• 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.

• Journal of Periodontal and Implant Science
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• v.23 no.3
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• pp.535-563
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• 1993

New techniques for regenerating the destructed periodontal tissue have been studied for many years. Current acceptable methods of promoting periodontal regeneration alre basis of removal of diseased soft tissue, root treatment, guided tissue regeneration, graft materials, biological mediators. Platelet-derived growth factor (PDGF) is one of polypeptide growth factor. PDGF have been reported as a biological mediator which regulate activities of wound healing progress including cell proliferation, migration, and metabolism. The purposes of this study is to evaluate the possibility of using the PDGF as a regeneration promoting agent for furcation involvement defect. Eight adult mongrel dogs were used in this experiment. The dogs were anesthetized with Pentobarbital Sodium (25-30 mg/kg of body weight, Tokyo chemical Co., Japan) and conventional periodontal prophylaxis were performed with ultrasonic scaler. With intrasulcular and crestal incision, mucoperiosteal flap was elevated. Following decortication with 1/2 high speed round bur, degree III furcation defect was made on mandibular second(P2) and fourth(P4) premolar. For the basic treatment of root surface, fully saturated citric acid was applied on the exposed root surface for 3 minutes. On the right P4 20ug of human recombinant PDGF-BB dissolved in acetic acid was applied with polypropylene autopipette. On the left P2 and right P2 PDGF-BB was applied after insertion of ${\beta}-Tricalcium$ phosphate(TCP) and collagen (Collatape) respectively. Left mandibular P4 was used as control. Systemic antibiotics (Penicillin-G benzathine and penicillin-G procaine, 1 ml per 10-25 1bs body weight) were administrated intramuscular for 2 weeks after surgery. Irrigation with 0.1% Chlorhexidine Gluconate around operated sites was performed during the whole experimental period except one day immediate after surgery. Soft diets were fed through the whole experiment period. After 2, 4, 8, 12 weeks, the animals were sacrificed by perfusion technique. Tissue block was excised including the tooth and prepared for light microscope with H-E staining. At 2 weeks after surgery, therer were rapid osteogenesis phenomenon on the defected area of the PDGF only treated group and early trabeculation pattern was made with new osteoid tissue produced by activated osteoblast. Bone formation was almost completed to the fornix of furcation by 8 weeks after surgery. New cementum fromation was observed from 2 weeks after surgery, and the thickness was increased until 8 weeks with typical Sharpey’s fibers reembedded into new bone and cementum. In both PDGF-BB with TCP group and PDGF-BB with Collagen group, regeneration process including new bone and new cementum formation and the group especially in the early weeks. It might be thought that the migration of actively proliferating cells was prohibited by the graft materials. In conclusion, platelet-derived growth factor can promote rapid osteogenesis during early stage of periodontal tissue regeneration.

• Proceedings of the Ginseng society Conference
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• 1980.09a
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• pp.87-113
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• 1980

