• Journal of Veterinary Clinics
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• v.24 no.1
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• pp.51-55
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• 2007

A 13-year-old male Yorkshire terrier was Presented with Persistent weight loss anorexia and dark brown urine of 3-month duration. On physical examination, a firm oval mass was palpated at left renal region. In hematology and blood chemistry, neutrophilia, anemia, thrombocytopenia and elevation of ALKP were found. Abdominal radiography, ultrasonography and ultrasound-guided percutaneous pyelogram revealed masses originated from left kidney, mildly dilated renal Pelvis and intact ureter. Urinalysis showed hematuria and proteinuria. Because the state of dog became deteriorated during transfusion and the frail renal tumor was suspected to be the cause of inflammation and anemia, nephrectomy was performed. Renal masses, approximately $2{\times}3cm\;and\;5{\times}4cm$ respectively in size, was surrounded by swollen and congested mesentery and ascites. Metastatic lesion was not found in other organs. During recovery, the dog showed cardiopulmonary arrest and did not respond to critical care. Histologically the kidney was affected by necrotic and hemorrhagic change. This hemangiosarcoma most likely arose from the renal parenchyma resulting In diffuse lesions in the kidneys thought to be the cause of chronic anorexia and weight loss.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.6
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• pp.533-543
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• 2021

Myocardial fibrosis (MF) is the result of persistent and repeated aggravation of myocardial ischemia and hypoxia, leading to the gradual development of heart failure of chronic ischemic heart disease. Triptolide (TPL) is identified to be involved in the treatment for MF. This study aims to explore the mechanism of TPL in the treatment of MF. The MF rat model was established, subcutaneously injected with isoproterenol and treated by subcutaneous injection of TPL. The cardiac function of each group was evaluated, including LVEF, LVFS, LVES, and LVED. The expressions of ANP, BNP, inflammatory related factors (IL-1β, IL-18, TNF-α, MCP-1, VCAM1), NLRP3 inflammasome factors (NLRP3, ASC) and fibrosis related factors (TGF-β1, COL1, and COL3) in rats were dete cted. H&E staining and Masson staining were used to observe myocardial cell inflammation and fibrosis of rats. Western blot was used to detect the p-P65 and t-P65 levels in nucleoprotein of rat myocardial tissues. LVED and LVES of MF group were significantly upregulated, LVEF and LVFS were significantly downregulated, while TPL treatment reversed these trends; TPL treatment downregulated the tissue injury and improved the pathological damage of MF rats. TPL treatment downregulated the levels of inflammatory factors and fibrosis factors, and inhibited the activation of NLRP3 inflammasome. Activation of NLRP3 inflammasome or NF-κB pathway reversed the effect of TPL on MF. Collectively, TPL inhibited the activation of NLRP3 inflammasome by inhibiting NF-κB pathway, and improved MF in MF rats.

• Parasites, Hosts and Diseases
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• v.57 no.1
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• pp.21-25
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• 2019

Trichomoniasis is the most common curable sexually-transmitted infection. Most Trichomonas vaginalis-infected men are asymptomatic and can remain undiagnosed and untreated, and this has been thought to result in chronic persistent prostatic infection. Chronic inflammation is regarded as the major factor in the pathogenesis and progression of benign prostatic hyperplasia (BPH) and prostatic cancer (PCa). The aim of this study is to identify seropositivity to T. vaginalis in men with prostate tumors (BPH or PCa) visited to Hanyang University Hospital. A total of 183 men were enrolled between October 2013 and November 2014. They consisted of 139 with BPH (mean age: $64.0{\pm}0.07$) and 44 with prostate cancer (mean age: $73.3{\pm}0.18$). We carried out ELISA to identify the seropositivity to T. vaginalis. Mixed lysate antigen extracted from 8 strains of T. vaginalis was used in the ELISA. Also 58 male outpatients visited to Health Promotion Center in Hanyang University Hospital were evaluated for comparing group. As a results, seropositivity to T. vaginalis in patients with prostatic diseases was 19.7% (BPH: 18.7%, PCa: 22.7%) and it was significantly higher than the 1.7% of the comparing healthy group (P=0.001). Therefore, prostatic tumor showed higher seropositivity against T. vaginalis than normal men. As far as we know, this is the first report about seroprevalence in prostatic tumor in Korea.

