Periodontitis: A multifaceted disease of tooth-supporting tissues

Periodontitis is an infection-driven inflammatory disease in which the composition of biofilms plays a significant role. Dental plaque accumulation at the gingival margin initiates an inflammatory response that, in turn, causes microbial alterations and may lead to drastic consequences in the periodontium of susceptible individuals. Chronic inflammation affects the gingiva and can proceed to periodontitis, which characteristically results in irreversible loss of attachment and alveolar bone. Periodontitis appears typically in adult-aged populations, but young individuals can also experience it and its harmful outcome. Advanced disease is the major cause of tooth loss in adults. In addition, periodontitis is associated with many chronic diseases and conditions affecting general health.</p

A Pilot Study - Comparison between a Novel Combination of Bioactive Glass with Clodronate and Bioactive Glass Alone as a Treatment for Chronic Periodontitis

Bioactive glass (BAG) and clodronate are both used for bone regeneration. In this pilot clinical study, we compared the effect of BAG and a novel BAG+clodronate combination as a topical maintenance phase treatment for chronic periodontitis. Two dental residual pockets were treated in each subject (n=10): one with BAG alone and the other with combination product, by applying the products subgingivally for 10 min once a week for four weeks. We describe the effects of these investigational products to the clinical parameters of periodontitis and two bone metabolism markers (osteoprotegerin and osteocalcin). Additionally, subjective satisfaction for the treatment was evaluated. The results must be considered as directional, understanding that further investigation is needed to confirm the findings. Based on clinical parameters measured both treatments could benefit as maintenance therapy for chronic periodontitis. The positive effect of the combination product on tooth sensitivity may bring additional benefits in comparison to the use of BAG alone. Both treatments were well tolerated and safe.  </p

Activation of gingival fibroblasts by bacterial cyclic dinucleotides and lipopolysaccharide

Human gingival fibroblasts (HGFs) recognize microbe-associated molecular patterns (MAMPs) and respond with inflammatory proteins. Simultaneous impacts of bacterial cyclic di-guanosine monophosphate (c-di-GMP), cyclic di-adenosine monophosphate (c-di-AMP), and lipopolysaccharide (LPS) on gingival keratinocytes have been previously demonstrated, but the effects of these MAMPs on other periodontal cell types, such as gingival fibroblasts, remain to be clarified. The present aim was to examine the independent and combined effects of these cyclic dinucleotides and LPS on interleukin (IL) and matrix metalloproteinase (MMP) response of HGFs. The cells were incubated with c-di-GMP and c-di-AMP, either in the presence or absence of Porphyromonas gingivalis LPS, for 2 h and 24 h. The levels of IL-8, -10, and -34, and MMP-1, -2, and -3 secreted were measured by the Luminex technique. LPS alone or together with cyclic dinucleotides elevated IL-8 levels. IL-10 levels were significantly increased in the presence of c-di-GMP and LPS after 2 h but disappeared after 24 h of incubation. Concurrent treatment of c-di-AMP and LPS elevated MMP-1 levels, whereas c-di-GMP with LPS suppressed MMP-2 levels but increased MMP-3 levels. To conclude, we produce evidence that cyclic dinucleotides interact with LPS-mediated early response of gingival fibroblasts, while late cellular response is mainly regulated by LPS.</p

Salivary cytokine levels in early gingival inflammation

Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, IL-1β, and IL-1 receptor antagonist (IL-1Ra) in gingival inflammation. Twenty-eight systemically and orally healthy nonsmokers abstained from oral hygiene protocols for 10 days. After that, self-performed cleaning was resumed for 14 days. Plaque and gingival indexes were measured, and saliva samples were collected at days 1, 4, 7, 10, and 24. Salivary cytokines were detected with Luminex®-xMAP™. Salivary IL-1β, IL-1Ra, and VEGF levels decreased after 10 days’ development of experimental gingivitis and reached baseline levels at the end of the 2-week resolution period. Salivary IL-8 levels decreased and remained low during development and resolution of experimental gingivitis. Initial inflammation in gingival tissues is associated with a decrease in inflammatory cytokines in saliva. Further studies are needed to evaluate if inflammatory cytokines bind to their functional receptors within the gingival tissue during early gingivitis, which may limits their spillover to the gingival crevice and ultimately saliva.</p

