• Biomedical Science Letters
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• v.12 no.3
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• pp.289-301
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• 2006

Cardiopulmonary bypass (CPB) for cardiac surgery triggers the production and release of numerous chemotactic substances and cytokines, ensuing systemic inflammatory response that leads to postoperative major organ dysfunction. Traditionally, corticosteroids (steroid) have been administered to patients undergoing cardiac surgery to ward off these detrimental physiologic alterations. However, the majority of the studies have been performed on adult patients with high-dose steroid. We carried out a randomized, prospective, double-blind study to compare the efficacy of low-dose steroid with that of high-dose steroid and to determine the adequate dose of pretreated-steroid for prophylactic effects in pediatric cardiac surgery. Thirty pediatric patients scheduled for elective cardiac surgery were randomly assigned to two groups; fifteen patients received low-dose methylprednisolone (10mg/kg intravenously, n=15, low-dose group) and the others received high-dose methylprednisolone (30mg/kg intravenously, n=15, high-dose group) 1 hour prior to CPB. Arterial blood samples were taken before CPB (Pre-CPB), 10 minutes after start of CPB (CPB-10), and immediately after CPB-end (CPB-OFF) for measuring total leukocyte counts (T-WBC) and diff-counts, platelet counts, interleukin-6 (IL-6), myeloperoxidase (MPO), total antioxidant (TAO), neuron-specific enolase (NSE), troponin I (TNI), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and blood urea nitrogen (BUN) levels. Other parameters such as volumes of urine output, pulmonary index $(PI,\;PaO_2/FiO_2)$, mechanical ventilating period, intensive care unit (ICU)-staying period, postoperative complications (fever, wound problem), postoperative 24 hrs and total volumes in blood loss, and hospitalized days were also assessed. All parameters were compared between two groups. There were no significant differences in T-WBC counts, monocyte fraction, platelet counts, TA levels, NSE levels, creatinine levels, BUN levels, the volumes of total urine output, PI, the incidences of fever and wound problem, postoperative 24hrs- and total-blood loss volumes and ICU-staying period between two groups (P>0.05). At CPB-OFF, neutrophil fraction, MPO level, TNI level, and AST level were higher in the high-dose group than in the low-dose group (P<0.05). IL-6 level at CPB-10 was higher in the high dose-group than in the low-dose group (P<0.05). Furthermore, mechanical ventilating periods and hospitalized days of the high-dose group were significantly longer than those of low-dose group (P<0.05). The high-dose group had significantly low lymphocyte fi-action at CPB-OFF compared with the low-dose group (P<0.001). These findings suggest that pretreatment of high-dose steroid is not superior to that of low-dose steroid regrading its potential benefits in pediatric cardiac surgery. Therefore, the conventional strategy of steroid treatment, high-dose pretreatment, should be modified in the cardiac surgery with CPB. However, further studies must be performed on the larger number of patients in as much as small number of patients in this study.

• Journal of fish pathology
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• v.27 no.1
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• pp.1-9
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• 2014

The olive flounder, Paralichthys olivaceus is susceptible to viral hemorrhagic septicaemia virus (VHSV) at $15^{\circ}C$ but no mortality at $20^{\circ}C$ even though the virus can grow well in vitro at $20^{\circ}C$. Thus, we designed an experiment to know immune response of olive flounder against VHSV when the host reared at $15^{\circ}C$ or $20^{\circ}C$. cDNA microarray analysis was performed to compare the gene expression patterns of the kidney cells between the host reared at $15^{\circ}C$ or $20^{\circ}C$. The expression of MHC class I, IL-8, myeloperoxidae and endonuclease G-like having function for the antigen presentation and chemokine-factor were up-regulted both the $15^{\circ}C$ and $20^{\circ}C$ during VHSV infection. MHC class II gene existing on antigen-presenting cells and B cell lymphocytes, immunoglobulin (Ig) genes and phagocytosis related genes were down-regulated at $15^{\circ}C$ but highly expressed at $20^{\circ}C$. It can be thought that innate immune related antigen presentation by MHC class I and phagocytosis reaction against VHSV are efficiently occur both the temperature but macrophage or B cell related antigen presentation via MHC class II fails to induce downstream immune reactions (adaptive immunity) to make antibody, and it can be one of the reason that causes high mortality only at $15^{\circ}C$.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.6
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• pp.874-885
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• 2012

