• Archives of Pharmacal Research
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• 제26권7호
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• pp.545-553
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• 2003

The expression of cyclooxygenase-2 (COX-2) is a characteristic response to inflammation, which can be inhibited with sodium salicylate. IL-1$\beta$ and TNF-$\alpha$ can induce extracellular signal-regulated kinase (ERK), IKK, IkB degradation and NF-$\kappa$B activation. Salicylate inhibited the IL-1$\beta$ and TNF-$\alpha$-induced COX-2 expressions, regulated the activation of ERK, IKK and IkB degradation, and the subsequent activation of NF-$\kappa$B, in neonatal rat ventricular cardiomyocytes. The inhibition of the ERK pathway, with a selective inhibitor, PD098059, blocked the expressions of IL-1$\beta$ and TNF-$\alpha$-induced COX-2 and $PGE_2$ release. The antioxidant, N-acetyl-cysteine, also reduced the glutathione or catalase- attenuated COX-2 expressions in IL-1$\beta$ and TNF-$\alpha$-treated cells. This antioxidant also inhibited the activation of ERK and NF-$\kappa$B in neonatal rat cardiomyocytes. In addition, IL-1$\beta$ and TNF-$\alpha$-stimulated the release of reactive oxygen species (ROS) in the cardiomyocytes. However, salicylate had no inhibitory effect on the release of ROS in the DCFDA assay. The results showed that salicylate inhibited the activation of ERK and IKK, I$\kappa$B degradation and NF-$\kappa$B activation, independently of the release of ROS, which suggested that salicylate exerts its anti-inflammatory action through the inhibition of ERK, IKK, IkB and NF-$\kappa$B, and the resultant COX-2 expression pathway in neonatal rat ventricular cardiomyocytes.

• 대한한의학회지
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• 제25권3호
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• pp.149-159
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• 2004

Backgrounds & Objectives : The water extract of Gyungokgo (GOG) has traditionally been used for treatment of general weakness and hemoptysis in oriental medicine. However, little is known about the mechanism by which the water extract of GOG rescues cells from these damages. This study was designed to investigate the protective mechanisms of GOG on H2O2­induced cell death in H9c2 cardiomyoblasts. Methods : In this study, we used H9c2 cells. Cells were treated with oxidative stress in the absence and presence of 1000㎍/ml GOG for 12hrs. Cells were treated with various concentrations of GOG for 12hrs. Cell viability was measured by MTT assay. Oxidative stress, which markedly decreased the viability of H9c2 cells, was characterized by apparent apoptotic features such as chromatin condensation as well as fragmentation of genomic DNA and nuclei. Results : GOG significantly reduced H₂O₂-induced cell death and apoptotic characteristics. The cotreatment of GOG and H₂O₂ in H9c2 cells also induced the phosphorylation of ERKs in a time-dependent manner. Moreover, PD098059, a MEK1 (upstream activator of ERK) inhibitor attenuated the protective effect of GOG on H₂O₂-induced cytotoxicity in H9c2 cardiomyoblast cells. Conclusions : These results suggest that MEK/ERK pathways play important roles in the protective effects of GOG in H9c2 cells. Taken together, they suggest that the protective effects of the water extracts of GOG against oxidative damages may be mediated by the regulation of HO-1, Fas/FasL and Bcl-XS proteins.

• 한국자원식물학회지
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• 제31권4호
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• pp.363-371
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• 2018

헐떡이풀은 우리나라에서 울릉도에서만 분포하는 자생식물로 전통적으로 약용으로 쓰여왔으며, 관상식물로의 활용도 기대되는 자원식물이다. 본 연구는 헐떡이풀 종자의 휴면타파와 발아를 위한 조건을 확립하고 종자휴면 유형을 분류하고자 수행되었다. 실험은 헐떡이풀 종자에 저온층적처리($5^{\circ}C$에서 0, 12주)와 고온층적처리($23^{\circ}C$에서 0, 4, 8, 12주 처리 후에 $5^{\circ}C$에서 8주, 다시 $23^{\circ}C$에서 배양함), $GA_3$ (0, 10, 100, 1000 mg/L)처리를 수행하였다. 이렇게 처리한 종자는 무균배지에 소독하여 파종하고 온도 $23^{\circ}C$, 광도 $40{\mu}mo{\ell}{\cdot}m^{-2}{\cdot}s^{-1}$ PPFD, 일장16시간 조건의 배양실에서 배양하였다. 헐떡이풀 종자는 자연상태에서 미숙배인 상태로 탈리되며, 종자 내부로의 수분흡수에 대한 물리적인 장벽은 없었다. 그러나 아무 처리 없이 파종하였을 때 30일이 지나도록 전혀 발아하지 않았다. 따라서 헐떡이풀 종자는 형태적 휴면(MD)과 생리적 휴면(PD)을 가지고 있는 것으로 판단하였다. 저온층적처리(0, 12주) 실험의 최종 발아율은 각각 66.7%, 45.6%로 나타났다. 저온처리는 오히려 발아를 약 3주 정도 지연시켰다. 고온층적처리(0, 4, 8, 12주) 실험에서는 최종 발아율이 각각 13.3%, 24.4%, 20.0%, 51.1%로 나타났다. 헐떡이풀 종자의 배는 상대적 고온에서 발달하였다. $GA_3$ 처리는 종자의 휴면을 극복하고 발아를 촉진하였다. $GA_3$ 처리에서의 최종 발아율은 0, 10, 100, 1000 mg/L 처리구에 대하여 각각 33.3%, 45.0%, 42.5%, 72.5%로 나타났다. 위의 결과를 종합하여 헐떡이풀 종자는 non-deep simple 형태생리적 휴면(MPD)을 가지고 있으며, $GA_3$ 처리를 통해 고온을 대체하고 종자의 휴면을 타파할 수 있었다. 이는 한국에 자생하는 헐떡이풀속의 종자휴면에 대해 처음으로 보고한 논문이다.

