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Banqiao, Taiwan

Guo C.-H.,Hungkuang University | Wang C.-L.,Kuang Tien General Hospital
International Journal of Medical Sciences

Background: Patients undergoing hemodialysis (HD) have low plasma levels of zinc (Zn), high plasma levels of copper (Cu), and exhibit increased oxidative stress, inflammation, and immune abnormalities. We evaluated the effects of Zn supplementation on abnormal plasma Cu/Zn ratios and clinical outcomes in HD patients. Design and Methods: Patients on long-term HD with lower than normal plasma concentrations of Zn (< 80 mg/dL) were randomized to receive daily oral Zn supplements (n = 40) or no supplements (n = 25) for eight weeks. Age- and sex-matched healthy individuals served as a control group (n = 38). A number of clinical parameters were measured before and after the supplementation period. Results: Compared with healthy subjects, patients had significantly elevated plasma Cu concentrations and Cu/Zn ratios, as well as higher levels of oxidative stress and pro-inflammatory cytokines. Patients who received Zn supplements for eight weeks had higher plasma concentrations of Zn and lower concentrations of Cu, along with reduced Cu/Zn ratios, oxidative stress status, and inflammatory responses compared to patients who did not receive Zn. Patients receiving Zn also showed significantly higher percentages of CD4 and CD19 lymphocytes, and elevated CD4/CD8 ratios. Conclusions: Zn supplementation ameliorates abnormally high plasma Cu/Zn ratios and may reduce oxidative stress, improve inflammatory status, and maintain immune function in patients undergoing long-term HD. © Ivyspring International Publisher. Source

Kok V.C.,Kuang Tien General Hospital | Kok V.C.,Asia University, Taiwan
Clinical Interventions in Aging

Background: The use of compassionate extubation (CE) to alleviate suffering by terminating mechanical ventilation and withdrawing the endotracheal tube requires professional adherence and efficiency. The Hospice Palliative Care Act, amended on January 9, 2013, legalizes the CE procedure in Taiwan. Methods: From September 20, 2013 to September 2, 2014, the hospice palliative care team at a community hospital received 20 consultations for CE. Eight cases were excluded because of non-qualification. Following approval from the Ethics Committee, the medical records of the remaining 12 patients were reviewed and grouped by the underlying disease: A, “terminal-stage cancer”; B, “non-cancer out-of-hospital cardiac arrest”; and C, “non-cancer organ failure”. Time to extubation using a cut-off at 48 hours was assessed. Results: The mean ages of patients (standard deviation) in groups A, B, and C were 66.3 (14.9) years, 72 (19.1) years, and 80.3 (4.0) years, respectively. The mean number of days of intubation at consultation were 6.8 (4.9), 7.3 (4.9), and 179.3 (271.6), respectively. The mean total doses of opioids (as morphine-equivalent dose) in the 24 hours preceding CE were 76 (87.5) mg, 3.3 (5.8) mg, and 43.3 (15.3) mg. The median times from extubation (range) to death were 97 (0.2–245) hours, 0.3 (0.2–0.4) hours, and 6.1 (3.6–71.8) hours. Compared to those requiring <48-hour preparatory time, patients requiring >48 hours to the moment of CE were younger (62.8 years vs 75.5 years), required a mean time of 122 hours (vs 30 hours) to CE (P=0.004), had shorter length of stay (33.3 days vs 77.8 days), required specialist social worker intervention in 75% of cases (vs 37.5%), and had a median duration of intubation of 11.5 days (vs 5.5 days). Conclusion: CE was carried out according to protocol, and the median time from extubation to death varies determined by the underlying disease which was 0.3 hour in patients admitted after out-of-hospital cardiac arrest and 97 hours in patients with advanced cancer. © 2015 Kok et al. Source

