• Title/Summary/Keyword: New drug development

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Recent Progress in Development of Vaccines against Avian Coccidiosis (조류 콕시듐증의 백신개발에 대한 최근의 진보)

  • Lillehoj, Hyun S.
    • Korean Journal of Poultry Science
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    • v.26 no.3
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    • pp.149-170
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    • 1999
  • Protozoa of the genus Eimeria are the etiologic agents of avian coccidiosis, the most economically important Parasitic disease for the poultry industry. Coccidia multiply in intestinal epithelial cells of a wide range of hosts, including livestock in addition to poultry. Chemotherapy is extensively used to control coccidiosis. However, development of drug resistance by Eimeria parasites, the intensive cost and labor involved in the identification of new anticoccidial compounds and public awareness of drug residues in foods warrant alternative methods to prevent coccidiocic in the fast growing poultry industry. For these reasons, there is a great interest in developing vaccines against avian coccidiosis. Live Eimeria vaccines confer protective immunity, however a significant disadvantage of using these types of vaccines is their pathogenicity. Live parasites with attenuated pathogenicity also usually produce immunity but may revert back to a pathogenic form and may be contaminated with other pathogenic organisms. Killed Eimeria vaccines are safer but, unlike live attenuated vaccines, are not able to generate cytotoxic T lymphocyte responses. Recombinant vaccines are biochemically purified proteins produced by genetic engineering that consist of particular epitopes or metabolites of Eimeria. Unlike live attenuated organisms, recombinant vaccines do not possess as much risk and generally are able to induce both humoral and cell mediated immunity. DNA vaccines consist of genes encoding immunogenic proteins of pathogens that are directly administered into the host in a manner that the gene is expressed and the resulting protein generates a protective immune response. Although all of these different types of vaccines have been applied to coccidiosis, this disease continues to cause substantial morbidity and mortality in the poultry industry. Future development of an effective vaccine against coccidiosis will depend on further investigation of protective immunity to Eimeria infection and identification of important immundgenic parasite molecules.

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A Study on the Development of Guideline for Assessing Anterior Nasal Cavity Using Nasal Endoscopy on Allergic Rhinitis Patients (비내시경을 활용한 알레르기 비염 환자의 전비경 소견 평가 척도 개발)

  • Yun, Young-Hee;Park, Jeong-Su;Kim, Kyu-Seok;Kim, Nam-Kwen;Kim, Kyung-Jun;Kim, Hee-Taek;Hong, Seung-Ug;Choi, In-Hwa;Ko, Seong-Gyu
    • Journal of Society of Preventive Korean Medicine
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    • v.17 no.1
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    • pp.199-207
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    • 2013
  • Objectives : The prevalence of Allergic Rhinitis (AR) has increased during the last decade. However, a lot of decisions on the assessment and treatment of AR are made depending on the personal experiences and choices of physicians. To suggest preferable approaches and to minimize the variations according to physicians, guidelines for assessing anterior nasal cavity using nasal endoscopy on AR is needed. Methods : The Korean Oriental Medical Ophthalmology, Otolaryngology and Dermatology Society and the Korean Oriental Preventive Medical Society has set out to develop the guidelines for the assessing anterior nasal cavity using nasal endoscopy on AR. Results & Conclusions : This is the first Korean guideline for the assessment of AR and should be revised and supplemented in the future as new evidence becomes available.

An Intercultural Experiment to Build Life Science Innovation in Korea

  • Nehrbass, Ulf
    • STI Policy Review
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    • v.3 no.1
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    • pp.96-116
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    • 2012
  • The establishment of Institut Pasteur Korea (IP-K) has been an intercultural experiment, which transplanted a French research organization with many foreign researchers into Korea to grow a new institution as a long-term collaboration. The Mission of the newly founded institute has been to develop more effective ways of generating value with basic life science research in the face of a world-wide Pharma crisis. The challenges have been i.) to invent new technologies and approaches in drug discovery, ii.) to convince the Korean stakeholders of their inherent value, iii.) to induce Pharma industry to adopt the new technologies and iv.) to create a context in the Korean R&D landscape where the new institute could contribute tangible benefits. If Institut Pasteur Korea has succeeded in all counts, then due to a somewhat skewed and unlikely set of cultural complementarities between Korea and France. The abstract and conceptual French approach was matched by Korean pragmatism, linearity and relentless improvement towards the defined development goal. IP-K has become an example for innovation made in Korea, which is now re-imported into Europe. As the project could arguably not have succeeded in either partner county alone, it highlights the benefits of longterm, in depth international collaborations.

