• Title/Summary/Keyword: Intestinal Transport

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Carrier-Mediated Tissue Distribution and Blood-Brain Barrier Transport of New Quinolones

  • Tsuji, Akira
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1997.04a
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    • pp.57-63
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    • 1997
  • Animal and clinical investigations have shown that fluoroquinolones, new quinolone antibacterial agents (NQs), are well absorbed across the intestinal tract, with a bioavailability of 60-90% after oral administration. Although some types of carrier-mediated intestinal transport mechanisms have been reported for enoxacin (ENX), ofloxacin (OFLX) and sparfloxacin (SPFX), recent results using a human intestinal epithelial cell line, Caco-2, indicated a passive or nonsaturable transport of SPFX, one of the most hydrophobic NQs. The mechanism underlying the intestinal absorption of NQs is still largely unknown. The distribution of NQs into peripheral tissues including erythrocytes is very rapid and their tissue-to-plasma concentration ratios (Kp) are considerably larger than those of inulin (an extracellular fluid space marker), in spite of almost complete ionization of NQs at the physiological pH. Our findings suggest that OFLX and lomefloxacin (LFLX) are taken up by rat erythrocytes via a transport system common to that of a water-soluble vitamin, nicotinic acid.

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IN VIVO INVESTIGATION ON THE INTESTINAL ABSORPTION OF VITAMIN A-ALCOHOL (RETINOL) IN RATS

  • Whang, Eun-Mi;Burger, Hans-Jurgen
    • Proceedings of the Korean Nutrition Society Conference
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    • 1995.05c
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    • pp.21-21
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    • 1995
  • Absorption of fat-soluble vi tamin, retinol occurs mainly in the proximal part of small intestine. But its intestinal transport mechanism isn't yet clear. The aim of the present study was to investigate on the mechanism of absorption of retinol by determining a concentration-dependent kinetic of retinol absorption in rats. The study was carried out by applying in vivo technique in which vitamin solution was infused to intestinal lumen and at the same time thoracic duct and choledochus duct were canulated to collect samples. The investigations showed that retinol is absorbed in the small intestine by a saturable, carrier-mediated transport system, i.e. wi thout signi ficant differences between the proximal and distal halves of the small intestine. The transport of retinol taken up by the enterocytes occured via different mechanisms: while the main vitamin A transport via the thoracic duct was saturated by limiting transport factors such as retinol-CRBP-II-complex formation and retinol esterification with increasing substrate concentrations, the transport of retinol metabolite product via the portal vein was proportional to the substrate concentration.ration.

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Water Transport during the Single-pass Perfusion Experiments : Effects of Some Perfusates and Their Osmolality (일회통과 관류실험시 물의 수송 : 관류액의 종류와 삼투압의 영향)

  • 이정화;이현주;용철순;오두만
    • YAKHAK HOEJI
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    • v.39 no.4
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    • pp.411-416
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    • 1995
  • The single-pass perfusion experiments were performed in anesthetized rats to investigate the effects of perfusates and their osmolality on the water transport and to determine the correlation between the extent of water transport and the volume change of perfusate. Phenol red was used as a nonabsorbable marker. In normal rats, when perfused at a flow rate of 0.5 ml/min, 2-(N-rnorpholino) ethanesulfonic acid (MES) and S$\phi$rensen's phosphate buffers showed minimal net water transport as 0.125 and 0.173 %/cm of intestinal length, respectively. Hypotonic perfusate of 200 mOsm/kg of water and hypertonic perfusate of 400 mOsm/kg of water generated significant water transport compared with isotonic perfusate of 300 mOsm/kg of water. There was a linear correlation between the extent of water transport and the volume change of perfusate, suggesting that the volume change can be used as a measure of water transport.

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Effect of Gaewool-Whadam-Jian on Transport Ability of Small Intestine and Secretion of Gastric Juice in the Rat (개울화담전(開鬱化痰煎)이 흰쥐 소장(小腸) 수송능(輸送能)과 위액분비에 미치는 영향)

  • Kim Hee-Chul;Lee Young-Soo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.5
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    • pp.1330-1336
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    • 2005
  • This study was carried out to investigate the motor activity and glucose transport and metabolism of Gaewool-Whadam-Jian(GWJ) in rat gastro-intestinal tract. The motor activity of the rat gastro-intestinal tract has been investigated by means of measuring barium sulfate passage degrees. Atropine treatment significantly delayed barium sulfate transit, and GWJ pretreatment increased intestinal motor activity, but not significant. GWJ administration showed no toxicity to kidney and liver. Transport and metabolism of glucose were studied in everted sac of rat small intestine with incubation under several conditions. The transport and metabolism of glucose were greater at jejunum than ileum. So, everted jejunum of rat were used to study the effect of GWJ. When GWJ were treated, the concentration of glucose were higher than untreated group. This result was thought to be influenced by the glucose in GWJ. When 2, 4 dinitrophenol and phlorizin were treated, the transport and metabolism of glucose were decreased, but GWJ treated together, the concentration of glucose in serosal solution increased. Gastric juice secretion and total acidity significantly decreased by administration of GWJ through duodenum region. The mechanism of effect of GWJ was still unidentified, Dut through continuous investigation, the effect of GWJ should be investigated.