Legal geographies of irregular migration : An outlook on immigration detention

In this article, I discuss legal geographies of irregular migration, drawing on a case study on immigration detention in Finland. Based on analysis of detention records, four different types of legal geographies are identified, relating to south–north movement of third‐country nationals inside Europe, criminalised Eastern European EU citizens, irregularity during the asylum process (in particular, related to the Dublin Regulation) and irregularly residing foreign nationals, including deportable long‐term residents. The analysis focuses on the relations between space, law and persons during detainees' irregular migration trajectories, paying attention to their varying entry routes, residence times, legal grounds for removal and detention and removal countries. I argue for the need for empirically contextualised analysis that addresses the complex relations between law and geography beyond a particular national context, in order to better understand the dynamics of irregular migration in all its variety.In this article, I discuss legal geographies of irregular migration, drawing on a case study on immigration detention in Finland. Based on analysis of detention records, four different types of legal geographies are identified, relating to south–north movement of third‐country nationals inside Europe, criminalised Eastern European EU citizens, irregularity during the asylum process (in particular, related to the Dublin Regulation) and irregularly residing foreign nationals, including deportable long‐term residents. The analysis focuses on the relations between space, law and persons during detainees' irregular migration trajectories, paying attention to their varying entry routes, residence times, legal grounds for removal and detention and removal countries. I argue for the need for empirically contextualised analysis that addresses the complex relations between law and geography beyond a particular national context, in order to better understand the dynamics of irregular migration in all its variety.Peer reviewe

Changes in the serum metabolite profile correlate with decreased brain gray matter volume in moderate-to-heavy drinking young adults

Our aim was to analyze metabolite profile changes in serum associated with moderate-to-heavy consumption of alcohol in young adults and to evaluate whether these changes are connected to reduced brain gray matter volumes. These study population consisted of young adults with a 10-year history of moderate-to-heavy alcohol consumption (n = 35) and light-drinking controls (n = 27). We used the targeted liquid chromatography mass spectrometry method to measure concentrations of metabolites in serum, and 3.0 T magnetic resonance imaging to assess brain gray matter volumes. Alterations in amino acid and energy metabolism were observed in the moderate-to-heavy drinking young adults when compared to the controls. After correction for multiple testing, the group of moderate-to-heavy drinking young adults had increased serum concentrations of 1-methylhistamine (p = 0.001, d = 0.82) when compared to the controls. Furthermore, concentrations of 1-methylhistamine (r = 0.48, p = 0.004) and creatine (r = 0.52, p = 0.001) were negatively correlated with the brain gray matter volumes in the females. Overall, our results show association between moderate-to-heavy use of alcohol and altered metabolite profile in young adults as well as suggesting that some of these changes could be associated with the reduced brain gray matter volume. (C) 2018 Elsevier Inc. All rights reserved.Peer reviewe

NFE2L2/NRF2, OGG1, and cytokine responses of human gingival keratinocytes against oxidative insults of various origin

