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.

Comedications and potential drug-drug interactions with direct-acting antivirals in hepatitis C patients on hemodialysis

( Po-yao Hsu ),( Yu-ju Wei ),( Jia-jung Lee ),( Sheng-wen Niu ),( Jiun-chi Huang ),( Cheng-ting Hsu ),( Tyng-yuan Jang ),( Ming-lun Yeh ),( Ching-i Huang ),( Po-cheng Liang ),( Yi-hung Lin ),( Ming-ye 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.1

Background/Aims: Direct-acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). Conclusions: HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs. (Clin Mol Hepatol 2021;27:186-196)

Predicting the surgical reparability of large-to-massive rotator cuff tears by B-mode ultrasonography: a cross-sectional study

Po-Cheng Chen,Kuan-Ting Wu,Yi-Cun Chen,Yu-Chi Huang,Ching-Di Chang,Wei-Che Lin,Wen-Yi Chou 대한초음파의학회 2022 ULTRASONOGRAPHY Vol.41 No.1

Purpose: This study aimed to compare the ability of B-mode ultrasonography and magnetic resonance imaging (MRI) to predict the repairability of large-to-massive rotator cuff tears (RCTs). Methods: This cross-sectional study included participants with large-to-massive RCTs who underwent arthroscopic repair. B-mode ultrasonography and MRI were conducted prior to arthroscopic repair. B-mode ultrasonography was used to evaluate the echogenicity of the rotator cuff muscle using the Heckmatt scale. Intra-rater and inter-rater reliabilities were examined for two independent physicians. MRI was used to evaluate the degrees of tendon retraction, fatty infiltration of rotator cuff muscles, and muscle atrophy. Finally, two experienced orthopedic surgeons performed surgery and decided whether the torn stump could be completely repaired intraoperatively. Results: Fifty participants were included, and 32 complete repairs and 18 partial repairs were performed. B-mode ultrasonography showed good intra-rater reliability and inter-rater reliability for assessment of the muscle echogenicity of the supraspinatus and infraspinatus muscles. The correlation coefficients between B-mode ultrasound findings and MRI findings showed medium to large effect sizes (r=0.4-0.8). The Goutallier classification of the infraspinatus muscles was the MRI predictor with the best discriminative power for surgical reparability (area under the curve [AUC], 0.89; 95% confidence interval [CI], 0.81 to 0.98), while the Heckmatt scale for infraspinatus muscles was the most accurate ultrasound predictor (AUC, 0.85; 95% CI, 0.74 to 0.96). No significant differences in AUCs among the MRI and ultrasound predictors were found. Conclusion: B-mode ultrasonography was a reliable examination tool and had a similar ability to predict surgical reparability to that of MRI among patients with large-to-massive RCTs. Purpose: This study aimed to compare the ability of B-mode ultrasonography and magnetic resonance imaging (MRI) to predict the repairability of large-to-massive rotator cuff tears (RCTs).Methods: This cross-sectional study included participants with large-to-massive RCTs who underwent arthroscopic repair. B-mode ultrasonography and MRI were conducted prior to arthroscopic repair. B-mode ultrasonography was used to evaluate the echogenicity of the rotator cuff muscle using the Heckmatt scale. Intra-rater and inter-rater reliabilities were examined for two independent physicians. MRI was used to evaluate the degrees of tendon retraction, fatty infiltration of rotator cuff muscles, and muscle atrophy. Finally, two experienced orthopedic surgeons performed surgery and decided whether the torn stump could be completely repaired intraoperatively.Results: Fifty participants were included, and 32 complete repairs and 18 partial repairs were performed. B-mode ultrasonography showed good intra-rater reliability and inter-rater reliability for assessment of the muscle echogenicity of the supraspinatus and infraspinatus muscles. The correlation coefficients between B-mode ultrasound findings and MRI findings showed medium to large effect sizes (r=0.4-0.8). The Goutallier classification of the infraspinatus muscles was the MRI predictor with the best discriminative power for surgical reparability (area under the curve [AUC], 0.89; 95% confidence interval [CI], 0.81 to 0.98), while the Heckmatt scale for infraspinatus muscles was the most accurate ultrasound predictor (AUC, 0.85; 95% CI, 0.74 to 0.96). No significant differences in AUCs among the MRI and ultrasound predictors were found.Conclusion: B-mode ultrasonography was a reliable examination tool and had a similar ability to predict surgical reparability to that of MRI among patients with large-to-massive RCTs.

