• 생약학회지
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• 제31권3호
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• pp.273-279
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• 2000

Leukotriene $B_4\;(LTB_4)$ is a pro-inflammatory mediator synthesized in myeloid cells from arachidonic acid. Elevated levels of $LTB_4$ have been found in a number of inflammatory diseases and levels are related to disease activity in some of these. Because $LTB_4$ interacts with cells through specific cell surface receptors, $LTB_4$ receptor blockade is the most specific approach to reduce the pathogenic role of $LTB_4$. In order to find $LTB_4$ receptor antagonist from plants, we screened the $LTB_4$ receptor antagonistic activity of the methanol extract and solvent fractions of herbal drugs. The ability of samples to inhibit specific binding of $[^3H]-LTB_4$ to human peripheral neutrophils was used as assay to evaluate the antagonistic activity of plant materials. Among the tested methanol extracts of herbal drugs, Mori Radicis Cortex, Perillae Semen, Armeniacae Semen and Sophorae subprostratae Radix showed potent inhibitory activity above 70% at the concentration of $100\;{mu}g/ml$. The inhibitory activities of $LTB_4$ binding to human neutrophils were evaluated for several solvent fractions at three different concentrations. Especially, hexane soluble fractions of Anemarrhenae Rhizoma and Embeliae Radix, and ethyl acetate soluble fractions of Aristolochiae Fructus, Magnoliae Cortex and Zingiberis Rhizoma crudus showed moderate activity at $25\;{mu}g/ml$. These fractions were promising candidates for the study of the activity-guided chromatographic purification of active compounds. Silica gel column chromatography of hexane soluble fractions of Anemarrhenae Rhizoma and Embeliae Radix gave very active sub-fractions, AA-4 and ES-4, and their inhibition activities of $LTB_4$ binding to human neutrophil at $30\;{mu}g/ml$ were 78% and 62%, respectively. From these results we could anticipate new $LTB_4$ receptor antagonist from herbal drugs, and the block of $LTB_4$ effects may provide beneficial in neutrophil mediated diseases such as inflammation and bronchial asthma.

• Molecules and Cells
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• 제27권4호
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• pp.403-408
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• 2009

Skeletal muscle regeneration is a highly orchestrated process initiated by activation of adult muscle satellite cells. Upon muscle injury, the inflammatory process is always accompanied by muscle regeneration. Leukotriene $B_4$ is one of the essential inflammatory mediators. We isolated and cultured primary satellite cells. RT-PCR showed that myoblasts expressed mRNA for $LTB_4$ receptors BLT1 and BLT2, and $LTB_4$ promoted myoblast proliferation and fusion. Quantitative real-time PCR and immunoblotting showed that $LTB_4$ treatment expedited the expression process of differentiation markers MyoD and M-cadherin. U-75302, a specific BLT1 inhibitor, but not LY2552833, a specific BLT2 inhibitor, blocked proliferation and differentiation of myoblasts induced by $LTB_4$, which implies the involvement of the BLT1 pathway. Overall, the data suggest that $LTB_4$ contributes to muscle regeneration by accelerating proliferation and differentiation of satellite cells.

• Restorative Dentistry and Endodontics
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• 제21권2호
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• pp.451-469
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• 1996

