• Tuberculosis and Respiratory Diseases
• /
• v.46 no.5
• /
• pp.685-696
• /
• 1999

Background : Idiopathic pulmonary fibrosis (IPF) is a diffuse inflammatory and fibrosing process that occurs within the interstitium and alveolus of the lung with invariably poor prognosis. The major problem in management of IPF results from the variable rate of disease progression and the difficulties in predicting the response to therapy. The purpose of this retrospective study was to evaluate the short-term efficacy of steroid and immunosuppressive therapy for IPF and to identify the pre-treatment determinants of favorable response. Method : Twenty patients of IPF were included. Diagnosis of IPF was proven by thoracoscopic lung biopsy and they were presumed to have active progressive disease. The baseline evaluation in these patients included clinical history, pulmonary function test, bronchoalveolar lavage (BAL), and chest high resolution computed tomography (HRCT). Fourteen patients received oral prednisolone treatment with initial dose of 1mg/kg/day for 8 to 12 weeks and then tapering to low-dose prednisolone (0.25mg/kg/day). Six patients who previously had experienced significant side effects to steroid received 2mg/kg/day of oral cyclophosphamide with or without low-dose prednisolone. Follow-up evaluation was performed after 6 months of therapy. If patients met more than one of followings, they were considered to be responders : (1) improvement of more than one grade in dyspnea index, (2) improvement in FVC or TLC more than 10% or improvement in DLco more than 20% (3) decreased extent of disease in chest HRCT findings. Result : One patient died of extrapulmonary cause after 3 month of therapy, and another patient gave up any further medical therapy due to side effect of steroid. Eventually medical records of 18 patients were analyzed. Nine of 18 patients were classified into responders and the other nine patients into nonresponders. The histopathologic diagnosis of the responders were all nonspecific interstitial pneumonia (NSIP) and that of nonresponders were all usual interstitial pneumonia (UIP) (p<0.001). The other significant differences between the two groups were female predominance (p<0.01), smoking history (p<0.001), severe grade of dyspnea (p<0.05), lymphocytosis in BAL fluid ($23.8{\pm}16.3%$ vs $7.8{\pm}3.6%$, p<0.05), and less honeycombing in chest HRCT findings (0% vs $9.2{\pm}2.3%$, p<0.001). Conclusion : Our results suggest that patients with histopathologic diagnosis of NSIP or lymphocytosis in BAL fluid are more likely to respond to steroid or immunosuppressive therapy. Clinical results in large numbers of IPF patients will be required to identify the independent variables.

• The Korea Journal of Herbology
• /
• v.36 no.1
• /
• pp.59-66
• /
• 2021

Objectives : Forsythiae Fructus has been reported to have anti-inflammatory effects in many diseases, and Corydalis Tuber has been used as a pain suppressor in Eastern Asia. However, the protective effects of individual water extract of Forsythiae Fructus (FF) and Corydalis Tuber (CT) and the mixture of FF and CT (FC) on chronic pancreatitis (CP) were not well-investigated. Therefore, we investigated the protective effects of FF, CT, and FC on CP in mice. Methods : To induce CP, cerulein was injected 6 times a day, 4 times a week for 3 weeks. 1 h before the every cerulein injection, 200 mg/kg of FF, CT, or FC was intraperitoneally injected to mice. Histological analysis of pancreas was examined by hematoxylin and eosin stain and collagen deposition was examined by Masson's trichrome stain. Fibrogenic parameters such as α-smooth muscle actin (α-SMA), extracellular matrix (ECM) deposition, and fibrotic cytokines such as transforming growth factor (TGF)-β1 and platelet-derived growth factor (PDGF) were also analyzed by immunofluorescence stain and real-time PCR. Results : Histological damages in pancreas were inhibited by pre-treatment of FF or FC but not CT. α-SMA and ECM in pancreas were inhibited by pre-treatment of CT or FC but not FF. Moreover, the expression of TGF-β1 and PDGF in pancreas were inhibited by FF, CT or FC. Conclusions : Our results suggest that FC have protective effect on CP in mice through inhibition of α-SMA, ECM, TGF-β1 and PDGF in pancreas, and these findings could suggest new clinical strategy for CP.

