Periapical Microsurgery: A 4-dimensional Analysis of Healing Patterns.

INTRODUCTION: Currently, the success of periapical microsurgery is determined by the restoration of the lamina dura and the elimination of symptoms. However, inadequate site preservation may prevent later implant placement. Although not possible before, the advent of cone-beam computed tomographic imaging and computer-aided registration allows for indirect and accurate 3-dimensional analysis of the surgical site over time. This study analyzed the volumetric healing pattern of the buccal plate after periapical microsurgery, with a specific focus on the buccolingual thickness of bone and the regression of the surface contour of the cortical plate. METHODS: Thirty-seven patients were scheduled for follow-up at least 1 year after periapical microsurgery (median = 25 months, total range = 12-31 months). Volumetric healing was analyzed by converting preoperative and postoperative cone-beam computed tomographic images into digital 3-dimensional models. The models were then registered to be able to analyze the changes in volume over time. Analysis was completed using Geomagic software (3D Systems, Rock Hill, SC), which allowed for registration of the volumes, calculation of volume change, and calculation of the margin of error. RESULTS: Twelve cases qualified for volumetric analysis. The median volumetric reduction of the cortical plate was -24.9 mm3 (interquartile range = -8.94 to -67 mm3), with an average linear error of 0.7 mm. This corresponded to an average loss in buccolingual dimension of 0.1-0.25 mm. Regression of the cortical plate was within the margin of error in all cases. CONCLUSIONS: After periapical microsurgery, and in the absence of grafting materials or membranes, healing occurs with little to no regression of the buccal cortical plate.

Periapical Healing in Single-visit Endodontics under General Anesthesia in Special Needs Patients.

INTRODUCTION: The aim of this study was to determine the prognostic factors of periapical healing of teeth after single-visit nonsurgical endodontic treatment under general anesthesia in special needs patients. METHODS: This retrospective study collected 448 teeth from 241 patients (mean age = 27.4 years, standard deviation = 13.9 years). A total of 271 teeth (60.5%) with clinical and radiographic follow-up records longer than 12 months (mean [standard deviation] = 56.1 [27.9]) were included in the outcome analysis. Demographic, systemic, and dental information about the cases were compared between the healed and nonhealed groups using the Pearson chi-square test. Factors contributing to periapical healing were determined with multivariate logistic regression analysis. RESULTS: Complete periapical healing without clinical signs was observed in 221 teeth (81.5%), uncertain healing with decreased size of the periapical lesion was shown in 43 teeth (15.9%), and no reduction in lesion size was observed in 7 cases (2.6%). In the multivariate analysis, diet type, oral hygiene maintenance, pulp vitality, and root filling length were detected as contributing factors for complete resolution of periapical lesions (P < .05). CONCLUSIONS: Successful outcomes of single-visit endodontic treatment under general anesthesia were shown in special needs patients. The prognoses were influenced by the clinical circumstances of the patients and the preoperative conditions of their teeth.

Craniofacial and oral alterations in patients with Neurofibromatosis 1.

ABTSRACT: Neurofibromatosis type 1 (NF1) is one of the most common inherited syndromes. The literature on craniofacial alterations associated with NF1 has been limited and partially contradictory. This review is based on literature search and the results of the clinical study "Craniofacial and Oral Alterations and Speech in patients with Neurofibromatosis 1", carried out at the University of Turku and Turku University Hospital, Finland in 2006-2012. By the end of 2012, a total of 110 NF1 patients, 54 female and 56 male patients, were examined.A part of our results confirms pre-existing understanding, a part is contradictory to previous considerations based mainly on case reports, and some are entirely novel. Specifically, our results confirmed that enlargement the mandibular canal is the most common abnormality of the mandible in patients with NF1. It should be noted, however, that this finding does not require treatment. Caries was not a major problem. In fact, it was less frequent in NF1 patients compared to reference population. These findings abrogate some previous perceptions. Novel findings of our project include periapical cemental dysplasia in females; short jaws, a finding which usually does not affect bite; and immunohistological analysis of oral mucosal abnormalities. Pioneering study on speech showed that various deviations were very common: As many as 94% of the participants showed some alterations.To conclude, the awareness of craniofacial alterations common in NF1would help avoiding unnecessary and even harmful involvement, e.g. of periapical cemental dysplasia or enlarged mandibular canal which do not require treatment.

