• Title/Summary/Keyword: Lead uptake

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Fibroin Enhances Insulin Sensitivity and Reverses Insulin Resistance in 3T3-L1 Adipocytes

  • Hyun Chang-Kee;Frost Susan C.
    • Proceedings of the Korean Society of Food Science and Nutrition Conference
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    • 2004.11a
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    • pp.185-197
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    • 2004
  • Type 2 diabetes is characterized by hyperglycemia and hyperinsulinemia, features of insulin resistance. In vivo treatment of ob/ob mice with hydrolyzed fibroin reverses these pathological attributes (6). To explore the mechanism underlying this effect, we have used the 3T3-Ll adipocytes as a cell type which would represent the periphery, in vivo. Exposure of 3T3-Ll adipocytes to chronic insulin leads to the a 50% loss of insulin-stimulated glucose uptake. Chronic exposure to fibroin blocked, in part, the response to chronic insulin but also increased the sensitivity of control cells to the acute action of insulin. The later effect was most robust at physiological concentrations of insulin. Fibroin did not prevent the insulin-induced down-regulation of the insulin receptor or the tyrosine kinase activity associated with the receptor. Further, fibroin had no affect on the loss in activity of the insulin-sensitive down-stream kinase, Akt. Interestingly, fibroin accelerated glucose metabolism and glycogen turnover independent of insulin action. In addition, fibroin up-regulated GLUT1 which increased its expression at the cell surface and caused the redistribution of GLUT4 to the plasma membrane. Together, these later effects would lead to an improvement in hyperglycemia in vivo which would in turn reduce the need for insulin.

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Drug-drug Interactions between Atorvastatin and Telmisartan (Atorvastatin과 Telmisartan의 약물상호작용)

  • Park, Jinhyun;Noh, Keumhan;Lim, Misun;Kang, Wonku
    • Korean Journal of Clinical Pharmacy
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    • v.23 no.4
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    • pp.316-321
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    • 2013
  • Purpose: Atorvastatin, a HMG-CoA reductase inhibitor is widely prescribed in hyperlipidemic patients and telmisartan, an angiotensin receptor blocker is frequently used in the treatment of hypertension. Both drugs are substrates of organic anion transporting polypeptide (OATP) expressed in basolateral membrane in the liver, and undergo high first pass metabolism. Therefore, OATP-mediated hepatic uptake is important for disposition and metabolism of these drugs. The present study was designed to investigate the pharmacokinetic interactions between atorvastatin and telmisartan in rats. Method: Young adult SD rats were divided into three groups (n=6, each) and atorvastatin (10 mg/kg) and telmisartan (4 mg/kg) were orally given alone and together. Heparinized blood was serially taken and plasma concentrations of both drugs were measured using HPLC-MS/MS. Pharmacokinetic parameters of two drugs were calculated. Results: No significant pharmacokinetic change was found except a delay of time to peak of telmisartan when administered with atorvastatin. Each drug at the present dosage seemed to be insufficient to alter the pharmacokinetic parameters of its counterpart drug. Conclusion: Conclusively, co-administration of atorvastatin and telmisartan may lead to negligible clinical consequences.

Selective Cytotoxicity of Novel Platinum(II) Coordination Complexes Containing DL-2-Hydroxy 3-Methylbutyric Acid (DL-2 하이드록시 3-메틸 부틸산물 배위자로 한 새로운 항암성 백금(II) 착체의 위암세포와 정상신장세포에 대한 선택적 세포독성)

  • 정지창;홍언표;최승기;장성구;육창수;노영수
    • Biomolecules & Therapeutics
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    • v.11 no.2
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    • pp.91-98
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    • 2003
  • A new series of highly water soluble platinum(II) complexes[Pt(II)(DL-2-hydroxy-3-methylbutyrate)(trans-l-1,2-dimninocyc1ohexane)] (PC-1) and [Pt(II)DL-2-hydroxy-3-methylbutyrate](cis-1,2-diaminocyclohexane)](PC-2) were synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared(IR), $^{13}C$-nuclear magnetic resonance (NMR)]. In vitro antitumor activity of new Pt(II)complexes was tested against MKN-45, MKN/ADM and MKN/CDDP human gastric adenocarcinoma cell lines using colorimetric MTT[3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay for cell survival and proliferation. PC-1 and PC-2 showed active against MKN-45/P, MKN/ADM and MKN/CDDP human gastric cancer cell lines, and the antitumor activity of these compounds were comparable or superior to that of cisplatin. The nephrotoxicities of PC-1 and PC-2 were found quite less then that of cisplatin using MTT and [$^3H$] thymidine uptake tests in rabbit proximal tubule cells, human kidney cortical cells human renal cortical tissues. Based on these results, these novel platinum(II) complex compounds(PC-1 & PC-2) represent a valuable lead in the development of the new anticancer chemotherapeutic agents capable of improving antitumor activity and low nephrotoxicity.

