Living beings have evolved over the past two billion years through adaptation, to an increasing atmospheric oxygen concentration, by both taking advantage of oxygen activating function and developing a complex control network. In these regards, potentially damaging species (reactive oxygen, nitrogen and chlorine species) arise as by-products of metabolism and also work as physiological mediators and signalling molecules. Oxidative stress may be an important factor in numerous pathological conditions, i.e. infection if micronutrients are deficient. Levels of these species are controlled by the antioxidant defence system, which is composed by antioxidants and pro-antioxidants. Several components of this system are micronutrients (e.g. vitamins C and E), are dependent upon dietary micronutrients (e.g. CuZn and Mn superoxide dismutase) or are produced by specific endogenous pathways. The antioxidant defences act, to control levels of these species, as a coordinated system where deficiencies in one component may affect the efficiency of the others. In this network some of the components act as direct antioxidants whereas others act indirectly (pro-antioxidants) either by modulation of direct agents or by regulation of the biosynthesis of antioxidant proteins. Thus, entities usually not considered as antioxidants, also act efficiently counteracting damaging effects of oxidative species. In this contest, the design of new molecules that take into account synergistic interactions among different antioxidants, could be useful both to address mechanistic studies and to develop possible therapeutic agents. In this review the principal categories of antioxidants and pro-antioxidants that goes from vitamins through phyto-derivatives to minerals, are critically reviewed, with particular emphasis on structure-function considerations, together with the perspective opened, in the design of possible therapeutic agents, by the antioxidants interplay.

Background: Nidogens are highly conserved proteins of basement membranes. Two nidogen proteins, nidogen 1 and nidogen 2, are known in mammals.

Background and purpose: Many in vitro and fewer in vivo studies have shown that tetracyclines present anti-inflammatory activity. We investigated if a novel non-antibacterial, non-chelating hydroxypyrazoline derivative of minocycline, 12S-hydroxy-1,12-pyrazolinominocycline (PMIN), also induced antinociceptive and anti-inflammatory effects. Experimental approach: Antibacterial effects against a minocycline-sensitive Staphylococcus aureus strain were evaluated by applying a cylinder-plate agar diffusion technique. Antibacterial effects of diluted serum from mice pre-treated with minocycline or PMIN were also evaluated. Ca 2 þ binding activity was assessed by spectrophotometry. Formalin-induced nociceptive responses and carrageenan-induced paw oedema were evaluated in mice. The rota-rod apparatus was used to evaluate motor coordination. Key results: Minocycline, but not PMIN, inhibited bacterial growth. Serum from mice treated with minocycline, but not with PMIN, also induced such an effect. The UV absorption spectrum of solutions of minocycline, but not those of PMIN, was markedly changed in the presence of Ca 2 þ . Minocycline or PMIN inhibited both phases of formalin-induced nociception and carrageenan-induced paw oedema. It is unlikely that antinociception resulted from lack of motor coordination, as tetracycline did not impair the performance of mice on the rotating rod. Conclusions and implications:These results indicate that inhibition of nociception and oedema by tetracyclines is neither necessarily linked to antibacterial nor to Ca 2 þ chelating activities. This study supports the evaluation of the potential usefulness of PMIN in the treatment of painful and inflammatory diseases, as its lack of antibacterial and Ca 2 þ chelating activities might confer greater safety over conventional tetracyclines.

The Flaviviridae virus family presents linear, plus sense, single-stranded RNA genome of 9.6 to 12.3-kilobases in length and is responsible for about seventy diseases, of which thirteen in humans. The viruses belonging to this family, are divided in three different genera, showing a great similarity in virion morphology, genome organization and replication strategy:1) Hepacivirus [Hepatitis C Virus (HCV)], Flavivirus [e.g. Yellow Fever Virus (YFV), Dengue Fever Virus (DFV), West Nile Virus (WNV)], and Pestivirus [Bovine Viral Diarrhea Virus (BVDV), Border Disease Virus (BDV)]. [2][3][4][5] Bovine viral diarrhea virus (BVDV), the prototype representative of the Pestivirus genus, is ubiquitous and causes a range of clinical manifestations, including abortion, teratogenesis, respiratory problems, chronic wasting syndrome, immune system dysfunction, and predisposition to secondary viral and bacterial infections. 5)Regardless of the availability of vaccines 6) against BVDV and the increasingly elaborate eradication or control of programs, BVDV continues to be a financial burden to the farming industry. An alternative approach against BVDV infections could be the use of antiviral agents that specifically inhibit the replication of the virus. Although not suited to treat large herds, it could be important to have selective anti-Pestivirus compounds on hand.Recently, a number of selective anti-BVDV compounds have been reported. These include the following: polymerase inhibitors i.e. N-propyl-N-[2-(2H-1,2,4-triazino[5,6-b]indol-3-ylthio)ethyl]-1-propanamine (VP32947), 7) a thiazole urea derivative, 8) a cyclic urea derivative 9) and inhibitors of the NS3/NS4A protease, for example, a boron-modified peptidyl mimetic.10) Aromatic cationic molecules have also been reported to inhibit BVDV replication, although the mechanism of action remains to be elucidated.11) Other BVDV inhibitors target cellular enzymes such as the a-glucosidase 12-14) and inosine monophosphate dehydrogenase (IMPDH).15) Recently, a new highly selective BVDV polymerase inhibitor of pestivirus replication, 5-[(4-bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (BPIP), was reported. 16)Like BVDV, HCV also belongs to the Flaviviridae family. It is an important cause of chronic hepatitis throughout the world and is the most common factor involved in the development of liver cirrhosis and hepatocellular carcinoma. 17,18) The licensed therapy based on the combination of pegylated interferon-a with the broad spectrum antiviral agent ribavirin, has a limited efficacy (about 60%) and there are important side effects associated with the therapy. Therefore, highly effective and selective inhibitors of HCV replication are urgently required. 19) BVDV is considered to be a valuable surrogate virus model for identifying and characterizing antiviral agents for use against HCV. 20) In some aspects of viral replication, BVDV is more advantageous than the currently used HCV replicon systems 21,22) because this latter does not present a complete replication cycle thus...