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  • SAGE Publications  (3)
  • Kim, Yong-Lim  (3)
  • 1
    Online Resource
    Online Resource
    SAGE Publications ; 2005
    In:  Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis Vol. 25, No. 3_suppl ( 2005-02), p. 22-25
    In: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis, SAGE Publications, Vol. 25, No. 3_suppl ( 2005-02), p. 22-25
    Abstract: Human peritoneal mesothelial cells (HPMCs) undergo a transition from an epithelial phenotype to a mesenchymal phenotype (EMT) during peritoneal dialysis (PD). That transition may be directly related to failure of peritoneal membrane function. ♦ Objective In a randomized prospective controlled study, we investigated the effect of low glucose degradation product (GDP) dialysis solution on the transition of HPMCs. ♦ Methods Among new continuous ambulatory PD patients, 60 patients completed a 12-month protocol (low-GDP solution group, n = 32; high-GDP solution group, n = 28). At the 1st, 6th, and 12th months, HPMCs drained from overnight effluent were cultured on T25. When they had nearly reached confluence, cell scores were measured blindly by the same person (score 1 = cobblestone-shaped HPMCs, score 2 = mixed, score 3 = fibroblast dominant). Cell scores and clinical indices, including peritoneal markers, were compared between the low-GDP and high-GDP groups at the 1st, 6th, and 12th months. The factors associated with EMT were analyzed with generalized estimating equations using STATA 7.0 (STATA Corp., College Station, Texas, USA). In addition, vimentin and cytokeratin 8/18 stains were used to verify EMT in cultured cells and peritoneal specimens in some patients. ♦ Results ( 1 ) The low-GDP group showed higher dialysate cancer antigen 125 levels from the 1st to 12th months (55.4 ± 24.8 vs 8.8 ± 1.7, 56.7 ± 28.1 vs 22.1 ± 11.3, and 54.2 ± 28.2 vs 24.6 ± 16.5 U/mL, at the 1st, 6th, and 12th months, respectively; all p = 0.000). ( 2 ) The low-GDP group showed lower cell scores at the 1st, 6th, and 12th months (1.22, 1.22, and 1.56 vs 1.61, 1.75, and 2.14; p 〈 0.05, p 〈 0.01, and p 〈 0.01, respectively). ( 3 ) At the 12th month, the number of fibroblast-dominant cultures (score 3) was significantly lower in the low-GDP group [4/32 (12.5%) patients vs 14/28 (50%), p 〈 0.05]. ( 4 ) Both cobblestone-shaped HPMCs and fibroblastoid cells were positively stained with cytokeratin and vimentin. ( 5 ) There were many cytokeratin- and vimentin-positive cells in the submesothelial area in the peritoneal biopsy specimens. (6) The consistent factor associated with EMT was only high-GDP solution (60 patients, n = 178, beta coefficient 0.312, p = 0.000; 46 patients, n = 137, beta coef: 0.228, p = 0.000) and not numbers of peritonitis episodes, duration of angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker medication, or diabetes. ♦ Conclusion Low-GDP solution showed beneficial effects such as rapid remesothelialization and less EMT in the peritoneum with time on PD.
