• Journal of Acupuncture Research
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• v.19 no.2
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• pp.51-64
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• 2002

We have compared(using the same series of experimental tissue samples) the levels of proteolytic enzyme activities and free radical-induced protein damage in synovial fluid from RA and CPH cases. Many protease types showed significantly increased (typically by a factor of approximately 2-3-fold) activity in RA, compared to normal rats. However, CPH significantly reduced the cytoplasmic enzyme activities of arginyl aminopeptidase, leucyl aminopeptidase, pyroglutamyl aminopeptidase, tripeptidyl aminopeptidase, and proline endopeptidase to almost about 1/10 each. For the Iysosomal proteases, synovial fluid samples from RA rats, CPH significantly reduced the enzyme activities of cathepsin B, dipeptidyl aminopeptidase I and dipeptidyl aminopeptidase II. In extracellular matrix degrading(collagenase, tissue elastase) and leukocyte as sociated proteases (leukocyte elastase, cathepsin G), CPH decreased these enzyme activities of collagenase, tissue elastase and leukocyte associated elastase in RA. In cytoplasmic and lysosomal protease activities in plasma from RA. CPH and normal plasma samples were not significantly different, suggesting that altered activity of plasma proteases (particularly those enzymes putatively involved in the immune response) is not a contributory factor in the pathogenesis of RA. In addition, the level of free radical induced damage to synovial fluid proteins was approximately twice that in RA, compared with CPH. CPH significantly decreased the level of ROS induced oxidative damage to synovial fluid proteins (quantified as protein carbonyl derivative). Therefore we conclude that both proteolytic enzymes and free radicals are likely to be of equal potential importance as damaging agents in the pathogenesis of inflammatory joint disease, and that the design of novel therapeutic strategies for patients with the latter disorder should include both protease inhibitory and free radical scavenging elements. In addition, the protease inhibitory element should be designed to inhibit the action of a broad range of protease mechanistic types (i.e. cysteine-, metallo- and serine- proteinases and peptidases). However, increased protein damage induced by ROS could not be rationalised in terms of compromised antioxidant total capacity, since the latter was not significantly altered in RA synovial fluid or plasma compared with CPH.

• Clinical and Experimental Pediatrics
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• v.48 no.2
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• pp.197-203
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• 2005

Purpose : Changes in metalloproteinases(MMP) activity have been demonstrated in several disease states, including rheumatoid arthritis and tumor metastasis. More importantly, increased myocardial MMP activity has been reported to occur in both clinical and experimental forms of dilated cardiomyopathy. There was no report about MMP in adriamycin(ADR)-induced cardiomyopathy. The purpose of this study was to investigate gene expression of MMP and tissue inhibitor of metalloproteinases(TIMP) in ADR-induced cardiomyopathy and clarify the relationship between MMP and cytokines. Methods : Male Sprague-Dawley rats were divided into two groups. The first group was control. The second group was given intraperitoneal injections of ADR(5 mg/kg) twice a week over two weeks. Serum concentrations of MMP, TIMP, interleukin(IL)-6 and tumor necrosis factor(TNF)-${\alpha}$ were measured. RNA extraction was performed from frozen rat hearts. Reverse transcription polymerase chain reaction(RT-PCR) was employed. cDNA Microarray analysis was performed by using a set of 5,184 sequence-verified rat cDNA clones. Results : Serum MMP and TIMP levels were not significantly different between the two groups. IL-6 was $36.8{\pm}2.8pg/mL$ and TNF-${\alpha}$ $2.2{\pm}2.7pg/mL$ in the ADR group. They were significantly higher than in the control group. Serum MMP correlated significantly with TNF-${\alpha}$(r=0.41, P<0.05). There was no gene expression of MMP, IL-6 or TNF-${\alpha}$ in the hearts of both groups. Gene expression of TIMP was significantly depressed in the hearts of the ADR group. Conclusion : These results suggested a potential role for TNF-${\alpha}$ in the regulation of extracellular matrix remodeling in ADR induced cardiomyopathy. Rapid screening of multiple decreased gene expression by DNA chip may be a useful diagnostic test to detect early cardiac injury before developing ADR induced cardiomyopathy.

