• Environmental Analysis Health and Toxicology
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• v.31
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• pp.10.1-10.8
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• 2016

Objectives Aromatase inhibitors that block estrogen synthesis are a proven first-line hormonal therapy for postmenopausal breast cancer. Although it is known that standardized extract of Ginkgo biloba (EGb761) induces anti-carcinogenic effects like the aromatase inhibitors, the effects of EGb761 on steroidogenesis have not been studied yet. Therefore, the effects of EGb761 on steroidogenesis and aromatase activity was studied using a H295R cell model, which was a good in vitro model to predict effects on human adrenal steroidogenesis. Methods Cortisol, aldosterone, testosterone, and $17{\beta}$-estradiol were evaluated in the H295R cells by competitive enzyme-linked immunospecific assay after exposure to EGb761. Real-time polymerase chain reaction were performed to evaluate effects on critical genes in steroid hormone production, specifically cytochrome P450 (CYP11/ 17/19/21) and the hydroxysteroid dehydrogenases ($3{\beta}$-HSD2 and $17{\beta}$-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis. Results H295R cells exposed to EGb761 (10 and $100{\mu}g/mL$) showed a significant decrease in $17{\beta}$-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and $17{\beta}$-HSD1) related to the estrogen steroidogenesis were significantly decreased by EGb761. EGb761 treatment of H295R cells resulted in a significant decrease of aromatase activity as measured by the direct and indirect assays. The coding sequence/Exon PII of CYP19 gene transcript and protein level of CYP19 were significantly decreased by EGb761. Conclusions These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and $17{\beta}$-HSD1, and lead to a decrease in $17{\beta}$-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer.

• Journal of the korean academy of Pediatric Dentistry
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• v.24 no.1
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• pp.204-219
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• 1997

The use of fluoride is one of the most effective methods for caries prevention. Fluoridation of public water supply has been recognized, for many years, as an effective way to reduce dental caries. The fluoride supplement has been recommended when the natural fluoride was unavailable or below the optimal range. However the mechanism of caries prevention by fluoride has not yet been clarified and it is well known that an overdose of fluoride results inacute and chronic toxicity, especially dental fluorosis. Fluoride mouthrinsing solution is widely used in dentistry due to its effectiveness in carrying anticariogenic action. Understanding the effects of fluoride mouthrinsing solution on human gingival fibroblasts will provide the safety rationale for its use during the caries preventive therapy. The purpose of this study was to evaluate the cytotoxic effect of fluoride mouthrinsing solution on the human gingival fibroblast in vitro. The human gingival fibroblasts were cultured from healthy gingiva on the extracted deciduous teeth of children. Cells were inoculated into a 24-well plate with $1{\times}10^4cells/well$ of medium at $37^{\circ}C$, 100% humidity, 5% $CO_2$ incubator for 24 hours. And the cells were counted by using the hemocytometer at each designed study. Human gingival fibroblasts were cultured in growth medium after one minute application range of 0.02%-0.2% NaF solution and 0.1% $SnF_2$ solution. The cells used in this study were between fifth to eighth passage number. The cell morphology was examined by inverted microscope and cell proliferation was measured by incorporating $[^3H]$-thymidine into DNA. DNA synthesis by human gingival fibroblasts was assessed by $[^3H]$-thymidine uptake assays while the cell activity was measured by MTT assay. Each concentrated fluoride mouthrinsing solution was estimated for its biocompatability with fibroblasts by the tissue culture technique. The results of this study were as follows : 1. It was observed that at 0.05%, 0.2% NaF mouthrinsing solution the cytoplasmic processes became globular. When 0.1% $SnF_2$ mouthrinsing solution was applied, the cytoplasmic process and cell morphology were disappeared. 2. DNA synthetic activity was reduced regardless of the concentration of the fluoride mouthrinsing solution. However, the result is statistically insignificant except 0.1% $SnF_2$ mouthrinsing solution(p<0.05). 3. Our results indicate that 0.02%, 0.05% concentrations of NaF mouthrinsing solution caused minimal cytotoxicity. But 0.2% NaF and 0.1% $SnF_2$ concentration were a significant difference between the cell activity in the experimental group and control group (p<0.05). 4. After appling 0.05% & 0.02% NaF fluoride mouthrinsing solution, cell activity was restored to the control groups level according to incubating time. The results suggest that direct exposure to fluoride solution inhibits gingival fibroblast activity. Therefore, for the most effective use of fluoride use, lowering the concentration of fluoride mouthrinsing is advisable because it maintains biocompatability and free ion in the oral fluid.

