Publications by authors named "Martin R Ling"

12 Publications

  • Page 1 of 1

Efficacy of an anhydrous stannous fluoride toothpaste for relief of dentine hypersensitivity: A randomized clinical study.

J Clin Periodontol 2020 08 8;47(8):962-969. Epub 2020 Jun 8.

GSK Consumer Healthcare, Weybridge, UK.

Aim: To compare efficacy of an anhydrous 0.454% w/w stannous fluoride/sodium fluoride toothpaste (Test) versus a sodium monofluorophosphate toothpaste (Negative control) and a stannous chloride/sodium fluoride toothpaste (Positive control) for dentine hypersensitivity relief after 8 weeks' twice-daily use.

Materials And Methods: In this randomized, examiner-blind, stratified, parallel study, primary and secondary efficacy variables were mean changes in Schiff score (evaporative [air] sensitivity) and tactile threshold (Yeaple probe), respectively, from baseline to Week 8 between Test (n = 62) and Negative control (n = 62). Test and Positive control (n = 61) comparisons were exploratory objectives.

Results: All groups significantly improved from baseline on both dentine hypersensitivity measures (p < .0001). Difference between adjusted mean changes from baseline in Schiff sensitivity scores at Week 8 for Test versus Negative control groups was 0.19 (95% CI 0.002, 0.374), in favour of the Negative control (p = .0476; 12.57% difference). Difference in tactile threshold was -7.20 g (95% CI -16.376, 1.975), and this was not statistically significant (p = .3715; -21.83% difference). Test group showed no significant difference versus Positive control for either measure. Toothpastes were generally well tolerated.

Conclusion: While twice-daily use of Test toothpaste significantly reduced dentine hypersensitivity from baseline, there was no significant advantage over negative or positive controls.

Study Registration: Clinicaltrials.gov; NCT03310268.
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http://dx.doi.org/10.1111/jcpe.13305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496273PMC
August 2020

A proof-of-principle bite force study using two experimental test denture adhesives and a currently marketed denture adhesive.

Clin Exp Dent Res 2020 04 6;6(2):266-273. Epub 2020 Feb 6.

TKL Research, Bloomfield, NJ, USA.

Objectives: This proof-of-principle, single-center, randomized, examiner-blind, crossover study compared two experimental polyvinyl acetate (PVA)-based denture adhesives (Test Adhesives 1 and 2) with a marketed reference polymethyl vinyl ether/maleic anhydride (PMV/MA)-based adhesive and no adhesive using incisal bite force area over baseline over 12 hr (AOB ) in participants with an at least moderately well-fitting complete maxillary denture. Previous in vitro studies suggested the experimental denture adhesives provided superior performance.

Materials And Methods: Participants were randomized to a treatment sequence such that each received each treatment once. Prior to treatment application (baseline) and at 0.5, 1, 3, 6, 9, and 12 hr following the application, participants bit on a force transducer until their maxillary denture dislodged. Between-treatment differences in AOB were analyzed using analysis of covariance. For study validity, the reference adhesive was compared with no adhesive. Participants were asked to rate sensory experiences and ease of denture removal.

Results: Twenty-three participants were included in the modified intent-to-treat population. Although Test Adhesives 1 and 2 had a higher mean AOB than no adhesive, differences were not statistically significant. No statistically significant difference was also found between the reference adhesive and no adhesive; hence, study validity was not attained. Participants did not report any clear differences between the test or reference adhesives in terms of taste or feel; however, dentures were easier to remove with the test adhesives versus reference. No treatment-related adverse events were reported.

Conclusion: Neither the experimental PVA-based denture adhesives nor the PMV/MA-based reference product demonstrated a statistically significant difference in incisal bite force AOB compared with no adhesive. The reasons for these unexpected results is unclear; they suggest that findings of in vitro tests for denture adhesive performance are not always translated to in vivo performance (Clinicaltrials.gov: NCT02937870).
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http://dx.doi.org/10.1002/cre2.256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133722PMC
April 2020

An exploratory study to investigate stain build-up with long term use of a stannous fluoride dentifrice.

