BACKGROUND: High-fat diet-induced obesity is one of the major cause of chronic renal failure. This obesity-related renal failure is mainly caused by inflammatory processes. However, the role of the major anti-inflammatory cytokine interleukin (IL)-10 has not been researched intensively. METHODS: To evaluate the effect of IL-10 deficiency on obesity-related renal failure, the in vivo study was carried with four animal groups; (1) Low-fat dieted C57BL/6 mice, (2) Low-fat dieted IL-10 knockout (KO) mice, (3) High-fat dieted C57BL/6 mice and (4) High-fat dieted IL-10 KO mice group. The analysis was carried with blood/urine chemistry, H&E, Oil-Red-O, periodic acid-Schiff and Masson’s trichrome staining immunohistochemistry and real-time PCR methods. RESULTS: At week 12, high-fat dieted IL-10 KO mice showed 1) severe lipid accumulation in kidneys, cholesterol elevation (in total, serum kidney) and low-density lipoprotein increasion through the SCAP-SREBP2-LDLr pathway; (2) serious histopathologic alterations showing glomerulosclerosis, tubulointerstitial fibrosis and immune cell infiltration; (3) increased pro-inflammatory cytokines and chemokines expression; (4) enhanced renal fibrosis; and (5) serious functional failure with high serum creatinine and BUN and proteinuria excretion compared to other groups. CONCLUSION IL-10 deficiency aggravates renal inflammation, fibrosis and functional failure in high-fat dieted obese mice, thus IL-10 therapy could be applied to obesity-related chronic renal failure.

BACKGROUND: High-fat diet-induced obesity is one of the major cause of chronic renal failure. This obesity-related renal failure is mainly caused by inflammatory processes. However, the role of the major anti-inflammatory cytokine interleukin (IL)-10 has not been researched intensively. METHODS: To evaluate the effect of IL-10 deficiency on obesity-related renal failure, the in vivo study was carried with four animal groups; (1) Low-fat dieted C57BL/6 mice, (2) Low-fat dieted IL-10 knockout (KO) mice, (3) High-fat dieted C57BL/6 mice and (4) High-fat dieted IL-10 KO mice group. The analysis was carried with blood/urine chemistry, H&E, Oil-Red-O, periodic acid-Schiff and Masson’s trichrome staining immunohistochemistry and real-time PCR methods. RESULTS: At week 12, high-fat dieted IL-10 KO mice showed 1) severe lipid accumulation in kidneys, cholesterol elevation (in total, serum kidney) and low-density lipoprotein increasion through the SCAP-SREBP2-LDLr pathway; (2) serious histopathologic alterations showing glomerulosclerosis, tubulointerstitial fibrosis and immune cell infiltration; (3) increased pro-inflammatory cytokines and chemokines expression; (4) enhanced renal fibrosis; and (5) serious functional failure with high serum creatinine and BUN and proteinuria excretion compared to other groups. CONCLUSION IL-10 deficiency aggravates renal inflammation, fibrosis and functional failure in high-fat dieted obese mice, thus IL-10 therapy could be applied to obesity-related chronic renal failure.

Objective: To assess the incremental prognostic value of coronary computed tomography angiography (CCTA) in comparison toa clinical risk model (Framingham risk score, FRS) and coronary artery calcium score (CACS) for future cardiac events in ischemicstroke patients without chest pain. Materials and Methods: This retrospective study included 1418 patients with acute stroke who had no previous cardiac diseaseand underwent CCTA, including CACS. Stenosis degree and plaque types (high-risk, non-calcified, mixed, or calcified plaques) wereassessed as CCTA variables. High-risk plaque was defined when at least two of the following characteristics were observed:low-density plaque, positive remodeling, spotty calcification, or napkin-ring sign. We compared the incremental prognosticvalue of CCTA for major adverse cardiovascular events (MACE) over CACS and FRS. Results: The prevalence of any plaque and obstructive coronary artery disease (CAD) (stenosis ≥ 50%) were 70.7% and 30.2%,respectively. During the median follow-up period of 48 months, 108 patients (7.6%) experienced MACE. Increasing FRS, CACS,and stenosis degree were positively associated with MACE (all p< 0.05). Patients with high-risk plaque type showed the highestincidence of MACE, followed by non-calcified, mixed, and calcified plaque, respectively (log-rank p< 0.001). Among theprediction models for MACE, adding stenosis degree to FRS showed better discrimination and risk reclassification compared toFRS or the FRS + CACS model (all p< 0.05). Furthermore, incorporating plaque type in the prediction model significantly improvedreclassification (integrated discrimination improvement, 0.08; p= 0.023) and showed the highest discrimination index(C-statistics, 0.85). However, the addition of CACS on CCTA with FRS did not add to the prediction ability for MACE (p> 0.05). Conclusion Assessment of stenosis degree and plaque type using CCTA provided additional prognostic value over CACS andFRS to risk stratify stroke patients without prior history of CAD better.

