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Effects of Atorvastatin on the Pharmacokinetics of Nicardipine after Oral and Intravenous Administration in Rats

  • Choi, Jun-Shik;Ha, Sung-Il;Choi, Dong-Hyun
    • Biomolecules & Therapeutics
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    • v.18 no.2
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    • pp.226-232
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    • 2010
  • The aim of this study was to investigate the effect of atrovasatatin on the pharmacokinetics of nicardipine after oral and intravenous administration of nicardipine to rats. Nicardipine was administered orally (12 mg/kg) or intravenously (i.v., 4 mg/kg) without or with oral administration of atrovasatatin (0.3 or 1.0 mg/kg) to rats. The effect of atorvastatin on the P-glycoprotein (P-gp) as well as CYP3A4 activity was also evaluated. Atorvastatin inhibited CYP3A4 enzyme activity in a concentration-dependent manner with 50% inhibition concentration ($IC_{50}$) of 48 ${\mu}M$. Compared to the controls (nicardipine alone), the area under the plasma concentration-time curve (AUC) of nicardipine was significantly (1.0 mg/kg, p<0.05) greater by 16.8-45.4%, and the peak plasma concentration ($C_{max}$) was significantly (1.0 mg/kg, p<0.05) higher by 28.0% after oral administration of nicardipine with atorvastatin, respectively. Consequently, the relative bioavailability (R.B.) of nicardipine was increased by 1.17- to 1.45-fold and the absolute bioavailability (A.B.) of nicardipine with atrovasatatin was significantly greater by 16.7-20.9% compared to that of the controls (14.3%). Compared to the i.v. control, atrovasatatin did not significantly change pharmacokinetic parameters of i.v. administration nicardipine. The enhanced oral bioavailability of nicardipine by atorvastatin suggests that CYP3A subfamily-mediated metabolism were inhibited in the intestine and/or in the liver rather than P-gp-mediated efflux of nicardipine. Based on these results, modification of nicardipine of dosage regimen is required in the patients. Human studies are required to prove the above hypothesis.

Biodegradation of Diazinon by Serratia marcescens DI101 and its Use in Bioremediation of Contaminated Environment

  • Abo-Amer, Aly E.
    • Journal of Microbiology and Biotechnology
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    • v.21 no.1
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    • pp.71-80
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    • 2011
  • Four diazinon-degrading bacteria were isolated from agricultural soil by using an enrichment technique. The biochemical analysis and molecular method including RFLP indicated that these isolates were identical, and one strain designated DI101 was selected for further study. Phylogenetic analysis based on 16S rDNA sequencing indicated that the strain DI101 clearly belongs to the Serratia marcescens group. The ability of the strain to utilize diazinon as a source of carbon and phosphorus was investigated under different culture conditions. The DI101 strain was able to completely degrade 50 mg/l diazinon in MSM within 11 days with a degradation rate of 0.226 $day^{-1}$. The inoculation of sterilized soil treated with 100 mg/kg of diazinon with $10^6$ CFU/g DI101 resulted in a faster degradation rate than was recorded in non-sterilized soil. The diazinon degradation rate by DI101 was efficient at temperatures from 25 to $30^{\circ}C$ and at pHs from 7.0 to 8.0. The degradation rate of diazinon was not affected by the absence of a phosphorus supplement, and addition of other carbon sources (glucose or succinate) resulted in the slowing down of the degradation rate. The maximum degradation rate ($V_{max}$) of diazinon was 0.292 $day^{-1}$ and its saturation constant ($K_s$) was 11 mg/l, as determined by a Michaelis-Menten curve. The strain was able to degrade diethylthiophosphate-containing organophosphates such as chlorpyrifos, coumaphos, parathion, and isazofos when provided as a source of carbon and phosphorus, but not ethoprophos, cadusafos, and fenamiphos. These results propose useful information for the potential application of the DI101 strain in bioremediation of pesticide-contaminated environments.

