Center for Translational Research in Biomedical science

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Center for Translational Research in Biomedical science

science, Taiwan
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Shih F.-Y.,Chang Gung University | Chuang Y.-C.,Chang Gung University | Chuang Y.-C.,Center for Translational Research in Biomedical science | Chuang Y.-C.,National University of Kaohsiung | And 7 more authors.
Seizure | Year: 2017

Purpose Patients with epilepsy are frequently required to take antiepileptic drugs (AEDs) for a long period of time. Many studies have shown that AEDs have a negative influence on endocrine function including the thyroid gland, however the risk factors for the development of low thyroid function in these patients are unclear. This study aimed to determine the potential risk factors of low thyroid function in patients with epilepsy. Method This was a cross-sectional study including 298 patients with epilepsy. Patients with previous thyroid disease were excluded. Epidemiologic data, type of epilepsy, etiology, the age of seizure onset, duration of epilepsy, intractable epilepsy, and number and dosage of AEDs were recorded. Levels of free thyroxine (fT4) and thyroid stimulating hormone (TSH) were measured.Results: Fifty-two of the 298 (17.4%) patients had low fT4. Older age (P = 0.004), female sex (P = 0.014), longer duration of epilepsy (P = 0.001), and intractable epilepsy (P = 0.009) were significantly associated with low fT4. Regarding individual AEDs, carbamazepine (30.1%), topiramate (28.6%), and levetiracetam (24.3%) were significantly associated with the presence of low fT4. After stepwise logistic regression of all significant variables, female sex, older age, three or more AEDs, and carbamazepine were independent risk factors for low fT4. Conclusions Female patients with epilepsy and an older age, AED polytherapy, and carbamazepine treatment had a higher risk of low fT4. Thyroid function in these patients should be monitored closely. © 2017 British Epilepsy Association


Lu Y.-T.,Kaohsiung Chang Gung Memorial Hospital | Hsu C.-W.,Kaohsiung Chang Gung Memorial Hospital | Tsai W.-C.,Kaohsiung Chang Gung Memorial Hospital | Cheng M.-Y.,Chang Gung Memorial Hospital | And 8 more authors.
Epilepsy and Behavior | Year: 2016

Background: Status epilepticus (SE) is a neurological emergency associated with a high mortality rate and long-term cognitive sequelae. Status epilepticus in pregnancy poses a tremendous threat to both mother and fetus, making a correct diagnosis and treatment a challenging task for clinicians. The prevalence, underlying etiology, and outcomes of pregnancy-related SE remain largely unknown. Methods: We retrospectively studied all SE episodes (n = 366) in patients admitted to our neurological ICU over a period of 8.5 years. The patients who developed SE during pregnancy and within 6 months after delivery were considered to have pregnancy-related SE. Patients with eclampsia were not included as they were usually cared for in our obstetric unit. Results: Seven patients with pregnancy-related SE were identified (2.1% of all cases of SE), with the majority (85%) occurring de novo except for one patient who had a previous history of epilepsy-related SE due to withdrawal of antiepileptic medication. In terms of etiology, limbic encephalitis and cerebral venous sinus thrombosis were the two main etiologies of de novo SE associated with pregnancy. The overall mortality rate was 28.5% at discharge, and poor outcomes were especially noted in the patients with limbic encephalitis compared to other etiologies. Conclusions: Pregnancy-associated SE is rare and predominantly occurs in patients without a history of epilepsy. An autoimmune etiology should be considered in pregnant patients with de novo SE, which was associated with poor outcomes. Thorough investigations and prompt treatment according to the etiology may be required to improve the final outcomes of both mother and fetus. © 2016 Elsevier Inc.


Tsai M.-H.,Kaohsiung Chang Gung Memorial Hospital | Fu T.-Y.,Kaohsiung Veteran General Hospital | Chen N.-C.,Kaohsiung Chang Gung Memorial Hospital | Shih F.-Y.,Kaohsiung Chang Gung Memorial Hospital | And 7 more authors.
Medicine (United States) | Year: 2015