This experiment was carried out to evaluate the effects of Korean ginseng extract on carcinogenesis induced by various chemical carcinogens. Red ginseng extract was used for this study and was administered orally to the experimental animals. Carcinogens that were injected in subscapsular region of ICR newborn mice within 24 hours after birth were 9,10-dimethyl-1,2-benzan-thracene (DMBA), urethane, N-2-fluorenylacetamide(AAF), aflatoxin $B_1$ and tobacco smoke condensate. N -methyl-N -nitroso-N'-nitroguani-dine(MNNG) was injected subcutaneously at the back of wistar rats. Experimental animals were autopsied in immediately after being sacrificed. All major organs were examined grossly and weighted. After fixation histopathological preparations were made for microscopical study. Following results were obtained. In DMBA group sacrificed at the 26th week after the treatment with DMBA, the incidence of lung adenoma was $77\%$ and the average number of the tumor was 17. However, in DMBA combined with red ginseng group, the incidence was $78\%$ and the average number of lung adenoma was 14.1. This indicates that ginseng extract had no effect on the incidence of lung adenoma but decreased the average number of lung adenoma by $17\%.$ In DMBA group sacrificed at the 48th week after the injection of DMBA, the lung adenoma incidence was $88\%.$ The average diameter of the largest lung adenoma was 3.5 cm, the incidence of diffuse pulmonary infiltration was $18\%$ and the average lung weight of male experimental mice was $528.2{\pm}469.1\;gm.$ On the other hand, in DMBA combined with red ginseng group sacrificed at the 48th week, the incidence of lung adenoma was $96\%.$ The average diameter of the largest adenoma was 2.7 cm, the incidence of diffuse pulmonary infiltration was $7\%$ and the average lung weight of male mice was $418.0{\pm}520\;gm.$ These observations show that ginseng extract did not have any inhibitory effect on the incidence of lung adenoma but decreased the average diameter of the largest lung adenoma by $23\%,$ the incidence of duffuse pulmonary infiltration by $63\%$ and the average lung weight of male experimental mice by $21\%.$ From these results we have found that the prolonged administration with ginseng extract showed no inhibitory effect on the incidence of adenoma but it had the inhibitory effect on the proliferation of lung adenomas induced by DMBA. In urethane group sacrificed at the 28th week after the injection of urethane, the incidence of lung adenoma was $94\%$ and the average number of lung adenoma was 8.6. In urethane combined with red ginseng group, the. incidence of lung adenoma was $73\%$ and the average number of adenoma was 6.0. These results indicate that there were $22\%$ decrease of the lung adenoma incidence and $31\%$ decrease of the average number of adenoma in urethane combined with red ginseng group. And in urethane group sacrificed at the 50th week, the incidence of lung adenoma was $98\%$ and the incidence of diffuse pulmonary infiltration was $14\%$. In urethane combined with ginseng group the incidence of lung adenoma was $85\%$ and the incidence of diffuse pulmonary infiltration was $12\%$. Therefore the ginseng administration resulted in $15\%$ decrease of the lung adenoma incidence and $14\%$ decrease of the diffuse pulmonary infiltration incidence. From these results we knew that the prolonged administration with ginseng extract inhibited the incidence and also the proliferation of the lung adenoma induced by urethane. Lung adenoma and hepatoma were induced in the experimental mice sacrificed at the 68th week but not in the experimental mice sacrificed at the 28th week after the injection of AAF. In AAF group sacrificed at the 68th week after the injection of AAF the incidence of lung adenoma was $18\%$ and the incidence of hepatoma was $27\%$. And in AAF combined with ginseng group the lung adenoma incidence was $12\%$ and the hepatoma incidence was $37\%$. So the ginseng seemed to decrease the lung adenoma incidence by AAF, but we were unable to conclude the significant inhibitory effect of the ginseng extract on the incidence of lung adenoma by AAF because the above incidence of lung adenoma were similar to that of control group which was $11\%$. And these experimental data revealed that ginseng extract didn't have any inhibitory effect on the incidence of hepatoma induced by AAF. In aflatoxin $B_1$ group sacrificed at the 56th week, the incidence of lung adenoma was $24\%$ and hepatoma was $11\%$. However in aflatoxin $B_1$ combined with ginseng group the incidence of lung adenoma was $17\%$ and hepatoma was $3\%$ These results indicate that there were $29\%$ decrease of the lung adenoma incidence and $75\%$ decrease of the hepatoma incidence in aflatoxin $B_1$ combined with ginseng group. In tobacco smoke condensate experimental group sacrificed at 67th week, no tumors were induced except just a few lung adenoma. The lung adenoma incidence both in tobacco smoke condensate group and in tobacco smoke condensate combined with ginseng group was $8\%$. And this incidence rate was similar to that of control group. These results indicate that the injection of 320 ug tobacco smoke condensate per ICR newborn mouse was unable to induce lung adenoma in our experiments. In MNNG group sacrificed at the 27th week the tumor incidence was $38.5\%$ and in MNNG combined with ginseng extract group was $37\%$. In MNNG group for investigation of the life span of tumor bearing rats the tumor incidence was $93\%$ and the average life span of tumor bearing rats was 318 days. And in MNNG combined with ginseng extract group the tumor incidence was $96\%$ and the average life span was 337 days. Tumor induced by MNNG was almost sarcoma. This indicates that there was no inhibitory effect of ginseng extract on the tumor incidence, but the extract prolonged the average life span of tumor bearing rats by approximately 19 days.

• Korean Journal of Environmental Agriculture
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• v.23 no.4
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• pp.203-210
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• 2004