In the present study, the possibility of whether the pharmacological effects of Scutellariae Radix Aqueous Extracts(SR) were favorably changed by report that lipopolysaccharide(LPS)-induced rat acute lung injury was treated with Red-Koji(Monascus purpureus 12002) fermentation. Three different dosages of Red-Koji fermented SR extract(fSR), 125, 250 and 500 mg/kg were orally administered once a day for 28 days before LPS(Escherichia coli 0111:B4) treatments, and then 5 hours after LPS treatment(500 ${\mu}g$/head, intra trachea instillation), all rats were sacrificed. Changes in the body weights, lung weights, pulmonary transcapillary albumin transit, arterial gas parameters(pH, $PaO_2$ and $PaCO_2$) bronchoalveolar lavage fluid(BALF) protein, lactate dehydrogenase(LDH) and proinflammatory cytokine tumor necrosis factor-${\alpha}$(TNF-${\alpha}$), interleukin-$1{\beta}$(IL-$1{\beta}$) contents, total cell numbers, neutrophil and alveolar macrophage ratios, lung malondialdehyde(MDA), myeloperoxidase(MPO), proinflammatory cytokine TNF-${\alpha}$ and IL-$1{\beta}$ contents were observed with histopathology of the lung, changes on luminal surface of alveolus(LSA), thickness of alveolar septum, number of polymorphonuclear neutrophils(PMNs). As results of LPS-injection, dramatical increases in lung weights, pulmonary transcapillary albumin transit increases in $PaCO_2$, decreases in pH of arterial blood and $PaO_2$, increases of BALF protein, LDH, TNF-${\alpha}$ and IL-$1{\beta}$ contents, total cells, neutrophil and alveolar macrophage ratios, lung MDA, MPO, TNF-${\alpha}$ and IL-$1{\beta}$ contents increases were detected with decreases in LSA and increases of alveolar septum and PMNs numbers, respectively as compared with intact control. Especially fSR 125 mg/kg showed quite similar favorable effects on the LPS-induced acute lung injuries as compared with 60 mg/kg of ${\alpha}$-lipoic acid and 250 mg/kg of SR. The results suggest that over 125 mg/kg of fSR extracts showed favorable effects on the LPS-induced acute lung injury mediated by their antioxidant and anti-inflammatory effects. Moreover, increases of the pharmacological effects of SR on LPS-induced acute lung injury were observed by Red-Koji fermentation in this study, at least 2-fold higher.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.2
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• pp.250-257
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• 2011

An experiment was conducted to determine the effects of different mycotoxin adsorbents including esterified glucomannan (EGM), hydrated sodium calcium aluminosilicate (HSCAS) and compound mycotoxin adsorbent (CMA) on performance, blood parameters, and liver pathological changes in broilers fed mold-contaminated feed. Two hundred and forty 10-day-old broilers were randomly assigned to one of the five dietary treatments including: i) control diet; ii) mold-contaminated diet; iii) moldcontaminated diet+0.05% EGM; iv) mold-contaminated diet+0.2% HSCAS; v) mold-contaminated diet+0.1% CMA. At 35-days-old, blood and liver tissue samples were collected for analysis. 0.1% CMA improved ADG and ADFI during 10-42 d compared to the moldcontaminated group (p<0.05). The mold-contaminated diet increased total white blood cell (WBC) number, haemoglobin (Hgb) concentration, hematocrit (Hct) level, serum aspartate aminotransferase (AST) and ${\gamma}$-glutamyl transferase (GGT) activities, and decreased red blood cell (RBC) number and serum globulin (GLB) and urea nitrogen (BUN) concentrations (p<0.05). The three mycotoxin adsorbents alleviated the alteration of RBC, WBC, Hgb and AST caused by the mold-contaminated diet. Furthermore, 0.1% CMA increased GLB concentration and decreased Hct level and GGT activity (p<0.05). Liver superoxide dismutase (SOD) activity was reduced, and myeloperoxidase (MPO) activity was increased by the mold-contaminated diet (p<0.05). Both EGM and HSCAS prevented the increase of MPO activity (p<0.05). Liver lesion, including severe vacuolar degeneration of hepatocytes, was observed in chicks fed the mold-contaminated diet. 0.05% EGM prevented these effects except for biliary hyperplasia and mild vacuolar degeneration. 0.2% HSCAS showed medium vacuolar degeneration of hepatocytes. Liver of broilers fed 0.1% CMA revealed a mild vacuolar degeneration. These results indicate that a mold-contaminated diet results in adverse effects on blood parameters and liver morphology. 0.05% EGM and 0.2% HSCAS partially alleviated the adverse effects. However, 0.1% CMA almost completely ameliorated the adverse effects.

