• Journal of Pharmaceutical Investigation
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• v.39 no.3
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• pp.207-216
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• 2009

Fluconazole is used as an orally administrated antifungal drug for the treatment of tinea corporis, candidiasis including skin mycotic pneumonia infections. The dosage of fluconazole varies with indication ranging from 50 mg/day to 400 mg/day. The fluconazole capsule 50 mg (3 capsules daily) is already available in Korean market. To improve the patient compliance, a fluconazole tablet 150 mg (once a day administration) was developed recently. The purpose of this study was to evaluate the bioequivalence of three doses of fluconazole capsule 50 mg (Diflucan 50 mg, Pfizer Korea Inc., as a reference drug) and a single dose of fluconazole tablet 150 mg (Plunazol 150 mg, Daewoong Pharm. Co., Korea) according to the guidelines of the Korea Food and Drug Administration (KFDA). The bioequivalence for three capsules of Diflucan 50 mg and a single tablet of Plunazol 150 mg was investigated in twenty-four healthy male volunteers under a randomized 2${\times}$2 crossover trial design. The average age of twenty-four volunteers was 24.78${\pm}$3.27 year-old, average height was 175.56${\pm}$5.45 cm and average weight was 67.24${\pm}$6.86 kg. After three capsules of Diflucan 50 mg or a single tablet of Plunazol 150 mg were orally administered, blood was taken at predetermined time intervals and the plasma concentrations of fluconazole in plasma were determined using LC-MS-MS. The 90% confidence intervals for the main parameters of statistical results after logarithmic transformation were AUCt 0.9272-1.0084 and Cmax 0.8423-0.9544 respectively, which are in the range of log 0.8 to log 1.25 and the statistical results of additional parameters (AUClast, t1/2 and MRT) were also in the 90% confidence interval that is in the range of log 0.8 to log 1.25. Therefore, the results of this study confirm the bioequivalence of three capsules of Diflucan 50 mg to one tablet of Plunazol 150 mg.

• Tuberculosis and Respiratory Diseases
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• v.57 no.4
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• pp.358-363
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• 2004

Background : Photodynamic therapy (PDT) involves the use of photosensitizing agents for treatment of malignant disease. PDT is approved by the U.S. Food and Drug Administration for the endobronchial microinvasive nonsmall cell lung cancer and for palliation in patients with obstructing tumors. We report our experience and results of PDT in lung cancer. Method : Ten patients with lung cancer who were diagnosed in Chosun university hospital by histologic confirm through bronchoscopy were included between August 2002 and May 2003. The photosensitizer (Photogem$^{(R)}$, Lomonosov institute of Fine Chemical, Russia/dose 2.0 mg/kg body weight) was injected 48 hours prior to the PDT session. For PDT with the photosensitizer (Photogem$^{(R)}$), Diode LASER system (Biolitec Inc., Germany, wavelength; 633nm) were used. PDTs were done at 48-72 hours after photogem injection. Follow up bronchoscopy and chest X-ray or thorax computerized tomography were done for evaluate PDT response. Results : 9 of 10 patients with endobronchial obstruction showed partial remission with bronchus opening after PDT. Direct reaction of the tumor to PDT was similar in despite of its localization. It was as follows; edema, hyperemia, in-situ bleeding, fibrin film occurrence. Any other complications such as sunburns of skin, inflammation within the PDT zone were not occurred by the end of the fourth week. Conclusion : In the advanced endobronchial disease, PDT has been shown to be useful in treating endobronchial tumors that are causing clinically significant dyspnea or are likely to progress and lead to further clinical complications, such as postobstructive pneumonia.

• Korean Journal of Veterinary Research
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• v.43 no.2
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• pp.181-188
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• 2003

Cordyceps has a reputation for its broad biological activities and as a tonic which replenishs vital function in Chinese traditional medicines. As an attempt to obtain fundamental data for the development of new type Cordyceps, the effects of the fruiting bodies of cultivated fungus of Paecilomyces japonica grown on silkworm larvae on radiationinduced damages were investigated. We performed this study to determine the effect of Dongchongxiacao (Paecilomyces japonica) on jejunal crypt survival, endogenous spleen colony formation, and apoptosis in jejunal crypt cells and hair follicles of mice irradiated with high and low dose of gamma-radiation. Treatment with Dongchongxiacao showed no significant modifying effects on the jejunal crypt survival and endogenous spleen colony formation. The frequency of radiationinduced apoptosis was reduced by pretreatment of Dongchongxiacao (i.p.: 50 mg/kg of body weight, at 12 and 36 hours before irradiation, p<0.01). The spontaneous levels of apoptotic cells are $0.082{\pm}0.041$ in intestinal crypts and $0.231{\pm}0.084$ per hair follicle section of skin. Pretreatment of Dongchongxiacao was associated with decreases of 26.86% in intestinal crypt and 66.36% in hair follicle decrease in the number of cells with nuclei positively stained for apoptosis compared with the irradiation control group. We demonstrated for the first time that Dongchongxiacao administration could reduce the extent of apoptosis produced by radiation in the hair follicle. The results presented herein that Dongchongxiacao given before irradiation is capable of reducing the severity of cell loss as a result of apoptosis.

