• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.248-254
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• 2011

Biotransformation of pharmacologically inactive lactone prodrug simvastatin (SV) into pharmacologically active simvastatin ${\beta}$-hydroxy acid (SVA) exhibits inter-species differences due to variations in amount and activity of esterase enzymes. In this study, we investigated the pharmacokinetics (PK) of SV and its metabolite SVA following oral doses of SV from controlled-release (CR) tablets and immediate-release (IR) tablets in rodent and canine animal models that features different esterase activity. In rat PK study, no SV was detected in plasma for both formulations due to rapid hydrolysis of SV into SVA by plasma esterase. Besides, no significant differences in PK parameters of SV or SVA were observed between both species. In dog PK study, the relative oral bioavailability of CR tablets in terms of SV was 72.3% compared to IR tablets. Regarding formulation differences in dogs, CR tablets exhibited significantly lower $C_{max}$ (p<0.05), and higher $T_{max}$ (p<0.01) and MRT (p<0.01) for both SV and SVA compared to IR tablets. Accordingly, CR tablets of SV with prolonged drug release profiles in both species might be a potential candidate for a more effective delivery of SV with reduced side effects. Besides, similar PK parameters of SV and SVA in both species despite variation in enzyme activities suggested involvement of equally potent biotransformation pathways in these animal species.

• Journal of Chest Surgery
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• v.33 no.6
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• pp.502-506
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• 2000

Background: Anticoagulant therapy can be required during pregnancy with prosthetic heart valves. Warfarin and heparin provide real protection against thromboembolic phenomena, but they also carry serious risks for the fetus and the mother. In an attempt to identify the best treatment for pregnant women with cardiac valve prostheses who are receiving anticoagulant, we studied 19 pregnancies, the warfarin was discontinued and heparin was administered every 12 hours by subcutaneous injection in doses adjusted to keep the midinterval aPTT in the therapeutic range(at least 2-2.5 control) from the conception to the 12th week of gestation and oral antiocagulant was then administered until the middle of the third trimester in the therapeutic range(at least 2 INR), and heparin therapy was restared until delivery. Also in order to avoid an anticoagulant effect during delivery, it has been our practice to instruct women to either discontinue their heparin injections with the onset of labur or to stop heparin injections 12 hours prior to the elective induction of labour. Result: The outcome of 19 pregnancies managed with above protocol was spontaneous abortion in 3 cases, voluntary termination in 2 cases, premature delivery at 35 weeks in 1 case and delivery at full-term in 14 cases. There was no maternal morbidity and moratality and fetopathy. Conclusion: We conclude that in the second and third trimester of pregnancy, warfarin provide effective protection against thromboembolism, Oral antiocagulant therapy should be avoided in 2 weeks before delivery because of the risk of serious perinatal bleeding caused by the trauma of delivery to the anticoagulated fetus. However, the substitution of heparin at first trimester and 2 weeks before delivery reduce the incidence of complications.

• Preventive Nutrition and Food Science
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• v.11 no.2
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• pp.115-119
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• 2006

The object of this study was to examine whether the germanium fortified yeast administered to SD rat is accumulated in the liver and kidney. The administration doses were within 2,000 mg/kg which is the level of NOAEL (no observed adverse effect level) proved through the previous study of single/consecutive oral toxicity test. There were no significant clinical symptoms and mortality following the administration of organic germanium-fortified yeast (0, 500, 1,000, 2,000 mg/kg) during the whole test period, and also no difference in the consumed amount of feed and water for each group. No significant abnormalities of hematology and blood chemistry parameters were found in all groups of organic germanium-fortified yeast (0, 500, 1,000, 2,000 mg/kg). The amount of germanium accumulated in liver and kidney was 0 g/kg by ICP-AES method in the group of organic germanium-fortified yeast. In the positive control group of $GeO_2$ (150 mg/kg), the amount of accumulation was shown to 3135.0 and 4277.2 g/kg in each female and male kidney and 1044.3 and 2135.8 g/kg in each female and male liver, respectively. Organic germanium-fortified yeast, a biosynthetic product resulting from putting germanium into yeast, did not show any clinical symptoms, blood chemical significance, and residues in kidney and liver. It could be inferred that the non-toxic amount of organic germanium-fortified yeast was up to 2,000 mg/kg.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.6
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• pp.797-804
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• 2016

