• 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.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.215-228
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• 1999

Background: Sarcoidosis is a chronic granulomatous inflammatory disease of unknown etiology often involving the lungs and intrathoracic lymph nodes. The natural course of sarcoidosis is variable from spontaneous remission to significant morbidity or death. But, the mechanisms causing the variable clinical outcomes or any single parameter to predict the prognosis was not known. In sarcoidosis, the number and the activity of CD4 + lymphocytes are significantly increased at the loci of disease and their oligoclonality suggests that the CD4 + lymphocytes hyperreactivity may be caused by persistent antigenic stimulus. Recently, it has been known that CD4+ lymphocytes can be subdivided into 2 distinct population(Th1 and Th2) defined by the spectrum of cytokines produced by these cells. Th1 cells promote cellular immunity associated with delayed type hypersensitivity reactions by generating IL-2 and IFN-$\gamma$. Th2 cells playa role in allergic responses and immediate hypersensitivity reactions by secreting IL-4, IL-5, and IL-10. CD4+ lymphocytes in pulmonary sarcoidosis were reported to be mainly Th1 cells. IL-12 has been known to play an important role in differentiation of undifferentiated naive T cells to Th1 cells. And, Moller et al. observed increased IL-12 in bronchoalveolar lavage fluid(BALF) in patients with sarcoidosis. So it is possible that the elevated level of IL-12 is necessary for the continuous progression of the disease in active sarcoidosis. This study was performed to test the assumption that IL-12 can be a marker of active pulmonary sarcoidosis. Methods: We measured the concentration of IL-12 in BALF and in conditioned medium of alveolar macrophage(AM) using ELISA(enzyme-linked immunosorbent assay) method in 26 patients with pulmonary sarcoidosis(10 males, 16 females, mean age: $39.8{\pm}2.1$ years) and 11 normal control. Clinically, 14 patients had active sarcoidosis and 12 patients had inactive. Results: Total cells counts, percentage and number of lymhocytes, number of AM and CD4/CD8 lymphocyte ratio in BALF were significantly higher in patients with sarcoidosis than in control group. But none of these parameters could differentiate active sarcoidosis from inactive disease. The concentration of IL-12 in BALF was significantly increased in sarcoidosis patients ($49.3{\pm}9.2$ pg/ml) than in normal control ($2.5{\pm}0.4$ pg/ml) (p<0.001). Moreover it was significantly higher in patients with active sarcoidosis ($70.3{\pm}14.8$ pg/ml) than in inactive disease ($24.8{\pm}3.l$ pg/ml) (p=0.001). Also, the concentration of IL-12 in BALF showed significant correlation with the percentage of AM(p<0.001), percentage(p<0.001) and number of lymphocyte(p<0.001) in BALF, suggesting the close relationship between the level of IL-12 in BALF and the inflammatory cell infiltration in the lungs. Furthermore, we found a significant correlation between the level of IL-12 and the concentration of soluble ICAM-1 : in serum(p<0.001) and BALF (p=0.001), and also between IL-12 level and ICAM-1 expression of AM(p<0.001). The AM from patients with pulmonary sarcoidosis secreted significantly larger amount of IL-12 ($206.2{\pm}61.9$ pg/ml) than those of control ($68.3{\pm}43.7$ pg/ml) (p<0.008), but, there was no difference between inactive and active disease group. Conclusion : Our data suggest that the BALF IL-12 level can be used as a marker of the activity of pulmonary sarcoidosis.

• Clinical and Experimental Pediatrics
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• v.50 no.3
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• pp.248-254
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• 2007

Purpose : Inflammation plays a major role in the pathogenesis of RDS and BPD in the immature lung. We investigated the possible role of IL-10 and IL-12 in the cord blood of preterm newborns with RDS or BPD. Methods : Forty preterm newborns whose mothers received antenatal care at Ewha Womans University Mokdong Hospital between January 2003 to June 2005, and agreed to testing their cord blood samples were enrolled. The gestational ages were below 34 weeks. Cord blood level of IL-10 and IL-12 were determined by ELISA. We separated the patients into 2 groups (RDS group and non-RDS group, BPD group and non-BPD group) and compared the cytokine levels and clinical records of the groups. Results : Cord blood IL-10 level showed a significant inverse correlation with gestational age and birth weight (P=0.001, P=0.005). Preterm infants with RDS showed higher IL-10 level (1.0 vs 0.1 pg/mL; P=0.001) in the cord blood than those without RDS. The differences remained statistically significant after correction for the effect of gestational age between both preterm groups. Despite similar cord blood IL-10 levels, preterm infants with BPD showed no significant difference with those without BPD. Conclusion : Cord blood IL-10 levels are increased in preterm infants which may be due to the immuno-suppression occurring during pregnancy and to fetal immaturity because these levels are inversely correlated with the gestational age. So, Cord blood IL-10 level can be used as the predictor of RDS.

