• The Korea Journal of Herbology
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• v.28 no.1
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• pp.65-71
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• 2013

Objectives : Asthma is a chronic, complex respiratory disease, caused by airway obstruction, airway eosinophilic inflammation(AEI), and airway hyperresponsiveness(AHR). This study was conducted to determine whether oral administration of crude water extracts of Pinellia ternate Breitenbach(PTB) has an antiasthmatic potential in the treatment of asthma in mice. Methods : Asthmatic AEI and AHR were induced by systemic sensitization to ovalbumin(OVA) by intratracheal instillation with 0.1 mg/mL suspension of diesel exhaust particles(DEP) once a week for 10 weeks in BALB/c mice. Crude PTB water extracts(50 mg/kg and 200 mg/kg) were orally administered 5 times a week for 10 weeks. Cyclosporin(10 mg/kg) was administrered the same manner as a positive control. Results : Long-term treatment with crude PTB water extracts suppressed the infiltration of inflammatory cells, including eosinophils, into airways from blood. It also reduced asthmatic AEI and AHR by attenuating the increase in the levels of cytokines such as interleukin(IL)-4, IL-5 and IL-13 in bronchoalveolar lavage fluid(BALF), as well as the levels of histamine and OVA-specific IgE in blood. However, the effect of crude PTB water extracts(200 mg/kg) was not likely to be stronger than that of cyclosporin(10 mg/kg). Conclusion : These results suggest that crude PTB water extracts have inhibitory effects on AEI and AHR in a mouse model of asthma and may act as a potential Th2 cytokine antagonist, and have a therapeutic effect on allergic asthma.

• IMMUNE NETWORK
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• v.20 no.6
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• pp.51.1-51.17
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• 2020

Respiratory syncytial virus (RSV) causes severe pulmonary disease in infants, young children, and the elderly. Formalin inactivated RSV (FI-RSV) vaccine trials failed due to vaccine enhanced respiratory disease, but the underlying immune mechanisms remain not fully understood. In this study, we have used wild type C57BL/6 and CD4 knockout (CD4KO) mouse models to better understand the roles of the CD4 T cells and cellular mechanisms responsible for enhanced respiratory disease after FI-RSV vaccination and RSV infection. Less eosinophil infiltration and lower pro-inflammatory cytokine production were observed in FI-RSV vaccinated CD4KO mice after RSV infection compared to FI-RSV vaccinated C57BL/6 mice. NK cells and cytokine-producing CD8 T cells were recruited at high levels in the airways of CD4KO mice, correlating with reduced respiratory disease. Depletion studies provided evidence that virus control was primarily mediated by NK cells whereas CD8 T cells contributed to IFN-γ production and less eosinophilic lung inflammation. This study demonstrated the differential roles of effector CD4 and CD8 T cells as well as NK cells, in networking with other inflammatory infiltrates in RSV disease in immune competent and CD4-deficient condition.

• Journal of Life Science
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• v.16 no.5
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• pp.780-787
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• 2006

Asthma is a chronic inflammatory disorder of the airways, which characterized by bronchial hyperresponsiveness, reversible airflow limitation and respiratory symptoms. Internationally, the prevalence of asthma has been increased over last 3 decades. Recently, several studies of asthma have been reported with gradually increasing importance. To tesify the hypothesis that interleukin (IL)-4 and IL-10 may be an important determinant of the severity of airway inflammation, their expression was studied in mouse model of asthma. BALB/c mouse, IL-4 Knockout (KO) mouse and IL-10 KO mouse were sensitized with intraperitoneal injection of ovalbumin adsorbed to aluminum potassium sulfate, followed by challenges with intranasal ovalbumin on 3 consecutive days. The severity of pulmonary inflammation was assessed by eosinophilia in BAL fluid, number of total BAL cells, histopathological changes in lung tissues, and immunohistochemical staining against IL-4 and IL-10. In BAL fluid, the number of total cells was significantly increased in asthma induced mouse compare to the control. In asthma induced mouse, eosinophil was increased to 56% and neutrophil was 0.2%. In H &E stains, eosinophilic infiltration and epithelium hyperplasia were clearly noticed in asthma induced mouse. In immunohistochemical staining for IL-4 and IL-10, there was no positive reaction in control group. However, very strong reactions were appeared in asthma induced group. In this research, IL-4 and IL-10, which seem to play a central role in allergic asthma, KO mouse was utilized to test the causative relationship between airway inflammation and role of specific cytokine. Asthma induced IL-4 and IL-10 KO mice showed much decreased inflammatory reactions in the number of total BAL cells, in eosinophilic infiltration, and in immunohistochemical stains against diverse inflammatory proteins. These results suggest that IL-4 and IL-10 increase the asthmatic reactions in vivo mice model.

