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Concept: Periodontal disease

272

Periodontitis is common in the elderly and may become more common in Alzheimer’s disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer’s disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer’s disease. We aimed to determine if periodontitis in Alzheimer’s disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer’s Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer’s Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation.

Concepts: Periodontitis, Gingiva, Dental hygienist, Alzheimer's disease, Cohort study, Cognition, Periodontal disease, Inflammation

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BACKGROUND: There are scarce evidences that evaluated the impact of periodontal disease on oral health-related quality of life (OHRQoL) taking marginal gingival alterations into consideration. Thus, this study aimed to verify the association between OHRQoL and gingival enlargement and gingival bleeding in subjects under fixed orthodontic treatment (FOT). METHODS: 330 participants under FOT for at least 6 months were examined by a single, calibrated examiner for periodontal variables. Socio-economic background, body mass index, time with orthodontic appliances, dental aesthetic index and use of dental floss were assessed by oral interviews. OHRQoL was evaluated using the oral health impact profile (OHIP-14) questionnaire. The assessment of associations used unadjusted and adjusted Poisson regression models. RESULTS: Higher impacts on the OHIP-14 overall were observed in subjects who presented higher levels of anterior gingival enlargement (RR 2.83; 95% CI 2.60-3.09), were non-whites (RR 1.29; 95% CI 1.15-1.45), had household income lower than five national minimum wages (RR 1.85; 95% CI 1.30-2.61), presented body mass index > 25 (RR 1.14; 95% CI 1.01-1.29), andshowed a dental aesthetic index > 30 (RR 1.32; 95% CI 1.20-1.46) . CONCLUSIONS: Anterior gingival enlargement seems to influence the OHRQoL in subjects receiving orthodontic treatment.

Concepts: Dental floss, Regression analysis, Gingiva, Periodontal disease, Periodontitis, Oral hygiene, Dentistry, Minimum wage

152

Plasminogen deficiency is a rare autosomal recessive disease, which is associated with aggressive periodontitis and gingival enlargement. Previously described treatments of plasminogen deficiency associated periodontitis have shown limited success. This is the first case report indicating a successful therapy approach consisting of a non-surgical supra- and subgingival debridement in combination with an adjunctive systemic antibiotic therapy and a strict supportive periodontal regimen over an observation period of 4 years.

Concepts: Success, Phage therapy, Periodontal disease, Gingiva, Antibiotic, Medicine, Periodontology, Periodontitis

147

Pregnancy is a period involving important metabolic changes that enable the maintenance of the mother’s health and development of the fetus. This study aimed to assess the relationship among periodontal disease, insulin resistance, salivary cortisol concentration and level of perceived stress in pregnant women. This was a cross-sectional study. The sample comprised 96 pregnant women between the fifth and seventh month of pregnancy registered at the Basic Health Units of the Unified Health System (SUS). The periodontal condition was assessed after obtainment free and informed consent from the participants. Participants were divided into three groups: control subjects with a healthy periodontal condition (CN; n=46), patients with gingivitis (GI; n=26), and patients with periodontitis (PI; n=24). Saliva and blood samples were collected for evaluation of salivary cortisol concentration, glycemia, insulinemia and Homeostasis Model Assessment-Insulin Resistance index. A validated survey for the assessment of perceived stress levels was also performed. PI group showed significantly higher (p<0.05) blood glucose levels (CN: 4.43±0.05; GI: 4.46±0.04; PI: 4.68±0.08), insulinemy (CN: 6.93±0.45; GI: 8.87±0.79; PI: 12.77±1.30), insulin resistance (CN: 1.40±0.10; GI: 1.81±0.18; PI: 2.66±0.29) compared with the CN and GI groups. The levels of perceived stress were higher (p<0.05) in PI and GI groups when compared to CN group (CN: 20.5±1.26; GI: 25.8±1.95; PI: 26.6±1.36). There was no significant difference in the concentration of salivary cortisol between the groups (CN: 11.13±0.58; GI: 11.96±0.74; PI: 11.47±0.74). It was concluded that there is a relationship between higher levels of perceived stress, insulin resistance and the occurrence of periodontal disease during pregnancy. This study emphasizes the importance of preventing periodontitis in order to avoid insulin resistance and stress during pregnancy since these can cause systemic complications for the mother and the fetus.

