• Title/Summary/Keyword: Tissue damage

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in vitro Anticancer Activity and in vivo Chronic Toxicity of Homoharringtonine (개비자나무 유효성분인 homoharringtonine의 in vitro 항암활성 및 in vivo 만성 독성)

  • Yoo, Gui-Jae;Cho, Chul-Hee;Lee, Gun-Soon;Ryoo, Zae-Young;Chae, Hee-Jeong
    • Applied Biological Chemistry
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    • v.51 no.2
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    • pp.124-128
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    • 2008
  • Cell proliferation inhibitory effects of homoharringtonine (HHT), an active drug substance in Cephalotaxus koreana, against blood cancer cell line K562 were evaluated. In addition, in vivo chronic toxicity test with mouse was carried out. When K562 cell line was treated everyday for 9, 6, 3 days, $IC_{50}$ values of HHT were determined as 0.27, 0.37, and 1.10 mM respectively. The anticancer activity of HHT was comparable to adriamycin, a known anticancer drug compound for blood cancer treatment. in vivo chronic toxicity test of the HHT, the number of red blood cell (RBC) showed no significant difference. From the analysis of the liver-functional enzymes in blood, all of liver damage related enzymes such as glutamate-oxalate-transferase (GOT), glutamate-pyruvate-transferase (GPT), cholesterol (Chol) and alkaline phosphatase (ALP) showed no significant change. However, from the histologic test, a neutrophil of the band type in liver tissue was observed.

Effect of Haepyoijin-tang on Airway Mucin Secretion, Production, Gene Expression and Hypersecretion of Mucus (해표이진탕이 기도 뮤신의 분비, 생성 및 유전자 발현에 미치는 영향)

  • Suk, Yun Hee;Min, Sang Yeon;Kim, Jang Hyun
    • The Journal of Pediatrics of Korean Medicine
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    • v.29 no.3
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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.

Desalinated underground seawater of Jeju Island (Korea) improves lipid metabolism in mice fed diets containing high fat and increases antioxidant potential in t-BHP treated HepG2 cells

  • Noh, Jung-Ran;Gang, Gil-Tae;Kim, Yong-Hoon;Yang, Keum-Jin;Lee, Chul-Ho;Na, O-Su;Kim, Gi-Ju;Oh, Won-Keun;Lee, Young-Don
    • Nutrition Research and Practice
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    • v.4 no.1
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    • pp.3-10
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    • 2010
  • This study was performed to investigate the effect of desalinated underground seawater (named as 'magma seawater', MSW) of Jeju Island in Korea on lipid metabolism and antioxidant activity. MSW was collected from underground of Han-Dong in Jeju Island, and freely given to high fat diet (HFD)-fed C57BL/6 mice for 10 weeks. Although there were no significant differences in the body weight changes and plasma lipid levels, hepatic triglyceride levels were significantly lower in the MSW group than in the normal tap water (TW)-drunken control group. Furthermore, the activity of fatty acid synthase (FAS) was significantly decreased and carnitine palmitoyltransferase (CPT) activity was increased in MSW group compared to TW group. Similarly, real-time PCR analysis revealed that mRNA expressions of lipogenic genes were lowered in MSW groups compared to the control group. In a morphometric observation on the liver tissue, accumulation of fats was remarkably reduced in MSW group. Meanwhile, in vitro assay, tree radical scavenging activity measured by using diphenylpicrylhydrazyl (DPPH) was increased in MSW group. The 2'-7'-dichlorofluorescein diacetate (DCF-DA) staining followed with fluorescent microscopy showed a low intensity of fluorescence in MSW-treated HepG2 cells, compared to TW-treated HepG2 cells, which indicated that the production of reactive oxygen species by tert-butyl hydroperoxide (t-BHP) in HepG2 cells was decreased by MSW treatment. The antioxidant effect of MSW on t-BHP-induced oxidative stress in HepG2 cells was supported by the increased activities of intracellular antioxidant enzymes such as catalase and glutathione reductase. From these results, we speculate that MSW has an inhibitory effect on lipogenesis in liver and might play a protective role against cell damage by t-BHP-induced oxidative stress.