• Tuberculosis and Respiratory Diseases
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• v.48 no.1
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• pp.33-44
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• 2000

Background: To evaluate airway responses and inflammation to antigen in Sprague-Dawley rat asthma model, we examined airway responses, serial histologic changes of the lung, and the relationship between airway responses and airway inflammation after antigen airway challenge. Methods: Sprague-Dawley rats were sensitized with subcutaneous injection of 10 ${\mu}g$ ovalbumin(OA). Antigen airway challenges were done 14~16 days after sensitization and the sensitized rats were sacrificed 1h($A_E$), 6~8h($A_L$) and 1day($A_D$) after airway challenge, to examine the histologic changes of the lung. Airway responses were measured by body plethysmograph and recorded by enhanced pause(Penh) as an index of airway obstruction 6~8h after antigen challenges. Nonsensitized controls(10 rats) were also challenged with antigen and sacrificed 1 day later. Histopathologic examination of two trachea, large bronchi, small bronchi, and vessels was performed to evaluate the severity of inflammation and eosinophilic infiltration with H&E stain. Results: In 17 of 20 rats(85%) in both groups, we observed airway responses. Among them, an early response(ER) in 15 rats(75%), an dual response in 5(25%), and an late response(LR) only in 2 rats(10%) displayed. There were no significant differences in the severity of inflammation among the trachea, large bronchi, small bronchi and vessels in all groups after antigen challenge(p>0.05) and between early and late responders. The significant eosinophil infiltration was observed in 5 rats(50%) of AL(p<0.05) compared with in AE and controls. Also, eosinophil infiltration was observed in higher trend in LR(57.1%) compared to ER(40%)(p>0.05). Conclusion: Sprague-Dawley rats sensitized with subcutaneous injection of OA showed a significant airway responses to antigen challenge. But antigen challenges caused a little eosinophil infiltration and no significant airway inflammation. Asthma model of Sprague-Dawley rats could be useful for antigen-induced airway responses, but this model has a limitation for the study of human asthma because of no significant pathologic change.

• Tuberculosis and Respiratory Diseases
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• v.46 no.3
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• pp.372-385
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• 1999

Background: The purpose of this study was to examine the causes and pathologic process of chronic non-productive cough as an isolated symptom with a normal spirometry and chest radiograph by investigating clinicopathologic findings. Method: We studied 25 adults with chronic non-productive cough over a 3-week period with a normal chest radiograph and pulmonary function tests without any other symptoms. Clinical assessment, cough score, chest and sinus radiograph, pulmonary function tests, methacholine challenge, allergic skin prick test, and bronchoscopy for bronchial biopsies were performed. Subjects were then treated with prednesolone 20 to 30 mg/day for 1 to 2 weeks. Results: The experimental group was divided into two subgroups-those infiltrated with eosinophils, and those infiltrated with lymphocytes depending on eosinophil and lymphocyte counts, both of which were respectively higher than those of the control group. Eosinophils infiltrated group had mean numbers of eosinophil of 89.8 $cells/mm^3$ while control group's mean was 0.4 $cells/mm^2$(p=0.005). Lymphocyte infiltrated group was 4 patients whose mean was 84.3 $cells/mm^2$ with 28.4 $cells/mm^2$ of control group(P=0.026). In addition, the mean thickness of the basement membrane of experimental group was $14.20{\pm}5.20{\mu}m$ in contrast of control group whose mean was $3.50{\pm}1.37{\mu}m$(P=0.001). With the methacholine challenge test, 7 of the 21 eosinophil infiltrated subjects were diagnosed with cough variant asthma ; the other 14 with eosinophilic bronchitis. Three subjects with eosinophilic bronchitis were atopic positive (21.4%) with the skin prick test In the lymphocyte dominant group, all four subjects were diagnosed with lymphocytic bronchitis. Cough score was improved after steroid treatment in 22 of 25 subjects in the experimental group (88.0%). Conclusion: These results suggest chronic non-productive cough as an isolated symptom with a normal spirometry and chest radiograph was associated with airway inflammation by eosinophil and lymphocyte infiltration. The causes for chronic non-productive cough were eosinophilic bronchitis, cough variant asthma, and lymphocytic bronchitis(written in frequency). They further suggest that therapeutic treatment with steroids can provide effective symptomatic relief.

