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1.
  • Bergemalm, Daniel, 1977-, et al. (författare)
  • Systemic Inflammation in Preclinical Ulcerative Colitis
  • 2021
  • Ingår i: Gastroenterology. - : AGA Institute. - 0016-5085 .- 1528-0012. ; 161:5, s. 1526-1539.e9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored.Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1β, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.
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  • Salihovic, Samira, Associate Senior Lecturer, 1985-, et al. (författare)
  • Identification and validation of a blood- based diagnostic lipidomic signature of pediatric inflammatory bowel disease
  • 2024
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Improved biomarkers are needed for pediatric inflammatory bowel disease. Here we identify a diagnostic lipidomic signature for pediatric inflammatory bowel disease by analyzing blood samples from a discovery cohort of incident treatment-naïve pediatric patients and validating findings in an independent inception cohort. The lipidomic signature comprising of only lactosyl ceramide (d18:1/16:0) and phosphatidylcholine (18:0p/22:6) improves the diagnostic prediction compared with high-sensitivity C-reactive protein. Adding high-sensitivity C-reactive protein to the signature does not improve its performance. In patients providing a stool sample, the diagnostic performance of the lipidomic signature and fecal calprotectin, a marker of gastrointestinal inflammation, does not substantially differ. Upon investigation in a third pediatric cohort, the findings of increased lactosyl ceramide (d18:1/16:0) and decreased phosphatidylcholine (18:0p/22:6) absolute concentrations are confirmed. Translation of the lipidomic signature into a scalable diagnostic blood test for pediatric inflammatory bowel disease has the potential to support clinical decision making.
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4.
  • Salihovic, Samira, Associate Senior Lecturer, 1985-, et al. (författare)
  • Identification and validation of a blood- based diagnostic lipidomic signature of pediatric inflammatory bowel disease
  • 2024
  • Ingår i: Nature Communications. - : NATURE PORTFOLIO. - 2041-1723. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Improved biomarkers are needed for pediatric inflammatory bowel disease. Here we identify a diagnostic lipidomic signature for pediatric inflammatory bowel disease by analyzing blood samples from a discovery cohort of incident treatment-na & iuml;ve pediatric patients and validating findings in an independent inception cohort. The lipidomic signature comprising of only lactosyl ceramide (d18:1/16:0) and phosphatidylcholine (18:0p/22:6) improves the diagnostic prediction compared with high-sensitivity C-reactive protein. Adding high-sensitivity C-reactive protein to the signature does not improve its performance. In patients providing a stool sample, the diagnostic performance of the lipidomic signature and fecal calprotectin, a marker of gastrointestinal inflammation, does not substantially differ. Upon investigation in a third pediatric cohort, the findings of increased lactosyl ceramide (d18:1/16:0) and decreased phosphatidylcholine (18:0p/22:6) absolute concentrations are confirmed. Translation of the lipidomic signature into a scalable diagnostic blood test for pediatric inflammatory bowel disease has the potential to support clinical decision making. Diagnostic blood-based biomarkers of pediatric IBD are limited. Here, the authors demonstrate a diagnostic lipidomic signature, comprising only of two molecular lipids. Translation of this signature into a scalable test has the potential to support clinical decision making.
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5.
  • Sundström, Johan, Professor, 1971-, et al. (författare)
  • Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
  • 2019
  • Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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6.
  • Yang, H, et al. (författare)
  • Bidirectional supply of glutamine maintains enterocyte ATP content in the in vitro Ussing chamber model
  • 2000
  • Ingår i: International Journal of Colorectal Disease. - 0179-1958 .- 1432-1262. ; 15:5-6, s. 291-296
  • Tidskriftsartikel (refereegranskat)abstract
    • Glutamine is the principal energy source for enterocytes, but it is not known whether parenteral or enteral supplementation is most beneficial to gut integrity. The aim of this study was to evaluate the effects of glutamine in uni- or bidirectional supply on the viability of intestinal mucosa of starved rats during incubation in Ussing chambers. Segments of jejunum from rats starved for 48 h were randomly mounted in Ussing chambers with three nutrient solutions: Krebs buffer without glutamine, 6 mM glutamine added to the mucosal side, 6 mM glutamine added to the mucosal side and 0.6 mM glutamine to the serosal side. ATP content of the mucosa, electrophysiology, and Cr-51-ethyl-enediaminetetraacetate (EDTA) permeability were studied during 180 min of incubation. The addition of glutamine to both sides of the stripped mucosa improved ATP levels compared to the Krebs solution (P<0.05), and the addition of glutamine resulted in an increase in short circuit current (P<0.05). No significant differences were seen in Cr-51-EDTA permeability or epithelial electrical resistance. Glutamine supplementation to both the luminal and serosal side in the Ussing chamber was more effective than luminal glutamine only in maintaining ATP levels of intestinal mucosa. Bidirectional supplementation of glutamine might improve intestinal energy metabolism and viability in in vitro studies.
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7.
  • Abdalla, Maie, et al. (författare)
  • Anorectal Function After Ileo-Rectal Anastomosis Is Better than Pelvic Pouch in Selected Ulcerative Colitis Patients
  • 2020
  • Ingår i: Digestive Diseases and Sciences. - : Springer-Verlag New York. - 0163-2116 .- 1573-2568. ; , s. 250-259
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: With a lifelong perspective, 12% of ulcerative colitis patients will need a colectomy. Further reconstruction via ileo-rectal anastomosis or pouch can be affected by patients' perspective of their quality of life after surgery.AIM: To assess the function and quality of life after restorative procedures with either ileo-rectal anastomosis or ileal pouch-anal anastomosis in relation to the inflammatory activity on endoscopy and in biopsies.METHOD: A total of 143 UC patients operated with subtotal colectomy and ileo-rectal anastomosis or pouches between 1992 and 2006 at Linköping University Hospital were invited to participate. Those who completed the validated questionnaires (Öresland score, SF-36, Short Health Scale) were offered an endoscopic evaluation including multiple biopsies. Associations between anorectal function and quality of life with type of restorative procedure and severity of endoscopic and histopathologic grading of inflammation were evaluated.RESULTS: Some 77 (53.9%) eligible patients completed questionnaires, of these 68 (88.3%) underwent endoscopic evaluation after a median follow-up of 12.5 (range 3.5-19.4) years after restorative procedure. Patients with ileo-rectal anastomosis reported better overall Öresland score: median = 3 (IQR 2-5) for ileo-rectal anastomosis (n = 38) and 10 (IQR 5-15) for pouch patients (n = 39) (p < 0.001). Anorectal function (Öresland score) and endoscopic findings (Baron-Ginsberg score) were positively correlated in pouch patients (tau: 0.28, p = 0.006).CONCLUSION: Patients operated with ileo-rectal anastomosis reported better continence compared to pouches. Minor differences were noted regarding the quality of life. Ileo-rectal anastomosis is a valid option for properly selected ulcerative colitis patients if strict postoperative endoscopic surveillance is carried out.
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  • Abdalla, Maie (författare)
  • Cancer and reconstructive surgery in Inflammatory bowel disease
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Ulcerative colitis (UC) is a chronic inflammatory disease that affects the colon. According to the literature, some thirty percent of UC patients may require a subtotal colectomy and ileostomy due to failure of medical treatment, acute toxic colitis or dysplasia/cancer diagnosis. Some patients choose to get continence restored with either an ileorectal anastomosis (IRA) or an ileal pouch-anal anastomosis (IPAA). Worldwide most surgeons prefer an IPAA to an IRA, despite reports of pouchitis, impaired fertility and fecundity. Fear of recurring proctitis and fear of rectal cancer in the remaining rectum is contributing to the choice of an IPAA. Little is known regarding the outcomes of IRA compared with IPAA in UC patients. We aimed to investigate the anorectal function, quality of life (QoL), risk of failure and rectal cancer in patients with UC restored with IRA and IPAA respectively. Methods: Data about all Inflammatory bowel disease (IBD) patients was obtained from the Swedish National Patient Register (NPR) between 1964-2014 and in one study from the Linköping University Hospital medical records 2006-2012. Patients who developed cancer were identified from the Swedish National Cancer Register. We investigated the risk of cancer and inflammation, functional outcome and failure as well as the quality of life for IRA and IPAA patients. Investigation of risk for cancer in IRA and IPAA compared with the background population was performed using survival analytic techniques: uni-and multivariate regression, Kaplan Meier curves and standardized incidence ratio. Results: Twelve percent (7,889 /63,795) of UC patients required colectomy according to the NPR. The relative risk for rectal cancer among patients with an IRA was increased (SIR 8.7). However, the absolute risk was 1.8% after a mean follow up of 8.6 years and the cumulative risk 10- and 20-years after IRA was 1.6% and 5.6%, respectively. Risk factors for rectal cancer were primary sclerosing cholangitis in patients with an IRA (hazard ratio 6.12), and severe dysplasia or cancer of the colon prior to subtotal colectomy in patients with a diverted rectum in place (hazard ratio 3.67). Regarding IPAA, the relative risk to develop rectal cancer was (SIR 0.4) compared with the background population and the absolute risk was only 0.06% after a mean of 12.2 years of follow up. Among patients operated at the Linköping University Hospital: IRA patients reported better overall continence according to the Öresland score with in median3 (IQR 2–5) for IRA (n=38) and 10 (IQR 5–15) for IPAA (n=39, p<0.001). There were no major differences regarding the QoL. According to the NPR, after a median follow up of 12.4 years failure occurred in 265(32%) out of 1112 patients, of which 76 were secondarily reconstructed with an IPAA. Failure of the IPAA occurred in 103 (6%) patients with primary and in 6 (8%) patients after secondary IPAA (log-rank p=0.38). Conclusion: IRA is a safe restorative procedure for selected UC patients. Patients should be aware of the annual postoperative endoscopic evaluation with biopsies as well as the need to the use of local anti-inflammatory preparations. However, IRA should not be offered for UC patients with an associated primary sclerosing cholangitis diagnosis due to the increased risk to develop rectal cancer in their rectal mucosa. In such case, IPAA is probably the treatment of choice.  
