• 제목/요약/키워드: Dose-rate effects

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Gene Expression Profiles and Antioxidant Effects of Houttuynia cordata Thunb Extract in Human Keratinocyte HaCaT Cells (인간 피부각질세포 HaCaT에서 어성초 추출물의 유전체 발현 분석 및 항산화 효과)

  • Kim, Jung Min;Bang, In Seok
    • Journal of Life Science
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    • v.28 no.12
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    • pp.1406-1415
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    • 2018
  • Based on the antioxidative effects in organic solvent fractions obtained from the main methanolic extract of Houttuynia cordata Thunb, the cytoprotective effects by oxidative-stress were here analyzed. Regarding the antioxidant activity of organic solvent fractions, the electron-donating ability of DPPH increased in a dose-dependent manner, and $ED_{50}$ exhibited the highest concentration at $175{\mu}g/ml$ in the Hc-EtOAc fraction. The cell viability of Hc-EtOAc fractions on $H_2O_2$-induced HaCaT cell death ($IC_{50}$) increased in a concentration-dependent manner and a visible cell survival rate of 74% was observed at a concentration of $100{\mu}g/ml$. Meanwhile, the gene expression patterns in HaCaT cells treated with $100{\mu}g/ml$ of the Hc-EtOAc fraction for 6 and 24 hr were identified with microarray analysis. The genes involved in signal transduction, cell division, antioxidant activity, and epithelial cell proliferation were found to be 2-fold up-regulated genes in HaCaT cells following the Hc-EtOAc fraction treatment. Especially, proinflammatory cytokines (IL1B, TNF, and IL6) were identified as involved in antioxidant activity based on the expression patterns of the HaCaT cells, and pathway analysis indicated that TLR4 might be considered an upstream regulator of these genes. In order to verify the activity of IL1B, TNF, and IL6, qRT-PCR showed that the expression increased more than 2 times in HaCaT cells treated with at least $100{\mu}g/ml$ of the Hc-EtOAc fraction. The activity of the upstream regulator TLR4 protein was also increased by the Hc-EtOAc fraction. As a result, the antioxidative activity of the Hc-EtOAc fraction is predicted to pass from TLR4 through cytokines such as IL1B, TNF, and IL6.

Clinical Efficacy of Belotecan (CKD-602), Newly Developed Camptothecin Analog, in the 2nd Line Treatment of Relapsed Small Cell Lung Cancer (재발된 소세포폐암환자에서 이차 약제로 사용되는 Belotecan (CKD-602)의 임상적 효용성)

  • Ban, Hee-Jung;Oh, In-Jae;Kim, Kyu-Sik;Ju, Jin-Yung;Kwon, Yong-Soo;Kim, Yu-Il;Lim, Sung-Chul;Kim, Young-Chul
    • Tuberculosis and Respiratory Diseases
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    • v.66 no.2
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    • pp.93-97
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    • 2009
  • Background: Belotecan (Camtobell, CKD-602, Chongkundang Pharm., Korea), a camptothecin derivative, has anticancer effects by inhibiting topoisomerase I such as topotecan. This study observed the response, survival and toxicity of belotecan monotherapy after the failure of etoposide and platinum (EP). Methods: Forty nine small cell lung cancer (SCLC) patients (M/F=41/8; age, 64.5${\pm}$7.6 (mean${\pm}$SD) years), who failed in their first line chemotherapy were enrolled in this study. Twenty one SCLC patients showed relapsed lung cancer more than 90 days after their priorEP chemotherapy (sensitive relapse group, SR) and 28 patients relapsed within 90 days (refractory relapse group, RR). Results: The response rate was 25%. Eleven patients showed partial responses and 5 patients could not be checked. The response rate of the SR and RR patients was similar. The relative dose intensity was lower in the responders (78${\pm}$15%) than non-responders (83${\pm}$13%, p=0.03). The median survival time (MST) was 10.3 months (290 days). The MST of the non-responders and responders was 186 days (95% CI; 67-305) and 401 days (95% CI; 234-568, p=0.07), respectively. The median progression free survival (MPFS) was similar in the SR (79 days) and RR (67 days) patients. Grade 3-4 neutropenia, anemia, and thrombocytopenia were observed in 59.6%, 12.8% and 23.4% of patients, respectively. Conclusion: The efficacy and survival were demonstrated in the second-line setting. However, a randomized comparative trial with topotecan will be needed.

