총상에 의한 하악결손의 재건술

황오열,박치영,김용배,안희창 大韓成形外科學會 1987 Archives of Plastic Surgery Vol.14 No.3

Most mandibulr reconstructions are performed primarily or secondarily for bony defects caused by injuries or removal of tumors. An autogenous bone greft is still the method of choice for the restoration of mandibular defec. But a conventional autogenous free bone graft does not possess an intact blood supply and is dependent on local nutrition to survive. Severely scarred or radiated tissue are unfavorable beds for bone graft and even more the risk of resorption and infection is inceased in these kinds of a pooly vascularized bed. To overcome this difficulty, free vascularized bone graft has been tried with microsurgical gical technuque. A free vascularized bone graft has significantly higher rate of survival, with less resorption and higher resistance to infextion than a connentional free bone graft. A free vascularized iliac bone graft pedicled on deep circumflex iliac vessels is used widely, as it have many advantages such as, availability of large bloc of composite tissue, simplicity of donor dissection, large and long vascular pedicle and few donor site morbidity. In this paper, we represent 4 cases of reconstruction of wide mandibular defects using free vascularized iliac bone graft and free dsteocutaneous groin flap, and review the characteristics of gunshot wound. The result is satisfactory.

총상에 의한 하악결손의 재건술

박치영,김용배,안희창,황오열 中央醫學社 1988 中央醫學 Vol.53 No.5

혈관평활근세포에서 산화에너지대사 억제에 의한 아밀로이드전구단백질 대사의 변화

한문구,최웅,김헌식,안희열,한설희 대한치매학회 2002 Dementia and Neurocognitive Disorders Vol.1 No.1

Background: A reduction in the activity of cytochrome c oxidase(COX) has been recently identified in mitochondria from platelets and postmortem brain tissue of AD patients Sodium azide (NaN₃). a COX inhibitor, is an effective chemical agent producing energy shortage and oxidative stress both in vitro and in vivo system Furthermore it has been suggested that vascular compromise could be either directly involved AD pathogenesis or indirectly associated with triggering pathogenetic events leading to AD This study was performed to investigate amyloid precursor protein (APP) metabolism by inhibition of mitochondrial energy metabolism in cultured vascular smooth muslce cells (VSMCs) Materials and Methods: VSMCs isolated from the aorta of seven weeks old Spraque-Dawley rat were treated with NaN₃in a low concentration (100-500μM) or in a high concentration (1-100mM) Cellular proliferation and viability were determined by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenly)-2H-tetrazolium) assay Cellular APP was detected with N-terminal specific antibody 22C11. Celldeath was determined by observation of morphology and terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick end labeling stain (TUNEL) We used ginkgo biloba extract(EGb761) and melatonin as anti-oxidants to investigate the mechanism of latered APP metabolism Results: The viability of VSMCs was increased after treatment with 1 mM and 10mM NaN₃(p<0.05) unitl 3 hr and then dimnished Many TUNEL positive cells were found in 10mM and 100mM treatment group. but were not apoptotic in nature 22C11 immunoreactivity was not changed at 3 hr, 6hr, 12hr Anti-oxidants reduced cellular proliferation (p<0.05). but did not block TUNEL positivities and did not influence the 22C11 immunoreactivity In a low concentration NaN₃ treatment group the viability of VSMCs was increased concentration dependently(p<0.05) Immunoblot with 22C11 showed the concentration dependent decrease at 145 kDa, 125 kDa. and high molecular weight range (>160kDa) TUNEL staining showed DNA fragmentations and condensations of nuclear chromatin suggesting apoptosis After treatment with anti-oxidants, the cellular proliferation was more decreased (p<0.05), and TUNEL positive cell deaths were blocked Immunoreactivities of 125 kDa (immature APP). 145 kDa (mature APP). and higher molecular weight bands were recovered below 400μM of NaN₃ Immunoreactivity of 145 kDa was recovered in 100 μM NaN₃ treated group Conclusions: The presumed mechanism of low concentration COX inhibitor is the overproduction of reactive oxygen species resulting from a depression of the mitochondiral electron transport chain. whereas potential consequence of high concentration COX inhibitor might be related to decreassion of ATP synthesis and bioenergetic impairment Reactive oxygen radicals in response to low concentration COX inhibitor alter the processing of APP in VSMCs This investigation demonstrated analtered APP metabolism as a peripheral marker of AD Therefore VSMCs treated with low concentration COX inhibitor could be concsidered as a novel in vitro model of AD.

