• YAKHAK HOEJI
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• v.49 no.2
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• pp.185-191
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• 2005

The absorption of a P-gp substrate, rhodamine 123, from a liposomal dosage form was investigated across Caco-2 cell monolayers, rat intestines and rat intestinal Peyer's patches in Ussing chamber, Rhodamine 123 was incorporated into liposomes according to the standard evaporation method, which led to a production of liposomes with a mean diameter of 71.3 nm. The permeability (Papp of rhodamine 123 from a water solution across the monolayer was $2.45{\times}10^{-6}$ cm/s for $A{\leftrightarrow}B$ (apical to basal) and $14.0{\times}10^{-6}$ cm/s for $B{\leftrightarrow}A$ (basal to apical) directions, consistent with the fact that rhodamine 123 is one of the P-gp substrates. The transport of rhodamine 123 from the liposomal dosage form was much lower for both directions compared to the solution of rhodamine 123. The transport of rhodamine 123 across the rat intestine was also significantly decreased for both directions, I.e., influx and efflux, by the liposomal incorporation of the compound. The transport of rhodamine 123 across the Peyer's patch was substantially reduced by liposomal incorporation. No difference was found in the transport between the Peyer's patch and non-Peyer's patch. These observations suggest that the contribution of transport via Peyer's patches in the uptake of liposomes may be minimal, especially for rapidly absorbed compounds like rhodamine 123. Therefore, the increased absorption of P-gp substrates does not appear to be feasible by incorporating the compounds in liposomes, due to negligible involvement of Peyer's patches in the uptake of particulate dosage forms like liposomes. Liposomes may rather represent a sustained release dosage form of incorporated compounds.

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.9
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• pp.1285-1292
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• 2014

An in vitro experiment was conducted to evaluate the effects of Aspergillus oryzae culture (AOC) and 2-hydroxy-4-(methylthio)-butanoic acid (HMB) on rumen fermentation and microbial populations between different roughage sources. Two roughage sources (Chinese wild rye [CWR] vs corn silage [CS]) were assigned in a $2{\times}3$ factorial arrangement with HMB (0 or 15 mg) and AOC (0, 3, or 6 mg). Gas production (GP), microbial protein (MCP) and total volatile fatty acid (VFA) were increased in response to addition of HMB and AOC (p<0.01) for the two roughages. The HMB and AOC showed inconsistent effects on ammonia-N with different substrates. For CWR, neither HMB nor AOC had significant effect on molar proportion of individual VFA. For CS, acetate was increased (p = 0.02) and butyrate was decreased (p<0.01) by adding HMB and AOC. Increase of propionate was only occurred with AOC (p<0.01). Populations of protozoa ($p{\leq}0.03$) and fungi ($p{\leq}0.02$) of CWR were differently influenced by HMB and AOC. Percentages of F. succinogenes, R. albus, and R. flavefaciens (p<0.01) increased when AOC was added to CWR. For CS, HMB decreased the protozoa population (p = 0.01) and increased the populations of F. succinogenes and R. albus ($p{\leq}0.03$). Populations of fungi, F. succinogenes (p = 0.02) and R. flavefacien (p = 0.03) were increased by adding AOC. The HMB${\times}$AOC interactions were noted in MCP, fungi and R. flavefacien for CWR and GP, ammonia-N, MCP, total VFA, propionate, acetate/propionate (A/P) and R. albus for CS. It is inferred that addition of HMB and AOC could influence rumen fermentation of forages by increasing the number of rumen microbes.

