• Title/Summary/Keyword: Half-life(t1/2)

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Induction of Peptide-specific CTL Activity and Inhibition of Tumor Growth Following Immunization with Nanoparticles Coated with Tumor Peptide-MHC-I Complexes

  • Sang-Hyun Kim;Ha-Eun Park;Seong-Un Jeong;Jun-Hyeok Moon;Young-Ran Lee;Jeong-Ki Kim;Hyunseok Kong;Chan-Su Park;Chong-Kil Lee
    • IMMUNE NETWORK
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    • v.21 no.6
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    • pp.44.1-44.15
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    • 2021
  • Tumor peptides associated with MHC class I molecules or their synthetic variants have attracted great attention for their potential use as vaccines to induce tumor-specific CTLs. However, the outcome of clinical trials of peptide-based tumor vaccines has been disappointing. There are various reasons for this lack of success, such as difficulties in delivering the peptides specifically to professional Ag-presenting cells, short peptide half-life in vivo, and limited peptide immunogenicity. We report here a novel peptide vaccination strategy that efficiently induces peptide-specific CTLs. Nanoparticles (NPs) were fabricated from a biodegradable polymer, poly(D,L-lactic-co-glycolic acid), attached to H-2Kb molecules, and then the natural peptide epitopes associated with the H-2Kb molecules were exchanged with a model tumor peptide, SIINFEKL (OVA257-268). These NPs were efficiently phagocytosed by immature dendritic cells (DCs), inducing DC maturation and activation. In addition, the DCs that phagocytosed SIINFEKL-pulsed NPs potently activated SIINFEKL-H2Kb complex-specific CD8+ T cells via cross-presentation of SIINFEKL. In vivo studies showed that intravenous administration of SIINFEKL-pulsed NPs effectively generated SIINFEKL-specific CD8+ T cells in both normal and tumor-bearing mice. Furthermore, intravenous administration of SIINFEKL-pulsed NPs into EG7.OVA tumor-bearing mice almost completely inhibited the tumor growth. These results demonstrate that vaccination with polymeric NPs coated with tumor peptide-MHC-I complexes is a novel strategy for efficient induction of tumor-specific CTLs.

A Study on the Dietary Behaviors of Female Baby Boomers and the Needs for Future Perspectives of Dietary Life (여성 베이비부머들의 식생활 태도와 미래 식생활 요구도 조사)

  • Nam, Haewon;Myung, Choonok;Park, Youngsim
    • The Korean Journal of Food And Nutrition
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    • v.26 no.4
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    • pp.895-908
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    • 2013
  • The purpose of this study is to examine female baby boomers' dietary habits and their attitudes together with their needs for future perspectives of dietary life. Our aim is to use these findings as a basic data when forecasting for food-related industries or policy making. A survey is being carried out for a total of 358 female baby boomers and analyzed by SPSS 12.0. The following is a summary of this study. The average age is 52.6 years old, most of them graduated from highschool (63.1%) and had a nuclear type of family (76.1%). Only 39.0% is composed of housewives, others had either full-time or part-time jobs. Self-assessment of stress is not so high and only 8.1% are dissatisfied with their lives. 38.2% are either overweight or obese in terms of BMI, and most of them are non-smokers (97.2%) or non-drinkers (63.0%). Their mean dietary habit scores are $70.6{\pm}11.8$, and the scores show significant relations with their education levels (p<0.01), monthly income (p<0.01), life satisfaction rates (p<0.001), stress levels (p<0.001), smoking habits (p<0.05), drinking habits (p<0.05), regular exercises (p<0.001) and regular health check-ups (p<0.05). The rate of skipping breakfast, lunch and dinner are 18.2%, 1.1%, 5.2% respectively. The main reason for skipping breakfast is the 'lack of time'. With regards to the frequency of grocery shopping, almost half of the subjects (55.7%) said '1~2 times per week' and bought mainly raw food sources such as vegetables, fruits, and meats. The majority of the subjects (91.3%) report that they cooked meals at homes, and took about 1 hour of time. The subjects also point out that cooking was a bothering task, and only 46.4% would prepare meals at home, while others would rather eat out or eat convenience foods. The main reasons for not wanting meal services in the elderly welfare facility are because they didn't want to live such places (48.4%) and the meals are tasteless (31.3%). As for delivery meal services, 60.1% are aware of it, and 39.9% would consider using it in the future. Factors to be considered when using the delivery meal service are sanitation (43.7%), nutrition (28.7%), taste (18.4%), price (6.3%), and brand name (2.9%). This study is expected to be used as useful information when developing food-related strategies for baby boomers in the future.

