| 31. |
- Nilsson, Per H., et al.
(författare)
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The creation of an antithrombotic surface by apyrase immobilization
- 2010
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 31:16, s. 4484-4491
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Tidskriftsartikel (refereegranskat)abstract
- Blood incompatibility reactions caused by surfaces often involve platelet activation and subsequent platelet-initiated activation of the coagulation and complement cascades. The goal of this study was to immobilize apyrase on a biomaterial surface in order to develop an enzymatically active surface that would have the capacity to inhibit platelet activation by degrading ADP. We were able to immobilize apyrase on a polystyrene surface with preservation of the enzymatic activity. We then analyzed the hemocompatibility of the apyrase surface and of control surfaces by incubation with platelet-rich plasma (PRP) or whole blood. Monitoring of markers of platelet, coagulation, and complement activation and staining of the surfaces revealed decreased levels of platelet and coagulation activation parameters on the apyrase surface. The formation of antithrombin-thrombin and antithrombin-factor XIa complexes and the extent of platelet consumption were significantly lower on the apyrase surface than on any of the control surfaces. No significant differences were seen in complement activation (C3a levels). Staining of the apyrase surface revealed low platelet adherence and no formation of granulocyte platelet complexes. These results demonstrate that it is possible to create an antithrombotic surface targeting the ADP amplification of platelet activation by immobilizing apyrase.
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| 32. |
- Nilsson, Per, et al.
(författare)
-
IMMOBILIZATION OF APYRASE CREATES AN ANTITHROMBOTIC BIOMATERIAL SURFACE
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Blood incompatibility reactions caused by surfaces often involve platelet activation and subsequent platelet-initiated activation of the coagulation and complement cascades. The goal of this proof-of-principle study was to immobilize apyrase on a biomaterial surface in order to develop an enzymatically active surface that would have the capacity to inhibit platelet activation by degradating ADP. We were able to immobilize apyrase on a polystyrene surface with preservation of the enzymatic activity. We then analyzed the hemocompatibility of the apyrase surface and of control surfaces (serum albumin, avidin, polystyrene, and glass) by incubation with platelet-rich plasma (PRP) or whole blood. Monitoring of markers of platelet, coagulation, and complement activation and staining of the surfaces revealed decreased levels of platelet and coagulation activation parameters on the apyrase surface. The level of complex formation between antithrombin and thrombin or factor XIa and the extent of the platelet loss were significantly lower on the apyrase surface than on any of the control surfaces. No significant differences were seen in complement activation (C3a levels). Staining of the apyrase surface revealed low platelet adherence and no formation of granulocyte-platelet complexes. These results demonstrate that it is possible to create an anti-thrombotic surface targeting the ADP amplification of platelet activation by immobilizing apyrase.
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| 33. |
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| 34. |
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| 35. |
- Nordeman, Patrik, et al.
(författare)
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C-11 and F-18 Radiolabeling of Tetra- and Pentathiophenes as PET-Ligands for Amyloid Protein Aggregates
- 2016
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Ingår i: ACS Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875. ; 7:4, s. 368-373
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Tidskriftsartikel (refereegranskat)abstract
- Three oligothiophenes were evaluated as PET ligands for the study of local and systemic amyloidosis ex vivo using tissue from patients with amyloid deposits and in vivo using healthy animals and PET-CT. The ex vivo binding studies revealed that all three labeled compounds bound specifically to human amyloid deposits. Specific binding was found in the heart, kidney, liver, and spleen. To verify the specificity of the oligothiophenes toward amyloid deposits, tissue sections with amyloid pathology were stained using the fluorescence exhibited by the compounds and evaluated with multiphoton microscopy. Furthermore, a in vivo monkey PET-CT study showed very low uptake in the brain, pancreas, and heart of the healthy animal indicating low nonspecific binding to healthy tissue. The biological evaluations indicated that this is a promising group of compounds for the visualization of systemic and localized amyloidosis.
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| 36. |
- Parvin, Farjana, et al.
