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- Rein-Hedin, Erik, et al.
(författare)
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Utilizing venous occlusion plethysmography to assess vascular effects: A study with buloxibutid, an angiotensin II type 2 receptor agonist
- 2024
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Ingår i: Clinical and Translational Science. - : WILEY. - 1752-8054 .- 1752-8062. ; 17:2
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Tidskriftsartikel (refereegranskat)abstract
- Buloxibutid (also known as C21) is a potent and selective angiotensin II type 2 receptor (AT2R) agonist, in development for oral treatment of fibrotic lung disease. This phase I, open-label, pharmacodynamic study investigated vascular effects of buloxibutid in five healthy male volunteers. Subjects were administered intra-arterial infusions of buloxibutid for 5 min in ascending doses of 3, 10, 30, 100, and 200 mu g/min, infused sequentially in the forearm. Infusions of sodium nitroprusside (SNP) solution in doses of 0.8-3.2 mu g/min were administered as a positive control. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Safety and tolerability of intra-arterial administrations of buloxibutid were evaluated. Following infusion of buloxibutid in doses of 3-200 mu g/min, the range of increase in FBF was 27.8%, 17.2%, 37.0%, 28.5%, and 60.5%, compared to the respective baseline. The largest increase was observed in the highest dose group. Infusions of SNP as a positive control, increased FBF 230-320% compared to baseline. Three adverse events (AEs) of mild intensity, not related to buloxibutid or SNP, were reported for two subjects. Two of these AEs were related to study procedures. There were no clinically relevant changes in arterial blood pressure during the study period. Intra-arterial infusion of buloxibutid in low, ascending doses increased FBF, indicating that buloxibutid may be effective in conditions associated with endothelial dysfunction. Venous occlusion plethysmography was found to be a useful method to explore pharmacodynamic vascular effects of novel AT2R agonists, while avoiding systemic adverse effects.
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- Salihovic, Samira, Associate Senior Lecturer, 1985-, et al.
(författare)
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Identification and validation of a blood- based diagnostic lipidomic signature of pediatric inflammatory bowel disease
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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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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| 5. |
- Salihovic, Samira, Associate Senior Lecturer, 1985-, et al.
(författare)
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Identification and validation of a blood- based diagnostic lipidomic signature of pediatric inflammatory bowel disease
- 2024
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Ingår i: Nature Communications. - : NATURE PORTFOLIO. - 2041-1723. ; 15:1
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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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- Broman, David, 1977-, et al.
(författare)
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A comparison of two metacompilation approaches to implementing a complex domaispecific language
- 2012
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Ingår i: Proceedings of the 27th Annual ACM Symposium on Applied Computing (SAC). - New York, NY, USA : ACM. - 9781450308571 ; , s. 1919-1921
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Konferensbidrag (refereegranskat)abstract
- Operational semantics and attribute grammars are examples of formalisms that can be used for generating compilers. We are interested in finding similarities and differences in how these approaches are applied to complex languages, and for generating compilers of such maturity that they have users in industry.As a specific case, we present a comparative analysis of two compilers for Modelica, a language for physical modeling, and which contains numerous compilation challenges. The two compilers are OpenModelica, which is based on big-step operational semantics, and JModelica.org, which is based on reference attribute grammars.
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- Chang, Ya-Ting, et al.
(författare)
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Perlecan heparan sulfate deficiency impairs pulmonary vascular development and attenuates hypoxic pulmonary hypertension
- 2015
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Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 107:1, s. 20-31
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Tidskriftsartikel (refereegranskat)abstract
- Aims Excessive vascular cell proliferation is an important component of pulmonary hypertension (PH). Perlecan is the major heparan sulfate (HS) proteoglycan in the vascular extracellular matrix. It binds growth factors, including FGF2, and either restricts or promotes cell proliferation. In this study, we have explored the effects of perlecan HS deficiency on pulmonary vascular development and in hypoxia-induced PH. Methods and results In normoxia, Hspg2(Delta 3/Delta 3) mice, deficient in perlecan HS, had reduced pericytes and muscularization of intra-acinar vessels. Pulmonary angiography revealed a peripheral perfusion defect. Despite these abnormalities, right ventricular systolic pressure (RVSP) and myocardial mass remained normal. After 4 weeks of hypoxia, increases in the proportion of muscularized vessels, RVSP, and right ventricular hypertrophy were significantly less in Hspg2(Delta 3/Delta 3) compared with wild type. The early phase of hypoxia induced a significantly lower increase in fibroblast growth factor receptor-1 (FGFR1) protein level and receptor phosphorylation, and reduced pulmonary artery smooth muscle cell (PASMC) proliferation in Hspg2(Delta 3/Delta 3). At 4 weeks, FGF2 mRNA and protein were also significantly reduced in Hspg2(Delta 3/Delta 3) lungs. Ligand and carbohydrate engagement assay showed that perlecan HS is required for HS-FGF2-FGFR1 ternary complex formation. In vitro, proliferation assays showed that PASMC proliferation is reduced by selective FGFR1 inhibition. PASMC adhesion to fibronectin was higher in Hspg2(Delta 3/Delta 3) compared with wild type. Conclusions Perlecan HS chains are important for normal vascular arborization and recruitment of pericytes to pulmonary vessels. Perlecan HS deficiency also attenuates hypoxia-induced PH, where the underlying mechanisms involve impaired FGF2/FGFR1 interaction, inhibition of PASMC growth, and altered cell-matrix interactions.
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- Dalin, Peter, et al.
(författare)
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A novel infrared imager for studies of hydroxyl and oxygen nightglow emissions in the mesopause above northern Scandinavia
- 2024
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Ingår i: Atmospheric Measurement Techniques. - 1867-1381 .- 1867-8548. ; 17:5, s. 1561-1576
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Tidskriftsartikel (refereegranskat)abstract
- The paper describes technical characteristics and presents the first scientific results of a novel infrared imaging system (imager) for studies of nightglow emissions coming from the hydroxyl (OH) and molecular oxygen (O2) layers in the mesopause region (80–100 km) above northern Scandinavia. The OH imager was put into operation in November 2022 at the Swedish Institute of Space Physics in Kiruna (67.86° N, 20.42° E; 400 m altitude). The OH imager records selected emission lines in the OH(3-1) band near 1500 nm to obtain intensity and temperature maps at around 87 km altitude. In addition, the OH imager registers infrared emissions coming from the O2 IR A-band airglow at 1268.7 nm in order to obtain O2 intensity maps at a slightly higher altitude, around 94 km. This technique allows the tracing of wave disturbances in both horizontal and vertical domains in the mesopause region. Validation and comparison of the OH(3-1) rotational temperature with collocated lidar and Aura Microwave Limb Sounder (MLS) satellite temperatures are performed. The first scientific results obtained from the OH imager for the first winter season (2022–2023) are discussed.
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