• The Korean Journal of Pain
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• v.35 no.3
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• pp.291-302
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• 2022

Background: Spinal cord injury (SCI) is one of the most debilitating disorders throughout the world, causing persistent sensory-motor dysfunction, with no effective treatment. Oxidative stress and inflammatory responses play key roles in the secondary phase of SCI. Naringenin (NAR) is a natural flavonoid with known anti-inflammatory and antioxidative properties. This study aims at evaluating the effects of intrathecal NAR administration on sensory-motor disability after SCI. Methods: Animals underwent a severe compression injury using an aneurysm clip. About 30 minutes after surgery, NAR was injected intrathecally at the doses of 5, 10, and 15 mM in 20 µL volumes. For the assessment of neuropathic pain and locomotor function, acetone drop, hot plate, inclined plane, and Basso, Beattie, Bresnahan tests were carried out weekly till day 28 post-SCI. Effects of NAR on matrix metalloproteinase (MMP)-2 and MMP-9 activity was appraised by gelatin zymography. Also, histopathological analyses and serum levels of glutathione (GSH), catalase and nitrite were measured in different groups. Results: NAR reduced neuropathic pain, improved locomotor function, and also attenuated SCI-induced weight loss weekly till day 28 post-SCI. Zymography analysis showed that NAR suppressed MMP-9 activity, whereas it increased that of MMP-2, indicating its anti-neuroinflammatory effects. Also, intrathecal NAR modified oxidative stress related markers GSH, catalase, and nitrite levels. Besides, the neuroprotective effect of NAR was corroborated through increased survival of sensory and motor neurons after SCI. Conclusions: These results suggest intrathecal NAR as a promising candidate for medical therapeutics for SCI-induced sensory and motor dysfunction.

• IMMUNE NETWORK
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• v.22 no.1
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• pp.8.1-8.20
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• 2022

Rheumatoid arthritis (RA) is a representative autoimmune disease that is primarily characterized by persistent inflammation and progressive destruction of synovial joints. RA has a complex and heterogeneous pathophysiology, involving interactions among various immune and joint stromal cells and a diverse network of cytokines and intracellular signaling pathways. With improved understanding of RA, over the past decades, therapeutic strategies have become considerably advanced and now included targeted molecular therapies, such as tumor necrosis factor inhibitors, IL-6 blockers, B-cell depletion agents, as well as inhibitors of T-cell co-stimulation and Janus kinases. However, a considerable proportion of RA patients experience refractory disease and interrupted treatment owing to the associated risk of developing serious infections and cancers. In contrast, although IL-1β, IL-17A, and p38α play significant roles in RA pathogenesis, several drugs targeting these factors have not been approved because of their low efficacy and severe adverse effects. In this review, we provide an overview of the working mechanism, advantages, and limitations of the currently available targeted drugs for RA. Additionally, we suggest potential mechanistic causes for clinically approved and failed drugs. Thus, this review provides perspectives on approaches for basic and translational studies that hold promise for identifying future next-generation therapeutics for RA.

• Clinical and Experimental Pediatrics
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• v.51 no.10
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• pp.1096-1101
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• 2008

