| 1. |
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| 2. |
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| 3. |
- Baliakas, Panagiotis, et al.
(författare)
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Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: a retrospective multicentre study
- 2014
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Ingår i: The Lancet Haematology. - 2352-3026. ; 1:2, s. 74-84
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Tidskriftsartikel (refereegranskat)abstract
- Background About 30% of cases of chronic lymphocytic leukaemia (CLL) carry quasi-identical B-cell receptor immunoglobulins and can be assigned to distinct stereotyped subsets. Although preliminary evidence suggests that B-cell receptor immunoglobulin stereotypy is relevant from a clinical viewpoint, this aspect has never been explored in a systematic manner or in a cohort of adequate size that would enable clinical conclusions to be drawn. Methods For this retrospective, multicentre study, we analysed 8593 patients with CLL for whom immunogenetic data were available. These patients were followed up in 15 academic institutions throughout Europe (in Czech Republic, Denmark, France, Greece, Italy, Netherlands, Sweden, and the UK) and the USA, and data were collected between June 1, 2012, and June 7, 2013. We retrospectively assessed the clinical implications of CLL B-cell receptor immunoglobulin stereotypy, with a particular focus on 14 major stereotyped subsets comprising cases expressing unmutated (U-CLL) or mutated (M-CLL) immunoglobulin heavy chain variable genes. The primary outcome of our analysis was time to first treatment, defined as the time between diagnosis and date of first treatment. Findings 2878 patients were assigned to a stereotyped subset, of which 1122 patients belonged to one of 14 major subsets. Stereotyped subsets showed significant differences in terms of age, sex, disease burden at diagnosis, CD38 expression, and cytogenetic aberrations of prognostic significance. Patients within a specific subset generally followed the same clinical course, whereas patients in different stereotyped subsets-despite having the same immunoglobulin heavy variable gene and displaying similar immunoglobulin mutational status-showed substantially different times to first treatment. By integrating B-cell receptor immunoglobulin stereotypy (for subsets 1, 2, and 4) into the well established Dohner cytogenetic prognostic model, we showed these, which collectively account for around 7% of all cases of CLL and represent both U-CLL and M-CLL, constituted separate clinical entities, ranging from very indolent (subset 4) to aggressive disease (subsets 1 and 2). Interpretation The molecular classification of chronic lymphocytic leukaemia based on B-cell receptor immunoglobulin stereotypy improves the Dohner hierarchical model and refines prognostication beyond immunoglobulin mutational status, with potential implications for clinical decision making, especially within prospective clinical trials.
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| 4. |
- Baliakas, Panagiotis, et al.
(författare)
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Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations.
- 2015
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 125:5, s. 856-859
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Tidskriftsartikel (refereegranskat)abstract
- An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset #2. Within subset #2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset #2/IGHV3-21 was enriched for IGHV-unmutated cases (P = .002). Subset #2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset #2/IGHV3-21 (22 vs 60 months, P = .001). No such difference was observed between non-subset #2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset #2 emerges as uniformly aggressive, contrasting non-subset #2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.
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| 5. |
- Barbu, Andreea, et al.
(författare)
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Blood flow in endogenous and transplanted pancreatic islets in anesthetized rats : Effects of lactate and pyruvate
- 2012
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Ingår i: Pancreas. - 0885-3177 .- 1536-4828. ; 41:8, s. 1263-1271
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The objective of this study was to evaluate the effects of exogenously administered lactate and pyruvate on blood perfusion in endogenous and transplanted islets. METHODS: Anesthetized Wistar-Furth rats were given lactate or pyruvate intravenously, and regional blood perfusion was studied 3 or 30 minutes later with a microsphere technique. Separate rats received a 30-minute infusion of pyruvate or lactate into the portal vein before blood flow measurements. We also administered these substances to islet-implanted rats 4 weeks after transplantation and measured graft blood flow with laser Doppler flowmetry. The expression of monocarboxylate transporter 1 and lactate dehydrogenase A was analyzed. RESULTS: The expression of monocarboxylate transporter 1 and lactate dehydrogenase A was markedly up-regulated in transplanted as compared with endogenous islets. Administration of pyruvate, but not lactate, increased mesenteric blood flow after 3 minutes. Pyruvate decreased mesenteric blood flow after 30 minutes, whereas lactate decreased only islet blood flow. These responses were absent in transplanted animals. A continuous intraportal infusion of lactate or pyruvate increased selectively islet blood flow but did not affect blood perfusion of transplanted islets. CONCLUSIONS: Lactate and pyruvate affect islet blood flow through effects mediated by interactions between the liver and the nervous system. Such a response can help adjust the release of islet hormones during excess substrate concentrations.
