Huang,Jau-Ching Wu,Henrich Cheng 대한척추신경외과학회 2018 Neurospine Vol.15 No.3

Objective: The Dynesys-Transition-Optima (DTO) hybrid system was designed to achieve arthrodesis and stabilization in patients with lumbar degeneration. Satisfactory outcomes were demonstrated previously. However, no study has evaluated the effects of using the DTO system in patients with lumbar spondylolisthesis or stenosis. Methods: This retrospective study included 35 consecutive patients with multilevel lumbar degeneration with or without spondylolisthesis who underwent surgery using the DTO system. Imaging studies included pre- and postoperative radiography, magnetic resonance imaging, and computed tomography. The clinical outcomes were measured by Japanese Orthopedic Association (JOA) scores, Oswestry Disability Index (ODI) scores, and a visual analogue scale (VAS) for back and leg pain. Results: Thirty patients (85.7%) with a mean age of 61.9 years completed the follow-up, with a mean duration of 35.1 months. There were 21 patients in the spondylolisthesis group and 9 in the stenosis group. The spondylolisthesis group had worse functional scores than the stenosis group preoperatively. After DTO surgery, all patients showed significant improvements in clinical outcomes, including VAS for back and leg pain, ODI, and JOA scores (p<0.05). There were no significant differences in clinical outcomes between the 2 groups. At a 2-year follow-up, lumbar alignment was well maintained in both groups (p=0.116). There were no significant differences in lumbar alignment between the 2 groups. Conclusion: During a follow-up period of over 2 years, both patients with spondylolisthesis and those with stenosis showed improvements and similar disability and pain scores after surgery using the DTO system. Lumbar alignment was also well maintained.

Eosinophilia in Pleural Effusions: a Speculative Negative Predictor for Malignancy

Chu, Fang-Yeh,Liou, Ching-Biau,Sun, Jen-Tang,Bei, Chia-Hao,Liou, Tse-Hsuan,Tan, N-Chi,Yu, Yun-Chieh,Chang, Chih-Chun,Yen, Tzung-Hai,Su, Ming-Jang Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.3

Background: Eosinophilic pleural effusion (EPE) is an eosinophil count more than 10% on cytology of pleural samples. Recently, it was reported that malignancy had been the most prevalent cause inducing EPE. Therefore, we conducted an analysis on the prevalence and etiology of EPE and investigated the relationship between EPE and malignancy. Materials and Methods: Data for pleural cell differential count from patients receiving thoracentesis during the period from January 2008 to December 2013 were compared with clinical data and established diagnosis of patients obtained via electronic chart review. Results: A total of 6,801 requests of pleural cytology from 3,942 patients with pleural effusion who had received thoracentesis were available at Far Eastern Memorial Hospital from 2008 to 2013, and of these subjects, 115 (2.9%) were found to have EPE. The most frequent cause of EPE was malignancy (33.0%, n=38), followed by parapneumonic effusions (27.8%, n=32), tuberculosis pleuritis (13.9%, n=16), transudate effusions (12.2%, n=14) and the presence of blood or air in pleural space (10.4%, n=12). Additionally, an inverse relationship of eosinophilia in pleural fluid was identified in patients with malignancy and EPE. The cut-off eosinophil count in pleural fluid was 15% for the most accurate discrimination between malignancy and benign disorders in patients with EPE. At the cut-off level, the sensitivity and specificity were 65.8% and 67.5%, respectively. Conclusions: Pleural fluid eosinophilia was a speculative negative predictor for malignancy, despite the fact that cancers, including lung cancers and metastatic cancers to lung, were the most leading cause of pleural fluid eosinophilia. An inverse correlation was observed between the pleural eosinophil percentage and the likelihood of malignancy in patients with EPE.