Purpose : Patients with chronic granulomatous disease (CGD) have genetic mutations in a component of the NADPH oxidase enzyme that is necessary for the generation of the superoxide anion. The profound defect in innate immunity is reflected by the patients susceptibility to catalase-positive bacteria and fungi. In addition, CGD patients display signs of persistent inflammation, which is not associated only with deficient superoxide anion production. The aim of this study was to elucidate the cytokine responses in CGD patients after $TNF-{\alpha}$ stimulation. Methods : Heparinized blood samples were collected from 8 CGD patients and 10 healthy volunteers. Monocytes ($1{\times}10^6cell/well$) isolated by the magnet cell isolation system were incubated with a constant amount of $TNF-{\alpha}$ (10 ng/mL) at $37^{\circ}C$ for 6 h. Incubated cells were harvested at 60-min intervals for IL-8 and IL-10 mRNA analysis, and the supernatant was collected at the same intervals to determine IL-8 and IL-10 expression. Monocytes from healthy volunteers were also incubated with antioxidants followed by $TNF-{\alpha}$ stimulation for IL-8 and IL-10 expression. Results : In CGD patients, a high expression of IL-8 together with a significantly higher IL-10 expression than in the healthy controls was seen after $TNF-{\alpha}$ stimulation. Moreover, normal monocytes treated with antioxidants exhibited increased IL-8 responses. Conclusion : The absence of phagocyte-derived reactive oxidants in CGD might be associated with a dysregulated production of pro- and antiinflammatory cytokines. Additional research related to reactive oxidants is needed to clarify the role of cytokines in CGD patients.

• Clinical and Experimental Pediatrics
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• v.61 no.8
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• pp.258-263
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• 2018

Purpose: Macrolide-resistant Mycoplasma pneumoniae pneumonia (MPP) is characterized by prolonged fever and radiological progression despite macrolide treatment. Few studies have examined serum procalcitonin (PCT) level in children with MPP. We aimed to investigate the association of acute inflammation markers including PCT with clinical parameters in children with MPP. Methods: A total of 147 children were recruited. The diagnosis of MPP relied on serial measurement of IgM antibody against mycoplasma and/or polymerase chain reaction. We evaluated the relationships between C-reactive protein (CRP), PCT, and lactate dehydrogenase (LDH) levels and white blood cell (WBC) counts, and clinical severity of the disease. We used multivariate logistic regression analysis to estimate the odds ratio for prolonged fever (>3 days after admission) and hospital stay (> 6 days), comparing quintiles 2-5 of the PCT levels with the lowest quintile. Results: The serum PCT and CRP levels were higher in children with fever and hospital stay than in those with fever lasting ${\leq}3days$ after admission and hospital stay ${\leq}6days$. CRP level was higher in segmental/lobar pneumonia than in bronchopneumonia. The LDH level and WBC counts were higher in children with fever lasting for >3 days before compared to those with fever lasting for ${\leq}3days$. The highest quintile of PCT levels was associated with a significantly higher risk of prolonged fever and/or hospital stay than the lowest quintile. Conclusion: Serum PCT and CRP levels on admission day were associated with persistent fever and longer hospitalization in children with MPP.

• Molecules and Cells
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• v.37 no.12
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• pp.899-906
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• 2014

Prostaglandin $E_2$ ($PGE_2$) promotes tumor-persistent inflammation, frequently resulting in cancer. Curcumin is a diphenolic turmeric that inhibits carcinogenesis and induces apoptosis. $PGE_2$ inhibits curcumin-induced apoptosis; however, the underlying inhibitory mechanisms in colon cancer cells remain unknown. The aim of the present study is to investigate the survival role of $PGE_2$ and whether addition of exogenous $PGE_2$ affects curcumininduced cell death. HCT-15 cells were treated with curcumin and $PGE_2$, and protein expression levels were investigated via Western blot. Reactive oxygen species (ROS) generation, lipid peroxidation, and intracellular glutathione (GSH) levels were confirmed using specific dyes. The nuclear factor-kappa B ($NF-{\kappa}B$) DNA-binding was measured by electrophoretic mobility shift assay (EMSA). $PGE_2$ inhibited curcumin-induced apoptosis by suppressing oxidative stress and degradation of PARP and lamin B. However, exposure of cells to the EP2 receptor antagonist, AH6809, and the PKA inhibitor, H89, before treatment with $PGE_2$ or curcumin abolished the protective effect of $PGE_2$ and enhanced curcumin-induced cell death. $PGE_2$ activates PKA, which is required for cAMP-mediated transcriptional activation of CREB. $PGE_2$ also activated the Ras/Raf/Erk pathway, and pretreatment with PD98059 abolished the protective effect of $PGE_2$. Furthermore, curcumin treatment greatly reduced phosphorylation of CREB, followed by a concomitant reduction of $NF-{\kappa}B$ (p50 and p65) subunit activation. $PGE_2$ markedly activated nuclear translocation of $NF-{\kappa}B$. EMSA confirmed the DNA-binding activities of $NF-{\kappa}B$ subunits. These results suggest that inhibition of curcumin-induced apoptosis by $PGE_2$ through activation of PKA, Ras, and $NF-{\kappa}B$ signaling pathways may provide a molecular basis for the reversal of curcumin-induced colon carcinoma cell death.

