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Inhibition of either P2Y12 receptor or the nucleotide-binding oligomerization domain- (NOD-) like receptor pyrin domain containing 3 (NLRP3) inflammasome provides cardioprotective effects. Here, we investigate whether direct NLRP3 inflammasome inhibition exerts additive effects on myocardial protection induced by the P2Y12 receptor antagonist Ticagrelor. Ticagrelor (150 mg/kg) was orally administered to rats for three consecutive days. Then, isolated hearts underwent an ischemia/reperfusion (30 min ischemia/60 min reperfusion; IR) protocol. The selective NLRP3 inflammasome inhibitor INF (50 μM) was infused before the IR protocol to the hearts from untreated animals or pretreated with Ticagrelor. In parallel experiments, the hearts isolated from untreated animals were perfused with Ticagrelor (3.70 μM) before ischemia and subjected to IR. The hearts of animals pretreated with Ticagrelor showed a significantly reduced infarct size (IS, 49±3% of area at risk, AAR) when compared to control IR group (69±2% of AAR). Similarly, ex vivo administration of INF before the IR injury resulted in significant IS reduction (38±3% of AAR). Myocardial IR induced the NLRP3 inflammasome complex formation, which was attenuated by either INF pretreatment ex vivo, or by repeated oral treatment with Ticagrelor. The beneficial effects induced by either treatment were associated with the protective Reperfusion Injury Salvage Kinase (RISK) pathway activation and redox defence upregulation. In contrast, no protective effects nor NLRP3/RISK modulation were recorded when Ticagrelor was administered before ischemia in isolated heart, indicating that Ticagrelor direct target is not in the myocardium. Our results confirm that Ticagrelor conditioning effects are likely mediated through platelets, but are not additives to the ones achieved by directly inhibiting NLRP3.

Introduction - Nutritionists have suggested the partial replacement of the saturated fatty acids (SFA) with polyunsaturated fatty acids (PUFAs) in animal diet. However, in the absence of antioxidant protection, PUFAs are subject to lipid peroxidation. Material and methods - In this investigation, three groups of pigs were fed three different diets, namely an SFA-rich diet (palm oil-based), a PUFA-rich diet (corn oil-based), and a PUFA-rich diet (corn oil-based), supplemented with freeze-dried organic red wine solids (RWS). The objective of this work was to compare the effects of the three diets on serum biochemical parameters (albumin, glucose, triglycerides, cholesterol and alanine aminotransferase) and on serum oxidative status (antioxidant power by anti-ROMs test and reactive oxygen species by d-ROMs test, Diacron s.r.l). Results and discussion - The results show that pigs fed a diet containing corn oil and RWS have a significantly higher serum antioxidant power, and a lower level of serum reactive oxygen species compared to the other two groups of pigs. Furthermore, in corn oil and RWS-fed pigs, alanine aminotransferase, cholesterol and triglycerides were significantly lower than in the other two groups of pigs. Conclusions - A diet rich in PUFAs and polyphenols, derived from RWS, may be effective in increasing the body's antioxidant defenses, in decreasing reactive oxygen species in serum, and in improving serum biochemical parameters.

Il connubio vino rosso e salute è stato recepito dall'intera comunità scientifica mondiale. Pur tuttavia, la presenza di etanolo pone problemi e condiziona l'uso di questa bevanda, anche per motivi culturali, religiosi e di intolleranza. Per questo motivo, l'azienda agricola Ca' Novella in collaborazione con Norton Technology ha concepito un prodotto denominato LiofenolTM, derivato da vino rosso piemontese certificato biologico, privo di alcool che mantiene inalterate le caratteristiche del fitocomplesso di origine con ottime percentuali medie in peso di polifenoli ed antociani. E' ben noto dalle linee guida nutrizionali per la salute dei consumatori che il contenuto in acidi grassi polinsaturi (PUFA) della carne animale dovrebbe aumentare anche attraverso formulazioni zootecniche concepite opportunamente. Per questo scopo, in collaborazione con il Dipartimento di Scienze Veterinarie dell'Università degli Studi di Torino e l'Istituto di Scienze delle Produzioni Alimentari del CNR, è stata avviata una sperimentazione per il miglioramento della qualità nutrizionale della carne attraverso l'integrazione del prodotto LiofenolTM nell'alimentazione dei suini da allevamento, inoltre sono state valutate e confrontate le caratteristiche di conservazione delle carni di gruppi di suini nutriti con diete contenenti alti livelli di grassi saturi e con diete contenenti prevalentemente PUFA addizionati o meno con LiofenolTM.

Nitric oxide (NO) is a polypotent regulatory molecule involved in a variety of activities, such as the modulation of the catalytic activity of cysteine-containing enzymes. The present study reports the modulation of the HIV-1 reverse transcriptase activity by NO, released by the NO donors 3,3-bis(aminoethyl)-1-hydroxy-2-oxo-1-triazene (NOC-18), (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]5-nitro-3-hexenamide (NOR-3), 3-morpholinosydnonimine (SIN-1), 4-(phenylsulfonyl)-3-((2-(dimethylamino) ethyl)thio)furoxan oxalate (SNO-102), and sodium nitroprusside (SNP). NO inhibits dose-dependently the HIV-1 reverse transcriptase activity, Likely due to oxidation of Cys residue(s). Present results, representing a new insight into the modulation mechanism of the HIV-1 reverse transcriptase activity, may be relevant to develop new strategies for inhibition of HIV-1 replication. (C) 1999 Academic Press.