• Journal of Microbiology and Biotechnology
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• v.18 no.12
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• pp.1975-1983
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• 2008

The neuropeptide ${\alpha}$-melanocyte-stimulating hormone (${\alpha}$-MSH) has anti-inflammatory property by down regulating the expressions of proinflammatory cytokines. Because ${\alpha}$-MSH elicits the anti-inflammatory effect in various inflammatory disease models, we examined the therapeutic effect of oral administration of recombinant Lactobacillus casei, which secretes ${\alpha}$-MSH (L. casei-${\alpha}$-MSH), on dextran sulfate sodium (DSS)-induced colitis in Balb/c mice. Thus, we constructed the ${\alpha}$-MSH-secreting Lactobacillus casei by the basic plasmid, pLUAT-ss, which was composed of a PldhUTLS promoter and ${\alpha}$-amylase signal sequence from Streptococcus bovis strain. Acute colitis was induced by oral administration of 5% DSS in drinking water for 7 days. To investigate the effect of L. casei-${\alpha}$-MSH on the colitis, L. casei or L. casei-${\alpha}$-MSH was orally administered for 7 days and their effects on body weight, mortality rate, cytokine production, and tissue myeloperoxidase (MPO) activity were observed. Administration of L. casei-${\alpha}$-MSH reduced the symptom of acute colitis as assessed by body weight loss (DSS alone: $14.45{\pm}0.2\;g$; L. casei-${\alpha}$-MSH: $18.2{\pm}0.12\;g$), colitis score (DSS alone: $3.6{\pm}0.4$; L. casei-${\alpha}$-MSH: $1.4{\pm}0.6$), MPO activity (DSS alone: $42.7{\pm}4.5\;U/g$; L. casei-${\alpha}$-MSH: $10.25{\pm}0.5\;U/g$), survival rate, and histological damage compared with the DSS alone mice. L. casei-${\alpha}$-MSH-administered entire colon showed reduced in vitro production of proinflammatory cytokines and $NF-{\kappa}B$ activation. The ${\alpha}$-MSH-secreting recombinant L. casei showed significant anti-inflammatory effects in the murine model of acute colitis and suggests a potential therapeutic role for this agent in clinical inflammatory bowel diseases.

• Fisheries and Aquatic Sciences
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• v.23 no.9
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• pp.26.1-26.9
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• 2020

Background: The study evaluated the effects of a butaphosphan and cyanocobalamin mixture on the immune system and stress in olive flounders, Paralichthys olivaceus. Methods: The mixture was intramuscularly injected into olive flounders at the current recommended dose. Furthermore, to determine the toxicity of overdose, a histological examination was performed after injection of 1-, 2-, and 4-fold higher than the recommended dose. Results: Immunity parameters were altered during the first 2 weeks after a single intramuscular injection of the mixture in olive flounders (average weight 20.5 ± 1.1 g). The levels of all tested items, except glutathione and antiprotease, were higher in the treated group than in the control group in the first week; the levels of all tested items were even higher in the second week in the treated group than in the control group. The level of nitro-blue tetrazolium, myeloperoxidase, and superoxide dismutase between the two groups differed significantly. Changes in the stress response to different seawater temperatures (increase or decrease in seawater temperature by 3-5 ℃ using 50 L heated or cooled seawater tanks) were studied by determining the changes in cortisol and glucose levels on days 1 and 7. Both cortisol and glucose levels were significantly lower in the treated group than in the control group. Histological analysis did not reveal any abnormalities after intramuscular injection of the mixture at doses that were 1-, 2-, and 4-fold higher than the recommended dose. Conclusions: Intramuscular injection of a butaphosphan and cyanocobalamin mixture is safe and effective in reducing stress and improving immunity in olive flounders.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.6
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• pp.515-523
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• 2000

