• Title/Summary/Keyword: PK-15

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Allometric analysis of tylosin tartrate pharmacokinetics in growing male turkeys

  • Pozniak, Blazej;Tikhomirov, Marta;Motykiewicz-Pers, Karolina;Bobrek, Kamila;Switala, Marcin
    • Journal of Veterinary Science
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    • v.21 no.3
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    • pp.35.1-35.11
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    • 2020
  • Background: Despite common use of tylosin in turkeys, the pharmacokinetic (PK) data for this drug in turkeys is limited. Within a few months of growth, PK of drugs in turkeys undergoes changes that may decrease their efficacy due to variable internal exposure. Objectives: The objective of this study was to investigate the influence of age on the PK of a single intravenous (i.v.) and oral administration of tylosin to turkeys at a dose of 10 and 50 mg/kg, respectively. Methods: Plasma drug concentrations were measured using high-performance liquid chromatography with UV detection. The PK parameters were assessed by means of non-compartmental approach and were subjected to allometric analysis. Results: During a 2.5-month-long period of growth from 1.4 to 14.7 kg, the median value for area under the concentration-time curve after i.v. administration increased from 2.61 to 7.15 mg × h/L and the body clearance decreased from a median of 3.81 to 1.42 L/h/kg. Over the same time, the median elimination half-life increased from 1.03 to 2.96 h. For the oral administration a similar trend was noted but the differences were less pronounced. Bioavailability was variable (5.76%-21.59%) and age-independent. For both routes, the plasma concentration of the major tylosin metabolite, tylosin D, was minimal. Protein binding was age-independent and did not exceed 50%. Allometric analysis indicated a relatively poor predictivity of clearance, volume of distribution and elimination half-life for tylosin in turkeys. Conclusions: Age has a significant impact on tylosin PK in turkeys and dosage adjustment may be needed, particularly in young individuals.

Comparison of Ethanol Fermentation Properties between Laboratorial and Industrial Yeast Strains using Cassava Hydrolysate (카사바 당화액을 이용한 실험실용 및 산업용 효모의 에탄올 발효성능 비교)

  • Chin, Young-Wook;Kim, Jin-Woo;Park, Yong-Cheol;Seo, Jin-Ho
    • Microbiology and Biotechnology Letters
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    • v.40 no.3
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    • pp.220-225
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    • 2012
  • In order to investigate the ethanol fermentation properties of alcohol yeasts a laboratorial strain (CEN.PK2-1D) and two industrial alcohol yeasts (JHS100 and JHS200) of Saccharomyces cerevisiae were cultured in a pure YP medium with 300 g/L glucose and cassava hydrolysate. Spot assay and cell viability tests showed that both the JHS100 and JHS200 strains exhibited higher ethanol tolerance than the CEN.PK2-1D strain. The JHS100 strain demonstrated the highest cell growth, glucose consumption and ethanol production. In particular, an anaerobic batch fermentation of the JHS100 strain using cassava hydrolysate with 250 g/L glucose resulted in a 106.1 g/L ethanol concentration, 0.42 g/g ethanol yield and 3.15 g/L-hr ethanol productivity, which were 53%, 13%, 53% higher than the corresponding values for the CEN.PK2-1D strain. By changing the pure YP medium to cassava hydrolysate, 19% and 17% decreases in ethanol yield and productivity for the CEN.PK2-1D strain were observed, whereas the cultures of the JHS100 and JHS200 stains showed similar ethanol productivities and only an 8% decrease in ethanol yield. Furthermore, the JHS100 and JHS200 stains produced lower levels of glycerol and acetate byproducts than the CEN.PK2-1D strain. Consequently, the outstanding ethanol fermentation performance of the industrial strains might be owing to rapid cell growth, high ethanol tolerance, low nitrogen requirements and the low formation of by-products.

