• Toxicological Research
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• v.26 no.3
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• pp.193-201
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• 2010

Hepatic fibrosis represents the main complication of most chronic liver disorders and, regardless of its etiology, is characterized by excessive deposition of extracellular matrix components. In this study, we examined that 1-O-Hexyl-2,3,5-Trimethylhydroquinone (HTHQ), a potent anti-oxidative agent, could prevent experimental hepatic fibrosis induced by dimethylnitrosamine (DMN) in male SD rats. Except for vehicle control group, other groups were induced hepatic fibrosis by intraperitoneal injection with DMN (10 mg/ml/kg) on 3 consecutive days weekly for 4 weeks. During the same 4 weeks, control and DMN groups were given vehicle and HTHQ 50, 100 and 200 groups were orally administered HTHQ (50, 100, 200 mg/kg respectively). In HTHQ 100 and 200 groups, relative liver weight and serum chemistry level improved significantly. HTHQ reduced hydroxyproline (p < 0.05) and malondialdehyde (p < 0.05) level in the liver. Histopathological examination of H&E, Masson's trichrome stain showed the reduced fibrotic septa in HTHQ 100 and 200 groups. HTHQ administration showed reduced mRNA level of PDGF (Platelet-derived growth factor), $\alpha$-SMA ($\alpha$-smooth muscle actin) and TGF-$\beta$ (transforming growth factor-$\beta$) than DMN-induced hepetic fibrosis animals in the liver tissue. In this study, we showed that HTHQ improves against DMN-induced liver fibrosis in male SD rats.

• Journal of The Korean Society of Clinical Toxicology
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• v.11 no.1
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• pp.49-52
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• 2013

Fentanyl, a synthetic, highly selective opioid ${\mu}$-receptor agonist, is 50 to 100 times more potent than morphine. The low molecular weight, high potency, great transdermal permeation rate and lipid solubility of fentanyl make it very suitable for transdermal administration. Durogesic is a novel matrix transdermal system providing continuous systemic delivery of fentanyl. In recently, there are many reports that misused or overused fentanyl transdermal patches result in severe intoxication of fentanyl. We present a case of fentanyl toxicity with misused durogesic transdermal patch and discuss the safe and appropriate application of the patches. In conclusion, fentanyl patches should be used in opioid tolerant patients and prescribed at the lowest possible dose and titrated upward as needed. All patients and their caregivers should be educated safe application of fentanyl patches and advised to avoid exposing the patches application site to direct external heat sources, such as heating pads, or electric blankets, heat lamps, sauna, hot tubs, and others. In addition, concomittant medications that affect fentanyl's metabolism should be avoided.

• Toxicological Research
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• v.22 no.3
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• pp.283-291
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• 2006

The survival and growth of epithelial cells depends on adhesion to the extracellular matrix. An adhesion signal may regulate the initiation of differentiation, since epidermal keratinocytes differentiate as they leave the basement membrane. A metabolically dead cornified cell envelope is the end point of epidermal differentiation so that this process may be viewed as a specialized form of programmed cell death. In order to investigate the precise cellular signaling events loading to terminal differentiation of keratinocytes, we have utilized HaCaT cells to monitor the biological consequences of $Ca^{2+}$ stimulation and numerous downstream signaling pathways, including activation of the extracellular signal-regulated protein kinase(ERK) pathway and activation of phosphatidylinositol 3-kinase(PI3K). The results presented in this study show that $Ca^{2+}$ function as potent agents for the differentiation of HaCaT keratinocytes, and this differentiation depends or the activation of ERK, Protein kinase B(PKB) and p70 ribosomal protein S6 kinase(p70S6K). Finally, the results show that the expression of Activator protein 1(AP-1; c-Jun and c-Fos) increased following $Ca^{2+}$-mediated differentiation of HaCaT cells, suggesting that ERK-mediated AP-1 expression is critical for initiating the terminal differentiation of keratinocytes.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.1
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• pp.63-71
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• 2004