Evaluation 4D-CT Simulation used of Motion Organ and Tumor for Respiratory Gated Radiation Therapy (호흡동조방사선치료를 위한 4D-CT simulation을 이용한 동적장기와 종양 움직임 평가)

  • Kim, Seung-Chul;Kim, Min-A
    • The Journal of the Korea Contents Association
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    • v.15 no.9
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    • pp.395-402
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    • 2015
  • when the radiation therapy of chest and abdomen, evaluation of the tumor motion and the data was used to minimize damage to normal tissues by separating the tumor and normal tissue and maximize tumor therapeutic effect. Lung and liver cancer each 20 patients based on the 50% top phase using 4D-CT simulation and Light speed-16 of shooting equipment 30 ~ 70 % gating phase interval and 0 ~90 % movement in the full phase interval was measured. If the full phase 0 ~ 90% with gating phase 30~70% of tumors in the liver and lung is shown the biggest difference compared to the motion and the size of the GTV was the largest difference in the I(inferior), full phase 0~90% degree of tumor motion only when a relatively large, gating phase to 30~70% of the tumor when the movement has been found that the reduced average 7.1mm. In the 4D-CT simulation comparing the motion value when the full phase 0~90 % and gating phase 30~70 % when the motion value, twice in the gating phase 30~70 % more than full phase 0~90 % showed a small movement value. The exposure to normal tissues, based on the results obtained from the 4D-CT simulation can be significantly alleviated, After treatment will reduce pain and disability in patients with radiation is expected to be able to effective treatment.

Effect of the Inhibition of PLA2 on Oxidative Lung Injury Induced by $Interleukin-1{\alpha}$

  • Lee, Young-Man;Cho, Hyun-Gug;Park, Yoon-Yub;Kim, Jong-Ki;Lee, Yoon-Jeong;Park, Won-Hark;Kim, Teo-An
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.5
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    • pp.617-628
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    • 1998
  • In order to understand the pathogenetic mechanism of adult respiratory distress syndrome (ARDS), the role of phospholipase A2 (PLA2) in association with oxidative stress was investigated in rats. $Interleukin-1{\alpha}\;(IL-1,\;50\;{\mu}g/rat)$ was used to induce acute lung injury by neutrophilic respiratory burst. Five hours after IL-1 insufflation into trachea, microvascular integrity was disrupted, and protein leakage into the alveolar lumen was followed. An infiltration of neutrophils was clearly observed after IL-1 treatment. It was the origin of the generation of oxygen radicals causing oxidative stress in the lung. IL-1 increased tumor necrosis factor (TNF) and cytokine-induced neutrophil chemoattractant (CINC) in the bronchoalveolar lavage fluid, but mepacrine, a PLA2 inhibitor, did not change the levels of these cytokines. Although IL-1 increased PLA2 activity time-dependently, mepacrine inhibited the activity almost completely. Activation of PLA2 elevated leukotriene C4 and B4 (LTC4 and LTB4), and 6-keto-prostaglandin $F2{\alpha}\;(6-keto-PGF2{\alpha})$ was consumed completely by respiratory burst induced by IL-1. Mepacrine did not alter these changes in the contents of lipid mediators. To estimate the functional changes of alveolar barrier during the oxidative stress, quantitative changes of pulmonary surfactant, activity of gamma glutamyltransferase (GGT), and ultrastructural changes were examined. IL-1 increased the level of phospholipid in the bronchoalveolar lavage (BAL) fluid, which seemed to be caused by abnormal, pathological release of lamellar bodies into the alveolar lumen. Mepacrine recovered the amount of surfactant up to control level. IL-1 decreased GGT activity, while mepacrine restored it. In ultrastructural study, when treated with IL-1, marked necroses of endothelial cells and type II pneumocytes were observed, while mepacrine inhibited these pathological changes. In histochemical electron microscopy, increased generation of oxidants was identified around neutrophils and in the cytoplasm of type II pneumocytes. Mepacrine reduced the generation of oxidants in the tissue produced by neutrophilic respiratory burst. In immunoelectron microscopic study, PLA2 was identified in the cytoplasm of the type II pneumocytes after IL-1 treatment, but mepacrine diminished PLA2 particles in the cytoplasm of the type II pneumocyte. Based on these experimental results, it is suggested that PLA2 plays a pivotal role in inducing acute lung injury mediated by IL-1 through the oxidative stress by neutrophils. By causing endothelial damage, functional changes of pulmonary surfactant and alveolar type I pneumocyte, oxidative stress disrupts microvascular integrity and alveolar barrier.

