[Non-surgical peri-implantitis treatment with or without systemic antibiotics]. / Initiële behandeling van peri-implantitis met of zonder systemische antibiotica.

This study investigated the effect of initial nonsurgical treatment in patients with peri-implantitis with or without prescription of an antibiotic regimen consisting of amoxicillin and metronidazole. For this purpose, patients with peri-implantitis were randomized into a group of initial treatment with antibiotics and a group without antibiotics. They were re-evaluated 12 weeks after treatment. Analyses were performed at the patient level at 1 peri-implant pocket per patient. Both groups showed significant peri-implant pocket depth reductions after initial treatment. Treatment with antibiotics resulted in a higher mean reduction in peri-implant pocket depth than when no antibiotics were used, but this difference did not reach statistical significance. Only 2 implants, 1 in each group, showed a successful outcome of a peri-implant pocket depth ofunder ≤ 5 mm and with an absence of bleeding and pus after probing. Initial treatment with or without antibiotics is ultimately not sufficient to fully treat peri-implantitis; additional surgical procedures will often be required.

[Periodontitis - infection or inflammation?] / Parodontitis; infectie of ontsteking?

Periodontitis is a complex, multifactorial disease. Multiple factors such as (epi)genetic factors, environmental factors (microbial biofilm), lifestyle (smoking, stress) and general health (diabetes mellitus) contribute to the development of periodontitis. A healthy subgingival microbiome is in balance with its host, is very stable and diverse, and keeps the host healthy. Changes, such as declining oral hygiene, lead to changes in the microbial composition in the subgingival sulcus: anaerobic and protein-degrading microorganisms with pro-inflammatory properties increase in number and disturb the proportions, leading in turn to changes in the subgingival environment and an increase in pro-inflammatory microorganisms. If the first line of the immune system is unable to restore subgingival equilibrium, microorganisms and their products invade the periodontal soft tissues, resulting in activation of osteoclasts and, ultimately, in the destruction of the periodontium and the onset of periodontitis.

[The relation between halitosis and saliva]. / De relatie tussen halitose en speeksel.

Halitosis (bad breath) is caused by a number of volatiles originating, in most cases, in the oral cavity (intra-oral halitosis). These unpleasant smelling gases are volatile sulphur compounds such as hydrogen sulphide, methyl mercaptan and dimethyl sulphide secreted as a result of bacterial metabolism. Bacteria on the tongue dorsum, as well as oral pathologies such as gingivitis and periodontitis, are the main causes of intra-oral halitosis. Saliva has a number of functions that can affect intra-oral halitosis, such as mechanical cleaning, moistening of the oral cavity and antibacterial properties. Very low secretion of saliva (hyposalivation) can affect intra-oral halitosis.

[Saliva testing in the daily practice]. / Speekselonderzoek in de dagelijkse praktijk.

Saliva is a very multifaceted fluid with many different functions and it plays an essential role in oral health. With an aging population, dental professionals will increasingly be confronted with patients with reduced saliva secretion (hyposalivation) or dry mouth (xerostomia). Clinical symptoms as a result of dry mouth vary from mild to severe damage to the hard and soft tissues. Therefore it is important to establish whether a patient is suffering from hyposalivation and if so, whether the patient is able to activate the saliva secretion. Based on saliva testing, hyposalivation and dry mouth can be diagnosed in the general dental practice and be taken into account in prevention and treatment plans.

[Periodontitis and proteases. Hardly a closed case]. / Parodontitis en proteasen? Geen uitgemaakte zaak.

During periodontal inflammation, a multitude of substances both from the host and of microbiological origin are released into the gingival crevicular fluid (GCV) and saliva. These substances, such as proteins and peptides, can therefore be regarded as biomarkers of the inflammatory process. With the help of sensitive and advanced laboratory technologies, the role of these biomarkers has been identified. However, the high costs, complexity and difficulty of interpretation of the results often hinder the introduction of biomarkers for diagnostic purposes in the dental practice. Certain salivary enzymes, proteases, can function as biomarkers and have interesting properties for producing rapid chairside diagnoses, because the presence of a protease or proteolytic activity can be demonstrated in a simple and rapid biochemical way, for example by colour signalling. Since other processes in the oral cavity influence the results of the test, such tests are especially useful as one element in a broader oral diagnostic investigation.

