• Title, Summary, Keyword: methotrexate

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Effect of Glutamine on the Methotrexate Induced Gut Barrier Damage, Bacterial Translocation and Weight Changes in a Rat Model (백서에서 Methotrexate에 의하여 유발된 장관장벽손상 및 장내세균전위와 중량 변화에 대한 글루타민의 효과)

  • Kim, Eun-Jeong;Kim, Jeong-Wook
    • YAKHAK HOEJI
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    • v.51 no.1
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    • pp.1-6
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    • 2007
  • The aim of this study was to examine whether administration of glutamine are able to prevent the methotrexate induced gut barrier damage, bacterial translocation, and weight changes. The animals with glutamine were fed with L-glutamine (1.2 and 2.4 mg/kg/day) for 7 days before methotrexate administration (20 mg/kg orally). 48 hour after methotrexate administration, intestinal permeability were measured for an assessment of the gut barrier dysfunction. Also, enteric aerobic bacterial counts, number of gram-negatives in mesenteric lymph node (MLN), liver spleen, kidney and heart were measured for an assessment of the enteric bacterial number and bacterial translocation. Amounts of food intake, body weight changes and organ weight changes of liver spleen, kidney and heart were measured. Methotrexate administration caused body and liver weight loss regardless amounts of food intakes. Methotrexate induced increasing intestinal permeability, enteric bacterial undergrowth and bacterial translocation to MLN, liver and spleen, but not kidney and heart. The supplements with glutamine reduced the intestinal permeability bacterial translocation, and not influences enteric bacterial number, and body and liver weight changes. This study suggested that glutamine might effectively reduce methotrexate induced intestinal damage and bacterial translocation, but not influence body and organ weight loss.

Carbamoyl-phosphate synthetase 2 is identified as a novel target protein of methotrexate from chemical proteomics

  • Kim, Eui-Kyung;Park, Jong-Bae;Ha, Sang-Hoon;Ryu, Sung-Ho;Suh, Pann-Ghill
    • Environmental Mutagens and Carcinogens
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    • v.22 no.4
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    • pp.236-242
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    • 2002
  • Using agarose-coupled methotrexate, we have successfully isolated two proteins, which have strong interactions with methotrexate. The two proteins were analyzed by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry and identified as carbamoyl-phosphate synthetase 2 and phosphoribosylglycinamide formyltransferase, respectively. Interestingly, both of these two proteins are essential key enzymes in nucleotide biosynthetic pathways, like dihydrofolate reductase, a well-known methotrexate target. We confirmed the specificity of their interactions between methotrexate and two target proteins by the methods of competition binding assay, which were followed by western blotting using antibody against carbamoyl-phosphate synthetase 2 and phosphoribosylglycinamide formyltransferase, respectively. Moreover, we could observe that carbamoyl-phosphate synthetase 2 is overexpressed in methotrexate-resistant MOLT-3 cells comparing with control MOLT-3 cells. This result indicates that carbamoyl-phosphate synthetase 2 may be a novel target of methotrexate in cancer therapy. We propose that chemical proteomics can be a powerful technique to identify target proteins of a chemical.

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Screening of Methotrexate-Resistant Strains with High Thymidylate Synthase Activity (티미딜산 생성효소 활성이 높은 메토트렉세이트-내성 균주의 검색)

  • Kwak, In-Young;Lee, Jong-Soo
    • YAKHAK HOEJI
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    • v.36 no.4
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    • pp.345-349
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    • 1992
  • Thymidylate synthase activity from extracts of various methotrexate-resistant strains was measured by spectrophotometric assay. Methotrexate-resistant strains of Lactobacillus, Pseudomonas sp., Micrococcus sp. HS-1, Klebsillela pneumonae, Cellulomonas fimi and Serratia marcescens elevated thymidylate synthase levels, especially, Pseudomonas sp. KL-9 resistant to $10^{-9}M$ methotrexate have a 156-fold increase in thymidylate synthase, which suggests that Pseudomonas sp. is a convenient source of thymidylate synthase. Several methotrexate strains of yeast were tested, however, their enzyme activity was generally lower than that of bacteria tested.

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Cost-Effectiveness Analysis of Etanercept in the Treatment of Methotrexate-resistant Rheumatoid Arthritis (메토트렉세이트 치료에 실패한 류마티스관절염 환자에서 에타너셉트 사용에 대한 비용-효과 분석)

  • Kim Jong-Joo;Park Eun-Ja;Park Se-Jung;Sung Yun-Kyung;Bae Sang-Cheol;Lee Eui-Kyung
    • YAKHAK HOEJI
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    • v.50 no.2
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    • pp.70-77
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    • 2006
  • A cost effective analysis was performed for comparing leflunomide+methotrexate, etanercept monotherapy and etanercept+methotrexate for 6 months. For the patients with methotrexate-resistant RA, ACR20 data were extracted from the published clinical trials searched from Pubmed. The direct medical cost was estimated based on ACR guideline and Korean National Health Insurance reimbursement. Combination therapy of etanercept+methotrexate was found to be more cost-effective than etanercept monotherapy, which meant it was a better therapeutic strategy for methotrexate- resistant RA.

