| 1. |
- Elliver, Matilda, et al.
(author)
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Associations between Th1-related cytokines and complicated pediatric appendicitis
- 2024
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In: Scientific Reports. - 2045-2322. ; 14:1
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Journal article (peer-reviewed)abstract
- The pathogenesis of appendicitis is not understood fully, and the diagnosis can be challenging. Previous research has suggested an association between a T helper (Th) 1-dependent immune response and complicated appendicitis. This prospective cohort study aimed to evaluate the association between serum concentrations of the Th1-associated cytokines interleukin (IL)-1α, IL-1β, IL-2, IL-6, IL-10, IL-17A and tumor necrosis factor beta (TNF-β) and the risk of complicated appendicitis in children. Appendicitis severity was determined through histopathological examination. A total of 137 children < 15 years with appendicitis were included with a median age of 10 years (IQR 8-12); 86 (63%) were boys, and 58 (42%) had complicated appendicitis. Children with complicated appendicitis had significantly higher concentrations of serum IL-6 and IL-10, and lower of TNF-β. After adjustment for age, symptom duration, and presence of appendicolith in a multivariable logistic regression, a higher concentration of IL-6 remained associated with an increased risk of complicated appendicitis (aOR 1.001 [95% CI 1.000-1.002], p = 0.02). Serum concentrations of IL-1α, IL-1β, IL-2, IL-10, IL-17A and TNF-β were not significantly associated with the risk of complicated appendicitis. In conclusion, our results suggests that the systemic inflammatory response in complicated appendicitis is complex and not solely Th1-dependent.
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| 2. |
- Roth, Bodil, et al.
(author)
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Auto-antibodies and their association with clinical findings in women diagnosed with microscopic colitis.
- 2013
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:6
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Journal article (peer-reviewed)abstract
- Microscopic colitis (MC) is a disease manifested by diarrhoea and is divided into collagenous and lymphocytic colitis. The aetiology is unknown, but auto-immunity is suggested. Auto-antibodies have been only rarely examined in this entity. The aim of the study was to examine the prevalence of auto-antibodies, and to examine associations between the presence of antibodies and clinical findings.
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| 3. |
- Salö, Martin, et al.
(author)
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Evaluation of the microbiome in children’s appendicitis
- 2017
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In: International Journal of Colorectal Disease. - : Springer Science and Business Media LLC. - 0179-1958 .- 1432-1262. ; 32:1, s. 19-28
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Journal article (peer-reviewed)abstract
- Background/aim: The role of the microbiome has been widely discussed in the etiology of appendicitis. The primary aim was to evaluate the microbiome in the normal appendix and in appendicitis specifically divided into the three clinically and histopathologically defined grades of inflammation. Secondary aims were to examine whether there were any microbiome differences between proximal and distal appendices, and relate the microbiome with histopathological findings. Methods: A prospective pilot study was conducted of children undergoing appendectomy for appendicitis. The diagnosis was based on histopathological analysis. Children with incidental appendectomy were used as controls. The proximal and distal mucosa from the appendices were analyzed with 16S rRNA gene sequencing. Results: A total of 22 children, 3 controls and 19 appendicitis patients; 11 phlegmonous, 4 gangrenous, and 4 perforated appendices, were prospectively included. The amount of Fusobacterium increased and Bacteroides decreased in phlegmonous and perforated appendicitis compared to controls, but statistical significance was not reached, and this pattern was not seen in gangrenous appendicitis. No relation could be seen between different bacteria and the grade of inflammation, and there was a wide variation of abundances at phylum, genus, and species level within every specific group of patients. Further, no significant differences could be detected when comparing the microbiome in proximal and distal mucosa, which may be because the study was underpowered. A trend with more abundance of Fusobacteria in the distal mucosa was seen in appendicitis patients with obstruction (25 and 13 %, respectively, p = 0.06). Conclusion: The pattern of microbiome differed not only between groups, but also within groups. However, no statistically significant differences could be found in the microbiome between groups or clinical conditions. No correlation between a specific bacteria and grade of inflammation was found. In the vast majority of cases of appendicitis, changes in microbiome do not seem to be the primary event. Since there seem to be differences in microbiome patterns depending on the sample site, the exact localization of biopsy sampling must be described in future studies.