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MAPK Activation and Cell Viability after $H_2O_2$ Stimulation in Cultured Feline Ileal Smooth Muscle Cells

  • Song, Hyun-Ju;Jeong, Ji-Hoon;Lee, Dong-Kyu;Lee, Tai-Sang;Min, Young-Sil;Sohn, Uy-Dong
    • The Korean Journal of Physiology and Pharmacology
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    • v.8 no.6
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    • pp.339-344
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    • 2004
  • Recent data have shown the importance of oxidative stresses in the pathogenesis of inflammatory bowel disease, crohn's disease and ulcerative colitis. $H_2O_2$, reactive oxygen species (ROS) donor, has been reported to act as a signaling molecule involved in a variety of cellular functions such as apo/ptosis and proliferation. In the present study, we investigated viability of cultured ileal smooth muscle cells (ISMC) after stimulation with $H_2O_2$. Trypan blue method revealed that the cell viability of ISMC treated with 1 mM $H_2O_2$ was not different from that of controls at up to 2 h time point, while treatment of ISMC with 1 mM $H_2O_2$ for 48 h finally induced significant decrease in the cell viability. Therefore, we evaluated whether $H_2O_2$ was capable of ERKs activation in ISMC for the short-term exposure and examined whether tyrosine kinase was involved in the process of ERK activation by $H_2O_2$ in ISMC. We also investigated the effects of $H_2O_2$ on activation of SAPK/JNK and p38 MAP kinase in ISMC. Thus, ISMC were cultured and exposed to $H_2O_2$, and western blot analysis was performed with phosphospecific MAP kinase antibodies. Robust activation of ERK occurred within 30 min of 1 mM $H_2O_2$ treatment. $H_2O_2-induced$ ERK activation was attenuated by a tyrosine kinase inhibitor, genistein, indicating that tyrosine kinase was probably involved in the ERK activation by $H_2O_2$. $H_2O_2$ was a moderate activator of SAPK/JNK, while p38 MAP kinase was not activated by $H_2O_2$. We suggest that ERK activation induced by short-term $H_2O_2$ treatment plays a critical role in cellular protection in the early stage of response to oxidative stress. The present study suggests the necessity of identification of MAPK signaling pathways affected by ROS, since it could ultimately elucidate cellular consequences involved in initiation and perpetuation of intestinal tissue damage in the diseases such as crohn's disease and ulcerative colitis, resulted from excessive ROS.

Influence of Hippocampectomy and Adrenalectomy upon Gastric Ulceration in Rats (흰쥐의 위궤양 발생에 미치는 뇌해마 제거 및 부신 적출의 영향)

