• Journal of Life Science
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• v.20 no.2
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• pp.169-175
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• 2010

Intestinally absorptive and distributive aspects of the subtoxic level of selenite in rats were investigated using a double perfusion system. The double-perfusion technique is an in situ, in vitro preparation in which the intestinal lumen and its vasculature are perfused simultaneously. In the previous study, the subtoxic level of sodium selenite was determined to be 1.2 mM through inhibition of 3-0-methyl glucose (3MG) absorption. Thus, the selenite used to identify the intestinally absorptive mechanism of selenite was perfused at a luminal concentration of 1, 10, 50, 100 and $200\;{\mu}M$. Appearance of radiolabeled-Selenium (Se) was identified in three compartments: luminal perfusate, small intestine and vascular perfusate. Dose-response curves for Se in the three compartments indicate that selenite is absorbed by non-mediated passive diffusion. Regarding the distributive aspect, $21.02{\pm}3.92%$ of the total amount of selenite in the lumen was transported into the blood vessels across the small intestine. However, $4.75{\pm}1.75%$ of the total amount of selenite in the lumen is retained by the small intestine. Therefore, a total of $25.67{\pm}4.46%$ of the test dose was taken up from the luminal perfusate.

• YAKHAK HOEJI
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• v.38 no.2
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• pp.114-122
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• 1994

A study on the absorption mechanism of cefixime(CF), an oral ${\alpha}-amino$ group deficient cephalosporin antibiotic, has been undertaken through the rat jejunum and nasal cavity using an in situ simultaneous perfusion technique developed in our laboratory. CF was well absorbed in the jejunum and nasal cavity of rats at pH 5.0, but not at pH 7.0. CF absorption was studied over four orders of magnitude in concentration to determine saturability. Disappearance of CF in the perfusate followed first-order kinetics at all tested concentrations. The apparent first-order absorption rate constant was found to be dependent on the concentration over the range of $0.1\;mM{\sim}3\;mM$ in the jejunum and nasal cavity of rats. Inhibitors were added to determine the competitive inhibition of CF absorption. The presence of L-tyrosine, L-phenylalanine, alanine-alanine, glycine-glycine and cefadroxil produced the significant inhibition of CF absorption in the nasal cavity and jejunum. However, there was no evidence of the inhibition in the presence of cefazolin. In addition, The CF absorption in the nasal cavity and jejunum was inhibited significantly by ouabain and 2,4-dinitrophenol(DNP). This study suggested that CF is absorbed across the rat nasal cavity and jejunum by carrier-mediated transport mechanism and energy consuming system.

• Food Science and Biotechnology
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• v.16 no.6
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• pp.879-883
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• 2007

This study examined whether dietary supplementation with sea tangle alters the intestinal morphology of streptozotocin-induced diabetic rats and affects the glucose absorption rate. Forty male Sprague-Dawley rats were divided into 2 groups and fed either a control (AIN76-based) diet or a sea tangle-supplemented diet. After 3 weeks, 10 rats in each group received an intramuscular injection of streptozotocin (45 mg/kg BW), and feeding was continued for 3 additional weeks. Dietary supplementation with sea tangle resulted in a lower fasting plasma glucose level compared with the control diet in diabetic rats. Scanning electron micrographs revealed serious damage to the jejunal villi of diabetic rats fed the control diet, whereas supplementation with sea tangle alleviated the damage. In a separate experiment, 20 male Sprague-Dawley rats were divided into 2 groups and fed either a control diet or a sea tangle-supplemented diet for 5 weeks, and fasted rats were subjected to in situ single-pass perfusion. The glucose absorption rate determined in the absence of digesta was decreased by 34% in the jejunum of rats fed a sea tangle diet compared with those fed a control diet. In conclusion, sea tangle supplementation lowered glucose absorption rate, altered intestinal morphology, and appeared to protect villi from damage caused by diabetes mellitus.