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| 4. |
- Stenberg, Pål, et al.
(author)
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Zinc is the modulator of the calcium-dependent activation of post-translationally acting thiol-enzymes in autoimmune diseases.
- 2015
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In: Medical Hypotheses. - : Elsevier BV. - 1532-2777 .- 0306-9877. ; 84:4, s. 331-335
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Journal article (peer-reviewed)abstract
- Post-translational modifications of proteins can generate antigenic conformations that may cause autoimmune diseases in persons with specific HLA-haplotypes. Monocytes and macrophages, attracted to an inflamed site, can release post-translationally acting enzymes, such as transglutaminases and peptidylarginine deiminases. In vivo, the activation of these enzymes is crucial for the further course of event. Our hypothesis is that zinc modulates the activation of these calcium-dependent thiol-enzymes. Persons with celiac disease carry antibodies against deamidated dietary gluten and against transglutaminase type 2. Similarly, antibodies against citrulline-containing peptides and against peptidylarginine deiminase are detected in patients with rheumatoid arthritis. Thus, in two major autoimmune diseases, antibodies are detected against post-translationally modified proteins and against the thiol-enzymes responsible for catalyzing the modifications. In vitro, physiological concentrations of zinc reversibly inhibit the calcium-dependent activation of transglutaminases. Zinc attenuates the calcium-induced increase in affinity between transglutaminase 2 and serum from patients with celiac disease. Peptidylarginine deiminases are also inhibited by zinc. Moreover, zinc is rapidly redistributed in animals when an infection is induced. This pathway starting with an unspecific inflammation and ending up with an immune reaction against a specific tissue constitutes a theme with variations in other autoimmune diseases, such as dermatitis herpetiformis, multiple sclerosis, and type 1 diabetes. Inhibitors against transglutaminases and peptidylarginine deiminases have a great pharmacological potential. Interestingly, a large portion of the population may have been exposed to such an inhibitor. The primary metabolite of ethanol, acetaldehyde, can probably function as an irreversible inhibitor of these enzymes by forming a hemithioacetal with the thiol group of the active site. Not surprisingly, epidemiological studies have shown that alcohol is beneficial in rheumatoid arthritis. We predict that a similar situation will be observed in multiple sclerosis. The affinity of chelators such as EDTA and EGTA for Zn(2+) is three orders of magnitude greater than that for Ca(2+). This frequently overlooked complication imposes problems in biomedical research since a restoration of the zinc level can never be achieved in a blood sample which has been anti-coagulated by calcium chelators. The new synthetic direct thrombin inhibitors may offer a better way of preventing coagulation in vitro.
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| 5. |
- Tufvesson, Hanna, et al.
(author)
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Sociodemographic Factors, Nutritional Status, and Inflammatory Markers in Patients with Postural Orthostatic Tachycardia Syndrome
- 2023
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In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 2023
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Journal article (peer-reviewed)abstract
- Objectives. Postural orthostatic tachycardia syndrome (POTS) is characterized by cardiovascular autonomic dysfunction of unknown etiology with high a prevalence of gastrointestinal symptoms. The aim of the present study was to examine sociodemographic, lifestyle, and nutritional factors as well as inflammatory markers in patients with POTS. Materials and Methods. Forty-three patients with POTS and 61 healthy controls completed questionnaires about sociodemographic factors, lifestyle habits, and gastrointestinal symptoms. Blood samples were analyzed for serum levels of cobalamins, folic acid, iron, total iron-binding capacity (TIBC), ferritin, sodium, potassium, magnesium, phosphorus, albumin, high-sensitive C-reactive protein (CRP), and 25-hydroxyvitamin D (25-OH vitamin D). Results. POTS patients were predominantly women with a lower education level and were more often working part-time, on sick leave, and living alone compared with healthy controls. They reported lower alcohol intake and physical activity levels than controls. The nutrient intake was in general similar in both groups, but POTS patients had a higher intake of different drinks and reported more gastrointestinal symptoms than controls. POTS was associated with higher CRP levels (β: 1.370; 95% CI: 0.004-2.737; p=0.049), lower albumin levels (β: -1.443; 95% CI: -2.648-(-0.238); p=0.019), and higher sodium levels (β: 1.392; 95% CI: 0.559-2.225; p=0.001). Abdominal pain (p=0.004) and intestinal symptoms' influence on daily life (p=0.025) were negatively associated with albumin levels. Abdominal pain (p=0.011), vomiting and nausea (p=0.003), and intestinal symptoms' influence on daily life (p=0.026) were associated with higher sodium levels. Serum levels representing iron and vitamin metabolism were equal between groups. Conclusions. POTS is associated with poorer sociodemographic status, but malnutrition cannot explain POTS or related gastrointestinal symptoms. Higher CRP and lower albumin levels suggest low-grade inflammation as one possible etiological factor.
