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Role of IL-15 in Sepsis-Induced Skeletal Muscle Atrophy and Proteolysis

  • Kim, Ho Cheol;Cho, Hee-Young;Hah, Young-Sool
    • Tuberculosis and Respiratory Diseases
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    • v.73 no.6
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    • pp.312-319
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    • 2012
  • Background: Muscle wasting in sepsis is associated with increased proteolysis. Interleukin-15 (IL-15) has been characterized as an anabolic factor for skeletal muscles. Our study aims to investigate the role of IL-15 in sepsis-induced muscle atrophy and proteolysis. Methods: Mice were rendered septic either by cecal ligation and puncture or by intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg i.p.). Expression of IL-15 mRNA and protein was determined by reverse transcriptase polymerase chain reaction and Western blot analysis in the control and septic limb muscles. C2C12 skeletal muscle cells were stimulated in vitro with either LPS or dexamethasone in the presence and absence of IL-15 and sampled at different time intervals (24, 48, or 72 hours). IL-15 ($10{\mu}g/kg$) was intraperitoneally administered 6 hours before sepsis induction and limb muscles were sampled after 24 hours of sepsis. Cathepsin L activity was determined to measure muscle proteolysis. Atrogin-1 and muscle-specific ring finger protein 1 (MuRF1) expressions in limb muscle protein lysates was analyzed. Results: IL-15 mRNA expression was significantly lower in the limb muscles of septic mice compared to that of controls. Cathepsin L activity in C2C12 cells was significantly lower in presence of IL-15, when compared to that observed with individual treatments of LPS or dexamethasone or tumor necrosis factor ${\alpha}$. Further, the limb muscles of mice pre-treated with IL-15 prior to sepsis induction showed a lower expression of atrogin-1 and MuRF1 than those not pre-treated. Conclusion: IL-15 may play a role in protection against sepsis-induced muscle wasting; thereby, serving as a potential therapeutic target for sepsis-induced skeletal muscle wasting and proteolysis.

Can Granisetron Injection Used as Primary Prophylaxis Improve the Control of Nausea and Vomiting with Low-Emetogenic Chemotherapy?

  • Keat, Chan Huan;Phua, Gillian;Kassim, Mohd Shainol Abdul;Poh, Wong Kar;Sriraman, Malathi
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.469-473
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    • 2013
  • Background: The purpose of this study is to examine the risk of uncontrolled chemotherapy-induced nausea and vomiting (CINV) among patients receiving low emetogenic chemotherapy (LEC) with and without granisetron injection as the primary prophylaxis in addition to dexamethasone and metochlopramide. Materials and Methods: This was a single-centre, prospective cohort study. A total of 96 patients receiving LEC (52 with and 42 without granisetron) were randomly selected from the full patient list generated using the e-Hospital Information System (e-His). The rates of complete control (no CINV from days 1 to 5) and complete response (no nausea or vomiting in both acute and delayed phases) were identified through patient diaries which were adapted from the MASCC Antiemesis Tool (MAT). Selected covariates including gender, age, active alcohol consumption, morning sickness and previous chemotherapy history were controlled using the multiple logistic regression analyses. Results: Both groups showed significant difference with LEC regimens (p<0.001). No differences were found in age, gender, ethnic group and other baseline characteristics. The granisetron group indicated a higher complete response rate in acute emesis (adjusted OR: 0.1; 95%CI 0.02-0.85; p=0.034) than did the non-granisetron group. Both groups showed similar complete control and complete response rates for acute nausea, delayed nausea and delayed emesis. Conclusions: Granisetron injection used as the primary prophylaxis in LEC demonstrated limited roles in CINV control. Optimization of the guideline-recommended antiemetic regimens may serve as a less costly alternative to protect patients from uncontrolled acute emesis.

