1.Fabry disease exacerbates renal interstitial fibrosis after unilateral ureteral obstruction via impaired autophagy and enhanced apoptosis
Sungjin CHUNG ; Mina SON ; Yura CHAE ; Songhee OH ; Eun Sil KOH ; Yong Kyun KIM ; Seok Joon SHIN ; Cheol Whee PARK ; Sung-Chul JUNG ; Ho-Shik KIM
Kidney Research and Clinical Practice 2021;40(2):208-219
Background:
Fabry disease is a rare X-linked genetic lysosomal disorder caused by mutations in the GLA gene encoding alpha-galactosidase A. Despite some data showing that profibrotic and proinflammatory cytokines and oxidative stress could be involved in Fabry disease-related renal injury, the pathogenic link between metabolic derangement within cells and renal injury remains unclear.
Methods:
Renal fibrosis was triggered by unilateral ureteral obstruction (UUO) in mice with Fabry disease to investigate the pathogenic mechanism leading to fibrosis in diseased kidneys.
Results:
Compared to kidneys of wild-type mice, lamellar inclusion bodies were recognized in proximal tubules of mice with Fabry disease. Sirius red and trichrome staining revealed significantly increased fibrosis in all UUO kidneys, though it was more prominent in obstructed Fabry kidneys. Renal messenger RNA levels of inflammatory cytokines and profibrotic factors were increased in all UUO kidneys compared to sham-operated kidneys but were not significantly different between UUO control and UUO Fabry mice. Protein levels of Nox2, Nox4, NQO1, catalase, SOD1, SOD2, and Nrf2 were not significantly different between UUO control and UUO Fabry kidneys, while the protein contents of LC3-II and LC3-I and expression of Beclin1 were significantly decreased in UUO kidneys of Fabry disease mouse models compared with wild-type mice. Notably, TUNEL-positive cells were elevated in obstructed kidneys of Fabry disease mice compared to wild-type control and UUO mice.
Conclusion
These findings suggest that impaired autophagy and enhanced apoptosis are probable mechanisms involved in enhanced renal fibrosis under the stimulus of UUO in Fabry disease.
2.Fabry disease exacerbates renal interstitial fibrosis after unilateral ureteral obstruction via impaired autophagy and enhanced apoptosis
Sungjin CHUNG ; Mina SON ; Yura CHAE ; Songhee OH ; Eun Sil KOH ; Yong Kyun KIM ; Seok Joon SHIN ; Cheol Whee PARK ; Sung-Chul JUNG ; Ho-Shik KIM
Kidney Research and Clinical Practice 2021;40(2):208-219
Background:
Fabry disease is a rare X-linked genetic lysosomal disorder caused by mutations in the GLA gene encoding alpha-galactosidase A. Despite some data showing that profibrotic and proinflammatory cytokines and oxidative stress could be involved in Fabry disease-related renal injury, the pathogenic link between metabolic derangement within cells and renal injury remains unclear.
Methods:
Renal fibrosis was triggered by unilateral ureteral obstruction (UUO) in mice with Fabry disease to investigate the pathogenic mechanism leading to fibrosis in diseased kidneys.
Results:
Compared to kidneys of wild-type mice, lamellar inclusion bodies were recognized in proximal tubules of mice with Fabry disease. Sirius red and trichrome staining revealed significantly increased fibrosis in all UUO kidneys, though it was more prominent in obstructed Fabry kidneys. Renal messenger RNA levels of inflammatory cytokines and profibrotic factors were increased in all UUO kidneys compared to sham-operated kidneys but were not significantly different between UUO control and UUO Fabry mice. Protein levels of Nox2, Nox4, NQO1, catalase, SOD1, SOD2, and Nrf2 were not significantly different between UUO control and UUO Fabry kidneys, while the protein contents of LC3-II and LC3-I and expression of Beclin1 were significantly decreased in UUO kidneys of Fabry disease mouse models compared with wild-type mice. Notably, TUNEL-positive cells were elevated in obstructed kidneys of Fabry disease mice compared to wild-type control and UUO mice.
