• Title/Summary/Keyword: 신생내막

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Understanding of Intrauterine Environment Changes based on Proteomics and Bioinformatics during Estrous Cycle (단백체학과 생물정보학을 이용한 자궁 내 환경의 이해)

  • Lee, Sang-Hee;Lee, Seunghyung
    • Journal of Life Science
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    • v.29 no.5
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    • pp.621-630
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    • 2019
  • Fertilization is the beginning of a new life that occurs in the female uterine. The female reproductive tract is composed ovary, oviduct, uterine, vagina and cervix, their physiological features are regulated by estrous cycle. Of these, uterine is a main point to establish embryo development and implantation, and intercommunication between embryo and uterine environment is necessary for suitable pregnancy. Endometrium is part of the uterine, its morphology is repetitively changed by hormones, and characteristic of uterine fluid from endometrium is also changed. Recently, massive proteins of endometrium and uterine fluid can be detected according to develop proteomics and bioinformatics and have been accelerated the understanding of the reproductive biology fields. Moreover, the massive protein information is actively studying with deeply studied theory such as sex hormone signal pathway and angiogenesis in mammals. In this paper, we review understanding of endometrium remodeling, uterine gland and fluid during estrous cycle, additionally studies on endometrium and uterine fluid based on proteomics techniques. Lastly, we introduced methods of the protein-protein correlation using bioinformatics tool that interaction with hormone receptors, representative angiogenetic factors and detected proteins using proteomics in endometrium and uterine fluid. This review will be useful to understanding the study on search of new cell mechanism in endometrium and uterine fluid.

Inhibition of Intimal Hyperplasia by Perivascular Delivery of Paclitaxel Using Poly(n-butylmethacrylate) or Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) in Balloon-Injured Rat Carotid Arteries (쥐 경동맥 손상 모델에서 Poly(n-butylmethacrylate) 혹은 Poly(3-hydroxybutyrate-co-4-hydroxybutyrate)를 이용한 Paclitaxel 국소 전달 요법의 신생내막 형성 억제 효과)

  • Kwon, Jin-Sook;Lee, Ho-Yeon;Heo, Shin-Haeng;Park, Rho-Kwan;Shim, Tae-Jin;Kim, Yu-Kyug;Kim, Beom-Soo;Kim, Dong-Woon
    • Polymer(Korea)
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    • v.32 no.3
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    • pp.284-289
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    • 2008
  • Polymer is a critical component of local drug delivery to prevent restenosis. This study tested whether poly(n-butylmethacrylate)(PBMA) and poly(3-hydroxybutyrate-co-4-hydroxybutyrate)(PHA) was candidates for this purpose. In vitro release of paclitaxel from PBMA and PHA loaded with 10% paclitaxel exhibited a triphasic release profile, with a fast initial and intermediate second phase followed by a slow release phase. Perivascular delivery of paclitaxel using these films inhibited neointimal hyperplasia in balloon-injured rat carotid arteries. The paclitaxel-loaded PBMA or PHA groups showed significant neointimal formation reductions versus the control groups (PBMA vs control: $0.03{\pm}0.02$ vs $0.10{\pm}0.01\;mm^2$, p<0.05; PHA vs control: $0.04{\pm}0.03$ vs $0.09{\pm}0.01\;mm^2$, p<0.05). This study suggests that PBMA and PHA could be good candidate polymers of local drug delivery to prevent restenosis. Perivascular delivery using these films represents a possible approach for prevention of restenosis. These can be candidate polymers for drug eluting stents.

