• Title/Summary/Keyword: PK

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Pharmacokinetics of 11-Hydroxyaclacinomycin X (ID-6105), a Novel Anthracycline, after i.v. Bolus Multiple Administration in Rats

  • Yoo Bo-Im;Ahan Kwang Bok;Kang Min Hee;Kwon Oh-Seung;Hong Young-Soo;Lee Jung Joon;Lee Hong Sub;Ryu Jung Su;Kim Tae Yong;Moon Dong-Cheul;Song Sukgil;Chung Youn Bok
    • Archives of Pharmacal Research
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    • v.28 no.4
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    • pp.476-482
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    • 2005
  • We investigated the pharmacokinetics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, after intravenous (i.v.) bolus administration at a multiple dose every 24 h for 5 days in rats. To analyze ID-6105 levels in biological samples, we used an HPLC-based method which was validated in a pharmacokinetic study by suitable criteria. The concentrations of ID-6105 after the multiple administration for 5 days were not significantly different from the results after the single administration. The $t_{1/2\alpha}, t_{l/2\beta}, V_{dss}, and CL_{t}$ after the multiple administration were not significantly different from the values after the single administration. Moreover, the concentrations of ID-6105 1 min at day 1-5 after i.v. bolus multiple administration did not show the significant difference. Of the various tissues, ID-6105 mainly distributed to the kidney, lung, spleen, adrenal gland, and liver after i.v. bolus multiple administration. ID-6105 concentrations in the kidney or lung 2 h after i.v. bolus administration were comparable to the plasma concentration shortly after i.v. bolus administration. However, the ID-6105 concentrations in various tissues 48 h after i.v. bolus administration decreased to low levels. ID-6105 was excreted largely in the bile after i.v. bolus multiple administration at the dose of 3 mg/kg. The amounts of ID-6105 found in the bile by 12 h or in the urine by 48 h after the administration were calculated to be $14.1\% or 4.55\%$ of the initial dose, respectively, indicating that ID-6105 is mostly excreted in the bile. In conclusion, ID-6105 was rapidly cleared from the blood and transferred to tissues, suggesting that ID-6105 might not be accumulated in the blood following i.v. bolus multiple dosages of 3 mg/kg every 24 h for 5 days. By 48 h after i.v. bolus administration, ID-6105 concentrations in various tissues had decreased to very low levels. The majority of ID-6105 appears to be excreted in the bile.

Hydrolysis characteristics and applications of silk sericin I. Control of molecular weight of sericin (실크 세리신의 가수분해 특성과 응용 I. 세리신의 분자량 제어)

  • 김정호;배도규
    • Journal of Sericultural and Entomological Science
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    • v.45 no.1
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    • pp.46-57
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    • 2003
  • This study was carried out to investigate the characteristics of the soluble sericins after degumming and after hydrolysis of insoluble sericin with various enzymes. Especially, the hydrolysis characteristics were examined in terms of molecular weight of the soluble sericin. Amino acid composition and molecular weight characteristics of the soluble sericins were also studied. When the insoluble sericin was hydrolyzed with kojizyme and flavourzyme, the solubility was highest at pH 7 and 50$^{\circ}C$. On the other hand, in the cases of protamex and alcalase, the highest solubility was obtained at 60$^{\circ}C$. In these cases, solubility increased with pH. In enzymatic hydrolysis, the solubility was increased with concentration of enzymes until 4 hours. After then, a slight difference was found along with treatment times. In enzymatic hydrolysis, the absorbance of the soluble sericin was increased with concentration of enzymes and treatment times. Average degree of polymerization was decreased with treatment time and concentration. The amino acid compositions were similar in low(low molecular weight by degumming) and high (high molecular weight by degumming). Those of PK (soluble sericin hydrolyzed with kojizyme), PP (soluble sericin hydrolyzed with protamex), and PA(soluble sericin hydrolyzed with alcalase) were similar to each other. Serine and tyrosine compositions were higher in low and high than those of PK, PP, and PA. However proline was absent in low and high. Molecular weights of the various sericins became higher as KP>high>PP>low>PA and those of KP and PA were 9,800 and 905 respectively.

