The steady-state level of amyloid b-peptide (Ab) represents a balance between its biosynthesis from the amyloid precursor protein (APP) through the action of the b-and c-secretases and its catabolism by a variety of proteolytic enzymes. Recent attention has focused on members of the neprilysin (NEP) family of zinc metalloproteinases in amyloid metabolism. NEP itself degrades both Ab 1)40 and Ab 1)42 in vitro and in vivo, and this metabolism is prevented by NEP inhibitors. Other NEP family members, for example endothelin-converting enzyme, may contribute to amyloid catabolism and may also play a role in neuroprotection. Another metalloproteinase, insulysin (insulin-degrading enzyme) has also been advocated as an amyloid-degrading enzyme and may contribute more generally to metabolism of amyloid-forming peptides. Other candidate enzymes proposed include angiotensin-converting enzyme, some matrix metalloproteinases, plasmin and, indirectly, thimet oligopeptidase (endopeptidase-24.15). This review critically evaluates the evidence relating to proteinases implicated in amyloid catabolism. Therapeutic strategies aimed at promoting Ab degradation may provide a novel approach to the therapy of Alzheimer's disease.

The mammalian neprilysin (NEP) family comprises at least seven members: NEP itself, Kell blood group antigen (KELL), the endothelin-converting enzymes (ECE-1 and ECE-2), the enzyme PEX, associated with X-linked hypophosphataemia, "X-converting enzyme" (XCE) a CNS-expressed orphan peptidase and a soluble, secreted endopeptidase (SEP). These zinc metallopeptidases are all type II integral membrane proteins. Where identified, these enzymes have roles in the processing or metabolism of regulatory peptides and therefore represent potential therapeutic targets. A distinct feature of ECE-1 species is their existence as distinct isoforms differing in their N-terminal cytoplasmic tails. These tails play a role in enzyme targeting and turnover with di-leucine and tyrosine-based motifs affecting localization. Additional anchorage of these enzymes can also occur through palmitoylation. Bacterial homologues of the neprilysin family exist, for example the products of the pepO genes from L. lactis and S. parasanguis, and a recently described gene product of P. gingivalis which is an ECE-1 homologue that can catalyse the conversion of big endothelin to endothelin. A genomics based approach to understanding the functions of this proteinase family is aided by the completion of the C. elegans and Drosophila genomes, both of which encode multiple copies of NEP-like enzymes.

Invasive aspergillosis (IA) is an opportunistic infection that is often life threatening in the immunocompromised host. Early diagnosis is critical, especially given the efficacy and availability of several new anti-fungal therapies. Current (2008) diagnostic criteria have limited ability to detect early infection and are aimed at establishing disease. Although histopathology and culture techniques have traditionally been used to make a proven diagnosis of IA, their dependence on tissue samples and slow turnaround times hamper early confirmation of IA. Serologic detection of circulating galactomannan and 1,3-β-D-glucan fungal biomarkers show promise for improving the diagnosis of IA, and their use is included in the EORTC/MSG diagnostic criteria for IA. Numerous studies have evaluated the diagnostic performance of these two biomarkers and shown that they have suboptimal sensitivity when used alone for early diagnosis of proven IA. Currently available molecular assays also suffer from a lack of standardization. Evaluation of the use of different combinations of test methods to enhance diagnostic accuracy is also being done but prompt, accurate diagnosis of IA remains a clinical and diagnostic challenge. The clinical validity and limitations of biomarkers and current molecular methods for the early diagnosis of IA are summarized in this review with respect to the different patient populations at risk for this serious infection.

The present report describes the first known case of an otherwise healthy child who developed a soft tissue infection due to Mycobacterium senegalense - a pathogen usually found in east Africa that is responsible for infecting various animals. The patient presented with nonhealing wounds after sustaining facial lacerations from the shattered glass of a fish tank. The patient responded well to scar revision and antibiotics, with no subsequent relapse.