• The Journal of Korean Medicine
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• v.41 no.4
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• pp.1-11
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• 2020

Objectives: Objectives: The object of this study was to elucidate the possible effects on the pharmacokinetics of tamoxifen after single oral co-administration of Gamisoyo-san (GMSYS) with 2.5 hr-intervals combination therapy of tamoxifen with GMSYS. Methods: After 2.5 hr of 50 mg/kg of tamoxifen treatment, GMSYS 100 mg/kg was administered. The plasma was collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of GMSYS treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen were analysis as compared with tamoxifen single administered rats. Results: Although single co-administration with GMSYS with 2.5 hr-interval induced increased trends of plasma tamoxifen concentrations, there are no significant changes on the plasma concentrations of tamoxifen were demonstrated in tamoxifen and GMSYS 100 mg/kg co-administrated rats with 2.5 hr-intervals as compared to those of tamoxifen single 50 mg/kg treated rats, and also GMSYS co-administrated rats did not showed any significant changes on the all pharmacokinetic parameters as compared to those of tamoxifen single formula treated rats. Conclusions: According to the this study, single co-administration of GMSYS with 2.5 hr-intervals did not critically influenced on the oral bioavailability of tamoxifen, suggesting GMSYS did not critically influenced on the absorption and excretion of tamoxifen, the oral bioavailability, when they were co-administered with 2.5 hr-intervals, at the dose levels of tamoxifen 50 mg/kg and GMSYS 100 mg/kg.

• Journal of Society of Preventive Korean Medicine
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• v.21 no.2
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• pp.127-137
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• 2017

Objectives : In our previous study, single co-administration GMODT within 5 min significantly inhibited the oral bioavailability of tamoxifen through variable influences on the absorption and excretion of tamoxifen. Therefore, the object of this study was to elucidate the possible effects on the pharmacokinetics of tamoxifen after single oral co-administration of GMODT with 2.5 hr-intervals. Methods : After 50 mg/kg of tamoxifen treatment, GMODT 100 mg/kg was administered with 2.5 hr-intervals. The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of GMODT treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen (Tmax, Cmax, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered rats. Results : Two-half hr-interval co-administration with GMODT induced variable changes on the plasma tamoxifen concentrations as compared with tamoxifen single treated rats, and especially significant (p<0.05) increases of plasma tamoxifen concentrations were demonstrated at 0.5 (199.61%) and 1 hr (101.06%) after end of co-administration with GMODT, and also related significant (p<0.05) decreases of $t_{1/2}$ (-39.54%) and $MRT_{inf}$ (-43.94%) as compared with tamoxifen single formula treated rats, at dosage levels of tamoxifen 50 mg/kg and GMODT 100 mg/kg with 2.5 hr-intervals, in this experiment. Conclusions : According to the results, GMODT critically decreased on the oral bioavailability of tamoxifen through variable influences on the absorption and excretion of tamoxifen. Hence, the co-administration of GMODT and tamoxifen should be avoided in the comprehensive and integrative medicine, combination therapy of tamoxifen with GMODT on the breast cancer.

• Journal of Society of Preventive Korean Medicine
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• v.17 no.2
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• pp.139-155
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• 2013

Purpose : This study was aim to evaluate effects of pharmacodynamics and toxicity in combination therapy of donepezil with Gongjindan. The effects of Gongjindan co-administration on the pharmacokinetics (PK) of donepezil were observed after single and 7-day repeated oral co-administration with 1.5hr-intervals, to evaluate synergic pharmacodynamics and reduce toxicity of combination therapy of donepezil with Gongjindan. Materials and Methods : After 10mg/kg of donepezil treatment, Gongjindan100mg/kg was administered with 1.5hr-intervals. The plasma were collected at 30min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24hrs after end of first and last 7th donepezil treatment, and plasma concentrations of donepezil were analyzed using LC-MS/MS methods. Results : Gongjindan markedly inhibited the absorption of donepezilregardless of sample time, from 30min to 8hrs after end of first 1.5hr-interval co-administration as compared with donepezil single treated rats. Especially the absorption of donepezil was significantly decreased at 2, 4, 6 and 8hrs after co-administration as compared with donepezilsingle treated rats. Accordingly, the Cmax (-26.236%), $AUC_{0-t}$(-26.02%) and $AUC_{0-inf}$(-25.90%) of donepezil in 1.5hr-interval co-administered rats were dramatically decreased as compared with donepezilsingle treated rats, respectively. However, no meaningful changes on the plasma donepezil concentrations and pharmacokinetic parameters were detected after end of last 7th 1.5hr-interval co-administration as compared with donerezil single treated rats, except for non-significant slight increases of Tmax(16.67%) detected in co-administered rats as compared with donepezil single treated rats. Conclusion : These findings are considered as direct evidences that Gongjindan also decreased oral bioavailability of donerezil as inhibited the absorptions, when they were co-administered with 1.5hr-intervals, but they may be adapted after 7 days continuous repeated l.5hr-interval co-administration.