Inhibition of Vascular Smooth Muscle Cell Proliferation by Epigallocatechin Gallate

Hee-Yul Ahn 충북대학교 약품자원개발연구소 1998 약학논문집 Vol.13 No.-

EPIGALLOCATECHIN-3 GALLATE, SELECTIVELY INHIBITS THE PLATELET-DERIVED GROWTH FACTOR-BB-INDUCED SIGNALING TRANSDUCTION PATHWAYS IN VASCULAR SMOOTH MUSCLE CELLS

Ahn, Hee-Yul,K.R. Hadizadeh Kharrazi,Yun, Y-P,Park, J-B,Choi, W,H. Vetter,A. Sachinidis 이화여자대학교 세포신호전달연구센터 2000 고사리 세포신호전달 심포지움 Vol. No.2

Vascular smooth muscle cells(VSMCs) proliferation may participate in the pathophysiology of cardiovascular diseases. Platelet-derived growth factor-BB(PDGF-BB) is a potent mitogenic factor for VSMCs. Epigallocatechin gallate(EGCG) is the main compound of green tea and is believed to be the active component in tea for the prevention against several diseases. We investigated the effect of EGCG on the PDGF-BB-induced proliferation of VSMCs. VSMCs were preincubated in serum-free medium for 24 h(quiescent VSMCs) before EGCG was added to the medium. Following 24 h incubation with EGCG per se, VSMCs were trypsinized and cell counts were determined using CASY-1 system based on the coulter counter principle(Scharfe). Treatment of the cells with 0μM, 20μM, 50μM and 100μM EGCG resulted in a decrease of cell counts from 1.49×10^(6) ± 1.2×10^(5)(0μM) to 9.7×10^(5) ± 1.1×10⁴, 5.3×10^(5) ± 6.3×10⁴, 3.8×10^(5) ± 2.5×10⁴ counts/ml(mean±SD, n=3), respectively. Stimulation of quiescent cells with 50 ng/ml PDGF-BB for 24 h resulted in a 35% increase in cell counts. In the presence of 50μM EGCG, the effect of PDGF-BB on cell counts was abrogated. Activation of the 42 and 44 kDa mitogen-activated protein kinase(MAP) kinases(p44^(mapk)/p42^(mapk)) was deteced by chemiluminescence western blotting method using primary antibodies which recognizes the Tyr204-phosphorylated active isoforms. Stimulation of quiescent VSMCs with 50 ng/ml PDGF-BB caused at 5 min an 8-fold increase of the the p44^(mapk)/p42^(mapk) phosphorylation above control levels. Pretreatment of cells for 24 h with 50㎍/ml EGCG resulted in 70% inhibition of the p44^(mapk)/p42^(mapk) phosphorylation. Stimulation of the cells with PDGF-BB caused a maximal increase in [Ca^(2+)]_(i) from 40±10(basal value) to 145±15nM(mean±SD, n=4) at 25 sec(determined by the fura-2 method). Preincubation of VSMCs for 24 h with EGCG resulted in a complete inhibition of the PDGF-BB-induced increase in [Ca^(2+)]_(i). These results demonstrate that EGCG may exert its anti-proliferative effects via inhibition of the PDGF-BB-induced intracellular signaling events like stimulation of the p44^(mapk)/p42^(mapk) and elevation of [Ca^(2+)]_(i).

Epigallocatechin-3-gallate Regulates Inducible Nitric Oxide Synthase Expression in Human Umbilical Vein Endothelial Cells

Hee Yul Ahn,Chan Hyung Kim 한국실험동물학회 2011 Laboratory Animal Research Vol.27 No.2

Inducible nitric oxide synthase (iNOS) is a main enzyme producing nitric oxide during inflammation and thus contributes to the initiation and development of inflammatory cardiovascular diseases such as atherosclerosis. Epigallocatechin-3-gallate (EGCG), the major catechin derived from green tea, has multiple beneficial effects for treating cardiovascular disease, but the effect of EGCG on the expression of vascular iNOS remains unknown. In this study, we investigated (i) whether EGCG inhibits the expression of vascular iNOS induced by angiotensin II in human umbilical vein endothelial cells and, if it does inhibit, (ii) mechanisms underlying the inhibition. Angiotensin II increased expression levels of vascular iNOS; EGCG counteracted this effect. EGCG increased the production of reactive oxygen species. Moreover, EGCG did not affect the production of reactive oxygen species induced by angiotensin II. These data suggest a novel mechanism whereby EGCG provides direct vascular benefits for treating inflammatory cardiovascular diseases.

