• Title/Summary/Keyword: repeated dose

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Anticonvulsant Compounds from the Wood of Caesalpinia sappan L.

  • Baek, Nam-In;Jeon, Seong-Gyu;Ahn, Eun-Mi;Hahn, Jae-Taek;Bahn, Jae-Hoon;Jang, Joong-Sik;Cho, Sung-Woo;Park, Jin-Kyu;Choi, Soo-Young
    • Archives of Pharmacal Research
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    • v.23 no.4
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    • pp.344-348
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    • 2000
  • 80% Aqueous MeOH extracts from the wood of Caesalpinia sappan, which showed remarkable anticonvulsant activity, were fractionated using EtOAc, n-BuOH, and $H_2$O. Among them, the EtOAc fraction significantly inhibited the activities of two GABA degradative enzymes, succinic semialdehyde dehydrogenase (SSADH) and succinic semialdehyde reductase (SSAR). Repeated column chromatographies for the fraction guided by activity test led to the isolation of the two active principal components. Their chemical structures were determined to be sappanchalcone and brazilin based on spectral data. The pure compounds, sappanchalcone (1) and brazilin (2), inactivated the SSAR activities in a dose dependent manner, whereas SSADH was inhibited partially by sappanchalcone and not by brazilin.

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Building a Graphite Calorimetry System for the Dosimetry of Therapeutic X-ray Beams

  • Kim, In Jung;Kim, Byoung Chul;Kim, Joong Hyun;Chung, Jae-Pil;Kim, Hyun Moon;Yi, Chul-Young
    • Nuclear Engineering and Technology
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    • v.49 no.4
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    • pp.810-816
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    • 2017
  • A graphite calorimetry system was built and tested under irradiation. The noise level of the temperature measurement system was approximately 0.08 mK (peak to peak). The temperature of the core part rose by approximately 8.6 mK at 800 MU (monitor unit) for 6-MV X-ray beams, and it increased as X-ray energy increased. The temperature rise showed less spread when it was normalized to the accumulated charge, as measured by an external monitoring chamber. The radiation energy absorbed by the core part was determined to have values of $0.798J/{\mu}C$, $0.389J/{\mu}C$, and $0.352J/{\mu}C$ at 6 MV, 10 MV, and 18 MV, respectively. These values were so consistent among repeated runs that their coefficient of variance was less than 0.15%.

일측성선조체의 6-OHDA손상 후 도파민효능약물 투여로 발현된 회전운동의 특성

  • 이순철;문민선
    • Journal of Ginseng Research
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    • v.21 no.1
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    • pp.61-67
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    • 1997
  • The present study examined the characteristics of behavior Induced by dopamine agonists following treatment with 6-hydroxydopamine(6-OHDA) unilaterally into left striatum in rats. 6-OHDA was administered at doses of 8,16 and 24 $\mu\textrm{g}$/$\mu\textrm{l}$(in 0.1% ascorbic acid) into dopaminergic neurons in left striatum of 7 weeks old rat under anesthetic. Locomotor activity was significantly decreased at 1 week following 6-OHDA-administration in 7 weeks old rats. The contralateral circling behavior was induced by apomorphine(5 mg/kg, i.v.) after 1 week following 6-OHDA(24$\mu\textrm{g}$/$\mu\textrm{l}$) treatment, and was further increased by repeated administration of apomorphine at 2, 3 and 4 weeks. The contralateral circling behavior was also induced by lisuride and 1-dopa in a dose dependent manner, but not by SK & F 82526 in 7 weeks old rats treated with 6-OHDA. The contralateral circling behavior was significantly higher in 21 weeks old rats but significantly lower In 35 weeks old rats when compared with 7 weeks old rats. The contralateral circling behavior induced by apomorphlne did not differ significantly in 7 and 35 weeks old male and female rats. These results suggest that 6-OHDA treatment into left striatum causes remarkable destrurtion of intrastriatal dopaminergic netcons leading to dopaminergic receptor supersensitivity. Thus, the contralateral circling behavior in duces by apomorphine may be used as indicator for neurodegenerative diseases.

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Inhibition of THIP on Morphine-Induced Hyperactivity, Reverse Tolerance and Postsynaptic Dopamine Receptor Supersensitivity

  • Oh, Ki-Wan;Yoon, In-Seup;Shin, Im-Chul;Hong, Jin-Tae;Lee, Myung-Koo
    • 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.