• Food Science of Animal Resources
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• v.33 no.3
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• pp.411-416
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• 2013

This study aimed to examine the mechanisms underlying the effects of Garcinia cambogia extract on the adipogenic differentiation of 3T3-L1 cells and long-chain saturated fatty acid-induced lipotoxicity of HepG2 cells. 3T3-L1 preadipocytes, mouse embryonic fibroblast-adipose like cell line, were treated with MDI solution (0.5 mM IBMX, 1 ${\mu}M$ dexamethasone, 10 ${\mu}g/mL$ insulin) to generate a cellular model of adipocyte differentiation. Using this cellular model, the anti-obesity effect of Garcinia cambogia extract was evaluated. MDI-induced lipid accumulation and expression of adipogenesis-related genes were detected by Oil red O staining, Nile Red staining, and Western blot analysis. Effects Garcinia cambogia extract on palmitate-induced lipotoxicity was also analyzed by MTT assay, LDH release, and DAPI staining in HepG2 cells. Garcinia cambogia extract significantly suppressed the adipogenic differentiation of preadipocytes and intracellular lipid accumulation in the differentiating adipocytes. Garcinia cambogia extract also markedly inhibited the expression of peroxisome proliferator- activated receptor ${\gamma}2$ ($PPAR{\gamma}2$), CCAT/enhancer-binding protein ${\alpha}$ ($C/EBP{\alpha}$), and adipocyte protein aP2 (aP2). In addition, Garcinia cambogia extract significantly attenuated palmitate-induced lipotoxicity in HepG2 cells. Palmitateinduced cellular damage and reactive aldehydes were also significantly reduced in the presence of Garcinia cambogia extract. These findings suggest that the Garcinia cambogia extract inhibits the adipogenic differentiation of 3T3-L1 preadipocytes, probably by regulating the expression of multiple genes associated with adipogenesis such as $PPAR{\gamma}2$, $C/EBP{\alpha}$, aP2, and thereby modulating fatty acid-induced lipotoxicity to reduce cellular injury in hepatocytes.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.319-327
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• 1994

Background: The pathogenetic mechanism of adult respiratory distress syndrome(ARDS) is not clearly defined yet, but it is well known that increased pulmonary capillary permeabilty is characteristic feature of ARDS. The increased alveolar-capillary permeability is usually preceded by damage of pulmonary artery endothelial cells. The released enzymes and oxygen free radicals from the activated neutrophils seem to play a predominant role in endothelial cell cytotoxicity. The activated neutrophils, however, probably are not the sole contributing factor in this type of damage because many cases of ARDS have been reported in severe neutropenia. Bacterial endotoxin perse and/or oxygen free radicals released from endothelial cells are suggested to be possible factors that contribute to the development of ARDS. The purpose of this study is to investigate the direct cytotoxicity of endotoxin and the role of oxygen free radicals released from the endothelial cells in endotoxin-induced endothelial cell cytotoxicity. Methods: First, to investigate whether endotoxin is cytotoxic to HUVE by itself, various doses of endotoxin were added to culture medium and cytotoxicity was measured. Second, to evaluate the possible role of oxygen free radical in endotoxin-induced HUVE cytotoxicity, various antioxidants were added on the endotoxin-induced HUVE cytotoxicity and cytotoxicity was measured. Third, to verify the release of oxygen free radicals from HUVE, the concentrations of hydrogen peroxide in the endotoxin-treated culture supernatant were measured. Finally, to observe the cytotoxic effect of hydrogen peroxide, HUVE cytotoxicity in the presence of various doses of hydrogen peroxide was measured. The fourth generations of subcultured HUVE from primary culture were used. The cell cytotoxicity was quantified by the chromium-51 release assay. Results: 1) Endotoxin alone showed HUVE cytotoxicity in a dose-dependent fashion. 2) Endotoxin-induced HUVE cytotoxicity was significantly attenuated by the pretreatment of catalase and DMTU. 3) Hydrogen peroxide was released from HUVE after endotoxin treatment in a dose-dependent fashion. 4) Exogenous hydrogen peroxide also showed HUVE cytotoxicity in a dose-dependent fashion. Conclusion: These results suggest that endotoxin alone can directly injure HUVE, and, oxygen-free radicals released from HUVE in response to endotoxin may also participate in the endotoxin-induced HUVE cytotoxicity.

