• Title/Summary/Keyword: Methotrexate

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Methotrexate-Incorporated Polymeric Micelles Composed of Methoxy Poly(ethylene glycol)-Grafted Chitosan

  • Jeong, Young-Il;Seo, Dong-Hyuk;Kim, Don-Gon;Choi, Chang-Yong;Jang, Mi-Kyeong;Nah, Jae-Woon;Park, Yoon-Kyung
    • Macromolecular Research
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    • v.17 no.7
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    • pp.538-543
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    • 2009
  • In this study, methotrexate (MTX)-encapsulated polymeric micelles using methoxy poly(ethylene glycol) (MPEG)-grafted chitosan (ChitoPEG) copolymer were prepared. The MIX-incorporated polymeric micelles of ChitoPEG copolymer has a particle size of around 50-100 nm. In 1H nuclear magnetic resonance (NMR) study, the specific peaks of MTX disappeared in heavy water ($D_2O$) and only the specific peak of MPEG was observed, while all of the peaks were confirmed in dimethyl sulfoxide (DMSO). These results indicated that MTX was complexed with chitosan and then formed an ion complex inner-core of the polymeric micelle in an aqueous environment. The drug contents of the polymeric micelle were around $4{\sim}12%$ and the loading efficiency of MTX in the polymeric micelles was higher than 60% (w/w) for all of the formulations. The cytotoxicity of MIX and MTX-incorporated polymeric micelle against CT26 tumor cells was not significantly changed.

Effects of Dangkwiyughwangtang and Okbyoungpoongsangamibang on the immune response induced by Methotrexate in mice (Methotraxate로 유발된 생쥐의 면역반응(免疫反應)에 대한 당귀육황탕(當歸六黃場)과 옥병풍산가미방(玉屛風散加味方)의 효과(效果))

  • Kim, Deog-Gon;Kim, Gyoung-Sun
    • The Journal of Pediatrics of Korean Medicine
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    • v.21 no.1
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    • pp.189-209
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    • 2007
  • Objectives : In order to study the effect of Dangkwiyughwangtang and Okbyoungpoongsangamibang on the immune response induced by methotrexate in mice. Method : Delayed type of hypersensitivity, hemagglutinin titer, hemolysin titer, rosette forming cells, phagocytic activity for immune response, lymphocyte transformation, and productivity of Interleukin-2 were measured. Results : Body weight decreasing was significantly inhibited as compared with control group in both the Dangkwiyughwangtang and Okbyoungpoongsangamibang groups. Delayed type of hypersensitivity was significantly increased as compared with control group in both groups Hemagglutinin titer was significantly increased as compared with control group in both groups. Hemolysin titer was significantly increased as compared with control group in the Okbyoungpoongsangamibang group. Rosette forming cells were significantly increased as compared with control group in both groups. Phagocytic activity for immune response was slightly decreased in the Dangkwiyughwangtang group and slightly increased in the Okbyoungpoongsangamibang group insignificantly as compared with the control group. Lymphocyte transformation was significantly increased as compared with the control group in both the Dangkwiyughwangtang and Okbyoungpoongsangamibang groups. Productivity of Interleukin-2 was significantly increased as compared with the control group in both the Dangkwiyughwangtang and Okbyoungpoongsangamibang groups. Conclusion : Both the Dangkwiyughwangtang and Okbyoungpoongsangamibang groups enhance immunity in mice.

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Delayed Diagnosis of a Tibial Stress Fracture Associated with Glucocorticoid and Methotrexate Therapy in a Patient with Rheumatoid Arthritis: A Case Report

  • Shin, Hye Jeong;Lim, Yi Gun;Lee, Gi Hyang;Lee, Hyun Seok;Song, Beom Yong;Choi, Yoo Min
    • Journal of Acupuncture Research
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    • v.39 no.1
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    • pp.64-69
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    • 2022
  • The risk of stress fractures is associated with rheumatoid arthritis (RA), which can aggravate bone loss. We report the case of a patient who was on long-term medication for RA presenting with lower extremity pain on the left and swelling without trauma. Magnetic resonance imaging and plain radiographs at the previous hospital showed no signs of fracture, but radiographs performed later, revealed a stress fracture of the left distal tibia. The stress fracture may have occurred due to multiple reasons such as long-term use of methotrexate and glucocorticoids, active RA, postmenopausal state, and immobility. Suspicion of a stress fracture should not be ruled out especially in RA patients with persistent pain, even if the radiographical findings are normal. Additional imaging and follow-ups are essential. The patient's pain was relieved with Korean medicine treatments, which suggests their potential application for stress fractures in RA patients.