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| 6. |
- Barbu, Andreea, et al.
(författare)
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The use of hydrogen gas clearance for blood flow measurements in single endogenous and transplanted pancreatic islets
- 2015
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Ingår i: Microvascular Research. - : Elsevier BV. - 0026-2862 .- 1095-9319. ; 97, s. 124-129
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Tidskriftsartikel (refereegranskat)abstract
- The blood perfusion of pancreatic islets is regulated independently from that of the exocrine pancreas, and is of importance for multiple aspects of normal islet function, and probably also during impaired glucose tolerance. Single islet blood flow has been difficult to evaluate due to technical limitations. We therefore adapted a hydrogen gas washout technique using microelectrodes to allow such measurements. Platinum micro-electrodes monitored hydrogen gas clearance from individual endogenous and transplanted islets in the pancreas of male Lewis rats and in human and mouse islets implanted under the renal capsule of male athymic mice. Both in the rat endogenous pancreatic islets as well as in the intra-pancreatically transplanted islets, the vascular conductance and blood flow values displayed a highly heterogeneous distribution, varying by factors 6-10 within the same pancreas. The blood flow of human and mouse islet grafts transplanted in athymic mice was approximately 30% lower than that in the surrounding renal parenchyma. The present technique provides unique opportunities to study the islet vascular dysfunction seen after transplantation, but also allows for investigating the effects of genetic and environmental perturbations on islet blood flow at the single islet level in vivo. (C) 2014 The Authors. Published by Elsevier Inc.
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| 7. |
- Barman, Malin, 1983, et al.
(författare)
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Short-chain fatty acids (SCFA) in infants’ plasma and corresponding mother's milk and plasma in relation to subsequent sensitisation and atopic disease
- 2024
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Ingår i: EBioMedicine. - 2352-3964. ; 101
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Tidskriftsartikel (refereegranskat)abstract
- Background: Short-chain fatty acids (SCFAs) in intestinal contents may influence immune function, while less is known about SCFAs in blood plasma. The aims were to investigate the relation between infants’ and maternal plasma SCFAs, as well as SCFAs in mother's milk, and relate SCFA concentrations in infant plasma to subsequent sensitisation and atopic disease. Methods: Infant plasma (N = 148) and corresponding mother's milk and plasma were collected four months postpartum. Nine SCFA (formic, acetic, propionic, isobutyric, butyric, succinic, valeric, isovaleric, and caproic acid) were analysed by UPLC-MS. At 12 months of age, atopic disease was diagnosed by a pediatric allergologist, and sensitisation was measured by skin prick test. All families participated in the Swedish birth cohort NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment). Findings: Infants with sensitisation, atopic eczema, or food allergy had significantly lower concentrations of five, three, and two SCFAs, respectively, in plasma at four months. Logistic regressions models showed significant negative associations between formic, succinic, and caproic acid and sensitisation [ORadj (95% CI) per SD: 0.41 (0.19–0.91); 0.19 (0.05–0.75); 0.25 (0.09–0.66)], and between acetic acid and atopic eczema [0.42 (0.18–0.95)], after adjusting for maternal allergy. Infants’ and maternal plasma SCFA concentrations correlated strongly, while milk SCFA concentrations were unrelated to both. Butyric and caproic acid concentrations were enriched around 100-fold, and iso-butyric and valeric acid around 3-5-fold in mother's milk, while other SCFAs were less prevalent in milk than in plasma. Interpretation: Butyric and caproic acid might be actively transported into breast milk to meet the needs of the infant, although mechanistic studies are needed to confirm this. The negative associations between certain SCFAs on sensitisation and atopic disease adds to prior evidence regarding their immunoregulatory potential. Funding: Swedish Research Council (Nr. 2013-3145 and 2019-0137 to A-S.S.), Swedish Research Council for Health, Working Life and Welfare FORTE, Nr 2018-00485 to A.W.), The Swedish Asthma and Allergy Association's Research Fund (2020-0020 to A.S.).
