• 약학회지
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• 제40권3호
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• pp.279-292
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• 1996

To assess their stability as a prodrug of 5-fluorouracil (5-FU), four N-acyloxycarbonyl derivatives (1-(N-tert-butyloxycarbonyl)glycyloxymethyl-5-FU :BGFU, 1-(N-tert-butyloxycar bonyl)-leucyloxymethyl-5-FU:BLFU, 1-(N-tert-carbobenzyloxymethyl) glycyloxymethyl-5-FU:CGFU and 1-(N-tert-carbobenzlyoxymethyl)leucyloxymethyl-5-FU:CLFU) possessing differently protected amino acids, and two acetic acid derivatives (5FU-1-acetylpentane:FUAP and 5-FU-1-acetylhexane:FUAH) were synthesized and their physicochemical properties, hydrolysis kinetics, acute toxicity and antitumor activity were evaluated. The lipid-water partition coefficients of six 5-FU prodrugs were higher than that of 5-FU and their aqueous solubilities were in the following rank order; BGFU>FUAP>CGFU>BLFU>CLFU${\simeq}$FUAH. The hydrolysis of N-acyloxycarboyl derivatives, greater at higher pH, was enhanced in presence of liver homogenate or human plasma. Meanwhile, acetic acid ester derivatives, very stable, were hydrolyzed by liver homogenate. Absorption rate constants were 0.181, 0.121, 0.111, 0.168, 0.168, 0.116 and 0.125 $hr^{-1}$ for 5-FU, BGFU, BLFU, CGFU, CLFU, FUAP and FUAH, respectively. The cytotoxicity of N-acyloxycarbonyl derivatives was 4 to 5 times lower than that of 5-FU, but that of acetic acid ester derivatives was negligeble. The $LD_{50}$ values were 204, 325.97 (133.59, amount as 5-FU), 708.16 (262.13), 663.50 (211.77), 382.33 (192.54) and 272.33 (130.09) mg/kg for 5-FU, BGFU, CGFU, CLFU, FUAP and FUAH, respectively. While N-acyloxycarbonyl derivatives showed enhanced antitumor activity and therapeutic ratio (3.30, 3.06, 4.19, 3.11 and 1.81 for BGFU, BLFU, CGFU, CLFU and 5-FU, respectively), FUAH and FUAP showed a smaller therapeutic ratio (0.79 and 0.83).

• Journal of Pharmaceutical Investigation
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• 제33권1호
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• pp.45-49
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• 2003

The solubility and stability of ondansetron hydrochloride (OS) in various vehicles were determined. The effect of cyclodextrins (CD) on the solubility of OS in water was determined by equilibrium solubility method. The solubility of OS at $32^{\circ}C$ increased in the rank order of isopropyl myristate (IPM) < propylene glycol laurate (PGL) ${\ll}$ propylene glycol monolaurate < propylene glycol monocaprylate (PGMC) < poly(ethylene glycol) 400 < diethylene glycol mono ethyl ether (DGME) < ethanol < poly(ethylene glycol) 300 < water (36.1 mg/ml) ${\ll}$ propylene glycol (PG) (283 mg/ml). The addition of PG or DGME to non-aqueous vehicles such as IPM, PGL and PGMC markedly increased the solubility of OS. The addition of CDs in water increased the solubility. Apparent stability constant for the CD complexation with OS was calculated to be $25.5\;M^{-1}$ for $2-hydroxypropyl-{\beta}-CD\;(2HP{\beta}CD)$. Twenty mM ${\beta}-CD$, 69.4 mM sulfobutyl ether ${\beta}-CD$ and 115.4 mM $2HP{\beta}CD$ increased the aqueous solubilty of OS 1.27, 2.18 and 1.85 times, respectively. OS was stable in buffered aqueous solution (pH 5.0). However, OS was relatively unstable in non-aqueous vehicles in the order of PG

• Reproductive and Developmental Biology
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• 제37권1호
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• pp.1-8
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• 2013

In order to investigate genetic stability and gene expression profile after cloning procedure, two groups of cloned pigs were used for swine leukocyte antigen (SLA) gene nucleotide alteration and microarray analyses. Each group was consist of cloned pigs derived from same cell line (n=3 and 4, respectively). Six SLA loci were analyzed for cDNA sequences and protein translations. In total, 16 SLA alleles were identified and there were no evidence of SLA nucleotide alteration. All SLA sequences and protein translations were identical among the each pig in the same group. On the other hand, microarray assay was performed for profiling gene expression of the cloned pigs. In total, 43,603 genes were analyzed and 2,150~4,300 reliably hybridized spots on the each chip were selected for further analysis. Even though the cloned pigs in the same group had identical genetic background, 18.6~47.3% of analyzed genes were differentially expressed in between each cloned pigs. Furthermore, on gene clustering analysis, some cloned pigs showed abnormal physiological phenotypes such as inflammation, cancer or cardiomyopathy. We assumed that individual environmental adaption, sociality and rank in the pen might have induced these different phenotypes. In conclusion, the results of the present study indicate that SLA locus genes appear to be stable following SCNT. However, gene expressions and phenotypes between cloned pigs derived from the same cell line were not identical even under the same rearing conditions.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.355-362
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• 2014

Objective: Altered regulation of many transcription factors has been shown to play important roles in the development of leukemia. hMSH2 can modulate the activity of some important transcription factors and is known to be a regulator of hematopoietic differentiation. Herein, we investigated epigenetic regulation of hMSH2 and its influence on cell growth and overall survival of acute lymphoblastic leukemia (ALL) patients. Methods: hMSH2 promoter methylation status was assessed by COBRA and pyrosequencing in 60 ALL patients and 30 healthy volunteers. mRNA and protein expression levels of hMSH2, PCNA, CyclinD1, Bcl-2 and Bax were determined by real time PCR and Western blotting, respectively. The influence of hMSH2 on cell proliferation and survival was assessed in transient and stable expression systems. Results: mRNA and protein expression of hMSH2 and Bcl-2 was decreased, and that of PCNA, CyclinD1 and Bax was increased in ALL patients as compared to healthy volunteers (P<0.05). hMSH2 was inactivated in ALL patients through promoter hypermethylation. Furthermore, hMSH2 hypermethylation was found in relapsed ALL patients (85.7% of all cases). The median survival of patients with hMSH2 methylation was shorter than that of patients without hMSH2 methylation (log-rank test, P=0.0035). Over-expression of hMSH2 in cell lines resulted in a significant reduction in growth and induction of apoptosis. Conclusions: This study suggests that aberrant DNA methylation and epigenetic inactivation of hMSH2 play an important role in the development of ALL through altering cell growth and survival.

• Archives of Plastic Surgery
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• 제45권2호
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• pp.165-170
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• 2018

Background To present the outcomes of the tarsal switch procedure using an anterior approach to correct severe ptosis with poor levator muscle function (<4 mm) with absent or poor Bell's phenomenon. Methods This retrospective case series included 11 patients with severe neurogenic or acquired myogenic palpebral ptosis. All patients underwent the tarsal switch procedure through an anterior approach from 2012 to 2015. Margin reflex distance (MRD1 and MRD2) and the palpebral fissure were evaluated preoperatively and postoperatively. Data were compared using the Wilcoxon signed-rank test. P-values <0.05 were considered to indicate statistical significance. Results Surgery was performed on 18 eyelids (11 patients). The median age at surgery was 57 years (range, 29-86 years). Four patients had unilateral ptosis and seven had bilateral ptosis. Nine patients had myogenic ptosis and two had neurogenic ptosis. Postoperatively, the chin-up position improved in all patients. The MRD1 increased statistically significantly, from 0 mm preoperatively to 1.0 mm postoperatively (P=0.001). The MRD2 decreased statistically significantly, from 4.5 mm preoperatively to 3.0 mm postoperatively (P=0.001). The palpebral fissure did not change (4.0 mm preoperatively to 4.0 mm postoperatively) (P=0.13). Conclusions The tarsal switch procedure through an anterior approach is an effective alternative for correcting severe ptosis, especially neurogenic or acquired myogenic ptosis. This procedure can be performed with minimal risk of ocular surface exposure and provides stable outcomes.

• 한국작물학회지
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• 제42권5호
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• pp.604-608
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• 1997

수원 작물시험장 등 전국 각도 9개 지역에서 1990 및 1991년에 걸쳐 수행된 콩 지방적응연락시험에서, 팔달콩 등 10개의 공시계통들의 평균 수량을 조사하였으며, 수량안정성을 여러가지 방법으로 분석하여 상호 비교하였다. 수량 안정성분석은 Francis와 Kannenberg의 coefficient of variability, Finlay와 Wilkinson의 regression coefficient, Eberhart와 Russell의 deviation parameter, Plaisted의 variance component, Wricke의 ecovalence등 5개 분석방법을 이용하였으며 그 결과를 요약하면 다음과 같다. 1. 분산성분 비교에 의하면, 수량에 대한 콩유전자와 지역간 상호작용 분산성분이 콩유전자 및 년차간 상호작용 분산성분보다 약 7배 높아서, 정확한 수량안정도 평가를 위해서는 여러 해 걸쳐서 콩계통을 평가하기보다는 더 많은 지역에서 평가되어야 할 것으로 보였다. 2. 2년차 9개지역에서 수원 14005('92년 태광콩으로 장려품종 지정)가 평균수량이 높았으며, 5개 안정성 분석결과 수량안정도도 높았다. 3. 안정도계수 종류들 간의 rank correlation 분석결과, Eberhart와 Russell, Plaisted, 그리고 Wricke의 방법들 간의 고도의 유의적인 상관관계가 있었으나, Francis와 Finlay 방법은 다른 분석방법들과는 상관관계가 인정되지 않았다.

• 대한치과의사협회지
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• 제55권2호
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• pp.116-127
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• 2017

Objectives : The aim of this study was to evaluate the cumulative survival rates of the implants placed into grafted sinus and determine the effect of age, gender, smoking, and systemic disease on the implant cumulative survival rates. Materials and Methods : The retrospective study was performed on 51 implants placed in 26 patients by one dentist at the Dental Implant Center, Seoul National University Dental Hospital in the years 2000-2010. The cumulative survival rates were calculated by the Kaplan-Meier method. The differences within the factors were analyzed using log-rank test and the correlations between the factors and implant survival rates were analyzed using Cox proportional hazard model. Results : 1. Among the total of 51 implants placed in 26 patients, 7 implants failed and 44 implants remained stable. The 1-year, 5-year, and 10-year cumulative survival rates were 92%, 88%, and 85%, respectively. 2. Patients in their 50s and in their 70s showed statistically significant difference in the cumulative survival rates (P < 0.05). Gender and the existence of systemic disease did not show significant results. 3. In the implant treatment, smokers showed 7.5 times higher risk of implant failure than non-smokers (P < 0.05). Conclusion: Implants installed in combination with sinus elevation can be considered as a reliable treatment method.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3111-3116
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• 2015

Background: This study was designed to investigate the value of CEA and CA199 in predicting the treatment response to palliative chemotherapy for advanced gastric cancer. Materials and Methods: We studied 189 patients with advanced gastric cancer who received first-line chemotherapy, measured the serum CEA and CA199 levels, used RECIST1.1 as the gold standard and analyzed the value of CEA and CA199 levels changes in predicting the treatment efficacy of chemotherapy. Results: Among the 189 patients, 80 and 94 cases had increases of baseline CEA (${\geq}5ng/ml$) and CA199 levels (${\geq}27U/ml$), respectively. After two cycles of chemotherapy, 42.9% patients showed partial remission, 33.3% stable disease, and 23.8% progressive disease. The area under the ROC curve (AUC) for CEA and CA199 reduction in predicting effective chemotherapy were 0.828 (95%CI 0.740-0.916) and 0.897 (95%CI 0.832-0.961). The AUCs for CEA and CA199 increase in predicting progression after chemotherapy were 0.923 (95%CI 0.865-0.980) and 0.896 (95%CI 0.834-0.959), respectively. Patients who exhibited a CEA decline ${\geq}24%$ and a CA199 decline ${\geq}29%$ had significantly longer PFS (log rank p=0.001, p<0.001). With the exception of patients who presented with abnormal levels after chemotherapy, changes of CEA and CA199 levels had limited value for evaluating the chemotherapy efficacy in patients with normal baseline tumor markers. Conclusions: Changes in serum CEA and CA199 levels can accurately predict the efficacy of first-line chemotherapy in advanced gastric cancer. Patients with levels decreasing beyond the optimal critical values after chemotherapy have longer PFS.