• Journal of Society of Preventive Korean Medicine
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• v.19 no.1
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• pp.145-159
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• 2015

Objective : In the previous study, co-administration of Gongjindan-gamibang (GJD) with sorafenib increased oral bioavailability of sorafenib through augment the absorption, therefore, the effects of GJD co-administration on the pharmacokinetics of sorafenib were observed after single and 7-day repeated oral co-administration with 3.5 hr-intervals in the present study. Method : After 50 mg/kg of sorafenib treatment, GJD 100 mg/kg was administered with 3.5 hr-intervals. The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of first and last 7th sorafenib treatment, and plasma concentrations of sorafenib were analyzed using LC-MS/MS methods. PK parameters of sorafenib ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with sorafenib single administered rats. Results : GJD markedly inhibited the absorption of sorafenib, from 1 hr to 24 hrs after end of first 3.5 hr-interval co-administration, the $C_{max}$ (-43.27%), $AUC_{0-t}$ (-56.29%) and $AUC_{0-inf}$ (-66.70%) of sorafenib in co-administered rats were dramatically decreased as compared with sorafenib single treated rats. However, GJD significantly increased the absorption of sorafenib, from 4 hr to 8 hrs after end of last 7th 3.5 hr-interval co-administration, the $AUC_{0-t}$ (34.08%) and $AUC_{0-inf}$ (37.31%) of sorafenib in co-administered rats were dramatically increased as compared with sorafenib single treated rats. Conclusion : Although GJD decreased the oral bioavailability of sorafenib through inhibition of gastrointestinal absorptions after end of first 3.5 hr-interval co-administration, it is observed that GJD increases the oral bioavailability of sorafenib as facilitated the absorption after end of last 7th repeated co-administration. Hence, the co-administration of GJD and sorafenib should be avoided in the combination therapy of sorafenib with GJD on anticancer therapy.

• Restorative Dentistry and Endodontics
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• v.38 no.3
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• pp.128-133
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• 2013

Objectives: This study was performed to evaluate the effect of blood contamination on the compressive strength (CS) of Root MTA (RMTA) modified with Calcium chloride ($CaCl_2$) and Disodium hydrogen phosphate ($Na_2HPO_4$) as setting accelerators over time. Materials and Methods: A total of 110 cylindrical specimens of RMTA were divided into 6 experimental groups as follows: Group1, RMTA; Group 2, RMTA modified with $CaCl_2$ (RMTA-C); Group 3, RMTA modified with $Na_2HPO_4$ (RMTA-N); Group 4, RMTA contaminated with blood; Group 5, RMTA-C contaminated with blood; Group 6, RMTA-N contaminated with blood. The CS of specimens in all groups was evaluated after 3 hr, 24 hr, and 1 wk. In the modified groups (groups 2, 3, 5, and 6) the CS of five specimens per group was also evaluated after 1 hr. Results: Blood contamination significantly reduced the CS of all materials at all time intervals (p < 0.05). After 3 hr, the CS of specimens in the RMTA groups (with and without blood contamination) was significantly lower than those in the RMTA-C and RMTA-N groups (p < 0.05). The CS values were not significantly different at the other time intervals. In all groups, the CS of specimens significantly increased over time (p < 0.05). Conclusions: Blood contamination decreased the CS of both original and accelerated RMTA.

• Journal of Life Science
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• v.17 no.9 s.89
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• pp.1255-1259
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• 2007

The purpose of this study was to elucidate incidence of $VO_2$ plateau by comparing data derived from different time averaging intervals during incremental cycling exercise to $VO_2max$. Seventeen subjects (age: $23.5{\pm}3.3$ years and $VO_2max$: $3.65{\pm}0.73$ L/min, respectively) completed $VO_2max$ tests on cycle ergometer which breath by breath gas ex-change data were obtained. These data were time-averaged into 11-breath, 15, 30 and 60 s sampling intervals. The incidence of plateau were 100, 35, 24 and 6% for the 11 breath, 15 s, 30 s and 60 s averaging, respectively. No correlation was between ${\Delta}$ $VO-2$ at $VO_2max$ and $VO_2max$ (r=0.008). 53% (maximal HR within 10 b/min) and 100% $(RER{\geq}1.15)$ of subjects met the criteria for attainment of $VO_2max$. This data indicate that shorter sampling intervals (11 breath) is the most suitable for de-tection of the $VO_2$ plateau and RER can be used for the criteria for attainment of $VO_2max$ but not maximal HR. Also, the incidence of a plateau is not related to training status or physical fitness of subjects.

• Journal of Pharmaceutical Investigation
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• v.30 no.1
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• pp.55-59
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• 2000

