• 한국식품위생안전성학회지
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• 제8권4호
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• pp.181-188
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• 1993

It is well known that bacterial lipopolysaccharide (LPS) stimulates the prostaglandin (PG) synthesis in various experimental system, but the mechanism and the detailed nature of its action are yet to be understood. Thus, this study was designed to characterize LPS induced PG synthesis in rat alveolar macrophage. Although results were not so much prominent, LPS stimulated PGE2 synthesis in macrophage with short term exposure, and this was thought to be mainly due to the activation of phopholipase A2+ But there was a burst in the PG synthesis 6 hours after the LPS treatment and this was accompanied with the increase of cyclooxygenase activity. This effect was not mediated by tumor necrosis factor (TNF) or platelet activating factor (PAF), and the existence of serum was prerequisite for its action. Growth factors such as epidermal growth factor (EGF) and platelet derived growth factor (PDGF) themselves did not stimulate PG synthesis and the showed stimulatory activities to some extent. Normal rat serum was more effective for the elicitation of the LPS action than growth factors. Thus, considering the amounts of growth fafctors contained in normal serum, it was suggested that another factors like LPS binding protein (LBP) might be involved in the serum effect on LPS action. Conclusively. it was thought that LPS could stimulate PG synthesis through interaction with serum factors such as EGF, PDGF and/or LBP.

• 대한한방내과학회지
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• 제31권3호
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• pp.500-512
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• 2010

Objectives : This study was designed to investigate the effects of SuJeom-san(SJS) extract in rats with caerulein-induced acute pancreatitis (AP). Methods : We examined changes of pancreatic weight, histological, immunohistochemical and gene expression of cyclooxygenase (COX-2). Thirty-six adult male Sprague-Dawley rats were divided into six groups as follow: normal(Nor), caerulein-induced (Con), caerulein + cefotaxime sodium(CT), caerulein + SJS 3 mg/kg(SJSA), caerulein + SJS 6 mg/kg(SJSB) and caerulein + SJS 12 mg/kg(SJSC) groups. Pancreatic tissues of rats from all groups were removed for histological observation and light, and electron microscopic examination. Platelet activating factor(PAF) and Interleukin-6(IL-6) levels were determined spectrophotometrically. Results : The ratio of pancreas/body weight was significantly(p<0.05) increased in the Con compared with Nor, but significantly(p<0.05) decreased in SJSA, SJSB, SJSC and CT groups compared with Con. Caerulein administration significantly increased(p<0.05) the levels of amylase, but SJSA, SJSB, SJSC and CT significantly(p<0.05) reduced the levels of these enzymes. The levels of platelet activating factor(PAF) increased in Con compared with Nor, but decreased in SJSA, SJSB, SJSC and CT groups compared with Con. Interleukin-6(IL-6) levels increased significantly in all groups compared to Nor at 6 hrs, but significantly(p<0.05) reduced in SJSA, SJSB, SJSC and CT groups compared with Con at 24 hrs. The levels of tumor necrosis factor(TNF)-${\alpha}$ levels increased in all groups compared to Nor at 6 hrs, but significantly(p<0.05) reduced in SJSA, SJSB, SJSC and CT groups compared with Con at 24 hrs. The COX-2 positive materials were observed in the pancreas of the Con, but these positive materials were decreased in the SJS extract treatment group. Conclusion : SJS is potentially capable of limiting pancreatic damage during AP by restoring the fine structure of acinar cells and tissue; therefore, we conclude that SJS may have beneficial effects in the treatment of caerulein-induced AP.

• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.479-491
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• 1998

In order to know the pathogenesis of adult respiratory distress syndrome (ARDS) in association with the oxidative stress by neutrophils, the role of platelet activating factor (1-0-alkyl-2-acetyl-snglycero-3-phosphocholine, PAF) was investigated during acute lung injury induced by interleukin- $1{\alpha}$ (IL-1) in rats. An insufflation of IL-1 into the rat's trachea increased the acetyltransferase activity in the lung and the increase of PAF content was followed. As evidences of acute lung injury by neutrophilic respiratory burst, lung leak index, myeloperoxidase activity, numbers of neutrophils in the bronchoalveolar lavage fluid, neutrophilic adhesions to endothelial cells and NBT positive neutrophils were increased after IL-1 treatment. In addition, a direct instillation of PAF into the trachea caused acute lung leak and the experimental results showed a similar pattern in comparison with IL-1 induced acute lung injury. For the confirmation of oxidative stress during acute lung leak by IL-1 and PAF, a histochemical electron microscopy was performed. In IL-1 and PAF treated lungs of rats, the deposits of cerrous perhydroxide were found. To elucidate the role of PAF, an intravenous injection of PAF receptor antagonist, WEB 2086 was given immediately after IL-1 or PAF treatment. WEB 2086 decreased the production of hydrogen peroxide and the acute lung leak. In ultrastructural study, WEB 2086 mitigated the pathological changes induced by IL-1 or PAF. The nuclear factor kappa B (NFkB) was activated by PAF and this activation was inhibited by WEB 2086 almost completely. Based on these experimental results, it is suggested that the PAF produced in response to IL-1 through the remodeling pathway has the major role for acute lung injury by neutrophilic respiratory burst. In an additional experiment, we can also come to conclude that the activation of the NFkB by PAF is thought to be the fundamental mechanism to initiate the oxidative stress by neutrophils causing release of proinflammatory cytokines and activation of phospholipase $A_2$.

• Biomolecules & Therapeutics
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• 제5권2호
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• pp.107-109
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• 1997

For metabolic study of pinusolide, a naturally occurring platelet activating factor antagonist, a synthetic method for preparation of radiolabeled pinusolide was studied. Pinusolide was first oxidized with $OsO_4/NaIO_4 $to 17-nor-8-oxo compound (2), which was subsequently converted to pinusolide by treatment with the Lombardo reagent $(Zn/CH_2Br_2/TiCI_4)$. The Wittily reaction was unsuccessful in the latter carbonyl methylenation of 2.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.137.3-138
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• 2003

The major active components of EGb 761, extract of Ginkgo biloba leaves, include flavonoid glycosides and unique diterpenes known as ginkgolides. Ginkgolides are potent inhibitors of platelet activating factor. In this study, we investigated antiinflammatory activity of ginkgolides on the Complete Freund"s Adjuvant (CFA)-induced mice. The ginkgolides were extracted from commercially available EGb 761. This extracting procedure was done by sequential treatments of the EGb 761 with chloroform, methanol, and water. (omitted)tted)

• 동의생리병리학회지
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• 제19권5호
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• pp.1391-1398
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• 2005

The anti-thrombic properties of the oriental herbal medicine Daejowhan(DJW, 大造丸) which consists of 11 kinds of herbs (indicated as ratio) of Rehmanniae Radix 24%, Hominis Placenta 5%, Testudinis Carapax 9%, Eucommiae Cortex 9%, Asparagi Radix 9%, Phellodendri Cortex 9%, Achyranthis Radix 7%, Liriopis Tuber 7%, Angelicae Sinensis Radix 7%, Ginseng Radix 5% and Schizandrae Fructus 3% were investigated. The water extracts from DJW inhibited Platelet-activating factor(PAF) induced platelet aggregation. DJW was extracted with methanol and further fractionated by ethylacetate. A 70% methanol extract showed a strong inhibition against PAF-induced aggregation in vitro and in vivo assays. The ethylacetate soluble fraction was shown to have inhibitory effect on PAF-induced platelet aggregation in vitro assay. The ethylacetate soluble fraction specially protected against the lethality of PAF, while verapamil did not afford any protection. These results indicate that the water extracts and alcoholic-fractions inhibit the action of PAF in vivo by an antagonistic effect on PAF, so that it may be useful in treating disorders caused by PAF, such as acute allergy, inflammation, asthma, gastrointestinal ulceration, toxic shock and so forth. DJW was investigated regarding its assumed anti-thrombic action on human platelets which was deduced from its ability to suppress Arachidonic acid(AA)-induced aggregation, exocytosis of ATP, and inhibition of Cyclooxygenase(COX) and Thromboxane synthase(TXS) activity. The latter two effects were estimated from the generation of Prostaglandin $E_2(PGE_2)$ and Thromboxane $A_2(TXA_2)$ respectively. Exogenously applied AA ($100{\mu}mol/{\ell}$) provoked a $89\%$ aggregation of platelets, the release of 14 pmol ATP, and the formation of either 225 pg $TXA_2$ or 45 pg $PGE_2$, each parameter being related to 106 platelets. An application of DJW 5 min before AA dose-dependently diminished aggregation, ATP-release and the synthesis of $TXA_2$ and $PGE_2$ with $IC_{50}$ values of 74, 108, 65, $72{\mu}g/m{\ell}$, respectively. The similarity of the $IC_{50}$ values suggest an inhibition of COX by DJW as primary target, thus suppressing the generation of $TXA_2$ which induces aggregation of platelets and exocytosis of ATP by its binding on $TXA_2$-receptors.

