한국인에서 치주질환과 관상동맥질환의 관련성에 대한 염증표지자와 IL-1 유전자 다변성의 영향

정하나,정현주,김옥수,김영준,김주한,고정태,Jeong, Ha-Na,Chung, Hyun-Ju,Kim, Ok-Su,Kim, Young-Joon,Kim, Ju-Han,Koh, Jung-Tae 대한치주과학회 2004 Journal of Periodontal & Implant Science Vol.34 No.3

Recently epidemiologic studies have indicated that the patients with periodontitis may have increased risk of ischemic cardiovascular events, and have suggested the important roles of blood cytokines and acute reactant proteins in the systemic infection and inflammatory response. Periodontitis and coronary heart disease (CHD) may share the common risk factors and the genetic mechanism associated with interleukin(IL)-1A, B and RA genotype may be involved in the production of IL-1. This study was aimed to investigate the relationship between angiographically defined CHD and periodontitis as chronic Gram-negative bacterial infection and to determine whether the IL-1 gene polymorphism is associated in both diseases. Patients under the age of 60 who had undergone diagnostic coronary angiography were enrolled in this study. Subjects were classified as positive CHD (+CHD, n=37) with coronary artery stenosis more than 50% in at least one of major epicardial arteries, and negative CHD (-CHD, n=30) without significant stenosis. After recording the number of missing teeth, periodontal disease severity was measured by means of plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), and radiographic bone loss around all remaining teeth. Gingival crevicular fluid (GCF) was collected from the 4 deepest periodontal pockets and assessed for cytokine ($IL-1{\beta}$, IL-6, IL-1ra, tumor necrosis $factor-{\alpha}$, and prostaglandin $E_2$). Additionally, blood CHD markers, lipid profile, and blood cytokines were analyzed. IL-1 gene cluster genotyping was performed by polymerase chain reaction and enzyme restriction using genomic DNA from buccal swab, and allele 2 frequencies of IL-1A(+4845), IL-1B(+3954), IL-B(-511), and IL-1RA(intron 2) were compared between groups. Even though there was no significant difference in the periodontal parameters between 2 groups, GCF level of $PGE_2$ was significantly higher in the +CHD group(p<0.05). Correlation analysis showed the positive relationship among PD, CAL and coronary artery stenosis(%) and blood $PGE_2$. There was also significant positive relationship between the periodontal parameters (PI, PD, CAL) and the blood CHD markers (leukocyte count, C-reactive protein, and lactic dehyrogenase). IL-1 gene genotyping showed that IL-1A(+3954) allele 2 frequency was significantly higher in the +CHD group compared with the -CHD group (15% vs. 3.3%, OR 5.118,p=0.043). These results suggested that periodontal inflammation is related to systemic blood cytokine and CHD markers, and contributes to cardiovascular disease via systemic inflammatory reaction. IL-1 gene polymorphism might have an influence on periodontal and coronary heart diseases in Korean patients.

Distribution of Aquaporins (Water Channels) in the Rat Salivary Glands

정지연(Ji-Yeon Jung),한창룡(Chang-Ryoung Han),정연진(Yeon-Jin Jeong),오원만(Won-Mann Oh),김미원(Mi-Won Kim1),김선헌(Sun-Hun Kim),김옥준(Ok-Joon Kim),김현진(Huyn-Jin Kim),고정태(Jeong-Tae Koh),최홍란(Hong-Ran Choi),김원재(Won-Jae Kim) 대한해부학회 2002 Anatomy & Cell Biology Vol.35 No.3

