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Effects of Preconceptional Ethanol Consumption on ADHD-Like Symptoms in Sprague-Dawley Rat Offsprings

  • Choi, In-Ah;Kim, Pitna;Joo, So-Hyun;Kim, Min-Kyeong;Park, Jin-Hee;Kim, Hee-Jin;Ryu, Jong-Hoon;Cheong, Jae-Hoon;Shin, Chan-Young
    • Biomolecules & Therapeutics
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    • v.20 no.2
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    • pp.226-233
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    • 2012
  • Ethanol exposure during gestational period is related to growth retardation, morphological abnormality, and even in neurological abnormalities including attention deficit/hyperactivity disorder (ADHD)-like behaviors on offspring. However, relatively little is known about the effects of maternal ethanol consumption prior to conception on their offspring. In this study, we investigated whether maternal ethanol administration during preconceptional phase produces ADHD-like behaviors in the rat offspring. Sprague-Dawley (SD) female rats were administrated ethanol via intragastric intubation with dosing regimen of 6 g/kg daily for 10 consecutive days and treated female rats then mated with non-treated male SD rats after 8 weeks. Another group subjected to the same procedure as those conducted on ethanol treated group except the saline administration instead of ethanol. Offspring was tested for their ADHD-like behaviors using open field test, Y maze test and impulsivity test that is performed in the aversive electronic foot shock paradigm. Offspring of preconceptional ethanol treated (EtOH) group showed hyperlocomotive activity, attention deficit and impulsivity. And reduction of striatal dopamine transporter (DAT) level was observed by Western blot in the EtOH group, compared to control (Con) group, while the immunohistochemical analysis exhibited increased expression of norepinephrine transporter (NET) in the frontal cortex. These results suggest that maternal ethanol consumption in the preconceptional phase induces ADHD-like behaviors in offspring that might be related to the abnormal expression of DAT and NET in rat.

LC15-0133, a DPP IV Inhibitor: Efficacy in Various Animal Models (LC15-0133, DPP IV 저해제: 여러 동물 모델에서의 효능)

  • Yim, Hyeon-Joo
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2008.04a
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    • pp.5-20
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    • 2008
  • GLP-1-based drugs (GLP-1 analogues and DPP IV inhibitors) and incretin mimetics are currently one of the most exciting classes of agents for type II diabetes. GLP-1, a gut peptide, is an incretin that potentiates glucose-dependent insulin release from the pancreas, slows GI-transit and stimulates the proliferation of beta-cells. DPP IV inhibitors act like incretins by inhibiting DPP IV which inactivates GLP-1. LC15-0133 is a competitive, reversible DPP IV inhibitor ($IC_{50}$ = 24 nM, Ki=0.247 nM) with excellent selectivity over other critical human proteases such as DPP II, DPP 8, elastase, trypsin. and urokinase. LC15-0133 showed long half-life and good bioavailability in rats and dogs. Inhibition of plasma DPP IV activity by LC15-0133 was kept more than 50% 24 hours after oral dosing in rats and dogs at 0.1 mg/kg and 0.02 mg/kg, respectively. The Minimum effective doses of LC15-0133 were 0.01 mg/kg for lowering blood glucose excursion during oral glucose tolerance test and 0.1 mg/kg for increasing glucose-induced GLP-1 response in C57BL/6 mice. Repeat oral administration of LC15-0133 for 1 month delayed the progression to diabetes and reduced HbA1c levels in a dose-dependent manner in Zucker Diabetic Fatty rats. In conclusion, LC15-0133 is a novel, potent, selective and orally active DPP IV inhibitor and showed an excellent blood glucose lowering effects in various animal models.

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Studies on the Disposition of Brazilin in rats (천연색소 Brazilin의 체내동태에 관한 연구)

  • 문창규;황지원;김지영;원현순;윤여표
    • Journal of Food Hygiene and Safety
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    • v.5 no.1
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    • pp.7-12
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    • 1990
  • The disposition of Brazilin including plasma concentration-time profiles, excretions via urine and bile, and plasma protein binding was investigated after intravenous or oral administration of radio labeled Brazilin ($^3H-Brazilin$) to male Wistar rats. The main pharmac:okinetic parameters were as follows; $t\;_{ 1/2}$, 13.71 hr; AUC, $53.38\;\mu\textrm{g}{\cdot}hr/ml$; AUMC, $1013.4I\;\mu\textrm{g}{\cdot}hr^2/ml$, MRT, 18.95 hr; Vss, 17778 mllkg and CL, 936.77 ml/hr.kg. The 2nd peak was found in the plasma concentration-time profiles indicating potential enterohepatic circulation. The enterohepatic circulation was supported by the bile excretion. After oral administration, about 64.4 % of administered radioactivity was excreted into the bile within 10 hours and its excretion rate reached maximum at 3 hours after administration. The Vss was extremely high, 17.8 l/kg indicating distribution of brazilin in most organs (tissues) with high concentration of brazilin in some organs. Brazilin was distributed into most of organs (spleen, adrenal, pancreas, kidney, thymus, lung, heart, liver, prostate, epididymus, testis, fat, muscle and done) except brain. High concentration of Brazilin was detected especially in liver, kidney, epididymus and testis. Approximately, 62.9% and 44.1% of the dose was excreted for intravenous and oral administration, respectively. About 80% of the dose eventually excreted into urine was excreted within 24 hr after dosing. Plasma protein binding of brazilin resulted in $40\;{\pm}\;4%$ by ultrafiltration method.