Am J Dent 2018 Apr;31(2):71-75

Salus Research, Fort Wayne, Indiana, USA.

Purpose: To monitor extrinsic stain formation over 24 weeks with twice-daily use of an anhydrous 0.454% SnF2 dentifrice containing 5% sodium tripolyphosphate (STP) ('Test'), compared to a standard fluoride dentifrice (0.76% fluoride as sodium monofluorophosphate [SMFP\) ('Comparator') following a professional prophylaxis.

Methods: Primary efficacy variables were between-treatment differences in extrinsic dental stain of anterior teeth after 4, 8, 12, and 24 weeks' use using mean area and intensity scores of the MacPherson modification of the Lobene stain index (MLSI), and to monitor oral tolerability.

Results: Overall, 214 subjects were randomized to treatment. The Test dentifrice group demonstrated statistically significantly less stain compared with the Comparator at each timepoint for all outcome variables (MLSI - Area × Intensity, Area only, and Intensity only) with the exception of MLSI (Area × Intensity) at Week 12. Products were generally well tolerated with 26 treatment-related adverse events (TRAEs) reported (10 with Test, 16 with Comparator). Five subjects withdrew from the 24-week study due to TRAEs, three in the Test group, two in the Comparator group. Statistically significantly less anterior tooth staining was observed with up to 24 weeks twice-daily brushing with a 0.454% SnF2/5% STP anhydrous dentifrice compared to a marketed fluoride dentifrice with 0.76% SMFP.

Clinical Significance: Long term use of a SnF2/STP dentifrice demonstrated minimal stain build-up after 24 weeks, twice-daily use; products were generally well-tolerated.
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April 2018

Characterization, Quantification, and Visualization of Neutrophil Extracellular Traps.

Methods Mol Biol 2017 ;1537:481-497

Institute of Clinical Sciences, College of Medical and Dental Sciences, The School of Dentistry, University of Birmingham, 5 Mill Pool Way, Edgbaston, Birmingham, B5 7EG, UK.

Following the discovery of neutrophil extracellular traps (NETs) in 2004 by Brinkmann and colleagues, there has been extensive research into the role of NETs in a number of inflammatory diseases, including periodontitis. This chapter describes the current methods for the isolation of peripheral blood neutrophils for subsequent NET experiments, including approaches to quantify and visualize NET production, the ability of NETs to entrap and kill bacteria, and the removal of NETs by nuclease-containing plasma.
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http://dx.doi.org/10.1007/978-1-4939-6685-1_29DOI Listing
January 2018

Oral Epithelial Cell Culture Model for Studying the Pathogenesis of Chronic Inflammatory Disease.

Methods Mol Biol 2017 ;1537:381-401

Institute of Clinical Sciences, College of Medical and Dental Sciences, The School of Dentistry, University of Birmingham, 5 Mill Pool Way, Edgbaston, Birmingham, B5 7EG, UK.

The interactions between bacteria, epithelium, and neutrophilic polymorphonuclear leukocytes (neutrophils) are the key to the initiation and progression of many chronic inflammatory-immune diseases. In addition, all can be influenced by external factors, such as micronutrients, thereby providing potentially novel approaches to therapy. This chapter will therefore provide detailed methods for core techniques involved in studying cellular and molecular epithelial responses to a bacterial challenge in relation to chronic inflammatory disease pathogenesis and therapy.
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http://dx.doi.org/10.1007/978-1-4939-6685-1_22DOI Listing
January 2018

Antioxidant Micronutrients and Oxidative Stress Biomarkers.

Methods Mol Biol 2017 ;1537:61-77

School of Dentistry, Institute of Clinical Sciences, Collegeof Medical and Dental Sciences, University of Birmingham, 5 Mill Pool Way, Edgbaston, Birmingham, B5 7EG, UK.