Nutrients removal on Oxic/Anoxic time ratio in 2-stage-intermittent-aeration reactor (2단 간헐 포기조의 포기/비포기 시간비에 따른 영양염류 제거특성)

  • Kim, Hong Tae;Sin, Seok U;O, Sang Hwa;Gwon, Seong Hyeon
    • Journal of Environmental Science International
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    • v.13 no.7
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    • pp.675-680
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    • 2004
  • This study was conducted to remove organics and nutrients using 2 stage intermittent aeration reactor. First reactor, using suspended microbial growth in intermittent aeration instead of anaerobic reactor in the typical BNR process, used minimum carbon source to release P, and it was possible to reduce ammonia loading going to second reactor. In the second reactor, using moving media intermittent aeration, it was effective to reduce nitrate in non-aeration time by attached microorganisms having long retention time. In aeration time, nitrification and P uptake were taken place simultaneously. From the experiment, two major results were as follows. First, the removal of organics was more than 90%, and optimum aeration/non-aeration time ratio for organic removal was corresponded with aeration/non-aeration time ratio for nitrogen removal. Second, in the first reactor, optimum aeration/non-aeration time ratio was 15/75 (min.) because it was necessary to maintain 75 min. of non-aeration time to suppress of impediment of return nitrate and to lead release of phosphate. In the second reactor, optimum aeration/non-aeration time ratio was 45/90 (min.).

Progress in the Direct Application of Pharmacogenomics to Patient Care: Sustaining innovation

  • Frueh, Felix W.;Lesko, Lawrence J.;Burckart, Gilbert J.
    • Biomolecules & Therapeutics
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    • v.15 no.1
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    • pp.1-6
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    • 2007
  • The application of the knowledge from the Human Genome Project to clinical medicine will be through both industrial drug development and the application of pharmacogenomics (PG) to patient care. The slow uptake of clinical innovations into clinical practice can be frustrating, but understanding the history of acceptance and sustaining medical innovation is critically important to position PG to succeed. This primarily means that PG tests must have legitimacy; they must be thoroughly validated, must be cost-effective, must be widely accepted by medical practitioners, must be supported by public policy, and must have a way of being easily incorporated into current medical practice. They must also lead to actionalble decisions by health care providers for their patients. Innovative PG assays should be tested in the best US laboratories, and reimbursement for testing must be accepted at the federal and state level. The companies providing these PG tests should be capable of sup-porting the interpretation and use of the test throughout medical practice. Advances such as the addition of PG information to drug labeling and the routine use of validated biomarkers to determine choice of cancer chemotherapy have been made. The PG research community must pay attention to the principles that have been previously described for acceptance and sustaining medical innovations in order for PG to be widely accepted in clinical medical practice.

Selective Cytotoxicity of Novel Platinum(II) Coordination Complexes on Human Bladder Cancer Cell-Lines and Normal Kidney Cells

  • Kim, Jung-Tae;Rho, Young-Soo;Jung, Jee-Chang
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.2
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    • pp.111-117
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    • 2003
  • Cisplatin is often effective in cancer treatment, but its clinical use is limited because of its nephrotoxicity. We have synthesized new platinum(II) coordination complexes (PC-1 & PC-2) containing trans-${\iota}$ and cis-1,2-diaminocyclohexane (DACH) as carrier ligands and L-3 -phenyllactic acid (PLA) as a leaving group with the aim of reducing nephrotoxicity but maintaining its anticancer activity. In this study, new platinum(II) complex compounds were evaluated for selective cytotoxicity on cancer cell-lines and normal kidney cells. The new platinum complexes have demonstrated high efficacy in the cytotoxicity against human bladder carcinoma cell-lines (T-24/HT-1376). The cytotoxicity of these compounds against rabbit proximal renal tubular cells and human renal cortical tissues, was determined by MTT assay, the [3H]-thymidine uptake and glucose consumption test, and found to be quite less than those of cisplatin. Based on our results, these novel platinum compounds appear to be valuable lead compounds with high efficacy and low nephrotoxicity.

Ecological Effects of Zinc and Lead on Plants (식물체에 미치는 연, 아연 ( Pb, Zn ) 의 영향)

  • Park, Bong-Kyu;Kim, Ok-Kyung
    • The Korean Journal of Ecology
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    • v.6 no.2
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    • pp.98-105
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    • 1983
  • This study was carried out to investigate the effects of Zn and Pb concentration on seed germination and plant growth in water and soil culture, and the frequency of chlorosis invegetation and the relationship between plants and soil in the Sambo mine. The inhibition of germination were observed in 1000ppm of Zn, 10ppm of Pb and 5000ppm of Zn + Pb, but germination was more stimulated in 10ppm of Zn than control. The symptoms of chlorosis and abnormality were occurred in plant leaves grown to the soils treated with more than 1000ppm of Pb. Reasons of chlorosis were considered as an antagonistic effect of other metals towards uptake of iron by the plant in Zn treatment. The contents of Zn and Pb in fruits were lower than those of leaves, and that was remarked in case of Pb. With increasing rate of Zn and Pb treatment, chemical components of soils in pot culture were accompanied by slight decrease in pH, total nitorgen and exchangeable K. Chlorotic individuals of 10 species were shown in the areas of the Sambo mine. Chlorotic symptoms were especially extensive and severe in Sophora angustifolia, Populus alba, Spiraea prunifolia, Amorpha fruticota, Lespedeza bicolor and Salix dependens. Plants in the investigated areas grew in soils containing Zn of 311ppm and Pb of 151ppm on an average, and accumulated Zn of 2084ppm and Pb of 49ppm.

