• Title/Summary/Keyword: 억제인자

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Population Pharmacokinetics of Cyclosporine after Hematopoietic Stem Cell Transplantation in Leukemic Patients (조혈모세포이식을 받은 한국 성인 백혈병환자에서 cyclosporine의 집단약동학 분석)

  • Kim, Seung-Hee;Kim, Kyung-Im;Yun, Hwi-yeol;Kang, Won-Ku;Yoon, Sung-Soo;Shin, Wan-Gyoon;Lee, Hye-Suk;Oh, Jung-Mi
    • Korean Journal of Clinical Pharmacy
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    • v.20 no.1
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    • pp.9-16
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    • 2010
  • Purpose: 본 연구는 한국인 성인 조혈모세포이식환자를 대상으로 경구용 사이클로스포린의 집단약동학 분석을 통하여 사이클로스포린의 약동학적 파라미터에 영향을 미치는 요인 분석을 실시하고자 하였다. Methods: 2000년 12월부터 2006년 8월까지 서울대학교병원에서 동종조혈모세포이식을 받고 면역억제제로 사이클로스포린을 복용한 성인 백혈병환자를 대상으로 후향적으로 자료를 수집하였다. 사이클로스포린의 약동학에 영향을 미치는 인자로는 연령, 성별, 이식 후 날짜, 신기능, 공여자와의 관계, 질병의 종류, 혈중 빌리루빈 농도, 사이클로스포린의 대사를 유도하는 프레드니솔론의 투여량, 헤마토크리트, 사이클로스포린의 대사를 저해하는 약물의 병용여부 등을 검토하였다. 분석은 NONMEM$^{(R)}$ VI 프로그램을 이용하였으며, 변수를 추가하지 않은 기본 모형을 만든 후에 단계적인 요인의 추가와 제거를 통해 최종모형을 제작하였다. Results: 최종 상관 모형은 다음과 같다; CL/F (L/h) = $85.6{\times}e^{(0.646\;{\times}\;HCT/28.9\;+\;0.0464\;{\times}\;Gender)}$. 사이클로스포린의 겉보기 클리어런스는 환자의 성별이 남자일 때 또는 헤마토크릿이 감소할수록 증가하였다. 그 외 파라미터는 다음과 같이 계산되었다; $K_{\alpha}=0.0787\;(h^{-1})$; Q=57.1(L/kg/h); $V_{d-central\;compartment}$=1,100 (L); $V_{d-peripheral\;compartment}$ = 213,000(L). 개체간 편차는 40% 미만이었으며, 개체내 편차를 포함하는 잔차는 24.02%였다. Conclusions: 사이클로스포린의 약동학적 특징과 그 클리어런스에 영향을 끼칠 수 있는 임상적 요인을 이해하는 것은 환자 개개인의 용량과 용법의 결정 및 이상반응 발생의 예방에 유용할 수 있다. 한국인 조혈모세포이식환자에서 사이클로스포린의 약동학에 영향을 미치는 최종 파라미터를 구한 본 연구의 결과는 조혈모세포이식을 받은 한국인 성인환자에서 사이클로스포린의 모니터링 및 용량조절에 유용할 것으로 전망된다.

Short-term Nutrient Enrichment Bioassays (NEBs) by Manipulation of TN:TP Ratios and the Response of Primary Productivity (as Chlorophyll-a) (N:P Ratio 조절에 의한 단기 영양염 첨가 바이오에세이(NEBs) 및 1차 생산력(엽록소-a)의 반응성 테스트)

  • Jeong, Da-Bin;An, Kwang-Guk
    • Korean Journal of Environmental Biology
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    • v.31 no.4
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    • pp.383-392
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    • 2013
  • The objective of this study was to determine the effects of N:P ratio on primary productivity measured as chlorophyll-a (CHL) using the approach of In Situ Nutrient Enrichment Bioassays (NEBs) in Daechung Reservoir. The effects of NEBs on the N:P mass ratios were compared with the field data obtained from monthly-chemical monitoring during 2009~2012. The short-term NEBs showed that the response of primary productivity in the phosphorus spiked treatments (5, 15, 20 and 30 N:P ratios) were greater than the responses in the control (C) and nitrogen spiked treatment (N:P ratio=150, $T_{VI}$). The response in the nitrogen treatment (N:P ratio=150, $T_{VI}$) was less compared to control and all five treatments ($T_I{\sim}T_{VI}$). The outcomes of the NEBs suggest that phosphorus limited the phytoplankton growth and nitrogen addition inhibited the algal growth. In the analysis of nutrients and CHL from the ambient epilimnetic water in Daechung Reservoir, minimum N:P ratios resulted in maximum concentrations of CHL. Overall, our results suggest that the N:P ratio was the key factor in regulating the phytoplankton growth in NEB experiments.