• Investigative Magnetic Resonance Imaging
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• v.15 no.1
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• pp.22-31
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• 2011

Purpose : To compare free-breathing and respiratory-triggered diffusion-weighted imaging on 1.5-T MR system in the detection of hepatic lesions. Materials and Methods: This single-institution study was approved by our institutional review board. Forty-seven patients (mean 57.9 year; M:F = 25:22) underwent hepatic MR imaging on 1.5-T MR system using both free-breathing and respiratory-triggered diffusion-weighted imaging (DWI) at a single examination. Two radiologists retrospectively reviewed respiratory-triggered and free-breathing sets (B50, B400, B800 diffusion weighted images and ADC map) in random order with a time interval of 2 weeks. Liver SNR and lesion-to-liver CNR of DWI were calculated measuring ROI. Results : Total of 62 lesions (53 benign, 9 malignant) that included 32 cysts, 13 hemangiomas, 7 hepatocellular carcinomas (HCCs), 5 eosinophilic infiltration, 2 metastases, 1 eosinophilic abscess, focal nodular hyperplasia, and pseudolipoma of Glisson's capsule were reviewed by two reviewers. Though not reaching statistical significance, the overall lesion sensitivities were increased in respiratory-triggered DWI [reviewer1: reviewer2, 47/62(75.81%):45/62(72.58%)] than free-breathing DWI [44/62(70.97%):41/62(66.13%)]. Especially for smaller than 1 cm hepatic lesions, sensitivity of respiratory-triggered DWI [24/30(80%):21/30(70%)] was superior to free-breathing DWI [17/30(56.7%):15/30(50%)]. The diagnostic accuracy measuring the area under the ROC curve (Az value) of free-breathing and respiratory-triggered DWI was not statistically different. Liver SNR and lesion-to-liver CNR of respiratory-triggered DWI ($87.6{\pm}41.4$, $41.2{\pm}62.5$) were higher than free-breathing DWI ($38.8:{\pm}13.6$, $24.8{\pm}36.8$) (p value < 0.001, respectively). Conclusion: Respiratory-triggered diffusion-weighted MR imaging seemed to be better than free-breathing diffusion-weighted MR imaging on 1.5-T MR system for the detection of smaller than 1 cm lesions by providing high SNR and CNR.

• Tuberculosis and Respiratory Diseases
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• v.67 no.6
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• pp.512-516
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• 2009

Background: Pulmonary paragonimiasis is a subacute to chronic inflammatory disease of the lung caused by lung flukes that result in prolonged inflammation and mechanical injury to the bronchi. However, there are few reports on the bronchoscopic findings of pulmonary paragonimiasis. This report describes the bronchoscopic findings of pulmonary paragonimiasis. Methods: The bronchosocpic findings of 30 patients (20 males, median age 50 years) with pulmonary paragonimiasis between May 1995 and December 2007 were reviewed retrospectively. Results: The diagnoses were based on a positive serologic test results for Paragonimus-specific antibodies in 13 patients (43%), or the detection of Paragonimus eggs in the sputum, bronchial washing fluid, or lung biopsy specimens in 17 patients (57%). The bronchoscopic examinations revealed endobronchial lesions in 17 patients (57%), which were located within the segmental bronchi in 10 patients (59%), lobar bronchi in 6 patients (35%) and main bronchi in 1 patient (6%). The bronchoscopic characteristics of endobronchial lesions were edematous swelling of the mucosa (16/17, 94%) and mucosal nodularity (4/17, 24%), accompanied by bronchial stenosis in 16 patients (94%). Paragonimus eggs were detected in the bronchial washing fluid of 9 out of the 17 patients with endobronchial lesions. The bronchial mucosal biopsy specimens showed evidence of chronic inflammation with eosinophilic infiltration in 6 out of 11 patients (55%). However, no adult fluke or ova were found in the bronchial tissue. Conclusion: Bronchial stenosis with mucosal changes including edematous swelling and mucosal nodularity is the most common bronchoscopic finding of pulmonary paragonimiasis.