Conserved Citrullinating Exoenzymes in Porphyromonas Species.

Porphyromonas gingivalis is one of the major oral pathogens implicated in the widespread inflammatory disorder periodontitis. Moreover, in recent years, P. gingivalis has been associated with the autoimmune disease rheumatoid arthritis. The peptidylarginine deiminase enzyme of P. gingivalis (PPAD) is a major virulence factor that catalyzes the citrullination of both bacterial and host proteins, potentially contributing to production of anticitrullinated protein antibodies. Considering that these antibodies are very specific for rheumatoid arthritis, PPAD appears to be a link between P. gingivalis, periodontitis, and the autoimmune disorder rheumatoid arthritis. PPAD was thus far considered unique among prokaryotes, with P. gingivalis being the only bacterium known to produce and secrete it. To challenge this hypothesis, we investigated the possible secretion of PPAD by 11 previously collected Porphyromonas isolates from a dog, 2 sheep, 3 cats, 4 monkeys, and a jaguar with periodontitis. Our analyses uncovered the presence of secreted PPAD homologues in 8 isolates that were identified as Porphyromonas gulae (from a dog, monkeys, and cats) and Porphyromonas loveana (from sheep). In all 3 PPAD-producing Porphyromonas species, the dominant form of the secreted PPAD was associated with outer membrane vesicles, while a minor fraction was soluble. Our results prove for the first time that the citrullinating PPAD exoenzyme is not unique to only 1 prokaryotic species. Instead, we show that PPAD is produced by at least 2 other oral pathogens.

[Preventive dentistry 7. Getting rid of halitosis]. / Preventieve tandheelkunde 7. Halitose de mond uit helpen.

Halitosis or bad breath is a problem that affects many people and its source is generally found in the oral cavity (intra-oral halitosis). Bacteria in the oral cavity produce volatile sulphur compounds such as hydrogen sulphide and methyl mercaptan that not only emit an unpleasant odour, but may also have toxic effects on the periodontal tissues. Good oral hygiene, a healthy periodontium and healthy teeth are the basis for the prevention of intra-oral halitosis and dentists and dental hygienists therefore play an essential role in its prevention.

Microbial profiles at baseline and not the use of antibiotics determine the clinical outcome of the treatment of chronic periodontitis.

Antibiotics are often used in the treatment of chronic periodontitis, which is a major cause of tooth loss. However, evidence in favour of a microbial indication for the prescription of antibiotics is lacking, which may increase the risk of the possible indiscriminate use of antibiotics, and consequent, microbial resistance. Here, using an open-ended technique, we report the changes in the subgingival microbiome up to one year post-treatment of patients treated with basic periodontal therapy with or without antibiotics. Antibiotics resulted in a greater influence on the microbiome 3 months after therapy, but this difference disappeared at 6 months. Greater microbial diversity, specific taxa and certain microbial co-occurrences at baseline and not the use of antibiotics predicted better clinical treatment outcomes. Our results demonstrate the predictive value of specific subgingival bacterial profiles for the decision to prescribe antibiotics in the treatment of periodontitis, but they also indicate the need for alternative therapies based on ecological approaches.

Reconstruction of Peri-implant Osseous Defects: A Multicenter Randomized Trial.

