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Sökning: WFRF:(Ekelund Mats)

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  • Ekelund, Mikael, et al. (författare)
  • Effects of total parenteral nutrition on rat enteric nervous system, intestinal morphology, and motility.
  • 2005
  • Ingår i: Journal of Surgical Research. - Elsevier. - 1095-8673. ; 124:2, s. 187-193
  • Tidskriftsartikel (refereegranskat)abstract
    • Total parenteral nutrition (TPN) is often crucial for patients not being able to feed enterally or having intestinal absorptive deficits. Enteral nutrition is, however, frequently regarded vital for maintaining functional and structural intestinal integrity. The aim of this study was to investigate possible effects of TPN on rat distal small intestine compared to enterally fed identically housed controls, regarding the enteric nervous system (ENS), motility in vitro, and morphology. This study shows that motor responses evoked by electrical stimulation or exposure to vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide-27 (PACAP-27), and nitric oxide (NO) donor were unchanged. By using immunohistochemistry, the numbers of submucous (P < 0.05) and myenteric (P < 0.05) nerve cells were found to increase, expressed as numbers per unit length. The percentage of neurons expressing VIP, PACAP-27, NO-synthase, and galanin remained unchanged, however. By in situ hybridization the number of submucous neurons expressing neuropeptide Y-mRNA was found to decrease (P < 0.05); the other populations were unaltered. Morphometry revealed an increased submucosal thickness (P < 0.05), while intestinal circumference markedly decreased (P < 0.0001) in TPN-treated rats. In conclusion, TPN treatment resulted in reduced intestinal circumference leading to condensation of enteric neurons. No marked changes in neurotransmitter expression of the enteric neurons or in motor activity were noted.
  • Ekelund, Mikael, et al. (författare)
  • Total Parenteral Nutrition Causes Circumferential Intestinal Atrophy, Remodeling of the Intestinal Wall, and Redistribution of Eosinophils in the Rat Gastrointestinal Tract.
  • 2007
  • Ingår i: Digestive Diseases and Sciences. - Springer. - 1573-2568. ; 52:8, s. 1833-1839
  • Tidskriftsartikel (refereegranskat)abstract
    • Total parenteral nutrition (TPN) is held to cause intestinal atrophy and weaken mechanical and immunological barriers. To monitor the degree of atrophy caused by TPN, female Sprague-Dawley rats were, for 8 days, maintained on TPN (n = 6) and compared to identically housed controls given food and water ad libitum (n = 6). Specimens from jejunum, ileum, and colon were taken for histology and morphometric analysis. Topographic distribution and presence of eosinophils, by eosinophil peroxidase (EPO) staining, were examined in the gastric fundus, jejunum, ileum, and colon. Atrophy in terms of a markedly reduced circumference was noted throughout the intestinal tract in all rats subjected to TPN. The width of jejunal and ileal villi was narrowed and the length of jejunal villi was decreased. Furthermore, submucosal thickness in the jejunum and ileum increased. The height of ileal enterocytes remained unaltered. The number of goblet cells decreased in jejunal but not in ileal villi. The Paneth cells, suggested to play important roles in innate defense, increased in size. In the gastric fundus a marked increase in eosinophils was revealed predominantly in the mucosa and submucosa. The number and distribution of jejunal and ileal eosinophils were identical to those of controls. In colon from TPN rats, a redistribution of eosinophils was noted, causing a "band-like" accumulation of eosinophils in the basal portion of the mucosa. In conclusion, TPN causes gut atrophy and an increase in Paneth cell size. Eosinophils increase in number in the gastric fundus and a topographic redistribution occurs in the colon.
  • Angenete, E, et al. (författare)
  • Physical activity before radical prostatectomy reduces sick leave after surgery - results from a prospective, non-randomized controlled clinical trial (LAPPRO).