Efficacy and Safety of a Newly Developed Self-Expanding Open-Cell Type Nitinol Stent for Peripheral Arteries: A Preclinical Study in Minipigs (새로 개발된 말초동맥용 자가팽창성 개방형 니티놀 스텐트의 유효성 및 안전성 평가: 미니피그 전임상실험)

  • Min Uk Kim;Jae Hwan Lee;Chang Jin Yoon;Won Seok Choi;Saebeom Hur;Jin Wook Chung
    • Journal of the Korean Society of Radiology
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    • v.81 no.4
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    • pp.899-911
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    • 2020
  • Purpose To evaluate the safety and efficacy of the newly designed open-cell type self-expandable nitinol stent (NiTi-stent) for peripheral arteries. Materials and Methods Twenty-eight limbs of 14 minipigs were randomly assigned to the NiTistent group or conventional nitinol stent group. Stents were symmetrically implanted into the iliac arteries of each animal using carotid artery approach and were observed for 1 month (n = 5) and 6 months (n = 9). The angiographic lumen diameter (ALD), late lumen loss, angiographic stenosis, histomorphometric lumen area, neointimal area, and area stenosis were analyzed and compared between the groups. Results Stent migration, stent fracture, or thrombus formation were not observed in either group. At the 1-month follow-up, the neointimal area (p = 0.008) and area stenosis (p = 0.016) were significantly smaller in the NiTi-stent group than in the control group. At the 6-months followup, the NiTi-stent group showed significantly larger ALD (p = 0.014), less late lumen loss (p = 0.019), less angiographic stenosis (p = 0.014), larger lumen area (p = 0.040), and smaller neointimal area and area stenosis (p = 0.004 and p = 0.014, respectively) compared with the control group. Conclusion The NiTi-stent is as safe and effective as the conventional nitinol stent and induces less neointimal hyperplasia in a minipig iliac artery model.

Inhibition of Vascular Endothelial Growth Factor-induced Endothelial Cell Differentiation by Intravenous Immunoglobulin and Methylprednisolone (혈관내막 성장인자에 의해 유도된 내막세포 분화에 대한 정맥용 면역글로불린과 메틸프레드니솔론의 효과)

  • Choi, Hyoun Ah;Ha, Kyung Hwa;Yoon, Jong Seo;Lee, Yoon;Lee, Joon Sung;Han, Ji Wwan
    • Clinical and Experimental Pediatrics
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    • v.48 no.8
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    • pp.886-893
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    • 2005
  • Purpose : Kawasaki disease is the most common cause of systemic vasculitis in children less than 5 years of age. Recent immunohistochemistry findings suggest that many vascular growth factors play a role in the formation of the coronary artery lesions. Active remodeling of the coronary artery lesions in Kawasaki disease continues in the form of intimal proliferation and neoangiogenesis for several years after the onset of the disease. Intravenous immunoglobulin(IVIG) and corticosteroid have been used in the treatment of Kawasaki disease but the exact mechanism is not clear. We have investigated that IVIG and corticosteroid inhibited vascular endothelial growth factor(VEGF)-induced tube formation of endothelial cells in vitro on Matrigel assay. Methods : Human umbilical vein endothelial cells(HUVECs) were cultured and seeded on Matrigel coated 24 well plates in medium with or without the following agents : VEGF, VEGF plus IVIG, VEGF plus VEGF antibody, VEGF plus methylprednisolone, VEGF, IVIG plus methylprednisolone for 18 hours. The total length of tube structures in each photograph was quantified. Results : IVIG significantly inhibited the proliferation of HUVECs. The inhibitory effect of IVIG was also reversible. In the meantime, VEGF induced the differentiation of HUVECs into capillary like structures on Matrigel, which was inhibited by VEGF antibody in a dose-dependent manner. Interestingly, IVIG and methylprednisolone inhibited VEGF-induced tube formation of HUVECs. IVIG was more effective in inhibition than methylprednisolone alone. Conclusion : We revealed that VEGF induced the differentiation of HUVECs and this effect was inhibited by IVIG and methylprednisolone.