The roles of autophagy and hypoxia in human inflammatory periapical lesions.

AIM: To determine the expressions of hypoxia-related [hypoxia-inducible transcription factors (HIF)-1α, BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) and phospho-adenosine monophosphate activated protein kinase (pAMPK)] and autophagy-related [microtubule-associated protein 1 light chain 3 (LC3), beclin-1 (BECN-1), autophagy-related gene (Atg)5-12, and p62] proteins in human inflammatory periapical lesions. METHODOLOGY: Fifteen samples of radicular cysts (RCs) and 21 periapical granulomas (PGs), combined with 17 healthy dental pulp tissues, were examined. Enzyme-linked immunosorbent assay (ELISA) was used to detect interleukin (IL)-1ß cytokine; immunohistochemical (IHC) and Western blot (WB) analyses were employed to examine autophagy-related and hypoxia-related proteins. Transmission electron microscopy (TEM) was used to explore the ultrastructural morphology of autophagy in periapical lesions. Nonparametric Kruskal-Wallis tests and Mann-Whitney U-tests were used for statistical analyses. RESULTS: ELISA revealed a significantly higher (P < 0.001) IL-1ß expression in periapical lesions than in normal pulp tissue. Immunoscores of IHC expressions of pAMPK, HIF-1α, BNIP3, BECN-1 and Atg5-12 proteins in periapical lesions were significantly higher (P < 0.001) (except BECN-1) than those in normal pulp tissue. The results of IHC studies were largely compatible with those of WB analyses, where significantly higher (P < 0.05) expressions of hypoxia-related and autophagy-related proteins (except BECN-1, p62 and LC3II in WB analyses) in periapical lesions were noted as compared to normal pulp tissue. Upon TEM, ultrastructural double-membrane autophagosomes and autolysosomes were observed in PGs and RCs. CONCLUSIONS: Autophagy associated with hypoxia may play a potential causative role in the development and maintenance of inflamed periapical lesions.

Role of Periapical Diseases in Medication-Related Osteonecrosis of the Jaws.

OBJECTIVE: The present study aimed to investigate the role of periapical diseases in inducing medication-related osteonecrosis of the jaws (MRONJ) using an ovariectomized (OVX) mice model. MATERIALS AND METHODS: Twenty C57BL/6N female mice were randomly assigned to two groups. All mice were subjected to bilateral ovariectomy and then treated with oncologic dose of zoledronic acid (ZA) or vehicle for twelve weeks. Eight weeks after commence of drug administration, a pulpal exposure (PE) operation was performed on the first right lower molar to induce periapical periodontitis; the contralateral non-PE tooth was used as control. All animals were sacrificed four weeks after pulpal exposure, and the mandibles were harvested for radiological and histomorphometrical analysis. RESULTS: Micro computed tomography (µ-CT) examination demonstrated that periapical diseases significantly increased alveolar bone resorption, and the resorption was greatly attenuated by ZA treatment. Concurrent ZA therapy significantly increased bone density and histological osteocyte necrosis in the presence of periapical lesions. CONCLUSION: ZA treatment reduced bone absorption resulting from periapical disease but increased the risk of developing MRONJ in the ovariectomized mouse model.

Periapical Lesions Increase Macrophage Infiltration and Inflammatory Signaling in Muscle Tissue of Rats.