Pulmonary Arterial Thrombosis in a Patient With an Atrial Septal Defect and Eisenmenger Syndrome

Ching-Wei Lee,Shao-Sung Huang,Po-Hsun Huang 대한심장학회 2012 Korean Circulation Journal Vol.42 No.11

Pulmonary hypertension is characterized by elevated pulmonary arterial pressure and secondary right ventricular failure. A thromboembolic occlusion of the proximal or distal pulmonary vasculature results in chronic thromboembolic pulmonary hypertension. We report an uncommon case that presented to our hospital with symptoms of dyspnea on exertion over 2 years. The patient had been treated for profound pulmonary thrombosis and right ventricular failure with adequate anticoagulation and sildenafil. Our echocardiography disclosed a large atrial septal defect with severe pulmonary hypertension and right ventricular failure. A diagnosis of Eisenmenger syndrome with pulmonary artery thrombosis was made. Although Eisenmenger syndrome with pulmonary thrombosis is well described in western societies,a huge pulmonary thrombosis is seldom reported in eastern countries. Profound pulmonary thrombosis may obfuscate the actual diagnosis of pulmonary artery hypertension with underlying congenital heart disease. A physical examination and echocardiography are essential in patients with pulmonary hypertension.

Can Elderly Patients with Severe Mitral Regurgitation Benefit from Trans-catheter Mitral Valve Repair?

Ching-Wei Lee,Shih-Hsien Sung,Wei-Ming Huang,Yi-Lin Tsai,Hsiang-Yao Chen,Chiao-Po Hsu,Chun-Che Shih,Kuo-Piao Chung 대한심장학회 2019 Korean Circulation Journal Vol.49 No.6

Background and ObjectivesAge is a traditional risk factor for open-heart surgery. The efficacy and safety of transcatheter edge-to-edge mitral valve repair, using MitraClip (Abbott Vascular), has been demonstrated in patients with severe mitral regurgitation (MR). Since octogenarians or older patients are usually deferred to receive open-heart surgery, the main interest of this study is to elucidate the procedural safety and long-term clinical impact of MitraClip in elderly patients. MethodsPatients with symptomatic severe MR were evaluated by the heart team. For those with high or prohibitive surgical risks, transcatheter mitral valve repair was performed in hybrid operation room. Transthoracic echocardiography (TTE), blood tests, and six-minute walk test (6MWT) were performed before, 1-month, 6-months, and 1 year after index procedure. ResultsA total of 46 consecutive patients receiving MitraClip procedure were enrolled. Nineteen patients (84.2±4.0 years) were over 80-year-old and 27 (73.4±11.1 years) were younger than 80. Compare to baseline, the significant reduction in MR severity was achieved after the procedure and sustained. All the patients benefited from significant improvement in New York Heart Association functional class. The 6-minute walk test (6MWT) increased from 259±114 to 319±92 meters (p=0.03) at 1 year. The overall 1-year survival rate was 80% in the elderly and 88% in those <80 years, p=0.590. Baseline 6MWT was a predictor for all-cause mortality (odds ratio, 0.99; 95% confidence interval, 0.982–0.999; p=0.026) after the MitraClip procedure. ConclusionsTrans-catheter edge-to-edge mitral valve repairs are safe and have positive clinical impact in subjects with severe MR, even in advanced age.

Correlation Between Fiber Orientation and Geometrical Shrinkage of Injected Parts Under the Influence of Flow-Fiber Coupling Effect

Chao-Tsai Huang,Jun-Zheng Wang,Cheng-Hong Lai,Sheng-Jye Hwang,Po-Wei Huang,Hsin-Shu Peng 한국정밀공학회 2023 International Journal of Precision Engineering and Vol.10 No.4