There is a paucity of data for the effectiveness of reconstructive procedures in the treatment of peri-implantitis. The objective of this study was to compare reconstruction of peri-implant osseous defects with open flap debridement (OFD) plus porous titanium granules (PTGs) compared with OFD alone. Sixty-three patients (36 female, 27 male; mean age 58.4 y [SD 12.3]), contributing one circumferential peri-implant intraosseous defect, were included in a multinational, multicenter randomized trial using a parallel-group design. After OFD and surface decontamination using titanium brushes and hydrogen peroxide, 33 defects received PTGs. The implants were not submerged. All patients received adjunctive perioperative systemic antibiotics. The primary outcome variable (defect fill) was assessed on digitalized radiographs. Clinical measurements of probing depth (PPD), bleeding on probing (BoP), suppuration, and plaque were taken by blinded examiners. After 12 mo, the test group (OFD plus PTG) showed a mean radiographic defect fill (mesial/distal) of 3.6/3.6 mm compared with 1.1/1.0 in the control group (OFD). Differences were statistically significant in favor of the test group (P < 0.0001). The OFD plus PTG group showed a mean reduction in PPD of 2.8 mm compared with 2.6 mm in the OFD group. BoP was reduced from 89.4% to 33.3% and from 85.8% to 40.4% for the test and control groups, respectively. There was no significant difference in complete resolution of peri-implantitis (PPD ≤4 mm and no BoP at six implant sites and no further bone loss), because this finding was accomplished at 30% of implants in the test group and 23% of implants in the control group. Reconstructive surgery using PTGs resulted in significantly enhanced radiographic defect fill compared with OFD. However, limitations in the lack of ability to discern biomaterial from osseous tissue could not be verified to determine new bone formation. Similar improvements according to clinical measures were obtained after both surgical treatment modalities (ClinicalTrials.gov NCT02406001).

A review and meta-analysis of the heritability of specific phobia subtypes and corresponding fears.

Evidence from twin studies suggests that genetic factors contribute to the risk of developing a fear or a phobia. The aim of the present study was to review the current literature regarding twin studies describing the genetic basis of specific phobias and their corresponding fears. The analysis included five twin studies on fears and ten twin studies on specific phobias. Heritability estimates of fear subtypes and specific phobia subtypes both varied widely, even within the subtypes. A meta-analysis performed on the twin study results indicated that fears and specific phobias are moderately heritable. The highest mean heritability (±SEM) among fear subtypes was found for animal fear (45%±0.004), and among specific phobias for the blood-injury-injection phobia (33%±0.06). For most phenotypes, variance could be explained solely by additive genetic and unique environmental effects. Given the dearth of independent data on the heritability of specific phobias and fears, additional research is needed.

Cytokine and matrix metalloproteinase expression in fibroblasts from peri-implantitis lesions in response to viable Porphyromonas gingivalis.

BACKGROUND AND OBJECTIVE: To assess inflammatory reactions of fibroblasts in the pathophysiology of peri-implantitis, we compared the pro-inflammatory and matrix-degrading responses of gingival and granulation tissue fibroblasts from periodontally healthy controls, peri-implantitis, and periodontitis lesions to an in vitro challenge with Porphyromonas gingivalis. METHODS: Fibroblasts from periodontally healthy, peri-implantitis and periodontitis donors were challenged with viable P. gingivalis. The inflammatory reactions of fibroblasts were analyzed before and after 6 h P. gingivalis challenge, and 2.5 and 18 h after removal of the challenge. Gene expression and induction of pro-inflammatory mediators, and matrix metalloproteinases (MMPs) were assessed by real-time polymerase chain reaction. Protein expression was measured by enzyme-linked immunosorbent assay. RESULTS: Non-challenged fibroblasts from peri-implantitis and periodontitis lesions expressed higher levels of interleukin (IL)-1ß, IL-8, and monocyte chemotactic protein (MCP)-1 than fibroblasts from periodontally healthy individuals. The P. gingivalis challenge induced expression of IL-1ß, IL-8, IL-6, MCP-1, and MMP-1 in periodontitis and peri-implantitis fibroblasts, but not in fibroblasts from periodontally healthy individuals. MMP-8 expression was higher in non-challenged peri-implantitis fibroblasts than in fibroblasts from periodontally healthy individuals. However, the P. gingivalis challenge downregulated MMP-8 gene expression in peri-implantitis fibroblasts. After removal of the P. gingivalis challenge, peri-implantitis fibroblasts sustained higher induction of IL-1ß, MCP-1, and MMP-1 compared to periodontitis fibroblasts. CONCLUSIONS: Fibroblasts from peri-implantitis and periodontitis lesions gave a more pronounced inflammatory response to the P. gingivalis challenge than fibroblasts from healthy donors. They may therefore be involved in the development of inflammation in peri-implantitis and periodontitis. Moreover, the sustained upregulation of inflammatory mediators and MMP-1 in peri-implantitis fibroblasts may play a role in the pathogenesis of peri-implantitis.