Distribution of Lawsonia intracellularis in livestock transport car of slaughterhouse, Korea (도축장 출하차량에서 Lawsonia intracellularis 분포율 조사)

  • Lee, Su-Ji;Lee, Hee-Seon;Seo, Ji-Soo;Kim, Tae-Gyeom;Jeong, Jae-Kyo
    • Korean Journal of Veterinary Service
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    • v.41 no.4
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    • pp.245-250
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    • 2018
  • Lawsonia intracellularis is the pathogenic agent of porcine proliferative enteritis (PPE). The bacterial pathogen infects the intestinal crypt cells which causes hyperplasia of the infected cells and leads to the process of intestinal pathogenesis. PPE includes some clinical maninfestations, including acute hemorrhagic diarrhea with sudden death in growing pigs and porcine intestinal adenomatosis, to a chronic diarrhea with reduced productivity of the infected pigs. The purpose of the present studies were carried out to determine L. intracellularis in livestock transport car of slaughterhouse. Distribution of L. intracellularis in livestock transport car were conducted using real-time polymerase chain reaction (real-time PCR) testing method, total 300 samples. Of 300 samples, 119 (39.7%) were detected as positive to L. intracellularis in livestock transport car. In seasonal analysis, 42 (28.0%) out of 150 samples in spring and summer season. 77 (51.3%) out of 150 sample in autumn and winter season. In regional analysis, 53 (88.3%) out of 60 cars and the detection ratio showed that regional variation in livestock transport car.

Effect of Amoxicillin on the Intestinal Membrane Permeability and Absorption Clearance of Benazepril (베나제프릴의 장관막 투과도와 흡수 클리어런스에 미치는 아목시실린의 영향)

  • Joo, Eun-Hee;Kim, Young-Man;Ko, Hyung-Seok;Lee, Yong-Bok;Na, Han-Kwang
    • Journal of Pharmaceutical Investigation
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    • v.28 no.1
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    • pp.25-33
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    • 1998
  • Intestinal absorption of ${\beta}-lactam$ antibiotics and angiotensin converting enzyme(ACE) inhibitors has been shown to use the carrier-mediated transport system. In vitro experiments have established that the efficacy of uptake by enterocytes depends on an inwardly directed proton gradient. It was suggested that benazepril was mediated by tripeptide transport system and that amoxicillin was transported by dipeptide transport carrier. The aim of this study is to assess the influence of amoxicillin on the intestinal absorption of benazepril using in vitro diffusion chamber and in situ single pass perfusion technique in the rat in order to elucidate whether the above transport systems are competitive or not. We obtained the gastrointestinal pemeability coefficient of amoxicillin, benazepril and both of them using in vitro diffusion chamber. And also the gastrointestinal absorption clearance of amoxicillin, benazepril and both of them using in situ single-pass perfusion method at steady state were calculated. Amoxicillin and benazepril were analyzed by HPLC. The results by the use of diffusion chamber in vitro indicated that the apparent intestinal permeability coefficient of benazepril was significantly(p<0.01) decreased by amoxicillin(45.2%) and vice versa significantly(p<0.01) decreased(89.1%). The results by the in situ gastrointestinal single-pass perfusion method indicated that the intestinal absorption clearance of benazepril was significantly(p<0.05) decreased by amoxicillin (40.2%) and vice versa significantly(p<0.05) decreased(54.8%). These results might suggest that they share the same peptide carrier pathway for oral absorption.

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Characterization of valacyclovir transport mechanism across the intestinal epithelium

