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Ho T.-Y.,Taipei Veterans General Hospital | Kao W.-F.,Taipei Veterans General Hospital | Lee S.-M.,Taipei Veterans General Hospital | Lin P.-K.,Taipei Veterans General Hospital | And 3 more authors.
Retina | Year: 2011

Background: Visual disturbances after high-altitude exposure were first reported in 1969. Manifestations may include retinal hemorrhage, papilledema, and vitreous hemorrhage. Methods: We observed a group of 6 experienced climbers who ascended Mt Aconcagua to an altitude of 6,962 m in February 2007. Visual acuity study, intraocular pressure study, visual field study, nerve fiber layer analysis, eye Doppler, laboratory studies, fundus photography, and intravenous fluorescein angiography were performed on the climbers before and after their exposures to high altitude. Results: In all six study subjects, retinal vascular engorgement and tortuosity were present in varying degrees in both eyes. One of the climbers had both retinal hemorrhage and pulmonary edema. Of the two subjects who had visual field defects, one had severe nerve fiber layer defects of both eyes. Furthermore, laboratory studies of this climber showed a high level of antiphospholipid antibody. Significant reduction of the left ocular blood flow was also noted on this subject's eye Doppler examination after the Mt Aconcagua expedition. Conclusion: Various high-altitude retinopathies were observed in the experienced climbers of this study. As high-altitude pursuits become more popular, attention should be paid to the increasing prevalence of high-altitude retinopathy. Copyright © by Ophthalmic Communications Society, Inc.


Chiu H.-Y.,National Taiwan Ocean University | Sun K.-H.,National Yang Ming University | Chen S.-Y.,National Taiwan Ocean University | Wang H.-H.,Cheng Hsin Rehabilitation Medical Center | And 5 more authors.
Cytokine | Year: 2012

The amount of monocyte chemoattractant protein-1 (MCP-1/CCL2) produced by a transitional cell carcinoma is directly correlated with high recurrence and poor prognosis in bladder cancer. However, the mechanisms underlying the effects of CCL2 on tumor progression remain unexplored. To investigate the role played by CCL2, we examined cell migration in various bladder cancer cell lines. We found that high-grade cancer cells expressing high levels of CCL2 showed more migration activity than low-grade bladder cancer cells expressing low levels of the chemokine. Although the activation of CCL2/CCR2 signals did not appreciably affect cell growth, it mediated cell migration and invasion via the activation of protein kinase C and phosphorylation of tyrosine in paxillin. Blocking CCL2 and CCR2 with small hairpin RNA (shCCL2) or a specific inhibitor reduced CCL2/CCR2-mediated cell migration. The antagonist of CCR2 promoted the survival of mice bearing MBT2 bladder cancer cells, and CCL2-depleted cells showed low tumorigenicity compared with shGFP cells. In addition to observing high-levels of CCL2 in high-grade human bladder cancer cells, we showed that the CCL2/CCR2 signaling pathway mediated migratory and invasive activity, whereas blocking the pathway decreased migration and invasion. In conclusion, high levels of CCL2 expressed in bladder cancer mediates tumor invasion and is involved with advanced tumorigenesis. Our findings suggest that this CCL2/CCR2 pathway is a potential candidate for the attenuation of bladder cancer metastases. © 2012 Elsevier Ltd.


Hung T.-H.,Chang Gung Memorial Hospital | Hung T.-H.,Chang Gung University | Hsieh T.-T.,Chang Gung Memorial Hospital | Chen S.-F.,Cheng Hsin Rehabilitation Medical Center | And 2 more authors.
PLoS ONE | Year: 2013

