1.Pan-Nox inhibitor treatment improves renal function in aging murine diabetic kidneys
Jeong Hoon PARK ; Sung Gi YOON ; Jung Yeon GHEE ; Ji Ae YOO ; Jin Joo CHA ; Young Sun KANG ; Sang Youb HAN ; Yun Jae SEOL ; Jee Young HAN ; Dae Ryong CHA
Kidney Research and Clinical Practice 2024;43(6):763-773
Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.
2.Pan-Nox inhibitor treatment improves renal function in aging murine diabetic kidneys
Jeong Hoon PARK ; Sung Gi YOON ; Jung Yeon GHEE ; Ji Ae YOO ; Jin Joo CHA ; Young Sun KANG ; Sang Youb HAN ; Yun Jae SEOL ; Jee Young HAN ; Dae Ryong CHA
Kidney Research and Clinical Practice 2024;43(6):763-773
Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.
3.Pan-Nox inhibitor treatment improves renal function in aging murine diabetic kidneys
Jeong Hoon PARK ; Sung Gi YOON ; Jung Yeon GHEE ; Ji Ae YOO ; Jin Joo CHA ; Young Sun KANG ; Sang Youb HAN ; Yun Jae SEOL ; Jee Young HAN ; Dae Ryong CHA
Kidney Research and Clinical Practice 2024;43(6):763-773
Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.
4.Pan-Nox inhibitor treatment improves renal function in aging murine diabetic kidneys
Jeong Hoon PARK ; Sung Gi YOON ; Jung Yeon GHEE ; Ji Ae YOO ; Jin Joo CHA ; Young Sun KANG ; Sang Youb HAN ; Yun Jae SEOL ; Jee Young HAN ; Dae Ryong CHA
Kidney Research and Clinical Practice 2024;43(6):763-773
Aging is a risk factor for development of chronic kidney disease and diabetes mellitus with commonly shared features of chronic inflammation and increased oxidative stress. Here, we investigated the effect of pan-Nox-inhibitor, APX-115, on renal function in aging diabetic mice. Methods: Diabetes was induced by intraperitoneal injection of streptozotocin at 50 mg/kg/day for 5 days in 52-week-old C57BL/6J mice. APX-115 was administered by oral gavage at a dose of 60 mg/kg/day for 12 weeks in nondiabetic and diabetic aging mice. Results: APX-115 significantly improved insulin resistance in diabetic aging mice. Urinary level of 8-isoprostane was significantly increased in diabetic aging mice than nondiabetic aging mice, and APX-115 treatment reduced 8-isoprostane level. Urinary albumin and nephrin excretion were significantly higher in diabetic aging mice than nondiabetic aging mice. Although APX-115 did not significantly decrease albuminuria, APX-115 markedly improved mesangial expansion, macrophage infiltration, and expression of fibrosis molecules such as transforming growth factor beta 1 and plasminogen activator inhibitor 1. Interestingly, the expression of all Nox isoforms including Nox1, Nox2, and Nox4 was significantly increased in diabetic aging kidneys, and APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. Furthermore, Klotho expression was significantly decreased in diabetic aging kidneys, and APX-115 restored Klotho level. Conclusion: Our results provide evidence that pan-Nox inhibition may improve systemic insulin resistance and decrease oxidative stress, inflammation, and fibrosis in aging diabetic status and may have potential protective effects on aging diabetic kidney.
5.Comparison of Different Types of Oral Adsorbent Therapy in Patients with Chronic Kidney Disease:A Multicenter, Randomized, Phase IV Clinical Trial
Youn Kyung KEE ; Sang Youb HAN ; Duk-Hee KANG ; Jung Woo NOH ; Kyung Hwan JEONG ; Gheun-Ho KIM ; Yang Wook KIM ; Beom Seok KIM
Yonsei Medical Journal 2021;62(1):41-49
Purpose:
Oral adsorbents delay disease progression and improve uremic symptoms in patients with chronic kidney disease (CKD). DW-7202 is a newly developed oral adsorbent with high adsorptive selectivity for uremic toxins. We evaluated patient preference for and adherence to DW-7202 versus AST-120 therapy and compared treatment efficacy and safety in patients with pre-dialysis CKD.
Materials and Methods:
A seven-center, randomized, open-label, two-way crossover, active-controlled, phase IV clinical trial was conducted. Patients with stable CKD were randomly assigned to receive DW-7202 (capsule type) or AST-120 (granule type) for 12 weeks. The groups then switched to the other adsorbent and took it for the next 12 weeks. Patient preference was the primary outcome. Secondary outcomes included changes in estimated glomerular filtration rate (eGFR) and serum creatinine, cystatin C, and indoxyl sulfate (IS) levels.
