Geometria dell’anello di distribuzione e materiale utilizzato

La qualità chimica e microbiologica delle acque di dialisi è un requisito fondamentale per la biocompatibilità del trattamento emodialitico. Numerosi lavori in letteratura mostrano infatti come la composizione del liquido di dialisi rappresenti uno dei fattori responsabili dello stato microinfiammatorio cronico del paziente emodializzato con importanti conseguenze cliniche Al fine di garantire al paziente un trattamento dialitico con elevati standard di qualità e sicurezza si dovrebbe giungere oggi alla produzione di un dialisato che si definisce ultrapuro (carica batterica <0.1 UFC/ml e concentrazione endotossinica <0.03 UI/ml). Questo ha particolare importanza nelle metodiche “on-line” che consentono l’autoproduzione del liquido di sostituzione durante i trattamenti convettivi

Plasma exchange in acute and chronic hyperviscosity syndrome: a rheological approach and guidelines study

Therapeutic plasma exchange is an extra-corporeal technique able to remove from blood macromolecules and/or replace deficient plasma factors. It is the treatment of choice in hyperviscosity syndrome, due to the presence of quantitatively or qualitatively abnormal plasma proteins such as paraproteins. In spite of a general consensus on the indications to therapeutic plasma exchange in hyperviscosity syndrome, data or guide lines about the criteria to plan the treatment are still lacking. We studied the rheological effect of plasma exchange in 20 patients with plasma hyperviscosity aiming to give data useful for a rational planning of the treatment. Moreover, we verified the clinical applicability of the estimation of plasma viscosity by means of Kawai's equation. Plasma exchange decreases plasma viscosity about 20-30% for session. Only one session is required to normalize plasma viscosity when it is 2.2 till to 6 mPas. A fourth session is useless, especially if the inter-session interval is < 15 days. By means of a polynomial equation, knowing basal-plasma viscosity and the disease of a patient, we can calculate the decrease of viscosity obtainable by each session of plasma exchange then the number of session required to normalize the viscosity. Kawai's equation is able to evaluate plasma viscosity in healthy volunteers, but it is not clinically reliable in paraproteinemias. [Pubmed] [Scholar] [EndNote] [BibTex

Protective effects of the melanocortin analog NDP-α-MSH in rats undergoing cardiac arrest

We previously reported that melanocortins afford cardioprotection in conditions of experimental myocardial ischemia/reperfusion, with involvement of the janus kinases (JAK), extracellular signal-regulated kinases (ERK) and signal transducers and activators of transcription (STAT) signalings. We investigated the influence of the melanocortin analog [Nle(4), D-Phe(7)]α-melanocyte-stimulating hormone (NDP-α-MSH) on short-term detrimental responses to cardiac arrest (CA) induced in rats by intravenous (i.v.) administration of potassium chloride, followed by cardiopulmonary resuscitation (CPR) plus epinephrine treatment. In CA/CPR rats i.v. treated with epinephrine (0.1mg/kg) and returned to spontaneous circulation (48%) we recorded low values of mean arterial pressure (MAP) and heart rate (HR), alteration of hemogasanalysis parameters, left ventricle low expression of the cardioprotective transcription factors pJAK2 and pTyr-STAT3 (JAK-dependent), increased oxidative stress, up-regulation of the inflammatory mediators tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and down-regulation of the anti-inflammatory cytokine IL-10, as assessed at 1h and 3h after CPR. On the other hand, i.v. treatment during CPR with epinephrine plus NDP-α-MSH (340μg/kg) almost completely restored the basal conditions of MAP and HR, reversed metabolic acidosis, induced left ventricle up-regulation of pJAK2, pTyr-STAT3 and IL-10, attenuated oxidative stress, down-regulated TNF-α and IL-6 levels, and improved survival rate by 81%. CA/CPR plus epinephrine alone or in combination with NDP-α-MSH did not affect left ventricle pSer-STAT3 (ERK1/2-dependent) and pERK1/2 levels. These results indicate that melanocortins improve return to spontaneous circulation, reverse metabolic acidosis, and inhibit heart oxidative stress and inflammatory cascade triggered by CA/CPR, likely via activation of the JAK/STAT signaling pathway

Polymeric nanoparticles enhance the sonodynamic activity of meso-tetrakis (4-sulfonatophenyl) porphyrin in an in vitro neuroblastoma model

