두개 악안면 수술시 새로운 골대체물로 이용될 수 있는 계란껍질에 대한 연구

윤창신,백롱민,백세민 大韓成形外科學會 1998 Archives of Plastic Surgery Vol.25 No.8

The first successful bone transplantation carried out in 1688 by Van Meek'ren, a Dutch surgeon. The ideal bone substitute should be biocompatible, osteoinductive or at least osteoconductive, available in unlimited quantity, low cost and have satisfactory mechanical properties. To accomplish these goals, autografts are still preferred material. However, bone harvesting procedures have been focused to solve the following problems; necessity of a second surgical site, morbidity and potential deformity of the donor site, an increased operative time, donor availability limitations, and resorption of autogenic bone grafts. Ten adult white New Zealand rabbits, three, 10 mm in diameter, full layer skull defects were made in the frontoparietal bone. Two bone defects were filled with hydroxyapatite and powdered eggshell, the other defect was not filled(control). All animals were sacrified at 10 weeks, the specimens were examined macroscopically to test for graft mobility. The graft with surrounding bone was then harvested and studied by histology. The results were as follows: 1. Control: Bone regeneration occurred nearly complete. 2. Hydroxyapatite: Macroscopically - No encapsulation. Despite a gross delineation between implant and bone, imlant was firmly united to bone. Histology - Bony trabeculae surrounded by proliferated connective tissue are observed in the defect site and implant. Osteoblastic rimming is noted along the bone fragments 3. Powdered eggshell: Macroscopically - Grafted site was encapsulated by proliferated connective tissue and palpable softer than the surrounding bone. Histology - The presence of eggshell particles encapsulated by fibrous connective tissue. Partial bone regeneration from the defect margin was noticed, but the bone healing was never complete. In conclusion, the use of safe and inexpensive material is recommended for filling limited bone defects in non-weight bearing areas. The use of powdered eggshell for bone substitute may also be considered, after further studies, to access its long term stability, porosity and biocompatibility.

비첨 하수의 교정: 7례

윤창신,오갑성 大韓成形外科學會 1998 Archives of Plastic Surgery Vol.25 No.8

The primary factors determining nasal tip outline are shape and position of the alar cartilages. The relation of the alar cartilages to the upper lateral cartilages, septum, and soft tissue envelope defines the conformation of the tip-lobule complex. Plunging tip is a condition as long nose, tip drooping and becomes more accentuated with aging. Hanging columella is a prominent downward bowing of the columella. Plunging tip and hanging columella are common causes of acute nasolabial angle. Correction of the plunging tip in the long nose is usually achieved satisfactorily through shortening of the lateral walls by excising an adequate amount of cartilage from the septal, lateral, and alar cartilage. Tip rotation in a cephalic direction can be achieved commonly by resection of the cephalic portion of the lateral crura, excision of a triangular segment of the caudal margin of the septum and a cartilaginous septal transfixion incision involving excision of a superiorly based triangle of septum with cephalic rotation of the entire nasal lobule. Modification of the caudal margin of the septum is done to achieve three goals: (1) cephalic rotation of the tip, (2) shortening of nasal length, and (3) alterations in the nasolabial angle. We have elevated and rotated in a cephalic direction nasal tip by means of resection of cephalic portion of lateral crura, resection of the caudal margin of the septum and mucous membrane, and /or invagination technique for correction of the plunging tip and hanging columella. From March 1996 to February 1998, we have performed the tip-plasty in 7 patients of the plunging tip and hanging columella. We have found good cosmetic results with improved nasolabial angle.

1H-NMR-based Metabolomic Study of Miamiensis avidus-infected Olive Flounder

윤다혜,윤창신,최현수,노현경,옥영준,김도형,김희수,김석만 대한화학회 2017 Bulletin of the Korean Chemical Society Vol.38 No.5

The scuticociliate Miamiensis avidus (M. avidus) is an aetiological agent of mass mortalities in cultured fish worldwide. The external signs of infection by this histiophagous parasite are hemorrhage, muscle ulceration, and exophthalmia. In this study, we infected olive flounder (Paralichthys olivaceus) with M. avidus under laboratory conditions, and used1H-nuclear magnetic resonance (NMR) spectroscopy to detect the metabolomic alterations during the infection. Multivariate data analysis showed that there were distinct differences in metabolomes between the control and the infected groups. Analysis of the metabolomic changes indicated that the olive flounder experienced severe metabolic shifts to anaerobic respiration and hypoxia.

