• Title/Summary/Keyword: Novel drugs

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AN EXPERIMENTAL STUDY ON THE CHEMOPREVENTIVE EFFECT OF CHLOROPHYLLIN IN HAMSTER CHEEK POUCH TUMOR INDUCED BY 7, 12-DIMETHYLBENZ[A]ANTHRACENE (7, 12-dimethylbenz[a]anthracene(DMBA)로 유발된 햄스터 협낭암에서 chlorophylln의 암예방효과에 관한 실험적 연구)

  • Yoon, Kyu-Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.26 no.2
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    • pp.137-145
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    • 2000
  • Carcinogenesis is a multi-stage process that generally consists of at least three steps; initiation, promotion, and progression. If one of these carcinogenic steps were suppressed or delayed, the cancer could be prevented. Cancer chemoprevention is defined to be inhibition or reversal of the carcinogenic process by the specific chemical agents and is a novel approach to cancer management alternative to conventional chemotherapy. Chlorophylln(CHL), a water-soluble derivative of chlorophyll, containing sodium and copper, has been known to be strong antimutagen in several test systems, but its mechanism of antimutagenic action is unknown. In the present experiment, the possibility of CHL as chemopreventive drugs on 7,12-dimethylbenz[a]anthracene(DMBA)-induced hamster buccal pouch carcinogenesis was investigated by mutagenicity test, carcinogenicity test, and frequency or spectrum of H-ras mutations in the both of DMBA-induced and chlorophylln-pretreated-DMBA induced tumor by polymerase chain reaction and non-isotopic restriction fragment length polymorphism. The treatment of CHL reduced the yields and multiplicity of the 0.5% DMBA-induced tumor, 86% to 62.5% and $3.7{\pm}0.6$ to $1.4{\pm}0.3$, respectively. The occurrence of histidine revertant by $20{\mu}mole$ DMBA was inhibited 25.6 to 81.7% by 1 to $5{\mu}M$ CHL in a dose-dependent manner. The mutation rates of H-ras gene in DMBA-induced and CHL-pretreated-DMBA induced tumor were 96%, 94% of which the most mutations were in codon 12/13. These results suggest that CHL inhibits the carcinogenic action of DMBA by the formation of complex between CHL and DMBA or the inhibition of the activation of DMBA in vivo. But CHL did not affect the mutation rates or its spectrum in already formed tumor.

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In Vitro and In Vivo Anti-Tobacco Mosaic Virus Activities of Essential Oils and Individual Compounds

  • Lu, Min;Han, Zhiqiang;Xu, Yun;Yao, Lei
    • Journal of Microbiology and Biotechnology
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    • v.23 no.6
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    • pp.771-778
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    • 2013
  • Essential oils are increasingly of interest for use as novel drugs acting as antimicrobial and antiviral agents. In the present study, we report the in vitro antiviral activities of 29 essential oils, extracted from Chinese indigenous aromatic plants, against the tobacco mosaic virus (TMV). Of these essential oils, those oils from ginger, lemon, tea tree, tangerine peel, artemisia, and lemongrass effected a more than 50% inhibition of TMV at 100 ${\mu}g/ml$. In addition, the mode of antiviral action of the active essential oils was also determined. Essential oils isolated from artemisia and lemongrass possessed potent inactivation and curative effects in vivo and had a directly passivating effect on TMV infection in a dose-dependent manner. However, all other active essential oils exhibited a moderate protective effect in vivo. The chemical constitutions of the essential oils from ginger, lemon, tea tree, tangerine peel, artemisia, and lemongrass were identified by gas chromatography and gas chromatography-mass spectrometry. The major components of these essential oils were ${\alpha}$-zingiberene (35.21%), limonene (76.25%), terpinen-4-ol (41.20%), limonene (80.95%), 1,8-cineole (27.45%), and terpinolene (10.67%). The curative effects of 10 individual compounds from the active essential oils on TMV infection were also examined in vivo. The compounds from citronellal, limonene, 1,8-cineole, and ${\alpha}$-zingiberene effected a more than 40% inhibition rate for TMV infection, and the other compounds demonstrated moderate activities at 320 ${\mu}g/ml$ in vivo. There results indicate that the essential oils isolated from artemisia and lemongrass, and the individual compound citronellal, have the potential to be used as an effective alternative for the treatment of tobacco plants infected with TMV under greenhouse conditions.

