• Title/Summary/Keyword: Suboptimal dose

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Effects of Substance P on the Release of Cytokines from Immune Cell Lines (면역세포의 cytokine 유리에 미치는 substance P의 영향)

  • Lee, Jin-Yong;Kim, Soo-Ah;Seo, Seok-Ran;Kim, Hyong-Seop
    • Journal of Periodontal and Implant Science
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    • v.27 no.2
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    • pp.425-441
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    • 1997
  • The neuropeptide substance P(SP) has been implicated in the mediation of inflammation and immune-mediated disease such as arthritis. Recently, it was reported that SP was markedly increased around the blood vessels in inflamed gingiva as well as in close association with the inflammatory cell infiltrate. These results support that SP may contribute to the pathophysiology of neuronal inflammation in human periodontal tissues. SP may regulate inflammatory/immune responses by stimulating the proliferation of human T cells, differentiation and antibody-secreting potential of B cells, macrophage respiratory burst, connective tissue proliferation, and the secretion of cytokines from monocytes and T cells. Here, I studied potential role of SP as a costimulatory chemical signal in inflammatory/immune responses, by determining the released proinflammatory cytokines such as $MIP-1{\alpha}$, $IL-1{\beta}$, and IL-6 from culture supernatants of homogeneous immune cell lines. Serum free cell supernatants were concentrated with TCA precipitation, fractionated with SDS-PAGE, and subjected into western blot analysis. Among 15 cell lines tested, macrophage/monocyte cell line RAW264.7 and WRl9m.1 showed the highest level of induction of $MIP-1{\alpha}$ when stimulated with LPS. Discrete IL-6 bands with multiple forms of molecular mass were detected from supernatants of B cell lines A20(32kDa), Daudi(32, 35kDa), and SKW6.4(29kDa), which were expressed constitutively. $IL-1{\beta}$ could not be detected by the method of western blot analysis from supernatants of all cell lines tested except RAW264.7, WRl9m.1, and erythroid cell line K562 which showed the least amount of $IL-{\beta}$ secretion. SP $10^{-9}M$ with suboptimal dose of LPS treatment showed synergistic induction of $MIP-1{\alpha}$ release from RAW264.7 or WR19m.1, and also IL-6 release from A20, but this synergism is not the case in costimulation of RAW264.7 or WRl9m.1 with SP $10^{-9}M$ and TPA. Although treatment of T cell line CTLL-R8 with SP $10^{-7}M$ or PHA+TPA induced modest level of $MIP-1{\alpha}$ secretion, synergism was not observed when they are applied together. These findings all together suggest the possibility of a regulatory role of SP in inflammatory/immune reaction through differential modulation of bioactivities of other chemical cosignals.

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Changes in Plasma Levels of Inhibin and Follicle Stimulating Hormone in Buffaloes Superovulated with eCG

  • Singh, Baljit;Dixit, V.D.;Dixit, V.P.;Singh, P.;Georgie, G.C.;Lohan, I.S.
    • Asian-Australasian Journal of Animal Sciences
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    • v.13 no.9
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    • pp.1205-1209
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    • 2000
  • The present study was undertaken to investigate the effect of stimulation of follicular development with eCG on the peripheral levels of inhibin and FSH in Murrah buffaloes. Estrus was synchronized in five normally cycling females by insertion of Crestar (Intervet, Boxmeer, Holland) implants for nine days. Estradiol valerate was administered i.m. on the day of implant insertion. On the 10th day of the induced estrous cycle a single dose of 3000 IU eCG (Folligon, Intervet, Boxmeer, Holland) was given, followed by treatment with 25 mg of $PGF_2$ alpha (Lutalyse, Upjohn, Belgium) 48 h later. Blood samples were obtained during the induced estrus, on cycle day 10 (luteal phase), at the superovulatory estrus (43 h after PGF) and during the periovulatory period (64 h after PGF). Ultrasonography was done daily to monitor follicular development. Plasma concentrations of inhibin and FSH were determined by specific radioimmunoassays. Differences between $mean{\pm}SEM$ values of different phases of the cycle were compared by ANOVA. The mean number of small (2-5 mm), medium (6-9 mm) and large (>10 mm) follicles observed two days after eCG treatment and on the day of superovulatory estrus was $2.8{\pm}0.31$, $5.2{\pm}0.30$ and $1.4{\pm}0.09$ and $1.9{\pm}0.21$, $2.8{\pm}0.40$ and $5.0{\pm}0.83$, respectively. The mean number of ovulations was $3.6{\pm}0.37$ and the mean number of unovulated follicles was $6.1{\pm}0.47$. Most of the follicles >10 mm in diameter had ovulated (72%). The mean ${\pm}SEM $ of plasma inhibin concentration $(2584.15{\pm}17.92pg/ml)$ during the superovulatory estrus was significantly higher $(p{\leq}0.05)$ than during the induced estrus $(749.87{\pm}17.29pg/ml)$, the luteal phase $(1099.54{\pm}24.98pg/ml)$ and periovulatory period $(1682.71{\pm}29.88pg/ml)$, respectively. $Mean{\pm}SEM$ plasma FSH concentration during the induced estrus $(10.35{\pm}0.41ng/ml)$ was not different from that during the superovulatory estrus $(8.52{\pm}0.39ng/ml)$, but was significantly higher $(p{\leq}0.05)$ than during the luteal phase $(2.81{\pm}0.42ng/ml)$ and periovulatory period $(5.7{\pm}0.28ng/ml)$. These data indicate that treatment with eCG in buffaloes for inducing superovulation results in a significant elevation in plasma inhibin levels and a decrease in plasma FSH levels during the superovulatory estrus. Thus, we suggest that the elevated plasma inhibin coming from fully developed follicles continued for a long time which results in inhibition of FSH leading to poor ovulation in the remaining follicles, which may be the cause of suboptimal superovulatory response.

