• Journal of Pharmaceutical Investigation
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• 제25권2호
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• pp.101-108
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• 1995

The surface of albumin microspheres could be modified with methotrexate (MTX) by using 1,3-dicyclohexylcarbodiimide (DCC). Surface-modified albumin microspheres entrapping no MTX (SAMS), free MTX (SAMSF) and MTX-bovine serum albumin (BSA) conjugates (SAMSC) were prepared. respectively, and their release characteristics were investigated in the presence of trypsin using a dissolution tester. The mean diameters of all the microspheres were $5{\sim}8\;{\mu}m$, and their shapes was small and uniform. MTX bound tn their surfaces was released slower than the entrapped free MTX, and laster than the entrapped MTX-BSA conjugates. Also, surface-modified MTX was scarcely released in the absence of a proteolytic enzyme. Therefore, the surface-modified MTX may be released rapidly from SAMSC at the target site, and thereafter MTX may be released slowly from the encapsulated MTX-BSA conjugates in SAMSC for a long period.

• 대한한의학회지
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• 제29권3호
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• pp.21-37
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• 2008

Objectives: The purpose of this study was to verify the effect of Palmiboshinwhan (PMBSW) in methotrexate (MTX)-induced immunosuppressed SD rats. Methods: The test articles were once a day dosed for 14 days by gastric gavage from 2 days after last MTX-dosing, and changes in body weight, spleen weight and total blood leukocyte numbers were observed with total lymphocyte numbers, B and T lymphocyte percentages, CD3+CD4+, CD3+/CD8+, CD4+/CD8+ T lymphocyte percentages in the blood and spleen, the serum interleukin (IL)-2 levels and the productivity of IL-2 of splenic cells. Result & Conclusion: It is concluded that PMBSW has relatively good immunostimulating effect in the MTX-induced immunosuppressed SD rats. Theefficient dosage was considered above 500mg/kg. In addition, it is considered that the immunostimulating effect of PMBSW was mediated to both the B and T lymphocytes. The more favorable effects were detected in T lymphocytes rather than B lymphocytes, and PMBSW showedrelatively good stimulating potential against CD4+ T lymphocytes but not any stimulating effect against CD8+ T lymphocytes in the present study.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.6061-6066
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• 2015

Methotrexate (Mtx), used for its anticancer and immunsuppresive properties, is known to be a nephrotoxic agent. We aimed to investigate the effects of lycopene (Lyc) alone or combined with melatonin (Mel) on Mtxinduced nephrotoxicity since both of these agents have antioxidant and anti-inflammatory effects. Nephrotoxicity was induced by intraperitoneal administration of methotrexate at a dose of 20 mg/kg. Treatment both with Lyc alone and Lyc combined with Mel provided significant reduction in tumor necrosis factor-alpha, interleukin 1-beta and ceruloplasmin levels in Mtx administered rats. Hovewer, Lyc combined with Mel provided a significant reduction also in NO levels. Hstopathological examination showed that there was an obvious improvement in the degenerative changes compared to Mtx administrated group with the Lyc combined Mel group giving best protection. In conclusion Lyc alone and combined with Mel provided significant improvement against renal damage caused by Mtx, preseumably via antioxidant and anti-inflammatory activities.

• Journal of Yeungnam Medical Science
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• 제16권1호
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• pp.131-136
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• 1999

자궁경관 임신은 최근에 인공유산의 증가와 인공 보조 생식술(assisted reproductive technology) 등에 의하여 증가되는 양상을 보인다. 과거에는 자궁경관 임신은 대량의 무통성 질출혈로 진단을 내리고 치료 방법은 천자궁적출술이 유일한 수단이었으나, 지금은 질식 초음파의 개발로 자궁경관 임신을 조기에 진단하고 자궁 보존적 방법으로 치료하여 차후 임신을 기대할 수 있게 되었다. 그 치료 방법 중 하나로 Methotrexate(MTX)를 주사하여 성공적으로 치유된 많은 보고들이 있었다. 본 저자들은 임신 8주에 자궁경관 임신으로 진단된 환자에서 전신적 MTX 투여와 복식 초음파 관찰 하에 양막강내 MTX 투여 병합 요법으로 치료한 1례를 보고하고 치료과정에서 자궁경부 병변의 지연 관해에 대해서 문헌 고찰과 함께 보고하는 바이다.

