• The Korea Journal of Herbology
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• v.27 no.5
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• pp.9-14
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• 2012

Objective : We investigated the effect of Poncirus trifoliata and Citrus aurantium extract in mice with cerulein-induced acute pancreatitis (AP) model. Methods : AP was induced via intraperitoneal injection of cerulein (50 ${\mu}g/kg$) given every hour for 6h. Poncirus trifoliata (PT: 200 or 400 mg/kg) and Citrus aurantium (CA: 200 or 400 mg/kg) extract were injected 1 h before in mice with cerulein-induced AP. Mice were sacrificed at 6 h after last injection of cerulein. Blood samples were taken to determine serum amylase and lipase levels. The pancreas and lungs were rapidly removed for morphological examination, myeloperoxidase assay. Results : PT pre-treatment significantly protected the pancreas and lung damages and reduced the MPO activity and serum amylase in cerulein-induced AP. However, CA pre-treatment did not significantly protected the pancreas and lung inflammation in cerulein-induced AP. Conclusion : These results suggest that PT but not CA could protect the cerulein-induced AP. Conclusion : These results suggest that PT but not CA could protect the cerulein-induced AP.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.3
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• pp.263-273
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• 1999

The role of phospholipase $A_2\;(PLA_2)$ in acute lung leak induced by intestinal ischemia was investigated in association with neutrophilic respiratory burst. To induce lung leak, we generated intestinal ischemia for 60 min prior to the 120 min reperfusion by clamping superior mesenteric artery in Sprague-Dawley rats. Acute lung leak was confirmed by the increased lung leak index and protein content in bronchoalveolar fluid. These changes were inhibited by mepacrine, the non-specific $PLA_2$ inhibitor. The lung myeloperoxidase (MPO) activity denoting the pulmonary recruitment of neutrophils was increased by intestinal I/R, but decreased by mepacrine. Simultaneously, the number of leukocytes in bronchoalveolar fluid was increased by intestinal ischemia/reperfusion (I/R) and decreased by mepacrine. Gamma glutamyl transferase activity, an index of oxidative stress in the lung, was increased after intestinal I/R but decreased by mepacrine, which implicates that $PLA_2$ increases oxidative stress caused by intestinal I/R. The $PLA_2$ activity was increased after intestinal I/R not only in the intestine but also in the lung. These changes were diminished by mepacrine. In the cytochemical electron microscopy to detect hydrogen peroxide, intestinal I/R increased the generation of the hydrogen peroxide in the lung as well as in the intestine. Expression of interleukin-1 (IL-1) in the lung was investigated through RT-PCR. The expression of IL-1 after intestinal I/R was enhanced, and again, the inhibition of $PLA_2$ suppressed the expression of IL-1 in the lung. Taken together, intestinal I/R seems to induce acute lung leak through the activation of $PLA_2$, the increase of IL-1 expression associated with increased oxidative stress by neutrophilic respiratory burst.

• Journal of Microbiology and Biotechnology
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• v.19 no.6
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• pp.616-621
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• 2009

To evaluate the effects of lactic acid bacteria (LAB) in inflammatory bowel diseases (IBD), we measured the inhibitory effect of several LAB isolated from intestinal microflora and commercial probiotics against the glycosaminoglycan (GAG) degradation by intestinal bacteria. Bifidobacterium longum HY8004 and Lactobacillus plantarum AK8-4 exhibited the most potent inhibition. These LAB inhibited colon shortening and myeloperoxidase production in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental colitic mice. These LAB also blocked the expression of the proinflammatory cytokines, IL-$1{\beta}$ and TNF-$\alpha$, as well as of COX-2, in the colon. LAB also blocked activation of the transcription factor, NF-${\kappa}B$, and expression of TLR-4 induced by TNBS. In addition, LAB reduced the TNBS-induced bacterial degradation activities of chondroitin sulfate and hyaluronic acid. These findings suggest that GAG degradation-inhibitory LAB may improve colitis by inhibiting inflammatory cytokine expression via TLR-4-linked NF-${\kappa}B$ activation and by inhibiting intestinal bacterial GAG degradation.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.3
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• pp.1-11
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• 2011

Objectives : This study was performed to evaluate the effects of root of Scutellariae Radix(SR) water extract against inflammatory response in the spinal cord injury(SCI). Methods : SCI was induced by mechanical contusion following laminectomy of 10th thoracic vertebra in Sprague-Dawley rat. SR was orally given once a day for 7days after SCI. Myeloperoxidase(MPO) positive neutrophils infiltration was examined. Inducible nitric oxide synthase(iNOS) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) expressions were observed with immunohistochemistry. Glial fibrillary acidic protein(GFAP) positive astrocytes were examined using immuno-fluorescence. Results : 1. SR reduced MPO-positive neutrophils infiltration in peri-damage regions of the contusive SCI-induced rats. 2. SR reduced iNOS positive cells in the white matter of the contusive SCI-induced rats. 3. SR reduced TNF-${\alpha}$ positive cells in the gray and white matter of the contusive SCI-induced rats. 4. SR reduced cell number and size of astrocytes in peri-damage regions of the contusive SCI-induced rats. Conclusions : These results suggest that SR plays an inhibitory role against inflammatory response in the SCI.