Bioequivalence of two cisapride tablets, test drug ($Cisple^{\circledR}$ tablet: Hanmi Pharm Co., Ltd.) and reference drug ($Prepulsid^{\circledR}$ tablet: Janssen Pharm. Co., Ltd.), was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty two healthy male volunteers were divided randomly into two groups and administered the drug orally at the dose of 10 mg as cisapride in a $2{\times}2$ crossover study. There was a week washout period between administrations. Blood samples were taken at predetermined time intervals for 36 hr and the plasma concentration of cisapride was determined by a HPLC method. $AUC_{0-36hr}$ (area under the plasma concentration-time curve from time zero to 36 hr), $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were estimated from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed no difference in $AUC_{0-36hr},\;C_{max}\;and\;T_{max}$ between two products. The apparent differences of these parameters between two products were less than 20% (i.e., 5.38, 6.17 and 0.00% for $AUC_{0-36hr},\;C_{max}\;and\;T_{max},$ respectively). The powers $(1-\beta)$ for $AUC_{0-36hr},\;C_{max}\;and\;T_{max}$ were over 0.9. Minimal detectable differences $(\Delta)$ at ${\alpha}=0.05,\;1-{\beta}=0.8$ were less than 20% (i.e. 17.67, 14.84 and 19.72% for $AUC_{0-36hr},\;C_{max}\;and\;T_{max},$ respectively). The 90% confidence intervals $(\delta)$ for these parameters were also within ${\pm}20%$ $(i.e.\;-4.97\;{\le}{\delta}{\le}\;15.73,\;-2.53{\le}{\delta}{\le}\;14.86\;and\;-11.55{\le}{\delta}{\le}\;11.55$ for $AUC_{0-36hr},\;C_{max}\;and\;T_{max},$ respectively). These results satisfied the criteria of KFDA guidelines for bioequivalence, indicating the two tablets of cisapride were bioequivalent.

• KSBB Journal
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• v.24 no.1
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• pp.70-74
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• 2009

For continuous culture of cellulolytic enzymes production to saccharify food wastes, refill concentration of Mandel's medium for continuous culture was 0.5%, and refill intervals were determined to 12 hours by analysis of COD and total nitrogen concentration after 4-days batch culture in flask level. As a result, amylase and FPase productivities were 3.5 and 1.0 U/L.hr, respectively. In 10 L bioreactor, the batch culture mode was compared with fed-batch, fill-and-draw for continuous production of cellulolytic enzyme. Enzyme productivities were most high at batch culture and followed by fed-batch culture. Amylase and FPase activities were 42.3 and 5.6 U/L.hr at batch culture, and 23.0, 2.8 U/L.hr at fed-batch culture, respectively. As a result, in continuous cultivation of cellulolytic enzymes by T. inhamatum KSJ1, the mode of fed-batch was most effective in 10 L bioreactor.

• Journal of Korean Neurosurgical Society
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• v.64 no.6
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• pp.957-965
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• 2021

Objective : Rapid increase in intracranial pressure (ICP) can result in hypertension, bradycardia and apnea, referred to as the Cushing phenomenon. During decompressive craniectomy (DC), rapid ICP decreases can cause changes in mean atrial blood pressure (mABP) and heart rate (HR), which may be an indicator of intact autoregulation and vasomotor reflex. Methods : A total of 82 patients who underwent DC due to traumatic brain injury (42 cases), hypertensive intracerebral hematoma (19 cases), or major infarction (21 cases) were included in this prospective study. Simultaneous ICP, mABP, and HR changes were monitored in one minute intervals during, prior to and 5-10 minutes following the DC. Results : After DC, the ICP decreased from 38.1±16.3 mmHg to 9.5±14.2 mmHg (p<0.001) and the mABP decreased from 86.4±14.5 mmHg to 72.5±11.4 mmHg (p<0.001). Conversly, overall HR was no significantly changed in HR, which was 100.1±19.7 rate/min prior to DC and 99.7±18.2 rate/min (p=0.848) after DC. Notably when the HR increased after DC, it correlated with a favorable outcome (p<0.001), however mortality was increased (p=0.032) when the HR decreased or remained unchanged. Conclusion : In this study, ICP was decreased in all patients after DC. Changes in HR were an indicator of preserved autoregulation and vasomotor reflex. The clinical outcome was improved in patients with increased HR after DC.

• Korean Journal of Exercise Nutrition
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• v.23 no.3
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• pp.22-28
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• 2019

[Purpose] The purpose of this study was to investigate the effect of diet plus exercise training and detraining for 12 weeks on body composition, aerobic performance, and stress-related variables in obese women. [Methods] Twenty-five women in their 20s-40s with 30% body fat and body mass indices above 25 kg/m² were divided into HR_LT (heart rate at lactate threshold) and HR_LT + 5% groups. Dietary intervention of 70% recommended dietary allowance (RDA) and exercise treatment composed of aerobic exercises on a bicycle (30 min) and treadmill (30 min) were then performed. These interventions were performed three times a week for 12 weeks. [Results] Dietary intake was significantly decreased, while daily activity significantly increased within the 12-week intervention period, and this effect was sustained after 12 weeks of detraining. Exercise training based on dietary intake and daily activity presented a significantly decreased weight and % body fat, improvement of aerobic performance, and a significant increase in heart rate variability (HRV) (e.g., average of all RR intervals and the square root mean squared differences of successive RR intervals) as stress-related variables. It was also confirmed that the improvement of body composition and stress-related variables were maintained even after detraining. [Conclusion] Our results suggest that 70% RDA of dietary intervention and exercise training corresponding to HR_LT and HR_LT + 5% for 12 weeks were effective in improving body composition and aerobic performance, and relieving stress. In particular, enhanced HRV persisted for up to 12 weeks after the end of exercise training in obese women.