This study was conducted to assessment organic compound and bioassay (density of inhabited animal, fluctuation of predominant fungi, and survival ratio of earthworm) for finding damage on red pepper by heavily amount application of sludges in soil, which was treated with 3 pharmaceutical byproducts and a cosmetic industry wastewater sludge as raw materials of compost, and for establishing estimation method. HEM contents in the soil treated with pharmaceutical byproducts sludge2 (PS2) and cosmetic sludge (CS) were 0.51, 1.10 mg/kg respectively. PAHs content of PS2 treatment in the soil was 3406.8 ug/kg on July 8. In abundance of soil faunas, the pharmaceutical byproducts sludge2 treatment was the most highest. The next was decreased in the order of pig manure (PM) and the cosmetic sludge treatment. However the other pharmaceutical sludge treatments were remarkably reduced populations of soil inhabited animals. In upland soil treated with organic sludges, the numbers of bacteria and fungi of the pharmaceutical sludge treatment were 736, 909 cfu/g and those of the cosmetic sludge treatment were 440, 236 cfu/g, respectively. The pharmaceutical sludge treatments and the cosmetic sludge treatment in identification of predominant bacteria were not any tendency to compare with non fertilizer and pig manure treatments, but they had diverse bacteria than NPK treatment. In microcosm tests, the survival of the tiger earthworm in five soil samples was hardly affected against the soil of PSI (20%) after three months treated in the upland But after six months, survival of PS1 was 80%. At present, raw material of compost was authorized by contents of organic matter, heavy metal (8 elements), and product processing according to 'The specified gist on possible materials of using after analysis and investigation among raw materials of compost', however, for preparing to change regulation of raw material of compost and for considering to possibility of application, this study was conducted to investigate toxic organic compound and bioassay methods using inhabited animal, fungi, and earthworm without current regulation.

• The Korean Journal of Nuclear Medicine Technology
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• v.20 no.2
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• pp.54-61
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• 2016

Purpose Precocious Puberty is defined as the development of secondary sexual characteristics in girls younger than 8 years, and boys 9 years. Cause premature closure of the epiphysis is a disease that eventually decreases the final adult height. In this study, we retrospectively analyzed to evaluate the diagnostic difference the GnRH (Gonado-tropin-releasing Hormone) stimulation test results with medical records of precocious puberty in girls. Materials and Methods From February 2015 to December 2015 it was enrolled in the girls 118 people who visited the Seoul National University Bundang Hospital, Pediatrics, Endocrinology Internal Medicine. True precocious puberty group (n=57), early puberty group (n=39), were divided into Premature thelarche (n=22) group. A Tanner stage, chronological age, bone age, height, body weight for each group was determined by examining the mean${\pm}$standard deviation. GnRH test result was compared LH (Basal, 30 min, 45 min, 60 min), FSH (Basal, 30 min, 60 min) for each group, Each group LH, FSH Peak value distribution, the mean${\pm}$standard deviation was calculated for the peak LH/LH basal ratio, peak LH/Peak FSH ratio. The significance probability (P-value) between the value of each third group was determined. Results The average height of the true precocious puberty group $131{\pm}14.85$, the mean weight was $28.80{\pm}4.93$, the average chronological age $7.1{\pm}0.81$, the mean bone age was $9.9{\pm}0.9$, The average height of early puberty group was $134{\pm}5.10$, the average weight $28.50{\pm}4.43$, the average chronological age $8.05{\pm}0.03$, the mean bone age was $10.0{\pm}0.62$, The average height of Premature thelarche $129{\pm}6,01$, the average weight was $28.65{\pm}5.98$, the average chronological age $7.02{\pm}0.58$, the mean bone age was $8.04{\pm}1.29$. There was no significant difference when compared to the height and weight. There was a significant difference between the groups in the chronologic age and bone age difference (P <0.0002) True precocious puberty group showed peak LH levels at 30'(82.5%), 45'(12.3%), 60'(5.3%), in Peak FSH 30'(8.8%), 60'(91.2%). Early Puberty group showed high values in Peak LH at 30'(79.5%), 45'(17.9%), 60'(2.6%), in peak FSH levels at 30'(7.7%), 60'(92.32%). In Premature thelarche Group it showed the Peak LH levels at 30'(30%), 45'(59%), 60'(9.09%), Peak FSH levels at 30'(0%) 60'(100%). When compared with the The Peak LH/basal LH ratio, True precocious puberty group was $19.09{\pm}17.15$, early puberty group was $15.23{\pm}10.88$, Premature thelarche group showed significant differences between the three groups as $4.93{\pm}4.36$.(P <0.0001) LH Peak/FSH Peak ratio, true precocious puberty group was $1.222{\pm}0.77$, early puberty group was $1.34{\pm}1.23$, Premature thelarche group showed significant differences between the three groups as $0.3{\pm}0.09$(P <0.0001) Conclusion In order to diagnose the true precocious puberty have a diagnostic value when the LH peak after GnRH stimulation is increased by more than two to three times compared to baseline or a predetermined level or more than 5~10 IU/L increases. GnRH Test is a test for a long time and the patient discomfort due to repeated blood sampling, but the hypothalamus-pituitary gland- gonad axis activity evaluate and is the most basic accurate test in the differential diagnosis of precocious puberty disorders.