• Journal of Chest Surgery
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• v.34 no.9
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• pp.704-710
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• 2001

Background: Extracorporeal circulation using pump-oxygenator is an inevitable process to keep vital sign during cardiac arrest for open heart surgery. However, the diversion of blood through nonendothelialized channels appears to stimulate inflammatory response, and leukocyte activation may lead to cardiopulmonary edema. Our study evaluated the effect of leukocyte-induced cardiopulmonary edema using three different pump-oxygenator priming solutions; non-hemic crystalloid solution ; leukocyte-depleted homologous blood; non leukocyte-depleted homologous blood in priming solutions. Material and Method: Each different priming solution was used on five dogs, and the effect of leukocyte-induced cardiopulmonary edema during cardiopulmonary bypass(CPB) was evaluated. For each dog after 2 hours of exracorporeal circulation and another 4 hours of post-pump period, the dog was sacrificed and its heart and lung tissues were obtained for measuring Wet/Dry ratio. Arterial $O_2$partial pressure(PaO$_2$) and $CO_2$partial pressure(Pa$CO_2$) were checked. For the evaluation of ventilatory function, $CO_2$partial pressure difference between arterial blood (Pa$CO_2$) and exhaled air(Et$CO_2$) was measured. Result: 1. No significant difference was seen in arterial PaO$_2$and Pa$CO_2$among groups. 2. Ventilatory function evaluated by Pa$CO_2$and Et$CO_2$showed no significant difference between non-hemic and blood-mixed priming solution (P<0.05). 3. Cardiac and lung Wet/Dry ratios were remarkedly lower in the leukocyte-depleted group. There was no significant difference between the non-hemic and blood-mixed groups. Conclusion: Based upon this result, we concluded that the leukocyte depletion from homologous blood of CPB priming solution has a beneficial effect in reducing cardiopulmonary edema compared with non leukocyte-depleted or crystalloid priming solutions.

• Neonatal Medicine
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• v.18 no.1
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• pp.42-48
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• 2011

Purpose: Several factors including prolonged inflammatory response are thought to contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). The clinical findings can be explained by an increased production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-$\alpha$ ). We investigated the relationship between susceptibility to BPD and TNF-$\alpha$ promoter polymorphisms to identify genetic factors of the disease. Methods: Thirty-eight preterm infants who had developed BPD and 55 controlled infants with a birth weight <1,500 g were analyzed for TNF-$\alpha$ genotypes. The alleles of five promoter sites (-1031/-863/-857/-308/-238) of TNF-$\alpha$ gene were determined using $Taqman^{(R)}$-based allelic discrimination assays. Results: Gestational age ($27^{+5}{\pm}2^{+0}$ wk vs. $29^{+2}{\pm}1^{+4}$ wk, P<0.0001) and birth weight (990${\pm}$270 g vs. 1,220${\pm}$230 g, P<0.0001) were lower in the BPD group compared to the control group. The incidence of respiratory distress syndrome (71.1% vs. 49.1%, P=0.035) and patent ductus arteriosus (71.1% vs. 50.9%, P=0.052) was higher in the BPD group compared to the control group. The frequencies of the alleles and genotypes of five promoter sites (-1031/-863/-857/-308/-238) of TNF-$\alpha$ gene did not show differences between the BPD group and the control group. Conclusion: TNF-$\alpha$ promoter polymorphisms are not associated with susceptibility to BPD in Korean preterm infants.

• Journal of Nutrition and Health
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• v.42 no.7
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• pp.605-614
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• 2009

Most cancer patients are treated with surgery, chemotherapy or radiation as anticancer therapies. Especially in the case of radiation, these treatments produce adverse effects such as vomiting, weight loss, anorexia, normal cell damage and malabsorption. The major goal of this study was to determine the effect of irradiation on the nutritional and immune status in irradiated rats. A secondary goal was to determine the effectiveness of high protein diet (HP) and resveratrol (Res) in minimizing the adverse effects of radiation. Rats were divided into four groups: normal diet (NP), HP, NP + Res and HP + Res groups. Each group was further divided into subgroups that received radiation (RT group) and one that did not (non-RT group). Each diet was supplied from $12^{th}$ day prior to irradiation treatment with irradiation dose of 17.5 Gy. The diets were continued until 10th day after radiation treatment and animals were sacrificed. The radiation treatment showed decreased body weight, serum protein and HDL levels and increased TG and LDL levels in nutritional status. HP, NP + Res and HP + Res groups reduced the level of serum LDL and TG in irradiated rats. NP + Res and HP + Res groups increased reduced albumin level of serum in RT group. In case of immune status, the radiation treat-ment showed decreased WBC, lymphocytes and increased neutrophil and eosinophil levels. The levels of serum IL-2 and IL-6 were significantly increased by radiation, however the cytokine levels decreased in all dietary treatment groups. These results showed that high protein diet and resveratrol supplementation seem to minimize the adverse effects of radiation on lipid nutritional status and inflammation response in the rat model.

