Carnosine (beta-alanyl-L-histidine) and carcinine (beta-alanylhistamine) are natural imidazole-containing compounds found in the non-protein fraction of mammalian tissues. Carcinine was synthesized by an original procedure and characterized. Both carnosine and carcinine (10-25 mM) are capable of inhibiting the catalysis of linoleic acid and phosphatidylcholine liposomal peroxidation (LPO) by the O2(-.)-dependent iron-ascorbate and lipid-peroxyl-radical-generating linoleic acid 13-monohydroperoxide (LOOH)-activated haemoglobin systems, as measured by thiobarbituric-acid-reactive substance. Carcinine and carnosine are good scavengers of OH. radicals, as detected by iron-dependent radical damage to the sugar deoxyribose. This suggests that carnosine and carcinine are able to scavenge free radicals or donate hydrogen ions. The iodometric, conjugated diene and t.l.c. assessments of lipid hydroperoxides (13-monohydroperoxide linoleic acid and phosphatidylcholine hydroperoxide) showed their efficient reduction and deactivation by carnosine and carcinine (10-25 mM) in the liberated and bound-to-artificial-bilayer states. This suggests that the peroxidase activity exceeded that susceptible to direct reduction with glutathione peroxidase. Imidazole, solutions of beta-alanine, or their mixtures with peptide moieties did not show antioxidant potential. Free L-histidine and especially histamine stimulated iron (II) salt-dependent LPO. Due to the combination of weak metal chelating (abolished by EDTA), OH. and lipid peroxyl radicals scavenging, reducing activities to liberated fatty acid and phospholipid hydroperoxides, carnosine and carcinine appear to be physiological antioxidants able to efficiently protect the lipid phase of biological membranes and aqueous environments.

No abstract

A major challenge for cancer treatment is the preferential and irreversible killing of tumor cells and minimal damage of normal tissues, both in the site of the malignancy and in the body. The agents used in boron neutron capture therapy (BNCT) are supposed to have the following advantages over many conventional chemotherapeutics: 1) when irradiated with thermal neutrons, an unstable isotope (11)B is formed whose rapid decay yields local and a thermal effect; 2) because the free path of the released particles is close to the cell diameter, the tissues outside the tumor should gain less damage; 3) local radioactivity and heat should be harmful for cells that, in the course of their natural history, acquired the determinants of altered response to many toxic stimuli. However, a higher specificity of damage would be achieved if the drugs accumulate mostly in cancer cells rather than in non-malignant counterparts. Therefore, optimization of agents for BNCT presumes the design of chemicals with improved accumulation/ retention in cancer cells. In particular, carboranyl-substituted porphyrins, the stable conjugates of macrocyclic porphyrins with complex boron-containing polyhedra, are considered good candidates for BNCT due to their uptake by cancer cells and high boron content. Importantly, the proposed mechanisms of pharmacological effects of carboranylporphyrins make these compounds potentially appropriate for elimination of pleiotropically resistant tumor cells.

No abstract

Working in the weak-field approximation, we study the scattering of quantum fields from a gravitational source. For definiteness, we consider the electromagnetic radiation field as well as a massive scalar field, both propagating in a slightly curved spacetime and employ the first-order Born approximation to deduce the scattering cross-sections of the process. We find that the (unpolarized) cross-section for the electromagnetic field coincides (at the tree level) with the classical value, predicted by general relativity; also our results fairly agree with those obtained by other authors in some previous works. On the other hand, our analysis of the massive scalar field leads to results which are quite different when compared with those presented, e.g., in the papers by Golowich et al (1990 Am. J. Phys. 58 688) and by Uno et al (1996 Phys. Lett . A 223 137). Actually, we find that the quantum behavior deviates from its classical counterpart, showing an enhancement in the cross-section as the massive field approaches the non-relativistic regime. We critically discuss and compare our results and those of the above references, attempting to give a possible physical justification of such a puzzling issue in terms of quantum non-locality.