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  • Alkaissi, Lina Y., et al. (författare)
  • Antagonism of Adherent Invasive E. coli LF82 With Human α-defensin 5 in the Follicle-associated Epithelium of Patients With Ileal Crohn’s Disease
  • 2021
  • Ingår i: Inflammatory Bowel Diseases. - : OXFORD UNIV PRESS INC. - 1078-0998 .- 1536-4844. ; 27:7, s. 1116-1127
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The first visible signs of Crohns disease (CD) are microscopic erosions over the follicle-associated epithelium (FAE). The aim of the study was to investigate the effects of human alpha-defensin 5 (HD5) on adherent-invasive Escherichia coli LF82 translocation and HD5 secretion after LF82 exposure in an in vitro model of human FAE and in human FAE ex vivo. Methods: An in vitro FAE-model was set up by the coculture of Raji B cells and Caco-2-cl1 cells. Ileal FAE from patients with CD and controls were mounted in Ussing chambers. The effect of HD5 on LF82 translocation was studied by LF82 exposure to the cells or tissues with or without incubation with HD5. The HD5 secretion was measured in human FAE exposed to LF82 or Salmonella typhimurium. The HD5 levels were evaluated by immunofluorescence, immunoblotting, and ELISA. Results: There was an increased LF82 translocation across the FAE-model compared with Caco-2-cl1 (P < 0.05). Incubation of cell/tissues with HD5 before LF82 exposure reduced bacterial passage in both models. Human FAE showed increased LF82 translocation in CD compared with controls and attenuated passage after incubation with sublethal HD5 in both CD and controls (P < 0.05). LF82 exposure resulted in a lower HD5 secretion in CD FAE compared with controls (P < 0.05), whereas Salmonella exposure caused equal secretion on CD and controls. There were significantly lower HD5 levels in CD tissues compared with controls. Conclusions: Sublethal HD5 reduces the ability of LF82 to translocate through FAE. The HD5 is secreted less in CD in response to LF82, despite a normal response to Salmonella. This further implicates the integrated role of antimicrobial factors and barrier function in CD pathogenesis.
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10.
  • Amasheh, Maren, et al. (författare)
  • Regulation of mucosal structure and barrier function in rat colon exposed to tumor necrosis factor alpha and interferon gamma in vitro : A novel model for studying the pathomechanisms of inflammatory bowel disease cytokines
  • 2009
  • Ingår i: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 44:10, s. 1226-1235
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. In Inflammatory bowel disease (IBD), elevated cytokines are responsible for disturbed intestinal transport and barrier function. The mechanisms of cytokine action have usually been studied in cell culture models only; therefore the aim of this study was to establish an in vitro model based on native intestine to analyze distinct cytokine effects on barrier function, mucosal structure, and inherent regulatory mechanisms. Material and methods. Rat colon was exposed to tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) in Ussing chambers. Transepithelial resistance (R-t) and H-3-mannitol fluxes were measured for characterization of the paracellular pathway. Transcellular transport was analyzed by horseradish peroxidase (HRP) flux measurements. Expression and distribution of tight junction proteins were characterized in immunoblots and by means of confocal laser-scanning microscopy (LSM). Results. Colonic viability could be preserved for 20 h in a specialized in vitro set-up. This was sufficient to alter mucosal architecture with crypt surface reduction. R-t was decreased (101 +/- 10 versus 189 +/- 10 Omega . cm(2)) with a parallel increase in mannitol permeability after cytokine exposure. Tight junction proteins claudin-1, -5, -7, and occludin decreased (45 +/- 10%, 16 +/- 7%, 42 +/- 8%, and 42 +/- 13% of controls, respectively), while claudin- 2 increased to 208 +/- 32%. Occludin and claudin- 1 translocated from the plasma membrane to the cytoplasm. HRP flux increased from 0.73 +/- 0.09 to 8.55 +/- 2.92 pmol . h(-1) . cm(-2). Conclusions. A new experimental IBD model with native colon in vitro is presented. One-day exposure to TNFa and IFNg alters mucosal morphology and impairs epithelial barrier function by up-regulation of the paracellular pore-former claudin-2 and down-regulation of the barrier-builders claudin-1, -5, and -7. These alterations resemble changes seen in IBD and thus underline their prominent role in IBD pathogenicity.
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  • Andersson, Magnus V., et al. (författare)
  • Kirurgi – omistligt komplement till medicinsk behandling
  • 2009
  • Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 106:45, s. 3003-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Kirurgi på rätt indikation och vid rätt tidpunkt är ett omistligt komplement till medicinsk behandling vid inflammatorisk tarmsjukdom, som förebygger sjukdomskomplikationer, förbättrar patienternas livskvalitet och ibland är livräddande. Kirurgi för ulcerös kolit görs oftast som ett tvåstegsförfarande: först kolektomi plus ileostomi med rektum lämnad intakt och i senare skede, med optimerad patient, tarmrekonstruktion anpassad efter patientens individuella livssituation. Kirurgi vid Crohns sjukdom korrigerar komplikationer (stenoser och fistlar) och sparar tarm genom begränsade resektioner och strikturplastiker. Laparoskopisk kir­urgi verkar ha viktiga fördelar vid primära tarmresektioner. Modern medicinsk behandling har förändrat indikationerna men ännu inte minskat behovet av kirurgi. Pågående antiinflammatorisk och immunmodulerande behandling är viktig att beakta i samband med kirurgi. Ett nära samspel mellan gastroenterolog och kolorektalkirurg är nödvändigt för att uppnå bästa möjliga långtidsprognos för de individer som lever med IBD.
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  • Andersson, Peter, et al. (författare)
  • Ileorectal anastomosis in comparison with ileal pouch anal anastomosis in reconstructive surgery for ulcerative colitis - a single institution experience
  • 2014
  • Ingår i: Journal of Crohn's & Colitis. - : Elsevier. - 1873-9946 .- 1876-4479. ; 8:7, s. 582-589
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION:Ileal pouch anal anastomosis (IPAA) is the standard procedure for reconstruction after colectomy for ulcerative colitis (UC). However, ileorectal anastomosis (IRA) as an alternative has, recently experienced a revival. This study from a single center compares the clinical outcomes of these procedures.METHODS:From 1992 to 2006, 253 patients consecutively underwent either IRA (n=105) or IPAA (n=148). Selection to either procedure was determined on the basis of rectal inflammation, presence of dysplasia/cancer or patient preferences. Patient-records were retrospectively evaluated. Mean follow-up time was 5.4 and 6.3 years respectively.RESULTS:Major postoperative complications occurred in 12.4% of patients after IRA and in 12.8% after IPAA (ns). Complications of any kind after IRA or IPAA, even including subsequent stoma-closure, occurred in 23.8% and 39.9% respectively (p<0.01). Estimated cumulative failure rates after 5 and 10 years were 10.1% and 24.1% for IRA and 6.1% and 18.6% for IPAA respectively (ns). The most common cause for failure was intractable proctitis (4.8%) and unspecified dysfunction (4.8%) respectively. At follow-up 76.9% of patients with IRA had proctitis and 34.1% with IPAA had pouchitis. Estimated cumulative cancer-risk after 10, 20 and 25 year duration of disease was 0.0%, 2.1% and 8.7% for IRA. Figures for IPAA were 0.7%, 1.8% and 1.8% (ns).CONCLUSION:Failure-rates did not significantly differ between patients operated with IRA or IPAA. Patients operated with IPAA had a higher cumulative number of postoperative complications. The high long-term cancer-risk after IRA indicates that this procedure should be an interim solution in younger patients.
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  • Andersson, Peter, et al. (författare)
  • Surgery in ulcerative colitis : indication and timing.
  • 2009
  • Ingår i: Digestive diseases (Basel, Switzerland). - : S. Karger AG. - 1421-9875 .- 0257-2753. ; 27:3, s. 335-340
  • Tidskriftsartikel (refereegranskat)abstract
    • Surgery continues to play an important role in the therapeutic arsenal in ulcerative colitis. In acute colitis, close collaboration between the gastroenterologist and the surgeon is pertinent. Absolute indications for surgery include toxic megacolon, perforation, and severe colorectal bleeding. In addition, surgery should always be considered upon deterioration during medical therapy. The recommended operation in acute colitis is colectomy and ileostomy, with the rectum left in situ; reconstruction is not an option in the acute setting. In chronic continuous colitis, often with long-term steroid therapy, healing conditions are poor. A staged procedure is preferred also in these cases. In cases with dysplasia, surgery should be done after verifying the dysplasia since these patients often have little symptoms from their colitis. The proctocolectomy should in these cases include total mesorectal excision. Ileal pouch-anal anastomosis is the standard bowel reconstruction in ulcerative colitis. The various options should, however, always be thoroughly discussed, considering the pros and cons in each individual patient, before a choice is made. Ileorectal anastomosis is a temporary alternative in select cases (e.g. young women not having had children). Reconstructive surgery is best done approximately 6 months after primary surgery. Surgery for ulcerative colitis should be seen as complementary to medical treatment and may prevent complications, improve the patients' quality of life and occasionally be life-saving. Correct assessment and optimised medical treatment are prerequisites for surgery on accurate indications and good surgical results. Therefore, close interactions between gastroenterologists and colorectal surgeons are mandatory for optimal patient outcome.
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  • Askarieh, Galia, 1983, et al. (författare)
  • Systemic and intrahepatic interferon-gamma-inducible protein 10 kDa predicts the first-phase decline in hepatitis C virus RNA and overall viral response to therapy in chronic hepatitis C.
  • 2010
  • Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 51:5, s. 1523-1530
  • Tidskriftsartikel (refereegranskat)abstract
    • High systemic levels of interferon-gamma-inducible protein 10 kDa (IP-10) at onset of combination therapy for chronic hepatitis C virus (HCV) infection predict poor outcome, but details regarding the impact of IP-10 on the reduction of HCV RNA during therapy remain unclear. In the present study, we correlated pretreatment levels of IP-10 in liver biopsies (n = 73) and plasma (n = 265) with HCV RNA throughout therapy within a phase III treatment trial (DITTO-HCV). Low levels of plasma or intrahepatic IP-10 were strongly associated with a pronounced reduction of HCV RNA during the first 24 hours of treatment in all patients (P < 0.0001 and P = 0.002, respectively) as well as when patients were grouped as genotype 1 or 4 (P = 0.0008 and P = 0.01) and 2 or 3 (P = 0.002, and P = 0.02). Low plasma levels of IP-10 also were predictive of the absolute reduction of HCV RNA (P < 0.0001) and the maximum reduction of HCV RNA in the first 4 days of treatment (P < 0.0001) as well as sustained virological response (genotype 1/4; P < 0.0001). To corroborate the relationship between early viral decline and IP-10, pretreatment plasma samples from an independent phase IV trial for HCV genotypes 2/3 (NORDynamIC trial; n = 382) were analyzed. The results confirmed an association between IP-10 and the immediate reduction of HCV RNA in response to therapy (P = 0.006). In contrast, pretreatment levels of IP-10 in liver or in plasma did not affect the decline of HCV RNA between days 8 and 29, i.e., the second-phase decline, or later time points in any of these cohorts. CONCLUSION: In patients with chronic hepatitis C, low levels of intrahepatic and systemic IP-10 predict a favorable first-phase decline of HCV RNA during therapy with pegylated interferon and ribavirin for genotypes of HCV.
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17.
  • Beeckmans, Dorien, et al. (författare)
  • Relationship between bile salts, bacterial translocation, and duodenal mucosal integrity in functional dyspepsia
  • 2020
  • Ingår i: Neurogastroenterology and Motility. - : WILEY. - 1350-1925 .- 1365-2982. ; 32:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Functional dyspepsia (FD) is a complex disorder, in which multiple mechanisms underlie symptom generation, including impaired duodenal barrier function. Moreover, an altered duodenal bile salt pool was recently discovered in patients with FD. We aimed to evaluate the relationship between bile salts, bacterial translocation, and duodenal mucosal permeability in FD. Methods Duodenal biopsies from patients with FD and healthy volunteers (HV) were mounted in Ussing chambers to measure mucosal resistance and bacterial passage in the absence and presence of fluorescein-conjugated Escherichia coli and glyco-ursodeoxycholic acid (GUDCA) exposure. In parallel, duodenal fluid aspirates were collected from patients and bile salts were analyzed. Key results The transepithelial electrical resistance of duodenal biopsies from patients was lower compared with HV (21.4 +/- 1.3 omega.cm(2) vs. 24.4 +/- 1.2 omega.cm(2); P = .02; N = 21). The ratio of glyco-cholic and glyco-chenodeoxycholic acid (GCDCA) to tauro- and GUDCA correlated positively with transepithelial electrical resistance in patients. Glyco-ursodeoxycholic acid slightly altered the mucosal resistance, resulting in similar values between patient and healthy biopsies (22.1 +/- 1.0 omega.cm(2) vs. 23.0 +/- 1.0 omega.cm(2); P = .5). Bacterial passage after 120 minutes was lower for patient than for healthy biopsies (0.0 [0.0-681.8] vs. 1684.0 [0.0-4773.0] E coli units; P = .02). Glyco-ursodeoxycholic acid increased bacterial passage in patient biopsies (102.1 [0.0-733.0] vs. 638.9 [280.6-2124.0] E coli units; P = .009). No correlation was found between mucosal resistance and bacterial passage. Conclusions amp; inferences Patients with FD displayed decreased duodenal mucosal resistance associated with bile salts, however, not associated with bacterial passage in vitro. In addition, the hydrophilic bile salt glyco-ursodeoxycholic acid abolished differences in mucosal resistance and bacterial passage between patient and control group.
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  • Bhattacharya, Pradyot, et al. (författare)
  • Complement opsonization of HIV affects primary infection of human colorectal mucosa and subsequent activation of T cells
  • 2020
  • Ingår i: eLIFE. - Cambridge, United Kingdom : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • HIV transmission via genital and colorectal mucosa are the most common routes of dissemination. Here, we explored the effects of free and complement-opsonized HIV on colorectal tissue. Initially, there was higher antiviral responses in the free HIV compared to complementopsonized virus. The mucosal transcriptional response at 24 hr revealed the involvement of activated T cells, which was mirrored in cellular responses observed at 96 hr in isolated mucosal T cells. Further, HIV exposure led to skewing of T cell phenotypes predominantly to inflammatory CD4+ T cells, that is Th17 and Th1Th17 subsets. Of note, HIV exposure created an environment that altered the CD8+ T cell phenotype, for example expression of regulatory factors, especially when the virions were opsonized with complement factors. Our findings suggest that HIV-opsonization alters the activation and signaling pathways in the colorectal mucosa, which promotes viral establishment by creating an environment that stimulates mucosal T cell activation and inflammatory Th cells.
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  • Biskou, Olga, et al. (författare)
  • Increased Numbers of Enteric Glial Cells in the Peyers Patches and Enhanced Intestinal Permeability by Glial Cell Mediators in Patients with Ileal Crohns Disease
  • 2022
  • Ingår i: Cells. - Basel, Switzerland : MDPI. - 2073-4409. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Enteric glial cells (EGC) are known to regulate gastrointestinal functions; however, their role in Crohns disease (CD) is elusive. Microscopic erosions over the ileal Peyers patches are early signs of CD. The aim of this work was to assess the localization of EGC in the follicle and interfollicular region of the Peyers patches and in the lamina propria and study the effects of EGC mediators on barrier function in CD patients and non-inflammatory bowel disease (non-IBD) controls. EGC markers, glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein β (S100β) were quantified by immunofluorescence and Western blotting. Both markers showed significantly more EGC in the Peyers patches and lamina propria of CD patients compared to the non-IBD controls. In CD patients there were significantly more EGC in Peyers patches compared to lamina propria, while the opposite pattern was seen in controls. Barrier function studies using Ussing chambers showed increased paracellular permeability by EGC mediators in CD patients, whereas permeability decreased by the mediators in controls. We show the accumulation of EGC in Peyers patches of CD patients. Moreover, EGC mediators induced barrier dysfunction in CD patients. Thus, EGC might have harmful impacts on ongoing inflammation and contribute to the pathophysiology of the disease.
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23.