BACKGROUND: We fabricated anti-inflammatory scaffold using Mg(OH)2-incorporated polylactic acid-polyglycolic acid copolymer (MH-PLGA). To demonstrate the anti-inflammatory effects of the MH-PLGA scaffold, an animal model should be sensitive to inflammatory responses. The interleukin-10 knockout (IL-10 KO) mouse is a widely used bowel disease model for evaluating inflammatory responses, however, few studies have evaluated this mouse for the anti-inflammatory scaffold. METHODS: To compare the sensitivity of the inflammatory reaction, the PLGA scaffold was implanted into IL-10 KO and C57BL/6 mouse kidneys. Morphology, histology, immunohistochemistry, and gene expression analyses were carried out at weeks 1, 4, 8, and 12. The anti-inflammatory effect and renal regeneration potency of the MH-PLGA scaffold was also compared to those of PLGA in IL-10 KO mice. RESULTS: The PLGA scaffold-implanted IL-10 KO mice showed kidneys relatively shrunken by fibrosis, significantly increased inflammatory cell infiltration, high levels of acidic debris residue, more frequent CD8-, C-reactive protein-, and ectodysplasin A-positive cells, and higher expression of pro-inflammatory and fibrotic factors compared to the control group. The MH-PLGA scaffold group showed lower expression of pro-inflammatory and fibrotic factors, low immune cell infiltration, and significantly higher expression of anti-inflammatory factors and renal differentiation related genes compared to the PLGA scaffold group. CONCLUSION: These results indicate that the MH-PLGA scaffold had anti-inflammatory effects and high renal regeneration potency. Therefore, IL-10 KO mice are a suitable animal model for in vivo validation of novel anti-inflammatory scaffolds.
Animals ; Ectodysplasins ; Fibrosis ; Gene Expression ; Immunohistochemistry ; Interleukin-10* ; Kidney ; Mice ; Mice, Knockout* ; Models, Animal ; Regeneration

Ginseng gintonin is an exogenous ligand of lysophosphatidic acid (LPA) receptors. Accumulating evidence shows LPA helps in rapid recovery of corneal damage. The aim of this study was to evaluate the therapeutic efficacy of gintonin in a rabbit model of corneal damage. We investigated the signal transduction pathway of gintonin in human corneal epithelium (HCE) cells to elucidate the underlying molecular mechanism. We next evaluated the therapeutic effects of gintonin, using a rabbit model of corneal damage, by undertaking histochemical analysis. Treatment of gintonin to HCE cells induced transient increases of [Ca²⁺](i) in concentration-dependent and reversible manners. Gintonin-mediated mobilization of [Ca²⁺](i) was attenuated by LPA1/3 receptor antagonist Ki16425, phospholipase C inhibitor U73122, inositol 1,4,5-triphosphate receptor antagonist 2-APB, and intracellular Ca²⁺ chelator BAPTA-AM. Gintonin facilitated in vitro wound healing in a concentration-dependent manner. When applied as an eye-drop to rabbits with corneal damage, gintonin rapidly promoted recovery. Histochemical analysis showed gintonin decreased corneal apoptosis and increased corneal cell proliferation. We demonstrated that LPA receptor activation by gintonin is linked to in vitro and in vivo therapeutic effects against corneal damage. Gintonin can be applied as a clinical agent for the rapid healing of corneal damage.
Apoptosis ; Cell Proliferation ; Corneal Injuries ; Epithelium, Corneal ; Humans ; In Vitro Techniques ; Inositol 1,4,5-Trisphosphate ; Mortuary Practice ; Panax ; Rabbits ; Receptors, Lysophosphatidic Acid ; Signal Transduction ; Therapeutic Uses ; Type C Phospholipases ; Wound Healing* ; Wounds and Injuries*

