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Biomedical subjects

Yong Soo Kim

Publications and source records attributed to Yong Soo Kim.

At least 19 recordsLinked to original sources

Changing prescribing practice in CAPD patients in Korea: increased utilization of low GDP solutions improves patient outcome.

BACKGROUND: Novel, biocompatible peritoneal dialysis (PD) solutions have become available in recent years. In 2001, low glucose degradation products (GDP), neutral pH solutions became commercially available in Korea. To date, there are no reports regarding the large scale adoption of these solutions in clinical practice and regarding what, if any, impact these solutions have on patient outcomes. METHODS: Using a database of almost 4000 patients treated by PD in Korea, we conducted a prospective, longitudinal observational study documenting the patterns of use of one novel low GDP solution (balance, Fresenius Medical Care, St Wendel, Germany) in 1909 PD incident patients between 1 January 2002 and midyear 2005. Outcomes including patient and technique survival and peritonitis rates were analysed using univariate and multivariate analysis. RESULTS: Prescription of low GDP solutions reached between 70 and 80% by the year 2003 and persisted at this level. Patients prescribed low GDP PD solution tended to be younger and were more likely to be treated in centres with larger enrollment in the database. Survival of diabetic patients treated with the new PD solution was identical to that of the non-diabetic patients treated with standard PD fluids (PDF) and treatment with low GDP PDF independently reduced the relative risk (RR) of death (RR = 0.613; CI 0.50-0.74; P < 0.00001) in a proportional hazards model which included age, diabetes and centre experience. In a univariate analysis, low GDP PD solution was associated with a longer technique survival (P = 0.049) but this effect was not significant in multivariate analysis. No significant differences in peritonitis-free interval or peritonitis rate could be attributed to the prescribed PDF. CONCLUSION: Prescription of low GDP, pH-neutral PD solutions has rapidly increased in Korea. This change has resulted in a significant improvement in patient and technique survival without any measurable change in peritonitis incidence or rate. Reasons for the improved patient survival cannot be determined from this analysis and require further study.

Adult↗

Effect of FTY720 on chronic cyclosporine nephropathy in rats.

BACKGROUND: Long-term treatment with cyclosporine A (CsA) causes tubulointerstitial inflammation and fibrosis in the kidney. To define the role of lymphocytes in this process, the novel lymphocyte-specific inhibitor FTY720 was administered to rats with experimental model of chronic CsA nephropathy. METHODS: Sprague-Dawley rats were treated daily for 4 weeks with CsA (7.5 mg/kg), or both CsA and FTY720 (0.125 mg/kg). The effects of FTY720 on CsA-induced renal injury were evaluated using renal function tests and histopathology, and the expression of mediators of CsA-induced renal injury (osteopontin, transforming growth factor-beta1 [TGF-beta1], betaig-h3, and angiotensin II). RESULTS: FTY720 treatment significantly decreased T-lymphocyte accumulation in kidneys compared with CsA treatment alone. FTY720 treatment improved not only CsA-induced renal dysfunction but also renal histopathology, demonstrated by decreased macrophage infiltration and interstitial fibrosis. Increased osteopontin, TGF-beta1, betaig-h3, and angiotensin II expression in CsA-treated rat kidneys were decreased with FTY720 treatment. CONCLUSIONS: FTY720 treatment prevents CsA-induced renal injury.

Angiotensin II↗

Ultrasonographic measurement of intima-media thickness of radial artery in pre-dialysis uraemic patients: comparison with histological examination.