The human skin is constantly exposed to environmental irritants such as ultraviolet, smoke, chemicals. Free radicals and reactive oxygen species (ROS) caused by these environmental facts play critical roles in cellular damage. These irritants are in themselves damaging to the skin structure but they also participate the immensely complex inflammatory reaction. The purpose of this study was to investigate the skin cell protective effect of Juniperus chinensis xylem extract on the UV and SLS-induced skin cell damages. We tested free radical and superoxide scavenging effect in vitro. We found that Juniperus chinensis xylem extracts had potent radical scavenging effect by 98％ at 100 $\mu\textrm{g}$/mL. Fluorometric assays of the proteolytic activities of matrix metalloproteinase-l(MMP-1, collagenase) were performed using fluorescent collagen substrates. UV A induced MMP-1 synthesis and activity were analyzed by enzyme-linked immunosorbent assay (ELISA) and gelatin-based zymography in skin fibroblasts. The extract of Juniperus chinensis showed strong inhibitory effect on MMP-1 activities by 97％ at 100 $\mu\textrm{g}$/mL and suppressed the UVA induced expression of MMP-1 by 79％ at 25 $\mu\textrm{g}$/mL. This extract also showed strong inhibition on MMP-2 activity in UVA irradiated fibroblast by zymography. We also examined anti-inflammatory effects by the determination test of proinflammatory cytokine, interleukin 6 in HaCaT keratinocytes. In this test Juniperus chinensis decreased expression of interleukin 6 about 30％. Expression of prostaglandin E$_2$, (PGE$_2$) after UVB irradiation was measured by competitive enzyme immunoassay (EIA) using PGE$_2$ monoclonal antibody. At the concentrations of 5-50 $\mu\textrm{g}$/mL of the extracts, the production of PGE$_2$ by HaCaT keratinocytes (24 hours after 10 mJ/$\textrm{cm}^2$ UVB irradiation) was significantly inhibited in culture supernatants (p〈0.05). The viability of cultured HaCaT keratinocytes was significantly reduced at the doses of above 10 mJ/$\textrm{cm}^2$ of UVB irradiation, but the presence of these extracts improved cell viability comparing to control after UVB irradiation. We also investigated the protective effect of this extract in sodium lauryl sulfate (SLS)-induced irritant skin reactions from 24 hour exposure. Twice a day application of the extract for reducing local inflammation in human skin was done. Irritant reactions were assessed by various aspects of skin condition, that is, erythema (skin color reflectance) and transepidermal water loss (TEWL). After 5 days the extract was found to reduce SLS-induced skin erythema and improve barrier regeneration when compared to untreated symmetrical test site. In conclusion, our results suggest that Juniperus chinensis can be effectively used for the prevention of UV and SLS-induced adverse skin reactions such as radical production, inflammation and skin cell damage.

• Korean Journal of Food Science and Technology
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• v.41 no.6
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• pp.700-705
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• 2009

Several studies have demonstrated that chlorophyll has many beneficial properties, including anti-inflammatory, anti-tumor, and antioxidant properties. Chlorophyll has been also shown to have an excellent chemopreventive potential against skin tumor. Its preventive mechanism against skin tumor, however, has not been examined in detail. Furthermore, the effects of chlorophyll on UVB-induced cellular responses have not been investigated. Solar UV radiation, in particular its UVB component, is the primary cause of many adverse biological effects, which is responsible for the photoaging and skin cancer. We investigated the preventive effects of chlorophyll a on UVB-mediated responses in human immortalized HaCaT kerationocytes and normal human fibroblast. We found that treatment of chlorophyll a markedly inhibited UVB-induced generation of reactive oxygen species and lipid peroxidation. Chlorophyll a also prevented UVB-induced MMP-1 expression and MMP-2 activation and increased Type I pN collagen synthesis. These results suggest that chlorophyll a is a potent candidate for the prevention and treatment of UVB-induced skin cancer and photoaging.

• Journal of Periodontal and Implant Science
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• v.26 no.4
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• pp.889-905
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• 1996

It is known that growth factors function as potent biologic mediators regulating numerous activities of wound healing via cell proliferation, migration and extracellular matrix formation and they also promote periodontal regeneration. But, method of growth factor application is controversial yet. So purpose of this study is to evaluate the effect of demineralized root surface as one of method of growth factor application. The ginigival fibroblasts were primary cultured and fifth or sixth subpassages were used in these experiments. In first experiment, root surface blocks demineralized with 100mg/ml tetracycline for 5 minutes and pH 1 citric acid for 3 minutes(experimental groups) and nonteminerilized root surface blocks (control groups) were placed in 100ng/ml PDGF-BB for 5 minutes. Then the cells were seeded on each root surface blocks and cultured for 6, 24, 48, 72 hours. In second experiment, root surface blocks deminerilized with tetracycline and citric acid and nondemineralized root surface blocks were placed in 200ng/ml PDGF-BB for 5 minutes and another non-demineralized root surfcae blocks were placed in DMEM without PDGF-BB. At 1, 2, 4, 6, 8 days, the cells were seeded in 24-well plate and using of each eluent, cultured for 72 hours. The results of the four determinants were presented as mean and S.D.. The results were as follows : The attachment and proliferation of human gingival fibroblast on root surface were more increased when PDGF-BB was applicated on root surfrace demineralized with tetracycline or citric acid than non-demineralized root surface. And, in comparision tetracycline with citric acid, there were more attachment and proliferation of human gingival fibroblast on root surface demineralized with tetracycline than citric acid, and proliferation of human gingival fibroblast on demineralized root surface was increased time dependently 1 day to 3 days. In second experiment using eluent, proliferation of human gingival fibroblast was more increased to 6 days when human gingival fibroblast was cultured in eluent that PDGF-BB was applicated on demineralized root surface than two control groups, and degree of proliferation was decreased time dependently 1 day to 6 days. Proliferation of human gingival fibroblast cultured in eluent without PDGF-BB was constant 1 day to 6 days. After 6 days, degree of proliferation of human gingival fibroblast was similar in four groups. This means that release duration of PDGF-BB from demineralized root surface is 6 days. And in comparision tetracycline with citric acid, there was more proliferation of human gingival fibroblast in tetracycline-treated group than citric acid. In conclusion, demineralized root surface as primary site for PDGF-BB application, especially demineralized with tetracycline has important roles in attachment and proliferation of human gingival fibroblast, and may be useful clinical applications in periodontal regenerative procedures.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.35 no.4
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• pp.287-292
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• 2009