• 동의생리병리학회지
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• 제27권5호
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• pp.644-649
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• 2013

In this study, we aimed to investigate the effect of GamiChungYi-tang(GCY-t) on caerulein-induced acute pancreatitis (AP). It is performed by detecting oxidative stress markers and observing histopathological examination. Thirty adult male rats(Sprague-Dawley) were divided into six groups as follows: normal (NOR,n=5), caerulein-induced (CON,n=5), caerulein+Cefotaxime Sodium(CT,n=5), caerulein+GCY-t (130 mg/kg, CHA,n=5), caerulein+GCY-t (260 mg/kg, CHB,n=5) and caerulein+GCY-t (520 mg/kg, CHC,n=5) groups. Pancreatic tissues of rats from all groups were removed for apoptosis and light, and electron microscopic examination. Blood of rats from all groups were collected for oxidative stress markers inspection and pathological examination. Pancreatic oxidative stress markers were evaluated by the measurements of leukocyte, serum amylase and platelet activating factor (PAF), Interleukin-6 (IL-6) levels were determined spectrophotometrically. CON group has a significant increase (p<0.05) in amylase compared with NOR, but CT and CHA, CHB, CHC groups reduced the levels of these enzyme. The levels of Platelet activating factor (PAF) were increased in CON compared with NOR, but decreased in CT and CHA, CHB, CHC groups compared with CON. Interleukin-6 (IL-6) levels were increased significantly in CON compared with NOR, but reduced in CT and CHA, CHB, CHC groups. In the observations of Optical microscopy and electron microscopy, The experimental groups showed the significant decreases in pancreatic tissue inflammation, edema, vacuolization, necrosis compared to the control group. After all, GCY-t is potentially capable of limiting pancreatic damage produced during AP by restoring the fine structure of acinar cells and tissue.

• The Korean Journal of Physiology
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• 제29권1호
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• pp.1-11
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• 1995

Alveolar macrophages play a pivotal role in the pathogenesis of silicosis since the macrophages may release a wide variety of toxic and inflammatory mediators as well as mitogenic growth factors. In the present study, the effects of in vitro exposure to silica on release of various mediator such as reactive oxygen species, platelet activating factor(PAF), and interleukin-1 (IL-1) by alveolar macrophages were examined. First, hydrogen peroxide release from alveolar macrophages was monitored by measuring the change in fluorescence of scopoletin in the absence or presence of graded concentration of silica. Significantly enhanced release of hydrogen peroxide was observed at 0.5 mg/ml and above. A maximal enhancement of 10 fold above control was observed at 5 mg/ml silica. Similarly, in vitro exposure to silica also significantly stimulated the generation of chemiluminescence from alveolar macrophages at 0.5 mg/ml and above with n maximal enhancement of 8 fold at 5 mg/ml silica. Second, PAF release from alveolar macrophages after 30 min incubation at $37^{\circ}C$ in absence or presence of zymosan and silica was determined by measuring $^{3}H-serotonin$ release ability of the conditioned macrophage supernates from platelets. 5 mg/ml zymosan as a positive control fur the PAF assay increased PAF release by 19 % of total serotonin release. Furthermore, silica also resulted in significant enhancement of the PAF release compared with that in unstimulated (control) cells, i.e., $17.7{\pm}5.8%$ and $24.0{\pm}4.9%$ of total serotonin release at 5 mg/ml and 10 mg/ml silica, respectively, which represents the release of nanomole levels of PAF. Lastly, IL-1 production by alveolar macrophages was analysed following their stimulation with lipopolysaccharide (LPS) and silica by their capacity to stimulate thymocyte proliferation. $10\;{\mu}g/ml$ LPS resulted in an 11 fold increase in IL-1 production. In comparison, $50\;{\mu}g/ml$ silica resulted in a 4 fold increase in IL-1 release. These data indicate that in vitro exposure of alveolar macrophages to silica activates the release of various bioactive mediators such as reactive oxygen species, PAF and IL-1 which thus contribute to amplification of inflammatory reactions and regulation of fibrotic responses by the lung after inhalation of silica.

