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Water Soluble Cyclosporine Monomethoxy Poly(ethyleneglycol) Conjugates as Potential Prod rugs

  • Cho, Hoon;Chung, Yong-Seog
    • Archives of Pharmacal Research
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    • 제27권6호
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    • pp.662-669
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    • 2004
  • The highly water-soluble monomethoxypoly(ethyleneglycol) (mPEG) prod rugs of cyciosporin A(CsA) were synthesized. These prod rugs were prepared by initially preparing intermediate in the form of carbonate at the 3'-positions of CsA with chloromethyl chloroformate, in the pres-ence of a base to provide a 3'-carbonated CsA intermediate. Reaction of the CsA intermediate with mPEG derivative in the presence of a base provides the desired water-soluble prod rugs. As a model, we chose molecular weight 5 kDa mPEG in the reaction with CsA to give water soluble prodrugs. To prove that the prod rug is decomposed in the body to produce CsA, the enzymatic hydrolysis test was conducted using human liver homogenate at $37^{\circ}C$. The prodrug was decomposed in human liver homogenate to produce the active material, CsA, and the hydrolysis half-life ($t_{1/2}$) of the prodrug, KI-306 was 2.2 minutes at $37^{\circ}C$. However, a demon-stration of non-enzymatic conversion in pH 7.4 phosphate buffer was provided by the fact that the half-life ($t_{1/2}$) is 21 hours at 37$^{\circ}C$. The hydrolysis test in rat whole blood was also conducted. The hydrolysis was seen with half-life ($t_{1/2}$) of about 9.9, 65.0, 14.2, 3.4, 2.1 9.5, and 1.6 minutes for KI-306, 309, 312, 313, 315, 316, and 317, respectively. This is the ideal for CsA prodrug. The pharmacokinetic study of the prodrug, KI-306, in comparison to the commer-cial product (Sandimmune Neoral Solution) was also carried out after single oral dose. Each rat received 7 mg/kg of CsA equivalent dose. Especially, the prodrug KI-306 exhibits higher AUC and $C_{max}$ than the conventional Neoral. The AUC and $C_{max}$ were increased nearly 1.5 fold. The kinetic value was also seen with $T_{max}$ of about 1.43 and 2.44 hours for KI-306 and Neoral, respectively.

Cardiorespiratory Responses of Qi-training: A Pilot Study

  • Lee, Myeong-Soo;Kim, Soo-Keun;Kim, Hye-Jung;Moon, Sun-Rock
    • Advances in Traditional Medicine
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    • 제4권1호
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    • pp.18-21
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    • 2004
  • Six volunteers (mean $age=25.7{\pm}1.7$, $height=173{\pm}1.9$ and $weight=63.4{\pm}2.3{\;}kg$) participated in a graded exercise test and one hour of basic form of ChunDoSunBup (CDSB) Qi-training to investigate the cardiorespiratory responses and exercise intensity of Qi-training, a Korean traditional psychosomatic training. In the maximal exercise, the trainee showed $96.2{\pm}8.89{\;}l/min$ in ventilation (VE), $46.0{\pm}4.4$ in breath frequency (BF), $1.31{\pm}0.05$ in respiratory exchange ratio (RER), $180.7{\pm}3.0$ in heart rate (HR), and $2.6{\pm}1.1{\;}l/min$ or $40.7{\pm}2.3{\;}ml/kg/ml$ in oxygen consumption $(VO_2)$. Qi-training induced significant changes in BF, RER, HR, and $VO_2$. The exercise intensity of Qi-training were 42.3%, 46.9% and 38.7% of $HR_{max}$ during the sound exercise, slow motion (haeng-gong) and meditation respectively and the average was 46.2% of $HR_{max}$. We conclude that Qi-training is an aerobic exercise of a light (mild) intensity exercise, and it leads to decrease the metabolic rate in the trainee by breathing efficiently and relaxing them. In addition, Qi-training may affect cardiorespiratory function of BF, RER, HR and $VO_{2max}$ in trainees.

마직물 및 마혼방직물의 온열특성에 대한 흡습의 영향 (The Effect of Absorption Water on Thermal Properties of Pure Linen and Linen Blended Woven Fabrics)

  • 권오경;이참미;성우경
    • 한국의류산업학회지
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    • 제1권2호
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    • pp.160-165
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    • 1999
  • The thermal properies of the pure linen fabrics available in the market and linen blended woven fabrics were measured at the moisture content of 0%, 20%, 40% and 60% using KES-F7 system (Thermo Iabo II type). The experimental properties were statistically analyzed by the rate of water absorbent. The main results were as follows; There is a positive correlation between the thermal insulation value (TIV) and thickness of pure linen fabrics and linen blended woven fabrics by water absorption. Whereas an negative correlation exists between the TIV and cover factor. There is a high positive correlation among the thermal conductivity (k), thickness and weight of pure linen fabrics and linen blended woven fabrics by water absorption. Wherase a high negative correlation exist between the k and air' permeability (Ap). There is a high positive correlation between the feeling of warmth/coldness and bulk density of pure linen and linen blended woven fabrics by water absorption. Wherase a high negative correlation exists between the feeling of warmth/coldness and porosity. There is a negative correlation between TIV and $q_{max}$ of pure linen fabrics and linen blended woven fabrics. The higher the rate of water absorbent, the lower the TIV. This means that TIV decreases by water absorption. As for the thermal property by rate of water absorbent $q_{max}$ and k increase by water absorption and reach max-value at 60% rate of water absorbent. The TIV decreases by water absorption and has +value at 0% rate of water absorbent, whereas it has -value with a feeling of coldness at 20%, 40%. and 60% rate of water absorbent.