The Advantage of Cyclosporine A and Methotrexate Rotational Therapy in Long-Term Systemic Treatment for Chronic Plaque Psoriasis in a Real World Practice

  • Choi, Chong Won;Kim, Bo Ri;Ohn, Jungyoon;Youn, Sang Woong
    • Annals of dermatology
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    • v.29 no.1
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    • pp.55-60
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    • 2017
  • Background: Psoriasis is a chronic inflammatory disease. In the treatment of psoriasis, cyclosporine is commonly prescribed systemic agents. However, long-term use of cyclosporine is not recommended because of side effects such as nephrotoxicity or hypertension. Objective: To ascertain the improved safety of rotational therapy using cyclosporine and methotrexate, we investigated the frequency of abnormal results in laboratory test after long term rotational therapy using cyclosporine and methotrexate. Methods: From January 2009 to June 2014, patients who were treated with cyclosporine or methotrexate were enrolled. The clinical data and usage of medications were reviewed. Laboratory tests were conducted before starting the treatment and regularly follow-up. The occurrences of any laboratory abnormalities during the treatments were investigated. Results: A total of 21 psoriatic patients were enrolled. The mean of medication period and cumulative dose of cyclosporine and methotrexate were $497.81{\pm}512.06days$ and $115.68{\pm}184.34g$ in cyclosporine and $264.19{\pm}264.71days$ and $448.71{\pm}448.63mg$ in methotrexate. Laboratory abnormalities were found in total two patients after rotational therapy: two patients (9.5%) in aspartate aminotransferase/alanine aminotransferase and one patient (4.8%) in uric acid. No laboratory abnormalities were found in renal function test. Conclusion: We found that the rotational approaches using cyclosporine and methotrexate reduced the possibility of the development of nephrotoxicity. In addition to other advantage such as quick switching from one agent to another, the rotational therapy using cyclosporine and methotrexate can minimize the adverse events during the systemic treatment of chronic plaque psoriasis.

A New Synthetic Studies on Anticancer Agent Methotrexate (Anticancer Agent인 Methotrexate에 대한 새로운 합성 연구)

  • Yu Euy Kyung;Ryu Seoung Ryuall
    • Journal of the Korean Chemical Society
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    • v.37 no.1
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    • pp.136-140
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    • 1993
  • New synthetic method for diethyl N-[4-{[(2,4-diamino-6-yl)methyl]-amino}benzoyl]-L-glutamate(10) which is an intermediate of methotrexate is described. p-Nitrobenzoyl-L-glutamate was obtained via a two-step sequence which involves condensation of p-nitrobenzoyl chloride with diethyl-L-glutamate and Fischer esterification reaction with ethanol. Reductive methylation of diethyl-p-nitrobenzoyl-L-glutamate were carried out by reaction with formic acid and paraformaldehyde in the presence of $PtO_2$ catalyst and yielded diethyl N-(4-methylaminobenzoyl)-L-glutamate(7). It was followed by allylation and iodoazidozation to give the diethyl-p-[N-(2-azido-3-iodopropyl)-N-methyl]aminobenzoyl-L-glutamate(9). The cyclization reaction of compound(9) with 2,4,5,6-tetraaminopyrimidine was carried out by intermolecular nucleophilic substitution to give the desired methotrexate diethylester.

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Effect of anticancer drug methortrexate on the biliary excretion kinetics of the reudced folate derivatives in rats (항암제 methotrexate가 랫드 담즙중 환원형엽산유도체의 배설동태에 미치는 영향)

  • Shin, Ho-chul;Cha, Shin-woo;Bae, Ju-hyun;Kim, Hyun-ju;Jeong, Tae-cheon;Park, Jong-il;Yoon, Jong-man;Kim, Gye-woong;Kim, Jin-suk;Han, Sang-seop
    • Korean Journal of Veterinary Research
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    • v.36 no.1
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    • pp.57-63
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    • 1996
  • The biliary excretion kinetics of the active folate derivatives were examined after an intravenous injection of methotrexate at doses of 0.3 and 10mg/kg to clarify the mechanism of the acute decrease in the plasma folate by the dihydrofolate reductase inhibitors. Even at a higher dose than used in the clinical therapy, methotrexate did not cause any acute depletion of folate denvatives in the excreted bile. Therefore, the decrease in the plasma folate appeared not to be related with the biliary excretion process of folates. A factor responsible for the plasma folate depletion by DHFR inhibitors may be due to the malabsorption of folate derivatives excreted into the small intestine.

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