• Title/Summary/Keyword: Uptake metabolism

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Effect of Drugs on the Cardiac Transport, Metabolism and Action of Idarubicin: Pharmacokinetic and Pharmacodynamic Modeling

  • Kang, Won-Ku
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.212-213
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    • 2002
  • Using the isolated perfused rat heart this study investigated 1) the cardiac uptake of idarubicin (IDA), 2) the role of P-glycoprotein (P-gp) in the uptake process, 3) the formation of IDOL from IDA in the heart, and 4) the effect of P-gp inhibitors (verapamil, amiodarone, PSC 833), doxorubicin, hypothermia, xanthine derivatives (caffeine, theophylline) and metabolism inhibitors (rutin, phenobarbital) on the pharmacokinetics and pharmacodynamics of IDA using a mathematical modeling approach. A minimal model was constructed; the differential equations were numerically solved and fitted to the data using the ADAPT II-software package using maximum likelihood estimation assuming that the measurement error has a standard deviation which is a linear function of the measured quantity[1]. (omitted)

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Imaging of Gastric Cancer Metabolism Using 18 F-FDG PET/CT

  • Yun, Mijin
    • Journal of Gastric Cancer
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    • v.14 no.1
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    • pp.1-6
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    • 2014
  • Aerobic glycolysis has been the most important hypothesis in cancer metabolism. It seems to be related to increased bioenergetic and biosynthetic needs in rapidly proliferating cancer cells. To this end, F-18 fluorodeoxyglucose (FDG), a glucose analog, became widely popular for the detection of malignancies combined with positron emission tomography/computed tomography (PET/CT). Although the potential roles of FDG PET/CT in primary tumor detection are not fully established, it seems to have a limited sensitivity in detecting early gastric cancer and mainly signet ring or non-solid types of advanced gastric cancer. In evaluating lymph node metastases, the location of lymph nodes and the degree of FDG uptake in primary tumors appear to be important factors affecting the diagnostic accuracy of PET/CT. In spite of the limited sensitivity, the high specificity of PET/CT for lymph node metastases may play an important role in changing the extent of lymphadenectomy or reducing futile laparotomies. For peritoneal metastases, PET/CT seems to have a poorer sensitivity but a better specificity than CT. The roles of PET/CT in the evaluation of other distant metastases are yet to be known. Studies including primary tumors with low FDG uptake or peritoneal recurrence seem suffer from poorer diagnostic performance for the detection of recurrent gastric cancer. There are only a few reports using FDG PET/CT to predict response to neoadjuvant or adjuvant chemotherapy. A complete metabolic response seems to be predictive of more favorable prognosis.

Evaluation of Adverse Drug Properties with Cryopreserved Human Hepatocytes and the Integrated Discrete Multiple Organ Co-culture (IdMOCTM) System

  • Li, Albert P.
    • Toxicological Research
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    • v.31 no.2
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    • pp.137-149
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    • 2015
  • Human hepatocytes, with complete hepatic metabolizing enzymes, transporters and cofactors, represent the gold standard for in vitro evaluation of drug metabolism, drug-drug interactions, and hepatotoxicity. Successful cryopreservation of human hepatocytes enables this experimental system to be used routinely. The use of human hepatocytes to evaluate two major adverse drug properties: drug-drug interactions and hepatotoxicity, are summarized in this review. The application of human hepatocytes in metabolism-based drug-drug interaction includes metabolite profiling, pathway identification, P450 inhibition, P450 induction, and uptake and efflux transporter inhibition. The application of human hepatocytes in toxicity evaluation includes in vitro hepatotoxicity and metabolism-based drug toxicity determination. A novel system, the Integrated Discrete Multiple Organ Co-culture (IdMOC) which allows the evaluation of nonhepatic toxicity in the presence of hepatic metabolism, is described.

Involvement of Mrs3/4 in Mitochondrial Iron Transport and Metabolism in Cryptococcus neoformans