Preventive effect of fermented red ginseng on cisplatin-induced nephrotoxicity mouse (Cisplatin으로 유도된 신손상 마우스 모델에 대한 발효홍삼의 예방효능)

  • Hyun, Ja-Kyoung;Kwon, O Jun;Lee, Joo Young;Roh, Seong-Soo;Seo, Young-Bae
    • Journal of Applied Biological Chemistry
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    • v.59 no.2
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    • pp.113-124
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    • 2016
  • Red ginseng is known to have many beneficial effects. Cisplatin, an effective antineoplastic drug, can cause many side effects like irreversible sensorineural hearing loss and serious tinnitus in humans. This study is aimed to reduce a cisplatin's side effect, nephrotoxicity by fermentated korean red ginseng. Korea ginseng was produced by steaming and dring and fermentation. And mice were divided into 4 groups- (A) normal mice, (B) Vehicle treated cisplatin mice, (C) RG0F0-treated cisplatin mice, (D) RG8F3-treated cisplatin mice. C and D groups were feed each material 200 mg/kg/day during 4 days. And cisplatin 20 mg/kg injected to B, C, and D groups as abdominal injection. After 24 h, blood sample was collected. The kidneys were harvested for histological, immuno histochemical and western blot analysis. 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity was depended on steaming hours. RG0F0 and RG8F3 (ginseng-8 h steamed and fermented by Saccharomyces cerevisiae) were showed antioxidants effect in DPPH and ABTS radical scavenging activity. Component amounts according to steaming hours. 8 h steamed red ginseng had the most ingredients of ginsenoside. Treatments with RG8F3 reduced cisplatin-induced nephrotoxicity in the mice resulting in increase of GSH and decrease of ROS, BUN, creatinine, and inflammatory mediators. This result seems to be involved with the restriction of the inflammation in the kidney. Therefore, fermented red ginseng might have therapeutic efficacy in reduce kidney injury induced by cisplatin treatment.

A Study on the Stretch-flangeability of Hot-Rolled High Strength Steel with Ferrite-Bainite Duplex Microstructure (페라이트-베이나이트 복합조직 고강도 열연강판의 신장플랜지 특성에 관한 연구)

  • Cho, Yeol-Rae;Chung, Jin-Hwan;Koo, Hwang-Hoe;Kim, In-Bae
    • Korean Journal of Materials Research
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    • v.9 no.12
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    • pp.1252-1262
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    • 1999
  • The effect of microstructures on the strength-flangeability of Nb bearing hot-rolled high strength steel was investigated in order to improve the strength-flangeability of conventional TS 580MPa grades HSLA steel for the automotive wheel disc. The low temperature coiling method using 3-step controlled cooling pattern after hot rolling was effective to produce the Nb-bearing high strength steel with the polygonal ferrite and bainite duplex microstructures. It was suggested that the suppressed precipitation of grain boundary cementites and the decreased hardness difference between ferrite matrix and bainite cause the excellent stretch-flangeability of ferrite-bainite duplex microstructure steel. Therefore, the formation and propagation of microcracks were suppressed relative to the conventional HSLA steel with ferrite and pearlite microstructure. In addition, the elongation was improved as compared with that of hot-rolled steel sheets using conventional early cooling pattern because the volume fraction of polygonal ferrite was increased.