Relationships between Social Support and Social Image Concerns in Turkish Women with Breast Cancer

  • Ozkaraman, Ayse;Culha, Ilkay;Fadiloglu, Zehra Cicek;Kosgeroglu, Nedime;Gokce, Serap;Alparslan, Guler Balci
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.1795-1802
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    • 2015
  • Background: Breast cancer is one of the most common cancer types in women and is amongst the most devastating and stressful events in the life of women. The external appearance of breast cancer patients usually changes due to the surgical and/or medical therapies used. An association may be found between social support perception and social appearance anxiety in patients with breast cancer in the period after mastectomy. Therefore, this study investigated the social appearance anxiety and social support status in women with breast cancer in our country. Materials and Methods: A descriptive cross-sectional study was conducted in breast cancer patients undergoing treatment or follow-up in Medical Oncology and General Surgery departments. Results: The mean age of the participants was $51.13{\pm}8.48$ years (range, 24-74 years) with nearly half of the patients (40.6%) aged 40-50 years. Of the patients, 39.1% had stage 3 breast cancer. The mean score on Cancer Patient's Social Support Scale (CPSSS) was $134.85{\pm}9.35$, and there was a significant difference in CPSSS total scores betweena the age groups, educational levels, self-reported income levels and stage of disease (p<0.05). The mean Social Image Anxiety Scale (SIAS) score was found to be $34.30{\pm}9.35$ (min:16, max:66) in women participating in this study. The CPSSS and SIAS scores of the participants were inversely correlated, and the SIAS score was found to decrease with the increasing CPSSS score but with no statistically significant difference (r=-0.110, p=0.217). Conclusions: Social appearance anxiety is higher in the patients with poor social support.

Purification and Characterization of a Thermostable Protease from Pseudomonas aeruginosa NS-83

  • Kim, Hyung-Kwoun;Kim, Kee-Hyun;Lee, Jung-Kee;Bae, Kyung-Sook;Sung, Chang;Oh, Tae-Kwang
    • Journal of Microbiology and Biotechnology
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    • v.4 no.2
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    • pp.113-118
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    • 1994
  • A bacterial strain NS-83 isolated from soil was able to produce an extracellular thermostable protease. The strain was identified as Pseudomonas aeruginosa based on its morphological and physiological characteristics. A thermostable protease from this strain has been purified to homogeneity as judged by SDS-PAGE and isoelectric focusing. The purification procedures included hydrophobic interaction, ion exchange, and gel filtration chromatography. The $M_r$ and the pl of the enzyme were 32,000 and 5.9, respectively. The optimal pH at 55$^{\circ}C$ and the optimal temperature at pH 7.0 were 8.0 and 60$^{\circ}C$, respectively. The D-values of the enzyme at 60, 65, and 70$^{\circ}C$ were 22, 2.1, and 0.75 hrs, respectively. The enzyme activity was significantly inhibited in the presence of 1 mM o-phenanthroline or EDTA, suggesting that the enzyme is metalloprotease. The $K_m$, and $V_{max}$ for Hammarsten casein were found to be 3.2 mg/ml and 0.918 unit/ml, respectively. These enzymatic properties were similar to those of elastase produced from P. aeruginosa IFO 3455, but the enzyme was clearly different from the reported elastase, in respect to $Ca^{++}$ effects on enzyme-thermostability. This property, together with amino acid composition analysis, confirmed that the enzyme differs from the known P. aeruginosa elastase.

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A Study on Parabolic Edge Planar Monopole Antenna for UWB Communication (초광대역(UWB) 통신을 위한 포물선 엣지 형태의 평면 모노폴 안테나에 대한 연구)

  • Chang, Tae-Soon;Hur, Jung
    • The Journal of Korean Institute of Electromagnetic Engineering and Science
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    • v.19 no.6
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    • pp.612-620
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    • 2008
  • In this parer, parabolic edge planar monopole antenna for UWB communication is presented. The antenna have broadband property structurally through planar monopole and ground which have parabolic edge. It is designed close to self-complementary structure as changing curvature of edge of monopole and ground. Monopole and ground of proposed antenna exist on coplanar plane, and excite as coaxial feeding. It used FR4 dielectric substrate of ${\varepsilon}_r=4.4$, and the size is $26{\times}31{\times}1.6mm$. Return loss is more than 10 dB in $3.1{\sim}10.6GHz$. Radiation pattern is about the same that of dipole antenna at all frequency. At measured result, max gain is $1.37{\sim}6.02dBi$ at E-plane.

