Effects of apical periodontitis treatment on hyperglycaemia in diabetes: A prospective cohort study.

AIM: This prospective cohort study was undertaken to evaluate the success rate of root canal treatment (RCT) in type 2 diabetes mellitus (T2DM) patients with targeted level and unachieved targeted level of glycaemic control as well as the impact of RCT on the glucose blood level in T2DM patients. METHODOLOGY: Patients needing RCT were divided into three groups: these without T2DM, that is, the control group (CG), those with targeted level of glycated haemoglobin HbA1c < 7% (TL A1c) and the third ones with unachieved targeted level (UTL A1c), that is, with HbA1c ≥ 7%. Before RCT, HbA1c and the periapical index (PAI) score were assessed, as well as 1 year later. RESULTS: Our results showed less favourable treatment results of RCT such as a reduction of radiographic lesions in T2DM patients, particularly in subjects with UTL A1c. The intergroup analysis of PAI score at the 12-month follow-up revealed a significant difference in TL A1C (p = .022) and CG (p = .001) with respect to UTL A1c. Total number of healed teeth (PAI≤2) at the 12-month after RCT in UTL A1c was significantly lower in comparison to CG (p = .008). Contrariwise, RCT may improve the glycaemic control in diabetic patients with UTL A1c after 12 months of posttreatment. Regression analysis showed that UTL A1c patients were more likely to have AP persistence after endodontic treatment (OR = 4.788; CI: 1.157-19.816; p = .031). CONCLUSIONS: T2DM retards the AP healing and conversely AP contributes to increasing the inflammatory burden in T2DM. RCT reduces the cumulative inflammatory burden in T2DM and thus may contribute to improvement of glycaemic control particularly in patients with UTL A1c.

Vesicular Messages from Dental Biofilms for Neutrophils.

The encounter between dental biofilm and neutrophils in periodontitis remains elusive, although it apparently plays a crucial role in the periodontal pathology and constitutes a key topic of periodontology. Dental biofilm and neutrophils were isolated from orally healthy persons and patients with periodontitis. We investigated biofilm and its particle-shedding phenomenon with electron microscopy and nanoparticle tracking analysis (NTA); biofilm shedding-neutrophil interactions were examined ex vivo with epi-fluorescence microscopy. For this purpose, we used acellular dental biofilm shedding, purified lipopolysaccharide (LPS), and phorbol 12-myristate 13-acetate (PMA) as activators, and the interleukin 8 receptor beta (CXCR2) inhibitor and the anti-interleukin 8 receptor alpha (CXCR1) antibody as modulators. The shedding of acellular dental biofilms overwhelmingly consists of bacterial extracellular vesicles (BEVs). The latter induced the moderate formation of neutrophil extracellular traps (NETs) in orally healthy subjects and a strong formation in patients with periodontitis. A CXCR2 inhibitor and an anti-CXCR1 antibody had a minor effect on NET formation. Neutrophils from patients with periodontitis exhibited NET hyper-responsiveness. BEVs were stronger inducers of NET formation than purified LPS and PMA. A plateau of neutrophil responsiveness is reached above the age of 40 years, indicating the abrupt switch of maladaptive trained immunity (TI) into the activated modus. Our results suggest that dental biofilms consist of and disseminate immense amounts of outer membrane vesicles (OMVs), which initiate NET formation via a non-canonical cytosolic LPS/caspase-4/11/Gasdermin D pathway. This modus of NET formation is independent of neutrophil elastase (NE), myeloperoxidase (MPO), peptidylarginine deiminase 4 (PAD4), and toll-like receptors (TLR). In periodontitis, the hyper-responsiveness of neutrophils to BEVs and the increased NET formation appear to be a consequence of TI.

Breaking the Gingival Barrier in Periodontitis.

The break of the epithelial barrier of gingiva has been a subject of minor interest, albeit playing a key role in periodontal pathology, transitory bacteraemia, and subsequent systemic low-grade inflammation (LGI). The significance of mechanically induced bacterial translocation in gingiva (e.g., via mastication and teeth brushing) has been disregarded despite the accumulated knowledge of mechanical force effects on tight junctions (TJs) and subsequent pathology in other epithelial tissues. Transitory bacteraemia is observed as a rule in gingival inflammation, but is rarely observed in clinically healthy gingiva. This implies that TJs of inflamed gingiva deteriorate, e.g., via a surplus of lipopolysaccharide (LPS), bacterial proteases, toxins, Oncostatin M (OSM), and neutrophil proteases. The inflammation-deteriorated gingival TJs rupture when exposed to physiological mechanical forces. This rupture is characterised by bacteraemia during and briefly after mastication and teeth brushing, i.e., it appears to be a dynamic process of short duration, endowed with quick repair mechanisms. In this review, we consider the bacterial, immune, and mechanical factors responsible for the increased permeability and break of the epithelial barrier of inflamed gingiva and the subsequent translocation of both viable bacteria and bacterial LPS during physiological mechanical forces, such as mastication and teeth brushing.

