New oral spherical carbon adsorbent effectively reduces serum indoxyl sulfate levels in moderate to advanced chronic kidney disease patients: a multicenter, prospective, open-label study

Background: Elevated levels of serum indoxyl sulfate (IS) have been linked to cardiovascular complications in patients with chronic kidney disease (CKD). Oral sorbent therapy using spherical carbons selectively attenuates IS accumulation in CKD patients. This study aimed to investigate whether oral administration of a new oral spherical carbon adsorbent (OSCA), reduces serum IS levels in moderate to severe CKD patients. Methods: This prospective, multicenter, open-label study enrolled patients with CKD stages 3-5. Patients were prescribed OSCA for 8 weeks (6 g daily in 3 doses) in addition to standard management. Serum IS levels were measured at baseline and 4 and 8 weeks of treatment with OSCA. Results: A total of 118 patients were enrolled and 87 eligible patients completed 8 weeks of study. The mean age of the study subjects was 62.8 ± 13.7 years, and 80.5% were male. Baseline levels of serum IS were negatively correlated with estimated glomerular filtration rate (eGFR) (r = - 0.406, P < 0.001) and increased with increasing CKD stages (stage 3, 0.21 ± 0.21 mg/dL; stage 4, 0.54 ± 0.52 mg/dL; stage 5, 1.15 ± 054 mg/dL; P for trend = 0.001). The patients showed significant reduction in serum total IS levels as early as 4 weeks after OSCA treatment (22.5 ± 13.9% reduction from baseline, P < 0.001) and up to 8 weeks (31.9 ± 33.7% reduction from baseline, P < 0.001). This reduction effect was noted regardless of age, kidney function, or diabetes. No severe adverse effects were reported. Gastrointestinal symptoms were the most commonly reported adverse effects. In total, 21 patients withdrew from the study, with dyspepsia due to heavy pill burden as the most common reason. The medication compliance rate was 84.7 ± 21.2% (min 9%, max 101%) for 8 weeks among those who completed the study. Conclusions: OSCA effectively reduced serum IS levels in moderate to severe CKD patients. Gastrointestinal symptoms were the most commonly reported complications, but no treatment-related severe adverse effects were reported.ope

Acute Fulminant Myocarditis Recovered from Electro-Mechanical Dissociation in Scrub Typhus

Scrub typhus, caused by Orientia tsutsugamushi, is an acute febrile illness. Characteristics of tsutsugamushi disease are fever, rash and eschar. However, severe complications might rarely occur, such as acute fulminant myocarditis caused by scrub typhus. Thus, there are few reports of recovery from seriously complicated cases. We report on an adult male with scrub typhus complicated with acute fulminant myocarditis with no previous comorbid illness who recovered successfully with proper treatment including antibiotics, ventilator support, percutaneous cardiopulmonary support, and continuous renal replacement therapy.ope

Microparticles derived from human erythropoietin mRNA-transfected mesenchymal stem cells inhibit epithelial-to-mesenchymal transition and ameliorate renal interstitial fibrosis

Background: Renal tubulointerstitial fibrosis (TIF) plays an important role in the progression of chronic kidney disease (CKD) and its pathogenesis involves epithelial-to-mesenchymal transition (EMT) upon renal injury. Recombinant human erythropoietin (rhEPO) has been shown to display novel cytoprotective effects, in part by inhibiting transforming growth factor (TGF)-β1-induced EMT. Here, we evaluated the inhibitory effects of microparticles (MPs) derived from human EPO gene-transfected kidney mesenchymal stem cells (hEPO-KMSCs) against TGF-β1-induced EMT in Madin-Darby canine kidney (MDCK) cells and against TIF in mouse kidneys with unilateral ureteral obstruction (UUO). Methods: EMT was induced in MDCK cells by treatment with TGF-β1 (5 ng/mL) for 48 h and then inhibited by co-treatment with rhEPO (100 IU/mL), mock gene-transfected KMSC-derived MPs (MOCK-MPs), or hEPO-KMSC-derived MPs (hEPO-MPs) for a further 48 h. UUO was induced in FVB/N mice, which were then treated with rhEPO (1000 IU/kg, intraperitoneally, every other day for 1 week), MOCK-MPs, or hEPO-MPs (80 μg, intravenously). Alpha-smooth muscle actin (α-SMA), fibronectin, and E-cadherin expression were evaluated in MDCK cells and kidney tissues, and the extent of TIF in UUO kidneys was assessed by immunohistochemical staining. Results: TGF-β1 treatment significantly increased α-SMA and fibronectin expression in MDCK cells and decreased that of E-cadherin, while co-treatment with rhEPO, MOCK-MPs, or hEPO-MPs markedly attenuated these changes. In addition, rhEPO and hEPO-MP treatment effectively decreased phosphorylated Smad2 and Smad3, as well as phosphorylated p38 mitogen-activated protein kinase (MAPK) expression, suggesting that rhEPO and rhEPO-MPs can inhibit TGF-β1-induced EMT via both Smad and non-Smad pathways. rhEPO and hEPO-MP treatment also significantly attenuated the extent of renal TIF after 1 week of UUO compared to MOCK-MPs, with hEPO-MPs significantly reducing myofibroblast and F4/80+ macrophage infiltration as well as EMT marker expression in UUO renal tissues in a similar manner to rhEPO. Conclusions: Our results demonstrate that hEPO-MPs modulate TGF-β1-induced EMT in MDCK cells via the Smad2, Smad3, and p38 MAPK pathways and significantly attenuated renal TIF in UUO kidneys.ope

