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Development of Self-microemulsifying Drug Delivery System for Enhancing the Bioavailability of Atorvastatin

  • Jin, Shun-Ji;Cho, Won-Kyung;Park, Hee-Jun;Cha, Kwang-Ho;Park, Jun-Sung;Koo, Ja-Seong;Wang, Hun-Sik;Kim, Jeong-Soo;Kim, Min-Soo;Hwang, Sung-Joo
    • Journal of Pharmaceutical Investigation
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    • v.41 no.2
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    • pp.103-109
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    • 2011
  • The objective of the study was to prepare self-microeulsifying drug delivery system (SMEDDS) incorporating atorvastatin calcium and evaluate its properties and oral bioavailability. Solubility of atorvastatin in various vehicles was determined. Pseudo-ternary phase diagrams were constructed to identify the good self-emulsification region. The droplet size distributions of the resultant emulsions were determined by dynamic light scattering measurement. The mean droplet size of chosen formulation (20% ethyl oleate, 40% tween-80, 40% Carbitol$^{(R)}$) was $23.4{\pm}1.3$ nm. The SMEDDS incorporating atorvastatin calcium appeared to be associated with better performance in dissolution and pharmacokinetic studies, compared with raw atorvastatin calcium. In dissolution test, the release percentage of atorvastatin from SMEDDS mixture could rapidly reach more than 95% within 3 min. Oral $AUC_{0{\rightarrow}8hr}$ values in SD rats was $1994{\pm}335\;ng{\cdot}hr/mL$, which significantly increased (P<0.05) compared with raw atorvastatin calcium. The SMEDDS formulation was relatively stable when stored at $4^{\circ}C$ during 3 months. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as atorvastatin, by the oral route.

Preparation and Characterization of Cy5.5-conjugated Biocompatible Polymeric Micellar Nanoparticles for Optical Imaging (광학 영상을 위한 Cy5.5가 결합된 생체적합성 고분자 마이셀 나노입자의 제조 및 특성분석)

  • Kim, Hyo-Jeong;Kim, Byung-Jin;Lee, Ha-Yeong;Jung, Suk Hyun;Jeong, Seo-Young;Yuk, Soon-Hong;Shin, Byung-Cheo;Seong, Ha-Soo;Choi, Youn-Woong;Ha, Dae-Chul;Choi, Sun-Hang;Lee, Soo-Min
    • Journal of Pharmaceutical Investigation
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    • v.39 no.6
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    • pp.393-400
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    • 2009
  • PHEA (hydroxyethyl-aspartamide)-mPEG (methoy-polyethyleneglycol)-$C_{16}$ (hexadecylamine)-ED (ethylenediamine) was prepared as a drug delivery carrier. The structure and molecular weight of polymers were characterized by $^1H$-NMR and gel permeation chromatography. Micelle size and shape were measured by electro-photometer light scattering and transmission electron microscope. The mean diameter of micelles was 23 nm in aqueous solution. To evaluate the potential of these polymeric micelles as a drug carrier, PSI-mPEG-$C_{16}$-ED was conjugated with Cy5.5 for Near-Infrared Fluorescent (NIRF) based optical imaging. PSI-mPEG-$C_{16}$-ED-Cy5.5 was injected intravenously into mice (n=5) and in vivo NIRF imaging was performed during 48 h after injection. The biodistribution study at 24 h after injection showed the longcirculation property of PSI-mPEG-$C_{16}$-ED-Cy5.5. Therefore, PSI-mPEG-$C_{16}$-ED micelles could be a promising drug carrier and imaging agent.

Purification, and Biochemical and Biophysical Characterization of Cellobiohydrolase I from Trichoderma harzianum IOC 3844

  • Colussi, Francieli;Serpa, Viviane;Da Silva Delabona, Priscila;Manzine, Livia Regina;Voltatodio, Maria Luiza;Alves, Renata;Mello, Bruno Luan;Nei, Pereira Jr.;Farinas, Cristiane Sanches;Golubev, Alexander M.;Santos, Maria Auxiliadora Morim;Polikarpov, Igor
    • Journal of Microbiology and Biotechnology
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    • v.21 no.8
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    • pp.808-817
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    • 2011
  • Because of its elevated cellulolytic activity, the filamentous fungus Trichoderma harzianum has a considerable potential in biomass hydrolysis applications. Trichoderma harzianum cellobiohydrolase I (ThCBHI), an exoglucanase, is an important enzyme in the process of cellulose degradation. Here, we report an easy single-step ion-exchange chromatographic method for purification of ThCBHI and its initial biophysical and biochemical characterization. The ThCBHI produced by induction with microcrystalline cellulose under submerged fermentation was purified on DEAE-Sephadex A-50 media and its identity was confirmed by mass spectrometry. The ThCBHI biochemical characterization showed that the protein has a molecular mass of 66 kDa and pI of 5.23. As confirmed by smallangle X-ray scattering (SAXS), both full-length ThCBHI and its catalytic core domain (CCD) obtained by digestion with papain are monomeric in solution. Secondary structure analysis of ThCBHI by circular dichroism revealed ${\alpha}$- helices and ${\beta}$-strands contents in the 28% and 38% range, respectively. The intrinsic fluorescence emission maximum of 337 nm was accounted for as different degrees of exposure of ThCBHI tryptophan residues to water. Moreover, ThCBHI displayed maximum activity at pH 5.0 and temperature of $50^{\circ}C$ with specific activities against Avicel and p-nitrophenyl-${\beta}$-D-cellobioside of 1.25 U/mg and 1.53 U/mg, respectively.