• Korean Journal of Veterinary Research
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• v.28 no.2
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• pp.227-239
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• 1988

In order to investigate the morphological characteristics of dendritic cells in the mammary gland, the appearance on the clear cells(CLs) or ATPase-positive dendritic cells(APDCs) have been observed by the light microscope. The results obtained were summarized as follows: CLs were observed in the mammary tissues of the experimental animals, such as mice, rats, guinea pigs, rabbits, cats, dogs, pigs, cows and Korean native goats, and these CLs were confirmed as the ATPase-positive cells of typical dendritic appearance(APDCs), The APDCs were distributed in between the secretory epithelial cells, between the secretory epithelial cells and the myoepithelial cells, the basal area of the secretory epithelial cells, the interalveolar and interlobular connective tissues, and in between the epithelial cells of secretory duct. The APDCs were observed more frequently during the middle period of lactation than the other periods, and were irregularly or uniformly distributed according to the location. During the middle period of lactation, there were notable quantitative differences in the APDSs depending on the mammary glands of mice, rats, guinea pigs, rabbits and cats, The most prominent differences were recognized among the mice, guinea pigs and cats. The number of AP DCs per unit area was statistically fewer in the guinea pigs($209.07{\pm}51.75cells/mm^2$) than in the mice($221.00{\pm}50.94cells/mm^2$) and cats($223.56{\pm}49.68cells/mm^2$) (respectively, p<0.05, p<0.05). Among the A/J, DBA/2, C57BL/6 and NIH(GP) mice, the mean densities of APDCs was statistically significantly fewer in the DBA/2($196.65{\pm}43.47cells/mm^2$) than in the C57BL/6($248.40{\pm}41.40cells/mm^2$) and NIH(GP) ($235.98{\pm}55.89cells/mm^2$) (respectively, p<0.0000, p<0.0000), however no significant difference between the C57BL/6 and the NIH(GP) was recognized (p>0.1). Among the F344, SD and W rats, the statistical analysis were confirmed that there were significantly fewer APDCs in the F344($198.72{\pm}47.61cells/mm^2$) than in the SD($227.70{\pm}41.40cells/mm^2$) and W($223.56{\pm}49.68cells/mm^2$) (respectively, p<0.0000, p<0.0001), however no significant difference between the SD and the W was recognized(p>0.1). The mean difference between the inbred and the noninbred counts in the mice was statistically significant (p<0.0001), and the similar result was presented in the rats(p<0.0000).

• Bulletin of the Korean Chemical Society
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• v.15 no.5
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• pp.379-386
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• 1994

Reactions of 1',2-bis(diphenylphosphino)-l-(N,N-dimethylaminomethyl)ferrocene (FcNPP) with $M(CO)_6$ (M=Cr, Mo, W) in the presence of TMNO (Trimethylamine oxide) in a stoichiometric ratio of 1 : 1.5 : 3.5 produced a series of Gp 6 metal carbonyl derivatives with a variety of coordination modes: M(CO)$_4({\eta}^2$-FcNPP-P,P) (M=Cr, Mo, W), $M(CO)_5({\eta}^1-FcNPP-P) (M=Mo, W)\;,\; M_2(CO)_9({\eta}^1\;,\;{\eta}^2-FcNPP-P,P,N) (M=Cr, Mo)\;,\;M_2(CO)_{10}({\eta}^1\;,\;{\eta}^1-FcNPP-P,P) (M=Cr, Mo, W)\;, and\;W(CO)_4({\eta}^2-FcNPP(O)-P,N)$. All these complexes were characterized by microanalytical and spectroscopic techniques. In one case, the structure of W(CO)$_4({\eta}^2$-FcNPP(O)-P,N) was determined by X-ray crystallography. Crystals are monocinic, space group P$2_{1/C}$, with a=10.147(2), b=19.902(3), c=19.821(4) ${\AA},\;{\beta}=96.88(2)^{\circ},\;V=3974(l){\AA}^3$, Z=4, and $D_{calc}=1.64 g cm^{-3}$. The geometry around the central tungsten metal is a distorted octahedron, with the nitrogen and phosphorus atoms being cis to each other. Some of these complexes exhibited catalytic activities in the allylic oxidation and epoxidation of cholesterly acetate. Other oxidation products were also formed with the different chemical yields and product distribution depending upon the ligand and the central metal.

