Serum uric acid is inversely proportional to estimated stroke volume and cardiac output in a large sample of pharmacologically untreated subjects: data from the Brisighella Heart Study

Serum uric acid is representative for xanthine-oxidase, the key enzyme involved in the production of uric acid, which is up-regulated in the failing heart, and may play an important role in the pathophysiologic process that leads to heart failure. In our study, we investigated the relation between stroke volume, cardiac output and serum uric acid in a large sample of overall healthy pharmacologically untreated subjects. The Brisighella Heart Study included 2,939 men and women between the ages of 14–84 without prior coronary heart disease or cerebrovascular disease who were not taking antihypertensive therapy at baseline. For this study, we selected 734 adult subjects enrolled in the last Brisighella population survey not taking antihypertensive, antidiabetic, lipid-lowering and uric acid-lowering drugs, and who were also not affected by chronic heart failure or by gout. The main predictors of cardiac functionality parameters were mean arterial pressure (MAP), HR, SUA and age (all p < 0.001), while gender, BMI, LDL-cholesterol, HDL-cholesterol, triglycerides, fasting plasma glucose, creatinine, estimated glomerular filtration rate, physical activity and smoking habit were not significantly associated (all p > 0.05). In particular, there is a strong relation between estimated cardiac output and serum uric acid (B = ?0.219, p < 0.001) and between stroke volume and serum uric acid (B = ?3.684, p < 0.001). These observations might have an impact on future considerations about serum uric acid as an early inexpensive marker of heart function decline in the general population.     

β (CCL2) and α (CXCL10) chemokine modulations by cytokines and peroxisome proliferator-activated receptor-α agonists in Graves' ophthalmopathy

No data are present in the literature about the effect of cytokines on the prototype β chemokine (C-C motif) ligand 2 (CCL2) or of peroxisome proliferator-activated receptor α (PPARα (PPARA)) activation on CCL2 and CXCL10 chemokines secretion in fibroblasts or preadipocytes in Graves' ophthalmopathy (GO). We have tested the effect of interferon γ (IFNγ (IFNG)) and tumor necrosis factor α (TNFα) on CCL2, and for comparison on the prototype α chemokine (C-X-C motif) ligand 10 (CXCL10), and the possible modulatory role of PPARα activation on secretion of these chemokines in normal and GO fibroblasts or preadipocytes in primary cell cultures. This study shows that IFNγ alone, or in combination with TNFα, stimulates the secretion of CCL2 in primary orbital fibroblasts or preadipocytes from patients with GO at levels similar to those observed in controls. IFNγ and TNFα also stimulated CXCL10 chemokine secretion as expected. The presence of PPARα and PPARγ (PPARG) in primary fibroblasts or preadipocytes of patients with GO has been confirmed. PPARα activators were able to inhibit the secretion of CXCL10 and CCL2, while PPARγ activators were confirmed to be able to inhibit CXCL10 but had no effect on CCL2. PPARα activators were stronger inhibitors of chemokine secretions than PPARγ agonists. In conclusion, CCL2 and CXCL10 are modulated by IFNγ and TNFα in GO. PPARα activators inhibit the secretion of the main prototype α (CXCL10) and β (CCL2) chemokines in GO fibroblasts or preadipocytes, suggesting that PPARα may be involved in the modulation of the immune response in GO.     

Evaluation of tuberculosis diagnostics in children: 1. Proposed clinical case definitions for classification of intrathoracic tuberculosis disease. Consensus from an expert panel

There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis.