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The acute toxicity and efficacy evaluation against Aeromonas salmonicida of aquatic drugs oxolinic acid, neomycin-oxytetracycline, and florfenicol in guppy (Poecilia reticulata) (구피(Poecilia reticulata)에서 수산용의약품 oxolinic acid, neomycin-oxytetracycline, florfenicol의 급성독성 및 Aeromonas salmonicida에 대한 약효 평가)

  • Jun Sung Bae;Chae Won Lee;Chan Yeong Yang;Eun Ha Jeong;Areum Kim;Young-Sik Chae;Jung-Jin Park;Kwan Ha Park
    • Journal of fish pathology
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    • v.36 no.2
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    • pp.293-302
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    • 2023
  • This study evaluated the acute toxicity induced by oxolinic acid (OA), neomycin-oxytetracycline combination (NEO-OTC) and florfenicol (FF) administered to guppy (Poecilia reticulata) by comparing standard formulations with commercial preparations (COOaqua curinpotion, COOaqua terafinpotion and COOaqua profenpotion, respectively) for ornamental fish at concentrations of 2-4%. NEO-OTC exhibited the highest acute toxicity in guppy, with no difference observed between the pstandard formulation and commercial preparation (LC50 = 126.08 mg/L and 112.44 mg/L, respectively). OA acute toxicity was assessed in the form of sodium salt, with an LC50 of 504.61 mg/L for the standard formulation and a slightly increased toxicity of 316.11 mg/L for the commercial preparation. In contrast, no mortality was observed during the 96-hour exposure period with the standard formulation in the form of oxolinic acid. The acute toxicity of FF was measured to be above 1,000 mg/L for the standard formulation; however, the commercial preparation significantly increased to 158.53 mg/L. These results indicate that toxicity can significantly increase in commercial formulations, especially those with low levels of active ingredients. This is presumed to be attributed to the organic solvents or solubilizing agents present in the commercial preparations, which may enhance toxicity. Additionally, guppy infected with Aeromonas salmonicida were effectively protected against mortality by administering OA, NEO-OTC and FF at concentrations of 50 mg/L, 100 mg/L and 15 mg/L, respectively, for 2 hours and at half the dose for 24 hours. This result indicates that liquid formulations containing low concentrations of antibiotics may partially increase toxicity, but there is no problem in effectively treating diseases in ornamental fish.

Bioequivqlence of Gabarep Tablet to Neurotin Tablet (Gabapentin 800 mg) (가바렙정 (가바펜틴 800 mg)의 생물학적 동등성 평가)

  • Seo, Young-Hwan;Jeong, Ju-Cheol;Lee, Jae-Young;Li, Zheng-Yi;Yoon, Hyoung-Jong;Sohn, Uy-Dong;Bang, Joon-Seok;Kim, Ho-Hyun;Jeong, Ji-Hoon
    • Journal of Pharmaceutical Investigation
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    • v.38 no.4
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    • pp.261-267
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    • 2008
  • The aim of the present study was to evaluate the bioequivalence of two gabapentin preparations. We used Neurontin tablet 800 mg (Pfizer Korea Inc.) as a reference drug for bioequivalence of Gabalep tablet 800 mg (Chong Kun Dang Pharmaceutical Co., Korea), and performed this whole study according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty five healthy male volunteers were administered with each drug in a randomized $2{\times}2$ cross-over study with one week washout interval. After drug administration, blood was taken at predetermined time intervals ($0{\sim}24$ hours) and the concentrations of gabapentin in serum were determined using an high performance liquid chromatography-tandem mass spectrometer (LC-MS/MS) employing electrospray ionization technique and operating in multiple reaction mornitoring (MRM). The analytical method was validated in specificity, accuracy, precision and linearity. The phar-macokinetic parameters such as AUCt and Cmax were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed AUCt and Cmax. $Mean{\pm}SD$. of AUCt and Cmax value for reference drug and test drug were $29.94{\pm}9.23\;({\mu}g/mL{\cdot}hr)$ and $3.12{\pm}1.11\;({\mu}g/mL{\cdot}hr)$, and $31.48{\pm}9.77\;({\mu}g/mL{\cdot}hr)$ and $3.15{\pm}1.03\;({\mu}g/mL)$, respectively. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) for AUCt and Cmax, respectively. These results indicate that Gabalep tablet 800 mg is bioequivalent to Neurontin tablet 800 mg.