Antithyroid antibodies (Abs) are associated with epilepsy in steroid-responsive encephalopathy, but have been rarely studied in unselected epilepsy patients. This study aimed to characterize the prevalence and associated factors of antithyroid Abs and other auto-Abs in adult patients with epilepsy. Epilepsy patients without autoimmune disorders were surveyed for antinuclear antibody (ANA), anti-b2 glycoprotein 1 antibody (ab2GP1), anticardiolipin IgG Ab, antimicrosomal antibody (AMA), antithyroglobulin antibody (ATA), and thyroid function test. Of 319 patients, 75 (23.5%) were positive for at least 1 Ab. The most common Ab was anticardiolipin antibody (aCL) (30/319, 9.4%), followed by AMA (24/319, 7.5%), ANA (18/319, 5.6%), ab2GP1 (18/319, 6.5%), and ATA (6/319, 3.25%). Antimicrosomal Abs were significantly more frequent in patients who were female, older at disease onset, older at the time of study, and had unknown seizure etiology. The presence of aCL was significantly associated with more frequent seizures. Most patients with antithyroid Ab were female and had focal seizures with unknown etiology. The association of different auto-Abs with different factors suggests that they may have different roles in adult patients with epilepsy. Recurrent seizures and certain antiepileptic medications may cause the production of aCL. The role of antithyroid Abs in adult focal epilepsy with unknown cause, especially in females, warrants further evaluation because of the potential implications on treatment. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Alving B.,Uniformed Services University of the Health Sciences | Dai K.,Shanghai JiaoTong University | Chan S.H.H.,Center for Translational Research in Biomedical science
Translational Research in Biomedicine | Year: 2013

During the past six years, multiple countries have embraced the concept of translational medicine. This is generally understood as improving prevention and treatment strategies for patients and for communities through translating discoveries in basic and clinical research into products and practices in an efficient, cost-effective manner. Although the emphasis on the different domains of translation vary among countries and institutions, all are developing an increasing ability to share ideas and practices through an international language of translation. Copyright © 2013 S. Karger AG, Basel.


Tsai M.-H.,Kaohsiung Chang Gung Memorial Hospital | Tsai M.-H.,Meiho University | Kuo P.-W.,National Yang Ming University | Myers C.T.,University of Washington | And 9 more authors.
European Journal of Paediatric Neurology | Year: 2016

Purpose To study the genetics and functional alteration of a family with X-linked lissencephaly and subcortical band heterotopia. Methods Five affected patients (one male with lissencephaly, four female with subcortical band heterotopia) and their relatives were studied. Sanger sequencing of DCX gene, allele specific PCR and molecular inversion probe technique were performed. Mutant and wild type of the gene products, namely doublecortin, were expressed in cells followed by immunostaining to explore the localization of doublecortin and microtubules in cells. In vitro microtubule-binding protein spin-down assay was performed to quantify the binding ability of doublecortin to microtubules. Key findings We identified a novel DCX mutation c.785A > G, p.Asp262Gly that segregated with the affected members of the family. Allele specific PCR and molecular inversion probe technique demonstrated that the asymptomatic female carrier had an 8% mutant allele fraction in DNA derived from peripheral leukocytes. This mother had 7 children, 4 of whom were affected and all four affected siblings carried the mutation. Functional study showed that the mutant doublecortin protein had a significant reduction of its ability to bind microtubules. Significance Low level mosaicism could be a cause of inherited risk from asymptomatic parents for DCX related lissencephaly-subcortical band heterotopia spectrum. This is particularly important in terms of genetic counselling for recurrent risk of future pregnancies. The reduced binding affinity of mutant doublecortin may contribute to developmental malformation of the cerebral cortex. © 2016 European Paediatric Neurology Society


Sun C.-K.,I - Shou University | Zhen Y.-Y.,Kaohsiung Chang Gung Memorial Hospital | Leu S.,Center for Translational Research in Biomedical science | Tsai T.-H.,Kaohsiung Chang Gung Memorial Hospital | And 10 more authors.
International Journal of Cardiology | Year: 2014

Background This study tested whether adipose-derived mesenchymal stem cells (ADMSC) embedded in platelet-rich fibrin (PRF) scaffold is superior to direct ADMSC implantation in improving left ventricular (LV) performance and reducing LV remodeling in a rat acute myocardial infarction (AMI) model of left anterior descending coronary artery (LAD) ligation. Methods Twenty-eight male adult Sprague Dawley rats equally divided into group 1 [sham control], group 2 (AMI only), group 3 (AMI + direct ADMSC implantation), and group 4 (AMI + PRF-embedded autologous ADMSC) were sacrificed on day 42 after AMI. Results LV systolic and diastolic dimensions and volumes, and infarct/fibrotic areas were highest in group 2, lowest in group 1 and significantly higher in group 3 than in group 4, whereas LV performance and LV fractional shortening exhibited a reversed pattern (p < 0.005). Protein expressions of inflammation (oxidative stress, IL-1β, MMP-9), apoptosis (mitochondrial Bax, cleaved PARP), fibrosis (Smad3, TGF-β), and pressure-overload biomarkers (BNP, MHC-β) displayed a pattern similar to that of LV dimensions, whereas anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), and anti-fibrotic (Smad1/5, BMP-2) indices showed a pattern similar to that of LV performance among the four groups (all p < 0.05). Angiogenesis biomarkers at protein (CXCR4, SDF-1α, VEGF), cellular (CD31 +, CXCR4 +, SDF-1α +), and immunohistochemical (small vessels) levels, and cardiac stem cell markers (C-kit +, Sca-1 +) in infarct myocardium were highest in group 4, lowest in group 1, and significantly higher in group 3 than in group 2 (all p < 0.005). Conclusion PRF-embedded ADMSC is superior to direct ADMSC implantation in preserving LV function and attenuating LV remodeling. © 2014 Elsevier Ireland Ltd.