The efficacy of optimal doses of intramuscular ketamine and midazolam injections for procedural sedation in laceration repair of children (소아 열상 처치에서 적절한 용량의 ketamine과 midazolam 병용 근육주사의 진정효과)

  • You, Je Sung;Cho, Young Soon;Choi, Young Hwan;Kim, Seung Hwan;Lee, Hahn Shick;Lee, Jin Hee
    • Clinical and Experimental Pediatrics
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    • v.49 no.7
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    • pp.726-731
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    • 2006
  • Purpose : We reported previously that intramuscular ketamine with adjunctive midazolam is more effective than ketamine alone in pediatric procedural sedation, but with limited satisfactory sedation by suboptimal ketamine dose. The optimal dose of intramuscular ketamine in children has never been studied in Korea. In this study, we investigated the effectiveness and adverse events of ketamine 4mg/kg with adjunctive midazolam in pediatric laceration repair. Methods : From Jan. 2005 to July 2005, we enrolled 60 children, aged 3 months-7 years, who needed laceration repair under sedation. After verbal consent from parents, patients were randomly assigned to KMA group(IM ketamine 4 mg/kg+atropine 0.01 mg/kg+intramuscular midazolam 0.05 mg/kg) or KA group(without midazolam). We compared both groups with the induction time, recovery time, total sedation time, efficacy of sedation, adverse effects, and the satisfaction score of treating physicians. Results : Potentially confounding variables, age, weight, injury site and anxiety score, were similar between groups. The induction time, recovery time and total sedation time were not different statistically. In KMA group, 90.9 percent of patients showed satisfactory sedation compared to 66.7 percent of KA group(P=0.02) and the occurrence rate of significant adverse effect was 0.0 percent and 37.0 percent respectively. Conclusion : We found adjunctive midazolam with ketamine doses of 4 mg/kg IM produced more effective, satisfactory sedation and less adverse effect than without midazolam in pediatric laceration repair. The emergence phenomenon(agitation during recovery) only occurred in 9 KA group patients. In spite of adverse effect, all patients recovered, were discharged and there were no reported delayed events.

Cooperative Induction of HL-60 Cell Differentiation by Combined Treatment with Eugenol and 1α,25-Dihydroxyvitamin D3 (Eugenol과 1α,25-dihydroxyvitamin D3의 병합처리에 의한 HL-60 세포의 분화 유도)

  • Oh, Mi-Kyung;Park, Seon-Joo;Kim, Nam-Hoon;Cho, Jin-Kyung;Jin, Jong-Youl;Kim, In-Sook
    • Journal of Life Science
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    • v.17 no.9 s.89
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    • pp.1191-1196
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    • 2007
  • Eugenol (4-allyl-2-methoxyphenol) is a main component of essential oils obtained from various spices. Recent reports have shown that eugenol induces growth inhibition and apoptosis of malignant tumor cells. In this study, the stimulatory effect of eugenol on cell differentiation was investigated in HL-60 promyelocytic leukemia cells. When HL-60 cells were treated in combination with 150 ${\mu}M$ of eugenol and 3 nM of $1{\alpha},25-dihydroxyvitamin$ $D_{3}$, cell growth was slower than that of cells treated with eugenol or $1{\alpha},25-dihydroxyvitamin$ $D_{3}$ alone. Eugenol enhanced low dose of $1{\alpha,25-dihydroxyvitamin }$ $D_{3}-induced$ a $G_{0}/G_{1}$ phase arrest in cell cycle. Consistent with this, combined treatment of eugenol and $1{\alpha},25-dihydroxyvitamin$ $D_{3}$ cooperatively increased p27 level and decreased cyclin A, cdk 2 and cdk 4 levels, which are cell cycle regulators related to $G_{0}/G_{1}$ arrest. According to flow cytometric analysis, the expression of CD14 (monocytic differentiation marker) was more increased in the cells co-treated with eugenol and $1{\alpha},25-dihydroxyvitamin$ $D_{3}$. These results indicate that eugenol potentiates cell differentiation mediated by $1{\alpha},25-dihydroxyvitamin$ $D_{3}$ of suboptimal concentration. The differentiation-inducing property of eugenol maybe contributes to chemopreventive activity of cancer.