Background: Autophagy has been reported to be essential for pre-implantation development and embryo survival. However, its role in placental development and regulation of autophagy during pregnancy remain unclear. The aims of this study were to (1) study autophagy by characterizing changes in levels of beclin-1, DRAM, and LC3B in human placenta throughout gestation; (2) determine whether autophagy is involved in regulation of trophoblast invasion in JEG-3 cells (a choriocarcinoma cell line); (3) examine the effects of reduced oxygen and glucose on the autophagic changes; and (4) investigate the effect of reoxygenation and supplementation of glucose after oxygen-glucose deprivation (OGD) on the autophagic changes in primary cytotrophoblasts obtained from normal term pregnancy. Methodology/Principal Findings: An analysis of 40 placental samples representing different gestational stages showed (1) no significant differences in beclin-1, DRAM, and LC3B-II levels in placentas between early and mid-gestation, and late gestation with vaginal delivery; (2) placentas from late gestation with cesarean section had lower levels of LC3B-II compared to early and mid-gestation, and late gestation with vaginal delivery; levels of DRAM were also lower compared to placentas from early and mid-gestation; and (3) using explant cultures, villous tissues from early and late gestation had similar rates of autophagic flux under physiological oxygen concentrations. Knockdown of BECN1, DRAM, and LC3B had no effects on viability and invasion activity of JEG-3 cells. On the other hand, OGD caused a significant increase in the levels of LC3B-II in primary cytotrophoblasts, while re-supplementation of oxygen and glucose reduced these changes. Furthermore, there were differential changes in levels of beclin-1, DRAM, and LC3B-II in response to changes in oxygen and glucose levels. Conclusions/Significance: Our results indicate that autophagy is involved in development of the human placenta and that changes in oxygen and glucose levels participate in regulation of autophagic changes in cytotrophoblast cells. © 2013 Hung et al.


Tung F.-L.,Cheng Hsin Rehabilitation Medical Center | Yang Y.-R.,National Yang Ming University | Lee C.-C.,Taipei Veterans General Hospital | Wang R.-Y.,National Yang Ming University
Clinical Rehabilitation | Year: 2010

Objective: To determine the effectiveness of sit-to-stand training in individuals with stroke. Design: Randomized controlled trial. Setting: Rehabilitation medical centre. Participants: Thirty-two subjects with stroke were randomly assigned to the control and experimental groups (n = 16 for each group). Interventions: Subjects in both groups received 30 minutes of general physical therapy three times a week for four weeks. Subjects in the experimental group received additional sit-to-stand training for 15 minutes each time. The total amount of therapy received was 45 minutes in the experimental group and 30 minutes in the control group each time. Main outcome measures: The weight-bearing distribution during quiet standing, the directional control and maximal excursion during limits of stability test, the scores of Berg Balance Scale and the extensor muscle strength of lower extremity were assessed before and after completing the 12 treatment sessions. Results: Our data showed significant improvements in directional control anteriorly in the experimental group (from 47.4 (36.6)% to 62.6 (26.1)%) compared with the control group (from 68.7 (16.7)% to 62.8 (29.7)%) (P = 0.028). A significant improvement in affected hip extensor strength was noted in the experimental group (from 19.3 (9.8)% to 22.6 (8.4)%) compared with the control group (from 24.4 (9.0)% to 22.8 (7.2)%) (P = 0.006). Significant improvements were noted only in the experimental group after treatment, including bilateral extensors, except the affected plantar flexors, the weight distribution in standing, the maximal excursion (P anterior = 0.049; Paffected = 0.023) and the directional control (Paffected = 0.013; Pnon-affected = 0.025). Conclusions: Additional sit-to-stand training is encouraged due to effects on dynamic balance and extensor muscles strength in subjects with stroke. © The Author(s), 2010.


Hung C.-H.,National Cheng Kung University | Liu K.-S.,Chia Nan University of Pharmacy and Science | Shao D.-Z.,Chung Hwa University of Medical Technology | Cheng K.-I.,Kaohsiung Medical University | And 2 more authors.
Anesthesia and Analgesia | Year: 2010

Background: Although proxymetacaine and oxybuprocaine produce topical ocular and spinal anesthesia, they have never been tested as cutaneous anesthetics. We compared cutaneous analgesia of proxymetacaine and oxybuprocaine with bupivacaine and tested their central nervous system and cardiovascular toxicity. Methods: After blockade of cutaneous trunci muscle reflex with subcutaneous injections, we evaluated the local anesthetic effect of proxymetacaine and oxybuprocaine on cutaneous analgesia in rats. After IV infusions of equipotent doses of oxybuprocaine, proxymetacaine, and bupivacaine, we observed the onset time of seizure, apnea, and impending death and monitored mean arterial blood pressure and heart rate. Results: Proxymetacaine and oxybuprocaine acted like bupivacaine and produced dose-related cutaneous analgesia. On a 50% effective dose basis, the ranks of potencies were proxymetacaine > oxybuprocaine > bupivacaine (P < 0.01). Under equipotent doses, the infusion times of proxymetacaine or oxybuprocaine required to cause seizure, apnea, and impending death were longer than that of bupivacaine (P < 0.05). The decrease in mean arterial blood pressure and heart rate was slower with oxybuprocaine and proxymetacaine compared with bupivacaine (P < 0.05 for the differences) at equipotent doses. Conclusions: Oxybuprocaine and proxymetacaine were more potent at producing cutaneous anesthesia but were less potent than bupivacaine at producing central nervous system and cardiovascular toxicity. Copyright © 2009 International Anesthesia Research Society.