Effects of Arsenic Compounds $(AS_2O_3\;and\;AS_4O_6)$ on the Induction of Apoptotic Cell Death in A549 Human Non-small Cell Lung Cancer Cells (비소화합물에 의한 A549 폐암세포의 증식억제에 관한 연구)

  • Choi, Yung-Hyun;Choi, Woo-Young;Choi, Byung-Tae;Lee, Yong-Tae;Lee, Won-Ho
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.4
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    • pp.1050-1054
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    • 2005
  • Recently, arsenic compounds were considered as novel agents for treatment of acute promyelocytic leukemia and malignant tumors. However, it showed severe toxicity effect on normal tissue at the same time. In this study, to investigate the possible molecular mechanism (s) of arsenic compounds as candidate of anti-cancer drugs, we compared the abilities of two arsenic compounds, tetraarsenic oxide $(AS_4O_6)$ and arsenic trioxide (diarsenic oxide, $As_2O_3$), to induce cell growth inhibition as well as apoptosis induction in A549 human non-small cell lung cancer cells. Both $As_4O_6\;and\;As_2O_3$ treatment declined the cell growth and viability of A549 cells in a concentration-dependent manner, which was associated with induction of G1 arrest of the cell cycle and apoptotic cell death. However, $As_4O_6$ induced growth inhibition and apoptosis in A549 cells at much lower concentrations than $As_2O_3.\;As_4O_6$ down-regulated the levels of anti-apoptotic Bcl-2 protein, however, the levels of Bax, a pro-apoptotic protein, were up-regulated in a dose-dependent manner. In conclusion, $As_4O_6$ might be a new arsenic compound which may induce apoptosis in A549 cells by modulation the Bcl-2 family and deserves further evaluation.

Effects of Rhus verniciflua Stokes Extract on Cell Viability, Cell Cycle Progression and Apoptosis of AGS Cell (건칠(乾漆)이 위암세포의 활성, 세포사멸 및 세포주기관련 유전자 발현에 미치는 영향)

  • An, Jin-Yeong;Ko, Seong-Gyu;Ko, Heung
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.3
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    • pp.701-709
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    • 2006
  • The Rhus verniciflua Stokes (乾漆-RVS) has been used in traditional East Asia medicine for the therapy of gastritis, stomach cancer, although the mechanism for the biological activity is unclear. In the present study aims to investigate RVS extract contributes to growth inhibitory effect and it's the molecular mechanism on the human gastric cancer cells. AGS (gastric cancer cells) and RIEI (normal cells) were treated to different concentrations and periods of RVS extract $(10{\;}{\sim{{\;}100{\;}ug/mil)$. Growth inhibitory effect was analyzed by measuring FACS study and MTS assay. Cell cycle inhibition was confirmed by measuring CDK2 kinase activity by immunoprecipitation and kinase assay. And apoptosis was confirmed by surveying caspase cascades activation using a pan caspase inhibitor Exposure to RVS extract (50 ug/mll) resulted in a synergistic inhibitory effect on cell growth in AGS cells. Growth inhibition was related with the inhibition of proliferation and induction of apoptosis. The extract induces Gl -cell cycle arrest through the regulation of cyclins, the induction of p27kip1, and the decrease CDK2 kinase activity. And upregulated p27kip1 level is caused by protein stability increment by the reduction of S-phase kinase-associated protein 2 (Skp2), a key molecule related with p27kip1 ubiquitination and degradation, and do novo protein synthesis. Besides, 乾漆 extract induces apoptosis through the expression of Bax, poly(ADP-ribose) polymerase (PARP) and activation of caspase-3. RVS extract induces Gl -cell cycle arrest via accumulation of p27kip1 and apoptosis in human gastric cancer cells but not in normal cells, therefore we suggest that the extract can be used as a novel class of anti-cancer drugs.

Study on Reception and Modification Process of Yaksung-ga in Korean Medicine at Late Chosun Dynasty (조선후기 한의학에서 공정현(龔廷賢) 약성가(藥性歌)의 수용과 변천과정에 대한 연구)

  • Hwang, Jong-Sun;Choi, Dall-Yeong;Jeong, Han-Sol;Shin, Sang-Woo;Ha, Ki-Tae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.6
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    • pp.924-934
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    • 2010
  • Yaksung-ga is a short Chinese poem, written for easy memorizing of properties and effects of various herbal drugs. It is very useful for teaching herbalogy and for using in clinical practice. In spite of its importance, research of the Yaksung-ga is very insufficient. Thus, we investigated literary works of Tingxian Gong and Korean medical books in the late Chosun dynasty, to explain how Yaksung-ga had been received and modified in Korean medicine. Manbinghuichun(萬病回春) and Shoushibaoyuan(壽世保元), the literatures of Tingxian Gong, are the origin of Yaksung-ga. Jejungshinpyun(濟衆新編) is the first book which recorded Yaksung-ga in Korea, having influenced Juchonshinbang(舟村新方) and Euijongsonik(醫宗損益). The classification system of Yaksung-ga was remarkably changed in Euijongsonik, according to the method of Bencaogangmu(本草綱目). And the Yaksung-ga of Bangyakhappyun(方藥合編), which is generally used in Korea at present, was shortened from the form of 8 Chinese characters in each line to 7 characters, so that it can be easily recited. In the end, the authors of Korean medical books selectively cited the Yaksung-ga of Tingxian Gong, and added many novel Yaksung-ga.