• 근관절건강학회지
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• 제3권1호
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• pp.23-36
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• 1996

This study was undertaken to evaluate the effect of long-term(6 Month) aquatic exercise through home nursing care demonstration on body weight, body fat, pain, muscle strength, self-efficacy and quality of life. Twenty-one women with rheumatoid arthritis were enrolled in the study. The sample was restricted to women in order to increase homogeneity. All patients were stable medication regimens in rheumatism center. The data was collected from October, 1994 to November, 1995. The data were analyzed Mean, Standard Deviation, $x^2$ Test, Mann-Whitney U-Wilcoxon Rank Sum W Test, Wilcoxon Matched-pairs signed-ranks test using SPSS $pc^+$ program. The results of this study were as follows : 1. There was no significant difference between the control and the experimental group on body weight. 2. There was no significant difference between the control and the experimental group on body fat. 3. There was no significant difference between the control and the experimental group on pain(RAI). 4. There was no significant difference between the control and the experimental group on muscle strength. 5. There was no significant difference between the control and the experimental group on quality of life. But in the experimental group, finding from additional analysis showed significant difference in the score of quality of life between pre and post experiment. 6. There was no significant difference between the control and the experimental group on self-efficacy. The findings in this study were not support the positive effect of long-term aquatic exercise in women with rheumatoid arthritis. A further study is necessary to determine the pure effect of aquatic exercise except the effect of home nursing care.

• Archives of Pharmacal Research
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• 제24권6호
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• pp.572-577
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• 2001

The feasibility of skin penetration was studied for aspalatone (AM, acetylsalicylic acid maltol ester), a novel antithrombotic agent. In this studys hairless mouse dorsal skins were used as a model to select composition of vehicle and AM. Based on measurements of solubility and partition coefficient, the concentration of PC that showed the highest flux for AM across the hairless mouse skin was found to be 40%. The cumulative amount permeated at 48 h, however, appear inadequate, even when the PC concentration was employed. To identify a suitable absorption enhancer and its optimal concentration for AM, a number of absorption enhancers and a variety of concentration were screened for the increase in transdermal flux of AM. Amongst these, linoleic acid (LOA) at the concentration of 5% was found to have the largest enhancement factor (i.e., 132). However, a further increase in AM flux was not found in the fatty acid concentration greater than 5%, indicating the enhancement effect is in a bell-shaped currie. In a study of the effect of AM concentration on the permeation, there was no difference in the permeation rate between 0.5 and 1% for AM, below its saturated concentration. At the donor concentration of 2%, over the saturated condition, the flux of AM was markedly increased. A considerable degradation of AM was found during permeation studies, and the extent was correlated with protein concentrations in the epidermal and serosal extracts, and skin homogenates. In rat dorsal skins, the protein concentration decreased in the rank order of skin homogenate > serosal extract > epidermal extract. Estimated first order degradation rate constants were $6.15{\pm}0.14,{\;}0.57{\pm}0.02{\;}and{\;}0.011{\pm}{\;}0.004{\;}h^{-1}$ for skin homogenate, serosal extract and epidermal extract, respectively. Therefore, it appeared that AM was hydrolyzed to some extent into salicylmaltol by esterases in the dermal and subcutaneous tissues of skin. taken together, our data indicated that transdermal delivery of AM is feasible when the combination of PC and LOA is used as a vehicle. However, since AM is not metabolically stable, acceptable degradation inhibitors may be nervessary to fully realize the transdermal delivery of the drug.