Hung T.-H.,Chang Gung Memorial Hospital at Taipei | Hung T.-H.,Chang Gung University | Chen S.-F.,Cheng Hsin Rehabilitation Medical Center | Li M.-J.,Chang Gung Memorial Hospital at Taipei | And 2 more authors.
PLoS ONE | Year: 2010

Background: Concomitant supplementation of vitamins C and E during pregnancy has been reportedly associated with low birth weight, the premature rupture of membranes and fetal loss or perinatal death in women at risk for preeclampsia; however, the cause is unknown. We surmise that hypoxia-reoxygenation (HR) within the intervillous space due to abnormal placentation is the mechanism and hypothesize that concomitant administration of aforementioned vitamin antioxidants detrimentally affects trophoblast cells during HR. Methodology/Principal Findings: Using villous explants, concomitant administration of 50 mM of vitamins C and E was observed to reduce apoptotic and autophagic changes in the trophoblast layer at normoxia (8% oxygen) but to cause more prominent apoptosis and autophagy during HR. Furthermore, increased levels of Bcl-2 and Bcl-xL in association with a decrease in the autophagy-related protein LC3-II were noted in cytotrophoblastic cells treated with vitamins C and E under standard culture conditions. In contrast, vitamin treatment decreased Bcl-2 and Bcl-xL as well as increased mitochondrial Bak and cytosolic LC3-II in cytotrophoblasts subjected to HR. Conclusions/Significance: Our results indicate that concomitant administration of vitamins C and E has differential effects on the changes of apoptosis, autophagy and the expression of Bcl-2 family of proteins in the trophoblasts between normoxia and HR. These changes may probably lead to the impairment of placental function and suboptimal growth of the fetus. © 2010 Hung et al.


Lu C.-C.,National Chung Hsing University | Yang J.-S.,China Medical University at Taichung | Huang A.-C.,St. Mary's College | Hsia T.-C.,China Medical University at Taichung | And 7 more authors.
Molecular Nutrition and Food Research | Year: 2010

Anthraquinone compounds have been shown to induce apoptosis in different cancer cell types. Effects of chrysophanol, an anthraquinone compound, on cancer cell death have not been well studied. The goal of this study was to examine if chrysophanol had cytotoxic effects and if such effects involved apoptosis or necrosis in J5 human liver cancer cells. Chryso-phanol induced necrosis in J5 cells in a dose- and time-dependent manner. Non-apoptotic cell death was induced by chrysophanol in J5 cells and was characterized by caspase independence, delayed externalization of phosphatidylserine and plasma membrane disruption. Blockage of apoptotic induction by a general caspase inhibitor (z-VAD-fmk) failed to protect cells against chrysophanol-induced cell death. The levels of reactive oxygen species production and loss of mitochondrial membrane potential (AC m) were also determined to assess the effects of chrysophanol. However, reductions in adenosine triphosphate levels and increases in lactate dehydrogenase activity indicated that chrysophanol stimulated necrotic cell death. In summary, human liver cancer cells treated with chrysophanol exhibited a cellular pattern associated with necrosis and not apoptosis. ©2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Yang S.,National Yang Ming University | Hwang W.-H.,National Yang Ming University | Tsai Y.-C.,National Yang Ming University | Liu F.-K.,Cheng Hsin Rehabilitation Medical Center | And 2 more authors.
American Journal of Physical Medicine and Rehabilitation | Year: 2011