  • 2016
  • Ingår i: BMC urology. - 1471-2490. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Studies have reported that early physical rehabilitation after surgical procedures is associated with improved outcome measured as shorter hospital stay and enhanced recovery. The aim of this study was to explore the relationship between the preoperative physical activity level and subsequent postoperative complications, sick-leave and hospital stay after radical prostatectomy for prostate cancer in the setting of the LAPPRO trial (LAParoscopic Prostatectomy Robot Open).METHODS: LAPPRO is a prospective controlled trial, comparing robot-assisted laparoscopic and open surgery for localized prostate cancer between 2008 and 2011. 1569 patients aged 64 or less with an occupation were included in this sub-study. The Gleason score was &lt;7 in 52 % of the patients. Demographics and the level of self-assessed preoperative physical activity, length of hospital stay, complications, quality of life, recovery and sick-leave were extracted from clinical record forms and questionnaires. Multivariable logistic regression, with log-link and logit-link functions, was used to adjust for potential confounding variables.RESULTS: The patients were divided into four groups based on their level of activity. As the group with lowest engagement of physical activity was found to be significantly different in base line characteristics from the other groups they were excluded from further analysis. Among patients that were physically active preoperativelly (n = 1467) there was no significant difference between the physical activity-groups regarding hospital stay, recovery or complications. However, in the group with the highest self-assessed level of physical activity, 5-7 times per week, 13 % required no sick leave, compared to 6.3 % in the group with a physical activity level of 1-2 times per week only (p &lt; 0.0001).CONCLUSIONS: In our study of med operated with radical prostatectomy, a high level of physical activity preoperatively was associated with reduced need for sick leave after radical prostatectomy compared to men with lower physical activity.TRIAL REGISTRATION: The trial is registered at the ISCRTN register. ISRCTN06393679 .
  • Axelson, Jan, et al. (författare)
  • The changes in the rat parotid glands following total parenteral nutrition and pancreatico-biliary diversion are not mediated by cholecystokinin
  • 1996
  • Ingår i: International Journal of Pancreatology. - Humana Press. - 0169-4197. ; 20:2, s. 109-118
  • Tidskriftsartikel (refereegranskat)abstract
    • CONCLUSIONS: The results of the present study suggest that the pancreas and parotid glands both respond with hypoplasia during absence of food in the digestive tract and with hyperplasia following pancreatico-biliary diversion (PBD). Factors other than cholecystokinin (CCK) are, however, involved in the effects on the parotid glands, since infusion of CCK-8S and devazepide was without influence. BACKGROUND AND AIM: Total parenteral nutrition (TPN) causes reduced pancreatic weight, whereas PBD evokes hyperCCKemia and enlargement of the rat pancreas. The pancreas and parotid glands have in part similar morphology and function. Therefore, we studied the possible presence of alterations also in the parotid glands during TPN, after PBD and during infusion of sulfated cholecystokinin (CCK-8S) and the CCK-A receptor antagonist devazepide, respectively. MATERIALS AND RESULTS: Rats either received TPN for 7 d, or were kept under otherwise identical conditions with free access to food and water. TPN markedly reduced both pancreatic and parotid wet weight and thereby also the protein and amylase contents, and pancreatic DNA content was decreased. There was a significant correlation between the pancreas and parotid glands when comparing these parameters. The concentration of plasma CCK was unaffected by TPN. PBD caused a sevenfold increase in plasma CCK and a three fold increase in the pancreatic weight compared to control rats 28 d after the operation. The protein and DNA contents in the pancreas were found to be increased. The parotid glands increased twofold in weight, but their protein and amylase contents were not affected. There was a significant correlation between the pancreas and parotid glands when comparing weight, and protein and amylase concentrations. Infusion of CCK-8S during 28 d caused a marked increase in pancreatic wet wt and protein and DNA contents. The CCK-A receptor antagonist devazepide induced a reduction in protein and DNA contents in the pancreas. The parotid glands were not affected by either treatment. No effect on the labeling index of serous and ductal cells of the parotid gland was seen at 36 h, 3, 7, and 28 d of infusion with CCK-8S or devazepide.
