• Title/Summary/Keyword: I.C.V. Injection

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INTRACEREBROVENTRICULARLY ADMINISTERED PHENYLALANINE AND TYROSINE: EFFECTS ON FEEDING BEHAVIOUR AND NOREPINEPHRINE CONCENTRATIONS OF SPECIFIC BRAIN SITES IN THE CHICKEN

  • Choi, Y.-H.;Furuse, M.;Okumura, J.;Shimoyama, Y.;Sugahara, K.;Denbow, D.M.
    • Asian-Australasian Journal of Animal Sciences
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    • v.9 no.3
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    • pp.255-259
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    • 1996
  • A study was carried out to investigate the action of central L-pheylalanine (Phe) and L-tyrosine (Tyr) on food intake of the chicken. In the first trial, Phe ($200{\mu}g/10{\mu}l$) or saline was acutely administered into the right lateral ventricle (i.c.v.) of chickens (5 birds per each group). Birds (4 birds per each group) were administered with the i.c.v. Tyr ($200{\mu}g/10{\mu}l$) or saline in the second trial. The brains of the birds were removed for catecholamine assy 30 min postadministration. Catecholamine concentrations were measured at specific sites of the brain (LH: lateral hypothalamus, PVN: paraventricular nucleus, and VMH: ventromedial hypothalamus). No significant effect of amino acids on the concentration of norepinephrine of brain sites investigated was detected. Food intake and rectal body temperature were also monitored for 6 h after central administrations of Phe, Tyr or saline (5 birds per each group). Both Phe and Tyr, up to $1mg/10{\mu}l$, failed to modulate food intake or rectal body temperature.

Administration Route Dependency of Distribution of Distribution pf PEGylated Recombinant Human Tumor Necrosis Factor Binding Protein (rhTNFbp-PEG20K dimer) following i.v. and s.c. Injection

  • Kim, Dong-Chool;Duane C. Bloedow
    • Archives of Pharmacal Research
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    • v.17 no.5
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    • pp.381-382
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    • 1994
  • Administration route dependency on the distribution of PEGylated recombinant human turor necrosis factor binding protein (rhTNFbp-PEG20K dimer) was observed following a subcutaneous (sc) and an intravenous (iv) administrationin rats. ehTNFbp-PEG20K dimer is composed of two rhTNGbp molecules (molecular weight 18, 278 daltons each) joined by polyethylene glycol 2000(PEG30K). The steady state distribution volume of rhTNFbp-PEG20K was 55 m/kg and 359 ml/kg following the i.v. and s.c. administrations, respectively. These results suggest that the distribution of ehTNFbp-PEG20K is limited within the cpillary space after i.v. administration, while rhTNFbp-PEG20K can distribute into a space (35.9% of body weight) which is between extracellylar space and total body water. A lymphatic absorption may paly a role in the distribution of rhTNFbp-PEF20K dimer following the sc administration. The present study suggests that the administration route of a lartge protein molecule should be determined depedning upon target sites.

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Pharmacokinetic Study on BR-28702-2, a New Anticancer Drug, in Rats (흰쥐에서의 신규 항암제 BR-28702-2의 체내동태)

  • 용철순;이신웅;전철수;채희상;신원섭;백우현
    • Biomolecules & Therapeutics
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    • v.3 no.2
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    • pp.97-103
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    • 1995
  • The purpose of this study was to determine pharmacokinetic parameters of BR-28702-2, a new antineoplastic agent which is the conjugate of nucleotide and phospholipid, and to compare them with those of ara-C. Male rats were cannulated in the left femoral vein and received a single i.v. bolus dose of either BR-28702-2 or ara-C. BR-28702-2 was also administered i.p. and plasma samples were analyzed by reversedphase HPLC. The t$_{1}$2($\beta$)/ of ara-C(1.22 hr.) was significantly smaller than that of BR-28702-2(4.420 hr.). The absolute bioavailability of BR-28702-2 after i.p. injection was 1.125%. This lower bioavailability, together with previous reports that marked antineoplastic activity was observed when given i.p., indicates that BR-28702-2 would act as a depot system to release active moieties. Further works, therefore, need to be done to characterize active metabolites.

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Performance Characteristics of p-i-n Type Organic Thin-film Photovoltaic Cell with CuPc: $F_4$-TCNQ Hole Transport Layer (CuPc: $F_4$-TCNQ 정공 수송층이 도입된 P-i-n형 유기 박막 태양전지의 성능 특성 연구)

  • Park, So-Hyun;Kang, Hak-Su;Senthilkumar, Natarajan;Park, Dae-Won;Choe, Young-Son
    • Polymer(Korea)
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    • v.33 no.3
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    • pp.191-197
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    • 2009
  • We have investigated the effect of strong p-type organic semiconductor $F_4$-TCNQ-doped CuPc hole transport layer on the performance of p-i-n type bulk heterojunction photovoltaic device with ITO/PEDOT:PSS/CuPc: $F_4$-TCNQ(5 wt%)/CuPc:C60(blending ratio l:l)/C60/BCP/LiF/Al, architecture fabricated via vacuum deposition process, and have evaluated the J-V characteristics, short-circuit current ($J_{sc}$), open-circuit voltage($V_{oc}$), fill factor(FF), and power conversion efficiency(${\eta}_e$) of the device. By doping $F_4$-TCNQ into CuPc hole transport layer, increased absorption intensity in absorption spectra, uniform dispersion of organic molecules in the layer, surface uniformity of the layer, and enhanced injection currents improved the current photovoltaic device with power conversion efficiency(${\eta}_e$) of 0.16%, which is still low value compared to silicone solar cell indicating that many efforts should be made to improve organic photovoltaic devices.

Functional Abnormalities of HERG Mutations in Long QT Syndrome 2 (LQT2)

  • Hiraoka, Masayasu
    • The Korean Journal of Physiology and Pharmacology
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    • v.5 no.5
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    • pp.367-371
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    • 2001
  • The chromosome 7-linked long QT syndrome (LQT2) is caused by mutations in the human ether-a- go-go-related gene (HERG) that encodes the rapidly activating delayed rectifier $K^+$ current, $I_{Kr},$ in cardiac myocytes. Different types of mutations have been identified in various locations of HERG channel. One of the mechanisms for the loss of normal channel function is due to membrane trafficking of channel protein. The decreased channel function in some deletion mutants appears to be due to loss of coupling with wild type HERG to form the functional channel as the tetramer. Most of missense mutants with few exceptions could interact with wild type HERG to form functional tetramer and caused dominant negative suppression with co-injection with wild type HERG showing variable effects on current amplitude, voltage dependence, and kinetics of activation and inactivation. Two missense mutants at pore regions of HERG found in Japanese LQT2 (A614V and V630L) showed accentuated inward rectification due to a negative shift in steady-state inactivation and fast inactivation. One mutation in S4 region (R534C) produced a negative shift in current activation, indicating the S4 serving as the voltage sensor and accelerated deactivation. The C-terminus mutation, S818L, could not express the current by mutant alone and did not show dominant negative suppression with co-injection of equal amount of wild type cRNA. Co-injection of excess amount of mutant with wild type produced dominant negative suppression with a shift in voltage dependent activation. Therefore, multiple mechanisms are involved in different mutations and functional abnormality in LQT2. Further characterization with the interactions between various mutants in HERG and the regulatory subunits of the channels (MiRP1 and minK) is to be clarified.

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Emission Properties of OLED Devices with Various Hole Injection Materials (정공주입층에 따른 OLED 소자의 발광 특성)

  • Lee, Bong-Sub;Gao, Xin-Wei;Park, Jong-Yek;Baek, Yong-Gu;Yang, Jae-Woong;Paek, Kyeong-Kap;Ju, Sung-Hoo
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.21 no.6
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    • pp.562-568
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    • 2008
  • In this paper, the hole injection layer(HIL) materials have been synthesized and analyzed. Their HOMO levels are $4.93{\sim}5.22\;eV$, and their energy band gaps are $2.74{\sim}3.19\;eV$. Their glass transition temperatures($T_g$) are all above $114^{\circ}C$, which implies that they are highly thermal-stable. The green OLED devices with a structure of ITO(150 nm)/NEW_HIL(50 nm)/NPB(30 nm)/$Alq_3$(50 nm)/Al:Li(100 nm) were fabricated and tested, incorporating these newly synthesized HIL materials. According to the test results of OLED devices, the I-V-L performances of these devices increase in the following sequence: ELM307 > ELM200 > ELM321 > ELM327 > ELM325. In addition, the OLED device with ELM307 as a HIL has the highest brightness and efficiency at the same driving voltage. These experimental results have shown that ELM307 can be used as one of the most promising candidates for HIL materials.

Effect of Brain Angiotensin II Receptor Antagonists and Antisense Oligonucleotide on Drinking and Renal Renin in Rats

  • Cho, Hyeon-Kyeong;Yang, Eun-Kyoung;Han, Hee-Suk;Lee, Won-Jung;Phillips, M. Ian
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.2
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    • pp.137-142
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    • 2000
  • The physiological roles of brain angiotensin II in mediating water deprivation-induced drinking and in regulating renal renin release were assessed in male Sprague-Dawley rats. Specific $AT_1$ receptor antagonists, losartan and SK 1080, and antisense oligonucleotide (AS-ODN) directed to $AT_1$ receptor mRNA were intracerebroventricularly (i.c.v.) administered in conscious unrestrained rats. When water was given 20 min after i.c.v. injection of $AT_1$ receptor antagonists in 48-h water-deprived rats, losartan and SK 1080 produced approximatly 20% and 50% decrease in 1-h water intake, respectively. In contrast, i.c.v. treatment of the AS-ODN to $AT_1$ receptor mRNA for 24-h did not alter 1-h water intake in 24-h water-deprived rats, but prevented the increase in overnight water intake after 24-h water-deprivation. Six-day i.c.v. treatment of AS-ODN did not alter either the basal plasma renin concentration or renal cortical levels of renin and renin mRNA. The present results suggest that endogenous brain Ang II plays an important role in thirst and water intake through $AT_1$ receptors, but further studies are required to elucidate its regulatory role in renal renin synthesis.