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| 6. |
- Ek, Malin, et al.
(author)
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Characteristics of endometriosis : A case-cohort study showing elevated IgG titers against the TSH receptor (TRAb) and mental comorbidity
- 2018
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In: European Journal of Obstetrics, Gynecology, and Reproductive Biology. - : Elsevier BV. - 0301-2115. ; 231, s. 8-14
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Journal article (peer-reviewed)abstract
- Objectives: Endometriosis has been associated with a wide range of factors. The disease share immunological features with autoimmune diseases, and the prevalence of both hypo- and hyperthyroidism has been reported to be increased. However, the associations have to be confirmed and the mechanisms explored. The aim of this observational study was to investigate socioeconomic factors, lifestyle habits, and somatic and mental comorbidities in endometriosis compared to the general population. Study design: In all, 172 women with endometriosis completed a study questionnaire and were interviewed regarding socioeconomic factors, lifestyle habits, psychological well-being, and medical history. Bowel symptoms were measured by the Visual Analogue Scale for Irritable Bowel Syndrome (VAS-IBS). Serum was analyzed for IgG levels of TSH receptor antibodies (TRAb) and anti-thyroid peroxidase (TPO) antibodies. Women from the general population served as controls. Differences were calculated by logistic regression, adjusted for confounders. Results: Alcohol intake, leisure time physical activity, body mass index and asthma were inversely, whereas IBS was positively associated with endometriosis. Hypothyroidism and anti-TPO antibodies did not associate, but elevated TRAb antibody titers were associated with endometriosis (odds ratio (OR): 539.26; 95% confidence interval (CI): 114.29–2544.32 for highest versus lowest tertile; p for trend < 0.001). Impaired psychological well-being (p for trend = 0.003) and current intake of antidepressant medication (OR: 3.54; 95% CI: 1.22–10.28; p = 0.020) associated with endometriosis, and impaired psychological well-being correlated with all gastrointestinal symptoms measured (all p < 0.001). Conclusions: Lifestyle habits and asthma are inversely associated, and IBS and impaired psychological well-being are positively associated with endometriosis. TRAb titers are associated with endometriosis, supporting a link between endometriosis, autoimmunity and thyroid pathophysiology, although overt thyroid diseases do not associate.
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| 7. |
- Hammersjö, Rebecka, et al.