PURPOSE: This study aimed to clarify the association between human epidermal growth factor receptor 2 (HER-2) status and the clinicopathologic factors of patients who underwent curative intent gastrectomy.METHODS: From June 2011 to May 2015, curative intent gastrectomy was performed in 441 patients at Konyang University Hospital. Among them, we evaluated the HER-2 status in 113 patients. Data on clinicopathologic parameters such as age, sex, histological subtype, endoscopic Lauren classification, tumor location, size, presence of lymphovascular invasion, invasion depth, pathologic stage, HER-2 overexpression, recurrence and survival were obtained. In this study, pathological HER-2 intensity scores of 0, 1+, and 2+ were assumed to be negative, 3+ only was to be positive for overexpression.RESULTS: In a total of 113 cases who underwent curative intent gastrectomy with HER-2 testing, 16 (14.2%) cases had positivity of HER-2 overexpression. HER-2 overexpression had significant associations with tumor stage (19.0% in I-IIIb vs. 2.9% in IIIc-IV, P=0.036). Survival analysis of HER2 overexpression has no significant difference.CONCLUSION: In this study, HER-2 overexpression rate was 14.2% and patient tumor stage had significant association with HER-2 overexpression.
Classification ; Epidermal Growth Factor ; Gastrectomy ; Humans ; Receptor, Epidermal Growth Factor ; Recurrence ; Stomach Neoplasms

Sleep, which is an essential part of human life, is modulated by neurotransmitter systems, including gamma-aminobutyric acid (GABA) and dopamine signaling. However, the mechanisms that initiate and maintain sleep remain obscure. In this study, we investigated the relationship between melatonin (MT) and dopamine D2-like receptor signaling in pentobarbital-induced sleep and the intracellular mechanisms of sleep maintenance in the cerebral cortex. In mice, pentobarbital-induced sleep was augmented by intraperitoneal administration of 30 mg/kg MT. To investigate the relationship between MT and D2-like receptors, we administered quinpirole, a D2-like receptor agonist, to MT- and pentobarbital-treated mice. Quinpirole (1 mg/kg, i.p.) increased the duration of MT-augmented sleep in mice. In addition, locomotor activity analysis showed that neither MT nor quinpirole produced sedative effects when administered alone. In order to understand the mechanisms underlying quinpirole-augmented sleep, we measured protein levels of mitogen-activated protein kinases (MAPKs) and cortical protein kinases related to MT signaling. Treatment with quinpirole or MT activated extracellular-signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and protein kinase C (PKC) in the cerebral cortex, while protein kinase A (PKA) activation was not altered significantly. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findings suggest that modulation of D2-like receptors might enhance the effect of MT on sleep.
Animals ; Cerebral Cortex ; Cyclic AMP-Dependent Protein Kinases ; Dopamine ; gamma-Aminobutyric Acid ; Humans ; Hypnotics and Sedatives ; Melatonin ; Mice* ; Mitogen-Activated Protein Kinases ; Motor Activity ; Neurotransmitter Agents ; p38 Mitogen-Activated Protein Kinases* ; Pentobarbital* ; Phosphotransferases ; Protein Kinase C ; Protein Kinases ; Quinpirole*

