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    Methionine Sulfoxide Reductase Enzymes: A Possible Virulence Factor for the Management of Antibiotic Resistance Crisis in the Climate Change Era

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    The problem of antibiotic resistance develops when bacteria are able to grow in the presence of conventional antimicrobial drugs and today represents a serious public health issue. The environmental effects of global warming, by unknown genomic mechanisms of adaption, could dramatically increase this phenomenon and support a more rapid progression to “post-antibiotic era”, in which common infections will be untreatable. Alternative approaches toward drug-resistant bacterial infections need to be explored to ensure effective therapies. Bacterial pathogens produce virulence factors that allow them to invade and to damage host cells. Methionine sulfoxide reductase (Msr) enzymes (MsrAs and MsrBs) are important, but poor studied, virulence factors for many bacterial strains. A deeper insight into their mechanism of action and regulation could help in developing novel therapeutic strategies toward drug-resistant bacteria, in order to overcome the antibiotic resistance crisis

    Amyloid-beta (25–35) peptide induces the release of pro-matrix metalloprotease 9 (pro-MMP-9) from human neutrophils

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    Alzheimer's disease (AD) is a degenerative process of the brain, leading to increasing impairment of cognitive functions, and is associated with accumulation in the brain of several amyloid-beta (Aβ) peptides (as amyloid plaques), including Aβ25-35. Neutrophils, the most abundant immune cell type infiltrated in the brain of AD patients, accumulate behind amyloid plaques. Aβ peptides can trigger activation of chemotaxis and oxidative burst in neutrophils, suggesting a role in modulating the neuroinflammation process. We have shown that Aβ25-35 can induce the release from human neutrophils of pro-MMP-9, a metalloprotease involved in the onset of inflammation, corroborating the hypothesis of the involvement of infiltrated neutrophils in the inflammatory processes, which occur in the AD brain

    Membrane rafts of the human red blood cell

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    The cell type of election for the study of cell membranes, the mammalian non-nucleated erythrocyte, has been scarcely considered in the research of membrane rafts of the plasma membrane. However, detergent-resistant-membranes (DRM) were actually first described in human erythrocytes, as a fraction resisting solubilization by the nonionic detergent Triton X-100. These DRMs were insoluble entities of high density, easily pelleted by centrifugation, as opposed to the now accepted concept of lipid raft-like membrane fractions as material floating in low density regions of sucrose gradients. The present article reviews the available literature on membrane rafts/DRMs in human erythrocytes from an historical point of view, describing the experiments that provided the solution to the above described discrepancy and suggesting possible avenue of research in the field of membrane rafts that, moving from the most studied model of living cell membrane, the erythrocyte’’s, could be relevant also for other cell types

    Susceptibility to hydrolysis of phenylboronic pinacol esters at physiological pH

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    Boronic acids and their esters are highly considered compounds for the design of new drugs and drug delivery devices, particularly as boron-carriers suitable for neutron capture therapy. However, these compounds are only marginally stable in water. Hydrolysis of some phenylboronic pinacol esters is described here. The kinetics is dependent on the substituents in the aromatic ring. Also the pH strongly influences the rate of the reaction, which is considerably accelerated at physiological pH. Therefore, care must be taken when considering these boronic pinacol esters for pharmacological purposes

    Survival and senescence of human young red cells in vitro

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    BACKGROUND: A number of experimental investigations in vivo suggest that in humans a decrease of circulating erythrocyte number ensues whenever erythropoietin (EPO) plasma level decreases. Since the process seems to selectively eliminate young red cells (neocytes), it has been named neocytolysis. The experimental models in vivo have revealed and documented multiple forms of neocytolysis but have not fully elucidated the specificity of the target red cells and the relation with EPO level changes. In an attempt to better characterize the neocytolytic process, we have undertaken an in vitro investigation on age-ranked human red cells. METHODS: By centrifugation on Percoll density gradient we separated the red cells population into three subsets, neocytes, middle-aged and old. Then we comparatively investigated the kinetics of survival of the subsets cultured under different conditions: with medium alone, with 10% autologous plasma, with EPO, alone or in combination with autologous monocytes. RESULTS: Neocytes showed a viability and a survival rate lower than the other red cells when cultured in medium or with 10% plasma. EPO at physiological doses increased their survival rate, but not that of the other subsets. This effect was enhanced by co-culture with monocytes. CONCLUSION: Likely neocytes are more sensitive than the other RBCs subsets to presence or absence of survival signals, such as EPO or plasma or monocytes derived factors. These observations could provide an insight into the link between the decrease in EPO plasma level and the reduction of circulating red cells mass and account for the specificity of neocytes clearance. © 2014 S. Karger AG, Basel

    Reduction of nitroblue tetrazolium to formazan by folic acid

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    The reduction of nitroblue tetrazolium (NBT) to formazan by folic acid, N-(4-aminobenzoyl) glutamic acid, and other amino acids was studied in this paper. The reduction involves only one of the two tetrazolium rings of NBT. The reaction is considerably more rapid with folic acid and N-(4-aminobenzoyl) glutamic acid than with the other amino acids under study. The electron donor moiety appears to be the carboxylic acid in the alpha position. N-ethyl-N'(3-dimethylaminopropyl)carbodiimide notably increases the rate of the reaction and promotes the reduction of both tetrazolium rings
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