New deferiprone derivatives as multi-functional cholinesterase inhibitors: design, synthesis and in vitro evaluation.

In order to obtain multi-functional molecules for Alzheimer's disease, a series of deferiprone derivatives has been synthesized and evaluated in vitro with the hypothesis that they can restore the cholinergic tone and attenuate the dyshomeostasis of the metals mainly involved in the pathology. These compounds were designed as dual binding site AChE inhibitors: they possess an arylalkylamine moiety connected via an alkyl chain to a 3-hydroxy-4-pyridone fragment, to allow the simultaneous interaction with catalytic active site (CAS) and peripheral anionic site (PAS) of the enzyme. Deferiprone moiety and 2-aminopyridine, 2-aminopyrimidine or 2,4-diaminopyrimidine groups have been incorporated into these compounds, in order to obtain molecules potentially able to chelate bio-metals colocalized in Aβ plaques and involved in the generation of radical species.

Standardizing the approach to late onset sepsis in neonates through antimicrobial stewardship: a quality improvement initiative.

Background: Antibiotics are the most prescribed medication in the neonatal intensive care unit (NICU) and there is marked variation in their use. While they are vital for treatment of infections, they put infants at risk for infections with drug resistant organisms, alteration in their microbiome and several other morbidities. Specific guidelines for neonates are often lacking and our NICU is not compliant with late onset sepsis (LOS) guidelines.

Staphylococcus aureus Cowan I. Potent stimulus of immunoglobulin M rheumatoid factor production.

These studies demonstrate that Staphylococcus aureus Cowan I (SAC), a protein A-positive Staphylococcal strain, is a potent and consistent inducer of IgM rheumatoid factor production by normal human peripheral blood mononuclear cells. The frequency and magnitude of this response greatly exceeded that of parallel cultures stimulated with pokeweed mitogen or the protein A-negative S. aureus Wood strain, although all three agents induced a similar amount of total IgM.

Analysis of in vitro polyclonal B cell differentiation responses to bacterial peptidoglycan and pokeweed mitogen in rheumatoid arthritis.

To gain insight into possible determinants of in vivo polyclonal B cell activation seen in rheumatoid arthritis (RA), we enumerated immunoglobulin secreting cells appearing in cultures of peripheral blood mononuclear cells that were stimulated with pokeweed mitogen (PWM) or a newly described polyclonal B cell activator, bacterial peptidoglycan. Peptidoglycan, the major constituent of the cell wall of gram positive bacteria, has properties which warrant its consideration in the pathogenesis of RA; including the ability to induce rheumatoid factor production as well as a RA like syndrome in experimental animals. RA patients as a group had similar immunoglobulin secreting cell responses in PWM stimulated cultures compared to arthritis controls and showed moderately depressed responses compared to healthy volunteers.