Changes in the Lung after Pulmonary Hypertension Induced by Obstruction of the Pulmonary Vein in Rats (흰쥐에서 폐정맥 폐쇄에 의해 유도된 폐동맥고혈압 발생 후의 폐장의 변화)

  • Jang Won-Chae;Jeong In-Suk;Cho Kyu-Sung;Oh Bong-Suk
    • Journal of Chest Surgery
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    • v.39 no.9 s.266
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    • pp.659-667
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    • 2006
  • Background: Experimental studies of vascular remodeling in the pulmonary arteries have been performed actively. These models required a persistent vascular insult for intimal injury induced by chronic hypoxia, monocrotaline intoxication or chronic air embolism and characterized medial hypertrophy and neointimal formation by active synthesis of the extracellular matrix protein. The purpose of this study was to determine the pattern of pulmonary vascular remodeling after obstruction of the pulmonary vein. Material and Method: Obstruction of the right pulmonary vein with a metal clip was performed in Sprague-Dawley rats $(352{\pm}18g,\;n=10)$ to cause pulmonary vascular disease. Fifteen days later, experimental studies were done and finally the both lungs and hearts were extirpated for experimental measurement. Pulmonary arterial pressure, weight ratio of right ventricle (RV) to left ventricle (LV) and ventricular septum (S) (RV/LV +S weight ratio), and pulmonary artery morphology (percent wall thickness, %WT) were evaluated and compared with normal control groups. Result: Pulmonary hypertension $(38{\pm}12mmHg\;vs\;13{\pm}4mmHg;\;p<0.05)$ and right ventricular hypertrophy (right ventricular/left ventricular and septal weight ratio, $0.52{\pm}0.07\;vs\;0.35{\pm}0.04;\;p<0.05$) with hypertrophy of the muscular layer of the pulmonary arterial wall (percent wall thickness, $22.4{\pm}6.7%\;vs\;6.7{\pm}3.4%;\;p<0.05$) were developed by 15 days after obstruction of the pulmonary vein. Conclusion: Obstruction of the pulmonary vein developed elevation of pulmonary blood pressure and medial hypertrophy of the pulmonary artery. These results are a part of the characteristic vascular remodeling. Theses results demonstrate that obstruction of the pulmonary vein can develope not only high pulmoanry blood flow of contralateral lung but also intima injury inducing vascular remodeling.

Inhibition of Neointima Formation and Migration of Vascular Smooth Muscle Cells by Anti-vascular Endothelial Growth Factor Receptor-1 (Flt-4) Peptide in Diabetic Rats (당뇨병 쥐에서 혈관내피 성장인자 수용체-1 차단 펩타이드를 이용한 신내막 형성과 혈관평활근세포 이동의 억제)

