• Radiation Oncology Journal
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• v.21 no.1
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• pp.66-74
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• 2003

Purpose : The matrix metalloprotelnases (MMPs) are a family of enzymes whose main function is the degradation of the extracellular matrix. Several studies have revealed that MMPs and TIMPS are related to the wound heating process and in photoaging caused by ultraviolet Irradiation. However, the expressions of MMP and TIMP after irradiation have not, to the best of our knowledge, been studied. This study investigates the expressions of MMP-2 and TIMP-2 in rat Intestinal mucosa following irradiation. Materials and Methods : The entire abdomen of Sprague-Dawley rats was irradiated using a single dose method. The rats were sacrificed on day 1, 2, 3, 5, 7 and 14 following irradiation. Histopathological observations were made using hematoxilin & eosin staining. The expressions of MMP-2 and TIMP-2 were examined using immunohistochemistry, Irnrnunoblotting and ELISA. Results : Radiation induced damage associated with atrophic villi, and infiltration of inflammatory cell was observed from the first postirradiation day, and severe tissue damage was observed on the second and the third postirradiation days. An increase in mitosis and the number of regenerating crypts, as evidence of regeneration, were most noticeable on the fifth postirradiation day. From the immunohistochemlstry, the MMP-2 expression was observed from the first postirradiation day, but was most conspicuous on the third and the fifth postirradiation days. The TIMP-2 expression was most conspicuous on the fifth postirradiation day. From the irnrnunoblotting, the MMP-2 expression was strongly positive on the third postirradlatlon day, and that of TIMP-2 showed a strong positive response on the fifth postirradiation day. In ELISA tests, the expressions of MMP-2 and TIMP-2 were increased in the postirradiation groups compared to those of the normal controls, and showed a maximum increase on the fifth postirradiatlon day. These results were statistically significant. Conclusion : The expressions of MMP-2 and TIMP-2 were increased in the intestinal mucosa of the rats following irradiation, and these results correlated with the histopathological findings, such as tissue damage and regeneration. Therefore, this study suggests that MMP-2 and TIMP-2 play roles in the mechanisms of radiation-induced damage and regeneration of intestinal mucosa of rats.

• Tuberculosis and Respiratory Diseases
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• v.52 no.3
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• pp.251-259
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• 2002

Background : Reduced lung compliance and increased lung resistance are the primary lung mechanical abnormalities in acute respiratory distress syndrome (ARDS). Although there is little information regarding the mechanisms responsible for the increases in the respiratory resistance of ARDS, bronchodilators have been frequently administered in mechanically ventilated ARDS patients. To determine the effect of a bronchodilator on the respiratory mechanics depending on the level of applied positive end-expiratory pressure (PEEP), the changes in the respiratory mechanics by salbutamol inhalation was measured under the variable PEEP level in patients with ARDS. Materials and Methods : Fifteen mechanically ventilated paralyzed ARDS patients (14 of male, mean age 57 years) were enrolled in this study. The respiratory system compliance, and the maximum and minimum inspiratory resistance were obtained by the end-inspiratory occlusion method during constant flow inflation using the CP-100 pulmonary monitor (Bicore, Irvine, CA, USA). The measurements were performed at randomly applied 8, 10 and 12 cm $H_2O$ PEEP before and 30 mins after administrating salbutamol using a meter-dose-inhaler (100ug${\times}$6). Results : 1) The maximum inspiratory resistance of the lung was higher than the reported normal values due to an increase in the minimal inspiratory resistance & additional resistance. 2) The maximum inspiratory resistance and peak airway pressure were significantly higher at 12cm $H_2O$ of PEEP compared with those at 10cm $H_2O$ of PEEP. 3) Salbutamol induced a significant decrease in the maximum and the minimum inspiratory resistance but no significant change in the additional resistance only was observed at 12cm $H_2O$ of PEEP(from $15.66{\pm}1.99$ to $13.54{\pm}2.41$, from $10.24{\pm}2.98$ to $8.04{\pm}2.34$, and from $5.42{\pm}3.41$ to $5.50{\pm}3.58cm$ $H_2O$/L/sec, respectively). 4)The lung compliance did not change at the applied PEEP and salbutamol inhalation levels. Conclusion : The bronchodilator response would be different depending on the level of applied PEEP despite the increased respiratory resistance in patients with ARDS.

