RESUMO
Considering the lack of consensus related to the impact of selective IL-6 receptor inhibition on bone remodeling and the scarcity of reports, especially on large bone defects, this study proposed to evaluate the biological impact of the selective inhibitor of interleukin-6 receptor (tocilizumab) in an experimental model of critical calvarial defect in rats. In this preclinical and in vivo study, 24 male Wistar rats were randomly divided into two groups (n=12/group): defect treated with collagen sponge (CG) and defect treated with collagen sponge associated with 2 mg/kg tocilizumab (TCZ). The defect in the parietal bone was created using an 8-mm diameter trephine drill. After 90 days, the animals were euthanized, and tissue samples (skull caps) were evaluated through micro-CT, histological, immunohistochemistry, cytokines, and RT-qPCR analyses. Tocilizumab reduced mononuclear inflammatory infiltration (P<0.05) and tumor necrosis factor (TNF)-α levels (P<0.01) and down-regulated tissue gene expression of BMP-2 (P<0.001), RUNX-2 (P<0.05), and interleukin (IL)-6 (P<0.05). Moreover, it promoted a stronger immunostaining of cathepsin and RANKL (P<0.05). Micro-CT and histological analyses revealed no impact on general bone formation (P>0.05). The bone cells (osteoblasts, osteoclasts, and osteocytes) in the defect area were similar in both groups (P>0.05). Tocilizumab reduced inflammatory cytokines, decreased osteogenic protein, and increased proteases in a critical bone defect in rats. Ninety days after the local application of tocilizumab in the cranial defect, we did not find a significant formation of bone tissue compared with a collagen sponge.
Assuntos
Citocinas , Modelos Animais de Doenças , Ratos Wistar , Receptores de Interleucina-6 , Crânio , Animais , Masculino , Citocinas/metabolismo , Receptores de Interleucina-6/antagonistas & inibidores , Crânio/efeitos dos fármacos , Ratos , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Microtomografia por Raio-X , Peptídeo Hidrolases/metabolismo , Imuno-Histoquímica , Distribuição AleatóriaRESUMO
Considering the lack of consensus related to the impact of selective IL-6 receptor inhibition on bone remodeling and the scarcity of reports, especially on large bone defects, this study proposed to evaluate the biological impact of the selective inhibitor of interleukin-6 receptor (tocilizumab) in an experimental model of critical calvarial defect in rats. In this preclinical and in vivo study, 24 male Wistar rats were randomly divided into two groups (n=12/group): defect treated with collagen sponge (CG) and defect treated with collagen sponge associated with 2 mg/kg tocilizumab (TCZ). The defect in the parietal bone was created using an 8-mm diameter trephine drill. After 90 days, the animals were euthanized, and tissue samples (skull caps) were evaluated through micro-CT, histological, immunohistochemistry, cytokines, and RT-qPCR analyses. Tocilizumab reduced mononuclear inflammatory infiltration (P<0.05) and tumor necrosis factor (TNF)-α levels (P<0.01) and down-regulated tissue gene expression of BMP-2 (P<0.001), RUNX-2 (P<0.05), and interleukin (IL)-6 (P<0.05). Moreover, it promoted a stronger immunostaining of cathepsin and RANKL (P<0.05). Micro-CT and histological analyses revealed no impact on general bone formation (P>0.05). The bone cells (osteoblasts, osteoclasts, and osteocytes) in the defect area were similar in both groups (P>0.05). Tocilizumab reduced inflammatory cytokines, decreased osteogenic protein, and increased proteases in a critical bone defect in rats. Ninety days after the local application of tocilizumab in the cranial defect, we did not find a significant formation of bone tissue compared with a collagen sponge.
RESUMO
AIMS: To investigate the presence of Staphylococcus aureus, enteropathogenic Escherichia coli (EPEC), Aeromonas spp. and Yersinia spp. in soft cheese commercialized in Rio de Janeiro, Brazil. METHODS AND RESULTS: A total of 45 samples of cheese from three different brands marketed in Rio de Janeiro city were analysed for faecal coliform levels using the Most Probable Number (MPN) technique. The samples were also analysed using conventional methodology for the investigation of food-borne pathogens. High levels of faecal contamination were detected in 95.5% of cheese samples. Staphylococcus aureus was isolated from 20% of samples, of which 17.7% were above the limits allowed by Brazilian legislation. Aeromonas hydrophila and Aer. caviae were detected in 17.7% of the samples. Yersinia spp. were not found in this study. EPEC was isolated from 21.1% of the samples and the most frequently found serogroups were O127, followed by O55 and O26. CONCLUSIONS: Our results showed that 95.5% of cheese samples had high levels of faecal coliforms. The isolation of Staph. aureus, serogroups of EPEC and Aeromonas spp. suggested that the soft cheese commercialized in the city of Rio de Janeiro may represent a health risk for the consumers. SIGNIFICANCE AND IMPACT OF THE STUDY: These results suggest that soft cheese may act as an important vehicle of transmission for well-established pathogens.