• 한국미생물·생명공학회지
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• 제42권2호
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• pp.194-201
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• 2014

본 연구에서는 국내 자생버섯의 일종인 Clitocybe aurantiaca KCTC11143BP 균주가 생산하는 주름개선 화장품 신소재 clitocybin A의 발효생산 최적조건, 추출정제조건, 세포독성 및 자외선 조사에 따른 MMP-1 발현 저해활성을 규명하였다. C. aurantiaca 균주를 5 L 발효조를 이용하여 회분식으로 배양하였을 경우, PD 액체배지보다 YM 액체배지에서 양호하게 생육하는 것을 확인하였다. 300 L 용량의 대형 발효조에서 modified된 YM 배지를 이용한 유가식 배양으로 14일간 배양한 결과, 12.5 kg/120 L의 총 균체량을 얻었다. 발효 추출물로부터 항노화 소재인 clitocybin A를 추출정제를 한 후 HPLC를 실시하여 배양 4일째부터 clitocybin A가 생산되고 있음을 확인하였다. Clitocybin A 화합물의 세포독성을 확인하기 위하여 MTT assay를 실시한 결과, 100 ${\mu}g/ml$ 농도로 처리하였을 경우 $134.6{\pm}10.4%$로 오히려 세포가 증식하여 안전한 소재임을 확인하였다. 반면, 대조군으로 사용한 oleanolic acid는 25 ${\mu}g/ml$ 농도에서도 강한 세포독성을 나타냈다. 또한, clitocybin A는 100 ${\mu}g/ml$ 처리시 33.1%의 MMP-1 발현 저해활성 보여 주름개선 기능성화장품 소재로 매우 우수한 화합물임을 확인하였다.

• Asian-Australasian Journal of Animal Sciences
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• 제10권4호
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• pp.364-370
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• 1997

Four local cattle were ($145{\pm}9.7kg$) used in a $4{\times}4$ Latin square design to study the effect of different levels of rumen degradable protein (RDP) in straw based ration on purine derivatives excretion and microbial N supply in cattle. The four rations were formulated at the same amount of energy but varying RDP approximately 50 (U0), 75 (U1), 100 (U2) and 150 (U3) percent levels of RDP requirement for maintenance. They were fed ranged from 101 to 304 g RDP/d. Apparent digestibility of all nutrients increased significantly (p < 0.01) in cattle fed ration U2 than other rations. Rumen $NH_3-N$ concentration increased from 43 to 130 mg/l in response of RDP intake. Purine derivatives excretion increased significantly (p < 0.01) with incremental level of 203 g RDP/d (U2) intake and positively correlated (r=0.69, p < 0.01, n=16) with amount of RDP intake. The rates of rumen microbial N supply were 16.8, 27.2, 39.1 and 32.9 g/d for rations U0, U1, U2 and U3 respectively. Efficiency of microbial N supply (EMNS) per kg of DOMR were 19.0, 25.3, 33.0, and 28.6 g and per MJ of ME. Intake were 0.62, 1.00, 1.44 and 1.21 g for U0, U1, U2 and U3 respectively and highest results were obtained in cattle fed U2 ration. Results of this study suggest that PD excretion and EMNS were increased as incremental level of RDP intake (U2) in local cattle.