Chronic inflammatory diseases are the major causes of mortality in humans and recent research has improved our understanding of the major impact of life-style factors upon inflammatory diseases and conditions. One of the most influential of these is nutrition, which may drive both pro-inflammatory as well as anti-inflammatory cascades at molecular and cellular levels. There are a variety of model systems that may be employed to investigate the impact of micronutrients and macronutrients upon inflammatory pathways, many of which operate through oxidative stress, either at the level of controlling the redox state of the cell and downstream redox-regulated gene transcription factors, and other acting as free radical generating or scavenging agents. This chapter focuses upon biological sample preparation prior to assay and details methods for analyzing certain antioxidant micronutrients and biomarkers of oxidative stress.
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http://dx.doi.org/10.1007/978-1-4939-6685-1_4DOI Listing
January 2018

Neutrophil superoxide release and plasma C-reactive protein levels pre- and post-periodontal therapy.

J Clin Periodontol 2016 08 7;43(8):652-8. Epub 2016 Jun 7.

Periodontal Research Group and MRC Centre for Immune Regulation, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, UK.

Aim: To determine peripheral blood neutrophil superoxide release and C-reactive protein (CRP) concentration in chronic periodontitis patients, before and after non-surgical periodontal treatment.

Materials And Methods: Neutrophils were isolated from patient and control volunteers (n = 20) and superoxide measured by lucigenin-enhanced chemiluminescence with and without stimulation with unopsonized Porphyromonas gingivalis, unopsonized Fusobacterium nucleatum and phorbol 12-myristate 13-acetate (PMA) before and 2-months following non-surgical therapy. Corresponding high-sensitivity plasma CRP concentrations were also determined.

Results: At pre-treatment baseline, patient neutrophils released more superoxide in the absence (p ≤ 0.032) and presence of periodontal bacteria (p ≤ 0.013) and after PMA stimulation (p = 0.041) compared to control cells. Post-therapy, patient neutrophil superoxide release was reduced to control cell levels. Median patient plasma CRP concentrations were non-significantly higher than control values and were reduced after therapy (1.80-1.36 mg/l). Patient pre-treatment baseline, unstimulated neutrophil superoxide release showed a significant, positive correlation with plasma CRP concentration (p = 0.01).

Conclusions: Chronic periodontitis is characterized by peripheral neutrophils exhibiting superoxide hyperactivity and hyper-reactivity to periodontal pathogens that is not a constitutive feature of periodontitis patients. The positive, pre-therapy relationship between unstimulated neutrophil superoxide release and plasma CRP is consistent with a protective role for CRP in reducing oxidative stress and systemic inflammation in vivo.
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http://dx.doi.org/10.1111/jcpe.12575DOI Listing
August 2016

Peripheral blood neutrophil cytokine hyper-reactivity in chronic periodontitis.

Innate Immun 2015 Oct 8;21(7):714-25. Epub 2015 Jun 8.

Periodontal Research Group and MRC Centre for Immune Regulation, College of Medical and Dental Sciences, The University of Birmingham, St Chad's Queensway, Birmingham B4 6NN, UK.