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| 8. |
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| 9. |
- Christoffersson, Gustaf, et al.
(författare)
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Matrix Metalloproteinase-9 Is Essential for Physiological Beta Cell Function and Islet Vascularization in Adult Mice
- 2015
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 185:4, s. 1094-1103
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Tidskriftsartikel (refereegranskat)abstract
- The availability of paracrine factors in the islets of Langerhans, and the constitution of the beta cell basement membrane can both be affected by proteolytic enzymes. This study aimed to investigate the effects of the extraceaular matrix-degrading enzyme gelatinase B/matrix metalloproteinase-9 (Mmp-9) on islet function in mice. Islet function of Mmp9-deficient (Mmp9(-/-)) mice and their wild-type Littermates was evaluated both in vivo and in vitro. The pancreata of Mmp9(-/-) mice did not differ from wild type in islet mass or distribution. However, Mmp9(-/-) mice had an impaired response to a glucose toad in vivo, with lower serum insulin levels. The glucose-stimulated insulin secretion was reduced also in vitro in isolated Mmp9(-/-) islets. The vascular density of Mmp9(-/-) islets was lower, and the capillaries had fewer fenestrations, whereas the islet blood flow was threefold higher. These alterations could partly be explained by compensatory changes in the expression of matrix-related proteins. This in-depth investigation of the effects of the loss of MMP9(-/-) function on pancreatic islets uncovers a deteriorated beta cell function that is primarily due to a shift in the beta cell phenotype, but also due to islet vascular aberrations. This likely reflects the importance of a normal islet matrix turnover exerted by MMP-9, and concomitant release of paracrine factors sequestered on the matrix.
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| 10. |
- Daelman, Bo, et al.
(författare)
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Frailty and cognitive function in middle-aged and older adults with congenital heart disease
- 2024
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 83:12, s. 1149-1159
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Tidskriftsartikel (refereegranskat)abstract
- Background: Life expectancy of patients with congenital heart disease (CHD) has increased rapidly, resulting in a growing and aging population. Recent studies have shown that older people with CHD have higher morbidity, health care use, and mortality. To maintain longevity and quality of life, understanding their evolving medical and psychosocial challenges is essential.Objectives: The authors describe the frailty and cognitive profile of middle-aged and older adults with CHD to identify predictor variables and to explore the relationship with hospital admissions and outpatient visits.Methods: Using a cross-sectional, multicentric design, we included 814 patients aged ≥40 years from 11 countries. Frailty phenotype was determined using the Fried method. Cognitive function was assessed by the Montreal Cognitive Assessment.Results: In this sample, 52.3% of patients were assessed as robust, 41.9% as prefrail, and 5.8% as frail; 38.8% had cognitive dysfunction. Multinomial regression showed that frailty was associated with older age, female sex, higher physiologic class, and comorbidities. Counterintuitively, patients with mild heart defects were more likely than those with complex lesions to be prefrail. Patients from middle-income countries displayed more prefrailty than those from higher-income countries. Logistic regression demonstrated that cognitive dysfunction was related to older age, comorbidities, and lower country-level income.Conclusions: Approximately one-half of included patients were (pre-)frail, and more than one-third experienced cognitive impairment. Frailty and cognitive dysfunction were identified in patients with mild CHD, indicating that these concerns extend beyond severe CHD. Assessing frailty and cognition routinely could offer valuable insights into this aging population.
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| 11. |
- de-Wahl Granelli, Anne, 1970, et al.
(författare)
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Impact of pulse oximetry screening on the detection of duct dependent congenital heart disease: a Swedish prospective screening study in 39,821 newborns.
