• Biomolecules & Therapeutics
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• v.1 no.1
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• pp.31-36
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• 1993

To evaluate the feasibility of transmucosal delivery of methionine enkephalin analog, [$D-Ala^2$]-me-thionine enkephalinamide (YAGFM), the influence of pH, temperature, ionic strength and initial peptide concentration on the physicochemical stability of YAGFM in aqueous buffered solutions were investigated using a stability-indicating HPLC method. The degradation of YAGFM followed the pseudo-first-order kinetics. From the pH-rate profile, the maximum stability of YAGFM was shown to be at the pH of about 5.0. The halflife for the degradation of YAGFM was found to be 181.3 days at pH 5.0 and $37^{\circ}C.$ Arrhenius plots of the data obtained at 25~$45^{\circ}C$ were reasonably linear with a correlation coefficient greater than 0.99, and the activation energy was calculated to be 8.9 kcal/mole. A higher ionic strength and/or a higher peptide concentration in buffered solutions retarded the degradation of YAGFM.

• Biomolecules & Therapeutics
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• v.14 no.1
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• pp.45-49
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• 2006

The purpose of this study was to clarify the efflux transport system of choline from brain to blood across the blood-brain barrier (BBB) in rats using the brain efflux index (BEI) method. $[^3H]$Choline was micro-injected into parietal cortex area 2 (Par2) of the rat brain, and was eliminated from the brain with elimination halflife of 45 min. The BBB efflux clearance of $[^3H]$choline was about 124 mL/min/g brain, which was determined from combination of an elimination rate constant $(1.54X10^{-2}min^{-1})$ and the distribution volume in the brain (8.05 mL/g brain). The efflux of $[^3H]$choline was inhibited by unlabeled choline in a dose-dependent manner and was significantly inhibited by cationic substrates, such as hemicholinium-3 and tetraethylammonium (TEA). These results suggest that the BBB may act as an efflux pump for choline to reduce the excessive choline concentration in the brain interstitial fluid.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.15 no.4
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• pp.271-282
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• 1982

The browning development, mainly through the Maillard reaction, occurring in the dried fish meat products during storage causes reduction of the nutritional value due to the loss of the essential amino acid such as available lysine as well as off -flavor resulting in the deterioration of the food quality thus shortening the shelflife. In the work, the changes in the amount of available lysine, extractable nitrogenous compounds (nonprotein-N, amino-N, trimethylamine oxide, trimethylamine, and free lysine) and development of browning were measured to assess the relationship between the shelflife and the quality loss in dried filefish under the steady state conditions (35,45, and $55^{\circ}C;a_{w}'s$ of 0.44 0.52, 0.65 and 0.75 at each temperature) and fluctuating temperature condition of $35/55^{\circ}C$ will. alternating 7 day periods at each water activity. The results indicated that the amount of available lysine and extractable nitrogenous compounds except TMA decreased rapidly with increasing temperatures and water activities while the rate of available lysine and extractable nitrogenous compounds must be involved in the initial stage of brown pigment formation. The available lysine loss of the dried filefish products stored under the fluctuating temperature conditions was greater than that stored under its fixed mean temperature, $45^{\circ}C$. The activation energies for lysine loss obtained from the Arrhenius plot ranged 6.9 to 4.4 Kcal/mol and $Q_{10}$ values at $40^{\circ}C$ were 1.4 to 1.2. The values for browning were 15.7 to 14.4 Kcal/mol and 2.2 to 2.0 respectively. Shelf-life, defined as the time to reach 0.15 O. D./g solid or the limit of off-color deterioration by browning reaction, was extented longer than the halflife of Iysine loss, actually corresponding $75\%$ loss of available lysine. This suggested that the halflife of lysine loss might not be adequate to assess the shelf-life of the food system with high potential of protein, nonproteinous nitrogen compounds, and lipids.

• Bulletin of the Korean Chemical Society
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• v.29 no.4
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• pp.785-789
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• 2008

The present study is the first report of utilizing $TiO_2$ photocatalyst to analytically calibrate the hydroperoxyl radical ($HO_2\;^{\cdot}$). An in-situ calibration method of $HO_2\;^{\cdot}$ is proposed for air monitoring by using an 2-methyl-6-(pmethoxyphenyl)- 3,7-dihydroimidazo-[1,2-a]pyrazin-3-one (MCLA)-chemiluminescence (CL) technique. In this method, $HO_2\;^{\cdot}$($pK_a$ = 4.80) is produced by the ultraviolet (UV) photolysis of immobilized $TiO_2$ using a constant flow rate of air equilibrated water, in which $HO_2\;^{\cdot}$ is controlled by using various lengths of knotted tubing reactor (KTR). The principle of the proposed calibration is based on the experimentally determined halflife ($t_{1/2}$) of $HO_2\;^{\cdot}$ and its empirically observed pH-dependent rate constant, $k_{obs}$, at a given pH. The concentration of $HO_2\;^{\cdot}$/$O_2\;^{\cdot}$− is increased as pH increases. This pH dependence is due to the different disproportionative reactivities between $HO_2\;^{\cdot}$/$O_2\;^{\cdot}$− and $HO_2\;^{\cdot}$/$O_2\;^{\cdot}$−. Experimental results indicate the practical feasibility of the approach, producing very promising method.