Conclusion
These findings suggest that impaired autophagy and enhanced apoptosis are probable mechanisms involved in enhanced renal fibrosis under the stimulus of UUO in Fabry disease.
3.Intranasal Vaccination with OuterMembrane Protein of Orientia tsutsugamushi induces Protective Immunity Against Scrub Typhus
Sung-Moo PARK ; Min Jeong GU ; Young-Jun JU ; In Su CHEON ; Kyu-Jam HWANG ; Byoungchul GILL ; Byoung-Shik SHIM ; Hang-Jin JEONG ; Young Min SON ; Sangho CHOI ; Woonhee JEUNG ; Seung Hyun HAN ; Hyuk CHU ; Cheol-Heui YUN
Immune Network 2021;21(2):e14-
Scrub typhus develops after the individual is bitten by a trombiculid mite infected with Orientia tsutsugamushi. Since it has been reported that pneumonia is frequently observed in patients with scrub typhus, we investigated whether intranasal (i.n.) vaccination with the outer membrane protein of O. tsutsugamushi (OMPOT) would induce a protective immunity against O. tsutsugamushi infection. It was particular interest that when mice were infected with O. tsutsugamushi, the bacteria disseminated into the lungs, causing pneumonia. The i.n. vaccination with OMPOT induced IgG responses in serum and bronchoalveolar lavage (BAL) fluid. The anti-O. tsutsugamushi IgA Abs in BAL fluid after the vaccination showed a high correlation of the protection against O. tsutsugamushi. The vaccination induced strong Ag-specific Th1 and Th17 responses in the both spleen and lungs. In conclusion, the current study demonstrated that i.n. vaccination with OMPOT elicited protective immunity against scrub typhus in mouse with O. tsutsugamushi infection causing subsequent pneumonia.
4.Efficacy and Safety of Voglibose Plus Metformin in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial
Tae Jung OH ; Jae Myung YU ; Kyung Wan MIN ; Hyun Shik SON ; Moon Kyu LEE ; Kun Ho YOON ; Young Duk SONG ; Joong Yeol PARK ; In Kyung JEONG ; Bong Soo CHA ; Yong Seong KIM ; Sei Hyun BAIK ; In Joo KIM ; Doo Man KIM ; Sung Rae KIM ; Kwan Woo LEE ; Jeong Hyung PARK ; In Kyu LEE ; Tae Sun PARK ; Sung Hee CHOI ; Sung Woo PARK
Diabetes & Metabolism Journal 2019;43(3):276-286
BACKGROUND: Combination of metformin to reduce the fasting plasma glucose level and an α-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect. We compared the efficacy and safety of a fixed-dose combination of voglibose plus metformin (vogmet) with metformin monotherapy in drug-naïve newly-diagnosed type 2 diabetes mellitus. METHODS: A total of 187 eligible patients aged 20 to 70 years, with a glycosylated hemoglobin (HbA1c) level of 7.0% to 11.0%, were randomized into either vogmet or metformin treatments for 24 weeks. A change in the HbA1c level from baseline was measured at week 24. RESULTS: The reduction in the levels of HbA1c was −1.62%±0.07% in the vogmet group and −1.31%±0.07% in the metformin group (P=0.003), and significantly more vogmet-treated patients achieved the target HbA1c levels of <6.5% (P=0.002) or <7% (P=0.039). Glycemic variability was also significantly improved with vogmet treatment, estimated by M-values (P=0.004). Gastrointestinal adverse events and hypoglycemia (%) were numerically lower in the vogmet-treated group. Moreover, a significant weight loss was observed with vogmet treatment compared with metformin (−1.63 kg vs. −0.86 kg, P=0.039). CONCLUSION: Vogmet is a safe antihyperglycemic agent that controls blood glucose level effectively, yields weight loss, and is superior to metformin in terms of various key glycemic parameters without increasing the risk of hypoglycemia.
