• Tuberculosis and Respiratory Diseases
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• 제45권3호
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• pp.546-552
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• 1998

연구배경: Macrolide란 구조식에 14-number macrocyclic lactone ring을 갖는 항생제를 총칭한다. 최근 개발된 clarythromycin, azythromycin, roxithromycin 등은 기존의 erythromycin에 비하여 소화관 흡수가 용이하고, 반감기가 길며, 위장관 부작용은 덜하면서 몇몇 세균속에 대해서는 더욱 강력한 항균 효과가 있다고 알려져 있다. Erythromycin은 간장의 cytochrome P-450 효소계에 의해 불활성화 되기 때문에, 특히 호흡기 질환 환자에서 사용되는 theophylline의 혈중농도를 증가시켜 theophylline toxicity를 초래할 수 있다고 알려져 있다. 그러나 현재까지 new macrolide에 있어서는 이러한 효과에 대해서는 임상 연구가 미미한 실정이다. 방 법: 기관지 천식환자에서 erythromycin (1000mg/day), clarithromycin(500mg/day), azithromycin(500mg/day), roxithromycin(300mg/day) 등을 theophylline(400mg/day)과 경구 복합 투여하여, 투여전, 투여 후 1주 및 4주(azythyromycin은 1주)에 각각 theophylline 혈중 농도와 청소율을 측정하여 혈중 theophylline 농도 및 청소율에 대한 erythromycin과 new macrolides 항생제의 영향을 평가하고자 하였다. 결 과: Erythromycin과 roxithromycin 투여군에서는 투여 1주 후부터 유의한 theophylline 혈중농도의 상승을 보였으며 특히, erythromycin 투여군에서는 2예에서 병합 투여를 중지하였다. 이러한 소견은 theophylline 청소율에서도 유사하였으나 1주 및 4주간에는 유의한 상승소견을 보이지 않았다. Clarithromycin, azithromycin 투여군에서는 병합 투여중 유의한 혈중 농도의 상승이나 청소율의 감소 소견은 관찰되지 않았다. 결 론: 이상의 결과로 erythromycin 혹은 roxithromycin 투여 환자에 대하여 theophylline을 동시에 복합 투여하는 경우 혈중 theophylline 농도가 예상보다 증가될 수 있으므로 적절한 주기적 관리가 요할 것으로 사료된다.

• 대한한방내과학회지
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• 제31권3호
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• pp.650-666
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• 2010

Objectives : In this study, the author tried to investigate whether wood vinegar produced from Morus alba (MA) significantly affects the increase in airway epithelial mucosubstances and hyperplasia of tracheal goblet cells of rats, and in vitro airway mucin secretion and PMA- or EGF- or TNF-alpha-induced MUC5AC mucin production / gene expression from human airway epithelial cells. Materials and Methods : For the in vivo experiment, the author induced hypersecretion of airway mucus and goblet cell hyperplasia by exposure of rats to SO2 over 3 weeks. Effect of orally-administered MA over 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats and hyperplasia of goblet cells were assessed using histopathological analysis after staining the epithelial tissue with alcian blue. For the in vitro experiment, confluent RTSE cells were chased for 30 min in the presence of MA to assess the effect of MA on mucin secretion by enzyme-linked immunosorbent assay (ELISA). Also, effects of MA on PMA- or EGF- or TNF-alpha-induced MUC5AC mucin production and gene expression from human airway epithelial cells (NCI-H292) were investigated. Confluent NCI-H292 cells were pretreated for 30 min in the presence of MA and treated with PMA (10 ng/ml), EGF (25 ng/ml) or TNF-alpha (0.2 nm) for 24 hrs, to assess both effects of MA on PMA- or EGF- or TNF-alpha-induced MUC5AC mucin production by enzyme-linked immunosorbent assay (ELISA) and gene expression by reverse transcription-polymerase chain reaction (RT-PCR). Possible cytotoxicities of MA in vitro were assessed by examining LDH release from RTSE cells and the rate of survival and proliferation of NCI-H292 cells. In vivo liver and kidney toxicities of MA were evaluated by measuring serum GOT/GPT activities and serum BUN/creatinine concentrations of rats after administering MA orally. Results : 1. MA decreased the amount of intraepithelial mucosubstances of rats exposed to sulfur dioxide inhalationally. 2. MA decreased in vitro mucin secretion from cultured RTSE cells. 3. MA significantly inhibited PMA-, EGF-, and TNF-alpha-induced MUC5AC mucin productions and the expression levels of MUC5AC mRNA from NCI-H292 cells. 4. MA did not show either in vitro or in vivo hepatic or renal toxicities. Conclusion : The results from this study suggests that MA can regulate the secretion, production and gene expression of airway mucin observed in diverse respiratory diseases accompanied by mucus hypersecretion and does not show in vivo toxicity to liver and kidney functions after oral administration. Effects of MA should be further studied using animal experimental models that simulate the diverse pathophysiology of respiratory diseases via future research.