• IMMUNE NETWORK
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• v.22 no.1
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• pp.5.1-5.22
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• 2022

The approval of immunotherapies such as checkpoint inhibitors (CPIs), adoptive cell therapies and cancer vaccines has revolutionized the way cancer treatment is approached. While immunotherapies have improved clinical outcome in a variety of tumor types, some cancers have proven harder to combat using single agents, underscoring the need for multi-targeted immunotherapy approaches. Efficacy of CPIs and cancer vaccines requires patients to have a competent immune system with adequate cell numbers while the efficacy of adoptive cellular therapy is limited by the expansion and persistence of cells after infusion. A promising strategy to overcome these challenges is combination treatment with common gamma-chain cytokines. Gamma-chain cytokines play a critical role in the survival, proliferation, differentiation and function of multiple immune cell types, including CD8 T-cells and NK cells, which are at the center of the anti-tumor response. While the short halflife of recombinant cytokines initially limited their application in the clinic, advancements in protein engineering have led to the development of several next-generation drug candidates with dramatically increased half-life and bioactivity. When combining these cytokines with other immunotherapies, strong evidence of synergy has been observed in preclinical and clinical cancer settings. This promising data has led to the initiation of 70 ongoing clinical trials including IL-2, IL-7, IL-15 and IL-21. This review summarizes the recent advancements of common gamma-chain cytokines and their potential as a cancer immunotherapy.

• Tuberculosis and Respiratory Diseases
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• v.38 no.4
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• pp.372-378
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• 1991

Some kinds of newer fluoroquinolone antibiotics are known to interact with theophylline, which is widely used as a potent bronchodilator in asthma or chronic obstructive lung disease. To evaluate the effect of enoxacin and ciprofloxacin on the metabolism of theophylline, aminophylline was administered intravenously in bolus (6 mg/kg) over 30 minutes to 6 healthy volunteers (age: $23.3{\pm}4.2$ year, body weight: $63.2{\pm}9.0\;kg$, height: $169.0{\pm}6.5\;cm$, female 3, male 3) before and after per oral 5-day medication of enoxacin and ciprofloxacin, respectively and we measured the level of theophylline in serum. The results were as follows: 1) Enoxacin and ciprofloxacin did not influence the volume of distribution significantly. 2) Enoxacin decreased the clearance of theophylline significantly (from $42.9{\pm}14.6\;ml/min$ to $30.1{\pm}6.3\;ml/min$: p<0.05), but ciprofloxacin did not cause significant decrease (to $32.8{\pm}6.2\;ml/min$: p>0.005). 3) Enoxacin increased the elimination half life of theophylline significantly (from $496{\pm}83\;min$ to $693{\pm}32\;min$: p<0.001), but ciprofloxacin did not cause significant increase (to $687{\pm}222\;min$: p>0.05). These results suggested that enoxacin influenced clearance and elimination half life significantly and thorough monitoring of the level of theophylline in patients with coadminstration of enoxacin and theophylline was necessary. In case of ciprofloxacin, the influence on the metabolism of theophylline was not statistically significant, but one exceptionally large decrease of the clearance and increase of the elimination halflife of theophylline suggested the necessity of monitoring of theophylline level during coadministration of ciprofloxacin and theophylline.

• Journal of Pharmaceutical Investigation
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• v.35 no.6
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• pp.453-460
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• 2005

4-Aminopyridine (AP) is a potassium channel blocker used in the treatment of neurological disorders such as multiple sclerosis and Alzheimer disease. AP‘s window of therapeutic effect appears to correlate with its plasma halflife (3.5 hours). It demonstrates pH-dependent solubility because of a weakly basic drug. In addition, the resulting release from conventional matrix tablets decreases with increasing pH-milieu of the gastrointestinal tract. The aim of this study is to design sustained release matrix tablet containing AP, overcoming this problem. $Eudragit^{\circledR}$ L 100 (EuL) and sodium alginate were used in an effort to achieve pH independent drug release. The effect of sodium alginate and EuL on drug release from matrix tablet was investigated. The drug release behavior from the different tablets was analyzed by $t_{20%},\;t_{40%},\;t_{60%}$, The exponential diffusion coefficient n, kinetic constant K were calculated according to the Korsmeyer-Peppas equation. The drug release from matrix tablets prepared with sodium alginate was decreased with increasing the content of sodium alginate in pH 7.4 while there is no significant difference in pH 1.2. The exponent n values were determined to be approximately 0.5 and 0.8 respectively, in both pH 1.2 and 7.4. These values indicate diffusion-based anomalous mechanism and erosion-based anomalous mechanism, respectively. The drug release from sodium alginate matrix tablets prepared with solid dispersion of EuL containing drug showed a slow drug release in an acidic medium and a more fast drug release in phosphate medium, compared with sodium alginate matrix tablets prepared with physical mixture. These results may be attributed to the gel forming ability of sodium alginate and pH dependent solubility of EuL. Therefore, sustained-release AP matrix tablets using sodium alginate and EuL were successfully prepared.