• Korean Journal of Food Science and Technology
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• v.40 no.6
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• pp.674-679
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• 2008

Scutellaria radix (SR) has been utilized as a traditional medicine for a variety of diseases including Rheumatoid arthritis and its major flavonoids - baicalein, baicalin, and wogonin - have been reported to exert beneficial health effects, including anti-bacterial, anti-viral, anti-inflammatory, and free-radical scavenging. However, the mechanisms underlying this effect remain poorly understood. The principal objective of this study was to determine the effect of SR on osteoblast and osteoclast cells. SR extract was prepared using 70% ethanol solvent. Osteoblastic MC3T3-E1 cells and osteoclast precursor Raw 264.7 macrophage cells were utilized. SR extract increased MC3T3-E1 cell proliferation and stimulated alkaline phosphatase activity dose-dependently, 152.0% of the control at concentration $1{\mu}g/mL$. Additionally, SR extract ($1{\mu}g/mL$) stimulated Bone nodule formation activity in MC3T3-E1 cells, approximately 223.3% of the control, 20 days after the exposure. In addition, SR extract significantly reduced the number of tartrate-resistant acid phosphatase-positive (TRAP+) multinucleated cells from Raw 264.7 cells. In conclusion, SR extract stimulates the proliferation and bioactivities of boneforming osteoblasts, and inhibits the activities of bone-resorbing osteoclasts to a certain degree.

• Journal of Periodontal and Implant Science
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• v.26 no.2
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• pp.448-468
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• 1996

To maintain its functional integrity, bone is continuously remodelled by a process involving resorption by osteoeclasts and formation by osteoblasts, In order to respond to changes in the physical environment or to trauma with the relevant action, this process is strictly regulated by locally synthesized or systemic fators, Prostaglandin $E_2(PGE_2$) is perhaps one of the best studied factors, having been known to affect bone cell function for several decades.$PGE_2$ has both anabolic and catabolic activities. Excess of $PGE_2$ has been implicated in a number of pathological states associated with bone loss in a number of chronic inflammatory conditions such as periodontal disease and rheumatoid arthritis. $PGE_2$ and other arachidonic acid metabolites have been shown to be potent stimulators of osteoclastic bone resorption in organ culture. The anabolic effects of $PGE_2$ were first noticed when an increase in periosteal woven bone formation was seen after the infusion of $PGE_2$ into infants in order to prevent closure of the ductus arteriosus. The cellular basis for the catabolic actions of $PGE_2$ has been well characterized. $PGE_2$increases osteoclast recruitment in bone marrow cell cultures. Also $PGE_2$ has a direct action on osteoclast serving to inhibit activity and can also indirectly activate osteoclast via other cells in the vicinity, presumably osteoblast. The cellular