Dexamethasone Prophylaxis in Pediatric Open Heart Surgery Is Associated with Increased Blood Long Pentraxin PTX3: Potential Clinical Implications

Glucocorticoid administration before cardiopulmonary bypass (CPB) can reduce the systemic inflammatory response and improve clinical outcome. Long pentraxin PTX3 is a novel inflammatory parameter that could play a protective cardiovascular role by regulating inflammation. Twenty-nine children undergoing open heart surgery were enrolled in the study. Fourteen received dexamethasone (1st dose 1.5 mg/Kg i.v. or i.m. the evening before surgery; 2nd dose 1.5 mg/kg i.v. before starting bypass) and fifteen children served as control. Blood PTX3, short pentraxin C-reactive protein (CRP), interleukin-1 receptor II (IL-1RII), fibrinogen and partial thromboplastin time (PTT) were assayed at different times. PTX3 levels significantly increased during CPB in dexamethasone-treated (+D) and dexamethasone-untreated (−D) subjects, but were significantly higher in +D than −D patients. CRP levels significantly increased both in +D and −D patients in the postoperative days, with values significantly higher in −D than +D patients. Fibrinogen and PTT values were significantly higher in −D than +D patients in the 1st postoperative day. IL-1RII plasma levels increased in the postoperative period in both groups. Dexamethasone prophylaxis in pediatric patients undergoing CPB for cardiac surgery is associated with a significant increase of blood PTX3 that could contribute to decreasing inflammatory parameters and improving patient clinical outcome

Determination of blood Cd in subjects living near dismessed mines and active industrial sites

The environmental exposure to Cd in 265 subjects living in a South-Western area of Sardinia (Sulcis-Iglesiente) with a great history of mining activities and large industrial settings was assessed. Individuals living near the industrial plants had geometric means (GM) of blood Cd (0.79 μg/l) significantly higher than controls (0.47 μg/l) and than residents of the mining sites (0.54 μg/l). Demographic and lifestyle variables were also investigated and data showed that smoke and age are important variables to consider

Novel heterozygous TREX1 mutation in a juvenile systemic lupus erythematosus patient with severe cutaneous involvement treated successfully with Jak-inhibitors: a case report

Juvenile systemic lupus erythematosus (jSLE) is a complex inflammatory autoimmune disorder. In the last decades, genetic factors and activation pathways have been increasingly studied to understand their potential pathogenetic role better. Genetic and transcriptional abnormalities directly involved in the type I interferon (IFN) signaling cascade have been identified through family-based and genome-wide association studies. IFNs trigger signaling pathways that initiate gene transcription of IFN-stimulated genes through the activation of JAK1, TYK2, STAT1, and STAT2. Thus, the use of therapies that target the IFN pathway would represent a formidable advance in SLE. It is well known that JAK inhibitors have real potential for the treatment of rheumatic diseases, but their efficacy in the treatment of SLE remains to be elucidated. We report the case of a 13-year-old girl affected by jSLE, carrying a novel heterozygous missense variant on Three prime Repair EXonuclease 1 (TREX1), successfully treated with baricitinib on top of mofetil mycophenolate. The TREX1 gene plays an important role in DNA damage repair, and its mutations have been associated with an overproduction of type 1 interferon. This report underlines the role of translational research in identifying potential pathogenetic pathways in rare diseases to optimize treatment

A Novel Mechanism of Soluble HLA-G Mediated Immune Modulation: Downregulation of T Cell Chemokine Receptor Expression and Impairment of Chemotaxis

BACKGROUND: In recent years, many immunoregulatory functions have been ascribed to soluble HLA-G (sHLA-G). Since chemotaxis is crucial for an efficient immune response, we have investigated for the first time the effects of sHLA-G on chemokine receptor expression and function in different human T cell populations. METHODOLOGY/PRINCIPAL FINDINGS: T cell populations isolated from peripheral blood were stimulated in the presence or absence of sHLA-G. Chemokine receptors expression was evaluated by flow cytometry. sHLA-G downregulated expression of i) CCR2, CXCR3 and CXCR5 in CD4(+) T cells, ii) CXCR3 in CD8(+) T cells, iii) CXCR3 in Th1 clones iv) CXCR3 in TCR Vdelta2gamma9 T cells, and upregulated CXCR4 expression in TCR Vdelta2gamma9 T cells. sHLA-G inhibited in vitro chemotaxis of i) CD4(+) T cells towards CCL2, CCL8, CXCL10 and CXCL11, ii) CD8(+) T cells towards CXCL10 and CXCL11, iii) Th1 clones towards CXCL10, and iv) TCR Vdelta2gamma9 T cells towards CXCL10 and CXCL11. Downregulation of CXCR3 expression on CD4+ T cells by sHLA-G was partially reverted by adding a blocking antibody against ILT2/CD85j, a receptor for sHLA-G, suggesting that sHLA-G downregulated chemokine receptor expression mainly through the interaction with ILT2/CD85j. Follicular helper T cells (T(FH)) were isolated from human tonsils and stimulated as described above. sHLA-G impaired CXCR5 expression in T(FH) and chemotaxis of the latter cells towards CXCL13. Moreover, sHLA-G expression was detected in tonsils by immunohistochemistry, suggesting a role of sHLA-G in local control of T(FH) cell chemotaxis. Intracellular pathways were investigated by Western Blot analysis on total extracts from CD4+ T cells. Phosphorylation of Stat5, p70 s6k, beta-arrestin and SHP2 was modulated by sHLA-G treatment. CONCLUSIONS/SIGNIFICANCE: Our data demonstrated that sHLA-G impairs expression and functionality of different chemokine receptors in T cells. These findings delineate a novel mechanism whereby sHLA-G modulates T cell recruitment in physiological and pathological conditions

Experimental study for the evaluation of creep in concrete through thermal measurements

This investigation, conducted at the Non-Destructive Testing Laboratory at the Politecnico di Torino, made it possible to establish an experimental relationship between specific creep values measured in concrete test pieces obtained from different mixes and the decrease in temperature observed in identical test pieces at the end of low-intensity short-duration compressive tests. This relationship is independent of type of mix and therefore has general validity: it can be used to make qualitative predictions about creep without having to perform long duration tests. It may lead to interesting developments in various applications, especially in the field of structural diagnosis