Combined Radiotherapy and Hyperthermia for Nonresectable Hepatocellular Carcinoma (절제 불가능한 원발성 간암의 온열 및 방사선 병용 요법)

  • Seong Jin Sil;Juhn Juhn Kyu;Suh Chang Ok;Kim Gwi Eon;Han Kwang Hyub;Lee Sang In;Roh Jae Kyung;Choi Heung Jai;Kim Byung Soo
    • Radiation Oncology Journal
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    • v.7 no.2
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    • pp.247-257
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    • 1989
  • Thirty patients with nonresectable hepatocellular carcinoma (HCC) due to either locally advanced lesion or association with liver cirrhosis, treated with combined radiotherapy and hyperthermia between April 1988 and July 1988, at Dept. of Radiation Oncology, Yonsei university College of medicine, were analysed. External radiotherapy of a total dose of 3060cGy/3.5 wks was given. Hyperthermia was given twice a week with a total of 6 treatment sessions using 8MHz radiofrequency capacitive type heating device, i.e., Thermotron RF-8 and Cancermia. In all cases hyperthermia was given within 30 minutes after radiotherapy for 30~60min. Temperature was measured by inserting thermocouple into the tumor mass under the ultrasonographic guidance only for those who had not bleeding tendency. As a result, partial response (PR) was achieved in 12 patients (40%), and symptomatic improvement was observed in 22 patients (78.6%) among 28 patients who had suffered from abdominal pain. The most significant factor affecting the tumor response rate was the type of tumor (single massive: 10/14, 71.4%; diffuse infiltrative: 2/10, 20%; multinodular:0/6, 0%; p<0.005). There were not any significant side effects relating to combined treatment. The overall 1 year survival rate was 34%, with 50% in the PR group and 22% in the no response group (NR), respectively. Median survival was 6.5 months and longer for those of PR than of NR (11 mos. vs 5, p<0.05). In conclusion, combined radiotherapy and hyperthermia appeared to be effective in local control and symptomatic palliation of HCC. Further study including a larger number of the patients to confirm its effect in survival and detrimental side effect should be urged.

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Toxic Evaluation of Antifouling Paint (Irgarol and Diuron) using the Population Growth Rate of Marine Diatom, Skeletonema costatum (해산 규조류(Skeletonema costatum)의 개체군 성장률 분석을 이용한 신방오도료(Irgarol, Diuron)의 독성평가)

  • Lee, Ju-Wook;Choi, Hoon;Park, Yun-Ho;Lee, Seung-Min;Choi, Yoon-Seok;Heo, Seung;Hwang, Un-Ki
    • Journal of Marine Life Science
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    • v.5 no.1
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    • pp.9-16
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    • 2020
  • We evaluated the toxic effects of antifouling paint (irgarol and diuron) on the population growth rate (r) of the marine diatom, Skeletonema costatum. The r of S. costatum was determined after 96 hrs of exposure to irgarol (0, 0.31, 0.63, 1.25, 2.5 and 5 ㎍ l-1) and diuron (0, 7.81, 15.63, 31.25, 62.5 and 125 ㎍ l-1). It was observed that r in the control (absence of irgarol and diuron) were greater than 0.04, while r in the treatment groups decreased with increasing irgarol and diuron concentrations. Irgarol and diuron reduced r in a dose-dependent manner with significant decreases occurring at concentrations above 0.63 and 15.63 ㎍ l-1, respectively. The EC50 values of r in irgarol and diuron exposure were 1.09 and 45.45 ㎍ l-1. No observed effect concentration (NOEC) were 0.31 and 7.81 ㎍ l-1, the lowest observed effect concentration (LOEC) were 0.63 and 15.63 ㎍ l-1. This result indicate that a concentration of greater than 0.63 ㎍ l-1 of irgarol and 15.63 ㎍ l-1 of diuron in marine ecosystems induced to decreasing r of S. costatum. Also, these toxic values can be useful as a baseline data for the toxic evaluation of irgarol and diuron in marine ecosystems.

