No abstract

In rodents, submandibular salivary glands accumulate a number of biologically active peptides, and release some of them to both saliva and the bloodstream. Surgical removal of these glands (sialoadenectomy) alters the ability of the liver to regenerate after partial hepatectomy. We show here that 5 weeks after surgery, the liver of sialoadenectomized mice contained 40% fewer hepatocytes than the liver of sham-operated mice. We did not obtain evidence of necrotic cell death after surgery. In contrast, sialoadenectomy transiently increased apoptotic hepatocyte death, as revealed by terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling (TUNEL) assay. DNA synthesis was determined in vivo by the incorporation of bromo-deoxyuridine (BrdU) into hepatocyte nuclei. BrdU-labeling progressively increased after sialoadenectomy. We conclude that sialoadenectomy induced a transient wave of apoptotic cell death followed by a rise in DNA synthesis but not by cell division. This reduced cell number but increased mean cell volume. In spite of these alterations in cellularity, the liver responded adequately to several stressful conditions, as judged by the lack of any differential effect of sialoadenectomy on liver glycogen and plasma glucose concentration after immobilization, aggressive encounter, or fasting. However, the liver of sialoadenectomized mice was more sensitive to the effect of a non-lethal dose of bacterial lipopolysaccharide (LPS) combined with d-galactosamine, as shown by the enhanced rise in plasma alanine aminotransferase and aspartate aminotransferase, and liver myeloperoxidase (MPO) activities. All these results indicate that a submandibular salivary glands-liver axis is involved in the maintenance of liver structure in mice. A disturbance of this axis induces an adaptive response that preserves the metabolic function of the liver but renders it more sensitive to bacterial endotoxins.

A Agonists. -Among the new compounds, derivatives (IIIa) and (IIIe) are the most interesting ones having a good in vitro affinity for the α1 receptor and a potent in vivo induction of sedation. -(FALCO*, J. L.; PIQUE, M.; GONZALEZ, M.; BUIRA, I.; MENDEZ, E.; TERENCIO, J.; PEREZ, C.; PRINCEP, M.; PALOMER, A.; GUGLIETTA, A.; Eur. J. Med. Chem. 41 (2006) 8, 985-990; Dep. Med. Chem., R&D Cent., Ferrer Int. S.A.,

No abstract

Fused pyridine derivatives R 0450Design, Synthesis and Biological Activity of Acyl Substituted 3-Amino-5-methyl-1,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones as Potential Hypnotic Drugs.-A library of pyrazolopyridine derivatives [cf. (VI), (X), (XI)] is synthesized and evaluated for α1-GABA4 receptor affinity. None of these compounds show significant inhibitory activity. -(FALCO*, J. L.; LLOVERAS, M.; BUIRA, I.; TEIXIDO, J.; BORRELL, J. I.; MENDEZ, E.; TERENCIO, J.; PALOMER, A.; GUGLIETTA, A.; Eur.