Effects of EGFR, CK19, CK20 and Survinin Gene Expression on Radiotherapy Results in Patients with Locally Advanced Head and Neck Cancer

  • Kekilli, Kezban Esra;Abakay, Candan Demioz;Tezcan, Gulcin;Tunca, Berrin;Egeli, Unal;Saraydaroglu, Ozlem;Esbah, Onur;Ekinci, Ahmet Siyar;Arslan, Sonay;Uslu, Nuri;Ozkan, Lutfi
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.3023-3027
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    • 2015
  • Purpose: To investigate the effects of epidermal growth factor receptor (EGFR), cytokeratin 19 (CK19), cytokeratin 20 (CK20) and survinin gene expression on local control (LC) and overall survival (OS) in patients with locally advanced head and neck cancer (LAHNC) who were administered radiotherapy (RT). Materials and Methods: Twenty-six patients who were admitted to Uludag University Medical Faculty Department of Radiation Oncology with a diagnosis of LAHNC (GIII-GIV) were included in this study. Gene expression was evaluated in tumor tissues and peripheral blood. RNA isolation was performed on paraffinized tumor tissues and peripheral blood samples obtained before RT (BR). The densities of the obtained RNAs were analyzed at 260/280 nm. cDNA samples obtained from total RNA,EGFR, CK19, CK20 and survinin gene expression levels were assessed via the Sybr Green method and data were analyzed with the ${\Delta}{\Delta}Ct$ method. The same process was repeated for peripheral blood samples taken after RT (AR). Results: The female/male ratio was 3:23 and the mean age was 56.5 years (38-75years). After radiotherapy, CK19 and CK20 levels in the peripheral blood were found to be correlated according to Pearson correlation analysis(p=0.049). This result indicates a possibility of remaining positive for CK19 and CK20 in the peripheral blood even after RT in patients with CK19, CK20, and EGFR positive tumors before RT. There was a statistically significant correlation between survinin levels measured BR and AR (p=0.028). Conclusions: In this study, we found that patients with any EGFR, CK19, CK20 or survinin positivity in their peripheral blood obtain less benefit from radiotherapy. A wider patient population and advanced protein analyses are necessary in order to increase the reliability of our findings.

Fluxless Bonding Method between Sn and In Bumps Using Ag Capping Layer (Ag층을 이용한 Sn과 In의 무 플럭스 접합)

  • Lee Seung-Hyun;Kim Young-Ho
    • Journal of the Microelectronics and Packaging Society
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    • v.11 no.2 s.31
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    • pp.23-28
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    • 2004
  • We utilized Ag capping layer for fluxless bonding. To investigate the effect of Ag capping layer, two sets of sample were used. One set was bare In and Sn solders. The other set was In and Sn solders with Ag capping layer. In ($10{\mu}m$) and Sn ($10{\mu}m$) solders were deposited on Cu/Ti/Si substrate using thermal-evaporation, and Ag ($0.1{\mu}m$) capping layers were deposited on In and Sn solders. Solder joints were made by joining two In and Sn deposited specimens at $130^{\circ}C$ for 30 s under 0.8, 1.6, 3.2 MPa using thermal compression bonder. The contact resistance was measured using four-point probe method. The shear strength of the solder joints was measured by the shear test of cross-bar sample in the direction. The microstructure of the solder joints was characterized with SEM and EDS. In and Sn solders without Ag capping layers were only bonded at $130^{\circ}C$ under high bonding pressure. Also the shear strength of the In-Sn solder joints under was lower than that of the Ag/In-Ag/Sn solder joints. The resistance of the solder joints was $2-4\;m{\Omega}$ The solder joints consisted of In-rich phase and Sn-rich phase and the intermixed compounds were found at the interface. As bonding pressure increased, the intermixed compounds formed more.

