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Prospective validation of a novel dosing scheme for intravenous busulfan in adult patients undergoing hematopoietic stem cell transplantation

  • Cho, Sang-Heon;Lee, Jung-Hee;Lim, Hyeong-Seok;Lee, Kyoo-Hyung;Kim, Dae-Young;Choe, Sangmin;Bae, Kyun-Seop;Lee, Je-Hwan
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.3
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    • pp.245-251
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    • 2016
  • The objective of this study was to externally validate a new dosing scheme for busulfan. Thirty-seven adult patients who received busulfan as conditioning therapy for hematopoietic stem cell transplantation (HCT) participated in this prospective study. Patients were randomized to receive intravenous busulfan, either as the conventional dosage (3.2 mg/kg daily) or according to the new dosing scheme based on their actual body weight (ABW) ($23{\times}ABW^{0.5}mg\;daily$) targeting an area under the concentration-time curve (AUC) of $5924{\mu}M{\cdot}min$. Pharmacokinetic profiles were collected using a limited sampling strategy by randomly selecting 2 time points at 3.5, 5, 6, 7 or 22 hours after starting busulfan administration. Using an established population pharmacokinetic model with NONMEM software, busulfan concentrations at the available blood sampling times were predicted from dosage history and demographic data. The predicted and measured concentrations were compared by a visual predictive check (VPC). Maximum a posteriori Bayesian estimators were estimated to calculate the predicted AUC ($AUC_{PRED}$). The accuracy and precision of the $AUC_{PRED}$ values were assessed by calculating the mean prediction error (MPE) and root mean squared prediction error (RMSE), and compared with the target AUC of $5924{\mu}M{\cdot}min$. VPC showed that most data fell within the 95% prediction interval. MPE and RMSE of $AUC_{PRED}$ were -5.8% and 20.6%, respectively, in the conventional dosing group and -2.1% and 14.0%, respectively, in the new dosing scheme group. These findings demonstrated the validity of a new dosing scheme for daily intravenous busulfan used as conditioning therapy for HCT.

The Configuration and Polyelectrolyte Behavior of Carboxymethyl Chitin in Low Concentration Solution (저농도 용액에서의 Carboxymethyl Chitin의 사슬배좌와 전해질 거동)

  • PARK Seong-Min;LEE Keun-Tae;KIM Sang-Moo
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.28 no.4
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    • pp.451-456
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    • 1995
  • To elucidate the intrinsic rheological properties of carboxymethyl chitin (CM-chitin) from the shell of red snow cyab (Chinonecetes japonicus), the configuration and polyelectrolyte behavior of CM-chitin in low concentration solution were investigated. Unperturbed dimensions were ranged from $127{\AA}\;to\;113{\AA}$ as root mean square end-to-end distance$(r_0)$, $52{\AA}$ to $46{\AA}$ as radius of gyration$(S_0)$. The intramolecular expansion tarter(a) was not varied with molecular weight and was 2.1. And effective bond length $(b_0)$ was $14.5{\AA}$. In perturbed condition, Flory constant was $2.35\times10^{21}$. When ionic strength were 0.02 and 1.0, intrinsic viscosity were 1.95dl/g and 1,06 dl/g, respectively. These results suggested that CM-chitin is a polyelectrolyte in aqueous media. At infinite ionic strength, intrinsic viscosity was 0.91dl/g. The intrinsic stiffness of CM-chitin backbone was estimated by evaluating the stiffness parameter (B) as 0.11 and agreed well with the results of k-carrageenan.

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Effect of Application of Water Treatment Sludge on the Yields and Chemical Properties of Soybean(Glycine max) and Carrot(Daucus carota) (정수장슬러지 시용이 대두 및 당근의 수량과 화학적 특성에 미치는 영향)

  • Chang, Ki-Woon;Lee, In-Bog;Lim, Jae-Shin;Kim, Young-Han;Lee, Sang-Suk;Lim, Hyun-Taek
    • Korean Journal of Soil Science and Fertilizer
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    • v.29 no.3
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    • pp.275-281
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    • 1996
  • The objective of the study was to investigate the effects of water treatment sludge (WTS) on the growth of soybean and carrot, and uptake of some inorganic components in the plants. WTS was incorporated to field at the rates of 0, 1, 3, and 5 tons per 10a on the basis of dry weight. With the application of the sludge, OM and CEC in the soil increased slightly while the concentration of available phosphorous decreased. And heavy metals, including Pb, Cd, Cr, As and Hg, were not detected at the harvest stage in crops. With an increase in the application of the sludge, the concentration of phosphorous in the seed of soybean and the root of carrot tended to be decreased. There seems no correlation between rate of application of the sludge and uptake of Al in the plants. The yield of soybean was the highest when applied to one ton sludge and the yield on carrot increased with an increase in rate of applied sludge. Also, the concentration of carotene increased with an increased application of the sludge. But, application of WTS showed to deteriorate the visual quality with an irregularity of carrot's surface. This results indicate that application of WTS will be give a positive and negative effects on soil and crops.

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Soil Acclimatization of Regenerated Plants by Gibberellic Acid Treatments of Panax ginseng C. A. Meyer (GA3 처리에 의한 인삼 재분화 식물체의 토양 순화)

  • Kim, Young Chang;Park, Hong Woo;Kim, Ok Tae;Bang, Kyong Hwan;Kim, Jang Uk;Hyun, Dong Yun;Kim, Dong Hwi;Cha, Seon Woo;Choi, Jae Eul
    • Korean Journal of Plant Resources
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    • v.26 no.1
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    • pp.84-89
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    • 2013
  • We established that regenerated plants of Panax ginseng were directly transplanted into the soil without the acclimatization process. When regenerated plants were treated at the concentration of $0.4mg\;l^{-1}$ for 9 hr before transplantation into the soil, our results showed that the survival rate of them was the highest. The optimal size of the root was above 4 cm in length and 0.4 g by weight before transplantation into the soil. The highest survival rate increased to 59.6%. After 4 years of cultivation in the fields, our results showed that there were no significant morphological differences between regenerated plants and wild-type ginseng. Also, we obtained healthy seeds from regenerated plants. This study provides the basis for a relatively rapid multiplication of selected genotypes and will allow a much more rapid evaluation of the germplasm of the unexplored and unstudied Korean ginseng.

Retention Time Prediction form Molecular Structure of Sulfur Compounds by Gas Chromatography (기체크로마토그래피에서 황화합물의 구조를 통한 용리시간 예측)

  • Kim, Young Gu;Kim, Won Ho;Pak, Hyung Suk
    • Journal of the Korean Chemical Society
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    • v.42 no.6
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    • pp.646-651
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    • 1998
  • The molecular structure of sulfur compounds and the retention relationship are studied by gas chromatography. Analyzed sulfur compounds are, hydrogen sulfide, sulfur dioxide, carbon disulfide, ethyl mercaptan, dimethyl sulfide, iso-propyl mercaptan, normal propyl mercaptan, ethyl methyl sulfide, tert-butyl mercaptan, tetrahydrothiophene, thiophene, and 2-chlorothiophene. Multiple linear regression explains the retention relationship of molecular descriptors. In GC the temperature program is 30$^{\circ}C$ held for 10.5 min, and then increased to 150$^{\circ}C$ at a rate 15$^{\circ}C$/min. Predicted equation for relative retention time (RRT) using SAS program is as follows; $RRT=0.121bp+14.39dp-8.94dp^2+0.0741sqmw-35.78\; (N=8,\; R^2=0.989, \;Variance=0.175,\;F=66.21)$. RRTs are function of boiling point, the square root of molecular weight, molecular dipole moment, and boiling point effects mostly on RRT. The RRT is maximized at the molecular dipole moment of 0.805D, when using nonpolar columns. The planar and highly symmetric compounds are eluted slowly. The square, of correlation coefficient $(R^2)$ using SAS program, is 0.989, and the variance is 0.175 in training sets. For three sulfur compounds, the variance between observed RRTs and predicted RRTs is 0.432 in testing sets.

