| 11. |
- van Baarlen, Peter, et al.
(författare)
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Differential NF-κB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance
- 2009
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - Washington, DC : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:7, s. 2371-2376
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Tidskriftsartikel (refereegranskat)abstract
- How do we acquire immune tolerance against food microorganisms and commensal bacteria that constitute the intestinal microbiota? We investigated this by stimulating the immune system of adults with commensal Lactobacillus plantarum bacteria. We studied the in vivo human responses to L. plantarum in a randomized double-blind placebo-controlled cross-over study. Healthy adults ingested preparations of living and heat-killed L. plantarum bacteria. Biopsies were taken from the intestinal duodenal mucosa and altered expression profiles were analyzed using whole-genome microarrays and by biological pathway reconstructions. Expression profiles of human mucosa displayed striking differences in modulation of NF-kappaB-dependent pathways, notably after consumption of living L. plantarum bacteria in different growth phases. Our in vivo study identified mucosal gene expression patterns and cellular pathways that correlated with the establishment of immune tolerance in healthy adults.
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| 12. |
- Veldhorst, Margriet A. B., et al.
(författare)
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Comparison of the effects of a high- and normal-casein breakfast on satiety, 'satiety' hormones, plasma amino acids and subsequent energy intake
- 2009
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Ingår i: British Journal of Nutrition. - Cambridge : Cambridge University Press. - 0007-1145 .- 1475-2662. ; 101:2, s. 295-303
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Tidskriftsartikel (refereegranskat)abstract
- The present study compared the effects of a high- and normal-casein-protein breakfast on satiety, 'satiety' hormones, plasma amino acid responses and subsequent energy intake. Twenty-five healthy subjects (BMI 23.9 (SEM 0.3) kg/m2; age 22 (SEM 1) years) received a subject-specific standardised breakfast (20% of daily energy requirements): a custard with casein as the single protein source with either 10, 55 and 35 (normal-casein breakfast) or 25, 55 and 20 (high-casein breakfast) % of energy (En%) from protein, carbohydrate and fat respectively in a randomised, single-blind design. Appetite profile (visual analogue scale; VAS), plasma glucose, insulin, glucagon-like peptide 1, ghrelin and amino acid concentrations were determined for 4 h; here the sensitive moment in time for lunch was determined. Subjects came for a second set of experiments and received the same custards for breakfast, and an ad libitum lunch was offered at 180 min after breakfast; energy intake was assessed. There were increased scores of fullness and satiety after the 25 En% casein-custard compared with the 10 En% casein-custard, particularly at 180 min (26 (SEM 4) v. 11 (SEM 5) mm VAS; P<0.01) and 240 min (13 (SEM 5) v. -1 (SEM 5) mm VAS; P<0.01). This coincided with prolonged elevated plasma amino acid concentrations; total amino acids and branched-chain amino acids were higher after the 25 En% casein-custard compared with the 10 En% casein-custard at 180 and 240 min (P<0.001). There was no difference in energy intake (3080 (SEM 229) v. 3133 (SEM 226) kJ for 25 En% and 10 En% respectively; NS) from the ad libitum lunch. In conclusion, a breakfast with 25% of energy from casein is rated as being more satiating than a breakfast with 10% of energy from casein at 3 and 4 h after breakfast, coinciding with prolonged elevated concentrations of plasma amino acids, but does not reduce subsequent energy intake.
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| 13. |
- Veldhorst, Margriet A. B., et al.
(författare)
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Dose-dependent satiating effect of whey relative to casein or soy
- 2009
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Ingår i: Physiology and Behavior. - Amsterdam : Elsevier. - 0031-9384 .- 1873-507X. ; 96:4-5, s. 675-682
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Tidskriftsartikel (refereegranskat)abstract
- Dietary protein plays a role in body weight regulation, partly because of its effects on appetite. The objective was to compare the effects of high or normal casein-, soy-, or whey-protein breakfasts on appetite, specific hormones, amino acid responses and subsequent energy intake. Twenty-five healthy subjects (mean+/-SEMBMI:23.9+/-0.3 kg/m2; age:22+/-1 years) received standardized breakfasts: custards with either casein-, soy, or whey-protein with either 10/55/35 (normal) or 25/55/20 (high)En% protein/carbohydrate/fat in a randomized, single-blind design. Appetite profile (Visual Analogue Scales) and amino acid concentrations were determined for 4 h whereas plasma glucose, insulin, active Glucagon-like Peptide 1 (GLP-1), and active ghrelin concentrations were determined for 3 h; the sensitive moment for lunch was determined. Subjects returned for a second set of experiments and received the same breakfasts, ad lib lunch was offered 180 min later; energy intake (EI) was assessed. At 10En%, whey decreased hunger more than casein or soy (p <0.05), coinciding with higher leucine, lysine, tryptophan, isoleucine, and threonine responses (p<0.05). At 25En% there were no differences in appetite ratings. Whey triggered the strongest responses in concentrations of active GLP-1 (p<0.05) and insulin (p<0.05) compared with casein and/or soy. There were no differences in EI. In conclusion, differences in appetite ratings between different proteins appeared at a normal concentration; at 10En% whey-protein decreased hunger more than casein- or soy-protein. At 25En% whey-protein triggered stronger responses in hormone concentrations than casein- or soy-protein. The results suggest that a difference in appetite ratings between types of protein appears when certain amino acids are above and below particular threshold values.