• BMB Reports
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• v.34 no.1
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• pp.66-72
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• 2001

To investigate the mechanism of adriamycin (ADM) resistance in the ADM resistant subline PC-14/ADM, we examined the expressions of p-glycoprotein (P-gp), topoisomerase I (Topo I) and II (Topo II), glutathione-S-transferases (GSTs), tissue transglutaminase (t-TG), epidermal growth factor receptor (EGFR), and E-cadherin and the activity of superoxide dismutase (SOD) in PC-14 and PC-14/ADM cells. There was no change in the cellular levels of P-gp, Topo I, Topo II, and the two isoforms of GSTs. However, SOD activity in PC-14/ADM cells was 2.38 fold higher than that in PC-14 cells. A marked induction of the t-TG expression was also observed in PC-14/ADM cells. In addition to those changes, expressions of EGFR and E-cadherin were down regulated in PC-14/ADM cells. Therefore, molecular modifications such as an increase in SOD activity, induction of the t-TG expression, and down regulation of EGFR and E-cadherin expressions may play important roles in PC-14/ADM cells during the development of ADM resistance.

• Journal of Pharmaceutical Investigation
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• v.41 no.5
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• pp.295-300
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• 2011

Paclitaxel is a well known anticancer agent and has been a pharmaceutical challenge because of its extremely poor water-solubility and susceptibility to the p-glycoprotein (p-gp)-mediated efflux in multi-drug resistant (MDR) cancer cells. Tributyrin (TB), a triglyceride with relatively short fatty acid chains, was chosen as solubilizing vehicle for paclitaxel based on the solubility study (26.6 mg/mL). Tributyrin (10%) o/w emulsion containing paclitaxel (5%), egg phosphatidylcholine (5%) and pegylated phospholipid (0.5%) was prepared by high pressure homogenization to obtain submicron-sized emulsion. The mean particle size of the resultant TB emulsion was 395.5 nm. Paclitaxel in TB emulsion showed higher anticancer activity against human breast cancer cell line, MCF-7, than free form delivered in DMSO solution. On the other hand, its anticancer activity was significantly reduced in MCF-7/ADR, a MDR variant cancer cell line of MCF-7, and recovered by the presence of verapamil, suggesting of the susceptibility to the p-gp mediated efflux even though paclitaxel was encapsulated into emulsion. The TB emulsion showed great potential as a promising vehicle for water-insoluble anticancer agent, paclitaxel.

• Proceedings of the Korean Institute of Navigation and Port Research Conference
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• 2013.10a
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• pp.366-369
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• 2013

위치, 항법 및 시각정보가 육상, 해상, 항공 등 지구상 거의 모든 공간에서 다양한 목적으로 활용되고 있는 위성항법시스템(GNSS, Global Navigation Satelite System)은 그 중요성이 더욱 높아지고 있으며 미국이 제공해 주는 GPS의 고의잡음(SA)제거 및 성능 향상을 통하여 GNSS를 이용한 응용분야의 발전은 더욱 확대되고 있는 실정이다. 이러한 위성항법시스템의 P.N.T(Position, Navigation and Timing) 서비스 기능을 사회의 전박적인 주요 인프라 시설에 기초적인 원리의 정확성을 더하고 지속성과 무결함성을 제공할 수 있기 때문에 신뢰성을 가지고 여러분야에 활용되고 있으나 지상에서 약20,200km 고도에 위치한 인공위성에서 미약한 신호를 송신함으로써 GNSS 수신기가 의도적이든 비의도적이든 동일한 주파수 밴드의 신호에 영향을 받을 경우 정상적인 역할을 할 수 없다. 우리나라의 경우 P.N.T 서비스 기반 자체가 GPS에 전적으로 의존하고 있으며 유사시 이를 대체할 항법 시스템을 별도로 갖추고 있지 않고 있어 미국의 고의적인 GPS 서비스의 중단이나 주변국가의 방해전파 송신으로 인한 GPS 신호 중단사태가 발생할 경우에는 우리나라 국가 주요 인프라에 치명적인 피해를 입힐 수 있기 때문에 대체항법을 시스템을 구축하여 독자적인 P.N.T 서비스를 제공할 수 있는 시스템 구축이 국가적인 차원에서 절실하게 필요하다.