• Tuberculosis and Respiratory Diseases
• /
• v.82 no.1
• /
• pp.42-52
• /
• 2019

Background: Transforming growth factor ${\beta}$ (TGF-${\beta}$), retinoic acid (RA), p38 mitogen-activated protein kinase (MAPK), and MEK signaling play critical roles in cell differentiation, proliferation, and apoptosis. We investigated the effect of RA and the role of these signaling molecules on the phosphorylation of Smad2/3 (p-Smad2/3) induced by TGF-${\beta}1$. Methods: A549 epithelial cells and CCD-11Lu fibroblasts were incubated and stimulated with or without all-trans RA (ATRA) and TGF-${\beta}1$ and with MAPK or MEK inhibitors. The levels of p-Smad2/3 were analyzed by western blotting. For animal models, we studied three experimental mouse groups: control, bleomycin, and bleomycin+ATRA group. Changes in histopathology, lung injury score, and levels of TGF-${\beta}1$ and Smad3 were evaluated at 1 and 3 weeks. Results: When A549 cells were pre-stimulated with TGF-${\beta}1$ prior to RA treatment, RA completely inhibited the p-Smad2/3. However, when A549 cells were pre-treated with RA prior to TGF-${\beta}1$ stimulation, RA did not completely suppress the p-Smad2/3. When A549 cells were pre-treated with MAPK inhibitor, TGF-${\beta}1$ failed to phosphorylate Smad2/3. In fibroblasts, p38 MAPK inhibitor suppressed TGF-${\beta}1$-induced p-Smad2. In a bleomycin-induced lung injury mouse model, RA decreased the expression of TGF-${\beta}1$ and Smad3 at 1 and 3 weeks. Conclusion: RA had inhibitory effects on the phosphorylation of Smad induced by TGF-${\beta}1$ in vitro, and RA also decreased the expression of TGF-${\beta}1$ at 1 and 3 weeks in vivo. Furthermore, pre-treatment with a MAPK inhibitor showed a preventative effect on TGF-${\beta}1$/Smad phosphorylation in epithelial cells. As a result, a combination of RA and MAPK inhibitors may suppress the TGF-${\beta}1$-induced lung injury and fibrosis.

• Tuberculosis and Respiratory Diseases
• /
• v.47 no.5
• /
• pp.650-659
• /
• 1999

Background/Aims: It is well recognized that all aerobic cells have the protective mechanisms in order to minimize the tissue damage induced by various reactive oxygen species(ROS). Thioredoxin peroxidase(TPX) which has been recently identified and characterized functions to convert peroxide to water. The protein is also found in various subtypes(TPX-A & B, MER5, HS22 and HORF-06) and is known to be ubiquitous in most human cells. Especially, ischemic brain injuries, partial hepatectomy and radiation induced DNA damages. In treating lung cancer, radiation therapy has a major place in the local control and the relief of symptoms, but radiation induced free radical injury and resulting pulmonary fibrosis has been the major drawback of the therapy. However, little is known about the protective mechanisms and biologic modulations against radiation-induced tissue damages. Methods: Eighteen mice were divided into six groups, 3 in each group, and fifteen had received 900cGy of radiation. The mice were sacrificed according to the pre determined time schedule; immediate, 1, 2, 3 and 6 weeks after irradiation. Extracts were made from the lungs of each mice, Western blot analysis of various subtypes of TPX were done after SDS-P AGE. Examination of H & E stained slides from the same irradiated specimens and the control specimens were also performed. Results: No difference in the intensity of the immunoreactive bands in the irradiated lung samples of the mice compared to the unirradiated control was observed regardless of the time intervals, although H & E examination of the sample specimens demonstrated progressive fibrotic changes of the irradiated lung samples. Conclusion: In conclusion, according to our data, it is suggested that various thioredoxin peroxidase subtypes and catalase which are known to be increased in many repair processes may not be involved in the repair of the radiation injury to the lung and subsequent fibrosis.

