Mouse anti-Human MLX monoclonal antibody, clone 2D4

An analysis of crystal structures of the type (eta5-C5H4R)MLx (x = 1-5) has been undertaken. A measure of the steric and electronic effects associated with L and R has been assessed from the arrangement of the L ligands relative to R and from the bending of R out of the cyclopentadienyl plane. The analysis revealed that when L and R were large, steric effects were dominant and the preferred conformer was such that L and R avoided each other as far as possible. Steric effects for small L and R were significant when x was large. For instance L groups were always staggered with respect to R for x = 4 but for x = 2 both staggered and eclipsed conformers were observed. Thus electronic factors were only dominant for a limited number of structures in which L, R and x were small. The results thus confirm an earlier proposal (N. J. Coville, K. E. du Plooy and W. Pickl, Coord. Chem. Rev., 116 (1991) 1) that significant steric interactions are anticipated between the ring and the ligand set in (eta5-C5H4R)MLx complexes.

Inducible (calcium-independent) nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are important in the regulation of the function of different organs during infection. A single dose of lipopolysaccharide (LPS; 5 mg/kg ip) within 6 h increased NOS activity (20%) and prostaglandin E (PGE) content (100%) in submandibular glands (SMG) and blocked stimulated salivary secretion in adult male rats. The administration of an iNOS synthesis inhibitor, aminoguanidine (AG), with LPS decreased NOS activity and PGE content. Furthermore, the administration of meloxicam (MLX), an inhibitor of COX-2, blocked the increase in PGE and the production of NO. The incubation of slices of SMG in the presence of 3-morpholinosydnonimine, a donor of NO, increased the release of PGE highly significantly. The incubation of SMG in the presence of a PGE(1) analog (alprostadil) increased the production of NO. These results indicate that LPS activates NOS, leading to NO release, which activates COX, generating PGEs that act back to further activate NOS, causing further generation of PGEs by activation of COX. Because the alprostadil administration inhibited stimulated salivation, LPS-induced inhibition of salivation appears to be caused by increased PGE production. Diminished salivary secretion produces poor oral health; thus the use of COX-2 inhibitors to counteract the effects of inhibited salivation should be considered.