• 대한한방소아과학회지
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• 제29권3호
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• pp.65-79
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• 2015

Objectives : In this study, effects of haepyoijintang (HIJ) on the increase in airway epithelial mucosubstances of rats and ATP-, PMA-, EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells were investigated. Methods : Hypersecretion of airway mucus was induced by exposure of rats to $SO_2$ during 3 weeks. Effect of orally-administered HIJ during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats was evaluated using histopathological analysis after staining the epithelial tissue with PAS-alcian blue. Possible cytotoxicity of HIJ was evaluated by examining the potential damage of kidney and liver functions by measuring serum GOT/GPT activities and serum BUN and creatinine concentrations of rats and the body weight gain during experiment, after administering HIJ orally. At the same time, the effect of HIJ on ATP-, PMA-, EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells (NCI-H292) were investigated. Confluent NCI-H292 cells were pretreated for 30 min in the presence of HIJ and treated with ATP ($200{\mu}M$), PMA (10 ng/ml), EGF (25 ng/ml) or TNF-${\alpha}$ (0.2 nM) for 24 hrs, to evaluate the effect of HIJ both on ATP-, PMA-, EGF- or TNF-${\alpha}$-induced MUC5AC mucin production using enzyme-linked immunosorbent assay (ELISA) and on gene expression by the same inducers using reverse transcription-polymerase chain reaction (RT-PCR). Results : (1) HIJ decreased the amount of intraepithelial mucosubstances of trachea of rats. (2) HIJ did not show renal and hepatic toxicities and did not affect body weight gain of rats during experiment. (3) HIJ significantly inhibited ATP-, PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin productions from NCI-H292 cells. (4) HIJ significantly inhibited ATP-, PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin gene expression from NCI-H292 cells. Conclusions : The result from the present study suggests that HIJ might control the production and gene expression of airway mucin observed in various respiratory diseases accompanied by mucus hypersecretion and do not show in vivo toxicity to liver and kidney functions after oral administration. Effect of HIJ with their diverse components should be further investigated using animal experimental models that can reflect the pathophysiology of airway diseases through future studies.

• 대한한방소아과학회지
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• 제27권1호
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• pp.69-81
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• 2013