Asymptomatic hyperuricemia is independently associated with coronary artery calcification in the absence of overt coronary artery disease: A single-center cross-sectional study

Recently, the pathogenic role of uric acid (UA) in both systemic metabolic and atherosclerotic diseases has been investigated. We sought to determine the independent correlation between serum UA levels and coronary artery calcification, as a marker of subclinical atherosclerosis. A total of 4188 individuals without prior coronary artery disease or urate-deposition disease were included. All of the participants underwent multidetector computed tomography (MDCT) for the evaluation of coronary artery calcification (CAC) during their health check-ups. The subjects were divided into thre groups according to CAC scores (group 1: 0; group 2: 1-299; group 3: ≥300). After controlling for other confounders, serum UA levels were found to be positively associated with increasing CAC scores (P = 0.001). Adjusted mean serum UA levels in each CAC group were estimated to be 5.2 ± 0.1 mg/dL, 5.3 ± 0.1 mg/dL, and 5.6 ± 0.2 mg/dL from groups 1, 2, and 3, respectively. Subsequent subgroup analyses revealed that this positive association was only significant in participants who were male, relatively older, less overweight, and did not have diabetes mellitus (DM), hypertension, smoking history, or renal dysfunction. In conclusion, serum uric acid levels were independently associated with CAC score severity and this finding is particularly relevant to the subjects who were male, relatively older, less overweight (body mass index < 25 kg/m), and without a history of DM, hypertension, smoking, or renal dysfunction.ope

Association of Serotonin 1A Receptor Polymorphism with Variation in Health-Related Quality of Life in Korean Hemodialysis Patients

OBJECTIVE: Hemodialysis patients may have psychological distress and reduced quality of life (QoL) related to chronic physical health problems. Genetic polymorphisms associated with reduced QoL in hemodialysis patients. The aim of this study was to investigate the relationship between genetic polymorphisms and variation in health-related QoL in Korean hemodialysis patients. METHODS: The 36-item Short-Form Health Survey and the Korean Hospital Anxiety and Depression Scale were used to assess health-related QoL and psychological distress, respectively. Twenty hundred and five clinically stable patients from 6 hemodialysis centers have participated with informed consents. Sociodemographic factors, clinical factors, and genotypes of serotonin 1A receptor, brain-derived neurotrophic factors, and glucocorticoid receptor were assessed. Independent t-tests, correlation analyses, multiple regression analyses were performed for statistical analyses. RESULTS: The serotonin 1A receptor CC genotype group showed significantly higher physical and mental QoL levels than those with the GG/GC genotypes. In the final linear regression analysis, serotonin 1A receptor CC genotype was significantly associated with positive physical and mental QoL levels. CONCLUSION: ConclusionaaSerotonin 1A receptor polymorphism, as well as age and depression, were significantly associated with mental and physical QoL in hemodialysis patients. Functional activity in the serotonin receptor system may have a modulating effect on health-related QoL in hemodialysis patients.ope

Incidentally Found Chronic Neutrophilic Leukemia in a Patient with Rectal Cancer

증례는 감염 및 악성종양과 동반되어 백혈병양 반응과의 감별이 어려웠고, 또한 악성종양의 전이와 유사하게 종괴를 형성하여 더욱 감별이 어려웠던 CNL 1예를 경험하였기에 문헌고찰과 함께 보고하는 바이다. Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm characterized by sustained neutrophilia, splenomegaly, and hypercellular bone marrow without Philadelphia chromosome. Diagnosis of CNL requires exclusion of identifiable causes of reactive neutrophilia, such as infection and tumors. Our patient presented with general weakness and weight loss. Computed tomography (CT) showed a mass in the distal rectum, which was confirmed to be an adenocarcinoma by colonoscopic biopsy. Positron emission tomography-CT showed multiple liver, bone, and lymph node metastases. Liver and lymph node biopsies revealed neutrophilic infiltration with no evidence of adenocarcinoma. The pathological findings of the bone marrow were compatible with CNL. Cytogenetic analysis revealed a normal karyotype, and molecular analysis was negative for BCR/ABL. Here, we present a 73 year-old man diagnosed with concurrent CNL and rectal cancer.ope

Transfusion-free Management for the Severe Anemia Developed after Nephrectomy

A 56-year-old woman with emphysematous pyelonephritis underwent an emergent left nephrectomy due to her religious creed. Postoperative hemoglobin level was decreased to 4.4 g/dL from preoperative value of 13.9 g/dL. The patient completely recovered without transfusion and was discharged on the 40th postoperative day without complication.ope

멀티채널 무선 메쉬 네트워크에서의 채널 그룹핑을 이용한 효율적인 채널 할당 알고리즘

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멀티 레이트 무선 메쉬 네트워크를 위한 멀티 채널 프로토콜 성능 비교

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Expression and function of YG-10, a thymocyte differentiation antigen, in peripheral T cells

학위논문(박사)--서울대학교 대학원 :의학과 병리학전공,2001.Docto