INTRODUCTION: Our previous studies have shown that periapical lesions (PLs) in rats cause systemic disorders such as increased tumor necrosis factor-α plasma levels, insulin resistance, and impairment in insulin signal transduction in muscle tissue. However, the mechanisms involved in these alterations are not fully understood. Under chronic inflammatory conditions such as obesity, it has been shown that the skeletal muscle is affected by inflammation, and the number of resident macrophages that are associated with impairments of insulin action and sensitivity is increased. This study aimed to investigate the presence of macrophages, activation of inflammatory pathways in muscle tissue, glycemia, and insulinemia of rats with PLs. METHODS: Sixty Wistar rats were distributed into a control group; a group with 1 PL (1PL), which was induced in the right maxillary first molar; and a group with 4 PLs (4PL), which were induced in the right upper and lower first and second molars. We quantified macrophage content by immunohistochemistry for the F4/80 protein. We evaluated Jun N-terminal kinase and IKKα/ß phosphorylation status in the muscle tissue by Western blotting. Serum levels of lipopolysaccharide (LPS) and HSP70 and plasma levels of glucose and insulin were assessed by using commercial kits. RESULTS: The 1PL and 4PL groups showed increase in macrophage content, IKKα/ß, and Jun N-terminal kinase phosphorylation status, serum LPS and HSP70 levels, and insulin resistance and no changes in glycemia and insulinemia compared with the control group. There was no difference in these parameters between the 1PL and 4PL groups. CONCLUSIONS: PLs promoted an increase in macrophage infiltration, activation of inflammatory pathways in muscle tissue, and serum concentrations of HSP70 and LPS in rats. The present study improves the knowledge on the impact of oral inflammations on the development of systemic alteration, which can induce insulin resistance.

[Endodontics in motion: new concepts, materials and techniques 5. The dynamics of the periapical laesion]. / Endodontologie in beweging: nieuwe concepten, materialen en technieken 5. De dynamiek van de periapicale laesie.

Periapical laesions are a frequently occurring phenomenon, in both untreated teeth and teeth which have undergone endodontic treatment. Various factors have been found to positively influence the effectiveness of endodontic treatment, which is defined by a lack of clinical symptoms and also the absence or shrinkage of the periapical laesion. The chance of a painful exacerbation of a persistent periapical laesion is small, even if the area of the laesion has expanded, which happens in approximately 50% of the cases. The survival of endodontically treated teeth with a periapical laesion is 87% after 10 years. Restorative reasons frequently are the main reason for extraction and the presence of a periapical laesion is seldom the reason for losing a tooth. The influence of the periapical laesion on general health is still unclear.

Combating inadequate anesthesia in periapical infections, with sodium bicarbonate: a clinical double blind study.

INTRODUCTION: Local anesthetics are generally much less effective when administered in inflamed tissues. PURPOSE: This study was conducted to validate the addition of sodium bicarbonate in local anesthetics to increase its effectiveness as local infiltrations in teeth associated with periapical infections. METHODS: Two hundred subjects requiring extraction of maxillary teeth with periapical infections were enrolled. These subjects were divided in two groups of 100 subjects each. One group received local infiltration with 2 % lignocaine and 1:80,000 adrenaline, and the other group received local infiltration with sodium bicarbonate as an adjunct to the above mentioned local anesthetic solution. All extractions were performed using a consistent intra-alveolar technique by a single operator. Both the patient and the operator were blinded to the contents of local anesthetic solution. Data related to the onset of action of local anesthesia, pain experienced by the patient while undergoing extraction on two scales-"the visual analog scale and the verbal response scale", and any requirement of repeated injections during the procedure was recorded. RESULTS: Clinical and statistical data confirmed that the addition of sodium bicarbonate in local anesthetics did increase the efficacy of local anesthesia in inflamed tissues. CONCLUSION: It has been observed in this study that the action of sodium bicarbonate in local anesthetics increases the pH levels of these solutions, thus possibly making them more effective in an acidic environment.

The dynamics of periapical lesions in endodontically treated teeth that are left without intervention: a longitudinal study.

INTRODUCTION: The long-term dynamics of periapical lesions in endodontically treated teeth is not fully elucidated, thus presenting a clinical dilemma regarding the need for an intervention. The aim of the study was to retrospectively evaluate the long-term dynamics of periapical lesions that were left without intervention in endodontically treated teeth. METHODS: Periapical status surveys of patients treated in a public dental clinic were retrospectively evaluated for the presence of periapical lesions in endodontically treated coronally restored teeth. The dynamics of the included periapical lesions was evaluated based on the periapical index (PAI) score changes between 2 consecutive periapical surveys of at least a 4-year interval. The influence of various factors on lesion dynamics was statistically evaluated. RESULTS: The study cohort consisted of 74 patients with a total of 200 endodontically treated teeth having periapical lesions that fulfilled the inclusion criteria. Fifty-seven (28.5%) lesions remained unchanged, 103 (51.5%) lesions worsened (PAI score increased), and 40 (20%) lesions improved (PAI score decreased). Poor root canal filling and poor restoration were found to adversely affect the long-term dynamics of the periapical lesions (P < .05). Age, sex, and the presence of a post had no statistically significant influence on lesion dynamics (P > .05). CONCLUSIONS: Poor root canal filling and poor restoration may adversely affect the long-term dynamics of periapical lesions that are left without intervention in endodontically treated teeth. Therefore, in cases of poor root canal filling or poor restoration, further intervention may be indicated.