(author)
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Esophageal and gastric dysmotilities are associated with altered glucose homeostasis and plasma levels of incretins and leptin
- 2016
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In: Review of Diabetic Studies. - 1613-6071. ; 13:1, s. 79-90
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Journal article (peer-reviewed)abstract
- BACKGROUND: Gastrointestinal complications in diabetes may affect glucose and endocrine homeostasis. Glucosedependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), and leptin regulate glucose homeostasis, food intake, and gastric emptying. AIM: The aim was to investigate associations between diabetes complications and glucose homeostasis and plasma levels of GIP, GLP-1, and leptin. METHODS: Sixteen diabetes patients (seven men) were examined with gastric emptying scintigraphy and 72-h continuous subcutaneous glucose monitoring, 14 with the deep-breathing test, and 12 with esophageal manometry. A fiber-rich breakfast was given during the second day of glucose registration. Blood samples were taken 10 min and right before a fat-rich breakfast, as well as 10, 20, 30, 45, 60, 90, 120, 150, and 180 min afterwards. 20 healthy volunteers acted as controls. Plasma was analyzed regarding GIP, GLP-1, and leptin by Luminex. RESULTS: Gastroparesis lowered maximal concentration (c-max) (p = 0.003) and total area under the curve (tAUC) (p = 0.019) of glucose levels as well as d-min (p = 0.043) of leptin levels. It tended to lower baseline (p = 0.073), c-max (p = 0.066), change from baseline (dmax) (p = 0.073), and tAUC (p = 0.093) of GLP-1 concentrations. Esophageal dysmotility tended to lower tAUC of glucose levels (p = 0.063), and c-min (p = 0.065) and tAUC (p = 0.063) of leptin levels. Diabetes patients had a higher baseline concentration of glucose (p = 0.013), GIP (p = 0.023), and leptin (p = 0.019) compared with healthy subjects. CONCLUSIONS: Gastric and esophageal dysmotility are associated with both lesser increases in postprandial glucose elevations and decreased postprandial changes in GLP-1 and leptin.
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| 8. |
- Manoharan, Lokeshwaran, et al.
(author)
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An Okinawan-Based Nordic Diet Leads to Profound Effects on Gut Microbiota and Plasma Metabolites Linked to Glucose and Lipid Metabolism
- 2023
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In: Nutrients. - : MDPI. - 2072-6643. ; 15:14
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Journal article (peer-reviewed)abstract
- Dietary interventions modify gut microbiota and clinical outcomes. Weight reduction and improved glucose and lipid homeostasis were observed after adopting an Okinawan-based Nordic diet (O-BN) in individuals with type 2 diabetes. The aim of the present study was to explore changes in metabolomics and gut microbiota during O-BN and correlate changes with clinical outcomes. A total of 30 patients (17 women), aged 57.5 ± 8.2 years, diabetes duration 10.4 ± 7.6 years, 90% over-weight, were included. Participants were provided an O-BN for 12 weeks. Before and after intervention, and 16 weeks afterwards, anthropometry and clinical data were estimated and questionnaires were collected, as well as samples of blood and stool. Plasma metabolomics were determined by gas- (GC-MS) or liquid- (LC-MS) chromatography-based mass spectrometry and fecal microbiota determination was based on 16S rRNA amplicons from regions V1-V2. During the intervention, weight (6.8%), waist circumference (6.1%), and levels of glucose, HbA1c, insulin, triglycerides, and cholesterol were decreased. Of 602 metabolites, 323 were changed for any or both periods; 199 (101 lipids) metabolites were decreased while 58 (43 lipids) metabolites were increased during the intervention. Changes in glucose homeostasis were linked to changes in, e.g., 1,5-anhydroglucitol, thyroxine, and chiro-inositol. Changes of microbe beta diversity correlated positively with food components and negatively with IL-18 (p = 0.045). Abundance differences at phylum and genus levels were found. Abundances of Actinobacteria, Bacteroidetes, Firmicutes, and Verrucomicrobia correlated with anthropometry, HbA1c, lipids, inflammation, and food. Changes in metabolites and microbiota were reversed after the intervention. The O-BN-induced changes in metabolomics and gut microbiota correspond to clinical outcomes of reduced weight and inflammation and improved glucose and lipid metabolism.
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| 9. |
- Svensson, Agnes, et al.
