Absence of medication-related jaw osteonecrosis after treatment with strontium ranelate in ovariectomized rats.

This study aimed to evaluate the potential of strontium ranelate (SR) in medication-related jaw osteonecrosis (MRONJ) after tooth extraction in ovariectomized rats. Thirty ovariectomized rats were divided into three groups (n = 10): bisphophonate (BP) group (zoledronic acid; 0.4 mg/kg/week), SR group (625 mg/kg/day), and control group (saline solution). The lower first molars were extracted after 60 days of drug therapy. Drug administration was continued for another 30 days after tooth extraction. The mandibles were subjected to clinical, histological, radiographic, and microtomographic evaluations. Only the BP group showed clinical changes, characterized by the presence of 70% (n = 7) and 20% (n = 2) of ulcers and extraoral fistulas. Radiographic evaluation demonstrated bone sequestration only in the BP group (n = 7, 70%). Microtomographic analysis revealed increased bone porosity after ovariectomy, particularly in the the control group (p < 0.05). The BP group showed a higher bone surface density, bone volume, and trabecular number than SR and control groups, but with less trabecular separation (p < 0.05). All the animals in the BP group demonstrated histological osteonecrosis. There was no evidence of osteonecrosis in the control and SR groups, which was characterized by the absence of empty osteocyte gaps and associated with the gradual healing of the extraction area. Also, an increased number of blood vessels and a reduced number of osteoclasts were observed in the SR group (p < 0.05). Therefore, SR treatment increased angiogenesis and osteoclastogenesis in the healing socket and was not associated with MRONJ development after tooth extraction in ovariectomized rats.

Absence of medication-related jaw osteonecrosis after treatment with strontium ranelate in ovariectomized rats

Abstract This study aimed to evaluate the potential of strontium ranelate (SR) in medication-related jaw osteonecrosis (MRONJ) after tooth extraction in ovariectomized rats. Thirty ovariectomized rats were divided into three groups (n = 10): bisphophonate (BP) group (zoledronic acid; 0.4 mg/kg/week), SR group (625 mg/kg/day), and control group (saline solution). The lower first molars were extracted after 60 days of drug therapy. Drug administration was continued for another 30 days after tooth extraction. The mandibles were subjected to clinical, histological, radiographic, and microtomographic evaluations. Only the BP group showed clinical changes, characterized by the presence of 70% (n = 7) and 20% (n = 2) of ulcers and extraoral fistulas. Radiographic evaluation demonstrated bone sequestration only in the BP group (n = 7, 70%). Microtomographic analysis revealed increased bone porosity after ovariectomy, particularly in the the control group (p < 0.05). The BP group showed a higher bone surface density, bone volume, and trabecular number than SR and control groups, but with less trabecular separation (p < 0.05). All the animals in the BP group demonstrated histological osteonecrosis. There was no evidence of osteonecrosis in the control and SR groups, which was characterized by the absence of empty osteocyte gaps and associated with the gradual healing of the extraction area. Also, an increased number of blood vessels and a reduced number of osteoclasts were observed in the SR group (p < 0.05). Therefore, SR treatment increased angiogenesis and osteoclastogenesis in the healing socket and was not associated with MRONJ development after tooth extraction in ovariectomized rats.

Effect of adrenaline and noradrenaline on biofilm formation and virulence factors of Streptococcus mutans UA159.

OBJECTIVES: To evaluate in vitro the effects of adrenaline and noradrenaline on the biofilm formation on orthodontic brackets, acid production and expression of virulence genes of Streptococcus mutans UA159 (S. mutans). DESIGN: S. mutans UA159 biofilm was formed on orthodontic brackets under exposure to adrenaline (100 µM), noradrenaline (50 µM) or PBS solution (control group) in triptone-yeast extract with 1 % sucrose. After 24 h, biofilm formation was quantified through Colony Forming Units / mL (CFU/mL) and RNA was extracted to perform gene expression analysis through real-time reverse transcriptase-PCR (RT-qPCR). Evaluation of acid production was carried out on planktonic cultures for 6 h. One-way ANOVA followed by Tukey's test was carried to determine statistical difference. The level of significance was set at 5 %. RESULTS: Catecholamines stimulated biofilm formation of S. mutans in orthodontic brackets (p < 0,05) but did not interfere with acid production (pH reduction) or the expression of the tested genes related to biofilm formation (gtfB, gtfC, gbpA, gbpB, gbpC, gbpD and brpA), aciduric (relA) and acidogenic properties (ldh). CONCLUSIONS: The present study was the first to demonstrate that catecholamines can stimulate S. mutans UA159 biofilm formation. These findings can contribute to clarify the role of stress on bacterial metabolism and contribute to the understanding of a possible role on caries development, mainly in orthodontic patients.