The Effectiveness of Ultrasound-guide Steroid Injection According to Morton's Neuroma Size (모톤씨 신경종 크기에 따른 초음파 유도하 스테로이드 주사 효과의 비교분석)

  • Kim, Hak Jun;Hur, Chang Ryong;Kim, Jae Kyun;Jang, Kyu Seon
    • The Journal of Korean Orthopaedic Ultrasound Society
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    • v.5 no.2
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    • pp.61-65
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    • 2012
  • Purpose: The aim of this study was to evaluate the effectiveness of ultrasound-guide steroid injection according to Morton's neuroma size. Materials and Methods: From October 2008 to September 2011, 17 patients (23 cases) diagnosed with Morton's neuroma were investigated. All cases were female and mean age was 52.6 years old. Neuroma were measured by the horizontal and longitudinal length of the mass and underwent ultrasound-guided steroid (5 mg dexamethasone) injection. The efficacy of the injection was determined by Visual Analogue Scale pain score and patient satisfaction(subdivided 4 group-much improved, improved, not improved, aggrevation) Results: 7 of 23(30.4%) cases showed much improved and improved satisfaction and mean longitudinal and horizontal length were $0.71{\pm}0.39cm$ and $0.47{\pm}0.24cm$, respectively. 16 of 23(69.6%) cases showed not improved and aggrevation satisfaction and mean longitudinal and horizontal length were $0.83{\pm}0.42cm$ and $0.54{\pm}0.14cm$, repectively. There was a significant difference in VAS and patient satisfaction in case longitudinal and horizontal length were smaller than 0.5 cm and 0.4 cm. (p<0.05) Conclusion: The ultrasonography is a important modality in diagnosis and treatment of morton's neuroma. Ultrasound-guide steroid injection is effective in case longitudinal and horizontal length were smaller than 0.5 cm and 0.4 cm, respectively.

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Effects of Jungcheonhwadamgangki-tang Plus Antler in Formalin-injected Chronic Inflammation Model in Mice (정천화담강기탕가녹용(定喘化痰降氣湯加鹿茸)이 Formalin으로 유발된 마우스의 만성 염증에 미치는 영향)

  • Jeon, Kwi-Ok;Son, Ji-Young;Choi, Hae-Yun;Park, Mee-Yeon;Kim, Jong-Dae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.4
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    • pp.849-855
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    • 2008
  • In the present study, the anti-inflammatory effect of Jungcheonhwadamgangki-tang plus antler water extract was tested in formalin-injected chronic inflammation model in mouse hind paw. The test articles were dosed once a day for 10 days, and changes on the body weight, paw weights were observed with histopathology of induced paw dorsum pedis. In addition, histomorphometry was also monitored at sacrifice. 15 mg/kg/10 mL of dexamethasone (DEXA) and diclofenac (DICLO) intraperitoneally dosed groups were used as reference groups. A significantly decrease of both absolute and relative paw weights were observed in all dosing groups including DEXA and DICLO groups compared to that of control, and a significantly decrease of the differences between intact and induced paw weights were also observed Jungcheonhwadamgangki-tang plus antler dosing groups compared to that of control. These histological signs-hypertrophy of paw dorsum pedis tissues were detected results from edematous changes on the cutaneous and subcutaneous tissues with severe infiltration of chronic inflammatory cells-were dramatically decreased in all dosing groups including DEXA and DICLO dosing groups compared to that of control. Especially, dose dependently decreases were detected in Jungcheonhwadamgangki-tang plus antler dosing groups compared to that of control. Base on these aforementioned results, it is concluded that Jungcheonhwadam- gangki-tang plus antler have clear anti-inflammatory effect on the chronic inflammation induced by formalin injection.

Effects of Haepyoejin-tang Plus Antler in Formalin-Injected Chronic Inflammation Model in Mice (해표이진탕가녹용(解表二陳湯加鹿茸)이 Formalin으로 유발된 마우스의 만성 염증에 미치는 영향)