• Tuberculosis and Respiratory Diseases
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• v.59 no.1
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• pp.30-38
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• 2005

Background : Arsenic trioxide ($As_2O_3$) has been used to treat acute promyelocytic leukemia, and it induces apoptosis in a variety of solid tumor cell lines including non-small cell lung cancer cells. However, nonsteroidal antiinflammatory drugs (NSAID) can enhance tumor response to chemotherapeutic drugs or radiation. It was previously demonstrated that a combination treatment with $As_2O_3$ and sulindac induces the apoptosis of NCI-H157 human lung carcinoma cells by activating the caspase cascade. This study aimed to determine if a combination treatment augmented its apoptotic potential through other pathways except for the activation of the caspase cascade. Material and Methods : The NCI-H157 cells were treated with $As_2O_3$, sulindac and antioxidants such as glutathione (GSH) and N-acetylcysteine (NAC). The cell viability was measured by a MTT assay, and the level of intracellular hydrogen peroxide ($H_2O_2$) generation was monitored fluorimetrically using a scopoletin-horse radish peroxidase (HRP) assay. Western blotting and mitochondrial membrane potential transition analysis were performed in order to define the mechanical basis of apoptosis. Results : The viability of the cells was decreased by a combination treatment of $As_2O_3$ and sulindac, and the cells were protected using antioxidants in a dose-dependent manner. The increased $H_2O_2$ generation by the combination treatment was inhibited by antioxidants. The combination treatment induced changes in the mitochondrial transmembrane potential as well as the expression of the Bcl-2 family proteins, and increased cytochrome c release into the cytosol. However, the antioxidants inhibited the effects of the combination treatment. Conclusion : Combination treatment with $As_2O_3$ and sulindac induces apoptosis in NCI-H157 human lung carcinoma cells via ROS generation with a mitochondrial dysfunction.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.11
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• pp.1493-1501
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• 2012

The antioxidant activities of volatile aroma extracts from Cudrania tricuspidata (Carr.) Bureau were examined using two antioxidant assays. Ten volatile aroma compounds identified in this plant were also tested for antioxidant activity. The volatile aroma extracts of stem and root from C. tricuspidata exhibited antioxidant activities with a clear dose response relationship in both aldehyde/carboxylic acid and lipid/malonaldehyde assays. Antioxidant activities of volatile aroma extracts from C. tricuspidata at $500{\mu}g/mL$ were $77.02{\pm}8.12%$ (stem) and $74.19{\pm}6.82%$ (root) in the aldehyde/carboxylic acid assay. Antioxidant activities of volatile aroma extracts from C. tricuspidata at $160{\mu}g/mL$ were $76.17{\pm}4.25%$ (stem) and $61.43{\pm}2.11%$ (root) in the lipid/malonaldehyde assay. Positively identified volatile aroma components in extracts of stem and root from C. tricuspidata were seven terpenes and terpenoides, 14 alkyl compounds, 11 nitrogen containing heterocyclic compounds, three oxygen containing heterocyclic compounds, 12 aromatic compounds, nine lactones, and seven miscellaneous compounds (possible contaminants). Among the positively identified compounds, eugenol, isoeugenol, and 2,4-bis (1,1-dimethylethyl)phenol exhibited antioxidant activities comparable to those of BHT and ${\alpha}$-tocopherol. Vanillin and 2-acetylpyrrole showed moderate activities in the lipid/malonaldehyde assay. These results suggest that consumption of antioxidant-rich beverages prepared from C. tricuspidata could have beneficial effects on human health by preventing diseases caused by oxidative damage.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.226-233
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• 2004

Background : Interferon-gamma (IFN-${\gamma}$) is a critical cytokine in the defense against a Mycobacterium tuberculosis infection. Even though IFN-${\gamma}$ has occasionally been used in the treatment of refractory multidrug-resistant tuberculosis (MDR-TB) with some promising results, there is still some controversy regarding the therapeutic efficacy of IFN-${\gamma}$. This study was performed to examine the effect of subcutaneous IFN-${\gamma}$ in the treatment of MDR-TB patients. Methods : Six patients with refractory MDR-TB were enrolled in this study. Two million IU of IFN-${\gamma}$ was administered subcutaneously three times a week with the concomitant administration of antituberculous drugs for at least for 28 weeks. During the IFN-${\gamma}$ therapy, the sputum smear and culture, radiological and clinical evaluations were performed every 4 weeks throughout the study period. Results : The mean age of the 6 patients was 37 years (ranges, 15-61 years). The drug susceptibility test to standard antituberculous drugs revealed resistance to an average of 6.8 (${\pm}1.2$) agents including isoniazid and rifampicin. An average of 10.8 (${\pm}1.3$) antituberculous drugs were prescribed before IFN-${\gamma}$ therapy. The culture became negative in 2 patients (33%) after initiating IFN-${\gamma}$ therapy; one at 8 weeks, and the other at 24 weeks. Finally, after stopping the IFN-${\gamma}$ therapy after 28 weeks, the culture became positive again in the two patients who were culture-negative. The other 4 patients who failed in the culture conversion are still on antituberculous treatment except for one who died of tuberculosis. Conclusion : Even though 28 weeks of subcutaneous IFN-${\gamma}$ therapy in combination with antituberculous drugs was successful in inducing the culture-negative conversion in some patients with refractory MDR-TB, the culture became positive again after stopping the IFN-${\gamma}$ therapy. This suggests that subcutaneous IFN-${\gamma}$ therapy may have suppressive effect on tuberculosis only during the IFN-${\gamma}$ therapy period in some patients. Further studies will be needed to determine the optimum dose, the administration route, the duration of therapy, and the predicting factors of the response to adjuvant IFN-${\gamma}$ therapy.

