Alendronate inhibits osteocyte apoptosis and inflammation via IL-6, inhibiting bone resorption in periapical lesions of ovariectomized rats.

AIM: To evaluate the effect of alendronate (ALN) on the development of periapical lesions induced in ovariectomized rats. METHODOLOGY: Twenty-five rats were divided into three groups: sham (control), ovariectomy (OVX) and OVX + ALN. One day after OVX, animals from the OVX + ALN group received the medication via gavage. After 9 weeks, the first molars of all animals were submitted to periapical lesion induction. After 21 days, the animals were euthanized. Femurs were analysed for bone mineral density. The blocks of bone tissue containing the mandibular first molars were submitted to histotechnical processing and staining with haematoxylin and eosin (HE) for periapical lesion analysis under conventional microscopy. At the same time, the morphometric analysis of the periapical lesion area was performed in the fluorescence mode, as well as the histoenzimology for the quantification of osteoclasts and 4'-6-diamidino-2-phenylindole staining for the quantification of apoptotic osteocytes. In addition, the first maxillary molars were used for analysis of the gene expression of proinflammatory cytokines (IL-1ß, IL-6 and TNF-α) and osteoclastogenesis markers (RANKL/OPG). The results were submitted to ANOVA and Kruskal-Wallis tests and Tukey and Dunn post-tests (significance level of 5%). RESULTS: Ovariectomy reduced bone mineral density of the femur, and treatment with ALN was able to prevent bone loss (P < 0.001). Regarding the microscopic analysis of the periapical region, the sham and OVX + ALN groups had moderately increased periodontal ligament and inflammatory infiltrate, while the OVX group had these parameters increased intensely. The periapical lesions of the OVX group were significantly larger in area in comparison to the other groups (P < 0.001). The OVX group had the largest amount of apoptotic osteocytes, and ALN was able to prevent the apoptosis of these cells, in addition to significantly reducing IL-6 expression (P < 0.05). OVX and ALN had no effect on RANKL/OPG expression and did not influence the number of osteoclasts around the periapical lesion (P > 0.05). CONCLUSION: The hypoestrogenic condition induced by OVX aggravated bone resorption, inducing the death of osteocytes and provoking larger periapical lesions. ALN treatment inhibited osteocyte apoptosis and inflammation via IL-6, inhibiting bone resorption in periapical lesions of ovariectomized rats.

Palatogingival groove and root canal instrumentation.

AIM: To evaluate the morphology and impact of root canal preparation in maxillary incisors with palatogingival grooves (PGG). METHODOLOGY: Twenty extracted human maxillary incisors with PGG were subjected to macroscopic analysis and scanning electron microscopy analysis (SEM). The following characteristics of the PGG were evaluated: depth, point of origin in the cingulum, extension and position on the lingual surface. Furthermore, the presence of calculus, communications between the root canal system and the PGG, and root resorptions were investigated. The root canals were subsequently instrumented with K-files of three consecutive sizes. The teeth were sectioned, and the axial plane of each tooth section was imaged using SEM before and after instrumentation. The distance between the root canal walls and the PGG was calculated according to the location. Additionally, the distance between canal walls and cementum was measured at three different sites, to verify if instrumentation influenced dentine removal on a specific wall in teeth with PGG. Statistical analysis was performed using the Mann-Whitney or Student's t-test (P < 0.05). RESULTS: Macroscopic analysis revealed that a deep groove was most frequently observed (75%), followed by a depression/shallow groove (25%) (P < 0.05). PGG typically originated in the distal margin ridge of the cingulum (65%) (P < 0.05), extending only to the middle (45%) or up to the apical (50%) third of the root (P < 0.05). Additionally, PGGs were typically located on the distal aspect of the lingual surface (70%) (P < 0.05). Calculus was concentrated on the surface of the crown and cementum-enamel junction (P < 0.05). Communication between the root canal and PGG was present in 35% of teeth, and root resorptions were noted in 50% of teeth. The distance between the external root surface and the pulp cavity was significantly narrower after instrumentation (P < 0.05); however, root canal preparation did not influence dentine removal on the specific wall associated with the groove (P > 0.05). CONCLUSIONS: Palatogingival grooves were characteristically deep and originated from the distal margin of the cingulum. Although it has been associated with a thinner root wall, root canal preparation did not influence the thickness of the specific wall in the maxillary incisors with PGG.

Novel endodontic sealers induce cell cytotoxicity and apoptosis in a dose-dependent behavior and favorable response in mice subcutaneous tissue.

