• Title/Summary/Keyword: 5-HT)

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Pharmacokinetics and Bioavailability of New Synthetic 5-HT2C Agonists, KKHQ80109 and KKHQ80114, in Sprague-Dawley Rats

  • Im, Hye-Yeon;Choo, Hyun-Ah;Pae, Ae-Nim;Kwon, Oh-Seung
    • Journal of Pharmaceutical Investigation
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    • v.39 no.5
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    • pp.327-331
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    • 2009
  • 5-HT$_{2C}$ receptors have been considered as therapeutic targets for the treatment of various central nervous system disorders such as depression, anxiety, epilepsy, schizophrenia and sleep disorders. We chemically synthesized KKHQ80109 (K09) and KKHQ80114 (K14), selective 5-HT$_{2C}$ agonists, with the purpose of developing therapeutic agents for the treatment of obesity. The objective of this work is to investigate pharmacokinetic parameters and bioavailability of K09 and K14 in rats given orally or intravenously. Oral administration of 20 mg/kg K09 results in 4.11 hr of the terminal half-life and 89.16 ng/mL of C$_{max}$ at 5.00 hr (T$_{max}$). The terminal half-life of K14 was 3.83 hr with 215.81 ng/mL of C$_{max}$ at 3.33 hr (T$_{max}$) after oral dosing of 20 mg/kg K14, indicating that K14 is more rapidly absorbed than K09. Bioavailability showed 0.17-0.21 for K09 and 0.19-0.23 for K14. Urinary excretion of parent K09 and K14 was less than 1%, indicating that K09 and K14 undergo very extensive hepatic metabolism.

Effect of Acupuncture on Depression and Cell Proliferation in Hippocampal Gyrus Dentatus of Maternal-separated Rat Pups (침술 치료가 모성분리 새끼 쥐의 우울증과 해마의 치상회 세포증식에 미치는 영향)

  • Park, Jung-Sik;Lim, Hyung-Ho
    • Journal of Korean Medicine Rehabilitation
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    • v.29 no.2
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    • pp.91-99
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    • 2019
  • Objectives The loss of maternal care during early postnatal period may increase development of mood-related disorders, such as depression, anxiety, and personality disorders. In this study, the effect of acupuncture on depression in relation with cell proliferation in the hippocampal gyrus dentatus was investigated using maternal-separated rat pups. Methods On the postnatal 14th day, rat pups from six dams were grouped into following groups: maternal care group, maternal separation group, maternal separation and non-acupoint-acupunctured group, maternal separation and Zusanli-acupunctured group, and maternal separation and fluoxetine-treated group. Acupuncture was performed from postnatal 28th day to postnatal 37th day. The rat pups that belong in the maternal separation and fluoxetine-treated group were injected subcutaneously with 5 mg/kg fluoxetine hydrochloride once a day for the same period of time. To evaluate activity of the rat pups, open field test was performed. Immunohistochemistry for serotonin (5-hydroxytryptamine, 5-HT) and tryptophan hydroxylase (TPH) in the dorsal raphe and for 5-bromo-2'-deoxyuridine (BrdU) in the hippocampal gyrus dentatus was conducted. Results The present results reveal that the activity was decreased by maternal separation. In contrast, acupuncture at Zusanli overcame maternal separation-induced hypoactivity. Maternal separation suppressed TPH expression and 5-HT synthesis in the dorsal raphe and decreased cell proliferation in the hippocampal gyrus dentatus of rat pups. In contrast, acupuncture at Zusanli alleviated maternal separation-induced decrease of 5-HT synthesisand TPH expression. Conclusions The present results demonstrate that acupuncture at Zusanli ameliorated depressive state through increasing cell proliferation and enhancing 5-HT synthesis.