• Tuberculosis and Respiratory Diseases
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• v.72 no.1
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• pp.93-97
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• 2012

Propylthiouracil (PTU) is one of the most common drugs used in the treatment of Graves' disease. There are a number of side effects found with PTU use including fever, rash, arthralgia, and flu-like symptoms. Recently antineutrophil cytoplasmic antibodies (ANCA) positive vasculitis after PTU treatment was reported as a rare side effect, which can cause diffuse alveolar hemorrhage and glomerulonephritis. A 45-year-old woman with Graves' disease had been treated with PTU for five months, complained of hemoptysis due to pulmonary alveolar hemorrhage causing anemia, and also had hematuria. Simple chest X-ray and HRCT showed bilateral consolidation and bronchoalveolar lavage fluid revealed alveolar hemorrhage. A serologic test was positive for ANCA against myeloperoxidase and proteinase-3. Such findings suggested that the presence of PTU induced ANCA positive vasculitis. Cessation of PTU and the administration of high dose steroids improved the clinical manifestation, radiologic and serologic findings. We observed ANCA titer serially for 6 years. During the follow up period, ANCA titer decreased slowly and stayed within the acceptable upper normal limit.

• Genomics & Informatics
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• v.4 no.3
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• pp.97-102
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• 2006

In acute leukemia patients, several successful methods of expression profiling have been used for various purposes, i.e., to identify new disease class, to select a therapeutic target, or to predict chemo-sensitivity and clinical outcome. In the present study, we tested the peripheral blood of 47 acute leukemia patients in an attempt to identify differentially expressed genes in AML and ALL using a Korean-made 10K oligo-nucleotide microarray. Methods: Total RNA was prepared from peripheral blood and amplified for microarray experimentation. SAM (significant analysis of microarray) and PAM (prediction analysis of microarray) were used to select significant genes. The selected genes were tested for in a test group, independently of the training group. Results: We identified 345 differentially expressed genes that differentiated AML and ALL patients (FWER<0.05). Genes were selected using the training group (n=35) and tested for in the test group (n=12). Both training group and test group discriminated AML and ALL patients accurately. Genes that showed relatively high expression in AML patients were deoxynucleotidyl transferase, pre-B lymphocyte gene 3, B-cell linker, CD9 antigen, lymphoid enhancer-binding factor 1, CD79B antigen, and early B-cell factor. Genes highly expressed in ALL patients were annexin A 1, amyloid beta (A4) precursor protein, amyloid beta (A4) precursor-like protein 2, cathepsin C, lysozyme (renal amyloidosis), myeloperoxidase, and hematopoietic prostaglandin D2 synthase. Conclusion: This study provided genome wide molecular signatures of Korean acute leukemia patients, which clearly identify AML and ALL. Given with other reported signatures, these molecular signatures provide a means of achieving a molecular diagnosis in Korean acute leukemia patents.

• Journal of Acupuncture Research
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• v.30 no.3
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• pp.61-73
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• 2013

Objectives : This study was designed to evaluate the effects of Phaseoli Semen Herbal-acupuncture(PS-HA) at $KI_{10}$ in acute nephritis induced by lipopolysaccharide(LPS) in rat. Methods : The rats were divided into 5 groups, which were control, LPS, PS-HA, NP and saline group. LPS, PS-HA, NP and saline groups were given LPS to induce acute nephritis and control group did not receive LPS. LPS group did not receive any treatment after the onset of acute nephritis. PS-HA, NP and saline group received PS-HA, normal acupuncture, and saline injection at $KI_{10}$ three times per week, respectively. To evaluate the effect of PS-HA at $KI_{10}$, the complete blood count, BUN, creatinine, TNF-${\alpha}$, and CINC-1 in serum were measured. To show its effect on renal function, creatinine, and total protein in urine was measured as well as urine output. The level of myeloperoxidase in renal tissue was quantified and complete histology was done in kidney samples obtained from the rats. Results : PS-HA group showed a significant reduction in the proportion of WBC and neutrophil, serum BUN, TNF-${\alpha}$, and CINC-1 compared to LPS group. Furthermore, a significant increase in urine output and a decrease in urinary creatinine level, MPO in renal tissue, and number of neutrophils at glomerulus was observed in PS-HA group compared to LPS group Conclusions : PS-HA at $KI_{10}$ was shown to have a significantly effect on treating LPS induced acute nephrits. Therefore, future study is needed to further evaluate the clinical usefulness of PS-HA at $KI_{10}$ in treating acute nephritis.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.377-384
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• 1998

