Effectiveness of Chitosan Films Impregnated With Ciprofloxacin for the Prophylaxis of Osteomyelitis in Open Fractures: An Experimental Study in Rats

Background: The systemic antimicrobial prophylaxis is the standard treatment in the prevention of osteomyelitis after open fractures, with topical application of antimicrobials as an alternative due to their high concentrations at the site of the fracture, low systemic concentrations and fewer side effects. Objectives: This study aimed to evaluate the effectiveness of prophylaxis of osteomyelitis through experimental model of open fractures with the use of chitosan films, whether or not impregnated with ciprofloxacin. Materials and Methods: In this experimental study, 24 Holtzman rats were distributed into 4 groups of 6 rats each. The CT (control of treatment) group: an open fracture model treated with systemic antimicrobial; the IC (infection control) group: an open fracture untreated model; the C (chitosan) group: an open fracture model treated using a chitosan film; and the CA (chitosan with antimicrobial) group: an open fracture model treated using a chitosan film impregnated with antimicrobial. After 3 weeks the animals were killed by an overdose of anesthetic, and a fragment osseous was removed for histological and microbiological analysis. The comparisons between the groups considered significant values of P ≤ 0.05. Results: In cultures of the CT group, there was less bacterial growth compared to the results of the cultures of the IC (P = 0.005), C (P = 0.005) and CA (P = 0.009) groups. The inflammation was lower in the CT group compared to the IC (P = 0.014), C (P = 0.001) and CA (P = 0.007) groups. Conclusions: In this experimental model of open fracture, the chitosan film pure or impregnated with ciprofloxacin was not effective in the prophylaxis of osteomyelitis

Absent in Melanoma 2 (AIM2) is an important mediator of interferon-dependent and -independent HLA-DRA and HLA-DRB gene expression in colorectal cancers

Absent in Melanoma 2 (AIM2) is a member of the HIN-200 family of hematopoietic, IFN-inducible, nuclear proteins, associated with both, infection defense and tumor pathology. Recently, AIM2 was found to act as a DNA sensor in innate immunity. In addition, we and others have previously demonstrated a high frequency of AIM2-alterations in microsatellite unstable (MSI-H) tumors. To further elucidate AIM2 function in colorectal tumors, we here addressed AIM2-responsive target genes by microarray based gene expression profiling of 22 244 human genes. A total of 111 transcripts were significantly upregulated, whereas 80 transcripts turned out to be significantly downregulated in HCT116 cells, constitutively expressing AIM2, compared with AIM2-negative cells. Among the upregulated genes that were validated by quantitative PCR and western blotting we recognized several interferon-stimulated genes (ISGs: IFIT1, IFIT2, IFIT3, IFI6, IRF7, ISG15, HLA-DRA, HLA-DRB, TLR3 and CIITA), as well as genes involved in intercellular adhesion and matrix remodeling. Expression of ISGs correlated with expression of AIM2 in 10 different IFN-γ treated colorectal cancer cell lines. Moreover, small interfering RNA-mediated knock-down of AIM2 resulted in reduced expression of HLA-DRA, HLA-DRB and CIITA in IFN-γ-treated cells. IFN-γ independent induction of HLA-DR genes and their encoded proteins was also demonstrated upon doxycyclin-regulated transient induction of AIM2. Luciferase reporter assays revealed induction of the HLA-DR promoter upon AIM2 transfection in different cell lines. STAT-signaling was not involved in IFN-γ independent induction of ISGs, arguing against participation of cytokines released in an autostimulating manner. Our data indicate that AIM2 mediates both IFN-γ dependent and independent induction of several ISGs, including genes encoding the major histocompatibility complex (MHC) class II antigens HLA-DR-α and -β. This suggests a novel role of the IFN/AIM2/ISG cascade likewise in cancer cells

HLA class I and II expression in oropharyngeal squamous cell carcinoma in relation to tumor HPV status and clinical outcome.

HPV-DNA positive (HPVDNA+) oropharyngeal squamous cell carcinoma (OSCC) has better clinical outcome than HPV-DNA negative (HPVDNA-) OSCC. Current treatment may be unnecessarily extensive for most HPV+ OSCC, but before de-escalation, additional markers are needed together with HPV status to better predict treatment response. Here the influence of HLA class I/HLA class II expression was explored. Pre-treatment biopsies, from 439/484 OSCC patients diagnosed 2000-2009 and treated curatively, were analyzed for HLA I and II expression, p16(INK4a) and HPV DNA. Absent/weak as compared to high HLA class I intensity correlated to a very favorable disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) in HPVDNA+ OSCC, both in univariate and multivariate analysis, while HLA class II had no impact. Notably, HPVDNA+ OSCC with absent/weak HLA class I responded equally well when treated with induction-chemo-radiotherapy (CRT) or radiotherapy (RT) alone. In patients with HPVDNA- OSCC, high HLA class I/class II expression correlated in general to a better clinical outcome. p16(INK4a) overexpression correlated to a better clinical outcome in HPVDNA+ OSCC. Absence of HLA class I intensity in HPVDNA+ OSCC suggests a very high survival independent of treatment and could possibly be used clinically to select patients for randomized trials de-escalating therapy