Psychometric properties of the Child Oral Impacts on Daily Performances (C-OIDP) index: a cross-sectional and an intervention study of adolescents in Bosnia and Herzegovina.

BACKGROUND: The clinical measures are not sufficient to assess oral health because they don't tell us anything about functional and psychosocial aspects of oral health and do not reflect person's concerns and subjectively perceived symptoms. This study aimed to investigate the validity, reliability and responsiveness of the child Oral Impacts on Daily Performances (C-OIDP) index among Bosnian 12-14 years old schoolchildren. METHODS: The study population comprised 203 primary schoolchildren aged 12-14 years attending three schools in the eastern part of Bosnia and Herzegovina. Data were collected through: a clinical oral examination, oral health questionnaire and C-OIDP questionnaire. The validity and reliability of the C-OIDP were tested on a sample of 203 school-going children while responsiveness of the C-OIDP was assessed on 42 randomly chosen participants requiring a dental treatment. RESULTS: In terms of reliability, Cronbach's alpha coefficient and the intraclass correlation coefficient were 0.86 and 0.85, respectively. Regarding the testing of construct validity, the C-OIDP score was increased as children's self-reported oral health changed from excellent to very bad and from very satisfied to dissatisfied. There was a significant improvement in C-OIDP post-treatment score compared with C-OIDP pre-treatment score. Overall, 63.4% of participants reported at least one oral impact in the last 3 months. The most affected performances were "eating" (38.4%) and "speaking" (25.1%). CONCLUSION: The Bosnian version of the C-OIDP showed satisfactory validity, reliability and responsiveness and can be used as an appropriate OHRQoL measure for further epidemiological researches.

Changes in pulp sensitivity across the menstrual cycle in healthy women and women with temporomandibular disorders.

BACKGROUND: Menstrual cycle may contribute to experimental pain measures in healthy women and women with chronic pain. OBJECTIVES: The present study aimed to investigate variation in pulp sensitivity across the menstrual cycle in healthy women and women with temporomandibular disorders (TMD) and to explore the effect of TMD pain and psychosocial variables on the pulp response. METHODS: This longitudinal study involved 47 regularly menstruating women aged 20-45, 24 healthy and 23 with diagnosed painful TMD. The electric and cold stimuli were performed by electric pulp tester and refrigerant spray, respectively, on mandibular lateral incisors, in five menstrual phases (menstrual, follicular, periovulatory, luteal and premenstrual). Research Diagnostic Criteria for TMD were used to assess TMD, chronic pain, depression and somatisation. Regression analysis was performed to investigate the effect of the predictor variables on the pulp sensitivity. RESULTS: Significant phase-related differences were observed for pain intensity to cold stimuli. Higher pain sensitivity was reported in menstrual in comparison with luteal phase (P = .019) among healthy women, and in menstrual in comparison with follicular (P = .033), periovulatory (P = .003) and luteal (P = .007) phases in TMD women. No significant differences were recorded for electric stimuli. Regression analysis identified depression as the determinant of cold and electric response in menstrual phase, regardless of age and presence of TMD. CONCLUSION: Menstrual phase in healthy and TMD women with regular menstrual cycle is characterised with higher pulp sensitivity to cold stimuli. Depressive symptoms independently influence pulp response in this phase.

Clinical antibacterial effectiveness and biocompatibility of gaseous ozone after incomplete caries removal.