  • Han, H.;Covitz, M.;Surendran, N.;Stewart, B.;Amidon, G.L.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1997.04a
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    • pp.119-119
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    • 1997
  • Valacyclovir is a L-valyl ester prodrug of acyclovir which is a highly effective and selective antiviral agent in the treatment of herpes virus diseases. Valacyclovir is rapidly and almost completely converted to acyclovir and increases the oral bioavailability of acyclovir three to five fold. However, the intestinal absorption mechanism of valacyclovir is not clear. If the improved absorption mechanism of valacyclovir is fully understood, it will provide a rationale of designing the amino acid ester prodrugs of polar drugs containing hydroxyl group. The main objective of our present study is to characterize the membrane transport mechanism of valacyclovir. Methods : Intestinal absorption of valacyclovir was investigated by using in-situ rat perfusion study and its wall permeability was estimated by modified boundary layer model. The membrane transport mechanism was also investigated through the uptake study in Caco-2 cells and in CHO-hPepTl cells. Results : In the rat perfusion study, the wall permeability of valacyclovir was ten times higher than acyclovir and showed concentration dependency, Valacyclovir also demonstrated a D,L stereo-selectivity with L-isomer having an approximately five-fold higher permeability than D-isomer. Mixed dipeptides and cephalexin, which are transported by dipeptide carriers, strongly competed with valacyclovir for the intestinal absorption, while L-valine did not show any competition with valacyclovir. This indicated that the intestinal absorption of valacyclovir could be dipeptide carrier-mediated. In addition, the competitive uptake study in Caco-2 cells presented that dipeptides reduced the valacyclovir uptake but valine did not. Also, in IC$\sub$50/ study, valacyclovir showed strong inhibition on the $^3$H-gly-sar uptake in CHO-hPepTl cells over-expressing a human intestinal peptide transporter. Taken together, the result from our present study indicated that valacyclovir utilized the peptide transporter for the intestinal absorption.

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Chinese Medicine Granule Affects the Absorption and Transport of Glucose in Porcine Small Intestinal Brush Border Membrane Vesicles under Heat Stress

  • Song, Xiaozhen;Xu, Jianqin;Wang, Tian;Liu, Fenghua
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.2
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    • pp.246-253
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    • 2009
  • This study was conducted to investigate the effects of Chinese medicine granule (CMG, including Cortex Phellodendron, Atractylodes Rhizome, Agastache Rugosa and Gypsum Fibrosum) on absorption and transport of glucose in porcine small intestinal brush border membrane vesicles (BBMVs) under heat stress. Forty-eight 2-month-old Chinese experimental barrows were screened according to weight and litter origin, and then allotted to three groups and treated as follows: Normal temperature control group (NTCG; $23^{\circ}C$), high temperature control group (HTCG; $26^{\circ}C$ for 19 h, $40^{\circ}C$ for 5 h); Chinese medicine granule anti-stress group (CMGG; $26^{\circ}C$ for 19 h, $40^{\circ}C$ for 5 h) (n = 16 per group). The results showed that high temperature treatment decreased (p<0.05) the growth performance and intestinal glucose absorption but there was no change (p>0.05) in the expression of SGLT1 and GLUT2 genes in the small intestine of pigs compared with the NTCG. Dietary supplementation with CMG improved the growth performance, and increased the activity of disaccharidases in duodenum and jejunum of heat stressed pigs (p<0.05). CMG treatment increased (p<0.05) the protein levels of SGLT1 and GLUT2 in the small intestine, and up-regulated (p<0.05) the expression of SGLT1 and GLUT2 genes in the duodenum and jejunum but without changing (p>0.05) them in the ileum compared with the HTCG. These results indicated that CMG treatment significantly improved porcine growth performance, and increased intestinal glucose absorption and transport by BBMVs under heat stress, in addition to up-regulating the expression of SGLT1 and GLUT2 genes in porcine duodenum and jejunum.

Plasma Membrane Transporters for Lead and Cadmium

  • Bressler Joseph P.;Olivi Luisa;Cheong Jae Hoon;Kim Yongbae;Bannon Desmond
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2004.11a
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    • pp.50-61
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    • 2004
  • Lead and cadmium are potent environmental toxicants that affect populations living in Europe, Americas, and Asia. Identifying transporters for lead and cadmium could potentially 1 help us better understand possible risk factors. The iron transporter divalent metal transporter 1(DMT1) mediates intestinal transport of cadmium, and lead in yeast and fibroblasts overexpressing DMT1. In human intestinal cells knocking down expression of DMT1 attenuated uptake of cadmium and iron but not lead. A possible explanation is the expression of a second transporter for lead in intestine. In astrocytes, however, DMT1 appears to transport lead in an extracellular buffer at pH value. At neutral pH, transport was not mediated by DMT1 but rather by a transporter that is stimulated by bicarbonate and inhibited by 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulfonic acid. The identity of this lead transporter is under study.

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Transport of Organic Cations across Caco-2 Cell Monolayers

  • Kim, Kyong;Chung, Suk-Jae;Shim, Chang-Koo
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.415.1-415.1
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    • 2002
  • Apical to basal transport of organic cations (OCs) such as tributylmethylammonium (TBuMA), triethyimethylammonium (TEMA). 1-methyl-4-phenylpyridinium (MPP), and berberine across Caco-2 cell monolayers was measured to elucidate the intestinal absorption of OCs. Basal to apical transport of MPP and berberine was larger than apical to basal transport and showed temperature dependency and concentration dependency. indicating that MPP and berberine are secreted into the inteslinal lumen. (omitted)

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