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( Ji Yong Kim ),( Jai Sung Lee ),( Yong Seok Han ),( Jun Hee Lee ),( Inhyu Bae ),( Yeo Min Yoon ),( Sang Mo Kwon ),( Sang Hun Lee ) 한국응용약물학회 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.6
Human mesenchymal stem cells (MSCs) have been used in cell-based therapy to promote revascularization after peripheral or myocardial ischemia. High levels of reactive oxygen species (ROS) are involved in the senescence and apoptosis of MSCs, causing defective neovascularization. Here, we examined the effect of the natural antioxidant lycopene on oxidative stress-induced apoptosis in MSCs. Although H2O2 (200 mM) increased intracellular ROS levels in human MSCs, lycopene (10 μmM) pretreatment suppressed H2O2-induced ROS generation and increased survival. H2O2-induced ROS increased the levels of phosphorylated p38 mitogen activated protein kinase (MAPK), Jun-N-terminal kinase (JNK), ataxia telangiectasia mutated (ATM), and p53, which were inhibited by lycopene pretreatment. Furthermore, lycopene pretreatment decreased the expression of cleaved poly (ADP ribose) polymerase-1 (PARP-1) and caspase-3 and increased the expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax), which were induced by H2O2 treatment. Moreover, lycopene significantly increased manganese superoxide dismutase (MnSOD) expression and decreased cellular ROS levels via the PI3K-Akt pathway. Our findings show that lycopene pretreatment prevents ischemic injury by suppressing apoptosis-associated signal pathway and enhancing anti-oxidant protein, suggesting that lycopene could be developed as a beneficial broad-spectrum agent for the successful MSC transplantation in ischemic diseases.
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Kim, Ji Yong,Lee, Jai-Sung,Han, Yong-Seok,Lee, Jun Hee,Bae, Inhyu,Yoon, Yeo Min,Kwon, Sang Mo,Lee, Sang Hun The Korean Society of Applied Pharmacology 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.6
Human mesenchymal stem cells (MSCs) have been used in cell-based therapy to promote revascularization after peripheral or myocardial ischemia. High levels of reactive oxygen species (ROS) are involved in the senescence and apoptosis of MSCs, causing defective neovascularization. Here, we examined the effect of the natural antioxidant lycopene on oxidative stress-induced apoptosis in MSCs. Although $H_2O_2$ ($200{\mu}M$) increased intracellular ROS levels in human MSCs, lycopene ($10{\mu}M$) pretreatment suppressed $H_2O_2$-induced ROS generation and increased survival. $H_2O_2$-induced ROS increased the levels of phosphorylated p38 mitogen activated protein kinase (MAPK), Jun-N-terminal kinase (JNK), ataxia telangiectasia mutated (ATM), and p53, which were inhibited by lycopene pretreatment. Furthermore, lycopene pretreatment decreased the expression of cleaved poly (ADP ribose) polymerase-1 (PARP-1) and caspase-3 and increased the expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax), which were induced by $H_2O_2$ treatment. Moreover, lycopene significantly increased manganese superoxide dismutase (MnSOD) expression and decreased cellular ROS levels via the PI3K-Akt pathway. Our findings show that lycopene pretreatment prevents ischemic injury by suppressing apoptosis-associated signal pathway and enhancing anti-oxidant protein, suggesting that lycopene could be developed as a beneficial broad-spectrum agent for the successful MSC transplantation in ischemic diseases.
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S-344 : The Role of Skeletal Muscle Mass in Development of Metabolic Syndrome
( Byung Sam Park ),( Jun Sung Moon ),( Ji Sung Yoon ),( Kyu Chang Won ),( Hyoung Woo Lee ) 대한내과학회 2013 대한내과학회 추계학술대회 Vol.2013 No.1
Introduction: It has been well known that abdominal adiposity is related with insulin resistance and greater risk of metabolic disorder. Skeletal muscle plays central role in insulin mediated glucose disposal of whole body, but we only know a little about the association between skeletal muscle mass and MetS (MetS). The aim of this study is to clarify the clinical role of skeletal muscle mass in developing MetS through using skeletal muscle parameters by body impedance analysis (BIA). Methods: 1,042 healthy adults aged from 20 to 75 years who visited Yeungnam university health promotion center from Jun. 2008 to Jun. 2010 were enrolled. 204 subjects who had prior MetS or chronic disease that can affect to skeletal muscle mass were excluded. After 24 months from baseline, the metabolic parameters were assessed and the development of MetS was diagnosed using modified NCEP-ATP III criteria. From the BIA (Inbody 720), we obtained skeletal muscle mass (SMM, Kg), body fat mass (BFM, Kg), and visceral fat area (VFA, cm2). Then, we had defined as follows; percent of skeletal muscle mass (SMM%, %): SMM (kg)/weight (Kg), skeletal muscle index (SMI, Kg/m2): SMM (Kg)/height (m)2, skeletal muscle to body fat ratio (MFR): SMM (kg)/BFM (Kg) and skeletal muscle to visceral fat ratio (SVR, Kg/cm2): SMM (Kg)/VFA (cm2) Results: Mean follow up periods were 28.7±5.4 months. Among total 838 subjects (46.9±9.9 years, M:F=477:361), 88 (10.5%) were newly diagnosed MetS. 5th quintile of the SMM%, MFR and SVR was associated with decreased risk of development of MetS after adjusting for confounding factors. Conclusion: Decreased skeletal muscle mass may play critical role in development of the MetS and not absolute amount of skeletal muscle mass but relative ratio to body composition may be more important.
