Oxidative stress mediated mitochondrial and vascular lesions as markers in the pathogenesis of Alzheimer disease.

Mitochondrial dysfunction plausibly underlies the aging-associated brain degeneration. Mitochondria play a pivotal role in cellular bioenergetics and cell-survival. Oxidative stress consequent to chronic hypoperfusion induces mitochondrial damage, which is implicated as the primary cause of cerebrovascular accidents (CVA) mediated Alzheimer's disease (AD). The mitochondrial function deteriorates with aging, and the mitochondrial damage correlates with increased intracellular production of oxidants and pro-oxidants. The prolonged oxidative stress and the resultant hypoperfusion in the brain tissues stimulate the expression of nitric oxide synthase (NOS) enzymes, which further drives the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The ROS and RNS collectively contributes to the dysfunction of the blood-brain barrier (BBB) and damage to the brain parenchymal cells. Delineating the molecular mechanisms of these processes may provide clues for the novel therapeutic targets for CVA and AD patients.

New Delhi metallo-ß-lactamase (NDM-1): an update.

New Delhi metallo-ß-lactamase (NDM-1) is a novel broad spectrum carbapenemase with ability to inactivate all ß-lactams except aztreonam. However, most of the NDM-1-producers also produce aztreonam hydrolysing-ß-lactamases thereby making these pathogens absolutely resistant to all ß-lactams. The bla(NDM-1) gene encodes a 27.5 kDa protein of 269 amino acids. It shares very little identity with other metallo-ß-lactamases. Maximum identity has been observed to VIM-1/VIM-2 (32.4%). This mini-review is an update of the scientific literature for the said enzyme. Following the recommendation of David livermore, we further propose to combine "aztreonam" and "inhibitor of the most frequently encountered aztreonam hydrolysing-ß-lactamases in a given setting" as a possible strategy against NDM-1-producers. The inhibitor should be 'versatile' as well, i.e. it should have the ability to inhibit most of the variants of aztreonam hydrolysing-ß-lactamases prevalent in the concerned setting. We strongly recommend surveillance studies using aztreonam/NXL-104-combination against NDM-1-producing pathogens in different geographical regions across the globe.