- 2009
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Ingår i: BMJ (Clinical research ed.). - 1468-5833. ; 338
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the use of pulse oximetry to screen for early detection of life threatening congenital heart disease. DESIGN: Prospective screening study with a new generation pulse oximeter before discharge from well baby nurseries in West Götaland. Cohort study comparing the detection rate of duct dependent circulation in West Götaland with that in other regions not using pulse oximetry screening. Deaths at home with undetected duct dependent circulation were included. SETTING: All 5 maternity units in West Götaland and the supraregional referral centre for neonatal cardiac surgery. PARTICIPANTS: 39,821 screened babies born between 1 July 2004 and 31 March 2007. Total duct dependent circulation cohorts: West Götaland n=60, other referring regions n=100. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values, and likelihood ratio for pulse oximetry screening and for neonatal physical examination alone. RESULTS: In West Götaland 29 babies in well baby nurseries had duct dependent circulation undetected before neonatal discharge examination. In 13 cases, pulse oximetry showed oxygen saturations
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| 12. |
- Dedic, Dina, et al.
(författare)
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Analysis of lignin and extractives in the oak wood of the 17th century warship Vasa
- 2014
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Ingår i: Holzforschung. - : Walter de Gruyter GmbH. - 0018-3830 .- 1437-434X. ; 68:4, s. 419-425
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Tidskriftsartikel (refereegranskat)abstract
- The wood in the 17th century Swedish warship Vasa is weak. A depolymerization of the wood's cellulose has been linked to the weakening, but the chemical mechanisms are yet unclear. The objective of this study was to analyze the lignin and tannin moieties of the wood to clarify whether the depolymerization of cellulose via ongoing oxidative mechanisms is indeed the main reason for weakening the wood in the Vasa. Lignin was analyzed by solid-state nuclear magnetic resonance [cross-polarization/magic-angle spinning (CP/MAS) C-13 NMR] and by means of wet chemical degradation (thioacidolysis) followed by gas chromatography-mass spectrometry (GC-MS) of the products. No differences could be observed between the Vasa samples and the reference samples that could have been ascribed to extensive lignin degradation. Wood extracts (tannins) were analyzed by matrix- assisted laser desorption ionization (MALDI) combined with time-of-flight (TOF) MS and C-13 NMR spectroscopy. The wood of the Vasa contained no discernible amounts of tannins, whereas still-waterlogged Vasa wood contained ellagic acid and traces of castalagin/vescalagin and grandinin. The results indicate that the condition of lignin in the Vasa wood is similar to fresh oak and that potentially harmful tannins are not present in high amounts. Thus, oxidative degradation mechanisms are not supported as a primary route to cellulose depolymerization.
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| 13. |
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| 14. |
- Dedic, Dina, et al.
(författare)
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Chemical analysis of wood extractives and lignin in the oak wood of the 380 year old Swedish warship Vasa
- 2011
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Konferensbidrag (refereegranskat)abstract
- In order to map the source of oxalic acid in the interior wood of the Vasa ship, an analysis of wood extractives (tannins) was conducted. Samples used for analysis were PEG-impregnated dry Vasa wood, waterlogged Vasa wood and a reference material (fresh oak). The wood material was ground and extracted with an acetone/water-mixture. In the reference sample, several types of tannins were found such as the isomers castalagin/vescalagin and grandinin and their dimmers roburin A/D and roburin B/C respectively. The results have been confirmed by NMR spectroscopy and MALDI-TOF. The interior of the waterlogged Vasa wood contained small amounts of monomers, whereas the dry, PEG treated Vasa revealed no discernible amounts of hydrolysable tannins or other easily soluble compounds. Furthermore, an analysis of lignin was made by means of chemical degradation (thioacidolysis). A decrease in the amount of β-O-4 bonds in the lignin structure would imply a formation of easily oxidized free phenolics. The products were analyzed by GC-MS, which revealed no dramatic differences between the Vasa samples and the reference. The results were confirmed by CP/MAS NMR by analyzing the differences in the aromatic region (150∼160 ppm) as well as the carbonyl region (190∼200 ppm).
