these results support the conclusion that a stable, CBAS-ePTFE surface provides improved thromboresistance and improved patency in canine interposition models. Maintenance of heparin catalytic activity on the graft surface in vivo likely contributes to this outcome and holds promise for the utility of this graft surface for clinical applications.

Abstract. Fisher J, Linder A (University of Lund, Lund, Sweden). Heparin-binding protein: a key player in the pathophysiology of organ dysfunction in sepsis. (Review). J Intern Med 2017; 281: 562-574.Infectious diseases remain a major health problem, and sepsis and other severe infectious diseases are common causes of morbidity and mortality. There is a need for clinical and laboratory tools to identify patients with severe infections early and to distinguish between bacterial and nonbacterial conditions. Heparin-binding protein (HBP), also known as azurocidin or cationic antimicrobial protein of 37 KDa, is a promising biomarker to distinguish between patients with these conditions. It is biologically plausible that HBP is an early and predictive biomarker because it is prefabricated and rapidly mobilized from migrating neutrophils in response to bacterial infections. HBP induces vascular leakage and oedema formation and has a pro-inflammatory effect on a variety of white blood cells and epithelial cells. The dysregulation of vascular barrier function and cellular inflammatory responses can then lead to organ dysfunction. Indeed, it has been shown that patients with sepsis express elevated levels of HBP in plasma several hours before they develop hypotension or organ dysfunction. HBP has a major role in the pathophysiology of severe bacterial infections and thus represents a potential diagnostic marker and a target for the treatment of sepsis.

sFRP-1 is expressed by osteoblasts and inhibits osteoclast formation. While sFRP-1 activity might involve the blocking of endogenous Wnt signaling, our results suggest that, alternatively, it could be because of direct binding to RANKL. This study describes a new mechanism whereby osteoblasts regulate osteoclastogenesis through the expression and release of sFRP-1.

Neutrophils are crucial mediators of host defense that are recruited to the central nervous system (CNS) in large numbers during acute bacterial meningitis caused by Streptococcus pneumoniae . Neutrophils release neutrophil extracellular traps (NETs) during infections to trap and kill bacteria. Intact NETs are fibrous structures composed of decondensed DNA and neutrophil-derived antimicrobial proteins. Here we show NETs in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis, and their absence in other forms of meningitis with neutrophil influx into the CSF caused by viruses, Borrelia and subarachnoid hemorrhage. In a rat model of meningitis, a clinical strain of pneumococci induced NET formation in the CSF. Disrupting NETs using DNase I significantly reduces bacterial load, demonstrating that NETs contribute to pneumococcal meningitis pathogenesis in vivo. We conclude that NETs in the CNS reduce bacterial clearance and degrading NETs using DNase I may have significant therapeutic implications.

Despite significant improvements in patient survival and local disease control, 25% of patients with osteosarcoma develop metastases and the surgery for many extremity lesions still includes amputation. Thus, modalities that inhibit tumour growth and the metastatic cascade will have a significant impact on patient survival and potential for limb sparing surgery.Tumours induce bone destruction by cellular processes, such as osteoclast-mediated bone lysis. The importance of osteoclastmediated lysis has been demonstrated in other malignancies, where the development of osseous metastases has been shown to be mediated by soluble tumour-related osteoclast activating factors (Galasko, 1976). More recently, the induction of specific osteoclast recruiting factors in osteoblasts/stromal cells following contact with myeloma and breast cancer cells has been demonstrated (Chikatsu et al, 2000). Bisphosphonates have recognized efficacy in reducing bone destruction, pain and pathological fracture in a variety of lytic primary and metastatic diseases of the skeleton (Thiébaud et al, 1991;Coleman and Purohit, 1993;Shipman et al, 1997;Bloomfield, 1998;Diel et al, 1998). They have more recently been shown to inhibit establishment and growth of prostate cancer metastases, which are generally considered to be osteoblastic in their growth pattern (Adami, 1997). We proposed that, as with the intraosseous growth of prostate cancer, the local spread of osteosarcoma involves proteolytic and osteoclast-mediated bone destruction. The bisphosphonates may reduce bone destruction by uncoupling close regulation of osteoclast activity by osteoblast-like cells.The aims of our study were to examine the effects on the regulation of proliferation and apoptosis by bisphosphonate treatment of a clonal osteosarcoma cell line. Further, we assessed the expression of an osteoclast differentiating factor, receptor activator of NF-κβ (RANKL) (Yasuda et al, 1998b) and an osteoclastogenesis inhibitory factor, osteoprotegerin (OPG) (Simonet et al, 1997;Yasuda et al, 1998a). Finally, we investigated the effects on osteoblast-related gene expression by an aminobisphosphonate and a non-aminobisphosphonate. The use of a bisphosphonate from each group allows comparison of their relative potencies with the known effects on osteoclasts and bone resorption studies (Fleisch, 1993). MATERIALS AND METHODS Cell cultureUMR 106-01 cells derived from a 32 P-induced osteosarcoma in rats (Martin et al, 1976) were used. Cells were cultured in 75 cm 2 tissue culture flasks (Greiner Cellstar) in α-modified Minimal Essential Medium (α-MEM) containing hepes 4 g l Ϫ1 , sodium bicarbonate 1.95 g 6 Ϫ1 , gentamicin 80 mg 6 Ϫ1 , pH 7.4 and 10% fetal bovine serum (FBS), incubated at 37˚C and equilibrated in 5% CO 2 in air. Subcultures were performed using 0.0125% trypsin in 0.5 mM Na 2 EDTA in calcium and magnesium-free phosphate buffer (1 ϫ versene) to harvest the cells. Summary Local growth of osteosarcoma involves destruction of host bone by proteolytic mechanisms and/or host osteocl...