Results:
Significantly more patients preferred DW-7202 than AST-120 (p<0.001). Patient adherence improved after switching from AST-120 to DW-7202; there was no apparent change in adherence after switching from DW-7202 to AST-120. Changes in eGFR and serum creatinine, cystatin C, and IS levels were not significantly different according to adsorbent type. There was also no significant difference in the incidences of adverse events during treatment with DW-7202 and AST-120.
Conclusion
DW-7202 can be considered as an alternative to AST-120 in patients who cannot tolerate or show poor adherence to granule type adsorbents. Further studies to evaluate factors affecting patient preferences and improved adherence are warranted (Clinical trial registration No. NCT02681952).
6.Esophagostomy as an Alternative to Gastrostomy for Dysphagia in Muscular Dystrophy: A Case Report
Jin Seok BAE ; Jong Keun KIM ; Jong Youb LIM ; Kang Jae JUNG ; Hyo Sik PARK
Journal of the Korean Dysphagia Society 2020;10(1):134-137
Many people with muscular dystrophy develop dysphagia that can result in an inability to use the oral route in severe cases. In such cases, an alternative feeding method is selected, including a nasogastric tube or a gastrostomy.This case report describes a 40-year-old man with muscular dystrophy who was managed for swallowing difficulty and respiratory failure. Oromotor muscle weakness caused prolonged mealtimes, difficulty with swallowing a solidform diet, aspiration signs, and weight loss. Consequently, an alternative feeding method was required. An abdominal radiograph showed massive aerophagia, and the transverse colon was located over the stomach. As a result, the colon interfered with the puncture route, which could lead to colon perforation. Therefore, cervical esophagostomy was selected, where the patient obtained nutrition through a cervical esophagostomy tube. This case showed that when gastrostomy cannot be performed due to aerophagia, cervical esophagostomy can successfully support nutrition for the mid to long-term in muscular dystrophy patients.
7.Polymicrobial Keratitis of Pseudomonas aeruginosa, Acinetobacter baumannii, and Ochrobactrum anthropi
Jung Youb KANG ; Ju Hwan SONG ; Ki Yup NAM ; Seung Uk LEE ; Sang Joon LEE
Journal of the Korean Ophthalmological Society 2019;60(5):474-479
PURPOSE: To report polymicrobial keratitis involving Pseudomonas aeruginosa, Acinetobacter baumannii, and Ochrobactrum anthropi. CASE SUMMARY: A 53-year-old female complained of pain and secretion in her right eye, which started 6 weeks before her visit. She applied steroid ointment, which was received from the dermatologist, to her eyelid 7 days prior to her visit but this treatment worsened her symptoms. At the initial visit, the visual acuity of the right eye was light perception, and purulent secretions were observed. Using a slit lamp, severe conjunctival hyperemia, hypopyon, and a ring-shaped central corneal ulcer were observed. The anterior chamber and fundus were not observed due to corneal lesions but ultrasonography showed no intraocular inflammation. Infectious keratitis was suspected and cultured by corneal scraping. During the incubation period, 0.5% moxifloxacin, 2% voriconazole, and 1% cyclopentolate were administered. A total of 400 mg of moxifloxacin and 100 mg of doxycycline were given orally. In the primary culture, Pseudomonas aeruginosa and Acinetobacter baumannii were identified so 5% ceftazidime, which was sensitive for the antibiotic susceptibility results was further instilled. Thereafter, the keratitis improved but the keratitis again worsened while maintaining the topical treatment. A secondary culture was positive for Ochrobactrum anthropi. Treatment with 1.4% gentamicin, which was sensitive for the antibiotic susceptibility test was added and the keratitis improved. A conjunctival flap was performed because of the increased risk of perforation. CONCLUSIONS: We report polymicrobial keratitis involving Pseudomonas aeruginosa, Acinetobacter baumannii, and Ochrobactrum anthropi for the first time in the Republic of Korea.