Effect of Heavy Metals (As, Cr, Pb) on the Population Growth Rates of Marine Diatom, Skeletonema castatum (중금속(As, Cr, Pb)이 해산 규조류(Skeletonema costatum)의 개체군 성장률에 미치는 영향)

  • Lee, Ju-Wook;Ryu, Hyang-Mi;Heo, Seung;Jang, Soo-Jung;Lee, Ki-won;Hwang, Un-Ki
    • Journal of Marine Life Science
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    • v.2 no.1
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    • pp.20-26
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    • 2017
  • In this study, we evaluated the toxic effects of heavy metals (As, Cr and Pb) on the population growth rate (r) of the marine diatom, Skeletonema costatum. The r of the species was determined after 96 h (4 days) exposure to As (0, 0.31, 0.63, 1.25, 2.50 and 5.00 mg L-1), Cr (0, 0.16, 0.31, 0.63, 1.25 and 2.50 mg L-1) and Pb (0, 1.25, 2.50, 5.00, 10.00 and 20.00 mg L-1). It was observed that r in the control (absence of As, Cr and Pb) were greater than 0.04, however suddenly decreased with increased heavy metal concentrations. As, Cr and Pb reduced r in a dose-dependent manner and a significant reduction were occurred at concentration of greater than 0.31, 0.31 and 5.00 mg L-1, respectively. Based on the toxicity, the heavy metal were ranked as Cr>As>Pb, with EC50 (50% effective concentration) values of 0.80, 2.57 and 13.88 mg L-1, respectively. The lowest-observed-effective-concentration (LOEC) of r in exposed to As, Cr and Pb were 0.63, 0.63 and 10.00 mg L-1, respectively. Precisely, a concentration of greater than 0.63 mg L-1 of As, 0.63 mg L-1 of Cr and 10.00 mg L-1 of Pb in marine ecosystems induced toxic effect on the r of S. costatum. Based on our results, we suggested that the r of S. costatum might be a useful bio-indicator for the toxicity assessment of heavy metals on the producer in marine ecosystems.

Organosulfur Compounds in Fermented Garlic Extracts and the Effects on Alcohol Induced Cytotoxicity in CYP2E1-Transfected HepG2 Cells (유산균발효마늘의 유기황화합물과 CYP2E1-Transfected HepG2 Cell에서 알코올 유발 세포독성에 미치는 영향)

  • Jung, Eun-Bong;Choi, Ji-Hwi;Yu, Heui-Jong;Kim, Ki-Ho;Lee, Sung-Ku;Hwang, Young-Il;Lee, Seung-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.3
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    • pp.342-347
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    • 2013
  • In this study, we investigated changes in the organosulfur compounds of garlic (by fermentation with lactic acid bacteria) and the effects of these fermented garlic extracts on alcohol-induced cytotoxicity in CYP2E1-transfected HepG2 cells. Lactobacillus plantarum has the highest growth rate in a garlic medium and the S-allyl-L-cysteine (SAC) in fermented garlic extracts with Lactobacillus plantarum and Pediococcus pentosaceus were significantly higher compared to other lactic acid bacteria strains (p<0.05). The SAC, S-ethyl cysteine (SEC) and S-methyl cysteine (SMC) in garlic extracts were all increased by fermentation with lactic acid bacteria. However, alliin in the fermented garlic extracts with lactic acid bacteria strains was lower than the original garlic extract and the contents of cycloalliin in the garlic extracts did not change with fermentation (p<0.05). The electron donating ability of the fermented garlic extracts increased with dose. The electron donating ability of the fermented garlic extract with L. plantarum and P. pentosaceus was over 90% efficient at 5 mg/g. The fermented garlic extracts (with lactic acid bacteria) and garlic extract were not influenced, up to $100{\mu}g/mL$, in CYPE1-transfected HepG2 cells. The CYPE1-transfected HepG2 cell viabilities were 92.60% and 92.23% when treated with both alcohol (200 mM) and fermented garlic extract ($100{\mu}g/mL$) with lactic acid bacteria respectively, for 6 days.