Toxicokinetic Modeling of Ethyl Paraben Administered Orally in Rats (랫드에 경구투여한 에틸파라벤의 독물동력학 모델링)

  • Kim, PanGyi
    • Journal of Environmental Health Sciences
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    • v.40 no.5
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    • pp.407-412
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    • 2014
  • Objectives: The internal dose of ethyl parabens is important in order to evaluate the risk of this chemical. However, there are little PK model data for parabens to apply this. This experiment attempted PK modeling to ascertain PK values. Methods: Twenty mg/kg ethyl paraben was administered orally to Sprague-Dawley rats at the same point in time. The rats were sacrificed at times 0, 15, 30 and minutes, and 1, 2, 4, 8, 12, 24 hours after oral gavage. Blood and urine were collected and pretreated for analysis. Accuracy, precision and LOD (limit of detection) were calculated for this analysis. Ethyl paraben, detected by HPLC-MS, was applied to PK modeling using Berkeley Madonna. Results: This study showed 100.1-103.7% accuracy, 1.4-3.7% precision and a 1.0 ng/mL limit of detection. Orally administered ethyl paraben reached maximum concentration after 30 minutes of dosing in serum and urine of rats. The concentrations were 2,354 ng/mL in serum and 386,000 ng/mL in urine samples. These peak concentrations were excreted after one hour of intubation over 12 hours. For the pharmacokinetic parameters of ethyl paraben revealed using Berkeley Madonna, the absorption rate was 5.539/hour, the excretion rate was 0.048/hour, the half-life was 14.441 hours and AUC was 481,186 ng hour/mL. Conclusion: Orally administered ethyl paraben was absorbed rapidly in rats and excreted in urine. This chemical, ethyl paraben, accumulated in the body but was excreted over 12 hours after dosing.

Pheromone Biosynthesis Activating Neuropeptide (PBAN) in Insects (곤충의 페로몬 생합성 활성화 신경펩타이드(PBAN))

  • Choi, Man-yeon
    • Korean journal of applied entomology
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    • v.61 no.1
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    • pp.15-28
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    • 2022
  • Neuropeptides produced in neurosecretory cells are the largest group of insect hormones. They regulate various physiological functions, such as fat body homeostasis, feeding, digestion, excretion, circulation, reproduction, metamorphosis, and behavior throughout all life stages. The PRXamide peptide family (X, a variable amino acid) is a well-characterized neuropeptide component with a common amino acid sequence, PRXamide (NH2), at the C-terminal end conserved across Insecta. The PRXamide peptides are classified into three subfamilies, each having diverse biological roles in insects: (1) pyrokinin (PK) includes the pheromone biosynthesis activating neuropeptide (PBAN) and the diapause hormone (DH), (2) the capability (CAPA) peptides, and (3) the ecdysis-triggering hormone (ETH). PBAN as a member of PK subfamily was first identified to stimulate pheromone biosynthesis in moths three decades ago. Since then, PBAN peptides have been extensively studied by various research groups from a broad spectrum of arthropods. In this paper, we briefly review insect PBAN molecules with emphasis on gene structure and expression, signal transduction, physiological mechanism in sex pheromone biosynthesis, and application for pest management.

Gradient Reduction of $C_1$ in /pk/ Sequences

  • Son, Min-Jung
    • Speech Sciences
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    • v.15 no.4
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    • pp.43-60
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    • 2008
  • Instrumental studies (e.g., aerodynamic, EPG, and EMMA) have shown that the first of two stops in sequence can be articulatorily reduced in time and space sometimes; either gradient or categorical. The current EMMA study aims to examine possible factors_linguistic (e.g., speech rate, word boundary, and prosodic boundary) and paralinguistic (e.g., natural context and repetition)_to induce gradient reduction of $C_1$ in /pk/ cluster sequences. EMMA data are collected from five Seoul-Korean speakers. The results show that gradient reduction of lip aperture seldom occurs, being quite restricted both in speaker frequency and in token frequency. The results also suggest that the place assimilation is not a lexical process, implying that speakers have not fully developed this process to be phonologized in the abstract level.

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A High-Resolution Dual-Loop Digital DLL

  • Kim, Jongsun;Han, Sang-woo
    • JSTS:Journal of Semiconductor Technology and Science
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    • v.16 no.4
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    • pp.520-527
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    • 2016
  • A new dual-loop digital delay-locked loop (DLL) using a hybrid (binary + sequential) search algorithm is presented to achieve both wide-range operation and high delay resolution. A new phase-interpolation range selector (PIRS) and a variable successive approximation register (VSAR) algorithm are adopted to resolve the boundary switching and harmonic locking problems of conventional digital DLLs. The proposed digital DLL, implemented in a $0.18-{\mu}m$ CMOS process, occupies an active area of $0.19mm^2$ and operates over a wide frequency range of 0.15-1.5 GHz. The DLL dissipates a power of 11.3 mW from a 1.8 V supply at 1 GHz. The measured peak-to-peak output clock jitter is 24 ps (effective pk-pk jitter = 16.5 ps) with an input clock jitter of 7.5 ps at 1.5 GHz. The delay resolution is only 2.2 ps.