Discovery of Novel DUSP4 Inhibitors through the Virtual Screening with Docking Simulations

  • Park, Hwangseo;Jeon, Tae Jin;Chien, Pham Ngoc;Park, So Ya;Oh, Sung Min;Kim, Seung Jun;Ryu, Seong Eon
    • Bulletin of the Korean Chemical Society
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    • v.35 no.9
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    • pp.2655-2659
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    • 2014
  • Dual specificity protein phosphatase 4 (DUSP4) has been considered a promising target for the development of therapeutics for various human cancers. Here, we report the first example for a successful application of the structure-based virtual screening to identify the novel small-molecule DUSP4 inhibitors. As a consequence of the virtual screening with the modified scoring function to include an effective molecular solvation free energy term, five micromolar DUSP4 inhibitors are found with the associated $IC_{50}$ values ranging from 3.5 to $10.8{\mu}M$. Because these newly identified inhibitors were also screened for having desirable physicochemical properties as a drug candidate, they may serve as a starting point of the structure-activity relationship study to optimize the medical efficacy. Structural features relevant to the stabilization of the new inhibitors in the active site of DUSP4 are discussed in detail.

Control of Avian Coccidiosis : Past, Present, and Future (닭 콕시듐병 방제의 과거, 현재, 그리고 미래)

  • Ruff, M.D.
    • Korean Journal of Poultry Science
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    • v.19 no.3
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    • pp.151-160
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    • 1992
  • Control of coccidiosis depends on medication, management, immunity, or some combination of these methods. Prophylactic medication with anticoccidials remains the primary method of control, although the development of drug resistance is a major problem. Shuttle and rotation programs are increasingly used to delay the onset of drug resistance. Sensitivity testing has become an important tool in the identification of what specific medications will be effective in specific poultry operations. Management techniques for the control of coccidiosis have not been totally effective because most disinfectants do not kill the coccidial oocysts. Present methods for vaccination are currently limited to the use of controlled doses of live coccidia. New vaccination methods under investigation include vaccination with attenuated strains or parasite antigens produced either by fractionating the parasites or genetically engineered sub unit vaccines.

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Targeting of Drugs Especially by Liposomes (담체(膽體)를 이용(利用)한 약물(藥物)의 표적조직집중기법(標的組織集中技法) -리포솜을 중심(中心)으로-)

  • Shim, Chang-Koo;Lee, Jun-Ho
    • Journal of Pharmaceutical Investigation
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    • v.13 no.4
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    • pp.153-172
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    • 1983
  • The use of carrier systems for the delivery of drugs to areas in the body in need of pharmacological intervention is now the subject of intense research in many laboratories. Because of its obvious advantages (e.g. protection of drugs from hostile environments, facilitated target penetration and avoidance of side effects), drug delivery is expected to ease the pressure and expense of new drug development by making better use of drugs in existence. Generally, carrier-mediated delivery has been envisaged either as direct transport of drugs to a biological target by a carrier that will associate with it selectively, or as release of drugs from a carrier circulating in the blood or immobilized in tissues, at rates compatible with optimal action. One system that has attracted considerable attention is the use of liposomes as carriers of pharmacologically active agents. 154 references were reviewed with special emphasis on the targeting of drugs by use of liposomes in this respect. Recent advances in the other carrier systems and in methods for the preparation of liposomes were also reviewed briefly.

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Acebutolol, a Cardioselective Beta Blocker, Promotes Glucose Uptake in Diabetic Model Cells by Inhibiting JNK-JIP1 Interaction

  • Li, Yi;Jung, Nan-Young;Yoo, Jae Cheal;Kim, Yul;Yi, Gwan-Su
    • Biomolecules & Therapeutics
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    • v.26 no.5
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    • pp.458-463
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    • 2018
  • The phosphorylation of JNK is known to induce insulin resistance in insulin target tissues. The inhibition of JNK-JIP1 interaction, which interferes JNK phosphorylation, becomes a potential target for drug development of type 2 diabetes. To discover the inhibitors of JNK-JIP1 interaction, we screened out 30 candidates from 4320 compound library with In Cell Interaction Trap method. The candidates were further confirmed and narrowed down to five compounds using the FRET method in a model cell. Among those five compounds, Acebutolol showed notable inhibition of JNK phosphorylation and elevation of glucose uptake in diabetic models of adipocyte and liver cell. Structural computation showed that the binding affinity of Acebutolol on the JNK-JIP1 interaction site was comparable to the known inhibitor, BI-78D3. Our results suggest that Acebutolol, an FDA-approved beta blocker for hypertension therapy, could have a new repurposed effect on type 2 diabetes elevating glucose uptake process by inhibiting JNK-JIP1 interaction.