• Journal of Veterinary Clinics
• /
• v.18 no.3
• /
• pp.257-264
• /
• 2001

This study was performed to investigate the effects of chitosan-trimer (CT) on the prevention of postoperative adhesion formation in the rate model. All animals divided into PBS (control), 1% CT, 3% CT, and chitin treated group. The mean adhesion score in 1% CT group (1.03$\pm$0.63), 3% CT group (0.64$\pm$0.53) and chitin group (1.67$\pm$0.71) was found to be lower than that in control group (2.07$\pm$0.81). More favorable adhesion prevention was achieved in 3% CT group (0.64$\pm$0.53) in comparison with the control group, 1% CT group, and chitin group without any hemorrhagic complications. A statistically significant difference was observed in adhesion formation between control group and 3% CT group (p<0.001). In control group, 44 of 45 sites (97.7%) formed adhesions between the intestine defects. In contrast, 3% CT was effective in reducing the incidence of adhesion formation to 17 to 45 sites (62.2%) (p<0.05). The locations of adhesions were observed in serosa-serosa (60%), serosa-mesentery (13.3%), serosa-connective tissue of testis (10%), omentum-liver (10%), serosa-omentum (3.3%), serosa-cecum (3.3%), and serosa-incision (0%). On the results of histological analysis, grade of inflammation and fibrosis at the sites of postoperative peritoneal adhesion formation were not significantly different in all groups. But, 3% CT showed the lowest score of inflammation and fibrosis. In 3% CT group, the rate of increase of plasma fibrinogen was significantly lower compared with that in control group from pre-operation to 10 days later (p<0.05). There were no appreciable difference in the CBC, leukocyte differential counts and total protein concentrations among four groups. In conclusion, our data suggested that CT should be effective on reducing adhesion formation in experimental rat models. The results also showed that 3% CT does not adversely affect normal wound healing and healthy recovery after operation.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.5
• /
• pp.2717-2722
• /
• 2013

Background: The objective of this research is the computed axial tomography (CT) imaging grading of radiation induced pneumonitis (RP) and its correlation with clinical and radiotherapeutic parameters. Materials and Methods: The chest CT films of 20 patients with non-small cell lung cancer who have undergone threedimensional conformal radiation therapy were reviewed. The proposed CT grading of RP is supported on solely radiological diagnosis criteria and distinguishes five grades. The manifestation of RP was also correlated with any positive pre-existing chronic obstructive pulmonary disease (COPD) history, smoking history, the FEV1 value, and the dosimetric variable V20. Results: The CT grading of RP was as follows: 3 patients (15%) presented with ground glass opacity (grade 1), 9 patients (45%) were classified as grade 2, 7 patients (35%) presented with focal consolidation, with or without elements of fibrosis (grade 3), and only one patient (5%) presented with opacity with accompanying atelectasis and loss of pulmonary volume (grade 4). Both univariate and multivariate analysis revealed as prognostic factors for the radiological grading of RP the reduction of FEV1 and the V20 (P=0.026 and P=0.003, respectively). There was also a significant (P<0.001) correlation of radiological grading of RP with FEV1 and V20 (spearman rho 0.92 and 0.93, respectively). Conclusions: The high correlation of the proposed radiological grading with the FEV1 and the V20 is giving a satisfactory clinical validity. Although the proposed grading scale seems relevant to clinical practice, further studies are needed for the confirmation of its validity and reliability.

• Herbal Formula Science
• /
• v.24 no.3
• /
• pp.163-174
• /
• 2016

Objectives : Rheum undulatum Linne and Glycyrriza uralensis Fischer are widely used herbal medicine. In this study, anti-oxidant and liver protective effects of R. undunlatum extract (RUE) and G. uralensis extract (GUE) were investigated in HepG2 cells, respectively. Oxidative stress and liver fibrosis were induced by arachidonic acid (AA) and iron, and CCl₄.Methods : MTT assay was assessed for cell viability, and immunoblotting analysis was performed to detect expression of apoptosis related proteins. In addition, reactive oxygen species (ROS) and mitochondrial dysfunction were measured. In vivo, BALB/c mouse were orally administrated with the aqueous extract of 10 mg/kg RUE and 100 mg/kg GUE for 3 days and then, injected with CCl₄ 0.5 ml/kg body weight to induce acute liver damage. Serum ALT level was measured, and histological change was observed in Harris's hematoxylin and eosin stainResults : RUE and GUE pre-treatment increased relative cell viability in concentration dependent manner and altered the expression levels of apoptosis-related proteins such as procaspase 3, PARP and Bcl-xL. RUE and GUE also inhibited the mitochondrial dysfunction and excessive reactive oxygen species (ROS) production induced by AA and iron. In addition, RUE and GUE activated liver kinase B1 (LKB1), by increasing phosphorylation. Moreover, RUE and GUE treatment decreased liver injuries induced by CCl₄, as evidenced by decreases in histological liver damage as well as serum alanine amino transferase (ALT) level.Conclusions : These data suggest that RUE and GUE has anti-oxidant and liver protective effects against AA and iron-induced oxidative stress and CCl₄-induced liver injury.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.27 no.3
• /
• pp.158-167
• /
• 2024