Pharmacokinetics of Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) Following Intravenous, Intramuscular and Subcutaneous Administration of HM10411 and Filgrastim to Rats and Mice (인과립구 콜로니 자극인자 제제인 HM10411와 필그라스팀의 정맥, 근육 및 피하 주사시 흰쥐와 마우스에서의 약물 동태)

  • Kim, In-Wha;Lee, Sang-Hoon;Kim, Young-Min;Jung, Sung-Youb;Kwon, Se-Chang;Lee, Gwan-Sun;Chung, Suk-Jae;Shim, Chang-Koo
    • Journal of Pharmaceutical Investigation
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    • v.31 no.2
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    • pp.89-94
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    • 2001
  • The pharmacokinetics of recombinant human granulocyte colony stimulating factor (rhG-CSF) following intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration of HM1041l-lyo and HM10411-liq (lyophilized and liquid formulations of rhG-CSF, recently under development by Hanmi Pharmaceutical Company) were studied in rats, and compared with that of Filgrastim (conventional formulation of rhG-CSF on market). The plasma concentration of rhG-CSF was quantified using a specific ELISA. The pharmacokinetic parameters of rhG-CSF, after i.v., i.m. and s.c. administration of Filgrastim, HM1041l-lyo and HM1041l-liq to rats at a rhG-CSF dose of $10\;{\mu}g/kg$, were almost identical among the three formulations. No dose-dependency was observed in the pharmacokinetic parameters of rhG-CSF following i.v. administration in the dose range of $5{\sim}100\;{\mu}g/kg$. rhG-CSF, after i.v. administration of the three preparations at a dose of $10\;{\mu}g/kg$ to rats, was detected at low levels in all of the body tissues with highest tissue/plasma ratio of $0.46{\sim}0.51$ for the kidney at 30 min after the administration. The pharmacokinetics of rhG-CSF, after i.v. administration to mice at a dose of $10\;{\mu}g/kg$, were comparable among the three formulations. In conclusion, HM10411-lyo and HM10411-liq exhibited similar pharmacokinetics for rhG-CSF with Filgrastim regandless of animal species. Considering the fact that HM10411 series, contrary to Filgrastim, are proteins lacking a methionine residue, the methionine moiety in rhG-CSF molecule does not appear to influence the pharmacokinetics of the protein significantly.

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Quality Characteristics of Kanjang Prepared with Meju Cultivated on Different Soybean Cultivars with Bacillus subtilis var. globigii Seed Culture (Bacillus subtilis var. globigii 종균접종 메주로 제조한 콩 품종별 간장의 품질 특성)

  • Choi, Cheong;Choi, Jong-Dong;Chung, Hyun-Chae;Kwon, Kwang-Il;Im, Moo-Hyeog;Kim, Young-Ji;Seo, Jung-Sik;Choi, Kwang-Soo
    • Applied Biological Chemistry
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    • v.42 no.4
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    • pp.283-287
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    • 1999
  • This study was carried out to select the most suitable soybean cultivars for the quality kanjang preparation. Six cultivars of soybean, Taekwangkong, Kumjungkong #1, Sinpaldalkong #2, Hwangkeumkong, Danbaegkong and Danyeobkong, were used as the raw materials for kanjang preparations. Grain type meju was prepared by the inoculation of Bacillus subtilis var. globigii seed culture on the cooked soybean of respective cultivar and cultivation at $30^{\circ}C$ for 10 days. Two month matured respective kanjang mash, which was prepared by mixing meju and 20% salt brine in the ratio of 1 : 3, was separated and the liquid portions were used as kanjang samples for this work. The highest crude protein content of 47.5% was obtained from Danbaegkong cultivar among six soybean cultivars tested. High sugar soybean cultivars were found to be Kumjungkong l and Danbaegkong and the content 15.87% and 13.33% respectively. The highest total nitrogen(TN) content of 1.18% was shown from Danbaegkong kanjang. Although the major free organic acid in kanjang was found to be succinic acid, no significant differences in free organic acid and sugars content were observed among cultivars. The highest free total amino acids(TA) and glutamic acid(GA) content in kanjang was observed to be 3365 mg% and 734.44 mg% respectively from Danbaegkong kanjang. Danbaegkong cultivar soybean which was shown to contain the highest crude protein was found to be the most suitable one for the preparation of quality kanjang with high TN, GA content and GA/TA ratio.

