Effects of Lidocaine Infusion during Experimental Endotoxemia in Horses

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Diminished CD4+/CD25+T cell and increased IFN-gamma levels occur in dogs vaccinated with Leishmune (R) in an endemic area for visceral leishmaniasis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Periodontal Disease Decreases Insulin Sensitivity and Insulin Signaling

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Mechanism of calcium hydroxide-induced neutrophil migration into air-pouch cavity

The aim of this study was to investigate cellular migration induced by calcium hydroxide to air-pouch cavities in mice. The migration was more specific to neutrophil and was dose and time dependent (peaking 96 h after stimulation). This migration was inhibited by pretreatment with thalidomide, indomethacin, MK886, meloxicam, dexamethasone, MK886 associated with indomethacin, and MK886 associated with indomethacin and dexamethasone. The air-pouch exudate from animals stimulated with calcium hydroxide showed an increase of leukotriene-B4 (LTB4), interleukin-1 beta, tumor necrosis factor alpha (TNF-alpha), cytokine-induced neutrophil chemoattractant (KC), and macrophage inflammatory protein 2 (MIP-2) release. Pretreatment with 3% thioglycollate increased the macrophage population in the air pouch but did not change neutrophil migration. Depleting the resident mast cells through chronic pretreatment with compound 48/80 did not alter neutrophil migration in response to calcium hydroxide. It was possible to conclude that calcium hydroxide-induced neutrophil migration to the air-pouch cavity in mice is mediated by LTB4, TNF-alpha, KC, MIP-2, and prostaglandins, but it was not dependent on macrophages or mast cells.

Hypertension favors the inflammatory process in rats with experimentally induced periodontitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Protective effects of Tacrolimus, a calcineurin inhibitor, in experimental periodontitis in rats

Objective: Periodontitis is a well-appreciated example of leukocyte-mediated bone loss and inflammation with pathogenic features similar to those observed in other inflammatory diseases, such as arthritis. Since Tacrolimus, is an immunomodulatory drug used for the treatment of some cases of arthritis, we hypothesized that it may modulate periodontal disease.Design: Using a murine model of ligature-induced periodontal disease, we assessed the effects of daily administrations of Tacrolimus (1 mg/kg body weight) on bone loss, enzymatic (myeloperoxidase) analysis, differential white blood cells counts, airpouch exudate and cytokine expression for 5-30 days.Results: Radiographic, enzymatic (myeloperoxidase) and histological analysis revealed that Tacrolimus reduced the severity of periodontitis. More specifically, Tacrolimus suppressed the expression of serum interleukin (IL-1 beta), tumour necrosis factor (TNF-alpha), IL-6, airpouch exudate PGE(2) and leukocytosis usually observed after the induction of periodontitis. Tacrolimus treatment in periodontitis-induced rats conferred protection against the inflammation-induced tissue and bone loss associated with periodontitis, through a mechanism involving IL-1 beta, TNF-alpha and IL-6.Conclusions: the effects of Tacrolimus on periodontal disease pathogenesis may provide clues to a novel approach to host modulation therapy in destructive periodontal disease. (C) 2007 Elsevier Ltd. All rights reserved.

Prostaglandin production by human gingival fibroblasts inhibited by triclosan in the presence of cetylpyridinium chloride

Background: the effect of triclosan plus the cationic detergent cetylpyridinium chloride (CPC) was evaluated for prostaglandin inhibition in human gingival fibroblasts. Since triclosan has previously been shown to inhibit proinflammatory cytokine induced prostaglandin E-2 (PGE(2)) production, we wanted to determine if triclosan, in the presence of CPC, could enhance these effects.Methods: Initial studies determined that both triclosan and CPC were cytotoxic to human gingival fibroblasts in concentrations exceeding 1.0 mu g/ml for either agent longer than 24 hours in a tissue culture. Therefore, subsequent studies measuring prostaglandin biosynthesis and cyclooxygenase (COX)-1 and COX-2 mRNA expression were performed in concentrations and times that did not significantly affect cell viability.Results: PGE2 biosynthesis was dose dependently inhibited by both triclosan and triclosan and CPC when challenged by tumor necrosis factor (TNF)-alpha or interleukin (IL)-1 beta. At pharmacologically relevant concentrations, triclosan and CPC inhibited ILAP-induced PGE(2) production to a greater extent than triclosan alone (P = 0.02). Moreover, enhanced COX-2 mRNA repression was observed with triclosan and CPC in comparison to triclosan alone in IL-1 beta and TNF-alpha stimulated cells. No effect on COX-I gene expression was observed. Further analysis of cell signaling mechanisms of triclosan and CPC indicates that nuclear factor-kappa B (NF-kappa B) and not p38 mitogen-activated protein kinase (MAPK) signaling may be impaired in the presence of triclosan and CPC.Conclusion: This study indicates that triclosan and CPC are more effective at inhibiting PGE(2) at the level of COX-2 gene regulation, and this combination may offer a potentially better anti -inflammatory agent in the treatment of inflammatory lesions in the oral cavity.