Effect of the Hexane Extract of Saussurea lappa on the Growth of HT-29 Human Colon Cancer Cells (목향 헥산추출물이 대장암세포인 HT-29 세포의 증식에 미치는 영향)

  • Kim, Eun-Ji;Park, Hee-Sook;Lim, Soon-Sung;Kim, Jong-Sang;Shin, Hyun-Kyung;Yoon, Jung-Han
    • Korean Journal of Food Science and Technology
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    • v.40 no.2
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    • pp.207-214
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    • 2008
  • In Asia Saussurea lappa (SL) has been used as a traditional herbal medicine to treat abdominal pain and tenesmus. Recently, in vitro cell culture studies have shown that SL has anti-ulcer, anti-inflammatory, and anti-tumor properties. To explore its potential chemopreventive and chemotherapeutic effects in colon cancer, we examined whether the hexane extract of SL (HESL) could inhibit the growth of HT-29 human colon cancer cells, and investigated the mechanisms for this effect. The cells were cultured with various concentrations (0-5 ${\mu}g/mL$) of HESL. The results indicated that HESL markedly decreased the numbers of viable HT-29 cells; whereas at the concentration of 5 ${\mu}g/mL$, HESL slightly decreased the viable cell numbers of CCD 1108Sk human skin normal fibroblasts at 72 hr. HESL substantially increased the numbers of cells in the sub G1 phase, and dose-dependently increased apoptotic cell numbers. Western blot analysis of the total cell lysates revealed that HESL increased Bax protein levels, but did not affect Bcl-2 levels. HESL induced the cleavage of poly (ADP-ribose) polymerase and caspases 8, 9, 7, and 3. This study demonstrated that HESL inhibits cell growth and induces apoptosis in HT-29 cells, which may be mediated by its ability to increase Bax levels and activate the caspase pathway. These findings may lead to the development of new therapeutic strategies for colon cancer treatment.

Fullerene derivatives for Polymer Bulk-heterojunction Solar Cells (고분자 태양전지용 플러렌 유도체)

  • Shin, Won-Suk;Hwang, Yong-Mook;Yoon, Sung-Cheol;Lee, Chang-Jin;Moon, Sang-Jin
    • 한국신재생에너지학회:학술대회논문집
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    • 2007.06a
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    • pp.246-249
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    • 2007
  • 현재까지 $P3HT:C_{60}-PCBM$계는 고분자 유기 태양전지에서 가장 좋은 효율을 보여주고 있다. 그러나 보다 고효율의 소자 제작을 위해 신재료에 대한 연구들이 활발히 진행되고 있으며, 본 연구에서는 $C_{60}-PCBM$ 대신 $C_{70}-PCBM$을 합성하여 소자를 제작하였다. $C_{70}-PCBM$$C_{60}-PCBM$에 비하여 가시광선 영역에서 상대적으로 높은 광흡수율을 보여 주었으며, 이것은 광전류의 향상을 가져왔다. 소자제작의 주요 변수로 $P3HT:C_{70}-PCBM$ 광활성층의 처리 조건, 즉, 용매, 조성비, 열처리 조건, 광활성층의 두께 등을 조절하였는데, buffer층(LiF 층) 등이 도입되지 않은 간단한 제작조건 하에서도 본 $C_{70}-PCBM$$C_{60}-PCBM$계에 버금가는 3.5% (AM 1.5G, 100 $mW/cm^{2}$ 조건) 이상의 효율을 나타내었다.

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Study on characteristics of SCC and AE signals for the weld HAZ of HT-60 steel under corrosion control (부식제어하에서 HT-60강 용접부의 SCC 및 AE 신호 특성에 관한 연구)

  • 나의균;고승기
    • Proceedings of the KWS Conference
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    • 1999.05a
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    • pp.241-244
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    • 1999
  • The purpose of this study is to examine the characteristics of stress corrosion cracking(SCC) and acoustic emission(AE) signals for the weld HAZ of HT-60 steel under corrosion control in synthetic seawater. Corrosive environment was controlled by potentiostat, and SCC experiment was conducted using a slow strain rate test method at strain rate of 10$^{-5}$ /sec. In order to verify the miroscopic fracture behaviour of the weldment during SCC phenomena, AE test was done simultaneously. Besides, correlationship between mechanical parameters and AE ones was investigated. In case of the parent, reduction of area(ROA) at -0.5V was samller than any other applied voltage such as -0.8V and -1.1V. In addition, reduction of area for the PWHT specimens at -0.8mV was larger than that of the weldment due to the softening effect according to PWHT. In case of the weldment, a lots of events was produced because of the singularities of the weld HAZ compared with the parent.