  • Jo, Min-Seop;Yoo, Ki-Dong;Park, Chan-Beom;Cho, Deog-Gon;Cho, Kue-Do;Jin, Ung;Moon, Kun-Woong;Kim, Chul-Min;Wang, Young-Pil;Lee, Sun-Hee
    • Journal of Chest Surgery
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    • v.40 no.4 s.273
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    • pp.264-272
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    • 2007
  • Background: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, including stimulating the proliferation and migration of vascular smooth muscle cells (VSMCs). It has been known that diabetes is associated with accelerated cellular proliferation via VEGF, as compared to that under a normal glucose concentration. We investigated the effects of selective blockade of a VEGF receptor by using anti-Flt-1 peptide on the formation and hyperplasia of the neointima in balloon injured-carotid arteries of OLETF rats and also on the in vitro VSMCS' migration under high glucose conditions. Material and Method: The balloon-injury method was employed to induce neointima formation by VEGF. For f4 days beginning 2 days before the ballon injury, placebo or vascular endothelial growth factor receptor-1 (VEGFR-1) specific peptide (anti-Flt-1 peptide), was injected at a dose of 0.5mg/kg daily into the OLETF rats. At 14 days after balloon injury, the neointimal proliferation and vascular luminal stenosis were measured, and cellular proliferation was assessed by counting the proliferative cell nuclear antigen (PCNA) stained cells. To analyze the effect of VEGF and anti-Flt-1 peptide on the migration of VSMCs under a high glucose condition, transwell assay with a matrigel filter was performed. And finally, to determine the underlying mechanism of the effect of anti-Flt-1 peptide on the VEGF-induced VSMC migration in vitro, the expression of matrix metalloproteinase (MMP) was observed by performing reverse transcription-polymerase chain reaction (RT-PCR). Result: Both the neointimal area and luminal stenosis associated with neointimal proliferation were significantly decreased in the anti-Flt-1 peptide injected rats, ($0.15{\pm}0.04 mm^2$ and $ 36.03{\pm}3.78%$ compared to $0.24{\pm}0.03mm^2\;and\;61.85{\pm}5.11%$, respectively, in the placebo-injected rats (p<0.01, respectively). The ratio of PCNA(+) cells to the entire neointimal cells was also significantly decreased from $52.82{\pm}4.20%\;to\;38.11{\pm}6.89%$, by the injected anti-Flt-1 peptide (p<0.05). On the VSMC migration assay, anti-Flt-1 peptide significantly reduced the VEGF-induced VMSC migration by about 40% (p<0.01). Consistent with the effect of anti-Flt-1 peptide on VSMC migration, it also obviously attenuated the induction of the MMP-3 and MMP-9 mRNA expressions via VEGF in the VSMCS. Conclusion: Anti-Flt-1 peptide inhibits the formation and hyperplasia of the neointima in a balloon-injured carotid artery model of OLETF rats. Anti-Flt-1 peptide also inhibits the VSMCs' migration and the expressions of MMP-3 and MMP-9 mRNA induced by VEGF under a high glucose condition. Therefore, these results suggest that specific blockade of VEGFR-1 by anti-Flt-1 peptide may have therapeutic potential against the arterial stenosis of diabetes mellitus patients or that occurring under a high glucose condition.

Metal Surface Coating Using Electrospray of Biodegradable Polymers and $\alpha$-Lipoic Acid Release Behavior for Drug-Eluting Stents (생분해성 고분자의 전기분사를 이용한 약물방출 스텐트용 금속표면 코팅 및 ALA방출 거동)

  • Kim, Dong-Min;Lee, Bong-Soo;Park, Cheol-Ho;Park, Kwi-Deok;Son, Tae-Il;Jeong, Myeong-Ho;Han, Dong-Keun
    • Polymer(Korea)
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    • v.34 no.2
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    • pp.178-183
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    • 2010
  • Medical metal stents inserted to patients with a cardiovascular disease associated with coronary artery system have relatively increased the survival rate. The development of new stents is, however, urgently required due to restenosis and late thrombosis generated in metal stents. To solve these problems, the biodegradable polymers such as poly(lactide-co-glycolide) (PLGA), poly(L-lactide)(PLLA), and poly ($\varepsilon$-caprolactone)(PCL) were mixed with alpha lipoic acid (ALA), which is well known to inhibit the proliferation of neointimal hyperplasia. Subsequently, the ALA-loaded polymers were coated on stainless steel by electrospray. The drug-eluting behaviors from the coated polymers were investigated according to kinds and concentrations of polymers, spray rates, and kinds of solvents. The drug-eluting rate from PCL with the lowest glass transition temperature was the fastest among three polymers and followed by PLGA and PLLA. The surface roughness increased as the spray rate was increased and also the drug-eluting rate was affected by kinds of solvents with different boiling point. It is expected that drug-eluting stent (DES) coated with ALA-loaded polymers can be applied practically for clinical applications by controlling the behavior of drug release.

