Spin-lattice relaxation time in water/graphene-oxide dispersion.

We present the results of the calculations of the spin-lattice relaxation time of water in contact with graphene oxide by means of all-atom molecular dynamics simulations. We fully characterized the water-graphene oxide interaction through the calculation of the relaxation properties of bulk water and of the contact angle as a function of graphene oxide oxidation state and comparing them with the available experimental data. We then extended the calculation to investigate how graphene oxide alters the dynamical and relaxation properties of water in different conditions and concentrations. We show that, despite the diamagnetic nature of the graphene oxide, the confining effects of the bilayers strongly affect the longitudinal relaxation properties of interfacial water, which presents a reduced dynamics due to hydrogen bonds with oxygen groups on graphene oxide. This property makes graphene oxide an interesting platform to investigate water dynamics in confined geometries and an alternative contrast-agent for magnetic resonance imaging applications, especially in view of the possibility to functionalize graphene oxide from theranostic perspectives.

YAP/TAZ mechano-transduction as the underlying mechanism of neuronal differentiation induced by reduced graphene oxide.

AIM: The aim of this work is the dissection of the molecular pathways underlying the differentiation effect of reduced graphene oxide (GO) materials in the absence of differentiation agents. MATERIALS & METHODS: Reduced GO is obtained either by drop casting method and heat-treated or biological reduction by the interaction between GO and wtPrxI. Cells were grown on both materials and the differentiation process studied by immunological and morphological detection. RESULTS & CONCLUSION: The results obtained indicate that both reduction methods of GO can determine the modulation of pathway involved in mechano-transduction and differentiation, by affecting YAP/TAZ localization outside the nuclei and increasing neuronal differentiation markers. This suggests that the mechano-transduction pathways are responsible for the differentiation process.

Influence of childhood trauma on diagnosis and substance use in first-episode psychosis.

BackgroundChildhood trauma has been significantly associated with first-episode psychosis, affective dysfunction and substance use.AimsTo test whether people with first-episode psychosis who had experienced childhood trauma, when compared with those who had not, showed a higher rate of affective psychosis and an increased lifetime rate of substance use.MethodThe sample comprised 345 participants with first-episode psychosis (58% male, mean age 29.8 years, s.d. = 9.7).ResultsSevere sexual abuse was significantly associated with a diagnosis of affective psychosis (χ2 = 4.9, P = 0.04) and with higher rates of lifetime use of cannabis (68% v 41%; P = 0.02) and heroin (20% v 5%; P = 0.02). Severe physical abuse was associated with increased lifetime use of heroin (15% v 5%; P = 0.03) and cocaine (32% v 17%; P = 0.05).ConclusionsPatients with first-episode psychosis exposed to childhood trauma appear to constitute a distinctive subgroup in terms of diagnosis and lifetime substance use.

Activation of nuclear inositide signalling pathways during erythropoietin therapy in low-risk MDS patients.

Inositide signaling pathways can have a role in the Myelodysplastic Syndromes (MDS) progression to acute myeloid leukemia. Erythropoietin (EPO) is currently used in low-risk MDS, where it successfully corrects anemia in 50-70% of patients. However, some MDS patients are refractory to this treatment and little is known about the exact molecular mechanisms underlying the effect of EPO in these subjects. Here, we investigated the role of inositide pathways in low-risk MDS treated with EPO, mainly focusing on the Akt/PI-PLC (Phosphoinositide-Phospholipase C) gamma1 axis, which is activated by the EPO receptor, and PI-PLCbeta1/Cyclin D3 signaling, as Cyclin D3 is associated with hematopoietic proliferation and differentiation. Interestingly, EPO responder patients showed a specific activation of both the Akt/PI-PLCgamma1 pathway and beta-Globin gene expression, while nonresponders displayed an increase in PI-PLCbeta1 signaling. Moreover, in normal CD34+ cells induced to erythroid differentiation, PI-PLCbeta1 overexpression abrogated both EPO-induced Akt phosphorylation and beta-Globin expression. Overall, these findings suggest that PI-PLCbeta1 can act as a negative regulator of erythroid differentiation and confirm the involvement of Akt/PI-PLCgamma1 pathway in EPO signaling, therefore contributing to the comprehension of the effect of EPO in low-risk MDS and possibly paving the way to the identification of MDS patients at higher risk of refractoriness to EPO treatment.