심바스타틴과 아토바스타틴이 치료적인 농도에서 TPC-1 세포의 NIS 발현에 미치는 영향

김태균,정혜숙,윤창신,고정해,전혜정,권민정,이순희,김미경,박정현 대한내분비학회 2010 Endocrinology and metabolism Vol.25 No.3

Background: Although so many experimental trials have been done to improve the redifferentiation and responsiveness of radioiodide therapy, they have not yet yielded any satisfactory results. As statins inhibit both farnesylation and geranylgeranylation, they have been reported to have an antineoplastic and redifferentiation effect in experimental and clinical studies. In this study, we investigated the relationship between statins and the alteration of the NIS expression and, TPC-1 cell apotosis to evaluate the possibility of using statins as adjuvant therapeutic agents for papillary thyroid cancer. Methods: We used the TPC-1 cell lines for our experiments. Cell viabilities were measured by CCK-8. The degrees of apoptosis and,the expressions of NIS mRNA and NIS protein were measured by flow cytometry, semi quantitative RT-PCR and Western blot assay. Results: Increased levels of NIS mRNA and NIS protein were observed under therapeutic blood concentrations (concentrations of simvastatin: 20, 50, 80 nM, concentrations of atorvastatin: 50, 80,110 nM), but the dose-response relationship was only manifested within simvastatin. The TPC-1 cells showed a concentration dependent decrease of viability and an increase of apoptosis not under therapeutic blood concentrations, but under excessively high concentrations (after treatment with 10-50 μM of atorvastatin and with 1-10 μM of simvastatin). Conclusion: The results of this study show that effective therapeutic blood concentrations of simvastatin and atorvastatin can give a favorable effect on the NIS expression under effective therapeutic blood concentrations. Therefore, we demonstrated the possibility that simvastatin and atorvastatin might have an important role as adjuvant therapeutic agents to improve the responsiveness of radioiodide therapy for papillary thyroid cancer. Further studies are needed to clarify this issue.

The Effects of Glyburide on Apoptosis and Endoplasmic Reticulum Stress in INS-1 Cells in a Glucolipotoxic Condition

권민정,정혜숙,윤창신,고정혜,전혜정,김태균,이순희,고경수,이병두,김미경,박정현 대한당뇨병학회 2011 Diabetes and Metabolism Journal Vol.35 No.5

Background: β-cell death due to endoplasmic reticulum (ER) stress has been regarded as an important pathogenic component of type 2 diabetes. The possibility has been suggested that sulfonylurea, currently being used as one of the main oral hypoglycemic agents of type 2 diabetes, increases ER stress, which could lead to sulfonylurea failure. The authors of the present study examined ER stress of β-cells in a glucolipotoxic condition using glyburide (GB) in an environment mimicking type 2 diabetes. Methods: Apoptosis was induced by adding various concentrations of GB (0.001 to 200 μM) to a glucolipotoxic condition using 33 mM glucose, and the effects of varied concentrations of palmitate were evaluated via annexin V staining. The markers of ER stress and pro-apoptotic markers were assessed by Western blotting and semi-quantitative reverse transcription-polymerase chain reaction. Additionally, the anti-apoptotic markers were evaluated. Results: Addition of any concentration of GB in 150 μM palmitate and 33 mM glucose did not increase apoptosis. The expression of phosphorylated eukaryotic initiation factor (eIF-2α) was increased and cleaved caspase 3 was decreased by adding GB to a glucolipotoxic condition. However, other ER stress-associated markers such as Bip-1, X-box binding protein-1, ATF-4 and C/EBP-homologous protein transcription factor and anti-apoptotic markers phosphor-p85 phosphatidylinositol 3-kinase and phosphorylation of Akt did not change significantly. Conclusion: GB did not show further deleterious effects on the degree of apoptosis or ER stress of INS-1 cells in a glucolipotoxic condition. Increased phosphorylation of eIF-2α may attenuate ER stress for adaptation to increased ER protein load.