Fiber reinforced thermoplastics (FRP) have been widely used in automotive industry. However, how does the flow-fiber coupling effect influence the micro fiber orientation and further affect the geometrical shrinkage of the final part that is not fully understood yet. In this study, a complex center-gated plate has been applied to study the influence of the flow-fiber coupling effect on the fiber orientation variation and the geometrical change through numerical simulation. Then the practical verification through the micro-computed tomography (micro-CT) and image processing technology was carried out. Results show that in the presence of the flow-fiber coupling the required spruce pressure will be higher compared to no coupling case. In addition, the melt flow front pattern will be changed from “convex-flat” to “convex-concave” under the influence of this coupling. Moreover, in the presence of the flow-fiber coupling effect, the wider core width for fiber orientation tensor in the flow direction (A11) can be obtained from upstream to downstream regions for the same model. However, in the downstream region (i.e. in the FR), the flow-fiber coupling effect is more significantly due to the action of less shear rate in that region. Finally, through the measurement of the left–right asymmetrical shape of the FR for Model I (or Model II), the reason is that the flow-fiber coupling effect will switch the fiber orientation from the flow direction (A11) dominate to the cross-flow direction (A22) dominate. This asymmetrical fiber orientation distribution will further create that asymmetrical shrinkage shape of final part. The correlation between fiber orientation and geometrical shrinkage can be achieved.

Nerve growth factor upregulates sirtuin 1 expression in cholestasis: a potential therapeutic target

Ming-Shian Tsai,Po-Huang Lee,Cheuk-Kwan Sun,Ting-Chia Chiu,Yu-Chun Lin,I-Wei Chang,Po-Han Chen,Ying-Hsien Kao 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

This study investigated the regulatory role of nerve growth factor (NGF) in sirtuin 1 (SIRT1) expression in cholestatic livers. We evaluated the expression of NGF and its cognate receptors in human livers with hepatolithiasis and the effects of NGF therapy on liver injury and hepatic SIRT1 expression in a bile duct ligation (BDL) mouse model. Histopathological and molecular analyses showed that the hepatocytes of human diseased livers expressed NGF, proNGF (a precursor of NGF), TrkA and p75NTR, whereas only p75NTR was upregulated in hepatolithiasis, compared with non-hepatolithiasis livers. In the BDL model without NGF therapy, p75NTR, but not TrkA antagonism, significantly deteriorated BDL-induced liver injury. By contrast, the hepatoprotective effect of NGF was abrogated only by TrkA and not by p75NTR antagonism in animals receiving NGF therapy. Intriguingly, a positive correlation between hepatic SIRT1 and NGF expression was found in human livers. In vitro studies demonstrated that NGF upregulated SIRT1 expression in mouse livers and human Huh-7 and rodent hepatocytes. Both NGF and proNGF induced protective effects against hydrogen peroxide-induced cytotoxicity in Huh-7 cells, whereas inhibition of TrkA and p75NTR activity prevented oxidative cell death. Mechanistically, NGF, but not proNGF, upregulated SIRT1 expression in human Huh-7 and rodent hepatocytes via nuclear factor (NF)-κB activity, whereas NGF-induced phosphoinositide-3 kinase/Akt, extracellular signal–regulated kinase and NF-κB signaling and SIRT1 activity were involved in its hepatoprotective effects against oxidative injury. These findings suggest that pharmacological manipulation of the NGF/SIRT1 axis might serve as a novel approach for the treatment of cholestatic disease.

A Systemic Review and Experts’ Consensus for Long-acting Injectable Antipsychotics in Bipolar Disorder

Yuan-Hwa Chou,Po-Chung Chu,Szu-Wei Wu,Jen-Chin Lee,Yi-Hsuan Lee,I-Wen Sun,Chen-Lin Chang,Chien-Liang Huang,I-Chao Liu,Chia-Fen Tsai,Yung-Chieh Yen 대한정신약물학회 2015 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.13 No.2

Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence, partial adherence, and in reducing relapse in BD. Various long-acting injectable (LAI) antipsychotics are available, including fluphenazine decanoate, haloperidol decanoate, olanzapine pamoate, risperidone microspheres, paliperidone palmitate, and aripiprazole monohydrate. Due to the increasing number of BD patients receiving LAI antipsychotics, treatment guidelines have been developed. However, the clinical applicability of LAI antipsychotics remains a global cause for concern, particularly in Asian countries. Expert physicians from Taiwan participated in a consensus meeting, which was held to review key areas based on both current literature and clinical practice. The purpose of this meeting was to generate a practical and implementable set of recommendations for LAI antipsychotic use to treat BD; target patient groups, dosage, administration, and adverse effects were considered. Experts recommended using LAI antipsychotics in patients with schizophrenia, rapid cycling BD, BD I, and bipolar-type schizoaffective disorder. LAI antipsychotic use was recommended in BD patients with the following characteristics: multiple episodes and low adherence; seldom yet serious episodes; low adherence potential per a physician’s clinical judgment; preference for injectable agents over oral agents; and multiple oral agent users still experiencing residual symptoms.

