Influence of age on combined effects of cyclosporin and nifedipine on rat alveolar bone

Background: There is some evidence showing that cyclosporin A (CsA) and nifedipine (NIF) affect bone metabolism. The purpose of this work was to study the effects of CsA and NIF, given alone or concurrently, on alveolar bone of rats of different ages. Methods: Rats 15, 30, 60, and 90 days old were treated daily with 10 mg/kg body weight of CsA subcutaneously injected and/or 50 mg/kg body weight of NIF/day given orally for 60 days. Alveolar bone of the first lower molars was morphologically and stereologically evaluated in serial 5 mum bucco-lingual paraffin sections, stained with hematoxylin and eosin. Serum calcium and alkaline phosphatase levels were measured in all animals at the end of the experimental period. Results: Rats treated with CsA or NIF alone or CsA and NIF concurrently showed decreased alveolar bone density. CsA was more effective than NIF. A significant decrease in serum calcium was found only in animals treated with CsA or CsA/NIF. The results were similar regardless of age. Conclusions: These results indicate that the decrease in the alveolar bone volume in rats caused by CsA and NIF alone or concurrently is not age dependent. Furthermore, NIF (50 mg/kg) did not further increase the loss of alveolar bone volume induced by CsA (10 mg/kg).75226827

Pulpal lesions in normal and cyclosporin A treated rats

The objective of this study was to examine the development of pulpal lesions in the lower molar of control and cyclosporin A (CyA) treated rats, The pulps of the first lower molars of 20 normal and 20 CyA treated rats were exposed and left open into the oral cavity, Five animals of each group were killed at 7, 14, 21, and 28 days after the pulp exposure, The specimens were sectioned sagittally at a thickness of 7 E-cm and stained with hematoxylin and eosin, The pulpal lesions were similar for both normal and CyA treated rats in all studied periods and the differences between both groups were not statistically significant by the Student t test at the 5% (0.05) level of significance, indicating that the immunosuppression did not alter the evolution of the inflammatory process.231525

Morphometric evaluation of gingival overgrowth and regression caused by cyclosporin in rats

Cyclosporin A is a selective immunosuppressant, used in organ transplants to prevent graft rejection. Cyclosporin A can cause various side effects including gingival overgrowth. The aim of this work was to evaluate gingival overgrowth of rats treated daily with 10 mg/kg body weight of cyclosporin A for 60 days, as well as the regression after the interruption of treatment. All rats treated with cyclosporin A developed gingival overgrowth, with increased thickness of the epithelium, height and width of the connective tissue. The density of fibroblasts and collagen fibers also increased. Five to 90 days after the interruption of treatment with cyclosporin A, there was a progressive reduction of the gingival volume and of collagen fibers and fibroblast densities. The reduction was more pronounced in the initial periods and after 90 days did not return to the normal values.36638438

Differential regulation of MMP-13 expression in two models of experimentally induced periodontal disease in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Objective: Evaluate expression of MMP-13 during the course of two models experimentally induced periodontal disease in rats. Design: Expression of MMP-13 at mRNA and protein levels was studied, respectively, by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Two experimental models were used: LPS injections and ligature placement. 30 jig of LPS from Eschericia coli was injected twice a week into the palatal aspect of upper molars. Ligatures were placed at the gingival margin around lower first molars. Controls received injections of PBS vehicle and no ligatures on lower molars. Samples were collected 5,15 and 30 days after initiation of periodontal disease and processed for extraction of total RNA, total protein, and routinely processed for histology. Results: Both experimental models produced a significant increase on the inflammatory infiltrate that paralleled elevated levels of MMP-13 mRNA and protein at 5 and 15 days. The LPS model was associated with a sustained level of inflammation and increased MMP-13 mRNA throughout the 30 days, whereas the ligature model showed a decrease on the severity of inflammation and MMP-13 mRNA at the 30-day period. interestingly, MMP-13 protein levels were diametrically contrary to the mRNA levels. Conclusion: MMP-13 expression during LPS- and ligature-induced experimental periodontal disease follows the increase on severity of inflammation at the earliest periods. At 30 days, there is a decrease on the severity of inflammation on the ligature model associated with decreased MMP-13 mRNA. There is a lack of transcription-translation coupling of MMP-13 gene in both experimental models. (C) 2009 Elsevier Ltd. All rights reserved.547609617Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)State of Sao Paulo, Brazil [2005/04428-9, 2006/07283-4]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2005/04428-9, 2006/07283-4]State of Sao Paulo, Brazil [2005/04428-9, 2006/07283-4

Signaling pathways associated with the expression of inflammatory mediators activated during the course of two models of experimental periodontitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Aims: Evaluate the signaling pathways associated with inflammatory mediators activated in two models of experimental periodontitis. Main methods: Two models were used: lipopolysaccharide (LPS) injections and ligature placement. Wistar rats were used and 30 mu g LIPS from Escherichia coli was injected twice a week into the palatal aspect of the upper molars. Ligatures were placed around lower first molars. A control group received injections of PBS on the palatal gingivae whereas no ligatures were placed on the lower molars. Samples were collected 5,15 and 30 days and processed for analysis by Western blotting and stereometry. Key findings: The ligature model was associated with rapid and transient activation of extracellular-regulated kinases (ERK) and p38 mitogen-activated protein kinase (MAPK) as well as of nuclear factor kappa B (NF-kappa B). Activation of these signaling pathways on the LPS model was delayed but sustained throughout the 30-day experimental period. Inflammatory changes induced by both models were similar; however there was a significant reduction on inflammation degree on the ligature model, which paralleled the decrease observed on the activation of the signaling pathways. Activation of signal transducer and activator of transcription (SEAT)-3 by phosphorylation of Tyrosine residues and of SPAT-5 was observed only on the ligature model. Significance: Regulation of gene expression results from the activation of signaling pathways initiated by receptor-ligand binding of external antigens and also of cytokines produced by the host immune system. Understanding the signaling pathways relevant fora given condition may provide information useful for novel therapeutic approaches. (C) 2009 Elsevier Inc. All rights reserved.8421-22745754Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2005/04428-9, 2006/07283-4