Effect of a new de-N-acetil-lysoglycosphingolipid on some tumour models

A new de-N-acetylated glycosphingolipid termed WILD20, a breakdown product of GM(1) obtained through alkaline hydrolysis, and characterized by nuclear magnetic resonance, mass spectrometry and elementary analysis, was found to inhibit phospholipase A(2) via phosphokinase C translocation blockade. The substance inhibited various tumour cell lines in vitro, in synergy with doxorubicin and cisplatin. In vivo, it showed an antitumoral effect when both the tumour cells and WILD20 were injected at the same site (peritoneal cavity). Tumour cells, incubated with WILD20, showed a dose-dependent decrease of oncogenicity without impairment of viability. WILD20 also down-regulated tumour cell adherence to laminin and fibronectin. When peritumorally administered, WILD20 impaired tumour growth and potentiated the peritumoral effects of recombinant interleukin 2. The results obtained merit exploration of the therapeutical possibilites of this agent in human cancer patients

Differential effects of short-term or prolonged cocaine exposure on peripheral blood cells in mice

The effects of cocaine on the number of murine peripheral blood cells and on phenotypic expression of lymphocyte subsets were examined using different regimens of drug exposure. Cocaine administered to mice for 7 consecutive days at 1 and 10 mg/kg/day reduced the absolute number of circulating white blood cells and the relative number of cells stained as lymphocytes, polymorphonuclear cells and monocytes. Cocaine did not modify the relative proportion between lymphocytes, polymorphonuclear cells and monocytes, Parallely, there were no changes in the percentage of circulating CD4+ and CD8+ lymphocytes, while the number of natural killer cells increased. In sharp contrast, we didn't observe any significant change in peripheral blood cells after 30 days of consecutive drug administrations

In vitro and in vivo impact of a new glycosphingolipid on neutrophils

A new water-soluble, orally absorbable de-N-acetyl-lysoganglioside (WILD20), breakdown product of the monosialoganglioside GM(1), was found to influence some parameters of neutrophil response to inflammation stimuli. Superoxide anion production appears inhibited, along with neutrophil killing properties. A block of both pathways of arachidonic acid cascade and PAF was also found, as well as neutrophil ICAM-1-mediated adhesion to endothelial cells. Of particular interest was the significant reduction of neutrophils observed at the site of inflammation, whichever agonist was used. The effects on neutrophil physiology found in normal or in pathological conditions, are in favour of a WILD20-related inhibitory effect on neutrophil contribution to inflammation

The Biotherapeutic Potential of Lactobacillus reuteri Characterized Using a Target-Specific Selection Process

A growing body of clinical and experimental data supports the view that the efficacy of probiotics is strain-specific and restricted to particular pathological conditions, which means that newly isolated probiotic strains need to be targeted to a specific disease. Following national and international guidelines, we used a conventional in vitro experimental approach to characterize a novel strain of Lactobacillus reuteri, LMG P-27481, for safety (sensitivity to antibiotics and genome analysis) and putative efficacy (resistance to gastro-intestinal transit, adhesiveness, induction of cytokines, and release of antimicrobial metabolites). In vitro assays, which were carried out to examine the probiotic’s effect on diarrhea (lactose utilization, inhibition of pathogens such as bacteria and Rotavirus), showed that it was more efficacious with respect to well-known reference strains in antagonizing Clostridioides difficile (CD). Data confirming that the probiotic can effectively treat CD colitis was gained from in vivo trials involving mice conditioned with large spectrum antibiotics before they were subjected to CD challenge. Two out of the three antibiotic-treated groups received daily LMG P-27481 for different time durations in order to simulate a preventive approach (LMG P-27481 administered prior to CD challenge) or an antagonistic one (LMG P-27481 administered after CD challenge). Both approaches significantly reduced, with respect to the untreated controls, CD DNA concentrations in caecum and C. difficile toxin titers in the gut lumen. In addition, LMG P-27481 supplementation significantly mitigated body weight loss and the extent of inflammatory infiltrate and tissue damage. The study results, which need to be confirmed by in vivo clinical trials, have demonstrated that the L. reuteri LMG P-27481 strain is a promising probiotic candidate for the treatment of CD infection