침샘은 하루 1.5 l의 침을 분비하며, 일반적으로 침샘에서 수분이동은 능동적 염분 이동에 따른 삼투현상에 의해 일어난다. 따라서 침샘에서 높은 수분투과성으로 인해 수분통로 단백인 aquaporin (AQP)들이 풍부하게 존재할 수 있다. 지금까지침샘에 4가지 형태의 AQP이 존재한다고 알려져 있지만 침샘에서 정확한 위치와 수분 이동에 대한 각 AQP들의 역할은 아직 확실치 않다. 본 연구는 300 g 정도의 흰쥐를 pentobarbital sodium (50 mg/kg, IP) 마취하에서 carbarchol (10 μg/kg)을 복강 내 투여한 후 AQP들의 역할과 분포를 면역조직화학방법으로 조사하였다. AQP1은 침샘의 미세혈관의 내피세포와 샘세포와 샘관 주위에 존재하는 근육상피세포에 존재하였다. AQP4는 침샘관의 마지막 부위인 배출관에 존재하였다. AQP5는 주로 장액세포의 바닥가쪽과 세포사이 분비소관을 포함한 세포꼭대기쪽막 에 존재하였으며 콜린성 분비 자극으로 세포꼭대기쪽막으로 이동되어 밀집되었다. AQP5는 모든 침샘의 사이관과 줄무늬 관에도 존재하였으며 점액세포는 약하게 존재하였다. AQP8은 AQP5처럼 장액세포의 바닥쪽막과 세포사이 분비소관을 포함한 세포꼭대기쪽막에 존재하였으며 콜린성 침분비 자극으로 세포꼭대기쪽막쪽으로 이동되어 밀집되었다. 이상의 실험결과는 AQP5와 AQP8이 장액세포에서 일차 침 형성시 일어나는 수분이동의 주된 통로임을 시사하였다. The salivary glands produce 1.5 l of fluid per day. As in other organs, the general paradigm in the salivary glands is that water movement occurs secondary to osmotic driving forces created by active salt transport. Therefore, high water permeability in salivary glands is expected to need a variety of aquaporin (AQP), a water channel. Although four AQPs have been known to reside in salivary glands, the precise location and roles of AQPs have been not well examined. This study is aimed to investigate the distribution of AQPs in 3 major salivary glands and their changes after cholinergic stimulation using immunohistochemical study in Sprague Dawley rats weighing 300 g under pentobarbital sodium anesthesia. AQP1 was localized in the endothelial cells of all salivary capillary vessels and the myoepithelial cells. AQP4 was demonstrated in the epithelium of the excretory ductal cells of all salivary glands. AQP5 and 8 were abundantly present in the basolateral membrane and apical membranes of the serous acini including intercellular secretory canaliculi, whereas AQP5 was weakly present in mucous acini. In addition, AQP5 was found in the epithelium of the intercalated and striated ducts. Upon stimulation of carbachol (10 μg/kg, I.P). AQP5 and 8 tended to translocate from basolateral membrane to the apical membrane, appearing as clusters of dots. These results suggest that AQP5 and 8 are the candidate molecules responsible for the water movement in salivary acinar cells.

치과용 타니타늄 임플란트의 최근 연구 개발 동향

이광민 ( Kwang Min Lee ),박상원 ( Sang Won Park ),임현필 ( Hyun Pil Lim ),고정태 ( Jeong Tae Koh ),강성수 ( Seong Soo Kang ),김현승 ( Hyun Seong Kim ),박광범 ( Kwang Bum Park ),류경호 ( Gyeong Ho Ryoo ),이경구 ( Kyung Ku Lee ) 대한금속·재료학회 2009 재료마당 Vol.22 No.4

중추내로 투여한 5-HT<SUB>1A</SUB> 작동제에 의한 마취 가토에 있어서 신장기능의 변동

임영채(Young Chai Lim),김경심(Kyung Shim Kim),국영종(Young Johng Kook),고정태(Jeong Tae Koh) 대한생리학회-대한약리학회 1997 The Korean Journal of Physiology & Pharmacology Vol.1 No.3