• Journal of Acupuncture Research
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• v.19 no.2
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• pp.51-64
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• 2002

We have compared(using the same series of experimental tissue samples) the levels of proteolytic enzyme activities and free radical-induced protein damage in synovial fluid from RA and CPH cases. Many protease types showed significantly increased (typically by a factor of approximately 2-3-fold) activity in RA, compared to normal rats. However, CPH significantly reduced the cytoplasmic enzyme activities of arginyl aminopeptidase, leucyl aminopeptidase, pyroglutamyl aminopeptidase, tripeptidyl aminopeptidase, and proline endopeptidase to almost about 1/10 each. For the Iysosomal proteases, synovial fluid samples from RA rats, CPH significantly reduced the enzyme activities of cathepsin B, dipeptidyl aminopeptidase I and dipeptidyl aminopeptidase II. In extracellular matrix degrading(collagenase, tissue elastase) and leukocyte as sociated proteases (leukocyte elastase, cathepsin G), CPH decreased these enzyme activities of collagenase, tissue elastase and leukocyte associated elastase in RA. In cytoplasmic and lysosomal protease activities in plasma from RA. CPH and normal plasma samples were not significantly different, suggesting that altered activity of plasma proteases (particularly those enzymes putatively involved in the immune response) is not a contributory factor in the pathogenesis of RA. In addition, the level of free radical induced damage to synovial fluid proteins was approximately twice that in RA, compared with CPH. CPH significantly decreased the level of ROS induced oxidative damage to synovial fluid proteins (quantified as protein carbonyl derivative). Therefore we conclude that both proteolytic enzymes and free radicals are likely to be of equal potential importance as damaging agents in the pathogenesis of inflammatory joint disease, and that the design of novel therapeutic strategies for patients with the latter disorder should include both protease inhibitory and free radical scavenging elements. In addition, the protease inhibitory element should be designed to inhibit the action of a broad range of protease mechanistic types (i.e. cysteine-, metallo- and serine- proteinases and peptidases). However, increased protein damage induced by ROS could not be rationalised in terms of compromised antioxidant total capacity, since the latter was not significantly altered in RA synovial fluid or plasma compared with CPH.

• Journal of Life Science
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• v.30 no.4
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• pp.359-369
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• 2020

Although many studies on immune modulatory materials have used RAW 264.7 cells, few have used T cell-derived TK-1 cell lines. Moreover, although some studies have investigated the efficacy of plant-derived β-sitosterol, few have examined the immunomodulatory activity of its analogue, daucosterol. In this study, β-sitosterol and daucosterol were isolated from D. batatas and identified by nuclear magnetic resonance spectroscopy. To evaluate the immune-enhancing or inhibitory effects of the isolated phytosterols, the expression levels of the inflammatory response genes COX-2, TNF-α, IL-6, and iNOS were analyzed by RT-PCR. The relative expression levels of TNF-α and iNOS in RAW 264.7 cells were increased more than threefold with β-sitosterol treatment comparing to those of untreated control. In the case of TK-1 cells, the expression level of TNF-α was decreased and the expression level of iNOS was increased in a β-sitosterol concentration-dependent manner. The expression levels of COX-2, TNF-α, and IL-6 increased by approximately 0.7-1.2 times in RAW 264.7 cells treated with daucosterol compared to those of untreated control, but iNOS expression decreased by 0.8-0.18 times. In the case of daucosterol-treated TK-1 cells, the expression levels of TNF-α, IL-6, and iNOS were markedly reduced from those of TK-1 cells treated only with lipopolysaccaride. As a conclusion, β-sitosterol treatment increased TNF-α and iNOS expression levels in RAW 264.7 cells, thus exerting an immune- boosting effect. However, in TK-1 cells, iNOS expression increased while TNF-α expression decreased, indicating an immunosuppressive activity of β-sitosterol. Daucosterol appears to exert an immunosuppressive effect in both macrophages and T cell lines by inhibiting iNOS expression in RAW 264.7 cells and greatly inhibiting the expression of TNF-α, IL-6, and iNOS in TK-1 cells.