• IMMUNE NETWORK
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• v.9 no.6
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• pp.236-242
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• 2009

Background: Melanoma is the most fatal form of skin cancer due to its rapid metastasis. Recently, several studies reported that selenium can induce apoptosis in melanoma cells. However, the precise mechanism remains to be elucidated. In this study, we investigated the effect of selenium on cell proliferation in murine melanoma and on tumor growth and metastasis in C57BL/6 mice. Methods: Cell proliferation was measured by MTT assay in selenium-treated melanoma cells. Cell cycle distribution was analysized by staining DNA with propidum iodide (PI). mRNA and protein expression related to cell cycle arrest was measured by reverse transcription PCR and western blot. Tumor growth and metastasis was measured by in vivo model. Results: Selenium was suppressed the proliferation of melanoma cells in a dose dependent manner. The growth inhibition of melanoma by selenium was associated with an arrest of cell cycle distribution at G0/G1 stage. The mRNA and protein level of CDK2/CDK4 was suppressed by treatment with selenium in a time-dependent manner. In vivo, tumor growth was not suppressed by selenium; however tumor metastasis was suppressed by selenium in mouse model. Conclusion: These results suggest that selenium might be a potent agent to inhibit proliferative activity of melanoma cells.

• Toxicological Research
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• v.33 no.1
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• pp.43-48
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• 2017

With ultraviolet and visible light exposure, some pharmaceutical substances applied systemically or topically may cause phototoxic skin irritation. The major factor in phototoxicity is the generation of reactive oxygen species (ROS) such as singlet oxygen and superoxide anion that cause oxidative damage to DNA, lipids and proteins. Thus, measuring the generation of ROS can predict the phototoxic potential of a given substance indirectly. For this reason, a standard ROS assay (ROS assay) was developed and validated and provides an alternative method for phototoxicity evaluation. However, negative substances are over-predicted by the assay. Except for ultraviolet A (UVA), other UV ranges are not a major factor in causing phototoxicity and may lead to incorrect labeling of some non-phototoxic substances as being phototoxic in the ROS assay when using a solar simulator. A UVA stimulator is also widely used to evaluate phototoxicity in various test substances. Consequently, we identified the applicability of a UVA simulator to the ROS assay for photoreactivity. In this study, we tested 60 pharmaceutical substances including 50 phototoxins and 10 non-phototoxins to predict their phototoxic potential via the ROS assay with a UVA simulator. Following the ROS protocol, all test substances were dissolved in dimethyl sulfoxide or sodium phosphate buffer. The final concentration of the test solutions in the reaction mixture was 20 to $200{\mu}M$. The exposure was with $2.0{\sim}2.2mW/cm^2$ irradiance and optimization for a relevant dose of UVA was performed. The generation of ROS was compared before and after UVA exposure and was measured by a microplate spectrophotometer. Sensitivity and specificity values were 85.7% and 100.0% respectively, and the accuracy was 88.1%. From this analysis, the ROS assay with a UVA simulator is suitable for testing the photoreactivity and estimating the phototoxic potential of various test pharmaceutical substances.

• Journal of Applied Biological Chemistry
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• v.59 no.3
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• pp.247-253
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• 2016

It confirmed the applicability as an anti-inflammatory material from Rubus occidentalis seed (RSE) extract. In HaCaT cells to evaluate the anti-inflammatory potential as a material RSE extract on the activity of the inflammatory factors caused by UVB and $IFN-{\gamma}/TNF-{\alpha}$. We measured the activity of ROS, interleukin-$1{\beta}$ ($IL-1{\beta}$), interleukin-6 (IL-6) and interleukin-8 (IL-8) by ROS-Glo $H_2O_2$ assay and ELISA kit. Our results showed that the RSE extracts inhibit the UVB and $IFN-{\gamma}/TNF-{\alpha}$-induced ROS activities and expression of $IL-1{\beta}$, IL-6 and IL-8 in a dose-dependent manner. Also it was found that inflammatory mediators of the expression of cyclooxygenase-2 (COX-2) inhibition were also brought, the expression of which is increased $PGE_2$ by COX-2 also inhibited. Finally RSE extracts measure the seed expression of filaggrin in the skin barrier, the main factor of the extract could be confirmed to increase the expression of the filaggrin damaged as a result of this concentration-dependent manner. Through this, it was able to confirm that the efficacy RSE extract to protect the inflammation by restoring the damaged layers of the epidermis. Results from more than RSE extract was able to confirm that the extract that has anti-inflammatory effects by improving the inflammation being produced from UVB.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.2
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• pp.83-88
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• 2004