  • Bonkhoff, A.K., et al. (författare)
  • Association of Stroke Lesion Pattern and White Matter Hyperintensity Burden With Stroke Severity and Outcome
  • 2022
  • Ingår i: Neurology. - 0028-3878. ; 99:13, s. 1364-1379
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and ObjectivesTo examine whether high white matter hyperintensity (WMH) burden is associated with greater stroke severity and worse functional outcomes in lesion pattern-specific ways.MethodsMR neuroimaging and NIH Stroke Scale data at index stroke and the modified Rankin Scale (mRS) score at 3-6 months after stroke were obtained from the MRI-Genetics Interface Exploration study of patients with acute ischemic stroke (AIS). Individual WMH volume was automatically derived from fluid-attenuated inversion recovery images. Stroke lesions were automatically segmented from diffusion-weighted imaging (DWI) images, parcellated into atlas-defined brain regions and further condensed to 10 lesion patterns via machine learning-based dimensionality reduction. Stroke lesion effects on AIS severity and unfavorable outcomes (mRS score >2) were modeled within purpose-built Bayesian linear and logistic regression frameworks. Interaction effects between stroke lesions and a high vs low WMH burden were integrated via hierarchical model structures. Models were adjusted for age, age2, sex, total DWI lesion and WMH volumes, and comorbidities. Data were split into derivation and validation cohorts.ResultsA total of 928 patients with AIS contributed to acute stroke severity analyses (age: 64.8 [14.5] years, 40% women) and 698 patients to long-term functional outcome analyses (age: 65.9 [14.7] years, 41% women). Stroke severity was mainly explained by lesions focused on bilateral subcortical and left hemispherically pronounced cortical regions across patients with both a high and low WMH burden. Lesions centered on left-hemispheric insular, opercular, and inferior frontal regions and lesions affecting right-hemispheric temporoparietal regions had more pronounced effects on stroke severity in case of high compared with low WMH burden. Unfavorable outcomes were predominantly explained by lesions in bilateral subcortical regions. In difference to the lesion location-specific WMH effects on stroke severity, higher WMH burden increased the odds of unfavorable outcomes independent of lesion location.DiscussionHigher WMH burden may be associated with an increased stroke severity in case of stroke lesions involving left-hemispheric insular, opercular, and inferior frontal regions (potentially linked to language functions) and right-hemispheric temporoparietal regions (potentially linked to attention). Our findings suggest that patients with specific constellations of WMH burden and lesion locations may have greater benefits from acute recanalization treatments. Future clinical studies are warranted to systematically assess this assumption and guide more tailored treatment decisions. © American Academy of Neurology.
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24.
  • Bonkhoff, A. K., et al. (författare)
  • Outcome after acute ischemic stroke is linked to sex-specific lesion patterns
  • 2021
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n=503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.
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25.
  • Bonkhoff, A. K., et al. (författare)
  • Sex-specific lesion pattern of functional outcomes after stroke
  • 2022
  • Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 4:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Relying on neuroimaging and clinical data of 822 acute stroke patients, Bonkhoff et al. report substantially more detrimental effects of lesions in left-hemispheric posterior circulation regions on functional outcomes in women compared to men. These findings may motivate a sex-specific clinical stroke management to improve outcomes in the longer term. Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale >2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men - women) = -0.295 (90% highest posterior density interval = -0.556 to -0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.
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26.
  • Carlsson, Anders H., et al. (författare)
  • Probiotics modulate mast cell degranulation and reduce stress-induced barrier dysfunction in vitro
  • 2013
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • BACKGROUND: Stress has well-established deleterious effects on intestinal barrier function and stressful life events are known to contribute to the development and perpetuation of inflammatory bowel diseases. Mast cells play a pivotal role in pathogenesis of stressinduced barrier dysfunction due to the release of barrier-disruptive content. Conversely, they also have recently been suggested to contribute to barrier protective properties of probiotics, through the release of 15d-PGJ2 and enhanced epithelial PPAR-γ activity. However, mechanisms remain to be elucidated.AIM: To study if probiotics can modulate mast cell mediator release, resulting in amelioration of stress-induced barrier dysfunction in vitro.METHODS: Confluent monolayers of the human colon-derived T84 epithelial cell line were co-cultured with rat basophilic leukemia (RBL)-2H3 mast cells and pretreated with probiotics (125x104 CFU/ml, 1hr) before addition of 100nM CRF to activate mast cells. Release of beta hexosaminidase, TNF-α and 15d-PGJ2 from mast cells was determined. Transepithelial resistance (TER), and permeability to microspheres (0.2μm) were measured over a 24h period. To determine dependence of PPAR-γ, monolayers were incubated with the specific PPAR-γ antagonist T0070907 before treatment with probiotics.RESULTS: CRF-induced activation of mast cells resulted in decreased TERs and increased permeability to microspheres. Both pretreatment with probiotics and filter-sterilized probiotic supernatant resulted in lower levels of mast cell-released beta hexosaminidase and TNF-α, and increased 15d-PGJ2. Furthermore, probiotics ameliorated epithelial barrier dysfunction in monolayers exposed to CRF-activated mast cells. However, when T84 monolayers were exposed to conditioned medium of CRF-activated mast cells or were incubated with T0070907, probiotics showed little or no effect.CONCLUSIONS: Probiotics modulate mast cell mediator release to a more barrier protective profile, resulting in amelioration of stress-induced epithelial barrier dysfunction, which is putatively mediated by a PPAR-γ dependent pathway.
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27.
  • Carlsson, Anders, 1980- (författare)
  • Role of mast cells and probiotics in the regulation of intestinal barrier function
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The intestinal mucosa is the largest contact area and one of the most important barriers to the outside environment. It is highly specialized in aiding us digest and absorb nutrients. It is daily exposed to several potentially dangerous substances and microorganisms, which if they were allowed to pass into the body, could give rise to diseases. Throughout the small intestine certain sites specialized in antigen sampling are found. These sites are named Peyer’s patches and are lymphoid follicles. The epithelium covering the Peyer’s patches is called follicle-associated epithelium and is specialized in antigen sampling and uptake. The special epithelium enables presentation of luminal antigen to immune cells in the underlying follicle.Persistent life stress and stressful life events affect the course of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) through largely unknown mechanisms. Regulation of epithelial permeability to antigens is crucial for the balance between inflammation and immune-surveillance, and increased intestinal permeability has been shown in patients with ulcerative colitis and Crohns disease. Vasoactive intestinal polypeptide (VIP) and corticotropin-releasing factor have been implicated as important mediators of stress-induced abnormalities in intestinal mucosal functions in animal models. Both of these mediators have been reported to regulate bowel ion secretion in humans during stress and uptake of horseradish peroxidase in rodents. Probiotics have been shown to ameliorate the deleterious effects of stress on intestinal function, but mechanisms remain to be elucidated.The aim of this thesis was to elucidate whether mast cells play an important role in intestinal barrier function during stress and inflammation. Moreover, we wanted to determine whether probiotics can ameliorate the mucosal barrier integrity during stress and inflammation.To study the function of mast cells we conducted in vitro experiments on cell lines and ex vivo experiments in Ussing chambers on mouse, rat and human intestinal tissue. The Ussing chamber technique measures electrophysiological properties of the tissue and also gives the possibility to study transcellular and paracellular passage of markers and bacteria. Immunohistology and confocal microscopy have been used to identify mast cells and receptors of interest.Our results show that stress affects the follicle-associated epithelium barrier by mechanisms involving VIP and mast cells. These findings were corroborated by the localization of VIP receptors on mucosal mast cells. Furthermore, pretreatment with probiotics was effective in protecting the gut against stress-induced intestinal barrier dysfunction and mucosal inflammation. This protection appeared to involve a mast cell and peroxisome proliferatoractivated receptor-γ dependent mechanism.
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28.
  • Casado Bedmar, Maria Teresa, 1990- (författare)
  • Neuro-immuno-regulation of inflammation in the colonic mucosa : Focus on mast cells and eosinophils in bowel disorders
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Intestinal homeostasis is key to control uptake across the mucosa and protect from harmful substances. Disturbances in the bidirectional communication between the gut and the brain are implicated in irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD), being Crohn’s disease (CD) and ulcerative colitis (UC) the two most common IBD subtypes. Although these chronic bowel-relapsing inflammatory disorders present different histopathology, they share similar pathological features. Both IBS and IBD are characterized by a disrupted intestinal barrier function, a pro-inflammatory chronic condition, and an altered gut-brain axis. Despite all the scientific effort, the sequence or exact combination of events that drive these diseases are still unknown, and so is the exact role of every single component. Growing evidence suggests altered neuro-immune interactions as a pathogenic factor.The general aim of this thesis was to elucidate the potential involvement of mast cells and eosinophils in IBS and IBD, and the neuro-immune intercellular circuit via vasoactive intestinal polypeptide (VIP) that might exacerbate mucosal inflammation and intestinal barrier disruption.Intestinal tissues from IBS, inactive IBD, healthy controls (HC), and murine colitis were collected. Electrophysiological and permeability studies were performed using the ex vivo Ussing chamber technique. Tissues were processed with immunohistological procedures to study cell numbers, activation, location, and interactions in relation to VIP.We demonstrated for the very first time an increased transcellular passage of live commensal and pathogenic bacteria through the colonic mucosa of IBS, identifying VIP as a key regulatory molecule together with mast cells activation. In vitro experiments revealed the ability of VIP to activate mast cells. Image analysis identified VIP-mast cells in closer proximity in IBD patients and murine colitis compared to controls. Communication between mast cells and VIP was shown upregulated in IBD and mice colitis via VIP receptor (VPAC)1. Similarities and differences between HC, IBS, and IBD were further studied. Results indicated a pronounced increased intestinal permeability in UC, even during remission, followed by IBS, compared to healthy controls. Surprisingly, permeability results did not correlate with mast cells, but with eosinophil number and activation. A further image analysis suggested an inhibitory effect of eosinophils and VIP on mast cells and an altered interaction between them under inflammatory conditions. Lastly, intestinal VIP levels were shown to increase in IBD patients after the treatment with biological agents and were suggested as a possible biomarker for biological treatment outcome.This thesis presents novel insights into the regulation of intestinal permeability, as well as into the pathophysiology of IBD and IBS by demonstrating the importance of neuro-immune interactions between mast cells, VIP, and eosinophils.Altogether, our findings have broadened the knowledge of neuro-immune interactions in IBS and IBD and might have the potential to onsight lead to new therapeutic approaches thereby improving the outcomes for patients suffering from these diseases.
