• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1118-1126
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• 2007

The purpose of this study was to examine the anti allergic effect in vivo and in vitro, and to observe single and four weeks repeated toxicity in mice of Bangpung-galgeun-tang (BGT). We investigated anti DNP IgE-mediated passive cutaneous anaphylaxis in rodents and compound 48/80-induced active systemic anaphylatic shock in mice after oral administration with BGT of 0.4 g/kg and 0.8 g/kg for 8 days, and also examined MTT assay, ${\beta}-hexosaminidase$ activity, IL-4 and $TNF-{\alpha}$ from RBL-2H3 and $TNF-{\alpha}$ from Raw264.7 after pre-treatment with BGT of 0.25 mg/ml, 0.5 mg/ml, 1 mg/ml and 2 mg/ml. To ascertain safety and toxicity of BGT, we divided into single and four weeks repeated administration test. In single test, three groups were administrated different dosages and routes (2 g/kg/i.p., 4 g/kg/i.p. and 15 g/kg /p.o.) of BGT, and in four weeks repeated test, 0.8 g/kg BGT was administrated. Control groups were administrated with only saline according to on Korean Food and Drug Administration, respectively. We observed attentively motality, abnormal clinical sign, body weight change, organ weight, AST and ALT of mice after BGT administration. BGT inhibited passive cutaneous anaphylaxis and active systemic anaphylatic shock by oral administration. All the concentrations of BGT from 0.25 to 2 mg/ml didn't have an effect on cell viability and cytotoxicity. In RBL-2H3, ${\beta}-hexosaminidase$ release, IL-4 and $TNF-{\alpha}$, and in Raw264.7, $TNF-{\alpha}$ were significantly reduced by treated all concentrations of BGT. During toxicity experiment period, there was no difference in body weight change, organ weight, AST and ALT among different dose groups. Death were found 3 mice from day 2 to day 3 in single test i.p. group. (2 g/kg, 4 g/kg). Several individuals of single test i.p. group were observed that decreased locomotor activity, exophthalmos, bloodshot eyes, loss of eyesight and so on in early period after administration. But there was no difference in clinical signs among p.o. group. These results indicate that BGT have inhibition effects on allergy and suggest that no observable effect level of the test orally administration was considered to be more than 2 g/kg in mice under the conditions employed in this study.

• 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.

• Biomedical Science Letters
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• v.5 no.1
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• pp.59-66
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• 1999

To evaluate the effect of repeated treatment of xylene on its metabolism, m-xylene (0.25 ml of 50% in olive oi1/100 g body weight) has been intraperitoneally given to the rats 1, 4, 8, 12 and 16 times every other day. m-Xylene was once more administered to the animals after 24 hrs since last injection of it. And then the animals were sacrificed after 24 hrs. Four times xylene treated rats showed the significantly elevated urinary m-methylhippuric acid, compared to those treated with the single dose of m-xylene with the continued similiar high levels of urinary m-methylhippuric acid up to the animals pretreated 12 times and then those treated 16 times defined the significantly decreased urinary m-methylhippuric acid compared to those treated 12 times. On the other hand, hepatic aniline hydroxylase and alcohol dehydrogenase activities demonstrated a gradual increase from the first group to the 12 times xylene-treated animals, but those treated 16 times showed the significantly decreased value compared with the 12 times treated-group. And aldehyde dehydrogenase activities in rats treated with m-xylene 8, 12 or 16 times were significantly decreased compared to those pretreated one or four times. In the early stage of xylene administration, proliferation of SERs were seen whereas SERs were decreased and RERs were clearly increased in xylene-treated rats 16 times. These results indicate that the frequency of xylene injection may influence upon the changes in xylene metabolite, m-methylhippuric acid and it may be due to induction of xylene metabolizing enzymes.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3945-3949
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• 2015