The Effect of Glucose Fluctuation on Apoptosis and Function of INS-1 Pancreatic Beta Cells

김미경,정혜숙,윤창신,고정혜,전혜정,김태균,권민정,이순희,고경수,이병두,박정현 대한당뇨병학회 2010 Diabetes and Metabolism Journal Vol.34 No.1

Background: Blood glucose level continuously fluctuates within a certain range in the human body. In diabetes patients, the extent of such fluctuation is large, despite the strict control of blood glucose. Blood glucose fluctuation has been shown to mediate more adverse effects on vascular endothelial cells and diabetes complications than chronic hyperglycemia, which has been explained as due to oxidative stress. As few previous studies have reported the effects of chronic and intermittent hyperglycemia on the apoptosis and function of pancreatic beta cells, this study reported herein was performed to investigate such effects on these cells. Methods: For chronic hyperglycemia, INS-1 cells were cultured for 5 days with changes of RPMI 1640 medium containing 33 mM glucose every 12 hours. For intermittent hyperglycemia, the medium containing 11 mM glucose was exchanged with the medium containing 33 mM glucose every 12 hours. Apoptosis was assessed by TUNEL assay Hoechst staining and cleaved caspase 3. Insulin secretory capacity was assessed, and the expression of Mn-SOD and Bcl-2 was measured by Western blotting. Results: In comparison to the control group, INS-1 cells exposed to chronic hyperglycemia and intermittent hyperglycemia showed an increase in apoptosis. The apoptosis of INS-1 cells exposed to intermittent hyperglycemia increased significantly more than the apoptosis of INS-1 cells exposed to chronic hyperglycemia. In comparison to the control group, the insulin secretory capacity in the two hyperglycemic states was decreased, and more with intermittent hyperglycemia than with chronic hyperglycemia. The expression of Mn-SOD and Bcl-2 increased more with chronic hyperglycemia than with intermittent hyperglycemia. Conclusion: Intermittent hyperglycemia induced a higher degree of apoptosis and decreased the insulin secretory capacity more in pancreatic beta cells than chronic hyperglycemia. This activity may be mediated by the anti-oxidative enzyme Mn-SOD and the anti-apoptotic signal Bcl-2.

Low glibenclamide concentrations affect endoplasmic reticulum stress in INS-1 cells under glucotoxic or glucolipotoxic conditions

권민정,정혜석,윤창신,이은주,김태균,이순희,고경수,이병두,김미경,박정현 대한내과학회 2013 The Korean Journal of Internal Medicine Vol.28 No.3

Background/Aims: β-Cell apoptosis caused by increased endoplasmic reticulum (ER) stress is an important pathogenic component of type 2 diabetes mellitus. In theory, sulfonylureas, used for the treatment of diabetes, can contribute to ER stress. We assessed changes in ER stress in pancreatic β-cells under glucotoxic or glucolipotoxic conditions using low concentrations of the sulfonylurea, glibenclamide (GB). Methods: Low concentrations of GB (10 or 100 nM) were added to INS-1 cells cultured under glucotoxic or glucolipotoxic conditions. The degree of viability, level of apoptosis and levels of markers associated with ER stress were measured. Results: Apoptosis decreased in response to low concentrations of GB under glucolipotoxic but not glucotoxic conditions. Most ER stress markers decreased upon the addition of GB. Under glucotoxic conditions, changes in the levels of ER stress markers were not consistent. However, all decreased significantly under glucolipotoxic conditions. Conclusions: Low concentrations of GB exerted antiapoptotic effects through the attenuation of ER stress under glucolipotoxic conditions.