  • Kim, Myung-Suk;Ahn, Byung-Tae;Kim, Chul
    • The Korean Journal of Physiology
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    • v.10 no.2
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    • pp.39-45
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    • 1976
  • This study was conducted to see whether the hippocampectomy exerted facilitatory influence upon gastric ulceration in animals, and if so, whether the effect of hippocampectomy could be suppressed by adrenalectomy. 107 male rats were divided into 5 groups: rats that had over 90% of their hippocampal tissue removed through an opening on each side of the cerebral cortex(hippocampal group, N=21), rats that received bilateral adrenalectomy(adrenal group, N=29), rats that received adrenalectomy as well as hippocampectomy(hippocampo-adrenal group, N=10), rats that received damage to each side of the cortex over the hippocampus(cortical control group, N=20), and rats that had solely their head skin incised(normal control group, N=27). All rats were kept without restraint or food deprivation until on the 25th day after surgery, the stomach of each rat was inflated with 7ml of physiological saline and then removed under deep anesthesia. The mucosal surface was sketched under dissecting microscope, and enlarged photographs$(4{\times})$ were taken. The percentage of animals developing gastric ulcer in each animal group was calculated, the number of ulcer in each stomach was counted, and the total area of ulceration per stomach was measured on the Photograph with the aid of superimposed graph paper and expressed as permillage of total area of the glandular mucosa. Results obtained were as follows: 1. The percentage of animals developing gastric ulcer was significantly larger in the hippocampal group than they were in the hippocampo-adrenal, the adrenal, the cortical, and the normal control groups. 2. The mean number of ulcer per stomach was significantly larger in the hippocampal group than they were in the adrenal, the cortical control, and the normal control groups, while no significant difference existed between the hippocampal and the hippocampo-adrenal groups. 3. Total area of ulcer per stomach was significantly larger in the hippocampal group than they were in the cortical control and the normal control groups, but no significant differ-ence existed among the hippocampal, the adrenal, and the hippocampo·adrenal groups. 4. All measured values of the adrenal group were not significantly different from those of the hippocampo-adrenal, the cortical control, and the normal control groups. It is inferred from the above results that the hippocampus exerts an inhibitory influence upon gastric ulceration and that the hippocampal influence is mediated only partly through suppression of pituitary·adrenal activity.

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Studies on Whitening and UV Damage Protection Effect of the Pterin Compounds (테린계 화합물의 미백 및 자외선 손상방어 효능에 관한 연구)

  • Kim, Nam-Kyoung;Kim, Mi-Hwa;Kang, Nae-Im;Choi, Shin-Wook
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.33 no.1 s.60
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    • pp.53-60
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    • 2007
  • (6R)-5,6,7,8-tetrahydrobiopterin ($6-BH_4$) cofactor is essential for various process, and is present in probably every cell or tissue of higher organism. $6-BH_4$ is required lot various enzyme activities, and for less defined functions at the cellular level. And it is well known about the antioxidant effects as a non-protein compound. Recently, scientists proposed another roles for $6-BH_4$ in melanogenesis. $6-BH_4$ is a well known tyrosinase inhibitor. In this study, we found that methyl-$BH_4$ and $6-BH_4$ have antioxidant activities and inhibitory activity for melanin synthesis. These pterin compounds were not toxic in HaCaT and B16F10 cells and showed scavenging activity against DPPH radicals. We also showed that pterin compounds decreased protein levels of tyrosinase and TRP-1. In a clinical test, pterin compounds showed the significant skin whiteining effect after treatment for 3 weeks. Furthermore pterin compounds significantly suppressed the UVB-induced expression of $PGE_2$ and IL-6 genes induced UVB In HaCaT and inhibited UVB-induced melanogenesis in B16F10 cells. These results showed the effect of pterin compounds as a cosmeceutical ingredient.