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Overproduction, Purification, and Characterization of Bacillus stearothermophilus Endo-xylanase A (XynA)

  • Cho, Ssang Goo;Jung Han Suh;Yong Jin Choi
    • Journal of Microbiology and Biotechnology
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    • 제6권2호
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    • pp.79-85
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    • 1996
  • By using a T7 expression system, a large amount of Bacillus stearothermophilus endo-xylanase A (XynA) could be produced in Escherichia coli cells. The overproduced enzyme formed inclusion bodies, and so the protein could be more easily purified to homogeneity. The molecular weight of the purified enzyme was estimated to be 22 kDa by SDS-polyacrylamide gel electrophoresis and 43 kDa by Sephacryl S-200 gel filtration, suggesting that the native enzyme was a homodimer. The pI value was determined to be 8.4. The Michaelis constants for birchwood xylan and oat spelts xylan were calculated to be 3.83 mg/ml and 5.03 mg/ml, respectively, and the $V_{max}$ max/ values for both xylans were 2.86 $\mu mole$/min. The purified enzyme was most active at $55^{\circ}C$ and pH 8.0, and stable up to $60^{\circ}C$ and in the near neutral pH range. From the zymogram, Bacillus stearothermophilus was found to have at least three xylanases and the purified one was the smallest among them.

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유방암 수술 후 방사선치료중인 환자를 위한 운동프로그램이 심폐기능 및 어깨관절기능에 미치는 효과 (Effects of Exercise on Cardiopulmonary Functions and Shoulder Joint Functioning in Breast Cancer Patients undergoing Radiation Therapy after Breast Surgery)

  • 채영란;최명애
    • 대한간호학회지
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    • 제31권3호
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    • pp.454-466
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    • 2001
  • Purpose: The purpose of this study was to determine the effects of exercise program on cardiopulmonary functions and shoulder joint functioning in breast cancer patients who under- went radiation therapy after surgery. Method: Subjects in the experimental group(N=12) participated in an exercise program for eight weeks. The Exercise program consisted of shoulder stretching, arm weight training, and walking on treadmill. Maximal oxygen uptake (v2max), maximal running time, shoulder joint range of motion, and shoulder functional assessment were determined before and after the exercise program. Baseline sociodemographic and medical data were compared between experimental group and control group using the Fisher's exact test and Mann- Whitney U test. For effects of the exercise program, repeated measures ANOVA were used. Result: 1) Following the exercise program for eight weeks, both v$\alpha$ max and maximal running time tended to increase in experimental group comparing with the control group. 2) Shoulder abduction, extension and flexion of the operated upper extremity in the experimental group comparing with control significantly increased after the exercise program(p<0.05). 3) Shoulder flexion of the normal upper extremity in the experimental group comparing with control significantly increased after the exercise program(p<0.05). Conclusion: The results suggest that the exercise program for breast cancer patients undergoing radiation therapy after breast surgery can improve shoulder functions and increase cardiopulmonary functions, which are maximal oxygen uptake and maximal running time.

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Pseudomonas aeruginosa에 의해 생성되는 Cephalosporinase의 특성 (Properties of Cephalosporinase Produced by Pseudomonas aeruginosa)

  • 이동준;이호용;최영길
    • 미생물학회지
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    • 제24권3호
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    • pp.302-307
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    • 1986
  • 내성 P.aeruginosa에 의해 생성되는 항생물질 파괴효소인 cephalosporinase는 cephaloridine을 기질로 하여 효소활성도는 $45^{\circ}C$와 pH 8.5에서 각기 최고의 활성도를 나타내었다. SDS. carbenicillin 빛 cephalosporin계 항생체에 의해 효소의 활성도는 현저하게 억제되었으며 효소의 cephaloridine에 대한 $V_{max}$ 값을 100으로 하였올때 cefo p perazone의 $V_{max}$ 값은 2.8로 나타났다. 측정된 효소의 분자량은 $37.500{\pm}3,000$이었다. 다른 Gram음성셰균이 분비하는 cephalosporinase와 비교해본 결과 균체 자체의 특성에 의해 cepha]osporinase는 서로 다름을 알 수 있였 으며 이로 인하여 각각의 균체가 cephalosporin계 항생제에 대한 내성의 차이를 나타내는 하나의 중요한 원인으로 판단되었다.