Modeling susceptibility to periodontitis.

Chronic inflammatory diseases like periodontitis have a complex pathogenesis and a multifactorial etiology, involving complex interactions between multiple genetic loci and infectious agents. We aimed to investigate the influence of genetic polymorphisms and bacteria on chronic periodontitis risk. We determined the prevalence of 12 single-nucleotide polymorphisms (SNPs) in immune response candidate genes and 7 bacterial species of potential relevance to periodontitis etiology, in chronic periodontitis patients and non-periodontitis control individuals (N = 385). Using decision tree analysis, we identified the presence of bacterial species Tannerella forsythia, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and SNPs TNF -857 and IL-1A -889 as discriminators between periodontitis and non-periodontitis. The model reached an accuracy of 80%, sensitivity of 85%, specificity of 73%, and AUC of 73%. This pilot study shows that, on the basis of 3 periodontal pathogens and SNPs, patterns may be recognized to identify patients at risk for periodontitis. Modern bioinformatics tools are valuable in modeling the multifactorial and complex nature of periodontitis.

Comparing culture, real-time PCR and fluorescence resonance energy transfer technology for detection of Porphyromonas gingivalis in patients with or without peri-implant infections.

BACKGROUND AND OBJECTIVE: The aim of the study was to compare the detection of Porphyromonas gingivalis using a fluorescence resonance energy transfer (FRET) technology with commonly used diagnostic methods in salivary and subgingival plaque samples from subjects with dental implants. P. gingivalis was considered as a marker for a pathogenic microbiota. MATERIAL AND METHODS: Ninety-seven adult subjects were recruited, including periodontally healthy controls with no dental implants, implant controls with no peri-implant disease and patients with peri-implant disease. Saliva and subgingival/submucosal plaque samples were collected from all subjects and were analyzed using culture, real-time PCR and FRET technology employing P. gingivalis-specific substrates. RESULTS: It was found that the P. gingivalis-specific substrates were highly suitable for detecting the presence of P. gingivalis in saliva and in subgingival plaque samples, showing comparable specificity to culture and real-time PCR. CONCLUSION: We applied the FRET technology to detect P. gingivalis in implant patients with or without an implant condition and in controls without implants. The technique seems suitable for detection of P. gingivalis in both plaque and saliva samples. However, with all three techniques, P. gingivalis was not very specific for peri-implantitis cases. Future work includes fine-tuning the FRET technology and also includes the development of a chair-side application.

Periodontal ligament and gingival fibroblasts from periodontitis patients are more active in interaction with Porphyromonas gingivalis.