• Progress in Medical Physics
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• v.12 no.2
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• pp.141-146
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• 2001

It is well known that assurance of the radiation therapy needs for an accuracy of $\pm$ 5 % in the delivery of an absorbed dose to target volume. Therefore, the dose evaluation of brachytherapy source and/or linear accelerate beam must be a stability with accuracy. In an advanced country, they recommended to use the radioactive check source for reference air ionization chamber for a stable response of radiation field chamber. In this experiments, the radioactive source Sr-90 and PR-05 air ionization chamber were used for standard source and reference ion chamber. The response of reference ion chamber showed as an 1.000$\pm$ 0.010 uncertainty for 10 years long and the evaliuation f dose discrepancy of clinical field ion chamber showed as 0.997 $\pm$0.011 in a $^{60}$ Co brachytherapy soruce. In our experiments, we can assuarance the long halflife standard source is reliable to preserve the calibration factor of reference chamber in stability.

• Journal of Information Management
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• v.36 no.3
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• pp.51-70
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• 2005

It is meaningful to develop the scholarly digital archives in a respect that it could preserve the research papers using digital media. The scholarly digital archives provide scientists with the information source with which scientists could actively accomplish research. This study measured based on the citation analysis to what extent PMC, which is life science scholarly digital archives, has an effect on the scholarly communication in the same subject field. The findings are as follows. First, the three citation indicators, impact factor, immediacy index, and half-life, have no remarkable difference in between pre and post-digital archives era. Second, there were more cases that the major citation indicators increased rather than ones decreased with the appearance of the scholarly digital archives, as a result of ranking the scholarly journals after classifying according to subjects.

• Archives of Pharmacal Research
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• v.19 no.4
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• pp.280-285
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• 1996

The sustained release dosage form which delivers melatonin (MT) in a circadian fashion over 8 h is of clinical value for those who have disordered circadian rhythms because of its short halflife. The purpose of this study was to evaluate the gelling properties and release characteristics of alginate beads varying multivalent cationic species $(Al^{+++}, \; Ba^{++}, \; Ca^{++}, \; Mg^{++}, \; Fe^{+++}, \; Zn^{++})$. The surface morphologies of Ca- and Ba-alginate beads were also studied using scanning electron microscope (SEM). MT, an indole amide pineal hormone was used as a model drug. The $Ca^{++}, \; Ba^{++}, \; Zn^{++}, \; Al^{++}\; and\; Fe^{+++}\; ions\; except\; Mg^{++}$ induced gelling of sodium alginate. The strength of multivalent cationic alginate beads was as follows: $Al^{+++}\llFe^{+++} the induced hydrogel beads were very fragile and less spherical. Fe-alginate beads were also fragile but stronger compared to Al-alginate beads. Ba-alginate beads had a similar gelling strength but was less spherical when compared to Ca-alginate beads. Zn-alginate beads were weaker than Ca- and Ba-alginate beads. Very crude and rough crystals of Ba- and Ca-alginate beads at higher magnifications were observed. However, the type and shape of rough crystals of Ba- and Ca-alginate beads were quite different. No significant differences in release profiles from MT-loaded multivalent cationic alginate beads were observed in the gastric fluid. Most drugs were continuously released upto 80% for 5 h, mainly governed by the passive diffusion without swelling and disintegrating the alginate beads. In the intestinal fluid, there was a significant difference iq the release profiles of MT-loaded multivalent cationic alginate beads. The release rate of Ca-alginate beads was faster when compared to other multivalent cationic alginate beads and was completed for 3 h. Ba-alginate beads had a very long lag time (7 h) and then rapidly released thereafter. MT was continuously released from Feand Zn-alginate beads with initial burstout release. It is assumed that the different release rofiles of multivalent cationic alginate beads resulted from forces of swelling and disintegration of alginate beads in addition to passive diffusion, depending on types of multivalent ions, gelling strength and drug solubility. It was estimated that 0.2M $CaCl_2$ concentration was optimal in terms of trapping efficiency of MT and gelling strength of Ca-alginate beads. In the gastric fluid, Ca-alginate beads gelled at 0.2 M $CaCl_2$ concentration had higher bead strength, resulting in the most retarded release when compared to other concentrations. In the intestinal fluid, the decreased release of Ca-alginate beads prepared at 0.2 M $CaCl_2$ concentration was also observed. However, release profiles of Ca-alginate beads were quite similar regardless of $CaCl_2$ concentration. Either too low or high $CaCl_2$ concentrations may not be useful for gelling and curing of alginate beads. Optimal $CaCl_2$ concentrations must be decided in terms of trapping efficiency and release and profiles of drug followed by curing time and gelling strength of alginate beads.