BACKGROUND: Increased intima-media thickness (IMT) of the radial artery is associated with early failure of radiocephalic arteriovenous fistula (AVF) in haemodialysis patients. Therefore, non-invasive measurements of radial artery IMT before AVF operations are very important in predicting AVF patency. This study was designed to evaluate the accuracy of high-resolution ultrasonography in measuring radial artery IMT in pre-dialysis uraemic patients. METHODS: This study enrolled 43 pre-dialysis uraemic patients awaiting radiocephalic AVF operations for the first time. In this study, 17 age- and sex-matched uncomplicated hypertensive patients and 15 healthy subjects were included as a control. We measured the internal diameter (ID) and IMT of the radial artery using high-resolution ultrasonography on the wrists of uraemic patients as well as the control group before the AVF operation. We obtained specimens of the radial artery during the AVF operation and directly measured the IMT by histological examination. RESULTS: The radial artery IMT of the uraemic patients (0.41 +/- 0.09 mm) was significantly thicker, compared to both those of the hypertensive (0.33 +/- 0.05 mm, P < 0.001) and the healthy patients (0.25 +/- 0.04 mm, P = 0.002). In contrast, the radial artery ID in the uraemic patients (1.85 +/- 0.48 mm) was smaller than both that of the hypertensive patients (2.08 +/- 0.31 mm, P = 0.023) and the healthy persons (2.34 +/- 0.37 mm, P = 0.001). Radial artery IMT had a negative correlation with radial artery ID in a total of 73 subjects (r = -0.290, P = 0.012). The value of the radial arterial IMT measured by sonographic examination correlated significantly with that by histological examination in 43 uraemic patients (r = 0.786, P < 0.001) and it correlated significantly with early AVF failure (r = 0.358, P = 0.027). CONCLUSION: Our data suggest that high-resolution ultrasonography is an effective tool in measuring radial artery IMT in uraemic patients before AVF operation.

Adult↗

Preconditioning with 1,25-dihydroxyvitamin D3 protects against subsequent ischemia-reperfusion injury in the rat kidney.

BACKGROUND/AIM: Induction of heat shock protein 70 (HSP70) is important in the tolerance of subsequent ischemia-reperfusion (I/R) injury. The aim of this study was to evaluate the effect of HSP70 induction by 1,25-dihydroxyvitamin D3 (VD3) on subsequent I/R injury in rats. METHODS: HSP70 was induced in Sprague-Dawley rats by VD3 treatment for 7 days, and the effect of VD3 pretreatment on subsequent I/R injury was evaluated in terms of renal function, tubular necrosis score, tumor necrosis factor alpha mRNA expression, mitogen-activated protein kinase expression, and proliferating cell nuclear antigen expression. RESULTS: VD3 treatment increased HSP70 expression which was localized to renal tubular cells in the outer medulla. Pretreatment with VD3 before I/R injury resulted in (1) decreased blood urea nitrogen and serum creatinine levels; (2) decreased tubular cell necrosis; (3) increased tubular cell proliferation as determined by proliferating cell nuclear antigen expression; (4) decreased tumor necrosis factor alpha mRNA expression, and (5) increased extracellular signal regulated protein kinase and decreased c-Jun N-terminal kinase expression. CONCLUSION: Our study demonstrates that VD3 is a nontoxic inducer of HSP70 and exerts a protective effect against subsequent I/R injury.

Animals↗

Attenuation of interstitial inflammation and fibrosis by recombinant human erythropoietin in chronic cyclosporine nephropathy.

BACKGROUND: Evidence suggests that recombinant human erythropoietin (rHuEPO) protects neurons and cardiomyocytes from acute insults. We investigated the protective effect of rHuEPO on cyclosporine (CsA)-induced renal injury. METHODS: CsA (15 mg/kg/day) was given to rats for 1 or 4 weeks, and rHuEPO was concurrently administered at a dose of 100 units/kg (thrice weekly). Effects of rHuEPO on CsA-induced renal injury were evaluated with tubulointerstitial fibrosis (TIF) score, macrophage infiltration, expression of proinflammatory and profibrotic cytokines, and apoptotic cell death. RESULTS: Administration of rHuEPO decreased TIF score and the number of macrophages, which increased significantly in CsA-treated rat kidneys. At the molecular level, rHuEPO treatment decreased proinflammatory mediators (osteopontin and C-reactive protein) and profibrotic mediators (transforming growth factor-beta1 and transforming growth factor-beta1-inducible gene-h3). Increased apoptotic cell death in CsA-treated rat kidneys was significantly decreased with rHuEPO cotreatment, and apoptosis-related genes were regulated in favor of cell survival (increased Bcl-2 and suppressed caspase-3). CONCLUSION: rHuEPO has a renoprotective effect against chronic CsA-induced renal injury.

Animals↗

Protective effect of peroxisome proliferator activated receptor gamma agonists on diabetic and non-diabetic renal diseases.

Peroxisome proliferator activated receptor gamma (PPARgamma) agonist has not only antidiabetic effect but also a protective effect against various types of injury of the kidney. The protective effects of PPARgamma agonists are observed in diabetic nephropathy and non-diabetic renal diseases such as 5/6 ablation model of renal failure, experimental glomerulonephritis, ischemia-reperfusion injury, hypertensive nephropathy and cyclosporin-induced renal injury. The mechanism of renoprotection by PPARgamma agonist is multifactorial. Anti-fibrotic and anti-inflammatory effects, suppression of renin-angiotensin system, vascular protective effect and antiapoptotic effect were proposed.

Animals↗

Blockade of angiotensin II with losartan attenuates transforming growth factor-beta1 inducible gene-h3 (betaig-h3) expression in a model of chronic cyclosporine nephrotoxicity.

BACKGROUND: We recently demonstrated that upregulation of the transforming growth factor (TGF)-beta1 inducible gene-h3 (betaig-h3) is associated with tubulointerstitial fibrosis (TIF) in a rat model of chronic cyclosporine A (CsA) nephrotoxicity. This study investigated the association between betaig-h3 expression and TIF during losartan treatment in this model. METHODS: Adult Sprague-Dawley rats kept on a salt-depleted diet (0.05% sodium) were treated daily for 4 weeks with vehicle (olive oil, 1 ml/kg), CsA (15 mg/kg) or both CsA and losartan (10 mg/kg in drinking water). The effect of losartan on betaig-h3 expression was evaluated using in situ hybridization, immunohistochemistry and immunoblotting. Histopathology, expressions of TGF-beta1 and intrarenal angiotensin II were compared across treatment groups. RESULTS: Concurrent administration of losartan significantly attenuated betaig-h3 mRNA and protein expression within the tubulointerstitium of CsA-treated kidneys. This was accompanied by the retardation of TIF (18 +/- 5 vs. 39 +/- 5%, p < 0.01 vs. CsA) and the expression of TGF-beta1 mRNA (336 +/- 49 vs. 685 +/- 63%, p < 0.01 vs. CsA) and the number of angiotensin II-positive glomeruli (18 +/- 5 vs. 38 +/- 6, p < 0.05 vs. CsA). CONCLUSION: Losartan is capable of abrogating the upregulation of TGF-beta1 and betaig-h3 expression, and this is associated with attenuated tubulointerstitial fibrosis in chronic CsA nephrotoxicity.

Angiotensin II Type 1 Receptor Blockers↗

Renal transplantation in a patient with idiopathic thrombocytopenic purpura.

The combination of idiopathic thrombocytopenic purpura (ITP) and chronic renal failure (CRF) is uncommon. This report highlights a case of renal transplantation in a patient with ITP. A 35-year-old man with ITP was admitted with uremic symptoms. A renal transplant and splenectomy was simultaneously performed. A prophylactic pneumococcous vaccination was performed and intravenous immunoglobulin (1 g/kg) was administered before and after the operation. The patient's platelet count increased gradually after the splenectomy. During a two-year follow up period, the graft function was well maintained. Renal transplantation in a patient with ITP is recommended with a well-designed strategy to prevent potential complications.

Adult↗

Non-Hodgkin's lymphoma manifest as gingival hyperplasia in a renal transplant recipient.

Gingival hyperplasia is a frequent complication in transplant patients who receive cyclosporine or calcium channel blockers. We studied an unusual case involving a renal transplant recipient with post-transplant non-Hodgkin's lymphoma that manifested as gingival hyperplasia. We initially consider that it was a side effect of cyclosporine and nifedipine. The lesion did not respond to dose reductions or the withdrawal of cyclosporine and nifedipine, and the gingival hyperplasia progressed in a localized fashion, becoming ulcerated and bleeding easily. Histological examination revealed the presence of malignant lymphoma.

Adult↗

Subacute bacterial endocarditis associated with upper endoscopy.

Transient bacteremia associated with various endoscopic procedures is a well-documented phenomenon. Clinically important bacteremias are very rarely seen, however, this malady has significant morbidity in susceptible patients with valvular heart disease, liver cirrhosis, malignancy and immune deficiency. This bacteremia is a complication that is generally observed secondary to upper endoscopy and other associated invasive procedures in at risk patients, and the more serious manifestations include spontaneous bacterial peritonitis, septic arthritis, meningitis, brain abscess and infective endocarditis. Infective endocarditis is an extremely rare complication of gastrointestinal endoscopy, and it has been convincingly documented in only seven cases. We report a case of native valve endocarditis due to Streptococcus intermedius in a patient with valvular heart disease as a consequence of routine upper endoscopy.

Endocarditis, Subacute Bacterial↗

Relations between eNOS Glu298Asp polymorphism and progression of diabetic nephropathy.

BACKGROUND: Nitric oxide (NO) is related to the pathogenesis of renal hemodynamics in diabetes mellitus. Endothelial nitric oxide synthase (eNOS) gene polymorphism is considered the deterioration factor for progressive renal disease. It has been reported that an interaction of angiotensin II (Ang II) and NO is involved in the control of glomerular hemodynamics. This study aimed to elucidate the roles of eNOS and the angiotensin-converting enzyme (ACE) gene polymorphism for the progression of type 2 diabetic nephropathy (DN). METHODS: Korean type 2 diabetic patients (n = 177) were studied. eNOS and ACE genotypes were determined by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) analysis. They were divided into three groups: group 1 consisted of patients with normoalbuminruia (n = 59), group 2 had microalbuminuria (n = 35) and group 3 had overt nephropathy (n = 83). RESULTS: Group 3 had a higher frequency of eNOS(GT) than groups 1 and 2. Patients with eNOS(GT) genotype showed more rapid deterioration in renal function, higher incidence of overt nephropathy and lower renal survival than those with eNOS(GG) genotype. However, there was no significant association between the ACE genotypes and DN, and no interaction between eNOS and ACE gene polymorphism. CONCLUSION: These results imply that eNOS(GT) genotype is associated with the progression of type 2 DN in Korean patients.

Cohort Studies↗

Expression of transforming growth factor-beta-inducible gene-h3 in normal and cyclosporine-treated rat kidney.

Up-regulation of transforming growth factor-beta (TGF-beta) is known to play an important role in the tubulointerstitial injury of chronic cyclosporin A (CsA) nephropathy, but the expression of the TGF-beta-inducible gene-h3 (betaig-h3) is undetermined. In this study we examined betaig-h3 expression and its relationship to tubulointerstitial injury in a rat model of chronic CsA nephropathy. Sprague-Dawley rats kept on a low-salt diet (0.05% sodium) were treated daily for 4 weeks with subcutaneous injections of vehicle (olive oil, 1 mL/kg) or CsA (15 mg/kg). The expression of betaig-h3 messenger RNA (mRNA) and protein was evaluated with the use of in situ hybridization, immunohistochemical methods, and immunoblotting. We also compared renal function, histologic findings (tubulointerstitial fibrosis), and expression of TGF-beta1 among treatment groups. In vehicle-treated kidney, betaig-h3 mRNA and protein were constitutively expressed in the outer medulla and cortex, which was confined to the terminal portion of afferent arterioles, the S3 segment of the proximal tubules, and distal convoluted tubules. CsA treatment significantly up-regulated betaig-h3 expression in the interstitium, especially in expanded and fibrotic areas. Quantitative analysis revealed that CsA induced a significant (twofold) increase in betaig-h3 mRNA and protein, and this increase was correlated with up-regulation of TGF-beta1 expression (r =.943, P <.001) and the tubulointerstitial fibrosis score (r =.746, P =.05). Our observations indicate that an increase in betaig-h3 expression, along with TGF-beta1 up-regulation, is closely associated with tubulointerstitial fibrosis in a rat model of chronic CsA nephropathy.

Animals↗

Refolding and purification of unprocessed porcine myostatin expressed in Escherichia coli.

Myostatin is a member of the transforming growth factor-beta (TGF-beta) superfamily, and it acts as a negative regulator for skeletal muscle growth. Like many other TGF-beta family member proteins, the mature form of myostatin is a homodimer that is processed post-translationally from a precursor form of myostatin. Since the presence of a prodomain is essential for proper folding and homodimer assembly for some members of the TGF-beta superfamily, we compared the refolding in vitro of porcine unprocessed and mature myostatin over-expressed in Escherichia coli as inclusion bodies. A high alkaline buffer solution containing a mild anionic detergent and a reducing agent was used to solubilize the myostatin inclusion bodies. An optimal condition for refolding was obtained by rapid dilution of the solubilized protein in a buffer system containing reduced and oxidized glutathione, and subsequent incubation at 4 degrees C for at least 7 days. The unprocessed porcine myostatin demonstrated reversible disulfide bond formation after refolding, a characteristic of the native form of myostatin. In contrast, the mature myostatin formed aggregates that did not demonstrate reversible disulfide bond formation in the refolding condition used in this study. These results demonstrate the importance of the myostatin prodomain in facilitating the proper folding of mature myostatin. Reaction of the refolded, unprocessed myostatin with furin, an endopeptidase cleaving between paired basic residues, yielded prodomain and mature myostatin, demonstrating that the unprocessed myostatin is a substrate for furin. The prodomain did not form disulfide bond formation but the mature myostatin demonstrated reversible disulfide-linked homodimer formation. It is concluded that myostatin prodomain facilitates the proper folding of myostatin, and the refolded, native form of unprocessed myostatin could be obtained in high yield (15%) after E. coli expression as inclusion bodies.

Animals↗

Eleven-year experience of low grade lymphoma in Korea (based on REAL classification).

Low grade lymphomas are malignancies of predominantly small lymphocytes that typically have long median survival periods due to low proliferative rates. It is considered an indolent disease, but patients with low grade lymphoma can almost never be cured with conventional treatment. New low- grade lymphoma entities have been classified by the International Lymphoma Study Group (ILSG) and are also categorized into the Revised European American Lymphoma (REAL) classification. The REAL classification utilizes a multiparameter definition of clinico-pathologic and biologic entities. According to this classification, we investigated the incidence, various clinical characteristics, treatment outcome and prognostic factors of low grade lymphoma. Many clinical characteristics of low grade lymphoma in Korea differed from those of Western countries, especially in the incidence, therapeutic outcome and prognostic factors. In Korea, although the general incidence of low grade lymphoma is relatively low, the relative number of mucosa-associated lymphoid tissue lymphoma (MALToma) is very high, and the overall survival rate is better than that reported of Western countries. Thus, further investigation on treatment outcome and prognosis of low grade lymphoma entities, other than mucosa- associated lymphoid tissue lymphoma, are warranted.

Adolescent↗

Pravastatin treatment attenuates interstitial inflammation and fibrosis in a rat model of chronic cyclosporine-induced nephropathy.

We investigated the effects of pravastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, on interstitial inflammation and fibrosis, using an animal model of chronic cyclosporine A (CsA)-induced nephropathy. Sprague-Dawley rats were maintained on a low-salt diet (0.05% sodium) and treated daily for 1 or 4 wk with vehicle (olive oil; 1 ml/kg sc), CsA (15 mg/kg sc), or both CsA and pravastatin (5 or 20 mg/kg in the drinking water). Anti-inflammatory and antifibrotic effects of pravastatin were studied by evaluating the concentrations of the inflammatory mediators osteopontin (OPN) and C-reactive protein (CRP), of fibrotic cytokine-transforming growth factor (TGF)-beta1, and the presence of ED-1-positive cells (macrophages). In addition, renal function, serum lipid levels, histopathology (arteriolopathy and tubulointerstitial fibrosis), and the expression of the vasoactive factors endothelial nitric oxide synthase (eNOS) and renin protein were also compared for different treatment groups. Pravastatin induced dose-dependent decreases in the expression of OPN, intrarenal CRP, and TGF-beta1, and in the numbers of ED-1-positive cells at 1 and 4 wk. These were accompanied by a significant attenuation of tubulointerstitial fibrosis at 4 wk. The downregulation of eNOS protein expression in CsA-treated rat kidney was markedly upregulated by pravastatin treatment, although intrarenal renin expression was unaffected. Renal dysfunction induced by CsA significantly improved with administration of pravastatin at a dose of 20 mg/kg. Neither CsA nor pravastatin influenced serum lipid or high-sensitivity CRP levels in the treatment groups. Thus in chronic CsA nephropathy, pravastatin effectively abrogates the progression of tubulointerstitial inflammation and fibrosis. This may support the clinical use of pravastatin.

Animals↗

Preconditioning with erythropoietin protects against subsequent ischemia-reperfusion injury in rat kidney.

Improving the ability of the kidney to tolerate ischemic injury has important implications. We investigated the effect of recombinant human erythropoietin (rHuEPO) treatment on subsequent ischemia/reperfusion (I/R) injury and evaluated the role of heat shock protein (HSP) 70 in rHuEPO-induced renal protection. rHuEPO (3000 U/kg) was administered 24 h before I/R injury, and rats were killed at 24, 48, and 72 h after I/R injury. Pretreatment of rHuEPO resulted in the following: i) decreased serum creatinine level; ii) decreased tubular cell apoptosis and necrosis, measured by DNA fragmentation analysis and TUNEL staining and histomorphological criteria; iii) decreased tubular cell proliferation as determined by proliferating cell nuclear antigen expression; iv) increased bcl-2 protein and decreased caspase 3 activity; and v) decreased JNK expression. rHuEPO treatment increased HSP70 expression in a dose-dependent manner in normal rat kidneys, and inhibition of HSP70 expression by quercetin eliminated the renoprotective effect of rHuEPO in ischemic kidneys. Our study demonstrates that rHuEPO has a protective effect on subsequent I/R injury and that this effect is associated with induction of HSP70. Our study provides a new avenue for therapy to prevent renal damage after I/R injury.

Animals↗

Synergistic effects of mycophenolate mofetil and losartan in a model of chronic cyclosporine nephropathy.

BACKGROUND: Combined treatments of mycophenolate mofetil (MMF) and losartan (LSRT) have synergistic effects on various renal diseases through their hemodynamic and anti-inflammatory effects. This study investigated whether MMF treatment is effective in inhibiting inflammatory processes in chronic cyclosporine A (CsA) nephrotoxicity, and whether combined treatment using MMF and LSRT affords superior protection compared with the respective monotherapies. METHODS: Rats on a low-salt diet were given vehicle (VH group, olive oil, 1 mg/kg per day), CsA (15 mg/kg per day), CsA and LSRT (CsA+LSRT group, 100 mg/L per day), CsA and MMF (CsA+MMF group; 40 mg/kg per day), or CsA, LSRT and MMF (CsA+LSRT MMF group). Control groups received each drug without CsA treatment. Renal function, histologic parameters (arteriolopathy, tubulointerstitial fibrosis, and inflammatory cell infiltration), and mediators of CsA-induced nephrotoxicity (angiotensin-II, osteopontin, and transforming growth factor [TGF]-beta1) were studied. RESULTS: The CsA-treated rats showed decreased renal function and increased histologic parameters compared with the VH-treated rats. The CsA+MMF treatment significantly improved renal function and histopathologic parameters compared with the CsA group, and combined treatment with MMF and LSRT further improved those parameters compared with the CsA+LSRT and CsA+MMF groups. At a molecular level, increased expression of angiotensin II protein, osteopontin, and TGF-beta1 mRNAs in the CsA group were significantly decreased with MMF, and further decrease was observed with the combined treatment using MMF and LSRT. CONCLUSIONS: MMF treatment decreases CsA-induced nephrotoxicity, and combined treatment with LSRT has a synergistic effect in preventing chronic CsA nephrotoxicity.

Angiotensin II↗