• Archives of Plastic Surgery
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• v.36 no.3
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• pp.254-261
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• 2009

Purpose: The objective of this study was to evaluate the heparin effect for a viability of random - pattern dorsal flap in hairless mouse. Methods: A caudally - based random dorsal flap, measuring $1.5{\times}5cm$, was designed and heparin was applied topically after microneeding. Twenty five male hairless mice were randomly divided into control (Group1, n=5); received only microneedling (Group 2, n=5), only heparin(Group3, n=5), microneedling with saline(Group 4, n=5), and microneedling with heparin group(group5,n=5) to the flap during 7 days. The number of the capillaries were compared between the experimental groups and control group with respect to neovascularization after heparin application using imaging analysis program under hematoxylin - eosin stain. The capillary blood flow was measured by laser Doppler flowmetry. After seven days each animal was evaluated for the percentage area of the flap survival. Mann - Whitnety U test and Kruskal - Wallis statistical analysis of survival relationships was performed. Results: It can be observed increased number of the blood vessels in the experimental groups however it was not statistically significant. Blood flow of the haparin with microneedling group maintained higher than other experimental groups. Treated microneeding and heparin mice were significantly better flap viability than in controls (flap survival 67% and $54.4mm^2$ respectively; p<.01). Positive correlation was shown between flap survival rate and laser Doppler flux value only at first day after surgery. Conclusion: Heparin has a beneficial effect on capillary flow and improve peripheral circulatory disturbances in random pattern flaps.

• Biomolecules & Therapeutics
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• v.23 no.6
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• pp.517-524
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• 2015

Human mesenchymal stem cells (MSCs) have been used in cell-based therapy to promote revascularization after peripheral or myocardial ischemia. High levels of reactive oxygen species (ROS) are involved in the senescence and apoptosis of MSCs, causing defective neovascularization. Here, we examined the effect of the natural antioxidant lycopene on oxidative stress-induced apoptosis in MSCs. Although $H_2O_2$ ($200{\mu}M$) increased intracellular ROS levels in human MSCs, lycopene ($10{\mu}M$) pretreatment suppressed $H_2O_2$-induced ROS generation and increased survival. $H_2O_2$-induced ROS increased the levels of phosphorylated p38 mitogen activated protein kinase (MAPK), Jun-N-terminal kinase (JNK), ataxia telangiectasia mutated (ATM), and p53, which were inhibited by lycopene pretreatment. Furthermore, lycopene pretreatment decreased the expression of cleaved poly (ADP ribose) polymerase-1 (PARP-1) and caspase-3 and increased the expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax), which were induced by $H_2O_2$ treatment. Moreover, lycopene significantly increased manganese superoxide dismutase (MnSOD) expression and decreased cellular ROS levels via the PI3K-Akt pathway. Our findings show that lycopene pretreatment prevents ischemic injury by suppressing apoptosis-associated signal pathway and enhancing anti-oxidant protein, suggesting that lycopene could be developed as a beneficial broad-spectrum agent for the successful MSC transplantation in ischemic diseases.

• The Journal of Internal Korean Medicine
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• v.22 no.4
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• pp.639-645
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• 2001

Angiogenesis is a fundamental process in reproduction and wound healing. Under these condition, neovascularization is tightly regulated. Unregulated angiogenesis may lead to several angiogenic diseases, and is thought to be indispensible for solid tumor growth and metastsis. The construction of new vascular network is a multistep cascade involving basement membrane degradation, endothelial cell proliferation, endothelial cell migration, and tube formation. Newly reported anti-angiogenic agents in oriental medical field have targeted both specific and multistep stages in the angiogenic process. From recent approach in oriental medical field with several herb medicines including activating blood flow and removing blood stasis medicine(活血化瘀藥), it may be possible in the future to develope specific anti-angiogenic agents that offer a less toxic potential therapy for cancer and angiogenic disease.

• Archives of Plastic Surgery
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• v.33 no.5
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• pp.592-600
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• 2006

Purpose: Numerous materials, both autologous and nonautologous, have been used for augmentation of sunken areas, but they have their own limitations. The purpose of this study is to determine the histologic response and volume change of the xenogenic collagen-based scaffold($Terudermis^{(R)}$) to the transfer into a subcutaneous soft tissue location in vivo rabbit model. Methods: Eighteen New Zealand white rabbits were used. Three $1.2{\times}1.2cm$ sized subcutaneous pockets were created on the dorsal surface of each ear. $1{\times}1cm$ sized collagen matrix($Terudermis^{(R)}$) and autologous dermal graft were implanted into each pocket. Full thickness of ear was harvested in 3 days, 1, 2, 4 weeks, 3, 6 months after implantation. Results: Histological analysis of implants demonstrated progressive neovascularization, fibroblast infilteration, neocollagen bundle synthesis and organization, and few foreign body reaction. The thickness of the collagen matrix in 3 days after the operation was 87.69% of the thickness of the collagen matrix in wet state. Then it decreased to 30.17% in 6 months after the operation. The rate of decrease was similar at all points at the same time compared with autologous dermal graft. Conclusion: Our experimental study suggests that $Terudermis^{(R)}$ could be a safe material as an implant for permanent augmentation in subcutaneous tissue. However the choice of graft for augmentation should be remained to the clinical situations.