The purpose of this study was to investigate the effect of calcium hydroxide and glass ionomer cement fillings on the levels of $LTB_4$ and $LTC_4$ in experimentally inflamed rat dental pulp. The dental pulp in the mandibular incisor of wistar rat was irritated by cutting a 5mm deep hole in the dentin with a twist drill bur of 0.5mm diameter, without cooling. The cavities were filled with calcium hydroxide(light-cured) and glass ionomer cement(light cured). The untreated pulp served as control tissue specimen. After cavity preparations, the rat with or without various treatment were sacrificed in various time by decapitation. The dental pulp tissue were carefully removed and the concentrations of $LTB_4$ and $LTC_4$ were determined by radioimmunoassay. And pulps were examined histologically to observe inflammatory feature. The result were obtained as follows : 1. The inflammatory features of pulps were observed microscopically in all experimental groups. And degree of inflammation was decreased with time. 2. The concentrations of $LTB_4$ and $LTC_4$ for all experimental groups were significantly higher than those for control group 6 hours after cavity preparation(p<0.05). 3. The group filled with calcium hydroxide was the lowest, and the group filled with glass ionomer cement, the group of irritation in that order showed increased concentrations of $LTB_4$ and $LTC_4$ 6 hours after cavity preparation. In the concentrations of $LTB_4$, significant differences among 3 groups were noted(p<0.05). 4. The group filled with calcium hydroxide was the lowest, and the group filled with glass ionomer cement, the group of irritation in that order showed increased concentrations of $LTB_4$ and $LTC_4$ 24 hours after cavity preparation. And there were statistically significant difference in concentrations of $LTB_4$ between the group of irritation and the group filled with calcium hydroxide(p<0.05). 5. The group filled with calcium hydroxide was the lowest, and the group filled with glass ionomer cement, the group of irritation in that order showed increased concentrations of $LTB_4$ and $LTC_4$ 48 hours after cavity preparation. But no statistically difference was found (p>0.05). 6. The concentrations of $LTB_4$ and $LTC_4$ in all experimental groups were highest level at 6 hour after experiment and decreased as time progresses(correlation coefficient>0.8).

• Restorative Dentistry and Endodontics
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• 제25권2호
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• pp.193-201
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• 2000

Prostaglandins (PGs) and Leukotrienes (LTs) have been implicated in the genesis of pulpal and periapical inflammation. In this study, the relationships among $PGE_2$, 6-keto-PG $F_1{\alpha}$ (a stable metabolite of $PGI_2$) and $LTB_4$ concentrations in inflamed pulp and periapical lesions were discussed. Pulp tissue were obtained in routine endodontic treatment and periapical lesions in periapical surgery after clinical diagnoses were made. These specimens were divided into four groups as normal pulp group (Control group), acute pulpitis group, chronic pulpitis group, and periapical lesion group. Pulp tissue and periapical lesions were stored in liquid nitrogen. The concentration of $PGE_2$, $PGI_2$ and $LTB_4$ were measured with ELISA. The data were analyzed by one-way ANOVA. Significantly higher levels of $PGE_2$, 6-keto-PG $F_1{\alpha}$ a and $LTB_4$ were found in acute pulpitis group than chronic pulpitis group and periapical lesion group(p<0.05). Periapical lesion group showed significantly higher mean concentrations of $PGE_2$ and $LTB_4$ than chronic pulpitis group. In control and chronic pulpitis group, significant higher levels of $PGI_2$ than $PGE_2$ and $LTB_4$ were found. These results suggested that the high levels of $PGE_2$ and $LTB_4$ in periapical lesions may be due to rich endothelium., fibroblast and lymphocyte known as the main producers of $PGE_2$ and $LTB_4$. $PGI_2$ may be thought to one of the most abundant PGs in normal pulp tissue.

• Journal of Microbiology
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• 제43권4호
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• pp.354-360
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• 2005

Heat-labile enterotoxin B subunit (LTB) of enterotoxigenic Escherichia coli (ETEC) is both a strong mucosal adjuvant and immunogen. It is a subunit vaccine candidate to be used against ETEC-induced diarrhea. It has already been expressed in several bacterial and plant systems. In order to construct yeast expressing vector for the LTB protein, the eltB gene encoding LTB was amplified from a human origin enterotoxigenic E. coli DNA by PCR. The expression plasmid pLTB83 was constructed by inserting the eltB gene into the pYES2 shuttle vector immediately downstream of the GAL1 promoter. The recombinant vector was transformed into S. cerevisiae and was then induced by galactose. The LTB protein was detected in the total soluble protein of the yeast by SDS-PAGE analysis. Quantitative ELISA showed that the maximum amount of LTB protein expressed in the yeast was approximately $1.9\%$ of the total soluble protein. Immunoblotting analysis showed the yeast-derived LTB protein was antigenically indistinguishable from bacterial LTB protein. Since the whole-recombinant yeast has been introduced as a new vaccine formulation the expression of LTB in S. cerevisiae can offer an inexpensive yet effective strategy to protect against ETEC, especially in developing countries where it is needed most.

