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Background: Human-beta defensins (HBD) belong to the family of acute phase peptides and hold a broad antimicrobial spectrum that includes gram-positive and gram-negative bacteria. HBD are up-regulated after severe injuries but the source of posttraumatic HBD expression has not been focused on before. In the current study we analysed the role of liver tissue in expression of HBD after multiple trauma in human and mice.Methods: HBD-2 expression has been detected in plasma samples of 32 multiple trauma patients (ISS > 16) over 14 days after trauma by ELISA. To investigate major sources of HBD-2, its expression and regulation in plasma samples, polymorphonuclear neutrophils (PMN) and human tissue samples of liver and skin were analysed by ELISA. As liver samples of trauma patients are hard to obtain we tried to review findings in an established trauma model. Plasma samples and liver samples of 56 male C57BL/6 N-mice with a thorax trauma and a femur fracture were analysed by ELISA, real-time PCR and immunohistochemistry for murine beta defensin 4 (MBD-4) and compared with the expression of control group without trauma. The induction of HBD-2 expression in cultured hepatocytes (Hep G2) was analysed after incubation with IL-6, supernatant of Staphylococcus aureus (SA) and Lipopolysaccharides (LPS). One possible signalling pathway was tested by blocking toll-like receptor 2 (TLR2) in hepatocytes.Results: Compared to healthy control group, plasma of multiple traumatized patients and mice showed significantly higher defensin levels after trauma. Compared to skin cells, which are known for high beta defensin expression, liver tissue showed less HBD-2 expression, but higher HBD-2 expression compared to PMN. Immunhistochemical staining demonstrated upregulated MBD-4 in hepatocytes of traumatised mice. In HepG2 cells HBD-2 expression could be increased by stimulation with IL-6 and SA. Neutralization of HepG2 cells with αTLR2 showed reduced HBD-2 expression after stimulation with SA.Conclusion: Plasma samples of multiple traumatized patients showed high expression of HBD-2, which may protect the severely injured patient from overwhelming bacterial infection. Our data support the hypothesis that liver is one possible source for HBD-2 in plasma while posttraumatic inflammatory response. [ABSTRACT FROM AUTHOR]

Background: Bisphosphonates are a main component in the therapy of osteoporosis and other bone resorptive diseases. Previous studies have shown a positive effect of systemically applied bisphosphonates on fracture healing. Nevertheless high doses are related to side effects like osteonecrosis of the jaw, nephrotoxis and gastrointestinal symptoms. In this study we investigated the effect of locally applied pamidronate on fracture healing.Methods: In a rodent model a simple femur fracture was set in female Wistar rats. We performed intramedullary fixation of the fracture and placed a collagen matrix around the fracture area. One group was treated with pamidronate, the other group with placebo via the matrix. To investigate the volume and quality of the callus we used micro-CT (μCT) and histology after 14 and 28 days.Results: Our results show a positive influence of local applied pamidronate on callus volume. After 14 days an insignificant increase of callus volume in the treated animals was seen. 28 days after trauma the increase of callus volume in the treatment group was significantly higher in comparison to the control group. Osteonecrosis was not seen.Conclusions: Locally applied bisphosphonates increase the callus volume in fracture healing. [ABSTRACT FROM AUTHOR]