• 약학회지
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• 제36권6호
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• pp.591-597
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• 1992

The organ distribution of $[^3H]$-methotrexate-lactosaminated bovine serum albumin conjugates ($[^3H]$-MTX-LBSA) was investigated to examine their role as a liver-specific anticancer drug. Synthesis of lactosaminated bovine serum albumin(LBSA) with BSA, lactose and sodium cyanoborohydride through reductive amination was followed by its conjugation with methotrexate (MTX) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), thereby synthesizing [$[^3H]$-MTX-LBSA conjugates. Organ distribution and plasma elimination profiles were studied in male Wistar rats after intravenous injection of [$[^3H]$-MTX-LBSA conjugates. The fates of $[^3H]$-MTX and the $[^3H]$-MTX-BSA conjugates´fates were also investigated for comparison. The results showed that the plasma level of $[^3H]$-MTX-LBSA conjugates declined more rapidly than those of $[^3H]$-MTX-BSA and their liver concentration was significantly higher than those of other treatment (p<0.01). In addition, their uptake compared to the amount taken up by the liver (1 : 33.1 at 10 min, 1 : 24.1 at 120 min). All these suggested that MTX-LBSA conjugate is one of the drug delivery system (DDS) that is advanced in concentrating MTX in the liver and minimizing the renal toxicity of MTX.

• 대한한방소아과학회지
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• 제12권1호
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• pp.211-230
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• 1998

Introduction The effects of Bojungikkitang on the immunosuppression induced by methotrexate in rats were investigated in this experiment. The multiple parameters of immunity assessed in. each rats includes the rate of body weight loss, weight changes in thymus, spleen and axillary lymphnode. The number of lymphocyte and CD4+ T cell count in blood, thymus, spleen and axillary lymphnode were also measured. Methodology Male Sprague-Dawley rats were chosen as an experiment object and were divided into 3 groups by a random selection. Each group consisted 6 rats. The normal group didn't receive any treatment. The control group was administered methotrexate for 4 days. The sample group was administered with both Bojungikkitang and methotrexate for 4 days. The dosage of medication was 2cc/day, 1cc given at 10AM and another 1cc given at 5PM. Results The rate of body weight loss was significantly decreased in the sample group. The weight of thymus was significantly increased in the sample group while the weight of spleen did not show much increase. Blood CD4+ T cell count, thymus lymphocyte count, thymus CD4+ T cell count, spleen lymphocyte count, spleen CD4+ T cell count and axillary lymph node CD4+ T cell count were significantly increased in the sample group while blood lymphocyte count and axillary lymphnode lymphocyte count did not show much increase. Conclusion As one can witness from the above results, administration of Bojungikkitang played potent role in increasing immune system among the rats treated with methotrexate which induces immunosuppression. Overall increase of lymphocyte count and CD4+ T cell count in the sample group with Bojungikkitang effectively proves its ability to boost the immune system.

• 대한한방소아과학회지
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• 제12권1호
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• pp.257-276
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• 1998

Introduction The effects of Samchulkunbitang on the immunosuppression induced by methotrexate in rats were investigated in this experument. The multiple parameters of immunity assessed in each rats includes the rate of body weight loss, weight changes in thymus, spleen and axillary lymphnode. The number of lymphocytes and CD4+ T cell count in the blood, thymus, spleen and axillary lymphnode were also measured. Methodology Male Sprague-Dawley rats were chosen as an experiment object and were divided into 4 groups by a random selection. Each group consisted of 6 rats. The normal group didn't receive any treatment. The control group was administered with methotrexate for 5 days. The sample Ⅰ group was administered with Samchulkunbitang for 5 days. The sample Ⅱ group was administered with both Samchulkunbitang and methotrexate for 5 days. The dosage of medication was 2cc/day, 1cc given at 10 AM and another 1cc given at 5 PM. Results The rate of body weight loss was significantly increased in the Sample Ⅰ and Sample Ⅱ group. The weight of thymus and spleen were significantly increased in Sample Ⅰ and Sample Ⅱ groups While the weight of axillary lymphnode did not show much increase. No significant differences were measured among the experimental groups. Blood lymphocyte count, blood CD4+ T cell count, spleen lymphocyte count, axillary lymphnode lymphocyte and CD4+ T cell count were significantly increased in Sample Ⅰ and Sample Ⅱ groups while spleen CD4+ T cell count did not show much increase. No significant differences were measured among the experimental groups. Conclusion As one can witness from the above results, administration of Samchulkunbitang played potent role in increasing immune system among the rats treated with methotrexate which induces immunosuppression. Overall increase of lymphocyte count and CD4+ T cell count in the sample groups with Samchulkunbitang effectively proves its ability to boost the immune system.