• Biomolecules & Therapeutics
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• v.25 no.4
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• pp.441-451
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• 2017

Imperatorin, a major bioactive furanocoumarin with multifunctions, can be used for treating neurodegenerative diseases. In this study, we investigated the characteristics of imperatorin transport in the brain. Experiments of the present study were designed to study imperatorin transport across the blood-brain barrier both in vivo and in vitro. In vivo study was performed in rats using single intravenous injection and in situ carotid artery perfusion technique. Conditionally immortalized rat brain capillary endothelial cells were as an in vitro model of blood-brain barrier to examine the transport mechanism of imperatorin. Brain distribution volume of imperatorin was about 6 fold greater than that of sucrose, suggesting that the transport of imperatorin was through the blood-brain barrier in physiological state. Both in vivo and in vitro imperatorin transport studies demonstrated that imperatorin could be transported in a concentration-dependent manner with high affinity. Imperatorin uptake was dependent on proton gradient in an opposite direction. It was significantly reduced by pretreatment with sodium azide. However, its uptake was not inhibited by replacing extracellular sodium with potassium or N-methylglucamine. The uptake of imperatorin was inhibited by various cationic compounds, but not inhibited by TEA, choline and organic anion substances. Transfection of plasma membrane monoamine transporter, organic cation transporter 2 and organic cation/carnitine transporter 2/1 siRNA failed to alter imperatorin transport in brain capillary endothelial cells. Especially, tramadol, clonidine and pyrilamine inhibited the uptake of [$^3H$]imperatorin competitively. Therefore, imperatorin is actively transported from blood to brain across the blood-brain barrier by passive and carrier-mediated transporter.

• Journal of Pharmaceutical Investigation
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• v.25 no.4
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• pp.353-363
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• 1995

The purpose of this study was to investigate the intestinal and nasal absorption enhancement of cefotaxime (CTX) by ion-pairing with counterions and to design an effective oral and intranasal drug delivery system for antibiotics. Counterions for absorption promotion were cationic surfactants [cetylpyridinium chloride (CP), cetrimide (CT) and benzalkonium chloride (BA)]. In the presence of counterions, the apparent partition coefficient of cefotaxime was increased depending on the molar concentration of the counterions. Anion interference was observed for ion-pairing of cefotaxime with counterions because of the counterbalance between an anion and counterions. The present study employed the in situ simultaneous nasal and intestinal perfusion technique in rats. The apparent permeabilities $(P_{app})$ of cefotaxime were $1.43{\pm}0.04{\times}10^{-5}\;cm/sec(mean{\pm}S.E)$ in the nasal cavity and 0 in the jejunum, respectively, which indicated that the intrinsic absorptivity of cefotaxime was greater in the nasal cavity than in the jejunum. When ionupairing formers were used, the decreasing order of apparent cefotaxime permeability $(P_{app},\;10^{-5}\;cm/sec)$, corrected for surface area of absorption, was as followings: $BA\;(7.50{\pm}0.36)\;>\;CT\;(4.92{\pm}0.24)\;>\;CP\;(3.01{\pm}0.17)$ in the jejunum and $BA\;(22.31{\pm}1.36)\;>\;CP\;(18.24{\pm}0.81)\;>\;CT \;(16.22{\pm}1.87)$ in the nasal cavity. The increase in permeability of cefotaxime was about 13-fold in the rat nasal cavity and was marked in the rat jejunum for ion-pairing with counterions as compared to those without ion-pairing. The damages of jejunal and nasal mucosal membrane by counterions were observed within approximately 2hrs after removal of ion-pair of cefotaxime with counterions from the nasal cavity and jejunum. These results suggest that CP can be used as an ion-pairing former in the jejunum and CP and CT can be used as ion-pairing formers in the nasal cavity for cefotaxime, as well as for poorly absorbed drugs with a negative charge due to ionization.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.59-64
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• 2012

