Human articular cartilage proteoglycans are not undersulfated in osteoarthritis

Chondroitin sulfate is the major constituent of cartilage. Inadequate sulfate availability results in the production of undersulfated proteoglycans. In osteoarthritis, there is a net loss of articular cartilage proteoglycans. Theoretically, it is possible that during the progress of disease undersulfated glycosaminoglycans are synthesized producing proteoglycans with poorer biological properties. In this study, we tested whether in early human osteoarthritic articular cartilage (Mankin's score of 2 and 3) or more advanced disease (Mankin's score over 3), there are proteoglycans that contain a higher relative amount of nonsulfated chondroitin disaccharide isomer in their chondroitin sulfate chains by analyzing the molar ratios of chondroitin sulfate disaccharide isoforms with fluorophore-assisted carbohydrate electrophoresis. Our results indicated that the nonsulfated disaccharide of chondroitin sulfate formed in average only 1-2% of the total chondroitin sulfate. More important, the molar ratio of nonsulfated disaccharide did not appear to be increased in the osteoarthritic articular cartilage. We conclude that undersulfation of articular cartilage proteoglycans is not present in the human osteoarthritic joint.     

Salbutamol‐induced Decrease in Augmentation Index is Related to the Parallel Increase in Heart Rate

The change in augmentation index following salbutamol inhalation has been applied to evaluate endothelial function. We examined the contribution of salbutamol‐induced increase in heart rate to the observed decrease in augmentation index. Haemodynamics were recorded using whole‐body impedance cardiography and continuous pulse wave analysis from tonometric radial blood pressure. All subjects (n = 335, mean age 46, body mass index 26, 48% men) were without medications with cardiovascular influences. The effects of salbutamol inhalation (0.4 mg) versus the endothelium‐independent agent nitroglycerin resoriblet (0.25 mg) were examined during passive head‐up tilt, as the haemodynamic influences of these compounds depend on body position. Salbutamol decreased augmentation index by ~3‐4% units in supine and upright positions. Although salbutamol moderately increased cardiac index (+4.5%) and decreased systemic vascular resistance (?8.5%), the significant haemodynamic explanatory factors for decreased augmentation index in multivariate analysis were increased supine heart rate, and increased upright heart rate and decreased ejection duration (p < 0.001 for all, r² = 0.36–0.37). Sublingual nitroglycerin decreased supine and upright augmentation index by ~15% units and ~23% units, respectively. The haemodynamic explanatory factors for these changes in multivariate analysis were increased heart rate, reduced ejection duration and reduced systemic vascular resistance (p ≤ 0.021 for all, r² = 0.22–0.34). In conclusion, the lowering influence of salbutamol on augmentation index may be largely explained by increased heart rate, suggesting that this effect may not predominantly reflect endothelial function.     

Incidence of low central venous oxygen saturation during unplanned admissions in a multidisciplinary intensive care unit: an observational study

Introduction  

It has been shown that early central venous oxygen saturation (ScvO₂)-guided optimization of hemodynamics can improve outcome in septic patients. The early ScvO₂ profile of other patient groups is unknown. The aim of this study was to characterize unplanned admissions in a multidisciplinary intensive care unit (ICU) with respect to ScvO₂ and outcome.     

Dual contrast in computed tomography allows earlier characterization of articular cartilage over single contrast

Cationic computed tomography contrast agents are more sensitive for detecting cartilage degeneration than anionic or non-ionic agents. However, osteoarthritis-related loss of proteoglycans and increase in water content contrarily affect the diffusion of cationic contrast agents, limiting their sensitivity. The quantitative dual-energy computed tomography technique allows the simultaneous determination of the partitions of iodine-based cationic (CA4+) and gadolinium-based non-ionic (gadoteridol) agents in cartilage at diffusion equilibrium. Normalizing the cationic agent partition at diffusion equilibrium with that of the non-ionic agent improves diagnostic sensitivity. We hypothesize that this sensitivity improvement is also prominent during early diffusion time points and that the technique is applicable during contrast agent diffusion. To investigate the validity of this hypothesis, osteochondral plugs (d = 8 mm, N = 33), extracted from human cadaver (n = 4) knee joints, were immersed in a contrast agent bath (a mixture of CA4+ and gadoteridol) and imaged using the technique at multiple time points until diffusion equilibrium. Biomechanical testing and histological analysis were conducted for reference. Quantitative dual-energy computed tomography technique enabled earlier determination of cartilage proteoglycan content over single contrast. The correlation coefficient between human articular cartilage proteoglycan content and CA4+ partition increased with the contrast agent diffusion time. Gadoteridol normalized CA4+ partition correlated significantly (P < .05) with Mankin score at all time points and with proteoglycan content after 4 hours. The technique is applicable during diffusion, and normalization with gadoteridol partition improves the sensitivity of the CA4+ contrast agent.     

