Seoyon Yang

Effect of Virtual Reality on Cognitive Dysfunction in Patients With Brain Tumor

Objective To investigate whether virtual reality (VR) training will help the recovery of cognitive function in brain tumor patients. Methods Thirty-eight brain tumor patients (19 men and 19 women) with cognitive impairment recruited for this study were assigned to either VR group (n=19, IREX system) or control group (n=19). Both VR training (30 minutes a day for 3 times a week) and computer-based cognitive rehabilitation program (30 minutes a day for 2 times) for 4 weeks were given to the VR group. The control group was given only the computer-based cognitive rehabilitation program (30 minutes a day for 5 days a week) for 4 weeks. Computerized neuropsychological tests (CNTs), Korean version of Mini-Mental Status Examination (K-MMSE), and Korean version of Modified Barthel Index (K-MBI) were used to evaluate cognitive function and functional status. Results The VR group showed improvements in the K-MMSE, visual and auditory continuous performance tests (CPTs), forward and backward digit span tests (DSTs), forward and backward visual span test (VSTs), visual and verbal learning tests, Trail Making Test type A (TMT-A), and K-MBI. The VR group showed significantly (p<0.05) better improvements than the control group in visual and auditory CPTs, backward DST and VST, and TMT-A after treatment. Conclusion VR training can have beneficial effects on cognitive improvement when it is combined with computer-assisted cognitive rehabilitation. Further randomized controlled studies with large samples according to brain tumor type and location are needed to investigate how VR training improves cognitive impairment.

Outcomes of Drug-Resistant Urinary Retention in Patients in the Early Stage of Stroke

Objective To investigate the prognosis of patients with stroke and urinary retention resistant to alpha blockers and cholinergic agents. Methods Post-void residual urine volume (PVR) was measured in 33 patients with stroke (14 men and 19 women) who were admitted to the department of rehabilitation medicine of our hospital within 30 days after stroke onset. An alpha-blocker and cholinergic agent were administered to patients with PVR >100 mL. If urinary retention had not improved despite the maximum drug doses, the patient was diagnosed with drug-resistant urinary retention. We retrospectively reviewed patients charts, including PVR at discharge and prognostic factors for PVR. Results Ten patients (30.3%) could not void or their PVR was >400 mL at discharge (45.7±15.4 days after onset) after rehabilitation. Twelve patients (36.4%) could void, and their PVR was 100-400 mL. PVR was consistently <100 mL in 11 patients (33.3%). These measurements correlated with the Korean version of the Modified Barthel Index score, Functional Ambulation Category, and the presence of a communication disorder. Conclusion The results show that 22 patients (66.7%) had incomplete bladder emptying or required catheterization at discharge. Outcomes correlated with functional status, walking ability, and the presence of a communication disorder. Patients with urinary retention and poor general condition require close observation to prevent complications of urinary retention.

The Effect of Stroke on Pharyngeal Laterality During Swallowing

Objective To investigate whether patterns of dysphagia and swallowing laterality differ according to the location of brain lesions in patients with stroke. Methods Patients with stroke >20 years of age were enrolled in this study. A videofluoroscopic swallowing study (VFSS) including the anterior-posterior view was used to assess swallowing. Patterns of swallowing were classified into three types according to the width of barium sulfate flow while passing the pharyngoesophageal segment: right-side-dominant flow, left-side-dominant flow, and no laterality in flow. Laterality was defined when the width of one side was twice or more the width of the other side. Results A total of 92 patients who underwent swallowing function evaluations by VFSS were enrolled from Sep-tember 2012 to May 2013. Of these, 72 patients had supratentorial lesions (group I) and 20 patients had infratento-rial lesions (group II). Only 10 patients (13.9%) in group I and three patients (15.0%) in group II showed laterality. Of these 13 patients, laterality occurred on the left side regardless of the side of the brain lesion. No relationships were found between swallowing laterality and location of stroke or motor weakness. Conclusion The results suggest that swallowing laterality was not prevalent among patients with stroke and that lesion side, location of the brain lesion, or motor weakness did not influence swallowing laterality. Although stroke can cause symptoms of dysphagia, it is difficult to conclude that stroke has a crucial impact on swallowing laterality.

Transcriptional Regulation of Th17 Cell Differentiation Mediates Ischemia-Reperfusion Injury.: Abstract# 2122