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Comparison of Utilization of Physical Therapy for Elderly Persons in Urban and Rural Areas in Honam
Ji, Sung Ha,Kim, Ki Jong,Jun, Hyun Ju,Lee, Young Sin International Academy of Physical Therapy Research 2014 Journal of International Academy of Physical Ther Vol.5 No.2
This study was carried out survey to compare using status of physical therapy for elderly persons between urban and rural area in Honam. There were 16 places consisting of general clinics, departments of family medicine, pain medicine, and orthopedics that run outpatient physical therapy. This study distributed 636 questionnaires in total and collected 400 responses. Regionally, 200 responses out of 311 questionnaires from Gwangju and 200 responses out of 325 questionnaires from Jeollanam-do and Jeollabuk-do were collected. Regionally speaking, Gwangju was 62% while Jeollanam-do and Jeollabuk-do regions were 88%, indicating patients in rural areas employed more public transportation, which was statistically significantly different. There was a difference between urban and rural areas with regard to questions regarding improvement with physical therapy. Factors related to the number of physical therapy visits per week that showed a significant difference between urban and rural areas found by the linear regression analysis result were working hours, whether the patient exercised or not, and pain stress. This result suggest that it is necessary to reduce working hours and pain stress experienced by rural elderlies as well as to encourage regular exercise via national polices.
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Daclatasvir and Asunaprevir for Chronic Hepatitis C Virus Genotype 1b Infection: Real Life Data
( Ji Hoon Kim ),( Yang Jae Yoo ),( Young-sun Lee ),( Sang Jun Suh ),( Young Kul Jung ),( Yeon Seok Seo ),( Hyung Joon Yim ),( Jong Eun Yeon ),( Kwan Soo Byun ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: We evaluated the real life efficacy and safety in Korean patients with genotype 1b HCV infection who were treated with daclatasvir and asunaprevir Methods: 410 patients with chronic HCV genotype 1b infection received RAS (resistance associated substitution) examination from July 2015 to September 2016 in three medical centers of Korea university. Among them, 241 patients received daclatasvir and asunaprevir and we analyzed the efficacy and safety in 150 patients who SVR (sustained virologic response) could be attained. HCV RNA at baseline, 4, 12, 24 weeks and SVR (post treatment 12 or 24 weeks) were assayed with laboratory tests. Lower limit of HCV RNA quantification was 20 IU/ml. Significant adverse events were defined as more than grade 3 according to CTCAE v4.0. Results: Among 410 patients, RAS were detected in 20.2% (83/410); L31(2.4%), Y93(16.6%) and both (1.2%). In 150 further analysis patients, mean age was 5.3 years, 107 (71.3%) patients were treatment naïve, and 45(30%) patients had liver cirrhosis (LC). All daclatasvir and asunaprevir treated patients did not have RAS except four (all Y93). Overall SVR rate was 90.7%(136/150). Among 146 patients with no RAS, 133(91.1%) showed SVR. In 4 RAS positive patients, 3 showed SVR. SVR rate according to presence of LC or not were 92.4% and 86.7%. SVR rate according to experience of interferon (IFN) or not were 90.7% in both. SVR rate according to presence of LC-/IFN-, LC-/IFN+, LC+/IFN- and LC+/IFN + were 94.5%, 87.5%, 82.4%, 100%. There was no statistically significant difference but a trend of lower SVR in LC+/IFN- than LC-/IFN- (p=0.07). Any adverse event occurred in 47.3% of patients. One patient showed ALT increase more than 5 upper normal limit and discontinued medication and then ALT increase recovered. Conclusions: In real-life data, daclatasvir and asunaprevir showed good efficacy in consistent with previous clinical studies.