  • Liu, Han-Hsiang;Choi, Hae-Yun;Park, Mee-Yeon;Naam, Yee-Hyun;Kim, Jong-Dae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.3
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    • pp.612-618
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    • 2008
  • In the present study, the anti-inflammatory effect of Haepyoejin-tang plus antler water extract was tested in formalin-injected chronic inflammation model in mouse hind paw. The test articles-100, 250, 500 mg/kg- were dosed once a day for 10 days, and changes on the body weight, paw weights were observed with histopathology of induced paw dorsum pedis. In addition, histomorphometry was also monitored at sacrifice. 15 mg/kg/10 mL of dexamethasone (DEXA) and diclofenac (DICLO) intraperitoneally dosed groups were used as reference groups. A significantly decrease of both absolute and relative paw weights were observed in all dosing groups including DEXA and DICLO groups compared to that of control, and a significantly decrease of the differences between intact and induced paw weights were also observed Haepyoejin-tang plus antler dosing groups compared to that of control. These histological signs-hypertrophy of paw dorsum pedis tissues were detected results from edematous changes on the cutaneous and subcutaneous tissues with severe infiltration of chronic inflammatory cells-were dramatically decreased in all dosing groups including DEXA and DICLO dosing groups compared to that of control. Especially, dose dependently decreases were detected in Haepyoejin-tang plus antler dosing groups compared to that of control. Base on these aforementioned results, it is concluded that Haepyoejin-tang plus antler have clear anti-inflammatory effect on the chronic inflammation induced by formalin injection.

Hematological and microbial analysis on a Holstein heifer with infectious bovine keratoconjunctivitis

  • Ha, Seungmin;Hur, Taiyoung;Kang, Seogjin;Jung, Younghun;Son, Junkyu;Kim, Donghyeon;Lee, Jihwan;Sung, Hyunhoon;Cho, Eunseok;Kim, Sangbeom
    • Korean Journal of Veterinary Service
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    • v.43 no.4
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    • pp.245-250
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    • 2020
  • Infectious bovine keratoconjunctivitis (IBK) is the most common ocular disease in cattle, manifesting as corneal opacity, corneal ulcerations and potentially vision loss. The present report describes a 10-month-old Holstein Friesian heifer with IBK treated by systemic tulathromycin, and subconjunctival injection of penicillin and dexamethasone. We investigated changes in the hematological indices and microorganisms related to IBK after treatment. Neutrophils and monocytes decreased during recovery, so it was assumed that these two types of white cells are associated with IBK. Moraxella bovoculi was cleared in the eye, nasal cavity, and oral cavity after treatment. The distribution of M. bovoculi before treatment indicated that a combined systemic and subconjunctival treatment was necessary. The lesioned eye was found to be overwhelmed by Mycoplasma bovoculi, while pathogen abundance was reduced in the nasal cavity and oral cavities. These results suggest that antibiotic treatment can alter the composition and relative abundance of microorganisms.

p38 MAPK Inhibitor NJK14047 Suppresses CDNB-Induced Atopic Dermatitis-Like Symptoms in BALB/c Mice

  • Lee, Ju-Hyun;Son, Seung-Hwan;Kim, Nam-Jung;Im, Dong-Soon
    • Biomolecules & Therapeutics
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    • v.30 no.6
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    • pp.501-509
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    • 2022
  • Atopic dermatitis (AD) is a chronic inflammatory skin disorder. Suppression of MAPKs and NF-κB is implicated as a vital mechanism of action of several traditional Chinese medicines for AD therapy. Although overexpression of MAPK mRNA in the skin tissue has been shown in the AD model, the roles of each MAPK in AD pathogenesis have rarely been studied. This study examined the effect of NJK14047, an inhibitor of p38 MAPKs, on AD-like skin lesions induced in BALB/c mice by sensitization and challenges with 1-chloro-2,4-dinitrobenzene (CDNB) on dorsal skin and ears, respectively. After induction of AD, NJK14047 (2.5 mg/kg) or dexamethasone (10 mg/kg) was administrated for 3 weeks via intraperitoneal injection. Following its administration, NJK14047 suppressed CDNB-induced AD-like symptoms such as skin hypertrophy and suppressed mast cell infiltration into the skin lesions. It also reduced CDNB-induced increase in TH2 cytokine (IL-13) and TH1 cytokines (interferon-γ and IL-12A) levels but did not decrease serum IgE level. Furthermore, NJK14047 blocked CDNB-induced lymph node enlargement. These results suggest that NJK14047, a p38 MAPK inhibitor, might be an optimal therapeutic option with unique modes of action for AD treatment.