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Immune-Enhancing Effects of Polysaccharides Isolated from Phellinus linteus Mycelium on Mori ramulus (상지에 배양한 상황버섯 균사체로부터 분리된 다당류의 면역증강 효과)

  • Park, Hye-Mi;Hong, Joo-Heon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.1
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    • pp.26-33
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    • 2017
  • The objective of this study was to examine the immune-enhancing effects of polysaccharides isolated from Phellinus linteus mycelium on Mori ramulus. Crude polysaccharides were isolated by pressurized extraction ($121^{\circ}C$, $1.2kgf/cm^2$, 3 h), ethanol precipitation, and lyophilization. In addition, crude polysaccharides were further fractionated into unabsorbed fractions (PF-1, fraction No. 3~15) and absorbed fractions (PF-2, fraction No. 24~33) by DEAE-sepharose CL-6B column chromatography in order to isolate immune-regulating polysaccharides. The major constituents in PF-1 and PF-2 were total sugar (75.51% and 52.38%), total protein (1.63% and 8.41%), uronic acid (17.53% and 15.04%), and ${\beta}-glucan$ (28.33% and 25.04%), respectively. PF-1 increased production of nitric oxide (NO) and cytokines, such as tumor necrosis factor-alpha ($TNF-{\alpha}$) and interleukin-6 (IL-6) in a dose-dependent manner. The mRNA expression levels of inducible NO synthetase, cyclooxygenase-2, $TNF-{\alpha}$, and IL-6 markedly increased as determined by polymerase chain reaction analysis. The above data led us to conclude that macrophage activation of purified polysaccharides was higher than that of crude polysaccharides. The polysaccharides isolated from P. linteus mycelium on M. ramulus investigated herein are useful as natural immune-enhancing agents.

A study on the Values of Total km Cholesterol in Healthy Non-Pregnant and Pregnant Women (건강 비임신 여성과 임신부들의 혈청 총코레스테롤 함량에 관한 조사)

  • Rhyu, Cheol-In;Kim, Don-Kyoun
    • Journal of Preventive Medicine and Public Health
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    • v.23 no.2 s.30
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    • pp.167-177
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    • 1990
  • The author investigated the values of total serum cholesterol and its coreelation with the physical factors to have potential as a line in the chain of basic investigation to establish maternal health program. The study group was composed of 167 healthy non-pregnant and 209 pregnant women in the age of 20-39 residing in Pusan area. The obtained results were as follows : 1. No significant differences were found in height and systolic and diastolic blood pressure in both groups except for the elevation of Broca's index by gaining the weight in pregnant women. 2. There were significant differences in the total serum cholesterol level of the healthy and pregnant women as 165.9 mg/dl and 212.6 mg/dl, repectively, not showing the differences in the age. Total serum cholesterol values in both group followed approximately normal distribution curve. 3. The significant correlation to the values of total serum cholesterol were found between weight and Broca's index in healthy women and between weight, Broca's index and duration of pregnancy in pregnant women. 4. The values of total serum cholesterol by weight were 162.9-189.4 mg/dl in healthy women and 167.2-246.2 mg/dl in pregnant women, showing the increasing tendency of values by weight, especially in pregnant women. 5. The values of total serum cholesterol in pregnant women showed increasing tendency with the duration of pregnancy as 168.1 mg/dl in 12 weeks and below, 209.6 mg/dl in 13-26 weeks and 235.4 mg/dl in 27 weeks and above group. Total nm cholesterol values by duration of pregnancy followed normal distribution curve.

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Comparison Study of AAS and ISE Method in the Lithium Analysis of Serum and Urine (혈액 및 소변의 Lithium치 측정에 있어서 AAS법과 ISE법의 비교)