Objective: The aim of this study was to evaluate the effects of virtual reality (VR) treadmill training on the balance skills of patients who have had a stroke. Design: A total of 14 patients with strokes were recruited and randomly assigned to receive VR treadmill or traditional treadmill training. The outcome measures that were included for the study were center of pressure (COP) sway excursion, COP maximum sway in anterior-posterior direction, COP maximum sway in medial-lateral direction, COP sway area, bilateral limb-loading symmetric index, the sway excursion values for the paretic foot (sway excursion/P), paretic limb stance time (stance time/P), number of steps of the paretic limb (number of steps/P), and contact area of the paretic foot (contact A/P) during quiet stance, sit-to-stand transfer, and level walking. Results: There were no significant improvements in COP-related measures and symmetric index during the quiet stance, either in the VR treadmill or traditional treadmill training group (P > 0.05). However, the difference between groups after training in COP maximum sway in medial-lateral direction during the quiet stance was significant (P = 0.038). Traditional treadmill training failed to improve sit-to-stand performance, whereas VR treadmill training improved symmetric index (P = 0.028) and sway excursion (P = 0.046) significantly during sit-to-stand transfer. The changes of symmetric index between groups were markedly different (P = 0.045). Finally, both groups improved significantly in stance time/P, but only VR treadmill training increased contact A/P (P = 0.034) after training during level walking. The difference between groups during level walking was not significant. Conclusions: Neither traditional treadmill nor VR treadmill training had any effect on balance skill during quiet stance, but VR treadmill training improved balance skill in the medial-lateral direction better than traditional training did. VR treadmill training also improved balance skill during sit-to-stand transfers and the involvement of paretic limb in level walking more than the traditional one did. Copyright © 2011 by Lippincott Williams & Wilkins.


Hung T.-H.,Chang Gung Memorial Hospital at Taipei | Hung T.-H.,Chang Gung University | Chen S.-F.,Cheng Hsin Rehabilitation Medical Center | Lo L.-M.,Chang Gung Memorial Hospital at Taipei | And 3 more authors.
PLoS ONE | Year: 2012

Background: Unexplained intrauterine growth restriction (IUGR) may be a consequence of placental insufficiency; however, its etiology is not fully understood. We surmised that defective placentation in IUGR dysregulates cellular bioenergic homeostasis, leading to increased autophagy in the villous trophoblast. The aims of this work were (1) to compare the differences in autophagy, p53 expression, and apoptosis between placentas of women with normal or IUGR pregnancies; (2) to study the effects of hypoxia and the role of p53 in regulating trophoblast autophagy; and (3) to investigate the relationship between autophagy and apoptosis in hypoxic trophoblasts. Methodology/Principal Findings: Compared with normal pregnant women, women with IUGR had higher placental levels of autophagy-related proteins LC3B-II, beclin-1, and damage-regulated autophagy modulator (DRAM), with increased p53 and caspase-cleaved cytokeratin 18 (M30). Furthermore, cytotrophoblasts cultured under hypoxia (2% oxygen) in the presence or absence of nutlin-3 (a p53 activity stimulator) had higher levels of LC3B-II, DRAM, and M30 proteins and increased Bax mRNA expression compared with controls cultured under standard conditions. In contrast, administration of pifithrin-α (a p53 activity inhibitor) during hypoxia resulted in protein levels that were similar to those of the control groups. Moreover, cytotrophoblasts transfected with LC3B, beclin-1, or DRAM siRNA had higher levels of M30 compared with the controls under hypoxia. However, transfection with Bcl-2 or Bax siRNA did not cause any significant change in the levels of LC3B-II in hypoxic cytotrophoblasts. Conclusions/Significance: Together, these results suggest that there is a crosstalk between autophagy and apoptosis in IUGR and that p53 plays a pivotal and complex role in regulating trophoblast cell turnover in response to hypoxic stress. © 2012 Hung et al.


Hsieh T.-T.,Chang Gung Memorial Hospital at Taipei | Chen S.-F.,Cheng Hsin Rehabilitation Medical Center | Lo L.-M.,Chang Gung Memorial Hospital at Taipei | Li M.-J.,Chang Gung Memorial Hospital at Taipei | And 3 more authors.
Reproductive Sciences | Year: 2012

Objective: To investigate the association between maternal oxidative stress at mid-gestation and subsequent development of pregnancy complications. Study design: A total of 503 healthy pregnant women provided their blood and urine samples at 24 to 26 weeks of gestation and were prospectively followed through postpartum. These samples were used to assess a variety of oxidative stress markers, including plasma total antioxidant capacity, 8-isoprostane, erythrocyte glutathione peroxidase and superoxide dismutase activity, and urinary 8-hydroxydeoxyguanosine (8-OHdG). Results: Compared with women with uncomplicated pregnancies, significantly higher plasma 8-isoprostane levels were noted in women who developed preeclampsia (P =.008) and small-for-gestational age infants (P =.002), while higher urinary 8-OHdG concentrations were noted in women who subsequently had low-birth-weight neonates (<2500 g, P =.043). Conclusion: Increased maternal oxidative stress at mid-gestation was associated with subsequent pregnancy complications. © The Author(s) 2012.

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