Yield Response of Soybean [Glycine max (L.) Merrill] to High Temperature Condition in a Temperature Gradient Chamber

  • Baek, Jae-Kyeong;Sang, Wan-Gyu;Kim, Jun-Hwan;Shin, Pyong;Cho, Jung-Il;Seo, Myung-Chul
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.65 no.4
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    • pp.339-345
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    • 2020
  • Recently, abnormal weather conditions, such as extreme high temperatures and droughts, have increased in frequency due to climate change, there has accordingly been growing concern regarding the detrimental effects on field crop, including soybean. Therefore, this study was conducted to examine the effects of increased temperatures on soybean growth and yield using a temperature gradient chamber (TGC). Two major types of soybean cultivar, a medium- seed cultivar such as Daepung-2 and a large-seed cultivar such as Daechan, were used and four temperature treatments, aT+1℃ (ambient temperature+1℃), aT+2℃ (ambient temperature+2℃), aT+3℃ (ambient temperature+3℃) and aT+4℃ (ambient temperature+4℃) were established to examine the growth response and seed yield of each cultivar. Seed yield showed a higher correlation with seed weight (r=0.713***) and an increase in temperature affected seed yield by reducing the single seed weight. In particular, the seed growth rate of the large-seed cultivar (Daechan) increased at high temperature, resulting in a reduction in the number of days for full maturity. Our results accordingly indicate that large-seed cultivar, such as Daechan, is potentially vulnerable to high temperature stress. The results of this study can be used as basic data in the development of cultivation technology to reduce the damage caused by elevated temperatures. Also, further research is required to evaluate the response of each process contributing to seed yield production under high temperatures.

Pharmacokinetic Drug Interaction between Carvedilol and Ticlopidine in Rats

  • Choi, Jun-Shik;Choi, Dong-Hyun
    • Biomolecules & Therapeutics
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    • v.18 no.3
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    • pp.343-349
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    • 2010
  • This study was designed to investigate the effects of ticlopidine on the pharmacokinetics of carvedilol after oral or intravenous administration of carvedilol in rats. Carvedilol was administered orally (3 mg/kg) or intravenously (1 mg/kg) without or with oral administration of ticlopidine (4, 12 mg/kg) to rats. The effects of ticlopidine on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 2C9 activity were also evaluated. Ticlopidine inhibited CYP2C9 activity in a concentration-dependent manner with 50% inhibition concentration ($IC_{50}$) of $25.2\;{\mu}M$. In addition, ticlopidine could not significantly enhance the cellular accumulation of rhodamine 123 in MCF-7/ADR cells overexpressing P-gp. Compared with the control group (given carvedilol alone), the area under the plasma concentration-time curve (AUC) was significantly (12 mg/kg, p<0.05) increased by 14-41%, and the peak concentration ($C_{max}$) was significantly (12 mg/kg, p<0.05) increased by 10.7-73.3% in the presence of ticlopidine after oral administration of carvedilol. Consequently, the relative bioavailability (R.B.) of carvedilol was increased by 1.14- to 1.41-fold and the absolute bioavailability (A.B.) of carvedilol in the presence of ticlopidine was increased by 36.2-38.5%. Compared to the i.v. control, ticlopidine could not significantly change the pharmacokinetic parameters of i.v. administered carvedilol. The enhanced oral bioavailability of carvedilol may result from inhibition of CYP2C9-mediated metabolism rather than P-gpmediated efflux of carvedilol in the intestinal and/or in liver and renal eliminatin of carvedilol by ticlopidine.

Tissue Culture Studies of Anthranilate Synthase the Tryptophan Biosynthetic Control Enzyme

