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Elton Dajti,1,2 Luigina Vanessa Alemanni,1,2 Giovanni Marasco,1,2 Marco Montagnani,1,2 Francesco Azzaroli1,2 1IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 2Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, ItalyCorrespondence: Francesco AzzaroliIRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalyEmail francesco.azzaroli@unibo.itAbstract: Portal hypertension is the main driver of complications in patients with advanced chronic liver disease (ACLD) and is defined by values of hepatic venous pressure gradient measurement (HVPG) > 5 mmHg. Values of HVPG ≥ 10 mmHg determine the presence of clinically significant portal hypertension (CSPH), the main predictor of the risk of variceal bleeding, hepatic decompensation, and mortality. However, its measurement is invasive and requires high expertise, so its routine use outside third level centers or clinical trials is limited. In the last decades, several non-invasive tests (NITs) have been developed and validated for the diagnosis of portal hypertension. Among these, liver (LSM) and spleen stiffness measurement (SSM) are the most promising tools available, as they have been proven accurate to predict CSPH, high-risk esophageal varices, decompensation, and mortality in patients with ACLD. In the last Baveno VI Consensus proceedings, LSM evaluation was recommended for the first time for diagnosis of CSPH (LSM > 20-25 kPa) and the screening of patients with a low probability of having high-risk varices (LSM < 20 kPa and platelet count > 150.000/mm3). In this review, we aimed to summarize the growing evidence supporting the use of non-invasive tests for the evaluation of portal hypertension in patients with chronic liver disease.Keywords: liver stiffness, spleen stiffness, portal hypertension, hepatic venous pressure gradient, liver cirrhosis

Byline: M. Montagnani, A. Rodis, C. Albertini, L.J. Griffiths Ceramic materials are characterized by unique combinations of properties that make them attractive for many specialized applications where metals are inadequate. On the other hand, their inherent brittleness makes the design and development of reliable ceramic structural members extremely difficult. In order to obtain engineering data to be introduced in computer codes, the following developments are presented: (i) A special specimen which permits the ceramic material to be subjected in one-dimensional shear or combined shear by loading it in compression (or tension) and torsion; (ii) A classical hydropneumatic press, capable of applying compressive loads and introducing one-dimensional shear on the specimen, at low strain rate (quasi-static); (iii) A new device (pressure-bar), based on the stress-wave technique, capable of applying on the new ceramic shear specimen, axial compression and torsion and subjecting it to one-dimensional or combined shear. This device operates in the field of strain rates up to 10[sup.3] s.SUP.−1. First results obtained by testing the new ceramic shear specimen of A1.SUB.2O.SUB.3 (92%) on the hydropneumatic press are reported.

OBJECTIVE: Pharmacological post-conditioning (PC) by intermittent but not continuous administration of exogenous bradykinin (BK) reduces ischemia/reperfusion (I/R) injury via the Reperfusion Injury Salvage Kinase (RISK) pathway activation. We evaluated whether intermittent administration with icatibant (HOE140), a BK2R antagonist, may represent an effective PC strategy, with the advantage of limiting the potential risks of supra-physiologic BK activity. MATERIALS AND METHODS: Hearts from male Sprague-Dawley (SD) rats on a Langendorff system were exposed to I/R injury (30/120 min). BK (100 nM) and HOE140 (1 µM) were administered post-ischemically during the first 3 min of reperfusion, under continuous or intermittent infusion (10 s/each). Hearts were randomly assigned to 5 groups: 1) I/R alone (n=5); 2) continuous HOE140 (cHOE n=6); 3) intermittent HOE140 (iHOE n=6); 4) continuous BK (cBK n=6); 5) intermittent BK (iBK n=6). End-diastolic left ventricular pressure (LVEDP), developed left ventricular pressure (dLVP) and coronary flow (CF) were monitored throughout reperfusion. Left ventricular infarct mass (IM) was quantified together with the phosphorylated levels of Akt and GSK3ß (RISK pathway kinases) at the end of reperfusion. RESULTS: IM was not significantly changed in cBK or cHOE groups (vs. I/R). Conversely, both iBK and iHOE groups showed a significant limitation in IM (vs. I/R, p<0.05, p<0.01, respectively). Akt and GSK3ß phosphorylation levels were higher in iBK and iHOE groups (vs. I/R, p<0.05). When compared to I/R group, both LVEDP values (p<0.05, first 60-min reperfusion), as well as dLVP values (p<0.01) were improved only in iHOE group. CF values did not vary among all groups. CONCLUSIONS: In isolated rat hearts, intermittent modulation of the endogenous kallikrein-kinin system by a selective BK2R antagonist mediates PC cardioprotection via RISK signaling. [ABSTRACT FROM AUTHOR]