Large-scale Synthesis of Uniform-sized Nanoparticles for Multifunctional Medical Applications

  • Hyeon, Taeg-Hwan
    • Proceedings of the Korean Vacuum Society Conference
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    • 2011.02a
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    • pp.1-1
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    • 2011
  • We developed a new generalized synthetic procedure, called as "heat-up process," to produce uniform-sized nanocrystals of many transition metals and oxides without a size selection process. We were able to synthesize uniform magnetite nanocrystals as much as 1 kilogram-scale from the thermolysis of Fe-oleate complex. Clever combination of different nanoscale materials will lead to the development of multifunctional nano-biomedical platforms for simultaneous targeted delivery, fast diagnosis, and efficient therapy. In this presentation, I would like to present some of our group's recent results on the designed fabrication of multifunctional nanostructured materials based on uniform-sized magnetite nanoparticles and their medical applications. Uniform ultrasmall iron oxide nanoparticles of <3 nm were synthesized by thermal decomposition of iron-oleate complex in the presence of oleyl alcohol. These ultrasmall iron oxide nanoparticles exhibited good T1 contrast effect. In in vivo T1 weighted blood pool magnetic resonance imaging (MRI), iron oxide nanoparticles showed longer circulation time than commercial gadolinium complex, enabling high resolution imaging. We used 80 nm-sized ferrimagnetic iron oxide nanocrystals for T2 MRI contrast agent for tracking transplanted pancreatic islet cells and single-cell MR imaging. We reported on the fabrication of monodisperse magnetite nanoparticles immobilized with uniform pore-sized mesoporous silica spheres for simultaneous MRI, fluorescence imaging, and drug delivery. We synthesized hollow magnetite nanocapsules and used them for both the MRI contrast agent and magnetic guided drug delivery vehicle.

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The Blood-Brain Barrier Permeability and Pharmacokinetics of Nitrone Based Spin Trapping Agent, $\alpha$-Phenyl-n-tert-Butyl Nitrone (PBN) in Rats (흰쥐에서 nitrone계 항산화제인 $\alpha$-phenyl-n-tert-butyl nitrone(PBN)의 뇌 투과성 및 체내동태)

  • 이나영;강영숙
    • YAKHAK HOEJI
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    • v.46 no.2
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    • pp.124-128
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    • 2002
  • The nitrone-based free radical trapping reagent, $\alpha$-phenyl-n-tert-butyl nitrone (PBN) has been proposed as therapeutic agent for stroke. We used this for model drug of development of new drug for neuroprotection. The purpose of this study was to evaluate the blood-brain barrier (BBB) permeability of PBN in Sprague-Dawly (SD) rats. The BBB transport of PBN was investigated in SD rats using internal carotid artery perfusion (ICAP) method at a rate of 4 mι/min for 15 second. We also obtained pharmacokinetic parameters of PBN using single intravenous injection technique. When we estimated BBB permeability of PBN with ICAP method, the brain volume of distribution of PBN was 60.0 $\pm$ 12.0 $\mu\textrm{g}$/ι. The brain uptake of PBN after IV injection at 120 min was 0.15 $\pm$ 0.01%ID/g. The PBN was transported to the brain through the BBB well in rats, because PBN is small molecule (MW 177) and lipid-soluble (log P 1.23) compound.

HPLC SEPARATION AND QUANTITATIVE DETERMINATION OF GINSENOSIDES FROM PANAX GINSENG, PANAX QUINQUEFOLIUM AND FROM GINSENG DRUG PREPARATIONS

  • Soldati F
    • Proceedings of the Ginseng society Conference
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    • 1980.09a
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    • pp.59-69
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    • 1980
  • A new HPLC-method for separation and quantitative determination of ginsenosides in Panax ginseng, Panax quinquefolium and in pharmaceutical drug preparations is elaborated. A reversed-phase-system with ${\mu}Bondapak\;C_{18}$ column (3.9 mm $I.D.{\times}30\;cm$) using acetonitrile-water (30:70) 2 ml/min and acetonitrile-water (18:82) 4 ml/min is suitable for the base-line separation of $Rb_1,\;Rb_2,\;Rc,\;Rd,\;Rf,\;Rg_2,\;respectively\;Re,\;Rg_1$ in 30 minutes. The ginsenosides are directly detected at 203 nm (without derivatization) with the LC-55 or LC-75 spectrophotometer (Perkin-Elmer) at $100\%$ transmission. Detection limit is 300 ng at a signal-to-noise ratio of 10:1. The ginsenosides-peak identification is carried out with HPTLC (high performance thin layer chromatography), with MIR-IR (multiple internal reflection-IR-spectros-copy) and with FD-MS (field desorption mass spectrometry). The calibration curve of each ginsenoside has a correlation coefficient very near to 1. Relative standard deviation for quantitative determinations depends upon the amount of ginsenosides and is approximately 1\%$ for ginsenoside contents of 1\%$. This method is adaptable for routine analysis in quality control laboratories.

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