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| 15. |
- Ehrström, Monica, 1970-
(författare)
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Uppmärksamhet för bedömning : att följa varje barns lärprocesser för en likvärdig utbildning i förskolan
- 2023
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this study was to contribute with knowledge about the tension between preschool teachers' mission to teach and support children's learning on the one hand and the mission to assess children's learning processes on the other hand, in relation to equality in education. In Swedish preschools, children with different experiences meet, all of whom should have the opportunity to develop and learn based on their varied circumstances and needs. According to the Education Act (SFS, 2010:800), preschool education must be equal, and all children must have the opportunity to learn and develop as far as possible based on their potential. However, previous research (Alasuutari, Vallberg Roth & Markström, 2014) indicates that assessment involves risks for children’s identity creation. This study examines how seven preschool teachers tackle the challenge of assessing and paying attention to individual children in their ongoing learning processes. A sociocultural perspective (Vygotskij, 1978) has been used to study preschool teachers' reasoning about assessment in relation to each child's possibilities for being supported in their proximal development zone. The sociocultural perspective stresses the importance of cultural tools for communication. Stimulated-recall interviews were conducted with seven preschool teachers in Sweden. Content analysis was used to reveal the views that emerged in preschool teachers’ descriptions.In the preschool teachers' reasoning, different strategies for assessment and methods for making the child's learning processes visible as well as approaches for following the progression in children's learning processes have emerged, which can create both opportunities and limitations for children to learn based on their potential. Findings indicate three areas significant for assessment in relation to an equivalent education in this study. Firstly, there is clarity regarding the approach to assessment, what is to be given attention and assessed and how the assessment should be carried out. Secondly, the preschool teachers in the study have knowledge about various methods to make children's learning processes visible and thus possible to follow over time. Thirdly, the preschool teachers in the study know how to draw attention to and make visible the child's learning from a holistic perspective. The Licentiate thesis highlights different strategies for assessment, methods for making the child's learning processes visible and approaches for following the progression in children's learning processes that emerged during the preschool teachers' reasoning. The study has shown that attentiveness (Elbaz, 1992) can be used as a concept to bridge the tension surrounding assessment.
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| 16. |
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| 17. |
- Fred, Rikard G., et al.
(författare)
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The human insulin mRNA is partly translated via a cap- and eIF4A-independent mechanism
- 2011
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 412:4, s. 693-698
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate whether cap-independent insulin mRNA translation occurs in human pancreatic islets at basal conditions, during stimulation at a high glucose concentration and at conditions of nitrosative stress. We also aimed at correlating cap-independent insulin mRNA translation with binding of the IRES trans-acting factor polypyrimidine tract binding protein (FTB) to the 5'-UTR of insulin mRNA. For this purpose, human islets were incubated for 2 h in the presence of low (1.67 mM) or high glucose (16.7 mM). Nitrosative stress was induced by addition of 1 mM DETA/NO and cap-dependent mRNA translation was inhibited with hippuristanol. Insulin biosynthesis rates were determined by radioactive labeling and immunoprecipitation. PTB affinity to insulin mRNA 5'-UTR was assessed by a magnetic micro bead pull-down procedure. We observed that in the presence of 1.67 mM glucose, approximately 70% of the insulin mRNA translation was inhibited by hippuristanol. Corresponding value from islets incubated at 16.7 mM glucose was 93%. DETA/NO treatment significantly decreased the translation of insulin by 85% in high glucose incubated islets, and by 50% at a low glucose concentration. The lowered insulin biosynthesis rates of DETA/NO-exposed islets were further suppressed by hippuristanol with 55% at 16.7 mM glucose but not at 1.67 mM glucose. Thus, hippuristanol-induced inhibition of insulin biosynthesis was less pronounced in DETA/NO-treated islets as compared to control islets. We observed also that PTB bound specifically to the insulin mRNA 5'-UTR in vitro, and that this binding corresponded well with rates of cap-independent insulin biosynthesis at the different conditions. In conclusion, our studies show that insulin biosynthesis is mainly cap-dependent at a high glucose concentration, but that the cap-independent biosynthesis of insulin can constitute as much as 40-100% of all insulin biosynthesis during conditions of nitrosative stress. These data suggest that the pancreatic beta-cell is able to uphold basal insulin synthesis at conditions of starvation and stress via a cap- and eIF4A-independent mechanism, possibly mediated by the binding of FIB to the 5'-UTR of the human insulin mRNA.
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| 18. |
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| 19. |
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| 20. |
- Gao, Xiang, et al.