Objectives In this study, effects of Macmundongtang (MMT) on ATP or TNF-${\alpha}$ or PMA or EGF induced MUC5AC mucin production and gene expression from human airway epithelial cells and the increase in airway epithelial mucosubstances of rats were investigated. Materials and Methods Confluent NCI-H292 cells were pretreated for 30min in the presence of MMT and treated with ATP ($200{\mu}M$) or PMA (10 ng/ml) or EGF (25 ng/ml) or TNF-${\alpha}$ (0.2 nM) for 24hrs, to assess the effect of MMT both on ATP- or PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production using enzyme-linked immunosorbent assay (ELISA) and on gene expression by the same inducers using reverse transcription-polymerase chain reaction (RT-PCR). At the same time, hypersecretion of airway mucus was induced by exposure of rats to SO2 during 3 weeks. Effect of orally-administered MMT during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats was assesed using histopathological analysis after staining the epithelial tissue with PAS-alcian blue. Possible cytotoxicity of MMT was assessed by investigating the potential damage of kidney and liver functions by measuring serum GOT/GPT activities and serum BUN concentration of rats and the body weight gain during experiment, after administering MMT orally. Results (1) MMT did not only inhibit but also increased MUC5AC mucin productions and expression levels of MUC5AC gene from NCI-H292 cells. (2) MMT did not decrease the amount of intraepithelial mucosubstances of trachea of rats. (3) MMT did not show renal and hepatic toxicities and did not affect body weight gain of rats during experiment. Conclusions The result from the present study suggests that MMT might normalize the production and gene expression of airway mucin observed in various respiratory diseases accompanied by yin-deficiency, without in vivo toxicity to liver and kidney functions after oral administration.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7303-7307
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• 2014

Objective: To explore the clinical efficacy of gemcitabine concomitant with nedaplatin and drug resistance in the treatment of non-small cell lung cancer (NSCLC) and associated molecular predicators. Materials and Methods: A total of 68 patients diagnosed with NSCLC by histology served as the study objects and were randomly divided into an observation group treated with gemcitabine concomitant with nedaplatin and a control group with cisplatin concomitant with gemcitabine, 34 cases for each group. Short-term and long-term efficacies, adverse responses as well as the expression of nucleotide excision repair cross complementing 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1) and lung resistance-related protein (LRP) in NSCLC tissues in both groups were assessed. Results: The short-term objective response rate (ORR) and disease control rate (DCR) were 35.3% (12/34) and 76.5% (26/34) in the observation group and 38.2% (13/34) and 85.3% (29/34) in the control group, respectively, the differences not being statistically significant. The time to progression (TTP) in both groups were 1~12 months, while the median TTP was 135 d and 144 d, respectively. Though the survival was slightly higher in the control group, there were no significant differences in TTP and survival time. The rates of decreased hemoglobin, vomiting and nausea as well as renal toxicity were evidently lower in the observation group, while other adverse responses demonstrated no significant difference. The positive expression rates of ERCC1, RRM1 and LRP were 47.1% (16/34), 61.8% (21/34) and 64.7% (22/34) in the observation group, respectively. Compared with negative ERCC1 expression, ORR had decreasing trend and the overall survival time (OS) decreased significantly in patients with positive ERCC1 expression, which were markedly decreased by the positive expressions of RRM1 and LRP. Conclusions: Gemcitabine concomitant with nedaplatin has significant effects in the treatment of NSCLC, with an adverse response rate obviously lower than for cisplatin concomitant with gemcitabine, suggesting that wider use in the clinic is warranted. Additionally, the positive expressions of ERCC1, RRM1 and LRP may increase patient drug resistance, so they can be applied as the chemotherapeutic predicators to guide individualized therapy of NSCLC patients.

• 대한한방소아과학회지
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• 제30권2호
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• pp.31-46
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• 2016