Protective effect of euonymus alatus extract on experimental liver injury in mice (Euonymus alatus 추출물의 실험적 간 손상 억제)

  • Shin, Sook-Jeong;Lee, Byung-Yong;Shin, Dong-Keun;Lee, Jeong-Ho
    • IMMUNE NETWORK
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    • v.1 no.3
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    • pp.213-220
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    • 2001
  • Background: A previous study has shown that Euonymus alatus (EA) has an antidotic activities against inflammation, suggesting possibility that EA can exert this beneficial effects to liver injury by an initial protection against drug-induced hepatocyte demage. The present study was undertaken to evaluate the protective effect of EA-extract on experimentally induced hepatitis in ICR mice and to investigate some mechanisms responsible for its action. Methods: Water EA extract was used in this experiments. The mice received i.p. a dose of 700 mg/kg galactosamine (GalN) together with $5{\mu}g/kg$ of endotoxin (LPS), or received i.v. 12 mg/kg of concanavalin A (Con A). EA (4 mg/mouse) was administrated on day -2, -1 and 0 before induction of liver injury. Liver injury was assessed by measurement of serum alanin amino-transferase (SGPT) levels on 9 hr after GaIN.LPS, or 8 hr after con A administration. Results: Treatment with either GaIN or LPS alone did not cause hepatitis. However, simultaneous administration of GalN and LPS to mice resulted in LPS-dose dependent fulminant hepatitis. GaLN/LPS-induced liver injury was reduced when mice were given EA for 3 days before induction. This preventive effect of Ea was more prominent when EA was given by intraperitoneal route rather then by oral route. Pretreatment of EA or dexamethasone inhibited significantly $TNF{\alpha}$ production in GalL/LPS-injured mice. However, EA-treatment did not influence $TNF{\alpha}$-induced hepatitis in GalN-sensitized mice, suggesting that $TNF{\alpha}$ is likely to act as one of final mediators of endotoxin action and the protective effect of EA might be manifested chiefly by inhibition of endotoxin-induced $TNF{\alpha}$ production, not by blocking the $TNF{\alpha}$-action. Injection of Con A into mice evoked remarkable liver injury in a dose dependent fashion. This liver damage was reduced by EA-pretreatment. Dexamethasone significantly reduced both GalL/LPS-induced and Con A-induced liver damages, showing synergism with EA. However, indomethacin reduced only GalN/ LPS-induced hepatitis, not for Con A-induced hepatitis. Conclusion: These results led to the conclusion that EA may be able to contribute at least in part to prevent the drug-induced hepatotoxicity, and that its anti-hepatitis effects might be manifested directly by modulation of endogenous mediators, such as leukotriese D4, $TNF{\alpha}$ and free radical, and indirectly by regulation of immune mediated responses. Also these results suggested that EA could be developed as a potential antidotic agent.

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Studies on the Antiallergic Effect of Aquillariae Lignum (침향(沈香)의 항알레르기 효과(效果)에 대한 연구(硏究))