Human skin is constantly exposed to environmental irritants such as smoke, chemicals and ultraviolet (UV). Free radicals and reactive oxygen species (ROS) caused by these environmental irritants play critical roles in cellular damage. In this study, to investigate the skin cell protective effect of Ophioglossum vulgatum extract, we investigated its effects on intercellular antioxidative activity and UVA-induced MMP expression in human dermal fibroblasts (HDFs). The dried O. vulgatum was extracted in a mixture of ethanol and water (1 : 1) for 24 h at room temperature. The extract was filtered and concentrated in vacuo and lyophilized. For testing intracellular ROS scavenging activity the cultured HDFs were analyzed by increase in DCF fluorescence upon exposure to UVB $20\;mJ/cm^2$. After treatment of O. vulgatum extracts, intracellular ROS levels were measured by luminescence spectrophotometer. Enzyme linked immuno sorbent assay (ELISA), and RT-PCR techniques were used for evaluating the effects of O. vulgatumon on MMP protein and mRNA expression in UVA irradiated HDFs. O. vulgatum extract was found to have ROS scavenging activity with the $IC_{50}$ values of $18.2\;{\mu}g/mL$ against superoxide radicals in the xanthine/xanthine oxidase system. After treatment of O. vulgatum extracts, the oxidation of CM-DCFDA was inhibited effectively and O. vulgatum extracts showed a potent free radical scavenging activity by 30.4 % at $100\;{\mu}g/mL$ in UVB-irradiated HDFs. UVA induced MMP protein expression was reduced 37.7 % by treatment with O. vulgatum extract, and MMP-1 mRNA expression was reduced in a dose-dependent manner. Taken together, these results suggest that O. vulgatum extract prevents the skin cell damage induced by UV irradiation, and implies that O. vulgatum extract may be useful as a new ingredient for anti-aging cosmetics.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.2
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• pp.227-233
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• 2004

Chronic exposure to solar radiation, particularly ultraviolet (UV) light, causes a variety of adverse reactions on human skin, such as sunburn, photoaging and photocarcinogenesis. Free radicals and reactive oxygen species (ROS) caused by UV exposure or other environmental facts play critical roles in cellular damage. And, repeated-UV irradiation activated the expression of the matrix metalloproteinase (MMP) and induced skin irritation. Therefore, the development of effective and safe photoprotectants that can reduce and improve the skin damage has been required. The purpose of this study was to investigate the photo-protective effect of several chinese medical plants (Juniperus chinensis) on the UV -induced skin cell damages. We tested free radical and superoxide scavenging effect in vitro. Fluorometric assays of the proteolytic activities of MMP-1 (collagenase) were performed using fluorescent collagen substrates. UVA induced MMP-1 synthesis and activity were analyzed by enzyme-linked immunosorbent assay (ELISA) and gelatin-based zymography in skin fibroblasts. We also examined anti-inflammatory effects by the determination test of proinflammatory cytokine, interleukin 6 in HaCaT keratinocytes. Expression of prostaglandin E$_2$ (PGE$_2$) after UVB irradiation was measured by competitive enzyme immunoassay(EIA) using PGE$_2$ monoclonal antibody. In the human skin we tested anti-irritation effect on the SLS-induced damage skin after appling the extract containing emulsion. We found that Juniperus chinensis extract had potent radical scavenging effect by 98% at 100$\mu\textrm{g}$/mL. The extract of Juniperus chinensis showed strong inhibitory effect on MMP-1 activities by 97% at 100 $\mu\textrm{g}$/mL and suppressed the UVA induced expression of MMP-1 by 79% at 25$\mu\textrm{g}$/mL. This extract also showed strong inhibition on MMP-2 activity in UVA irradiated fibroblast by zymography. In the test of proinflammatory cytokines of human keratinocytes Juniperus chinensis extract decreased expression of interleukin 6 about 30%. The amount of PGE$_2$ by HaCaT keratinocytes was significantly increased at the doses of above 10 mJ/$\textrm{cm}^2$ of UVB (p < 0.05). At the concentrations of 3.2-25$\mu\textrm{g}$/mL of this extract, the production of PGE$_2$ by HaCaT keratinocytes (24 h after 10mJ/$\textrm{cm}^2$ UVB irradiation) was significantly inhibited in culture supernatants (p < 0.05). In SLS-induced skin irritation model in vivo, we found to reduce skin erythema and improve barrier recovery after appling Juniperus chinensis extract containing emulsion when compared to irritated non-treated and placebo-treated skin. Our results suggest that Juniperus chinensis extract can be effectively used for the prevention of UV and SLS-induced adverse skin reactions and applied as anti-aging and anti-irritation cosmetics.