title: Acetylcholinesterase biogenesis is impaired in lung cancer tissues.
abstract: Studies cited by Cowan et al. [J. Appl. Toxicol. 23, 177 (2003)] indicate existence of inflammatory and cholinergic pathways in both nerve agents and sulfur mustard (HD) injury. Increase in AChE synthesis and neurite extension was noted after exposure to HD [K.W. Lanks et al., Exp. Cell Res. 355 (1975)]. Moreover, anti-inflammatory drugs reduce the dermal, respiratory and ocular damage caused by exposure to HD. On the other hand, recent studies have noted the involvement of neuro-inflammatory processes during exposure to the nerve agents sarin or soman [Cowan et al., 2003]. The use of various anti-inflammatory drugs in addition to the classical antidotal drugs (e.g. atropine and oximes) caused decrease in certain toxic symptoms and inflammation-induced brain damage. Our new bifunctional drugs (Scheme 1) are based on CNS-permeable molecular combination of pseudo-reversible AChE inhibitor (pyridostigmine, PYR) coupled via a hydrophobic spacer (octyl or decyl hydrocarbon chain) to a non-steroidal anti-inflammatory drug (NSAID) such as Ibuprofen or Diclofenac (Scheme 1). This study evaluates the efficacy of certain bifunctional compounds against HD and soman poisoning in mice in vivo.
authors.affiliation: Research Unit of Clinical Analysis Service, University Hospital Virgen de la Arrixaca. Ctra. Murcia-Cartagena s/n. El Palmar, Murcia, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Martínez-Moreno
authors.forename: Susana
authors.initials: S
authors.lastname: Nieto-Cerón
authors.forename: Francisco
authors.initials: F
authors.lastname: Ruiz-Espejo
authors.forename: Juan
authors.initials: J
authors.lastname: Torres-Lanzas
authors.forename: Isabel
authors.initials: I
authors.lastname: Tovar-Zapata
authors.forename: Pedro
authors.initials: P
authors.lastname: Martínez-Hernández
authors.forename: Cecilio J
authors.initials: CJ
authors.lastname: Vidal
authors.forename: Juan
authors.initials: J
authors.lastname: Cabezas-Herrera
mesh_terms: D000110:Acetylcholinesterase / Q000096:biosynthesis / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology*; D011134:Polysaccharides / Q000378:metabolism*
chemical_list: D011134:Polysaccharides; D000110:Acetylcholinesterase