2122 Transcriptional Regulation of Th17 Cell Differentiation Mediates Ischemia-Reperfusion Injury. J. Park,1 J. Lee,2 R. Cha,3 K. Yoo,1 S. Han,1 Y. Kim,1,4 S. Yang.4 1Internal Medicine, Seoul National University College of Medicine, Seoul, Korea, Republic of; 2Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea, Republic of; 3Internal Medicine, National Medical Center, Seoul, Korea, Republic of; 4Seoul National University Kidney Research Institute, Seoul, Korea, Republic of. Interleukin (IL)-17-producing CD4+T cells (Th17) have been known to play an important role in the pathogenesis of acute kidney injury (AKI). IL-17 is the major cytokine of Th17 cells and signal transducer and activator of transcription3 (STAT3) is the essential transcriptional factor for Th17 cell differentiation. However, the underlying mechanisms have not been identifi ed. We evaluated the role of STAT3/ Th17 pathway focusing on IL17, STAT3 and RORγt in bilateral renal ischemia/ reperfusion injury (IRI). The severity of renal injury signifi cantly improved for T-cell specifi c deletion of STAT3 mice (Stat3fl /fl Lck-CRE+/-) compared to control mice (Stat3fl /fl Lck-CRE-/-) at day 2. Intra-renal mRNA expressions of IL-6, IL-12p40, IL-23, IL-23R, TGFβ, STAT3, IL-17R and IL-17 were up-regulated in control mice rendered IRI, whereas the levels of those mRNA were suppressed following the deletion of T-cell specifi c STAT3. Precisely, both in the kidney and spleen tissues, mRNA expressions of SOCS3 and RORγt were mitigated, while mRNA expressions of CTR9 (a component of PAFc) was elevated in T-cell specifi c deletion of STAT3 mice than in control mice. The expressions of CTR9 mRNA effectively decreased during the differentiation processes of Th17 cells. Blocking the JAK2/STAT3 pathway with caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE) signifi cantly protected kidneys from IRI. CADPE decreased STAT3 phosphorylations and apoptosis of mouse tubular epithelial cells on hypoxia condition. Therefore, we conclude that STAT3/Th17 pathway mediates kidney tissue damage in murine IRI and that blocking JAK2/STAT3 may provide a potential strategy for treating AKI. Abstract# 2123 Subtance P Inhibits Kidney Damage and Fibrosis in Long-Term Ischemia-Reperfrusion Injury. S. Lee,1 D. Kim,1 J. Seo,1 J. Moon,1 A. Lee,1 S. Kim,1 K. Jeong,1 Y. Kim.2 1Nephrology, Kyung Hee University, Seoul, Korea, Republic of; 2Nephrology, Inje University, Pusan, Korea, Republic of. 2123 Subtance P Inhibits Kidney Damage and Fibrosis in Long-Term Ischemia-Reperfrusion Injury. S. Lee,1 D. Kim,1 J. Seo,1 J. Moon,1 A. Lee,1 S. Kim,1 K. Jeong,1 Y. Kim.2 1Nephrology, Kyung Hee University, Seoul, Korea, Republic of; 2Nephrology, Inje University, Pusan, Korea, Republic of. Background: Role of Bone marrow, a reservoir for endothelial precursor cells (EPCs) and mesenchymal stem cells (MSCs), in kidney regeneration is still obscure. Recently substance-P (SP), an injury-inducible messenger to mobilize bone marrow stem cells, has been suggested to be a novel target of regenerative medicine. We investigated the long-term effects of the SP on kidney exposed to IRI. Methods: Unilateral renal ischemia–reperfusion injury (IRI) model was established in C57BL/6 mice and 5 ng/kg/day SP or saline was administered twice a week for 5 weeks after the surgery. Renal function was monitored, and histological changes and fi brosis in the kidney were evaluated in both two weeks and fi ve weeks. TGF-β1 and α-SMA expressions, markers of renal fi brosis were determined by Western blot. The infi ltration of macrophages in renal tissues was also assessed by immunohistochemistry. Results: Renal IRI increased SP levels in peripheral blood. Mobilized EPCs and MSCs in peripheral blood showed peak at 1 day after IRI, followed by subsequently decreased at 3 and 5 days. Administration of SP maintained the peripheral mobilization of EPCs to 5 days. Tubular injury scores of the SP group were signifi cantly lower than those of the saline group at both two and fi ve weeks. Interstitial fi brosis was also consistent with the result of tubular damage as there was signifi cantly lower degree of interstitial fi brosis in SP group at 5 weeks. Intrarenal TGF-β1 and α-SMA expressions in SP treated group were signifi cantly lower than those in saline treated group. Infi ltration of macrophage was also signifi cantly decreased in SP treated group. Conclusion: Our data show that long-term administration of SP ameliorates kidney damage and fi brosis after ischemic reperfusion injury and suggest the possible role of SP and bone marrow derived stem cells in kidney regeneration. Abstract# 2124 Modulation of Anti-Ageing Gene Klotho (KL) in Patients With Delayed Graft Function (DGF) and Ischemia/Reperfusion (I/R) Injury: Possible Role of Complement in the Regulation of Transplant Cellular Senescence. G. Castellano,1 A. Intini,1 A. Stasi,1 C. DIvella,1 M. Gigante,1 A. Zito,1 P. Pontrelli,1 G. Lucarelli,1 P. Ditonno,1 