Blood Glucose
;
Diabetes Mellitus, Type 2
;
Fasting
;
Glucose
;
Hemoglobin A, Glycosylated
;
Humans
;
Hypoglycemia
;
Metformin
;
Weight Loss
5.Glomangiopericytoma of the Spinal Cord.
Sung Shik KANG ; Hee Seok JEONG ; Hee Young SON ; Tae Yong MOON
Korean Journal of Spine 2017;14(4):166-169
Glomangiopericytoma, also referred to as a hemangiopericytoma-like tumor or sinonasal type hemangiopericytoma, is a rare tumor of the nasal cavity and paranasal sinus that has never been reported in the spinal cord. Here, we report a case of a 47-year-old man who developed glomangiopericytoma in the thoracic spine. This lesion showed a heterogeneous high signal intensity compared to the spinal cord on a T2-weighted image and an easily enhanced isointense signal on a T1-weighted image.
Hemangiopericytoma
;
Humans
;
Middle Aged
;
Nasal Cavity
;
Spinal Cord*
;
Spine
6.Single center experience of laparoscopic hepatectomy: the comparison of perioperative outcomes between early and late period.
Seung Hyeon SON ; Hong Jin KIM ; Sung Su YUN ; Dong Shik LEE ; Dong Hyeon LEE
Korean Journal of Hepato-Biliary-Pancreatic Surgery 2012;16(1):7-12
BACKGROUNDS/AIMS: The aim of this study is to clarify the safety and feasibility of laparoscopic hepatectomy, through comparing the early and late periods of perioperative outcomes. METHODS: We retrospectively analyzed 138 patients who underwent laparoscopic hepatectomy from January 2003 to June 2011, at Yeungnam University Hospital. We divided the total patients to early period (from January 2003 to February 2007, n=49) and late period (from March 2007 to June 2011, n=89) groups and compared the perioperative outcomes including the mean operation time, intra-operative blood loss, postoperative hospital stay, intensive care unit (ICU) stay, and duration of liver function test (LFT) normalization. RESULTS: The mean operation time was 308 minutes (range: 140-510) in the early group and 193 minutes (range: 40-350) in the late period group (p<0.001). The mean intraoperative blood loss was 171 ml (range: 50-1,200) in the early and 44 ml (range: 0-400) in the late group (p=0.005). The postoperative hospital stay was 9.7 days (range: 4-31) in the early and 6.8 days (range: 2-9) in the late period (p<0.001). The ICU stay hour was 21.6 hours (range: 0-120) in the early and 2.8 hour (range: 0-24) in the late period (p<0.001). The duration of LFT normalization was 5.7 days (range: 0-39) in the early and 2.1 days (range: 0-20) in the late period (p=0.003). The perioperative outcomes in the late period were better than the early period, which showed a statistically significant difference. CONCLUSIONS: Laparoscopic hepatectomy is feasible and can be safely performed in selected patients but requires a long experience in open liver resection and mastery of laparoscopic surgical skills.
Hepatectomy
;
Humans
;
Intensive Care Units
;
Laparoscopy
;
Length of Stay
;
Liver
;
Liver Function Tests
;
Postoperative Hemorrhage
;
Retrospective Studies
7.Isolation and Antimicrobial Susceptibility of Microorganisms from Milk Samples of Jindo Dogs (Canis familiaris var. jindo).
Ju Dan LEE ; Youn Kyong LEE ; Suck Il O ; Ji Young JUNG ; Chang Ho SON ; Sung Shik SHIN ; Ki Seok OH ; Tai Young HUR ; Guk Hyun SUH
Korean Journal of Veterinary Research 2011;51(1):29-35
Lack of hygiene and puerperal mastitis are common causes of bacterial diseases in nursing neonates. The aim of this study was to isolate microorganisms from milk samples of healthy female Jindo dogs with suckling puppies and to investigate antimicrobial susceptibility against the isolated bacteria. Milk samples were collected from 120 udders of 12 lactating Jindo dogs that were 2~4 years old without any clinical diseases including mastitis. Bacteria were isolated from 64 milk samples (53.3%), either singly (76.6%) or in combination (23.4%). Staphylococcus (S.) spp. was the most common microorganisms (74.7%) isolated from canine milk, followed by Haemophillus spp. (10.9%), Streptococcus spp. (9.6%), Gardnerella spp. (2.4%) and Moraxella spp. (2.4%). The most frequently isolated organism was S. warneri (31.3%). Antimicrobial susceptibility of these bacteria was tested with 17 antimicrobial agents by Kirbyand Bauer standardized disc diffusion method. Results indicated that bacteria isolated from healthy canine milk were mostly susceptible to amoxicillin-clavulanic acid, cephalothin and ceftiofur, but were resistant to erythromycin, neomycin and tetracycline.
