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- Casselbrant, Anna, 1970, et al.
(författare)
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Angiotensin II exerts dual actions on sodium-glucose transporter 1-mediated transport in the human jejunal mucosa
- 2015
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 50:9, s. 1068-1075
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. Intestinal glucose absorption is mainly mediated via the sodium-glucose transporter 1 (SGLT1) at the apex of the enterocytes, whereas the glucose transporter 2 (GLUT2) provides a basolateral exit. It has been shown in rats that Angiotensin II (AngII), the principal mediator of renin-angiotensin system (RAS), inhibits jejunal SGLT1-mediated glucose absorption. The aim of the present study was to investigate if a similar mechanism exists also in the human jejunal mucosa. Material and methods. Enteroscopy with mucosal biopsy sampling was performed in 28 healthy volunteers. Functional assessments were performed in Ussing chambers using a pharmacological approach. Western blotting and immunohistochemistry were used to assess the presence of the AngII type 1 (AT1R) and type 2 receptor (AT2R), as well as the glucose transporters SGLT1 and GLUT2. Results. Exposure of the mucosa to 10 mM glucose elicited a »50% increase in the epithelium-generated current (Iep). This glucose-induced electrogenic response was sensitive to the competitive SGLT1 inhibitor phlorizin, but not to AngII when given alone. AngII combined with the AT2R blocker PD123319 markedly inhibited the response. AngII in combination with the AT1R antagonist losartan tended to increase the electrogenic response, whereas direct activation of AT2R using the agonist C21 significantly enhanced the mucosal response to glucose. The AT1R and AT2R as well as SGLT1 and GLUT2 were detected inside the human enterocytes. Conclusions. The pharmacological analysis indicated that activation of AT1R inhibits, whereas activation of AT2R enhances SGLT1-mediated glucose transport in the human jejunal mucosa.
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| 2. |
- Casselbrant, Anna, 1970, et al.
(författare)
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Luminal Polyethylene Glycol Alleviates Intestinal Preservation Injury Irrespective of Molecular Size
- 2018
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Ingår i: Journal of Pharmacology and Experimental Therapeutics. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0022-3565 .- 1521-0103. ; 366:1, s. 29-36
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal preservation injury (IPI) and the resulting mucosa injury raise several serious challenges early after intestinal transplantation. The current clinical approach using only vascular perfusion allows the shortest preservation period among the abdominal organs. The experimental addition of luminal polyethylene glycol (PEG) solutions has been repeatedly suggested to alleviate preservation injury, improve graft quality, and prolong the preservation time. We investigated whether the molecular mass of PEG in solution influences the development of intestinal preservation injury. Small intestines of Sprague-Dawley rats were perfused with University of Wisconsin solution. Group 1 underwent vascular perfusion only (clinical control), group 2 received additional luminal PEG3350 Da, group 3 received luminal PEG10000 Da, and group 4 received luminal PEG20000 Da (n = 8/group). Tissue samples were obtained after 4, 8, and 14 hours. We studied the tissue damage (Chiu/Park score, Goblet cells, apoptosis, tight junctions), activation of c-Jun NH2-terminal kinase (JNK), and p38-mitogen-activated protein kinase (MAPK), and we performed Ussing chamber assessments. Mucosal morphologic and electrophysiologic parameters were significantly improved in the groups receiving luminal PEG. There was significantly less apoptotic activity in groups 2, 3, and 4. Both MAPKs revealed an activation peak after 4 hours with group 3 showing lesser p38-MAPK activation. PEG 20 kDa interfered with protein immunodetection. The results indicate that luminal solutions of PEG of medium and large molecular mass significantly delay the onset and development of IPI, providing further evidence that luminal interventions may allow for longer cold storage intervals of intestinal grafts.
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| 3. |
- Lin, Yuanbao, et al.