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Effect of Sulfonylureas Administered Centrally on the Blood Glucose Level in Immobilization Stress Model

  • Sharma, Naveen;Sim, Yun-Beom;Park, Soo-Hyun;Lim, Su-Min;Kim, Sung-Su;Jung, Jun-Sub;Hong, Jae-Seung;Suh, Hong-Won
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.3
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    • pp.197-202
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    • 2015
  • Sulfonylureas are widely used as an antidiabetic drug. In the present study, the effects of sulfonylurea administered supraspinally on immobilization stress-induced blood glucose level were studied in ICR mice. Mice were once enforced into immobilization stress for 30 min and returned to the cage. The blood glucose level was measured 30, 60, and 120 min after immobilization stress initiation. We found that intracerebroventricular (i.c.v.) injection with $30{\mu}g$ of glyburide, glipizide, glimepiride or tolazamide attenuated the increased blood glucose level induced by immobilization stress. Immobilization stress causes an elevation of the blood corticosterone and insulin levels. Sulfonylureas pretreated i.c.v. caused a further elevation of the blood corticosterone level when mice were forced into the stress. In addition, sulfonylureas pretreated i.c.v. alone caused an elevation of the plasma insulin level. Furthermore, immobilization stress-induced insulin level was reduced by i.c.v. pretreated sulfonylureas. Our results suggest that lowering effect of sulfonylureas administered supraspinally against immobilization stress-induced increase of the blood glucose level appears to be primarily mediated via elevation of the plasma insulin level.

Evaluation of Pharmacological Effect of Soybean Trypsin Inhibitor-Chondroitin Sulfate Conjugates (Soybean Trypsin Inhibitor와 황산 콘드로이친 포합체의 약리 효과 평가)

  • Choi, Youn-Lim;Nam, Hyun-Gu;Shin, Young-Hee
    • Journal of Pharmaceutical Investigation
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    • v.30 no.3
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    • pp.159-166
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    • 2000
  • Kunitz-type soybean trypsin inhibitor (SBTI) and chondroitin sulfate (A, and C type) were conjugated using sodium periodate method. And the physicochemical, pharmacokinetic properties and immunogenecity of the conjugates (Chon-A-SBTI or Chon-C-SBTI) were characterized. We expected the conjugation using chondroitin sulfate to reduce the immunogenecity and to improve the pharmacological effect. As the results, the mean molecular weight of the conjugate highly increased. After I.V. injection of the radiolabeled conjugates or native SBTI into mice, it was found that native SBTI showed rapid elimination from plasma, whereas Chon-A-SBTI and Chon-C-SBTI were slowly eliminated. Organ distribution of the two agents at 30 min after I.V. injection was different : Chon-A-SBTI or Chon-C-SBTI accumulated to a large extent in the liver (13% in Chon-A-SBTI and 16% in Chon-C-SBTI), whereas native SBTI was taken up more rapidly by the kidney (107% dose/g of tissue) and excreated into the urine (26%). In addition we evaluated the therapeutic value of the conjugates by using the sublethal septic shock model caused by pseudomonal elastase and tested the immunogenecity by passive cutaneous anaphylaxis shock (PCA). The conjugates were more effective than native SBTI against pseudomonal elastase induced septic shock in guinea pig. In case of the conjugates, the pharmacological and therapeutic effect lasted over 3 hours long. In immunogenecity test, both of the conjugates showed the reduction of their immunogenecity, especially Chon-A-SBTI looked most effective.

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Inhibitory Effects of Tumor Metastasis by Chitosan Derivative, of Sulfated N-acetyl Chitosan (키토산 유도체인 Sulfated N-acetyl Chitosan의 종양전이 억제효과)

  • 류병호;김동석필립그린스판
    • KSBB Journal
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    • v.10 no.5
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    • pp.525-532
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    • 1995
  • Chitosan derivative, of a sulfated N-acetyl chitosan was synthesized, and the inhibitory effects of this compound on the experimental and spontaneous lung metastallc B16/BL6 melanoma bearing mice were investigated. Position of substitution with sulfate in water-soluble sulfated derivatives of chitosan were analysed by 13C-nmr. The structure of N-acetyl chitosan 3,6 0-disulfate were confirmed. The tumor growth inhibition of B16/BL6 melanoma cells has been shown at the highest level of 77.6% when sulfated N-acetyl chitosan were administered at the dose of 100mg/kg. In the lung metastasls, the sulfated N-atetyl chitosan was administered to C57BL/6B mice bearing B16/BL6 melanoma cells by I.V. injection and the number of metastasis foci of melanoma were decreased by the dose dependent manner ranging from 20 to 100mg/kg. In the spontaneous metastasis, I.V. administrations of sulfated N-acetyl chitosan after tumor inoculation resulted in marked reduction of metastatic colonies. A sulfated N-acetyl chitosan was able to partially inhibit the tumor cell adhesion by migration to laminin. These results suggested that chitosan derivative, a sulfated N-acetyl chitoasn was able to inhibit to the experimental and spontaneous metastasis models as well as cell adhesion ability.

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