• Title/Summary/Keyword: Dexamethasone treatment

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Effects of high dose of dexamethasone on $PLA_2$, GGT activity and lung morphology in NNNMU-induced ARDS rats (NNNMU로 유도된 급성호흡곤란증후군 흰쥐 폐장에서의 dexamethasone에 의한 $PLA_2$, GGT의 활성도 및 형태학적인 변화)

  • Lee, Young Man;Park, Yoon Yub;Koh, Younsuck
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.6
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    • pp.925-935
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    • 1996
  • Background : In order to elucidate one of the pathogenic mechanisms of ARDS associated with pulmonary surfactant and oxidant injury, acute lung injury was induced by N-nitroso N-methylurethane (NNNMU). In this model, the role of phospholipase $A_2$ ($PLA_2$), surfactant, gamma glutamyl transferase (GGT) and morphology were investigated to delineate one of the pathogenic mechanisms of ARDS by inhibition of $PLA_2$ with high dose of dexamethasone. Method: Acute lung injury was induced in Sprague-Dawley rats by NNNMU which is known to induce acute lung injury in experimental animals. To know the function of the alveolar type II cells, GGT activity in the lung and bronchoalveolar lavage was measured. Surfactant phospholipid was measured also. $PLA_2$ activity was measured to know the role of $PLA_2$ in ARDS. Morphological study was performed to know the effect of $PLA_2$ inhibition on the ultrastructure of the lung by high dose of dexamethasone. Results : Six days after NNNMU treatment (4 mg/kg), conspicuous pulmonary edema was induced and the secretion of pulmonary surfactant was decreased significantly. In the acutely injured rats' lung massive infiltration of leukocytes was observed. At the same time rats given NNNMU had increased $PLA_2$ and GGT activity tremendously. Morphological study revealed bizarre shaped alveolar type II cells and hypertrophied lamellar bodies in the cytoplasm of the alveolar type II cells. But after dexamethasone treatment (20 mg/kg, for six days) in NNNMU-treated rats, these changes were diminished i.e. there were decrease of pulmonary edema and increase of surfactant secretion from alveolar type D cells. Rats given dexamethasone and NNNMU had decreased $PLA_2$ and GGT activity in comparison to NNNMU induced ARDS rats. Conclusion : Inhibition of $PLA_2$ by high dose of dexamethasone decreased pathological findings caused by infiltration of leukocytes and respiratory burst. Based on these experimental results, it is suggested that an activation of $PLA_2$ is the one of the major factors to evoke the acute lung injury in NNNMU-induced ARDS rats.

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Pooled Analysis of Pomalidomide for Treating Patients with Multiple Myeloma

  • Sun, Jia-Jia;Zhang, Chi;Zhou, Jun;Yang, Hui-Lin
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3163-3166
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    • 2015
  • Background: Patients with refractory or relapsed multiple myeloma are considered to have a very poor prognosis, and new regimens are needed to improve this setting. Pomalidomide is a new immunomodulatory drug with high in vitro potency. Immunomodulatory drugs are hypothesized to act through multiple mechanisms. Here we performed a systemic analysis to evaluate pomalidomide-based chemotherapy (pomalidomide in combination with low-dose dexamethasone) as salvage treatment for patients with refractory and relapsed multiple myeloma. Methods: Clinical studies evaluating the efffectiveness of pomalidomide based regimens on response and safety for patients with refractory and relapsed multiple myeloma were identified using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: For pomalidomide based regimens, 4 clinical studies which including 291 patients with refractory and relapsed multiple myeloma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 41.2% (120/291). Major adverse effects were hematologic toxicity, including grade 1 or 2 anemia, leucopenia and thrombocytopenia with pomalidomide based treatment. No treatment related death occurred. Conclusion: This pooled analysis suggests that pomalidomide in combination with low-dose dexamethasone is active with good tolerability in treating patients with refractory or relapsed multiple myeloma.

A Detrimental Role of Immunosuppressive Drug, Dexamethasone, During Clostridium difficile Infection in Association with a Gastrointestinal Microbial Shift

  • Kim, Hyeun Bum;Wang, Yuankai;Sun, Xingmin
    • Journal of Microbiology and Biotechnology
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    • v.26 no.3
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    • pp.567-571
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    • 2016
  • We investigated the increased risk of Clostridium difficile infection (CDI) caused by the combined use of antibiotics and an immunosuppressive drug in a mouse model. Our data showed that an approximate return to pretreatment conditions of gut microbiota occurred within days after cessation of the antibiotic treatment, whereas the recovery of gut microbiota was delayed with the combined treatment of antibiotics and dexamethasone, leading to an increased severity of CDI. An alteration of gut microbiota is a key player in CDI. Therefore, our data implied that immunosuppressive drugs can increase the risk of CDI through the delayed recovery of altered gut microbiota.

