Uptonfagan8870

Systemic lupus erythematosus (SLE) is a chronic multi-system autoimmune disease characterized by circulating autoantibodies, prevalent hypertension, renal injury, and cardiovascular disease. Onset of the disease often occurs in young women of child-bearing age. Although kidney involvement is common to patients with SLE, little is known about temporal changes in renal hemodynamic function and its relationship to the pathogenesis of hypertension during autoimmune diseases. We hypothesized that the loss of immunological tolerance and subsequent production of autoantibodies in SLE leads to impaired renal hemodynamic function that precedes the development hypertension. Female NZBWF1 (SLE) mice and female NZW/LacJ (control) mice were instrumented with carotid artery and jugular vein catheters to determine mean arterial pressure (MAP) and glomerular filtration rate (GFR) respectively at ages 15, 20, 24, 28, 31, and 34 weeks. In addition, urinary albumin excretion, blood urea nitrogen (BUN), circulating autoantibodies, and glomerulosclerosis were assessed at each age. Levels of circulating autoantibodies are increased between 24 and 28 weeks of age in NZBWF1 mice, whereas autoantibodies are unchanged in control mice. GFR is significantly increased at 28 weeks of age in NZBWF1 mice followed by a sharp decline at 34 weeks of age. NZBWF1 mice have an increase in MAP that occurs by 34 weeks of age. These data show that changes in circulating autoantibodies, renal hemodynamic function, and glomerular injury occur in NZBWF1 mice prior to changes in MAP, suggesting an important mechanistic role for autoimmunity to directly impair renal hemodynamic function and promote the development of hypertension.Studies examining mechanisms of Dahl Salt-Sensitive (SS) hypertension have implicated the infiltration of leukocytes into the kidneys, which contribute to the renal disease and elevated blood pressure. However, the signaling pathways by which leukocytes traffic to the kidneys remain poorly understood. The present set of studies nominated a signaling pathway by analyzing a kidney RNA-seq dataset from SS rats fed either a Low Salt (LS-0.4% NaCl) or a High Salt (HS-4.0% NaCl) diet. From this analysis, the chemokine (C-C motif) ligand 2 (CCL2) and receptor CCR2 were nominated as a potential pathway modifying renal leukocyte infiltration and contributing to SS hypertension. PQR309 The functional role of the CCL2/CCR2 pathway was tested by daily administration of CCR2 antagonist (RS102895 at 5mg/kg/day in DMSO) or DMSO Vehicle for 3- or 21-days by intraperitoneal injections during the HS challenge. Blood pressure, renal leukocyte infiltration and renal damage were evaluated. Results demonstrate that RS201895 treatment ameliorated renal damage (urinary albumin excretion; 43.4±5.1 vs 114.7±15.2 mg/day in Vehicle, P less then 0.001) and hypertension (144.3±2.2 vs 158.9±4.8 mmHg in Vehicle treated, P less then 0.001) after 21 days of HS diet. It was determined that renal leukocyte infiltration was blunted by day 3 of the HS diet (1.4±0.1 vs 1.9±0.2 in Vehicle x106 CD45+ cells/kidney, P=0.034). An in vitro chemotaxis assay validated the effect of RS102895 on leukocyte chemotaxis towards CCL2. The results suggest that increased CCL2 in SS kidney is important in early recruitment of leukocytes and blockade of this recruitment by administering RS102895, subsequently blunted the renal damage and hypertension.BACKGROUND Patients with posterior shoulder instability may have bone and cartilage lesions (BCLs) in addition to capsulolabral injuries, although the risk factors for these intra-articular lesions are unclear. HYPOTHESIS We hypothesized that patients with posterior instability who had a greater number of instability events would have a higher rate of BCLs compared with patients who had fewer instability episodes. STUDY DESIGN Cross-sectional study; Level of evidence, 3. METHODS Data from the Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Group instability patient cohort were analyzed. Patients aged 12 to 99 years undergoing primary surgical treatment for shoulder instability were included. The glenohumeral joint was evaluated by the treating surgeon at the time of surgery, and patients were classified as having a BCL if they had any grade 3 or 4 glenoid or humeral cartilage lesion, reverse Hill-Sachs lesion, bony Bankart lesion, or glenoid bone loss. The effects of the number of instability events endent predictor; increased risk of bone lesion was present for patients with 1 instability event (OR, 6.1; P = .012), patients with 2 to 5 instability events (OR, 4.2; P = .033), and patients with more than 5 instability events (OR, 6.0; P = .011). CONCLUSION Bone and cartilage lesions are seen significantly more frequently with increasing patient age and in patients with 2 to 5 instability events. Early surgical stabilization for posterior instability may be considered to potentially limit the extent of associated intra-articular injury. The group of patients with more than 5 instability events may represent a different pathological condition, as this group showed a decrease in the likelihood of cartilage injury, although not bony injury.BACKGROUND Recently, a hypertrophic labrum has been reported in the absence of hip dysplasia, which can possibly contribute to an acetabular labral tear. PURPOSE To compare the clinical outcomes and complications, including the incidence of iatrogenic acetabular labrum and cartilage injury, in patients with tears of hypertrophic versus morphologically normal acetabular labra over a minimum follow-up period of 2 years and to assess the morphologic changes at follow-up computed tomography arthrography in the 2 groups. STUDY DESIGN Cohort study; Level of evidence, 3. METHODS Between January 2010 and December 2016, 20 patients (22 hips) with a hypertrophic labrum underwent arthroscopic hip surgery. A total of 22 patients (22 hips) without a hypertrophic labrum were assigned to the control group based on matching criteria, including age, sex, body mass index, labral tear, and labral repair. Clinical outcomes were assessed with the visual analog scale score, UCLA activity scale score (University of California, Los Angeles), and modified Harris Hip Score.