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( Ji Won Han ),( Pil Soo Sung ),( Seon-hui Hong ),( Eui-cheol Shin ),( Myeong Jun Song ),( Su-hyung Park ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: There is a possibility that small amount of HCV RNA in the liver and circulation, risk of relapse, and risk of reinfection still remain in patients with SVR after DAA treatment; however, it remains unclear whether functionally exhausted HCV-specific T cells can be restored after complete viral clearance and its association with clinical outcomes. In this study, we prospectively investigated the functional restoration of HCV-specific CD8+ T cells, which is most important immune cells in anti-HCV immunity, in 33 DAA-treated patients with chronic hepatitis C. Methods: 33 HCV-genotype Ib patients, who treated with Daclatasvir/ Asunaprevir from Daejeon St. Mary`s hospital were recruited. PBMC samples were collected at regular clinical visits at pre-treatment, week 4, week 12, week 24, and week 36 after treatment. To assess T cell responses, IFN-γ ELISpot assay was performed, stimulated with HCV OLPs or HLA-A2 restricted HCV immunodominent epitopes. To characterize HCV-specific CD8 T cells, fluorochrome-conjugated monoclonal antibodies with pentamer or dextramer corresponding HCV-immunodominent epitopes were used for multicolor low cytometry. Results: By using ELISpot with overlapping peptides corresponding non-structural proteins of HCV, which are relatively well conserved than other HCV proteins, we found that early, transient restoration of CD8+ dominant, HCV-specific IFN-γ responses. Restored CD8+ T cells also showed polyfunctionality, which expressed TNF-α and CD107a simultaneously after HCV-peptide stimulation; Interestingly, in 3 patients with viral breakthrough, this transient T cell restoration was not observed. In addition, in line with previous study, proliferative capacity of HCV-specific CD8+ T cells also tended to be improved after DAA treatment, especially at 12 weeks of treatment. HCV-specific T cell exhaustion, represented by PD-1 expression, had a tendency to be improved and maintained after DAA treatment also at the early timepoint, but terminally differentiated phenotype of HCV-specific T cells was maintained constantly. Conclusions: These results suggest that transiently increased T cell responses may have a role to clear HCV completely at early timepoint. Furthermore, even in patients with SVR, due to insufficient immune response at late timepoint, the possibility of re-infection and relapse still exists. In conclusion, long-term, careful observation is needed in patients with chronic hepatitis C after DAA treatment.
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Interstitial granulomatous dermatitis associated with rheumatoid arthritis
( Sang Soo Choi ),( Yoon Seob Kim ),( Ji Hyun Lee ),( Jun Young Lee ),( Young Min Park ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.1
Interstitial granulomatous dermatitis (IGD) is a rare and peculiar disorder with cutaneous and joint manifestations. It may be associated with rheumatologic and hematologic disorders or underlying malignancies. Herein, we report an interesting case of IGD that began to occur after withdrawal of methotrexate in a patient with rheumatoid arthritis (RA) accompanied by elevation of activity markers of RA such as ESR and CRP. A 59-year-old Korean woman presented with multiple erythematous plaques on both extremities for 10 days. The lesions were non-tender, palpable, and linear-shaped. She had been diagnosed with RA 17 years earlier. For the treatment of RA she had been taking prednisolone, nonsteroidal anti-inflammatory drugs, and methotrexate for 7 years, and she stopped methotrexate 1 month ago. Laboratory findings revealed an elevated and ESR level Histopathologic findings showed a dense perivascular and interstitial lymphohistiocytic infiltration through the dermis with collagen degeneration and chronic granulomatous inflammation in the upper dermis. Immunohistochemically, most inflammatory cells were CD68-positive. Alcian blue staining revealed no mucin deposition in the areas of granulomatous inflammation. A 7.5-mg methotrexate dose was restarted and the daily prednisolone dose was increased from 5 mg to 15 mg. After 2-month treatment the lesions were nearly cleared, and ESR and CRP were found to be within normal limits.
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Multiple acquired periungal fibrokeratoma
( Sang Soo Choi ),( Yoon Seob Kim ),( Ji Hyun Lee ),( Young Min Park ),( Jun Young Lee ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.1
Acquired periungal fibrokeratoma (APF) is a rare, benign periungal tumor, and it usually presents as a solitary,fibrous and hyperkeratotic lesion. Multiple APF is rarely reported in the literature. Herein, we describe a rare case of symmetrical, bilateral presentation of multiple APF, which could be misdiagnosed as Koenen tumors. A 19- year-old Korean girl presented for evaluation of periungal tumors. Physical examination revealed four, asymptomatic, firm, skin-colored tumors with longitudinal grooves of subjacent nails on both great toes. She denied any recent trauma history. There was no specific past medical or familial history of dermatological, neurological and other systemic manifestations suggesting tuberous sclerosis complex. Histopathologic examination from lateral nodule of left great toe revealed hyperkeratosis, acanthosis, and hypergranulosis in the epidermis, and thick collagen bundle with proliferation of capillaries which were arranged parallel to the axis of tumor was present in the dermis. Total excision of four lesions was done, and histopathological findings were consistent with previous findings of lateral nodule of left great toe. Based on these clinical and histological findings, she was diagnosed with multiple APF. There was no recurrence for 6 months follow up.
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