BACKGROUND/AIMS: Capsule endoscopy (CE) is widely used. However, CE has limitations including incomplete examination, inadequate bowel preparation, and retention. The aim of this study was to estimate the indications for and detection, completion, and retention rates of small intestine CE based on the 10-year data from the Korean Capsule Endoscopy Registry. METHODS: Twenty-four hospitals participated in this study. Clinical information, such as reasons for CE, method and quality of bowel preparation, and incomplete examination and capsule retention rates, was collected and analyzed. RESULTS: A total of 2,914 CEs were registered. The most common reason for CE was obscure gastrointestinal bleeding (59%). Significant lesions were detected in 66% of cases. Positive CE diagnosis occurred in 63% of cases. The preparation method did not significantly affect the quality of bowel preparation for CE. The overall incomplete rate was 33%, and was high in the elderly and those with poor bowel preparation. Capsule retention was 3% and high in patients with small bowel tumors and Crohn's disease and in children under 10 years of age. CONCLUSIONS: CE is a valuable technique; while the overall detection rate is high, incompletion and retention rates are also relatively high. CE should be carefully considered in the elderly and children less than 10 years of age, as well as in patients with small bowel tumors and Crohn's disease.
Aged ; Capsule Endoscopy* ; Child ; Crohn Disease ; Diagnosis ; Hemorrhage ; Humans ; Intestine, Small

BACKGROUND/AIMS: We evaluated the long-term outcome and clinical course of patients of nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal injury by performing capsule endoscopy (CE). METHODS: A multicenter retrospective study was conducted using data collected from the CE nationwide database registry, which has been established since 2002. RESULTS: A total of 140 patients (87 males; mean age, 60.6+/-14.8 years) from the CE nationwide database registry (n=2,885) were diagnosed with NSAID-induced small intestinal injury and enrolled in our study. Forty-nine patients (35.0%) presented with a history of aspirin use and an additional 49 (35.0%) were taking NSAIDs without aspirin. The most prominent findings after performing CE were multiple ulcerations (n=82, 58.6%) and erosions or aphthae (n=32, 22.9%). During the follow-up period (mean, 15.9+/-19.0 months; range, 0 to 106 months), NSAID-induced small intestinal injury only recurred in six patients (4.3%). Older age and hypertension were positive predictive factors for recurrence. CONCLUSIONS: These results suggest that the recurrence of NSAID-induced small bowel injury was not frequent in the presence of conservative treatment. Therefore, the initial diagnosis using CE and the medication history are important.
Age Factors ; Aged ; Anti-Inflammatory Agents, Non-Steroidal/*adverse effects ; Aspirin/adverse effects ; *Capsule Endoscopy ; Female ; Humans ; Intestinal Diseases/chemically induced/*pathology ; Intestine, Small/*drug effects/injuries/*pathology ; Male ; Middle Aged ; Recurrence ; Republic of Korea ; Retrospective Studies ; Time Factors ; Ulcer/chemically induced/*pathology

BACKGROUND/AIMS: Capsule endoscopy (CE) has become an important tool for the diagnosis of small bowel disease. Although CE does not require the skill of endoscope insertion, the images should be interpreted by a person with experience in assessing images of the gastrointestinal mucosa. This investigation aimed to document the number of cases needed by trainees to gain the necessary experience for CE competency. METHODS: Fifteen cases were distributed to 12 trainees with no previous experience of CE during their gastroenterology training as clinical fellows. Twelve trainees and an expert were asked to read CE images from one patient each week for 15 weeks. The diagnosis was reported using five categories (no abnormalities detected, small bowel erosion or ulcer, small bowel tumor, Crohn disease, and active small bowel bleeding with no identifiable source). We then examined, using the kappa coefficient, how the degree of mean agreements between the trainees and the expert changed as the training progressed each week. RESULTS: The agreement rate of CE diagnosis increased as the frequencies of interpretation increased. Most of the mean kappa coefficients were >0.60 and >0.80 after week 9 and 11, respectively. CONCLUSIONS: Experience with approximately 10 cases of CE is appropriate for trainees to attain CE competency.
Capsule Endoscopy* ; Crohn Disease ; Diagnosis ; Endoscopes ; Gastroenterology ; Hemorrhage ; Humans ; Learning Curve* ; Learning* ; Mucous Membrane ; Ulcer