Prevalence of anti-FVIII antibodies in severe haemophilia A patients with inversion of intron 22

The aim of our study was to investigate whether haemophilia A patients with inversion of intron 22 are at high risk for non-inhibitory anti-FVIII antibodies development detected by ELISA. It is known that patients with severe forms of haemophilia A are more likely to develop anti-FVIII antibodies. The incidence of inhibitory anti-FVIII antibodies in patients with factor VIII gene inversion has been extensively evaluated, but if this defect has to be considered a predisposing factor is still debatable. Non-inhibitory anti-FVIII antibodies are attracting interest, due to the potential influence on FVIII half-life. Our data show that FVIII gene inversion was a major predisposing factor for anti-FVIII antibodies development.     

Pseudotumoral form of neuroschistosomiasis: report of three cases.

Central nervous system (CSN) involvement in schistosomiasis is an ectopic manifestation with a large variety of clinical forms, including pseudotumoral, which occurs in isolated cases and is rare. Three patients with epidemiological indications of this pathology were examined; the clinical picture included lower-back pain irradiating to lower limbs, associated with progressive flaccid paraparesis and sphincterial disturbances in cases in which the spinal chord was involved; while in cases with encephalitic impairment, headache, dizziness and cerebellar syndrome, characterized by dysarthria and right-side dysgraphia, were present. Magnetic resonance imaging (MRI) showed a growing process in all cases; cerebrospinal fluid (CSF) characteristics and biological markers were compatible with neuroschistosomiasis (NS). Biopsy of the lesions confirmed this diagnosis in one case. After specific treatment with schistosomicides and corticosteroids, clinical, radiological and laboratorial improvement was observed.     

Monocyte-derived tissue factor contributes to stent thrombosis in an in vitro system

OBJECTIVES: This study evaluated the role of circulating tissue factor (TF) in mediating thrombus formation on stents in an in vitro model of stent perfusion. BACKGROUND: The traditional view of coagulation has recently been challenged by the demonstration that TF is present in circulating blood. The potential contribution of this intravascular pool of TF to thrombus formation on stents is not known. METHODS: Coronary stents were placed in parallel silicone tubes connected to a roller pump that was set to pump blood at a flow rate of 10 ml/min. Stents were then exposed to heparinized blood from healthy volunteers for 120 min. RESULTS: The presence of the stent in the circuit caused a significant increase in monocyte TF expression, but only monocytes with attached platelets stained positive for TF. Thrombi formed on stents and the thrombi stained positive for TF. Pretreatment of blood with a monoclonal antibody against TF (cH36) caused a 56% reduction in (125)I-fibrin(ogen) deposition on stents compared with controls (p = 0.002). Monocyte depletion of blood reduced (125)I-fibrin(ogen) deposition by 45% (p = 0.01) and TF staining in the thrombus by 83% (p = 0.01). Pretreatment of blood with a monoclonal antibody against P-selectin reduced (125)I-fibrin(ogen) deposition by 24% (p = 0.04). Perfusion of stents with leukocyte-reduced platelet-rich plasma (PRP) produced small thrombi and treatment of PRP with cH36 reduced (125)I-fibrin(ogen) deposition by 43% (p = 0.01). CONCLUSIONS: Circulating TF plays a pivotal role in thrombus formation on stents. Monocytes appear to be the main, but not only, source of TF depositing in the thrombus.     

Abnormal T cell selection on nod thymic epithelium is sufficient to induce autoimmune manifestations in C57BL/6 athymic nude mice

To investigate the role of primary T cell repertoire selection in the immunopathogenesis of autoimmune diseases, pure thymic epithelium (TE) from nonobese diabetic (NOD) embryos was grafted into non autoimmune prone newborn C57BL/6 athymic mice. The results show that NOD TE selects host T cell repertoires that establish autoimmunity in otherwise nondiabetic animals. Thus, such chimeras regularly show CD4 and CD8 T cell-mediated insulitis and sialitis, in contrast with syngeneic or allogeneic chimeras produced with TE from nonautoimmune strains. This is the first demonstration that autoimmunity to pancreatic β cells and salivary glands can be established by the sole alteration of the thymic environment involved in T cell selection, regardless of the nature and presentation of both major histocompatibility complex and tissue-specific antigens on the target organ. These data indicate that T cell repertoire selection by the NOD thymic epithelium is sufficient to induce specific autoimmune characteristics in the context of an otherwise normal host.     

Postprandial serum induces apoptosis in endothelial cells: Role of polymorphonuclear-derived myeloperoxidase and metalloproteinase-9 activity

Postprandial state is a pro-inflammatory condition associated with a transient impairment of endothelial function. Recent evidence suggests that myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9) are involved in the pathogenesis of inflammatory vascular diseases such as atherosclerosis. The present study was carried out to investigate whether a fat meal induces polymorphonuclear (PMN) activation and increases the plasma activity of MPO and MMP-9 and whether postprandial serum exerts pro-apoptotic effects on endothelial cells. Fifteen healthy young men underwent a high-fat challenge containing 60g butter. Blood samples were drawn before, and 1, 2, and 4h after the meal. Leukocyte reactive oxygen species (ROS) production, plasma MPO and MMP-9 activity, endothelial-derived soluble CD146 levels, and advanced oxidation protein product (AOPP) levels were determined. Human umbilical vein endothelial cells (HUVECs) were treated with human sera to evaluate mitochondrial membrane potential, ROS production, annexin PI staining, and caspase-3 activity. Triglycerides, ROS production, MPO activity, AOPP levels, pro-MMP-9 zymographic activity, and soluble CD146 levels significantly increased during the 4h after the test meal. Postprandial serum significantly decreased the mitochondrial membrane potential, and increased the rate of ROS production, the percentage of annexin-positive HUVECs, and caspase-3 activity. A strong relationship was observed between postprandial increase in PMN-derived MPO and pro-MMP-9 activity, and the increased rate of apoptosis of endothelial cells exposed to postprandial serum. Data show that postprandial serum exerts pro-apoptotic effects on endothelial cells. The close relationships between markers of endothelial cell apoptosis and MPO and pro-MMP-9 activity suggest that the latter may contribute to the development of fat meal induced endothelial damage.     

RS 10767664 gene variant in Brain Derived Neurotrophic Factor (BDNF) affect metabolic changes and insulin resistance after a standard hypocaloric diet

Background

Role of BDNF variants on change in body weight and cardiovascular risk factors after weight loss remains unclear in obese patients.