• Journal of Life Science
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• v.28 no.10
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• pp.1147-1155
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• 2018

Agaricus blazei mycelial liquid culture extract (ABMLCE) promoted the production of testosterone (TS) in TM-3 mouse Leydig testis cells. Now, we report that ABMLCE containing eritadenine (EA) as a minor constituent (15.3 mg/100 g) reduced $5{\alpha}-reductase$ 2 ($5{\alpha}-R2$) enzyme activity and dihydrotestosterone (DHT) content which are key constituents for the benign prostatic hyperplasia (BPH) inductions. RWPE-1 prostate cells were grown in a Keratinocyte serum-free medium (K-SFM) containing ABMLCE (0~50 ppm), EA (0~10 ppm,), and finasteride (FS $10{\mu}M$: a positive control) in a 24-well plate for 24 hr. Supernatants collected from cell-cultured media were used for the assay of $5{\alpha}-R2$, superoxide dismutase (SOD), catalase (CAT) and cyclooxygenase-2 (COX-2) enzyme activities, and for TS, DHT, tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) and $interleukin-1{\beta}$ ($IL-1{\beta}$) contents by their assay kits. The $5{\alpha}-R2$ activity and DHT content were proportionally reduced (p<0.05) to concentrations of ABMLCE. The SOD and CAT enzyme activities were significantly (p<0.05) elevated concomitant with ABMLCE concentrations, while COX-2, $TNF-{\alpha}$ and $IL-1{\beta}$ showed reverse results (p<0.05). Similarly, the effects of EA were similar to those of ABMLCE. Efficacies of ABMLCE 50 ppm and EA 10 ppm in $5{\alpha}-R2$ and DHT reduction were similar to those of $10{\mu}M$ FS. These results suggest that ABMLCE and EA reduced $5{\alpha}-R2$ and DHT through their anti-inflammatory and anti-oxidative actions. This implies that ABMLCE containing EA could be a beneficial material in the cure of BPH in humans.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.922-931
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• 2000

Background : It has been well known that bronchia1 asthma is a chronic airway inflammatory disorder. Recently, sputum induced with hypertonic saline was introduced as a simple and useful nonivasive medium to investigate airway inflammation and symptom severity in patients with asthma. We examined the eosinophil, eosinophil cationic protein (ECP), interleukin(IL)-3, IL-5, granulocyte-macrophage colony-stimulating facta (GM-CSF), and nitric oxide (NO) derivatives in induced sputum from patients with bronchia1 asthma in order to determine the role of NO and various inflammatory cytokines as a useful markers of airway inflammation or changes in pulmonary function tests and symptoms. Methods : A total 30 patients with bronchia1 asthma received oral prednisolone 30 mg daily for 2 weeks. Forced expiratory volume in one second ($FEV_1$), total blood eosinophil count and induced sputum eosinophil count, ECP, IL-3, IL-5, GM-CSF, and NO derivatives were determined before and after the administration of prednisolone. Results : Of the 30 patients, 13 (43.3%) were male and 17 (56.7%) were female. The mean age of patients was 41.8 years (range 19-64 years). Two patients could not produce sputum at the second study and 3 could not be followed up after their first visit. Two weeks after the prednisolone administration, there was a significant increase in $FEV_1$ (% of predicted value) from 78.1$\pm$20.6 % to 90.3$\pm$ 18.3 % (P<0.001). The eosinophil percentages in induced sputum were significantly decreased after treatment with prednisolone, with values of 56.1$\pm$27.2 % versus 29.6$\pm$21.3 % (P<0.001), and ECP were $134.5\pm68.1\;{\mu}g/L$ versus $41.5\pm42.4\;{\mu}g/L$ (P<0.001) respectively. After the prednisolone treatments, the eotaxin concentration also showed a decreasing tendency from 26.7$\pm$12.8 pg/ml to 21.7$\pm$8.7 pg/ml. There was a decreasing tendency but no significant differences in total blood eosinophil count (425.7$\pm$265.9 vs 287.7$\pm$294.7) and in the concentration of NO derivatives ($70.4\pm44.6{\mu}mol/L$ vs $91.5\pm48.3\;{\mu}mol/L$) after the prednisolone treatments. IL-3, IL-5, GM-CSF were undetectable in the sputum of most subjects either before the prednisolone treatments or after the treatments. Before the prednisolone treatments, a significant inverse correlation was observed between FEV1 and sputum ECP (r=-D.364, P<0.05) and there was a significant correlation between sputum eosinophils and eotaxin (r=0.369, P<0.05) Conclusion : The eotaxin and ECP concentration in induced sputum may be used as markers of airway inflammation after treatments in bronchia1 asthma. In addition, the measurement of sputum eosinophil percent ages is believed to be a simple method displaying the degree of airway inflammation and airway obstruction before and after the prednisolone treatment in bronchia1 asthma. However, unlike exhaled NO, the examination of NO derivatives with Griess reaction in induced sputum is considered an ineffective marker of changing airway inflammation and obstructing symptoms.