Effects of Anticonvulsants on Acute and Tonic Pains in the Rat

  • Shin, Hong-Kee
    • The Korean Journal of Physiology
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    • v.30 no.1
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    • pp.97-104
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    • 1996
  • Different neural substrates have been reported to be implicated in analgesic mechanisms in the acute phasic and the sustained tonic pains. To explore the differential antinociceptive action of diphenylhydantoin (DPH) and carbamazepine (CBZ) on the acute phasic and the tonic pains, changes in tail flick latency, hot plate latency and the formalin-induced nociceptive score were assessed prior to and after intraperitoneal administration of DPH (20 & 40 mg/Kg) and CBZ (20 mg/Kg). In 11 rats, CBZ was administered repeatedly for 6 days at the dose of 20 mg/Kg/day. Also studied were the effects of strychnine and picrotoxin (1 mg/Kg, i.p.) on the CBZ-produced changes in the formalin-induced pain behaviors. The tail flick and hot plate ltencies were not changes after administration of DPH and CBZ. However DPH strongly suppressed the formalin-induced tonic pain. A single and the repeated administration of CBZ inhibited both the early phasic and the late tonic pain responses to formalin in n similar manner. On the other hand, the antinociceptive actions of CBZ were not altered by strychnine or picrotoxin. These experimental findings lead to the conclusion that DPH and CBZ have differential antinociceptive action on the acute and the tonic pains and that their antinociceptive actions are independent of the GABA- and glycine-receptors.

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An Epithermal Neutron Beam Design for BNCT Using $^2H(d,n)^3He$ Reaction

  • Han, Chi-Young;Kim, Jong-Kyung;Chung, Kyu-Sun
    • Nuclear Engineering and Technology
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    • v.31 no.5
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    • pp.512-521
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    • 1999
  • A feasibility study was performed to design an epithermal neutron beam for BNCT using the neutron of 2.45 MeV on the average produced from $^2H(d,n)^3$He reaction induced by plasma focus in the z-pinch instead of the conventional accelerator-based $^3H(d, n)^4$He neutron generator. Flux and spectrum were analyzed to use these neutrons as the neutron source for BNCT. Neutronic characteristics of several candidate materials in this neutron source were investigated Using MCNP Code, and $^7LiF$ ; 40%Al + 60%$AIF_3$, and Pb Were determined as moderator, filter, and reflector in an epithermal neutron beam design for BNCT, respectively. The skin-skull-brain ellipsoidal phantom, which consists of homogeneous regions of skin-, bone-, or brain-equivalent material, was used in order to assess the dosimetric effect in brain. An epithermal neutron beam design for BNCT was proposed by the repeated work with MCNP runs, and the dosimetric properties (AD, AR, ADDR, and Dose Components) calculated within the phantom showed that the neutron beam designed in this work is effective in tumor therapy. If the neutron source flux is high enough using the z-pinch plasma, BNCT using the neutron source produced from $^2H(d,n)^3$He reaction will be very feasible.

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Treatment of Calcinosis Cutis with Minocycline in Five Dogs

  • Cho, Dae-Hee;Lee, Wang-Hui;Park, Seong-Jun
    • Journal of Veterinary Clinics
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    • v.34 no.2
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    • pp.119-122
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    • 2017
  • Calcinosis cutis is a chronic condition characterized by insoluble calcified deposits in the skin and subcutaneous tissue. Although there is no uniformly effective treatment for calcinosis cutis, minocycline therapy has demonstrated varying degrees of benefit in humans. Five client-owned dogs with calcinosis cutis were included. Minocycline was administered orally in a dose of 10 mg/kg bodyweight twice a day. Treatment was repeated every day until complete remission. The efficacy of minocycline was evaluated within this period. The side effects of minocycline were monitored and reported by the owners and veterinarians. Of the 5 dogs with calcinosis cutis, which was classified as the dystrophic form, four dogs had a complete remission of calcinosis cutis and one dog had a partial response. The major improvement was a reduction in the size of the calcified deposits and reduction in inflammation associated with them. The duration of remission was $9.1{\pm}2.2$ weeks. The adverse effects, observed in one dog, were anorexia and vomiting. Minocycline may be effective in the control of calcinosis cutis in dogs.