OBJECTIVES: To evaluate local effect of gaseous ozone on bacteria in deep carious lesions after incomplete caries removal, using chlorhexidine as control, and to investigate its effect on pulp vascular endothelial growth factor (VEGF), neuronal nitric oxide synthase (nNOS), and superoxide dismutase (SOD). MATERIALS AND METHODS: Antibacterial effect was evaluated in 48 teeth with diagnosed deep carious lesion. After incomplete caries removal, teeth were randomly allocated into two groups regarding the cavity disinfectant used: ozone (open system) or 2% chlorhexidine. Dentin samples were analyzed for the presence of total bacteria and Lactobacillus spp. by real-time quantitative polymerase chain reaction. For evaluation of ozone effect on dental pulp, 38 intact permanent teeth indicated for pulp removal/tooth extraction were included. After cavity preparation, teeth were randomly allocated into two groups: ozone group and control group. VEGF/nNOS level and SOD activity in dental pulp were determined by enzyme-linked immunosorbent assay and spectrophotometric method, respectively. RESULTS: Ozone application decreased number of total bacteria (p = 0.001) and Lactobacillus spp. (p < 0.001), similarly to chlorhexidine. The VEGF (p < 0.001) and nNOS (p = 0.012) levels in dental pulp after ozone application were higher, while SOD activity was lower (p = 0.001) comparing to those in control pulp. CONCLUSIONS: Antibacterial effect of ozone on residual bacteria after incomplete caries removal was similar to that of 2% chlorhexidine. Effect of ozone on pulp VEGF, nNOS, and SOD indicated its biocompatibility. CLINICAL RELEVANCE: Ozone appears as effective and biocompatible cavity disinfectant in treatment of deep carious lesions by incomplete caries removal technique.

Periodontal Disease in Young Adults as a Risk Factor for Subclinical Atherosclerosis: A Clinical, Biochemical and Immunological Study.

Although a strong relationship between periodontal disease (PD) and atherosclerosis was shown in adults, little data are published in younger PD patients. Therefore, this study aimed to investigate and correlate clinical parameters of PD, pro- and immunoregulatory cytokines in gingival crevicular fluid (GCF) and serum, biochemical and hematological parameters associated with atherosclerosis risk, and carotid intima-media thickness (IMT) in our younger study participants (n = 78) (mean age 35.92 ± 3.36 years) who were divided into two equal groups: subjects with and without PD. PD patients had higher values of IMT, hs-CRP, triglycerides, total cholesterol, and LDL; most proinflammatory and Th1/Th17-associated cytokines in GCF; and IL-8, IL-12, IL-18, and IL-17A in serum compared to subjects without PD. These cytokines in GCF positively correlated with most clinical periodontal parameters. Clinical periodontal parameters, TNF-α and IL-8 in GCF and IL-17A, hs-CRP, and LDL in serum, had more significant predictive roles in developing subclinical atherosclerosis (IMT ≥ 0.75 mm) in comparison with other cytokines, fibrinogen, and other lipid status parameters. Hs-CRP correlated better with the proinflammatory cytokines than the parameters of lipid status. Except for serum IL-17A, there was no significant association of clinical and immunological PD parameters with lipid status. Overall, these results suggest that dyslipidemia and PD status seem to be independent risk factors for subclinical atherosclerosis in our younger PD population.

Periodontitis-Derived Dark-NETs in Severe Covid-19.

The frequent severe COVID-19 course in patients with periodontitis suggests a link of the aetiopathogenesis of both diseases. The formation of intravascular neutrophil extracellular traps (NETs) is crucial to the pathogenesis of severe COVID-19. Periodontitis is characterised by an increased level of circulating NETs, a propensity for increased NET formation, delayed NET clearance and low-grade endotoxemia (LGE). The latter has an enormous impact on innate immunity and susceptibility to infection with SARS-CoV-2. LPS binds the SARS-CoV-2 spike protein and this complex, which is more active than unbound LPS, precipitates massive NET formation. Thus, circulating NET formation is the common denominator in both COVID-19 and periodontitis and other diseases with low-grade endotoxemia like diabetes, obesity and cardiovascular diseases (CVD) also increase the risk to develop severe COVID-19. Here we discuss the role of propensity for increased NET formation, DNase I deficiency and low-grade endotoxaemia in periodontitis as aggravating factors for the severe course of COVID-19 and possible strategies for the diminution of increased levels of circulating periodontitis-derived NETs in COVID-19 with periodontitis comorbidity.

Apolipoprotein ɛ4 Allele and Dental Occlusion Deficiency as Risk Factors for Alzheimer's Disease.

