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.
Kim, Eun Kyung;Shim, Tae Sun;Lee, Jung Yeon;Oh, Yeon-Mok;Lim, Chae-Man;Lee, Sang Do;Koh, Younsuck;Kim, Dong Soon;Kim, Won Dong;Kim, Woo Sung
Tuberculosis and Respiratory Diseases
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v.57
no.3
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pp.226-233
/
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.
Lee, Hyunju;Park, So Eun;Lim, Soo Young;Choi, Kyong Min;Lee, Hoan Jong;Kim, Kyung Hyo
Clinical and Experimental Pediatrics
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v.50
no.5
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pp.449-456
/
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.
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.
Jung, Heehoon;Cho, Uk Min;Hwang, Hyung Seo;Cho, Kun;Lee, Sang Rin;Kim, Moo Sung
Journal of the Society of Cosmetic Scientists of Korea
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v.44
no.3
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pp.239-247
/
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.
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.
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.
Hur, Hae Young;Kwak, Ji Hee;Kim, Hyoung Yun;Jung, Da Wun;Shin, Yoon Ho;Han, Man Yong
Clinical and Experimental Pediatrics
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v.51
no.8
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pp.842-847
/
2008
Purpose : Measurement of forced expiratory volume in 1 second ($FEV_1$) is usually difficult to obtain in children under six years of age because it requires active cooperation. This study evaluates the sensitivity of impulse oscillometry system (IOS) parameters for detecting airway obstruction in comparison with $FEV_1$. Methods : We studied 174 children who performed the lung function and methacholine challenge tests to diagnose asthma by IOS and spirometry. Children were divided into two subgroups according to their $PC_{20}$, which is a parameter for bronchial sensitivity. We compared IOS parameters with $FEV_1$ at the baseline, post-methacholine challenge, and evaluated their correlation. Results : At the baseline, reactance at 5 Hz (X5) and resistance at 5 Hz (R5) significantly differed between the $PC_{20}$ positive ($PC_{20}{\leq}16mg/mL$) group and $PC_{20}$ negative ($PC_{20}$ >16 mg/mL) group; however, $FEV_1$, $FEV_1$ % predicted, $FEV_1_-Zs$ (Z score) did not differ. $FEV_1$ is correlated with X5 (r=0.45, P<0.01) and R5 (r=-0.69, P<0.01). $FEV_1_-Zs$ is also correlated with X5_Zs (r=-0.26, P<0.01) and R5_Zs (r=-0.31, P<0.01). After the methacholine challenge test, dose-response slopes in $FEV_1$ and X5 significantly differed between the two subgroups (P<0.05). Conclusion : IOS parameters were more discriminative than $FEV_1$ for detecting decreased baseline lung function between two subgroups and have a good correlation with $FEV_1$.
Kim, Kyoung-Ok;Chun, Mi-Son;Kang, Seung-Hee;Kim, Hyun-Sook
Journal of Nutrition and Health
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v.42
no.7
/
pp.605-614
/
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.
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