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Single-dose Oral Toxicity Study of β-glucosidase 1 (AtBG1) Protein Introduced into Genetically Modified Rapeseed (Brassica napus L.) (GM 유채에 도입된 β-glucosidase 1 (AtBG1)의 단회투여독성시험)

  • Lee, Soonbong;Jeong, Kwangju;Jang, Kyung-Min;Kim, Sung-Gun;Park, Jung-Ho;Kim, Shinje
    • Journal of Life Science
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    • v.27 no.2
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    • pp.194-201
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    • 2017
  • Rapeseed (Brassica napus L.) is an oil crop classified as Brassicaceae, and it is widely grown worldwide. To develop a drought-resistant rapeseed, the ${\beta}$-glucosidase 1 (AtBG1) gene was introduced into rapeseed because drought- and salt-resistance phenotypes were observed when the AtBG1 gene was overexpressed in arabidopsis. Newly developed genetically modified crop must be proved to be safe. Safety assessments are based on the historical usage and scientific reports of a crop. In this study, we examined the potential acute oral toxicity of AtBG1 protein expressed in genetically modified (GM) rapeseed and calculated the minimum lethal dose at 6 weeks in both male and female ICR mice. AtBG1 protein was fed at a dose of 2,000 mg/kg body weight in five male and five female mice according to the marginal capacity concentration of OECD, 2,000 mg/15 ml/kg. Mortalities, clinical findings, and body weight changes were monitored for 14 days after dosing, and postmortem necropsy was performed on day 14. This study showed that no deaths occurred in the test group, and AtBG1 protein did not result in variations in common symptoms, body weight, and postmortem findings between the two groups. This showed that the minimum lethal dose of AtBG1 protein expressed in transgenic rapeseed exceed 2,000 mg/kg body weight in both sexes.

Fatty Acid Composition of Serum and Liver in Mice and Sancho(Zanthoxylum schinifolium) Seed Oil (산초유의 지방산 조성과 마우스 혈청 및 간장의 지방산 조성변화)

  • Cha, Jae-Young;Shin, Seung-Ryeul;Cho, Young-Su
    • Food Science and Preservation
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    • v.7 no.3
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    • pp.308-312
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    • 2000
  • The major fatty acids in the Zanthoxylum schinifolium seed oil were eicosenoic acid 30.88%, oleic acid 29.94%, linoleic acid 23.55% and palmitic acid 10.52%. Fatty acid profiles in the each lipid fractions by TLC of the Z. schinifolium seed oil showed the highest composition of eicosenoic acid in triglyceride fraction and oleic acid in other fractions. Mice (ddY male strain) being starved for 24 hr were injected into gastric directly 500 mg of the Z. schinifolium seed oil, and then blood samples were obtained 0, 3 and 6 hr after dosing. In our results, eicosenoic acid appeared to be significantly increased in the serum obtained from 3 and 6 hr after injection of the Z. schinifolium seed oil. In the control mice, however, the serum samples did not exhibited any change of the Z. schinifolium seed oil. Interestingly, eicosenoic acid was significantly increased in the liver of 6 hr mice after injection. In conclusion, eicosenoic acid was the major fatty acid in the Z. schinifolium seed oil, and this fatty acid was significantly increased in the serum obtained 3 and 6 hr after injection in mice.