Concepts: Periodontal disease, Abortion, Embryo, Uterus, Fetus, Periodontitis, Pregnancy, Blood sugar

147

Hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) are proteins that stimulate the proliferation and migration of endothelial cells. These proteins have been described in many pathologic and inflammatory conditions, but their involvement in the development of periodontitis has not been thoroughly investigated. This study compared the immunohistochemical expression of these proteins, involved in angiogenesis and hypoxia, by imunnostained inflammatory and endothelial cells in periodontal disease and healthy gingival tissues. Gingival tissue samples were divided as follows: 30 samples with chronic periodontitis, 30 with chronic gingivitis, and 30 of healthy gingiva. Results were analyzed statistically by the Kruskal-Wallis, Mann-Whitney and Spearman correlation tests (p=0.01). Inflammatory and endothelial cells were found to express these proteins. Periodontitis showed median percentage of HIF-1α-positive cells of 39.6%, 22.0% in cases of gingivitis and 0.9% in the healthy gingiva group (p=0.001). For VEGF, median percentage of immunopositive cells was 68.7% for periodontitis, 66.1% in cases for gingivitis, and 19.2% for healthy gingival specimens (p<0.001). Significant correlation between VEGF and HIF-1α was also observed in healthy gingiva (p<0.001).The increased expression of HIF-1αα and VEGF in periodontitis, compared to gingivitis and healthy gingiva, suggests possible activation of the HIF-1α pathway in advanced periodontal disease. The correlation between HIF-1α and VEGF expression in healthy gingiva suggests a physiological function for these proteins in conditions of homeostasis. In periodontal disease, HIF-1 and VEGF expression may be regulated by other factors, in addition to hypoxia, such as bacterial endotoxins and inflammatory cytokines.

Concepts: Oral hygiene, Gingival fibers, Angiogenesis, Periodontology, Gingivitis, Periodontal disease, Gingiva, Periodontitis

28

OBJECTIVE.: First Degree Relatives (FDR) of Rheumatoid Arthritis (RA) patients sharing genetic and environmental risk factors for RA may represent a pre-RA state. Anti-cyclic citrullinated protein/peptide antibodies (ACPA) appear years before the onset of RA. We determined the prevalence of various ACPA in RA FDR. METHODS.: Subjects were RA patients (n=88), unaffected FDR (n=50) and healthy controls (n=20). Six different types of ACPA were determined by ELISA. Joint and periodontal disease symptoms were self-reported. Patients and FDR were HLA-typed for the Shared Epitope (SE) and the RA-protective alleles, HLA-DRB*1301/1302. RESULTS.: FDR had a high prevalence of ACPA (48%) compared to controls (10%). The prevalence of the SE and smoking in FDR were also high (62% and 49% respectively). 13/32 (41%) of all ACPA in FDR was of the IgA isotype. The most commonly expressed IgG ACPA targeted citrullinated vimentin, occurring in 20% of FDR. FDR had an average of 1 type of ACPA, whereas, RA patients expressed a median of 5 different ACPA. The only FDR to later develop RA expressed 4 different ACPA. Joint and PD symptoms in FDR were significantly associated with smoking (OR 5.714; 95%CI: 1.151-28.3 and OR 12.25; 95%CI: 2.544-58.99 respectively), but not with ACPA. CONCLUSIONS.: The rate of ACPA positivity in unaffected FDR of RA patients with a high prevalence of the SE and smoking was 48%; whereas, ACPA were rare in healthy controls. ACPA in FDR was most commonly of the IgA isotype, but IgG ACPA targeting citrullinated vimentin was also frequently found. © 2013 American College of Rheumatology.

Concepts: Anti-citrullinated protein antibody, Epidemiology, Periodontal disease, Antibodies, Rheumatology, Immune system, Antibody, Rheumatoid arthritis

28

Ehlers-Danlos syndrome (EDS) type VIII (periodontitis type) is a distinct form of EDS characterized by periodontal disease leading to precocious dental loss and a spectrum of joint and skin manifestations. EDS type VIII is transmitted in an autosomal dominant pattern; however, the mutated gene has not been identified. There are insufficient data on the spectrum of clinical manifestations and natural history of the disorder, and only a limited number of patients and pedigrees with this condition have been reported. We present a four-generation EDS type VIII kindred and show that EDS VIII is clinically variable and although some cases lack the associated skin and joint manifestations, microscopic evidence of collagen disorganization is detectable.We further propose that the diagnosis of EDS type VIII should be considered in familial forms of periodontitis, even when the associated skin and joint manifestations are unconvincing for the diagnosis of a connective tissue disorder. This novel observation highlights the uncertainty of using connective tissue signs in clinical practice to diagnose EDS type VIII.

