• Journal of Applied Biological Chemistry
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• v.59 no.3
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• pp.227-231
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• 2016

Deep sea water (DSW) is located 100 to 500 m below the sea surface. DSW is widely used in various fields, and is an important source of minerals that can be used to treat mineral deficiency. In the present study, the oral toxicity of DSW-mineral extracts was determined using single-dose and 14-day repeated dose oral toxicity tests in ICR mice. For the single-dose oral toxicity tests, mineral extracts of magnesium (Mg) and calcium (Ca) at doses of 0, 6, 270, 810, and 1,350 mg/kg, respectively, were orally administered to mice once at the beginning of the experiment, and the mice were observed for 14 days. For the 14-day repeated dose oral toxicity tests, Mg and Ca mineral extracts at doses of 0, 3, 135, 405, 675 mg/kg, respectively, were orally administered to mice daily, and the mice were observed for 14 days. Various tests were performed including visual observation; analysis of relative organ weight, food intake, and organ weight; biochemical analysis, and histopathology. The results indicated that mortality and changes in appearance were not observed among differentially administered groups of male and female ICR mice during the experimental period. Differences in body weight gain, food intake, organ weight, and histopathology parameters were not significant between the control and mineral-administered groups. Some results of the biochemical analyses were significantly different, but showed no specific tendencies. Overall, no evidence of toxicity was observed from the oral administration of DSW extracts of Ca and Mg in ICR mice.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.193-193
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• 2002

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.307.1-307.1
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• 2001

• Toxicological Research
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• v.14 no.3
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• pp.393-400
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• 1998

As a series of safety studies on DA-3585, a recombinant human erythropoietin, its local irritancy was examined in rabbits after the following treatments; application into the conjunctival sac of the eye(single), subcutaneous injection (single and -day repeated)and intravenous injection (7-day repeated.)In addition, perivascular irritation of DA-3585 was investigated in mice. In the result of ocular irritation test, 10,000IU/ml solution of DA-3585 could be considered as a non-irritating material. The local irritation of DA-3585 by a single and 7-day repeated subcutaneous injection was negligible and not so much different from that of saline. In the vascular irritancy test, macro-and microscopic observations revealed that local irritation of DA-3585 was comparable to that of saline when injected into retroauricular vein of rabbits for 7 consecutive days. Furthermore the perivascular administration of DA-3585 upto the concentration of 10,000 IU/ml did not induce any morphological abnormalities at injection sites. The results obtained from the present study suggest that the local irritancy of DA-3585 is not different from that of saline when injected through intravenous or subcutaneous route for clinical practice.

• Korean Journal of Radiology
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• v.22 no.9
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• pp.1547-1554
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• 2021

Objective: We aimed to investigate whether repeated intravascular administration of iodinated contrast media (ICM) or gadolinium-based contrast agents (GBCAs) within a short interval was associated with an increased risk of post-contrast acute kidney injury (PC-AKI). Materials and Methods: This retrospective study included 300 patients (mean age ± standard deviation, 68.5 ± 8.1 years; 131 male and 169 female) who had undergone at least one ICM-enhanced perfusion brain CT scan, had their baseline and follow-up serum creatinine levels available, and had not undergone additional contrast-enhanced examinations 72 hours before and after a time window of interest were included. The study population was divided into three groups: single-dose group and groups of patients who had received multiple contrast administrations in the time window of interest with the minimum contrast repeat interval either within 4 hours (0-4-hour group) or between 4 to 48 hours (4-48-hour group). Multivariable logistic regression analysis was conducted to evaluate the association between AKI and repeated ICM administrations. A similar supplementary analysis was performed including both ICM and GBCA. Results: When ICM was only considered ignoring GBCA, among 300 patients, 207 patients received a single dose of ICM, 58 had repeated doses within 4 hours (0-4-hour group), and 35 patients had repeated doses between 4 to 48 hours (4-48-hour group). Most patients (> 95%) had a baseline estimated glomerular filtration rate (eGFR) of ≥ 30 mL/min/1.73 m². AKI occurred in 7.2%, 13.8%, and 8.6% of patients in the single-dose, 0-4-hour, and 4-48-hour groups, respectively. In the 0-4-hour and 4-48-hour groups, additional exposure to ICM was not associated with AKI after adjusting for comorbidities and nephrotoxic drugs (all p values > 0.05). Conclusion: Repeated intravascular administrations of ICM within a short interval did not increase the risk of AKI in our study patients suspected of acute stroke with a baseline eGFR of ≥ 30 mL/min/1.73 m².

• The korean journal of orthodontics
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• v.47 no.4
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• pp.222-228
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• 2017

Objective: To evaluate soft- and hard-tissue changes in the mandibular angle area after the administration of botulinum toxin type A (BoNT-A) injection to patients with masseteric hypertrophy by using three-dimensional cone-beam computed tomography (3D-CBCT). Methods: Twenty volunteers were randomly divided into two groups of 10 patients. Patients in group I received a single BoNT-A injection in both masseter muscles, while those in group II received two BoNT-A injections in each masseter muscle, with the second injection being administered 4 months after the first one. In both groups, 3D-CBCT was performed before the first injection and 6 months after the first injection. Results: Masseter muscle thicknesses and cross-sectional areas were significantly reduced in both groups, but the reductions were significantly more substantial in group II than in group I. The intergonial width of the mandibular angle area did not change significantly in either group. However, the bone volume of the mandibular gonial angle area was more significantly reduced in group II than in group I. Conclusions: The repeated administration of BoNT-A injections may induce bone volume changes in the mandibular angle area.