Background: For brachytherapy of cervical cancer, applicator shifts can not be avoided. The present investigation concerned Utrecht interstitial applicator shifts and their effects on organ movement and DVH parameters during 3D CT-based HDR brachytherapy of cervical cancer. Materials and Methods: After the applicator being implanted, CT imaging was achieved for oncologist contouring CTVhr, CTVir, and OAR, including bladder, rectum, sigmoid colon and small intestines. After the treatment, CT imaging was repeated to determine applicator shifts and OARs movements. Two CT images were matched by pelvic structures. In both imaging results, we defined the tandem by the tip and the base as the marker point, and evaluated applicator shift, including X, Y and Z. Based on the repeated CT imaging, oncologist contoured the target volume and OARs again. We combined the treatment plan with the repeated CT imaging and evaluated the change range for the doses of CTVhr D90, D2cc of OARs. Results: The average applicator shift was -0.16 mm to 0.10 mm for X, 1.49 mm to 2.14 mm for Y, and 1.9 mm to 2.3 mm for Z. The change of average physical doses and EQD2 values in Gy${\alpha}/{\beta}$ range for CTVhr D90 decreased by 2.55 % and 3.5 %, bladder D2cc decreased by 5.94 % and 8.77 %, rectum D2cc decreased by 2.94 % and 4 %, sigmoid colon D2cc decreased by 3.38 % and 3.72 %, and small intestines D2cc increased by 3.72 % and 10.94 %. Conclusions: Applicator shifts and DVH parameter changes induced the total dose inaccurately and could not be ignored. The doses of target volume and OARs varied inevitably.

• Journal of Embryo Transfer
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• v.24 no.1
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• pp.47-55
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• 2009

This study was performed to investigate the possibility of repeated superovulation treatment at interval from 27 days to 41 days in Hanwoo cattle and to compare with superovulation effect between doses of FSH 200 mg and FSH 400 mg. Different doses of FSH (200 mg or 400 mg) were injected at Day 8 after controlled internal drug release (CIDR) treatment for superovulation of Hanwoo donors following CIDR treatment (Day 8 after the estrus). Superovulation was repeated four times for one donor and number of corpus luteum (CL), number of embryos, number of transferable embryos and pregnancy rate after embryo transfer (ET) were investigated. 5 cows were used for each FSH treatment (10 cows in total). Average number of CL were $10.16{\pm}3.85$ and $11.56{\pm}2.35$ for the donors treated with FSH 200mg and FSH 400mg, respectively. Average number of embryos collected were $8.85{\pm}4.05$ and $8.30{\pm}1.73$ for the donors treated with FSH 200 mg and FSH 400 mg, respectively. Average number of transferable embryos were $5.48{\pm}2.45$ and $4.58{\pm}2.23$ for the donors treated with FSH 200 mg and FSH 400 mg, respectively. The pregnancy rate following ET with embryos collected from 200 mg FSH treated donors and 400 mg FSH treated donors were 61.9% and 53.8% respectively. The numbers of embryos tended to be decreased as the numbers of repeat of superovulation were elapsed. These results indicated that superovulation treatment by about a month to Hanwoo donors is usable and 200 mg of FSH is preferable for simple FSH treatment following CIDR treatment.

• Journal of Food Hygiene and Safety
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• v.27 no.1
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• pp.96-102
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• 2012

This study was designed to evaluate a repeated oral dose toxicity and immunomodulating activity of $Pulsatilla$ $koreana$ and $Artemisiae$ $annuae$ in Sprague-Dawley rats. The female rats were treated with $Pulsatilla$ $koreana$ and $Artemisiae$ $annuae$ of control group, low group (0.5 ml/kg), medium group (1 ml/kg), high group (2 ml/kg) for distilled water, intragastrically for 4 weeks, respectively. To ensure the safety of $Pulsatilla$ $koreana $ and $Artemisiae$ $annuae$ such as the following were observed and tested. We examined the body weight, the feed intake, the clinical signs, the ophthalmological test, the hematological and the serum biochemical analysis. We also observed the histopathological changes of liver and kidney in rats. Hematological results were the increase of neutrophils, lymphocytes and monocytes in the high dose group of $Pulsatilla$ $koreana$. The increase immune cells in the high dose group of $Pulsatilla$ $koreana$ might immunomodulating activity. No significant differences in body weight, feed intake, serum biochemical analysis and histopathological between control and fed group were found. In conclusion, $Pulsatilla$ $koreana$ and $Artemisiae$ $annuae$ is physiologically safe and improve immunomodulating activity.

