Astrocytic Ion Dynamics: Implications for Potassium Buffering and Liquid Flow

We review modeling of astrocyte ion dynamics with a specific focus on the implications of so-called spatial potassium buffering, where excess potassium in the extracellular space (ECS) is transported away to prevent pathological neural spiking. The recently introduced Kirchoff-Nernst-Planck (KNP) scheme for modeling ion dynamics in astrocytes (and brain tissue in general) is outlined and used to study such spatial buffering. We next describe how the ion dynamics of astrocytes may regulate microscopic liquid flow by osmotic effects and how such microscopic flow can be linked to whole-brain macroscopic flow. We thus include the key elements in a putative multiscale theory with astrocytes linking neural activity on a microscopic scale to macroscopic fluid flow.Comment: 27 pages, 7 figure

Increased expression of carbonic anhydrase I in the synovium of patients with ankylosing spondylitis

<p>Abstract</p> <p>Background</p> <p>One of the most distinctive features of ankylosing spondylitis (AS) is new bone formation and bone resorption at sites of chronic inflammation. Previous studies have indicated that the hyperplasia and inflammation of synovial tissues are significantly related to the pathogenic process of AS. The present study used a proteomic approach to identify novel AS-specific proteins by simultaneously comparing the expression profiles of synovial membranes from patients with AS, rheumatoid arthritis (RA) and osteoarthritis (OA).</p> <p>Methods</p> <p>Synovial tissues were collected from the hip joints of patients with AS and knee joints of patients with RA or OA (n = 10 for each disease) during joint replacement surgery. Proteins extracted from the synovial tissues were separated by 2-D electrophoresis (2-DE), and the proteins with significantly increased expression in the AS samples were subjected to MALDI-TOF/TOF-MS analysis. The results were verified using western blotting and immunohistochemistry. Levels of the candidate proteins in synovial fluids from knee joints (n = 40 for each disease) were measured using ELISA.</p> <p>Results</p> <p>The proteomic approach revealed significantly increased expression of carbonic anhydrase I (CA1) in the synovial membrane of patients with AS as compared with the RA and OA tissue samples. Immunohistochemistry and western blotting analysis confirmed the findings described above. The ELISA detected a higher level of CA1 in synovial fluids from patients with AS than those with OA. The mean value of the CA1 level was also higher in AS patients as compared with RA patients. This study also detected increased expression of alpha-1-antitrypsin in the synovial tissues from AS patients, which is in agreement with other reports.</p> <p>Conclusion</p> <p><it>In vitro </it>experiments by other groups indicated that CA1 catalyzes the generation of HCO₃^-through the hydration of CO₂, which then combines with Ca²⁺to form a CaCO3 precipitate. Calcification is an essential step of bone formation. Substantial evidence indicates that carbonic anhydrase also stimulates bone resorption. Hence, overexpression of CA1 in the synovial tissues of AS patients may promote improper calcification and bone resorption in AS.</p

Bone mineral density and body composition in postmenopausal women with psoriasis and psoriatic arthritis

Introduction: the aim of the present study was to compare bone mineral density (BMD) and body composition (BC) measurements as well as identify risk factors for low BMD and osteoporotic fractures in postmenopausal women with psoriasis (Ps) and psoriatic arthritis (PsA).Methods: A cross-sectional study was carried out in 45 PsA women, 52 Ps women and 98 healthy female controls (HC). Clinical risk factors for low bone density and osteoporotic fracture were evaluated by a specific questionnaire. An X-ray absorptiometry (DXA) at the lumbar spine, total femur and total body was performed on all patients. Skin and joint outcomes were measured by specific tools (PASI, HAQ and DAS28). Morphometric vertebral fractures were evaluated by lumbar and thoracic spine X-ray, according to Genant's method.Results: There were no significant differences in age, body mass index (BMI), total lean mass and bone mineral density among the groups. However, the PsA group had a significantly higher body fat percentage (BF%) than the Ps and HC groups. Osteoporotic fractures were more frequently observed in PsA and Ps groups than in the HC group (P = 0.01). Recurrent falls and a longer duration of disease increased the risk of fracture (odds ratio (OR) = 18.3 and 1.08, respectively) in the PsA group (P = 0.02). Disability was the main factor related to osteoporotic fracture in the Ps group (odds ratio (OR) = 11.1) (P = 0.02).Conclusions: Ps and PsA patients did not present lower BMD. However, they had a higher prevalence of osteoporotic fractures and higher risk of metabolic syndrome. Patients with a longer duration of disease, disability and recurrent falls need preventive measures.Rheumatology Division at UNIFESP/EPMUniversidade Federal de São Paulo, UNIFESP Paulista Sch Med, Div Rheumatol, EPM, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP Paulista Sch Med, Div Rheumatol, EPM, BR-04023900 São Paulo, BrazilWeb of Scienc