The Mechanism of Nephrotoxicity Formation of Methotrexate in STZ-Induced Hyperglycemic Rats (Streptozotocin 유도 당뇨성 흰쥐에서 methotrexate의 신독성 생성기전에 관한 연구)

  • Kim Seok-Hwan;Kim Yeo-Jeong;Lee Joo-Yeon;Kang Hye-Ok;Lee Hang-Woo;Choi Jong-Won
    • Journal of Life Science
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    • v.16 no.2 s.75
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    • pp.259-265
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    • 2006
  • This study is investigated the effect on mechanism of nephrotoxicity formation of methotrexate(MTX) by hyperglycemic by streptozotocin(STZ). MTX was injected daily at two doses of 3, 6 mg/kg for 1 week in STZ-induced hyperglycemic rats. Activities of BUN, creatinine and LDH were significantly increased by treatment with MTX in STZ-induced diabetic group when compared to MTX treatment group in normal rats' Renal lipid peroxide content and activities of cytosolic enzyme were significantly increased in the treatment of MTX in diabetic group. The concentration of glutathione and glutathione biosynthesis enzymes were decreased by treatment with MTX in STZ-induced diabetic group. These results suggest that nephrotoxicity of MTX in STZ-induced hyperglycemic rat was caused by activation of renal metabolizing enzymes in cytosol and decrease of glutathione concentration.

Quantitative Analysis of Methotrexate using Hitach-7600 P-module (Hitach-7600 P-module을 이용한 Methotrexate 정량분석 평가)

  • Kim, Min-Eui;Cha, Kyong-Ho;Kim, Seung-Hee;Kim, Nam-Joo;Chae, Hyo-Jin
    • Korean Journal of Clinical Laboratory Science
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    • v.41 no.4
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    • pp.167-172
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    • 2009
  • Methotrexate (MTX) in one of the antineoplastic drug and it is known to effective to management of acute lymphoblastic leukemia in children, management of choriocarcinoma and related trophoblastic tumors in women, management of carcinomas of the breast, tongue, pharynx, and tests, maintenance of remission in leukemia and treatment of serve, debilitating psoriasis. Intermediate to high-dose methotrexate administration followed by leucovorin rescue is effective in treatment of carcinoma of the lung and osteogenic sarcoma. Intrathecal administration is effective in treating meningeal leukemia or lymphoma. There are FPIA (Fluorescence polarization immunoassay) and EMIT (Enzyme multiplied immunotechique) methods that measure for MTX. We evaluated the FPIA and EMIT methods. MTX were measured by Hitachi-7600 P-module using EMIT and FPIA using TDX in the sera 60 patients. The performance characteristics evaluated were, light influence, linearity, comparison with FPIA. Also, precision evaluated were three level controls through put following CLSI evaluation protocols (EP10-A). When the MTX value of $4.16{\pm}5.78{\mu}{\mu}mol/L$ (mean, SD) by the Hitachi-7600 P-module was compared with that of $4.05{\pm}5.47{\mu}{\mu}mol/L$ by FPIA, coefficients of correlation of 0.988 was obtained. The regression equation was Y (Hitachi-7600 P-module) = 0.9408 x (FPIA) + 0.1316 (r=0.9885, n=60). CVs of MTX measured by Hitachi 7600 P-module was 6.78% at $0.33{\mu}{\mu}mol/L$, 0.96% at $1.16{\mu}{\mu}mol/L$, and 0.96% at $8.04{\mu}{\mu}mol/L$. The precision was excellent in each group. The linearity was acceptable. We evaluated that MTX is light-sensitive on prolonged exposure to direct sunlight. Comparing with the FPIA using TDX, the Hitachi-7600 P-module using EMIT showed good coefficient of correlation and precision. Therefore the Hitachi-7600 P-module can replace the FPIA for quantitative analysis of MTX.

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PREPARATION AND PHARMACOKINETICS OF METHOTREXATE DELIVERY SYSTEM USING LONG-CIRCULATING LIPOSOMES

  • Hong, Myo-Sook;Kim, Chong-Kook
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.287-287
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    • 1996
  • Long-circulating liposomes have prompted interests in using them as a drug delivery system. This improvements in delivery has been thought to be the results from sustained action of liposomes in plasma without RES uptake. Although methotrexate(MTX) has been one of the most widely used antineoplastc drug, its use was limited by prompt RES uptake. The purpose of this study was to prepare long-circulating liposomes for MTX using highly water-soluble polymer (PEG-PE). In vitro, release of MTX from liposomes in phosphate buffer (pH 7.4), rat liver homogenate, and rat plasma was investigated. The pharmacokinetics and organ distribution of fee drug, conventional and long-circulating liposomes were also compared with one another after intravenous administration to rats.

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Influence of Pretreatment with Immunosuppressive Drugs on Viral Proliferation

  • Lee, Ga-Eun;Shin, Cha-Gyun
    • Journal of Microbiology and Biotechnology
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    • v.28 no.10
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    • pp.1716-1722
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    • 2018
  • Immunosuppressive drugs are used to make the body less likely to reject transplanted organs or to treat autoimmune diseases. In this study, five immunosuppressive drugs including two glucocorticoids (dexamethasone and prednisolone), one calcineurin inhibitor (cyclosporin A), one non-steroid anti-inflammatory drug (aspirin), and one antimetabolite (methotrexate) were tested for their effects on viral proliferation using feline foamy virus (FFV). The five drugs had different cytotoxic effects on the Crandell-Ress feline kidney (CRFK) cells, the natural host cell of FFV. Dexamethasone-pretreated CRFK cells were susceptible to FFV infection, but pretreatment with prednisolone, cyclosporin A, aspirin, and methotrexate showed obvious inhibitory effects on FFV proliferation, by reducing viral production to 29.8-83.8% of that of an untreated control. These results were supported by western blot, which detected viral Gag structural protein in the infected cell lysate. As our results showed a correlation between immunosuppressive drugs and susceptibility to viral infections, it is proposed that immune-compromised individuals who are using immune-suppressive drugs may be especially vulnerable to viral infection originated from pets.

Leukoencephalopathy and Disseminated Necrotizing Leukoencephalopathy Following Intrathecal Methotrexate Chemotherapy and Radiation Therapy for Central Nerve System Lymphoma or Leukemia

  • Kim, Ji-Yeon;Kim, Sung-Tae;Nam, Do-Hyun;Lee, Jung-Il;Park, Kwan;Kong, Doo-Sik
    • Journal of Korean Neurosurgical Society
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    • v.50 no.4
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    • pp.304-310
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    • 2011
  • Objective : Intrathecal methotrexate (MTX) therapy combined with whole brain radiotherapy (WBRT) is one of the major treatment modalities for leukemia and lymphoma involving the central nervous system (CNS). The purpose of this study was to retrospectively determine the incidences of leukoencephalopathy and disseminated necrotizing leukoencephalopathy (DNL) following intrathecal MTX therapy for CNS lymphoma or leukemia and to assess the potential risk factors. Methods : Between January 2000 and August 2009, 143 patients with CNS lymphoma or leukemia received intrathecal MTX therapy alone or in combination with WBRT at a single institution. Patients were followed up clinically and radiologically at regular two- or three-month intervals. Medical records were reviewed to obtain information regarding the patients' demographics, medical histories, radiologic characteristics, treatments, and clinical courses. Results : On follow-up MR images, leukoencephalopathy was found in 95 of 143 patients (66.4%). The median time to develop leukoencephalopathy was 6.6 months. Among those with leukoencephalopathy, four patients showed seven extensive white-matter changes with strongly enhancing lesions demonstrating DNL. Histological confirmation was done in six lesions of three patients and radiological diagnosis alone in one patient. Four lesions spontaneously disappeared on MR images without any treatment, with a mean duration of 14 months before disappearance of DNL. Conclusion : Leukoencephalopathy is a common phenomenon that occurs following intrathecal MTX therapy; however, DNL occurs at a very low incidence. For newly developed enhancing lesions, consideration for the occurrence of DNL should be taken to avoid unnecessary invasive procedures or therapies.