OBJECTIVES: The objective of the present study is to evaluate the in vitro cytotoxicity and in vivo biocompatibility of two novel endodontic sealers: RealSeal XT1 and Sealapex Xpress on the subcutaneous connective tissue of mice. MATERIALS AND METHODS: The cytotoxicity was assessed by cell viability using the MTT assay (one-way ANOVA), trypan blue test (Mann-Whitney) and cell apoptosis by flow cytometer. For the subcutaneous study, polyethylene tubes filled with the sealers were implanted in 70 BALB/c mice: 6 experimental groups (n = 10/group) and 2 control groups with empty tubes (n = 5/group). At the end of experimental periods (7, 21, and 63 days), the tissue was removed and histotechnically processed. Angioblastic proliferation and edema (Fisher's exact test) were evaluated, besides thickness measurement (µm) of the reactionary granulomatous tissue and neutrophil counts (Kruskal-Wallis and Dunn's post test; Mann-Whitney) (α = 0.05). RESULTS: MTT assay, trypan blue, and analysis of apoptotic cells showed a dose-dependent direct effect: the more diluted the sealer, the less cytotoxic. Regarding the angioblastic proliferation and edema, difference between the sealers at 7 and 63 days occurred (p < 0.05). Both endodontic sealers initially promoted perimaterial tissue reaction as a foreign body granuloma and thus stimulated favorable tissue responses. CONCLUSIONS: Both sealers showed a dose-dependent effect and promoted satisfactory subcutaneous tissue response; the sealer Sealapex Xpress was less cytotoxic and more biocompatible than RealSeal XT. CLINICAL RELEVANCE: The step of root canal filling during endodontic treatment is highly important for the preservation of the periapical tissue integrity. Subcutaneous reaction to endodontic sealers enables scientific basis for clinical use.

The EULAR Outcome Measures Library: development and an example from a systematic review for systemic lupus erythematous instruments.

OBJECTIVES: Patient reported outcomes (PROs) are relevant in rheumatology. Variable accessibility and validity of commonly used PROs are obstacles to homogeneity in evidence synthesis. The objective of this project was to provide a comprehensive library of "validated PROs". METHODS: A launch meeting with rheumatologists, PROs methodological experts, and patients, was held to define the library's aims and scope, and basic requirements. To feed the library we performed systematic reviews on selected diseases and domains. Relevant information on PROs was collected using standardised data collection forms based on the COSMIN checklist. RESULTS: The EULAR Outcomes Measures Library (OML), whose aims are to provide and to advise on PROs on a user-friendly manner albeit based on scientific grounds, has been launched and made accessible to all. PROs currently included cover any domain and, are generic or specifically target to the following diseases: rheumatoid arthritis, osteoarthritis, spondyloarthritis, low back pain, systemic lupus erythematosus, gout, osteoporosis, juvenile idiopathic arthritis, and fibromyalgia. Up to 236 instruments (106 generic and 130 specific) have been identified, evaluated, and included. The systematic review for SLE, which yielded 10 specific instruments, is presented here as an example. The OML website includes, for each PRO, information on the construct being measured and the extent of validation, recommendations for use, and available versions; it also contains a glossary on common validation terms. CONCLUSIONS: The OML is an in progress library led by rheumatologists, related professionals and patients, that will help to better understand and apply PROs in rheumatic and musculoskeletal diseases.

Optimisation of disease assessments in juvenile idiopathic arthritis.

A variety of clinical measures are available for assessment of disease status of children with juvenile idiopathic arthritis (JIA) in clinical trials, clinical care and long-term outcome surveys. The American College of Rheumatology (ACR) Pediatric 30 remains the preferred primary outcome measure for registrative trials, although in most therapeutic studies performed in the 2000s patients were also evaluated for more stringent levels of improvement, that is, applying the ACR Pediatric 50, 70, 90, and 100 response criteria. Because the recent therapeutic advances have made inactive disease an achievable goal in most patients, it has been suggested that endpoints for future clinical trials incorporate the evaluation of disease activity state, namely the assessment of inactive disease and low disease activity. The introduction of the Juvenile Arthritis Disease Activity Score (JADAS) and the establishment of its cut-offs for various disease activity states may foster the implementation of the treat-to-target strategy in both clinical trials and routine practice. In recent years, there has been an increased focus on the inclusion of patient and child perspectives in health outcome measures through the use of parent/child-reported outcomes. Integration of these measures in the clinical evaluation is considered important as they reflect the parent's and child's perception of the disease course and effectiveness of therapeutic interventions. Future studies will show whether the newer imaging modalities, namely magnetic resonance imaging and ultrasound, can replace conventional radiography for the assessment of structural joint damage and its progression.