Amoxicillin-Potassium Clavulanate Combination
;
Animals
;
Anti-Infective Agents
;
Bacteria
;
Cephalosporins
;
Cephalothin
;
Diffusion
;
Dogs
;
Erythromycin
;
Female
;
Gardnerella
;
Humans
;
Hygiene
;
Infant, Newborn
;
Mammary Glands, Animal
;
Mastitis
;
Milk
;
Moraxella
;
Neomycin
;
Staphylococcus
;
Streptococcus
;
Tetracycline
8.Incidence of Diabetic Foot and Associated Risk Factors in Type 2 Diabetic Patients: A Five-year Observational Study.
Shin Ae PARK ; Seung Hyun KO ; Seung Hwan LEE ; Jae Hyoung CHO ; Sung Dae MOON ; Sang A JANG ; Hyun Shik SON ; Ki Ho SONG ; Bong Yun CHA ; Ho Young SON ; Yu Bae AHN
Korean Diabetes Journal 2009;33(4):315-323
BACKGROUND: The frequency of lower extremity amputation due to diabetic foot has been increasing in type 2 diabetic patients. The aim of this study was to observe the incidence, clinical aspects and associated risk factors for diabetic foot. METHODS: We evaluated the incidence of diabetic foot through a five-year observation of type 2 diabetic patients who presented to St. vincent's Hospital between January and December 2003. To identify the risk factors for diabetic foot, we evaluated mean glycosylated hemoglobin A1c (HbA1c) every six months and assessed renal function based on the existence of proteinuria and estimated glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) equation. Patients were also evaluated for retinopathy, peripheral neuropathy and autonomic neuropathy using Ewing's method. RESULTS: From an initial pool of 613 patients, the observational study of 508 patients (82.9%) was completed. The mean age, duration of diabetes and HbA1c were 50.3 +/- 10.6 yrs, 7.2 +/- 6.5 yrs and 8.8 +/- 2.1%, respectively. Diabetic foot occurred in 32 patients (6.3%). The incidence of diabetic foot increased when diabetic retinopathy (OR = 6.707, 2.314~19.439), peripheral neuropathy (OR = 2.949, 1.075~8.090), and autonomic neuropathy (OR = 3.967, 1.476~10.660) were present and when the MDRD GFR (OR = 5.089, 1.712~15.130) decreased. Mean HbA1c (OR = 12.013, 1.470~98.179) was found to be an independent risk factor for diabetic foot. CONCLUSION: The present study confirmed the importance of intensive glycemic control and the role of autonomic dysfunction in the development of diabetic foot. In addition, diabetic retinopathy and impaired renal function proved to be factors associated with the occurrence of diabetic foot. Therefore, intensive glycemic control, as well as periodic examination of renal function, are essential for the prevention of diabetic foot.
Amputation
;
Diabetic Foot
;
Diabetic Neuropathies
;
Diabetic Retinopathy
;
Diet
;
Glomerular Filtration Rate
;
Hemoglobin A, Glycosylated
;
Humans
;
Incidence
;
Lower Extremity
;
Peripheral Nervous System Diseases
;
Proteinuria
;
Risk Factors
9.Clinical study of shade improvement and safety of polymer-based pen type BlancTic Forte whitening agent containing 8.3% Carbamide peroxide.