mechanisms for the anabolic actions of $PGE_2$ are not nearly so well understood. The purpose of this paper was to study the effects of $PGE_2$ and dibutyl(DB)cAMP on osteoblastic clone MC3T3El cells and on the generation of osteoclasts from their precursor cells. The effect of $PGE_2$ and DBcAMP on the induction of alkaline phoaphatase(AlP) was investigated in osteoblastic clone MC3T3El cells cultured in medium containing 0.4% fetal bovine serum. $PGE_2$ and DBcAMP stimulated ALP activity and MTT assay in the cells in a dose-dependent manner at concentrations of lO-SOOng/ml. Cycloheximide, protein synthesis inhibitor, inhibited the stimulative effect of $PGE_2$ and DBcAMP on ALP activity in the cells. $PGE_2$also increased the intracellular cAMP content in a dose-dependent fashion with a maximal effect at 500ng/ml. The effect of $PGE_2$ on the generation of osteoclasts was investigated in a coculture system of mouse bone marrow cells with primary osteoblastic cells cultured in media containing 10% fetal bovine serum.After cultures, staining for tartrate-resistant acid phosphatase(TRAP)-marker enzyme of osteoclast was performed. The TRAP(+) multinucleated cells(MNCs), which have 3 or more nuclei, were counted. More TRAP(+) MNCs were formed in coculture system than in control group. $PGE_2(10^{-5}10^{-6}M)$ stimulated the formation of osteoclast cells from mouse bone marrow cells in culture. $PGE_2(10^{-6}M)$ stimulated the formation of osteoclast cells from mouse bone marrow cells in coculture of osteoblastic clone MC3T3E1 cells This results suggest that $PGE_2$ stimulates the differentiation of osteoblasts and generation of osteoclast, and are involved in bone formation, as well as in bone resorption.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.15 no.2
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• pp.271-288
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• 2002

Authors investigated the pathogenesis and treatment of dennatosurgical diseases in the ImJeungJiNamUiAn(臨證指南醫案). 1. The symptoms and diseases of dermatosurgery were as follows; 1) BanSaJinRa(반사진라) : eczema, atopic dermatitis, seborrheic dermatitis, psoriasis, lichen planus, pityriasis rosea, hives, dermographism, angioedema, cholinergic urticaria, urticaria pigmentosa, acne, milium, syringoma, keratosis pilaris, discoid lupus erythematosus, hypersensitivity vasculitis, drug eruption, polymorphic light eruption, rheumatic fever, juvenile rheumatoid arthritis(Still's disease), acute febrile neutrophilic dermatosis(Sweet's syndrome), Paget's disease, folliculitis, viral exanthems, molluscum contagiosum, tinea, tinea versicolor, lymphoma, lymphadenitis, lymphangitis, granuloma annulare, cherry angioma 2) ChangYang(瘡瘍) : acute stage eczema, seborrheic dermatitis, stasis ulcer, intertrigo, xerosis, psoriasis, lichen planus, ichthyosis, pityriasis rosea, rosacea, acne, keratosis pilaris, dyshidrosis, dermatitis herpetiformis, herpes gestationis, bullae in diabetics, pemphigus, lupus erythematosus, fixed drug eruption, erythema multiforme, toxic epidermal necrolysis, toxic shock syndrome, staphylococcal scaled skin syndrome, scarlet fever, folliculitis, impetigo, pyoderma