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Triglyceride Down-regulates Expression of MSR-1 in PMA-induced THP-1 Macrophages

  • Jung, Byung Chul;Kim, Sung Hoon;Woo, Sung-Hun;Lim, Jaewon;Kim, Yoon Suk
    • Biomedical Science Letters
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    • v.26 no.3
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    • pp.164-169
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    • 2020
  • Atherosclerosis is a cardiovascular disease in which plaque builds up inside of an artery and can lead to various complications such as myocardial infarction, stroke, and thrombosis. Recently, hypertriglyceridemia has attracted significant attention as contributors to development of atherosclerosis. However, molecular mechanism of its contribution to atherosclerosis is poorly understood. Here we proposed a potential link between triglyceride (TG) and atherosclerosis. TG treatment promoted downregulation of certain scavenger receptor, macrophage scavenger receptor-1 (MSR-1) in phorbol myristate acetate (PMA)-derived human macrophages. TG treatment caused reduction of MSR-1 mRNA expression in a time- and dose-dependent manner. Using chemical inhibitors, we found that inhibition of signaling pathways associated with PI3K and PLC enhances TG-induced reduction of MSR-1 expression in THP-1 macrophages implying that PI3K and PLC is implicated in the expression of MSR-1 in macrophages. Since MSR-1 is associated with uptake and clearance of atherogenic lipoprotein, oxidized low density lipoprotein (oxi-LDL), our data suggest that increase of oxi-LDL due to TG-mediated reduction of its receptor MSR-1 can promote atherosclerosis.

Selective Cytotoxicity of a Novel Platinum(II) Coordination Complex on Human Bladder Cancer Cell Lines and Normal Kidney Cells

  • Jung, Jee-Chang;Chung, Joo-Ho;Chang, Sung-Goo;Rho, Young-Soo
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.2
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    • pp.159-167
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    • 2000
  • We have synthesized a novel platinum(II) coordination complex containing cis-1,2-diaminocyclohexane (DACH) as a carrier ligand and 1,2-dichloroethane (DCE) as a leaving group. In addition, nitrate was added to improve the water-solubility. A new series of [Pt(cis-DACH)(DCE)] $2NO_3(PC)$ was evaluated for its cytotoxic activity on T-24 and J-82 human bladder carcinoma cells and normal primary cultured kidney cells. PC has demonstrated high levels of cytotoxicity against T-24 and J-82 cells. The cytotoxicity of PC against rabbit proximal renal tubular cells, human renal cortical cells and human renal cortical tissues, determined using the MTT assaying technique, the $[^3H]-thymidine$ uptake and glucose consumption tests, was found to be quite less than those of cisplatin. Based on these results, this novel platinum(II) coordination complex appears to be better for improving antitumor activities with low nephrotoxicity and is a valuable lead in the development of new clinically available anticancer chemotherapeutic agents.

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Selective Cytotoxicity Platinum (II) Complex Containing Carrier Ligand of cis-1,2-Diaminocyclohexane (Cis-Diaminocyclohexan을 배위자로 하는 배금(II)착체의 선택적 세포독성)

  • 노영수;정세영;정지창
    • Environmental Analysis Health and Toxicology
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    • v.13 no.3_4
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    • pp.87-94
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    • 1998
  • The use of cisplatin is limited by severe side effects such as renal toxicity. Our platinum-base drug discovery is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (II) complex analogue [Pt (cis-DACH)(DPPP)]. 2NO$_3$ (PC) containing cis-1,2-diaminocyclohexane as a carrier ligand and 1,3-bis(diphenylphosphino) propane as a leaving group. Furthermore, nitrate was added to improved the solubility. In this study, its structure was determined and its antitumor activity against SKOV-3 and NIH-OVCAR-3 human ovarian adenocarcinoma, and in vitro cytotoxicity was determined against primary cultured rabbit kidney proximal tubular and renal cortical cells of human kidney using colorimetric MTT assay. PC demonstrated acceptable antitumor activity against SKOV-3 and NIH-OVCAR-3 human ovarian adenocarcinoma and significant activity as compared with that of cisplatin. The toxicity of PC was found quite less than that of cisplatin using MTT and $^3$H-thymidine uptake tests in rabbit proximal tubular cells and human kidney cortical cells. PC was used for human cortical tissue in 7 weeks hitoculture by the glucose-consumption tests. We determined that the new platinum drug has lower nephrotoxicity than cisplatin. Based on these results, this novel platinum (II) complex compound (PC) represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.

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