  • Kim, Young-Hak;Lee, Eon-Jeong;Song, Bong-Keun;Kim, Hyeong-Kyun
    • The Journal of Korean Medicine
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    • v.18 no.2
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    • pp.167-186
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    • 1997
  • The inhibitory activity of Aquillariae Lignum (Thymelaeaceae) on type Ⅰ immediate hypersensitivity of the anaphylactic type in the wistar rat model of passive cutaneous anaphylaxis, an IgE-mediated, mast cell-dependent reaction. Administered orally at 250, 500 mg/kg body weight 1 h before the challenge, Aquillariae Lignum potently inhibited PCA in rats which disodium cromoglycate showed poor inhibitory activity. Aquillariae Lignum inhibited compound 48/80-induced anaphylaxis 100% with a dose of 0.5 g/kg body weight at 1 h before or 5 and 10 min after injection of compound 48/80. Aquillariae Lignum (0.05-1.6 mg/ml) also exhibited the dose-related inhibitory effect on compound 48/80-induced histamine release from rat_peritoneal mast cells. Moreover, it was clearly demonstrated that Aquillariae Lignum and disodium cromoglycate disodium cromoglycate potently inhibited such type Ⅰ allergic reactions as anaphylactic shocks, suggesting that these drugs, at least in part, share the same mechanism of action It is suggested that Aquillariae Lignum may exert a stronger inhibition on the mast cell degranulation process. Since Aquillariae Lignum (1.0 mg/ml) inhibited about 90% of histidine decarboxylase activity, the inhibitory activity of Aquillariae Lignum for histamine release was considered to be derived from the inhibition of histidine decarboxylase activity. It results from increased expression of the mRNA coding for histidine decarboxylase, as assessed by Northern blot analysis after a 12 h incubation to P-815 cells with dexamethasone plus 12-O-tetradecanoylphorbol-13-acetate. The addition of Aquillariae Lignum to P-815 cells with dexamethasone plus 12-O-tetradecanoyl-phorbol-13-acetate, significantly inhibited the histidine decarboxylase gene expression. Tumor necrosis $factor-{\alpha}$ was not constitutively expressed in P-815 cells. Substance P selectively activates the tumor necrosis $factor-{\alpha}$ gene expression in P-815 cells. Aquillariae Lignurm inhibited substance P-induced tumor necrosis $factor-{\alpha}$ gene expression. Furthennore, The effect of Aquillariae Lignum on the mRNA expression of novel protein kinase C ${\delta}$ a major isoform of mast cells, was examined by Northern blot analysis. The expression of novel protein kinase C ${\delta}$ mRNA in the presence of Aquillariae Lignum was significantly lower than in the absence of Aquillariae Lignum. These results suggest the possibility that the inhibition of allergic reaction by Aquillanae Lignum should be regulated by tumor necrosis $factor-{\alpha}$ and novel protein kinase C ${\delta}$.

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The effects of Socheongryong-Tang on LPS-induced lung inflammation rats model (소청룡탕이 LPS로 유도된 폐손상 동물모델에 미치는 영향)

  • Jin, Bo-Ram;Choi, In Young;Hwang, Do Young;Ham, Seong-Ho;An, Hyo-Jin
    • The Korea Journal of Herbology
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    • v.34 no.5
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    • pp.21-28
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    • 2019
  • Objectives : In present study, we investigated a therapeutic effect and optimum dose of Socheongryong-Tang (SCT) on LPS-induced lung inflammation rats model. Methods : Male Sprague-Dawley rats ($260{\pm}10g$) were divided into 12 groups : Group 1 included the normal rats, and Group 2-12 were administrated LPS by intranasal injection to induce experimental lung inflammation. After 1 day of LPS administration, Group 3-9 were treated with SCT ${\times}1/4$, ${\times}1/2$, ${\times}1$, ${\times}3$, ${\times}6$, ${\times}12$ or ${\times}18$, respectively. Group 10-12 (positive control) were treated with dexamethasone 1 mg/kg or acetylcystein 1.5 mg/kg or diclofenac sodium 0.4 mg/kg, respectively. After sacrifice, bronchoalveolar lavage fluid (BALF) was isolated. The levels of IL-$1{\beta}$, TNF-${\alpha}$, mucin glycoprotein 5AC (MUG5AC) were measured in BALF using enzyme-linked immunosorbent assay (ELISA). Results : LPS injected rats exhibited outstanding lung inflammation manifestations, including increased amount of total cells and neutrophil, and upregulated inflammatory cytokines level in BALF. However, the administration of SCT ${\times}1/4$, ${\times}1/2$ and ${\times}1$ decreased total cells and neutrophil, and suppressed the production of inflammatory cytokines, including $IL-1{\beta}$ and TNF-${\alpha}$, and MUG5AC in BALF. Notably, inhibitory effect of SCT ${\times}1/2$ and ${\times}1$ on the level of TNF-${\alpha}$ was markedly better than that of positive controls, dexamethasone and acetylcystein. Conclusions : Taken together, these results suggest that SCT ${\times}1/2$ and ${\times}1$ has therapeutic effects on LPS-induced lung inflammation rats model.