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Identification of ${\gamma}-Glutamylamine$ Cyclotransferase, as the Preform Enzyme at the Dormant Stage, From Soybean (Glycine max) Seeds

  • Kang, Hyeog;Park, Sung-Joon;Cho, Young-Dong
    • BMB Reports
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    • 제30권6호
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    • pp.438-442
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    • 1997
  • ${\gamma}-Glutamylamine$ cyclotransferase was purified to homogeneity from soybean (Glycine max) seeds. To our knowledge, it is the first purification of the enzyme from plant origins. The molecular weight of the enzyme estimated by Sephacryl S-300 gel filtration and SDS-PAGE was 27,000, indicating that the enzyme is a monomer. The optimal pH for activity was 8.6. The Km value for ${\gamma}-glutamyldansylcadaverine$ was 11 ${\mu}M$. The enzymatic activity was substantially inhibited by the addition of p-chloromercuribenzoate and partially inhibited by the $Cu^{2+}$ ion. However, neither other modification reagents nor other divalent metal ions affected the enzymatic activity. The comparison between the enzymatic activities of seed extracts treated with cycloheximide and control extracts, and the detection of the same single protein band by western blot analysis at the dormant stage without inhibition with distilled water indicate that ${\gamma}-Glutamylamine$ cyclotransferase is already present at the dormant stage and gradually activated during germination in soybean seeds.

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고감성 의류용 직물의 수분이동특성 -섬유소재와 실 특성 및 실험방법에 따른 수분이동특성- (Moisture Transmission Characteristics of Fabric for High Emotional Garments -Moisture Transmission Characteristics according to Fiber Properties, Yarn Characteristics and Test Method-)

  • 김승진;김현아
    • 한국의류학회지
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    • 제41권1호
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    • pp.28-42
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    • 2017
  • Moisture transfer characteristics of high emotional garments are important to evaluate wear comfort. Wicking and drying measurement methods are also critical for perspiration absorption and quick dry fabric made of high functional fibers. In this study, the wicking and drying properties of high emotional fabrics made from hybrid composite yarns using CoolMax, Tencel, Bamboo staple fibers and PP. PET CoolMax filaments were also measured and analyzed according to various measuring methods. The wicking property of hybrid composite yarn fabrics by Bireck method was mostly influenced by the structure of hybrid yarns than the absorption rate of constituent fibers; however, both the hygroscopicity of fibers and the composite yarn structure affected the wicking property of the fabrics in the drop method. Concerning drying properties, the KSK 0815B method measuring distilled moisture weight was more relevant to explain the drying characteristics of hybrid yarn fabrics than the KSK 0815A method measuring the time to drying. This study revealed that the drying properties of hybrid yarn fabrics were influenced by the hygroscopicity of constituent fibers, wicking properties of constituent yarns and structure of composite yarns.

대장균에서 발현되는 Clostridium thermocellum의 섬유소 분해 효소의 특성 (Properties of a Novel Clostridiclm thermocellum Endo-$\beta$-1,4-glucanase Expressed in Escherichia coli)

  • 정경화;이진호;이용택;김하근;박무영
    • 한국미생물·생명공학회지
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    • 제20권5호
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    • pp.505-510
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    • 1992
  • 고온성 혐기성 세균인 Clostridium thermocellum의 섬유소 분해 효소 유전자를 pUC9 플라스미드를 이용하여 대장균에 클로닝하였고, 지금까지 클로닝 된 C.thermocellum의 섬유소 분해 유전자들과 제한효소 양상을 비교하여 새로운 유전자임을 알 수 있었다. 대장균에서 섬유소 분해 효소를 열처리와 column chromatography에 의해서 정제를 하였고, 분자량은 40, 000이었다. 이 효소는 pH 5.0과 $65^{\circ}C$에서 CMC에 대해서 최대 활성을 보였고 최종 산물인 포도당과 cellobiose에 의한 활성의 저해는 크게 나타나지 않았다. CMC에 대한 이 효소의 $K_{m}$$V_{max}$값은 각각 0.39(w/v)와 268 U/mg protein이었다.

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Interspecies Comparison of the Oral Absorption of Itraconazole in Laboratory Animals

  • Yoo, Sun-Dong;Kang, Eun-Hee;Shin, Beom-Soo;Lee, Hun-Jun;Lee, Sang-Heon;Lee, Kang-Choon;Lee, Kyu-Hyun
    • Archives of Pharmacal Research
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    • 제25권3호
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    • pp.387-391
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    • 2002
  • The oral absorption and disposition of itraconazole were studied in rats, rabbits and dogs. Serum levels of itraconazole and its active metabolite, hydroxyitraconazole, were determined by a validated HPLC method. The absorption of itraconazole was relatively rapid in rats and dogs but was slower in rabbits. The terminal elimination half-life ($T_{1/2,{\lambda}z}$), time to the peak concentration ($T_{max}$), dose and weight normalized area under the curve (AUC) and the peak concentration ($C_{max}$) of itraconazole found in the dog were comparable to those reported in humans. As in humans, the metabolite to parent drug AUC ratios in rats and dogs were greater than unity but was less in rabbits. The dog appears to be an appropriate animal model while the rat, not the rabbit, may be used as an alternative animal model in predicting the oral absorption of itraconazole in humans.