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Synthesis and evaluation of PDLs22 recombinant protein (PDLs22 재조합 단백질의 합성과 평가)

  • Lee, Kyoung Yeon;Choi, Yong-Seok;Lee, You-Jin;Bae, Hyun-Sook;Kim, Heung-Jeong;Cho, Kwang-Hee;Jang, Hyun-Seon;Park, Joo-Cheol
    • Journal of Periodontal and Implant Science
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    • v.37 no.1
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    • pp.35-44
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    • 2007
  • Periodontal ligament (PDL) is the connective tissue located between the tooth root and alveolar bone. In a previous study, PDLs22 was isolated as a PDL-specific gene by using subtractive hybrid-ization between cultured PDL fibroblasts and gingival fibroblasts. It was also suggested that PDLs22 plays important roles in the development, differentiation and maintenance of periodontal tissues. However, little is known about functional study of PDLs22 using recombinant protein in PDL fibroblast differentiation and periodontium formation. In this study, in order to produce the PDLs22 recombinat protein, PDLs22 expression vector were constructed and expressed its protein in various host cell and temperature conditions. The results were as follows: 1. PDLs22 protein was not strongly expressed In the induction system using pRSET-PDLs22 construct. 2. When the BL21(DE3) pLysS was used as a expression host, PDLS22 protein was strongly ex-pressed in the induction system using pHCEIIBNd-PDLs22 construct. 3. The PDLs22 protein was recognized at a molecular weight of 28 kDa in western blots. 4. Almost of the expressed PDLs22 protein was not soluble and observed like as inclusion body. 5. The protein solubility was not improved after modification of induction time and temperature during PDLs22 protein production. In this study, the system for the PDLs22 protein production was connstructed. However, the re-results suggest that further studies will be needed to produce the considerable amount of PDLs22 re-combinat protein, which can use for the periodontal regeneration.

Investigation of Growth Characteristics of Salix gracilistyla Clones for Promoting Woody Biomass Resources (목질계 바이오매스 생산을 위한 갯버들의 생장특성)

  • Lee, Hyunseok;An, Chanhoon;Kang, Junwon;Lee, Wiyoung;Yi, Jae-Seon
    • Journal of Korean Society of Forest Science
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    • v.107 no.1
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    • pp.16-24
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    • 2018
  • This study was investigated to select superior population and clones of Salix gracilistyla for promoting woody biomass resources through creating of short rotation coppices (SRC). Plant materials were collected from seven different population groups of S. gracilistyla and planted at two different nursery sites in Chuncheon and Yongin. Height and root collar diameter showed statistically significant differeces among population, nursery, and annual growth for three years (p<0.01). Aboveground biomass was harvested to investigate dry weight after 3 years from planting, the Youngwol population showed the highest yield as $4.8kg\;DW\;plant^{-1}$ in Chuncheon nursery which was more than double yield compared to the other nursery planted plants. However, Hongcheon and Wonju populations as $3.3kg\;plant^{-1}$, showed the best yield in Yongin nursery. In addition, there was a significant difference between collected populations and nurseries. But there was statistically significant different interaction between population (Pop) and nursery (Nur) (F value = 3.51, p<0.01). Therefore, the superior populations selected by this experiment could be cultivated as an excellent variety for woody biomass resources through the clonal test.

Growth Responses of Pinus densiflora Seedlings to High Temperature in Container Culture (시설내 고온에 대한 소나무 유묘의 생장반응)

  • Kim, Jong-Jin;Hong, Sung-Gak;Yoon, Taek-Seong
    • Journal of Bio-Environment Control
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    • v.12 no.4
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    • pp.217-220
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    • 2003
  • This study was carried out to investigate the growth response of Pinus densiflora seedling to relatively high day temperature during the container culture in summer season. The experiment was performed with three maximum day temperature regimes, 30~35$^{\circ}C$, 35~40$^{\circ}C$ and above 40$^{\circ}C$ in the PE house. The reduction in plant height was observed since 6 weeks after germination in the seedlings grown at relatively high day temperatures, especially the seedlings at above 40$^{\circ}C$. High temperature also reduced the root collar diameter during growth of the seedlings, therefore 17.3% of the reduction was observed in the seedlings grown at above 40$^{\circ}C$ compared with the seedlings at 30~35$^{\circ}C$. The dry weight of the seedlings grown for 16 weeks was apparently reduced by elevated dat temperature in the PE house, and the seedlings at relatively high day temperature resulted in increased T/R ratio.