Concepts: Periodontitis, Gingiva, Periodontal disease, Bone, Marfan syndrome, Connective tissue, Ehlers-Danlos syndrome, Collagen

28

Background: The aim of this study is to evaluate proinflammatory and anti-inflammatory cytokine levels in gingival crevicular fluid (GCF) and serum of rheumatoid arthritis (RA) and chronic periodontitis (CP) patients to assess whether cytokine profiles distinguish patients with RA and patients with CP while using healthy patients as background controls. Methods: A total of 49 patients, 17 patients with RA (three males and 14 females; mean age: 47.82 ± 10.74 years), 16 patients with CP (10 males and six females; mean age: 44.00 ± 7.00 years), and 16 controls (eight males and eight females; mean age: 28.06 ± 6.18 years) were enrolled. Patients with RA were under the supervision of rheumatologists; 15 of the patients with RA were being treated with methotrexate-sulfasalazine combined therapy, and two of the patients were being treated with leflunomid therapy. Periodontal parameters (plaque index, gingival index, probing depth, and clinical attachment level) were recorded. Interleukin (IL)-1β, IL-4, IL-10, and tumor necrosis factor-α (TNF-α) were determined in GCF and IL-1β and IL-10 in serum by enzyme-linked immunosorbent assay. Results: There were significant differences found among RA, CP, and control groups for all periodontal parameters (P <0.05). The total amount and concentration of GCF IL-1 β, IL-4, IL-10, and TNF-α were similar in RA and CP patients (P >0.05). Although the total amount and concentration of serum IL-10 was not significantly different among the groups (P >0.05), serum IL-1β was significantly lower in the RA group compared to CP patients and controls and was higher in GCF of the RA group compared to the CP group. Conclusions: Although clinical periodontal disease parameters indicated more severe periodontal disease in CP compared to RA patients, immunologic evaluation did not reveal consistent results regarding proinflammatory and anti-inflammatory cytokine levels. This might be a result of the use of non-steroidal anti-inflammatory drugs and rheumatoid agents by patients with RA.

Concepts: Anti-inflammatory, Gingiva, Inflammation, Antibody, Periodontology, Periodontal disease, Periodontitis, Rheumatoid arthritis

28

Recent advancements in the periodontal research field are consistent with a new model of pathogenesis according to which periodontitis is initiated by a synergistic and dysbiotic microbial community rather than by select ‘periopathogens’, such as the ‘red complex’. In this polymicrobial synergy, different members or specific gene combinations within the community fulfill distinct roles that converge to shape and stabilize a disease-provoking microbiota. One of the core requirements for a potentially pathogenic community to arise involves the capacity of certain species, termed ‘keystone pathogens’, to modulate the host response in ways that impair immune surveillance and tip the balance from homeostasis to dysbiosis. Keystone pathogens also elevate the virulence of the entire microbial community through interactive communication with accessory pathogens. Other important core functions for pathogenicity require the expression of diverse molecules (e.g. appropriate adhesins, cognate receptors, proteolytic enzymes and proinflammatory surface structures/ligands), which in combination act as community virulence factors to nutritionally sustain a heterotypic, compatible and proinflammatory microbial community that elicits a non-resolving and tissue-destructive host response. On the basis of the fundamental concepts underlying this model of periodontal pathogenesis, that is, polymicrobial synergy and dysbiosis, we term it the PSD model.

Concepts: Holism, Periodontitis, Campylobacter, Protease, Periodontal disease, Immune system, Bacteria, Microbiology

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Porphyromonas gingivalis is considered as a major etiological agent in periodontal diseases and implied to result in gingival inflammation under orthodontic appliance. rag locus is a pathogenicity island found in Porphyromonas gingivalis. Four rag locus variants are different in pathogenicity of Porphyromonas gingivalis. Moreover, there are different racial and geographic differences in distribution of rag locus genotypes. In this study, we assessed the prevalence of Porphyromonas gingivalis and rag locus genotypes in 102 gingival crevicular fluid samples from 57 cases of gingivitis patients with orthodontic appliances, 25 cases of periodontitis patients and 20 cases of periodontally healthy people through a 16S rRNA-based PCR and a multiplex PCR. The correlations between Porphyromona.gingivalis/rag locus and clinical indices were analyzed. The prevalence of Porphyromonas gingivalis and rag locus genes in periodontitis group was the highest among three groups and higher in orthodontic gingivitis than healthy people (p<0.01). An obviously positive correlation was observed between the prevalence of Porphyromonas gingivalis/rag locus and gingival index. rag-3 and rag-4 were the predominant genotypes in the patients of orthodontic gingivitis and mild-to-moderate periodontitis in Shandong. Porphyromonas.gingivalis carrying rag-1 has the strong virulence and could be associated with severe periodontitis.

Concepts: Genetics, Correlation and dependence, Porphyromonas gingivalis, Oral hygiene, Gingiva, Periodontal disease, Gingivitis, Periodontitis