    Type of Medium: Online Resource
    ISSN: 0896-8608 , 1718-4304
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2005
    detail.hit.zdb_id: 2075957-5
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  • 2
    Online Resource
    Online Resource
    SAGE Publications ; 2004
    In:  Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis Vol. 24, No. 2 ( 2004-03), p. 115-122
    In: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis, SAGE Publications, Vol. 24, No. 2 ( 2004-03), p. 115-122
    Abstract: Long-term use of the peritoneal membrane as a dialyzing membrane is hampered by its eventual deterioration. One of the contributing factors is glucose degradation products (GDPs) in the dialysis solution. In this study, we evaluated the effect of a low GDP solution on peritoneal permeability, the structural stability of the peritoneal membrane, and vascular endothelial growth factor (VEGF) production in a chronic inflammatory infusion model of peritoneal dialysis (PD) in the rat. Methods Male Sprague–Dawley rats were divided into 3 groups: a conventional solution group (group C, n = 12), a test solution group (group T, n = 12), and a normal control group (group NC, n = 8). Group T rats were infused with low GDP solution (2.3% glucose solution with two compartments), and group C rats with conventional dialysis solution (2.3% glucose solution), adjusted to pH 7.0 before each exchange. Animals were infused through a permanent catheter with 25 mL of dialysis solution. In both groups, peritoneal inflammation was induced by infusing dialysis solution supplemented with lipopolysaccharide on days 8, 9, and 10 after starting dialysate infusion. Peritoneal membrane function was assessed before and 6 weeks after initiating dialysis using the 1-hour peritoneal equilibration test (PET) employing 4.25% glucose solution. Both VEGF and transforming growth factor β 1 (TGFβ 1 ) in the dialysate effluent were measured by ELISA. The number of vessels in the omentum was counted after staining with anti-von Willebrand factor, and the thickness of submesothelial matrix of the trichrome-stained parietal peritoneum was measured. Peritoneal tissue was analyzed for VEGF protein using immunohistochemistry. Results At the end of 6 weeks, the rate of glucose transport (D/D 0 , where D is glucose concentration in the dialysate and D 0 is glucose concentration in the dialysis solution before it is infused into the peritoneal cavity) was higher in group T ( p 〈 0.05) than in group C. Dialysate-to-plasma ratio (D/P) of protein was lower in group T ( p 〈 0.05) than in group C; D/P urea , D/P sodium , and drain volumes did not differ significantly between groups C and T. Dialysate VEGF and TGFβ levels were lower in group T ( p 〈 0.05) than in group C. Immunohistochemical studies also revealed less VEGF in the peritoneal membranes of group T. There were significantly more peritoneal blood vessels in group C ( p 〈 0.05) than in group T, but the thickness of submesothelial matrix of the parietal peritoneum was not different between the two groups. The VEGF levels in the dialysate effluent correlated positively with the number of blood vessels per field ( r = 0.622, p 〈 0.005). Conclusion Using a chronic inflammatory infusion model of PD in the rat, we show that dialysis with GDP-containing PD fluid is associated with increased VEGF production and peritoneal vascularization. Use of low GDP solutions may therefore be beneficial in maintaining the function and structure of the peritoneal membrane during long-term PD.
    Type of Medium: Online Resource
    ISSN: 0896-8608 , 1718-4304
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2004
    detail.hit.zdb_id: 2075957-5
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    SAGE Publications ; 2009
    In:  Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis Vol. 29, No. 1 ( 2009-01), p. 44-51
    In: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis, SAGE Publications, Vol. 29, No. 1 ( 2009-01), p. 44-51
    Abstract: Glucose degradation products (GDPs) are formed during heat sterilization and storage of peritoneal dialysis (PD) fluids. 3,4-dideoxyglucosone-3-ene (3,4-DGE) has been identified as the most bioreactive GDP. 3,4-DGE induces apoptosis in leukocytes and renal tubular epithelial cells. Our aim was to evaluate the apoptotic effects of 3,4-DGE on human peritoneal mesothelial cells (HPMCs). Methods Primary cultured HPMCs were treated with 25 or 50 μmol/L 3,4-DGE. MTT assay was used to determine cell viability. Apoptosis was measured using TUNEL assay and flow cytometry. Expressions of procaspase-3, Bax, and Bcl-2 were estimated by Western blot. Activity of caspase-3 was measured and the effect of the caspase inhibitor zVAD-fmk (Z-Val-Ala-DL-Asp-fluoromethylketone) was evaluated by TUNEL assay. Results 3,4-DGE treatment accelerated cell death in HPMCs in a dose- and time-dependent manner. Treatment with 3,4-DGE (25 and 50 μmol/L) significantly increased apoptosis compared to control ( p 〈 0.05 and p 〈 0.01 respectively) by TUNEL assay. Flow cytometry showed treatment with 50 μmol/L 3,4-DGE significantly increased apoptosis compared to control ( p 〈 0.05). Decreased expression of procaspase-3 and increased activity of caspase-3 were observed in the presence of 50 μmol/L 3,4-DGE compared to control and 25 μmol/L 3,4-DGE ( p 〈 0.05). 3,4-DGE-induced HPMC apoptosis was decreased after pretreatment with the pan-caspase inhibitor zVAD-fmk in the 50 μmol/L 3,4-DGE-treated group ( p 〈 0.001). The ratio of Bcl-2 to Bax expression was decreased in the 25 μmol/L and the 50 μmol/L 3,4-DGE-treated groups compared to control ( p 〈 0.05). Conclusions 3,4-DGE promotes apoptosis in HPMCs by a caspase-related mechanism.
    Type of Medium: Online Resource
    ISSN: 0896-8608 , 1718-4304
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2009
    detail.hit.zdb_id: 2075957-5
    Location Call Number Limitation Availability
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