Effect of Gibberellic Acid on Seed Germination and Early Growth of Kentucky Bluegrass and Tall Fescue Turfgrass (Gibberellic acid 처리가 Kentucky bluegrass와 Tall fescue 잔디종자의 발아와 초기생육에 미치는 영향)

  • Kang, Jum-Soon;Kim, Yong-Chul;Choi, In-Soo
    • Journal of Bio-Environment Control
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    • v.16 no.1
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    • pp.32-39
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    • 2007
  • This study was carried out to find the optimum treatment condition for the improving germination using the plant growth regulators with $GA_3$ and BAP, to Kentucky bluegrass and Tall fescue showing low germination. $GA_3$ treatment was more effective on the germination of Kentucky bluegrass than BAP single treatment or the combination treatment of $GA_3$ and BAP, regardless of their treatment concentration. Seed germinability was 6 days treatment was significantly better than that of 3 days treatment in the experiment for treatment period of the plant growth regulators. When seeds were treated with $1000{\mu}M$ of $GA_3$ for 6 days, on the percent germination was improved as much as between 10% and 38% comparing with the control. In Tall fescue seed, the percent germination was not significantly improved, although it was slightly increased when the plant growth regulators were treated. For the optimum condition, on percent germination was improved as much as 10% comparing with the control of Tall fescue treated with $1000{\mu}M$ of $GA_3$ for 3 days. Percent emergence fur the seeds of Kentucky bluegrass and Tall fescue treated $GA_3$ in the field was improved as much as $8{\sim}9%$ comparing with the control, and mean emergence time $(E_{50})$ was also faster for $1{\sim}2$ days than that of the control. However, dry weight, plant height and root length showed no significant effects, although those were slightly improved more than those of the control.

Growth, Deficiency Symptom and Tissue Nutrient Contents of Leaf Perilla (Perilla frutesens Britt) Influenced by Phosphorus Concentrations in Fertigation Solution (인산 시비농도가 잎들깨의 생육, 결핍증상 및 무기원소 함량에 미치는 영향)

  • Choi, Jong-Myung;Park, Jong-Yoon
    • Journal of Bio-Environment Control
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    • v.16 no.4
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    • pp.358-364
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    • 2007
  • This study was carried out to investigate the effect of phosphorus concentrations in fertilizer solution on growth and development of nutrient deficiency in leaf perilla (Perilla frutesens). The nutrient concentrations in above ground plant tissue, petiole sap and soil solution of root media were also determined. Phosphorus deficiency resulted in a slow growth, lustreless leaves, suffused purple tining in older leaves and falling prematurely. Elevation of P concentrations in fertilizer solution increased the crop growth at 75 days after transplanting. The fresh weight in 0, 0.5 and 4.0 mM treatments were 0.48 g, 9.28 g, and 25.5 g, respectively, and dry weights were 0.06 g, 1.46 g and 4.13 g, respectively. The P concentrations in above ground plant tissue and petiole sap in 4.0 mM treatment were 1.78% and $2.040mg{\cdot}kg^{-1}$, respectively, at 75 days after transplanting. The soil P concentration in 4.0 mM treatment was $1.26mg{\cdot}kg^{-1}$ when it was determined by the 1:2 (sample:water) method. These results indicated that P concentrations higher than 0.3% in above ground plant tissue, $900mg{\cdot}kg^{-1}$ in petiole sap, and $0.57mg{\cdot}kg^{-1}$ in soil solution should be maintained to ensure proper growth of leaf perilla (Perilla frutesens).