Epigallocatechin-3-gallate Regulates NADPH Oxidase Expression in Human Umbilical Vein Endothelial Cells

Ahn, Hee-Yul,Kim, Chan-Hyung,Ha, Tae-Sun The Korean Society of Pharmacology 2010 The Korean Journal of Physiology & Pharmacology Vol.14 No.5

Vascular NADPH oxidase plays a pivotal role in producing superoxide in endothelial cells and thus acts in the initiation and development of inflammatory cardiovascular diseases such as atherosclerosis. Epigallocatechin-3-gallate (EGCG), the major catechin derived from green tea, has multiple beneficial effects for treating cardiovascular disease but the effect of EGCG on the expression of vascular NADPH oxidase remains unknown. In this study, we investigated the mechanism(s) by which EGCG might inhibit the expression of subunits of NADPH oxidase, namely $p47^{phox}$, $p67^{phox}$ and $p22^{phox}$, induced by angiotensin II (Ang II) in human umbilical vein endothelial cells. Ang II increased the expression levels of $p47^{phox}$, $p67^{phox}$, and $p22^{phox}$, but EGCG counteracted this effect on $p47^{phox}$. Moreover, EGCG did not affect the production of reactive oxygen species induced by Ang II. These data suggest a novel mechanism whereby EGCG might provide direct vascular benefits for treating inflammatory cardiovascular diseases.

Epigallocatechin-3-gallate Regulates NADPH Oxidase Expression in Human Umbilical Vein Endothelial Cells

Hee Yul Ahn,Chan Hyung Kim,Tae-Sun Ha 대한생리학회-대한약리학회 2010 The Korean Journal of Physiology & Pharmacology Vol.14 No.5

Vascular NADPH oxidase plays a pivotal role in producing superoxide in endothelial cells and thus acts in the initiation and development of inflammatory cardiovascular diseases such as atherosclerosis. Epigallocatechin-3-gallate (EGCG), the major catechin derived from green tea, has multiple beneficial effects for treating cardiovascular disease but the effect of EGCG on the expression of vascular NADPH oxidase remains unknown. In this study, we investigated the mechanism(s) by which EGCG might inhibit the expression of subunits of NADPH oxidase, namely p47^phox, p67^phox and p22^phox, induced by angiotensin II (Ang II) in human umbilical vein endothelial cells. Ang II increased the expression levels of p47^phox, p67^phox, and p22^phox, but EGCG counteracted this effect on p47^phox. Moreover, EGCG did not affect the production of reactive oxygen species induced by Ang II. These data suggest a novel mechanism whereby EGCG might provide direct vascular benefits for treating inflammatory cardiovascular diseases.

Sodium nitroprusside와 Forskolin의 Phorbol ester 수축에 대한 혈관이완작용의 기전

안희열(Hee Yul Ahn) 대한약리학회 1995 대한약리학잡지 Vol.31 No.3

본 연구의 목적은 protein kinase C의 활성물질인 phorbol ester의 수축에 대한 cGMP 및 cAMP의 조절기전을 명확히 하기 위하여 흰쥐의 대동맥을 재료로 실험을 수행하였다. Sodium nitroprusside는 guanylyl cyclase를 활성화시켜 cGMP를, forskolin은 adenylyl cyclase를 활성화시켜서 cAMP를 증가시키는 것으로 보고되어 있으므로 위의 두 약물을 선택하였다. Phorbol ester는 시간경과와 함께 지속적인 수축을 발생하였으며 30분경 안정상태에 도달하였다. 동시에 20-kDa myosin light chain (MLC)의 인산화도 증가하였으며 30분경 최대치를 나타내었다. Sodium nitroprusside와 forskolin은 phorbol ester에 의한 수축을 농도의존적으로 억제하였으나 sodium nitroprusside가 forskolin보다 더욱 민감하게 억제하였다. Phorbol ester는 ⁴⁵Ca²⁺의 유입을 증가시켰고 sodium nitroprusside와 forskolin은 이 증가된 ⁴⁵Ca²⁺을 유의하게 억제하였다. Phorbol ester에 의하여 증가된 MLC의 인산화는 sodium nitroprusside 및 forskolin 각각의 최대농도로 억제되었다. 이상과 같은 결과로 볼때 아마도 cGMP와 cAMP는 phorbol ester에 의한 수축을 ⁴⁵Ca²⁺ 유입억제에 이은 MLC 인산화 억제에 의하여 이완작용을 나타내는 것으로 추측되며 cGMP가 cAMP보다 protein kinase C 매개의 수축조절에 더 중요하게 작용하리라 추측된다. The objectives of this study is to compare the inhibitory mechanism of sodium nitroprusside and forskolin on the phorbol ester, activator of protein kinase C (PKC), -induced contractions in rat aorta. 0.1μM phorbol dibutyrate (PDBu) induced sustained contractions and increased phosphorylations of myosin light chain (MLC) time-dependently. At 30 min, the contractions and phosphorylations of MLC by PDBu were augmented maximally and remained constant. Moreover, ⁴⁵Ca²⁺ uptake was increased 30 min after PDBu stimulation from resting values. Sodium nitroprusside which activates guanylyl cyclase followed by increasing cGMP, inhibited the PDBu-induced contractions concentration-dependently. On the other hand, forskolin which activates adenylyl cyclase followed by increasing cAMP, also inhibited the PDBu-induced contractions concentration-dependently. However, sodium nitroprusside was more potent to inhibition of the PDBu-induced contractions than forskolin. Sodium nitroprusside inhibited ⁴⁵Ca²⁺ uptake by PDBu stimulation. Forskolin also inhibited ⁴⁵Ca²⁺ uptake by PDBu stimulation. Sodium nitroprusside and forskolin inhibited the phosphorylations of MLC by PDBu, respectively. However, sodium nitroprusside was more potent to inhibition of phosphorylations of MLC by PDBu than forskolin. From these results, Sodium nitroprusside via cGMP or forskilin via cAMP may reduce myoplasmic Ca²⁺ followed by suppression of phosphorylations of MLC of PKC-mediated contractions, which results in vasodilation. However, cGMP may play a role more importantly than cAMP on the regulation of protein kinase C-mediated contraction in vascular smooth muscle.