Influence of Adrenergic Neuromodulation during Induction of Periodontitis in Rats.

The action of the sympathetic nervous system in the control of bone remodeling and immunoinflammatory responses is the basis of the hypothesis that its modulation can influence the progress of periodontal disease. The aim of this study was to analyze the effects of the blockade and of the activation of ß-adrenergic receptors in periodontal disease in rats. Thirty-two rats were divided into four groups: 1) animals with induced periodontitis that received propranolol (a non-selective ß-adrenergic antagonist) 0.1 mg/kg (PRO); 2) animals with induced periodontitis that received isoproterenol (a non- selective ß-adrenergic agonist) 0.75 mg/kg (ISO); 3) animals with induced periodontitis and without drug treatment (L); and 4) animals without induced periodontitis and without drug treatment - control (C). After 14 days of treatment, the rats were euthanized. Right hemi-mandibles were removed and lingual alveolar bone loss measurements were made under a stereomicroscope. Left hemi-mandibles were decalcified and submitted to routine histological preparation for the evaluation of alveolar bone loss in furcation regions, amount of gingival collagen, and immunohistochemistry for receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) ratio. Animals treated with isoproterenol had significantly more lingual alveolar bone loss than others. The percentage of collagen in gingiva was greater in the propranolol group than in the isoproterenol group. No statistical differences were found among groups with periodontal disease in any other evaluations. The activation of ß-adrenergic receptors increased the lingual alveolar bone loss; however, in the model used, the use of ß-adrenergic antagonist drugs was not able to modulate the host response significantly. Activation and inhibition of ß-receptors have antagonistic actions in collagen degradation in animals with periodontal disease.

Bioassay guided purification of the antimicrobial fraction of a Brazilian propolis from Bahia state.

BACKGROUND: Brazilian propolis type 6 (Atlantic forest, Bahia) is distinct from the other types of propolis especially due to absence of flavonoids and presence of other non-polar, long chain compounds, but presenting good in vitro and in vivo antimicrobial activity. Several authors have suggested that fatty acids found in this propolis might be responsible for its antimicrobial activity; however, so far no evidence concerning this finding has been reported in the literature. The goals of this study were to evaluate the antibacterial activity of the main pure fatty acids in the ethanolic extract and fractions and elucidate the chemical nature of the bioactive compounds isolated from Brazilian propolis type 6. METHODS: Brazilian propolis type 6 ethanolic extract (EEP), hexane fraction (H-Fr), major fatty acids, and isolated sub-fractions were analyzed using high performance liquid chromatography (HPLC), high resolution gas chromatography with flame ionization detection (HRGC-FID), and gas chromatography-mass spectrometry (GC-MS). Three sub-fractions of H-Fr were obtained through preparative HPLC. Antimicrobial activity of EEP, H-Fr, sub-fractions, and fatty acids were tested against Staphyloccus aureus ATCC 25923 and Streptococcus mutans Ingbritt 1600 using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). RESULTS: EEP and H-Fr inhibited the growth of the microorganisms tested; nevertheless, no antimicrobial activity was found for the major fatty acids. The three sub-fractions (1, 2, and 3) were isolated from H-Fr by preparative HPLC and only sub-fraction 1 showed antimicrobial activity. CONCLUSION: a) The major fatty acids tested were not responsible for the antimicrobial activity of propolis type 6; b) Sub-fraction 1, belonging to the benzophenone class, was responsible for the antimicrobial activity observed in the present study. The identification of the bioactive compound will improve the development of more efficient uses of this natural product.

Identification of a bioactive compound isolated from Brazilian propolis type 6.

A prenylated benzophenone, hyperibone A, was isolated from the hexane fraction of Brazilian propolis type 6. Its structure was determined by spectral analysis including 2D NMR. This compound exhibited cytotoxic activity against HeLa tumor cells (IC(50)=0.1756microM), strong antimicrobial activity (MIC range-0.73-6.6microg/mL; MBC range-2.92-106microg/mL) against Streptococcus mutans, Streptococcus sobrinus, Streptococcus oralis, Staphylococcus aureus, and Actinomyces naeslundii, and the results of its cytotoxic and antimicrobial activities were considered good.