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| 14. |
- Willing, Ben, et al.
(författare)
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Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease
- 2009
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Ingår i: Inflammatory Bowel Diseases. - New York : John Wiley & Sons. - 1078-0998 .- 1536-4844. ; 15:5, s. 653-660
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Large interindividual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease (CD).METHODS: To reduce variations in exposure during establishment of the gut flora and the influence of genotype, we studied the mucosa-associated microbiota of monozygotic twin pairs that were discordant (n = 6) or concordant (n = 4) for CD. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing, and quantitative real-time polymerase chain reaction (PCR).RESULTS: The microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal CD had a dramatically lower abundance (P < 0.001) of Faecalibacterium prausnitzii and increased abundance (P < 0.03) of Escherichia coli compared to healthy co-twins and those with CD localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype.CONCLUSIONS: The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal CD phenotype, distinct from colonic CD, and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of CD and eventually customized treatment.
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| 15. |
- Rajani, Rupesh, et al.
(författare)
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Budd-Chiari syndrome in Sweden : epidemiology, clinical characteristics and survival - an 18-year experience
- 2009
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Ingår i: Liver international (Print). - Oxford : Blackwell Munksgaard. - 1478-3223 .- 1478-3231. ; 29:2, s. 253-259
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The exact incidence and prevalence of Budd-Chiari syndrome (BCS) is unknown in the general population. Published reports differ in terms of the clinical characteristics, effects of therapy and survival. AIMS: To investigate the epidemiology, clinical presentation and survival in patients with BCS. METHODS: Retrospective multicentre study in Sweden reviewing the medical records of all patients with BCS 1986-2003, identified from the computerised diagnosis database of 11 hospitals, including all university hospitals and liver transplantation centres. RESULTS: Forty-three patients with BCS were identified, of whom nine (21%) had concomitant portal vein thrombosis. The mean age-standardised incidence and prevalence rates in 1990-2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. Myeloproliferative disorders (38%), thrombophilic factors (31%) and oral contraceptives (30%) were common aetiological factors. Two or more risk factors were present in 44%. In 23%, no risk factor was evident. The median follow-up time was 2.7 years. Seventy-two percent were on anticoagulant therapy during follow-up. Transjugular intrahepatic portosystemic shunting, surgical shunting procedures and liver transplantation were performed in 4, 6 and 18 patients respectively. Nineteen patients died. The overall transplantation-free survival at 1, 5 and 10 years was 47, 28 and 17% respectively. CONCLUSIONS: Budd-Chiari syndrome is a rare disorder; the mean age-standardised incidence and prevalence rates in Sweden in 1990-2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. The presence of a myeloproliferative disorder was a common aetiological factor in our cohort and about half of the patients had a multifactorial aetiology. The transplantation-free survival was poor.
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| 16. |
- Gustafsson, U. O., et al.
(författare)
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Haemoglobin A1c as a predictor of postoperative hyperglycaemia and complications after major colorectal surgery
- 2009
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Ingår i: British Journal of Surgery. - Oxford : Blackwell. - 0007-1323 .- 1365-2168. ; 96:11, s. 1358-1364
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hyperglycaemia following major surgery increases morbidity, but may be improved by use of enhanced-recovery protocols. It is not known whether preoperative haemoglobin (Hb) A1c could predict hyperglycaemia and/or adverse outcome after colorectal surgery. METHODS: Some 120 patients without known diabetes underwent major colorectal surgery within an enhanced-recovery protocol. HbA1c was measured at admission and 4 weeks after surgery. All patients received an oral diet beginning 4 h after operation. Plasma glucose was monitored five times daily. Patients were stratified according to preoperative levels of HbA1c (within normal range of 4.5-6.0 per cent, or higher). RESULTS: Thirty-one patients (25.8 per cent) had a preoperative HbA1c level over 6.0 per cent. These had higher mean(s.d.) postoperative glucose (9.3(1.5) versus 8.0(1.5) mmol/l; P < 0.001) and C-reactive protein (137(65) versus 101(52) mg/l; P = 0.008) levels than patients with a normal HbA1c level. Postoperative complications were more common in patients with a high HbA1c level (odds ratio 2.9 (95 per cent confidence interval 1.1 to 7.9)). CONCLUSION: Postoperative hyperglycaemia is common among patients with no history of diabetes, even within an enhanced-recovery protocol. Preoperative measurement of HbA1c may identify patients at higher risk of poor glycaemic control and postoperative complications.
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| 17. |
- Hörer, Tal M., 1971-, et al.
(författare)
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Complications but not obesity or diabetes mellitus have impact on the intraperitoneal lactate/pyruvate ratio measured by microdialysis
- 2010
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 45:1, s. 115-121
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Studies have shown a higher risk of postoperative complications in diabetic and obese patients. An increased intraperitoneal lactate/pyruvate ratio as measured by microdialysis has been reported before postoperative complications have been discovered. It is not known whether diabetes or obesity have any influence on the intraperitoneal metabolism (lactate/pyruvate ratio, glucose, glycerol) in relation to major abdominal surgery. The aim of this study was to investigate the postoperative intraperitoneal and subcutaneous carbohydrate and fat metabolism as measured by microdialysis in obese and diabetic patients after major abdominal surgery without postoperative complications.Material and methods: Seven obese patients (body mass index > 30 kg/m(2)) and six diabetic but non-obese patients were studied up to 48 h after major abdominal surgery and were compared with 31 non-diabetic, non-obese patients, all without complications. Microdialysis was performed to measure glucose, lactate, pyruvate and glycerol intraperitoneally and subcutaneously. The lactate/pyruvate ratio was calculated.Results: The lactate/pyruvate ratio did not differ between the groups. In the diabetic patients, glucose levels were higher intraperitoneally at both Days 1 and 2 compared to controls. Higher glycerol levels were found subcutaneously in obese patients at Day 2. CONCLUSIONS: The lactate/pyruvate ratio does not increase intraperitoneally after non-complicated major abdominal surgery in diabetic and obese patients. Obese patients have increased release of free fatty acids and glycerol subcutaneously, while diabetic patients show higher glucose levels intraperitoneally than controls.
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| 18. |
- Lundin, Anna-Carin
(författare)
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Tendinosis in Trigger Finger
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Trigger finger is one of the most common hand conditions, with a prevalence of almost 3%. The aetiology remains unclear even though many causes have been suggested. The prevailing paradigm is that the pathogenesis of trigger finger is ascribed to primary changes in the first fibrous condensation of the tendon sheath (A1-pulley). Several studies have investigated pathology in the pulley, but few have investigated the tendon. The general aim of this thesis was to find out if there is pathology in the trigger finger tendon and to define it.We first looked at trigger finger tendon biopsies in a light microscope, and found that they were histologically different from healthy tendons. They showed signs of micro-ruptures, collagen degradation, increased amounts of ground substance, both hyper- and hypo-cellular areas, round active cell nuclei and absence of inflammatory cells, all similar to tendinosis. The histological picture was further assessed by using a scoring system for Achilles tendinosis. The trigger finger tendons scored high, suggesting a similar histopathology.Next, we performed a quantitative real-time polymerase chain reaction (qPCR) on trigger finger tendons. We assessed the mRNA expression of 10 genes, which have been described to be differently expressed in Achilles tendinosis (collagen 1 and 3, versican, decorin, biglycan, aggrecan, MMP-2, MMP-3, ADAMTS-5, and TIMP-3). The overall expression pattern agreed with previous studies on Achilles tendinosis, suggesting that the cellular function in trigger finger tendons is disturbed in a similar way as in Achilles tendinosis.Recent experimental and observational research has suggested potential side effects of statin treatment on tendons, but firm evidence was lacking. We performed an epidemiological study on two large population-based cohorts. Statin use was found to increase the risk of both trigger finger and tendinosis in the shoulder and Achilles tendons, especially among men. This suggests a similar pathology in trigger finger and tendinosis.We have also studied the time to treatment effect after a single injection of glucocorticoid in trigger finger. Our results suggest that 60-80% of patients can expect resolution of the triggering within 14 days, and half of them within seven days. This result allows correct information to be given to the patient and proper planning of follow-ups.In conclusion, the pathology in trigger finger tendons is similar to tendinosis in other tendons.
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| 19. |
- Åkerman, Linda, 1983-
(författare)
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Aspects of the Pre-Diabetic Period in Type 1 Diabetes
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 1 diabetes (T1D) is an autoimmune disease characterized by insulin deficiency, due to immune-mediated destruction of beta cells. Current knowledge regarding the period preceding disease onset comes, to a large extent, from studying risk cohorts based on relatives of T1D-patients, as they have an increased disease risk. Among T1D patients in general, however, few have the disease in their immediate family. It is therefore important to study risk cohorts from the general population as well. An ongoing autoimmune reaction can often be seen in the blood long before disease onset, by detection of autoantibodies directed towards beta cell antigens. By autoantibody screening among participants in the ABIS (All Babies in the South-east of Sweden) cohort, we could identify a group of children from the general population with increased risk for T1D, positive for multiple autoantibodies. They were enrolled in a 2-year prospective follow-up aiming to characterize the prediabetic period and to identify factors indicative of progression/non-progression to T1D. We assessed glucose homeostasis and autoantibody titers over time, and searched for risk-biomarkers by analyzing the expression of immune-related genes (Th1-Th2-Th3) in peripheral blood mononuclear cells (PBMC) from these children, in comparison to healthy children and newly diagnosed T1D patients. In the same groups we also compared serum micro RNA (miRNA) profiles, knowing that miRNA molecules have desirable biomarker properties. We found that two specific autoantibodies, IA2A and ZnT8A, were detected at higher concentrations in risk-individuals who progressed to overt T1D during or after the follow-up period, compared to those who still have not. We also observed disturbed glucose homeostasis long before onset in the progressors, but it was seen among those who remain symptom free as well. Further, we found support for the possible role of insulin resistance as an accelerator of the disease process. For gene expression and serum miRNA, few differences were observed between risk-individuals and healthy children overall. However, for PBMC gene expression and serum miRNA both, there were associations to beta cell function and glucose homeostasis, and for miRNA also to islet autoantibodies. Although specific profiles for prediction of disease onset or identification of risk-individuals could not be found, these results are interesting and deserve to be evaluated further. As part of another sub-study within ABIS, the effects of physical activity on glucose homeostasis were assessed in healthy schoolchildren. The level of physical activity, measured by pedometers, was related to insulin resistance and beta cell-stress, and decreased physical activity was associated with increased insulin resistance and load on the insulin-producing beta cells, already at school-age.
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| 20. |
- Nord, Maria, et al.
(författare)
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Levodopa Pharmacokinetics in Brain after Both Oral and Intravenous Levodopa in One Patient with Advanced Parkinson’s Disease
- 2017
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Ingår i: Advances in Parkinsons Disease. - : Scientific Research Publishing Inc. - 2169-9712 .- 2169-9720. ; 6:2, s. 52-66
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Tidskriftsartikel (refereegranskat)abstract
- Objective: One patient received oral levodopa during a study aiming for better understanding of the basal ganglia and of the mechanisms of deep brain stimulation of the subthalamic nucleus (STN DBS) with and without intravenous (IV) levodopa infusion in patients with Parkinson’s disease (PD). The results from oral and IV levodopa treatment are presented.Methods: Five patients with advanced PD were included in the original study. During planned STN DBS surgery microdialysis probes were implanted in the right putamen and in the right and left globus pallidus interna (Gpi). During the study, microdialysis was performed continuously and STN DBS, with and without IV levodopa infusion, was performed according to a specific protocol. After DBS surgery, but before STN DBS was started, one patient received oral levodopa/ benserazide and entacapone tablets out of protocol due to distressing parkinsonism.Results: The levodopa levels increased prompt in the central nervous system after the first PD medication intakes but declined after the last. Immediately the levodopa seemed to be metabolized to dopamine (DA) since the levels of DA correlated well with levodopa concentrations. Left STN DBS seemed to further increase DA levels in left Gpi while right STN DBS seemed to increase DA levels in the right putamen and right Gpi. There was no obvious effect on levodopa levels.Conclusions: The results indicate that PD patients still have capacity to metabolize levodopa to DA despite advanced disease with on-off symptoms and probably pronounced nigral degeneration. STN DBS seems to increase DA levels with a more pronounced effect on ipsilateral structures in striatum.
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