  • Choi, Yoojeong;Do, Eunsoo;Hu, Guanggan;Caza, Melissa;Horianopoulos, Linda C.;Kronstad, James W.;Jung, Won Hee
    • Journal of Microbiology and Biotechnology
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    • v.30 no.8
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    • pp.1142-1148
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    • 2020
  • Mitochondria play a vital role in iron uptake and metabolism in pathogenic fungi, and also influence virulence and drug tolerance. However, the regulation of iron transport within the mitochondria of Cryptococcus neoformans, a causative agent of fungal meningoencephalitis in immunocompromised individuals, remains largely uncharacterized. In this study, we identified and functionally characterized Mrs3/4, a homolog of the Saccharomyces cerevisiae mitochondrial iron transporter, in C. neoformans var. grubii. A strain expressing an Mrs3/4-GFP fusion protein was generated, and the mitochondrial localization of the fusion protein was confirmed. Moreover, a mutant lacking the MRS3/4 gene was constructed; this mutant displayed significantly reduced mitochondrial iron and cellular heme accumulation. In addition, impaired mitochondrial iron-sulfur cluster metabolism and altered expression of genes required for iron uptake at the plasma membrane were observed in the mrs3/4 mutant, suggesting that Mrs3/4 is involved in iron import and metabolism in the mitochondria of C. neoformans. Using a murine model of cryptococcosis, we demonstrated that an mrs3/4 mutant is defective in survival and virulence. Taken together, our study suggests that Mrs3/4 is responsible for iron import in mitochondria and reveals a link between mitochondrial iron metabolism and the virulence of C. neoformans.

The Mechanism of Hematoxylin on Glucose Metabolism Improvement in Sciatic Nerves from Streptozotocin-induced Diabetic Rats (Streptozotocin으로 유도한 당뇨쥐의 대퇴신경에서 Hematoxylin의 당대사 개선 메커니즘)

  • Chung, Myung-Kiu;Kang, Soon-Kook
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.12 no.7
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    • pp.3310-3316
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    • 2011
  • Hematoxylin is the main component of Hematoxylon campechianum which has been utilized in the southern provinces of Korea as a folk remedy for diabetic complications. In the present study, to investigate the hypoglycemic mechanism of hematoxylin, the 2-deoxyglucose uptake and phospholipid metabolism were examined in sciatic nerves from three groups of rats : normal control, diabetic control, diabetic hematoxylin-treated group. Hematoxylin significantly reduced blood glucose levels in diabetic control rats. On a wet weight basis, the nerves from diabetic rats showed a 20% decrease in total phospholipid from that of controls and a relative decrease in phosphatidylinositide. Hematoxylin treatment increased the incorporation rate of 2-[3H] myo-inositol into total phosphoinositids in diabetic rat. The effectiveness were more potent in higher dose hematoxylin-treated rats than lower dose hematoxylin-treated rats. These results suggest that hematoxylin increases glucose transport and lipid metabolism by partially normalizing concerned with myo-inositol metabolism in diabetic rat. Therefore we propose that hematoxylin can be a promising candidate for diabetes medication.

Nitrogen metabolism and mammary gland amino acid utilization in lactating dairy cows with different residual feed intake

  • Xie, Yunyi;Miao, Chao;Lu, Yi;Sun, Huizeng;Liu, Jianxin
    • Animal Bioscience
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    • v.34 no.10
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    • pp.1600-1606
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    • 2021
  • Objective: This study was conducted to enhance our understanding of nitrogen (N) metabolism and mammary amino acid (AA) utilization in lactating cows with divergent phenotypes of residual feed intake (RFI). Methods: Fifty-three multiparous mid-lactation Holstein dairy cows were selected for RFI measurements over a 50-d experimental period. The 26 cows with the most extreme RFI values were classified into the high RFI (n = 13) and low RFI (n = 13) groups, respectively, for analysis of N metabolism and AA utilization. Results: Compared with the high RFI cows, the low RFI animals had lower dry matter intake (p<0.01) with no difference observed in milk yield between the two groups (p>0.10). However, higher ratios of milk yield to dry matter intake (p<0.01) were found in the low RFI cows than in the high RFI cows. The low RFI cows had significant greater ratios of milk protein to metabolizable protein (p = 0.02) and milk protein to crude protein intake than the high RFI cows (p = 0.01). The arterial concentration and mammary uptake of essential AA (p<0.10), branched-chain AA (p<0.10), and total AA (p<0.10) tended to be lower in the low RFI cows. Additionally, the low RFI cows tended to have a lower ratio of AA uptake to milk output for essential AA (p = 0.08), branched-chain AA (p = 0.07) and total AA (p = 0.09) than the high RFI cows. Conclusion: In summary, both utilization of metabolizable protein for milk protein and mammary AA utilization are more efficient in cows with lower RFI than in the high RFI cows. Our results provide new insight into the protein metabolic processes (related to N and AA) involved in feed efficiency.