• Clinical and Experimental Pediatrics
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• v.50 no.5
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• pp.449-456
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• 2007

Purpose : Antibody persistence after primary series of Haemophilus influenzae type b (Hib) vaccine and responses to a boosters are little known in Korean children. We performed this study to evaluate the antibody titer in relation with a booster immunization of Hib vaccine in Korean children. Methods : One hundred forty-four children aged 12-23 months old were enrolled in three university hospitals. The immunogenicity of a boosters with Hib vaccine was assessed in children previously primed with Hib vaccine. Antibody persistence was also assessed in children who had received 3 doses of Hib vaccine without a booster. Anti-polyribosylribitol phosphate (PRP) IgG antibody levels and bactericidal titers were determined by enzyme immunoassay and bactericidal assay at the Center for Vaccine Evaluation and Study, Medical Research Institute, Ewha Womans University. Results : Prior to a booster in the second year of life, geometric mean antibody concentrations were $2.39{\mu}g/mL$ and the percent of subjects who had a anti-PRP antibody level ${\geq}1{\mu}g/mL$ was 68.6%. After boosting, antibody concentration was $19.09{\mu}g/mL$ and the percent of subjects who had a anti-PRP antibody level ${\geq}1{\mu}g/mL$ was 96.5%, which reflects previous immune priming. In subjects who had finished primary immunization only, the bactericidal titer was 3,946 and in subjects who had a booster, it was 11,205. Anti-PRP antibody level was correlated with serum bactericidal titer. Conclusion : Many children aged 12-23 month old still had protective antibodies after recommended primary immunization only. A booster dose seemed to induce good anamnestic antibody responses in Korean children.

• Pediatric Infection and Vaccine
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• v.15 no.2
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• pp.180-187
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• 2008

Purpose : We wanted to determine the characteristics of patients with Kawasaki disease (KD) who were unresponsive to intravenous immunoglobulin (IVIG). Methods : The patients with KD were divided into two groups: the IVIG responsive group (25 cases) and the IVIG unresponsive group (14 cases). We analyzed various parameters before and after the administration of IVIG, including the complete blood cell count with the differential count (%), the erythrocyte segmentation rate (ESR), the C-reactive protein (CRP) level and the protein and lipid profiles. Results : The IVIG unresponsive group had a prolonged duration of fever and a higher incidence of CAL compared to the IVIG responsive group (P<0.001, respectively). Before IVIG infusion, the neutrophil differential, the ESR and the CRP values were higher (P<0.001), and the total protein and albumin values were lower in the IVIG unresponsive group (P=0.01) compared to the IVIG responsive group. After IVIG infusion, there were no significant changes in the WBC count and CRP levels in the IVIG unresponsive group. The reduction of the HDL-cholesterol levels by IVIG was more significant in the unresponsive group (P=0.02). Conclusion : A more severe and prolonged inflammatory response occurred in the IVIG unresponsive group at an early stage, and this finding can be detected by such inflammatory parameters as the neutrophil count and the CRP and HDL-cholesterol levels after IVIG infusion.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.44 no.3
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• pp.239-247
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• 2018

Chronic inflammation is known to have effects on various diseases such as gout, cancer, dementia, atopic disease, and obesity. In addition, since some signal cascades involved in the development of inflammation are known to affect the damage and aging of the skin tissue, studies are being conducted actively to control the inflammation mechanism. In order to mitigate or prevent inflammatory response, a number of researches have been made to develop anti-inflammatory materials from some plants. In particular, Stevia rebaudiana produces steviol glycosides (SG), a natural sweetener with a distinctive flavor. Studies on some of SG have been shown to have anti-inflammatory activity. Researchers of this study expected that more SG also possess anti-inflammatory activity, besides stevioside, rebaudioside A, and steviol. In order to confirm this possibility, the researchers screened inhibition activity of various steviol glucosides for NO production in RAW 264.7 cell lines. As a result, steviol ${\beta}-glucopyranosyl$ ester (SGE) showed the highest inhibitory activity among steviol derivatives treated at the same molar concentration. In addition, we found that mRNA expression level of $interleukin-1{\alpha}$ ($IL-1{\alpha}$), $interleukin-1{\beta}$ ($IL-1{\beta}$), cyclooxygenase-2 (COX-2), nuclear factor kappa-light chain-enhancer of activated B cells ($NF-{\kappa}B$) and inducible nitric oxide synthase (iNOS) was also decreased in a dose-dependent manner. These results show that SGE inhibits anti-inflammatory activity and NO production in mouse macrophage RAW 264.7 cells. It was confirmed that SGE has potential to be applied as an anti-inflammatory material.

• Korean Journal of Environmental Agriculture
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• v.33 no.2
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• pp.103-110
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• 2014

BACKGROUND: Azadirachta indica has been widely used as environment-friendly organic materials because of its insecticidal properties. This study was carried out to investigate the acute toxicity and the subacute toxicity of Azadirachta indica extract(AIE) in rats. METHODS AND RESULTS: For the oral acute toxicity test, Sprague-Dawley rats were gavaged with 2.0 g/Kg bw of AIE. The $LD_{50}$ value was greater than 2.0 g/Kg bw for both male and female rats. For the subacute toxicity study, rats were treated with AIE at doses of 0.5, 1.0, 2.0 mg/Kg bw once a day for 4 weeks(n=10 animals per each group). There were no significant changes in body weight, food intake and water consumption observed during the experimental duration. In addition, no difference of relative kidney weight was observed among all treated groups. Serum creatinine level in the AIE 2.0 g/Kg group increased significantly compared with that of control group in male rats, but serum blood urea nitrogen was significantly decreased in a dose-dependent manner (p<0.05). Significant increase of serum cholesterol levels were observed in all AIE groups, compared with the control group, in the female rats (p<0.05). However, histopathological examination of the kidney did not reveal any significant lesions in all groups. CONCLUSION: On the basis of results, it could be concluded that oral administration AIE didn't cause any toxic response in kidney, except the increased serum cholesterol.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.11 no.2
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• pp.143-149
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• 2008

Purpose: To estimate the long-term therapeutic efficacy and safety of adefovir dipivoxil in children and adolescents with chronic hepatitis B who have developed lamivudine resistance. Methods: Sixteen patients (12 boys and 4 girls; ages 4.3~20.9 years; mean age 14.2 years) with chronic hepatitis B infection resistant to lamivudine therapy received adefovir (0.3 mg/kg/day, maximal dose 10 mg) orally for at least 9 months between March 2004 and April 2008. Each patient was followed up for a mean period of 27 months (range 9~49 months) until April 2008 at Kyungpook National University Hospital in Korea. Therapeutic responses to adefovir were evaluated at 12, 24, 36, and 48 months from the initiation of therapy using the Kaplan-Meier method. Response measurements included ALT normalization, HBV DNA negativization, 2 $log_{10}$ IU/mL decrement of HBeAg titer, HBeAg loss, and HBeAg/Ab seroconversion rate. Results: Three (18.8%) of the 16 patients treated with adefovir showed HBeAg/Ab seroconversion. Kaplan-Meier estimates of cumulative ALT normalization were 12.5% (12 months), 43.8% (24 months), 63.5% (36 months), and 92.7% (48 months), respectively. Cumulative HBV DNA negativization was 6.7%, 30.0%, 45.6%, and 78.2% at 12, 24, 36, and 48 months, respectively. Cumulative 2 $log_{10}$ copies/mL decrement of HBeAg titer was 12.5%, 43.8%, 56.3%, and 86.9% at 12, 24, 36, and 48 months, respectively. Cumulative HBeAg loss and HBeAg/Ab seroconversion were 6.7% (12 months) and 22.2% (24 months), respectively. Conclusion: The long-term therapeutic efficacy of adefovir dipivoxil was favorable in children and adolescents with chronic hepatitis B who had developed lamivudine resistance. The long-term use of adefovir should be safe in children.