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The Formulation and Bioavailability of Oral Sustained Release Sulindac Delivery System (설린닥의 경구용 지속성 제제설계 및 생체이용율)

  • Rhee, Gye-Ju;Park, Sun-Hee;Whang, Sung-Joo
    • YAKHAK HOEJI
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    • v.41 no.1
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    • pp.60-73
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    • 1997
  • In order to design a 24 hr sustained release preparation of sulindac for oral administration, fast release pellet (FR), slow release pellet (SR) and two combined formulation (1 : 1 and 1 : 2) were prepared. The pharmacokinetic effect of such preparations has been evaluated using rabbits as a suitable in vivo model, and tested in man. Dose determination was carried out using curve fitting according to RSTPJP II program. In bioavailability test using rabbit, AUCs of sulindac in a few designed formulations were similar to each other. $C_{max}$- of RF and SR were 1.8 times and 1.2 times higher, respectively, compared to that of combined formulation (FR:SR=1:1). While plasma concentration of FR and SR decreased rapidly, that of combined formulation (FR:SR 1:1) lasted at the level close to $C_{max}$ for 24 hrs. Plasma concentration of sulfide form from the combined pellet(FR:SR=1:1) lasted for 24 hrs, and its AUC value was 1.4-fold, 2.7-fold. and 1.2-fold greater than FR pellet, SR pellet and combined pellet (FR:SR 1 : 2). Thus, the combined pellet of 1:1 ratio was found to be the most effective for oral sustained release formulation. Bioavailability test in human showed that AUC of sulfide from TSRP (1 : 1) was approximately 1.5 times greater than total AUC of Immbaron$^{\circledR}$ administered twice in a day. While $T_{max}$ of sulfide from lmmbaron$^{\circledR}$ was 4.33 +/- 1.37 hr (lst administration) and 3.33 ${pm}$ 0.82 hr (2nd administration), respectively, that of sulfide from TSRP increased to 7.17 ${pm}$ 2.86 hr. Plasma concentration of sulfide from TSRP was sustained at more, than 1.0 ${\mu}g{\cdot}$hr/ml until 24 hrs after one dose administration. In addition, TSRP may decrease local adverse reaction in the stomach, since plasma concentration of sulfide from the combined pellet was low within 2hrs in the stomach. In conclusion, it is suggested that TSRP formulation may be effective for oral 24 hr sustained release formulation of sulindac dosing 300 ~ 350mg once a day.

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Organic Wastewater Treatment Using Modified Fenton's Oxidation (변형 펜턴산화법을 이용한 유기폐수의 처리)

  • Kim, Ji Yeon;Yoon, Tai Il;Park, Se Jin
    • Clean Technology
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    • v.5 no.1
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    • pp.49-61
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    • 1999
  • Fenton's oxidation can improve the biodegradability of refractory organic wastewater by generating $OH{\cdot}$ which is one of the most reactive species. Fenton's reagent is used to treat a variety of industrial waste containing a range of toxic organic compounds. But this process cannot be economical because of high chemical cost of $H_2O_2$, ferrous ion solution and high sludge disposal cost. In this study, we proposed a modified Fenton's oxidation process which can reduce the reagent cost and obtain better removal efficiencies with less Fenton's reagents, and have a good potential of sludge recycling. In modified Fenton reaction, ferrous ion solution is adjusted to optimal pH with NaOH. Then it added to the sample and reacted to $H_2O_2$. For the experiment, synthetic wastewater made of phenol, which is one of the typical water pollutants, was used and the ionic strength of this wastewater was controlled by adding $NaHCO_3$. The effects of DO, ionic strength, and $H_2O_2$ dosing methods were investigated. As a result, modified Fenton's treatment efficiencies are better than conventional Fenton's reaction treating leachate and dyeing wastewater. And modified Fenton's treatment efficiencies combined to the sludge recycling for a half of Iron dosage are as good as the conventional Fenton's for a normal Iron dosage.

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A Study on the Applicability of PDA Technique in the P-CAP System for T-P Removal of STP Effluent (하수처리장 방류수의 총인 제거를 위한 P-CAP 시스템에서 PDA 기법의 활용가능성에 대한 연구)

  • Choi, Choongho;Maeng, Sungkyu;Sim, Jaehwi;Choi, Jinho;Song, Kyungguen;Lee, Byungha;Cha, Hoyoung
    • Journal of Korean Society on Water Environment
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    • v.28 no.5
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    • pp.729-742
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    • 2012
  • Recently, to using chemical coagulation process for T-P removal in STP effluent as tertiary treatment process is generalized in the country. The importance of analysis technique to save the treatment & maintenance cost during coagulation process is becoming more increased each day. Thus, it is necessary for the analysis technique during coagulation process to be presented well the characteristic of coagulation in field apply. There are a few analysis techniques such as Jar Test, zeta potential analysis and streaming current detecting techniques. But there are difficult to apply in field immediately due to long test time and difficult analysis techniques. And using PDA technique, it is reviewed applicability of the techniques as field index on pilot plant of P-CAP system The P-CAP system is composed of an in-line static mixer, a Flocculation Tank and the CAP reactor with 2 stage weir for effluent. Pre-test is performed to fix the mixing velocity in the Flocculation Tank using the PDA equipment and it fixed with 30RPM. Also, Jar Test is performed to select optimum dose of each coagulant for each T-P concentration level of influent. Result of continuous test on pilot plant of P-CAP system, the FSI in the Flocculation Tank is increased consistently by increasing each dosing concentration of coagulant such as LAS and PAC in the low level influent T-P concentration comparatively. It is considered that formed Al-hydroxide complexes for dosed coagulant are caused FSI variation. Furthermore, it seems that FSI value in the high level influent T-P concentration appeared lower than the opposite influent condition relatively because it is formed simultaneously Al-hydroxide complexes as solid type and Al-phosphorus complexes as soluble type. Thus, relation of FSI by PDA technique and T-P removal of final effluent on pilot plant of P-CAP system are very limited for the kind of coagulant and the characteristics of influent. And it though that FSI value by PDA technique with analyzing of turbidity in Flocculation Tank will be used restrictedly on field as the relative field-index.