Analysis of Diffuse Hepatic Visualization after Iodine-131 Treatment in Patients with Thyroid Carcinoma (갑상선암 환자에서 전절제술 후 I-131 치료에서 미만성 간침착 정도의 분석)

  • Jung Jin-Hyung;Bae Keum-Seok;Kang Seong-Joon
    • Korean Journal of Head & Neck Oncology
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    • v.16 no.2
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    • pp.206-211
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    • 2000
  • Objectives: Any uptake of I-131 after total thyroidectomy means the remant thyroid tissue or distant metastasis of the thyroid cancer. However diffuse hepatic uptake of I-131 without abnormal uptake was showen in many cases on I-131 whole body scan. The aim of this study was to classify the liver uptake after I-131 scan and to evaluate the analysis of this finding. Materials and Methods: Between 1982 and 1998, 104 patients(l4 males, 90 females) with normal liver function underwent I-131 scan after total thyroidectomy. Prospectively we reviewed the films of the whole body scan and analysed the correlations between results of radioiodine uptake, pathologic diagnosis, prognostic factors, lymphatic metastasis, and thyroid function test. Result: Diffuse hepatic uptake was found in 44 of 104(42%) patients. 10 of 39(26%) patients on I-131 100mCi, and 34 of 63(54%) on I-131 150mCi showed hepatic uptake. 52 of 104(50%) patients was locally invasive thyroid cancer. The rate of the hepatic uptake was no significant differences with the thyroid hormone levels(T3, Free T4) and thyroglobulin between uptake group and non-uptake group. Conclusion: The rate of I-131 uptake was high in high-dose radioiodine treatment group. However, we can not find any correlation among the thyroid functions, the extent of metastasis or the extent of local invasion. We need further study to find out the causes of the hepatic uptake of I-131 after total thyroidectomy, besides liver metabolism of I-131 attached thyroid hormones.

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Researches using radio-labelled Herbicide in Korea

  • Lee, Kyu-Seung
    • Korean Journal of Environmental Agriculture
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    • v.27 no.2
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    • pp.191-204
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    • 2008
  • The research results using radio-labelled herbicides performed by Korean researchers were reviewed. All the research works were used $^{14}C$-labelled chemicals and generally carried out to know the behavior of herbicides in soils and plants. The degradation, mineralization and bound-residues formation are the major concerning area in soil studies, and uptake, translocation, metabolism, selectivity and resistance are in plant studies. Also few papers covered synthesis, formulation and animal metabolism.

Metabolism of Dimethylphthalate by Aspergillus niger

  • Pradeepkmar;Sharanagouda;Karegoudar, T.B.
    • Journal of Microbiology and Biotechnology
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    • v.10 no.4
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    • pp.518-521
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    • 2000
  • Aspergillus niger is capable of metabolizing dimethyphthalate. The maximum weight of mycelium wa observed afterabout 6-8 dys of incubation. A TLC analysis revealed the accumulation of metabolites in the resting cell culture. Monomethylphthalate, phthalate, and protocatechuate were shown to be the intermediates by thin layer chromatographic and spectrophotometric analyses. The fungus metabolized dimethylphthalate through monomethylphthalate, phthalate, and protocatechuate as evidenced by the oxygen uptake and an enzymatic analysis. The terminal aromatic metabolite, protocatechuate, is metabolized via the ortho-cleavage pathway.

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Regulation of Sulfur Metabolism in Cephalosporium acremonium (Cephalosporium acremonium에서 황화합물 대사의 조절)

  • Lee, Kyoung;Park, Sang-Ho;Lee, Jung-Joon;Mheen, Tae-Ick
    • Microbiology and Biotechnology Letters
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    • v.15 no.5
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    • pp.361-367
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    • 1987
  • A DL-seleno-methionine resistant mutant, Cephalosporium acremonium MS-92 showed increased activities of sulfate and L-methionine uptake than the parent strain, and accumulated excess methionine and S-adenosylmethionine (SAM) intracellularly. And the sulfate uptake system was severely inhibited by L-cysteine. In crude enzyme extracts, the mutant MS-92 showed lower L-serine sulfhydrylase (identical with cystathionine $\beta$-synthase) activity than the parent. Also, cysteine desulfhydrylase activity, an index of intracellular L-cysteine concentration, of the mutant MS-92 was decreased by about 50% as com-pared with that of the parent. Thus, it was supposed that the mutant MS-92 should have n lower level of L-cysteine than the parent. In C. acremonium like A. nidulans, the enzymes related to the biosynthesis of methionine might be regulated by L-cysteine, but not by methionine or SAM.

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