| 1. |
- Barbu, Andreea R., et al.
(författare)
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A perfusion protocol for highly efficient transduction of intact pancreatic islets of Langerhans
- 2006
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 49:10, s. 2388-2391
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Tidskriftsartikel (refereegranskat)abstract
- Successful gene transfer to pancreatic islets might be a powerful tool for dissecting the biological pathways involved in the functional impairment and destruction of beta cells in type 1 diabetes. In the long run, such an approach may also prove useful for promoting islet graft survival after transplantation in diabetic patients. However, efficient genetic modification of primary insulin-producing cells is limited by the specific compact structure of the pancreatic islet. We present here a whole-pancreas perfusion-based transduction procedure for genetic modification of intact pancreatic islets. We used flow cytometry analysis and confocal microscopy to evaluate the efficiency of in vitro and perfusion-based transduction protocols that use adenoviral and lentiviral vectors expressing green fluorescent protein. Islet cell viability was assessed by fluorescence microscopy and beta cell function was determined via glucose-stimulated insulin secretion. In intact rat and human pancreatic islets, adenoviral and lentiviral vectors mediated gene transfer to about 30% of cells, but they did not reach the inner cellular mass within the islet core. Using the whole-pancreas perfusion protocol, we demonstrate that at least in rodent models the centrally located insulin-producing cells can be transduced with high efficiency, while preserving the structural integrity of the islet. Moreover, islet cell viability and function are not impaired by this procedure. These results support the view that perfusion-based transduction protocols may significantly improve the yield of successfully engineered primary insulin-producing cells for diabetes research.
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| 2. |
- Carlsson, Per-Ola, et al.
(författare)
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Carbon monoxide and pancreatic islet blood flow in the rat : inhibition of haem oxygenase does not affect islet blood perfusion
- 2006
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 66:7, s. 543-548
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To determine whether carbon monoxide, a known gaseous vasorelaxator, affects pancreatic islet blood flow in rats. Material and methods. Sprague-Dawley rats were anaesthetized with thiobutabarbital and injected intravenously with the haem oxygenase inhibitor tin-protoporphyrin IX dichloride ( SnPP; 4, 10 or 20 mg/kg body-weight). After 15 min, blood flow measurements were performed using a microsphere technique. Results. There was a slight increase in mean arterial blood pressure with the highest dose of SnPP. No effects on total pancreatic, islet, duodenal, colonic, renal or adrenal blood flow were seen with any of the applied doses. Conclusions. The findings of this study suggest that the haem oxygenase-carbon monoxide system is likely to be of limited importance in the regulation of blood perfusion to the pancreas, the islets of Langerhans or any of the other studied organs.
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| 3. |
- Gao, Xiang, et al.
(författare)
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Effects of Mn-DPDP and manganese chloride on hemodynamics and glucose tolerance in anesthetized rats
- 2014
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 55:3, s. 328-334
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Tidskriftsartikel (refereegranskat)abstract
- Background Previous studies have demonstrated that magnetic resonance imaging may be a method of choice to visualize transplanted pancreatic islets. However, contrast agents may interfere with microcirculation and affect graft function. Purpose To evaluate the effects manganese-containing contrast media on regional blood flow and glucose tolerance. Material and Methods Anesthetized rats were injected intravenously with MnCl2 (10 mu M/kg body weight) or Mn-DPDP (Teslascan; 5 mu M/kg body weight). Blood flow measurements were made with a microsphere technique 10min later. In separate animals vascular arteriolar reactivity in isolated, perfused islets was examined. Furthermore, an intraperitoneal glucose tolerance test was performed in separate rats. Results Glucose tolerance was unaffected by both agents. No changes in regional blood flow were seen after administration of Mn-DPDP, except for an increase in arterial liver blood flow. MnCl2 increased all blood flow values except that of the kidney. MnCl2, but not Mn-DPDP, caused a vasoconstriction in isolated rat islet arterioles but only at very high doses. Conclusion Mn-DPDP administration does not affect glucose tolerance or regional blood flow, besides an increase in arterial hepatic blood flow, and may therefore be suitable for visualization of islets.
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| 4. |
- Gao, Xiang, et al.
(författare)
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Important role of P2Y receptors for islet blood flow regulation in anesthetized rats during acute and chronic hyperglycemia
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Pancreatic islet blood flow is regulated through a complex interplay between nervous, metabolic and local endothelial factors. We have previously shown that adenosine is an important vasodilator in the metabolic regulation of islet blood flow and now wanted to examine whether also ATP/ADP/AMP could affect islet blood perfusion through P2Y receptors. To achieve this we examined local blood flow values in normoglycemic and acutely hyperglycemic Sprague-Dawley rats as well as GK rats, a type 2 diabetes model. We inhibited P2Y receptors in general with suramine and, since P2Y13 receptors are known to inhibit insulin secretion, we also examined the effects of a selective P2Y13 receptor inhibitor, viz. MRS2211. We found that all GK rats were hyperglycemic and hypertensive when compared to SD rats. Basal islet blood flow in SD rats was decreased by MRS2211, and there was a trend for this to occur also after suramine administration. The glucose-induced islet blood flow increase in SD rats was impaired after suramine and MRS2211 treatment. GK rats had higher islet blood flow, but not islet vascular conductance, than SD rats, which did not react to acute hyperglycemia or the P2Y receptor inhibitors. Similar findings were made in an islet arteriole perfusion model, suggesting that local P2Y receptors are involved. A surprising finding was that especially suramine markedly increased colonic blood flow in SD rats, and decreased this blood flow in GK rats. We conclude that not only adenosine, but also also ATP and especially ADP stimulate both basal and glucose-stimulated islet blood flow in anesthetized SD rats, but this response is not seen in GK rats. Also colonic blood flow seems to be sensitive to P2Y receptors and increase its blood flow when these receptors are inhibited. The mechanisms behind this are unknown.