Bioequivalence of Cefaclor (250 mg) Capsule (세파클러 250 mg 캅셀의 생물학적 동등성)

  • Yun, MH;Kim, HS;Choi, YP;Kwon, KI
    • Korean Journal of Clinical Pharmacy
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    • v.12 no.2
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    • pp.71-75
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    • 2002
  • This study was carried out to compare the bioavailability of $Ceclex^{(R)}$ (test drug, cefaclor 250 mg/capsule) with that of $Ceclor^{(R)}$ (reference drug) and to estimate the pharmacokinetic parameters of cefaclor in healthy Korean adult. The bioavailability was examined on 20 healthy volunteers who received a single dose (250 mg) of each drug in the fasting state in a randomized balanced 2-way crossover design. After dosing, blood samples were collected for a period of 6hours. Plasma concentrations of cefaclor were determined using HPLC with UV detection. The pharmacokinetic parameters $(AUC_{0-6hr},\;C_{max},\;T_{max},\;AUC_{int},\;K_e,\;t_{1/2},\;Vd)$ F, and CL/F) were calculated with non-compartmental pharmacokinetic analysis. The ANOVA test was utilized for the statistical analysis of the $T_{max},\;log-transformed\;AUC_{0-6hr}\;log-transformed\;C_{max},\;t_{l/2},\;V_d/F$, and CL/F. The ratios of geometric means of AUC0-6hr and $C_{max}$ between test drug and reference drug were $103.2\%\;(6.74\;{\mu}g{\cdot}hr/ml\;vs\;6.53{\pm}g{\cdot}hr/ml)\;and\;100.4\%\;(4.85\;{\mu}g\ml\;vs\;4.82\;{\mu}g/ml)$, respectively. The $T_{max}$ of test drug and reference drug were $0.9\pm0.38\;hr\;and\;0.83\pm0.34$ hrs, respectively. The $90\%$ confidence intervals of mean difference of logarithmic transformed $AUC_{0-6h},\;and\;C_{max}$ were log $0.98{\sim}log$ 1.08 and log $0.88{\sim}log1.15$, respectively. It shows that the bioavailability of test drug is equivalent with that of reference drug. The estimated half-life of this study was longer $(1.21\pm0.27\;hrs\;vs\;0.5-1\;hr)$, the Vd/F was larger $(68.89\pm25.72L$ vs 24.9L), and the CL/F was higher $(38.62\pm7.09\;L/hr$ vs 24.9 L/hr) than the previously reported values.

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Toxicokinetics of paraquat in Korean patients with acute poisoning

  • Kim, Hak-Jae;Kim, Hyung-Ki;Lee, Hwayoung;Bae, Jun-Seok;Kown, Jun-Tack;Gil, Hyo-Wook;Hong, Sae-Yong
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.1
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    • pp.35-39
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    • 2016
  • To conduct a kinetic study of paraquat (PQ), we investigated 9 patients with acute PQ intoxication. All of them ingested more than 20 ml of undiluted PQ herbicide to commit suicide and arrived at our hospital early, not later than 7 h after PQ ingestion. The urine dithionite test for PQ in all of the nine patients was strongly positive at emergency room. Blood samples were obtained every 30 min for the first 2~3 h and then every 1 or 2 h, as long as the clinical progression was stable among the patients for 30 h after PQ ingestion. The area under the plasma concentration-time curve ($AUC_{inf}$), which was extrapolated to infinity, was calculated using the trapezoidal rule. Toxicokinetic parameters, such as the terminal elimination half-life, apparent oral clearance, and apparent volume of distribution ($V_d/F$) were calculated. The maximum PQ concentration ($C_{max}$) and the time to reach maximum PQ concentration ($T_{max}$) were also obtained. Plasma PQ concentrations in nine patients were well described by a bi-exponential curve with a mean terminal elimination half-life of $13.1{\pm}6.8h$. $C_{max}$ and $AUC_{inf}$ were $20.8{\pm}25.7mg/l$ and $172.5{\pm}160.3h{\cdot}mg/l$, respectively. Apparent volume of distribution and apparent oral clearance were $50.9{\pm}61.3l/kg$ and $173.4{\pm}111.2l/h$, respectively. There were a significant correlation (r=0.84; p<0.05) between the PQ amount ingested and $C_{max}$. $AUC_{inf}$ also showed a significant correlation (r=0.83; p<0.05) with the PQ amount ingested. These correlations provide evidence that PQ has dose-linear toxicokinetic characteristics.