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Catalytic Supplementation of Urea-molasses on Nutritional Performance of Male Buffalo (Bubalus bubalis) Calves

  • Sahoo, A.;Elangovan, A.V.;Mehra, U.R.;Singh, U.B.
    • Asian-Australasian Journal of Animal Sciences
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    • v.17 no.5
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    • pp.621-628
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    • 2004
  • Twenty male buffalo calves of 6-9 months of age (average body weight, 97 kg) were randomly allocated into two main groups of four (control) and sixteen (supplemented) calves. The supplemented group was further divided in to four equal sub-groups, with the two groups supplemented with a liquid preparation of urea-molasses, UML1, containing fish meal and UML2, containing formaldehyde treated deoiled mustard cake (FDMC) and the other two, with a semi-solid preparation, UMC1 with FDMC and deoiled rice bran (DORB) contributing similar level of CP as in UML2 and UMC2 with double the level of FDMC to that in UMC1. The control group was fed with DORB along with ad libitum wheat straw at 40:60 ratios. The rest of the groups were fed on the above diet supplemented with 500 g (as fed basis) of urea-molasses preparations. The experimental feeding was carried out for 24 weeks including a metabolism trial towards the end of experimental feeding. Daily feed intake and fortnightly change in live weight were also recorded during the study. Catalytic supplementation of 500 g urea-molasses induced 8-25% higher voluntary feed intake of wheat straw, resulting in 15-25% higher DM and OM intake. The digestibility of DM, OM, total carbohydrate, NDF, ADF, hemicellulose and cellulose in all the dietary groups were comparable. The CP digestibility of calves in supplemented groups were higher (p<0.05) than the control group. The balance of nutrients, viz. N, Ca and P, was also higher in the supplemented groups. Significantly higher intake of digestible CP coupled with other digestible nutrients attributed to higher TDN (1.67-1.78 vs. 1.37 kg) and ME (5.94-6.31 vs. 4.87 Mcal) intake in urea-molasses supplemented groups which resulted in higher live weight gain compared to that in control group (p<0.01). Between the supplements, UML2 and UMC2 faired non-significantly, indicating formalin treated mustard cake as a suitable replacement to fishmeal in the supplement. The overall ranking based on intake and digestibility of nutrients, live weight gain, economic evaluation and input-output relationship revealed that the rations with UML2 and UMC1 to be of greater value compared to other types. From the study it can be concluded that young ruminants can be reared successfully on a basal diet of deoiled rice bran and wheat straw supplemented with cheaper urea-molasses-mineral mix.

Feasibility as a Laundry Detergent Additive of an Alkaline Protease from Bacillus clausii C5 Transformed by Chromosomal Integration (Chromosomal Integration에 의해 제조한 Bacillus clausii C5 유래의 alkaline protease의 세제 첨가제 응용성)