• Journal of Veterinary Clinics
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• v.28 no.6
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• pp.549-554
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• 2011

FK506 is a widespread immunosuppressive drug after liver transplantion in patients with advanced-stage hepatocellular carcinoma. Dexamethasone is frequently used as co-treatment in cytotoxic cancer therapy, e.g. to prevent nausea, to protect normal tissue or for other reasons. Our aim was to investigate antitumor effects of FK506 in Hep3B cells, one of differentiated human hepatocellular carcinoma cell lines and inhibitory effects of dexamethsone on FK506- induced antitumor effects. Cell injury was evaluated by biochemical assays as cell viability, lactate dehydrogenase (LDH) and reactive oxygen species (ROS) in Hep3B cells. Intracellular calcium concentration ([$Ca^{2+}$]i) and the level of activation of the c-Jun-N-terminal kinase (JNK) and the Bax protein in cultured Hep3B cells was measured. Exposure of 0.1 ${\mu}M$ FK506 to Hep3B cells led to cell death accompanied by a decrease in cell viability and an increase in LDH, ROS and [$Ca^{2+}$]i. FK506 induced an increase in activity of Bax and JNK protein but inhibited the activity of Bcl-2 protein. Treatment of dexamethsone, per se, had no effects on cell viability, LDH and ROS. However, co-treatment of FK506 and dexamethasone diminished the FK506-induced LDH release, ROS generation and JNK activation. These results demonstrate that FK506 has antitumor effect in Hep3B cells but the combination of FK506 and dexamethasone antagonizes the FK506-induced antitumor effects.

• Journal of Korean Neurosurgical Society
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• v.29 no.8
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• pp.1008-1018
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• 2000

Objective : Glutamate induced excitotoxicity is one of the leading causes of cell death under pathologic condition. However, there is controversy whether excitotoxicity may also participate in the neuronal death under low intensity insult such as simple hypoxia or hypoglycemia. To investigate the role of NMDA receptor in low intensity insult, we chose anoxia as the method of injury and used organotypically cultured hippocampal slice as the material of experiment. Materials & Methods : The hippocampal slices cultured for 2-3 weeks were exposed to 60 minutes of complete oxygen deprivation(anoxia). Neuronal death was assessed with Sytox stain. Corrected optical density of fluorescence in gray scale, used as cellular death indicator, was obtained from pictures taken at 24 and 48 hours following the insult. The well-known in vivo phenomenon of regional difference in susceptibility of hippocampal sub-fields to ischemic insult was reproduced in HOSC(hippocampal organotypic slice culture) by complete oxygen deprivation injury. Results : $CA_1$ was the most vulnerable to complete oxygen deprivation in hippocampus while $CA_3$ was resistant. Oxygen deprivation for 10 and 20 minutes with glucose(6.5g/l) present was insufficient to induce neuronal death in the cultured hippocampal slice. However, after 30 minutes exposure under anoxic condition, neuronal death was able to be detected in the center of $CA_1$ area. The intensity and area of fluorescence indicating cell death correlated with the duration of oxygen deprivation. NMDA receptor and non-NMDA receptor blocking with MK-801(30 & $60{\mu}M$) and CNQX($100{\mu}M$) did not provide cellular protection to HOSC against damage induced by oxygen deprivation, but increased intracellular calcium buffering capacity with BAPTA-AM($10{\mu}M$) was effective in preventing neuronal death (p=0.01, Student's t-test). Cycloheximide($1{\mu}g/ml$, $10{\mu}g/ml$) provided no protection to HOSC against insult of complete oxygen deprivation for 60 minutes and combined therapy of MK-801(30 & $60{\mu}M$) and cycloheximide(1 & $10{\mu}g/ml$) was also ineffective in preventing neuronal death. Conclusion : The results of this study show that the another mechanism not associated with glutamate receptor(NMDA & non NMDA) may play major role in cell death mechanisms induced by complete oxygen deprivation and increased intracellular calcium during anoxia may participate in the neuronal death mechanism of oxygen deprivation. Further investigation of the calcium entry channel activated during oxygen deprivation is necessary to understand the neuronal death of anoxia.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1357-1362
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• 2014