A 1.25 GHz Low Power Multi-phase PLL Using Phase Interpolation between Two Complementary Clocks

  • Jin, Xuefan;Bae, Jun-Han;Chun, Jung-Hoon;Kim, Jintae;Kwon, Kee-Won
    • JSTS:Journal of Semiconductor Technology and Science
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    • v.15 no.6
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    • pp.594-600
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    • 2015
  • A 1.25 GHz multi-phase phase-rotating PLL is proposed for oversampling CDR applications and implemented with a low power and small area. Eight equidistant clock phases are simultaneously adjusted by the phase interpolator inside the PLL. The phase interpolator uses only two complementary clocks from a VCO, but it can cover the whole range of phase from $0^{\circ}$ to $360^{\circ}$ with the help of a PFD timing controller. The output clock phases are digitally adjusted with the resolution of 25 ps and both INL and DNL are less than 0.44 LSB. The proposed PLL was implemented using a 110 nm CMOS technology. It consumes 3.36 mW from 1.2 V supply and occupies $0.047mm^2$. The $jitter_{rms}$ and $jitter_{pk-pk}$ of the output clock are 1.91 ps and 18 ps, respectively.

Identification of the Pig β-1,3-N-acetylglucosaminyltransferase 1 (pB3GNT1) that is Involved in Poly-N-acetyllactosamine (poly-LacNAc) Synthesis (Poly-N-acetyllactosamine (poly-LacNAc) 합성에 관여하는 돼지 β-1,3-N-acetylglucosaminyltransferase I (pB3GNT1) 유전자 동정)

  • Kim, Ji-Youn;Hwang, Hwan-Jin;Chung, Hak-Jae;Hochi, Shinichi;Park, Mi-Ryung;Byun, Sung June;Oh, Keon Bong;Yang, Hyeon;Kim, Kyung-Woon
    • Journal of Life Science
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    • v.28 no.4
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    • pp.389-397
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    • 2018
  • The structure of glycan residues attached to glycoproteins can influence the biological activity, stability, and safety of pharmaceutical proteins delivered from transgenic pig milk. The production of therapeutic glycoprotein in transgenic livestock animals is limited, as the glycosylation of mammary gland cells and the production of glycoproteins with the desired homogeneous glycoform remain a challenge. The ${\beta}$-1,3-N-acetylglucosaminylatransferase1 (B3GNT1) gene is an important enzyme that attaches N-acetylglucosamine (GlcNAc) to galactose (Gal) residues for protein glycosylation; however, there is limited information about pig glycosyltransferases. Therefore, we cloned the pig B3GNT1 (pB3GNT1) and investigated its functional properties that could attach N-acetylglucosamine to galactose residue. Using several different primers, a partial pB3GNT1 mRNA sequence containing the full open reading frame (ORF) was isolated from liver tissue. The ORF of pB3GNT1 contained 1,248 nucleotides and encoded 415 amino acid residues. Organ-dependent expression of the pB3GNT1 gene was confirmed in various organs from adult and juvenile pigs. The pB3GNT1 mRNA expression level was high in the muscles of the heart and small intestine but was lower in the lungs. For functional characterization of pB3GNT1, we established a stable expression of the pB3GNT1 gene in the porcine kidney cell line (PK-15). As a result, it was suggested that the glycosylation pattern of pB3GNT1 expression in PK-15 cells did not affect the total sialic acid level but increased the poly N-acetyllactosamine level. The results of this study can be used to produce glycoproteins with improved properties and therapeutic potential for the generation of desired glycosylation using transgenic pigs as bioreactors.

Disruption of Sphingolipid Metabolism as a Potential Mechanism of Fumonisin Inhibition of Cell Growth in $LLC-PK_1$ Cells