Hsu L.-W.,Center for Translational Research in Biomedical science | Hsu L.-W.,Kaohsiung Chang Gung Memorial Hospital | Nakano T.,Center for Translational Research in Biomedical science | Nakano T.,Chang Gung University | And 21 more authors.
Hepatology Research | Year: 2015

Aim: Despite the great advances and excellent outcomes of liver transplantation (LT), small-for-size (SFS) graft syndrome is a life-threatening complication that remains to be overcome. In the present study, we investigated the therapeutic effect of combined treatment with granulocyte colony-stimulating factor (G-CSF) and a dipeptidyl peptidase IV (DPP-IV) inhibitor on SFS liver graft syndrome. Methods: The transplantation of small-sized Lewis donor livers into green fluorescent protein (GFP) transgenic Wistar rats was performed and the recipients were randomly assigned to one of four groups (without treatment, DPP-IV inhibitor treatment, G-CSF treatment and G-CSF/DPP-IV inhibitor combination). Recombinant human G-CSF was injected s.c. at a dose of 2μg/kg per day starting 5 days prior to transplantation. G-CSF was combined with the p.o. administration of a DPP-IV inhibitor (2mg/kg per day) after transplantation until the end of the observation period. Results: The post-transplant survival and liver function of rats treated with G-CSF/DPP-IV inhibitor combination therapy were significantly improved with an increased number of recipient-derived GFP positive cells into the liver grafts. A confocal microscopy study showed cytokeratin (CK)-18 and GFP positive hepatic progenitor cells in the parenchyma of the liver allografts. Untreated rats and rats treated with either G-CSF or DPP-IV inhibitor did not exhibit the prolonged survival and had less GFP and CK-18 positive cells in the liver grafts after SFS LT. Conclusion: Our results suggest that combined treatment with G-CSF and DPP-IV inhibitor may synergistically induce migration and differentiation of recipient-derived stem cells into the hepatic progenitor cells, resulting in the amelioration of SFS liver graft syndrome. © 2014 The Japan Society of Hepatology.


PubMed | Center for Translational Research in Biomedical science and Kaohsiung Chang Gung Memorial Hospital
Type: Journal Article | Journal: Hepatology research : the official journal of the Japan Society of Hepatology | Year: 2015

Despite the great advances and excellent outcomes of liver transplantation (LT), small-for-size (SFS) graft syndrome is a life-threatening complication that remains to be overcome. In the present study, we investigated the therapeutic effect of combined treatment with granulocyte colony-stimulating factor (G-CSF) and a dipeptidyl peptidase IV (DPP-IV) inhibitor on SFS liver graft syndrome.The transplantation of small-sized Lewis donor livers into green fluorescent protein (GFP) transgenic Wistar rats was performed and the recipients were randomly assigned to one of four groups (without treatment, DPP-IV inhibitor treatment, G-CSF treatment and G-CSF/DPP-IV inhibitor combination). Recombinant human G-CSF was injected s.c. at a dose of 2g/kg per day starting 5 days prior to transplantation. G-CSF was combined with the p.o. administration of a DPP-IV inhibitor (2mg/kg per day) after transplantation until the end of the observation period.The post-transplant survival and liver function of rats treated with G-CSF/DPP-IV inhibitor combination therapy were significantly improved with an increased number of recipient-derived GFP positive cells into the liver grafts. A confocal microscopy study showed cytokeratin (CK)-18 and GFP positive hepatic progenitor cells in the parenchyma of the liver allografts. Untreated rats and rats treated with either G-CSF or DPP-IV inhibitor did not exhibit the prolonged survival and had less GFP and CK-18 positive cells in the liver grafts after SFS LT.Our results suggest that combined treatment with G-CSF and DPP-IV inhibitor may synergistically induce migration and differentiation of recipient-derived stem cells into the hepatic progenitor cells, resulting in the amelioration of SFS liver graft syndrome.

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