Structural and Biochemical Analysis of 3-Dehydroquinate Dehydratase from Corynebacterium glutamicum

  • Chan Hwi Lee;Sangwoo Kim;Hogyun Seo;Kyung-Jin Kim
    • Journal of Microbiology and Biotechnology
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    • v.33 no.12
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    • pp.1595-1605
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    • 2023
  • Dehydroquinate dehydratase (DHQD) catalyzes the conversion of 3-dehydroquinic acid (DHQ) into 3-dehydroshikimic acid in the mid stage of the shikimate pathway, which is essential for the biosynthesis of aromatic amino acids and folates. Here, we report two the crystal structures of type II DHQD (CgDHQD) derived from Corynebacterium glutamicum, which is a widely used industrial platform organism. We determined the structures for CgDHQDWT with the citrate at a resolution of 1.80Å and CgDHQDR19A with DHQ complexed forms at a resolution of 2.00 Å, respectively. The enzyme forms a homododecamer consisting of four trimers with three interfacial active sites. We identified the DHQ-binding site of CgDHQD and observed an unusual binding mode of citrate inhibitor in the site with a half-opened lid loop. A structural comparison of CgDHQD with a homolog derived from Streptomyces coelicolor revealed differences in the terminal regions, lid loop, and active site. Particularly, CgDHQD, including some Corynebacterium species, possesses a distinctive residue P105, which is not conserved in other DHQDs at the position near the 5-hydroxyl group of DHQ. Replacements of P105 with isoleucine and valine, conserved in other DHQDs, caused an approximately 70% decrease in the activity, but replacement of S103 with threonine (CgDHQDS103T) caused a 10% increase in the activity. Our biochemical studies revealed the importance of key residues and enzyme kinetics for wild type and CgDHQDS103T, explaining the effect of the variation. This structural and biochemical study provides valuable information for understanding the reaction efficiency that varies due to structural differences caused by the unique sequences of CgDHQD.

Toxicokinetics of rifapentine in beagle dogs (Beagle dog에 있어서 rifapentine의 독성동태연구)

  • Shin, Ho-chul;Lee, Hye-suk;Cha, Shin-woo;Han, Sang-seop;Roh, Jung-ku;Kim, Jin-suk;Lee, Won-chang
    • Korean Journal of Veterinary Research
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    • v.35 no.4
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    • pp.815-822
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    • 1995
  • The toxicokinetics of rifapentine was studied after an oral administration to beagle dogs. High-performance liquid chromatography(HPLC) using column-switching technique was performed to determine the serum concentrations of rifapentine. The pharmacokinetic profiles of rifapentine were analysed using one-compartment open model. Following a single oral administration of 10mg/kg, pharmacokinetic parameters were determined as follows: maximum serum concentration($C_{max}$), $28.90{\mu}g/ml$; maximum concentration time($T_{max}$), 3.7hr; elimination half-life($t_{1/2}$, 4.7hr; area under the curve(AUC), $339.0{\mu}g{\cdot}hr/ml$; volume of disiribution/bioavailability (Vd/F), 0.21 l/kg; lag time, 24min; absorption rate constant($k_a$), $0.445hr^{-1}$; elimination rate constant($k_{el}$), $0.148hr^{-1}$. After 6 month multiple oral doses of 10mg/kg/day, parameters were as follows: $C_{max}$, $34.40{\mu}g/ml$; $T_{max}$, 2.6hr; $t_{1/2}$, 6.7hr; AUC, $391.3{\mu}g{\cdot}hr/ml$; Vd/F, 0.291/kg; $k_a$, $0.976hr^{-1}$; $k_{el}$, $0.104hr^{-1}$. The consistant kinetic parameters after a single and multiple oral administration show that there was no accumulation of rifapentine after 6 month oral administration. We also simulated the concentration of rifapentine after oral multiple administration of 10 and 50mg/kg/ day, based on the parameters obtained form the single administration. The measured serum concentrations of rifapentine were well fitted to the simulated results. The simulated results show that rifapentine readily reaches to steady-state after about 3 doses and the steady-state serum concentrations($C_{ss}$) are fluctuated in between $2.2{\sim}25.2{\mu}g/ml$, and $10.6{\sim}125.2{\mu}g/ml$ at the doses of 10 and 50mg/kg/day, respectively.