The purpose of this study was to provide a basis for studying the molecular mechanism of pharmacological action of chlorhexidine digluconate. Large unilamellar vesicles (OPGTL) were prepared with total lipids extracted from cultured Porphyromonas gingivalis outer membranes (OPG). The anthroyloxy probes were located at a graded series of depths inside a membrane, depending on its substitution position (n) in the aliphatic chain. Fluorescence polarization of n-(9-anthroyloxy)stearic acid was used to examine effects of chlorhexidine digluconate on differential rotational mobility, while changing the probes' substitution position (n) in the membrane phospholipids aliphatic chain. Magnitude of the rotational mobility of the intact six membrane components differed depending on the substitution position in the descending order of 16-(9-anthroyloxy)palmitic acid (16-AP), 12, 9, 6, 3 and 2-(9-anthroyloxy)stearic acid (12-AS, 9-AS, 6-AS, 3-AS and 2-AS). Chlorhexidine digluconate increased in a dose-dependent manner the rate of rotational mobility of hydrocarbon interior of the OPGTL prepared with total lipids extracted from cultured OPG, but decreased the mobility of membrane interface of the OPGTL. Disordering or ordering effects of chlorhexidine digluconate on membrane lipids may be responsible for some, but not all of its bacteriostatic and bactericidal actions.

• KSBB Journal
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• v.25 no.4
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• pp.330-336
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• 2010

In this study, a new compound, 1-(2-hydroxy-3,4,5,6-tetramethoxyphenyl)-1-methoxy-3-phenylpropane; (Jeju-Erythrane) was isolated and identified from the bark of Lindera erythrocarpa Makino. Also, we investigated the effects of Jeju-Erythrane on alpha melanocyte-stimulating hormone (MSH)-induced melanogenesis in mouse B16F10 melanoma cells. The new compound dose dependently inhibited the tyrosinase activity and melanin synthesis in B16F10 cells. The new compound showed inhibitory effect on the Tyrosinase and TRP-1 gene transcription but not on the TRP-2 gene. These results suggest that the new compound of L. erythrocarpa could be used as a functional biomaterial in developing skin whitening agent.

• Journal of Life Science
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• v.22 no.6
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• pp.807-814
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• 2012

Saururus chinensis has long been widely used in oriental folk medicines to treat diseases. In the current study, organic solvent fractions obtained from the main methanolic extract of S chinensis were evaluated for their antioxidative and related physiological activities. The antioxidant activity of the fractions was measured using DPPH free radical scavenging activity, increased in a dose-dependent manner, and the $ED_{50}$ of the ethyl acetate fractions exhibited a value of 12.84 ${\mu}g/ml$ higher than 27.22 ${\mu}g/ml$ compared to the BHT. Also, the cell viability of S. chinensis on $H_2O_2$-induced HDF cell death ($IC_{50}$) showed the highest cell viability of 89.39% in 50 ${\mu}g/ml$ of ethyl acetate fraction and 67.98% of visible cell survival rate in n-butanolic fraction. Meanwhile, all fractions of the S. chinensis extract led to a slight down regulation of the mRNA expression of fibulin-5, which is related to skin elasticity, and the ethyl acetate fraction having high antioxidant activity showed a markedly inhibitory effect on chick embryonic angiogenesis using the CAM assay. These results suggest that the ethyl acetate fraction of S. chinensis extract could be a good material in therapeutic application for antioxidant and related anti-angiogenesis activities.

• Journal of Life Science
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• v.24 no.5
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• pp.498-504
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• 2014

Mammalian hyaluronidases (HAase, EC 3.2.1.35) are a family of enzymes that hydrolyse N-acetyl-D-glucosamine (1-4) glycosidic bonds in hyaluronic acid, which is found in skin, cartilage, and the vitreous body. Although HAase is generally present in an inactive form within subcellular lysosomes, it is released in an active form in some types of inflammation and tissue injuries, thereby contributing to the inflammatory response. The HAase inhibitory activity of 500 methanolic extracts of 500 species from medicinal plants was screened using a Morgan microplate assay. The viscosity of the hyaluronic acid was measured with an Ubbelohde viscometer. Three MeOH extracts inhibited more than 50% of HAase activity at a concentration of 2 mg/ml. HAase inhibitory rates (%) of three species of medicinal plant extracts, Styrax japonica, Deutzia coreana, and Osmanthus insularis were 57.28%, 53.50%, and 53.19%, respectively. The rate of HAase inhibition of the extracts was dose dependent. In the HAase inhibitory assay using the Ubbelohde viscometer, the results were in good agreement with the results from the Morgan assay. The results suggest that HAase inhibitory compounds extracted from the stem of S. japonica, D. coreana, and O. insularis might be multifunctional and prevent the degradation of hyaluronic acid and the induction of allergic reactions and inflammation.