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A Computational Study on the Adsorption Characteristics of Hydrocarbons (Propylene, n-Butane and Toluene) by uing Cation-exchanged ZSM-5 Zeolites

  • Lee, Hyun Chul;Kim, Kyung Min;Choi, Sung Il;Kim, Yong Ha;Woo, Hee Chul;Won, Yong Sun
    • Korean Chemical Engineering Research
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    • v.56 no.6
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    • pp.909-913
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    • 2018
  • A hydrocarbon trap (HT) plays an important role of controlling vehicle emissions in the so-called cold emission period by holding hydrocarbons until three way catalysts (TWCs) are thermally activated. In this study, we have investigated the adsorption characteristics of cation (H, La, K, and Ag)-exchanged ZSM-5 zeolites for hydrocarbons (propylene, n-butane, and toluene) by DFT (density functional theory)-based computational chemistry. Cation exchange is to improve the hydrothermal stability of zeolites and their adsorption capacity, thereby rendering cation-exchanged zeolites promising materials for HT. The idea of cluster approximation makes the calculation of adsorption energies superbly efficient in computation. The results showed that Ag-exchanged ZSM-5 would be the best for the adsorption of all three adsorbates, without often encountered Ag oxidation in experiments. Besides, the hydrothermal stability of La-exchanged ZSM-5 was confirmed from the change of geometrical parameters by cation exchange, and it showed good adsorption capacity for propylene and toluene. Hydrogen-exchanged ZSM-5 was also good for hydrogen adsorption, but had poor hydrothermal stability.

Effect of Fluoxetine on the Induction of Long-term Potentiation in Rat Frontal Cortex

  • Kim, Hwang-Soo;Kim, Hyun-Sok;Hahn, Sang-June;Kim, Myung-Jun;Yoon, Shin Hee;Jo, Yang-Hyeok;Kim, Myung-Suk;Rhie, Duck-Joo
    • The Korean Journal of Physiology and Pharmacology
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    • v.8 no.6
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    • pp.295-300
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    • 2004
  • Serotonin (5-hydroxytroptamine, 5-HT) has been shown to affect the induction of long-term potentiation (LTP) in the cortex such as the hippocampus, the visual cortex and the prefrontal cortex. Fluoxetine, as a selective serotonin reuptake inhibitor, is used in the management of a wide variety of psychological diseases. To study the effect of fluoxetine on the induction of LTP, we recorded the field potential in layer II/III of the frontal cortex from 3-wk-old. LTP was induced in horizontal input by theta burst stimulation (TBS). TBS with two-folds intensity of the test stimulation induced LTP, which was blocked by application of D-AP5 $(50 {\mu}M)$, an NMDA receptor antagonist. Whereas bath application of 5-HT $(10 {\mu}M)$ inhibited the induction of LTP, treatment with the 5-HT depleting agent, para-chloroamphetamine $(PCA,\;10{\mu}M)$, for 2hr did not affect the induction of LTP. Bath application of fluoxetine (1, 3, and $10 {\mu}M)$ suppressed the induction of LTP in concentration-dependent manner, however, fluoxetine did not inhibit the induction of LTP in 5-HT-depleted slices. These results indicate that fluoxetine may inhibit the induction of LTP by modulating serotonergic mechanism in the rat frontal cortex.

Antidepressant-Like Effects of Lycii Radicis Cortex and Betaine in the Forced Swimming Test in Rats

  • Kim, Soo Jeong;Lee, Mi-Sook;Kim, Ji Hyun;Lee, Tae Hee;Shim, Insop
    • Biomolecules & Therapeutics
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    • v.21 no.1
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    • pp.79-83
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    • 2013
  • The purpose of the present study was to examine the effect of Lycii Radicis Cortex (LRC) and betaine (BT) on immobility and neurochemical change in the forced swimming test (FST) in the rat. LRC, BT or fluoxentine was administered intraperitoneally to Sprague-Dawley rats three times (1, 5 and 23.5 h) before the FST. To investigate antidepressant-like effect, serotonin (5-HT) and norepinephrine (NE) were examined in the hippocampus and hypothalamus of rats. LRC (100 mg/kg) and BT (30, 100 mg/kg) significantly decreased the immobility time in the FST. LRC (100 mg/kg) significantly increased both 5-HT and NE levels in the hypothalamus of rats exposed to FST. BT (100 mg/kg) significantly increased 5-HT levels in the hypothalamus and hippocampus of rats. Taken together, these results demonstrated that improvement in the behavioral changes after LRC and BT administration may be mediated by elevation of 5-HT level in the hypothalamus and hippocampus, indicating a possible antidepressant-like activity. The present results suggest that the efficacy of LRC and BT in an animal model of depression may provide anti-depressant effects in human, which remains to be determined.