• 약학회지
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• 제33권6호
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• pp.319-323
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• 1989

Polymorphonuclear leukocyte (PMNL) was obtained from peritoneal cavity in rat treated with casein. Effects of divalent cations and drugs on leukotriene $B_4(LTB_4)$ formation from arachidonic acid in the PMNL were determined by HPLC assay. 5-Lipoxygenase, a key enzyme for $LTB_4$ formation from arachidonic acid, exhibited $V_{max}$ at $1\;{\times}\;10^{-5}M$, and $K_m$ at $9.89\;{\times}\;10^{-5}M$ of arachidonic acid. Optimal $Ca^{++}$ concentration for the enzyme activity was $1\;{\times}\;10^{-5}M$ but $Zn^{++}$ did not show any significant effects on the $LTB_4$ formation. Indomethacin and caffeic acid exhibited inhibitory effects on the $LTB_4$ formation at $1\;{\times}\;10^{-5}M$ and $4\;{\times}\;10^{-5}M$, respectively. However, 6-aminohexanoic acid did not show any significant effects on the $LTB_4$ formation.

• Steel and Composite Structures
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• 제4권4호
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• pp.281-301
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• 2004

The paper begins by presenting a unified variational approach to the lateral-torsional buckling (LTB) analysis of doubly symmetric prismatic and tapered thin-walled beams with open cross-sections, which accounts for the influence of the pre-buckling deflections. This approach (i) extends the kinematical assumptions usually adopted for prismatic beams, (ii) consistently uses shell membrane theory in general coordinates and (iii) adopts Trefftz's criterion to perform the bifurcation analysis. The proposed formulation is then applied to investigate the influence of the pre-buckling deflections on the LTB behaviour of prismatic and web-tapered I-section simply supported beams and cantilevers. After establishing an interesting analytical result, valid for prismatic members with shear centre loading, several elastic critical moments/loads are presented, discussed and, when possible, also compared with values reported in the literature. These numerical results, which are obtained by means of the Rayleigh-Ritz method, (i) highlight the qualitative differences existing between the LTB behaviours of simply supported beams and cantilevers and (ii) illustrate how the influence of the pre-buckling deflections on LTB is affected by a number of factors, namely ($ii_1$) the minor-to-major inertia ratio, ($ii_2$) the beam length, ($ii_3$) the location of the load point of application and ($ii_4$) the bending moment diagram shape.

• Nutrition Research and Practice
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• 제4권4호
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• pp.311-316
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• 2010

The purpose of this study was to investigate the relationship between birth weight and appetite related hormones, insulin resistance, and antioxidant status in overweight children aged 9-10 years. Thirty-four healthy overweight children (18 boys, 16 girls) were evaluated with respect to anthropometric measurement, lipid profiles, leptin, ghrelin, glucose, insulin, C-peptide, lipid soluble vitamins, and antioxidant enzyme activities. I found that birth weight was negatively correlated with insulin resistance parameters, ghrelin, and coenzyme Q10 levels. There was a significant positive correlation between present BMI and leptin level, while a negative correlation was noted between the BMI and $\alpha$-tocopherol and lycopene levels. When total subjects were classified into three groups by tertiles of birth weight, the lowest tertile of birth weight (LTB) group showed higher levels of fasting glucose, HOMA-IR, and ghrelin level than the highest tertile of birth weight (HTB) groups. On the other hand, HTB group showed an increased oxidative stress (decreased coenzyme Q10 level and catalase activity) compared to the LTB group. In conclusion, plasma ghrelin level might play an important role in accelerated growth in overweight children with LTB. Increased insulin resistance is present in overweight children with LTB, while decreased coenzyme Q10 and catalase activity in overweight children with HTB. These results suggest that birth weight might be an important factor for determination of treatment for obesity related complications in childhood obesity.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.825-830
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• 1997

