Preventive oral surgery before bisphosphonate administration to reduce osteonecrosis of the jaws.

OBJECTIVES: The intravenous injection of bisphosphonates, currently used for osteoporosis, myeloma, or bone metastases, can cause ONJ especially in consequence of trauma. To avoid trauma during bisphosphonate treatment, preventive oral surgery is recommended. The research aimed to evidence whether inflammatory and osteoclastogenic factors are not induced in oral mucosa after bisphosphonate treatment in patients receiving oral preventive surgery procedure and whether proliferation factors are not inhibited. PATIENTS AND METHODS: Specimens of oral mucosa were removed from healthy subjects and from patients undergoing preventive oral surgery before bisphosphonate treatment. The expression of cytokines and factors involved in osteoclast activity, cell proliferation, and angiogenesis were examined. RESULTS: Cytokines and RANK-L levels decreased significantly in mucosa from patients undergoing preventive oral surgery procedure before bisphosphonate treatment in comparison with their levels at the beginning of procedure and also in comparison with the level in patients treated only with bisphosphonates and not developing ONJ; conversely, osteoprotegerin and hydroxymethylglutaryl coenzyme A reductase significantly increased or not changed. CONCLUSIONS: The results suggest that preventive oral surgery could be able to prevent ONJ due to bisphosphonate treatment: The mucosa is not stimulated by bisphosphonates to cause ONJ, as bisphosphonates are probably not released from the bone.

Effect of a combined nutraceutical containing Orthosiphon stamineus effect on blood pressure and metabolic syndrome components in hypertensive dyslipidaemic patients: a randomized clinical trial.

Effect of a nutraceutical containing Ortosiphon stamineus leaf extract on blood pressure and metabolic syndrome components in hypertensive dyslipidaemic patients treated with calcium-channel blockers, or angiotensin converting enzyme inhibitors: a randomized clinical trial.

A novel mechanism of action for statins against diabetes-induced oxidative stress.

AIMS/HYPOTHESIS: Atorvastatin exerts beneficial vascular effects in diabetes, but the underlying mechanisms are yet to be elucidated. The aim of the present study was to determine whether Rac-1 is involved in the effect of atorvastatin on oxidative stress and vascular dysfunction. MATERIALS AND METHODS: Using human aortic endothelial cells (HAECs) we evaluated the effect of high glucose levels on peroxide production by dihydrodichlorofluorescein and on Rac-1 activity using immunocytochemistry to detect Rac-1 translocation to the membrane. We evaluated vascular function, peroxide production by dihydroethidium and NADPH oxidase activity in vessels from atorvastatin-treated mice. Rac-1 activity was also assessed, both by immunoprecipitation of the Rac-p21-activated kinase complex and by analysis of Rac-1 translocation to the membrane. These experiments were also conducted in vessels infected with an adenoviral vector carrying a constitutively active mutant of Rac-1. RESULTS: In HAECs exposed to high glucose levels, atorvastatin prevented oxidative stress, and this protection was associated with impaired Rac-1 activation. This effect was also observed in a murine model of diabetes mellitus. More importantly, the addition of geranylgeranyl pyrophosphate (GGPP) blocked the effects of atorvastatin in both glucose-exposed HAECs and diabetic vessels. Atorvastatin failed to afford protection against vascular abnormalities in the presence of a constitutively active mutant of Rac-1. CONCLUSIONS/INTERPRETATION: The results of this study demonstrate that the vascular antioxidant effect of atorvastatin in diabetes is mediated through inhibition of Rac-1 via a reduction in GGPP. Thus, selective Rac-1 inhibition should be considered in the design of novel pharmacological strategies to reduce the impact of diabetes mellitus on vascular function.