• Tuberculosis and Respiratory Diseases
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• v.42 no.5
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• pp.744-751
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• 1995

Background: Asthma is an inflammatory disease because there are many inflammatory changes in the asthmatic airways. Axon reflex mechanisms may be involved in the pathogenesis of asthma. Sensory neuropeptides are involved in this inflammation, which is defined as neurogenic inflammation. Substance p, neurokinin A, and neurokinin B may be main neuropeptides of neurogenic inflammation in airways. These tachykinins act on neurokinin receptors. Three types of neurokinin receptors, such as $NK_1$, $NK_2$, and $NK_3$, are currently recognized, at which substance p, neurokinin A, and neurokinin B may be the most relevant natural agonist of neurogenic inflammation in airways. The receptor subtypes present in several tissues have been characterized on the basis of differential sensitivity to substance p, neurokinin A, and neurokinin B. Plasma extravasation and vasodilation are induced by substance p more potently than by neurokinin A, indicating NK1 receptors on endothelial cells mediate the response. But airway contraction is induced by neurokinin A more potently than by substance P, indicating the $NK_2$ receptors in airway smooth muscles. These receptors are used to evaluate the pathogenesis of brochial asthma. FK224 was identified from the fermentation products of Streptomyces violaceoniger. FK224 is a dual antagonist of both $NK_1$ and $NK_2$ receptors. Purpose: For a study of pathogenesis of bronchial asthma, the effect of FK224 on plasma extravasation induced by vagal NANC electrical stimulation was evaluated in rat airway. Method: Male Sprague-Dawley rats weighing 180~450gm were anesthetized by i.p. injection of urethane. Plasma extravasation was induced by electrical stimulation of cervical vagus NANC nerves with 5Hz, 1mA, and 5V for 2 minutes(NANC2 group) and for sham operation without nerve stimulation(control group). To evaluate the effect of FK224 on plasma extravasation in neurogenic inflammation, FK224(1mg/kg, Fujisawa Pharmaceutical Co., dissolved in dimethylsulphoxide; DMSO, Sigma Co.) was injected 1 min before nerve stimulation(FK224 group). To assess plasma exudation, Evans blue dye(20mg/kg, dissolved in saline) was used as a plasma marker and was injected before nerve stimulation. After removal of intravascular dye, the evans blue dye in the tissue was extracted in formamide($37^{\circ}C$, 24h) and quantified spectrophotometrically by measuring dye absorbance at 629nm wavelength. Tissue dye content was expressed as ng of dye per mg of wet weight tissue. The amount of plasma extravasation was measured on the part of airways in each groups. Results: 1) Vagus nerve(NANC) stimulation significantly increased plasma leakage in trachea, main bronchus, and peripheral bronchus compared with control group, $14.1{\pm}1.6$ to $49.7{\pm}2.5$, $17.5{\pm}2.0$ to $38.7{\pm}2.8$, and $12.7{\pm}2.2$ to $19.1{\pm}1.6ng$ of dye per mg of tissue(mean ${\pm}$ SE), respectively(p<0.05). But there was not significantly changed in lung parenchyma(p>0.05) 2) FK224 had significant inhibitory effect upon vagal nerve stimulation-induced airway plasma leakage in any airway tissues of rat,such as trachea, main bronchus, and peripheral bronchus compared with vagus nerve stimulation group, 49%, 58%, and 70%, respectively(p<0.05). Inhibitory effect of FK224 on airway plasma leakage in neurogenic inflammation was revealed the more significant in peripheral bronchus, but no significant in lung parenchyma. Conclusion: These results suggest that FK224 is a selective NK receptor antagonist which effectively inhibits airway plasma leakage induced by the endogenous neurotransmitters relased by neurogenic inflammation in rat airway. Tachykinin receptor antagonists may be useful in the treatment of brochial asthma.

