No abstract

Fetal brain iron deficiency occurs in human pregnancies complicated by diabetes mellitus or intrauterine growth retardation. Because neurocognitive deficits are more common in the offspring of these pregnancies, we tested the hypothesis that perinatal brain iron deficiency predisposes the neonatal hippocampus, a structure important for memory processing, to injury. Brain iron concentration was reduced by 45% in 45 neonatal rats by maternal dietary iron restriction during gestation. Right-sided neuronal injury in four hippocampal subareas was induced by hypoxic-ischemic insult (ipsilateral carotid artery ligation and subsequent hypoxia on postnatal d 7) and was quantified histochemically on d 8 by cytochrome c oxidase activity (n = 30), and on d 14 by Nissl staining (n = 15). Acute right-sided cytochrome c oxidase activity loss occurred in CA1 (P = 0.02), CA3c (P < 0.001) and dentate gyrus (P < 0.001) in the iron-deficient group, whereas only CA1 (P = 0. 003) was affected in the iron-sufficient group. Long-term right-sided Nissl substance loss occurred in CA1 (P = 0.001), CA3a,b (P < 0.001) and dentate gyrus (P = 0.008) in the iron-deficient group, but only in CA1 (P = 0.004) in the iron-sufficient group. No increase in right-sided free-iron staining was present in either group. Perinatal iron deficiency predisposes the neonatal hippocampus to a greater acute loss of neuronal metabolic activity after an hypoxic-ischemic event, suggesting compromised cellular energetics. The subsequently greater loss of hippocampal neuronal integrity suggests poorer recoverability after injury in the perinatal iron-deficient brain.

Objectives To investigate risk factors in the subclinical atherosclerosis progression as measured by coronary artery calcium (CAC) and aorta calcium (AC) in women with Systemic Lupus Erythematosus (SLE) (cases) and in comparison with a control population. Methods A cohort of 149 cases and 124 controls participated in the Study of Lupus Vascular and Bone Long-term Endpoints (SOLVABLE). Demographic information, cardiovascular and SLE risk factors, and laboratory assessments were collected at an initial visit. CAC and AC were measured by electron beam computed tomography (CT) or multi-detector CT at an initial and a follow-up visit. Logistic regression models were used to identify predictors of progression in CAC and AC; multivariate models were adjusted for age, hypertension, and total cholesterol/HDL ratio. Results Higher modified ACR/SLICC-DI (OR 2.15, 95%CI 1.33–3.57), use of a corticosteroid (OR 2.93, 95%CI 1.14–7.86), and use of aspirin (OR 4.23, 95%CI 1.53–11.74) were associated with CAC progression in multivariate models. Presence of SLE (OR 2.64, 95%CI 1.26–5.72), lower C3 (OR 0.54, 95%CI 0.33–0.87), lower C4 (OR 0.49, 95% CI 0.27–0.86), use of a corticosteroid (OR 2.73, 95%CI 1.03–7.64), higher corticosteroid dose (OR 1.77, 95%CI 1.12–3.00), higher lipoprotein(a) (OR 1.80, 95%CI 1.11–2.98), higher homocysteine (OR 2.06, 95%CI 1.06–4.29) were associated with AC progression in multivariate models. Conclusions Higher disease damage at the first study visit, as measured by the modified ACR/SLICC-DI, may predict increased risk in CAC progression, whereas higher disease activity at the first study visit, as measured by hypocomplementemia and use of corticosteroids, may predict increased risk in AC progression.

Tumor necrosis factor (TNF)-targeted therapies are increasingly being prescribed in the management of a variety of inflammatory and autoimmune diseases. The use of this class of medications also pose risks of developing an assortment of pulmonary side effects including infections (TB, bacterial, and fungal infections), pulmonary nodules, chronic pneumonitis/fibrosis, SLE-like reactions, vasculitis, and exacerbations of underlying lung disease. In addition to surveillance for tuberculosis prior to initiation of TNF-targeted therapy, a high level of vigilance should be maintained during administration for infectious and non-infectious complications, even years into a patient’s course. The available evidence argues for caution in using these agents in patients with pre-existing lung disease and heightened suspicion of accelerated nodule formation in those with preexisting rheumatoid nodules. Management centers on excluding infection, identifying confounders (especially methotrexate or pre-existing lung disease), and promptly discontinuing TNF-targeted therapy. In some instances, invasive procedures (e.g. bronchoscopy or VATS lung biopsy) will be necessary to establish the proper diagnosis, and the administration of steroids may be beneficial.

Objective An association between 25-hydroxyvitamin D (25[OH]D; vitamin D) deficiency and increased cardiovascular (CV) risk factors and CV disease (CVD) has been shown in general population studies. Vitamin D deficiency has been noted in systemic lupus erythematosus (SLE), and CVD is a major cause of morbidity and mortality in SLE. The objectives of this study were to estimate the associations of 25(OH)D levels with CV risk factors and to determine whether low baseline 25(OH)D levels predict future CV events in patients participating in an international inception cohort. Methods Data were collected on 890 participants, including demographics, SLE activity and damage assessments, CV risk factors and events, medications, laboratory assessments of 25(OH)D levels, and inflammatory markers. Multiple logistic and Cox regressions were used to estimate the associations of baseline 25(OH)D levels with baseline CV risk factors and CVD events. The models were adjusted for age, sex, race, season, and country, with and without body mass index. Results Patients in the higher quartiles of 25(OH)D were less likely to have hypertension and hyperlipidemia and were more likely to have lower C-reactive protein levels and lower Systemic Lupus Erythematosus Disease Activity Index 2000 scores at baseline when compared with the first quartile. Vitamin D levels were not independently associated with CVD event incidence; however, hazard ratios for CVD event incidence decreased with successively higher quartiles. Conclusion Lower baseline 25(OH)D levels are associated with higher risk for CV risk factors and more active SLE at baseline. There may be a trend toward a lower likelihood of CVD events in those with higher baseline 25(OH)D levels.