PURPOSE: Sonodynamic therapy is a developing noninvasive modality for cancer treatment, based on the selective activation of a sonosensitizer agent by acoustic cavitation. The activated sonosensitizer agent might generate reactive oxygen species leading to cancer cell death. We investigated the potential poly-methyl methacrylate core-shell nanoparticles (NPs) loaded with meso-tetrakis (4-sulfonatophenyl) porphyrin (TPPS) have to function as an innovative sonosensitizing system, ie, TPPS-NPs. METHODS: Shockwaves (SWs) generated by a piezoelectric device were used to induce acoustic cavitation. The cytotoxic effect of the sonodynamic treatment with TPPS-NPs and SWs was investigated on the human neuroblastoma cell line, SH-SY5Y. Cells were exposed for 12 hours to TPPS-NPs (100 μg/mL) and then to SWs (0.43 mJ/mm(2) for 500 impulses, 4 impulses/second). Treatment with SWs, TPPS, and NPs alone or in combination was carried out as control. RESULTS: There was a statistically significant decrease in SH-SY5Y cell proliferation after the sonodynamic treatment with TPPS-NPs and SWs. Indeed, there was a significant increase in necrotic (16.91% ± 3.89%) and apoptotic (27.45% ± 3.03%) cells at 48 hours. Moreover, a 15-fold increase in reactive oxygen species production for cells exposed to TPPS-NPs and SWs was observed at 1 hour compared with untreated cells. A statistically significant enhanced mRNA (messenger ribonucleic acid) expression of NRF2 (P<0.001) and a significant downregulation of TIGAR (P<0.05) and MAP3K5 (P<0.05) genes was observed in cells exposed to TPPS-NPs and SWs at 24 hours, along with a statistically significant release of cytochrome c (P<0.01) at 48 hours. Lastly, the sonosensitizing system was also investigated in an in vitro three-dimensional model, and the sonodynamic treatment significantly decreased the neuroblastoma spheroid growth. CONCLUSION: The sonosensitizing properties of TPPS were significantly enhanced once loaded onto NPs, thus enhancing the sonodynamic treatment’s efficacy in an in vitro neuroblastoma model

PO-435 Photoactivation of nanoparticles delivered by mesenchymal stem cells induces osteosarcoma cell death in in vitro 3D co-culture models

Introduction Osteosarcoma (OS) is a rare and aggressive tumour that mainly affects long bones of adolescents. Currently, OS patients are treated with a combination of multi-agent chemotherapy and surgery. However, 30% of patients do not respond to standard treatment. Therefore, innovative therapeutic agents are needed. Mesenchymal stem cells (MSCs) display a specific tumour-tropism and have been previously used in successful preclinical studies to deliver several therapeutic agents. Furthermore, the safety of genetically engineered MSCs was demonstrasted in ongoing clinical trial. The goal of the present study was to test in vitro whether MSCs could uptake photoactivable nanoparticles (NPs) and induce cell death of OS cells upon photoactivation. Material and methods Ptl@PMMA NPs were produced by adding tetrasulfonate aluminium phthalocyanine (Ptl) to an aqueous solution of positively charged poly-methylmethacrylate (PMMA) nanoparticles. The photosensitizer Ptl is activated in near-infrared light allowing a deep tissue penetration. Human MSC lines, isolated from the bone marrow of multiple donors, were loaded with Ptl@PMMA NPs. The MSCs' ability to internalise and retain NPs, along with their migratory properties, were tested. Cell death upon photoactivation (PDT) was evaluated in vitro, on a monolayer co-culture of MSCs and OS cells and in 3D multicellular spheroids, generated via cell suspension in ultralow attachment plates Results and discussions MSCs showed an internalisation rate of Plt@PMMA>95%, which did not alter cell viability and migratory capacity. When Ptl@PMMA-MSCs were co-cultured with a human OS cell line (SaOS-2) in monolayers, they efficiently triggered cell death upon PDT. In particular, AnnexinV/PI and CalceinAM/EthD staining showed 70% of cell death in the co-culture system. These results were also validated by a metabolic assay. Interestingly, in a 3D co-culture of the OS cell line MG63 and Ptl@PMMA-MSCs, we observed a marked reduction of the viability ( Conclusion For the first time, we demonstrated that photoactivation of MSCs loaded with Ptl@PMMA NPs can successfully induce OS cell death in a three-dimensional OS model. These results encourage further in vivo evaluation to demonstrate the specific targeting of Plt@PMMA loaded MSCs to the tumour stroma and the efficacy of PDT treatmen

Periodontitis is associated with significant hepatic fibrosis in patients with non-alcoholic fatty liver disease

This work was funded by the Diabetes Research and Wellness Fund. WA is in receipt of an MRC New Investigator Award