Purpose: To evaluate the prevalence of vertebral fracture (VF) in children with chronic liver disease (CLD) with and without liver transplantation (LT) and to determine the associated factors. Methods: A cross-sectional study was conducted. Patients aged 3-21 years with CLD both before and after LT were enrolled in the study. Lateral thoracolumbar spine radiographs were obtained and assessed for VF using Mäkitie's method. Clinical and biochemical data were collected. Results: We enrolled 147 patients (80 females; median age 8.8 years [interquartile range 6.0-11.8]; 110 [74.8%] in the LT group and 37 [25.2%] in the non-LT group). VF was identified in 21 patients (14.3%): 17/110 (15.5%) in the LT group and 4/37 (10.8%) in the non-LT group (p=0.54). Back pain was noted in only three patients with VF. In the univariate analysis, a height z-score below -2.0 (p=0.010), pre-LT hepatopulmonary syndrome (p=0.014), elevated serum direct and total bilirubin levels (p=0.037 and p=0.049, respectively), and vitamin D deficiency at 1-year post-LT (p=0.048) were associated with VF in the LT group. In multivariate analysis, height z-score below -2.0 was the only significant associated factor (odds ratio, 5.94; 95% confidence interval, 1.49-23.76; p=0.012) for VF. All VFs in the non-LT group were reported in males. Conclusion: In children with CLD, VF is common before and after LT. Most patients with VF are asymptomatic. Screening for VF should be considered in patients with a height z-score below -2.0 after LT.

• Clinical and Experimental Pediatrics
• /
• v.51 no.3
• /
• pp.293-298
• /
• 2008

Purpose : The aim of our study was to evaluate the therapeutic response to cyclosporine, time to remission and side effects in steroid resistant nephrotic syndrome (SRNS). Methods : This study included 22 children with idiopathic SRNS who were treated with cyclosporine between June 1989 and August 2006. Medical records were reviewed retrospectively. Results : The mean age of patients at diagnosis was $5.2{\pm}3.3\;years$. The male to female ratio was 1.2:1. Pre-treatment renal biopsies showed minimal change (MCD) in 12 (54.5%), focal segmental glomerulosclerosis (FSGS) in 8 (36.4%), membranous nephropathy (MGN) in one (4.5%) and mesangioproliferative glomerulonephritis in one (4.5%). 15 (68.2%) patients responded to cyclosporine, of whom 11 (91.6%) patients were MCD, 3 (37.5%) patients FSGS, and 1 patient MGN (MCD vs FSGS, P<0.05). The time to remission in patients who responded to cyclosporine was $31.5{\pm}15.2\;days$. Four of the 15 cyclosporine responders maintained complete remission even after cessation of the medication Seven still received cyclosporine, 2 were intermittently treated with steroids after discontinuation of cyclosporine, and two were treated with cyclosporine and steroids. The mean duration of cyclosporine therapy was $546.5{\pm}346.2$, $1,392.9{\pm}439.7$, $439.5{\pm}84.1$, and $433.5{\pm}74.2$ days, respectively. We performed post-treatment biopsies in 8 patients and partial interstitial fibrosis and tubular atrophy were found in two. Conclusion : The thrapeutic response of cyclosporine is good in steroid resistant nephrotic syndrome, especially in minimal change. But, there is a problem of long term cyclosporine dependency.