Periapical lesions decrease insulin signal and cause insulin resistance.

INTRODUCTION: Inflammatory cytokines are associated with decreased insulin signal transduction. Moreover, local oral inflammation, such as that accompanying periodontal disease, is associated with insulin resistance and type 2 diabetes mellitus. The aim of this study was to evaluate the effect of periapical lesions (PLs) on insulin signaling and insulin sensitivity in rats. We hypothesized that PLs alter systemic insulin signaling and insulin sensitivity via elevated plasmatic tumor necrosis factor α (TNF-α). METHODS: Wistar rats were divided into control (CN) and PL groups. PLs were induced by exposing pulpal tissue to the oral environment. After 30 days, insulin sensitivity was measured using the insulin tolerance test. After euthanization, maxillae were processed for histopathology. Plasmatic concentrations of tumor necrosis factor α (TNF-α) were determined via the enzyme-linked immunosorbent assay. Insulin signal transduction was evaluated using insulin receptor substrate tyrosine phosphorylation status and serine phosphorylation status in periepididymal white adipose tissue via Western blotting. For insulin signaling and insulin tolerance tests, the analyses performed were analysis of variance followed by the Tukey post hoc test. For TNF-α analysis, the Student's t test was used. In all tests, P < .05 was considered significant. RESULTS: The rats with PLs showed higher plasmatic TNF-α, lower constant rate for glucose disappearance values, and reduced pp185 tyrosine phosphorylation status but no change in serine phosphorylation status in white adipose tissue after insulin stimulation. CONCLUSIONS: PLs can cause alterations to both insulin signaling and insulin sensitivity, probably because of elevation of plasmatic TNF-α. The results from this study emphasize the importance of the prevention of local inflammatory diseases, such as PLs, with regard to the prevention of insulin resistance.

Spontaneous resolution of a periapical lesion during orthodontic treatment: a case report.

UNLABELLED: Teeth with periapical lesions can undergo successful orthodontic treatment, but conventional protocols indicate that such teeth should be endodontically stabilized prior to such treatment. A case report is presented where such endodontic stabilization was not possible, yet a chronic periapical lesion resolved as orthodontic treatment progressed. This paper will discuss the possible causes of the initial lesion, and reasons why it resolved without endodontic treatment. CLINICAL RELEVANCE: This report illustrates the possible combined roles of trauma, occlusion and periodontal disease in the development of a perio-endo lesion, and how orthodontic treatment potentially relieved some of the exacerbating factors, thus enabling resolution of the infection without endodontic treatment.

Periapical disease and bisphosphonates induce osteonecrosis of the jaws in mice.

Osteonecrosis of the jaw (ONJ) is a well-recognized complication of antiresorptive medications, such as bisphosphonates (BPs). Although ONJ is most common after tooth extractions in patients receiving high-dose BPs, many patients do not experience oral trauma. Animal models using tooth extractions and high BP doses recapitulate several clinical, radiographic, and histologic findings of ONJ. We and others have reported on rat models of ONJ using experimental dental disease in the absence of tooth extraction. These models emphasize the importance of dental infection/inflammation for ONJ development. Here, we extend our original report in the rat, and present a mouse model of ONJ in the presence of dental disease. Mice were injected with high dose zoledronic acid and pulpal exposure of mandibular molars was performed to induce periapical disease. After 8 weeks, quantitative and qualitative radiographic and histologic analyses of mouse mandibles were done. Periapical lesions were larger in vehicle-treated versus BP-treated mice. Importantly, radiographic features resembling clinical ONJ, including thickening of the lamina dura, periosteal bone deposition, and increased trabecular density, were seen in the drilled site of BP-treated animals. Histologically, osteonecrosis, periosteal thickening, periosteal bone apposition, epithelial migration, and bone exposure were present in the BP-treated animals in the presence of periapical disease. No difference in tartrate-resistant acid phosphatase (TRAP)+ cell numbers was observed, but round, detached, and removed from the bone surface cells were present in BP-treated animals. Although 88% of the BP-treated animals showed areas of osteonecrosis in the dental disease site, only 33% developed bone exposure, suggesting that osteonecrosis precedes bone exposure. Our data further emphasize the importance of dental disease in ONJ development, provide qualitative and quantitative measures of ONJ, and present a novel mouse ONJ model in the absence of tooth extraction that should be useful in further exploring ONJ pathophysiological mechanisms.