Curcumin modulates the immune response associated with LPS-induced periodontal disease in rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Intermittent Therapy with 1,25 Vitamin D and Calcitonin Prevents Cyclosporin-Induced Alveolar Bone Loss in Rats

Bone loss associated with cyclosporin A (CsA) therapy can result in serious morbidity to patients. Intermittent administration of 1,25 Vitamin D and calcitonin reduces osteopenia in a murine model of postmenopausal osteoporosis. The purpose of this study was to evaluate the effects of this therapeutic approach on CsA-induced alveolar bone loss in rats. Forty male Wistar rats were allocated to four experimental groups according to the treatment received during 8 weeks: (1) CsA (10 mg/kg/day, s.c.); (2) 1,25 Vitamin D (2 mu g/kg, p.o.; in weeks 1, 3, 5, and 7) plus calcitonin (2 mu g/kg, i.p.; in weeks 2, 4, 6, and 8); (3) CsA concurrently with intermittent 1,25 Vitamin D and calcitonin administration; and (4) the control treatment group (vehicle). At the end of the 8-week treatment period, serum concentrations of bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase (TRAP-5b), osteocalcin, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) were measured and an analysis of bone volume, bone surface, number of osteoblasts, and osteoclasts was performed. CsA administration resulted in significant alveolar bone resorption, as assessed by a lower bone volume and an increased number of osteoclasts, and increased serum bone-specific alkaline phosphatase, TRAP-5b, IL-1 beta, IL-6, and TNF-alpha concentrations. The intermittent administration of calcitriol and calcitonin prevented the CsA-induced osteopenic changes and the increased serum concentrations of TRAP-5b and inflammatory cytokines. Intermittent calcitriol/calcitonin therapy prevents CsA-induced alveolar bone loss in rats and normalizes the production of associated inflammatory mediators.

The Potential of p38 MAPK Inhibitors to Modulate Periodontal Infections

Periodontal disease initiation and progression occurs as a consequence of the host immune inflammatory response to oral pathogens. The innate and acquired immune systems are critical for the proper immune response. LPS, an outer membrane constituent of periodontal pathogenic bacteria, stimulates the production of inflammatory cytokines IL-1 beta TNF alpha IL-6 and RANKL either directly or indirectly. In LPS-stimulated cells, the induction of cytokine expression requires activation of several signaling pathways including the p38 MAPK pathway. This review will discuss the significance of the p38 MAPK pathway in periodontal disease progression and the potential therapeutic consequences of pharmacological antagonism of this pathway in the treatment of periodontal diseases.

Effect of periodontal treatment on metabolic control, systemic inflammation and cytokines in patients with type 2 diabetes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Antigenic Activity of Bacterial Endodontic Contents from Primary Root Canal Infection with Periapical Lesions against Macrophage in the Release of Interleukin-1 beta and Tumor Necrosis Factor alpha

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of Antiplatelet Drugs in the Pathogenesis of Experimental Periodontitis and Periodontal Repair in Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sequential IL-23 and IL-17 and increased Mmp8 and Mmp14 expression characterize the progression of an experimental model of periodontal disease in type 1 diabetes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

MAP Kinase Phosphatase-1 Protects against Inflammatory Bone Loss

The mitogen-activated protein (MAP) kinase phosphatase (MKP) family plays an important function in regulating the pro-inflammatory cytokines by deactivating MAP kinases. MKP-1 is essential for the dephosphorylation of p38 MAP kinase that regulates expression of IL-6, TNF-alpha, and IL-1 beta. We hypothesized that MKP-1 regulates inflammatory bone loss in experimental periodontitis. Wild-type and Mkp-1(-/-) mice received A. actinomycetemcomitans LPS injection in the palatal region or PBS control 3 times/wk for 30 days. Mice were killed, and maxillae were assessed by microcomputed tomography, histological analysis, and TRAP staining for measurement of bone loss, extent of inflammation, and degree of osteoclastogenesis. Results indicated that, in LPS-injected Mkp-1(-/-) mice, significantly greater bone loss occurred with more inflammatory infiltrate and a significant increase in osteoclastogenesis compared with Mkp-1(-/-) control sites or either wild-type group. Analysis of these data indicates that MKP-1 plays a key role in the regulation of inflammatory bone loss.