<P> Central tryptaminergic system has been shown to play an important role in the regulation of renal function: 5-HT<SUB>1</SUB>(5-hydroxytryptamine<SUB>1</SUB>) receptors might seem to mediate the diuresis and natriuresis, whereas the 5-HT<SUB>2</SUB> and 5-HT<SUB>3</SUB> receptors mediate the antidiuretic and antinatriuretic effects. This study attempted to delineate the role of central 5-HT<SUB>1A</SUB> subtype in the regulation of rabbit renal function by observing the renal effects of intracerebroventricularly(icv)-administered PAPP(p-aminophenylethyl-m-trifluoromethylphenyl piperazine, LY165163), a selective agonist of 5-HT<SUB>1A</SUB> receptors. PAPP in doses ranging from 40 to 350 ㄍg/kg icv induced significantly diuresis, natriuresis, and kaliuresis, along with increased renal perfusion and glomerular filtration. Systemic blood pressure was also increased. Free water reabsorption(T<SUP>c</SUP>H<SUB>2</SUB>O), a measure of ADH(antidiuretic hormone) secretion, was increased also. Intravenous 350 ㄍg/kg of PAPP elicited antidiuresis and antinatriuresis together with decreased blood pressure, thus indicating that the effects of icv PAPP were brought about through the central mechanisms, not by direct peripheral effects of the drug on kidney. Ketanserin, a selective 5-HT<SUB>2</SUB> antagonist, 40 ㄍg/kg icv, did not affect the renal effects of the icv PAPP. Methysergide, a non-selective 5-HT<SUB>1</SUB> antagonist, also did not block the renal functional responses by the icv PAPP. NAN-190, a 5-HT<SUB>1A</SUB> antagonist, also did not antagonized the renal action of the icv PAPP. However the increased free water reabsorption was abolished by both methysergide or ketanserin pretreatment. The increments of blood pressure by icv PAPP was blocked only by NAN-190 pretreatment. These observations suggest that the central 5-HT<SUB>1A</SUB> receptor might be involved in the central regulation of rabbit renal function by exerting the diuretic and natriuretic influences.

중추에 의한 가토 신장기능조절에 미치는 Forskolin의 영향

고정태,김경근,국영종 전남대학교 치과대학 1993 전남치대논문집 Vol.5 No.1

Various endogenous neurotransmitter systems have been shown to take part in central regulation of renal function through the medium of intracellular cAMP, a second messenger of cellular events in response to activation of membrane receptors. This study was undertaken to observe further the influence of adenylate cyclase activation, leading to increased cAMP levels, on the central regulation of renal function. Forskolin, an activator of adenylate cyclase, was administered into a lateral ventricle (icv) of rabbit brain in doses ranging from 13 to 130 ㎍/㎏ and changes in renal function were observed. With 13 ㎍/㎏ icv no marked changes in renal function were noted. Tripling the does to 40 ㎍/㎏ icv produced marked increases in urine flow rate and excretory rate of Na and K along with increased renal perfusion (=C_(Na)) and the fraction of sodium excreted (=FE_(Na)). Increasing the does further up to 130 ㎍/㎏ icv elicited marked diuresis, natriuresis and kaliuresis for about 20 min, with increased renal hemodynamics. The fraction of filtered sodium excreted (=FE_(Na)), indicative of the degree of inhibition of tubular sodium reabsorption, also increased. No significant changes in systemic pressure were noted. DMSO, the solvent employed to dissolve forskoin, given icv in 0.15㎖ up to the concentration of 63%, did not produce significant diuresis, natriuresis, kaliuresis, nor any significant changes in systemic blood pressure. Therefore, forskolin was dissolved in 63% DMSO. When given intravenously, however, forskolin 130 ㎍/㎏, a dose which elicits marked diuresis and natriuresis when given icv, did not produce diuretic effect, but rather tended to decrease urinary output and sodium excretion, implicating central mechanism of the icv effect. In preparations in which one kidney was denervated, with the other serving as control, the denervated kidney responded to icv forskolin with more prominent diuresis and natriuresis, suggesting humoral mediation of the effect. Plasma levels of ANP significantly increased, up to more than double the control level at 20 min after 130 ㎍/㎏ forskolin icv, when the natriuresis reached the peak. These observations suggest that endogenously produced cAMP, by activating adenylate cyclase cause the renal effects, mediated by ANP, and indicate that the adenylate cyclase-cAMP system in involved in central regulation of renal function.

