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Jakobsen L.A.,University of Aalborg | Jensen A.,University of Aalborg | Larsen L.E.,University of Aalborg | Sorensen M.R.,University of Aalborg | And 3 more authors.
International Journal of Physiology, Pathophysiology and Pharmacology | Year: 2011

Absorption of drugs from subcutaneous tissue depends on several factors, including tissue perfusion at the administration site. Tissue perfusion can be manipulated by e.g. application of local heat. This may subsequently alter the rate or amount of absorption of drugs from a subcutaneous depot. The aim of the present study was to investigate if increased tissue perfusion after controlled local heating can change the absorption of subcutaneously administered short-acting insulin (Actrapid®, 100IU/ml). Thirteen healthy Caucasian males participated in two randomized experimental sessions; one session with locally applied controlled heat at the injection site, and a control session without local heat application. Tissue perfusion (blood flow) was monitored with Laser Doppler Imaging, and blood samples were taken to assess the levels of glucose and insulin. Local heat application at the site of insulin injection significantly enhanced tissue perfusion by approximately 145%. However, no correlation was found between insulin absorption and tissue perfusion. Based on our findings, it was concluded that tissue perfusion is not the ratelimiting factor in the absorption of high-concentration short-acting insulin from a subcutaneous depot. It is suggested that dissociation of insulin hexamers into dimers and monomers is a major rate limiting factor to the absorption. Source

Siebuhr A.S.,Biomarkers and Research | Petersen K.K.,University of Aalborg | Arendt-Nielsen L.,University of Aalborg | Egsgaard L.L.,University of Aalborg | And 7 more authors.
Osteoarthritis and Cartilage | Year: 2014

Objectives: Osteoarthritis (OA) is a degenerative disease with a subset of patients experiencing joint inflammation, but C-reactive protein (CRP) has shown limited use in OA as a diagnostic marker. The aim was to identify subpopulations of patients with high or low levels of acute (high sensitive CRP (hsCRP)) and/or matrix metalloproteinase (MMP) derived inflammation (CRPM) and investigate the subpopulations' association with biomarkers of collagen degradation and Kellgren-Lawrence (KL) score. Methods: hsCRP, CRPM and MMP-degraded type I, II and III collagen (type I collagen degraded by MMP (C1M), type II collagen degraded by MMP (C2M) and type III collagen degraded by MMP (C3M)) were quantified by enzyme linked immunosorbent assays (ELISA) in serum of 342 patients with symptomatic knee OA of which 60 underwent total knee replacement (TKR). KL was obtained. Patients were divided into quartiles by hsCRP and CRPM levels, where Q1 and Q4 were low or high in both. The biomarker levels of healthy adults provided in the ELISA kits were used as reference level. Results: hsCRP was elevated in TKR (5.9(3.6-8.2 95% confidence interval (CI))μg/mL) compared to reference level (3μg/mL), while CRPM was highly elevated with OA independent of KL (10-14ng/mL) compared to reference level (5ng/mL). Q4 had higher KL than Q1 (P<0.001), Q2 (P=0.017) and Q3 (P<0.001). C1M, C2M and C3M were lowest in Q1. C1M was elevated in Q3 compared to Q2 (P<0.001), whereas C3M was lower (P=0.019). Conclusion: A bigger proportion of patients were elevated in CRPM compared to hsCRP, indicating MMP-derived inflammation as a component of OA. Moreover, the levels of MMP-degraded collagens differed between the subgroups segregated by inflammation, indicating distinctively different subpopulation selected by inflammation. © 2013 Osteoarthritis Research Society International. Source

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