• Archives of Plastic Surgery
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• v.33 no.5
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• pp.621-626
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• 2006

Purpose: Erythropoietin is traditionally known to regulate erythropoiesis, but recently its protective effect against ischemia-reperfusion injury has been studied mainly in cardiovascular and neuronal systems. This study was planned to investigate the effects of recombinant human erythropoietin on ischemia-reperfusion injury in rat TRAM flap model. Methods: Superiorly based TRAM flap was elevated and ischemic insult was given for four hours. Thirty minutes before reperfusion, single dose recombinant human Erythropoietin(5000IU/kg) was injected via intraperitoneal route in the treatment group. At 24 hours postoperatively, systemic neutrophil count, tissue myeloperoxidase activity, malonyldialdehyde amount, nitric oxide content, tissue water content and histologic finding of inflammation was evaluated. On 10 days postoperatively, flap survival rate, angiogenesis and change in hematocrit level was evaluated. Results: Tissue nitric oxide level was significantly higher and myeloperoxidase activity was significantly lower in the treatment group 24 hours after reperfusion. Tissue water content was significantly lower in the treatment group. Perivascular neutrophil infiltration and intravascular adhesion was marked in the control group. Mean flap survival after ten days was 69% in the treatment group, and 47% in the control group, demonstrating a significant difference. Neovascularization in the treatment group also outnumbered the control group. No significant hematocrit rise was noted ten days after erythropoietin administration. Conclusion: Recombinant human Erythropoietin improved flap survival in ischemia-reperfusion injured rat TRAM flaps, at least partially owing to suppressed inflammation, increased nitric oxide, and enhanced angiogenesis.

• Journal of Korean Neurosurgical Society
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• v.29 no.10
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• pp.1303-1308
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• 2000

Objectives : It has been known that vascular endothelial growth factor(VEGF), as an endothelial cell-specific mitogen, induces angiogenesis, and possesses vascular permeability and procoagulant properties. Peritumoral brain edema(PTBE) is a common accompaniment of malignant gliomas. It results from microvascular extravasation of plasma and proteins through the interendothelial spaces. The correlation between pathological grading, PTBE, neovascularization, and the expression of VEGF were analyzed in 31 patients with astrocytic tumors. Methods : Astrocytic tumor samples(8 astrocytomas, 14 anaplastic astrocytomas, and 9 glioblastomas) from 31 patients( 21 males and 10 females : average age $37{\pm}24$ years) who underwent surgery were examined retrospectively for the expression of VEGF and CD31(microvasculature) immunohistochemically. The extent of PTBE was examined by using preoperative CT or MRI as an edema index(EI). In addition to VEGF and CD31, several causative factors including tumor size, histologic type were compared with EI. Results : Only one of 8 astrocytomas, and majority of high grade(21 of 23 anaplastic astrocytomas and glioblastomas) tumors demonstrated PTBE(p<0.05). The majority of high grade tumors showed higher expression of VEGF (p<0.01). High grade tumors showed even higher CD31 expression(p<0.05), however, there was no close correlation between expression of VEGF and CD31. The EI was increased significantly, just as VEGF(p<0.01), but CD31 expression was not correlated with high EI. Conclusion : These data suggest that VEGF expression is closely correlated with PTBE and histological grading in astrocytic tumors. Microvasculature(CD31) in tumors is highly correlated with histological grading, however, shows no correlation with the expression of VEGF and PTBE.

• Journal of Veterinary Clinics
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• v.28 no.1
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• pp.28-32
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• 2011

This study was performed to evaluate the efficacy of 0.8% sodium hyaluronic acid solution and crosslinked hyaluronic acid mixture for the prevention of postoperative intraperitoneal adhesion in rats. Forty-five animals were divided into three groups ; 0.9% saline treated control group, 1% sodium carboxymethyl cellulose treated group (SCMC), and 0.8% sodium hyaluronic acid solution and crosslinked hyaluronic acid mixture treated group (SHCH). Adhesions were induced by suturing both the ileal serosa and peritoneum abrased until petechial bleeding occurred. Fourteen days later, adhesions were evaluated clinically and histopathologically. The mean tensile strength was significantly decreased in the SCMC and SHCH groups compared to the control group (p < 0.05), and the SHCH group had the lowest tensile strength. The distance of adhesion site was highest in the control group and significantly decreased in the SHCH group comparing control group (p < 0.05). The inflammatory cell infiltration, collagen hyperplasia and neovascularization of the SCMC and SHCH groups were significantly lower than the control group (p < 0.05). Therefore, it was concluded that the SHCH may be useful to prevent postoperative intraperitoneal adhesion in rats.