(author)
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TSH receptor antibodies (TRAb) – A potential new biomarker for endometriosis
- 2022
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In: European Journal of Obstetrics and Gynecology and Reproductive Biology. - : Elsevier BV. - 0301-2115. ; 278, s. 115-121
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Journal article (peer-reviewed)abstract
- Objectives: The prevalence of several autoimmune diseases, including thyroid dysfunction, has been reported to be increased in patients with endometriosis. Upregulated thyroid stimulation hormone (TSH) receptors in ectopic endometrium and elevated serum titers of TSH receptor antibodies (TRAb) IgG in endometriosis patients indicates an overlap in pathophysiology. However, cross-reactivity with other antibodies must be excluded. The objective of this study was to compare the expression of autoantibodies in women with endometriosis and two control groups to evaluate the potential of TRAb IgG as a diagnostic marker for endometriosis. Study design: This cross-sectional study was carried out in 172 women with surgically confirmed endometriosis and two control groups consisting of 50 healthy blood donors and 114 women from Malmö Offspring Study consisting of people from the general population. Serum levels of thyroid hormones, TSH and TRAb autoantibodies, AXIN1, and autoantibodies against follicle stimulating hormone (FSH), human chorionic gonadotropin (hCG), luteinizing hormone (LH), and their receptors, were analyzed. The patients answered a questionnaire and estimated their gastrointestinal symptoms using the Visual Analogue Scale for Irritable Bowel Syndrome. Results: Of the endometriosis patients, 29.1 % had TRAb IgG above the present detection limit of ≥ 1.0 IE/L compared to 2.6 % of the controls from MOS (p < 0.001) and 94.5 % had levels of TRAb over the previous detection limit ≥ 0.3 IE/L compared to 7.9 % of the controls (p < 0.001). Titers of both TRAb IgG and IgM were increased in patients compared to controls from MOS and blood donors, respectively (p < 0.001). There was no increase of autoantibodies against FSH, FSH receptor (FSHR), hCG, LH, LH receptor (LHR) or TSH compared to the blood donor controls. TRAb titers did not correlate with age, disease duration, AXIN1, TSH, thyroid hormones or gastrointestinal symptoms. Conclusion: TRAb IgG and IgM are slightly elevated in patients with endometriosis with no cross-reactivity with other autoantibodies. The results indicate that TRAb is truly elevated and thereby has the potential to be used to support the diagnosing of endometriosis.
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| 10. |
- Cordeddu, Lina, et al.
(author)
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Severe gastrointestinal dysmotility developed after treatment with gonadotropin-releasing hormone analogs
- 2015
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 50:3, s. 291-299
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Journal article (peer-reviewed)abstract
- Background. Sporadic cases of abdominal pain and dysmotility has been described after treatment with gonadotropin-releasing hormone (GnRH) analogs. The aim of the present study was to scrutinize for patients with severe gastrointestinal complaints after treatment with GnRH analogs, to describe the expression of antibodies against progonadoliberin-2, GnRH1, GnRH receptor (GnRHR), luteinizing hormone (LH), and LH receptor in serum in these patients, and to search for possible triggers and genetic factors behind the development of this dysmotility. Methods. Patients suffering from prolonged gastrointestinal complaints after treatment with GnRH analogs at the Department of Gastroenterology, Skane University Hospital, were included. GnRHR and LH receptor (LHCGR) genes were exome-sequenced. Serum was analyzed by enzyme-linked immune sorbent assays for the presence of antibodies. Healthy blood donors and women treated with GnRH analogs because of in vitro fertilization (IVF) were used as controls. Results. Seven patients with severe gastrointestinal complaints after GnRH treatment were identified, of whom six suffered from endometriosis. Several variants were found within the 11 exons of LHCGR. The minor allele G, at the single nucleotide polymorphism rs6755901, was detected in homozygosity in two patients (28.5%) who had developed chronic intestinal pseudo-obstruction and in 5.5% of the IVF controls. Three patients expressed IgM antibodies against progonadoliberin-2 and three against GnRH1 (42.9%) when cut off was set to a titer >97.5th percentile in blood donors. Conclusion. A high prevalence of endometriosis, polymorphism in the LHCGR and GnRH1 and progonadoliberin-2 antibodies in serum was found among the patients with severe dysmotility after treatment with GnRH analogs.
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