Prophylactic Effects of γ-Aminobutyrylhistidine (Homocarnosine) on Experimental Staphylococcal Infections in Mice

Prophylactic administration of the dipeptide homocarnosine induced a high degree of resistance to staphylococcal infections in Swiss albino mice. It expressed its antistaphylococcal properties 1 hr after administration, and this protection lasted for at least 1 month. Although 5 mg per animal (approximately 200 to 250 mg/kg) was routinely used in our studies, experiments showed that comparable results could be obtained with 1.5 mg per animal. Rechallenge experiments indicated that an active infection by itself may confer immunity up to 4 weeks, but an infection after treatment with homocarnosine gave complete immunity to reinfection for at least 2 months. Studies in vitro showed that homocarnosine had no effect on the growth or certain other characteristics (ability to ferment mannitol, liquefy gelatin, and to produce coagulase, deoxyribonuclease, and pigment) of S. aureus. It appears that resistance induced by this peptide is an indirect effect mediated by some nonimmunological host reaction. The possible involvement of homocarnosine, among other compounds, in the protective action of deproteinized beef extract against staphylococcal infections is suggested.     

Activity of homocarnosine and other compounds against staphylococcal infections in mice

Homocarnosine and carnosine have been identified in bovine brain extracts which are effective in protecting mice against infections by Staphylococcus aureus. These peptides, as well as l-1-methylhistidine, beta-alanine, gamma-aminobutyric acid, delta-aminovaleric acid, epsilon-aminocaproic acid, 1-aminomethylcyclohexane-4-carboxylic acid, and anserine, were tested as prophylactic agents against S. aureus infections in C3H and Swiss mice. Histidine and methylhistidine were ineffective in preventing mortality in both mouse strains. Carnosine, anserine, and epsilon-aminocaproic acid were effective in C3H but not in Swiss mice. beta-Alanine and gamma-aminobutyric acid were weakly effective (C3H) or ineffective (Swiss). delta-Aminovaleric and 1-aminomethylcyclohexane-4-carboxylic acid (tested only in Swiss) were somewhat effective in early stages of the infection. Homocarnosine was the best compound and was highly effective in protecting both mouse strains against S. aureus infections by the testing procedure employed.     

Role of the N-methyl-d-aspartate receptors complex in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease pathologically characterized by the massive loss of motor neurons in the spinal cord, brain stem and cerebral cortex. There is a consensus in the field that ALS is a multifactorial pathology and a number of possible mechanisms have been suggested. Among the proposed hypothesis, glutamate toxicity has been one of the most investigated. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor mediated cell death and impairment of the glutamate-transport system have been suggested to play a central role in the glutamate-mediated motor neuron degeneration. In this context, the role played by the N-methyl-d-aspartate (NMDA) receptor has received considerable less attention notwithstanding its high Ca^2 + permeability, expression in motor neurons and its importance in excitotoxicity. This review overviews the critical role of NMDA-mediated toxicity in ALS, with a particular emphasis on the endogenous modulators of the NMDAR.