Behavioral effects of pulp exposure in mice lacking cannabinoid receptor 2.

INTRODUCTION: Cannabinoid receptor 2 (CB2) is an intriguing target for the treatment of pain because of its ability to mediate analgesia without psychoactive effects, but little is known about the role of CB2 in pain of endodontic origin. The purpose of this study was to determine the behavioral effects of dental pulp exposure in wild-type (WT) mice and to explore the contribution of CB2 to these behaviors using CB2 knockout (CB2 KO) mice. METHODS: Pulp exposures were created unilaterally in the maxillary and mandibular first molars of female WT and CB2 KO mice. The open field test was used before pulp exposure or sham surgery, and postoperatively at 1 day, 1 week, 2 weeks, and 3 weeks. Mouse body weight and food consumption were recorded preoperatively and postoperatively at 1 day, 2 days, and 1 week. RESULTS: At baseline, CB2 KO mice weighed significantly more and had significantly greater food intake than WT mice. CB2 KO mice exhibited greater anxiety-like behavior in the baseline open field test, having significantly fewer center crossings and less distance traveled than WT mice. Pulp exposure had relatively little effect on the behavior of WT mice. CB2 KO mice with pulp exposures showed a decrease in food intake and body weight after surgery, and pulp exposure resulted in significantly fewer center crossings in the open field test in CB2 KO mice. CONCLUSIONS: Pulp exposure in CB2 KO mice resulted in behaviors consistent with an increase in pain and/or anxiety.

Healing of extraction sockets in collagenase-2 (matrix metalloproteinase-8)-deficient mice.

Matrix metalloproteinase-8 (MMP-8) participates in skin wound healing and inflammation. We hypothesized that MMP-8 plays a role in wound healing after tooth extraction and in periapical inflammation. Bone formation, collagen metabolism, and inflammation in tooth extraction socket and in periapical lesions were analyzed in wild-type mice and in MMP-8-deficient (MMP-8(-/-)) mice. New trabecular bone area in the extraction sockets and in periapical lesions were similar in both groups. In extraction sockets significantly more type III procollagen was synthesized, and the neutrophil and MMP-9 levels were lower in MMP-8(-/-) mice. The amount of Fas ligand, identified as a substrate for MMP-8, was lower in alveolar mucosa but higher in alveolar bone of MMP-8(-/-) mice. These results indicate that MMP-8 can modulate inflammation and collagen metabolism of alveolar bone and mucosa.

IL-17 is involved in bone resorption in mouse periapical lesions.

Periapical lesions are induced by bacterial infection of the dental pulp and result in destruction of the surrounding alveolar bone. Although various immunological studies concerning periapical bone resorption have been reported, the role of cytokines in the formation of periapical lesions remains unclear. In this study, the role of IL-17A in periapical lesions in mice was investigated. Normal C57BL/6, IFN-gamma(-/-), TNF-alpha(-/-), and IL-17A(-/-) mice were subjected to pulp exposure and infected with Prevotella intermedia (ATCC25611) and Porphyromonas gingivalis (ATCC33277) in the mandibular first molar. Periapical lesions were determined by muCT on day 21 after infection, and 3D visual construction was performed using 3D picture quantification software. The expression of IL-17A mRNA in periapical lesions was determined by the RT-PCR and real-time RT-PCR method. Periapical lesions developed in wild-type, IFN-gamma(-/-), and TNF-alpha(-/-) mice after infection with P. intermedia and P. gingivalis. However, periapical lesions were not observed in IL-17A(-/-) mice. The expression of IL-17A mRNA was significantly induced in periapical lesions of wild-type mice after infection. These results suggest that IL-17A, but not IFN-gamma or TNF-alpha, plays an important role in the formation of periapical lesions.