α-독으로 처리한 토끼창간막동맥에서 Norepinephrine과 GTP에 의한 마이오신 인산화의 증가에 대한 Ca²⁺/calmodulin-dependent Protein Kinase II의 역할

안희열(Hee Yul Ahn),김헌식(Hun Sik Kim),Robert S. Moreland 대한약리학회 1994 대한약리학잡지 Vol.30 No.1

수용체작동약물과 GTP에 의한 수축단백질의 칼슘이온의 감수성의 증가에 대하여 Ca²⁺/calmodulin-dependent protein kinase II의 역할을 α-독으로 처리한 토끼장간막동맥에서 조사하였다. 0.3μM의 칼슘이온은 마이오신의 인산화를 시간의존적으로 증가시켰고 5분 이후부터 평형에 도달하였다. 한편, 10μM의 norepinephine과 10μM의 GTP는 칼슘이온 존재하에 칼슘이온 단독에 의한 것 보다 더 마이오신의 인산화를 증가시켰는데, 5분 후에 최대에 달하였고 그 후는 감소하기 시작하여 20분 후에는 칼슘이온 단독에 의한 마이오신 인산화 증가와 거의 차이가 없었다. Ca²⁺/calmodulin-dependent protein kinase II 억제제인 KN-62를 전처치하여 norepinephrine과 GTP에 의한 마이오신 인산화 증가의 변화를 경시적으로 관찰하였다. 10μM KN-62는 1분에서 norepinephrine과 10μM GTP에 의한 마이오신의 인산화의 증가를 억제하였다. 그러나 5분에서 관찰되는 norepinephrine과 GTP에 의한 마이오신 인산화의 증가의 최대치에는 영향이 없었고 그 이후에도 KN-62는 아무 영향을 끼치지 못하였다. 이상과 같은 결과로 볼때 norepinephrine과 GTP에 의하여 일어나는 평활근 수축단백의 칼슘이온의 감수성의 증가는 이미 알려진 바와 같이 마이오신 인산화의 증가에 기인하며 이 증가는 일과성임을 확인하였다. 이때 Ca²⁺/calmodulin-dependent protein kinase II의 역할은 시간의존적으로 norepinephrine과 GTP의 자극 초기에 관여되는 것으로 생각되며 그 이후에는 관여가 없는 것으로 사료된다. The role of Ca²⁺/calmodulin-dependent protein kinase II in the increase of myofilament Ca²⁺ sensitivity by agonist and GTP was investigated in rabbit mesenteric α-toxin permeabilized artery. 0.3μM Ca²⁺ increased myosin light chain phosphorylations monotonically. 10μM norepinephrine and 10μM GTP potentiated increase of myosin light chain phosphorylations by 0.3μM Ca²⁺, which reaches a peak at 5 min and gradually declines to the Ca²⁺ alone level at 20 min. At the early phase (1 min), 10μM KN 62, the inhibitor of Ca²⁺/calmodulin-dependent protein kinase II , decreased myosin light chain phosphorylation levels by 10μM norepinephrine and 10μM GTP in the presence of 0.3μM Ca²⁺. However 10μM KN-62 did not affect the myosin light chain phosphorylations by 10μM norepinephrine and 10μM GTP in the presence of 0.3μM Ca²⁺ at the peak (5 min) and plateau phases (20 min). From these results, the role of Ca²⁺/calmodulin-dependent protein kinase II may be different depending on time, which may play a role in increase of myofilamint Ca²⁺ sensitivity by norepinephrine and GTP resulting from increase of myosin light chain phosphorylations at the early phase. However, at plateau phase, Ca²⁺/calmodulin-dependent protein kinase II may not be involved in the increase of myofilament Ca²⁺ sensitivity by norepinephrine and GTP in rabbit mesenteric α-toxin permeabilized artery.