Compromised dentition has been suggested to pose a significant risk factor for dementia. It was mainly investigated through insufficient tooth number, disregarding contact between opposing teeth (dental occlusion). The ɛ4 allele of apolipoprotein (APOE4) is the primary genetic marker for the late onset of Alzheimer's disease (AD). However, APOE4 and dental occlusion have not yet been investigated as possible associated risk factors for AD. The study was aimed to examine the impact of dental status and different APOE gene variants on AD occurrence. Secondly, sociodemographic variables were investigated as factors potentially associated with AD. The case-control study included two groups: 116 patients with AD (according to the NINDS-ADRDA criteria) and 63 controls (Mini-Mental State Examination scores ≥24). The analysis of APOE gene polymorphism was conducted through PCR reaction. Dental examination included recording of number of teeth, presence of fixed or removable dentures, and number of functional tooth units (FTU). Regression analysis was used to investigate the joint effect of the clinical and genetic variables on AD. Results showed that patients with AD were more often carriers of ɛ3/ɛ4 genotype and ɛ4 allele, had lower number of teeth and FTU, and were less likely to be married, live in home, and had less chronic diseases, compared to the controls. Regression analysis showed that presence of APOE4 allele and the number of total FTU remained associated with AD, even when adjusted for age, sex, and level of education. In conclusion, deficient dental occlusion and presence of APOE4 may independently increase risk for AD.

Prevalence of non-carious cervical lesions among the general population of the Republic of Srpska, Bosnia and Herzegovina.

INTRODUCTION: As non-carious cervical lesions (NCCLs) may compromise aesthetics and function, knowledge of their aetiological covariables enhances management of clinical complaints and success of restorative treatments. AIMS: The primary aim of this study was to assess the presence of NCCLs among the general population of the Republic of Srpska, Bosnia and Herzegovina and the potential association with patient-related risk factors. METHODS: A prevalence study of NCCLs included 738 respondents from eight towns/municipalities. Two dental practitioners examined all respondents. NCCLs were diagnosed according to the Smith and Knight tooth wear index, measured using a Williams periodontal probe. Data regarding risk factors were obtained through a structured questionnaire. Multivariate logistic regression was used to analyse the association of risk factors and the occurrence of NCCLs. RESULTS: Non-carious cervical lesions were diagnosed in 384 (52%) respondents. Multivariate regression analysis showed that several variables were independently associated with the risk of developing NCCLs, including frequent consumption of acid food (P = 0.001), frequent consumption of acid drinks (P = 0.001), retaining drink in the mouth (P = 0.001), alcohol consumption (P = 0.030), bruxism (P = 0.018) and gastro-oesophageal reflux (P = 0.023). First mandibular premolars were the most affected teeth (left: 46.0%; right: 44.0%), followed by the second right maxillary premolars (37.3%), second left maxillary premolars (33.6%) and finally by the first right maxillary premolars (34.0%). CONCLUSION: The results of the current study suggest that NCCLs occur frequently and have a multifactorial aetiology. The lowest prevalence was recorded among individuals younger than 20 years of age. As the majority of risk factors are modifiable, regular dental care could lead to the early detection of NCCLs.

Limited Jaw Movements and Somatization (But Not Pain) May Play a Role in Salivary Flow in Female Patients with Temporomandibular Disorders.

AIMS: To explore the unstimulated salivary flow rate and subjective feeling of oral dryness in young adult women with temporomandibular disorders (TMD) and their relation to the presence of chronic pain, depression, somatization, and limited mandibular mobility. METHODS: Unstimulated whole saliva flow rate and presence of oral dryness were determined in 45 women with TMD and 30 healthy controls. The Research Diagnostic Criteria for TMD (RDC/TMD) were used for assessment of TMD, chronic pain, depression, somatization, and mandibular mobility. Factors with P < .05 in the bivariate analysis were included in multivariate modeling. RESULTS: The TMD patients showed significantly diminished unstimulated salivary flow (P = .010) in comparison to controls, but there was no difference in subjective oral dryness. Within the TMD group, patients with mandibular hypomobility and free from somatization exhibited significantly lower salivary output (P = .037; P = .015, respectively). No relationship between salivary flow and depression or TMD pain was observed. Multivariate linear regression identified somatization as the single variable contributing to salivary flow (P = .044) in the TMD patients. CONCLUSION: The present study shows a relationship between TMD and lower salivary flow but no evidence of a relationship between TMD and subjective oral dryness in young adult women. Somatization was the single variable to emerge from the evaluation of potential factors contributing to salivary output in TMD patients.

Pulp Sensitivity: Influence of Sex, Psychosocial Variables, COMT Gene, and Chronic Facial Pain.