  • Joo, Han-Seung;Choi, Jang Won
    • KSBB Journal
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    • v.27 no.6
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    • pp.352-360
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    • 2012
  • Bacillus clausii I-52 which produced SDS- and $H_2O_2$-tolerant extracellular alkaline protease (BCAP) was isolated from heavily polluted tidal mud flat of West Sea in Incheon, Korea and stable strain (transformant C5) of B. clausii I-52 harboring another copy of BCAP gene in the chromosome was developed using the chromosome integration vector, pHPS9-fuBCAP. When investigated the production of BCAP using B. clausii transformant C5 through pilot-scale submerged fermentation (500 L) at $37^{\circ}C$ for 30 h with an aeration rate of 1 vvm and agitation rate of 250 rpm, protease yield of approximately 105,700 U/mL was achieved using an optimized medium (soybean meal 2%, wheat flour 1%, sodium citrate 0.5%, $K_2HPO_4$ 0.4%, $Na_2HPO_4$ 0.1%, NaCl 0.4%, $MgSO_4{\cdot}7H_2O$ 0.01%, $FeSO_4{\cdot}7H_2O$ 0.05%, liquid maltose 2.5%, $Na_2CO_3$ 0.6%). The enzyme stability of BCAP was increased by addition of polyols (10%, v/v) and also, the stabilities of BCAP towards not only the thermal-induced inactivation at $50^{\circ}C$ but also the SDS and $H_2O_2$-induced inactivation at $50^{\circ}C$ were enhanced. Among the polyols examined, the best result was obtained with propylene glycol (10%, v/v). The BCAP supplemented with propylene glycol exhibited extreme stability against not only the detergent components such as ${\alpha}$-orephin sulfonate (AOS) and zeolite but also the commercial detergent preparations. The granulized enzyme of BCAP was prepared with approximately 1,310,000 U/g of granule. Wash performance analysis using EMPA test fabrics revealed that BCAP granule exhibited high efficiency for removal of protein stains in the presence of anionic surfactants as well as bleaching agents. When compared to Savinase 6T$^{(R)}$ and Everlase 6T$^{(R)}$ manufactured by Novozymes, BCAP under this study probably showed similar or higher efficiency for the removal of protein stains. These results suggest that the alkaline protease produced from B. clausii transformant C5 showing high stability against detergents and high wash performance has significant potential and a promising candidate for use as a detergent additive.

Bioequivalence of Etodin Capsule to Kuhnillodin Capsule (Etodolac 200 mg) (건일로딘 캡슐(에토돌락 200mg)에 대한 에토딘 캡슐의 생물학적동등성)

  • Lee, Myung-Jae;Kang, Jong-Min;Choi, Sang-Jun;Lee, Jin-Sung;Tak, Sung-Kwon;Seo, Ji-Hyung;Rew, Jae-Hwan;Yim, Sung-Vin;Lee, Kyung-Tae
    • Journal of Pharmaceutical Investigation
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    • v.38 no.6
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    • pp.421-427
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    • 2008
  • The purpose of the present study was to evaluate the bioequivalence of two etodolac capsules, Kuhnillodin capsule (Kuhnil. Co., Ltd., Seoul, Korea) as reference drug and Etodin capsule (Myungmun Pharm. Co., Ltd., Seoul, Korea) as test drug, according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-three healthy male Korean volunteers received one capsule at the dose of 200 mg etodolac in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of etodolac were monitored by a high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) for over a period of 24 hr after the administration. $AUC_{0-24\;hr}$ was calculated by the linear trapezoidal rule method. $C_{max}$ and $T_{max}$ were compiled from the plasma concentration-time data. Analysis of variance (ANOVA) was carried out using logarithmically transformed $AUC_{0-24\;hr}$ and $C_{max}$. The 90% confidence intervals of the $AUC_{0-24\;hr}$ ratio and the $C_{max}$ ratio for Etodin/Kuhnillodin were $\log\;0.97{\sim}\log\;1.08$ and $\log\;0.89{\sim}\log\;1.19$, respectively. These values were within the acceptable bioequivalence intervals of $\log\;0.80{\sim}\log\;1.25$. Thus, our study demonstrated that Etodin was bioeqiovalent to Kuhnillodin preparation when the rate and extent of absorption between two preparations were compared.

Bioequivalence of pioglitazone tablet to Actos® tablet (Pioglitazone 30 mg) (액토스정®(피오글리타존 30 mg)에 대한 염산피오글리타존정의 생물학적동등성)

  • Yeom, Hyesun;Lee, Tae Ho;Youm, Jeong-Rok;Song, Jin-Ho;Han, Sang Beom
    • Analytical Science and Technology
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    • v.22 no.1
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    • pp.101-108
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    • 2009
  • The bioequivalence of two pioglitazone tablets, Actos$^{(R)}$ tablet (Takeda Chemical Industries, reference drug) and Pioglitazone tablet (Boryung Company, test drug) was evaluated according to the guidelines of Korea Food and Drug Administration. Twenty-eight healthy male Korean volunteers received each medicine (pioglitazone dose of 30 mg) in a $2{\times}2$ crossover study with one week washout interval. After drug administration, blood samples were collected at specific time intervals from 0-36 hours. The plasma concentrations of pioglitazone were determined by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The total chromatographic run time was 5 min and calibration curves were linear over the concentration range of 5-2000 ng/mL for pioglitazone. The method was validated for selectivity, sensitivity, linearity, accuracy and precision. The pharmacokinetic parameters were determined from the plasma concentration-time profiles of both formulations. The primary calculated pharmacokinetic parameters were compared statistically to evaluate bioequivalence between the two preparations. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for Pioglitazone tablet and Actos$^{(R)}$ tablet were log0.9422~log1.1040 and log0.9200~log1.1556, respectively. Based on the statistical considerations, we can conclude that the test drug, Pioglitazone tablet was bioequivalent to the reference drug, Actos$^{(R)}$ tablet.

