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Lee T.-M.,Tainan Municipal An Nan Hospital China Medical University | Lee T.-M.,China Medical University at Taichung | Lee T.-M.,Taipei Medical University | Lin S.-Z.,China Medical University at Taichung | And 4 more authors.

Cardiac remodeling was shown to be associated with reduced gap junction expression after myocardial infarction. A reduction in gap junctional proteins between myocytes may trigger ventricular arrhythmia. Therefore, we investigated whether N-acetylcysteine exerted antiarrhythmic effect by preserving connexin43 expression in postinfarcted rats, focusing on cAMP downstream molecules such as protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac). Male Wistar rats after ligating coronary artery were randomized to either vehicle, or N-acetylcysteine for 4 weeks starting 24 hours after operation. Infarct size was similar between two groups. Compared with vehicle, cAMP levels were increased by N-acetylcysteine treatment after infarction. Myocardial connexin43 expression was significantly decreased in vehicle-treated infarcted rats compared with sham operated rats. Attenuated connexin43 expression and function were blunted after administering N-acetylcysteine, assessed by immunofluorescent analysis, dye coupling, Western blotting, and real-time quantitative RT-PCR of connexin43. Arrhythmic scores during programmed stimulation in the N-acetylcysteine-treated rats were significantly lower than those treated with vehicle. In an ex vivo study, enhanced connexin43 levels afforded by N-acetylcysteine were partially blocked by either H-89 (a PKA inhibitor) or brefeldin A (an Epac-signaling inhibitor) and completely blocked when H-89 and brefeldin A were given in combination. Addition of either the PKA specific activator N6Bz or Epac specific activator 8-CPT did not have additional increased connexin43 levels compared with rats treated with lithium chloride alone. These findings suggest that N-acetylcysteine protects ventricular arrhythmias by attenuating reduced connexin43 expression and function via both PKA- and Epac-dependent pathways, which converge through the inactivation of glycogen synthase kinase-3β. © 2013 Lee et al. Source

Cheng C.-H.,China Medical University at Taichung | Cheng C.-H.,Tainan Municipal An Nan Hospital China Medical University | Huang H.-M.,China Medical University at Taichung | Lin H.-L.,China Medical University at Taichung | Chiou S.-M.,China Medical University at Taichung
British Journal of Neurosurgery

Background. Accurate stereotactic placement of the electrode into the subthalamic nucleus (STN) is imperative to the therapeutic efficacy of deep brain stimulation (DBS). However, it is not always possible to directly visualize the very small STN using 1.5T MR imaging. Objective. To evaluate whether 3T MR imaging can provide better identification of the STN and clinical outcome than 1.5T MR imaging. Methods. Thirty-nine patients with advanced Parkinson's disease underwent 1.5T (n = 16) or 3T (n = 23) fast spin echo T2-weighted (FSE-T2WI) MR imaging for targeting the STN. A semi-quantitative 3-point scoring system was proposed to rank the clearness of STN contour: Score "0" if non-visible; Score "1" if visible but with blurred margin; and "2" if visible with clear margin. The unified Parkinson's disease rating scale (UPDRS) was also compared before operation and post-operation. Results. The STN score was 2 in all the patients of the 3T group, whereas it was relatively blurred (mean score, 1.19) in the 1.5T group (P < 0.001). The number of microelectrode trajectories (1.2 versus 1.5; P < 0.05) was lower in the 3T group; consequently, the operative time was also less (P < 0.05) as compared with that in the 1.5T group. The outcome of UPDRS motor examination showed no significant difference in two groups. Conclusion. 3T MR imaging is a reliable and more accurate method for direct targeting of the STN for DBS surgery. However, the technique of high-sequence MR imaging may not influence the clinical outcome significantly. © 2014 The Neurosurgical Foundation. Source

Chang K.-C.,Jianan Psychiatric Center | Chang K.-C.,National Cheng Kung University | Wang J.-D.,National Cheng Kung University | Tang H.-P.,Tainan Municipal An Nan Hospital China Medical University | And 2 more authors.
Health and Quality of Life Outcomes