Pharmacokinetics and Tissue Distribution of a New Fluoroquinolone Containing C7-Bicyclic Structure in Rats (C7-이환체 구조를 갖는 새로운 플루오로퀴놀론계 항생물질의 흰쥐 체내동태와 조직분포)

  • 조재열;한승희;김병오;남권호;손호정;이재욱;유영효;박명환
    • Biomolecules & Therapeutics
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    • v.5 no.4
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    • pp.419-425
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    • 1997
  • The pharmacokinetics of DWP20364 (1-cyclopropyl -5-amino-6,8-difluoro-7-(2,7-diazabiclo [3,3,0] oct-4-ene-7-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid), a novel fluoroquinolone containing C7-bicyc-talc structure, were compared with those of ciprofloxacin (CPFX) after single intravenous (i.v.) and oral (p.o.) administration to rats using microbiological assay (bioassay). After i.v. administration to rats, the plasma concentrations of the two drugs declined biexponentially. The terminal half-lives (t$_{1}$2$\beta$/) of DWP20364 were 110$\pm$ 13.2 min and 117$\pm$3.09 min after i.v. and p.o. administration, respectively, and they were significantly higher than those of CPFX (45.5$\pm$9.52 min and 48.3$\pm$ 12.1 min, respectively). Similar results were also obtained from plasma concentrations and area under the plasma concentration-time curves. The total body clearance of DWP20364, 7.82$\pm$0.37 ml/min/kg was significantly slower than that of CPFX, 27.3 $\pm$ 11.1 m1/ min/kg. Above data suggested that the antimicrobial activity of DWP20364 could be longer than that of CPFX. The urinary recovery after i.v. and p.o. administration of DWP20364 was significantly lower than those of CPFX suggesting that the effect of DWP20364 on urinary tract infection could be lower than that of CPFX. The serum protein binding values of DWP20364 at 2$\mu$g/ml were apparently 91.5~93.1% in rats and human. DWP20364 was distributed by the order of liver, lung, kidney, sf)leon, heart, muscle and brain collected at 30 min after orally administered.

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Glutamate Receptor Abnormalities in Schizophrenia: Implications for Innovative Treatments

  • Rubio, Maria D.;Drummond, Jana B.;Meador-Woodruff, James H.
    • Biomolecules & Therapeutics
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    • v.20 no.1
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    • pp.1-18
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    • 2012
  • Schizophrenia is a devastating psychiatric illness that afflicts 1% of the population worldwide, resulting in substantial impact to patients, their families, and health care delivery systems. For many years, schizophrenia has been felt to be associated with dysregulated dopaminergic neurotransmission as a key feature of the pathophysiology of the illness. Although numerous studies point to dopaminergic abnormalities in schizophrenia, dopamine dysfunction cannot completely account for all of the symptoms seen in schizophrenia, and dopamine-based treatments are often inadequate and can be associated with serious side effects. More recently, converging lines of evidence have suggested that there are abnormalities of glutamate transmission in schizophrenia. Glutamatergic neurotransmission involves numerous molecules that facilitate glutamate release, receptor activation, glutamate reuptake, and other synaptic activities. Evidence for glutamatergic abnormalities in schizophrenia primarily has implicated the NMDA and AMPA subtypes of the glutamate receptor. The expression of these receptors and other molecules associated with glutamate neurotransmission has been systematically studied in the brain in schizophrenia. These studies have generally revealed region- and molecule-specifi c changes in glutamate receptor transcript and protein expression in this illness. Given that glutamatergic neurotransmission has been implicated in the pathophysiology of schizophrenia, recent drug development efforts have targeted the glutamate system. Much effort to date has focused on modulation of the NMDA receptor, although more recently other glutamate receptors and transporters have been the targets of drug development. These efforts have been promising thus far, and ongoing efforts to develop additional drugs that modulate glutamatergic neurotransmission are underway that may hold the potential for novel classes of more effective treatments for this serious psychiatric illness.