Determination of Lethal Concentrations and Lethal Times of Extracts from Tanacetum cineariaiaefolium, Derris elliptica, and Sophora flavescens, to Control Green Peach Aphid, Myzus persicae (복숭아혹진딧물, Myzus persicae, 방제를 위한 제충국, 데리스, 고삼 추출물의 살충농도와 살충시간 결정)

  • Ka Hee Cho;Hyo Jung Kim;Song Hee Han;Young Cheol Kim
    • Korean journal of applied entomology
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    • v.62 no.4
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    • pp.267-275
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    • 2023
  • Botanical extracts are employed in management of aphids. Extracts from Tanacetum cineariaiaefolium, Derris elliptica, and Sophora flavescens are widely used to control various insects. In this study, we determined concentrations of insecticidal active ingredients in commercial botanical extracts of these plants, and we investigated the time and concentration for lethal results with the green peach aphid, Myzus persicae. The concentrations of active ingredients, pyrethrins from T. cineariaiaefolium, rotenone from D. elliptica, and matrine and oxymatrine from S. flavescens, were determined after their fractionation by liquid chromatography followed by mass analysis and comparison with standard compounds. The extracts were tested for lethality in a bioassay with green peach aphids. Sprays at defined doses were applied to tobacco leaves infested with aphid nymphs. The lethal concentrations (LC50) were 20.4 ppm for pyrethrins, 34.1 ppm for rotenone, and 29.6 ppm for matrine at 48 h after treatments. At 100 ppm application levels, the lethal time LT50 was 13.4 h for pyrethrin, 15.1 h for rotenone, and 14.4 h for matrine. Kaplan-Meier analysis indicated the lethal times for the three botanical extracts at 100 ppm were significantly faster than application of a chemical insecticide, Sulfoxaflor, applied at the recommended level. These results provide baselines to develop and formulate single or mixed preparations containing botanical extracts to control green peach aphids on commercial crops.

The Impact of BIS Regulation on Bank Behavior in Asset Management (신 BIS 자기자본규제가 은행자산운용행태에 미치는 영향)

  • Oh, Hyun-Tak;Choi, Seok-Gyu
    • The Korean Journal of Financial Management
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    • v.26 no.3
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    • pp.171-198
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    • 2009
  • The primary purpose of this study is to examine the impact of new BIS regulation, which is the preparations to incorporate not only credit risk but also market and operation risk, on the bank behaviors. As methodology, SUR(seemingly unrelated regression) and pool unit test are used in the empirical analysis of banks survived in Korea. It is employed that quarterly data of BIS capital ratio, ratio of standard and below loans to total loans, ratio of liquid assets to liquid liabilities, allowances for credit losses, real GDP, yields of corporate bonds(3years, AA) covering the period of 2000Q1~2009Q1. As a result, it could be indicated that effectiveness and promoting improvements of BIS capital regulation policy as follows; First, it is explicitly seen that weight of lending had decreased and specific gravity of international investment had increased until before BIS regulation is built up a step for revised agreement in late 2001. Second, after more strengthening of BIS standard in late 2002, banks had a tendency to decrease the adjustment of assets weighted risk through issuing of national loan that is comparatively low profitability. Also, it is implicitly sought that BIS regulation is a bit of a factor to bring about credit crunch and then has become a bit of a factor of economic stagnation. Third, as the BIS regulation became hard, it let have a effort to raise the soundness of a credit loan because of selecting good debtor based on its credit ratings. Fourth, it should be arranged that the market disciplines, the effective superintendence system and the sound environment to be able to raise enormous bank capital easily, against the credit stringency and reinforce the soundness of banks etc. in Korea capital market.

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