The SHP-1 expression is associated with cytokines and psychopathological status in unmedicated first episode schizophrenia patients.

BACKGROUND: Recent lines of research have boosted awareness of the immunological facets of schizophrenia. However, associations with protein tyrosine phosphatase regulators have never been reported. The aim of our study was to investigate the expression and promoter status methylation of phosphatase SHP-1, a key negative regulator of the inflammatory process, in Peripheral blood mononuclear cells (PBMCs) of Schizophrenic patients. METHODS: We enrolled fifty-four (28 men and 26 women) unmedicated first episode subjects (SC) who met DSM-IV and thirty-eight (22 men and 16 women) healthy controls (HC). The SC psychopathological status was assessed using the Positive and Negative Syndrome Scale. We evaluated SHP-1 expression by Quantitative Real-time PCR (qPCR) and Western blotting (WB) methods and promoter status methylation through PCR bisulfate. IKK/NFkB signaling was detected by WB, and medium and plasma levels of pro-inflammatory cytokines (IL-1ß, IL-2, and TNF-α) by the ELISA method. SHP-1 was silenced by treating cells with specific siRNA. RESULTS: We found a significantly lower level of SHP-1 gene expression in PBMCs from SC vs. HC, consistently with which the promoter region analyzed presented significant hypermethylation. Silencing of SHP-1 expression induced higher activation of IKK/NF-kB signaling and pro-inflammatory cytokine production in ex vivo PBMCs from both SC and HC. Linear regression among patients generated a model in which SHP-1 expression explained 30% of the clinical negative symptom variance (adjusted R(2)=0.30, ANOVA p<0.001). CONCLUSIONS: Our findings are the first to suggest that impairment of SHP-1 expression is involved in the physiopathology of schizophrenia, opening fruitful new avenues for ameliorating treatment at least of negative symptoms.

Negative feedback interaction of HO-1/INOS in PBMC of acute congestive heart failure patients.

Heart failure (HF) is a common clinical syndrome with frequent exacerbations requiring hospitalization. Among the various mechanisms that underlie the pathogenesis of HF, the activation of the immune system leads to a progressive and redundant release of proinflammatory cytokines responsible for a variety of deleterious effects in heart failure, such as endothelial dysfunction, apoptosis of myocytes, activation of MMPs (Matrix Metallo Proteinases) and oxidative stress, with the result of decreased inotropism and clinical syndrome such as pulmonary edema,. The condition of oxidative stress induces the expression of genes coding for the proteins inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1). Twenty-five hospitalized cardiology patients with symptomatic acute congestive HF (NYHA Class III-IV) and impaired left ventricular (LV) function (ejection fraction less than 35 percent) were included in the study. The aim of this study was to evaluate the cytokines plasma concentrations and the expression and activity of iNOS and HO-1 proteins in peripheral blood mononuclear cell (PBMC) extracted from patients in comparison to control group. In ACHF; left ventricular ejection fraction (LVEF) percent was reduced. Furthermore; iNOS and HO-1 expression and cytokines plasma levels were significantly higher in patients with ACHF as compared to controls group. Moreover the enzyme activity presents an opposite trend compared to that obtained in the analysis of the transcript and proteins. Our studies suggest a negative feedback interaction between iNOS and HO-1 important in the physiopathology of heart failure that could be considered a good candidate as a future therapeutic target for the development of new drugs.

The plasmatic and salivary levels of IL-1ß, IL-18 and IL-6 are associated to emotional difference during stress in young male.

Saliva collection is considered a non-invasive method to detect inflammatory markers in response to emotional states within natural social contexts. Numerous studies have prompted an important role of cytokines in modulating distinct aspects of social and emotional behavior. The aim of this study was to investigate the reliability of plasma and saliva as investigative tools for measure some inflammatory marker levels (CRP, IL-1ß, IL-18, and IL-6). At the same time, the relationships between these markers and emotional states in response to a socio-cognitive stress (Academic Exam, AE), were considered. It was demonstrated that the plasma and saliva concentrations of all immune-mediators analyzed were significantly related across the socio-cognitive stress. In addition, when there was a close correlation to AE, the anger state, the IL-1ß, the IL-18 salivary and plasmatic concentrations were significantly higher, while they decreased during the AE. On the other hand, the anxiety state and the IL-6 levels significantly increased throughout the AE. The IL-1ß and IL-6 were positively associated to the anger and the anxiety state, respectively. In conclusion, our data highlight that different immune markers are similarly detectable in plasma and saliva during socio-cognitive stress. Also, they could be related to different emotional responses.

Extremely low-frequency electromagnetic fields accelerates wound healing modulating MMP-9 and inflammatory cytokines.

