• 한국환경성돌연변이발암원학회지
• /
• 제19권1호
• /
• pp.46-55
• /
• 1999

To develop a chemopreventive strategy based on the different stages of premalignant lesions, we hypothesized that the inhibitory effect of chemopreventive agents is influenced by different promotion stages during carcinogenesis. DMBA-TPA-induced skin carcinogenesis was used with ICR mice and chlorophyllin (CHL) was applied as a chemopreventive agent. In vitro assay was performed with Salmonella typhi. TA100 to observe any anti-mutagenic activity of CHL against DMBA. Pre-initiation and pre-promotion effects of CHL were observed by CHL treatment before initiation and before promotion. To evaluate the inhibitory effect at different promotion stages, each group was divided into three subgroups after TPA promotion for 6, 18 and 24 weeks, respectively ; the first subgroup was immediately sacrificed after termination of TPA, the second subgroup was treated with CHL, and the third subgroup was sacrificed 8 weeks after termination of TPA without CHL treatment. The degrees of epithelial dysplasia, papilloma formation, and invasive carcinoma were observed histologically, and GST-Pi expression was observed immunohistochemically. ODC mRNA level was analyzed by reverse transcriptase-polymerase chain reaction. Results showed : CHL dose-dependently inhibited the mutation of Salmonella typhi. TA100; the incidence of epithelial dysplasia and papilloma formation was lower in pre-initiation and pre-promotion CHL-treated mice than DMBA-TPA-treated mice; no invasive carcinoma developed in pre-initiation CHL-treated groups, while 67% of DMBA-TPA treated mice had carcinomas; GST-Pi expression decreased when CHL was treated before initiation and before promotion; and when CHL was treated after termination of TPA application at 18 and 24- week-TPA promotion stages, respectively, the incidence of epithelial dysplasia and papilloma was markedly reduced compared to non-treated groups. When comparing the incidence of epithelial dysplasia and papilloma between the immediately-sacrificed subgroup and the non-treated group with a waiting period, we speculated that the 18-week-TPA promotion stage might belong to the promoter-independent progression stage. At the 18-week-TPA promotion stage, the level of ODC mRNA in the CHL-treated group was clearly reduced to the level of normal tissue. Taking these results together, CHL showed both anti-initiation and anti-promotion effects, while the inhibitory effect of CHL was prominent in the 18-week-TPA promotion stage. However, CHL seems to be incapable of completely blocking the progression in the 24-week-TPA promotion stage.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제17권2호
• /
• pp.137-152
• /
• 1995

This study was designed to evaluate the bone formation capability of the bone substitute when compared with autogenic bone, freeze-dried demineralized allogeneic bone and bioglass into parietal bone of the rats. We made the parietal bone defects in $7{\times}7mm$ size on rats and has performed the bone graft in each experimental groups. Postoperatively 1, 2, 4, 6, 8, weeks, each specimen stained with H & E, Masson's trichrome methods. We evaluated the osteogensis capability in each groups. The result were as follow : 1. Inflammatory cell infiltration approached at 1 week and disappeared at 4 weeks in all experimental group, expecially severe in freeze-dried demineralized allogeneic bone group. 2. New capillry proliferation was increased in autogeneic bone graft group than any other groups and was increased till 2 weeks and decreased in freeze-dried demineralized allogeneic bone group and was few in bioglass group. 3. Osteoblastic activity increased in autogeneic bone and freeze-dried demineralized allogeneic bone groups till 4 weeks, and decreased in 6 weeks which no difference between these groups. But, few occurred in bioglass group till 6 weeks. 4. Initial osteoclastic activity was prominent in freeze-dried demineralized allogeneic bone group and few in autogeneic bone group. 5. New bone formation bega at 1 week in autograft and freeze-dried demineralized allogenic bone groups, but, mild new bone formation at 8 weeks in bioglass.

• Biomolecules & Therapeutics
• /
• 제18권2호
• /
• pp.226-232
• /
• 2010

The aim of this study was to investigate the effect of atrovasatatin on the pharmacokinetics of nicardipine after oral and intravenous administration of nicardipine to rats. Nicardipine was administered orally (12 mg/kg) or intravenously (i.v., 4 mg/kg) without or with oral administration of atrovasatatin (0.3 or 1.0 mg/kg) to rats. The effect of atorvastatin on the P-glycoprotein (P-gp) as well as CYP3A4 activity was also evaluated. Atorvastatin inhibited CYP3A4 enzyme activity in a concentration-dependent manner with 50% inhibition concentration ($IC_{50}$) of 48 ${\mu}M$. Compared to the controls (nicardipine alone), the area under the plasma concentration-time curve (AUC) of nicardipine was significantly (1.0 mg/kg, p<0.05) greater by 16.8-45.4%, and the peak plasma concentration ($C_{max}$) was significantly (1.0 mg/kg, p<0.05) higher by 28.0% after oral administration of nicardipine with atorvastatin, respectively. Consequently, the relative bioavailability (R.B.) of nicardipine was increased by 1.17- to 1.45-fold and the absolute bioavailability (A.B.) of nicardipine with atrovasatatin was significantly greater by 16.7-20.9% compared to that of the controls (14.3%). Compared to the i.v. control, atrovasatatin did not significantly change pharmacokinetic parameters of i.v. administration nicardipine. The enhanced oral bioavailability of nicardipine by atorvastatin suggests that CYP3A subfamily-mediated metabolism were inhibited in the intestine and/or in the liver rather than P-gp-mediated efflux of nicardipine. Based on these results, modification of nicardipine of dosage regimen is required in the patients. Human studies are required to prove the above hypothesis.

• Biomolecules & Therapeutics
• /
• 제19권3호
• /
• pp.364-370
• /
• 2011

The purpose of this study was to investigate the effects of curcumin on the pharmacokinetics of loratadine in rats. The effect of curcumin on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activity was evaluated. Pharmacokinetic parameters of loratadine were also determined after oral and intravenous administration in the presence or absence of curcumin. Curcumin inhibited CYP3A4 activity with an IC50 value of 2.71 ${\mu}M$ and the relative cellular uptake of rhodamine-123 was comparable. Compared to the oral control group, curcumin significantly increased the area under the plasma concentration-time curve and the peak plasma concentration by 39.4-66.7% and 34.2-61.5%. Curcumin also significantly increased the absolute bioavailability of loratadine by 40.0-66.1% compared to the oral control group. Consequently, the relative bioavailability of loratadine was increased by 1.39- to 1.67-fold. In contrast, curcumin had no effect on any pharmacokinetic parameters of loratadine given intravenously, implying that the enhanced oral bioavailability may be mainly due to increased intestinal absorption caused via P-gp and CYP3A4 inhibition by curcumin rather than to reduced renal and hepatic elimination of loratadine. Curcumin enhanced the oral bioavailability of loratadine in this study. The enhanced bioavailability of loratadine might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced fi rst-pass metabolism of loratadine via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by curcumin.

• 한국치위생학회지
• /
• 제16권3호
• /
• pp.417-426
• /
• 2016

Objectives: The objective of the study was to investigate the related factors of preventive behavior experience toward dental caries and periodontal disease in Korean adolescents. Methods: The study subjects were 72,060 adolescents in 800 schools who completed 2014 Korean Youth Risk Behavior Web-based survey. Dependent variables included general characteristics of the subjects, oral health behavior, and oral disease experience. The experience rate of sealant and scaling showed the prevention behavior of dental caries and periodontal disease. Data were analyzed by IBM SPSS statistics 20.0. Results: The experience rate of sealant accounted for 26.9%. The experience of sealant was related with gender, school, maternal education level, economic status, vigorous physical activity, smoking, usual stress, fruit consumption, milk consumption, soda consumption, snack consumption, tooth brushing, oral health education experience, periodontal bleeding and pain, mucosal disorders, and bad breath. The experience rate of scaling was 22.6%. The experience of scaling was related with gender, school, city division, learning achievement, maternal education level, economic status, residential type, vigorous physical activity, usual stress, fruit consumption, milk consumption, tooth brushing, oral health education experience, periodontal bleeding and pain, mucosal disorders, and bad breath. Conclusions: To expand preventive oral health behavior in the adolescents, it is necessary to support the systematic policy making and monetary establishment in the future.

