pGlu-serpinin protects the normotensive and hypertensive heart from ischemic injury

Serpinin peptides derive from proteolytic cleavage of Chromogranin-A at C-terminus. Serpinin and the more potent pyroglutaminated-Serpinin (pGlu-Serp) are positive cardiac beta-adrenergic-like modulators, acting through β1-AR/AC/cAMP/PKA pathway. Since in some conditions this pathway and/or other pro-survival pathways, activated by other Chromogranin-A fragments, may cross-talk and may be protective, here we explored whether pGlu-Serp cardioprotects against ischemia/reperfusion injury under normotensive and hypertensive conditions. In the latter condition cardioprotection is often blunted because of the limitations on pro-survival Reperfusion-Injury-Salvage-Kinases (RISK) pathway activation. The effects of pGlu-Serp were evaluated on infarct size (IS) and cardiac function by using the isolated and Langendorff perfused heart of normotensive (WKY) and spontaneously hypertensive (SHR) rats exposed to ischemic pre-conditioning (PreC) and post-conditioning (PostC). In both WKY and SHR rat, pGlu-Serp induced mild cardioprotection in both PreC and in PostC. pGlu-Serp administered at the reperfusion (Serp-PostC) significantly reduced IS, being more protective in SHR than in WKY. Conversely, developed Left Ventricular Pressure (LVDevP) post-ischemic recovery was greater in WKY than in SHR. pGlu-Serp-PostC reduced contracture in both strains. Co-infusion with specific RISK inhibitors (PI3K/AkT, MitoK(ATP) channels, and PKC) blocked the pGlu-Serp-PostC protective effects. To show direct effect on cardiomyocytes, we pre-treated H9c2 with pGlu-Serp which were thus protected against hypoxia/reoxygenation. These results suggest pGlu-Serp as a potential modulatory agent implicated in the protective processes which can limit infarct size and overcome the hypertension-induced failure of PostC

Noble metal nanoparticles networks stabilized by rod-like organometallic bifunctional thiols

Rod-like organometallic dithiol containing square-planar Pt(II) centers, i. e., trans,trans-[(H3COCS)Pt(PBu3)(2)(C equivalent to C-C6H4-C6H4-C equivalent to C)(PBu3)(2)Pt(SCOCH3)] was used as bifunctional stabilizing agent for the synthesis of Pd-, Au-, and AgNPs (MNPs). All the MNPs showed diameters of about 4 nm, which can be controlled by carefully modulating the synthesis parameters. Covalent MNPs stabilization occurred through a single S bridge between Pt(II) and the noble metal nanocluster surfaces, leading to a network of regularly spaced NPs with the formation of dyads, as supported by SR-XPS data and by TEM imaging analysis. The chemical nature of NPs systems was also confirmed by EDS and NMR. Comparison between SR-XPS data of MNPs and self-assembled monolayers and multilayers of pristine rod-like dithiols deposited onto polycrystalline gold surfaces revealed an electronic interaction between Pt(II) centers and biphenyl moieties of adjacent ligands, stabilizing the organic structure of the network. The possibility to obtain networks of regularly spaced MNPs opens outstanding perspectives in optoelectronics

Fluid therapy in neurotrauma: basic and clinical concepts

The patient with head trauma is a challenge for the emergency physician and for the neurosurgeon. Currently traumatic brain injury constitutes a public health problem. Knowledge of the various therapeutic strategies to provide support in the prehospital and perioperative are essential for optimal care. Rapid infusion of large volumes of crystalloids to restore blood volume and blood pressure quickly is now the standard treatment for patients with combined TBI and HS The fluid in patients with brain and especially in the carrier of brain injury is a critical topic; we present a review of the literature about the history, physiology of current fluid preparations, and a discussion regard the use of fluid therapy in traumatic brain injury and decompressive craniectomy

Catestatin Improves Post-Ischemic Left Ventricular Function and Decreases Ischemia/Reperfusion Injury in Heart

The Chromogranin A (CgA)-derived anti-hypertensive peptide catestatin (CST) antagonizes catecholamine secretion, and is a negative myocardial inotrope acting via a nitric oxide-dependent mechanism. It is not known whether CST contributes to ischemia/reperfusion injury or is a component of a cardioprotective response to limit injury. Here, we tested whether CST by virtue of its negative inotropic activity improves post-ischemic cardiac function and cardiomyocyte survival. Three groups of isolated perfused hearts from adult Wistar rats underwent 30-min ischemia and 120-min reperfusion (I/R, Group 1), or were post-conditioned by brief ischemic episodes (PostC, 5-cycles of 10-s I/R at the beginning of 120-min reperfusion, Group 2), or with exogenous CST (75 nM for 20 min, CST-Post, Group-3) at the onset of reperfusion. Perfusion pressure and left ventricular pressure (LVP) were monitored. Infarct size was evaluated with nitroblue-tetrazolium staining. The CST (5 nM) effects were also tested in simulated ischemia/reperfusion experiments on cardiomyocytes isolated from young-adult rats, evaluating cell survival with propidium iodide labeling. Infarct size was 61 ± 6% of risk area in hearts subjected to I/R only. PostC reduced infarct size to 34 ± 5%. Infarct size in CST-Post was 36 ± 3% of risk area (P < 0.05 respect to I/R). CST-Post reduced post-ischemic rise of diastolic LVP, an index of contracture, and significantly improved post-ischemic recovery of developed LVP. In isolated cardiomyocytes, CST increased the cell viability rate by about 65% after simulated ischemia/reperfusion. These results suggest a novel cardioprotective role for CST, which appears mainly due to a direct reduction of post-ischemic myocardial damages and dysfunction, rather than to an involvement of adrenergic terminals and/or endothelium