  • Yoo, Hwan-Soo;Yun, Yeo-Pyo
    • Toxicological Research
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    • v.11 no.1
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    • pp.1-8
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    • 1995
  • Fumonisins are a family of mycotoxins produced by the fungus Fusarium moniliforme which is a common contaminant in corn. Fumonisins are potent inhibitors of sphingosine and sphinganine N-acyltransferase (ceramide synthase), key enzymes in sphingolipid metabolism. The purpose of this study was to provide the evidence that the elevated levels of free sphingoid bases (primarily sphinganine) and depletion of complex sphingolipids were closely related to the inhibition of cell growth in LLC-$PK_1$ cells exposed to fumonisin $B_1$$(\leq 35 {\mu}M)$. Concentrations of fumonisin $B_1$ between 10 and $35 {\mu}M$ were known to inhibit cell growth without cytotoxicity in $LLC-PK_1$ cells (Yoo et al. Toxicol. Appl. Pharmacol. 114, 9-15, 1992). Cells exposed to 35$\mu M$ fumonisin B$_1$ for 48 and 72 hr developed a fibroblast-like (elongated and spindle-shaped) appearance and were less confluent than normal cells. At between 24 and 48 hr after exposure to fumonisin $B_1$ cells were beginning to show the inhibition of cell growth and at 72 hr the number of viable cells in fumonisin-treated cultures was about 50% of concurrent control cultures. During the 24 hr lag period preceding inhibition of cell growth, the free sphinganine levels in cells exposed to $35 {\mu}M$ fumonisin $B_1$ were highly elevated (approximately 230 fold higher than normal cells). The elevated levels of free sphinganine were $435\pm14$$pmoles/{10^6}$ cells at 48 hr and approximately TEX>$333\pm11$$pmoles/{10^6}$ cells in cells exposed to $35{\mu}M$ fumonisin$B_1$ at 72 hr, while the levels of free sphinganine in normal cells were less than 2$pmoles/{10^6}$ cells. Under the same condition, depletion of intracellular complex sphingolipids as a consequence of fumonisin inhibition of de novo sphingolipid biosynthesis and turnover pathway was appeared. Content of free sphingold bases in dividing cells was more elevated than in confluent cells at 24-48 hr after cells were exposed to $20{\mu}M$ fumonisin $B_1$. The dividing cells were showing the inhibition of cell growth at 48-72 hr and $20{\mu}M$ fumonisin $B_1$. The results of this study support the hypothesis that the inhibition of cell growth is very well related to the disruption of sphingolipid metabolism in $LLC-PK_1$ cells.

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The Association of Intra-Annual Cambial Activities of Pinus koraiensis and Chamaecyparis pisifera planted in Mt. Worak with Climatic Factors (월악산에 식재된 잣나무와 화백나무의 형성층 활동과 기후인자와의 관계)

  • Seo, Jeong-Wook;Choi, En-Bi;Ju, Jeong-Deok;Shin, Chang-Seop
    • Journal of the Korean Wood Science and Technology
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    • v.45 no.1
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    • pp.43-52
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    • 2017
  • This study was fulfilled to verify the durations of cambial activity and analyze the associations of degree days and precipitation with the initiation of cambial activity and intra-annual wood formation for Pinus koraiensis and Chamaecyparis pisifera planted at Mt. Worak, respectively, by monitoring of their intra-annual cambial activities. And more, the reason was also analyzed why the DBH of Chamaecyparis pisifera known as planted in the same year could be classified as two groups (CPL: ${\phi}30cm$, CPS: ${\phi}15cm$). The intra-annual cambial activity was monitored using mini-cores (${\phi}2mm$) and they were collected in 2-week interval between April and October. However, between April and May and between middle September and October expected as the initiation and cessation of the cambial activity, respectively, it was fulfilled in 1-week interval. The average number of tree rings for PK (30) was less than CPS (37) and CPL (38), whereas the average ring width of PK (4.12 mm) was wider than CPS (1.84 mm) and CPL (3.97 mm). In the comparison of ring widths between CPL and CPS, CPL was 2.13 mm wider than CPS, however, excepting CPS 1 (0.83 mm), the average ring widths of CPS 2 (2.42 mm) and CPS 3 (2.73 mm) in the last 3 years were close to the average of CPL (2.71 mm). The initiation of cambial activity for PK was between 1 and 21 April, which was 1 week earlier than CPL and CPS (excepting CPS 1) and the cessation was between 1 and 22 September. The longest growing season therefore was 157.3 days (${\pm}3.3$) and it was longer than CPL ($145.7{\pm}6.6days$) and CPS ($148.0{\pm}15.1days$). In CP groups there were wide variations for the cessation of cambial activity and also there were the meaningful linear relationship between the growing seasons and the ring widths (r = 0.69, p < 0.064). The cambial activity in PK was initiated when degree days were between 99 and 134 and in CPS (excepting PCS 1) and CPL between 134 and 200. Excepting CPS 3, the false ring was observed in all samples collected on 21 July when drought stress was high due to low precipitation from June to the beginning of July.