Acinetobacter baumannii
;
Acinetobacter
;
Anterior Chamber
;
Ceftazidime
;
Corneal Ulcer
;
Cyclopentolate
;
Doxycycline
;
Eyelids
;
Female
;
Gentamicins
;
Humans
;
Hyperemia
;
Inflammation
;
Keratitis
;
Middle Aged
;
Ochrobactrum anthropi
;
Ochrobactrum
;
Pseudomonas aeruginosa
;
Pseudomonas
;
Republic of Korea
;
Slit Lamp
;
Ultrasonography
;
Visual Acuity
;
Voriconazole
8.Circulating renalase predicts all-cause mortality and renal outcomes in patients with advanced chronic kidney disease
Seon Ha BAEK ; Ran hui CHA ; Shin Wook KANG ; Cheol Whee PARK ; Dae Ryong CHA ; Sung Gyun KIM ; Sun Ae YOON ; Sejoong KIM ; Sang Youb HAN ; Jung Hwan PARK ; Jae Hyun CHANG ; Chun Soo LIM ; Yon Su KIM ; Ki Young NA
The Korean Journal of Internal Medicine 2019;34(4):858-866
BACKGROUND/AIMS:
Patients with chronic kidney disease (CKD) have been found to show markedly increased rates of end-stage renal disease, major adverse cardiovascular and cerebrovascular events (MACCEs), and mortality. Therefore, new biomarkers are required for the early detection of such clinical outcomes in patients with CKD. We aimed to determine whether the level of circulating renalase was associated with CKD progression, MACCEs, and all-cause mortality, using data from a prospective randomized controlled study, Kremezin STudy Against Renal disease progression in Korea (K-STAR; NCT 00860431).
METHODS:
A retrospective analysis of the K-STAR data was performed including 383 patients with CKD (mean age, 56.4 years; male/female, 252/131). We measured circulating renalase levels and examined the effects of these levels on clinical outcomes.
RESULTS:
The mean level of serum renalase was 75.8 ± 34.8 μg/mL. In the multivariable analysis, lower hemoglobin levels, higher serum creatinine levels, and diabetes mellitus were significantly associated with a higher renalase levels. Over the course of a mean follow-up period of 56 months, 25 deaths and 61 MACCEs occurred. Among 322 patients in whom these outcomes were assessed, 137 adverse renal outcomes occurred after a mean follow-up period of 27.8 months. Each 10-μg/mL increase in serum renalase was associated with significantly greater hazards of all-cause mortality and adverse renal outcomes (hazard ratio [HR] = 1.112, p = 0.049; HR = 1.052, p = 0.045). However, serum renalase level was not associated with the rate of MACCEs in patients with CKD.
CONCLUSIONS
Our results indicated that circulating renalase might be a predictor of mortality and adverse renal outcomes in patients with CKD.
9.Erratum: Sustained uremic toxin control improves renal and cardiovascular outcomes in patients with advanced renal dysfunction: post-hoc analysis of the Kremezin Study against renal disease progression in Korea Volume 36, Issue 1, March 2017, Pages 68–.
Ran hui CHA ; Shin Wook KANG ; Cheol Whee PARK ; Dae Ryong CHA ; Ki Young NA ; Sung Gyun KIM ; Sun Ae YOON ; Sejoong KIM ; Sang Youb HAN ; Jung Hwan PARK ; Jae Hyun CHANG ; Chun Soo LIM ; Yon Su KIM
Kidney Research and Clinical Practice 2018;37(1):98-99
The values of y axis in Fig. 3 should be corrected. The authors would like to apologize for any inconvenience this has caused.
10.Time Series Changes in Cataract Surgery in Korea.
Ju Hwan SONG ; Jung Youb KANG ; Ki Yup NAM ; Seung Uk LEE ; Sang Joon LEE
Korean Journal of Ophthalmology 2018;32(3):182-189
PURPOSE: We analyzed time series changes in cataract surgeries in Korea, and provide basic data to enhance the efficiency of medical services for cataract surgery. METHODS: Among cataract surgery statistics registered in the Korean National Health Insurance Cooperation from 2006 to 2012, we used data regarding the number of patients and operations and the number of patients and operations per 100,000 people. We analyzed various time series changes, including differences by sex and age. RESULTS: The total numbers of patients from 2006 to 2012 by year were 207,370; 228,170; 250,289; 268,548; 289,867; 308,111; and 302,182, respectively. The total numbers of operations from 2006 to 2012 by year were 272,920; 305,807; 338,332; 365,874; 398,338; 428,158; and 420,905, respectively. The number of patients and operations per 100,000 people were highest in men 80 to 84 years old and women 75 to 79 years old. Comparing the number of operations in 2006 and after, the patient age group with the highest increase rate changed from over 85 years old to 75–79 years old since 2010 in men and from over 85 years old to 50–54 years old since 2009 in women. For each year investigated, the number of operations performed was higher than the number of patients who received operations. CONCLUSIONS: Over the study period, the number of cataract surgeries increased, while the age of cataract patients decreased. Additionally, the number of cataract-related surgeries increased in relation to the number of patients.
Cataract Extraction
;
Cataract*
;
Epidemiology
;
Female
;
Humans
;
Korea*
;
Male
;
National Health Programs

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