• The Journal of Korean Society for Radiation Therapy
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• v.20 no.1
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• pp.1-9
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• 2008

Purpose: For head and neck cancer patients treated with radiation therapy, proper immobilization of intra-oral structures is crucial in reproducing treatment positions and optimizing dose distribution. We produced a man-made tongue immobilization device for each patient subjected to this study. Reproducibility of treatment positions and dose distributions at air-and-tissue interface were compared using man-made tongue immobilization devices and conventional tongue-bites. Materials and Methods: Dental alginate and putty were used in producing man-made tongue immobilization devices. In order to evaluate reproducibility of treatment positions, all patients were CT-simulated, and linac-gram was repeated 5 times with each patient in the treatment position. An acrylic phantom was devised in order to evaluate safety of man-made tongue immobilization devices. Air, water, alginate and putty were placed in the phantom and dose distributions at air-and-tissue interface were calculated using Pinnacle (version 7.6c, Phillips, USA) and measured with EBT film. Two different field sizes (3$\times$3 cm and 5$\times$5 cm) were used for comparison. Results: Evaluation of linac grams showed reproducibility of a treatment position was 4 times more accurate with man-made tongue immobilization devices compared with conventional tongue bites. Patients felt more comfortable using customized tongue immobilization devices during radiation treatment. Air-and-tissue interface dose distributions calculated using Pinnacle were 7.78% and 0.56% for 3$\times$3 cm field and 5$\times$5 cm field respectively. Dose distributions measured with EBT (international specialty products, USA) film were 36.5% and 11.8% for 3$\times$3 cm field and 5$\times$5 cm field respectively. Values from EBT film were higher. Conclusion: Using man-made tongue immobilization devices made of dental alginate and putty in treatment of head and neck cancer patients showed higher reproducibility of treatment position compared with using conventional mouth pieces. Man-made immobilization devices can help optimizing air-and-tissue interface dose distributions and compensating limited accuracy of radiotherapy planning systems in calculating air-tissue interface dose distributions.

• The Journal of Korean Society for Radiation Therapy
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• v.17 no.2
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• pp.155-160
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• 2005

Purpose : Many authors have been introduced field in field technique and 3-D conformal radiotherapy that increased the tumor dose as well as decreased the dose of abutting critical organ. These technique have multiple beam direction and small beam segments even below 10 MU(monitor unit)for each field. we have confirmed the influence of low MU on dose output and beam stability. Materials and Methods : To study the dose output, the dose for each field was always 90MU, but it divided into different segment size: 1, 2, 3, 5, 10, 15 segments, 90, 45, 30, 18, 9, 6 MU the measurements were carried out for X-ray energy 4 MV, 6 MV, 10 MV of three LINAC(Varian 600C, 2100C, 2100C, 2100C/D), in addition each measurement was randomly repeated three times for each energy. To study the field symmetry and flatness, X-omat V films were irradiated. After being developed, films were scanned and analyzed using densitometer. Results : Influence of low MU on dose is slightly more increase output about $1.2{\sim}2.9%$ in cGy/mu than 90MU, but may not changed beam quality(flatness or symmetry), Output stability depends on dose rate(PRF)rather than beam energy, field size. Conclusion : Presented result are under the limits(out put<3%, flatness<${\pm}3%$, symmetry<2%). The 3 accelerators are safe to use and to perform conformal radiotherapy treatments in small segments, small MU around 10MU. but Even if the result presented here under the limits, continuous adjustments and periodic QA should be done for use of small MU

• The Korean Journal of Nuclear Medicine Technology
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• v.17 no.2
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• pp.59-66
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• 2013