Objectives In this study, the effects of Ja-eum-gang-hwa-tang (JGT) on the increase in airway epithelial mucosubstances of rats and ATP- or PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells were investigated. Materials and Methods Hypersecretion of airway mucus was produced by exposure of $SO_2$ to rats for 3 weeks. The effect of orally-administered JGT for 2 weeks on increased epithelial mucosubstances from tracheal goblet cells of rats was assessed by using histopathological analysis after staining the epithelial tissue with Hematoxylin-eosin and PAS-alcian blue. Possible cytotoxicity of JGT was assessed by investigating the potential damage on kidneys and liver functions by measuring serum GOT/GPT activities and serum BUN concentration of rats and the body weight gain during experiment. Also, the effect of JGT on ATP- or PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production and gene expression from human airway epithelial cells (NCI-H292) were investigated. Confluent NCI-H292 cells were pretreated for 30 min in the presence of JGT and treated with ATP ($200{\mu}M$) or PMA ($10ng/ml$) or EGF ($25ng/ml$) or TNF-${\alpha}$ (0.2 nM) for 24 hrs to assess the effect of JGT both on ATP- or PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production by using enzyme-linked immunosorbent assay (ELISA) and on gene expression by the same inducers using reverse transcription-polymerase chain reaction (RT-PCR). Results (1) JGT decreased the amount of intraepithelial mucosubstances of trachea of rats. (2) JGT did not show any renal and hepatic toxicities, and did not affect body weights either. (3) JGT significantly inhibited ATP-, PMA-, EGF-, and TNF-${\alpha}$-induced MUC5AC mucin productions from NCI-H292 cells. (4) JGT inhibited EGF-, and PMA-induced expression levels of MUC5AC gene in NCI-H292 cells. However, ATP- and TNF-${\alpha}$-induced MUC5AC gene expression levels were not affected in NCI-H292 cells. Conclusions The result from the present study suggests that JGT might control the production and gene expression of airway mucin observed in various respiratory diseases which accompanied by mucus hypersecretion. Also, JGT did not show liver toxicity or impact on kidney functions. The effect of JGT should be further studied by using animal experimental models which can show proper pathophysiology of airway diseases.

• 한국수산과학회지
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• 제19권3호
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• pp.249-256
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• 1986

암모니아 농도 10, 20 및 30ppm, pH 6.5, 7.0 및 8.0의 조건하에서 수온 20, 25 및 $30^{\circ}C$로 각각 유지하고 잉어 당년생치어 (평균체중 5.96g)를 24, 48 및 72시간 노출시켜 아가미, 간 및 신장의 조직병리학적인 관찰을 했다. 1. 아가미, 간 및 신장의 조직변화는 pH 및 수온이 높고 암모니아 농도가 증가되고, 노출시간이 길어짐에 따라 조직의 이상비대나 붕괴가 증대하는 경향이 뚜렷했다. 2. 아가미는 수온 $20^{\circ}C$에서 pH 7.0이상의 암모니아 30 ppm 농도구에서 24시간 노출시킨 것에서는 새엽의 표피분리가 생기기 시작했고, pH 7.5 및 8.0에서는 암모니아 30ppm 농도구의 72시간 노출시킨것은 수온에 관계없이 새엽표피의 분리가 심해졌다. 3. 새엽표피의 분리는 새엽의 기저부에서부터 진행되었고 격렬해짐에 따라 새엽의 선단부에 까지 확대되었다. 4. 간은 수온 $20^{\circ}C$에서 pH 8.0, 암모니아농도 30ppm 및 48시간 노출구에서 조직에 공포가 나타나기 시작했고, 간장의 공포는 간조직중에 생긴 수종화의 결과라고 본다 5. 신장은 pH 6.5에서는 세요관상피세포의 붕괴는없었고, pH 8.0에서는 수온 $20^{\circ}C$, 암모니아 30ppm 농도에서 24시간 노출시킨 것에서도 세요관상피세포의 붕괴가 일이기 시작했다.

• 한국수산과학회지
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• 제44권6호
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• pp.577-583
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• 2011

In 2007, pet food contaminated with melamine caused hundreds of dogs and cats to develop renal failure all over the world. In 2008, over 294,000 infants consumed infant formula and developed kidney stones in China. Further investigation revealed that fish feed also contained melamine; this raised concerns about melamine residues in edible fish tissues, which could have caused the urinary tract stone epidemic. In Korea, catfish fed with assorted feed that included cuttlefish organs that contained melamine developed whitening syndrome and fell dead in some populations in 2008. This event raised suspicions about the toxicity of melamine and all feeds containing melamine were immediately recalled. In this study, we investigated the rates of melamine accumulation and depletion in muscle and viscera of catfish to propose proper withdrawal periods. One group of catfish was fed a commercially available diet that contained 30, 100 and 300 mg melamine per kg diet for 14 days. To investigate residual melamine contents in muscle and viscera, other experimental groups were fed a melamine free diet after being fed melamine for 7 days. The residual amount of melamine was analyzed by LC-MS/MS. The melamine concentration in muscle was estimated to be 3.7 mg/kg after 6 days of feeding with a diet containing 300 mg melamine/kg. After 2 days of culture with a melamine free diet, the residual melamine was depleted and the concentration had decreased from 1.15 mg/kg to 0.19 mg/kg in the muscle of catfish fed a diet containing 300 mg melamine/kg for 7 days. The residual amount of melamine was reduced to 0.03 mg/kg in muscle after 7 days of culture with a melamine free diet and was undetectable after a prolonged culture period of 14 days. Catfish tend to excrete melamine rapidly after oral administration and changes in body color were not observed during the short dosing period.

