MASked-unconTrolled hypERtension management based on office BP or on ambulatory blood pressure measurement (MASTER) Study: a randomised controlled trial protocol.

INTRODUCTION: Masked uncontrolled hypertension (MUCH) carries an increased risk of cardiovascular (CV) complications and can be identified through combined use of office (O) and ambulatory (A) blood pressure (BP) monitoring (M) in treated patients. However, it is still debated whether the information carried by ABPM should be considered for MUCH management. Aim of the MASked-unconTrolled hypERtension management based on OBP or on ambulatory blood pressure measurement (MASTER) Study is to assess the impact on outcome of MUCH management based on OBPM or ABPM. METHODS AND ANALYSIS: MASTER is a 4-year prospective, randomised, open-label, blinded-endpoint investigation. A total of 1240 treated hypertensive patients from about 40 secondary care clinical centres worldwide will be included -upon confirming presence of MUCH (repeated on treatment OBP <140/90 mm Hg, and at least one of the following: daytime ABP ≥135/85 mm Hg; night-time ABP ≥120/70 mm Hg; 24 hour ABP ≥130/80 mm Hg), and will be randomised to a management strategy based on OBPM (group 1) or on ABPM (group 2). Patients in group 1 will have OBP measured at 0, 3, 6, 12, 18, 24, 30, 36, 42 and 48 months and taken as a guide for treatment; ABPM will be performed at randomisation and at 12, 24, 36 and 48 months but will not be used to take treatment decisions. Patients randomised to group 2 will have ABPM performed at randomisation and all scheduled visits as a guide to antihypertensive treatment. The effects of MUCH management strategy based on ABPM or on OBPM on CV and renal intermediate outcomes (changing left ventricular mass and microalbuminuria, coprimary outcomes) at 1 year and on CV events at 4 years and on changes in BP-related variables will be assessed. ETHICS AND DISSEMINATION: MASTER study protocol has received approval by the ethical review board of Istituto Auxologico Italiano. The procedures set out in this protocol are in accordance with principles of Declaration of Helsinki and Good Clinical Practice guidelines. Results will be published in accordance with the CONSORT statement in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NCT02804074; Pre-results.

Atividade do óleo de melaleuca alternifólia sobre o crescimento e expressão gênica de Porphyromonas gingivalis / Evaluation of Melaleuca alternifolia activity on growth and gene expression of Porphyromonas gingivalis

As doenças periodontais são infecções causadas por microrganismos que colonizam a superfície dental na margem gengival ou abaixo dela. Entre eles estão os patógenos periodontais, como Porphyromonas gingivalis. Estudos demonstraram que o óleo essencial extraído de Melaleuca alternifolia tem atividade inibitória e bactericida contra microrganismos da cavidade oral. Este estudo teve como objetivo avaliar a interferência do óleo de Melaleuca (MO) sobre o crescimento e virulência de P. gingivalis, comparando com a atividade da clorexidina (CL). Culturas dessa bactéria foram expostas a diferentes concentrações de MO e CL a fim de avaliar a atividade antimicrobiana através dos testes de concentração inibitória mínima (CIM) e concentração bactericida mínima (CBM). Foi realizada uma análise da expressão diferencial de genes relacionados ao estresse oxidativo e à virulência de P. gingivalis através da técnica de RT-PCR, utilizando concentrações sub-CIM de MO e CL. As CIM e CBM encontradas para MO foram de 0,007% e para CL 1,5 μg/mL. O óleo de melaleuca reduziu significativamente a expressão dos genes de virulência kgp e ragA, e do estresse oxidativo dps, oxyR e sodB, enquanto que a CL reduziu a expressão do gene tpx (ANOVA, Bonferroni, p<0,05). O presente estudo concluiu que o óleo de Melaleuca possui ótima atividade inibitória e bactericida contra a bactéria P. gingivalis, além de reduzir de forma significante a expressão dos genes relacionados à virulência e ao estresse oxidativo, podendo ter um valor terapêutico futuro, principalmente no tratamento das periodontites.

Periodontal diseases are infections caused by microorganisms that colonize the tooth surface at the gingival margin or beneath it. Porphyromonas gingivalis is considered an important pathogen for chronic periodontitis. Studies have shown that the essential oil extracted from Melaleuca alternifolia has inhibitory and bactericidal activity against microorganisms from the oral cavity. Therefore, this study aimed to evaluate the effects of Melaleuca essential oil (MO) on growth and virulence of P. gingivalis, comparing to the activity of chlorhexidine (CL). Cultures of P. gingivalis were exposed to different concentrations of CL and MO to evaluate the antimicrobial activity by testing the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). An analysis of differential expression of genes related to oxidative stress and virulence of P. gingivalis was carried out through RT-PCR method, using sub-MIC concentrations of MO and CL. The MIC and MBC were found to be 0.007% for MO and 1.5 μg/mL for CL. MO significantly reduced the expression of virulence genes kgp and ragA, and oxidative stress genes dps, oxyR and sodB, while CL reduced the expression of the tpx gene (ANOVA, Bonferroni, p<0.05). This study concluded that Melaleuca essential oil presents an excellent inhibitory and bactericidal activity against the bacterium P. gingivalis, and significantly reduces the expression of genes related to virulence and oxidative stress, so may have a therapeutic value, particularly for periodontitis.