A Practical Public Key Broadcast Encryption Scheme for Multiple Channels (다중채널을 위한 실용적인 공개키 Broadcast Encryption Scheme)

  • 정지현;김종희;황용호;이필중
    • Proceedings of the Korea Institutes of Information Security and Cryptology Conference
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    • 2003.07a
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    • pp.11-16
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    • 2003
  • 본 논문에서는 새로운 공개키 다중채널 broadcast encryption scheme(이하 PK-MCBE라 부른다)을 제안한다. 일반적인 broadcast encryption은 하나의 채널스트림을 전송하는 반면 PK-MCBE는 다수채널의 컨텐츠 스트림을 전송한다. 본 논문에서 제안하는 방식에서 수신자는 단지 하나의 비밀키만을 필요로 하며 한번 받은 비밀키는 변경되지 않는다. 제안하는 방식에서는 각 채널당 송신자가 전송하는 메세지의 공통부분을 한번만 전송하여 전체 전송 메세지의 길이를 줄일 수 있다. 또한 배신자(traitors)를 추적하여 효과적으로 강제 탈퇴시킬 수 있다.

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Inhibitory Effect of Mori Ramulus on Oxidative Stress Induced by High Glucose in LLC-$PK_1$ Cells (고농도 포도당에 노출된 마우스 신장상피세포에서 상지(桑枝)의 산화 스트레스 억제 효과)

  • Jang, Soo-Young;Shin, Hyeon-Cheol
    • The Journal of Internal Korean Medicine
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    • v.32 no.1
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    • pp.56-67
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    • 2011
  • Objectives : Recent etiological studies show that oxidative stress might play a major role in the diabetes and its complications. Mori Ramulus (MR) has been known to have antioxidative, anti-inflammatory and antidiabetic effects. The methanol extract of MR was tested for its effectiveness in LLC-PK1 cells exposed to high glucose. Methods : The cytoprotective effect of MR was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The antioxidative effect was measured in terms of generation amount of ${\cdot}O_2^-$ by 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), NO by 4,5-diaminofluorescein (DAF-2), $ONOO^-$ by dihydrorhodamine 123 (DHR 123) in the high glucose -treated LLC-$PK_1$ cells. Western blotting was performed using anti-AGE, anti-RAGE, anti-MAPKs(ERK1/2, JNK, p38), anti-PI3K, anti-Akt, and anti-NF-${\kappa}$B (p50, p65) respectively. Results : MR extract reduced cell death and inhibited the generation of ${\cdot}O_2^-$, NO, $ONOO^-$ in the high glucose-treated LLC-$PK_1$ cells. MR inhibited the expression of AGE, RAGE, MAPKs, PI3K, and Akt by means of decreasing NF-${\kappa}$B activation. MR also inhibited NF-${\kappa}$B activation itself. Conclusions : These results indicate MR has cytoprotective, antioxidative, and anti-inflammatory effects. Therefore it is suggested that MR might prevent and cure diabetes and its complications.

Anti-MRSA action of Papenfussiella kuromo

  • Lee, Sun-Ae;Mun, Su-Hyun;Kang, Ok-Hwa;Joung, Dae-Ki;Seo, Yun-Soo;Kang, Da-Hye;Kim, Sung-Bae;Kong, Ryong;Yang, Da-Wun;Kwon, Dong-Yeul
    • Natural Product Sciences
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    • v.20 no.1
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    • pp.39-43
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    • 2014
  • Papenfussiella kuromo (PK) is a marine plant and an abundant ecological resource for the future; it is found in almost 80% of the terrestrial biosphere. The aim of this study was to investigate the antibacterial activity of PK against methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant pathogen. The minimum inhibitory concentrations (MICs) of PK hexane fraction (PKH) against 7 strains of MRSA ranged from 1.0 to 2.0 mg/mL. In the checkerboard dilution method, a synergistic effect of the PKH and the antibiotics (oxacillin and norfloxacin) was seen. PKH markedly reduced the MIC of each of the 4 antibiotics against MRSA. The time-kill assay showed that the synergistic activity of PKH and an antibiotic reduced the bacterial counts below the lowest detectable limit after 24 h. These findings suggest that PKH has antibacterial activity, and may be important baseline data in future extensive studies of living marine resources as a source of compounds active against MRSA.

Effect of Cisplatin on Sodium-Dependent Hexose Transport in LLC-$PK_1$ Renal Epithelial Cells

  • Lee, Suk-Kyu;Kim, Jee-Yeun;Yu, Tai-Hyun;Kim, Kyoung-Ryong;Kim, Kwang-Hyuk;Park, Yang-Saeng
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.1
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    • pp.35-43
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    • 1997
  • Cis-dichlorodiammine platin${\mu}M$II (Cisplatin), an effective chemotherapeutic agent, induces acute renal failure by unknown mechanisms. To investigate direct toxic effects of cisplatin on the renal proximal tubular transport system, LLC-$PK_1$ cell line was selected as a cell model and the sugar transport activity was evaluated during a course of cisplatin treatment. Cells grown to confluence were treated with cisplatin for 60 min, washed, and then incubated for up to 5 days. At appropriate intervals, cells were tested for sugar transport activity using ${\alpha}-methyl-D-[^{14}C]glucopyranoside$ (AMG) as a model substrate. In cells treated with 100 ${\mu}M$ cisplatin, the AMG uptake was progressively impaired after 3 days. The viability of cells was not substantially changed with cisplatin of less than 100 ${\mu}M$, but it decreased markedly with 150 and 200 ${\mu}M$. In cisplatin-treated cells, the $Na^+$ -dependent AMG uptake was drastically inhibited with no change in the $Na^+$ -independent uptake. Kinetic analysis indicated that Vmax was suppressed, but Km was not altered. The $Na^+$ -dependent phlorizin binding was also decreased in cisplatin-treated cells. However, the AMG efflux from preloaded cells was not apparently retarded by cisplatin treatment. These data indicate that the cisplatin treatment impairs $Na^+$ -hexose cotransporters in LLC-$PK_1$ cells and suggest strongly that defects in transporter function at the luminal plasma membrane of the proximal tubular cells constitute an important pathogenic mechanism of cisplatin nephrotoxicity.

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Effect of Nephrotoxicants on $\alpha$-Methylglucose Uptake in LLC-$PK_1$ (LLC-$PK_1$을 이용한 신독성 물질들의 $\alpha$-methyl glucose uptake에 미치는 영향의 평가)

  • Seo, Kyung-Won;Kim, Hyo-Jung;Chung, Se-Young
    • Environmental Analysis Health and Toxicology
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    • v.9 no.1_2
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    • pp.25-35
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    • 1994
  • Many nephrotoxic agents exert their effect primarily on the cells of the proximal tubules. We used the LLC-$PK_1$, kidney epithelial cell line as a model system for studies on nephrotoxicity and investigated whether the uptake of $\alpha$-methylglucose($\alpha$-MG) could serve as a parameter to assess effects of nephrotoxicants on the functional integrity of the cells at an early time of toxicity. The enzyme leakage test which has been used to be as a conventional cytotoxic parameter in vitro, was conducted to compare with $\alpha$-MG uptake. Treatment with cisplatin for 24 and 48 hours significantly increased activities of lactate dehydrogenase and $\gamma$-glutamyltransferase in culture medium at a concentration of 50$\mu$M. However, above 100$\mu$M of concentration, activities of these enzymes in media were dramatically decreased by cisplatin. These observations indicate that cisplatin has direct inhibitory effect on the activities of these enzymes and make it doutful to use enzyme leakage test to demonstrate damage of kidney cells by chemicals such as cisplatin over the appropriate range of concentration. Cisplatin inhibited $\alpha$-MG uptake at a low concentration which enzymes were not leaked. Also cadmium chloride and mercuric chloride which are acutely nephrotoxic in vivo, significantly inhibited $\alpha$-MG uptake at a low concentration. These results indicate that the uptake of $\alpha$-methylglucose in LLC-$PK_1$cell line is a useful biomarker for the study of nephrotoxicity.

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Optimization of Laccase Production from Bacillus sp. PK4 through Statistical Design of Experiments