• Tuberculosis and Respiratory Diseases
• /
• v.42 no.3
• /
• pp.277-294
• /
• 1995

Background: The prevalence of tuberculosis in Korea decreased remarkably for the past 30 years, while the incidence of disease caused by mycobacteria other than tuberculosis is unknown. Korean Academy of Tuberculosis and Respiratory Diseases performed national survey to estimate the incidence of mycobacterial diseases other than tuberculosis in Korea. We analyzed the clinical data of confirmed cases for the practice of primary care physicians and pulmonary specialists. Methods: The period of study was from January 1981 to October 1994. We collected the data retrospectively by correspondence with physicians in the hospitals that referred the specimens to Korean Institute of Tuberculosis, The Korean National Tuberculosis Association for the detection of mycobacteria other than tuberculosis. In confirmed cases, we obtained the records for clinical, laboratory and radiological findings in detail using protocols. Results: 1) Mycobacterial diseases other than tuberculosis were confirmed that 1 case was in 1981, 2 cases in 1982, 4 cases in 1983, 2 cases in 1984, 5 cases in 1985, 1 case in 1986, 3 cases in 1987, 1 case in 1988, 6 cases in 1989, 9 cases in 1990, 14 cases in 1990, 10 cases in 1992, 4 cases in 1993, and 96 cases in 1994. Cases since 1990 were 133 cases(84.2%) of a total. 2) Fifty seven percent of patients were in the age group of over 60 years. The ratio of male to female patients was 2.6:1. 3) The distribution of hospitals in Korea showed that 61 cases(38.6%) were referred from Double Cross Clinic, 42 cases(26.6%) from health centers, 21 cases(13.3%) from tertiary referral hospitals, 15 cases(9.5%) from secondary referral hospitals, and 10 cases(6.3%) from primary care hospitals. The area distribution in Korea revealed that 98 cases(62%) were in Seoul, 17 cases(10.8%) in Gyeongsangbuk-do, 12 cases(7.6%) in Kyongki-do, 8 cases(5.1%) in Chungchongnam-do, each 5 cases(3.2%) in Gyeongsangnam-do and Chungchongbuk-do, 6 cases(3.8%) in other areas. 4) In the species of isolated mycobacteria other than tuberculosis, M. avium-intracellulare was found in 104 cases(65.2%), M. fortuitum in 20 cases(12.7%), M. chelonae in 15 cases(9.5%), M. gordonae in 7 cases(4.4%), M. terrae in 5 cases(3.2%), M. scrofulaceum in 3 cases(1.9%), M. kansasii and M. szulgai in each 2 cases(1.3%), and M. avium-intracellulare coexisting with M. terrae in 1 case(0.6%). 5) In pre-existing pulmonary diseases, pulmonary tuberculosis was 113 cases(71.5%), bronchiectasis 6 cases(3.8%), chronic bronchitis 10 cases(6.3%), and pulmonary fibrosis 6 cases(3.8%). The timing of diagnosis as having pulmonary tuberculosis was within 1 year in 7 cases(6.2%), 2~5 years ago in 32 cases(28.3%), 6~10 years ago in 29 cases(25.7%), 11~15 years ago in 16 cases(14.2%), 16~20 years ago in 15 cases (13.3%), and 20 years ago in 14 cases(12.4%). Duration of anti-tuberculous treatment was within 3 months in 6 cases(5.3%), 4~6 months in 17 cases(15%), 7~9 months in 16 cases(14.2%), 10~12 months in 11 cases(9.7%), 1~2 years in 21 cases(18.6%), and over 2 years in 8 cases(7.1%). The results of treatment were cure in 44 cases(27.9%) and failure in 25 cases(15.8%). 6) Associated extra-pulmonary diseases were chronic liver disease coexisting with chronic renal failure in 1 case(0.6%), diabetes mellitus in 9 cases(5.7%), cardiovascular diseases in 2 cases(1.3%), long-term therapy with steroid in 2 cases(1.3%) and chronic liver disease, chronic renal failure, colitis and pneumoconiosis in each 1 case(0.6%). 