• Journal of Life Science
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• v.26 no.1
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• pp.50-58
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• 2016

The root bark of Ulmus macrocarpa has been used in traditional medicine for the treatment of various diseases such as edema, infection and inflammation. Nevertheless, the biological activities and underlying mechanisms of the immunomodulatory effects remain unclear. In this study, as part of our ongoing screening program to evaluate the immunomodulatory potential of new compounds from traditional medicinal resources, we investigated the effects of U. macrocarpa water extract (UME) on immune modulation in a murine RAW 264.7 macrophage model. As immune response parameters, the productions of as nitric oxide (NO) and cytokines such tumor necrotic factor (TNF)-α, interleukin (IL)-1β and IL-10 were evaluated. Although the release of IL-1β remained unchanged in UME-treated RAW 264.7 macrophages, the productions of NO, TNF-α and IL-10 were significantly increased, along with the increased expression of inducible NO synthase, TNF-α and IL-10 expression at concentrations with no cytotoxicity. UME treatment also induced the nuclear translocation of nuclear factor κB (NF-κB), and phosphorylation of Akt and mitogen-activated protein kinases (MAPKs) indicating that UME activated macrophages through the activation of NF-κB, phosphoinositide-3-kinase (PI3K)/Akt and MAPKs signaling pathways in RAW 264.7 macrophages. Furthermore, pre-treatment with UME significantly attenuated the production of NO, but not TNF-α, IL-1β and IL-10, in lipopolysaccharide-stimulated RAW 264.7 cells suggesting that UME may be useful in preventing inflammatory diseases mediated by excessive production of NO. These findings suggest that the beneficial therapeutic effects of UME may be attributed partly to its ability to modulate immune functions in macrophages.

• Journal of Life Science
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• v.21 no.11
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• pp.1518-1525
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• 2011

Sorafenib is the only approved systemic, therapeutic agent for hepatocellular carcinoma (HCC). The use of Ginseng Extract (GE) in cancer patients is growing worldwide; however, drug interaction between sorafenib and GE has not been illuminated. Four different human cancer cell lines including HepG2 were used and immunocompetent mice were implanted subcutaneously with a mouse HCC cell line. Treatment with low dose GE stimulated cell growth, while a high dose inhibited growth. pERK (phosphorylation of extracellular signal-regulated kinase) was concomitantly increased and decreased respective of different doses of GE. Antitumoral effect of sorafenib decreased in non-proliferating phase cells but was sensitized after low dose GE (LDG) treatment. PD98059 (ERK phosphorylation inhibitor) efficiently blocked ERK phosphorylation, resulting in loss of sorafenib sensitization even after LDG treatment. In the HCC mouse model, LDG alone slightly increased tumor size while sorafenib alone significantly decreased it. However, a combination of LDG and sorafenib significantly decreased tumor size compared with sorafenib alone. Increase of pERK was observed in some normal mice organs and mild inflammatory change was observed in some of these organs, suggesting pERK activation by LDG may cause unexpected toxicity in normal cells. GE, dose-dependently, induced stimulation or inhibition in some human cancer cell lines. Combinational use of GE and sorafenib possibly potentiated an antitumoral response to sorafenib. pERK level has been provided as a potential predictive marker for sorafenib. Our result may suggest GE's dual effects in relation to pERK level in HCC cancer cell lines, and that certain doses of GE can sensitize sorafenib.

• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.386-394
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• 2003

Background : ATS(American Thoracic Society) defined new guidelines for COPD(chronic obstructive lung disease) in April 2001, following the results of the global initiative for chronic obstructive lung disease. The most important concept of COPD is an airflow limitation which is not fully reversible compared to bronchial asthma(BA). The criteria for COPD are postbronchodilator $FEV_1$ less than 80% of the predicted value and an $FEV_1$ per FVC ratio less than 70%. The global initiative for asthma(GINA) study defined asthma, which included immune-mediated chronic airway inflammatory airway disease, and found that airflow limitation was wide spread, variable and often completely reversible. Taken together COPD and BA may be combined in airflow limitation. This study was designed to evaluate the prevalence of BA in patients with COPD of moderate to severe airflow limitation. Methods : COPD was diagnosed by symptoms and spirometry according to ATS guidelines. Enrolled subjects were examined for peak flow meters(PFM), sputum eosinophils and eosinophil cationic protein(ECP) levels, serum total IgE with allergy skin prick test, and methacholine bronchial provocation test(MBPT). Results : About 27% of COPD patients with moderate to severe airflow limitation were combined with BA. There was significantly decreased response to PFM in severe COPD. However, there was no significant relationship between BA and COPD according to the degree of severity. The BA combined with COPD group showed significantly high eosinophil counts and ECP level in induced sputum. However, neutrophil counts in induced sputum showed significant elevation in the pure COPD group. Conclusion : Twenty-seven percent of COPD patients with moderate to severe ventilation disorder were combined with BA, but there were no significant differences according to the degree of severity.

• Tuberculosis and Respiratory Diseases
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• v.65 no.4
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• pp.301-307
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• 2008

Background: The triggering receptor expressed on myeloid cells-1 (TREM-1) is an activating receptor that is expressed on the surface of neutrophils and mature monocytes when stimulated with several microbial components, which can amplify the inflammatory response. This study analyzed the prognostic value of the sTREM-1 levels in patients with acute respiratory distress syndrome (ARDS). Methods: The bronchoalveolar lavage (BAL) fluid and blood was collected prospectively from 32 patients with ARDS, 15 survivors and 17 nonsurvivors. An enzyme-linked immunosorbent assay was performed to measure the sTREM-1. The following data was obtained: APACHE II score, Clinical Pulmonary Infection Score (CPIS), BAL fluid analysis, C-reative protein. Mortality in the ICU was defined as the end point. Results: The serum sTREM-1 level was significantly higher in the nonsurvivors than survivors ($54.3{\pm}10.3pg/ml$ vs. $22.7{\pm}2.3pg/ml$, p<0.05). The sTREM-1 level in the serum, but not in the BAL fluid, was an independent predictor of the ICU mortality (OR: 22.051, 95% CI: 1.780~273.148, p<0.016), and a cut-off value of ${\geq}33pg/ml$ yielded a diagnostic sensitivity of 71% and specificity of 93%. Conclusion: The serum sTREM-1 level may be a useful predictor of the outcome of ARDS patients.

• Journal of dental hygiene science
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• v.17 no.6
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• pp.495-500
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• 2017

Hippophae rhamnoides L. (sea buckthorn) is a shrub wood that belongs to the bamboo tree family, and is rich in vitamin C, D, and E; it is referred to as a vitamin tree. It is mainly grown in the high mountains of Europe and Central Asia, and has been widely used in China and Russia as natural medicine. Recent studies have shown that it is effective in the treatment of cancer, liver diseases, cardiovascular diseases, and gastrointestinal diseases. However, results of studies on its effect on the regulation of pain are insufficient. In this study, we investigated the effect of sea buckthorn on the development and control of pain in two facial areas. The experimental animals included 7- to 8-week-old Sprague-Dawley rats (240~260 g). Formalin (5%), which is known as an inflammation inducer, was injected into the vibrissa pad or temporomandibular joints to induce orofacial acute pain. Rubbing or scraping of the region injected with formalin was regarded as a pain index, and the behavioral response was observed for 45 minutes after the injection. Sea buckthorn extract diluted to 150, 300 mg/kg (in 1 ml of distilled water) was orally administered 30 minutes prior to the acute pain. The facial pain behavior was effectively reduced in the 300 mg/kg group when compared to the control group (vehicle). Likewise, in an experiment in which formalin was injected into the temporomandibular joints, effective pain alleviation was confirmed at the same drug concentration. These results suggest that sea buckthorn extract may be useful in the development of therapeutic agents for acute inflammatory pain in the orofacial area and for controlling temporomandibular joint pain.