(författare)
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Effects of GIP on regional blood flow during normoglycemia and hyperglycemia in anesthetized rats
- 2018
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 6:8
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Tidskriftsartikel (refereegranskat)abstract
- The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-stimulated insulin secretion, and affects -cell turnover. This study aimed at evaluating if some of the beneficial effects of GIP on glucose homeostasis can be explained by modulation of islet blood flow. Anesthetized Sprague-Dawley rats were infused intravenously with different doses of GIP (10, 20, or 60ng/kg*min) for 30min. Subsequent organ blood flow measurements were performed with microspheres. In separate animals, islets were perfused exvivo with GIP (10(-6)-10(-12)mol/L) during normo- and hyperglycemia and arteriolar responsiveness was recorded. The highest dose of GIP potentiated insulin secretion during hyperglycemia, but had no effect in normoglycemic rats. The highest GIP concentration decreased blood perfusion of whole pancreas, pancreatic islets, duodenum, colon, liver and kidneys. The decrease in blood flow was unaffected by ganglion blockade or adenosine receptor inhibition. In contrast to this, in single perfused islets GIP induced a dose-dependent arteriolar dilation. Thus, high doses of GIP exert a direct dilatory effect on islet arterioles in isolated islets, but induce a generalized vasoconstriction in splanchnic organs, including the whole pancreas and islets, invivo. The latter effect is unlikely to be mediated by adenosine, the autonomic nervous system, or endothelial mediators.
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| 21. |
- 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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| 22. |
- 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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| 23. |
- Gao, Xiang, et al.
(författare)
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Short-term glucosamine infusion increases islet blood flow in anesthetized rats
- 2013
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Ingår i: ISLETS. - : Informa UK Limited. - 1938-2014 .- 1938-2022. ; 5:5, s. 201-206
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Tidskriftsartikel (refereegranskat)abstract
- Impaired glucose tolerance and type 2 diabetes in rodents are associated with increased islet blood flow. If this is important for modulation of the endocrine function is at present unknown. We evaluated if glucosamine infusion, which induces peripheral insulin resistance and glucose intolerance, could be used to acutely increase islet blood flow. We infused anaesthetized Sprague-Dawley rats for 2 h with glucosamine (6 mg/kg body weight), in some cases followed by glucose administration. The former induced a 2-fold increase in serum insulin concentrations while plasma glucose remained unchanged. In vitro an augmented insulin response to hyperglycemia and decreased insulin content in batch type islet incubations with glucosamine for 24 h were seen. After 2 h glucosamine exposure in vitro, insulin release was decreased. In vivo glucosamine infusion increased islet blood flow, without affecting other regional blood flow values. Glucose increased islet blood flow to the same extent in control and glucosamine-infused rats. When exposed to 10 mmol/L glucosamine arterioles of isolated perfused islets showed a 10% dilation of their vascular smooth muscle. Thus, application of this model leads to acute hyperinsulinemia in vivo but a decreased insulin release in vitro, which suggests that effects not located to beta cells are responsible for the effects seen in vivo. An increased islet blood flow in previously healthy animals was also seen after glucose administration, which can be used to further dissect the importance of blood flow changes in islet function.
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| 24. |
- Gio-Batta, Monica, et al.
(författare)
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Fecal short chain fatty acids in children living on farms and a link between valeric acid and protection from eczema.
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Children growing up on farms have low rates of allergy, but the mechanism for this protective effect has not been fully elucidated. Short chain fatty acids (SCFAs) produced by the gut microbiota may play a role in protection from allergy. We measured fecal SCFA levels in samples collected from 28 farming and 37 control children over the first 3years of life using gas chromatography. Data on diet and other host factors were recorded and allergy was diagnosed at 8years of age. Among all children, median propionic and butyric acid concentration increased over the first 3years, and longer SCFAs typically appeared by 1year of age. Farm children had higher levels of iso-butyric, iso-valeric and valeric acid at 3years of age than rural controls. In addition, children with elder siblings had higher levels of valeric acid at 3years of age, and dietary factors also affected SCFA pattern. High levels of valeric acid at 3years of age were associated with low rate of eczema at 8years of age. The fecal SCFA pattern in farm children suggests a more rapid maturation of the gut microbiota. Valeric acid or associated microbes may have protective potential against eczema.
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| 25. |
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