Effect of Picrorrhizae Rhizoma Aqueous Extracts on Paw Chronic Inflammation In Mice

  • Leem, Ji-Young;Ku, Sae-Kwang;Seo, Bu-Il;Jeon, Mi-Hye;Park, Ji-Ha
    • The Journal of Korean Medicine
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    • v.36 no.2
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    • pp.21-35
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    • 2015
  • Objectives: The purpose of this study was to examine the efficacy of Picrorrhizae Rhizoma (PR) aqueous extracts on the formalin-induced paw chronic inflammation in mice. Methods: PR extracts (500, 250 and 125mg/kg) or distilled water (DW) were orally administered once a day for 10 days to formalin-injected chronic inflammatory mice. The paw thicknesses and volumes were measured daily and the paw wet-weight and histological profiles were conducted at termination with paw tumor necrosis factor (TNF)-${\alpha}$ contents measurement. The anti-inflammatory effects of PR extracts were compared with dexamethasone. Results: In DW treated control group, the paw thickness, paw wet-weights and paw TNF-${\alpha}$ contents were markedly increased. Severe chronic inflammation signs such as severe fibrosis, the formation of necrotic debris, and infiltration of inflammatory cells were detected in histopathological observations. However, these formalin-induced changes were dramatically decreased by treatment of dexamethasone and all three different dosages of PR extracts. The anti-inflammatory effects of PR at highest dose were slighter than that of dexamethasone, but it did not show any harmful effects on the body weight contrary to dexamethasone. Conclusion: These results suggest that PR extracts have safe and favorable effects on formalin-induced chronic inflammation.

The Effect of Red Ginseng on Sarcopenic Rat (홍삼의 Dexamethasone 유도 근감소증 모델 백서에 대한 효과 연구)

  • Seo, Yoon-jeong;Lew, Jae-hwan
    • The Journal of Internal Korean Medicine
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    • v.39 no.6
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    • pp.1168-1180
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    • 2018
  • Objective: As the number of sarcopenic patients worldwide is increasing, the need for the treatment of sarcopenia is increasing. Ginseng has been reported to be a major herbal supplement. We tested whether red ginseng would be effective for sarcopenia using red ginseng preparation which can be easily obtained locally in Korea. Methods: 30 rats were randomly divided into three groups: the control group (n=10) (Group C), the group with Dexamethasone -induced sarcopenia (n=10) (Group D), and the group to which red ginseng was administered group after induced sarcopenia with Dexamethasone (n=10) (Group DH). Dexamethasone was intraperitoneally administered to group D and group DH for 7 days to make sarcopenic model. After that, the red ginseng tablets prepared by Korea Ginseng Corporation were diluted in distilled water and administered orally to the DH group for 2 weeks. Body weight and grip strength were measured 8 times during the experiment. At the end of the experiment, blood was collected by cardiac puncture. In addition, the tibialis muscle was extracted, a myofibril cross section was measured by immunohistochemical staining and MyHC (myosin heavy chain) was quantified by Western blotting. Results: The ratio of the area on myofibril cross-section showed significant differences after administration of the red ginseng tablet. Conclusions: Red ginseng has a significant effect on the recovery of myofibril cross-section on sarcopenia. This experiment will be helpful for future clinical studies on drug effects in sarcopennia.

Effect of water extract Phellinus linteus-discard Schisandra chinensis solid fermented extracts in an Animal Model of Dexamethasone-Induced Muscle Loss (Dexamethasone으로 유도한 근감소 동물모델에서 상황버섯-오미자박 고상발효 열수추출물의 근감소 개선에 대한 효과)