  • Berggren, Sofia, et al. (författare)
  • Gene and protein expression of P-glycoprotein, MRP1, MRP2 and CYP3A4 in the small and large human intestine
  • 2007
  • Ingår i: Molecular Pharmaceutics. - 1543-8384. ; 4:2, s. 252-257
  • Tidskriftsartikel (refereegranskat)abstract
    • The cytochrome P450 3A4 enzyme and the ABC-transporters may affect the first-pass extraction and bioavailability of drugs and metabolites. Conflicting reports can be found in the literature on the expression levels of efflux transporters in human intestine and how they vary along the intestine. The relative levels of mRNA and protein of CYP3A4 and the ABC tranporters Pgp (ABCB1), MRP1 (ABCC1), and MRP2 (ABCC2) were determined using RT-PCR and Western blot for human intestinal tissues (n = 14) from jejunum, ileum and colon. The expression of mRNA for CYP3A4, Pgp, and MRP2 was highest in jejunum and decreased toward more distal regions, whereas MRP1 was equally distributed in all intestinal regions. For CYP3A4, a more significant correlation could be established between mRNA and protein expression than for the ABC transporters. The samples showed considerable interindividual variability, especially at the protein level. The apically located Pgp and MRP2 showed a similar expression pattern along the human intestine as for CYP3A4. The gene expression of MRP1 exhibited a more uniform distribution.
  • Berggren, S, et al. (författare)
  • Regional transport and metabolism of roivacaine and its CYP3A4 metabolite PPX in human intestine
  • 2003
  • Ingår i: Journal of Pharmacy and Pharmacology. - Pharmaceutical Press. - 0022-3573. ; 55:7, s. 963-972
  • Tidskriftsartikel (refereegranskat)abstract
    • The major aim of this study was to investigate the CYP3A4 metabolism and polarized transport of ropivacaine and its metabolite 2',6'-pipecoloxylidide (PPX) in tissue specimens from the human small and large intestine. Ropivacaine has been shown to be effective in the treatment of ulcerative colitis in human colon. This study was conducted using a modified Ussing-chamber technique with specimens from jejunum, ileum and colon collected from 11 patients. The local kinetics of ropivacaine and PPX were assessed from their concentration-time profiles in mucosal and serosal compartments. The permeability (P-app) in the absorptive direction for both ropivacaine and PPX increased regionally in the order jejunum <ileum<colon. Ropivacaine was not found to be subjected to any carrier-mediated intestinal efflux. However, the CYP3A4 metabolite left the human enterocyte in a polarized manner and both the extent of CYP3A4 metabolism of ropivacaine and the extrusion of its metabolite to the mucosal chamber were more efficient in jejunum than in ileum. P-glycoprotein was probably not involved in the metabolite extrusion. No other metabolite than PPX was found. This in-vitro study with human intestinal tissues provides new mechanistic insights into regional transport and metabolism of drugs.
  • Ekelund, Mats, et al. (författare)
  • A Higher Score on the Dermatology Life Quality Index, Being on Systemic Treatment and Having a Diagnosis of Psoriatic Arthritis is Associated with Increased Costs in Patients with Plaque Psoriasis
  • 2013
  • Ingår i: Acta Dermato-Venereologica. - Acta Dermato-Venereologica. - 0001-5555. ; 93:6, s. 684-688
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to examine the relationship between measures of disease severity and costs from a socie-tal perspective in patients with plaque psoriasis. Dermatologists in Sweden recruited 443 consecutive patients who had had no biological treatment during the past 12 months. Following a Psoriasis Area and Severity Index (PASI) assessment, subjects completed self-assessments on health status/quality of life and a healthcare resource utilization/work status questionnaire. The costs of healthcare resources and sick-leave due to plaque psoriasis were estimated and related to the subject's health status. A patient's Dermatology Life Quality Index (DLQI) and being on systemic therapy, or having diagnosis of psoriatic arthritis, appeared to be more strongly associated with direct and indirect costs than did their PASI. The cost of biological therapy should be considered from the perspective of the already high costs of patients with high DLQI undergoing traditional systemic treatment.