Hypoxic pulmonary vasoconstriction (HPV) is physiologically important response for preventing mismatching between ventilation and perfusion in lungs. The HPV of isolated pulmonary arteries (HPV-PA) usually require a partial pretone by thromboxane agonist (U46619). Because the HPV of ventilated/perfused lungs (HPV-lung) can be triggered without pretone conditioning, we suspected that a putative tissue factor might be responsible for the pretone of HPV. Here we investigated whether HPV can be also observed in precision-cut lung slices (PCLS) from rats. The HPV in PCLS also required partial contraction by U46619. In addition, $K^+$ channel blockers (4AP and TEA) required U46619-pretone to induce significant contraction of PA in PCLS. In contrast, the airways in PCLS showed reversible contraction in response to the $K^+$ channel blockers without pretone conditioning. Also, the airways showed no hypoxic constriction but a relaxation under the partial pretone by U46619. The airways in PCLS showed reliable, concentration-dependent contraction by metacholine ($EC_{50}$, ~210 nM). In summary, the HPV in PCLS is more similar to isolated PA than V/P lungs. The metacholineinduced constriction of bronchioles suggested that the PLCS might be also useful for studying airway physiology in situ.

• Journal of Pharmaceutical Investigation
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• v.25 no.4
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• pp.291-298
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• 1995

The purpose of this study is to verify the interaction between food and ampicillin which is one of the aminopenicillins known to be absorbed by a specified dipeptide transporter in the small intestine. The absorption of ampicillin was measured in the presence of the high carbohydrate food, high fat food, and high protein food, and compared with that in the presence of the control normal food. In situ single-pass perfusion method was chosen in these experiments using two jejunal segments in the rat. Reduction in the absorption of ampicillin was not shown, when both high carbohydrate food and high fat food were co-perfused with ampicillin. When the high protein food was co-perfused with ampicillin, the difference of $C_{out}/C_{in}$ of ampicillin ratio was $0.084\;{\pm}\;0.082$, showing a trend of reduced absorption without a significance. Further, glyclysarcosine (Gly-Sar) which is a stable dipeptide in the small intestine was used in order to see the direct competitive inhibition with ampicillin on the dipeptide transporter. The difference of $C_{out}/C_{in}$ ratio was $0.078\;{\pm}\;0.020$ in the presence of 10 mM Cly-Sar, showing a significant inhibition of ampicillin absorption (p < 0.02). It suggests that dietary di- and tripeptides, the digestive products of protein food, might have influence on the absorption of ampicillin, and that ampicillin could be given at the lasting state for better absorption.

• 대한예방의학회:학술대회논문집
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• 1994.02b
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• pp.169-179
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• 1994

B-mode ultrasound is being used to assess carotid atherosclerosis in epidemiological studies and clinical trials. Recently the interpretation of measurements made from ultrasound images has been questioned. This study examines the anatomical correlates of B-mode ultrasound of carotid arteries in vitro and in situ in cadavers. Twenty-seven segments of human carotid artery were collected at autopsy. pressure perfusion fixed in buffered 2.5% gluteraldehyde and 4% paraformaldehyde and imaged using an ATL UM-8 (10 MHz single crystal mechanical probe). Each artery was then frozen, sectioned and stained with van Gieson or elastin van Gieson. The thickness of the intima. media and adventitia were measured 'to an accuracy of 0.01 mm from histological sections using a calibrated eye graticule on a light microscope. Shrinkage artifact induced by histological preparation was determined to be 7.8%. Digitised ultra sound images of the artery wall were analysed off-line. The distance from the leading edge of the first interface ($LE_{1}$) to the leading edge of the second interface ($LE_2$) was measured using a dedicated programme. $LE_{1}$-$LE_{2}$ measurements were correlated against histological measurements corrected for shrinkage. Mean values for the far wall were: ultra sound $LE_{1}$-$LE_{2}$ (0.97 mm, S.D. 0.26), total wall thickness (1.05 mm, S.D. 0.37), adventitia (0.35 mm, S.D. 0.16), media (0.61 mm, S.D. 0.18). intima (0.09 mm, S.D. 0.13). Ultrasound measurements corresponded best with total wall thickness, rather than elastin or the intima-media complex. Excision of part of the intima plus media or removal of the adventitia resulted in a corresponding decrease in the $LE_{1}$-$LE_{2}$ distance of the B-mode image. Furthermore. increased wall thickness due to intimal atherosclerotic thickening correlated well with $LE_{1}$-$LE_{2}$ distance of the B-mode images. B-mode images obtained from the carotid arteries in situ in four cadavers also corresponded best with total wall thickness measured from histological sections and not with the thickness of the intima plus media. In conclusion, the $LE_{1}$-$LE_{2}$ distance measured on B-mode images of the carotid artery best represents total wall thickness of intima plus media plus adventitia and not intima plus media alone.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.2
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• pp.186-193
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• 2007