Shih C.-J.,Kuang Tien General Hospital | Chiou Y.-L.,Hungkuang University

Inflammation of airway smooth muscle cells (ASMCs) is believed to be important in causing airway hyperresponsiveness. However, zinc has been reported to be implicated in many kinds of cell inflammation. Little is known about the effect of zinc treatment on Der p2 (group II Dermatophagoides pteronyssinus)-induced inflammation from ASMCs. This study investigated effects and mechanisms of zinc in Der p2-treated ASMCs. Der p2-treated primary ASMCs were cultured with various concentrations of zinc sulfate (ZnSO4) 6 μM, 12 μM, 24 μM, and 96 μM. The proteins and mRNAs of cytokines in ASMCs were examined by ELISA and real-time PCR. Intracellular zinc was stained with Zinquin fluorescence. The cell signaling protein expression was detected by Western blot. Der p2 was used to induce interleukin (IL)-6, IL-8, IL-1, and monocyte chemotactic protein-1 production of ASMCs. However, we found that 24 μM ZnSO4 reduced these inflammatory mediators production of Der p2-treated primary ASMCs. Der p2-induced extracellular signal-regulated kinases (ERK) and nuclear factor-kappa B (NF-κB) phosphorylation were suppressed by supplementation of 24 μM ZnSO4. Zinc is an anti-inflammatory agent that reduces inflammation of Der p2-treated ASMCs through the suppression of the ERK and NF-κB pathway. The results may be helpful for the development of effective treatments. © 2012 Springer Science+Business Media New York. Source

Huang G.-S.,National Taiwan University | Dai L.-G.,Kuang Tien General Hospital | Dai L.-G.,National Chung Hsing University | Yen B.L.,National Health Research Institute | And 2 more authors.

Stem cells can lose their primitive properties during in vitro culture. The culture substrate may affect the behavior of stem cells as a result of cell-substrate interaction. The maintenance of self-renewal for adult human mesenchymal stem cells (MSCs) by a biomaterial substrate, however, has not been reported in literature. In this study, MSCs isolated from human adipose (hADAS) and placenta (hPDMC) were cultured on chitosan membranes and those further modified by hyaluronan (chitosan-HA). It was observed that the MSCs of either origin formed three-dimensional spheroids that kept attached on the membranes. Spheroid formation was associated with the increased MMP-2 expression. Cells on chitosan-HA formed spheroids more quickly and the size of spheroids were larger than on chitosan alone. The expression of stemness marker genes (Oct4, Sox2, and Nanog) for MSCs on the materials was analyzed by the real-time RT-PCR. It was found that formation of spheroids on chitosan and chitosan-HA membranes helped to maintain the expression of stemness marker genes of MSCs compared to culturing cells on polystyrene dish. The maintenance of stemness marker gene expression was especially remarkable in hPDMC spheroids (vs. hADAS spheroids). Blocking CD44 by antibodies prevented the spheroid formation and decreased the stemness gene expression moderately; while treatment by Y-27632 compound inhibited the spheroid formation and significantly decreased the stemness gene expression. Upon chondrogenic induction, the MSC spheroids showed higher levels of Sox9, aggrecan, and collagen type II gene expression and were stained positive for glycosaminoglycan and collagen type II. hPDMC had better chondrogenic differentiation potential than hADAS upon induction. Our study suggested that the formation of adhered spheroids on chitosan and chitosan-HA membranes may sustain the expression of stemness marker genes of MSCs and increase their chondrogenic differentiation capacity. The Rho/Rho-associated kinase (ROCK) signaling pathway may be involved in spheroid formation. © 2011 Elsevier Ltd. Source

Guo C.-H.,Hungkuang University | Chen P.-C.,Hungkuang University | Hsu G.-S.W.,University of Taipei | Wang C.-L.,Kuang Tien General Hospital

End stage renal disease patients undergoing long-term dialysis are at risk for abnormal concentrations of certain essential and non-essential trace metals and high oxidative stress. We evaluated the effects of zinc (Zn) supplementation on plasma aluminum (Al) and selenium (Se) concentrations and oxidative stress in chronic dialysis patients. Zn-deficient patients receiving continuous ambulatory peritoneal dialysis or hemodialysis were divided into two groups according to plasma Al concentrations (HA group, Al > 50 μg/L; and MA group, Al > 30 to ≤ 50 μg/L). All patients received daily oral Zn supplements for two months. Age- and gender-matched healthy individuals did not receive Zn supplement. Clinical variables were assessed before, at one month, and after the supplementation period. Compared with healthy subjects, patients had significantly lower baseline plasma Se concentrations and higher oxidative stress status. After two-month Zn treatment, these patients had higher plasma Zn and Se concentrations, reduced plasma Al concentrations and oxidative stress. Furthermore, increased plasma Zn concentrations were related to the concentrations of Al, Se, oxidative product malondialdehyde (MDA), and antioxidant enzyme superoxide dismutase activities. In conclusion, Zn supplementation ameliorates abnormally high plasma Al concentrations and oxidative stress and improves Se status in long-term dialysis patients. © 2013 by the authors; licensee MDPI, Basel, Switzerland. Source

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