• Biomedical Science Letters
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• v.2 no.2
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• pp.133-151
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• 1996

After cardiac surgery, it has been recognized that various complications were associated with injured humoral and cellular immunity by cardiopulmonary bypass(CPB). Especially, in postoperative pulmonary dysfunction, transpulmonary leukostasis followed complement activation and inflammatory responses are major pathogen. Some studies have showed that pretreated-corticosteroids before CPB protected postoperative pulmonary dysfunction. Corticosteroids may inhibit complement and leukocyte activation. On based previous studies, present investigator determined changes of leukocyte counts and transpulmonary leukostasis during cardiac surgery and postoperative periods. For the evaluation of postoperative pulmonary function and edema, $PaO_2$ and chest X-ray were compared between pre-CPB and post-CPB. Fever and other parameters were also observed postoperatively. The aim of this study was to define for the prophylactic effects of corticosteroid(Solu-Medrol: 30mg/kg) on all the researched parameters. This study was prospectively designed with randomized-blind fashion for 50 patients undergoing cardiac surgery. According to the purpose of study, all patients were divided into placebo and steroid group. : Placebo group was 25 patients received normal saline(not corticosteroid), and steroid group was 25patients received corticosteroid(Solu-Medrol: 30mg/kg) before initiation of CPB. The results of study were summarized as follows. 1. Total peripheral leukocyte counts decreased significantly at 5 minutes of CPB in all patients(P<0.01), and began to increase progressively at later periods of CPB with neutrophilia. The significant rise remained at postoperative 7th day(P<0.05). 2. During partial CPB, transpulmonary leukostasis occurred in placebo group(P<0.001), whereas it was prevented in steroid group. 3. In both groups, peripheral lymphocyte counts were stable during CPB, but began to reduce at time of intensive care unit(ICU) and the lymphocytopenia remained until postoperative 3rd day. The lymphocyte counts recovered on postoperative 7th day. 4. In both groups, peripheral counts of monocyte were relatively stable in the early peroid of CPB, and increased gradually in the later periods of CPB. This significant monocytosis remained throughout postoperlative periods(P<0.05). 5. The mean value of postoperative $paO)_2$ was lower than that of pre-CPB in placebo group(P=0.01) but didn't significant in steroid group(P=0.90). In the incidence of pulmonary edema signs and fever, placebo group was higher than steroid group(P=0.001, p=0.01, respectively). However mechanical respiratory supporting and care periods at intensive care unit were not significant difference between two groups(P>.0.05).With the above results, the investigator concluded that leukocyte activation and pulmonary sequestration were caused by cardiac surgery with CPB and demonstrated that high dose corticosteroid will provide prophylactic effect for pulmonary leukostasis and higher neutrophilia. These effects may ameliorate postoperative pulmonary dysfunction and contribute to postoperative less morbidity. However, further study should be performed because postoperative lymphocytopenia continued for 3 days in both groups, which may suspected damage or suppression of cell-mediated immunity with used corticosteroid.

• Tuberculosis and Respiratory Diseases
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• v.63 no.4
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• pp.353-361
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• 2007

Background: Malignancies are a common and important causes of exudative pleural effusions. Several tumor markers have been studied because the pleural fluid cytology and pleural biopsy specimens do not provide a diagnosis in a high percentage of malignant effusions. In an attempt to overcome this limitation, procalcitonin and C-reactive protein (CRP) in pleural effusions and serum, which are known to be inflammation markers, were measured to determine if they can differentiate an exudate from trasndate as well as the diverse causes of exudative pleural effusion. Methods: 178 consecutive patients with pleural effusion (malignant 57, tuberculous 51, parapneumonic 31, empyema 5, miscellaneous benign 7, transudative 27)were studied prospectively. The standard parameters of pleural effusion and measured serum and pleural procalcitonin were examined using in immunoluminometric assay. The level of CRP in serum and pleural fluid was determined by turbidimetric immunoassay. Results: The pleural procalcitonin levels in the exudate were significantly higher than those in the transudate, $0.81{\pm}3.09ng/mL$ and $0.12{\pm}0.12ng/mL$, respectively (p=0.007). The pleural CRP levels were significantly higher in the exudate than the transudate, $2.83{\pm}3.31mg/dL$ and $0.74{\pm}0.67mg/dL$, respectively (p<0.001). The pleural procalcitonin levels in the benign effusion were significantly higher than those in the malignant effusion, $1.15{\pm}3.82ng/mL$ and $0.25{\pm}0.92ng/mL$, respectively (p=0.032). The pleural CRP levels were significantly higher in the benign effusion than in the malignant effusion, $3.68{\pm}3.78mg/dL$ and $1.42{\pm}1.54mg/dL$, respectively (p<0.001). The pleural procalcitonin levels in the non-tuberculous effusion were significantly higher than those in the tuberculous effusion, $1.16{\pm}3.75ng/mL$ and $0.13{\pm}0.37ng/mL$, respectively (p=0.008). Conclusion: Measuring the level of procalcitonin and CRP in the pleural fluid is helpful for differentiating between transudates and exudates. In addition, it is useful for differentiating between benign and malignant pleural effusions.