1H NMR Based Metabolomics Studies of the Toxicity of Titanium Dioxide Nanoparticles in Zebrafish (Danio rerio)

Ganesan Raja,김시원,윤다혜,윤창신,김석만 대한화학회 2018 Bulletin of the Korean Chemical Society Vol.39 No.1

Titanium dioxide nanoparticles (TiO2-NPs) are widely used in foods, cosmetics, and pharmaceuticals. In the present study, male and female zebrafish (Danio rerio) were exposed to sub-lethal concentrations of TiO2-NPs dosed at 0.1 mg/L (low) and 5.0 mg/L (high), respectively. 1H–nuclear magnetic resonance (NMR) profiling combined with univariate and multivariate statistics was used to assess metabolic alterations in the TiO2-NP-treated fish. Purine metabolism—including the anabolism/catabolism of ATP, ADP, AMP, xanthine, and inosine—was significantly influenced, which may indicate some genotoxicity resulting from TiO2-NP exposure. Increasing the dose and duration of TiO2-NP exposure led to additional metabolic disturbances in glycerophospholipid metabolism and the Krebs cycle. Our findings demonstrate the potential applicability of using a metabolomics approach to determine underlying metabolic disturbances caused by TiO2-NPs.

1H-NMR-based Metabolomics Studies of the Toxicity of Mesoporous Carbon Nanoparticles in Zebrafish (Danio rerio )

Ganesan Raja,김시원,윤다혜,윤창신,김석만 대한화학회 2017 Bulletin of the Korean Chemical Society Vol.38 No.2

Mesoporous carbon nanoparticles (MCNs) have been applied in a variety of drug/gene carriers. In addition to their potential benefits, many studies of their potential toxicity have been reported, showing the limitations of metabolic contextualization. In this study, we conducted1H-nuclear magnetic resonance (NMR) profiling combined with statistical methods such as orthogonal partial least squares discriminant analysis and Pearson correlation analysis to assess metabolic alterations in the whole body of zebrafish (Danio rerio) in the presence of various concentrations of MCNs. The MCN exposure influenced numerous metabolites in energy metabolism (e.g., metabolites involved in glycolysis and tricarboxylic acid cycle) and disturbed the balance of neurotransmitters and osmoregulators. Our findings demonstrate the potential applicability of using a metabolomics approach to determine underlying metabolic disturbances caused by MCNs.

Comparison of EGF with VEGF Non-Viral Gene Therapy for Cutaneous Wound Healing of Streptozotocin Diabetic Mice

고정해,전혜정,정혜숙,윤창신,김태균,권민정,이순희,정수진,김미경,박정현 대한당뇨병학회 2011 Diabetes and Metabolism Journal Vol.35 No.3

Background: To accelerate the healing of diabetic wounds, various kinds of growth factors have been employed. It is the short half-life of administered growth factors in hostile wound beds that have limited wide-spread clinical usage. To overcome this limitation, growth factor gene therapy could be an attractive alternative rather than direct application of factors onto the wound beds. We administered two growth factor DNAs, epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) into a cutaneous wound on diabetic mice. We compared the different characteristics of the healing wounds. Methods: Streptozotocin was injected intraperitoneally to induce diabetes into C57BL/6J mice. The ultrasound micro-bubble destruction method with SonoVue as a bubbling agent was used for non-viral gene delivery of EGF^(828) and VEGF^(165) DNAs. Each gene was modified for increasing efficacy as FRM-EGF^(828) or minicircle VEGF^(165). The degree of neoangiogenesis was assessed using qualitative laser Doppler flowmetry. We compared wound size and histological findings of the skin wounds in each group. Results: In both groups, accelerated wound closure was observed in the mice receiving gene therapy compared with non treated diabetic control mice. Blood flow detected by laser doppler flowmetry was better in the VEGF group than in the EGF group. Wound healing rates and histological findings were more accelerated in the EGF gene therapy group than the VEGF group, but were not statistically significant. Conclusion: Both non-viral EGF and VEGF gene therapy administrations could improve the speed and quality of skin wound healing. However, the detailed histological characteristics of the healing wounds were different.