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Cnestis palala (Lour.) Merr. extract suppresses Propionibacterium acnes-induced inflammation (Propionibacterium acnes에 의해 유도되는 염증반응에서 Cnestis palala (Lour.) Merr. 추출물의 억제효과)

  • Shin, Jin Hak;Lee, Eun Hye;Kim, Seon Sook;Sydara, Kongmany;Seo, Su Ryeon
    • Korean Journal of Microbiology
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    • v.54 no.1
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    • pp.38-45
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    • 2018
  • Acne is an inflammatory skin disease that occurs in puberty and young people. Propionibacterium acnes (P. acnes) is known to be a major cause of inflammation in acne. P. acnes proliferates within hair follicles blocked by overproduced sebum in the skin, and thereby activates monocytic cells to promote the secretion of pro-inflammatory cytokines. In this study, we investigated the possibility of Cnestis palala (Lour.) Merr. extract to diminish P. acnes-mediated inflammatory responses. We found that C. palala extract significantly attenuated P. acnes-induced pro-inflammatory cytokine expressions, such as $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, iNOS, and COX-2 in mouse macrophage RAW264.7 cells. Moreover, we observed that C. palala extract inhibited $NF-{\kappa}B$ transcriptional activation, which is the major transcription factor of inflammatory cytokine expression. Therefore, it is expected that C. palala extract has a potential as a therapeutic agent or supplement for the treatment P. acnes-induced inflammatory responses.

Hitological Changes on the Wound Healing Process of Alkali Burned Mouse Cornea (알칼리 화상을 입은 마우스 각막에서 상처 치유과정 중 관찰된 조직학적 변화)

  • Lee, Ji-Young;Lee, Koon-Ja
    • Journal of Korean Ophthalmic Optics Society
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    • v.13 no.4
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    • pp.161-169
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    • 2008
  • Purpose: To better understand the corneal regeneration after alkali burn regarding the initial clinical progression and the therapy, we investigated the changes of the multi factors following chemical injury in cornea. Methods: This study was performed to observation on the healing process of alkali burned cornea in aspect of immunohistochemistry by immunofluorescence or H-E staining and TUNEL assay. Results: The results showed that although a healing process occurred after alkali burn, apoptosis of epithelial, stromal and endothelial cells in the cornea was continuously observed. Neovascularization and expression of ${\alpha}$-smooth muscle actin (${\alpha}$-SMA) from limbus and from injured cornea, respectively, were observed after 3 days of alkali burn. Formation of collagen III in corneal stroma and increased expression of chondroitin sulfate are coincident with expression of ${\alpha}$-SMA and transforming growth factor-${\beta}$ (TGF-${\beta}$). Conclusions: These data suggest that medical treatment within 3 days of alkali burn will be effective to inhibit neovascularization and formation of collagen III and chondroitin sulfate. This study extends our immumohistochemical understanding of healing process in alkali burned cornea, and the results get in this study will be cornerstones in the development of therapeutic agent for accelerating renewal of chemical damaged cornea.

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Water Extract of Allium sativum L. Induces Apoptosis in Human Leukemia U937 Cells through Reactive Oxygen Species Generation (마늘 열수 추출물의 활성산소종 생성을 통한 인체백혈병세포의 apoptosis 유발)

  • Choi, Woo-Young;Chung, Kyung-Tae;Yoon, Tae-Kyung;Choi, Byung-Tae;Lee, Yong-Tae;Lee, Won-Ho;Ryu, Chung-Ho;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.17 no.12
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    • pp.1709-1716
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    • 2007
  • The health benefits of garlic (Allium sativum L.) are derived from a wide variety of components and from the different ways it is administered. The known health benefits of garlic include cardiovascular protective effects, stimulation of immune function, reduction of blood glucose level, protection against microbial, viral and fungal infections, as well as anticancer effects. In the present study, it was examined the effects of water extract of A. sativum (WEAS) on the growth of cultured human tumor cells in order to investigate its anti-proliferative mechanism. Treatment of WEAS to tumor cells resulted in the growth inhibition, especially in leukemia cells, which was associated with induction of G2/M arrest of the cell cycle and apoptosis. In order to further explore the critical events leading to apoptosis in WEAS-treated U937 human leukemia cells, the following effects of WEAS on components of the mitochondrial apoptotic pathway were examined: generation of reactive oxygen species (ROS), alteration of the mitochondrial membrane potential (MMP), and the expression changes of Bcl-2 and IAP family proteins. The cytotoxic effect of WEAS was mediated by its induction of apoptosis as characterized by the occurrence of DNA ladders, apoptotic bodies and chromosome condensation in U937 cells. The WEAS-induced apoptosis in U937 cells was correlated with the generation of intracellular ROS, collapse of MMP, activation of caspase-3 and down-regulation of anti-apoptotic proteins. The quenching of ROS generation with antioxidant N-acetyl-L-cysteine conferred significant protection against WEAS-elicited ROS generation, caspase-3 activation, G2/M arrest and apoptosis. In conclusion, the present study reveals that the cellular ROS generation plays a pivotal role in the initiation of WEAS-triggered apoptotic death in U937 cells.