• Clinical and Experimental Pediatrics
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• v.52 no.6
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• pp.680-688
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• 2009

Purpose : Cysteinyl leukotrienes are important proinflammatory mediators in asthma. Recently, it was suggested that a promoter polymorphism in the genes encoding for leukotriene C4 synthase (LTC4S), a key enzyme in the leukotriene synthetic pathway, and cysteinyl leukotriene receptor 1 (CysLTR1) might be associated with aspirin-intolerant asthma. We investigated whether polymorphisms in LTC4S and CysLTR1 genes or their interactions were associated with the asthma phenotype, lung function, or bronchial hyperreactivity (BHR) in Korean children. Methods : A total of 856 asthmatic children and 254 non-asthmatic controls were enrolled; a skin prick test, lung function test and bronchial provocation test were performed. Of those enrolled, 395 children underwent exercise challenge tests. The LTC4S A(-444)C and CysLTR1 T(＋927)C were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. Results : Of those enrolled, 699 children were classified as having atopic asthma and 277 children, as having exercise-induced asthma (EIA). LTC4S and CysLTR1 polymorphisms were not associated with atopic asthma, EIA, or asthma per se. Lung function and BHR were not significantly different between the wild type (AA or TT) and the variant (AC＋CC or TC＋CC) genotypes in asthmatics, atopic asthmatics, and EIA (＋) asthmatics, while total eosinophil counts were higher in the variant type of LTC4S than in the wild type in atopic asthmatics. There were no associations between the gene-gene interactions of LTC4S and CysLTR1 genotypes and the asthma phenotypes. Conclusion : LTC4S A(-444)C and CysLTR1 T(＋927)C polymorphisms and their gene-gene interactions are not associated with asthma phenotype, lung function, or BHR in Korean children.

• Tuberculosis and Respiratory Diseases
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• v.50 no.2
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• pp.171-181
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• 2001

Background : Angiogenesis is an essential process for the growth and metastatic ability of solid tumors. One of the key factors known to be capable of stimulating tumor angiogenesis is the vascular endothelial growth factor (VEGF). The serum VEGF concentration has been shown to be a useful parameter related to the clinical features and prognosis of lung cancer and has been recently applied to a the malignant pleural effusion showing a correlation with the biochemical parameters. The VEGF has been shown to play a role in the inflammatory diseases, but rarely in the tuberculosis (TB). The serum and pleural fluid VEGF levels were measured in patients with lung cancer and TB. Their relationship with the clinical and laboratory parameters and repeated measurement 3 months after various anticancer treatments were evaluated to assess the utility of the VEGF as a tumor marker. Methods : Using a sandwich enzyme-linked immunosorbent assay, the VEGF conoentration was measured in both sera and pleural effusions collected from a total of 85 patients with lung cancer, 13 patients with TB and 20 healthy individuals. Results : The serum VEGF levels in patients with lung cancer ($619.9{\pm}722.8pg/ml$) were significantly higher than those of healthy controls ($215.9{\pm}191.1pg/ml$), However, there was no significant difference between the VEGF levels in the lung cancer and TB patients. The serum VEGF levels were higher in large cell and undifferentiated carcinoma than in squamous cell carcinoma and adenocarcinoma. The serum VEGF levels of lung cancer patients revealed no significant relationship with the various clinical parameters. The VEGF concentrations in the malignant effusion ($2,228.1{\pm}2,103.0pg/ml$) were significantly higher than those in the TB effusion ($897.6{\pm}978.8pg/ml$). In the malignant pleural effusion, the VEGF levels revealed significant correlation with the number of red blood cells (r=0.75), the lactate dehydrogenase (LDH)(r=0.70), and glucose concentration (r=-0.55) in the pleural fluid. Conclusion : The serum VEGF levels were higher in the lung cancer patients. The VEGF levels were more elevated in the malignant pleural effusion than in the tuberculous effusion. In addition, the VEGF levels in the pleural fluid were several times higher than the matched serum values suggesting a local activation and possible etiologic role of VEGF in the formation of malignant effusions. The pleural VEGF levels showed a significant correlation with the numbers of red blood cells, LDH and glucose concentrations in the pleural fluid, which may represent the tumor burden.

• 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.