Increased transendothelial migration of scleroderma lymphocytes

Background: CD4+ T lymphocytes play an important part in the pathogenesis of scleroderma (systemic sclerosis, SSc) and predominate in perivascular SSc skin lesions. Both soluble and membrane bound adhesion molecules are overexpressed in SSc, possibly influencing lymphocyte/endothelial cell (EC) contact. Objective: To assess the transendothelial migration capacity of peripheral lymphocytes in vitro. Patients and methods: Collagen was covered with human umbilical vein endothelial cells (HUVEC), and peripheral blood mononuclear cells (PBMC) of patients and matched healthy controls (HC) were added in parallel experiments. Before and after fractionated harvest of non-adherent, bound, and migrated lymphocytes, the CD4/CD8 ratio and the lymphocytic expression of activation markers and adhesion molecules were analysed by fluorocytometry. Results: 13 (SD 12)% of the SSc PBMC migrated compared with only 5 (5)% HC PBMC (p<0.0002); this increase was primarily due to the migration of CD3+ T lymphocytes and mainly to a larger proportion of CD4+ cells within this CD3+ fraction (71 (SD 14)% for SSc v 56 (14)% for HC, p<0.03), leading to an increased CD4/CD8 ratio among migrated SSc lymphocytes in comparison with controls (3.3 (1.5) v 1.62 (0.93), p<0.006). Among migrated SSc CD4+ T lymphocytes, the frequency of HLA-DR+ cells was increased; migrated lymphocytes highly expressed the adhesion molecules CD11a, CD49d, CD29, and CD44. Conclusion: Transendothelial migration of CD4+ T lymphocytes is enhanced in SSc, and migrating cells exhibit an activated phenotype. The data suggest that activated CD3+CD4+ lymphocytes as found in SSc peripheral blood are prone to transvascular migration, thus contributing to the formation of typical perivascular lymphocytic infiltrates

Osteoporosis in psoriatic arthritis: is there any?

AIMS: Although considered as a feature of inflammatory rheumatic diseases, there is a lot of controversy around low bone mass in patients with psoriatic arthritis. The aim of this cross-sectional study was to analyze bone mineral density in patients with psoriatic arthritis, as well as to investigate its possible association with some measures of disease activity and functional capacity. ----- SUBJECTS AND METHODS: Sixty-nine patients with established psoriatic arthritis (mean age 56.20 ± 12.23 years) and who have not been treated with specific antiosteoporotic drugs were recruited from the out-patient clinic database. Bone mineral density was measured by dual-energy X-ray absorptiometry at the lumbar spine and at the left hip. Disease activity measures included: duration of morning stiffness, tender and swollen joint count, patient's and physician's global assessment, presence of dactylitis and enthesitis, ESR, CRP and Disease Activity Score 28. Health Assessment Questionnaire was used to assess functional status. ----- RESULTS: According to WHO definition, spinal osteoporosis was found in 7.2% of patients, total hip osteoporosis in 1.4% of patients and femoral neck osteoporosis in 2.9% of patients. There was no significant association of any of the measures of disease activity with BMD at any site. Higher HAQ scores were associated with lower total hip BMD. ----- CONCLUSIONS: In our sample of patients with psoriatic arthritis we did not find increased prevalence of osteoporosis. There was no association of BMD with indices of disease activity, while negative correlation was found between HAQ and total hip BMD