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29.
  • Casado Bedmar, Maria Teresa, et al. (författare)
  • Upregulation of intestinal mucosal mast cells expressing VPAC1 in close proximity to vasoactive intestinal polypeptide in inflammatory bowel disease and murine colitis
  • 2019
  • Ingår i: Neurogastroenterology and Motility. - : Wiley-Blackwell Publishing Inc.. - 1350-1925 .- 1365-2982. ; 31:3
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundMast cells (MCs) and vasoactive intestinal polypeptide (VIP) have been proposed as regulators of the intestinal barrier and inflammation. Our aim was to map the distribution in inflammatory bowel disease (IBD) and murine colitis.MethodsMCs, VIP, and VIP‐receptors (VPACs) were quantified by immunofluorescence and enzyme‐immunoassay (EIA) in ileal tissues (villus epithelium (VE) and adjacent VE, ie, VE next to the follicle‐associated epithelium, (FAE)) from Crohn's disease (CD; n = 16) and non‐IBD patients, and in colonic specimens of ulcerative colitis (UC; n = 12) and healthy controls (HCs). In addition, VIP levels were measured in plasma from HCs, non‐IBD, and IBD in remission (CD n = 30; UC n = 30). Colon, ileum, and plasma from mice with dextran sulfate sodium (DSS)‐induced colitis and control mice were analyzed likewise.Key ResultsFAE‐adjacent VE in ileum of CD possessed more MCs (P < 0.05) and MCs expressing VPAC1 (P < 0.05), but not VPAC2, compared to controls. Both adjacent and regular VE of CD had more MCs co‐localizing/in close proximity to VIP (P < 0.05). In UC colon, more MCs (P < 0.0005), MCs close to VIP (P < 0.0005), and MCs expressing VPAC1 (P < 0.05) were found compared to controls. VIP levels were elevated in plasma from CD and UC compared to controls (P < 0.0005). Colon of DSS mice showed more MCs and MCs close to VIP (P < 0.05) compared to control mice. In vitro experiments revealed MCs expressing VPACs and internalized VIP after 120 minutes of VIP‐stimulation.Conclusions and InferencesCommunication between MCs and VIP is upregulated during IBD and mice colitis. In CD patients, the epithelium next to FAE seems to be more involved than the surrounding VE, suggesting increased MC‐VIP‐interactions in this intestinal region.
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30.
  • Chassaing, Benoit, et al. (författare)
  • Crohn disease-associated adherent-invasive E. coli bacteria target mouse and human Peyers patches via long polar fimbriae
  • 2011
  • Ingår i: JOURNAL OF CLINICAL INVESTIGATION. - : American Society for Clinical Investigation. - 0021-9738. ; 121:3, s. 966-975
  • Tidskriftsartikel (refereegranskat)abstract
    • Crohn disease (CD) is a multifactorial disease in which an abnormal immune response in the gastrointestinal (GI) tract leads to chronic inflammation. The small intestine, particularly the ileum, of patients with CD is colonized by adherent-invasive E. coil (AIEC) a pathogenic group of E. coil able to adhere to and invade intestinal epithelial cells. As the earliest inflammatory lesions are microscopic erosions of the epithelium lining the Peyers patches (PPs), we investigated the ability of AIEC bacteria to interact with PPs and the virulence factors involved. We found that AIEC bacteria could interact with mouse and human PPs via long polar fimbriae (LPF). An LPF-negative AIEC mutant was highly impaired in its ability to interact with mouse and human PPs and to translocate across monolayers of M cells, specialized epithelial cells at the surface of PPs. The prevalence of AIEC strains harboring the lpf operon was markedly higher in CD patients compared with controls. In addition, increased numbers of AIEC, but not LPF-deficient AIEC, bacteria were found interacting with PPs from Nod2(-/-) mice compared with WT mice. In conclusion, we have identified LPF as a key factor for AIEC to target PPs. This could be the missing link between AIEC colonization and the presence of early lesions in the PPs of CD patients.
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31.
  • Christerson, Ulrika, 1970-, et al. (författare)
  • Cytosolic phospholipase A2 and activity upon stimulation with A23187, trypsin and TNF-2 (cPLA2) and calcium-independent2 (iPLA2) in the human mast cell line HMC-1
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background    : Mast cells (MC) are considered to be involved in the pathogenesis of Crohn´s disease (CD). A key regulatory event in the production of eicosanoids in MC is the mobilization of arachidonic acid (AA) by the action of phospholipases A2 (PLA2s). The expression of protease activated receptor-2 (PAR-2) is increased on intestinal mast cells in CD, but it is not known if this receptor may influence the PLA2 activity in MC. Although extensively studied in rodent mast cells, not much is known about the PLA2s in human mast cells. The principle aims of the present study were to investigate if the cell line HMC-1 could serve as a model for studies on cytosolic PLA2 (cPLA2) and calcium-independent PLA2 (iPLA2) in human mast cells, and if stimulation of PAR-2 may influence the activity of the two enzymes. Methods: A human mast cell line, HMC-1, was used for the studies. PLA2 activity was analyzed by quantification of radiolabeled fatty acids. PLA2 expression was investigated by RT-PCR and immunocytochemistry. Results: A23187 and the PAR-2-activator trypsin induced a fatty acid release that was not restricted to AA. Only the A23187-induced AArelease was reduced by a combined cPLA2 and iPLA2 inhibitor and by a specific iPLA2 inhibitor. The protein expression of cPLA2, as determined by immunocytochemistry, was very low compared to the expression of iPLA2. TNF-α specifically increased the cPLA2 mRNA expression but had no effect on the protein expression of the PLA2s, as determined by immunocytochemistry. Conclusions: Stimulation with a calcium ionophore may activate iPLA2-dependent AA release, but neither cPLA2 nor iPLA2 seems to be involved in PAR-2-stimulated AA release. TNF-α stimulates cPLA2 mRNA expression, but does not influence the immunocytochemically detected protein level. The expression of cPLA2 and iPLA2 in HMC-1 cells, together with its ability to release radiolabeled fatty acids upon stimulation, makes this cell line a promising model for further studies on cPLA2 and iPLA2 in human MCs. 
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32.
  • Christerson, Ulrika, 1970-, et al. (författare)
  • Group IIA secretory phospholipase A2 (sPLA2- IIA) and group V secretoryphospholipase A2 (sPLA2-V) in the human mast cell line HMC-1
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Mast cells (MC) are considered to be major effector cells in the pathophysiology of Crohn´s disease (CD). The variety of agents released from activated MC includes secretory phospholipase A2s (sPLA2s), small enzymes known to have both autocrine and paracrine actions of potential importance in inflammatory conditions. The expression of protease-activated receptor-2 (PAR-2) is increased on ileal mucosal MC in CD, however it is not known if this receptor influences the release of sPLA2s from MC. Despite extensive studies in rodent MC, not much is known about sPLA2s in human MC. The principle aims of this study were to investigate if the human mast cell line HMC-1 could serve as a model for studies on two sPLA2s implicated in inflammation, namely sPLA2-IIA and sPLA2-V, and if stimulation of PAR-2 influences the release of the two enzymes.Methods: HMC-1 cells were used for studies on sPLA2 expression by RT-PCR and immunocytochemistry. Degranulation and sPLA2 release was investigated by β-hexosaminidase assay and ELISA, respectively. sPLA2 expression in ileal CD specimens was investigated by immunohistochemistry. Results: In HMC-1 cells the basal expression of sPLA2-IIA seemed to be more pronounced than of sPLA2-V but only sPLA2-V was induced by TNF-α. A23187, but not the PAR-2 stimulator trypsin, caused release of the two enzymes. Both sPLA2-IIA and -V were detected in ileal MC of the CD specimens, but sPLA2-IIA seemed to be more abundant. Conclusions: HMC-1 cells express both sPLA2-IIA and sPLA2-V but the expression may bedifferently regulated by inflammatory cytokines. HMC-1 cells release sPLA2-IIA and sPLA2-V upon appropriate stimulation, although not by PAR-2 stimulation. These results make HMC-1 promising as a model for studies on these two enzymes in human MC. Indeed, the finding that both sPLA2-IIA and sPLA2-V are present in ileal MC in CD strengthens the relevance of such a model.