  • Widholm, Jack.M.
    • Journal of Plant Biotechnology
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    • v.2 no.2
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    • pp.55-60
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    • 2000
  • Experiments initiated 30 years ago to obtain selectable markers have led to a series of studies of Trp biosynthesis and anthranilate synthase (AS) the control enzyme using largely plant tissue cultures since they have experimental properties that can be readily exploited. Enzymological and compound feeding studies provided evidence that AS is the control point in the Trp biosynthesis branch and that altering the AS feedback control by the selection of mutants resistant to the Trp analog 5-methyl-tryptophan (5MT) can lead to the overproduction of this important amino acid. Plants regenerated from these Trp overproducing lines of most species also had high free Trp levels but Nicotiana tabaum (tobacco) plants expressed the feedback altered AS only in cultured cells and not in the regenerated plants. further tests by transient and stable expression of the cloned promoter for the naturally occurring tobacco feedback-insensitive AS, denoted ASA2, confirmed the tissue culture specific nature of the expression control. The 5MT caused by the expression of a feedback-insensitive AS from tobacco has been used to select protoplast fusion hybrids with several species since the resistance is expressed dominantly. Recently the ASA2 gene has been used successfully as a selectable marker to select transformed Astragalus sinicus and Glycine max hairy roots induced by Agrobactetium rhizogenes. These results show that the ASA2y-subunit can interact with the y-subunit of another species to form active feedback-insensitive enzyme that may be useful for selecting transformed cells. Plastid DNA transformation of tobacco has also effectively expressed ASA2 in the compartment in which Trp biosynthesis is localized in the cell.

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Fatigue Behavior of the Single Spot Welded Joint of Zinc Galvanized Steel Sheets (아연도금 강판의 점용접재의 피로균형에 관한 연구)

  • 서창민;강성수;오상표
    • Journal of Ocean Engineering and Technology
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    • v.6 no.2
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    • pp.21-34
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    • 1992
  • The behavior of fatigue crack growth in the single spot welded joint of zinc galvanized steel sheets was studied experimentally and analytically based on fracture mechanics. Axial tension fatigue tests were carried out with the BSxGAB specimen that the bare plane(GAB) of monogalvanized steel sheet was spot welded to the double thickness bare steel sheet(BS), and with the GAxGAB specimen that the galvanized plane (GA) was spot welded to the equal thickness bare plane (GAB) 1. The relation between maximum stress intensity factor, K sub(max) and the number of cycles to failure, N sub(f) has shown a linear relation on log-log plot in the spot weld of the zinc galvanized steel sheet. 2. The fatigue strength of BSxGAB specimens is about 23% higher than that of GAxGAB specimens at the fatigue strength of $1\times10^6$ cycles. And the fatigue life of BSxGAB specimens at the same load range increases 6~9 times higher than that of GAxGAB specimens. 3. The general tendency at the angle of bending($\theta$) in an applied load has changed rapidly at the initial 20% of its life. After then, it has changed slowly. The change at the angle of bending has increased linearly as the load range increases. 4. It has shown a linear relation between the location ratio of initiation ${\gamma}$ and fatigue life $N_f$ on the semi-log graph paper. Here $\gamma$ means that the crack distance between main crack and sub-crack, 2L is divided by the nugget diameter, 2r. $\gamma=a{\cdot}log N_f+n$ (where a and n are material constant.)

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Shear induced damage of red blood cells monitored by the decrease of their deformability

  • Lee, Sung Sik;Ahn, Kyung Hyun;Lee, Seung Jong;Sun, Kyung;Goedhart, Petrus T.;Hardeman, Max. R.
    • Korea-Australia Rheology Journal
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    • v.16 no.3
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    • pp.141-146
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    • 2004
  • Shear-induced damage of Red Blood Cell (RBC) is an imminent problem to be solved for the practical application of artificial organs in extra corporeal circulation, as it often happens and affects physiological homeostasis of a patient. To design and operate artificial organs in a safe mode, many investigations have been set up to correlate shear and shear-induced cell damage. Most studies were focused on hemolysis i.e. the extreme case, however, it is important as well to obtain a clear understanding of pre-hemolytic mechanical damage. In this study, the change in deformability of RBC was measured by ektacytometry to investigate the damage of RBC caused by shear. To a small magnitude of pre-shear, there is little difference, but to a large magnitude of pre-shear, cell damage occurs and the effect of shear becomes significant depending on both the magnitude and imposed time of shearing. The threshold stress for cell damage was found to be approximately 30 Pa, which is much less than the threshold of mechanical hemolysis but is large enough to occur in vitro as in the extra corporeal circulation during open-heart surgery or artificial heart. In conclusion, it was found and suggested that the decrease of deformability can be used as an early indication of cell damage, in contrast to measuring plasma hemoglobin. As cell damage always occurs during flow in artificial organs, the results as well as the approach adopted here will be helpful in the design and operation of artificial organs.