Diazepam의 중추성 신장기능조절과 그 작용기전에 관하여

고정태,김경근 전남대학교 치과대학 1995 전남치대논문집 Vol.7 No.1

The renal function is under regulatory influence of central nervous system, in which various neurotransmitter and neuromodulator systems take part, and it is known that diazepam have antianxiety and anticonvulsant effects through the benzodiazepine site coupled GABA receptor-CI- ion channel complex. This study was, therefore, undertaken to delineate the renal effects of diazepam and its mechanism in the regulation of renal function. Diazepam given into a lateral ventricle (icv) of rabbit brain in does ranging from 10 to 100㎍/㎏ icv elicited increases, in roughly dose dependent manner, in Na excretion, renal plasma flow (RPF), glomerular filtration rate(GFR), fraction of filtered sodium excreted(FE_NA) and K excretion, as well as in urine flow rate. NO significant changes in systemic blood pressure were shown. The vehicle alone did not produce any effect. When the same dose were given intravenously, all the parameters of renal function and systemic blood pressure did not show any changes, indicating that the icv effects were indeed of the central origin. The experiments in which renal nerve activity was monitored showed that diazepam, 100㎍/㎏ icv, transiently elicited decrease in the activity, and then recovered after 5 min. In experiments in which the plasma levels of atrial natriuretic peptides(ANP) were measured, plasma ANP level increased about 7 times over the control level after 100㎍/㎏ icv, the peak coinciding with natriuresis and diuresis. Muscimol, a specific agonist of GABA receptor, produced no significant changes in the does of 0.1 to 0.3㎍/㎏, but elicited antidiuresis and antinatriuresis, in 1.0㎍/㎏ related to decreases in systemic blood pressure. When muscimol 0.3㎍/㎏ icv. a dose minimally affecting the renal function, was given 3 min prior to 30㎍/㎏ diazepam icv, the renal effects of the latter tended to decreases in urine flow rate and Na excretion with decrease in systemic blood pressure. It is indicated that renal effect of icv diazepam is not mediated to GABAergic system. β-CCM, a benzodiazepine inverse agonist, 10~100㎍/㎏ icv, tended to diuresis and natriuresis without hemodynamic changes. When 100㎍/㎏ diazepam icv was given 3 min after β-CCM, urine flow rate and Na excretion of diazepam 100㎍/㎏ was not affected. These may be resultant to inhibition of diazepam binding to tis receptor by the icv β-CCM and the renal effects of β-CCM itself. These results suggested that diazepam may participate in the central regulation of renal function, bringing about natriuresis and diuresis which are related to increased plasma ANP levels and partly decreased renal nerve activity, and that the effect many not be mediated to activation of GABAergic system.

치근 천공 치료 재료의 생체친화성의 비교

강민경,배인호,고정태,황윤찬,황인남,오원만 대한치과보존학회 2009 Restorative Dentistry & Endodontics Vol.34 No.3

This study was carried out in order to determine in vitro biocompatibility of white mineral trioxide aggregate (MTA), and to compare it with that of the commonly used materials, i. e. calcium hydroxide liner(Dycal), glass ionomer cement (GIC), and Portland cement which has a similar composition of MTA. To assess the biocompatibility of each material, cytotoxicity was examined using MG-63 cells. The degree of cytotoxicity was evaluated by scanning electron microscopy (SEM) and a colorimetric method, based on reduction of the tetrazolium salt 2,3 bis {2methoxy 4nitro 5〔(sulfenylamino) carbonyl〕2H tetrazolium hydroxide} (XTT) assay. The results of SEM revealed the cells in contact with GIC, MTA, and Portland cement at 1 and 3 days were apparently healthy. In contrast, cells in the presence of Dycal appeared rounded and detached. In XTT assay, the cellular activities of the cells incubated with all the test materials except Dycal were similar, which corresponded with the SEM observation. The present study supports the view that MTA is a very biocompatible root perforation repair material. It also suggests that cellular response of Portland cement and GIC are very similar to that of MTA. 이번 연구는 치근 천공의 치료 재료인 white mineral trioxide aggregate (MTA)를 흔히 사용되는 calcium hydroxideliner(Dycal^(R), glass ionomer cement (GIC), 그리고 MTA와 유사한 성분을 가진 Portland cement와 세포독성 실험으로 생체 친화성을 평가하는 것이다. 세포독성의 정도는 MG-63 세포를 이용해 주사전자 현미경적 관찰과 수용성 tetrazolium salt를 이용한 흡광도를 측정 (XTT assay)하여 평가하였다. SEM 관찰에서, 1일과 3일째 모두에서 GIC와 MTA, Portland cement표면에서는 잘 부착된 세포를 보여주었다. 반면에, Dycal 표면의 세포들은 둥글고 부착되지 않은 양상을 보여주었다. XTT assay에서는 Dycal을 제외한 모든 재료에서 유사하게 높은 세포 활성도를 보여주었으며, 이는 SEM 관찰 소견과 일치하였다. 이번 연구는 MTA가 생체친화적인 재료라는 견해를 뒷받침한다. 또한 Portland cement와 GIC에서도 MTA와 유사한 세포반응을 보여주었다.