Background: Vitamin D deficiency is a potentially modifiable risk factor that may be targeted for breast cancer (BC) prevention. It may also be related to prognosis after diagnosis and treatment. The aim of our study was to determine the prevalence of vitamin D deficiency as measured by serum 25-hydroxy vitamin D (25-OHD) levels in patients with BC and to evaluate its correlations with life-style and treatments. Materials and Methods: This study included 186 patients with stage 0-III BC treated in our breast center between 2010-2013. The correlation between serum baseline 25-OHD levels and supplement usage, age, menopausal status, diabetes mellitus, usage of bisphosphonates, body-mass index (BMI), season, dressing style, administration of systemic treatments and radiotherapy were investigated. The distribution of serum 25-OHD levels was categorized as deficient (<10ng/ml), insufficient (10-24 ng/ml), and sufficient (25-80 ng/ml). Results: The median age of the patients was 51 years (range: 27-79 years) and 70% of them had deficient/insufficient 25-OHD levels. On univariate analysis, vitamin D deficiency/insufficiency was more common in patients with none or low dose vitamin D supplementation at the baseline, high BMI (${\geq}25$), no bisphosphonate usage, and a conservative dressing style. On multivariate analysis, none or low dose vitamin D supplementation, and decreased sun-exposure due to a conservative dressing style were found as independent factors increasing risk of vitamin D deficiency/insufficiency 28.7 (p=0.002) and 13.4 (p=0.003) fold, respectively. Conclusions: The prevalence of serum 25-OHD deficiency/insufficiency is high in our BC survivors. Vitamin D status should be routinely evaluated for all women, especially those with a conservative dressing style, as part of regular preventive care, and they should take supplemental vitamin D.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.5043-5047
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• 2014

Nowadays increasing effectiveness in cancer therapy and investigation of formation of new strategies that enhance antiproliferative activity against target organs has become a subject of interest. Although the molecular mechanisms of apoptosis can not be fully explained, it is known that cell suicide program existing in their memory genetically is activated by pathophysiological conditions and events such as oxidative stress. Low pressure (hypobaric) conditions that create hypoxia promote apoptosis by inhibiting cell cycling. In this study, determination of the effects of fractional hypobaric applications at different times on HeLa cells at cellular and molecular levels were targeted. Experiments were carried out under hypobaric conditions (35.2 kPa) in a specially designed hypobaric cabin including 2% $O_2$ and 98% N. Application of fractional hypobaric conditions was repeated two times for 3 hours with an interval of 24 hours. At the end of the implementation period cells were allowed to incubate for 24 hours for activation of repair mechanisms. Cell kinetic parameters such as growth rate (MTT) and apoptotic index were used in determination of the effect of hypobaric conditions on HeLa cells. Also in our study expression levels of the Bcl-2 gene family that have regulatory roles in apoptosis were determined by the RT-PCR technique to evaluate molecular mechanisms. The results showed that antiproliferative effect of hypobaric conditions on HeLa cells started three hours from the time of application and increased depending on the period of exposure. While there was a significant decrease in growth rate values, there was a significant increase in apoptotic index values (p<0.01). Also molecular studies showed that hypobaric conditions caused a significant increase in expression level of proapoptotic gene Bax and significant decrease in antiapoptotic Bfl-1. Consequently fractional application of hypobaric conditions on HeLa cell cultures increased both antiproliferative and apoptotic effects and these effects were triggered by the Bax gene.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.41
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• pp.30.1-30.8
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• 2019

Background: Advancements in the field of microvascular surgery and the widespread adoption of microvascular surgical techniques have made the use of osteocutaneous fibula free flaps the standard of care in the surgical management of segmental mandibular defects. Although the literature possesses abundant evidence to support the effectiveness of fibula free flaps as a reconstructive method, there are relatively few studies reporting on outcomes as objectively measured by videofluoroscopic swallowing studies (VFSS). The purpose of this study is to explore the potential correlation between early postoperative VFSS and the long-term swallowing outcomes in patients who underwent mandibular reconstruction with fibula free flaps. Methods: We performed a retrospective chart review of 36 patients who underwent mandibular reconstruction with osteocutaneous fibular free flaps between 2009 and 2012. Demographics, clinical variables, VFSS data, and diet information were retrieved. Penetration and aspiration findings on VFSS, long-term oral feeding ability, and the need for gastrostomy tube were statistical endpoints correlated with postoperative clinical outcomes. Results: Thirty-six patients were reviewed (15 females and 21 males) with a mean age of 54 years (7-81). Seventeen cases were treated for malignancy. The size of the bony defect ranged from 3 to 15 cm (mean = 9 cm). The cutaneous paddle, a surrogate for soft tissue defect, ranged from 10 to 125 ㎠ (mean = 52 ㎠). A gastrostomy tube was present in patients preoperatively (n = 8), and postoperatively (n = 14). Seventeen patients had neoadjuvant exposure to radiation. Postoperative VFSS showed penetration in 13 cases (36%) and aspiration in seven (19%). Overall, 29 patients (80.6%) achieved unrestricted diet, and this was statistically correlated with age (p = 0.037), radiation therapy (p = 0.002), and preoperative gastrostomy tube (p = 0.03). The presence of penetration or aspiration on VFSS was a strong predictor for long-term unrestricted oral diet (p < 0.001). Conclusion: Early postoperative VFSS is an excellent predictor for long-term swallowing outcomes in patients undergoing mandibular reconstruction with osteocutaneous fibula free flaps.