Effect of Sodium Butyrate on Blood Glucose, Serum Lipid Profile and Inflammation in Streptozotocin-induced Diabetic Mice (스트렙토조토신으로 유도한 당뇨마우스에서 Sodium Butyrate의 혈당, 혈청 지질 성상 및 염증 억제에 미치는 영향)

  • Yun, Jung-Mi
    • The Korean Journal of Food And Nutrition
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    • v.28 no.2
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    • pp.171-177
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    • 2015
  • Sodium butyrate is a short-chain fatty acid derivative found in foods, such as Parmesan cheese and butter and is produced by anaerobic bacteria fermentation of dietary fibers in the large intestine. There have been reports that butyrate prevented obesity, protected insulin sensitivity, and ameliorated dyslipidemia in dietary obese mice. This study investigated the effects of sodium butyrate on fasting blood glucose level and serum lipid profile in streptozotocin(STZ)-induced diabetic mice. Male C57BL/6 mice were fed AIN-93G for four weeks prior to intraperitoneal injections with STZ (100 mg/kg body weight). Diabetic mice had supplements of 5% sodium butyrate for four weeks. The 5% sodium butyrate diet significantly improved fasting blood glucose level and lipid profile in STZ-induced diabetic mice. Inflammation has been recognized to decrease beta cell insulin secretion and increase insulin resistance. Circulating cytokines can directly affect beta cell function, leading to secretory dysfunction and increased apoptosis. Thus, anti-inflammatory therapies represented a potential approach for the therapy of diabetes and its complications. In this animal study, the 5% sodium butyrate supplementation also inhibited inflammatory cytokine production in STZ-induced diabetic mice. These results suggested that sodium butyrate can be a potential candidate for the prevention of diabetes and its complications.

Sex-Hormone Replacement Effect of Silkworm Pupa and Mixture with Herbs (미성숙 흰쥐에서 누에 번데기 및 한약재 혼합물의 여성호르몬 대체효과)

  • Yang Ji-Won;Choi Eun-Mi;Kwon Mu-Gil;Koo Sung-Ja
    • Korean journal of food and cookery science
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    • v.21 no.6 s.90
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    • pp.769-775
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    • 2005
  • In this study we isolate substances to serve as dietary resources in order to replace the female hormone. Silkworm (Bombyx mori) is one of the most attractive hosts for large-scale production of eukaryotic proteins which have been proven safe as a dietary resource. We report on the estrogenicity of a mixture of silkworm pupa and herbs (Ginseng,Ulkeum, and Hasuo) using the immature rat uterotrophic assay in vivo. Silkworm pupa aqueousextract (KW) and silkworm oil extract (KO) induced effects on the immature rat uterotrophic assay. KO showed neither positive uterotrophic response nor inhibition on E2 induced effect, while KW and MK (mixture of KW and herbs) showed both of the effects. It is concluded that ethanol extracts from silkworm might be a good, therapeutic, natural product for hormone-deficient diseases.

An Experimental Study on the Fundamental Characteristics of LPG Gas Injections System (LPG 가스분사시스템의 기초특성에 대한 실험적 연구)

  • Jang, Yeol-Sung;Woo, Sung-Dong;Kim, Hyeong-Sig;Park, Chan-Jun;Ohm, In-Yong
    • Journal of Energy Engineering
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    • v.15 no.4 s.48
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    • pp.277-283
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    • 2006
  • In this study, butane 100% was used as fuel to verify the real fuel effect such as vapor pressure variation due to temperature change. A MPI fuel injection system for V-6 engine, which has reverse 'L' type cross section to minimize the possibility of liquid phase injection, was composed and one bank was operated under sequential injection scheme. Flow rate were measured according to injection duration, interval, and pressure. Also occurring of liquid phase injection was monitored with varying vaporizer and fuel rail temperature. The result shows that basic characteristics of injection is a relatively difference between air and LPG injection. Under cold start condition, however, the occurrence of liquid injection becomes more severe as the pressure increases, and sufficiently high temperature both in vaporizer and fuel rail is very important to insure gaseous injection. In addition, the temperature of vaporizer plays more important role in keeping LPG vapor state and the reverse 'L' type cross section of the rail is available to prevent liquid injection.