• 동의신경정신과학회지
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• 제3권2호
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• pp.87-96
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• 1992

In order to see the variation of human nature, M.M.P.I. was carried on 2, April 1992 (the last day of the second lunar month) and 15, June 1992 (the fifteenth day of the fifth lunar month). These experiments took male and female students who were in Won kwang University as subjects (108 students on 2, April, 105 students on 15, June). The results of it suggested the followings. 1) Every students' average of T-grades on each measure were in a normal scope. 2) There were no significant differences in comparison between the fifteenth day and the last day of the month. 3) On every measure except L, Mf, Si, the female students showed higher grade in the fifteenth day than the last day of the month. But there was no significant difference in male students. Both male and female students didn't show the significant one. 4) On the fifteenth day of the month, the female students showed higher T-grade then male did on every measure except Mf, Ma, Si. There was a significant difference on D, Pd, Mf(P<0.05) measure. 5) On the last day of the month, male students showed higher T-grade then female did on every measure except L, K, Hy, Pt. There was a significant difference on L(P<0.001), K(P<0.01). 6) On experiments about female students, there was no symptom of neurosis and psychosis on the last day of the month. But three of sixteen students(18.7%) showed symptom of neurosis, one of thirteen(6%) showed symptom of psychosis on the fifteenth day of the month. On experiments about male students, eleven of ninety-two(11.9%), four of ninety-two(4.3%) showed symptom of neurosis and psychosis respectively on the fifteenth day of the month. Ten of ninety-two(10.8%), six of ninety-two(6.5%) showed symptom of neurosis and psychosis respectively on the last day of the month. As the results of the above, human nature changes to some extend according to lunar cycle. And there are many changes in female than male. But it is difficult to generalize this fact by limited subject and only one experiments. So the controlled studies are needed on the basis of this result and have to take many person as a subject.

• Clinical and Experimental Pediatrics
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• 제50권12호
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• pp.1200-1205
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• 2007

목 적 : SRT는 주로 RDS이 있는 미숙아에서 시행되어 왔다. 저자들은 폐질환을 주소로 인공 환기 요법이 필요했던 재태 주령 36주 이상의 신생아에서 폐표면 활성제를 이용한 보충요법의 투여 성적를 알아보고자 본 연구를 시행하였다. 방 법 : 1999년 7월부터 2004년 6월까지 계명대학교 동산의료원 신생아 집중치료실에 입원한 후 폐질환을 주소로 인공 환기 요법을 받았던 재태 주령 36주 이상의 환아 중 SRT를 시행 받았던 48명의 환아를 대상으로 원인 질환에 따라 MAP군과 RDS군 그리고 PN군으로 나누어서 후향적으로 의무기록을 분석하였다. 모든 대상 환아들에서 SRT를 시행하였으며 폐표면 활성제(Newfacten: 유한양행, Seoul, Korea)는 120 mg을 생리식염수 2-4 mL에 용해하여 평균 120 mg/kg 용량으로 투여하였는데, RDS 군에서는 투여 6시간 후에도 임상적 호전이 미약할 때는 1회 더 투여하였다. 각 군에서 폐표면 활성제 사용 전 후의 임상지표(흡입 산소 농도 및 산소화 지수)와 폐표면 활성제 투여 시점으로부터의 총 인공 환기기 사용 및 산소 투여 기간을 알아보았으며 성적(합병증 및 생존율)를 분석하였다. 결 과 : 총 48례의 환아 중 MAP 군: 15명, RDS 군: 27명, PN 군: 6명 이었다. 폐표면 활성제 투여 전의 산소화 지수는 MAP 군이 $21.8{\pm}3.2$, RDS 군에서 $18.3{\pm}4.5$, PD 군에서 $18.6{\pm}6.0$였고, SRT 후 12시간째의 산소화 지수는 MAP 군이 $8.61{\pm}6.75$, RDS 군에서 $4.98{\pm}0.69$, PD 군에서 $5.8{\pm}1.19$로 통계적으로 유의하게 개선되었다(P<0.05). 총 인공 환기기 사용기간은 MAP 군이 $4.9{\pm}1.2$일, RDS 군이 $5.5{\pm}2.8$일, PN 군이 $7.2{\pm}4.8$일 이었고 산소 투여기간은 MAP 군이$9.4{\pm}1.7$일, RDS 군이 $8.8{\pm}3.5$일, PN 군이 $10.3{\pm}5.6$일 이었다. 기흉, 신생아 폐 고혈압 지속증 등의 합병증 발생은 MAP 군에서 20%, RDS 군에서 25.9%, PD 군에서 50%로 나타났으며, 이중 RDS 군에서 SRT를 처음 시행한 시간에 따른 합병증의 발생 정도는 생후 12시간 전에 시행한 경우의 발생률이 15례 중 2례(13.3%)로 12시간 이후에 시행한 경우의 12례 중 7례(58.3%) 보다 유의하게 낮았다(P<0.05). 생존율은 MAP 군이 86.7%, RDS군과 PN 군이 모두 100%로 모든 군에서 양호한 예후를 보였다. 결 론 : 중증 폐 질환을 주소로 인공 환기 요법이 필요한 임신기간 36주 이상의 준 만삭 이상아에서의 폐표면 활성제 보충요법은 좋은 임상경과를 가지며 특히 RDS인 경우 생후 12시간 내 투여가 합병증을 줄여서 치료성적의 향상에 도움이 될 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제19권2호
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• pp.99-104
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• 2015