Antimicrobial Effect of Mouthwash against Streptococcus mutans by Visual Staining Method (시각적 염색 방법을 이용한 마우스워시의 구강균에 대한 항균효과 확인)

  • Park, Taehun;Cho, Jeong Hun;Sung, Youngeun;Cho, Jun-Cheol;Shin, Kyeho
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.40 no.2
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    • pp.187-193
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    • 2014
  • Dental caries are one of the most common oral diseases and Streptococcus mutans (S. mutans) plays an important role in the initiation and progression of dental caries. Oral malodor is primarily the result of microbial metabolism such as Porphyromonas gingivalis (P. gingivalis) that produce volatile sulfur compounds (VSCs), causing oral malodor. Prevotella intermedia (P. intermedia) is known as typical periodontopathic bacteria, and periodontal disease is chronic inflammatory disease that leads to damage of gingival connective tissue and alveolar bone, eventually loss of teeth. In this study, we investigated antimicrobial effect of mouthwash containing cetylpyridinium chloride (CPC), sodium fluoride (NaF), green tea water extract and pine needles water extract against cariogenic and periodontopathic bacteria sucn as S. mutans, P. gingivalis and P. intermedia. As a result, the reduction ratios of S. mutans and P. gingivalis were 4.00 Log and 4.68 Log reduction for 30 s, and P. intermedia were 2.40 Log reduction for 30 s and 2.70 Log reduction for 60 s. Dentocult SM Strip mutans (SM Strip) provides easy detection of visual data showing a significant inhibition on S. mutans. In conclusion, we expected that mouthwash containing CPC, NaF, green tea water extract and pine needles water extract could help preventing the dental disease like dental caries and oral malodor.

Effect of Suppressing the Activation of Macrophage Migration Inhibitory Factor by $Sambucus$ $williamsii$ $H_{ANCE}$ Extract & Pharmacopuncture Solution on Type II Collagen-induced Arthritis (접골목(接骨木)추출물 및 약침액에 의한 MIF 활성 조절능이 생쥐의 제2형 Collagen 유발 관절염에 미치는 영향)

  • Lee, Dong-Gun;Kim, Eun-Jung;Lee, Eun-Sol;Wang, Kai-Hsia;Cho, Hyun-Seok;Lee, Seung-Deok;Kim, Kap-Sung;Kim, Kyung-Ho
    • Journal of Acupuncture Research
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    • v.29 no.1
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    • pp.103-113
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    • 2012
  • Objectives : The purpose of this study is to evaluate effect of suppressing the expression of cyclo-oxygenase-type-2 (COX-2) as a consequence of inhibition macrophage migration inhibitory factor (MIF) activation by $Sambucus$ $williamsii$ $Hance$ (SWH) pharmacopunctureon rheumatoid arthritis (RA). Methods : In vitro test, synoviocytes extracted from type II collagen-induced arthritis (CIA) mouse's knee joint were cultivated After that, each well of synoviocytes was mixed with the extract of SWH at the dosage of $0.4mg/m{\ell}$, $0.6mg/m{\ell}$, $0.8mg/m{\ell}$, and $1.0mg/m{\ell}$ respectively, and cultivated for 24 hours after the addition. Reverse transcriptase - polymerase chain reaction (RT-PCR) is used to investigate the expression of MIF, Tumor necrosis factor (TNF)-${\alpha}$, COX-2 mRNA. $In$ $vivo$ test, thirty DBA female mice were used, and each ten mice were allocated into three group; normal group, CIA-elicitated group, and group treated with SWH pharmacopuncture on it's the point of $ST_{35}$ after CIA elicitation. It is investigated that change of mice foot thickness, histologic change of sliced synovial joint of mouse, and extent change of MIF, TNF-${\alpha}$, COX-2 in synovial membrane. Results : $In$ $vitro$ test, the expressions of cytokine(MIF, TNF-${\alpha}$, COX-2) mRNAs related to RA were dose-dependent decreased. In the SWH pharmacopuncture group, foot thickness and histologic change of sliced synovial joint were decreased comparing with CIA-elicitated group's change. In the SWH pharmacopuncture group, the suppression of MIF, TNF-${\alpha}$, COX-2 in synovial membrane was clearly shown comparing with CIA-elicitated group's change. Conclusions : It might be suggested that SWH pharmacopuncture mitigate tissue damage originated from rheumatoid arthritis by suppressing the expression of COX-2 as a consequence of inhibition MIF activation.