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Factors Influencing the Intention of Admission into a Charged Nursing Home for the Elderly (유료노인전문요양원 입주의사 결정요인에 관한 연구)

  • Yoo, Young-Soon;Cho, Eun-Hi;Yu, Byung-Chul;Jeong, Ki-Won;Urm, Sang-Hwa;Kim, Sung-Jun;Chun, Jin-Ho
    • Journal of Preventive Medicine and Public Health
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    • v.34 no.1
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    • pp.1-8
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    • 2001
  • Objectives : To gather information about the factors which influence the interest and intention of admission into charging nursing hones for the elderly(CNH), as these homes represent an important method for resolving the problems related to the rapid population aging occurring in Korea. Methods : A face-to-face interview survey was carried out with 320(men 159, women 165) patients over 60 years old who were admitted at 2 university hospitals and 5 general hospitals in the Busan area between December 1998 and March 1999. Data were analyzed through t-test, ANOVA, correlation and multiple regression analysis. Results : The mean age and years of education of the study population was 67.0 and 7.7 years, and the types of chronic degenerative disease included musculoskeletal disorders(20.1%), cerebrovascular disease(17.1%), and diabetes(14.3%). The major forms of household living arrangement prior to admission were elderly alone(22.6%), and elderly couple(33.5%), while about half of them(55.5%) didn't want to live with their children id the future. Almost half were paying medication fees by themselves(46.6%). The level of actual intention of admission$(3.07{\pm}1.39)$ into a CNH was lower than that of interest$(3.22{\pm}1.33)$(p<0.01). Multiple analysis revealed that the intention of admission increased with decreasing number of future supportive persons$(\beta=-0.107)$, lower level of activity in daily life$(\beta=-0.447)$, and longer years of education$(\beta=-0.447)$ with 32.7% of $R^2$. As for the factors which determined the admission into a CNH, the fee and facilities were considered to be most important, and professional nursing and physician's care were the most desired services. In nomenclature, they preferred 'elderly hospital' or 'elderly health center' to CNH. Conclusions : Interest in CNH is increasing recently, but existing studies about patient experiences in CHN are still limited. This study may form a basis for future examinations of the needs and uses for CNH. Active financial support and public information are considered by the authors to be important factors for the induction of welfare services for the elderly, though CNH.

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Pharmacokinetics of oxytetracycline in olive flounder (Paralichthys olivaceus) by intramuscular injection (Oxytetracycline을 근육 주사한 넙치 (Paralichthys olivaceus)의 약물동태학적 특성)