  • Ekelund, Mats, et al. (författare)
  • Effects of total parenteral nutrition on lipid metabolism in rats
  • 1994
  • Ingår i: JPEN. - American Society for Parenteral and Enteral Nutrition. - 0148-6071. ; 18:6, s. 503-509
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The pathophysiologic mechanisms behind the development of liver steatosis during total parenteral nutrition (TPN) and the possible relationship to alterations of lipoprotein lipase activities in different tissues are not fully known. It is also unknown whether continuous and discontinuous administration of TPN affect lipid metabolism differently. METHODS: TPN, including 8.4 g of triglycerides per kilogram per day, was given for 10 days to two groups of male Sprague-Dawley rats that received the infusions discontinuously and continuously, respectively. Freely fed rats were used as controls. RESULTS: TPN led to hyperlipidemia and accumulation of triglycerides in the liver. High-density lipoproteins were enriched in triglycerides, whereas high-density lipoprotein cholesterol and phospholipid levels were low. The activities of hepatic lipase were markedly decreased, and lipoprotein lipase activities in adipose tissue and in cardiac muscle were both up-regulated. The increased levels of cholesterol and phospholipids in the serum of TPN animals were more pronounced after discontinuous administration. CONCLUSIONS: TPN including lipids interferes with the normal regulation of lipid metabolism. Although the mechanisms remain obscure, the elevation of lipoprotein lipase activities seems functionally important to accommodate the increased input of triglycerides during TPN. Possibly, the observed alterations in lipase activities may be attributed to a state of hypothyroidism.
  • Ekelund, Mats, et al. (författare)
  • Selective induction of inducible nitric oxide synthase in pancreatic islet of rat after an intravenous glucose or intralipid challenge.
  • 2006
  • Ingår i: Nutrition. - Elsevier. - 1873-1244. ; 22:2006 Apr 22, s. 652-660
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Constant exposure of pancreatic islets to high levels of glucose or free fatty acids can lead to irreversible beta-cell dysfunction, a process referred to as glucotoxicity or lipotoxicity, respectively. In this context a role for nitric oxide generated by pancreatic islet has been suggested. The present investigation examined whether the route of glucose administration, i.e., given orally (OG) or infused intravenously (IVG), could have any effect on the expression and activity of inducible nitric oxide synthase (iNOS) in pancreatic islets. Methods: Rats were infused with glucose (50%) or Intralipid intravenously for 24 h or given glucose orally. A freely fed control group (FF) was also included. At 24 h rats were killed and blood samples were drawn for analysis of plasma insulin, glucagon, and glucose. Pancreatic islets were harvested from each animal and investigated for the occurrence of iNOS by the use of confocal microscopy, western blot, and high-performance liquid chromatographic analysis. The effect of intravenously infused glucose was then compared with the effect of an intravenous infusion of Intralipid (IL). Results: Plasma insulin levels were markedly decreased after 24 h of infusion of glucose (IVG group) or Intralipid (IL group) compared with the FF or OG group. Plasma glucagon and glucose levels were markedly increased in the IVG group, whereas both parameters were decreased in the IL group. No significant differences in plasma insulin, glucagon, or glucose were found between the OG and FF groups. Immunocytochemical (confocal microscopy), western blot, and biochemical (high-performance liquid chromatographic) analyses showed that a sustained increase in plasma level of glucose or free fatty acids by an intravenous infusion of either nutrient for 24 h resulted in a marked expression and activity of iNOS in pancreatic islets. No sign of iNOS expression could, however, be detected in the islets of FF control or OG rats. Conclusion: The data suggest that impaired beta-cell function found after 24 It of an intravenous infusion of glucose or Intralipid might be mediated, at least in part, by the induction of iNOS in pancreatic islets. This may subsequently result in an exclusive production of nitric oxide, which is deleterious for beta-cells. (C) 2006 Elsevier Inc. All rights reserved.
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