(författare)
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18.9% Efficient Organic Solar Cells Based on n-Doped Bulk-Heterojunction and Halogen-Substituted Self-Assembled Monolayers as Hole Extracting Interlayers
- 2022
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Ingår i: Advanced Energy Materials. - : Wiley. - 1614-6840 .- 1614-6832. ; 12:45
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Tidskriftsartikel (refereegranskat)abstract
- The influence of halogen substitutions (F, Cl, Br, and I) on the energy levels of the self-assembled hole-extracting molecule [2-(9H-Carbazol-9-yl)ethyl]phosphonic acid (2PACz), is investigated. It is found that the formation of self-assembled monolayers (SAMs) of [2-(3,6-Difluoro-9H-carbazol-9-yl)ethyl]phosphonic acid (F-2PACz), [2-(3,6-Dichloro-9H-carbazol-9-yl)ethyl]phosphonic acid (Cl-2PACz), [2-(3,6-Dibromo-9H-carbazol-9-yl)ethyl]phosphonic acid (Br-2PACz), and [2-(3,6-Diiodo-9H-carbazol-9-yl)ethyl]phosphonic acid (I-2PACz) directly on indium tin oxide (ITO) increases its work function from 4.73 eV to 5.68, 5.77, 5.82, and 5.73 eV, respectively. Combining these ITO/SAM electrodes with the ternary bulk-heterojunction (BHJ) system PM6:PM7-Si:BTP-eC9 yields organic photovoltaic (OPV) cells with power conversion efficiency (PCE) in the range of 17.7%-18.5%. OPVs featuring Cl-2PACz SAMs yield the highest PCE of 18.5%, compared to cells with F-2PACz (17.7%), Br-2PACz (18.0%), or I-2PACz (18.2%). Data analysis reveals that the enhanced performance of Cl-2PACz-based OPVs relates to the increased hole mobility, decreased interface resistance, reduced carrier recombination, and longer carrier lifetime. Furthermore, OPVs featuring Cl-2PACz show enhanced stability under continuous illumination compared to ITO/PEDOT:PSS-based cells. Remarkably, the introduction of the n-dopant benzyl viologen into the BHJ further boosted the PCE of the ITO/Cl-2PACz cells to a maximum value of 18.9%, a record-breaking value for SAM-based OPVs and on par with the best-performing OPVs reported to date.
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| 5. |
- Mantas, Malinauskas, 1985, et al.
(författare)
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Angiotensin IV induced contractions in human jejunal wall musculature in vitro
- 2014
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781. ; 59:C, s. 63-69
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin II (AngII) has been reported to mediate contractile actions in rats and human jejunal wall musculature. However, except for one report showing the Angiotensin IV (AngIV) contractile effects on the internal anal sphincter of rats, no data is available describing the action of AngIV on smooth muscle in human small intestine. The aim of this study was to investigate the expression and localization of the enzymes responsible to AngIV formation, as well as the receptor, and to elucidate the contractile function of AngIV in the muscular layer of human jejunum in vitro. Jejunal smooth muscle was taken from 23 patients undergoing Roux-en-Y gastric bypass surgery and was used to record isometric tension in vitro in response to AngIV alone and in presence of losartan or PD123319. ELISA, western blot and immunohistochemistry were used to investigate the expression and localization of key components for AngIV formation: the enzymes Aminopeptidases-A, B, M, and the AngIV receptor insulin-regulated aminopeptidase (IRAP). AngIV elicited concentration-dependent contraction in both longitudinal and circular smooth-muscle preparation. Presence of losartan abolished AngIV-induced contraction, but not PD123319. The main peptide AngII, as well as the enzymes Aminopeptidase-A, B and M were detected in all muscle samples. Immunohistochemistry localized the enzymes and IRAP in the myenteric plexus between longitudinal and circular muscle layers. The present study indicates that all enzymes necessary for AngIV formation exist in human jejunal smooth muscle and that the contractile action elicited by AngIV is primarily mediated through the AngII type 1 receptor.
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