The prevalence of diabetes has increased to 8% of population. Unlike type 2 diabetes in the western countries, Korean diabetic patients are nonobese and have low serum insulin levels. As the increased prevalence of diabetes and the peculiar characteristics may be related to dietary fat contents, we determined their effects on insulin resistance, insulin secretion and pancreatic $\beta-cell$ mass in 90% pancreatectomized (Px) diabetic rats in the present study. The rats were provided with low fat diet (LF, 10 energy% fat), moderate fat diet (MF, 25 energy% fat) and high fat diet (HF, 40 energy% fat) for 6 months. HF increased body weight and epidydimal fat pads parallel with increased food intake compared to LF and MF. Fasting serum glucose and insulin levels and homeostasis model assessment of insulin resistance were higher in HF, compared to LF and MF, indicating that HF increased insulin resistance. Rats fed LF and MF diets reduced insulin resistance, but only rats fed MF improved pancreatic $\beta-cell$ mass and insulin secretion capacity, measured by hyperglycemic clamp and in situ pancreatic perfusion. LF had low insulin secretion capacity and pancreatic $\beta-cell$ mass, indicating the increased possibility of diabetic prevalence and progression. MF increased $\beta-cell$ mass by stimulating $\beta-cell$ proliferation and neogenesis and reducing $\beta-cell$ apoptosis. In conclusion, MF is effective for the prevention of prevalence and progression of diabetes.

• Toxicological Research
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• v.23 no.3
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• pp.279-287
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• 2007

Copper (Cu) is an essential trace element indispensable for brain development and function; either excess or deficiency in Cu can cause brain malfunction. While it is known that Cu and Fe homeostasis are strictly regulated in the brain, the question as to how systemic Fe status may influence brain Cu distribution was poorly understood. This study was designed to test the hypothesis that dietary Fe condition affects Cu transport into the brain, leading to an altered brain distribution of Cu. Rats were divided into 3 groups; an Fe-deficient (Fe-D) group which received an Fe-D diet ($3{\sim}5 mg$ Fe/kg), a control group that was fed with normal diet (35mg Fe/kg), and an Fe-overload group whose diet contained an Fe-O diet (20g carbonyl Fe/kg). Following a 4-week treatment, the concentration of Cu/Fe in serum, CSF (cerebrospinal fluid) and brain were determined by AAS, and the uptake rates of Cu into choroids plexus (CP), CSF, brain capillary and parenchyma were determined by an in situ brain perfusion, followed by capillary depletion. In Fe-D and Fe-O, serum Fe level decreased by 91% (p<0.01) and increased by 131% (p<0.01), respectively, in comparison to controls. Fe concentrations in all brain regions tested (frontal cortex, striatum, hippocampus, mid brain, and cerebellum) were lower than those of controls in Fe-D rats (p<0.05), but not changed in Fe-O rats. In Fe-D animals, serum and CSF Cu were not affected, while brain Cu levels in all tested regions (frontal cortex, striatum, hippocampus, mid brain, and cerebellum) were significantly increased (p<0.05). Likewise, the unidirectional transport rate constants $(K_{in})$ of Cu in CP, CSF, brain capillary and parenchyma were significantly increased (p<0.05) in the Fe-D rats. In contrast, with Fe-O, serum, CSF and brain Cu concentrations were significantly decreased as compared to controls (p<0.05). Cu transport was no significant change of Cu transport of serum in Fe-O rats. The mRNA levels of five Cu-related transporters were not affected by Fe status except DMT1 in the CP, which was increased in Fe-D and decreased in Fe-O. Our data suggest that Cu transport into brain and ensuing brain Cu levels are regulated by systemic Fe status. Fe deficiency appears to augment Cu transport by brain barriers, leading to an accumulation of Cu in brain parenchyma.