In vitro stimulation of murine peritoneal monocytes induced by alginates

In this trial we assessed the effect of soluble alginates on murine cells. Mouse peritoneal monocytes were stimulated in vitro with a solution of alginate. The production of TNF-alpha and nitric oxide (NO), the expression of surface molecules CD80 and CD86, and the ability of monocytes to phagocyte bacteria were assessed, in order to evaluate the effect of alginate on cell functionality. We showed that mouse peritoneal monocytes stimulated with alginate produce NO and TNF-alpha. In addition, alginate is able also to increase their phagocytic activity and to a lesser extent also to increase the expression of CD80. Even with different degrees, it implies that alginates per se act directly on immune response, being able to effectively stimulate proinflammatory activity. These findings corroborate the idea that alginates can represent interesting adjuvants to use to increase the efficacy of antigenic stimulation.     

In uremia, plasma levels of anti-protein C and anti-protein S antibodies are associated with thrombosis

BACKGROUND: Vascular access thrombosis is an important cause of morbidity in patients with end-stage renal failure on maintenance hemodialysis (MHD). However, little is known about its risk factors. The present study was undertaken to evaluate the role of coagulation factors, fibrinolytic factors, and anti-phospholipid antibodies (aPL). In particular, we have evaluated the role of anti-protein C and anti-protein S antibodies in patients on MHD with and without thrombosis because no data are available in the literature. METHODS: The study group comprised 30 patients with thrombotic complications (TC), 40 patients matched for age, sex, and dialytic age with no thrombotic complications (NTC) and 400 controls. We have measured: anti-protein C antibodies, anti-protein S antibodies, anticardiolipin antibodies (ACA), anti-beta2-glycoprotein antibodies (beta2-GPI), and anti-prothrombin antibodies (aPT), along with prothrombin time, fibrinogen, plasminogen, protein C, protein S, anti-thrombin III, APC-resistance test, D-dimer, tissue-type plasminogen's activator, plasminogen activator inhibitor-1 (PAI-1), prothrombin fragment 1+2, factors of the intrinsic and extrinsic pathway, C-reactive protein, and homocysteine. RESULTS: There were no significant differences between groups for prothrombin time, fibrinogen, plasminogen, protein C, protein S, anti-thrombin III, activated protein C (APC) resistance, D-dimer, tPA, C-reactive protein, Factors II, X, and VII. The anti-beta2-GP1 and aPT were elevated in both TC and NTC patients, compared to the control group. Significant differences between TC and NTC groups were found for anti-protein C and anti-protein S antibodies, ACA-IgM, PAI-1, Factor VIII, prothrombin fragments 1+2, and homocysteine. CONCLUSION: The most novel finding was a significant elevation of anti-protein C antibodies and anti-protein S antibodies in the TC group (i.e., in patients on MHD with thrombosis of vascular access). It indicates that other pathogenetic mechanisms in addition to endothelial damage may cause hypercoagulability in uremia.     

Impact of dose and volume on rectal tolerance

Based on the successful results achieved in survival and local control with radiotherapy of prostate cancer recent studies tried to establish some models to reliably predict late rectal toxicity. In fact, the rectum, due to its location, represents an organ at risk of acute and late toxicity with the onset of acute or chronic radiation proctitis. The concept of late consequential effect has gained ground. It implies that the late damage might be a direct consequence of the acute damage. Dose-escalation studies, conformal radiotherapy (3D-CRT) and intensity modulated radiotherapy (IMRT) led to the identification of parameters, based on dose-volume histograms (DVH), able to separate patients at low and high risk of toxicity. Precise predictive dosimetric factors play a major role in the definition of the onset of toxicity. The monitoring system of late toxicity used by the authors is presented.     

Norepinephrine protects cortical neurons against microglial-induced cell death

Interleukin-1 beta (IL-1beta) is one of the main cytokines involved in the inflammatory response; it has multiple effects that can contribute to cell damage, one of which is the upregulation of the inducible form of nitric oxide (NO) synthase (NOS2) in certain cell types. We demonstrated previously that in vivo, cortical microglial inflammatory responses were increased when noradrenaline (NE) levels were depleted, suggesting that NE can reduce microglial activation. In the present report, we examined the role of IL-1beta in neurotoxicity induced by microglial-conditioned media, and possible neuroprotective effects of NE. Incubation of cortical neurons with conditioned media (CM) obtained from lipopolysaccharide (LPS)-treated microglia induced neuronal NOS2 expression and increased neuronal cell death, and these responses were reduced if the neurons were coincubated with interleukin-1 receptor antagonist. Cotreatment of microglial cells with LPS plus NE potently blocked IL-1beta production and reduced the ability of the CM to induce neuronal NOS2 and cell death. These results suggest that microglial release of IL-1beta is an important activator of neuronal inflammatory responses, and that protective effects of NE upon neurons involve a reduction of microglial-derived IL-1beta.     

Expression and Membrane Association of Hepatitis C Virus Envelope 1 Protein

The expression of hepatitis C virus (HCV) E1 protein is toxic for Escherichia coli cells. For this reason, we have cloned the E1 gene in the pET3a vector and analyzed the inducible expression of the protein in two strains of E. coli characterised by a different level of reduction of basal synthesis. The results indicated that synthesis of E1 was supported only by the BL21(DE3)pLysS strain which provides a tightest control of protein expression before the induction. The BL21(DE3)pLysS cells were then used for the expression of E1 gene, varying at its carboxy terminus in order to retain (E1, aa 192–383) or delete (E1t, aa 192–340) a C-terminal hydrophobic region that may be involved in membrane association. Following cell fractionation, E1 protein was found associated with the membrane fraction. By contrast, the truncated mutant E1t, was identified in the soluble phase suggesting a direct role for the C-terminal domain in E1 membrane association.     

Clinical manifestations and management of four children with Pearson syndrome

Pearson marrow-pancreas syndrome is a fatal disorder mostly diagnosed during infancy and caused by mutations of mitochondrial DNA. We hereby report on four children affected by Pearson syndrome with hematological disorders at onset. The disease was fatal to three of them and the fourth one, who received hematopoietic stem cell transplantation, died of secondary malignancy. In this latter patient transplantation corrected hematological and non-hematological issues like metabolic acidosis, and we therefore argue that it could be considered as a useful option in an early stage of the disease.     

De novo mosaic ring chromosome 18 in a child with mental retardation, epilepsy and immunological problems

Ring chromosome 18 [r(18)] is a disorder in which one or both ends of chromosome 18 are lost and joined forming a ring-shaped figures. R(18) patients can therefore show features of 18q-, 18p- syndrome or a combination of both, depending on the size of the 18p and 18q deleted regions. The phenotype of the r(18) is characterized by developmental delay/mental retardation, typical facial dysmorphisms, major abnormalities and immunological problems. Here we report a case of de novo mosaic r(18) with a characterization by array-based comparative genomic hybridization analysis, and discuss the phenotypic correlation in r(18) also through a comparison with previously described cases of the literature.