12 research outputs found

    The many faces of protease–protein inhibitor interaction

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    Proteases and their natural protein inhibitors are among the most intensively studied protein–protein complexes. There are about 30 structurally distinct inhibitor families that are able to block serine, cysteine, metallo- and aspartyl proteases. The mechanisms of inhibition can be related to the catalytic mechanism of protease action or include a mechanism-unrelated steric blockage of the active site or its neighborhood. The structural elements that are responsible for the inhibition most often include the N- or the C-terminus or exposed loop(s) either separately or in combination of several such elements. During complex formation, no major conformational changes are usually observed, but sometimes structural transitions of the inhibitor and enzyme occur. In many cases, convergent evolution, with respect to the inhibitors' parts that are responsible for the inhibition, can be inferred from comparisons of their structures or sequences, strongly suggesting that there are only limited ways to inhibit proteases by proteins

    Prevention of catheter-related bloodstream infection in patients on hemodialysis

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    Central venous catheters (CVCs) are frequently used as vascular access for patients who require hemodialysis, but infectious complications remain a major clinical problem. Specifically, catheter-related bloodstream infections (CRBSIs) have an adverse effect on survival, hospitalization, mortality, and the overall cost of care in this setting. The growing number of patients who require hemodialysis, combined with an increasing number of patients who cannot use any vascular access other than a CVC, stress the importance of strategies to prevent CRBSI. Various interventions aimed at reducing the incidence of CRBSI are available, but they have not yet been integrated into evidence-based, consensus guidelines. In this Review, the results from several CVC infection prevention studies-of patients from dialysis and nondialysis settings-are combined to outline a rational approach to CRBSI prevention. Prevention of intraluminal contamination of the CVC is pivotal and of proven efficacy, as are strict aseptic CVC insertion and handling protocols, use of chlorhexidine in alcohol solutions for skin cleansing, topical application of antimicrobial ointments, and antimicrobial lock solutions. Adherence to a meticulous catheter care protocol can achieve a CRBSI incidence well below one episode per 1,000 catheter days, even without the need for antimicrobial ointments or lock solutions.</p
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