Nowadays, the use of minimally invasive plate osteosynthesis (MIPO) in the management of fracture of the distal tibia is common. The various advantages of the MIPO technique, namely, preserving blood supply and better bone healing, have been described extensively in the literature. However, this technique is not without complication. Among all the complications, infection is one of the commonest. In the last 3 years, we have performed 48 cases of MIPO in treating distal tibia fractures. Our study was to evaluate the clinical outcome of these cases, with special attention to the infection rate and our experience in managing these infection cases. Our results showed that the average time until the patient started to bear full weight was 9.4 weeks. The average time for bony union was 18.7 weeks. There were 7 cases of late infection among these 48 cases. The rate was 15%. The presence of late infection had no obvious effect on the time to bony union. Twenty-five patients (52%) had the implants removed and the most common reason was skin impingement by the implant. The clinical presentation and management of these late infections are discussed. In conclusion, MIPO fixation of distal tibia fractures using a metaphyseal locking plate is safe and efficient. However, complications such as late wound infection and impingement are relatively common. The overall clinical outcome is still good despite the presence of these complications.
Background and aims Myeloid derived suppressor cells (MDSC) are immature myeloid cells with immunosuppressive activity. They accumulate in tumor-bearing mice and humans with different types of cancer, including hepatocellular carcinoma (HCC). The aim of this study was to examine the biology of MDSC in murine HCC models and to identify a model, which mimics the human disease. Methods: The comparative analysis of MDSC was performed in mice, bearing transplantable, diethylnitrosoamine (DEN)-induced and MYC-expressing HCC at different ages. Results: An accumulation of MDSC was found in mice with HCC irrespectively of the model tested. Transplantable tumors rapidly induced systemic recruitment of MDSC, in contrast to slow-growing DEN-induced or MYC-expressing HCC, where MDSC numbers only increased intra-hepatically in mice with advanced tumors. MDSC derived from mice with subcutaneous tumors were more suppressive than those from mice with DEN-induced HCC. Enhanced expression of genes associated with MDSC generation (GM-CSF, VEGF, IL-6, IL-1β) and migration (MCP-1, KC, S100A8, S100A9) was observed in mice with subcutaneous tumors. In contrast, only KC levels increased in mice with DEN-induced HCC. Both KC and GM-CSF over-expression or anti-KC and anti-GM-CSF treatment controlled MDSC frequency in mice with HCC. Finally, the frequency of MDSC decreased upon successful anti-tumor treatment with sorafenib. Conclusions: Our data indicate that MDSC accumulation is a late event during hepatocarcinogenesis and differs significantly depending on the tumor model studied.
Bacterial exopolysaccharides provide protection against phagocytosis, opsonization, and dehydration and act as a major structural component of the extracellular matrix in biofilms. They contribute to biofilmrelated resistance by acting as a diffusion barrier to positively charged antimicrobial agents including cationic antimicrobial peptides (CAPs). We previously created novel CAPs consisting of a nonamphipathic hydrophobic core flanked by Lys residues and containing a Trp residue in the hydrophobic segment as a fluorescent probe. Peptides of this type above a specific hydrophobicity threshold insert spontaneously into membranes and have antimicrobial activity against Gram-positive and Gram-negative bacteria at micromolar concentrations. Here we show that alginate, a polymer of -Dmannuronate and ␣-L-guluronate secreted by the cystic fibrosis pathogen Pseudomonas aeruginosa, induces an ␣-helical conformation detected by circular dichroism spectroscopy and blue shifts in Trp fluorescence maxima in peptides above the hydrophobicity threshold, changes typically observed upon association of such peptides with nonpolar (membrane) environments. Parallel effects were observed in the archetypical CAPs magainin II amide and cecropin P1. Fluorescence resonance energy transfer studies indicated that alginate induces peptide-peptide association only in peptides above the hydrophobicity threshold, suggesting that the hydrophilic alginate polymer behaves as an "auxiliary membrane" for the bacteria, demonstrating a unique protective role for biofilm matrices against CAPs.Pseudomonas aeruginosa is the predominant respiratory tract pathogen in cystic fibrosis (CF) 1 patients, where chronic infection is due to the bacteria growing as a mucoid biofilm, a state characterized by overproduction of alginate (1-3). Alginate is a secreted extracellular polysaccharide composed of the uronic acid -D-mannuronate and its C-5 epimer ␣-L-guluronate (4), which is partially O-acetylated at the second and/or third position(s) of the D-mannuronate residues. The chronicity of P. aeruginosa infections in CF; its high level intrinsic antimicrobial resistance, a result of the low permeability of its outer membrane to antibiotics and multidrug efflux systems; and its propensity to develop resistance during prolonged antimicrobial therapy have all presented major therapeutic challenges to CF caregivers.Our laboratory has developed a new category of cationic antimicrobial peptides that display antibacterial activity (5). The peptides consist of a nonamphipathic hydrophobic core sequence (11-19 residues) flanked at one or both termini by a number of Lys or Arg residues. These peptides, which were originally designed as transmembrane mimetic model peptides (6, 7), have the prototypic sequence KKAAAXAAAAAX-AAWAAXAAAKKKK-NH 2 with several key features: (i) Ala is the preferred background residue because of its mid-range hydropathy and frequent occurrence in membrane protein transmembrane domains; (ii) a Trp residue is inserted into the hydrophobic segment ...
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