Purpose: Recently, there is an increase of the number of hospitals using auto dispenser to reduce occupational radiation exposure when drawing up of the $^{18}F-FDG$ dose (5.18 MBq/kg) in a syringe from the dramatic high activity of $^{18}F-FDG$ multidose vial. The aim of this study is to confirm that using auto dispenser actually reduces the radiation exposure for technologists. Also we analyzed the reproducibility of auto dispenser to find optimized dispensing method for the device. Materials and Methods: We conducted three experiments. Comparison of radiation exposure on chest and hands: The chest and hands exposure dose received by technologists during the injection were measured by electronic personal dosimeter (EPD) and ring TLD respectively. Reproducibility of dispensed volume: We draw up the normal saline into 5 and 2 mL syringe using auto dispenser by changing the volume from 1 to 15 mm for 5 times in the same setting of the volume. The weight of 5 normal saline dispensed from the device at same volume was measured using micro balance and calculated standard deviation and coefficient of variation. Reproducibility of dispensed radioactivity: We dispensed 362.6 $MBq{\pm}10%$ of $^{18}F-FDG$ in 5 and 2 mL syringes from the multidose vial of different specific activity. In the same setting of volume, we repeated dispensing for 4 times and compared standard deviation and coefficient of variation of radioactivity between 5 syringes. Results: There was significant difference in the average of chest exposure dose according to the dispensing methods (P<0.05). Also, when dispensing $^{18}F-FDG$ in manual method, exposure dose was 11.5 times higher in right hand and 4.8 times higher in left hand than in auto method. In the result of reproducibility of dispensed volume, standard deviation and coefficient of variation shows decline as the dispensing volume increases. As a result of reproducibility of dispensed radioactivity, standard deviation and coefficient of variation increases as the specific activity increases. Conclusion: We approved that the occupational radiation exposure dose of technologists were reduced when dispensing $^{18}F-FDG$ using auto dose dispenser. Secondly, using small syringes helps to increase reproducibility of auto dose dispense. And also, if you lower the specific activity of $^{18}F-FDG$ in multidose vial below 915-1,020 MBq/mL, you can use auto dispenser more effectively keeping the coefficient of variation lower than 10%.

• Radiation Oncology Journal
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• v.13 no.3
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• pp.205-214
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• 1995

Purpose : To investigate the effect of Ginkgo biloba extract (GBE) on hypoxic cell fraction and metabolic status in fibrosarcoma (FSa II) of C3H mouse. Materials and Methods : Fibrosarcoma (FSa II) 6 mm in diameter, growing in the right hindleg muscle of C3H mouse was used for estimation of hypoxic cell fraction using comparison of $TCD_{50}$. Radiation was given one hour after administration of GBE (100 mg/kg. i.p.) with or without priming dose of GBE (100 mg/kg, i.p.) given 24 hours earlier. Radiation was also given under air breathing condition or clamp hypoxia without GBE as controls. $^{31}p$ NMR spectroscopy was performed before and one hour after administration of GBE with or without priming dose of GBE. Results : $TCD_{50/120's}$ were 81.7 (77.7-86.0) Gy when irradiated under clamped hypoxia 69.6 (66.8-72.5) Gy under air breathing condition. 67.5 (64.1-71.1) Gy with a single dose of GBE (100 mg/kg) given one hour before irradiation, and 62.2 (59.1-65.5) Gy with two doses of GBE given at 25 hours and one hour before irradiation. The hypoxic cell fractions, estimated from $TCD_{50/120's}$, were $10.6{\%}$ under air breathing condition, $7.2{\%}$ after a single dose of GBE, and $2.7{\%}$ after two doses of GBE. The results of $^{31}P$ NMR spectroscopy were as follow. PCr/Pi ratio was $0.27{\pm}0.04$ and $0.40{\pm}0.04$ before and one hour after a single dose of GBE (p<0.05), respectively, without priming dose and $0.30{\pm}0.02$ and $0.71{\pm}0.04$, respectively, with priming dose (p<0.01). These findings indicate that the metabolic status is slightly improved after a single dose and markedly after repeated administrations. Conclusion : GBE decreases the hypoxic cell fraction and imprvoes the meta bolic status of tumor, probably by increasing the blood flow and delivery of oxygen and nutrients, resulting in increased radiosensitivity of tumor.