Use of Hydrogen Peroxide with Ozone to Simultaneously Reduce MIB and Quench Ozone Residual in Existing Water Treatment Plants Sourcing Water from the Han River (한강을 원수로 하는 오존/과산화수소 고도정수처리공정에서의 MIB제거 및 잔류오존 농도에 관한 연구)

  • McAdams, Stephen R.;Koo, Bon Jin;Jang, Myung Hoon;Lee, Sung Kyoo
    • Journal of Korean Society on Water Environment
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    • v.28 no.5
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    • pp.704-716
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    • 2012
  • This paper provides a detailed account of pilot testing conducted at South Lake Tahoe (California), the Ddukdo (Seoul) water treatment plant (WTP) and the Bokjung (Seongnam) WTP between February, 2010, and February, 2012. The objectives were first, to characterize the reactions of ozone with hydrogen peroxide (Peroxone) for Han River water following sand filtration, second to determine empirical ozone and hydrogen peroxide doses to remove a taste-and-odor surrogate 2-methylisoborneol (MIB) using an advanced oxidation process (AOP) configuration and third, to determine the optimum dosing configuration to reduce residual ozone to a safe level at the exit of the process. The testing was performed in a real-time plant environment at both low- and high seasonal water temperatures. Experimental results including ozone decomposition rates were dependent on temperature and pH, consistent with data reported by other researchers. MIB in post-sand-filtration water was spiked to 40-50 ng/L, and in all cases, it was reduced to below the specified target level (7 ng/liter) and typically non-detect (ND). It was demonstrated that Peroxone could achieve both MIB removal and low effluent ozone residual at ozone+hydrogen peroxide doses less than those for ozone alone. An empirical predictive model, suitable for use by design engineers and operating personnel and for incorporation in plant control systems was developed. Due to a significant reduction in the ozone reaction/decomposition at low winter temperatures, results demonstrate the hydrogen peroxide can be "pre-conditioned" in order to increase initial reaction rates and achieve lower ozone residuals. Results also indicate the method, location and composition of hydrogen peroxide injection is critical to successful implementation of Peroxone without using excessive chemicals or degrading performance.

An Effect of Visual Acuity Protection by Natural Pigment (Anthocyanine) Extracted from Fermented Purple Sweet Potato (발효 자색고구마 추출 천연색소(anthocyanine)에 의한 시력보호 효과)

  • Seo, Eun-Sun;Ryu, Geun-Chang
    • Journal of Korean Ophthalmic Optics Society
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    • v.17 no.4
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    • pp.395-401
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    • 2012
  • Purpose: The purpose of this study was to research any effect on vision protecting or decreasing VDT syndrome of extracted anthocyanine from fermented purple sweet potato and blueberry. Methods: Subjects were aged 19-20 years old who do not have ophthalmic and systemic diseases and over -N4.00 D of refraction error. 40 mg of extracted anthocyanine from fermented purple sweet potato, from blueberry, and control group, placebo were dosed at separate try. After 2 hours later, subjects were directed perform visual display terminal (VDT) work for 2 hours. Objective refractive error was measured before dosing anthocyanine and after VDT work for 2 hours. Degree of head ache, eye pain and strain and subjective symptoms of neck, shoulder and waist was also examined through interviews by dividing its degree into severe, moderate, slight or none. Results: After 2 hours VDT work, vision protection effect in terms of refractive error for dominant eye was decreased by $0.031{\pm}0.21$ D in the group of extracted anthocyanine from fermented purple sweet potato, $0.006{\pm}0.32$ D in the group of extracted anthocyanine from blueberry. However, there was significantly myopic progression in the placebo group by $0.144{\pm}0.28$ D (t=2.27, p=0.03). Conclusions: It is considered that extracted anthocyanine from fermented purple sweet potato inhibits increase of refraction anomalies of dominant eye rather than non-dominant eye after VDT work.