• Pediatric Infection and Vaccine
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• v.23 no.1
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• pp.25-30
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• 2016

Purpose: We undertook this study to investigate discrepancies in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values, and variations following intravenous immunoglobulin (IVIG) therapy in Kawasaki disease (KD). Methods: A total of 123 KD patients were retrospectively enrolled. Patients were treated with IVIG 2 g/kg at 2 to 9 days after disease onset. We obtained white blood cell (WBC) count, percentage of neutrophils (% neutrophils), CRP, ESR, and N-terminal pro-brain natriuretic peptide (NT-proBNP) values before and 48 to 72 hours after IVIG treatment. Discrepancy was defined as $CRP{\geq}10mg/dL$ and ESR <50 mm/hr (Group 1), or CRP <10 mg/dL and $ESR{\geq}50mm/hr$ (Group 2). Results: Thirty-six of 123 subjects (29.2%) had a discrepancy: 25 (20.3%) in Group 1 and 11 (8.9%) in Group 2. In Group 1, 15 patients (60%) had fever for <5 days (early presenter) and 10 (40%) had fever for ${\geq}5days$ (late presenter). There were six early presenters (55%) and five late presenters (45%) in Group 2. Late presenters had higher ESR than early presenters ($34.3{\pm}21.0mm/hr$ vs. $26.3{\pm}19.3mm/hr$, P=0.029). After IVIG treatment, elevated WBC count, % neutrophils, CRP, and NT-proBNP levels normalized. In contrast, ESR increased from $37.4{\pm}21.9mm/hr$ to $48.0{\pm}22.7mm/hr$ (n=36, P=0.051). Conclusions: A discrepancy may be related to the duration of fever. Due to discrepancies in CRP and ESR values in acute KD, both should be measured to assess the degree of inflammatory activity before IVIG treatment. After IVIG treatment, the ESR should not be used as a marker of response to therapy in KD.

• Clinical and Experimental Pediatrics
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• v.46 no.7
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• pp.695-701
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• 2003

Purpose : It had been suggested that pain arising from deep somatic body regions influences neural activity within periaqueductal gray(PAG) of midbrain via distinct spinal pathways. Aspirin is one of the popular non-steroidal anti-inflammatory drugs used in the management of pain. Fos expression was used as a marker for neuronal activity throughout central neurons following painful peripheral stimulation. This study was prepared to investigate changes of c-Fos immunoreactivity in midbrain by deep pain and effects of aspirin. Methods : Male Sprague-Dawley rats were injected with 0.1 mL of 5% formalin in the plantar muscle of the right hindpaw. For experimental group II, aspirin was injected intravenously before injection of formalin. An aspirin-untreated group was utilized as group I. Rats were sacrificed at 0.5, 1, 2, 6 and 24 hours after formalin injection. Rat's brains were removed and sliced in rat brain matrix. Brain slices were coronally sectioned at interaural 1.00-1.36 mm. Serial sections were immunohistochemically reacted with polyclonal c-Fos antibody. The numbers of c-Fos protein immunoreactive neurons in ventrolateral periaqueductal gray(VLPAG) and dorsomedial periaqueductal gray(DMPAG) were counted and analyzed statistically with Mann-Whitney U tests. Results : Higher numbers of c-Fos protein immunoreactive neurons were found in VLPAG. In both VLPAG and DMPAG of formalin-treated group, the numbers of c-Fos protein immunoreactive neurons were significantly higher at all time points than the formalin-untreated group, which peaked at two hours. The numbers of c-Fos immunoreactive neuron of the aspirin-treated group were less compared to the aspirin-untreated group at each time point. Conclusion : These results provide some basic knowledge in understanding the mechanism of formalin-induced deep somatic pain and the effects of aspirin.