  • Su-Jin, Hwang;Young-Suk, Kim;Tae Woo, Oh
    • Herbal Formula Science
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    • v.30 no.4
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    • pp.269-280
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    • 2022
  • Objectives : In this study, it was investigated the effects of solid-phase fermentation extraction with Phellinus linteus of discarded Schisandra chinensis extract (PS) and its action mechanism on dexamethasone-induced muscle atrophy in mice. Methods : In mice, muscle atrophy model was induced by dexamethasone (5 mg/kg, I.p) once daily for 2 weeks and with PS extract administration (100 and 300 mg/kg, p.o.) as treatment groups. The changes in body weights, grip strength, Treadmill test, muscle weights, and the expression of atrophy-related genes were measured in muscle atrophy mice. The histological changes of gastrocnemius tissues were also observed by H&E staining with measurement of myofiber size. Results : The administration of PS extract increased significantly body weights, grip strength, treadmill test and muscle weights in muscle atrophy mice. PS extract administration increased significantly the area of myofibers and inhibited structural damages of muscle and increased significantly the expression of myogenin and decreased significantly the expression of MuRF1, Atrogin1 and phosphorylation of AMPK and PGC1α in muscle tissues of muscle atrophy mice. Conclusions : These results indicate that PS extract has a improvement effects on muscle atrophy with stimulation of myogenic differentiation and inhibition of mRNA degradation that could be related with the activation of AMPK and PGC1α signaling pathways in muscle. This suggests that PS extract can apply to treat muscle atrophy in clinics.

Study on IL -8 Expression in Peripheral Blood Monocytes (말초 혈액 단핵구에서 IL-8 발현에 관한 연구)

  • Kim, Jae-Yeol;Lee, Jae-Cheol;Kang, Min-Jong;Park, Jae-Seok;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Lee, Jae-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.5
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    • pp.703-712
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    • 1995
  • Background: Peripheral blood monocytes are important immune effector cells that play a fundamental role in cellular immunity. In addition to their antigen-presenting and phagocytic activities, monocytes/macrophage produce a vast array of regulatory and chemotactic cytokines. Interleukin-8(IL-8), a potent neutrophil-activating and chemotactic peptide, is produced in large quantities by mononuclear phagocytes and may be an important mediator of local and systemic inflammation. Overexpression by IL-8 of such inflammation may be an important step of tissue injury frequently seen in inflammatory reaction. So it could be hypothesized that the agents which block the production of IL-8 can decrease the inflammatory reaction and tissue injury. To evaluate this, we described the effect of Dexamethasone, $PGE_2$, Indomethacin and Interferon-$\gamma$(IFN-$\gamma$) on IL-8 mRNA and protein expression from LPS-stimulated human peripheral blood monocytes(PBMC). Method: PBMC was isolated from healthy volunteers. To evaluate the effect of Dexamethasone, $PGE_2$ & Indomethacin, these drug were treated for 1 hour before and after LPS stimulation and IFN-$\gamma$ was only treated I hour before the LPS stimulation. Northern blot analysis for IL-8 mRNA and ELISA for immunoreactive IL-8 protein in culture supernatant were performed. We repeated above experiment three times for Northern blot analysis and two times for ELISA and got the same result. Results: 1) Pre- and post-treatment of Dexamethasone suppressed both the LPS stimulated IL-8 mRNA expression and IL-8 protein release in PBMC. 2) IFN-$\gamma$ pre-treatment suppressed the IL-8 mRNA expression and IL-8 protein release in unstimulated cells. 3) In LPS stimulated cells, IFN-$\gamma$ suppressed the IL-8 mRNA expression but IL-8 protein release suppression was not observed. 4) $PGE_2$ and Indomethacin exert no effect on the LPS-stimulated IL-8 mRNA and protein expression in concentration used in this experiment ($PGE_2;10^{-6}M$, Indomethacin; $10{\mu}M$). Conclusion: One of the mechanism of antiinflammatory action of Dexamethasone can be explained by the suppressing effect of IL-8 production in some extent and by this antiinflammatory effect, dexamethasone can be used to suppress local and systemic inflammation mediated by IL-8.

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Phosphoproteomic Analysis of AML14.3D10 Cell Line as a Model System of Eosinophilia