• Biomolecules & Therapeutics
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• v.6 no.1
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• pp.37-44
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• 1998

This study was performed to examine the effects of DA-9601, a novel antiulcer agent extracted from Artemisiae Herba, on radiation colitis in the rat. Female Wistar rats received a 30 Gy dose of irradiation to the 2 cm of distal colon in length using an intrarectal applicator system. 30 mg/tg or 100 mg/kg of DA- 9601 was administered orally 30 min before and 4 h after radiation on day 1. And the same dose of DA-9601 was given to the animals twice a day from day 2 to 14. As a reference control, sucralfate suspension (100 or 300 mg/head) was given as an enema based on the same treatment schedule of DA-9601. Body weight change and the frequency of diarrhea were recorded during the observation period as markers of radiationinduced injury, All animals were sacrificed on day 15 for evaluation of macro- and microscopic findings and mucosal myeloperoxidase (MPO) activity. Radiated animals showed diarrhea, mucosal redness and histologic changes characterized by edema and eosinophilic infiltration of the periglandular lamina propria with loss of colonic epithelium. Radiation also significantly increased mucosal MfO activity of affected colon f\\\\\\\\`<0.05). However, most of these changes were completely protected by oral administration with DA-9601. DA-9601 reduced radiation-induced histologic alteration significantly in a dose-related manner (P<0.05). In addition, mucosal MPO activity in rats receiving high dose of DA-9601 decreased significantly when compared with that in radiated control. High dose of sucralfate (300 mg/head) alleviated radiation-induced histologic lesion, but failed to reach statistical significance. The results of this study suggest that DA-9601 can be useful for the prevention of acute clinical symptoms of radiation proctocolitis and that decrease of mucosal MPO by DA-9601 plays a role in its protective mechanism(s), at least in part.

• Journal of Mushroom
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• v.14 no.4
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• pp.155-161
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• 2016

A recent study reported that Pleurotus ostreatus has the potential to be used as a ${\beta}-glucan-based$ cream for supportive complementary therapy of atopic dermatitis. KH054 is a new herbal prescription consisting of P. ostreatus and Panax ginseng. The effects of atopic dermatitis-induced materials on the expression of cytokine genes in human monocytes (THP-1, EoL- 1) have been examined. Some reports demonstrated that P. ginseng augments the activity of natural killer cells, which plays an important role in innate immunity against infection and tumor development. Monocyte chemotactic protein 1 (MCP-1), interleukin (IL)-6, and IL-8 have important roles in mediating the infiltration of various cells into the skin of atopic dermatitis and psoriasis. The present study investigated whether KH054 on induced IL-6, IL-8, and MCP-1 secretion by house dust mite (Dermatophagoides pteronissinus) in THP-1 (human acute monocytic leukemia) and EoL-1(Human eosinophilic leukemia) cell. D. pteronissinus functions in the pathogenesis of allergic diseases, including atopic dermatitis and asthma. The inhibitory effect of KH054 on the induction of IL-6, IL-8, and MCP-1 secretion by D. pteronissinus extract in THP-1 and EoL-1 cells was examined. KH054 potently suppressed the elevated production of IL-6 and IL-8 induced by D. pteronissinus treatment in THP-1 and EoL-1 cells. Based on the present results, KH054 may be useful for developing functional foods to treat atopic dermatitis.

• Journal of Pharmacopuncture
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• v.17 no.1
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• pp.27-34
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• 2014

Objectives: This experiment was conducted to examine the toxicity of Water soluble Carthmi-Flos herbal acupuncture (WCF) by administering a single intramuscular dose of WCF in 6-week-old, male and female Sprague-Dawley rats and to find the lethality dose for WCF. Methods: The experiment was conducted at Biotoxtech according to Good Laboratory Practices under a request by the Korean Pharmacopuncture Institute. This experiment was performed based on the testing standards of "Toxicity Test Standards for Drugs" by the Ministry of Food and Drug Safety. Subjects were divided into 4 groups: 1 control group in which normal saline was administered and 3 test groups in which 0.1, 0.5 or 1.0 mL of WCF was administered; a single intramuscular dose was injected into 5 males and 5 females in each group. General symptoms and body weights were observed/measured for 14 days after injection. At the end of the observation period, hematological and clinical chemistry tests were performed, followed by necropsy and histopathological examinations of the injected sections. Results: No mortalities were observed in any group. Also, symptoms, body weight, hematology, clinical chemistry and necropsy were not affected. However, histopathological examination of the injected part in one female in the 1.0-mL group showed infiltration of mononuclear cells and a multi-nucleated giant cell around eosinophilic material. Conclusion: Administration of single intramuscular doses of WCF in 3 groups of rats showed that the approximate lethal dose of WCF for all rats was in excess of 1.0 mL, as no mortalities were observed for injections up to and including 1.0 mL.