• Journal of Oral Medicine and Pain
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• v.35 no.2
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• pp.155-163
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• 2010

Dermatomyositis (DM) is an idiopathic inflammatory connective tissue disorder and a systemic autonomic immune disease which shows a progressive muscle weakness and characteristic rash. It is identified by a characteristic rash accompanying, or more often preceding muscle weakness. Pathognomonic skin lesions are a blue-purple discoloration on the upper eyelids with edema (heliotropic rash), a flat red rash on the face and upper trunk, and erythema of the knuckles with a raised violaceous scaly eruption (Gottron's papule). The myopathy represents inflammatory and degenerative changes primarily affecting proximal muscles. DM often involves GI tract and respiratory system with as risk of 15-25% internal malignancy. It's managed with sun protection since muscle weakness as well as a rash could be aggravated by sun exposure. Systemic corticosteroid is an initial therapy and other immunosuppressive agent has been used as alternatives. Facial muscles are unaffected and masticatory muscles are rarely affected in DM. We present trismus close to muscle contracture in a patient with DM. Therefore, it needs continuous mouth-opening exercise to prevent progressive muscle contracture and to ensure normal mouth opening.

• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.320-327
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• 2020

In current study, we aimed to investigate whether the gentiopicroside (GPS) derived from Gentiana manshurica Kitagawa could block the progression of alcoholic hepatic steatosis to fibrosis induced by chronic ethanol intake. C57BL/6 mice were fed an ethanol-containing Lieber-DeCarli diet for 4 weeks. LX-2 human hepatic stellate cells were treated with GPS 1 h prior to transforming growth factor-β (TGF-β) stimulation, and murine hepatocyte AML12 cells were pretreated by GPS 1 h prior to ethanol treatment. GPS inhibited the expression of type I collagen (collagen I), α-smooth muscle actin (α-SMA) and tissue inhibitor of metal protease 1 in ethanol-fed mouse livers with mild fibrosis. In addition, the imbalanced lipid metabolism induced by chronic ethanol-feeding was ameliorated by GPS pretreatment, characterized by the modulation of lipid accumulation. Consistently, GPS inhibited the expression of collagen I and α-SMA in LX-2 cells stimulated by TGF-β. Inhibition of lipid synthesis and promotion of oxidation by GPS were also confirmed in ethanol-treated AML12 cells. GPS could prevent hepatic steatosis advancing to the inception of a mild fibrosis caused by chronic alcohol exposure, suggesting GPS might be a promising therapy for targeting the early stage of alcoholic liver disease.

• Journal of Preventive Medicine and Public Health
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• v.17 no.1
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• pp.5-24
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• 1984

There has been an immense need for elaborate studies on the complications and the neuological sequelae generated by acute carbon monoxide (CO) poisoning which is highly prevalent in Korea due to widespread adoption of the anthracite coal briquette as domestic fuel for heating and for cooking. For this epidemiological study, a total of 444 subjects who received hospital emergency care for acute CO poisoning during the period of March 1982 to February 1983 were randomly selected from the emergency patients's lists of 13 general hospitals in Seoul area. Informations on the neurological sequelae were elucidated by means of home visiting with prearranged questionnaire consisting questions and concise neurological examination. The findings obtained were summarized as follows; 1. The complications were found in 18% of the surveyed and acute decubitus was comprised 67.5% of the complications. 2. The total cumulative incidence of the neurological sequelae was 41.2 per 100 patients and the absolute incidence rate regardless of the duration after poisoning was 40.8%. 3. The incidence of the neurological sequelae was higher in the older age than in the younger and also higher in female than in male. Twice higher incidence was observed in the admitted patients than in the non-admitted patients and the incidence became higher in proportion to the duration of CO exposure, coma and admission. The poorer the consciousness level of patients found, at emergency room and at discharge, the higher the incidence. The incidence of the neurological sequelae by emergency care was higher in hyperbaric oxygen therapy group(51.9%) than in 100% $O_2$ group(38.0%) 4. A total of five variables significantly associated with the occurrence of the neurological sequelae were selected by the stepwise discriminant analysis. The variables were following course of emergency care, age, consciousness level at discharge, admission duration, and consciousness level at emergency room in their sequence of discriminant power. Eight variables were selected as those associated with the degree of the neurological sequelae through the stepwise multiple regression analysis. Of these variables, the acute decubitus alone explained 21.1% of the total variation ana all the eight variables could explain 36.5% of the same. The remaining seven variables listed in the order of their relative importance were: age, consciousness level at discharge, admission duration, coma duration and consciousness level at emergency room. 5. It was postulated that unexpectedly high incidence of the neurological sequelae of the CO poisoning in this epidemiological study was mainly due to the inadequate emergency care and the lack of efficient and sophisticated treatment measure. In the effort to minimize the incidence of grave neurological sequelae of acute CO poisoning, new guidelines for the emergency care and treatment should be pursued with efficient ways.