Root canal morphology of primary molars: a micro-computed tomography study.

AIM: This was to investigate the root canal morphology of primary molar teeth using micro-computed tomography. METHODS: Primary maxillary (n = 20) and mandibular (n = 20) molars were scanned at a resolution of 16.7 µm and analysed regarding the number, location, volume, area, structured model index (SMI), area, roundness, diameters, and length of canals, as well as the thickness of dentine in the apical third. Data were statistically compared by using paired-sample t test, independent sample t test, and one-way analysis of variance with significance level set as 5%. RESULTS: Overall, no statistical differences were found between the canals with respect to length, SMI, dentine thickness, area, roundness, and diameter (p > 0.05). A double canal system was observed in the mesial and mesio-buccal roots of the mandibular and maxillary molars, respectively. The thickness in the internal aspect of the roots was lower than in the external aspect. Cross-sectional evaluation of the roots in the apical third showed flat-shaped canals in the mandibular molars and ribbon- and oval-shaped canals in the maxillary molars. CONCLUSIONS: External and internal anatomy of the primary first molars closely resemble the primary second molars. The reported data may help clinicians to obtain a thorough understanding of the morphological variations of root canals in primary molars to overcome problems related to shaping and cleaning procedures, allowing appropriate management strategies for root canal treatment.

MRI versus conventional measures of disease activity and structural damage in evaluating treatment efficacy in juvenile idiopathic arthritis.

OBJECTIVE: To compare the American College of Rheumatology paediatric (ACRp) response criteria and conventional radiography with MRI findings in a cohort of patients with juvenile idiopathic arthritis. METHODS: Forty consecutive patients (30 girls, 10 boys; median age 10.8 years) with arthritis of the wrist starting treatment with disease-modifying antirheumatic drugs or biological agents were recruited. At 1-year follow-up the treatment response was assessed by ACRp criteria and radiographic progression using the adapted Sharp/van der Heijde method. Wrist MRIs were evaluated using both the paediatric-MRI and the OMERACT rheumatoid arthritis MRI scores. Sensitivity to change of clinical and imaging variables was assessed by standardised response mean (SRM) and relative efficiency (RE) was used to compare SRMs. RESULTS: ACRp90 responders showed a significantly higher decrease in MRI synovitis score (median change -4) than non-responders (median change 0), ACRp30-50 responders (median change 0) and ACRp70 responders (median change -1) (p=0.0006, Kruskal-Wallis test). Non-responders showed significantly higher radiographic progression than ACRp90 responders (pB=0.016). The MRI synovitis score showed a greater responsiveness to change (SRM 1.69) compared with the majority of ACR core set of variables. MRI erosion scores were less responsive than conventional radiography in detecting destructive changes (RE <1). MRI follow-up revealed no signs of inflammation in four out of 24 wrists with clinically inactive disease. CONCLUSION: Only ACRp90 responders showed a significant decrease in synovitis and the halting of structural damage, suggesting that levels of response higher than ACRp30 are more appropriate for assessing drug efficacy. The excellent responsiveness of MRI and its ability to detect subclinical synovitis make it a promising outcome measure.

Evaluation of cell culture cytotoxicity of five root canal sealers.

The cytotoxicity of four calcium hydroxide-based root canal sealers (Sealapex, CRCS, Apexit, and Sealer 26) and one zinc oxide-eugenol-based sealer (Fill Canal) was evaluated microscopically for morphological changes in rat peritoneal macrophages. The least cytotoxic sealer was Fill Canal, followed in increasing order of cytotoxicity by CRCS, Sealer 26, Apexit, and Sealapex.

Macroscopic and microscopic analysis of the palato-gingival groove.

With the objective of correlating the anatomical aspects of the palato-gingival groove with its etiology, diagnosis, and alternative treatments, 13 permanent maxillary incisors with palato-gingival grooves were selected from a large sample and subjected to macroscopic and microscopic analysis of groove morphology. The palato-gingival groove occurred most frequently on the lingual aspect of the lateral incisor (11 of 13), and its coronal and radicular extensions were on the disto-lingual surface of the incisors (7 of 13 and 6 of 13, respectively). Deformation of the contour of the pulp cavity was noted subjacent to the groove (9 of 13), along with diminished enamel and dentin thickness (11 of 13 and 13 of 13, respectively) and an increase in cement (12 of 13). The groove was observed extending to the apical third in nine specimens, and a direct communication between the pulp and periodontium was observed in only one case. From these examinations it is concluded that the palato-gingival groove can be clinically diagnosed, preventing subsequent problems; however microscopic analysis of the affected tooth is necessary to allow precise evaluation of the groove's extension and damage to the dental structure.