• 대한한방소아과학회지
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• 제18권1호
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• pp.27-48
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• 2004

Objective: The purpose of this study was to investigate the effect of Hwanggigunjungtang(HGT) on white rats with deteriorated immunity caused by methotrexate. Methods: First, methotrexate was fed to the white rats once a day for 4 days. After the immune responses of the rats are deteriorated, dried extracts of HGT mixed in water was fed to the rats once a day for 14 days. And then we measured the percentage of B-cell and T-cell in peripheral blood, the percentage of CD3+CD4+ T-cell and CD3+CD8+ T-cell of blood sampled from spleen and peripheral region. Results: The percentage of B-cell of peripheral blood was not different statistically. The percentage of T-cell of peripheral blood was increased significantly in HGT group as compared with control group. The percentage of CD3+CD4+ T-cell of peripheral blood was increased significantly in HGT group as compared with control group. The percentage of CD3+CD8+ T-cell of peripheral blood was decreased in HGT group as compared with control group. The percentage of CD3+CD4+ T-cell of spleen was increased significantly in HGT group as compared with control group. The percentage of CD3+CD8+ T-cell of spleen was not different statistically. Conclusion: According to the above results, HGT has an effect of increasing immune responses on white rats with deteriorated immunity caused by methotrexate.

• 대한한방내과학회지
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• 제28권1호
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• pp.12-24
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• 2007

Objective : To investigate the effect of Samilshinkihwan(SISKW) on white rats with deteriorated immunity caused by methotrexate. Methods : The test articles were dosed once a day for 14 days by gastric gavage at a dosage 1000, 500 and 250mg/kg/10ml of SISKW from 2 days after last MTX-dosing, and changes in body weight, spleen weight, total blood leukocyte numbers, total lymphocyte numbers, B and T lymphocyte ratio, CD3+CD4+, CD3+/CD8+ and CD4+/CD8+ T lymphocyte ratio in the blood and spleen were measured. In addition, the serum interleukin (IL)-2 levels and the productivity of IL-2 of splenic cells were also demonstrated in this study. Results : The changes on body weight increased significantly in the 1000mg/kgof SISKW group. The changes on the spleen weight, the total blood leukocytenumbers, the total lymphocyte numbers in the blood and spleen, the ratio of T-cell in the blood and spleen and the ratio of CD3+CD4+ T-cell in spleen increased significantly in all SISKW groups as compared with the control group. The ratio of CD4+/CD8+ T-cells in blood increased significantly. The serum IL-2 levels and productivity of IL-2 of splenic cells increased significantly in 1000 and 500mg/kg SISKW groups as compared with the control group. Conclusions : Samilshinkihwanhas an effect of increasing immune responses, especially on cellular immune responses, in white rats with deteriorated immunity caused by methotrexate.

• Biomolecules & Therapeutics
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• 제6권4호
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• pp.383-388
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• 1998

The present study was aimed to investigate the preventive effects of rebamipide on the multiple organ dysfunction in a rat model of circulatory shock induced by bacterial endotoxin (E. coli lipopolysaccharide; LPS) in comparison with that of methotrexate. Endotoxemia for 6 hours resulted in little change in the levels of hemoglobin and neutrophils. However, treatment with methotrexate decreased significantly the numbers of circulating neutrophils. Significant increases in serum alanine aminotransferase (ALT,958 $\pm$ 250 lU/L, p<0.001) and aspartate aminotransferase (AST, 1350 $\pm$ 295 lU/L, p<0.001) levels induced by endotoxemia were significantly decreased by rebamipide and methotrexate. The increased level of lactic acid dehydrogenase (LDH) by LPS (2850 $\pm$ 467 lU/L, p<0.05) was significantly inhibited by rebamipide, but not by methot.elate. The elevated serum creatinine (1.2$\pm$0.1, p.0.05) and urea levels (55.3$\pm$6.5 mg/dL, p.0.01) by LPS were also decreased by rebamipide, but not by methotrexate. In line with these results, the plasma concentration of tumor necrosis factor-$\alpha$ (TNF-7,167 $\pm$ 20 pg/mL) was significantly increased upon injection of endotoxin at 1 hour by 1570$\pm$100 pg/mL, and declined to 312$\pm$35 pg/mL at 6 hours. The TNF-$\alpha$ level at 6 hours was significantly decreased by rebamipide to 207$\pm$8 pg/mL (P<0.05). Taken together, it is summarized that rebamipide inhibits the development of multiple ogran dysfunction by inhibition of neutrophil activation in association with inhibition of TNF-$\alpha$ formation in a murine model of endotoxemia.