In an acute toxicity test for Chrysanthemum indicum Linne, 0.5~10 g/kg of Chrysanthemum indicum Linne extracts were administered. Chrysanthemum indicum Linne did not produce acute toxicity even at high doses of 10 g/kg, making it a highly safe material. In the chronic toxicity test, oral administration of Chrysanthemum indicum Linne up to 2 g/kg was carried out for 13 weeks, showing liver non-toxicity. The gout inhibitory effect of Chrysanthemum indicum Linne extracts was measured by inflammatory cytokine expression and foot thickness after 24 h of monosodium urate crystal (MSU) oral administration when inflammatory cytokine production reached a maximum. The group administered 2~4 g/kg of Chrysanthemum indicum Linne extract showed an inhibitory effect on gout inflammation and edema, whereas the 10 g/kg administered group showed an increase in inflammation. Therefore, the moderate concentration of Chrysanthemum indicum Linne extract for gout inhibitory effect was under 4 g/kg. Chrysanthemum indicum Linne extract showed an anti-inflammatory effect on MSU as a relatively safe material at high capacity. These results indicate that Chrysanthemum indicum Linne extract is thought to be an excellent substance for gout prevention.

• The Korea Journal of Herbology
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• v.23 no.4
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• pp.1-7
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• 2008

Objectives: Ephedrae herba, also known as Ma-huang, is a traditional Korean medicinal herb. It has been used to treat asthma, nose and lung congestion, and fever with anhidrosis for centuries. Recently, Ma-huang was used as a source of ephedrine in many dietary supplements for weight reduction in the United States. The objective of this study was to investigate the subacute toxicity of ephedrae herba extract in rats. Methods: SPF Sprague-Dawley male rats were administered orally with ephedrae herba extract for 4 weeks as several doses(0, 125, 250, 500, 1,000, and 2,000 mg/kg). We examined number of deaths, clinical signs, body weights and gross findings for experimental period. Results: No dead animals were found during the experimental period. In addition, no differences were found between control and treated groups in clinical signs, hematology, serum biochemistry, and other findings. Conclusions: In conclusion, above data suggest that no observed adverse effect level of ephedrae herba extract in SD rats might be over 2,000 mg/kg/day in this study.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.25 no.1
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• pp.27-38
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• 1995

The organ or tissue doses were determined with head and neck phantom measurement for multiple axial scans (36 slices), multiple coronal scans (13 slices), 3 types of single axial scans(orbit, maxillary sinus and mandibular canal) and single coronal scan (maxillary sinus). For each scan sequence 30 TLDs were placed in selected sites(16 internal sites and 14 external sites) in a tissue-equivalent phantom. The exposure was made at 120kVp, 500mAs with 5 mm slice width. The results were as follows : 1. In multiple axial scans, the greatest effective dose recorded was that delivered to the thyroid glands(2.77 mSv) and the least was that received by the skin(0.05 mSv). From these data, stochastic effects were 202.2x10/sup -6/ and 3.7×10/sup -6/, respectively. 2. In multiple coronal scans, the greatest effective dose recorded was that delivered to the salivary glands(0.58 mSv) and the least was that received by the skin(0.01 mSv). From these data, stochastic effects were 42.2×10/sup -6/ and 0.7×10/sup -6/, repectively. 3. Among single axial scans, the greatest effective dose recorded was that delivered to the salivary gland(0.38 mSv) in maxillary sinus scan. From this data, stochastic effect was 27.7×10/sup -6/. 4. In single coronal scan, the greatest effective dose recorded was that delivered to the salivary gland(0.01 mSv). From this data, stochastic effect was 1.0×10/sup -6/. 5. The equivalent dose measured that delivered to the lens of the eyes was 69.64 mSv in multiple axial scan, 39.32 mSv in multiple coronal scan and 36.77 mSv in single axial scan(orbit).

• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.23 no.1
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• pp.71-85
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• 1993