gangrenosum, tinea, candidiasis, scabies, herpes simplex, herpes zoster, chicken pox, Kawasaki syndrome, lipoma, goiter, thyroid nodule, thyroiditis, hyperthyroidism, thyroid cancer, benign breast disorder, breast carcinoma, hepatic abscess, appendicitis, hemorrhoid 3) Yeok(疫) : scarlet fever, chicken pox, measles, rubella, exanthem subitum, erythema infectiosum, Epstein-Barr virus infection, cytomegalovirus infection, hand-foot-mouth disease, Kawasaki disease 4) Han(汗) : hyperhidrosis 2. The pathogenesis and treatment of dermatosurgery were as follows; 1) When the pathogenesis of BalSa(발사), BalJin(發疹), BalLa(발라) and HangJong(項腫) are wind-warm(風溫), exogenous cold with endogenous heat(外寒內熱), wind-damp(風濕), the treatment of evaporation(解表) with Menthae Herba(薄荷), Arctii Fructus(牛蒡子), Forsythiae Fructus(連翹) Mori Cortex(桑白皮), Fritillariae Cirrhosae Bulbus(貝母), Armeniaoae Amarum Semen(杏仁), Ephedrae Herba(麻黃), Cinnamomi Ramulus(桂枝), Curcumae Longae Rhizoma(薑黃), etc can be applied. 2) When the pathogenesis of BuYang(부양), ChangI(瘡痍) and ChangJilGaeSeon(瘡疾疥癬) are wind-heat(風熱), blood fever with wind transformation(血熱風動), wind-damp(風濕), the treatment of wind-dispelling(疏風) with Arctii Fructus(牛蒡子), Schizonepetae Herba(荊芥), Ledebouriellae Radix(防風), Dictamni Radicis Cortex(白鮮皮), Bombyx Batrytioatus(白？?), etc can be applied. 3) When the pathogenesis of SaHuHaeSu(사후해수), SaJin(사진), BalJin(發疹), EunJin(은진) and BuYang(부양) are wind-heat(風熱), exogenous cold with endogenous heat(外寒內熱), exogenous warm pathogen with endogenous damp-heat(溫邪外感 濕熱內蘊), warm pathogen's penetration(溫邪內陷), insidious heat's penetration of pericardium(伏熱入包絡), the treatment of Ki-cooling(淸氣) with TongSeongHwan(通聖丸), Praeparatum(豆？), Phyllostachys Folium(竹葉), Mori Cortex(桑白皮), Tetrapanacis Medulla(通草), etc can be applied. 4) When the pathogenesis of JeokBan(적반), BalLa(발라), GuChang(久瘡), GyeolHaek(結核), DamHaek(痰核), Yeong(？), YuJu(流注), Breast Diseases(乳房疾患) and DoHan(盜汗) are stagnancy's injury of Ki and blood(鬱傷氣血), gallbladder fire with stomach damp(膽火胃濕), deficiency of Yin in stomach with Kwolum's check (胃陰虛 厥陰乘), heat's penetration of blood collaterals with disharmony of liver and stomach(熱入血絡 肝胃不和), insidious pathogen in Kwolum(邪伏厥陰), the treatment of mediation(和解) with Prunellae Spica(夏枯草), Chrysanthemi Flos(菊花), Mori Folium (桑葉), Bupleuri Radix(柴胡), Coptidis Rhizoma(黃連), Scutellariae Radix(黃芩), Gardeniae Fructus(梔子), Cyperi Rhizoma(香附子), Toosendan Fructus(川？子), Curcumae Radix(鬱金), Moutan Cortex(牧丹皮), Paeoniae Radix Rubra(赤芍藥), Unoariae Ramulus Et Uncus(釣鉤藤), Cinnamorni Ramulus(桂枝), Paeoniae Radix Alba(白芍藥), Polygoni Multiflori Radix (何首烏), Cannabis Fructus (胡麻子), Ostreae Concha(牡蠣), Zizyphi Spinosae Semen(酸棗仁), Pinelliae Rhizoma(半夏), Poria(백복령). etc can be applied. 5) When the pathogenesis of BanJin(반진), BalLa(발라), ChangI(瘡痍), NamgChang(膿瘡). ChangJilGaeSeon(瘡疾疥癬), ChangYang(瘡瘍), SeoYang(署瘍), NongYang(膿瘍) and GweYang(潰瘍) are wind-damp(風濕), summer heat-damp(暑濕), damp-warm(濕溫), downward flow of damp-heat(濕熱下垂), damp-heat with phlegm transformation(濕熱化痰), gallbladder fire with stomach damp(膽火胃濕), overdose of cold herbs(寒凉之樂 過服), the treatment of damp-resolving(化濕) with Pinelliae Rhizoma(半夏), armeniacae Amarum Semen(杏仁), Arecae Pericarpium(大腹皮), Poria(백복령), Coicis Semen(薏苡仁), Talcum(滑石), Glauberitum(寒水石), Dioscoreae Tokoro Rhizoma(？？), Alismatis Rhizoma(澤瀉), Phellodendri Cortex(黃柏), Phaseoli Radiati Semen(？