7) The clinical presentations of mycobacterial diseases other than tuberculosis were 86 cases (54.4%) of chronic pulmonary infections, 1 case(0.6%) of cervical or other site lymphadenitis, 3 cases(1.9%) of endobronchial tuberculosis, and 1 case(0.6%) of intestinal tuberculosis. 8) The symptoms of patients were cough(62%), sputum(61.4%), dyspnea(30.4%), hemoptysis or blood-tinged sputum(20.9%), weight loss(13.3%), fever(6.3%), and others(4.4%). 9) Smear negative with culture negative cases were 24 cases(15.2%) in first examination, 27 cases(17.1%) in second one, 22 cases(13.9%) in third one, and 17 cases(10.8%) in fourth one. Smear negative with culture positive cases were 59 cases(37.3%) in first examination, 36 cases (22.8%) in second one, 24 cases(15.2%) in third one, and 23 cases(14.6%) in fourth one. Smear positive with culture negative cases were 1 case(0.6%) in first examination, 4 cases(2.5%) in second one, 1 case (0.6%) in third one, and 2 cases(1.3%) in fourth one. Smear positive with culture positive cases were 48 cases(30.4%) in first examination, 34 cases(21.5%) in second one, 34 cases(21.5%) in third one, and 22 cases(13.9%) in fourth one. 10) The specimens isolated mycobacteria other than tuberculosis were sputum in 143 cases (90.5%), sputum and bronchial washing in 4 cases(2.5%), bronchial washing in 1 case(0.6%). 11) Drug resistance against all species of mycobacteria other than tuberculosis were that INH was 62%, EMB 55.7%, RMP 52.5%, PZA 34.8%, OFX 29.1%, SM 36.7%, KM 27.2%, TUM 24.1%, CS 23.4%, TH 34.2%, and PAS 44.9%. Drug resistance against M. avium-intracellulare were that INH was 62.5%, EMB 59.6%, RMP 51.9%, PZA 29.8%, OFX 33.7%, SM 30.8%, KM 20.2%, TUM 17.3%, CS 14.4%, TH 31.7%, and PAS 38.5%. Drug resistance against M. chelonae were that INH was 66.7%, EMB 66.7%, RMP 66.7%, PZA 40%, OFX 26.7%, SM 66.7%, KM 53.3%, TUM 53.3%, CS 60%, TH 53.3%, and PAS 66.7%. Drug resistance against M. fortuitum were that INH was 65%, EMB 55%, RMP 65%, PZA 50%, OFX 25%, SM 55%, KM 45%, TUM 55%, CS 65%, TH 45%, and PAS 60%. 12) The activities of disease on chest roentgenogram showed that no active disease was 7 cases(4.4%), mild 20 cases(12.7%), moderate 67 cases(42.4%), and severe 47 cases(29.8%). Cavities were found in 43 cases(27.2%) and pleurisy in 18 cases(11.4%). 13) Treatment of mycobacterial diseases other than tuberculosis was done in 129 cases(81.7%). In cases treated with the first line anti-tuberculous drugs, combination chemotherapy including INH and RMP was done in 86 cases(66.7%), INH or RMP in 30 cases(23.3%), and not including INH and RMP in 9 cases(7%). In 65 cases treated with the second line anti-tuberculous drugs, combination chemotherapy including below 2 drugs were in 2 cases(3.1%), 3 drugs in 15 cases(23.1%), 4 drugs in 20 cases(30.8%), 5 drugs in 9 cases(13.8%), and over 6 drugs in 19 cases (29.2%). The results of treatment were improvement in 36 cases(27.9%), no interval changes in 65 cases(50.4%), aggravation in 4 cases(3.1%), and death in 4 cases(3.1%). In improved 36 cases, 34 cases(94.4%) attained negative conversion of mycobacteria other than tuberculosis on cultures. The timing in attaining negative conversion on cultures was within 1 month in 2 cases(1.3%), within 3 months in 11 cases(7%), within 6 months in 14 eases(8.9%), within 1 year in 2 cases(1.3%) and over 1 year in 1 case(0.6%). Conclusion: Clinical, laboratory and radiological findings of mycobacterial diseases other than tuberculosis were summarized. This collected datas will assist in the more detection of mycobacterial diseases other than tuberculosis in Korea in near future.