Polymorphonuclear leukocytes (PMNs) play an important role in myocardial ischemia/reperfusion (MI/R) injury. Moreover, platelets are also important blood cells that can aggravate myocardial ischemic injury. This study was designed to test the effects of PMNs and platelets separately and together in provoking cardiac dysfunction in isolated perfused rat hearts following ischemia and reperfusion. Additional control rat hearts were perfused with $75{\times}10^6$ PMNs, with $75{\times}10^6$ platelets, or with $75{\times}10^6\;PMNs+75{\times}10^6$ platelets over a five minute perfusion followed by a 75 min observation period. No significant reduction in coronary flow (CF), left ventricular developed pressure (LVDP), or the first derivative of LVDP (dP/dt max) was observed at the end of the observation period in any non-ischemic group. Similarly, global ischemia (I) for 20 min followed by 45 minutes of reperfusion (R) produced no sustained effects on the final recovery of any of these parameters in any group of hearts perfused in the absence of blood cells. However, I/R hearts perfused with either PMNs or platelets alone exhibited decreases in these variables of $5{\sim}10%$ (p＜0.05 from control). Furthermore, I/R hearts perfused with both PMNs and platelets exhibited decreases of 50 to 60% in all measurements of cardiac function (p＜0.01). These dual cell perfused I/R hearts also exhibited marked increases in cardiac myeloperoxidase (MPO) activity indicating a significant PMN infiltration, and enhanced P-selectin expression on the coronary microvascular endothelium. All cardiaodynamic effects as well as PMN accumulation and P-selectin expression were markedly attenuated by a recombinant soluble PSGL-1 which inhibits selectin mediated cell adhesion. These results provide evidence that platelets and PMNs act synergistically in provoking post-reperfusion cardiac dysfunction, and that this may be largely due to cell to cell interactions mediated by P-selectin. These results also demonstrate that a recombinant soluble PSGL-1 reduces myocardial reperfusion injury by platelet and PMNs interaction.

• Applied Microscopy
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• v.33 no.1
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• pp.1-16
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• 2003

As is well known that N-nitroso-N-methylurethane (NNNMU) causes acute lung injury (ALI) in experimental animals. And ALI caused by NNNMU is very similar to ARDS in human being in its pathology and progress. In its context, we investigated the pathogenetic mechanism of ARDS associated with oxidative stress by neutrophils in Sprague-Dawley rat model of NNNMU-induced ALI. NNNMU had increased lung weight/body weight ratio (L/B ratio), lung myeloperoxidase (MPO) activity, protein content and number of neutrophils in bronchoalveolar fluid (BALF) compared with those of control rat (p<0.001, respectively). In contrast, the amount of pulmonary surfactant in BALF was decreased by NNNMU (p<0.001). Morphologically, light microscopic examination denoted pathological findings such as formation of hyaline membrane, infiltration of neutrophils and perivascular cuffing in the lungs of NNNMU-treated rats. In addition, ultrastructural changes such as the necrosis of endothelial cells, swelling and vacuolization of lamellar bodies of alveolar type II cells, and the degeneration of pulmonary surfactant were identified after treatment of NNNMU. Very interestingly, cerium chloride electron microscopic cytochemistry showed that NNNMU had increased the production of cerrous-peroxide granules in the lung, which signified the increased production of hydrogen peroxide in the lung. Collectively, we conclude that NNNMU causes acute lung leak by the mechanism of neutrophilic oxidative stress of the lung.

