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

Schistosome-induced cholangiocyte proliferation and osteopontin secretion correlate with fibrosis and portal hypertension in human and murine schistosomiasis mansoni

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-07-25T19:19:13Z No. of bitstreams: 1 Pereira TA Schistosome-induced....pdf: 1592116 bytes, checksum: 5dcd2e5f5e6a53407b91145c1607643e (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-07-25T19:35:53Z (GMT) No. of bitstreams: 1 Pereira TA Schistosome-induced....pdf: 1592116 bytes, checksum: 5dcd2e5f5e6a53407b91145c1607643e (MD5)Made available in DSpace on 2016-07-25T19:35:54Z (GMT). No. of bitstreams: 1 Pereira TA Schistosome-induced....pdf: 1592116 bytes, checksum: 5dcd2e5f5e6a53407b91145c1607643e (MD5) Previous issue date: 2015-11Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Duke University Medical Center. Department of Medicine. Division of Gastroenterology. Durham, U.S.A. / Fundação Gonçalo Moniz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia Experimental. Salvador, BA, BrasilFoundation for Liver Research. Institute of Hepatology. Liver Regeneration and Repair Research Group. London, U.K. / Loyola University. Department of Surgery. Chicago, Maywood, U.S.A.Duke University Medical Center. Department of Medicine. Division of Gastroenterology. Durham, U.S.A.Universidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, BrasilDuke University Medical Center. Department of Medicine. Division of Gastroenterology. Durham, U.S.A.Universidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, BrasilFundação Gonçalo Moniz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia Experimental. Salvador, BA, BrasilFundação Gonçalo Moniz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia Experimental. Salvador, BA, BrasilDuke University Medical Center. Department of Medicine. Division of Gastroenterology. Durham, U.S.A.Universidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, BrasilDuke University Medical Center. Department of Medicine. Division of Gastroenterology. Durham, U.S.A.Life Technologies. Frederick, MD, U.S.A.Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, BrasilCenters for Disease Control and Prevention. Atlanta, GA, U.S.A.Fundação Gonçalo Moniz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia Experimental. Salvador, BAUniversidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, BrasilDuke University Medical Center. Department of Medicine. Division of Gastroenterology. Durham, U.S.A.Schistosomiasis is a major cause of portal hypertension worldwide. It associates with portal fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated the hypothesis that schistosome eggs release factors that directly stimulate liver cells to produce osteopontin (OPN), a pro-fibrogenic protein that stimulates hepatic stellate cells to become myofibroblasts. We also investigated the utility of OPN as a biomarker of fibrosis and/or severity of portal hypertension. Cultured cholangiocytes, Kupffer cells and hepatic stellate cells were treated with soluble egg antigen (SEA); OPN production was quantified by quantitative reverse transcriptase polymerase chain reaction (qRTPCR) and ELISA; cell proliferation was assessed by BrdU (5-bromo-2'-deoxyuridine). Mice were infected with Schistosoma mansoni for 6 or 16 weeks to cause early or advanced fibrosis. Liver OPN was evaluated by qRTPCR and immunohistochemistry (IHC) and correlated with liver fibrosis and serum OPN. Livers from patients with schistosomiasis mansoni (early fibrosis n=15; advanced fibrosis n=72) or healthy adults (n=22) were immunostained for OPN and fibrosis markers. Results were correlated with plasma OPN levels and splenic vein pressures. SEA-induced cholangiocyte proliferation and OPN secretion (P<0.001 compared with controls). Cholangiocytes were OPN (+) in Schistosoma-infected mice and humans. Liver and serum OPN levels correlated with fibrosis stage (mice: r=0.861; human r=0.672, P=0.0001) and myofibroblast accumulation (mice: r=0.800; human: r=0.761, P=0.0001). Numbers of OPN (+) bile ductules strongly correlated with splenic vein pressure (r=0.778; P=0.001). S. mansoni egg antigens stimulate cholangiocyte proliferation and OPN secretion. OPN levels in liver and blood correlate with fibrosis stage and portal hypertension severity