Dyslipidemia can reduce the immunosuppressive effects of cyclosporine.

AIMS: Dyslipidemia is a significant risk factor for the development of atherosclerotic disease and of chronic allograft rejection. Few data are available on the effects of dyslipidemia on the immunosuppressive action of immunosuppressive agents. We investigate the in vitro effects of lipids solution on the immunosuppressive action of cyclosporine (CsA). METHODS: Peripheral blood mononuclear cells (PBMC) were PHA or OKT3 activated in vitro with/without different concentrations of Intralipid solution (INT, range 0.5% to 15%). CsA inhibition of activation was measured after a 3 day incubation, by adding H3-thimidine. The intracellular concentration of CsA was measured by radioimmunoassay and related to the CsA inhibitory effects. RESULTS: Increasing INT concentration in the medium, CsA inhibition of PBMC activation by PHA or OKT3 was reduced from 72+/-13% to 8+/-2% and from 80+/-10% to 18+/-3%, respectively. A significant reduction of the intracellular CsA concentration was also evident with increasing INT concentrations and was related to the inhibitory activity of CsA. CONCLUSIONS: These results suggest that dyslipidemia may reduce the availability of intracellular CsA concentration to inhibit the immune activation process and may explain the relationship between dyslipidemia and chronic allograft loss.

Cord blood mononuclear cell responsiveness to beta-lactoglobulin: T-cell activity in 'atopy-prone' and 'non-atopy-prone' newborns.

We have studied the T-cell-mediated response to the major allergen of cow's milk, in a group of newborns at risk of developing cow's milk allergy, and in a control group. Before any atopic status has developed, we observe beta-lactoglobulin-specific primary proliferation only in the group at risk for food-related allergies. In this group, the capability to proliferate is not due to placental transmission of 'factors' from allergic mothers. The recognition of the tested beta-lactoglobulin peptides does not show major differences between the responder and nonresponder populations. In the responder population, the response to p145-161 appears linked to a primary response to ovalbumin, another frequent food allergen. On the basis of our findings, we propose a model in which development of allergic diseases is linked to an alteration of T-cell activation through the engagement by the antigen; the HLA phenotype determines the allergen(s) involved, and other genetic or environmental factors dictate the clinical characteristics of the disease.

A comparative study of doxazosin versus atenolol in mild-to-moderate hypertension.

Doxazosin, a quinazoline derivative, is a selective alpha 1-inhibitor that reduces calculated coronary heart disease risk by lowering blood pressure while favorably affecting blood lipid levels. The aim of this study was to compare the efficacy and toleration of doxazosin with atenolol, one of the most frequently used cardioselective beta-blockers in Italy. Forty patients with mild-to-moderate hypertension were treated with either atenolol (100 mg) or doxazosin (mean dose, 3.3 mg) once daily for 8 weeks. Both drugs significantly reduced supine and standing systolic and diastolic blood pressures. Atenolol induced marked bradycardia, whereas doxazosin had very little effect on heart rate. Doxazosin produced a favorable effect on blood lipid levels by decreasing triglyceride and total cholesterol levels and increasing high-density lipoprotein cholesterol and high-density lipoprotein total cholesterol ratio. Atenolol had exactly the opposite effect on blood lipid levels. Both drugs had equivalent toleration profiles. It was concluded that doxazosin was as effective as atenolol in reducing elevated supine and standing blood pressures. In addition, doxazosin had a beneficial effect on lipid profiles and minimal effect on heart rate. Therefore doxazosin may reduce calculated coronary heart disease risk in hypertensive patients.