• Journal of Pharmaceutical Investigation
• /
• 제41권5호
• /
• pp.273-278
• /
• 2011

The aim of this study was to investigate the effect of efonidipine on the pharmacokinetics of warfarin after oral and intravenous administration of warfarin in rats. Warfarin was administered orally (0.2 mg/kg) or intravenously (0.05 mg/kg) without or with oral administration of efonidipine (1 or 3 mg/kg) in rats. The effect of efonidipine on the cytochrome P450 (CYP) 3A4 activity was also evaluated. Efonidipine inhibited CYP3A4 enzyme activity with 50% inhibition concentration ($IC_{50}$) of $0.08{\mu}M$. Compared to those in the oral control group (warfarin without efonidipine), the area under the plasma concentration-time curve (AUC) of warfarin was significantly greater (1 mg/kg, P<0.05; 3 mg/kg, P<0.01) by 25.9-59.0%, and the peak plasma concentration ($C_{max}$) was significantly higher (3 mg/kg, P<0.05) by 26.2% after oral administration of warfarin with efonidipine, respectively. The total body clearance of warfarin was significantly (3 mg/kg, P<0.05) decreased by efonidifine. Consequently, the relative bioavailability of warfarin was increased by 1.26- to 1.59-fold and the absolute bioavailability of warfarin with efonidipine was significantly greater by 59.7-75.4 % compared to that in the control group (47.4%). In contrast, efonidipine had no effect on any pharmacokinetic parameters of warfarin given intravenously. Therefore, the enhanced oral bioavailability of warfarin may be due to inhibition of CYP 3A4-mediated metabolism in the intestine and/or liver and to reduction of total body celarance rather than renal elimination, resulting in reducing first-pass metabolism by efonidipine.

• International Journal of Oral Biology
• /
• 제42권3호
• /
• pp.91-97
• /
• 2017

Although anti-aging activities of melatonin, a hormone secreted by the pineal gland, have been reported in senescence-accelerated mouse models and several types of cells, its impact and mechanism on the senescence of human dental pulp cells (HDPCs) remains unknown. In this study, we examined the impact of melatonin on cellular premature senescence of HDPCs. Here, we found that melatonin markedly inhibited senescent characteristics of HDPCs after exposure to hydrogen peroxide ($H_2O_2$), including the increase in senescence-associated ${\beta}$-galactosidase (SA-${\beta}$-gal)-positive HDPCs and the upregulation of p21 protein, an indicator for senescence. In addition, as melatonin attenuated $H_2O_2$-stimulated phosphorylation of c-Jun N-terminal kinase (JNK), while selective inhibition of JNK activity with SP600125 significantly attenuated $H_2O_2$-induced increase in SA-beta-gal activity. Results reveal that melatonin antagonizes premature senescence of HDPCs via JNK pathway. Thus, melatonin may have therapeutic potential to prevent stress-induced premature senescence, possibly correlated with development of dental pulp diseases, and to maintain oral health across the life span.

• Journal of Oral Medicine and Pain
• /
• 제25권4호
• /
• pp.345-353
• /
• 2000

This study was to investigate normal salivary flow rates and normal indices of Quantitative analysis of salivary scintigraphy. 96 adult volunteers were studied by Questionnaire evaluating salivary conditions and clinical examinations. 35(male 23, female 12, age range 23-31years) that absented subjective and objective symptoms related saliva were classified as normal group. The normal group underwent measurement unstimulated and stimulated salivary flow rates and salivary scintigraphy. The obtained results were as follows: 1. There were not significant in sex differences of unstimulated and stimulated salivary flow rates. The unstimulated salivary flow rate was $0.66{\pm}0.41g/min$, stimulated salivary flow rates was $1.61{\pm}0.69g/min$. 2. As comparing of parameters of salivary scintigraphy, the Uptake ratio(UR), $T_{max}$, $T_{min}$, Maximum accumulation (MA), Maximum secretion(MS) of parotid and submandibular glands were not significant in sex and side-ralated differences. 3. The UR, $T_{max}$, MA, MS of parotid gland were significantly higher than those of submandibular gland; in the parotid gland, UR, $3.67{\pm}0.88$, $T_{max}$, $18.77{\pm}0.43min$, MA, $41.35{\pm}9.22%$, MS, $43.13{\pm}9.13%$; in the submandibular gland, UR, $3.04{\pm}0.10$, $T_{max}$, $18.48{\pm}0.52min$, MA, $36.47{\pm}14.18%$, MS, $36.88{\pm}12.20%$. 4. As classifying of time-activity curve, the most of parotid gland was N-type(97.1%), submandibular gland was observed in order of M-type(67.1%), N-type(21.4%), F-type(11.4%), however, was not observed S-type. 5. As the type of time-activity curve of submandibular gland was more flattened, the UR, $T_{max}$, MA, MS were significantly decresed.

• Journal of Oral Medicine and Pain
• /
• 제40권3호
• /
• pp.115-123
• /
• 2015

Purpose: The aim of this study was to elucidate the coordination patterns of the sternocleidomastoid and posterior cervical muscles in response to symmetrical and asymmetrical jaw functions in normal adults. Methods: Twenty-seven healthy volunteers (8 females, 19 males; mean age, $30.4{\pm}2.5$ years) participated in this study. Surface electromyography (EMG) was used to record activities in the masseter, suprahyoid, sternocleidomastoid, and posterior cervical muscles at rest and during maximum tooth clenching, biting of a cotton roll with the anterior teeth, unilateral biting of a cotton roll with the posterior teeth, bilateral biting of cotton rolls with the posterior teeth, and jaw opening while seated. Normalized amplitude, activity indices, and asymmetry indices were compared between the muscles and the jaw tasks. Results: During symmetrical jaw functions (e.g., tooth clenching, biting with the anterior teeth, bilateral biting with the posterior teeth, jaw opening), the sternocleidomastoid and posterior cervical muscles showed elevated EMG amplitudes compared with the resting condition. The co-activation pattern of the sternocleidomastoid muscle was more pronounced than those of the posterior cervical muscles during these tasks. During asymmetrical jaw functions (e.g., unilateral biting with the posterior teeth), the ipsilateral sternocleidomastoid and masseter muscles showed higher contraction activity than did the contralateral muscles, but the contralateral posterior cervical muscles were more active than the ipsilateral muscles. Conclusions: The sternocleidomastoid and posterior cervical muscles were shown to be co-activated and coordinated anteroposteriorly or bilaterally according to symmetrical or asymmetrical jaw function. These results suggest an integrated neural control mechanism for the jaw and neck muscles, and provide further evidence supporting the intimate functional coupling between the trigeminal and cervical neuromuscular systems.

• 대한구순구개열학회지
• /
• 제7권2호
• /
• pp.123-132
• /
• 2004

The purpose of this study was to obtain normative nasalance scores for adult subjects speaking the Korean language. Additional objectives of the study were to determine if speaker sex played a role in differences in nasalance score and there was significantly correlation of nasalance score with nasalance slope score. The subjects include 75 healthy young Korean adults with normal oral and velopharyngeal resource and function. They had no history of speech problem, were judged as having normal speech and resonance at the time of testing, and had no upper respiratory tract infections or allergies at the time of testing. The Nasometer II 6400 was used to obtain nasalance scores and nasalance slope scores for /a/, /i/, /e/, /o/, /u/, /ja/, /je/, /wi/, /p'ap'i/ and /sasi/. The data of nasalance and nasalance slope were analyzed statistically. The mean nasalance score of the female was significantly higher than that of male at /a/, /i/, /wi/, /p'ap'i/ and /sasi/(p <0.10). The mean nasalance score of /i/ was highest and that of /o/ was the lowest. In this study, we could not and the relationship of the nasalance score and the closing slope score. However, there was negative correlation between the mean nasalance score and the opening slope score at ie/ and /;ai, positive to /sasi/. These normative nasalance scores for normal young adults speaking the Korean language provide important reference information for Korean cleft palate teams. In the future study of velopharygneal activity with the Nasometer, the opening slope score will be able to be the important parameter.