Search

OBJECTIVE: Overweight/obesity is characterized by decreased growth hormone (GH) secretion whereas circulating IGF-I levels are less severely reduced. Yet, the activity of the circulating IGF-system appears to be normal in overweight/obese subjects, as estimated by the ability of serum to activate the IGF-I receptor in vitro (bioactive IGF). We hypothesized that preservation of bioactive IGF in overweight/obese women is regulated by an insulin-mediated suppression of IGF-binding protein-1 (IGFBP-1) and IGFBP-2, and by suppression of IGFBP-3, mediated by low GH. We additionally hypothesized that increases in bioactive IGF would drive changes in body composition with low-dose GH administration.DESIGN: Cross-sectional analysis and 3-month interim analysis of a 6-month randomized, placebo-controlled study of GH administration in 50 overweight/obese women without diabetes mellitus. Bioactive IGF (kinase receptor activation assay) and body composition (DXA) were measured.RESULTS: Prior to treatment, IGFBP-3 (r = -0.33, p = 0.02), but neither IGFBP-1 nor IGFBP-2, associated inversely with bioactive IGF. In multivariate analysis, lower IGFBP-3 correlated with lower peak stimulated GH (r = 0.45, p = 0.05) and higher insulin sensitivity (r = -0.74, p = 0.003). GH administration resulted in an increase in mean serum IGF-I concentrations (144 ± 56 to 269 ± 66 μg/L, p CONCLUSIONS: Our data suggest that in overweight/obesity, insulin sensitivity and GH have opposing effects on IGF bioactivity through effects on IGFBP-3. Furthermore, increases in bioactive IGF, rather than IGF-I concentration, predicted GH administration-related body composition changes.CLINICAL TRIAL REGISTRATION NUMBER: NCT00131378.

AIM: Survivors after cardiac arrest (CA) exhibits a systemic inflammatory response as part of post-cardiac arrest syndrome (PCAS). We investigated the association between systemic inflammation and severity of PCAS and whether level of targeted temperature management (TTM) modifies level of the inflammatory response.METHODS: We studied 169 patients included at a single center in the TTM-trial, randomly assigned to TTM at 33 °C or 36 °C for 24 h. Plasma samples were analyzed for inflammatory markers including interleukin (IL) IL-1β,IL-4,IL-6,IL-10, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and procalcitonin (PCT) at randomization and 24, 48 and 72 h after CA. Severity of PCAS was assessed by Sequential Organ Failure Assessment (SOFA) score.RESULTS: Plasma levels of both IL-6 and IL-10 determined at randomization correlated with severity of PCAS at day 2 (r=0.36 and r=0.27, pCONCLUSIONS: Level of inflammatory response was associated with severity of PCAS with IL-6 being consistently and more strongly associated with severity of PCAS than the inflammatory markers CRP and PCT. The systemic inflammatory response after CA was not modified by TTM at 33 °C or 36 °C.

Adiponectin exerts anti-inflammatory and antiatherogenic effects and appears to protect against arteriosclerosis. Accordingly, an association between low concentrations of plasma adiponectin and cardiovascular (CV) disease has been demonstrated in several studies. In contrast, elevated plasma adiponectin has been associated with increased mortality and an increasing number of major adverse CV events (MACE). Because of these conflicting results, the true role of adiponectin remains to be elucidated. In the Copenhagen City Heart Study, we prospectively followed up 5,624 randomly selected men and women from the community without CV disease. Plasma adiponectin was measured at the beginning of the study. The median follow-up time was 7.8 years (interquartile range 7.3 to 8.3). The end point was all-cause mortality (n = 801), and the combined end point was MACE, consisting of CV mortality or nonfatal myocardial infarction or ischemic stroke (n = 502). High adiponectin was inversely associated with an increasing number of traditional CV risk factors (p0.0001). The geometric mean adiponectin concentrations were 10.0 mg/L (95% confidence interval [CI] 9.7 to 10.4) for persons with no CV risk factors present versus 8.1 mg/L (95% CI 7.8 to 8.4) for persons with 4 CV risk factors. After adjustment for confounding risk factors by Cox regression analysis, adiponectin remained an independent predictor of death and MACE. The hazard ratio for each increase in adiponectin of 5 mg/L for death and MACE was 1.20 (95% CI 1.14 to 1.27; p0.0001) and 1.14 (95% CI 1.05-1.23; p0.0001), respectively. In conclusion, an increasing number of risk factors for CV disease is associated with decreased plasma adiponectin. High plasma adiponectin independently predicted death and MACE in a large community-based population. These results have confirmed the dual expression indicated by previous studies.

Inflammation is believed to play a role in the pathogenesis of both cardiovascular disease and depressive disorders. We hypothesized that circulating concentrations of the novel inflammatory and cardiovascular biomarkers osteoprotegerin (OPG) and adiponectin as well as high sensitivity C-reactive protein (hsCRP) are associated with the severity of depressive symptoms and presence of major depressive disorder (MDD).In a cross-sectional population-derived study (Akershus Sleep Apnea Project) 520 persons underwent clinical examination and venous blood sampling. Medical history was obtained and the participants completed the Beck Depression Inventory (BDI). Structured clinical interviews for axis-I disorders including MDD were performed in a subgroup of 288 participants. OPG and adiponectin concentrations were determined by in-house time-resolved immunofluorometric assays.Despite significant correlation with hsCRP (r=0.162, p0.001), the sum-score of BDI did not correlate with OPG or adiponectin levels (r=0.011, p=0.811 and r=0.055, p=0.210, respectively). Neither circulating OPG nor adiponectin differed between persons with (n=34) and without (n=246) MDD (median±interquartile range: 1.18 (0.96-1.49) vs. 1.17 (0.93-1.57) ug/l and 7.26 (5.13-9.91) vs. 7.39 (5.23-11.37) mg/l, respectively).Causal considerations are not possible, and results in the sub-group of diagnosed participants need careful interpretation due to small sample size.hsCRP was independently associated with depressive symptoms, but no association between depression severity or presence of MDD and OPG- or adiponectin concentrations was observed in community-residing persons at high risk for obstructive sleep apnea.

Udgivelsesdato: 2009-Feb-19 Multiplex assays for analysis of human and rodent cytokines are highly developed, while development of porcine cytokine assays needs further attention. In order to follow the cytokine response in consecutive porcine samples, in which the sample volume may be limited, we have developed multiplex immunoassays for simultaneous detection of porcine cytokines interleukin (IL)-1beta, IL-6, IL-8, IL-10, tumour necrosis factor alpha (TNF-alpha), and heat shock protein 32 (Hsp32). Antibodies against porcine cytokines were coupled to magnetic microspheres. Quantification was obtained with biotinylated antibodies followed by PE-labelled streptavidin and measurements by Luminex(100). Validation and cross-reaction experiments revealed detection limits below 5-20ng/L, recovery of recombinant cytokines in spiked plasma between 80 and 110%, and intra- and inter-assay variation between 5 and 15%. No cross-reaction between assays was found. However, for optimal sensitivity the assays were performed as a 2-plex (IL-1beta and Hsp32) and a 4-plex (IL-6, IL-8, IL-10, and TNF-alpha). Cytokine levels were determined in plasma samples from a porcine model of acute endotoxaemia and the levels correlated to previously published concentrations.