  • Rajeswari, Murugesan;Bhuvaneswari, Vembu
    • Microbiology and Biotechnology Letters
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    • v.45 no.4
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    • pp.330-342
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    • 2017
  • Statistical design of experiments was employed to optimize the media composition for the production of laccase from Bacillus sp. PK4. In order to find the key ingredients for the best yield of enzyme production from the selected eleven variables viz yeast extract, glucose, zinc sulphate, copper sulphate, potassium chloride, magnesium sulphate, calcium chloride, ferrous sulphate, sodium chloride, potassium dihydrogen phosphate ($KH_2PO_4$) and dipotassium hydrogen phosphate ($K_2HPO_4$), Plackett-Burman design was applied. The $MgSO_4$, $FeSO_4$, and $CuSO_4$ showed positive estimate, and their concentration optimized further. The steepest ascent method and Box-Behnken method revealed that 1.5 mM $MgSO_4$, 0.33 g/l $FeSO_4$ and 1.41 mM $CuSO_4$ were optimal for the laccase production by Bacillus sp. PK4. This optimization strategy leads to enhancement of laccase production from 2.13 U/ml to 40.79 U/ml. Agro-wastes residues replace the carbon source glucose in the optimized media namely sugarcane bagasse, wheat bran, rice husk, and groundnut shell, among these groundnut shells (117 U/ml) was found to enhance the laccase production significantly. The laccase produced by Bacillus sp. PK4 was found to have the potential to degrade persistent organic pollutant benzo[a]pyrene.

The Butanol Fraction of Bitter Melon (Momordica charantia) Scavenges Free Radicals and Attenuates Oxidative Stress

  • Kim, Hyun Young;Sin, Seung Mi;Lee, Sanghyun;Cho, Kye Man;Cho, Eun Ju
    • Preventive Nutrition and Food Science
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    • v.18 no.1
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    • pp.18-22
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    • 2013
  • To investigate radical scavenging effects and protective activities of bitter melon (Momordica charantia) against oxidative stress, in vitro and a cellular system using LLC-$PK_1$ renal epithelial cells were used in this study. The butanol (BuOH) fraction of bitter melon scavenged 63.4% and 87.1% of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals at concentrations of 250 and $500{\mu}g/mL$, respectively. In addition, the BuOH fraction of bitter melon effectively scavenged hydroxyl radicals (${\cdot}OH$). At all concentrations tested, the scavenging activity of the BuOH fraction was more potent than that of the positive control, ascorbic acid. Furthermore, under the LLC-$PK_1$ cellular model, the cells showed a decline in viability and an increase in lipid peroxidation through oxidative stress induced by pyrogallol, a generator of superoxide anion ($O_2{^-}$). However, the BuOH fraction of bitter melon significantly and dose-dependently inhibited cytotoxicity. In addition, 3-morpholinosydnonimine (SIN-1), a generator of peroxynitrite ($ONOO^-$) formed by simultaneous releases of nitric oxide and $O_2{^-}$, caused cytotoxicity in the LLC-$PK_1$ cells while the BuOH fraction of bitter melon ameliorated oxidative damage induced by $ONOO^-$. These results indicate that BuOH fraction of bitter melon has protective activities against oxidative damage induced by free radicals.

Protective effect of ginsenoside Rb1 against tacrolimus-induced apoptosis in renal proximal tubular LLC-PK1 cells

  • Lee, Dahae;Lee, Dong-Soo;Jung, Kiwon;Hwang, Gwi Seo;Lee, Hye Lim;Yamabe, Noriko;Lee, Hae-Jeong;Eom, Dae-Woon;Kim, Ki Hyun;Kang, Ki Sung
    • Journal of Ginseng Research
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    • v.42 no.1
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    • pp.75-80
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    • 2018
  • Background: The aim of the present study was to evaluate the potential protective effects of six ginsenosides (Rb1, Rb2, Rc, Rd, Rg1, and Rg3) isolated from Panax ginseng against tacrolimus (FK506)-induced apoptosis in renal proximal tubular LLC-PK1 cells. Methods: LLC-PK1 cells were treated with FK506 and ginsenosides, and cell viability was measured. Protein expressions of mitogen-activated protein kinases, caspase-3, and kidney injury molecule-1 (KIM-1) were evaluated by Western blotting analyses. The number of apoptotic cells was measured using an image-based cytometric assay. Results: Reduction in cell viability by $60{\mu}M$ FK506 was ameliorated significantly by cotreatment with ginsenosides Rg1 and Rb1. The phosphorylation of p38, extracellular signal-regulated kinases, and KIM-1, and cleavage of caspase-3, increased markedly in LLC-PK1 cells treated with FK506 and significantly decreased after cotreatment with ginsenoside Rb1. The number of apoptotic cells decreased by 6.0% after cotreatment with ginsenoside Rb1 ($10{\mu}M$ and $50{\mu}M$). Conclusion: The antiapoptotic effects of ginsenoside Rb1 on FK506-induced apoptosis were mediated by the inhibition of mitogen-activated protein kinases and caspase activation.