Pro-inflammatory cytokine release (IL-8, IL-6, TNF-α, IL-1β) by peripheral blood neutrophils, isolated from periodontitis patients (before/after therapy) and matched controls, was determined after 18 h culture in the presence/absence of Escherichia coli LPS, opsonised Staphylococcus aureus, heat-killed Fusobacterium nucleatum and Porphyromonas gingivalis. All cultures demonstrated differences in the amounts of each cytokine detected (P < 0.0001), with a clear release pattern (IL-8 > IL-6 > TNF-α = IL-1β). Median cytokine release from unstimulated patient neutrophils was consistently, but non-significantly, higher than from control cells. Stimulated cytokine release from untreated patient neutrophils was also consistently higher than from control cells. This hyper-reactivity was significant for all tested cytokines when data for all stimuli were combined (P < 0.016). In terms of individual stimuli, significant hyper-reactivity was detected with LPS (IL-8), F. nucleatum (IL-8, TNF-α), opsonised S. aureus (IL-8, TNF-α, IL-1β) and P. gingivalis (IL-8, IL-1β). Cytokine production by patient neutrophils did not reduce following successful non-surgical periodontal therapy and, except for responses to F. nucleatum, the cytokine hyper-reactivity detected pre-therapy was retained. These data demonstrate that chronic periodontitis is characterised by neutrophils that constitutively exhibit cytokine hyper-reactivity, the effects of which could modulate local and systemic inflammatory-immune responses and influence the risk and severity of periodontitis-associated systemic inflammatory diseases.
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http://dx.doi.org/10.1177/1753425915589387DOI Listing
October 2015

Impaired neutrophil directional chemotactic accuracy in chronic periodontitis patients.

J Clin Periodontol 2015 Jan 8;42(1):1-11. Epub 2015 Jan 8.

Periodontal Research Group and MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK.

Aim: To investigate the chemotactic accuracy of peripheral blood neutrophils from patients with chronic periodontitis compared with matched healthy controls, before and after non-surgical periodontal therapy.

Material & Methods: Neutrophils were isolated from patients and controls (n = 18) by density centrifugation. Using the Insall chamber and video microscopy, neutrophils were analysed for directional chemotaxis towards N-formyl-methionyl-leucyl-phenylalanine [fMLP (10 nM), or CXCL8 (200 ng/ml)]. Circular statistics were utilized for the analysis of cell movement.

Results: Prior to treatment, neutrophils from patients with chronic periodontitis had significantly reduced speed, velocity and chemotactic accuracy compared to healthy controls for both chemoattractants. Following periodontal treatment, patient neutrophils continued to display reduced speed in response to both chemoattractants. However, velocity and accuracy were normalized for the weak chemoattractant CXCL8 while they remained significantly reduced for fMLP.

Conclusions: Chronic periodontitis is associated with reduced neutrophil chemotaxis, and this is only partially restored by successful treatment. Dysfunctional neutrophil chemotaxis may predispose patients with periodontitis to their disease by increasing tissue transit times, thus exacerbating neutrophil-mediated collateral host tissue damage.
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http://dx.doi.org/10.1111/jcpe.12326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340045PMC
January 2015

Effects of C-reactive protein on the neutrophil respiratory burst in vitro.

Innate Immun 2014 May 9;20(4):339-49. Epub 2013 Jul 9.

Periodontal Research Group and MRC Centre for Immune Regulation, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, UK.

This study determined the influence of physiologically relevant concentrations of C-reactive protein (CRP) on reactive oxygen species (ROS) production by neutrophils. Neutrophils from healthy individuals were incubated with soluble pentameric CRP prior to TLR stimulation with Fusobacterium nucleatum, or FcγR stimulation with IgG-opsonised Staphylococcus aureus or heat-aggregated IgG. ROS generation by unstimulated cells and those after stimulation were determined using luminol, isoluminol and lucigenin chemiluminescence, detecting predominantly intracellular hypochlorous acid (HOCl), extracellular hydrogen peroxide (detected as HOCl) and extracellular superoxide respectively. Baseline (unstimulated) neutrophil ROS generation and release was reduced compared with vehicle control by 10 µg/ml CRP. There was no consistent effect of CRP on FcγR-stimulated HOCl production, but the extracellular superoxide response was reduced by 10 µg/ml CRP. By contrast, CRP reduced intracellular (10 µg/ml) and extracellular (3 and 10 µg/ml) HOCl generation, but increased superoxide release (1-10 µg/ml) in response to TLR stimulation. Physiologically relevant concentrations of CRP inhibited baseline ROS generation and reduced FcγR-stimulated extracellular superoxide and TLR-stimulated HOCl release, suggesting that CRP may offer some degree of host protection from neutrophil-associated, low-level oxidative stress. However, CRP enhanced TLR-mediated superoxide release from neutrophils, potentially increasing oxidative stress but aiding host protection from infection.
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http://dx.doi.org/10.1177/1753425913493199DOI Listing
May 2014

Neutrophil superoxide production in the presence of cigarette smoke extract, nicotine and cotinine.