ObjectiveBacterial or tobacco-related insults induce oxidative stress in gingival keratinocytes. The aim of this study was to investigate anti-oxidative and cytokine responses of human gingival keratinocytes (HMK cells) against Porphyromonas gingivalis lipopolysaccharide (Pg LPS), nicotine, and 4-nitroquinoline N-oxide (4-NQO).Materials and methodsHMK cells were incubated with Pg LPS (1 µl/ml), nicotine (1.54 mM), and 4-NQO (1 µM) for 24 h. Intracellular and extracellular levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1Ra), IL-8, monocyte chemoattractant protein (MCP)-1, and vascular endothelial growth factor (VEGF) were measured with the Luminex® xMAP™ technique, and nuclear factor, erythroid 2 like 2 (NFE2L2/NRF2) and 8-oxoguanine DNA glycosylase (OGG1) with Western blots. Data were statistically analyzed by two-way ANOVA with Bonferroni correction.ResultsAll tested oxidative stress inducers increased intracellular OGG1 levels, whereas only nicotine and 4-NQO induced NFE2L2/NRF2 levels. Nicotine, 4-NQO, and their combinational applications with Pg LPS induced the secretions of IL-1β and IL-1Ra, while that of IL-8 was inhibited by the presence of Pg LPS. MCP-1 secretion was suppressed by nicotine, alone and together with Pg LPS, while 4-NQO activated its secretion. Treatment of HMK cells with PgLPS, nicotine, 4-NQO, or their combinations did not affect VEGF levels.ConclusionPg LPS, nicotine, and 4-NQO induce oxidative stress and regulate anti-oxidative response and cytokine expressions in human gingival keratinocytes differently. These results may indicate that bacterial and tobacco-related insults regulate distinct pathways.</div

Elevated Baseline Salivary Protease Activity May Predict the Steadiness of Gingival Inflammation During Periodontal Healing: A 12-Week Follow-Up Study on Adults

Aim was to profile salivary total protease, Porphyromonas gingivalis gingipain, and neutrophil elastase activities in relation to the resolution of periodontal inflammation, salivary macrophage-derived chemokine (MDC), and macrophage inflammatory protein-1α concentrations. Nonsurgical periodontal treatment was performed in 24 periodontitis patients in a prospective interventional study design. Periodontal clinical parameters were recorded, and stimulated saliva samples were collected at baseline and 2, 6, and 12 weeks after treatment. Salivary total protease and gingipain activities were determined using fluorogenic substrates, elastase activity by chromogenic substrates, and cytokine concentrations by Luminex immunoassay. For statistical analyses, generalized linear mixed models for repeated measures were used. Salivary total protease activity elevated, while gingival inflammation and plaque accumulation decreased 2 and 6 weeks after periodontal therapy. Salivary MDC concentration was elevated 12 weeks after periodontal treatment. Patients with elevated protease activities at baseline in comparison to patients with low baseline total protease activities, had higher levels of gingival inflammation before and after periodontal treatment. In conclusion, elevations in salivary total protease activity seem to be part of periodontal healing at its early phases. Higher levels of salivary total protease activities before periodontal treatment may predict the severity and steadiness of unresolved gingival inflammation.</p

Role of microbial biofilms in the maintenance of oral health and in the development of dental caries and periodontal diseases. Consensus report of group 1 of the Joint EFP/ORCA workshop on the boundaries between caries and periodontal disease.

BACKGROUND AND AIMS: The scope of this working group was to review (1) ecological interactions at the dental biofilm in health and disease, (2) the role of microbial communities in the pathogenesis of periodontitis and caries, and (3) the innate host response in caries and periodontal diseases. RESULTS AND CONCLUSIONS: A health-associated biofilm includes genera such as Neisseria, Streptococcus, Actinomyces, Veillonella and Granulicatella. Microorganisms associated with both caries and periodontal diseases are metabolically highly specialized and organized as multispecies microbial biofilms. Progression of these diseases involves multiple microbial interactions driven by different stressors. In caries, the exposure of dental biofilms to dietary sugars and their fermentation to organic acids results in increasing proportions of acidogenic and aciduric species. In gingivitis, plaque accumulation at the gingival margin leads to inflammation and increasing proportions of proteolytic and often obligately anaerobic species. The natural mucosal barriers and saliva are the main innate defence mechanisms against soft tissue bacterial invasion. Similarly, enamel and dentin are important hard tissue barriers to the caries process. Given that the present state of knowledge suggests that the aetiologies of caries and periodontal diseases are mutually independent, the elements of innate immunity that appear to contribute to resistance to both are somewhat coincidental