HEN Simulation of a Controlled Fluid Flow-Based Neural Cooling Probe Used for the Treatment of Focal and Spontaneous Epilepsy

  • Mohy-Ud-Din, Zia;Woo, Sang-Hyo;Qun, Wei;Kim, Jee-Hyum;Cho, Jin-Ho
    • Journal of Sensor Science and Technology
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    • v.20 no.1
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    • pp.19-24
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    • 2011
  • Brain disorders such as epilepsy is a condition that affects an estimated 2.7 million Americans, 50,000,000 worldwide, approximately 200,000 new cases of epilepsy are diagnosed each year. Of the major chronic medical conditions, epilepsy is among the least understood. Scientists are conducting research to determine appropriate treatments, such as the use of drugs, vagus nerve stimulation, brain stimulation, and Peltier chip-based focal cooling. However, brain stimulation and Peltier chip-based stimulation processes cannot effectively stop seizures. This paper presents simulation of a novel heat enchanger network(HEN) technique designed to stop seizures by using a neural cooling probe to stop focal and spontaneous seizures by cooling the brain. The designed probe was composed of a U-shaped tube through which cold fluid flowed in order to reduce the temperature of the brain. The simulation results demonstrated that the neural probe could cool a 7 $mm^2$ area of the brain when the fluid was flowing atb a velocity of 0.55 m/s. It also showed that the neural cooling probe required 23 % less energy to produce cooling when compared to the Peltier chip-based cooling system.

A Docking Study of Newly Found Natural Neuraminidase Inhibitor: Erystagallin A

  • Madhavan, Thirumurthy
    • Journal of Integrative Natural Science
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    • v.4 no.4
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    • pp.273-277
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    • 2011
  • It's a threat for the public health that H1N1 (Influenza virus A) causes disease and transmits among humans. WHO (world health organization) declared that the infections caused by the new strain had reached pandemic proportions. The approved neuraminidase inhibitors (Zanamivir and Oseltamivir) and related investigative drug (BCX-1812) are potent, specific inhibitors of influenza A and B viruses. These drugs are highly effective to prevent influenza A and B infections. Early therapeutic use reduces illness duration and respiratory complications. Recently, we found one of the potent inhibitor of erystagallin A ($IC_{50}$ of 2.04 ${\mu}M$) for neuraminidase target, this inhibitor shows most similar structure to its natural substrate, sialic acid. Therefore, we chose 1l7f to get the receptor structure for docking study among many crystal structures. A docking study has been performed in Surflex-Dock module in SYBYL 8.1. In the present study, we attempt to compare the docking studies of pterocarpin and erystagallin A with neuraminidase receptor structure. In the previous report, the methoxy group of pterocarpin had H-bonding with Arg residues. The present docking results for erystagallin A showed the backbone of hydroxyl group shows significant H-bonding interactions with Arg152 and Arg292. The results showed that erystagallin A interacts more favorably with distinctive binding site rather than original active site. Therefore, we tried to reveal plausible binding mode and important amino acid for this inhibitor using docking and site id search calculations of Sybyl. The results obtained from this work may be utilized to design novel inhibitors for neuraminidase.

Fabrication of Biodegradable Disc-shaped Microparticles with Micropattern using a Hot Embossing Process with Porous Microparticles

  • Hwang, Ji-Yea;Choy, Young-Bin;Seo, Soon-Min;Park, Jung-Hwan
    • Journal of Pharmaceutical Investigation
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    • v.41 no.3
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    • pp.147-151
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    • 2011
  • This paper demonstrates the development of a method for preparing micropatterned microdiscs in order to increase contact area with cells and to change the release pattern of drugs. The microdiscs were manufactured with hot embossing, where a polyurethane master structure was pressed onto both solid and porous microparticles made of polylactic-co-glycolic acid at various temperatures to form a micropattern on the microdiscs. Flat microdiscs were formed by hot embossing of porous microparticles; the porosity allowed space for flattening of the microdiscs. Three types of micro-grooves were patterned onto the flat microdiscs using prepared micropatterned molds: (1) 10 ${\mu}M$ deep, 5 ${\mu}M$ wide, and spaced 2 ${\mu}M$ apart; (2) 10 ${\mu}M$ deep, 9 ${\mu}M$ wide, and spaced 5 ${\mu}M$ apart; and (3) 10 ${\mu}M$ deep, 50 ${\mu}M$ wide, and spaced 50 ${\mu}M$ apart. This novel microdisc preparation method using hot embossing to create micropatterns on flattened porous microparticles provides the opportunity for low-cost, rapid manufacture of microdiscs that can be used to control cell adhesion and drug delivery rates.