• Tuberculosis and Respiratory Diseases
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• v.58 no.1
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• pp.78-82
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• 2005

Propylthiouracil(PUT) is a drug which used at Grave's disease. But PTU has recently been observed to associated with antineutrophil cytoplasmic antibody(ANCA)-positive vasculitis resulting in, infrequently, diffuse alveolar hemorrhage. We report the case of a patient who developed diffuse pulmonary hemorrhage after she had been taking PTU for two years. She had received a diagnosis of Grave's disease at two years ago. The serologic study was positive for ANCA with myeloperoxidase(MPO) specificity. Bronchoalveloar lavage(BAL) fluid analysis revealed hemosiderinladen macrophages. Such findings suggested propylthiouracil-induced dffuse pulmonary hemorrhage associated with antineutrophil cytoplasmic antibody. To our knowledge, this represents the first documentation in a case of PTU-induced diffuse pulmonary hemorrhage in Korea.

• Tuberculosis and Respiratory Diseases
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• v.60 no.1
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• pp.49-56
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• 2006

배경 : 급성 폐손상은 폐내, 외의 원인질환들에 의해 폐포-모세혈관의 투과성이 증가하며, 폐부종에 의해 급성 저산소성 호흡곤란이 유발되는 증후군이다. 헤파린은 항응고작용 외에 자체적으로 항염증효과를 가지고 있으나, 염증성질환에 헤파린을 투여하면 출혈성 합병증이 발생하기 때문에 실제로 임상에서 이용하는데 제약이 있다. 하지만 헤파린에서 2-O와 3-O sulfate를 제거하면, 항응고 효과가 제거되고 항염증효과는 지니고 있는 비항응고성 헤파린 (nonanticoagulant heparin)으로 변화한다. 본 연구에서는 흰쥐에게 내독소 (LPS)를 투여하거나, 출혈성 쇼크를 일으켜서 유발된 급성폐손상에서 비항응고성 헤파린의 치료효과를 살펴보았다. 방법 : 각 군당 5 마리 이상의 흰쥐 (Balb/c mouse)를 이용하였다. 미정맥 (tail vein)을 통해 생리식염수 또는 비항응고성 헤파린 (50 mg/kg)을 투여한 직후에 내독소를 복강으로 투여하거나 (1 mg/kg), 심장천자를 통해 총 혈액의 1/3 정도로 제거하여 출혈성 쇼크를 유도하여 급성폐손상을 유발하였다. 내독소 투여 또는 출혈성 쇼크 유발 1 시간 후에 흰쥐를 희생시키고 폐를 적출하였고, 폐의 염증성 변화는 사이토카인 ($TNF-{\alpha}$, MIP-2, $IL-1{\beta}$)을 측정하여 살펴보았고, 폐손상의 정도는 myeloperoxidase (MPO) assay와 wet-to-dry weight ratio를 측정하여 알아보았다. 결 과 : 내독소를 투여한 흰쥐의 폐에서 대조군의 폐에 비해 사이토카인의 발현이 증가하고 ($TNF-{\alpha}$; $196.1{\pm}10.8$ vs $83.7{\pm}18.4pg/ml$, MIP-2; $3,000{\pm}725$ vs $187{\pm}26pg/ml$, $IL-1{\beta}$; $6,500{\pm}1167$ vs $266{\pm}25pg/ml$, p<0.05, respectively), 폐의 MPO 활성이 증가하였다 ($27.9{\pm}6.2$ vs $10.5{\pm}2.3U/g$ of lung protein, p<0.05). 출혈성 쇼크를 일으킨 흰쥐의 폐에서 대조군의 폐에 비해 사이토카인의 발현은 증가되지 않았으나, MPO 발현은 증가되었다 ($16.5{\pm}3.2$ vs $10.5{\pm}2.3U/g$ of lung protein, p<0.05). 내독소 투여 또는 출혈성 쇼크에 의해 급성폐손상이 유발된 흰쥐에서 생리적 식염수를 투여하거나 비항응고성 헤파린을 투여한 군 사이에 사이토카인의 발현이나 MPO 활성에 의미있는 차이는 관찰되지 않았다. 결론 : 이상의 결과로 비항응고성 헤파린은 내독소를 투여하거나 출혈성 쇼크를 일으키고 한 시간 뒤에 측정한 흰쥐의 급성폐손상에서 의미있는 치료효과를 보이지 않았다.