Sulforaphane restores cellular glutathione levels and reduces chronic periodontitis neutrophil hyperactivity in vitro

The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN) to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O2 . - by the nicotinamide adenine dinucleotide (NADPH) oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients' neutrophils exhibit a low reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC), and modifier (GCLM) subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O2 . - production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis. © 2013 Dias et al

Enhanced skills in periodontology:Evaluation of a pilot scheme for general dental practitioners and dental care professionals in London

Background The need for periodontal management is great and increasing; thus, the oral and dental workforce should be suitably equipped to deliver contemporary care. Health Education London developed a training scheme to extend the skills of dentists and dental care professionals (DCPs).Aim To examine the feasibility of assessing a skill-mix initiative established to enhance skills in clinical periodontology involving the views of patients, clinicians and key stakeholders, together with clinical and patient outcomes in London.Methods This mixed methods feasibility and pilot study involved four parallel elements: A postal questionnaire survey of patients; analysis of clinical logbooks; self-completion questionnaire survey of clinicians; and semi-structured interviews of key stakeholders, including clinicians.Results Twelve of the 19 clinicians participated in the evaluation, returning completed questionnaires (63%) and providing access to log diaries and patients. Periodontal data from 42 log-diary cases (1,103 teeth) revealed significant improvement in clinical outcomes (P = 0.001 for all). Eighty-four percent (N = 99) of the 142 patients returning a questionnaire reported improved dental health; however, responses from hospital patients greatly exceeded those from dental practice. Interviews (N = 22) provided evidence that the programme contributed to professional healthcare across four key domains: 'service', 'quality care', 'professional' and 'educational'. Clinicians, while supportive of the concept, raised concerns regarding the mismatch of their expectations and its educational and service outcomes.Discussion The findings suggest that it is feasible to deliver and evaluate inter-professional extended skills training for dentists and dental care professionals, and this may be evaluated using mixed methods to examine outcomes including clinical log diaries, patient questionnaires and stakeholder interviews. This inter-professional course represents a positive development for patient care using the expertise of different members of the dental team; however, its formal integration to the health and educational sectors require further consideration