The purpose of the study was to investigate the effects of the single and fractionated irradiation on the microvascular structure of the submandibular gland in rats. For this study, 90 Sprague-Dawley strain rats were irradiated to their neck region with equal split doses of 9Gy for a 4 hours interval and 15Gy single dose by 6MV X-irradiation and sacrificed on the 1st, 3rd, 7th, 14th and 27th day after irradiation. The author observed histological changes at Hematoxylin and Eosin staining and PAS staining under a light microscope, and also observed distribution and structural changes of the microvasculature in rat submandibular gland using a scanning electron microscope by forming vascular resin casting. The results were as follows: 1. In the light microscopic examination, the microvasculature was slightly dilated and decreased in number on the 1st day after irradiation, and increase in number of microvasculature was observed on the 3rd day after irradiation. And then distribution of microvasculature was markedly increased on the 7th day after iradiation, but decreased on th 14th day after irradiation again. Such changes were greater in the single irradiated group than in the fractionated irradiated group. 2. The reaction to PAS staining on glandular cell was decreased on the 1st and the 3rd day after irradiation, and recovered on the 7th day after irradiation. The reaction was decreased on the 14th day after irradiation again, and recovered on the 28th day after irradiation. Changes were more apparent in the single irradiated group. 3. In the scanning electron microscopic examination, early changes of microvasculature were decreased capillary density, dilation of conduits and meandering. Increased capillary dentsity or anastomosis due to vascular reproduction and smooth curved running were observed on the 7th and 14th day after irradiation. Decreased capillary and smooth running tendency were observed on the 28th day after irradiation again. Such changes were greater in the single irradiated group than in the fractionated irradiated group.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.656-661
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• 2005

The study was conducted to investigate per oral (PO) effects of Black raspberry wine on testosterone levels in Sprague-Dawley rats oral administrated with Methoxychlor in order to establish the experimental clinical model for evaluating the influences on the sexual hormones of SD-Rat administrated with Methoxychlor(MET), it was dissolved in acetone and olive oil (1:19), which was administrated orally at doses of 200mg/kg body weight/ day for 7days. Black raspberry wine of 13% alcohol concentration, was prepared from ripen fruits of Rubus coreanus fermented with Saccharomyces cervisiae. PO administration of Black raspberry wine for 15 week produced dramatic increases of serum testosterone levels. Increase in the testosterone level was observed, using gamma counter with 125I testosterone, starting from 1 week post administration. Maximum increase in testosterone level was observed at 4 week post administration, 5.18${\pm}$0.76ng/mL, which was 10.1 times higher than before and at 15 weeks post administration it was recorded as 1.67${\pm}$0.19ng/mL indicating Black raspberry wine as an effective phyto-testosteronic beverage of the future.

• Journal of Sasang Constitutional Medicine
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• v.22 no.1
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• pp.59-65
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• 2010

1. Objectives: The aim of this study is data analysis for acute toxicity and safety of Cheongsimyeonja-tang. 2. Methods: We investigated the acute toxicity for water-extracted Cheongsimyeonja-tang. Fifty five male and female mice were observed for 14 days after one day oral administration of Cheongsimyeonja-tang at the respective doses of 0 (control group), 2560, 3200, 4000 and 5000 mg/kg. 3. Results: We observed survival rates, general toxicity, change of body weight and autopsy. In animals administered with Cheongsimyeonja-tang, there were nither dead animals nor significant changes of body weights. In addition, no differences were found between control and treated groups in clinical sign and autopsy. 4. Conclusion: The data confirmed that Cheongsimyeonja-tang is free from the toxicity and safety problems in treated groups. Compared with the control group, we could not find any toxic alteration in all treated groups(2560, 3200, 4000 and 5000 mg/kg). Lethal Dose 50 (LD50) value for mice was more than 5000 mg/kg per oral for both male and females. It suggest that Cheongsimyeonja-tang in mice is considered to be safe.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.9 no.1
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• pp.25-31
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• 1979

The utilization of x-ray for diagnosis and examination is increasing by about 5-15% every year, therefore, it would be mandatory to protect the patients from exposures and so, studies in this field are performed even now. In dental field, the area of irradiation is limited any to the head and neck area, but the irradiated angle is varied following the objected tooth, so the adjacent structures lens and thyroid gland would be fragile to radiation. And the scattered radiation is one of the complicated problems in the protection because of specificity of dental x-ray and its object structures. The author, by using TLD (Thermo luminescent Dosimeter; Teledyne Isotopes-Model 7300, Element; TLD 200(CaF₂:Dy) and Capintec(Capintec Model 192, PM-30 Diagnostic chamber 28㎖ active volume), tried a measurement of air dose distribution of the scattered radiation and the irradiated dose of lens and thyroid gland under the condition of taking the film on the left maxillary molar. The results were as follows: 1. The half value layer of adapted dental x-ray machine was measured, and is 1.44㎜ Al. 2. The time of irradiation on the left maxillary molar in the Alderson Rando Phantom, the measured doses of left and right lens, and thyroid gland were 8,9mR, 1,2mR and 2,8mR. Under the same conditions, the scattered radiation at the distance of 1 meter from the phantom were 84 μR at the front side, 11μR at the back side, 18μR at the right side and 72μR at the left side. 3. Under the same conditions, the dose showed higher value by about 5% in the presence of object(phantom) than in the case of absence.