BACKGROUND AND OBJECTIVE: Inflammatory responses of host cells to oral pathogenic bacteria, such as Porphyromonas gingivalis, are crucial in the development of periodontitis. Host cells, such as periodontal ligament and gingival fibroblasts, from periodontitis patients may respond to P. gingivalis in a different manner compared with cells from healthy persons. The aim of this study was to investigate inflammatory responses to viable P. gingivalis by periodontal ligament and gingival fibroblasts from periodontitis patients and healthy control subjects. MATERIAL AND METHODS: Primary periodontal ligament and gingival fibroblasts from periodontitis patients (n=14) and healthy control subjects (n=8) were challenged in vitro with viable P. gingivalis. Gene expression of Toll-like receptors (TLRs) 1, 2, 4, 6, 7 and 9, CD14, nuclear factor-κB1 and its putative inhibitor NF-κB inhibitor-like protein1, and of interleukin-1ß, interleukin-6, interleukin-8, tumour necrosis factor-α, monocyte chemotactic protein-1 and regulated upon activation, normal T-cel expressed, and secreted, were assessed by real-time PCR. RESULTS: Periodontal ligament fibroblasts from periodontitis patients had a higher mRNA expression of TLR1, TLR4, TLR7 and CD14, and a lower expression of NFKBIL1, both before and after P. gingivalis challenge. In contrast, gingival fibroblasts from periodontitis patients had stronger induction of TLR1, TLR2 and TLR7 by P. gingivalis. Cytokine responses were not different between patients and control subjects. Interestingly, periodontal ligament, but not gingival, fibroblasts from P. gingivalis culture-positive persons responded more strongly to P. gingivalis than periodontal ligament fibroblasts from P. gingivalis-negative persons. CONCLUSION: Periodontal ligament and gingival fibroblasts respond to P. gingivalis in a different manner and may play different roles in periodontitis. Both subsets of fibroblasts from patients appear more active in interaction with P. gingivalis. Moreover, periodontal ligament fibroblasts from P. gingivalis-positive donors are more responsive to an in vitro P. gingivalis challenge.

[Halitosis. A common problem]. / Halitose. Een probleem van velen.

Halitosis is a frequently occurring problem, the cause of which is generally to be found in the mouth. The challenge for oral health care providers is to diagnose it correctly and treat it effectively. Differential diagnosis is of great importance in making a distinction between halitosis which originates in the mouth and which does not originate in the mouth. Oral halitosis can be treated effectively by good oral health care. Plaque accumulation on the tongue is the most common cause of oral halitosis. Tongue cleansing, possibly in combination with a specific mouth wash, is consequently recommended as an element of oral hygiene care. Other oral health problems, such as periodontal disease, caries and ill-fitting removable dentures should be treated adequately to eliminate these problems as potential causes of halitosis.

[Stress and periodontal health]. / Stress en parodontale gezondheid.

Periodontitis and periimplant infections are complex manifestations associated with several disease-modifying factors, such as causative pathogens and smoking. Although research into these factors has led to important progressions in the treatment of these infections in recent decades, the contribution of mental stress in the absence of pathogens or smoking is still unclear. Qualitative and quantitative assessment of mental stress might be an important instrument in periodontal and periimplant therapy.

COX-2 is associated with periodontitis in Europeans.

COX-2 plays an important role in periodontitis by mediating inflammatory reactions in periodontal tissues, and the COX-2 polymorphisms rs20417 and rs689466 have been reported to be associated with periodontitis in populations of Taiwanese and Chinese ethnicity. To test whether these variants were associated with periodontitis in populations of European ethnicity, we genotyped the single-nucleotide polymorphisms (SNPs) rs689466 and rs6681231, the latter a haplotype tagging SNP (htSNP) for rs20417 (r2>0.95), in our large-analysis population of individuals with aggressive (n = 532) and chronic periodontitis (n = 1052), and 2873 healthy control individuals. The rare G allele of htSNP rs6681231 was associated with aggressive periodontitis prior to and after adjustment for the covariates smoking, diabetes, and gender, with an odds ratio of 1.57 (95% confidence interval 1.18-2.08; p = 0.002). The validation of the association of rs20417 by the htSNP rs6681231 provides evidence for a general genetic risk of COX-2 variants in the pathogenesis of periodontitis.

Gingival and periodontal ligament fibroblasts differ in their inflammatory response to viable Porphyromonas gingivalis.

BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis is an oral pathogen strongly associated with destruction of the tooth-supporting tissues in human periodontitis. Gingival fibroblasts (GF) and periodontal ligament fibroblasts (PDLF) are functionally different cell types in the periodontium that can participate in the host immune response in periodontitis. This study aimed to investigate the effects of viable P. gingivalis on the expression of genes associated with inflammation and bone degradation by these fibroblast subsets. MATERIAL AND METHODS: Primary human GF and PDLF from six healthy donors were challenged in vitro with viable P. gingivalis W83 for 6 h. Gene expression of inflammatory cytokines in GF and PDLF was analyzed using real-time PCR, and protein expression was analyzed using ELISA. RESULTS: Viable P. gingivalis induced a strong in vitro inflammatory response in both GF and PDLF. We found increased gene expression of interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha, monocyte chemotactic protein-1 and regulated upon activation, normal T-cell expressed and secreted (RANTES). Macrophage colony-stimulating factor was induced and the expression of osteoprotegerin was decreased in GF, but not in PDLF. In nonchallenged cells, a higher level of expression of IL-6 was observed in GF than in PDLF. Between individual donors there was large heterogeneity in responsiveness to P. gingivalis. Also, in each individual, either GF or PDLF was more responsive to P. gingivalis. CONCLUSION: Considerable heterogeneity in responsiveness to P. gingivalis exists both between GF and PDLF and between individuals, which may be crucial determinants for the susceptibility to develop periodontitis.

A 3' UTR transition within DEFB1 is associated with chronic and aggressive periodontitis.

Periodontal diseases are complex inflammatory diseases and affect up to 20% of the worldwide population. An unbalanced reaction of the immune system toward microbial pathogens is considered as the key factor in the development of periodontitis. Defensins have a strong antimicrobial function and are important contributors of the immune system toward maintaining health. Here, we present the first systematic association study of DEFB1. Using a haplotype-tagging single nucleotide polymorphism (SNP) approach, including described promoter SNPs of DEFB1, we investigated the associations of the selected variants in a large population (N=1337 cases and 2887 ethnically matched controls). The 3' untranslated region SNP, rs1047031, showed the most significant association signal for homozygous carriers of the rare A allele (P=0.002) with an increased genetic risk of 1.3 (95% confidence interval: 1.11-1.57). The association was consistent with the specific periodontitis forms: chronic periodontitis (odds ratio=2.2 (95% confidence interval: 1.16-4.35), P=0.02), and aggressive periodontitis (odds ratio=1.3 (95% confidence interval 1.04-1.68), P=0.02). Sequencing of regulatory and exonic regions of DEFB1 identified no other associated variant, pointing toward rs1047031 as likely being the causative variant. Prediction of microRNA targets identified a potential microRNA-binding site at the position of rs1047031.

Host and microbiological factors related to dental caries development.

Studies on dental caries suggest that in severe cases it may induce a systemic immune response. This occurs particularly when caries progresses into pulpal inflammation and results in abscess or fistula formation (AFF). We hypothesized that severe dental caries will affect the general health of children. The acute phase proteins alpha-1-acid glycoprotein (AGP), C-reactive protein (CRP) and the cytokine neopterin were chosen as parameters to monitor general health. Also, a polymorphism in the bacterial ligand CD14 (-260) was studied to investigate the relationship between genotype sensitivity for bacterial infections and AFF. In Suriname, children aged 6 years were recruited and enrolled into a dental care scheme, randomly assigned to 4 groups with different treatment strategies and monitored longitudinally. 348 children were included in the present study. Blood and saliva samples were taken at baseline and 1 year, and concentrations of serum AGP, CRP, neopterin, salivary Streptococcus mutans and CD14-260 C>T polymorphism were determined. There was no significant association between different treatment strategies and the serum parameters. Binary logistic regression analyses revealed a significant association between AFF as the outcome variable and the CD14 genotype and the concentrations of CRP and of neopterin as factors (p < 0.05). A significant negative association was found between the CD14-260 TT and AFF (p = 0.035, OR = 3.3) for the whole population. For children who had 4 or more carious lesions at baseline, the significance increased (p = 0.005, OR = 4.8), suggesting that the CD14-260 TT genotype was protective for AFF as a consequence of dental caries.