Gram-positive bacterial bone infections are an important cause of morbidity particularly in immunocompromised patients. Antimicrobial peptides (AP) are effectors of the innate immune system and directly kill microorganisms in the first hours after microbial infection. The aim of the present investigation was to study the expression and regulation of gram-positive specialized human beta-defensin-3 (HBD-3) in bone. Samples of healthy and osteomyelitic human bone were assessed for the expression of HBD-3. Using primary and immortalized osteoblasts (SAOS-2 cells), release and regulation of HBD-3 was evaluated after exposure to Staphylococcus aureus supernatant and/or corticosteroids using PCR, immunohistochemistry, Western blot and ELISA. To determine the role of toll-like-receptors-2 and -4 (TLR-2/-4), shRNA was used to downregulate TLRs. An osteomyelitis mouse model was created performed to investigate the release of murine beta-defensins using immunohistochemistry and RT-PCR. Cultured osteoblasts and human bone produce HBD-3 under standard conditions. The release increases within hours of bacterial supernatant exposure in cultured osteoblasts. This observation was not made in chronically infected bone samples. The shRNA-technology revealed the necessity of TLR-2 and -4 in HBD-3 induction in osteoblasts. Blocking protein synthesis with cycloheximide showed that the rapid release of HBD-3 is not dependent on a translational de novo synthesis and is not affected by glucocorticoids. The murine osteomyelitis model confirmed the in vivo release uptake of mouse beta-defensins-4 (MBD-4) in bone. This report shows the bacterial induction of HBD-3 via TLR-2 and -4 in osteoblasts and suggests a central role of antimicrobial peptides in the prevention of bacterial bone infection. The rapid and effective induction of HBD-3 in osteoblasts incubated with conditioned media from bacteria is more likely a result of a rapid secretion of preformed HBD-3 by osteoblasts rather than a result of enhanced biosynthesis. The increased incidence of gram-positive bacterial bone infection in patients with regular intake of glucocorticoids does not seem to be caused by a deranged HBD-3 release in osteoblasts.
Osteomyelitis often causes functional impairment due to tissue destruction. This report demonstrates a novel previously unappreciated role of osteoblasts. Samples of osteomyelitic bone and bacterially challenged osteoblasts produce increased amounts of antimicrobial peptides in order to combat bacterial bone infection. An osteomyelitis mouse model confirmed the osseous induction of the murine homologue of human β -defensin-2, suggesting a central role in the prevention of bacterial bone infection. Antimicrobial peptides are effectors of the innate defence system and play a key role in host protection at cellular surfaces. Some of them are produced constitutively, whereas others are induced during infection. Human β -defensins represent a major subclass of antimicrobial peptides and act as a first line of defence through their broad spectrum of potent antimicrobial activity. The aim of the present in-vitro and in-vivo investigations was to study the expression and regulation of human β -defensin-2 in the case of bacterial bone infection and to analyse the effects of immunosuppressive drugs on bone-derived antimicrobial peptide expression. Samples of healthy human bone, osteomyelitic bone and cultured osteoblasts (hFOB cells) were assessed for the expression of human β -defensin-2. Regulation of human β -defensin-2 was studied in hFOB cells after exposure to bacterial supernatants, proinflammatory cytokines and immunosuppressive drugs (glucocorticoids and methotrexate) and was assayed by enzyme-linked immunosorbent assay. An osteomyelitis mouse model was performed to demonstrate the regulation of the murine homologue of human β -defensin-2, named murine β -defensin-3, by real-time reverse transcription-polymerase chain reaction and immunohistochemistry. Healthy human bone and cultured osteoblasts are able to produce human β -defensin-2 under standard conditions. Samples of infected bone produce higher levels of endogenous antibiotics, such as human β -defensin-2, when compared with samples of healthy bone. A clear induction of human β -defensin-2 was observed after exposure of cultured osteoblasts to Gram-positive bacteria or proinflammatory cytokines. Additional treatment with glucocorticoids or methotrexate prevented bacteria-mediated antimicrobial peptide induction in cultured osteoblasts. The osteomyelitis mouse model demonstrated transcriptional upregulation of the murine homologue of human β -defensin-2, namely murine β -defensin-3, in bone after intraosseous contamination of the tibia. Human and murine bone have the ability to produce broad-spectrum endogenous antibiotics when challenged by microorganisms in vitro and in vivo . Immunosuppressive drugs, such as glucocorticoids or methotrexate, may increase the susceptibility to bone infection by decreasing antimicrobial peptide expression levels in case of microbial challenge. The induction of human β -defensin-2 following bacterial contact suggests a central role of antimicrobial peptides in the prevention of bacterial bone infection.
The majority of patients in both groups was free of pain or suffered minor pain as determined by the Constant score. Safe fixation of the tuberosities is a prerequisite for functional exercises and is better achieved in primary arthroplasty. A computed tomography scan before operative therapy aids in making the decision between open reduction and internal fixation or hemiarthroplasty.
Background:Today, humerus nails have become the surgical method of choice in the treatment of humerus shaft fractures. Whether or not the radial nerve should be intraoperatively examined by default in case of primary paresis is currently under discussion.Patients and Methods:Clinical findings from 38 patients with humeral shaft fractures surgically treated with unreamed humerus nail (UHN) at the Department of Accident Surgery, University Clinics Bonn, Germany, between 2000 and 2003 were retrospectively assessed. Constant Score was applied for evaluation of functional results.Results:In 40% of patients, primary radial nerve paresis was present. This was especially common after high energy trauma (e.g. traffic accident) and significantly increased in fractures of the middle third. In 93% of cases, spontaneous remission of motor and sensory loss was observed. No iatrogenic radial nerve impairment occurred.Conclusion:Due to the high rates of spontaneous remissions of radial nerve palsy after treatment with UHN in humerus shaft fractures, primar exploration of the radial nerve does not appear to be necessary.
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