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| 5. |
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| 6. |
- Hultström, Michael, et al.
(författare)
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Moderate hypothermia induces a preferential increase in pancreatic islet blood flow in anesthetized rats
- 2007
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 293:3, s. R1438-R1443
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to characterize the effects of induced moderate hypothermia on splanchnic blood flow, with particular reference to that of the pancreas and the islets of Langerhans. We also investigated how interference with the autonomic nervous system at different levels influenced the blood perfusion during hypothermia. For this purpose, hypothermia (body temperature of 28°C) was induced by external cooling, whereas normothermic (37.5°C) anesthetized Sprague-Dawley rats were used as controls. Some rats were pretreated with either propranolol, yohimbine, atropine, hexamethonium, or a bilateral abdominal vagotomy. Our findings suggest that moderate hypothermia elicits complex, organ-specific circulatory changes, with increased perfusion noted in the pylorus, as well as the whole pancreas and the pancreatic islets. The pancreatic islets maintain their high blood perfusion through mechanisms involving both sympathetic and parasympathetic mediators, whereas the increased pyloric blood flow is mediated through parasympathetic mechanisms. Renal blood flow was decreased, and this can be prevented by ganglionic blockade and is also influenced by β-adrenoceptors.
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| 7. |
- Ingemarson, Maria, et al.
(författare)
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Implementation of a school-wide prevention programme-teachers' and headmasters' perceptions of organizational capacity.
- 2014
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Ingår i: Evaluation and Program Planning. - : Elsevier BV. - 0149-7189 .- 1873-7870. ; 43, s. 48-54
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Tidskriftsartikel (refereegranskat)abstract
- This study focuses on schools' organizational capacity to implement a Swedish school-wide programme, Prevention in School (PS). It is based on semi-structured interviews with seven headmasters and 13 teachers from seven Swedish schools. The interviews were analyzed by the use of qualitative content analysis. The findings show that the adoption of a comprehensive intervention like PS challenges the school organization as the staff encountered a variety of organizational barriers when implementing the programme. Factors connected to lack of consensus, collaboration and insufficient programme management were the main barriers that were identified. Teachers wanted a more extensive support from their headmasters in terms of participation in different programme activities. It was emphasized that peer coaches need to be prepared for their task, although the headmasters found it difficult to be able to choose those teachers who they perceived as the most suitable. It is concluded that leadership, coaching and staff selection need particular attention when implementing a programme like PS, since those factors have been defined as important implementation drivers, both in this study and previously.
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| 8. |
- Ingemarson, Maria, et al.
(författare)
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The implementation of a behavioural support programme Teachers' perceptions of the programme and themselves as providers
- 2016
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Ingår i: Health Education. - : EMERALD GROUP PUBLISHING LTD. - 0965-4283 .- 1758-714X. ; 116:6, s. 526-540
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Tidskriftsartikel (refereegranskat)abstract
- Purpose - The purpose of this paper is to investigate how teachers received and perceived the school programme Prevention in School (PS), a positive behavioural support programme; how did the teachers perceive the programme characteristics and themselves as providers; and how did this affect programme implementation? Design/methodology/approach - Qualitative methods with semi-structured interviews with 13 teachers and thematic content analysis were used. Findings - The teachers were heterogeneous in their views, with professional identity, programme understanding and experiencing change being important factors for the implementation. Ambiguities regarding the boundaries of the social assignment, opposition against the theoretical underpinnings and an unclear nomenclature in a core component affected the implementation negatively. Among the perceived benefits were instant rewards in the form of aha moments and increased self-awareness. The nature of the implementation barriers indicates that PS is in need of further development. Practical implications - Compatibility with teachers' ideologies, clarification of the social assignment and enough time to consider programme adoption are vital when implementing a programme like PS. Originality/value - The study provides context-specific understanding of teachers' perceptions of a behavioural support programme and of their role when trying to implement it. It is known that providers' perceptions affect the implementation and this study contributes to the field of implementation research, with particular respect to the school setting and comprehensive programmes like PS.
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| 9. |
- Jansson, Leif, et al.
(författare)
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Arginase increases total pancreatic and islet blood flow in anaesthetized mice
- 2007
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 112:2, s. 165-173
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous studies have demonstrated that the high basal pancreatic islet blood perfusion is crucially dependent on nitric oxide formation. Arginase can interfere with the formation of nitric oxide by limiting substrate availability. The aim of the present study was to evaluate the influence of arginase on islet blood perfusion in anaesthetized mice. METHODS: The blood perfusion of the pancreatic islets was measured with a microsphere technique in anaesthetized NMRI mice after administration of arginase. RESULTS: Arginase administration increased both total pancreatic and islet blood flow to the same degree. Also adrenal blood flow was increased, whereas other organ blood flow values were unaffected. CONCLUSION: Arginase induces a paradoxical increase in pancreatic and islet blood flow, the reasons for which are still unknown.
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| 10. |
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