A Study of Drug Content and Cell Cytotoxicity of Paclitaxel-eluting Stents Coated with Various Biopolymer (다양한 생체고분자로 코팅된 Paclitaxel Eluting Stent의 약물함량과 세포독성 연구)

  • Kim, Dong-Gon;Shin, Il-Gyun;Kim, Gi-Han;Kim, Seong-Hyeon;Lee, Ju-Ho;Ki, Byoyng-Yun;Nah, Jae-Woon;Suh, Tae-Suk;Kim, Sang-Ho
    • Progress in Medical Physics
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    • v.20 no.3
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    • pp.125-131
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    • 2009
  • In this study, the paclitaxel eluting stent (PES) was prepared by coating a biliary stent with paclitaxel using various biopolymer such as poly (vinyl acetate) (PVAc), poly (lactic-co-glycolic acid) (PLGA), Silicone rubber for restenosis prevention in gastrointestinal disease by a dip-coating method. Drug contents of PES were increased as surface area of stent, concentration and molecular weight of coating polymer increase. In $^1H-NMR$ specta, we know that drug did not change by confirming specific peaks of paclitaxel in PES. As shown in SEM image, PES prepared using various biopolymer is coated clearly and regularly except Silicone rubber coating polymer. In in vitro cell cytotoxicity test, bare stent showed low cytotoxic effect against CT-26 colon carcinoma cell line on 3 day. However, PES coated with PLGA 502H showed the highest cytotoxicity because PLGA 502H is biodegradable polymer and has less molecular weight than other coating polymer. These results suggest that PES coated various biopolymer can be prevented restenosis in gastrointestinal disease.

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Time-related Histopathologic Changes of Fresh Frozen Vascular Xenograft in Pig-to-goat Model (돼지-염소 모델에서 신선 동결된 이종 경동맥 이식편의 시간 경과에 따른 조직병리학적 변화)

  • Chang, Ji-Min;Kim, Won-Gon
    • Journal of Chest Surgery
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    • v.40 no.3 s.272
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    • pp.180-192
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    • 2007
  • Background: As determined from the recent investigations of discordant cardiac xenotransplantation, hyperacute rejection occurs mainly at the endothelial cells in donor microvascular systems, but this does not occur at cardiac valve leaflets or at medium-to-large caliber vessels. On the basis of this background, this study was performed to look into the biocompatibility for transplantation of a middle or large diameter xenogenic blood vessel by conducting xenogenic arterial transplantation with the carotid artery in a pig-to-goat model. Material and Method: The experimental group was composed of 10 pairs of pig-to-goat combinations. They were divided into each period of 1 week, and 1, 3, 6 and 12 months. Four carotid artery grafts obtained through collection of the bilateral carotid arteries from two pigs were preserved at $-70^{\circ}C$ without other treatment, and then they were transplanted into the bilateral carotid arteries of two goats. Doppler ultrasonography was done on a periodic basis after transplantation to evaluate the patency of the grafted blood vessel. At the ends of a predetermined period, the grafts were explanted from the goats and they underwent gross examination. Hematoxylin-eosin and Masson's trichrome staining were conducted. In addition, in order to examine the immunological rejection of the grafted xenogenic blood vessel, immunohistochemical staining was conducted with T-lymphocyte indicator and von Willebrand factor. Result: Two goats at the each one-week period and the one-year period died during the experimental period because of a reason unrelated to the experimental procedure, and the remaining 8 goats survived until the end of each experiment period. On Doppler ultrasonography, unilateral carotid artery occlusion was found in a goat, whose period was specified as 3 months, among the 8 survived goats. However, the vascular patency was maintained well and there was no graft that formed aneurysms in the other goats. On gross examination, the region of vascular anastomosis was preserved well, and calcification of the grafted blood vessel was not shown. Histologically, the endothelial cells of the graft disappeared one week after transplantation, and then there was progressive spread of the recipients' endothelial cells from the anastomotic site. The reendothelialization occurred over the whole graft at one month after transplantation. The neointimal thickening and adventitial inflammation became severe by 3 months after transplantation, but this lessened at 6 months and 12 months, respectively. The rate of CD3 positive cells was very low among the infiltrated inflammatory cells. Conclusion: The fresh-frozen xenogenic artery kept its patency without being greatly influenced by xenogenic immune reaction.