• Tuberculosis and Respiratory Diseases
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• 제53권6호
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• pp.595-611
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• 2002

Akt/PKB protein kinase B, ALI acute lung injury, ARDS acute respiratory distress syndrome, CREB C-AMP response element binding protein, ERK extracelluar signal-related kinase, fMLP fMet-Leu-Phe, G-CSF granulocyte colony-stimulating factor, IL interleukin, ILK integrin-linked kinase, JNK Jun N-terminal kinase, LPS lipopolysaccharide, MAP mitogen-activated protein, MEK MAP/ERK kinase, MIP-2 macrophage inflammatory protein-2, MMP matrix metalloproteinase, MPO myeloperoxidase, NADPH nicotinamide adenine dinucleotide phosphate, NE neutrophil elastase, NF-kB nuclear factor-kappa B, NOS nitric oxide synthase, p38 MAPK p38 mitogen activated protein kinase, PAF platelet activating factor, PAKs P21-activated kinases, PMN polymorphonuclear leukocytes, PI3-K phosphatidylinositol 3-kinase, PyK proline-rich tyrosine kinase, ROS reactive oxygen species, TNF-${\alpha}$ tumor necrosis factor-a.

• IMMUNE NETWORK
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• 제3권1호
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• pp.38-46
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• 2003

Background: Platelet-activating factor (PAF) induces nuclear factor $(NF)-{\kappa}B$ activation and angiogenesis and increases tumor growth and pulmonary tumor metastasis in vivo. The role of $NF-{\kappa}B$ activation in PAF-induced angiogenesis in a mouse model of Matrigel implantation, and in PAF-mediated pulmonary tumor metastasis were investigated. Methods: Angiogenesis using Matrigel and experimental pulmonary tumor metastasis were tested in a mouse model. Electrophoretic mobility shift assay was done for the assessment of $NF-{\kappa}B$ translocation to the nucleus. Expression of angiogenic factors, such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\alpha}$, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were tested by RT-PCR and ELISA. Results: PAF induced a dose- and time-dependent angiogenic response. PAF-induced angiogenesis was significantly blocked by PAF antagonist, CV6209, and inhibitors of $NF-{\kappa}B$ expression or action, including antisense oligonucleotides to p65 subunit of $NF-{\kappa}B$ (p65 AS) and antioxidants such as ${\alpha}$-tocopherol and N-acetyl-L-cysteine. In vitro, PAF activated the transcription factor, $NF-{\kappa}B$ and induced mRNA expression of $TNF-{\alpha}$, $IL-1{\alpha}$, bFGF, VEGF, and its receptor, KDR. The PAF-induced expression of the above mentioned factors was inhibited by p65 AS or antioxidants. Also, protein synthesis of VEGF was increased by PAF and inhibited by p65 AS or antioxidants. The angiogenic effect of PAF was blocked when anti-VEGF antibodies was treated or antibodies against $TNF-{\alpha}$, $IL-1{\alpha}$, and bFGF was co-administrated, but not by antibodies against $TNF-{\alpha}$, $IL-1{\alpha}$, and bFGF each alone. PAF-augmented pulmonary tumor metastasis was inhibited by p65 AS or antioxidants. Conclusion: These data indicate that PAF increases angiogenesis and pulmonary tumor metastasis through $NF-{\kappa}B$ activation and expression of $NF-{\kappa}B$-dependent angiogenic factors.