Transarterial embolization of renal artery in dogs with experimental hydronephrosis (개의 실험적 수신증에 실시한 신동맥 색전술)

  • Chang, Dongwoo
    • Korean Journal of Veterinary Research
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    • v.41 no.3
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    • pp.437-445
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    • 2001
  • This study was performed to validate the procedure of transarterial embolization of the renal artery (TAE-RA) using iohexol-ethanol solution in dogs with unilateral experimental hydronephrosis and to evaluate the embolized kidney using B-mode ultrasonography and selective angiography. Experimental hydronephrosis was induced by ligation of unilateral ureter in 12 dogs. Ultrasonographic findings revealed that size of the kidney was significantly increased at 9 days and 17 days and the length of renal cortex was significantly decreased at 17 days after ligation of the unilateral ureter and it was in accordance with dilation of ipsilateral renal pelvis. No significant change of BUN, creatinine, ALT, calcium, and phosphorus was found immediately after unilateral experimental hydronephrosis. Therefore, it was concluded that unilateral hydronephrosis was established in 12 dogs at 17 days after ligation of ureter. Renal artery embolization was performed using selective catheterization in the hydronephrotic kidney of seven dogs and EKG, $SpO_2$, body temperature, pulse, and respiratory rate were within normal ranges during procedures. Iohexol-ethanol solution was used as embolic material. Average ethanol dose for renal artery embolization was $1.94{\pm}1.24ml/kg$. There were no dogs expired after TAE-RA and no side effects associated with regurgitation of iohexol-ethanol solution. Revascularization of renal artery was not found in angiography in dogs treated by TAE-RA at immediately after TAE-RA and 14 days after TAE-RA. Ultrasonographically, the mean longitudinal length of the embolized kidney decreased significantly at 2 and 3 months after TAE-RA compared to that of contralateral normal kidney. In summary, marked shrinkage of the embolized kidney was observed in dogs with unilateral experimental hydronephrosis treated by TAE-RA with iohexol-ethanol and no adverse effects were observed throughout the observation period. It is concluded that TAE-RA with iohexol-ethanol solution is a viable alternative to nephrectomy in dogs with unilateral hydronephrosis.

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The effects of ibuprofen and indomethacin therapy for patent ductus arteriosus in preterm infants (미숙아 동맥관 개존 치료에서 indomethacin과 ibuprofen의 효과)

  • Choi, Wooksun;Shin, Jung-Yeon;Choi, Byung Min;Eun, Baik-Lin;Yoo, Kee Hwan;Hong, Young Sook;Lee, Joo Won
    • Clinical and Experimental Pediatrics
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    • v.49 no.12
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    • pp.1315-1323
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    • 2006
  • Purpose : This study was conducted to compare the efficacy and safety of ibuprofen and indomethacin in the treatment of patent ductus arteriosus (PDA) in preterm infants and to determine whether ibuprofen can be an alternative drug. Methods : A total of 32 preterm infants with symptomatic PDA were enrolled in the study. Twelve infants received intravenous ibuprofen 10 mg/kg, followed by 5 mg/kg after 24 and 48 hours. As a comparative group, twenty premature infants received three doses of indomethacin 0.1-0.2 mg/kg every 12 hours. Results : PDA was closed in 11 of 12 infants of the ibuprofen group (92 percent) and in 18 of 20 infants of the indomethacin group (90 percent). Serum sodium concentration decreased along with time significantly (P<0.0001) and to its lowest level at 48 hours after administration of the third dose (P=0.0011) in both groups, but showed no significant difference between two groups. Serum BUN and creatinine concentrations were not changed significantly before or after treatment in each group and showed no difference between thetwo groups. The amount of urine output did not change along with time significantly in both groups (P=0.0725), and showed no significant difference between two groups. Conclusion : Ibuprofen has similar effects to indomethacin in the rate of PDA closure and complication when compared. It has similar changes in serum sodium level and complications when compared to indomethacin for the treatment of PDA in preterm infants. Therefore, intravenous ibuprofen may be used as an alternative agent in the treatment of symptomatic PDA in preterm infants.