Background: The brief version of World Health Organization Quality of Life assessment (WHOQOL-BREF), a useful outcome measure for clinical decision making, has been evaluated using classical test theory (CTT) for psychometric properties on heroin-dependent patients. However, CTT has a major disadvantage of invalid summated score, and using Rasch models can overcome the shortcoming. The purpose of this study was using Rasch models to evaluate the psychometric properties of the WHOQOL-BREF for heroin-dependent patients, and the hypothesis was that each WHOQOL-BREF domain is unidimensional.Methods: Two hundred thirty six participants (24 females, mean [SD] age = 38.07 [7.44] years, first used heroin age = 26.13 [6.32] years), with a diagnosis of opioid dependence, were recruited from a methadone maintenance treatment program. Each participant filled out the WHOQOL-BREF. Parallel analysis (PA) and Rasch rating scale models were used for statistical analyses.Results: Based on the PA analyses, four domains of the WHOQOL-BREF were unidimensional. The Rasch analyses showed three negatively worded items (2 in Physical and 1 in Psychological) reported as misfits that may not contribute to the Physical and Psychological domains; one positively worded item in the Physical domain may be redundant. All values for the separation indices were above 2 except for the person separation index in the Physical domain (1.93). Category functioning and item independency of four WHOQOL-BREF domains were supported by the Rasch analyses, and there were 5 items showing the differential item function (DIF) for positive versus negative HIV (human immunodeficiency virus) infection.Conclusions: The WHOQOL-BREF is a valid outcome measure for assessing general quality of life for substance abusers in terms of physical, psychological, social, and environmental factors. It can also be used as a treatment outcome measure to evaluate the effect of treatments for substance abusers. However, the three misfit negatively worded items should be used with caution because the substance abuser may not fully understand their meaning. Future research may apply cognitive interviews to determine the cognitive functioning of substance abusers and their interpretation of negatively worded items. © 2014 Chang et al.; licensee BioMed Central Ltd. Source

Yeh D.-C.,China Medical University Beigan Hospital | Chan T.-M.,China Medical University Beigan Hospital | Chan T.-M.,China Medical University An Nan Hospital | Harn H.-J.,China Medical University at Taichung | And 7 more authors.
Cell Transplantation

Adipose tissue-derived stem cells (ADSCs) have two essential characteristics with regard to regenerative medicine: the convenient and efficient generation of large numbers of multipotent cells and in vitro proliferation without a loss of stemness. The implementation of clinical trials has prompted widespread concern regarding safety issues and has shifted research toward the therapeutic efficacy of stem cells in dealing with neural degeneration in cases such as stroke, amyotrophic lateral sclerosis, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, cavernous nerve injury, and traumatic brain injury. Most existing studies have reported that cell therapies may be able to replenish lost cells and promote neuronal regeneration, protect neuronal survival, and play a role in overcoming permanent paralysis and loss of sensation and the recovery of neurological function. The mechanisms involved in determining therapeutic capacity remain largely unknown; however, this concept can still be classified in a methodical manner by citing current evidence. Possible mechanisms include the following: 1) the promotion of angiogenesis, 2) the induction of neuronal differentiation and neurogenesis, 3) reductions in reactive gliosis, 4) the inhibition of apoptosis, 5) the expression of neurotrophic factors, 6) immunomodulatory function, and 7) facilitating neuronal integration. In this study, several human clinical trials using ADSCs for neuronal disorders were investigated. It is suggested that ADSCs are one of the choices among various stem cells for translating into clinical application in the near future. © 2015 Cognizant Comm. Corp. Source

Hsu S.-Y.,Tainan Municipal An Nan Hospital China Medical University | Hsu S.-Y.,Zu Chi University | Chang M.-S.,Academia Sinica, Taiwan | Ko M.-L.,National Tsing Hua University | Harnod T.,Tzu Chi University
Clinical and Experimental Optometry

Background: The retinal nerve fibre layer (RNFL) thickness is reportedly decreased in myopia; however, magnification adjustment is an important consideration when using optical coherence tomography (OCT) to evaluate myopic eyes. In this study, RNFL thickness and optic nerve head (ONH) size were measured in highly myopic eyes with and without magnification adjustments. The measurements were compared with magnification-adjusted OCT measurements of emmetropic control eyes. Methods: In this cross-sectional study, RNFL thickness (global circle and quadrants) and ONH size (disc and rim areas) were measured in one eye of each of 70 participants with high myopia. Magnification-adjusted measurements taken in the high myopes were then compared with magnification-adjusted measurements taken in 70 emmetropic controls. Results: Comparisons of magnification-adjusted measurements between highly myopic and emmetropic control eyes showed that the highly myopic eyes had significantly thicker global and temporal RNFLs (p < 0.05), significantly thinner nasal RNFL (p < 0.05), and significantly larger disc and rim areas (p < 0.05). Superior and inferior RNFL thickness measurements did not differ significantly between the two groups (p > 0.05). Conclusion: The OCT measurements obtained with magnification adjustment show global and temporal RNFL thicknesses and ONH size increase in highly myopic eyes. © 2012 The Author Clinical and Experimental Optometry © 2012 Optometrists Association Australia. Source

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