J Clin Periodontol 2012 Jul 21;39(7):626-34. Epub 2012 May 21.

Periodontal Research Group and MRC Centre for Immune Regulation, College of Medical and Dental Sciences, The University of Birmingham, Birmingham, UK.

Aim: To determine the effect of cigarette smoke extract, nicotine and cotinine on lucigenin-detectable neutrophil superoxide production.

Materials & Methods: Neutrophils from periodontally healthy individuals were treated with aqueous smoke extract, nicotine and cotinine, prior to stimulation or at the same time as stimulation with Fusobacterium nucleatum, IgG-opsonized Staphylococcus aureus and Escherichia coli Lipopolysaccharide (LPS). Superoxide generation was determined by lucigenin chemiluminescence.

Results: Smoke extract induced superoxide release from neutrophils (p <0.0001) in a dose-dependent manner. By contrast, superoxide generation by neutrophils in response to pathologically relevant stimuli was inhibited by pre-treatment with smoke extract (p <0.01). This inhibition did not require the continued presence of the extract. A similar reduction in stimulated superoxide production by smoke extract was detected when neutrophils were simultaneously exposed to the extract and stimuli. Nicotine and cotinine (0-10 μg/ml) had no effect on superoxide release from unstimulated or stimulated neutrophils.

Conclusions: Stable water-soluble components of cigarette smoke directly induce superoxide generation by otherwise unstimulated neutrophils, but reduce superoxide responses of cells to pathologically relevant stimuli. These data suggest potential neutrophil-mediated mechanisms by which smoking may initiate and maintain oxidative stress at periodontally healthy sites and participate in disease progression, by reducing innate immune responses.
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http://dx.doi.org/10.1111/j.1600-051X.2012.01894.xDOI Listing
July 2012

Proteomic analysis of a noninvasive human model of acute inflammation and its resolution: the twenty-one day gingivitis model.

J Proteome Res 2010 Sep;9(9):4732-44

Periodontal Research Group, School of Dentistry, College of Medical and Dental Sciences, University of Birmingham, St. Chads Queensway, Birmingham, B4 6NN, United Kingdom.

The 21-day experimental gingivitis model, an established noninvasive model of inflammation in response to increasing bacterial accumulation in humans, is designed to enable the study of both the induction and resolution of inflammation. Here, we have analyzed gingival crevicular fluid, an oral fluid comprising a serum transudate and tissue exudates, by LC-MS/MS using Fourier transform ion cyclotron resonance mass spectrometry and iTRAQ isobaric mass tags, to establish meta-proteomic profiles of inflammation-induced changes in proteins in healthy young volunteers. Across the course of experimentally induced gingivitis, we identified 16 bacterial and 186 human proteins. Although abundances of the bacterial proteins identified did not vary temporally, Fusobacterium outer membrane proteins were detected. Fusobacterium species have previously been associated with periodontal health or disease. The human proteins identified spanned a wide range of compartments (both extracellular and intracellular) and functions, including serum proteins, proteins displaying antibacterial properties, and proteins with functions associated with cellular transcription, DNA binding, the cytoskeleton, cell adhesion, and cilia. PolySNAP3 clustering software was used in a multilayered analytical approach. Clusters of proteins that associated with changes to the clinical parameters included neuronal and synapse associated proteins.
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http://dx.doi.org/10.1021/pr100446fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950674PMC
September 2010