INTRODUCTION: The purpose of this study was to evaluate the associations of variability in pulp sensitivity with sex, psychosocial variables, the gene that encodes for the enzyme catechol-O-methyltransferase (COMT), and chronic painful conditions (temporomandibular disorders [TMDs]). METHODS: The study was composed of 97 subjects (68 women and 29 men aged 20-44 years). The electric (electric pulp tester) and cold (refrigerant spray) stimuli were performed on mandibular lateral incisors. The results were expressed as pain threshold values for electric pulp stimulation (0-80 units) and as pain intensity scores (visual numeric scale from 0-10) for cold stimulation. The Research Diagnostic Criteria for TMD were used to assess TMD, depression, and somatization. DNA extracted from peripheral blood was genotyped for 3 COMT polymorphisms (rs4680, rs6269, and rs165774) using the real-time TaqMan method. Multivariate linear regression was used to investigate the joint effect of the predictor variables (clinical and genetic) on pulp sensitivity (dependent variables). RESULTS: Threshold responses to electric stimuli were related to female sex (P < .01) and the homozygous GG genotype for the rs165774 polymorphism (P < .05). Pain intensity to cold stimuli was higher in TMD patients (P < .01) and tended to be higher in women. Multivariate linear regression identified sex and the rs165774 COMT polymorphism as the determinants of electric pain sensitivity, whereas TMD accounts for the variability in the cold response. CONCLUSIONS: Our findings indicate that sex/a COMT gene variant and TMD as a chronic painful condition may contribute to individual variation in electric and cold pulp sensitivity, respectively.

Prevalence of Enterococcus faecalis and Porphyromonas gingivalis in infected root canals and their susceptibility to endodontic treatment procedures: a molecular study.

INTRODUCTION: Because apical periodontitis is recognizably an infectious disease, elimination or reduction of intracanal bacteria is of utmost importance for optimum treatment outcome. OBJECTIVE: The prevalence of Enterococcus faecalis and Porphyromonas gingivalis in infected root canals was studied Also, the effect of endodontic therapy by using intracanal medicaments, calcium hydroxide paste (CH) or gutta-percha points containing calcium hydroxide (CH-GP) or chlorhexidine (CHX-GP) on these microorganisms was assessed by polymerase chain reaction (PCR) assay. METHODS: Fifty-one patients with chronic apical periodontitis were randomly allocated in one of the fol- lowing groups according to the intracanal medicament used: CH, CH-GP and CHX-GP group. Bacterial samples were taken upon access (S1), after chemomechanical instrumentation (S2) and after 15-day medication (S3). PCR assay was used to detect the presence of selected bacteria. RESULTS: E. faecalis was detected in 49% (25/51) and P. gingivalis in 17.6% (9/51) of the samples. Samples which showed no bacterial presence at S1 were excluded from further analysis. Overall analysis of all 29 samples revealed significant differences between S1 and S2 (p < 0.001), S2 and S3 (p < 0.05), and S1 and S3 (p < 0.001). When distinction was made between the intracanal medications, there was a significant difference in the number of PCR positive samples between S1 and 52, S1 and S3, but not between S2 and S3 samples. CONCLUSION: E. faecalis is more prevalent than P. gingivalis in primary endodontic infection. Intracanal medication in conduction with instrumentation and irrigation efficiently eliminates E. faecalis and P. gingivalis from infected root canals.

[Oral health status in patients with diabetes mellitus type 2 in relation to metabolic control of the disease].

INTRODUCTION: As a systemic disease, diabetes mellitus may lead to several complications affecting both the quality and the length of life. While periodontal disease is one of the major oral health problems in patients with diabetes, reports of an increased risk of dental caries among diabetics are controversial. OBJECTIVE: The aim of this study was to investigate oral health status in patients with diabetes mellitus type 2 in relation to metabolic control of the disease. METHODS: The study included 47 randomly sampled diabetics patients, divided into two groups; those with poorly controlled diabetes (glycosylated haemoglobin--HbA1c > or =9%) and those with better controlled diabetes (HbA1c < 9%). All patients completed a questionnaire about their medical and oral health. Decayed, missing, and filled teeth (DMFT) and plaque index (PI), bleeding on probing (BOP), probing pocket depth (PPD) and clinical attachment loss (CAL) were recorded. RESULTS: The patients with poorly controlled diabetes had a significantly higher number of tooth caries compared to those with better controlled diabetes (6.5 +/- 4.3 vs. 4.3 +/- 2.9; p < 0.05). Of periodontal parameters, only PPD was significantly higher in the patients with poorly controlled diabetes than in those with better controlled diabetes (5.8 +/- 0.9 vs. 5.2 +/- 0.8; p < 0.05). DMFT index, PI, PPD and CAL exhibited positive correlation only with patients' age. CONCLUSION: The study indicates that there is a relationship between poor control of diabetes and caries, and periodontal disease.