Antioxidant, Antidiabetic, and Antihypertensive Properties of Echinacea purpurea Flower Extract and Caffeic Acid Derivatives Using In Vitro Models

Shiow-Ying Chiou,Jih-Min Sung,Po-Wei Huang,Sheng-Dun Lin 한국식품영양과학회 2017 Journal of medicinal food Vol.20 No.2

The extraction yield, total phenols, caffeic acid derivatives (CAD), and antioxidant properties of 50% ethanolic Echinacea purpurea flower extract were determined. The in vitro inhibitory effects of 50% ethanolic extract and CAD on α-amylase, α-glucosidase, and angiotensin-converting enzyme (ACE) linked with type 2 diabetes were also investigated. The extraction yield, total phenols, and total CAD of the extract were 27.04%, 195.69 mg CAE/g and 78.42 mg/g, respectively. Cichoric acid (56.03 mg/g) was the predominant CAD compound in the extract. The extract exhibited good antioxidant properties. The extract and CAD inhibited α-amylase, α-glucosidase, and ACE activities in a concentration-dependent manner. Among the tested samples, chlorogenic acid, and caffeic acid (IC50 of 1.71–1.81 mg/mL) had the highest α-amylase inhibitory activity, cichoric acid (IC50 of 0.28 mg/mL) showed higher α-glucosidase inhibitory activity. Both chlorogenic acid and caffeic acid (IC50 of 0.11–0.14 mg/mL) demonstrated higher ACE-inhibitory activity. The in vitro results suggest that E. purpurea extract and CAD have good potential for managing hyperglycemia and hypertension. Overall, the data suggest it is a choice for developing antihyperglycemia and antihypertension compounds from field-grown E. purpurea.

Infusion of Human Mesenchymal Stem Cells Improves Regenerative Niche in Thioacetamide-Injured Mouse Liver

Kao Ying-Hsien,Lin Yu-Chun,Lee Po-Huang,Lin Chia-Wei,Chen Po-Han,Tai Tzong-Shyuan,Chang Yo-Chen,Chou Ming-Huei,Chang Chih-Yang,Sun Cheuk-Kwan 한국조직공학과 재생의학회 2020 조직공학과 재생의학 Vol.17 No.5

Background: This study investigated whether xenotransplantation of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) reduces thioacetamide (TAA)-induced mouse liver fibrosis and the underlying molecular mechanism. Methods: Recipient NOD/SCID mice were injected intraperitoneally with TAA twice weekly for 6 weeks before initial administration of WJ-MSCs. Expression of regenerative and pro-fibrogenic markers in mouse fibrotic livers were monitored post cytotherapy. A hepatic stallate cell line HSC-T6 and isolated WJ-MSCs were used for in vitro adhesion, migration and mechanistic studies. Results: WJ-MSCs were isolated from human umbilical cords by an explant method and characterized by flow cytometry. A single infusion of WJ-MSCs to TAA-treated mice significantly reduced collagen deposition and ameliorated liver fibrosis after 2-week therapy. In addition to enhanced expression of hepatic regenerative factor, hepatocyte growth factor, and PCNA proliferative marker, WJ-MSC therapy significantly blunted pro-fibrogenic signals, including Smad2, RhoA, ERK. Intriguingly, reduction of plasma fibronectin (pFN) in fibrotic livers was noted in MSC-treated mice. In vitro studies further demonstrated that suspending MSCs triggered pFN degradation, soluble pFN conversely retarded adhesion of suspending MSCs onto type I collagen-coated surface, whereas pFN coating enhanced WJ-MSC migration across mimicked wound bed. Moreover, pretreatment with soluble pFN and conditioned medium from MSCs with pFN strikingly attenuated the response of HSC-T6 cells to TGF-β1-stimulation in Smad2 phosphorylation and RhoA upregulation. Conclusion: These findings suggest that cytotherapy using WJ-MSCs may modulate hepatic pFN deposition for a better regenerative niche in the fibrotic livers and may constitute a useful anti-fibrogenic intervention in chronic liver diseases.