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33.
  • Christerson, Ulrika, et al. (författare)
  • Increased expression of protease-activated receptor-2 in mucosal mast cells in Crohn's ileitis
  • 2009
  • Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press (OUP). - 1873-9946 .- 1876-4479. ; 3:2, s. 100-108
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aimsActivation of protease-activated receptor-2 (PAR-2) may stimulate various events of importance in inflammatory processes, including release of inflammatory mast cell mediators. PAR-2 is frequently up-regulated during inflammatory conditions, but it is not known if the expression is altered in Crohn's disease. The aim of the present study was to investigate the ileal mucosal PAR-2 expression in Crohn's ileitis, with particular emphasis on the expression in ileal mucosal mast cells.MethodsSurgical specimens from the distal ileum were collected from patients with Crohn's ileitis and patients with colonic cancer as controls. The overall expression of PAR-2 was investigated by Western blot, and the presence of PAR-2 expressing mucosal mast cells by immunohistochemistry and cell counting. The effect of tumor necrosis factor-α (TNF-α) on the PAR-2 expression in a human mast cell line (HMC-1) was investigated by RT-PCR and immunocytochemistry.ResultsIn Crohn's specimens, the fraction of PAR-2-expressing mucosal mast cells was increased about 2.5 times (P < 0.001; n = 14) compared with specimens from control patients (n = 6). No difference was found between inflamed (n = 6) and uninflamed Crohn's specimens (P > 0.05; n = 8). Exposure to TNF-α for 48 h up-regulated PAR-2 mRNA and protein expression in the HMC-1 cell line.ConclusionPAR-2 is up-regulated on ileal mucosal mast cells in Crohn's ileitis, possibly due to the action of inflammatory cytokines, such as TNF-α. This may contribute to perpetuating the inflammatory process in the intestinal mucosa in Crohn's ileitis.
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34.
  • Christerson, Ulrika, 1970-, et al. (författare)
  • Possible Involvement of Intracellular Calcium-Independent Phospholipase A(2) in the Release of Secretory Phospholipases from Mast Cells-Increased Expression in Ileal Mast Cells of Crohn's Disease
  • 2019
  • Ingår i: Cells. - : MDPI. - 2073-4409. ; 8:7, s. 1-15
  • Tidskriftsartikel (refereegranskat)abstract
    • Increased activity of secretory phospholipases A(2) (sPLA(2)) type-II was previously observed in ileum of Crohn's disease (CD). Our aims were to explore the involvement of calcium-independent (i)PLA(2 beta) in the release of sPLA(2)s from the human mast cell (MC) line (HMC-1) and investigate expressions of cytosolic (c)PLA(2) alpha, iPLA(2)beta, sPLA(2)-IIA and sPLA(2)-V in MCs of CD ileum. The release of sPLA(2) was investigated in HMC-1 by immunocytochemistry and ELISA. The expression intensities of PLA(2)s in mucosal MCs, and the proportion of PLA(2)-positive MCs, were investigated in normal ileum and in ileum from patients with CD by immunohistochemistry. The calcium ionophore-stimulated release of sPLA(2)-IIA and sPLA(2)-V from HMC-1 was reduced by the iPLA(2)-inhibitor bromoenol lactone. All four PLA(2)s were detectable in mucosal MCs, both in normal ileum and in CD, but the proportion of iPLA(2)beta-containing mucosal MCs and the expression intensity of sPLA(2)-IIA was increased in CD. Results indicate that iPLA(2)beta is involved in the secretion of sPLA(2)s from HMC-1, and suggest that iPLA(2)beta-mediated release of sPLA(2) from intestinal MCs may contribute to CD pathophysiology. Ex vivo studies on isolated mucosal mast cells are however needed to clarify the precise role of MC PLA(2)s in the inflammatory processes of CD.
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35.
  • Christerson, Ulrika, et al. (författare)
  • Potential role of protease-activated receptor-2-stimulated activation of cytosolic phospholipase A2 in intestinal myofibroblast proliferation : Implications for stricture formation in Crohn´s disease
  • 2009
  • Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press (OUP). - 1873-9946 .- 1876-4479. ; 3:1, s. 15-24
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aimsMyofibroblast hyperplasia contributes to muscularis mucosae thickening and stricture formation in Crohn's disease (CD). Protease-activated receptor-2 (PAR-2) and cytosolic phospholipase A2 (cPLA2) are known regulators of cell growth, but their significance in intestinal myofibroblast proliferation remain to be elucidated. The principle aims of the present study were to investigate if PAR-2 is expressed in the expanded muscularis mucosa in ileal CD specimens, if inflammatory cytokines may stimulate PAR-2 expression in intestinal myofibroblasts, and if PAR-2 and cPLA2 may regulate intestinal myofibroblast growth.MethodsImmunohistochemistry was used for detection of PAR-2 in ileal CD specimens. Studies on PAR-2 expression, PLA2 activation and cell growth were performed in a human intestinal myofibroblast cell line, CCD-18Co. PAR-2 expression was investigated by RT-PCR and immunocytochemistry. PLA2 activity was analyzed by quantification of released 14C-arachidonic acid (14C-AA). Cell growth was examined by 3H-thymidine incorporation and cell counting.ResultsThe thickened muscularis mucosae of the CD specimens showed strong PAR-2 expression. In cultured myofibroblasts, tumor necrosis factor-α (TNF-α) up-regulated PAR-2 mRNA and protein, and potentiated PAR-2-stimulated 14C-AA release by two known PAR-2 activators, trypsin and SLIGRL-NH2. The release of 14C-AA was dependent on cPLA2. Trypsin stimulated the proliferation of serum-starved cells, and inhibition of cPLA2 reduced normal cell growth and abolished the growth-promoting effect of trypsin.ConclusionsThe results suggest that PAR-2-mediated cPLA2 activation might be of importance in intestinal myofibroblast proliferation. The results also point to the possibility that PAR-2 up-regulation by inflammatory cytokines, like TNF-α, may modulate this effect.     
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36.
  • Da Silva, Stéphanie, et al. (författare)
  • A novel topical PPARγ agonist induces PPARγ-activity in ulcerative colitis mucosa and prevents and reverses inflammation in induced-colitis models
  • 2018
  • Ingår i: Inflammatory Bowel Diseases. - : Lippincott Williams & Wilkins. - 1078-0998 .- 1536-4844. ; 24:4, s. 792-805
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Peroxisome proliferator-activated receptor-gamma (PPARγ) exerts anti-inflammatory effects and is therefore a potential target in ulcerative colitis (UC). A novel PPARγ agonist (AS002) developed for local action was evaluated ex vivo in biopsies from UC patients and in vivo in mice with low-grade dextran sodium sulfate (DSS)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis.Methods: Colonic biopsies from UC patients (n = 18) and healthy controls (n = 6) were incubated with AS002 or rosiglitazone (positive control) to measure mRNA expression of the PPARγ-responsive gene ADIPOPHILIN and protein levels of UC-related cytokines (enzyme-linked immunosorbent assay). AS002 absorption was determined in the colonic mucosa of UC patients. DSS-colitis mice received PPARγ agonists or vehicle daily by intrarectal administration starting 2 days before induction of colitis (preventive) or from days 3 to 8 (curative). Myeloperoxidase (MPO) and cytokine levels in colonic mucosa were determined. In addition, AS002 effects were studied in TNBS colitis.Results: AS002 displayed an absorption pattern of a lipophilic drug totally metabolized in the mucosa. AS002 and rosiglitazone increased ADIPOPHILIN mRNA expression (3-fold) and decreased TNF-α, IL-1β, and IL-13 levels in human UC biopsies. In DSS, in both preventive and curative treatment and in TNBS colitis, AS002 protected against macroscopic and histological damage and lowered MPO and TNF-α, IL-1β, and IL-13 levels.Conclusions: AS002 triggers anti-inflammatory PPARγ activity in the human colonic mucosa of UC patients and prevents and reverses colitis in mice. Our data suggest that AS002 has potential for topical maintenance treatment of UC, which warrants further studies in vivo in patients.
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37.