Leukotrienes(LTs) are hewn to act as a mediator provoking tissue response in inflammation. This finding implicates that LTs also play important roles in the pathogenesis of H, pylori-induced gastritis and gastric ulceration. Rebamipide is being currently used as a therapeutics for gastritis and peptic ulcer, but their mechanisms of action have not been known clearly yet. One possibility is that their therapeutic effects are ascribed to interfering with the H. pylori-induced release of LTs from neutrophils and gastric mucosal cells. In the present study, this possibility was tested using $LTB_4$ as the test material in human neutrophils and Kato III cells(gastric adenoma cells as a substitute for gastric mucosal cells). The release of $LTB_4$ from both neutrophils and Kato III cells was time and H. pylori-dose dependent. The maximum release of $LTB_4$ was induced by neutrophils and Kato III cells when these cells incubated with H. pylori $(4.8{\times}10^8\;cells/ml$ for 30min. But in the presence of rebamipide the release of $LTB_4$ from these cells was suppressed in dose dependent manners. The release was completely suppressed at 1.0 mM of rebamipide in neutrophils and 2.0 mM of this drug in Kato III cells, respectively. We also obtained the results that the release of $LTB_4$ was induced by A23187$(Ca^{2+}\;ionophore)$ and the A23187-induced release was also inhibited by rebamipide. It seems that the machanism of action of rebamipide is through its interaction with the level of intracellular $Ca^{2+}$. In view of the roles of $LTB_4$ in inflammatory reaction and the roles of H. pylori in gastritis and peptic ulcer, the effects of this drug observed in this study may contribute to their therapeutic action in these gastric disorders.

• Tuberculosis and Respiratory Diseases
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• 제39권4호
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• pp.304-309
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• 1992

연구배경 : 폐포대식세포에서 아라카돈산 대사산물의 생성을 자극하는 일부 인자에 의해서 지속적인 자극시 이와같은 자극으로 인해 생산된 아라키돈산 대사산물이 만성적인 기관지 수축과 섬유화, 계속되는 독성 산소기의 분비를 통하여 잘환의 진행을 항진시키게 된다고 알려져 있고 또한 폐가 외부 물질에 만성적으로 폭로됨으로 인한 질환은 진폐증이 그 대표적인 예라고 할 수 있다. 그러으로 대식세포나 호중구 또는 섬유모세포에서 생산하는 prostaglandin이나 leukotriene등 대사산물의 측정을 통하여 진폐증의 질환의 진행정도를 파악하려는 노력이 계속되고 있으나 아직 명백한 결론을 얻지 못하고 있다. 본 연구는 시험관내에서 폐포대식세포를 유리규산으로 자극시 아라키돈산 대사산물의 측정을 통하여 섬유화 과정에 미치는 prostaglandin $E_2$와 leukotriene $B_4$의 영향을 연구하기 위하여 시행되었다. 방법 : 쥐의 폐포대식세포를 유리규산분진, 자연산 석탄 분진, Lipopolysaccharide, calcium ionophore과 같은 자극제와 같이 배양하고 24, 48시 간후 방사선 동위원소를 이용하여 $PGE_2$와 $LTB_4$를 측정하였다. 결과 : 1) 정상 흰쥐의 폐포대식세포에서 $PGE_2$는 유리규산 자극시 48시간에서 무자극군에 비하여 유의한 감소를 보였다. 2) 실험규폐증군의 폐포대식세포에서 유리된 $PGE_2$는 유리규산 및 자연산 석탄분진으로 자극시 48시간에서 무자극군에 비하여 유의하게 감소하였다. 3) 정상 흰쥐의 폐포대식세포에서 $LTB_4$는 유리규산 자극후 24시간 및 48시간, 그리고 자연산 석탄분진으로 자극시 48시간에서 무자극군에 비하여 유의한 증가를 보였다. 4) 실험 규폐증의 폐포대식세포에서 유리된 $LTB_4$는 유리규산 및 자연산 석탄분진 자극시 장시간 및 48시간에서 무자극군에 비하여 모두 유의하게 증가하였다. 결론 : 본 실험 결과 시험관에서 유리규산과 자연산 석탄분진에 폐포대식세포가 폭로시 폐에 염증반응을 항진시킬 수 있는 방향으로 아라키돈산 대사가 이루어짐을 알았고 이와갈은 아라키돈산 대사의 변화가 진폐증의 병태생리에 중요한 인자로서 작용할 가능성이 있다고 하겠다.