The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intra-abdominal infected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profiles in various tissues in intra-abdominal infected human. 12 male rats with intra- abdominal infections, induced by Escherichia coli, received a single dose of 40 mg/kg body weight of moxifloxacin. Blood plasma was collected at 5, 10, 20, 30, 60, 120, 240, 480, 1440 min after drug injection. A PBPK model was developed in rats and extrapolated to human using GastroPlus software. The predictions were assessed by comparing predictions and observations. In the plasma concentration versus time profile of moxifloxcinin rats, $C_{max}$ was $11.151{\mu}g/mL$ at 5 min after the intravenous injection and $t_{1/2}$ was 2.936 h. Plasma concentration and kinetics in human were predicted and compared with observed datas. Moxifloxacin penetrated and accumulated with high concentrations in redmarrow, lung, skin, heart, liver, kidney, spleen, muscle tissues in human with intra-abdominal infection. The predicted tissue to plasma concentration ratios in abdominal viscera were between 1.1 and 2.2. When rat plasma concentrations were known, extrapolation of a PBPK model was a method to predict drug pharmacokinetics and penetration in human. Moxifloxacin has a good penetration into liver, kidney, spleen, as well as other tissues in intra-abdominal infected human. Close monitoring are necessary when using moxifloxacin due to its high concentration distribution. This pathological model extrapolation may provide reference to the PK/PD study of antibacterial agents.

• Biomolecules & Therapeutics
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• 제16권2호
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• pp.126-131
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• 2008

Immunosuppressive therapy after organ transplantation is routinely used to prevent rejection of the organ, because this decreases the risk of adverse events, infection, and malignancies. Recently, ursodeoxycholic acid (UDCA), which is isolated from the dried bile of adult Chinese bears, has been shown to reduce the incidence and severity of acute rejection of liver allograft during early phase of liver transplantation. Therefore, in this study, we investigated the effect of UDCA on the proliferation of splenocytes exposed to PMA plus ionomycin. Our results demonstrated that UDCA decreased the splenocytes' proliferation in a dose-dependent manner. The decreased cell proliferation was accompanied with the decreased secretion of cytokines such as IL-2, IFN-${\gamma}$ and TNF-${\alpha}$. In addition, the pretreatment of UDCA on splenocytes stimulated with PMA plus ionomycin decreased the mRNA levels of cytokines (IL-2, IFN-${\gamma}$ and TNF-${\alpha}$) and costimulatory molecules (B7.2 and PD-L1). These results suggest the beneficial effect of UDCA on organ transplantation by decreasing lymphocyte proliferation.

• Archives of Pharmacal Research
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• 제27권3호
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• pp.324-333
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• 2004

To determine whether Insulin-like growth factor (IGF-I) treatment represents a potential means of enhancing the survival of cardiac muscle cells from adriamycin (ADR)-induced cell death, the present study examined the ability of IGF-I to prevent cell death. The study was performed utilising the embryonic, rat, cardiac muscle cell line, H9C2. Incubating cardiac muscle cells in the presence of adriamycin increased cell death, as determined by MTT assay and annexin V-positive cell number. The addition of 100 ng/mL IGF-I, in the presence of adriamycin, decreased apoptosis. The effect of IGF-I on phosphorylation of PI, a substrate of phosphatidylinositol 3-kinase (PI 3-kinase) or protein kinase B (AKT), was also examined in H9C2 cardiac muscle cells. IGF-I increased the phosphorylation of ERK 1 and 2 and $PKC{\;}{\zeta}{\;}kinase$. The use of inhibitors of PI 3-kinase (LY 294002), in the cell death assay, demonstrated partial abrogation of the protective effect of IGF-I. The MEK1 inhibitor-PD098059 and the PKC inhibitor-chelerythrine exhibited no effect on IGF-1-induced cell protection. In the regulatory subunit of PI3K-p85- dominant, negative plasmid-transfected cells, the IGF-1-induced protective effect was reversed. This data demonstrates that IGF-I protects cardiac muscle cells from ADR-induced cell death. Although IGF-I activates several signaling pathways that contribute to its protective effect in other cell types, only activation of PI 3-kinase contributes to this effect in H9C2 cardiac muscle cells.