| 1. |
- Izumi, Takuma, et al.
(författare)
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ALMA OBSERVATIONS OF THE SUBMILLIMETER DENSE MOLECULAR GAS TRACERS IN THE LUMINOUS TYPE-1 ACTIVE NUCLEUS OF NGC 7469
- 2015
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 811:1
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Tidskriftsartikel (refereegranskat)abstract
- We present Atacama Large Millimeter/submillimeter Array (ALMA) Cycle 1 observations of the central kiloparsec region of the luminous type. 1 Seyfert galaxy NGC 7469 with unprecedented high resolution (0.'' 5x0.'' 4 = 165 x 132 pc) at submillimeter wavelengths. Utilizing the wide. bandwidth of ALMA, we simultaneously obtained HCN(4-3), HCO+(4-3), CS(7-6), and partially CO(3-2) line maps, as well as the 860 mu m continuum. The region consists of the central similar to 1 '' component and the surrounding starburst ring with a radius of similar to 1.'' 5-2.'' 5. Several structures connect these components. Except for CO(3-2), these dense gas tracers are significantly concentrated toward the central similar to 1 '', suggesting their suitability to probe the nuclear regions of galaxies. Their spatial distribution resembles well those of centimeter and mid-infrared continuum emissions, but it is anticorrelated with the optical one, indicating the existence of dust-obscured star formation. The integrated intensity ratios of HCN(4-3)/HCO+(4-3) and HCN(4-3)/CS(7-6) are higher at the active galactic nucleus (AGN) position than at the starburst ring, which is consistent with our previous findings (submillimeter-HCN enhancement). However, the HCN(4-3)/HCO+(4-3) ratio at the AGN position of NGC 7469 (1.11 +/- 0.06) is almost half of the corresponding value of the low-luminosity type. 1 Seyfert galaxy NGC 1097 (2.0 +/- 0.2), despite the more than two orders of magnitude higher X-ray luminosity of NGC 7469. But the ratio is comparable to that of the close vicinity of the AGN of NGC 1068 (similar to 1.5). Based on these results, we speculate that some heating mechanisms other than X-ray (e.g., mechanical heating due to an AGN jet) can contribute significantly for shaping the chemical composition in NGC 1097.
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| 2. |
- Lazorova, Lucia, et al.
(författare)
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Structural Features Determining the Intestinal Epithelial Permeability and Efflux of Novel HIV-1 Protease Inhibitors
- 2011
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 100:9, s. 3763-3772
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Tidskriftsartikel (refereegranskat)abstract
- The primary aim of this study was to identify structural features that alter the intestinal epithelial permeability and efflux in a series of novel HIV-1 protease inhibitors (PIs). Eleven PIs were selected containing a tertiary alcohol in a transition-state mimicking scaffold, in which two substituents (R1 and R2) were varied systematically. Indinavir was selected as a reference compound. The apical-to-basolateral permeability was investigated in 2/4/A1 and Caco-2 monolayers. In addition, the basolateral-to-apical permeability was investigated in the Caco-2 monolayers and the efflux ratios were calculated. The absence of active drug transport processes in 2/4/A1 cells allowed identification and modeling of structural elements affecting the passive permeability. For instance, small aromatic R1 substituents and a small (bromo-) R2 substituent were associated with a high passive permeability. Efflux studies in Caco-2 cells indicated that amide-substituted neutral hydrophobic amino acids, such as valine and leucine, in the R1 position, reduced the apical-to-basolateral transport and enhanced the efflux. We conclude that our investigation revealed structural features that alter the intestinal epithelial permeability and efflux in the series of PIs and hope that these results can contribute to the synthesis of PIs with improved permeability and limited efflux properties.
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| 3. |
- Miyake, Masateru, et al.
(författare)
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Effect of proinflammatory cytokine IL-6 on efflux transport of rebamipide in Caco-2 cells
- 2017
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Ingår i: Xenobiotica. - : Taylor & Francis. - 0049-8254 .- 1366-5928. ; 47:9, s. 821-824
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Tidskriftsartikel (refereegranskat)abstract
- 1. Effect of IL-6, a pro-inflammatory cytokine, on efflux transport of rebamipide, an antiulcer drug, was investigated in Caco-2 cells. 2. Rebamipide had a greater basal-to-apical than apical-to-basal transport rate. Efflux transport of rebamipide was inhibited by cyclosporine A, a P-gp inhibitor, and probenecid, which is a general MRP inhibitor, but not by Ko143, a BCRP inhibitor. 3. By the addition of IL-6, mannitol transport was slightly increased in a concentration-dependent manner in both directions of absorption and efflux. The addition of IL-6 did not change efflux transport of rebamipide even though efflux transport of digoxin, a typical substrate of P-gp, was significantly decreased by the addition of IL-6, indicating decrease of the function of P-gp. 4. Therefore, it was suggested that increase of MRP(s)-mediated transport compensates for the decrease of P-gp mediated transport of rebamipide. These findings suggested that rebamipide absorption is unlikely to be changed in IBD patients.
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| 4. |
- Miyake, Masateru, et al.