• Journal of Acupuncture Research
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• v.24 no.5
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• pp.23-32
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• 2007

Objectives : Angiogenesis consists of the proliferation, migration, and differentiation of endothelial cells, and angiogenic factors and matrix protein interactions modulate this process. The aim of this study was to determine whether herbs medicine(KHBJs) could induce angiogenic activity in human umbilical vein endothelial cells(HUVECs). Methods : The angiogenic activity of KHBJs were evaluated by proliferation using BrdU assay, chemotactic migration assay, tube formation assay, and measurement of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor(VEGF) in HUVECs. Also, In order to identify enhance angiogenic activity by activity guided fractionation, the angiogenic activity of fractions of KHBJs such as KHBJB or KHBJR were evaluated in vitro and in vivo Matrigel plug angiogenesis asaay. Results : About 9 KHBJs significantly increased HUVECs proliferation in a dose-dependent manner. In addition, 9 herbs medicine(KHBJs) increased migration and tube-like formation in HUVECs. Interestingly the expression of bFGF and VEGF, an angiogenesis-inducing growth factor, were dose-dependently increased by KHBJs. However, angiogenic activity of fractionated KHBJs(KHBJB or KHBJR) not enhanced more than KHBJs in HUVECs and Matrigel plug in vivo angiogenesis assay. Conclusions : 9 KHBJs significantly induces angiogenesis in in vitro and in vivo. These results suggest that 9 KHBJs potent angiogenic agents and promising drug for the induction of neovascularization.

• Journal of Periodontal and Implant Science
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• v.50 no.5
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• pp.327-339
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• 2020

Purpose: The purpose of this study was to examine the local tissue reactions associated with 3 different poly(lactic-co-glycolic acid) (PLGA) prototype membranes and to compare them to the reactions associated with commercially available resorbable membranes in rats. Methods: Seven different membranes-3 synthetic PLGA prototypes (T1, T2, and T3) and 4 commercially available membranes (a PLGA membrane, a poly[lactic acid] membrane, a native collagen membrane, and a cross-linked collagen membrane)-were randomly inserted into 6 unconnected subcutaneous pouches in the backs of 42 rats. The animals were sacrificed at 4, 13, and 26 weeks. Descriptive histologic and histomorphometric assessments were performed to evaluate membrane degradation, visibility, tissue integration, tissue ingrowth, neovascularization, encapsulation, and inflammation. Means and standard deviations were calculated. Results: The histological analysis revealed complete integration and tissue ingrowth of PLGA prototype T1 at 26 weeks. In contrast, the T2 and T3 prototypes displayed slight to moderate integration and tissue ingrowth regardless of time point. The degradation patterns of the 3 synthetic prototypes were similar at 4 and 13 weeks, but differed at 26 weeks. T1 showed marked degradation at 26 weeks, whereas T2 and T3 displayed moderate degradation. Inflammatory cells were present in all 3 prototype membranes at all time points, and these membranes did not meaningfully differ from commercially available membranes with regard to the extent of inflammatory cell infiltration. Conclusions: The 3 PLGA prototypes, particularly T1, induced favorable tissue integration, exhibited a similar degradation rate to native collagen membranes, and elicited a similar inflammatory response to commercially available non-cross-linked resorbable membranes. The intensity of inflammation associated with degradable dental membranes appears to relate to their degradation kinetics, irrespective of their material composition.

• Journal of Korean Academy of Nursing
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• v.36 no.3
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• pp.523-531
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• 2006

Purpose: The purpose of this study was to examine the effects of the ulmus root-bark dressing on tissue regeneration in experimentally-induced pressure ulcers in rats. Method: A randomized pretest/post-test control group time-series study design was used. Thirty-three male Sprague-Dawley rats were used in this study. The rats were anesthetized with 100mg/kg of ketamine. Pressure ulcers were induced at 140mmHg for three hours using a personally-designed pressing apparatus. For four weeks, the ulmus root-bark dressing was applied every other day in the experimental group (n=18) and a wet gauze dressing in the control group (n=15). For data analysis, the statistical program SPSS WIN 12 was used. The wounds were examined by light microscopy andelectron microscopy. Result: There were significant statistical differences in the size of the pressure ulcers as time went by(p=0.006). It should be noted that there were no significant statistical differences in the number of capillaries. Using light microscopy the inflammatory infiltration and neovascularization in the dermis in the experimental group emerged densely in the early stages, but recovered rapidly at the latter stages. In addition, the reepithelization of the epidermis occurred earlier than in the control group. By electron microscopy, the cell organelles of the capillary endothelial cells and the basal lamina of capillaries in the experimental group showed a more rapid maturation during the latter stages, compared with the control group. Conclusion: According to this study, it can be concluded that the ulmus root-bark dressing is effective regarding the healing of pressure ulcers.