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Sökning: WFRF:(Nordenfelt Patrik) > Lunds universitet

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1.
  • Lindqvist, Anders, et al. (författare)
  • Long-term effects of Ca(2+) on structure and contractility of vascular smooth muscle
  • 1999
  • Ingår i: American Journal of Physiology: Cell Physiology. - 1522-1563. ; 277:1, s. 64-73
  • Tidskriftsartikel (refereegranskat)abstract
    • Culture of dispersed smooth muscle cells is known to cause rapid modulation from the contractile to the synthetic cellular phenotype. However, organ culture of smooth muscle tissue, with maintained extracellular matrix and cell-cell contacts, may facilitate maintenance of the contractile phenotype. To test the influence of culture conditions, structural, functional, and biochemical properties of rat tail arterial rings were investigated after culture. Rings were cultured for 4 days in the absence and presence of 10% FCS and then mounted for physiological experiments. Intracellular Ca(2+) concentration ([Ca(2+)](i)) after stimulation with norepinephrine was similar in rings cultured with and without FCS, whereas force development after FCS was decreased by >50%. The difference persisted after permeabilization with beta-escin. These effects were associated with the presence of vasoconstrictors in FCS and were dissociated from its growth-stimulatory action. FCS treatment increased lactate production but did not affect ATP, ADP, or AMP contents. The contents of actin and myosin were decreased by culture but similar for all culture conditions. There was no effect of FCS on calponin contents or myosin SM1/SM2 isoform composition, nor was there any appearance of nonmuscle myosin. FCS-stimulated rings showed evidence of cell degeneration not found after culture without FCS or with FCS + verapamil (1 microM) to lower [Ca(2+)](i). The decreased force-generating ability after culture with FCS is thus associated with increased [Ca(2+)](i) during culture and not primarily caused by growth-associated modulation of cells from the contractile to the synthetic phenotype.
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2.
  • Sundler Björkman, Linda, et al. (författare)
  • Comorbidities in hereditary angioedema—A population-based cohort study
  • 2022
  • Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 12:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In hereditary angioedema (HAE), low levels (type 1) or defect in function (type 2) of the serine-protease inhibitor C1 Inhibitor protein results in activation of the classical pathway of the complement system as well as the contact system. Here, we investigated the risk of comorbidities in HAE. Methods: Individuals with HAE (n = 239; identified through a physician made diagnosis) and a control cohort from the general population (n = 2383; matched for age, gender, and county of residence) were compared with the Swedish inpatient, cause of death, cancer, and prescription registers. Conditional logistic regression was used to analyze the data. Results: Increased risk of cardiovascular disease (odds ratio [OR] 1.83; 95% confidence interval [CI] 1.32–2.54), including arterial (OR 6.74; 95% CI 1.89–24.06) and venous thromboembolic disease (OR 4.20; 95% CI 2.42–7.23) as well as hypertension (OR 1.64; 95% CI 1.12–2.39) was seen in HAE. There was also an increased number of individuals diagnosed with hyperlipidemia (OR 2.01; 95% CI 1.16–3.50) among HAE patients. Furthermore, the risk of autoimmune disease was increased (OR 1.65; 95% CI 1.15–2.35) being particularly pronounced for systemic lupus erythematosus (OR 71.87; 95% CI 8.80–586.7). The risk of having two or more autoimmune diseases was also higher among HAE patients (p = 0.017). In contrast, the risk of cancer was not increased. Data from the prescription register revealed higher prescription rates of drugs against hypertension, hypothyroidism, and hyperlipidemia among HAE patients. Conclusions: The results warrant for awareness and prevention of comorbid conditions, in particular, thromboembolic and autoimmune diseases in HAE. Future prophylactic interventions may modify these risks.
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3.
  • Sundler Björkman, Linda, et al. (författare)
  • Trends in Treatments With Disease-Specific and Interfering Drugs in Patients With Hereditary Angioedema in Sweden
  • 2023
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 2213-2198 .- 2213-2201. ; 11:2, s. 621-628
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Hereditary angioedema (HAE) is caused by low levels of or defects in C1 inhibitor. Although disease activity may be modified by prophylaxis, emergency treatment, treatment for comorbidities, and oral contraceptives, the extent of their use is unclear. OBJECTIVE: To investigate trends in the use of disease-specific and interfering drugs in patients with HAE compared with the general population in Sweden. METHODS: In a nationwide, longitudinal study, 239 patients with HAE and 2 383 controls were compared with the Prescribed Drug Register (2005e2019). These data reflect rates of dispensed prescriptions from pharmacies in Sweden. RESULTS: Attenuated androgens were used by approximately 10% of patients with HAE. The number of individuals treated with prophylactic plasma-derived C1 inhibitor increased during this period to reach almost 25% in men and 35% in women in 2019. Tranexamic acid was prescribed to 5% to 15% of patients, primarily children and young adults. Rates of prescriptions for icatibant, an emergency medication, showed a steady increase since its introduction in 2010, in particular among middle-aged women, suggesting poorly controlled disease. The use of di-uretics, calcium channel blockers, and gestagens was more common in patients with HAE than in controls, whereas angiotensin-converting enzyme inhibitors were rarely collected. CONCLUSIONS: Despite concerns regarding side effects, approximately 10% of patients with HAE received attenuated androgens for long-term prophylaxis. The common use of emergency medication also suggests poorly controlled disease in many patients, highlighting the need for increased focus on prophylactic treatment.
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