  • Dabrosin-Söderholm, Johan, 1958- (författare)
  • Epithelial barrier dysfunction in ileal Crohn's disease
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The study aimed at investigating the intestinal barrier in Crohn's disease, with special reference to epithelial responses to luminal stimuli, and to permeation of proteins.Ileal mucosa from patients undergoing intestinal resection was studied in vitro in Ussing chambers. Intestinal permeability was also studied in vivo, by oral load of lactulose and mannitol.The Ussing chamber was evaluated for intestinal barrier studies. Normal ileal mucosa from patients with colon cancer was subjected to long-term experiments, and investigated in regard to various viability parameters. Mucosal permeability, structural integrity and metabolism were maintained for 90 minutes, and specimens with poor viability were detected by a low transepithelial potential difference. In rat ileal mucosa, luminal sodium caprate, a constituent of milk fat, induced dilatation of the tight junctions as visualised by electron microscopy, and a reversible increase in tight junction permeability. The findings indicate that the Ussing chamber is suitable for studies of the intestinal barrier, including tight junction regulation, provided that experiments are monitored by measurements of transepithelial potential difference and are limited in time.In vitro studies of human ileal mucosa showed that luminal sodium caprate caused uncoupling of oxidative phosphorylation, as shown by a fall in epithelial ATP contents, and mitochondrial swelling seen by electron microscopy, paralleled by an increased permeability. Non-inflamed Crohn's disease specimens had an exaggerated permeability increase and an augmented fall in transepithelial electrical resistance. Confocal microscopy revealed rearrangements of perijunctional filamentous actin, causing dilatation of the tight junctions. In Crohn's disease, a more pronounced reorganisation of actin filaments was seen, suggesting the tight junctions to be hyperreactive to luminal stimuli due to a disturbed cytoskeletal regulation.In vivo, an increased intestinal permeability was induced by ingestion of acetylsalicylic acid. One third of both Crohn's disease patients and their first-degree relatives showed an augmented permeability increase, whereas spouses were equal to controls, suggesting a genetically determined vulnerability of the intestinal barrier.In vitro, non-inflamed ileum from Crohn's disease patients had an increased permeation of ovalbumin. Confocal microscopy suggested this to be caused by an augmented transcytosis, a previously unrecognised defect in the epithelial barrier in Crohn's disease, with a subsequent exposure of antigenic proteins to the subepithelial immunocytes.The Crohn's disease patients without residual inflammation after surgery were followed with endoscopy within twelve months, and all revealed recurrent ileal inflammation.The study indicates a perturbed intestinal barrier in Crohn's disease, possibly genetically determined. The impaired barrier function is demonstrated both by an augmented epithelial transcytosis and by hyperreactive tight junctions. The epithelial barrier dysfunction precedes the recurrent intestinal inflammation in ileal Crohn's disease. The findings suggest an interplay between an impaired epithelial barrier and luminal factors in the initiation of intestinal inflammation.
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38.
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39.
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40.
  • Ellegård, Rada, 1985- (författare)
  • Effects of Complement Opsonization of HIV on Dendritic Cells : and Implications for the Immune Response
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Dendritic cells are key players during HIV pathogenesis, and shape both the immediate immune response at the site of infection as well as directing the adaptive immune response against the virus. HIV has developed a plethora of immune evasion mechanisms that hijack dendritic cell functions, suppressing their ability to mount an accurate immune response and exploiting them for efficient viral transfer to target T cells.To achieve successful replication within dendritic cells without triggering danger signaling, HIV accomplishes a delicate balance where only a low level of transcription can be sustained without triggering antiviral responses that would harm the virus. Here, we describe how the presence of HSV2 coinfection, which is very common in geographic areas with a high HIV prevalence and almost triples the risk of HIV acquisition, alters dendritic cell state to support much higher levels of HIV infection. We found this effect to be mediated by the STING pathway, which is involved in the sensing of DNA in the cell cytosol. STING activation led to an upregulation of factors such as IRF3 and NFkB that can be used for HIV transcription and a degradation of factors that restrict HIV replication.In addition, we describe how HIV exploits the human complement system, a group of proteins that usually help the human body to identify dangerous pathogens while avoiding reaction towards self. HIV can coat itself, i.e. become opsonized, in complement fragments that are typically only present on the body’s own cells, allowing it to activate signaling pathways that are associated with tolerance. Dendritic cells that come into contact with complement opsonized HIV do not mount danger responses, despite the fact that HIV-derived single stranded RNA triggers the pathogen recognition receptor TLR8. The suppression of danger responses is mediated by activation of complement receptor 3, and leads to an increased infection of the dendritic cell and affects its interactions with other immune cells. There is a lack of recruitment of NK cells to the site of infection, and an inhibition of NK cell killing, which plays an important role in the destruction of HIV-infected cells in vivo. T cells primed by dendritic cells exposed to complement opsonized HIV have a lower ability to develop towards effector phenotype, and have an increased expression of the markers PD1, TIM3 and LAG3 which are associated with T cell dysfunction and exhaustion. In addition, T cells primed by these dendritic cells in the presence of NK cells upregulate markers CD38, CXCR3 and CCR4, which have been linked to an increased susceptibility to HIV infection.In summary, we add to the current knowledge on HIV immune evasion mechanisms that allow the virus to establish infection, as well as describing mechanisms that govern whether dendritic cells mount danger signaling and an immune response or not.  
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41.
  • Emami, Nazanin, et al. (författare)
  • Cure kinetic behavior of light-cure dental composites
  • 2003
  • Ingår i: Journal of Dental Research. - 0022-0345 .- 1544-0591. ; :Suppl.
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Objective: To investigate differences in cure kinetic behaviours of different photo and co-initiator systems used in dental light-cure composites. Method: A resin system (50 wt.% of bisGMA and 50 wt.% of TEGDMA) was mixed with either campherquinone (CQ) or 1-phenyl-1,2-propanedione (PPD) as photo-initiator. N,N-dimethyl-p-aminobenzoic acid ethylester (DABE), N,N-cyanoethylmethylaniline (CEMA), N,N-diethanol-p-toluidine (DEPT) and 2-dimethylaminoethyl methacrylate (DMAEMA) were used as co-initiators respectively. Complex cure behaviour of 24 experimental mixtures made from 2 photoinitiators, 4 co-initiators, 3 curing light/time was studied with differential Scanning Calorimetery (DSC). Six specimens of each composition were cured either with 800 mW/cm2 for 40 s, soft start curing for 60 s or LED for 40 s. The DSC results were analysed using ANOVA and Duncan's multiple range test and regular t-test. Result: Rate of polymerisation was significantly (p<0.05) higher when materials were cured with 800 mW/cm2 compare to soft start and LED curing methods when the final degree of conversion values did not differ significantly (p>0.05). Compared to campherquinone, the photo-initiator PPD reduced the maximal DC% and rate of the polymerisation significantly (p<0.05). PPD was not a suitable photo-initiator when cured with LED since the blue spectra emitting from the used LED lamp does not cover the optimal activation wavelength for PPD properly. The highest DC% measured at the end of curing was for CQ & DABE 74%±1 cured with 800 mw/cm2 for 40s and the lowest was for PPD&DMAEMA 22%±1.1 when material was cured with LED for 40s. Use of DEPT resulted in significant decreases in degree of conversion (p<0.05). Conclusion: It was concluded that intrinsic slow cure might be obtained with certain compositions of photo & co-initiators and curing methods without impairing the final extent of degree polymerzation.
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42.
  • Emami, Nazanin, et al. (författare)
  • Dynamic mechanical thermal analysis of two light-cured dental composites
  • 2005
  • Ingår i: Dental Materials. - : Elsevier BV. - 0109-5641 .- 1879-0097. ; 21:10, s. 977-983
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesClinical observations suggest that some composite resins are more often linked to post-operative sensitivity than others. These differences may relate to differences in modulus of elasticity and polymerization rates among materials. The aim of this study was to identify viscoelastic behavior of two light curable composites and determine whether significant differences in viscoelastic behavior exist between the two materials when light cured at each of three different irradiance values.MethodsTwo composites (Z100 and Z250 by 3M ESPE) were evaluated. Six specimens per composite and irradiance value (250, 500 and 850 mW/cm2) were made. The curing times were chosen to produce a fixed energy value of 30 J/cm2 independent of irradiation value. Dynamic mechanical thermal analysis (DMTA) was performed in single cantilever clamped mode.ResultsThere were significant differences in transition temperatures between the two materials and the three frequencies at their glass transition temperatures, while significant differences did not exist at the lower transitions. The glass transition of Z250 was lower and narrower than that of Z100. Z250 exhibited lower storage modulus values. The irradiance values did not affect any of the transition temperatures significantly.SignificanceThe lower and more distinct Tg of Z250 suggests that Z250 cures more efficiently than Z100. The lower storage modulus of Z250 suggests that Z250 develops less stress in the tooth than Z100 during curing if shrinkage is the same for the two materials. The findings suggest that the material chosen, rather than irradiance, determines the stress level developed during light curing.
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43.