Growth and Energy Budgets of Greenling Hexagrammos otakii Larvae and Juveniles Reared on Different Diets and Temperatures (쥐노래미(Hexagrammos otakii)자치어의 먹이와 수온에 따른 성장 및 에너지 수지)

  • Park, Jun Woo;Kwon, O-Nam;Park, Kie-Young
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.46 no.3
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    • pp.287-295
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    • 2013
  • The growth, respiration, ingestion, and ecological efficiencies of Hexagrammos otakii larvae and juveniles reared on different diets and temperatures were estimated. A factorial experiment using two diets [non-enriched hatched Artemia nauplii (NEA) and enriched Artemia nauplii (EA)] crossed with two temperatures [natural seawater temperature (NT, $5.1-8.5^{\circ}C$) and heated seawater (HT, $13{\pm}0.5^{\circ}C$)] was conducted to investigate growth and energy budgets of Hexagrammos otakii larvae and juveniles. The energy used by larvae and juveniles for 6 weeks was calculated using data on ingestion, growth, respiration, excretion, and egestion. In the NT trials, the energy used for growth by larvae and juveniles was 0.121 and 0.129 Kcal in the NEA and EA treatments, respectively. Assimilation efficiency at NT were 78.0% and 80.2% in the NEA and EA trials, respectively. Gross growth efficiency ($K_1$) were 60.5% and 62.3% and net growth efficiency ($K_2$) was 77.56% and 77.71% in the NEA and EA trials, respectively. In the HT trials, the energy used for growth by juveniles was 0.189 and 0.212 Kcal in the NEA and EA trials, respectively. Assimilation efficiency at HT was 86.4% and 95.1% in the NEA and EA trials, respectively. Values of $K_1$ and $K_2$ at HT were 69.5% and 80.43%, respectively, in the NEA trials, and 73.9% and 77.66%, respectively, in the EA trials. These results suggest that enriched Artemia nauplii and higher temperatures ($13{\pm}0.5^{\circ}C$) are effective for rearing larvae and juveniles of H. otakii.

Anticancer Effects of Black Soybean Doenjang in HT-29 Human Colon Cancer Cells (HT-29 인체 대장암 세포에서 검정콩 된장의 in vitro 항암 효과)

  • Park, Eui Seong;Lee, Jae-Yang;Park, Kun-Young
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.9
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    • pp.1270-1278
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    • 2015
  • In vitro anticancer effects of black soybean doenjang on HT-29 human colon cancer cells were studied. SD (soybean doenjang prepared with nine-time baked bamboo salt) and BD (black soybean doenjang prepared with nine-time baked bamboo salt) were compared with CD (commercial doenjang). There were no significant differences between experimental groups in terms of pH, amino-type nitrogen, and ammonia-type nitrogen levels of the doenjang samples. BD showed the highest antioxidative effect, followed by SD and CD in that order. BD also showed the highest total polyphenol concentration of all samples. CD, SD, and BD extracts showed no toxic effects on normal RAW 264.7 cells at a concentration ranging from 0.1 to 0.5 mg/mL. BD exhibited anticancer effect on HT-29 cells by MTT assay. Also, BD manipulated mRNA expressions in certain factors; it suppressed pro-inflammatory cytokines such as $TNF-{\alpha}$, IL-6, and COX-2, promoted cell-cycle-related genes of p21, and p53, suppressed expression of cyclin D1, and suppressed anti-apoptotic Bcl-2; such manipulation by BD was the strongest, followed by SD and CD in order. From the results above, BD exhibited the highest anticancer effects by inhibiting growth of HT-29 cells, probably by regulating pro-inflammatory cytokines, cell cycling related genes, etc. These results might be due to using black soybeans containing high levels of polyphenol, including anthocyanins.