Local Gentamicin Fixation with Sprayed Fibrin-An In Vivo Animal Study Reveals New Options to Treat Soft Tissue Infections.

For acute and chronic soft tissue infections, radical surgical debridement is required and is considered the gold standard, along with its immediate systemic antibiotic therapy. Treatment with local antibiotics and/or antibiotic-containing materials is commonly used as an additional tool in clinical practice. Spraying with fibrin and antibiotics is a newer technique that has been studied for some antibiotics. However, for gentamicin, data are not yet available on absorption, optimal application, antibiotic fate at the site and transfer of antibiotic into the blood. In an animal study involving 29 Sprague Dawley rats, 116 back wounds were sprayed with gentamicin using either gentamicin alone or one of two possible spray combinations of gentamicin and fibrin. Simultaneous application of gentamicin and fibrin via a spray system to soft tissue wounds resulted in significant antibiotic concentration over a long period of time. The technique is easy and cost-effective. The systemic crossover was significantly minimized in our study, which may have led to fewer side effects in patients. These results could lead to an improvement in local antibiotic therapy.

LRP1 mediates bidirectional transcytosis of amyloid-ß across the blood-brain barrier.

According to the "amyloid hypothesis", the amyloid-ß (Aß) peptide is the toxic intermediate driving Alzheimer's disease (AD) pathogenesis. Recent evidence suggests that the low density lipoprotein receptor-related protein 1 (LRP1) transcytoses Aß out of the brain across the blood-brain barrier (BBB). To provide genetic evidence for LRP1-mediated transcytosis of Aß across the BBB we analyzed Aß transcytosis across primary mouse brain capillary endothelial cells (pMBCECs) derived from wild-type and LRP1 knock-in mice. Here, we show that pMBCECs in vitro express functionally active LRP1. Moreover, we demonstrate that LRP1 mediates transcytosis of [(125)I]-Aß(1-40) across pMBCECs in both directions, whereas no role for LRP1-mediated Aß degradation was detected. Analysis of [(125)I]-Aß(1-40) transport across pMBCECs generated from mice harboring a knock-in mutation in the NPxYxxL endocytosis/sorting domain of endogenous LRP1 revealed a reduced Aß clearance from brain-to-blood and blood-to-brain compared with wild-type derived pMBCECs. Therefore, for the first time, we present genetic evidence that LRP1 modulates the pathogenic actions of soluble Aß in the brain by clearing Aß across the BBB.