The FAST-STEMI Network in Biella From 2013 to 2019: Impact of the Delocalization of the Hospital Facilities on Ischemia Time and In-hospital Outcomes.

Background: The optimization of the strategies for myocardial revascularization has improved the outcomes of patients with ST-segment elevation myocardial infarction. In Piedmont, the FAST-STEMI regional network was created for improving the management and transportation of ST-segment elevation (STEMI) patients to primary percutaneous coronary intervention facilities, reducing the time to reperfusion. Within this network, the Hospital of Biella was delocalized in December 2014 to a new suburban structure designed for an easier access, which might have shortened the duration of patients' transportation and ischemia, with potential positive prognostic effects.

Effect of tamoxifen feeding on metabolic activation of tamoxifen by the liver of the rhesus monkey: does liver accumulation of inhibitory metabolites protect from tamoxifen-dependent genotoxicity and cancer?

Tamoxifen induces hepatocellular carcinomas in rats and is converted by rat hepatic cytochrome P450 enzymes into reactive metabolites capable of forming adducts with nucleic acids, proteins and chromosomal aberrations. In rats tamoxifen has also been shown to induce liver cytochrome P450 enzymes, to stimulate its own metabolism leading to greater covalent binding and to induce a higher degree of unscheduled DNA synthesis. This suggests that, at least in the rat, a sensitive species, tamoxifen may contribute significantly to its genotoxic and carcinogenic potential, by assisting its own metabolic activation.

Scavenging effect of silipide, a new silybin-phospholipid complex, on ethanol-derived free radicals.

Ethanol metabolism by cytochrome P4502E1 (CYP2E1) produces free radical intermediates, identified as hydroxyethyl radicals. We have observed that in vitro addition or in vivo pretreatment of rats with Silipide, a new 1:1 complex of silybin with phosphatidyl-choline, is able to decrease the spin trapping of hydroxyethyl radicals in microsomes from chronic alcohol-fed rats. This effect is not due to an interference with the metabolism of ethanol by CYP2E1, but is rather related to the capacity of the silybin molecule to scavenge hydroxyethyl radicals.

Activation of alkylhydrazines to free radical intermediates by ethanol-inducible cytochrome P-4502E1 (CYP2E1).

Electron spin resonance (EPR) spectroscopy analysis using the spin trapping agent 4-pyridyl-1-oxide-t-butyl nitrone (4-POBN) was used to measure the formation of free radical intermediates during NADPH-dependent oxidation of 1-methyl-, 1-ethyl-, and 1-isopropylhydrazine in rat liver microsomes and in reconstituted enzyme systems. The experiments in microsomes revealed that the specific activation of the hydrazines, as measured by the EPR signal intensities, was about two-fold higher, when expressed per nmol of P-450, in microsomes from rats treated with ethanol (EtOH) as compared to membranes isolated from either phenobarbital (PB)-, beta-naphthoflavone (beta-NF)-treated or control rats. Furthermore, kinetic experiments revealed that EtOH-microsomes had an apparent affinity for 1-ethylhydrazine about one order of magnitude higher than PB-microsomes.

Free radical activation of acetaldehyde and its role in protein alkylation.

The formation of carbon centered free radicals, identified as methylcarbonyl species, was observed using ESR spectroscopy and the spin trapping agent 4-pyridyl-1-oxide-N-t-butyl nitrone (4-POBN) during the oxidation of acetaldehyde by xanthine oxidase. The reaction was dependent upon the presence of OH. radicals and was inhibited by the addition of superoxide dismutase, catalase or OH.

Evidence for the covalent binding of hydroxyethyl radicals to rat liver microsomal proteins.

It is well known that acetaldehyde is capable of covalent binding to liver proteins. However, in experiments using liver microsomes prepared from chronically ethanol-fed rats we have observed that the addition of EDTA-iron complex to the microsomes increases by about 4-5 fold both the spin trapping of hydroxyethyl radicals and the covalent binding of 14C-ethanol to proteins, while it only doubles acetaldehyde formation. Conversely, the presence of GSH strongly decreases the trapping of hydroxyethyl radicals and completely inhibits the covalent binding, without affecting acetaldehyde production.

Lipid peroxidation and irreversible damage in the rat hepatocyte model. Protection by the silybin-phospholipid complex IdB 1016.

IdB 1016 is a new silybin-phospholipid complex which is more bioavailable than the flavonoid silybin itself and displays free radical scavenging and antioxidant properties in liver microsomes. We report here that the addition of increasing concentrations of IdB 1016 to isolated rat hepatocytes caused a dose-dependent inhibition of lipid peroxidation induced by ADP-Fe3+ or cumene hydroperoxide. Moreover, IdB 1016 at the concentration which completely prevented MDA formation also protected isolated hepatocytes against the toxicity of pro-oxidant agents such as allyl alcohol, cumene hydroperoxide and bromotrichloromethane, without interfering with the activation mechanism of these xenobiotics.

Inducible bilirubin-degrading system of rat liver microsomes: role of cytochrome P450IA1.

The ability of 3,3',4,4'-tetrachlorobiphenyl to stimulate bilirubin degradation by liver microsomes from rats treated with a polycyclic aromatic hydrocarbon-type inducer has been confirmed and extended to another planar biphenyl, 3,3',4,4',5,5'-hexachlorobiphenyl. The following evidence indicates the involvement of an inducible cytochrome P450 isoenzyme in this reaction, with a role, specifically, for cytochrome P450IA1. (a) The biphenyl-dependent bilirubin degradation and 7-ethoxyresorufin O-deethylase (EROD) activity were both markedly inhibited by a monoclonal antibody raised against cytochrome P450IA1; the two dose-inhibition curves were essentially superimposable, with maximum inhibition observed for both activities at a ratio of antibody to total cytochrome P450 of about 1.

Lipid peroxidation and irreversible cell damage: synergism between carbon tetrachloride and 1,2-dibromoethane in isolated rat hepatocytes.

The combination of 1,2-dibromoethane (DBE) with carbon tetrachloride (CCl4) in the isolated rat hepatocyte model produces a significant potentiation of both lipid peroxidation and plasma membrane damage induced by the latter compound. The increase in malondialdehyde production precedes the hepatocyte damage, evaluated in terms both of lactate dehydrogenase leakage and trypan blue exclusion. When hepatocytes are isolated from vitamin E pretreated rats, both the prooxidant and the cytotoxic effects of CCl4 are prevented.

CCl4-induced increase of hepatocyte free arachidonate level: pathogenesis and contribution to cell death.

A significant increase of the intracellular level of free arachidonic acid was observed in intact rat hepatocytes after poisoning with very low concentrations of CCl4 (0.129-0.172 mM), shown not to exert direct solvent effect.

Studies on the antioxidant and free radical scavenging properties of IdB 1016 a new flavanolignan complex.

Silybin has been complexed in 1:1 ratio with phosphatidyl choline to give IdB 1016 in order to increase its bioavailability. The antioxidant and free radical scavenger action of this new form of silybin has been evaluated. One hour after the intragastric administration to rats of IdB 1016 (1.