  • Ryu, Su-In;Kim, Won-Kon;Cho, Hyun-Ju;Lee, Phil-Young;Jung, Hye-Yun;Yoon, Tae-Sung;Moon, Jeong-Hee;Kang, Sung-Hyun;Poo, Ha-Ryoung;Bae, Kwang-Hee;Lee, Sang-Chul
    • BMB Reports
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    • v.40 no.5
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    • pp.765-772
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    • 2007
  • Eosinophils act as effectors in the inflammatory reactions of allergic diseases including atopic dermatitis. Atopic dermatitis patients and others with allergic disorders suffer from eosinophilia, an accumulation of eosinophils due to increased survival or decreased apoptosis of eosinophils. In this study, a differential phosphoproteome analysis of AML14.3D10 eosinophil cell line after treatment with IL-5 or dexamethasone was conducted in an effort to identify the phosphoproteins involved in the proliferation or apoptosis of eosinophils. Proteins were separated by 2-DE and alterations in phosphoproteins were then detected by Pro-Q Diamond staining. The significant quantitative changes were shown in nineteen phosphoproteins including retinoblastoma binding protein 7, MTHSP75, and lymphocyte cytosolic protein 1. In addition, seven phosphoproteins including galactokinase I, and proapolipoprotein, were appeared after treatment with IL-5 or dexamethasone. Especially, the phospho-APOE protein was down-regulated in IL-5 treated AML14.3D10, while the more heavily phosphorylated APOE form was induced after dexamethasone treatment. These phosphoproteome data for the AML14.3D10 cell line may provide clues to understand the mechanism of eosinophilia as well as allergic disorders including atopic dermatitis.

Effect of Sopung-san Extracts on the Passive Cutaneous Anaphylaxis of Wistar Rats (Type I Allergic Dermatitis) (소풍산(消風散) 추출물이 수동 피부 아나팔락시스(1형 알러지 피부염)에 미치는 효과)

  • Ryu, Ji-Chul;Lee, Jae-Geun;Ku, Sae-Kwang;Jee, Seon-Young
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.22 no.3
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    • pp.1-10
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    • 2009
  • Purpose : The objective of present study is to detect the effect of Sopungsan aqueous extracts (SPS) on the passive cutaneous anaphylaxis (PCA; type I allergic dermatitis) Method : 500, 250 and 125mg/kg of SPS were orally administered 12 hr-interval before antigen challenge (total 4 times administered). PCA reactions were induced using rat anti-ovalbumin (OVA) serum contain IgE (titer 1:32) as sensitization and OVA as antigen challenge. 30 min after antigen challenge, the diameter of blue-dye spots (evans blue) and leaked amount of dye were observed with histology and histomorphometry at the PCA induced sites. In addition, serum total IgE and histamine levels were also observed by ELISA, respectively. The effects of SPS were compared with dexamethasone 1mg/kg treated rats in the present study. Results : As results of PCA reaction, vasodilation related increase of diameter of blue-dye spot and amount of leaked dye were observed with swelling and edematous changes in the dermis of PCA induced sites. However, these changes on PCA reactions were dramatically and dose-dependently decreased by treatment of SPS as compared with vehicle control. In addition, serum elevations of IgE and histamine were also dose-dependently inhibited by treatment of SPS as compared with vehicle control respectively. The effects of SPS 500mg/kg were similar to that of dexamethasone 1mg/kg in the present study. Conclusion : Base on the results of the present study, it is concluded that SPS has favorable effect on the PCA-induced allergic dermatitis, and SPS 500mg/kg showed similar favorable effects as compared with dexamethasone 1mg/kg. The present findings demonstrate that SPS can be effective for the prevention and treatment of allergic dermatitis.

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The Effects of Corticosteroid Solutions in OLP Patients (구강편평태선에 대한 스테로이드 가글의 효과비교 연구)

  • Jeong, Sung-Hee;Park, Su-Hyeon;Ok, Soo-Min;Huh, Joon-Young;Ko, Myung-Yun;Ahn, Yong-Woo
    • Journal of Oral Medicine and Pain
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    • v.37 no.1
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    • pp.27-33
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    • 2012
  • Oral lichen planus(OLP) is a chronic inflammatory disease with cell-mediated immune responses, but the exact cause is unknown. The treatment aim of OLP is not complete cure but to alleviate symptoms. In this study, two kinds of corticosteroid gargling solutions used for comparing the effects. From 2002 to 2010, 180 patients diagnosed with oral lichen planus and received topical steroid therapy in the Pusan National University Dental Hospital. Each of two types of solution contained dexamethasone (dexamethasone disodium phosphate) and prednisolone ($solondo^{(R)}$). A period of relief of symptoms and recurrence was recorded. The group using solution containing dexamethasone(dexa gargle) was prescribed to 33 patients(25 female, 8 male) and another group containing prednisolone (solon gargle) included 147 patients (114 female, 33 male). The effect of dexa gargle seemed faster than the solon gargle. There was no significant difference for recurrent rate between the groups using dexa and solon gargle.