(författare)
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Inhibitory Potency of Marketed Drugs for Ulcerative Colitis and Crohn's Disease on PEPT1
- 2017
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Ingår i: Biological and Pharmaceutical Bulletin. - : PHARMACEUTICAL SOC JAPAN. - 0918-6158 .- 1347-5215. ; 40:9, s. 1572-1575
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the inhibitory effect of marketed drugs for treatment of inflammatory bowel disease (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD) on the uptake transporters of peptide transporter 1 (PEPT1), which are up-regulated under the inflamed condition. The uptake transport of glycylsarcosine, a typical substrate for PEPT1, was reduced to 60% only by 5-aminosalicylate at the clinically relevant concentration among tested marketed drugs in PEPT1 transfected HEK293 cell lines. These findings suggest that the inhibition of PEPT1, which were up-regulated in inflamed or non-inflamed site on UC and CD patients, contribute to the clinical effect of commercially available drugs for IBD patients through the inhibition of uptake of antigenic proinflammatory oligopeptides such as formyl-methionine (Met)-leucine (Leu)-phenylalanine (Phe) via PEPT1.
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| 5. |
- Miyake, Masateru, et al.
(författare)
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The Pro-inflammatory Cytokine Interleukin-6 Regulates Nanoparticle Transport Across Model Follicle-Associated Epithelium Cells
- 2016
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 105:7, s. 2099-2104
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate whether the pro-inflammatory cytokines improved the function of the cell monolayer model of the human follicle-associated epithelium (FAE) of co-culture of Caco-2 cells on permeable filters with Raji B-cells underneath from the viewpoint of particle transport. Exposure to tumor necrosis factor-a resulted in an almost maintained epithelial integrity/paracellular permeability combined with an increased nanoparticle transport in a dose-dependent manner while the effects of interleukin (IL)-1 beta were limited. Exposure to IL-6 significantly enhanced the nanoparticle transport with the limited disruption of the cell monolayer integrity. The addition of IL-6 or tumor necrosis factor-a to Caco-2 monolayers without Raji B-cells did not enhance nanoparticle transport. In our IL-6 treated FAE model, the nanoparticle transport almost disappeared at 4 degrees C or after the addition of 5-(N-ethyl-N-isopropyl) amiloride, an inhibitor of macropinocytosis. Furthermore, IgA binding, presumably by a secretory IgA receptor, a marker of M-cells was observed on the apical side of our model FAE. These results indicate that the combined effect of IL-6 with unknown factors from Raji-B cells made the FAE model more functional with regard to nanoparticle transport. The IL-6 enhanced FAE model will be a useful platform for nanoparticle drug delivery research across the intestinal epithelium.
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| 6. |
- Nakai, Daisuke, et al.
(författare)
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Comparison of the Intestinal Drug Permeation and Accumulation Between Normal Human Intestinal Tissues and Human Intestinal Tissues With Ulcerative Colitis
- 2020
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier. - 0022-3549 .- 1520-6017. ; 109:4, s. 1623-1626
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to examine drug absorption profile utilizing human intestinal tissues from ulcerative colitis (UC) patients and to compare with normal tissues from intestinal cancer patients. Human intestinal tissues from UC and cancer patients mounted in a mini-Ussing chamber were used to evaluate the permeation of drugs, including FD-4, a very low permeable marker, rebamipide, a low permeable marker, and metoprolol, a high permeable marker. The transport index, an index of sum of permeated and tissue-accumulated molecules, of the model drugs was in accordance with their absorption rank order, and was almost kept constant irrespective of autopsy grade based on tissue fibrosis. On the other hand, UC tissues of grade 2 showed the decreased X-corr, an index of permeated amount of molecules and increased T-corr, an index of tissue-accumulated molecules for every tested compound. Our finding of the transport characteristics in intestinal tissues of severe UC patients in mini-Ussing chamber system demonstrated that autopsy grade of UC patients did not drastically change membrane permeability of the tested compounds. Furthermore, it was suggested that morphological changes of intestinal tissues caused by fibrosis led to limited permeation and subsequently increased accumulation with little change of total absorption. (C) 2019 American Pharmacists Association (R) . Published by Elsevier Inc. All rights reserved.
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| 7. |
- Nakai, Daisuke, et al.
(författare)
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The change of the electrophysiological parameters using human intestinal tissues from ulcerative colitis and Crohn's disease
- 2022
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Ingår i: Journal of Pharmacological Sciences. - : Elsevier. - 1347-8613 .- 1347-8648. ; 150:2, s. 90-93
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate how disease state of the UC and CD patients affect tissue function determined from electrophysiology viewpoint the electrophysiological parameters on normal, ulcerative colitis (UC) and Crohn's disease (CD) patients. Potential differences (PD), short circuit current (Isc) and resistance (R) as electrophysiological parameters were determined using human large intestinal tissues. The measure of autoptical abnormality was quantified on an arbitrary scale of 0-2. A severe effect of ulcer and thickened mucosa by fibrosis was scored as Grade 2. The larger number of autopsy grade on both UC and CD tissues, the lower values of PD and R than those of normal tissues were observed, although Isc values were not statistically changed irrespective of autopsy grade. This electrophysiological observation of reduced PD indicated functional impairment of active ion transport via ion pumps. Additionally, the R values of CD tissues on each autopsy grade tended to be lower than those of UC tissues. These results suggest that the effect of inflammatory bowel disease on barrier function is different between UC and CD tissues. Therefore, the fibrosis on CD patients might affect the electro-physiological parameters than that of UC patients. (C) 2022 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.
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| 8. |
- Proletov, Ian, et al.
(författare)
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Primary and secondary glomerulonephritides 1.
- 2014
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 29 Suppl 3:May, s. 186-200
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Tidskriftsartikel (refereegranskat)
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