• Korean Journal of Veterinary Research
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• v.46 no.4
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• pp.327-335
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• 2006

A stable and reliable Helicobacter pylori (H. pylori) infection animal model would be necessary for evaluating vaccine efficacy and helpful for understanding the pathological mechanism of the organism. The aim of the present study is to investigate the effect of ethanol treatment prior to H. pylori inoculation on associated gastric mucosal injury and to establish ethanol-pretreating animal model to study H. pylori infection. Male Mongolian gerbils were used for the study. H. pylori was orally inoculated after 12 h fasting. 3 h prior to H. pylori inoculation, a group of gerbils was orally treated with absolute ethanol, 60% and 40% ethanol respectively. Another group of animals was treated either with H. pylori culture media alone or with different concentrations of ethanol plus culture media. Gerbils were killed 4 or 8 weeks after H. pylori inoculation. The colonization of H. pylori was confirmed by both histological examination and rapid urease test. Mucosal damage was evaluated grossly and histologically according to the criteria. The colonization of H. pylori and pathological changes in gastric mucosa of the animals were also observed. Although no significant change to the gastric mucose was observed in the animals treated either with H. pylori culture media alone or with different concentrations of ethanol plus culture media, persistent H. pylori infection was seen in the mucosa and mucosal leucocyte infiltration and severe epithelial damage was observed in the Helicobacter and ethanol + Helicobacter groups after 4 weeks. The gross and histological scores were higher in the ethanol + Helicobacter than in the Helicobacter alone group. As the results, ethanol-pretreatment with 60% concentration induced severe pathogenic changes by H. pylori infection in 5 weeks-old Mongolian gerbils. These results suggested that ethanol-pretreatment before H. pylori inoculation could increase the severity of gastric mucosal inflammation and enhance the colonization of H. pylori. The established ethanol-pretreating animal model would contribute to screen new drugs against H. pylori and be used as an useful tool for various animal experiments with H. pylori strains.

• Pediatric Infection and Vaccine
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• v.28 no.3
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• pp.173-180
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• 2021

After initial reports of multisystem inflammatory syndrome in children (MIS-C) in April 2020 in Europe, this disease has been known to occur in children with recent history of coronavirus disease 2019 (COVID-19) and most cases have been reported in Europe and the Unites States of America. We report a case of a 14-year-old girl who was diagnosed with MIS-C with acute myocarditis and successfully treated with intravenous immunoglobulin (IVIG), methylprednisolone, and anakinra. At initial presentation, she had persistent high fever, generalized rash, generalized swelling, abdominal pain, and low blood pressure. She showed a remarkably elevated level of inflammation and cardiac enzyme markers and had a previous history of COVID-19 5 weeks before the initial presentation. After extensive work up, other infectious and non-infectious causes were excluded. She was diagnosed with MIS-C and initially treated with IVIG and high-dose methylprednisolone; however, despite treatment, her heart function deteriorated and coronary artery dilatation progressed. Therefore, anakinra, an interleukin-1 receptor antagonist, was administered on hospital day 6, after which her cardiac function exhibited improvement. She was discharged on hospital day 19 without any symptoms, and follow-up echocardiography after 1 month revealed fully recovered heart function with normal coronary arteries.