Epressions of Angiogenic and Angiostatic Genes in Cyclosporin A-induced Gingival Overgrowth

Park, Young-Seob,Koh, Jeong-Tae,Kim, Kyung-Keun 전남대학교 치의학연구소 2002 구강과학 Vol.14 No.1

Cyclosporine A (CyA)는 장기 이식 및 자가면역 질환의 치료제로 널리 사용되는 면역억제제로서, 신독성, 간독성, 구강 내 치은비대증 등의 부작용을 초래한다. 치은 조직 내 섬유아세포, 세포외 기질, 혈관조직의 증가를 동반한 치은비대증의 기전으로는 콜라젠 섬유의 생성 증가와 파괴 감소 등이 제시되고 있으나 명확하게 규명되고 있지는 않다. 특히, 치은 증식에서의 혈관조직 변화와 관련하여 혈관 생성 인자의 관여와 그 역할에 대해서는 알려진 바 없다. 본 연구에서는 CyA를 흰쥐에 피하 주사하여 치은 비대증을 유발한 후, 치은 조직에서 혈관생성 촉진인자 [angiopoietin1(AGP1), basic fibroblast growth factor(bFGF), vascular endothelial growth factor(VEGF)]와 혈관생성 억제인자 [angiopoietin2(AGP2), brain-specific angiogenesis inhibitors (BAIs), thrombospondin 2 (TSP2)]의 발현정도를 역전사 중합 반응법(RT-PCR)으로 비교함으로 치은 비대증 발생과 혈관생성과의 관계를 알아보고자 하였다. 또한, CyA에 의한 혈관생성인자의 발현 변화가 치은 비대증의 주 작용세포로 알려진 치은 섬유아세포에서 초래되는지를 알아보고자 일차 배양한 치은 섬유아세포에서의 혈관생성 관련 유전자들의 발현을 역전사 중합 반응법과 Western blot분석을 통하여 비교 관찰하였다. CyA 10 mg/kg를 6주간 투여한 흰쥐의 치은 조직으로부터 RT-PCR을 시행한 결과, AGP1, bFGF, VEGF, AGP2, BAI1의 mRNA 발현은 정상 흰쥐에 비해 뚜렷한 변화를 보이지 않았으나, TSP2 발현은 현저히 감소되었다. 치은 조직에서의 TSP2발현 정도는 5, 10, 15 mg/kg의 CyA에 의해 용량 의존적으로 감소하였으며, 10 mg/kg를 투여한 3주, 6주, 12주의 치은조직에서도 모두 감소하였다. 흰쥐의 치은조직으로부터 일차 배양한 치은 섬유아세포에 치은 비대증을 유발하는 CyA 혈중 농도로 알려진 1000 ng/ml을 투여한 후에는, VEGF, AFP1, bFGF, AgP2, BAI1, BAI2의 mRNA발현이 정상 섬유아세포에 비해 뚜렷한 변화를 보이지 않았으나, TSP2 mRNA 발현은 현저히 감소하였다. 정상 인간의 치은 조직으로부터 배양한 치은 섬유아세포에서도 TSP2 mRNA 발현은 CyA의 투여 용량 (250, 500, 750, 1000 ng/ml)과 시간(1, 2, 3, 4일)에 따라 감소하였으며, 배양한 치은 섬유아세포에서 TSP 단백 발현도 투여한 CyA의 농도 (250∼1000 ng/ml)에 의존적으로 감소하였다. 이상의 결과로 CyA 투여에 의해 혈관증식과 함께 초래되는 치은 비대증에서 혈관생성 촉진인자의 변동은 관찰할 수 없는 반면 혈관생성 억제인자인 TSP2 발현은 억제되며, 이러한 작용은 치은 섬유아세포에서도 나타남을 알 수 있었다. 이는 치은 비대증의 병인 중에 하나인 혈관증식에는 혈관생성 촉진인자보다는 혈관생성 억제인자가 주로 관여하고 있음을 시사한다.