Four-Week Repeated Oral Toxicity Study of AIP1, a Water-soluble Carbohydrate Fraction from Artemisia iwayomogi in Mice

  • Ryu, Sung-Ha;Jo, Hae-Ran;Kim, Ji-Won;Youn, Hyun-Joo;Kim, Kyu-Bong
    • Toxicological Research
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    • v.27 no.4
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    • pp.261-267
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    • 2011
  • Artemisia iwayomogi, a member of the Compositae, is a perennial herb easily found in Korea and used as a traditional medicine to treat liver disease. AIP1, a water-soluble carbohydrate fraction from Artemisia iwayomogi, showed anti-tumor and immuno-modulating activities in animal studies. A subacute toxicological evaluation of AIP1 was performed for 4 weeks in ICR mice. After administration of AIP1 (0, 20, 100, 500 mg/kg/day), the clinical signs, mortalities, body weight changes, hematology, blood clinical biochemistry, urinalysis, organ histopathology, organ weights and gross finding were examined. The results showed that there were no significant differences in body weight changes, food intakes, water consumptions, or organ weights among different dose groups. Also we observed no death and abnormal clinical signs during the experimental period. Between the groups orally treated with AIP1 and the control group, there was no statistical significance in hematological test or serum biochemical values. Histopathological examination showed no abnormal changes in AIP1 groups. These results suggest that no observed adverse effect level (NOAEL) of the oral administration of AIP1 for 4 weeks was considered to be more than 500 mg/kg/day in mice under the condition investigated in current study.

A Four-Week Intravenous Toxicity Study of DA-l131/betamipron in Rats (DA-l131/betamipron의 랫드에 대한 4주반복 정맥투여 독성시험)

  • Kim, Dong-Hwan;Cho, Hyeon;Kang, Kyung-Koo;Baik, Nam-Gi;Kim, Won-Bae
    • Biomolecules & Therapeutics
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    • v.6 no.2
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    • pp.204-212
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    • 1998
  • This study was conducted to evaluate the repeated dose toxicity of DA-1131/betamipron, newly developed carbapenem antibiotic, in rats. DA-1131/ betamipron was administered intravenously once a day for 4 weeks to 10 males and 10 females per group at the doses of 0(control),40, 160 and 640 mg/kg. Throughout the study period, all rats survived. The administration of DA-1131/betamipron induced soft stool or diarrhea in rats of both sexes receiving 160 or 640 mg/kg. The water consumption was increased with a statistical significance in 640 mg/kg during observation period. At the end of administration, hematological and serum biochemical examination showed no toxicological changes in DA-1131/betamipron treated groups compared with control group. Histopathologic examination revealed inflammatory cell infiltration, tubular dilatation and focal necrosis of kidney in two males and three females in 640 mg/kg. On the basis of these results, the noobserved-adverse-effect-level of DA-1131/betamipron was estimated to be 40 mgtg under the present test condition.

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Biosafety and Toxicological Evaluation of Tissue-Cultured Echinacea purpurea Adventitious Roots

  • Murthy, Hosakatte Niranjana;Park, So-Young;Lee, Eun Jeong;Paek, Kee Yoeup
    • Horticultural Science & Technology
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    • v.33 no.1
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    • pp.124-132
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    • 2015
  • Echinacea purpurea (L.) Moench (purple cone flower) is an important medicinal plant; it can enhance immunity, relieve pain, and reduce inflammation, and also has hormonal, antiviral, and antioxidant effects. Adventitious root biomass of Echinacea purpurea was produced in commercial-scale bioreactors for use as a dietary supplement in the food industry and in traditional medicine. Biosafety and toxicological evaluations of tissue-cultured Echinacea purpurea adventitious roots (TCEPARs) were performed. Reverse mutation and chromosomal aberration tests showed no significant mutagenicity. Furthermore, repeated four-week oral dose tests performed in Sprague-Dawley rats did not show any notable changes in the general behavior of the rats, in the gross appearance of their internal organs, or in their mortality rate. There were no differences between the control group and the treatment group in parameters such as absolute body weight, hematology, blood chemistry, and absolute and relative organ weights. These findings indicate that TCEPARs are safe and nontoxic when consumed at an average dietary level and can be used as raw material for traditional medicine and the food industry.