Characterization of macrophage polarizing cytokines in the aseptic loosening of total hip replacements

Aseptic loosening of hip replacements is driven by the macrophage reaction to wear particles. The extent of particle‐induced macrophage activation is dependent on the state of macrophage polarization, which is dictated by the local cytokine microenvironment. The aim of the study was to characterize cytokine microenvironment surrounding failed, loose hip replacements with an emphasis on identification of cytokines that regulate macrophage polarization. Using qRT‐PCR, the expression of interferon gamma (IFN‐γ), interleukin‐4 (IL‐4), granulocyte–macrophage colony‐stimulating factor (GM‐CSF), IL‐13, and IL‐17A was low and similar to the expression in control synovial tissues of patients undergoing primary hip replacement. Using immunostaining, no definite source of IFN‐γ or IL‐4 could be identified. IL‐17A positive cells, identified as mast cells by double staining, were detected but their number was significantly reduced in interface tissues compared to the controls. Significant up‐regulation of IL‐10, M‐CSF, IL‐8, CCL2‐4, CXCL9‐10, CCL22, TRAP, cathepsin K, and down regulation of OPG was seen in the interface tissues, while expression of TNF‐α, IL‐1β, and CD206 were similar between the conditions. It is concluded that at the time of the revision surgery the peri‐implant macrophage phenotype has both M1 and M2 characteristics and that the phenotype is regulated by other local and systemic factors than traditional macrophage polarizing cytokines. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1241–1246, 2014.     

High prevalence of gastroesophageal reflux symptoms and esophagitis with or without symptoms in the general adult Swedish population: a Kalixanda study report

OBJECTIVE: Gastroesophageal reflux disease has been reported to be a common burden on health-care resources in the Western world, but its manifestations in the general population are as yet unclear. The aim of this study was to estimate the prevalence of, and to identify the risk factors for gastroesophageal reflux symptoms (GERS) and erosive esophagitis (EE) in the adult population of two Swedish municipalities. MATERIAL AND METHODS: A random sample (n =3000) of the adult population (20-81 years of age) of two Swedish municipalities (n =21,610) was surveyed using a validated postal questionnaire assessing gastrointestinal symptoms. The response rate was 74%. A subsample (n = 1000) of the responders was subsequently invited, in random order, for esophago-gastro-duodenoscopy with evaluation of GERS, risk factors and tests for Helicobacter pylori. RESULTS: GERS were reported by 40.0% and EE was found in 15.5% of the population that had undergone endoscopy. Of those with GERS, 24.5% had EE while 36.8% of those with EE reported no GERS. Hiatus hernia and obesity remained significant risk factors for GERS and/or EE, with or without symptoms in a main effect model (OR up to 14 at EE). Those with active H. pylori infection had a higher risk of GERS without EE than those without H. pylori infection (OR = 1.71 (1.23 2.38)). CONCLUSIONS: GERS and EE (of which one-third is asymptomatic) are highly prevalent in the Swedish adult population. H. pylori infection seems to play a role in the manifestations of gastroesophageal reflux.     

Immunological comparison of patients with rheumatoid arthritis with and without nephropathy.

Serum immunoglobulins IgG, IgA, and IgM, serum complement components C3 and C4, circulating immune complexes, antinuclear antibodies, and rheumatoid factor were measured in 56 patients with rheumatoid arthritis (RA) and nephropathy (23 with mesangial glomerulopathy; 13 with membranous glomerulonephritis; and 20 with amyloidosis) and 35 patients with RA without nephropathy (controls). Renal immunofluorescence findings in patients with mesangial glomerulopathy were compared with the serologic data. There were no differences in the occurrence of rheumatoid factor, antinuclear antibodies, and circulating immune complexes and the concentrations of serum complement C3 and C4 between various RA nephropathy groups and controls. Serum IgA and IgM concentrations were significantly higher in patients with mesangial glomerulopathy and amyloidosis than in controls. In patients with mesangial glomerulopathy glomerular IgM, IgA, and C3 were the most prominent findings in immunofluorescence examination. The serum IgA concentration was significantly higher in those patients with mesangial glomerulopathy with mesangial IgA deposits than in those without (4.97 (SD 1.03) g/l v 2.07 (1.21) g/l). The highest serum IgA concentrations (5.08 (1.39) g/l) were seen in the four patients with IgA glomerulonephritis. The prevalence of IgA glomerulonephritis in the renal biopsy material of the patients with RA was 5%, which possibly differs little from that seen in the general population. The results suggest that circulating immune complexes may not have any major role in the pathogenesis of various nephropathy types in patients with RA, contrary to their role in most extra-articular manifestations of RA.     

Relation of apolipoprotein E polymorphism to markers of early atherosclerotic changes in young adults--the Cardiovascular Risk in Young Finns Study.

BACKGROUND: Carotid artery intima-media thickness (IMT), which is measured by ultrasound, is used in the assessment of early atherosclerotic changes, and has been associated with apolipoprotein E (APOE) polymorphism in many studies comprising elderly subjects. However, results are still inconclusive and data relating to young adults are missing. Whether common APOE polymorphism is related to carotid IMT was studied in a population of young adults. Also brachial flow-mediated dilatation (FMD) and carotid artery compliance (CAC) were determined to clarify their relation to this genetic factor. METHODS AND RESULTS: A total of 1,188 young adults (aged 24-39 years) participating in the Cardiovascular Risk in Young Finns Study with complete data of common APOE polymorphism underwent a carotid and brachial ultrasound. Patients' lipid levels and blood pressure were also examined. There was no significant association between the APOE phenotypes and carotid IMT, brachial FMD or CAC either in young men or in young women. The results were similar for systolic and diastolic blood pressure. In the same population, the well-known association between APOE phenotypes and lipids was seen. CONCLUSIONS: Common APOE polymorphism does not seem to be an independent genetic determinant of carotid IMT, brachial FMD or CAC.