Gold compounds depress phagocytic cell responses, including chemotaxis, and respiratory burst. However, the effects of gold compounds on the function of phagocytic cells are variable according to the preparation of medicine. In this study, effect of tetrachloroauric acid on activated neutrophil responses, including respiratory burst, lysosomal enzyme release and change of intracellular $Ca^{2+}$ level and on the synthesis of interleukin-8 and granulocyte-macrophage colony stimulating factor by macrophages was studied. This study further examines how gold compounds affect the activation processes. The respiratory burst stimulated by complement C5a, degraded IgG and PMA in neutrophils was inhibited by tetrachloroauric acid. In contrast to C5a and degraded IgG, PMA-stimulated superoxide production was weakly inhibited by tetrachloroauric acid. Staurosporine, genistein, EGTA and verapamil inhibited superoxide and $H_2O_2$ production caused by C5a and degraded IgG. PMA-stimulated superoxide production was inhibited by staurosporine but was not affected by genistein. Tetrachloroauric acid, genistein, EGTA and verapamil inhibited the release of acid phosphatase and myeloperoxidase, while the effect of staurosporine was not detected. The synthesis of interleukin-8 and granulocyte-macrophage colony stimulating factor by $interleukin-1{\beta}$ in macrophages was inhibited by tetrachloroauric acid. Preincubation with tetrachloroauric acid, genistein, EGTA and verapamil, the elevation of [$Ca^{2+}_i$] evoked by C5a was inhibited. Store-regulated $Ca^{2+}$ entry in thapsigargin-pretreated neutrophils was decreased by the addition of tetrachloroauric acid and genistein. The effect of staurosporine on intracellular $Ca^{2+}$ mobilization was not observed. In conclusion, tetrachloroauric acid may suppress neutrophil responses through its inhibitory action on elevation of intracellular $Ca^{2+}$ level and protein kinase C. It might exhibit an inhibitory effect on the action of protein tyrosine kinase. Tetrachloroauric acid depresses cytokine production by macrophages.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.2
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• pp.85-94
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• 2006

A splanchic artery occlusion for 90 min followed by reperfusion of the mesenteric circulation resulted in a severe form of circulatory shock, characterized by endothelial dysfunction, severe hypotension, marked intestinal tissue injury, and a high mortality rate. The effect of defibrotide, a complex of single-stranded polydeoxyribonucleotides having antithrombotic effect, was investigated in a model of splanchnic artery occlusion (SAO) shock in urethane anesthetized rats. Occlusion of the superior mesenteric artery for 90 min produced a severe shock state, resulting in a fatal outcome within 120 min of reperfusion in many rats. Defibrotide (10 mg/kg body weight) 10 min prior to reperfusion significantly improved mean arterial blood pressure in comparison to vehicle treated rats (p＜0.05). Defibrotide treatment also significantly attenuated in the increase of plasma amino nitrogen concentration, intestinal myeloperoxidase activity, intestinal lipid peroxidation, infiltration of neutrophils in intestine and thrombin induced adherence of neutrophils to superior mesentric artery segments. Superoxide anion and hydrogen peroxide production in $1{\mu}M$ formylmethionylleucylphenylalanine (fMLP)-activated PMNs was inhibited by defibrotide in a dose-dependent fashion. Defibrotide effectively scavenged hydrogen peroxide, but not hydroxyl radical. Treatment of SAO rats with defibrotide inhibited tumor necrosis factor-${\alpha}$, and interleukin-1${\beta}$ productions in blood in comparison with untreated rats. These results suggest that defibrotide partly provides beneficial effects by preserving endothelial function, attenuating neutrophil accumulation, and antioxidant in the ischemic reperfused splanchnic circulation

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.1
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• pp.43-50
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• 2004

Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in a marked cardiac contractile dysfunction. Amrinone, a specific inhibitor of phosphodiesterase 3, has an antioxidant activity against PMNs. Therefore, we hypothesized that amrinone could attenuate PMNs-Induced cardiac dysfunction by suppression of reactive oxygen species (ROS) produced fby PMNs. In the present study, we examined the effects of amrinone on isolated ischemic (20 min) and reperfused (45 min) rat hearts perfused with PMNs. Amrinone at $25\;{\mu}M$, given to hearts during the first 5 min of reperfusion, significantly improved coronary flow, left ventricular developed pressure (P<0.001), and the maximal rate of development of left ventricular developed pressure (P<0.001), compared with ischemic/reperfused hearts perfused with PMNs in the absence of amrinone. In addition, amrinone significantly reduced myeloperoxidase activity by 50.8%, indicating decreased PMNs infiltration (p< 0.001). Superoxide radical and hydrogen peroxide production were also significantly reduced in fMLP- and PMA-stimulated PMNs pretreated with amrinone. Hydroxyl radical was scavenged by amrinone. fMLP-induced elevation of $[Ca^{2+}]_i$ was also inhibited by amrinone. These results provide evidence that amrinone can significantly attenuate PMN-induced cardiac contractile dysfunction in the ischemic/reperfused rat heart via attenuation of PMNs infiltration into the myocardium and suppression of ROS release by PMNs.