Novel molecular cues for dental defects in hypophosphatasia.

Mineralization disorders with a broad range of etiological factors represent a huge challenge in dental diagnosis and therapy. Hypophosphatasia (HPP) belongs to the rare diseases affecting predominantly mineralized tissues, bones and teeth, and occurs due to mutations in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (TNAP). Here we analyzed stem cells from bone marrow (BMSCs), dental pulp (DPSCs) and periodontal ligament (PDLSCs) in the absence and presence of efficient TNAP inhibitors. The differentiation capacity, expression of surface markers, and gene expression patterns of donor-matched dental cells were compared during this in vitro study. Differentiation assays showed efficient osteogenic but low adipogenic differentiation (aD) capacity of PDLSCs and DPSCs. TNAP inhibitor treatment completely abolished the mineralization process during osteogenic differentiation (oD). RNA-seq analysis in PDLSCs, comparing oD with and without TNAP inhibitor levamisole, showed clustered regulation of candidate molecular mechanisms that putatively impaired osteogenesis and mineralization, disequilibrated ECM production and turnover, and propagated inflammation. Combined alteration of cementum formation, mineralization, and elastic attachment of teeth to cementum via elastic fibers may explain dental key problems in HPP. Using this in vitro model of TNAP deficiency in DPSCs and PDLSCs, we provide novel putative target areas for research on molecular cues for specific dental problems in HPP.

Oral manifestations of Langerhans cell histiocytosis with unusual histomorphologic features.

Langerhans cell histiocytosis (LCH) is a bone marrow-derived immature myeloid dendritic cell proliferative disorder with diverse clinical manifestations commonly involves bone, skin, lymph node and lung. Oral involvement is uncommon. Intraoral lesions can be the first sign of either a localized LCH or clinically undiagnosed systemic LCH, predates systemic manifestations of LCH, or an early indicator of recurrence in known cases. Clinically, it can be mistaken for primary oral and dental inflammatory, infectious and neoplastic lesions. Histologically, diagnostic challenges may arise because of the nature of oral and dental specimens, different tissue reaction patterns and variations in histomorphology of LCH. We performed a retrospective review study over 10 years. We searched for diagnosed cases of LCH. We retrieved and reviewed cases of LCH with oral involvement. We found 54 cases of LCH, four (7.4%) with oral involvement. The age range was between 1 and 27 years with an average age of 13.7 years. They were males. They were clinically confused with abscess, cysts, infection, granulation tissue and other neoplastic lesions. Histologically, they showed different histopathologic features including different patterns of necrosis, granulomas, allergic-like inflammation, superimposed infection, stomatitis, cyst and sinus formation, foreign body giant cell reaction, and foci mimicking lymphomas and metastasis. Certain cytologic features were helpful hints. In doubtful cases, immunohistochemistry helped confirm the diagnosis. Because of the multiple fragmented nature of oral specimens with different tissue reaction patterns, the diagnostic Langerhans cells may be missed or misinterpreted. Oral LCH may be confused with infectious, inflammatory, benign and malignant neoplastic lesions because of its variable clinical presentations and its heterogeneous histomorphologic features. Pathologists have an important role in guiding clinicians to the correct diagnosis and patients' management. They should be familiar with the different histomorphologic patterns to avoid pitfalls. Attention to certain morphologic features and immunohistochemistry should help resolve challenging cases.

Oral lymphoid lesions: a 47-year clinicopathological study in a Brazilian population.

We performed an epidemiological, clinical and histopathological analysis of oral lymphoid lesions (OLLs) during a 47-year period. Data regarding patient age, sex, duration, location, symptomatology, type of growth, implantation, staining, presence of ulceration and bleeding of all cases were compiled from the clinical data. For the histopathological analyses, all slides stained by H/E were reassessed. During the analyzed period, 14,565 patients with oral and maxillofacial lesions were diagnosed, with 45 cases diagnosed as OLLs. The most prevalent location was the tongue. Females were more affected, and the mean age was 40.8 years. OLLs presented a heterogeneous frequency, with the prevalence of reactive lesions (42.3%) followed by developmental lesions (35.6%). Among the reactive lesions, foreign body granulomas were the most common. Regarding diagnosed neoplasms, malignant represented 13.2% of the cases. The average time of evolution of OLLs in general was of 22.2 months. Regarding the histopathological characteristics, the presence of primary lymphoid follicles was observed in 37.8% of the cases, while inflammatory infiltrates were diffuse in 66.7% and epimyoepithelial islands were observed in 13.3%. Our study concludes that OLLs involves a broad spectrum of lesions that share the presence of the lymphoid component, which can range from indolent to more aggressive behavior.

Orthodontically Relevant Manifestations in People with Rare Diseases.

BACKGROUND: Approximately 15% of all rare diseases occur with orofacial manifestations. Symptoms and manifestations of relevance to orthodontists represent a considerable proportion of these diseases and require appropriate strategies for their treatment. This article provides an overview of the orthodontically relevant manifestations of rare diseases. MATERIAL AND METHODS: Overall, 3,639 rare diseases listed at the Orphanet, OMIM or Pubmed database were evaluated for orofacial manifestations. All rare diseases which were indicated with at least one orofacial manifestation were recorded in a database for rare diseases with orofacial manifestations called "ROMSE," which was developed by the authors. All the rare diseases were analysed with regard to orthodontically relevant orofacial manifestations, such as dysgnathia, changes in the number of teeth, failures of eruption, pathologies of bone metabolism or orofacial clefts. For all rare diseases with orthodontic relevance, an exact analysis was undertaken. RESULTS: The orthodontically relevant orofacial manifestation termed dysgnathia is described in 151 of 535 identified rare diseases (28.2%). In these 151 rare diseases, 15 different subforms of dysgnathia, in the sense of skeletal misdevelopments of the jaws but without dental abnormalities, were described. Also changes in the number of teeth (17.9%), orofacial clefts (27.6%), failures of eruption (8.4%) and pathologies of the bone (2.1%) were described. CONCLUSIONS: Orthodontics play an important role in the diagnosis and treatment of orofacial manifestations in rare diseases. Databases such as ROMSE are a first step toward providing valid information in publicly accessible databases.

A Clinicopathologic Study of Oral Changes in Gastroesophageal Reflux Disease, Gastritis, and Ulcerative Colitis.

OBJECTIVES: The aim and objectives of this study are to identify oral changes in certain gastrointestinal (GI) diseases, namely gastroesophageal reflux disease (GERD), ulcerative colitis, gastritis, and to evaluate these oral symptoms as indicators for assessing GI disorders. MATERIALS AND METHODS: In this study, the oral manifestations of various GI disorders were assessed in a varying age group of 250 patients in Government Stanley Medical College and Hospital, Chennai. Out of 250 patients, 142 were affected by GERD, 99 were affected by gastritis, and 9 patients were affected by ulcerative colitis. