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S B Park

Publications and source records attributed to S B Park.

At least 19 recordsLinked to original sources
PubMed2006

Cyclosporine-induced apoptosis in osteosarcoma cells.

INTRODUCTION: Posttransplant bone disease is one of the complications of cyclosporine (CsA), which is widely used as an immunosuppressive agent in the field of kidney transplantation. Cyclosporine treatment causes osteopenia as a result of altered bone turnover, but the pathogenic mechanisms of this process remain unclear. This study examined the ability of CsA to induce apoptosis in a rat osteoblast cell line. RESULTS: We induced apoptosis in rat osteoblastic ROS 17/2.8 cells by exposure to CsA. MTT assay showed that CsA exhibited significant cytotoxic effects on ROS 17/2.8 cells in a dose-dependent manner. Western blot analysis showed enhanced processing of caspase-8, Bax, and p53 after CsA treatment. Expression of cleaved poly (ADP-ribose) polymerase (PARP) was elevated by CsA treatment. Pro-caspase-3 and Bcl-2 proteins were decreased by CsA. CONCLUSIONS: These results suggested that CsA induced apoptosis of osteoblasts.

Animals↗
PubMed2006

Apoptosis by cyclosporine in mesangial cells.

INTRODUCTION: The immunosuppressive agent cyclosporine (CsA) is widely used to treat allograft rejection and various autoimmune disorders. A major limiting factor in the use of CsA is chronic nephrotoxicity. The pathogenesis of CsA-induced nephrotoxicity is not fully understood. Several recent studies have suggested that CsA treatment directly induces apoptosis in several cell types. The present study was undertaken to investigate the effects of CsA on apoptosis of cultured rat mesangial cells (RMCs). METHODS: RMCs were treated with CsA at concentrations of 0.1 to 40 mumol/L. Cell viability was determined by MTT assay. Apoptotic protein expression was determined by Western blot analysis. RESULTS: Cell viability was decreased with increasing concentrations of CsA in dose-dependent manner. CsA produced dose-dependent induction of p53, caspase-6, and Bax protein expression. CsA treatment caused proteolytic cleavage of caspase-3 and induced the degradation of 116-kDa PARP into 89-kDa fragment. RMCs with CsA reduced Bcl-2 and cIAP expression. CONCLUSIONS: In this study, CsA induced apoptosis by up-regulating proapoptotic factors, caspase-3 and -6, p53, Bax, cleaving PARP, and down-regulating antiapoptotic factor, Bcl-2, and cIAP. These results suggested that the increased cell apoptosis exerted by CsA may be one of the mechanisms promoting CsA-induced nephrotoxicity.

Animals↗
PubMed2006

Effect of tacrolimus on the production of oxygen free radicals in hepatic mitochondria.

OBJECTIVES: Cyclosporine (CsA) causes side effects that occur mainly in the kidney but also in the liver. Several reports have strongly suggested that the production of oxygen free radicals (OFRs) is a common mechanism of CsA toxicity. However, tacrolimus is believed to suppress the production of OFRs. METHODS: We obtained the mitochondrial fraction with 96% purity from rat liver using a sucrose density gradient solution. Zero to 100 micromol/L tacrolimus was incubated with the mitochondrial fraction for 6 hours at 37 degrees C. OFRs were evaluated by measuring the fluorescent product from the oxidation of an oxidant-sensitive 2,7-dichlorefluorescein using a VICTOR3 multilabel counter. RESULTS: The fluorescence units for OFR production were increased as the time of exposure to tacrolimus passed from 1 to 6 hours. The fluorescence units in 0.1 micromol/L tacrolimus were 6.0 x 10(5) at 1 hour, 7.8 x 10(5) at 2 hours, 9.0 x 10(5) at 3 hours, 10.0 x 10(5) at 4 hours, 11.1 x 10(5) at 5 hours, and 11.4 x 10(5) at 6 hours. However, the fluorescence units were similar although the tacrolimus concentration increases from 0.1 to 100 micromol/L. CONCLUSIONS: The results in this experiment suggested that tacrolimus induced the production of OFRs depending on the exposure time.

Animals↗
PubMed2006

Effects of cyclosporine and tacrolimus on the oxidative stress in cultured mesangial cells.

OBJECTIVES: Cyclosporine (CsA) and tacrolimus (Tac) are two primary immunosuppressive agents used for the prevention of graft rejection. However, their use is associated with significant side effects, most notably nephrotoxicity. The mechanisms of this toxicity are not fully understood, but they seem to be associated with increases in the production of oxygen free radicals (OFRs). This present work examined the effect of CsA and Tac on the production of OFRs in cultured rat renal mesangial cells (RMCs). METHODS: Varying concentrations of CsA and Tac (0 to 40 micromol/L) were added to RMCs and incubated for 60 minutes at 37 degrees C. The production of OFRs was evaluated by measuring the fluorescent product from the oxidation of an oxidant-sensitive 2', 7'-dichlorofluorescin. RESULTS: At 60 minutes, the relative fluorescence units (RFU) for OFRs production in RMCs exposure to CsA were increased by 2.5%, 11.5%, 22.5%, 57.2%, and 174% at 2.5, 5, 10, 20, and 40 micromol/L, respectively. Tac increased the RFU by 15.9%, 13.6%, 14.8%, 13.2%, 21.4%, 13.2%, and 28.1% at 0.1, 1, 2.5, 5, 10, 20, and 40 micromol/L, respectively. In RMCs, the RFU produced by CsA was higher than that by Tac. CONCLUSIONS: The results of this experiment suggest that CsA and Tac induced renal injury by OFRs.

Animals↗
PubMed2006

Polyoma virus-associated nephropathy and concurrent cytomegalovirus infection in the kidney transplant recipients.

INTRODUCTION: Cytomegalovirus (CMV) and polyoma virus BK (BKV) may both establish latency following primary infection. Frequent reactivation of these viruses can occur in the kidney transplant recipients. BKV may induce CMV gene expression by stimulating cellular regulator proteins or by its own gene regulator proteins. A high rate of concurrent CMV infections has been noted in kidney transplant recipients with polyoma virus-associated nephropathy (PVAN). METHODS: PVAN was identified in 10 of 191 patients who received kidney transplants between October 1998 and September 2003. PVAN was confirmed by allograft kidney biopsy. Four of the 10 patients were complicated by concurrent CMV infection. RESULTS: Two patients had only serological evidence of CMV infection and one patient had CMV gastritis. These three patients were treated with intravenous ganciclovir with good results. Disseminated ganciclovir-resistant CMV disease was demonstrated in the remaining patient. This 34-year-old kidney transplant recipient with PVAN died of multiorgan failure despite antiviral therapy with both ganciclovir and foscarnet. CONCLUSION: PVAN with concurrent CMV infection in kidney transplant recipients showed variable clinical courses including mortality. Further studies are needed to elucidate the influence of PVAN on the pathogenesis of CMV infection.

Adult↗
PubMed2006

Total antioxidant status and oxygen free radicals during hepatic regeneration.

OBJECTIVES: The damage induced by oxygen free radicals (OFRs) is caused by an imbalance of the production of versus the antioxidant defenses against OFRs. METHODS: To understand hepatic damage induced by oxygen free radicals after hepatectomy in rats, total antioxidant status and total production of oxygen free radicals were serially measured in regeneration liver. At 1, 2, 3, 7, and 10 days after hepatectomy of Sprague-Dawley rats, blood was obtained into a capillary tube from a tail vein. Total antioxidant status and total production of oxygen free radicals were measured using the Randox kit, a colorimetric method, and the Free Radical Analytical System. We also measured the amount of malonyldialdehyde, which provides an indirect index of oxidative injury. RESULTS: The level of malonyldialdehyde after hepatectomy was higher compared with that before hepatectomy. The level of total oxygen free radicals after hepatectomy was higher compared with that before hepatectomy. Total antioxidant status after hepatectomy was lower compared with that before hepatectomy. CONCLUSIONS: The results suggested that the damage by OFRs to the regenerating liver was caused by increased production of OFRs and decreased antioxidant defense against OFRs.

Animals↗
PubMed2005

Genome-wide linkage analysis of mandibular prognathism in Korean and Japanese patients.

The existence of familial aggregation of mandibular prognathism (MP) suggests that genetic components play an important role in its etiology. In this study, a genome-wide linkage analysis to identify loci susceptible to MP was conducted with 90 affected sibling-pairs in 42 families, comprised of 40 Korean sibling-pairs and 50 Japanese sibling-pairs. Two non-parametric linkage analyses, GENEHUNTER-PLUS and SIBPAL, were applied and detected nominal statistical significance of linkage to MP at chromosomes 1p36, 6q25, and 19p13.2. The best evidence of linkage was detected near D1S234 (maximum Z(lr) = 2.51, P = 0.0012). In addition, evidence of linkage was observed near D6S305 (maximum Z(lr) = 2.23, P = 0.025) and D19S884 (maximum Z(lr) = 1.93, P = 0.0089). Identification of the susceptible genes in the linkage regions will pave the way for insights into the molecular pathways that cause MP, especially overgrowth of the mandible, and may lead to the development of novel therapeutic tools.

Adolescent↗
PubMed2004

Primary immunosuppression with tacrolimus in kidney transplantation: three-year follow-up in a single center.

INTRODUCTION: The 1-year results of the phase III US Multicenter Trial comparing tacrolimus- and cyclosporine (Sandimmun)-based immunosuppressive therapy in kidney transplantation revealed a significant reduction in the incidence and severity of acute rejection episodes among patients maintained on tacrolimus. This retrospective, nonrandomized, single-center study represented 3-year data for patient and graft survival and safety in the tacrolimus-treated patients. METHODS: Among 97 consecutive kidney transplant recipients 41 who received tacrolimus and 56 cyclosporine-based immunosuppression were followed for 3 years for patient and graft survivals and for the incidence of acute rejection episodes as well as serious adverse events. RESULTS: The 3-year patient and graft survival rates for tacrolimus and cyclosporine were similar (91.0% vs 90.2%, 96.5% vs 95.0%). However, the incidence of acute rejection episodes was significantly lower in the tacrolimus (17.1%) compared with the cyclosporine group (35.7%, P = .043). There was a higher incidence of headache, posttransplant diabetes, and alopecia reported in the tacrolimus group, whereas hypertension, hypercholesterolemia, and hirsutism were more frequent in the cyclosporine group. The incidences of hand tremor, hyperkalemia, and viral infections were comparable in both groups. Two patients in the tacrolimus group were converted to cyclosporine due to nephrotoxicity and posttransplant diabetes, respectively, whereas 12 patients in the cyclosporine group were converted to tacrolimus as rescue therapy for acute rejection (41.7%), gingival hyperplasia (33.3%), nephrotoxicity (8.3%), neurotoxicity (8.3%), and hirsutism (8.3%), respectively. CONCLUSION: The 3-year results of tacrolimus treatment show excellent efficacy and safety in kidney transplantation. Due to different side-effect profiles, it is necessary to develop individualized immunosuppressive strategies in kidney transplant recipients.

Cyclosporine↗
PubMed2004

BK virus infection in kidney transplant recipients.

INTRODUCTION: Nephropathy associated with the polyomavirus type BK virus (BKV) has emerged as a cause of allograft failure linked to immunosuppressive regimens containing tacrolimus or mycophenolate mofetil (MMF). The outcome in BKV nephropathy is generally unfavorable, namely 50% of patients lose graft function. We herein report nine cases of BKV nephropathy after kidney transplantation. METHODS: From October 1998 to May 2003, 138 of 169 consecutive kidney transplant patients received tacrolimus-based immunosuppression, and 31 received cyclosporine-based immunosuppression. Additionally, 88.2% of the patients received mycophenolate mofetil (MMF). The diagnosis of BK infection was made by the presence of decoy cells in the urine and by allograft biopsy. RESULTS: There were nine cases of BKV nephropathy in kidney transplant recipients, an incidence of 5.3%. All patients with BKV nephropathy received tacrolimus, MMF, and steroids. The median time to diagnosis of BKV infection was 7.8 months after transplantation. All patients experienced an elevated serum creatinine, which stabilized or decreased in seven patients with altered or decreased immunosuppression. After a mean follow-up of 11.1 months, 2 (22.2%) of nine patients lost the graft. CONCLUSION: Because BKV nephropathy is a rare but serious complication after kidney transplantation, it should be included in the clinical differential of transplant dysfunction. In the absence of documented antiviral treatment, early diagnosis and judicious use of immunosuppressive agents is indicated to minimize the occurrence of BKV infection.

Adult↗
PubMed2004

Viral infection following kidney transplantation: long-term follow-up in a single center.

INTRODUCTION: Viral infections are a leading cause of posttransplantation morbidity and mortality. The use of more potent immunosuppressive agents is responsible in part for the increasing incidence of some viral infections. This study summarized our experience with viral infections in 561 kidney transplant recipients. METHODS: The spectrum of viral infections in 561 consecutive kidney transplant recipients was examined retrospectively from November 1982 to November 2002. RESULTS: During a mean follow-up of 64.0 months, 193 virus infections in 156 of 561 kidney transplant recipients were recorded, an incidence of 34.2%. The most common viruses were cytomegalovirus (36.3%), varicella zoster virus (29.0%), herpes simplex virus (23.8%), BK virus (4.7%), hepatitis B virus (3.6%), and hepatitis C virus (2.6%). Among the CMV infections, 77.1% developed subclinical CMV infection and 22.9% had CMV disease. Generalized herpes zoster infection occurred in three cases and chicken pox in six cases. During a mean follow-up of 64.0 months, two of 159 patients died of CMV pneumonia. CONCLUSION: Viral infections among the kidney transplant recipients continue to be a major problem despite significant progress in understanding the pathogenesis of viral infection and the advent of antiviral therapy.

Cyclosporine↗
PubMed2004

A case of fungal sepsis due to aspergillus spondylitis followed by cytomegalovirus infection in a renal transplant recipient.

UNLABELLED: Although advances in immunosuppressive therapy have led to increased survival of renal transplant recipients, there are greater risks of developing infectious complications. Because of its rarity and the lack of medical awareness, aspergillus spondylitis is often misdiagnosed as tuberculous spondylitis, especially in its early stages. We report a case of aspergillus spondylitis in a renal transplant followed by cytomegalovirus (CMV) retinitis. CASE: A 59-year-old woman was admitted due to general weakness and abdominal discomfort. She had undergone renal transplantation 3 years previously. One month before admission, she was diagnosed with CMV retinitis and treated with IV ganciclovir. On admission, she suffered from lower abdominal pain. Colonoscopy revealed multiple circular or patchy ulcers with surrounding severe mucosal edema in the sigmoid colon findings consistent with intestinal tuberculosis. On hospital day 30, she complained of lower extremity paresthesia and weakness. An MRI of the spine revealed a well-demarcated paraspinal mass around the L2-4 body; tuberculous spondylitis was initially considered. But despite antituberculosis medication, the patient progressed to spastic paraparesis and sensory changes in both lower legs, requiring urgent surgical decompression. At hospital day 60, she suffered persistent fever and developed thrombocytopenia. Wound discharge continued and paraparesis became denser. A CT of the spine showed progression of the paraspinal abscess from the L2 body to the iliac crest. CT-guided psoas muscle drainage was performed. Fungal culture showed Aspergillus species. Despite antifungal therapy, the patient died after a prolonged hospital stay due to fungal sepsis and septic shock from aspergillosis.

Aspergillosis↗
PubMed2004

A case of primary cutaneous aspergillosis in a renal transplant recipient.

UNLABELLED: Opportunistic fungal infections are life-threatening complications which are a major cause of morbidity and mortality in immunocompromized hosts such as those who have undergone organ transplantation. Aspergillosis comprises a spectrum of disease caused by a ubiquitous saprophytic mold. Invasive aspergillus is a serious life-threatening complication in immunocompromised hosts. Primary cutaneous aspergillosis occurs relatively less frequently and is poorly characterized. We report a case of cutaneous aspergillosis in a 51-year-old renal transplant recipient, which was successfully treated with local excision and concomitant antifungal therapy. CASE: A 51-year-old male renal transplant recipient presented with cutaneous nodules on the dorsum of the right hand. He underwent renal transplantation for end-stage renal disease due to adult dominant polycystic kidney disease (ADPKD) 3 years prior. Initially he suffered an acute rejection episode that was treated with steroid pulse and OKT3 therapy. Eventually he was stabilized on a combination of tacrolimus, prednisone, and mycophenolate mofetil. Three years after transplantation, he developed painless multiple (largest one 5 x 3 cm sized) nodules on the dorsum of his right hand. He was afebrile with no systemic symptoms. A skin biopsy showed a dense solid infiltration of giant cells, histiocytes, and lymphoplasma cells admixed with intra- and extracellular fungal hyphae and spores. The hyphae were septate and acute angle branching, which was consistent with aspergillosis. Oral itraconazole 200 mg/d for 5 weeks was ineffective. Treatment with liposomal amphotericin B for 4 weeks was initiated and MMF was discontinued. The medication was well tolerated with no hepatotoxic effects. Although new lesions did not appear, existing ones did not significantly improve after 4 weeks of treatment. Therefore, most lesions were excised surgically and liposomal amphotericin B continued for 2 weeks followed by treatment with oral fluconazole for 2 months. Ten moths later there was no evidence of recurrence.

Antifungal Agents↗
PubMed2001

Effect of dominant follicle removal before superstimulation on follicular growth, ovulation and embryo production in Holstein cows.

This study was to investigate whether removing the dominant follicle 48 h before superstimulation influences follicular growth, ovulation and embryo production in Holstein cows. After synchronization, ovaries were scanned to assess the presence of a dominant follicle by ultrasonography with a real-time linear scanning ultrasound system on Days 4, 6 and 8 of the estrus cycle (Day 0 = day of estrus). Twenty-six Holstein cows with a dominant follicle were divided into 2 groups in which the dominant follicle was either removed (DFR group, n=13) by ultrasound-guided follicular aspiration or left intact (control group, n=13) on Day 8 of the estrus cycle. Superovulation treatment was initiated on Day 10. All donors were superovulated with injections of porcine FSH (Folltropin) twice daily with constant doses (total: 400 mg) over 4 d. On the 6th and 7th injections of Folltropin, 30 mg and 15 mg of PGF2alpha (Lutalyse) were given. Donors were inseminated twice at 12 h and 24 h after the onset of estrus. Embryos were recovered on Day 6 or 7 after AI. During superstimulation, the number of follicles 2 to 5 mm (small), 6 to 9 mm (medium) and > or = 10 mm (large) was determined by ultrasonography on a daily basis. At embryo recovery, the number of corpora lutea (CL) was also determined by ultrasonography and blood samples were collected for analysis of progesterone concentration. Follicular growth during superstimulation was earlier in the DFR group than in the control group. The number of medium and large follicles was greater (P < 0.01) in the DFR group than in the control group on Days 1 to 2 and Days 3 to 4 of superstimulation, respectively. The numbers of CL (9.6+/-1.1 vs 6.1+/-0.9) and progesterone concentration (30.9+/-5.4 vs 18.6+/-3.5 ng/mL) were greater (P < 0.05) in the DFR group than in the control group, respectively. The numbers of total ova (7.7+/-1.3 vs 3.9+/-1.0) and transferable embryos (4.6+/-0.9 vs 2.3+/-0.8) were also greater (P < 0.05) in the DFR group than in the control group, respectively. It is concluded that the removal of the dominant follicle 48 h before superstimulation promoted follicular growth, and increased ovulation and embryo production in Holstein cows.

Animals↗
PubMed2001

A novel pH-sensitive membrane from chitosan--TEOS IPN; preparation and its drug permeation characteristics.

A novel organic-inorganic composite membrane was prepared, using tetra ethyl ortho silicate (TEOS) as an inorganic material and chitosan as an organic compound. Equilibrium and oscillatory swelling studies were conducted to investigate swelling behaviors of the membrane according to the pH of the swelling medium. Drug permeation experiments were also performed in phosphate buffer solution of the pH of 2.5 and 7.5, respectively. Lidocaine HCl, sodium salicylate and 4-acetamidophenol were selected as model drugs to examine the effect of ionic property of drug on the permeation behavior. The effects of membrane composition and the external pH on the swelling and the drug permeation behavior of IPN membrane could be summarized as follows; chitosan incorporated into TEOS IPN swelled at pH 2.5 while shrunk at pH 7.5. This swelling behavior was completely reversible and the membrane responded rapidly to the change in environmental pH condition. According to swelling behavior, an increase in pH from 2.5 to 7.5 yielded an increase in the rate of drug permeation because of the shrinking of the incorporated chitosan in TEOS IPN, while decrease in pH resulted in low permeation rate. The optimal TEOS-chitosan ratio for maximum pH-sensitivity existed and drug permeation was influenced not only with the external pH but also with the ionic interactions between the drug and membrane.

Chitin↗