M. Battaglia,1 G. Pertosa,1 L. Gesualdo,1 G. Grandaliano.2 1Emergency and Organ Transplantation, University of Bari, Bari, Italy; 2University of Foggia, Foggia, Italy. BACKGROUND. The KL aging suppressor gene encodes a trans-membrane protein that is mainly produced at renal level and is released into blood as an endocrine anti-aging factor. Recent studies demonstrated a reduction of circulating KL in acute kidney injury. Aim of our study was to investigate the modulation of KL in a swine model of I/R injury and in DGF patients. METHODS Ten pigs underwent to 30 min of renal warm ischemia followed by 24h of reperfusion. To investigate the role of Complement in this setting, recombinant C1inhibitor (rhC1-Inh) was administered in 5 pigs 5 min before the start of reperfusion. KL expression was investigated by immune-histochemical analysis in renal biopsies from animal model and transplant patients. We also evaluated KL in renal tubular epithelial cells (HK2) in vitro and in patients by ELISA and western blot. RESULTS BY immunohistochemical analysis we found that I/R injury induced a signifi cant reduction in tissue KL at 24h from reperfusion compared to basal (T24:30.4%±1.2% vs. T0:72.5%±2.1%,p<0.05). Complement inhibition signifi cantly preserved KL protein expression in renal tubular epithelial cell in vivo (T24 rhC1-inh: 70.7%±1.9% vs. T24 control pigs, p<0.05). In accordance, activation of renal HK2 cells by Complement anaphylotoxin C3a in vitro (5x10-7M for 24h) led to signifi cant down regulation of KL protein as showed by Western Blot analysis. When we analyzed biopsies from patients with DGF, we found a signifi cant reduction in tubular KL compared to pre-transplant expression levels (DGF:10.8%±0.6% vs. preTX:73.1%±2.5%,p<0.05). Finally, when we compared DGF patients AT 2 years from TX, we found a signifi cant difference in KL serum levels compared with EGF patients with similar renal function (DGF: 412pg/ml±106 vs. EGF:900.25pg/ ml±153.9,p=0.03) by ELISA assay. CONCLUSIONS Our study showed for the fi rst time that the Complement system is pivotal in regulating KL production in tubular epithelial cells in I/R injury. Considering the central role of KL in preventing cellular senescence and apoptosis, we hypothesize that local and systemic KL defi ciency might play a central role in DGF-associated chronic allograft dysfunction. Abstract# 2125 Inhibition of Puringergic Receptors By Oxidized Adenosine Triphosphate Protects the Kidneys Against Ischemia-Reperfusion Injury. T. Koo,1,2 J. Yang,2 J. Jeong,1 S. Hurh,2 B. Cho,2 H. Kim,2 S. Lee,2 K. Han,2 H. Jeon,1 J. Park,3 I. Yoon,4 C. Ahn,1,2,5 J. Yang.1,2 1Transplantation Center, Seoul National University Hospital, Seoul, Korea, Republic of; 2Transplantation Research Institute, Seoul National University, Seoul, Korea, Republic of; 3Department of internal Medicine, Konkuk University, Seoul, Korea, Republic of; 4Department of Surgery, Konkuk University, Seoul, Korea, Republic of; 5Department of internal Medicine, Seoul National University Hospital, Seoul, Korea, Republic of. Background: Extracellular adenosine triphosphate (ATP) plays a crucial role in promoting infl ammatory immune responses. The extracellular ATP can stimulate effector T cells, dendritic cells (DCs) through P2X receptor, and oxidized ATP (oATP), a P2X receptor antagonist, can induce regulatory T cells (Tregs). Here, we investigated whether oATP can attenuate renal ischemia-perfusion injury (IRI). Methods: Bilateral renal IRI was induced in male wild type and RAG-1 knockout (KO) C57BL/6 mice. oATP or PBS was administered intraperitoneally to the mice for 7 consecutive days beginning 6 days before bilateral IRI in a prevention model, or 4 consecutive days beginning 1 day after IRI in a treatment model. Results: In the prevention model, both serum BUN and creatinine on D1 were signifi cantly lower in the oATP than in the PBS. Both tubular injury score and tubular epithelial cell apoptosis were also signifi cantly lower in the oATP. oATP signifi cantly attenuated the infi ltration of MHC II+, CD40+, or CD86+ DCs, neutrophils and macrophages into the renal tissue after IRI. It decreased infi ltration of activated CD69+CD4+ or CD44+CD4+ T cells, while signifi cantly increased infi ltration of Foxp3+CD4+ Tregs in renal tissue. Expression of both IL-6 and CCL2 was reduced in the oATP group. Treg depletion using PC61 abrogated the benefi cial effects of oATP. oATP also decreased infi ltration of innate immune cells, and attenuated renal functional deterioration after IRI in RAG-1 KO as well as wild type mice.In the treatment model, renal function on D5 was signifi cantly better in the oATP than the PBS. oATP decreased infi ltration of innate and adaptive effector cells, and increased infl itration of Foxp3+CD4+ Tregs in renal tissue. In addition, oATP increased renal tubular cell proliferation on D5 and reduced renal fi brosis on D28. Conclusion: oATP can attenuate acute renal damage, and im