(författare)
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Divergent Age-Dependent Conformational Rearrangement within Aβ Amyloid Deposits in APP23, APPPS1, and AppNL-F Mice
- 2024
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Ingår i: ACS Chemical Neuroscience. - : AMER CHEMICAL SOC. - 1948-7193. ; 15:10, s. 2058-2069
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid plaques composed of fibrils of misfolded A beta peptides are pathological hallmarks of Alzheimer's disease (AD). A beta fibrils are polymorphic in their tertiary and quaternary molecular structures. This structural polymorphism may carry different pathologic potencies and can putatively contribute to clinical phenotypes of AD. Therefore, mapping of structural polymorphism of A beta fibrils and structural evolution over time is valuable to understanding disease mechanisms. Here, we investigated how A beta fibril structures in situ differ in A beta plaque of different mouse models expressing familial mutations in the A beta PP gene. We imaged frozen brains with a combination of conformation-sensitive luminescent conjugated oligothiophene (LCO) ligands and A beta-specific antibodies. LCO fluorescence mapping revealed that mouse models APP23, APPPS1, and App(NL-F) have different fibril structures within A beta-amyloid plaques depending on the A beta PP-processing genotype. Co-staining with A beta-specific antibodies showed that individual plaques from APP23 mice expressing A beta PP Swedish mutation have two distinct fibril polymorph regions of core and corona. The plaque core is predominantly composed of compact A beta 40 fibrils, and the corona region is dominated by diffusely packed A beta 40 fibrils. Conversely, the A beta PP knock-in mouse App(NL-F), expressing the A beta PP Iberian mutation along with Swedish mutation has tiny, cored plaques consisting mainly of compact A beta 42 fibrils, vastly different from APP23 even at elevated age up to 21 months. Age-dependent polymorph rearrangement of plaque cores observed for APP23 and APPPS1 mice >12 months, appears strongly promoted by A beta 40 and was hence minuscule in App(NL-F). These structural studies of amyloid plaques in situ can map disease-relevant fibril polymorph distributions to guide the design of diagnostic and therapeutic molecules.
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| 37. |
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| 38. |
- Vicari, Marco, et al.
(författare)
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Spatial multimodal analysis of transcriptomes and metabolomes in tissues
- 2024
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Ingår i: Nature Biotechnology. - : Nature Research. - 1087-0156 .- 1546-1696. ; 42:7, s. 1046-1050
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Tidskriftsartikel (refereegranskat)abstract
- We present a spatial omics approach that combines histology, mass spectrometry imaging and spatial transcriptomics to facilitate precise measurements of mRNA transcripts and low-molecular-weight metabolites across tissue regions. The workflow is compatible with commercially available Visium glass slides. We demonstrate the potential of our method using mouse and human brain samples in the context of dopamine and Parkinson’s disease.
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| 39. |
- Wierup, Per, et al.
(författare)
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The prevalence of moderate mitral regurgitation in patients undergoing CABG.
- 2009
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Ingår i: Scandinavian cardiovascular journal : SCJ. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 43:1, s. 46-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to determine the prevalence of moderate ischemic mitral regurgitation (IMR) in the contemporary CABG population. We also aimed to correlate the effective regurgitant orifice area (ERO) of any regurgitant mitral valve in patients with coronary artery disease with the semiquantitative integrated scale of IMR. DESIGN: From March 15 through June 15, 2006, 510 consecutive CABG patients in three tertiary centres were included in the study. All patients showing any sign of mitral regurgitation (MR) at the referring hospital underwent a preoperative transthoracic echocardiographic estimation of the degree of MR using the integrated scale (1-4) and ERO. RESULTS: IMR was found in 141 patients (28%). The prevalence of moderate 2+ or worse IMR was 4% (95% CI; 2.5-6.1%) and the ERO corresponding to 2+ IMR or more ranged from 5 to 30 mm(2). Fourteen patients had an ERO between 15-30 mm(2). CONCLUSIONS: According to our study, patients with moderate IMR, defined as an ERO between 15-30 mm(2), account for only 2.7% (95% CI; 1.5-4.7%) of a non-emergency CABG population.
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| 40. |
- Wiklund, Per-Gunnar, et al.
(författare)
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Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of stroke : replicated findings in two nested case-control studies based on independent cohorts.
- 2005
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 36:8, s. 1661-1665
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Impaired fibrinolytic function secondary to elevated plasminogen activator inhibitor-1 (PAI-1) levels has been implicated in ischemic stroke. PAI-1 levels are determined by genetic factors and environmental factors, triglyceride levels in particular. The aim of this study was to investigate the common functional 4/5 guanosine (4G/5G) polymorphism in the promoter region of the PAI-1 gene and the risk of stroke. METHODS: A nested case-control study design was applied, using baseline data for 2 independent cohorts obtained at population-based surveys in northern Sweden. In study A, there were 113, and in study B, there were 275 individuals without major concomitant disease at baseline who later experienced a first-ever stroke. Blood samples obtained at baseline were analyzed for potential risk factors, including the 4G/5G polymorphism of the PAI-1 gene. RESULTS: The 4G allele of the PAI-1 polymorphism was associated with an increased risk of future ischemic stroke in both studies (odds ratio [OR] of 4G homozygosity, 1.87; 95% CI, 1.12 to 3.15 in study A; OR of 4G homozygosity, 1.56; 95% CI, 1.12 to 2.16 in study B). Individuals with the combination of hypertriglyceridemia and 4G homozygosity were at the greatest risk of developing stroke. Multiple logistic regression analysis identified 4G homozygosity, systolic blood pressure, and diabetes as independent predictors of ischemic stroke. CONCLUSIONS: Identical findings in 2 independent studies strongly suggest a true and clinically important association between PAI-1 4G/5G genotype and risk of future ischemic stroke. The observed modification of the genotype effect by triglycerides may be interpreted as a gene-environment interaction.
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