  • Lee, Soo-In;Lee, Chae-Hoon;Kim, Kyung-Dong;Kim, Chung-Sook
    • Journal of Yeungnam Medical Science
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    • v.10 no.2
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    • pp.409-416
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    • 1993
  • In the method for lithium (Li) analysis, flame emission photometry and atomic absorption spectrophotometry (AAS) have been used most frequently. In addition, lithium can be analyzed by ion-selective electrode (ISE) or fluorscence polarization immunoassay. We evaluated the comparison between AAS method based on the principle of absorption of light at 670.8 nm by Li and ISE method based on the principle of voltage difference generated by Li in contact with lithium ionophore. We compared with those obtained by AAS (AA/AE Spectrophotometer 551, Instrumentation Laboratory Co.) and ISE(CSYNCHRON EL-ISE, Beckman Co.) in the serum and urine of 6 patients and evaluated time-related changes of serum lithium concentration after dosing in both methods. The results are summarized as follows : 1. In within-run precision study for lithium concentration, coefficient variations (CVs, %) ranged from 1.34 to 2.17 for AAS and from 0.34 to 0.85 for ISE method. In between-run precision study for lithium concentration, CVs ranged from 1.23 to 1.72 for AAS and from 0.61 to 1.38 for ISE method. 2. The correlation study between AAS and ISE method resulted in Y=0.946X+0.137 (N=32, r=0.933, X=AAS, Y=ISE) for serum lithium and Y=1.092X+0.977 (N=28, r=0.943, X=AAS, Y=ISE) for urine lithium. 3. Time-related changes of serum lithium concentration in both AAS and ISE method resulted in peak serum levels about 2 hours after dosing and then rapidly decreased after the peak serum level and finally arrived at nearly initial levels about 9 hours after dosing. 4. The reference range of serum lithium was found as undetectable level for both AAS and ISE method and the reference range of urine lithium to the urine creatinine was 0-0.00014 mmol/mg(mean 0.00002 mmol/mg) for AAS method.

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Hepatitis C Virus - Proteins, Diagnosis, Treatment and New Approaches for Vaccine Development

  • Keyvani, Hossein;Fazlalipour, Mehdi;Monavari, Seyed Hamid Reza;Mollaie, Hamid Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.5917-5935
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    • 2012
  • Background: Hepatitis C virus (HCV) causes acute and chronic human hepatitis infection and as such is an important global health problem. The virus was discovered in the USA in 1989 and it is now known that three to four million people are infected every year, WHO estimating that 3 percent of the 7 billion people worldwide being chronically infected. Humans are the natural hosts of HCV and this virus can eventually lead to permanent liver damage and carcinoma. HCV is a member of the Flaviviridae family and Hepacivirus genus. The diameter of the virus is about 50-60 nm and the virion contains a single-stranded positive RNA approximately 10,000 nucleotides in length and consisting of one ORF which is encapsulated by an external lipid envelope and icosahedral capsid. HCV is a heterogeneous virus, classified into 6 genotypes and more than 50 subtypes. Because of the genome variability, nucleotide sequences of genotypes differ by approximately 31-34%, and by 20-23% among subtypes. Quasi-species of mixed virus populations provide a survival advantage for the virus to create multiple variant genomes and a high rate of generation of variants to allow rapid selection of mutants for new environmental conditions. Direct contact with infected blood and blood products, sexual relationships and availability of injectable drugs have had remarkable effects on HCV epidemiology. Hundreds of thousands of people die each year from hepatitis and liver cancer caused by HCV virus infection. Approximately 80% of patients with acute hepatitis C progress into a chronic disease state leading to serious hepatic disorders, 10-20% of which develop chronic liver cirrhosis and hepatocellular carcinoma. The incubation period of HCV is 6-8 weeks and the infection is often asymptomatic so it is very hard to detect at early stages, making early treatment very difficult. Therefore, hepatitis C is called a "silent disease". Neutralizing antibodies are produced against several HCV proteins during infection but the virus mutates to escape from antibodies. Some patients with chronic hepatitis C may have some symptoms such as fatigue, muscle aches, nausea and pain. Autoimmune and immunecomplex-mediated diseases have also been reported with chronic HCV infection.

Improvement of Electrical/optical Characteristics Using Mg-doped GaN Spacers and Quantum Barriers for Nonpolar GaN light-emitting Diodes (마그네슘이 도핑된 GaN 공간층과 양자장벽층을 이용한 무분극 GaN 발광다이오드의 전기적/광학적 특성 향상)

  • Kim, Dong-Ho;Son, Sung-Hun;Kim, Tae-Geun
    • Journal of the Institute of Electronics Engineers of Korea SD
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    • v.48 no.7
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    • pp.10-16
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    • 2011
  • We report on the simulation results of electrical/optical characteristics for nonpolar GaN LED having Mg-doped GaN spacer and quantum barrier, in comparison with those of the typical nonpolar GaN LED. In order to reduce the band-gap energy distortion and conduction-band discontinuity in InGaN/GaN multiple quantum wells(MQWs) of nonpolar GaN LED, and thereby to increase their current-voltage, light output power and emission peak intensity, we applied 6 nm-thick p-type($1{\times}10^{18}\;cm^{-3}$) GaN spacer and GaN QB schemes to the typical nonpolar GaN LED epitaxial structure. As a result, we found that the radiative recombination rate was increased by 23% in MQWs at 20 mA current injection. Also, the forward voltage($V_f$) and the light output power($P_{out}$) were improved by 3.7% and 7%, respectively, for the proposed nonpolar LED epitaxial structure, compared with those of the typical nonpolar GaN LED.