Influence of Intracerebroventricular Haloperidol on the Renal Function of the Rabbit (가토신장기능에 미치는 측뇌실내 Haloperidol의 영향)

  • Kim, Joong-Ky;Choi, Bong-Kyu;Kook, Young-Johng
    • The Korean Journal of Pharmacology
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    • v.18 no.2
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    • pp.103-117
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    • 1982
  • In an effort to provide evidence as to the regulatory role of the central dopaminergic system on the renal function, the effects of centrally administered dopamine and its specific antagonist haloperidol were investigated. Haloperidol (HA) given intracerebroventricularly (i.c.v.) induced antidiuresis in doses of 15 and $50{\mu}g/kg$. With $15{\mu}g/kg$ sodium reabsorption in the tubules was increased, while with $50{\mu}g/kg$ free-water reabsorption was increased. However, a marked diuresis with increased sodium and potassium was observed with $150{\mu}g/kg$. Hemodynamic changes were not evident, indicating that the diuresis is of tubular origin. Dopamine (DA), on the other hand, produced antidiuresis when given i.c.v. in a dose-related fashion. With smaller doses of 5 and $15{\mu}g/kg$ the antidiuresis was related to increased reabsorption of sodium in the tubules, but higher doses of 50 and $150{\mu}g/kg$ the decreases in renal blood flow and glomerular filtration rate were evident in addition to the tubular action. After pretreatment with $150{\mu}g/kg$ HA, the effects of $15{\mu}g/kg$ DA was abolished, but the antidiuretic actions of 50 and $150{\mu}g/kg$ were not blocked, and the natriuretic diuretic action of HA was overcome and became inconspicuous. These observations indicate that the central dopaminergic system influences the renal function by producing antidiuresis, and HA elicits diuresis and natriuresis by competitively antagonizing DA specifically on the central dopaminegic receptors. The antidiuresis observed with smaller doses of HA can be best explained by the facts that there are more than two types of DA-receptors in the brain and that the presynaptic autoreceptors on the dopaminergic neurones which affect the dopamine release at the synapse are more sensitive than the postsynaptic receptors. Overall, these data provide an evidence indicating that the central dopaminergic system plays a role in the regulation of renal function in the rabbit.

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Comparison of Effect of Various Types of Soybeans on Mutagenicity and Growth of Human Cancer Cell Lines (콩 종류별 항돌연변이 및 암세포 증식 억제 효과 비교)

  • Lim, Sun-Young
    • Journal of Life Science
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    • v.20 no.10
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    • pp.1532-1537
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    • 2010
  • This study compared the inhibitory effects of methanol extracts from yellow and black soybeans (black soybean, Seomoktae and Seoritae) on mutagenicity using the Ames test and growth of human cancer cells (AGS human gastric adenocarcinoma, HT-29 human colon cancer, Hep 3B hepatocellular carcinoma cells). In the Ames test system using Salmonella typhimurium TA100, aflatoxin $B_1$ ($AFB_1$)-induced mutagenicity was significantly inhibited by treatments with the methanol extracts from either yellow or black soybeans in a dose dependent manner (p<0.05). The methanol extracts from various black soybeans tended to have a greater inhibitory effect compared to those from yellow soybeans. As for N-methyl-N'-nitro-N-nitrosoguamidine (MNNG)-induced mutagenicity, the methanol extracts (5 mg/assay) from black soybean, Seomoktae and Seoritae showed 51%, 61% and 53% inhibitory rates, respectively, indicating that Seomoktae, a type of black soybean, had a stronger antimutagenic activity against mutagens (both $AFB_1$ and MNNG). Methanol extracts from black soybeans showed an inhibitory rate of greater than 50% on the growth of human cancer cells (AGS, HT-29 and Hep 3B) and the inhibition was more effective in the methanol extract from Seomoktae. Our results suggested that the methanol extracts from black soybeans showed stronger inhibitory effects on mutagenicity and growth of cancer cells than those from yellow soybean. It is concluded that intake of black soybean can be recommended for improving health.