  • Emami, Nazanin, et al. (författare)
  • Effect of light intensities variations on bulk curing of dental composites
  • 2002
  • Ingår i: Journal of Dental Research. - 0022-0345 .- 1544-0591. ; 81:Suppl. 1
  • Tidskriftsartikel (refereegranskat)abstract
    • The light intensity used during curing of light curable dental composites is believed to affect the residual stress level. In this study we tested the hypothesis that low light intensity and long but clinically acceptable light curing time, can produce composites with physical/clinical properties (e.g. volumetric shrinkage, linear contraction stress, degree of conversion (DC%) and Young's modulus) comparable to those of high light intensity cured composites. Methods: Two dental composites, Z100 and Z250, were investigated. Specimens were cured with light intensities of 200, 450 and 800 mW/cm2 for 140, 60 and 35 s from a distance of 7 mm. Linear contraction strains were measured with strain-gages attached to stainless steel rings serving as molds (8 mm in diameter and 4 mm high). DC% was measured at the top and the bottom of samples as well through the bulk using FTIR. Volumetric polymerization shrinkage was determined using a water displacement method. Young's modulus was determined in tension on composite specimens with dimensions of 8 x 50 x 1 mm. Results: Polymerization stress level decreased significantly (p<0.05) when cured with 200 mW/cm2 rather than with 800 mW/cm2. Reduction in light intensity did not decrease the DC% values significantly, nevertheless the most dramatic differences existed between top and bottom surfaces (p<0.05) rather than among curing groups. Measured modulus and volumetric shrinkage values were no significantly different (p>0.05) between different light intensity groups. Conclusion: Low light intensity decreased the residual stress and DC% values (through the depth of cure) significantly (p<0.05), but did not significantly affect the Young's modulus and the volumetric shrinkage values. The lower residual stress values, reflected by lower strain levels in the metal rings used during measurement, suggest that more stress relaxation occurs in the low light intensity group during cure. Our results support the proposed hypothesis
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44.
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45.
  • Emami, Nazanin, et al. (författare)
  • Effect of light power density variations on bulk curing properties of dental composites
  • 2003
  • Ingår i: Journal of Dentistry. - 0300-5712 .- 1879-176X. ; 31:3, s. 189-196
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. The hypothesis that low light intensity and long but sufficient curing time can produce composites with volumetric shrinkage, degree of conversion (DC%) and Young's modulus (E-modulus) comparable to those of high light intensity cured composite was tested, when the contraction strain and heat generation were lower with low light intensity curing. Methods. Dental composites (Z100 and Z250, 3M ESPE) were investigated. Specimens were cured with light intensities of 200, 450 and 800 mW/cm2 for 140, 60 and 35 s from a distance of 7 mm. Strain-gages were used for contraction strain measurements. DC% was measured at the top and the bottom of 4 mm thick samples using FT-Raman spectroscopy. Volumetric polymerization shrinkage was determined using a water displacement method. E-modulus was determined in tension on composite specimens. Results. The results were analyzed using ANOVA and Duncan's multiple range tests and regular t-test. Polymerization stress level decreased significantly (p<0.05) when cured with 200 mW/cm2 rather than with 800 mW/cm2. Temperature rises were significantly different (p<0.05) for different composites and light intensity values. Reduction in light intensity did not decrease the DC% values significantly at the top surfaces. The most dramatic differences existed between top and bottom surfaces (p<0.05) rather than among curing groups. Measured E-modulus and volumetric shrinkage values were not significantly different (p>0.05) between different light intensity groups. Conclusion. DC%, E-modulus and the volumetric shrinkage values in cured composites were not affected by low light intensity, however, the contraction strain and polymerization's exotherm were decreased. Thus our results support the proposed hypothesis.
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46.
  • Emami, Nazanin, et al. (författare)
  • How degree of conversion and E-modulus of light-cure dental-resins interact
  • 2006
  • Ingår i: 84th General Session and Exhibition of the IADR and 1st Meeting of the Pan-Asian-Pacific Federation. - : IADR.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Objectives: To investigate how E-modulus, degree of conversion (DC%) and rate of polymerization of the most used monomer resins in dental light-cure composites interact. Methods: Young's modulus and DC% were studied for 21 different resin combinations of three commonly used dental monomers, bis-GMA, TEGDMA and UEDMA (combinations of 0, 20, 40, 60 and 100 wt% as it is illustrated in the figure). For each resin combination 6 specimens were tested. Small Instron and differential scanning calorimetry (photo-calorimetry) were used as testing machines. The results were tested using ANOVA and Duncan's multiple range tests and regular t-test. Results: Rate of polymerization was significantly (p<0.05) higher when the wt% of the TEGDMA was high in the mixtures compare to highly concentrated bis-GMA. DC% was significantly high (p<0.05) for binary mixture of UEDMA and TEGDMA. The DC% was significantly lower for 100 wt% bis-GMA (p<0.05). The calculated values for DC% were between 53.1%± 0.9% and 85.6%±1%. Young's modulus values varied between 2.37± 0.15 GPa and 4.15± 0.2 GPa. It was noticeable that by adding TEGDMA to bisGMA or UEDMA, the Young's modulus decreased significantly (p<0.05). There were no significant (p>0.05) differences between Young's modulus values when the monomer mixtures contained bis-GMA, TEGDMA and UEDMA at different concentration levels. The higher the concentration of bisGMA in the monomer mixture, the lower was the degree of conversion. However, Young's modulus increased at higher concentration of bis-GMA. Conclusions: The differences in the values for degree of conversion were mostly justified by the differences in the molecular structures of the different monomers. It was also revealed that higher degree of conversion does not always result in a higher Young's modulus, because molecular and network structural parameters play major roles in the final mechanical/physical properties of the mixtures.
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47.
  • Emami, Nazanin, et al. (författare)
  • How filler properties, filler fraction, sample thickness and light source affect light attenuation in particulate filled resin composites
  • 2005
  • Ingår i: Dental Materials. - : Elsevier BV. - 0109-5641 .- 1879-0097. ; 21:8, s. 721-730
  • Tidskriftsartikel (refereegranskat)abstract
    • The way by which variables such as filler type, filler surface treatment and light source affect light attenuation in particulate filled resin composites was presented. Mixture of 50 wt% bisGMA and 50wt% TEGDMA consisting of a photo-initiatior and a co-initiator was prepared. Three different filler types, HBB, SBB, and KU, which were either silane surface treated or not, were added to that mixture in eight different volume percentage. It was observed that of the two light sources, more light was absorbed by the composite when the laser light was used. It was also observed that the HBB filler absorbed most light and the KU filler the least.
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48.
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49.
  • Emami, Nazanin, et al. (författare)
  • How light irradiance and curing time affect monomer conversion in light-cured resin composites
  • 2003
  • Ingår i: European Journal of Oral Sciences. - : Wiley. - 0909-8836 .- 1600-0722. ; 111:6, s. 536-542
  • Tidskriftsartikel (refereegranskat)abstract
    • We tested the hypothesis that the degree of conversion of a light-cured dental composite relates to the calculated (s × mW cm-2 = mJ cm-2) rather than to the irradiance value (mW cm-2) of the light source. Two light-curable composite resins were cured with three different light irradiance values over different curing times. The specimens tested were 2, 4 or 6 mm thick, and the degree of conversion values were measured with Raman spectroscopy on the top and the bottom surfaces of the specimens. The highest conversion value of one of the materials was just below 60%, while the maximal conversion value of the other material was just below 65%. That difference in conversion values could be related to differences in monomer systems used in the two composites. By considering light energy per square centimeter (J cm-2) rather than light irradiance (mW cm-2), we found that equivalent energy values gave similar conversion values for a certain sample thickness. From these findings, we conclude that our experimental results support our hypothesis.
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50.
  • Emami, Nazanin, et al. (författare)
  • Influence of light-curing procedures and photo-initiator/co-initiator composition on the degree of conversion of light-curing resins
  • 2005
  • Ingår i: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 16:1, s. 47-52
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The hypothesis that the degree and rate of conversion can be modified favourably by using different light-curing procedures and different photo initiator/co-initiator combinations was tested.Method: A photo-initiator (0.02 mM/g resin); either camphorquinone (CQ) or 1-phenyl-1,2-propanedione (PPD), was mixed with bisGMA:TEGDMA (50:50 by weight). In addition, a co-initiator (0.04 mM/g resin); either N,N-dimethyl-p-aminobenzoic acid ethylester (DABE), N,N-cyanoethylmethylaniline (CEMA), or 2-dimethylaminoethyl methacrylate (DMAEMA), was added. These six combinations were subjected to three curing conditions (standard curing, soft-start curing or LED curing). The conversion levels (DC) were determined with differential scanning calorimetry (DSC). The DSC results were analysed using a general linear model (GLM) and Duncans multiple range test and regular t-test.Results: The fastest conversion initially was obtained by standard curing, followed by LED curing and soft-start curing. After 40 s of curing, conventional curing and soft-start curing produced a higher DC than LED curing. However, strong interactions occurred between the different variables (curing method, initiator and co-initiator). Initially, CQ was more efficient than PPD, but after 40 s, this difference was insignificant.Conclusion: By using soft-start curing and an appropriate photo initiator/co-initiator combination it is possible to achieve slow curing and a high DC at within a curing time of 40 s.
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