OBJECTIVES: In our previous reports, we have demonstrated that extremely low-frequency electromagnetic fields (ELF-EMF) exposure enhances the proliferation of keratinocyte. The present study aimed to clarify effects of ELF-EMF on wound healing and molecular mechanisms involved, using a scratch in vitro model. MATERIALS AND METHODS: The wounded monolayer cultures of human immortalized keratinocytes (HaCaT), at different ELF-EMF and Sham exposure times were monitored under an inverted microscope. The production and expression of IL-1ß, TNF-α, IL-18 and IL-18BP were measured by enzyme-linked immunosorbent assay and quantitative real-time PCR. The activity and the expression of matrix metalloproteinases (MMP)-2/9 was evaluated by zymography and Western blot analysis, respectively. Signal transduction proteins expression (Akt and ERK) was measured by Western blot. RESULTS: The results of wound healing in vitro assay revealed a significant reduction of cell-free area time-dependent in ELF-EMF-exposed cells compared to Sham condition. Gene expression and release of cytokines analysed were significantly increased in ELF-EMF-exposed cells. Our results further showed that ELF-EMF exposure induced the activity and expressions of MMP-9. Molecular data showed that effects of ELF-EMF might be mediated via Akt and ERK signal pathway, as demonstrated using their specific inhibitors. CONCLUSIONS: Our results highlight ability of ELF-EMF to modulate inflammation mediators and keratinocyte proliferation/migration, playing an important role in wound repair. The ELF-EMF accelerates wound healing modulating expression of the MMP-9 via Akt/ERK pathway.

Super-oxide anion production and antioxidant enzymatic activities associated with the executive functions in peripheral blood mononuclear cells of healthy adult samples.

Executive Functions (EFs) involve a set of high cognitive abilities impairment which have been successfully related to a redox omeostasis imbalance in several psychiatric disorders. Firstly, we aimed to investigate the relationship between executive functioning and some oxidative metabolism parameters in Peripheral Blood Mononuclear Cells (PBMCs) from healthy adult samples. The Brown Attention-Deficit Disorder Scales were administered to assess five specific facets of executive functioning. Total superoxide anion production, Super Oxide Dismutase (SOD), Catalase (CAT), Glutathione Reductase (GR) and Glutathione Peroxidase (GPx) activities were evaluated on proteins extracted from the PBMCs. We found significant positive correlations between superoxide anion production and the total score of the 'Brown' Scale and some of its clusters. The GPx and CAT activities were negatively associated with the total score and some clusters. In a linear regression analysis, these biological variables were indicated as the most salient predictors of the total score, explaining the 24% variance (adjusted R(2)=0.24, ANOVA, p<.001). This study provides novel evidence that Executive Functions have underpinnings in the oxidative metabolism, as ascertained in healthy subjects.

A miniaturized electrolytic pump sensorized with a strain gauge based on thermoplastic nanocomposite for drug delivery systems.

In this paper we present a miniature electrolytic pump sensorized with a novel strain sensor to be used as active component of a drug delivery system. It consists of an electrolytic solution reservoir where inert electrodes are immersed. By polarizing the electrodes, the electrolytic reaction is activated and the produced gases (i.e. oxygen and hydrogen) displace an elastic membrane delimiting the electrolytic solution reservoir. In order to measure and monitor the membrane displacement, and therefore the volume of drug ejected, a strain gauge sensor has been prepared using a conductive thermoplastic nanocomposite elastomer (CTPE). The sensor has been fixed on the deformable membrane. The conductive thermoplastic elastomer is a good candidate for this application because of its high sensitivity. Furthermore, the CTPE allows to customize the resistance of the device in order to obtain low power consumption.

Does the location of the arterial input function affect quantitative CTP in patients with vasospasm?

BACKGROUND AND PURPOSE: In recent years, there has been increasing use of CTP imaging in patients with aneurysmal SAH to evaluate for vasospasm. Given the critical role of the arterial input function for generation of accurate CTP data, several studies have evaluated the effect of varying the arterial input function location in patients with acute stroke. Our aim was to determine the effect on quantitative CTP data when the arterial input function location is distal to significant vasospasm in patients with aneurysmal SAH. MATERIALS AND METHODS: A retrospective study was conducted of patients with aneurysmal SAH admitted from 2005 to 2011. Inclusion criteria were the presence of at least 1 anterior cerebral artery or MCA vessel with a radiologically significant vasospasm and at least 1 of these vessels without vasospasm. We postprocessed each CTP dataset 4 separate times by using standardized methods, only varying the selection of the arterial input function location in the anterior cerebral artery and MCA vessels. For each of the 4 separately processed examinations for each patient, quantitative data for CBF, CBV, and MTT were calculated by region-of-interest sampling of the vascular territories. Statistical analysis was performed by using a linear mixed-effects model. RESULTS: One hundred twelve uniquely processed CTP levels were analyzed in 28 patients (mean age, 52 years; 24 women and 4 men) recruited from January 2005 to December 2011. The average Hunt and Hess scale score was 2.89 ± 0.79. The average time to CTP from initial presentation was 8.2 ± 5.1 days. For each vascular territory (right and left anterior cerebral artery, MCA, posterior cerebral artery), there were no significant differences in the quantitative CBF, CBV, and MTT generated by arterial input function locations distal to significant vasospasm compared with nonvasospasm vessels (P > .05). CONCLUSIONS: Arterial input function placement distal to significant vasospasm does not affect the quantitative CTP data in the corresponding vascular territory or any other vascular territory in aneurysmal SAH.