• 한국약용작물학회지
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• 제25권4호
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• pp.231-237
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• 2017

Background: Cisplatin is one of the most extensively used chemotherapeutic agents for the treatment of cancer, including bladder, and ovarian cancers. However, it has been shown to induce nephrotoxicity, despite being an outstanding anti-cancer drug. In this study, we investigated the protective effect of dopaol ${\beta}$-D-glucoside (dopaol) on cisplatin-induced nephrotoxicity. Methods and Results: To confirm the protective effect of dopaol on cisplatin-induced nephrotoxicity, HK-2 cells were treated with $20{\mu}M$ cisplatin and $80{\mu}M$ dopaol. Cisplatin increased apoptosis, caspase-3 activity and mitochondrial dysfunction; however pretreatment with $80{\mu}M$ dopaol successfully attenuated apoptosis, caspase-3 activity and mitochondrial dysfunction. To evaluate the protective effect dopaol on cisplatin-induced nephrotoxicity in vivo, we used an animal model (balb/c mice, 20 mg/kg, i.p. once/day for 3 day). The results were similar to those obtained using HK-2 cells; renal tubular damage and neutrophilia induced by cisplatin reduced following dopaol injection (10 mg/kg, i.p. once/day for 3 day). Conclusions: These results indicate that dopaol treatment reduced cisplatin-induced nephrotoxicity in vitro and in vivo, and can be used to treat cisplatin-induced nephrotoxicity. However, further studies are required to determine the toxicity high dose dopaol and the signal pathways involved in its mechanism of action in animal models.

• 한국약용작물학회지
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• 제25권5호
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• pp.322-327
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• 2017

Background: Cynaroside is a flavone, a flavonoid-like compound, known by different names (luteoloside and cinaroside). It is commonly found in Lonicera japonica Thunb., Chrysanthemum moriflium, and Angelica keiskei. The process of cell death has been classified as necrosis and apoptosis. Necrosis refers to unregulated cell death induced by a chemotherapeutic agent. Doxorubicin is an anthracycline anti-cancer drug used to treat acute leukemia, cancer, and lymphoma. However, it induces nephrotoxicity including tubular damage. Therefore, we investigated the protective effect of cynaroside against doxorubicin-induced necrosis in HK-2 cells. Methods and Results: To confirm the beneficial effect of cynaroside on doxorubicin-induced necrosis, HK-2 cells, a human proximal tubule epithelial cell line were treated with $10{\mu}M$ doxorubicin and $80{\mu}M$ cynaroside. Doxorubicin treatment resulted in increased DNA fragmentation, caspase-3 activity and mitochondria hyperactivation during cell necrosis. However, pretreatment with $80{\mu}M$ cynaroside attenuated DNA fragmentation, caspase-3 activity and mitochondria hyperactivation induced by $10{\mu}M$ doxorubicin in HK-2 cells. Conclusions: These results indicated that pretreatment with cynaroside ameliorated doxorubicin-induced necrosis in HK-2 cells. Therefore, cynaroside be used as a therapeutic agent for improving doxorubicin-induced nephrotoxicity. However, further studies are required to evaluated the toxicity of cynaroside treatment in animals and to determine its protective effect against doxorubicin-induced nephrotoxicity in an animal model.