  • Jung, Sung-Hee;Choi, Dong-Lim;Kim, Jin-Woo;Jo, Mi-Ra;Seo, Jung-Soo;Ji, Bo-Young
    • Journal of fish pathology
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    • v.22 no.1
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    • pp.91-95
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    • 2009
  • The pharmacokinetic properties of oxytetracycline (OTC) were studied after intramuscular injection to cultured olive flounder, Paralichthys olivaceus. Plasma concentrations of OTC were determined after dosage of 12.5, 25 and 50 ㎎/㎏ body weight in olive flounder (average 600 g, $23{\pm}1{^{\circ}C}$). Plasma samples were taken at 3, 5, 10, 15, 24, 32, 48, 72, 120, 168, 240 and 360 h post-dose. With 25 and 50 ㎎/㎏, the peak plasma concentrations of OTC, which attained at 5 h post-dose, were 0.99 and 1.49 $\mu{g}/m\ell$, respectively. However, the peak plasma concentration of 12.5 ㎎/㎏ was 0.35 $\mu{g}/m\ell$ after 10 h post-dose. Plasma concentrations of OTC were not measurable at 360 h post-dose in all doses. The kinetic profile of absorption, distribution and elimination of OTC in plasma were analyzed fitting to a 1-compartment model by Win-Nonlin program. The following parameters were calculated for 12.5, 25 and 50 ㎎/㎏ body weight, respectively: AUC (the area under the concentration-time curve)?D���D24.98, 44.67 and 50.45 $\mu{g}$ $h/m\ell$ $T_{1/2}$ (half-life) ?D���D0.42, 0.59 and 0.41 h; $T_{max}$ (time for maximum concentration)?D���D8.46, 6.34 and 2.66 h; $C_{max}$ (maximum concentration)?D���D0.30, 0.63 and 1.13 $\mu{g}/m\ell$.

A Study on Bedding in Korea - The Cases in 1990~2000 - (전국 이부자리 사용에 관한 실태조사 - 1990~2000년의 비교 -)

  • Yun, Chong-Hee;Kim, Jung-Sook;Sung, Su-Kwang
    • Fashion & Textile Research Journal
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    • v.4 no.3
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    • pp.248-253
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    • 2002
  • The purpose of this study was to improve consumer sleeping life in quality and to suggest producers meet new consumer needs and demands, by examining the nationwide use of bedding, analyzing consumer sleeping life by category and age group, comparing the results with the findings of the nationwide studies by Sung Su-kwang (1992) and Lee Song ja (1995), and identifying the major trend of consumer sleeping life. Results and Discussion The findings of this study were as below: 1. The General Characteristics of the Subjects : Most of the housewives investigated were in their 30s and 40s, with 41.7% and 50.8% respectively. 2. Bedroom : When it comes to bedroom style, 47.8% put beds in their rooms with the Korean under-floor heating system, and 45.4% didn't place beds in their rooms with the same heating system. 3. The Purchase of Bedding : 49.0%, approximately half the homemakers, bought their current bed-clothes at bedding shops, and just 3.2% made them on their own at home. 4. The Use of Bedclothes : In summer, yam (flax, ramie fabric) and a single-layer bed sheet (41.9%) were in use most, followed by a single-layer quilt (34.5%). 5. Bedding Management The most common frequency of bedding disinfection by sunning was once a month (29.4%), followed by once per two weeks (23.9%) and once a week (19.0%) in the order named.

Extracellular Tannase from Aspergillus ochraceus: Influence of the Culture Conditions on Biofilm Formation, Enzyme Production, and Application

  • Aracri, Fernanda Mansano;Cavalcanti, Rayza Morganna Farias;Guimaraes, Luis Henrique Souza
    • Journal of Microbiology and Biotechnology
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    • v.29 no.11
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    • pp.1749-1759
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    • 2019
  • Aspergillus ochraceus biofilm, developed on an inert support, can produce tannase in Khanna medium containing 1.5% (w/v) tannic acid as the carbon source, at an initial pH of 5.0, for 72 h at 28℃. Addition of 0.1% (w/v) yeast extract increased enzyme production. The enzyme in the crude filtrate exhibited the highest activity at 30℃ and pH 6.0. At 50℃, the half-life (T50) was 60 min and it was 260 min at pH 6.0. In general, addition of detergents and surfactants did not affect tannase activity significantly. Tannase has potential applications in various biotechnological processes such as the production of propyl gallate and in the treatment of tannin-rich effluents. The content of tannins and total phenolic compounds in effluents from leather treatment was reduced by 56-83% and 47-64%, respectively, after 2 h of enzyme treatment. The content of tannins and total phenolic compounds in the sorghum flour treated for 120 h with tannase were reduced by 61% and 17%, respectively. Interestingly, the same A. ochraceus biofilm was able to produce tannase for three sequential fermentative process. In conclusion, fungal biofilm is an interesting alternative to produce high levels of tannase with biotechnological potential to be applied in different industrial sectors.