Cementoenamel junction: microscopic analysis and external cervical resorption.

There is a lack of data regarding the shapes and distribution of the mineralized tissue that composes the cementoenamel junction. A sample of 198 permanent human teeth was analyzed by optical microscopy and scanning electron microscopy. Scanning electron microscopy showed three types of tissue interrelations: enamel overlapped by cementum; enamel and cementum edge-to-edge; and a gap, revealing a strip of exposed dentin. Using optical microscopy, a fourth type of cementoenamel junction was observed: cementum overlapped by enamel. The distribution of the hard tissues found at the cementoenamel junction is unpredictable and irregular both for any tooth type (e.g. on cuspids) and on any one individual tooth. Based on these results and on analysis of the mechanisms involved in cervical root resorption, it is possible to consider the cervical region as prone to external resorption.

Nickel hypersensitivity reaction before, during, and after orthodontic therapy.

Nickel is a strong biological sensitizer and consequently may induce a delayed hypersensitivity reaction (type IV immune response). Because nickel is a component of the majority of the orthodontic alloys, the objectives of this cross-sectional study were to determine the prevalence of nickel hypersensitivity reaction before, during, and after orthodontic therapy with conventional stainless steel brackets and wires; to evidence the induction of this reaction by the orthodontic appliances; and to characterize the nickel hypersensitive persons. Nickel patch tests and a questionnaire were used to evaluate the hypersensitivity to this metal. The total sample consisted of 170 patients, 105 females and 65 males, from the orthodontic department at Bauru Dental School, University of São Paulo. They were divided into three groups as follows: A (n = 60), patients before the beginning of orthodontic therapy; B (n = 66), patients currently undergoing orthodontic treatment, and C (n = 44), patients who had undergone orthodontic treatment previously. The chi-square test (chi2) showed an allergic reaction in 28.3% of the total sample with 23% female and 5.3% male. This indicated a gender difference (chi2 = 10.75, p < 0.001). There was a positive association between nickel hypersensitivity and previous personal allergic history to metals (chi2 = 34.88, p < 0.0001) as well as with the daily use of metal objects (chi2 = 11.95, p < 0.0005). There was no statistically significant difference in the prevalence of contact dermatitis among the three groups (chi2 = 0.39, p = 0.848). This suggests that orthodontic therapy with conventional stainless steel appliances does not initiate or aggravate a nickel hypersensitivity reaction.

Assessment of the antiexudative and antiproliferative activities of non-steroidal anti-inflammatory drugs in inflammatory models developed in rats by subcutaneous implantation of bacterial cell walls from the dental plaque.

A purified bacterial cell walls suspension from human dental plaque were biochemically prepared to serve as flogogenous agent in producing experimental inflammatory models in rats. In the vascular permeability inhibition assay (edemogenic test), the subcutaneous implantation of the flogogenous agent elicited an acute inflammatory reaction highly susceptible to the effects of the non-steroidal anti-inflammatory drugs (NSAIDs). The intradermal injection of the flogogenous agent in the dorsum of rats developed experimental granulomas also susceptible to the anti-inflammatory effects of the NSAIDs. Otherwise, the antimitotic effect of drugs was carried out in the model of cellular proliferation of duodenal mucosa of rats by incorporation of tritiated thymidine (3H TdR) in the DNA. These models of acute and chronic inflammation, and the antimitotic model permitted us to evaluate the anti-inflammatory and antimitotic effects of sulindac, ibuprofen, naproxen and glucametacin. In the antiexudative activity, evaluated by the edemogenic test, naproxen was the more effective drug followed by sulindac, ibuprofen and glucametacin (in a decreasing order of potency) to inhibit the exudative response induced by the bacterial cell walls suspension, in all experimental periods. In the chronic anti-inflammatory activity, evaluated by the granuloma inhibition assay, all drugs were capable to demonstrate effectiveness against the development of the experimental granulomas induced by an intradermal injection of the flogogenous agent. In the model of cellular proliferation, all tested drugs demonstrated antimitotic activity in all experimental periods (4, 6 and 8 days), also. Sulindac induced the higher antimitotic effect, in all experimental periods, followed by ibuprofen, naproxen and glucametacin in a decreasing order of efficacy. There was a positive correlation between the antiexudative, anti-proliferative, and antimitotic effects.

Secondary caries around amalgam restorations.