豆皮), Bombycis Excrementum(?沙), Bombyx Batryticatus(白？?), Stephaniae Tetrandrae Radix(防己), etc can be applied. 6) When the pathogenesis of ChangPo(瘡泡), hepatic abscess(肝癰) and appendicitis(腸癰) are food poisoning(食物中毒), Ki obstruction & blood stasis in the interior(기비혈어재과), damp-heat stagnation with six Bu organs suspension(濕熱結聚 六腑不通), the treatment of purgation(通下) with DaeHwangMokDanPiTang(大黃牧丹皮湯), Manitis Squama(穿山甲), Curcumae Radix(鬱金), Curcumae Longae Rhizoma(薑黃), Tetrapanacis Medulla(通草), etc can be applied. 7) When the pathogenesis of JeokBan(적반), BanJin(반진), EunJin(은진). BuYang(부양), ChangI(瘡痍), ChangPo(瘡泡), GuChang(久瘡), NongYang(膿瘍), GweYang(潰瘍), Jeong(정), Jeol(癤), YeokRyeo(疫？) and YeokRyeolpDan(疫？入？) are wind-heat stagnation(風熱久未解), blood fever in Yangmyong(陽明血熱), blood fever with transformation(血熱風動), heat's penetration of blood collaterals(熱入血絡). fever in blood(血分有熱), insidious heat in triple energizer(三焦伏熱), pathogen's penetration of pericardium(心包受邪), deficiency of Yong(營虛), epidemic pathogen(感受穢濁), the treatment of Yong & blood-cooling(淸營凉血) with SeoGakJiHwangTang(犀角地黃湯), Scrophulariae Radix(玄參), Salviae Miltiorrhizae Radix(丹參), Angelicae Gigantis Radix(當歸), Polygoni Multiflori Radix(何首烏), Cannabis Fructus(胡麻子), Biotae Semen(柏子仁), Liriopis Tuber(麥門冬), Phaseoli Semen(赤豆皮), Forsythiae Fructus(連翹), SaJin(사진), YangDok(瘍毒) and YeokRyeoIpDan(역려입단) are insidious heat's penetration of pericardium(伏熱入包絡), damp-warm's penetration of blood collaterals(濕溫入血絡), epidemic pathogen's penetration of pericardium(심포감수역려), the treatment of resuscitation(開竅) with JiBoDan(至寶丹), UHwangHwan(牛黃丸), Forsythiae Fructus(連翹), Curcumae Radix(鬱金), Tetrapanacis Medulla(通草), Acori Graminei Rhizoma(石菖蒲), etc can be applied. 9) When the pathogenesis of SaHuSinTong(사후신통), SaHuYeolBuJi(사후열부지), ChangI(瘡痍), YangSon(瘍損) and DoHan(盜汗) are deficiency of Yin in Yangmyong stomach(陽明胃陰虛), deficiency of Yin(陰虛), the treatment of Yin-replenishing(滋陰) with MaekMunDongTang(麥門冬湯), GyeongOkGo(瓊玉膏), Schizandrae Fructus(五味子), Adenophorae Radix(沙參), Lycii Radicis Cortex (地骨皮), Polygonati Odorati Rhizoma(玉竹), Dindrobii Herba(石斛), Paeoniae Radix Alba(白芍藥), Ligustri Lucidi Fructus (女貞子), etc can be applied. 10) When the pathogenesis of RuYang(漏瘍) is endogenous wind in Yang collaterals(陽絡內風), the treatment of endogenous wind-calming(息風) with Mume Fructus(烏梅), Paeoniae Radix Alba (白芍藥), etc be applied. 11) When the pathogenesis of GuChang(久瘡), GweYang(潰瘍), RuYang(漏瘍), ChiChang(痔瘡), JaHan(自汗) and OSimHan(五心汗) are consumption of stomach(胃損), consumption of Ki & blood(氣血耗盡), overexertion of heart vitality(勞傷心神), deficiency of Yong(營虛), deficiency of Wi(衛虛), deficiency of Yang(陽虛), the treatment of Yang-restoring & exhaustion-arresting(回陽固脫) with RijungTang(理中湯), jinMuTang(眞武湯), SaengMaekSaGunjaTang(生脈四君子湯), Astragali Radix (황기), Ledebouriellae Radix(防風), Cinnamomi Ramulus(桂枝), Angelicae Gigantis Radix(當歸), Ostreae Concha(牡蠣), Zanthoxyli Fructus(川椒), Cuscutae Semen(兎絲子), etc can be applied.