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Background: miRNA‐based strategies have recently emerged as a promising therapeutic approach in several neurodegenerative diseases. Unregulated cation influx is implicated in several cellular mechanisms underlying neural cell death during ischemia. The brain constitutively active isoform of transient receptor potential melastatin 7 (TRPM7) represents a glutamate excitotoxicity‐independent pathway that significantly contributes to the pathological Ca2+ overload during ischemia. Aims: In the light of these premises, inhibition of TRPM7 may be a reasonable strategy to reduce ischemic injury. Since TRPM7 is a putative target of miRNA135a, the aim of the present paper was to evaluate the role played by miRNA135a in cerebral ischemia. Therefore, the specific objectives of the present paper were: (1) to evaluate miR135a expression in temporoparietal cortex of ischemic rats; (2) to investigate the effect of the intracerebroventricular (icv) infusion of miR135a on ischemic damage and neurological functions; and (3) to verify whether miR135a effects may be mediated by an alteration of TRPM7 expression. Methods: miR135a expression was evaluated by RT‐ PCR and FISH assay in temporoparietal cortex of ischemic rats. Ischemic volume and neurological functions were determined in rats subjected to transient middle cerebral artery occlusion (tMCAo) after miR135a intracerebroventricular perfusion. Target analysis was performed by Western blot. Results: Our results demonstrated that, in brain cortex, 72 h after ischemia, miR135a expression increased, while TRPM7 expression was parallelly downregulated. Interestingly, miR135a icv perfusion strongly ameliorated the ischemic damage and improved neurological functions, and downregulated TRPM7 protein levels. Conclusions: The early prevention of TRPM7 activation is protective during brain ischemia. [ABSTRACT FROM AUTHOR]

Antifungal prophylaxis may be required in high-risk patients undergoing liver transplantation and for that reason we aimed to verify its role and its related impact on the graft. From January 2006 throughout 2012, 250 liver transplants were evaluated and 54 patients identified as being at higher risk were randomly selected to undergo the following schedule: 28 patients received liposomal amphotericin B and 26 received caspofungin. We evaluated, throughout 12 months, renal and liver function tests, bacterial and fungal infection episodes, and intensive care unit (ICU) stay, as well as the Th1 and Th2 cytokine network. Differences were analyzed according to non-parametric tests (two-tailedpvalues). Neither of the groups showed episodes of invasive fungal infection during the 12 months follow-up; however, patients receiving prophylaxis with liposomal amphotericin B had reduced episodes of bacterial infections coupled with an improved immune system response compared with those receiving caspofungin. Finally, a reduced stay in the ICU was also observed. In conclusion, even if the results of liposomal amphotericin B and caspofungin prophylaxis strategies did not differ in terms of invasive fungal infection rate, patients receiving prophylaxis with liposomal amphotericin B had a reduced ICU stay and an improved Th2 status, as well as a reduced number of post-transplant bacterial infections. Further studies are required to better address and evaluate these findings. [ABSTRACT FROM AUTHOR]

Over the last few years, although extensive studies have focused on the relevant function played by the sodium–calcium exchanger (NCX) during focal ischemia, a thorough understanding of its role still remains a controversial issue. We explored the consequences of the pharmacological inhibition of this antiporter with conventional pharmacological approach, with the synthetic inhibitory peptide, XIP, or with an antisense strategy on the extent of brain damage induced by the permanent occlusion of middle cerebral artery (pMCAO) in rats. Collectively, the results of these studies suggest that ncx1 and ncx3 genes could be play a major role to limit the severity of ischemic damage probably as they act to dampen [Na+]i and [Ca2+]i overload. This mechanism seems to be normally activated in the ischemic brain as we found a selective upregulation of NCX1 and NCX3 mRNA levels in regions of the brain surviving to an ischemic insult. Despite this transcript increase, NCX1, NCX2, and NCX3 proteins undergo an extensive proteolytic degradation in the ipsilateral cerebral hemisphere. All together these results suggest that a rescue program centered on an increase NCX function and expression could halt the progression of the ischemic damage. On the basis of this evidence we directed our attention to the understanding of the transductional and transcriptional pathways responsible for NCX upregulation. To this aim, we are studying whether the brain isoform of Akt, Akt1, which is a downstream effector of neurotrophic factors, such as NGF can, in addition to affecting the other prosurvival cascades, also exert its neuroprotective effect by modulating the expression and activity of ncx1, ncx2, and ncx3 gene products. [ABSTRACT FROM AUTHOR]

Evaluates the anesthetic management and perioperative course in right-lobe living liver-donor surgery in Great Britain. Characteristics of donors; List of right-lobe living liver-donors; Elevation on liver function tests of donors.

Introduction We previously found that FK did not induce a severe reduction of immune response compared to other clacineurin inhibitor (ILTS 2009 oral presentation). Aim We aimed to evaluate the in vitro effect of tacrolimus on hepatitis C virus (HCV)-specific immune response by ELISpot to establish early the possible effect of immunosuppression and so tailoring immunosuppressive schedule before OLTx to minimize or delay HCV recurrence. Method Twenty-five HCV+ve patients (20 male and 5 female) on waiting list were enrolled. Blood samples were taken and at least on 2–2.5×10 cells per well ELISpot was performed to evaluate IFN-specific response after coculturing with 1 ng/ml or 5 ng/ml of FK for 24 h. CMV and a specific stimulation with PMI-Ionomicin were used as control on HCV patients. Ten healthy donors were used as control. Results After 24 h of FK stimulation, PMA-Ion IFN-response was reduced in all patients (p<0.05) compared to basal values both with 1 ng/ml that 5 ng/ml while CMV- specific showed reduction only when cocultured with 5 ng/ml. Among patients on waiting list, we had that 8 out 25 had a major reduction of HCV and CMV specific response (p <0.05) while 17 out 25 had no statistical significant changes in their IFN response. Conclusion Based on these results and our previous data, ELISpot assay before OLTx may useful to establish the impact of immunosuppressive schedule. In those having a major reduction of HCV specific immune response after CNI stimulation (FK) a different drug should be used to minimize or delay the possible HCV recurrence. Further studies are required to establish in vitro effects. Results p<0.05; p>0.05. [ABSTRACT FROM PUBLISHER]