Secondary caries is one of the greatest causes for replacement of amalgam restorations. This study verified whether marginal defects in class I restorations could be a determining factor in the development of secondary caries. Fifty-five extracted premolars and molars whose occlusal surfaces were already restored with amalgam were selected. A macroscopic examination of these teeth was carried out to see whether there was a difference in the prevalence of caries beneath ditched and nonditched margins. To assess the presence of caries, a section was ground in each tooth so that the cut passed through a ditched margin and a better margin. This permitted assessment of the two types of margins that had been exposed to the same oral environment. Macroscopic examination revealed caries in 3.6% of the nonditched margins and caries in 20% of the ditched margins. Microscopic examination revealed caries in 47.06% of the nonditched margins and caries in 58.82% of the ditched margins. Statistical analysis supports the conclusion that the marginal defect itself is insufficient to determine the presence of secondary caries that surround the amalgam restoration on the occlusal surface.

Effect of intracanal dressings on repair and apical bridging of teeth with incomplete root formation.

Periapical repair and apical bridging were studied in dog's teeth with incomplete root formation and induced chronic periapical lesions treated with different dressings. A total of 75 root canals from the upper and lower premolars of 4 dogs approximately 6 months of age were chemo-mechanically prepared and filled with the following dressings: antibacterial dressing consisting of a calcium hydroxide+camphorated p-monochlorophenol paste applied for 7 days and followed by monthly renewed calcium hydroxide paste as temporary dressing at 30, 60 and 90 days (Group A); antibacterial dressing consisting of camphorated p-monochlorophenol alone for 7 days, followed by temporary dressing with calcium hydroxide paste renewed at 30, 60 and 90 days (Group B). A control group (Group C) received no dressings. Ninety days after the last calcium hydroxide paste (Groups A, B) and after the last irrigation/aspiration (Group C), the animals were killed, the maxillae and mandibles were removed, and the material submitted to routine histological processing and examination. Both root canal dressings, were of fundamental importance for apical repair and bridging. The apical bridging was predominantly complete in Group A, incomplete in Group B, and absent in Group C. The calcium hydroxide+camphorated p-monochlorophenol combination gave better results than camphorated p-monochlorophenol alone.

Histopathological spectrum of 112 cases of mucocele.

Mucoceles are mucous cysts related to obstruction or trauma of the minor salivary glands. The mucoceles may be lined by epithelium (mucous retention cyst) or covered by granulation tissue (extravasation cyst). This clinical and microscopic study of 112 cases of diagnosed mucoceles was carried out at the Department of Oral Pathology, School of Dentistry of São Paulo. Microscopically, the mucous extravasation cyst was the most commonly found (92.45%); however, mucous retention cysts were also observed (7.54%). Inflammatory cells mainly polymorphonuclear leukocytes and macrophages were found in the inner part of the mucus. The minor glands involved showed degeneration and metaplasia.

[Simultaneous oral and skin manifestations of herpes zoster. Report of a case]. / Manifestações bucais e cutâneas simultâneas do herpes zoster; relato de um caso.

A case of herpes zoster involving the trigeminal nerve, with simultaneous skin and oral manifestation is presented. The diagnostic and treatment used are discussed, emphasizing the necessity of an intraoral examination, when skin facial lesions are observed by professionals.

[Oral manifestations of acute leukemia]. / Manifestações bucais das leucemias agudas.

The oral manifestation of leukemias is in some cases, the first clinical sign of the disease, being its recognition by the Dentist of capital importance to the adequate orientation of patient. In this manifestation had been shown, and the function of Dentist in the control and maintenance of oral health of leukemic patients in treatment had been emphasized.

Comparison of subcutaneous connective tissue responses among three different formulations of gutta-percha used in thermatic techniques.

A study of the subcutaneous connective tissue response of 24 white rats to three different formulations of gutta-percha was undertaken. The prepared specimens were examined under the light microscope after intervals of 7, 21, 60 and 120 days. The results showed identical tissue responses after the initial period of 7 days. However, after 120 days the gutta-percha supplied with the Ultrafil system presented mature granulation tissue with neither oedema nor vascular congestion, in contrast to the responses observed with the McSpadden and Obtura formulations.

Keratoacanthoma versus squamous cell carcinoma of the lower lip.

The authors' aim in this study is to discuss and review, from the presentation of a keratoacanthoma case with a clinical diagnosis of squamous cell carcinoma, the clinical and histologic criteria for a differential diagnosis between these two lesions, as well as to analyze the factors presumably involved in keratoacanthoma formation.