Biocompatibility of experimental mixture of mineral trioxide aggregate and glass ionomer cement

Oh, Min-Jae,Jeong, Yu-Na,Bae, In-Ho,Yang, So-Young,Park, Bum-Jun,Koh, Jeong-Tae,Hwang, Yun-Chan,Hwang, In-Nam,Oh, Won-Mann 大韓齒科保存學會 2010 Restorative Dentistry & Endodontics Vol.35 No.5

Objectives: The purpose of the present in vitro study was to evaluate the biocompatibility of mineral trioxide aggregate (MTA) mixed with glass ionomer cement (GIC), and to compare it with that of MTA, GIC, IRM and SuperEBA. Materials and Methods: Experimental groups were divided into 3 groups such as 1 : 1, 2 : 1, and 1 : 2 groups depending on the mixing ratios of MTA powder and GIC powder. Instead of distilled water, GIC liquid was mixed with the powder. This study was carried out using MG-63 cells derived from human osteosarcoma. They were incubated for 1 day on the surfaces of disc samples and examined by scanning electron microscopy. To evaluate the cytotoxicity of test materials quantitatively, XTT assay was used. The cells were exposed to the extracts and incubated. Cell viability was recorded by measuring the optical density of each test well in reference to controls. Results: The SEM revealed that elongated, dense, and almost confluent cells were observed in the cultures of MTA mixed with GIC, MTA and GIC. On the contrary, cells on the surface of IRM or SuperEBA were round in shape. In XTT assay, cell viability of MTA mixed with GIC group was similar to that of MTA or GIC at all time points. IRM and SuperEBA showed significantly lower cell viability than other groups at all time points (p < 0.05). Conclusions: In this research MTA mixed with GIC showed similar cellular responses as MTA and GIC. It suggests that MTA mixed with GIC has good biocompatibility like MTA and GIC. 연구목적: 본 연구의 목적은 glass ionomer cement (GIC)와 혼합된 mineral trioxide aggregate (MTA)의 생체친화성을 평가하고 이것을 MTA, GIC, IRM, SuperEBA와 비교해보는 것이다. 연구 재료 및 방법: 재료의 세포독성을 평가하기 위해 MG-63세포를 이용해 주사전자 현미경 관찰과 XTT assay를 실시하였다. 결과: 주사전자 현미경 관찰에서는 GIC와 혼합한 MTA, MTA, GIC의 표면에서 세포질 돌기를 가진 많은 세포들이 밀집되고 융합된 형태로 관찰되었다. 반면 IRM과 SuperEBA에서는 세포들의 수가 적고 둥근 양상을 보여주었다. XTT assay에서는 GIC와 혼합한 MTA에서의 세포 활성도는 모든 시점에서 MTA 또는 GIC와 유사하였다. 반면 IRM과 SuperEBA에서는 모든 시점에서 세포활성도가 다른 그룹에 비해 유의하게 더 낮았다. 결론: 본 연구에서 GIC와 혼합된 MTA는 MTA, GIC와 유사한 세포 반응을 나타냈다. 이것은 GIC와 혼합된 MTA가 MTA, GIC와 마찬가지로 좋은 생체친화성을 가진 재료라는 것을 시사한다.

AT-1 심근세포를 대상으로 자발적인 박동을 나타내는 전.후단계에서 수종의 세포주기 조절 유전자의 벌현에 관한 연구

김경근,오창원,서국헌,고정태 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.4