• Clinical and Experimental Pediatrics
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• v.48 no.5
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• pp.481-487
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• 2005

Purpose : Adiponectin, adipose tissue-specific protein, has anti-inflammatory and anti-atherogenic properties. It has been found to have a negative correlation with obesity and to play a role in modulating glucose tolerance and insulin sensitivity. Serum adiponectin concentrations are decreased in adults with obesity and type 2 diabetes. We investigated the difference in adiponectin levels between obese and non-obese children, and evaluated the relationship of serum adiponectin with body mass index(BMI), serum fasting insulin, lipid profiles and homeostasis model assessment(HOMA) in children. Methods : We measured serum adiponectin levels by radioimmunoassay in 113 children(82 obese children and 31 non-obese controls) from 8 to 15 years of age, and also checked BMI, fasting serum glucose, insulin and lipid profiles. Fasting and postprandial serum adiponectin concentrations were compared by oral glucose tolerance tests in 27 obese children. The correlations of adiponectin with BMI, insulin, low density lipoprotein(LDL)-cholesterol and HOMA were analyzed by Pearson's correlation. Results : The serum adiponectin levels were significantly lower in the obese group(19.7 mg/mL) than in the non-obese group(27.5 mg/mL)(P<0.01). Serum adiponectin concentrations were negatively correlated with BMI(r=-0.39, P<0.01), serum insulin(r=-0.28, P<0.01), LDL-C(r=-0.20, P<0.01) and HOMA(r=-0.22, P<0.01). At oral glucose tolerance tests in obese children, postprandial 2 hours adiponectin level(19.8 mg/mL) was decreased compared to fasting level(25.8 mg/mL)(P<0.01). Conclusion : Serum adiponectin concentrations were inversely related to adiposity and insulin resistance in children. We suggest the serum adiponectin level could be used as an early marker of insulin resistance in obese children.

• Clinical and Experimental Pediatrics
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• v.46 no.3
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• pp.284-290
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• 2003

Purpose : A new airway inflammatory marker, exhaled nitric oxide(ENO) has been reported to correlate with bronchial hyperresponsiveness(BHR) and atopy. The purpose of this study was to analyze the relationship of ENO with BHR or atopy in patients with asthma and with allergic rhinitis. Methods : The subjects consisted of 55 children with asthma, 17 with allergic rhinitis, and 14 healthy controls. The asthma group was subdivided into the atopic asthma group(n=37) and the nonatopic asthma group(n=18) and the allergic rhinitis group into BHR group(n=7) and non-BHR group(n=10). All were investigated with spirometry and measurements of ENO concentration. The correlations between ENO concentration and both methacholine $PC_{20}$(provocative concentration causing a 20% decrease in forced expiratory volume in one second) and the number of allergen skin test positivity were analyzed. Results : ENO concentrations of both asthma and allergic rhinitis groups were significantly greater than that of control(P<0.01). ENO concentration of atopic asthma was significantly greater than that of nonatopic asthma(P<0.01). In allergic rhinitis, ENO concentration did not differ according to the presence or absence of BHR(P=0.50). ENO concentrations correlated significantly with the number of skin test positivity(r=0.32, P=0.02) or methacholine $PC_{20}$(r=-0.38, P<0.01) in asthma group, but not in the allergic rhinitis group(r=0.42, P=0.09; r=-0.06, P=0.83). Conclusion : In asthma patients, some pathogenetic mechanisms associated with atopy and BHR seem to influence ENO concentration. In allergic rhinitis patients, some factors other than BHR may be important in determining ENO concentration.