• Archives of Pharmacal Research
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• v.25 no.2
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• pp.202-207
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• 2002

This study was performed to investigate the effect of tetrahydroisoxazolopyridine (THIP), a $GABA_A$ agonist, on the morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity in mice. A single administration of morphine induced hyperactivity in mice. However, the morphine-induced hyperactivity was inhibited dose-dependently by the administration of THIP (0.2, 0.4 and 0.8 mg/kg, i.p.). In contrast, daily administration of morphine resulted in a reverse tolerance to the hyperactivity caused by morphine (10 mg/kg ,s.c.). THIP inhibited the development of reverse tolerance in the mice that had received the repeated same morphine (10 mg/kg s.c.) doses. The postsynaptic dopamine receptor supersensitivity, which was evidenced by the enhanced ambulatory activity its after the administration of apomorphine (2 mg/kg s.c.), also developed in the reverse tolerant mice. THIP also inhibited the development of the postsynaptic dopamine receptor supersensitivity indulged by the chronic morphine administration. These results suggest that the hyperactivity, reverse toterance and postsynaptic dopamine receptor supersensitivity induced by morphine can be inhibited activating the $GABA_A$ receptors.

• Toxicological Research
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• v.23 no.1
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• pp.87-96
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• 2007

Single and repeated-dose toxicity of anti-diabetic herb extract microcapsule (ADHEM) were evaluated according to Toxicity Test Guidelines of Korea Food and Drug Administration using Sprague-Dawley rats. For single-dose toxicity test, kneading ADHEM with sterilized water were administered orally once at dose levels of 0 and 2,000 mg/kg and examined for 14 days. No dead animals, clinical signs and abnormal necropsy findings were observed and also no significant difference in body weights was found. Therefore, the $LD_{50}$ of ADHEM was considered to be higher than 2,000 mg/kg in both male and female rats. For repeated-dose toxicity test, ADHEM were mixed with powder fodder and administerd orally for 28 days at dose levels of 0, 500, 1000 and 2000 mg/kg/day. No dead animals, clinical signs and significant difference in body weights were found. In hematology and serum biochemistry, all values were included within the normal ranges. In relative organ weights, kidney or liver were significantly increased in the 500, 1000 or 2000 mg/kg/day male groups, uterus was significantly increased in the 500 mg/kg/day female group and left adrenal glands were significantly decreased in the 2000 mg/kg/day female group. In histopathological examinations, vacuolation and microgranuloma in the liver, chronic progressive nephropathy and inflammation in the kidney were observed in the 500, 1000 or 2000 mg/kg/day both male and female groups. Therefore, the no observed adverse effect level (NOAEL) of ADHEM was considered to be lower than 500 mg/kg/day in both male and female rats.

• Toxicological Research
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• v.29 no.4
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• pp.263-278
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• 2013

The silkworm extract powder contain 1-deoxynojirimycin (DNJ), a potent ${\alpha}$-glycosidase inhibitor, has therapeutic potency against diabetes mellitus. Therefore, natural products containing DNJ from mulberry leaves and silkworm are consumed as health functional food. The present study was performed to evaluate the safety of the silkworm extract powder, a health food which containing the DNJ. The repeated toxicity studies and gentic toxicity studies of the silkworm extract powder were performed to obtain the data for new functional food approval in MFDS. The safety was evaluated by a single-dose oral toxicity study and a 90 day repeated-dose oral toxicity study in Sprague-Dawley rats. The silkworm extract powder was also evaluated for its mutagenic potential in a battery of genetic toxicity test: in vitro bacterial reverse mutation assay, in vitro chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay. The results of the genetic toxicology assays were negative in all of the assays. The approximate lethal dose in single oral dose toxicity study was considered to be higher than 5000 mg/kg in rats. In the 90 day study, the dose levels were wet at 0, 500, 1000, 2000 mg/kg/day, and 10 animals/sex/dose were treated with oral gavage. The parameters that were monitored were clinical signs, body weights, food and water consumptions, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathological examination. No adverse effects were observed after the 90 day administration of the silkworm extract powder. The No-Observed-Adverse-Effect-Level (NOAEL) of silkworm extract powder in the 90 day study was 2000 mg/kg/day in both sexes, and no target organ was identified.

• Korean Management Science Review
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• v.13 no.1
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• pp.57-70
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• 1996

This paper develops an adaptive scheduling policy for flexible manufacturing systems. The inductive learning methodology used for constructing this state-dependent scheduling policy provides and understanding of the relative importance of the various system parameters in determining the appropriate scheduling rule. Experimental studies indicated the superiority of the suggested approach over the alternative approach involving the repeated application of a single scheduling rule for randomly generated test problems as well as a real system, and under both stationary and nonstationary conditions. In particular, its relative performance improves further when there are frequent disruptions, and when disruptions are caused by the introduction of tiiight due date jobs, one of the most common surces of disruptions in most manufacturing systems.