Parasite resistance was also observed in assays performed with LAAO from B. atrox, since mTOR inhibitor a dose of 32 μmol/L was necessary to kill 41.7 ± 2.4% of trypomastigotes ( Alves Paiva et al., 2011). In conclusion, LmLAAO shows a low toxicity in vivo when compared with other enzymes or toxins from snake venoms, but it might be used as cytotoxic tool toward pathogens or cancer cells, as verified by in vitro toxicity experiments. Additionally this study showed, for the first time, the cytotoxic effects of LAAO on AGS cell line (gastric adenocarcinoma) and MCF-7 cell line (breast adenocarcinoma). Furthermore, our analyses show evolutionary sequence and structural

conservation of LAAOs across snake

species, suggesting the existence of selective pressures in the evolution of this enzyme. Therefore, the biochemical, structural and functional characterizations of LmLAAO, demonstrates that it is a novel LAAO molecule with several important biological functions. The work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil, under Gramts No 479873/2009-7 and No São Paulo (FAPESP), Brazil, under Grant No 2005/54855-0 BTK inhibitor and Instituto Nacional de Ciência e Tecnologia de Toxinas (INCTTox, Fapesp/CNPq). Model data are available in the PMDB (Protein Model Data Base) under accession number PM0077706 (http://mi.caspur.it/PMDB/user/search.php). The amino acid sequence data are available in the DDBJ/EMBL/GenBank database under the accession number JX171244

(http://www.ebi.ac.uk/ena/data/view/JX171244) and Nucleotide sequence data are available in Topoisomerase inhibitor the DDBJ/EMBL/GenBank databases under the accession number LMUT0069C (http://www.ebi.ac.uk/ena/data/view/JX171244). We are grateful to Dra Elizabeth Abrahams, Departamento de Parasitología, Facultad de Microbiología, Universidad de Costa Rica, for her contribution with some of Trypanosoma strains tested in cytotoxicity experiments. Thanks are also due to Karla de Castro Figueredo Bordon and Aarón Gómez Argüello for technical assistance. The work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil, under Grants No479873/2009-7 and No142711/2007-1 (Ph.D. scholarship), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Brazil, under Grant No2005/54855-0 and Instituto Nacional de Ciência e Tecnologia de Toxinas (INCTTox, Fapesp/CNPq). “
“Physiological pain serves as a warning mechanism that indicates imminent tissue damage. Chronic pain lacks such protective function, since it persists for years without reflecting the severity of a lesion or disease, nor does chronic pain necessarily respond to treatment of the underlying disease cause (McGreevy et al., 2011).