Jin Kyung LEE ; Sun Hong MIN ; Sung Tae HONG ; So Ram OH ; Shin Hye CHUNG ; Young Hye HWANG ; Sung Yeop YOU ; Kwang Shik BAE ; Seung Ho BAEK ; Woo Cheol LEE ; Won Jun SON ; Kee Yeon KUM
Journal of Korean Academy of Conservative Dentistry 2009;34(2):154-161
This clinical study evaluated the whitening effect and safety of polymer based-pen type BlancTis Forte (NIBEC) containing 8.3% carbamide peroxide. Twenty volunteers used the BlancTis Forte whitening agent for 2 hours twice a day for 4 weeks. As a control, Whitening Effect Pen (LG) containing 3% hydrogen peroxide was used by 20 volunteers using the same protocol. The change in shade (DeltaE*, color difference) was measured using Shadepilot(TM) (DeguDent) before, during, and after bleaching (2 weeks, 4 weeks, and post-bleaching 4 weeks). A clinical examination for any side effects (tooth hypersensitivity or soft tissue complications) was also performed at each check-up. The following results were obtained. 1. Both the experimental and control groups displayed a noticeable change in shade (DeltaE) of over 2. No significant differences were found between the two groups (p > 0.05), implying that the two agents have a similar whitening effect. 2. The whitening effect was mainly due to changes in a and b values rather than in L value (brightness). The experimental group showed a significantly higher change in b value, thus yellow shade, than the control (p < 0.05). 3. None of the participants complained of tooth hypersensitivity or soft tissue complications, confirming the safety of both whitening agents.
Bleaching Agents
;
Hydrogen Peroxide
;
Hypersensitivity
;
Peroxides
;
Polymers
;
Tooth
;
Urea
10.Average Daily Risk Range-Index of Glycemic Variability-Related Factor in Type 2 Diabetic Inpatients.
Shin Ae PARK ; Seung Hyun KO ; Seung Hwan LEE ; Jae Hyung CHO ; Sung Dae MOON ; Sang A JANG ; Ki Ho SONG ; Hyun Shik SON ; Kun Ho YOON ; Bong Yun CHA ; Ho Young SON ; Yu Bae AHN
Korean Diabetes Journal 2009;33(1):31-39
BACKGROUND: It is known that chronic sustained hyperglycemia and its consequent oxidative stress causes diabetic complication in type 2 diabetes. It has been further proven that glycemic variability causes oxidative stress. The aim of this study is to measure the average daily risk range (ADDR)-index of glycemic variability, and to evaluate relevant variables. METHODS: We measured the blood glucose level of type 2 diabetic patients who were treated with multiple daily injections from January to July, 2008. The blood glucose levels were checked four times a day for 14 days and were conversed according to the ADRR formula. The degree of glycemic variability was categorized into non-fluctuation and fluctuation groups. We collected patient data on age, sex, duration of diabetes, body mass index, HOMA(IR), HOMA(betacell) and HbA1c. RESULTS: A total of 97 patients were enrolled in this study. The mean age, duration of diabetes, HbA1c and mean ADRR were 57.6 +/- 13.4, 11.5 +/- 8.5 years, 10.7 +/- 2.5%, and 26.6 +/- 9.8, respectively. We classified 18.5% of the patients to the non-fluctuation group, and 81.5% to the fluctuation group. ADRR was significantly correlated with duration of diabetes, fasting and postprandial glucose, fructosamine, HbA1c and BMI and HOMAbetacell. In addition, this study confirmed that BMI, HOMAbetacell and HbA1c were ADRR-related independent variables. CONCLUSION: ADRR can be used as an index for blood glucose fluctuation in type 2 diabetic patients. Measuring ADRR in patients with low BMI and a long duration of diabetes is helpful to improve the effectiveness of their care.
Blood Glucose
;
Body Mass Index
;
Diabetes Complications
;
Diabetes Mellitus, Type 2
;
Fasting
;
Fructosamine
;
Glucose
;
Humans
;
Hyperglycemia
;
Inpatients
;
Oxidative Stress

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