Pain associated with root canal treatment.

AIM: To determine the pain experienced by patients during root canal treatment and to correlate with age and gender, pulpal diagnosis, previous periapical status, dental characteristics and length of treatment. METHODOLOGY: One hundred and seventy-six patients (68 men and 108 women), with ages ranged from 6 to 83 years, were randomly recruited. Patients completed a 10-cm visual analogue scale (VAS) that ranked the level of pain experienced during root canal treatment. RESULTS: The mean pain level during root canal treatment was 1.2 +/- 0.8 in a VAS between 0 and 10. Fifty-four per cent of patients did not experience pain. There were no significant differences in relation to gender or age groups. Mandibular teeth had a significantly (P < 0.05) higher percentage incidence of pain in comparison with maxillary teeth. Pain was absent in 63% of anterior teeth compared with 44% in posterior ones (P < 0.01). Interventions shorter than 45 min resulted in a significantly higher percentage of pain absence (P < 0.05). Root canal treatment was significantly (P < 0.05) more painful in teeth with irreversible pulpitis and acute apical periodontitis compared to the group with necrotic pulps and chronic apical periodontitis (P = 0.049). CONCLUSIONS: Root canal treatment in teeth with irreversible pulpitis and acute apical periodontitis was more painful. Age, tooth type and length of the treatment were factors associated with increased risk for pain experienced during the procedure. Knowledge of pain levels endured by patients will allow dentists to decide when to use supplemental local anaesthesia.

Nitric oxide promotes the progression of periapical lesion via inducing macrophage and osteoblast apoptosis.

This study aimed to elucidate the modulation by nitric oxide (NO) of the apoptosis of macrophages and osteoblasts, the essential cellular components in the development of periapical lesions. Lipopolysaccharide (LPS) induced prominent nitrite synthesis in J774 mouse macrophage cell lines. Exposure to LPS induced obvious apoptosis in J774 cells, whereas transient transfection with murine inducible nitric oxide synthase (iNOS), small interfering RNA (siRNA) diminished this effect. Tumor necrosis factor-alpha (TNF-alpha) and S-nitroso-N-acetyl-DL-penicillamine (SNAP) (a NO donor) triggered apoptosis in UMR-106 rat osteoblastic cell lines and a synergistic effect was noted when TNF-alpha and SNAP were added to the medium together. Administration of siRNAs for c-Fos and c-Jun: components of activator protein-1 (AP-1) and transforming growth factor-beta1 attenuated the combined effect markedly. Terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) stain in a rat model of induced periapical lesion showed positive apoptotic signals in macrophages and osteoblasts. Administration of N(G)-monomethyl-l-arginine markedly diminished the extent of bone loss and the amounts of apoptotic macrophages and osteoblasts. In conclusion, NO mediates LPS-stimulated apoptosis of macrophages. It also induces osteoblast apoptosis and augments the pro-apoptotic effect of cytokines. Inhibition of NO synthesis in vivo attenuates apoptosis and the size of periapical lesions. Taken together, these results suggest that NO may promote the progression of periapical lesion by inducing the apoptosis of macrophages and osteoblasts.

Roots of the maxillary first and second molars in horizontal relation to alveolar cortical plates and maxillary sinus: computed tomography assessment for infection spread.

The purposes of this study were to investigate the horizontal relationship of the roots of maxillary molars with the cortical plates and the maxillary sinus and to investigate the influence of these relationships on the spread of odontogenic infection. Computed tomography images of 120 control subjects and 49 patients with infection originating in the maxillary first or second molar were investigated. In the control group, more than 60% of the first molar roots contacted both palatal and buccal cortical plates (type A), while such contact was not seen in more than 60% of second molars. The floor of maxillary sinus was most frequently observed at the level between the bifurcation and apices of roots in both first and second molars. In patients with infection, cortical changes were more frequently seen on the buccal side than on the palatal side, and 80% of patients with buccal cortical change showed the position in which the buccal roots were close to the buccal cortical plate. Mucosal thickening of the maxillary sinus was found in 87.8%. The buccopalatal spread of odontogenic infection originating in the maxillary first and second molars was influenced by the horizontal root position in relation to the cortices.