• Tuberculosis and Respiratory Diseases
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• v.52 no.3
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• pp.241-250
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• 2002

Background : Coal-worker's pneumoconiosis(CWP) is characterized by a chronic inflammatory lung reaction associated with macrophage accumulation in the alveolar spaces. CWP is usually divided into two stage : simple pneumoconiosis(SP) where there are a limited number of fibrotic lesions remain limited, with radiological opacities smaller than 1cm and progressive massive fibrosis(PMF), which is characterized by the development of a perifocal extensive fibrotic response of the lung and severe alterations in pulmonary function. In this study, the lymphocyte compartment and cytokine were evaluated by measuring the serum levels in the control, SP and PMF groups. Materials and Methods : The coal workers selected for this study were employees(patients?) of the Tae-Baek and Dong-Hae hospital. All were men, 45-76 years old and the mean duration of their exposure to coal dust was 23.2 years in the lymphocyte compartment and 24.3 years in the cytokine checked group. According to X-ray examination results, the patients were classified into either one of the SP, PMF categories. The normal controls examined were 26-70 years old men. The serum cytokine levels were estimated by using an end point enzyme immunoassay technique. Results : T lymphocyte, helper and suppressor T cells were highly related to pneumoconiosis in this study. A statistically significant decrease in the number of suppressor T lymphocytes was observed in the simple pneumoconiosis patients and at the same time, there was an increase in the lymphocyte index. Howevere, there was no statistically difference in the serum cytokines levels among the SP, PMF and control groups. Conclusion : T lymphocyte, helper T, and suppressor T cells may be highly related to the development of CWP compared to the control group particularly in the early stage of pneumoconiosis. The changes observed in the immunological system in patients with pneumoconiosis may lie at the bottom of the pathogenesis of fibrosis. Further study is needed to evaluate the lymphocyte compartment as a marker for pneumoconiosis development in the early stage.

• Tuberculosis and Respiratory Diseases
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• v.62 no.4
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• pp.290-298
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• 2007

Background: The currently available diagnostic markers for pleural effusion have a limited role. The soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a molecule recently reported to play an important role in the myeloid cell mediated inflammatory response, and is up regulated in the body fluid by bacterial or fungal products. This study examined the expression of sTREM-1 in pleural effusion. Methods: Between April 2004 and December 2005, 48 patients with pleural effusions were enrolled in this study. The pleural fluids were taken and analyzed for the total protein, glucose, lactate dehydrogenase (LDH), adenosine deaminase (ADA), and sTREM-1. Bacterial cultures and cytology tests were also performed. Results: The clinical diagnoses were 17 parapneumonic, 14 tuberculous, and 13 malignant effusions. Four patients presented with transudates. The mean ages of the parapneumonic, tuberculous and malignant effusion groups were $57.1{\pm}19.7$, $49.5{\pm}18.6$, $66.9{\pm}15.5$, and $76.0{\pm}18.1$. respectively. The level of sTREM-1 expression was significantly higher in the parapneumonic effusions ($344.0{\pm}488.7$) than in the tuberculous effusions ($81.7{\pm}56.6$) and malignant effusions ($39.3{\pm}19.6$). With a cut-off value of 55.4pg/ml, the sensitivity and specificity for a parapneumonic effusion was 70.6% and 74.1%. Conclusion: sTREM-1 expression is significantly higher in parapneumonic effusions, suggesting its potential role as an additional diagnostic marker for pleural effusions.

• 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.