Tripodal molecules for the promotion of phosphoester hydrolysis

A series of low molecular weight tripodal amide/histidine-containing compounds (1–2) have been synthesised and shown to increase the rate of bis-(p-nitrophenyl) phosphate (BNPP) and soman (GD) breakdown in buffered aqueous solution

Selective iNOS inhibition for the treatment of sepsis-induced acute kidney injury.

Contains fulltext : 81592.pdf (publisher's version ) (Closed access)The incidence and mortality of sepsis and the associated development of acute kidney injury (AKI) remain high, despite intense research into potential treatments. Targeting the inflammatory response and/or sepsis-induced alterations in the (micro)circulation are two therapeutic strategies. Another approach could involve modulating the downstream mechanisms that are responsible for organ system dysfunction. Activation of inducible nitric oxide (NO) synthase (iNOS) during sepsis leads to elevated NO levels that influence renal hemodynamics and cause peroxynitrite-related tubular injury through the local generation of reactive nitrogen species. In many organs iNOS is not constitutively expressed; however, it is constitutively expressed in the kidney and, in humans, a relationship between the upregulation of renal iNOS and proximal tubular injury during systemic inflammation has been demonstrated. For these reasons, the selective inhibition of renal iNOS might have important implications for the treatment of sepsis-induced AKI. Various animal studies have demonstrated that selective iNOS inhibition-in contrast to nonselective NOS inhibition-attenuates sepsis-induced renal dysfunction and improves survival, a finding that warrants investigation in clinical trials. In this Review, the selective inhibition of iNOS as a potential novel treatment for sepsis-induced AKI is discussed

The involvement of aβ in the neuroinflammatory response

In the same year as Alzheimer described the case of Auguste D. as a peculiar disease of the cerebral cortex, Fischer published his classic paper about miliary plaque formation in a large number of brains from patients with senile dementia [1]. In this paper and a following one from 1910, Fischer stated that plaque formation is the result of the deposition of a peculiar foreign substance in the cortex that induces a regenerative response of the surrounding nerve fibers [2]. He described spindle-shaped thickening of nerve fibers terminating with club forms in the corona of plaques (Fig. 4.1). These altered nerve fibers were considered as axonal sprouting, and the terminal club forms showed a strong similarity with the clubshaped buddings of axons found in developing nerve fibers and after transections of peripheral nerves as described by Cajal some years earlier. According to Fischer, the crucial step of the plaque formation is the deposition of a foreign substance that provokes a local inflammatory response step followed by a regenerative response of the surrounding nerve fibers. However, Fischer could not find morphological characteristics of an inflammatory process around the plaques after extensive histopathological observations including complement binding studies. The only tissue reaction appeared to be an overgrowth of club-formed neurites