• Macromolecular Research
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• v.12 no.5
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• pp.507-511
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• 2004

We have developed an injectable thermosensitive hydrogel for local drug delivery to treat cancers clinically. We selected chitosan as a polymer matrix because of its biocompatibility and biodegradability. Glycerol 2-phosphate disodium salt hydrate (${\beta}$-GP) was used to neutralize the chitosan solution to physiological pH. The chitosan solution displayed a sol-gel phase transition in a pH-and temperature-dependent manner and formed an endothermic hydrogel after subcutaneous injection into mouse in the presence of ${\beta}$-GP. Additionally, we evaluated the biodegradation of chitosan hydrogel in mice by measuring the volume of injected chitosan hydrogel after subcutaneous injection. The injected chitosan hydrogel in mice was sected and stained with hematoxylin-eosin reagent for histological observation to confirm biodegradation of the hydrogel by the infiltrated cells. Chitosan hydrogel systems that possess biocompatibility and biodegradability could be promising thermosensitive injectable materials useful as depot systems for local anti-cancer drug delivery.

• Biomolecules & Therapeutics
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• v.15 no.2
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• pp.102-107
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• 2007

Cimetidine, a substrate for P-glycoprotein (P-gp), is a well known drug interacting with a variety of drugs and results in alteration of pharmacokinetic parameters by concomitant administration. The aim of present study was to investigate whether cimetidine affects the transport of various quinolone antibiotics in human colorectal cancer cell line (Caco-2) system which has been typically used to investigate drug transport via P-gp. The apparent permeability coefficients (P$_{app}$) value of 9 quinolone antibiotics in the co-treatment with cimetidine was examined. Apical to basolateral (AP-to-BL) transport of fleroxacin in the co-treatment with cimetidine was increased to 1.5-fold (p<0.01) compared with that of fleroxacin alone, whereas basolateral to apical (BL-to-AP) transport of fleroxacin was decreased to 0.83-fold significantly (p<0.05). Ofloxacin was decreased to 0.8-fold (p<0.01) and 0.72-fold (p<0.01) significantly in AP-to-BL and BL-to-AP direction, respectively by cimetidine cotreatment. The P$_{app}$ values of gatifloxacin, moxifloxacin, ciprofloxacin and rufloxacin also were changed by cimetidine. These results have a potential that cimetidine influences on the pharmacokinetics of quinolone antibiotics. It suggests that careful drug monitoring and dosage adjustment may be necessary during the co-administration of quinolone antibiotics with cimetidine.

• Korean Journal of Pharmacognosy
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• v.49 no.2
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• pp.85-102
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• 2018

A drug interaction is a situation in which a substance affects the activity of a drug, synergistically or antagonistically, when both are administered together. It has been shown that orally taken ginsenosides are deglycosylated by intestinal bacteria to give ginsenosides metabolites, which has been considered to be genuine pharmacological constituents and to exhibit drug interactions. Animal experimental results demonstrated that ginsenoside metabolites play an important role in the inhibitory or inductive action of both CYPs (cytochrome p450) and P-gp (p-glycoprotein), thereby can be applied as metabolic modulator to drug interactions. Very few are known on the possibility of drug interaction if taken the recommended dose of ginseng, but it has been found to act as CYPs inductor and P-gp inhibitor in any clinical trial, suggesting the risk that side effects will occur. It has been recently reported that interactions might also exist between ginseng and drugs such as warfarin, phenelzine, imatinib and raltegravir. Moreover, medicinal plants are increasingly being taken in a manner more often associated with prescription medicines. Therefore, considering the extensive applications of ginseng for safety, the aim of this review is to present a comprehensive overview of ginseng and drug interactions based upon pharmacodynamic and pharmacokinetic evidences.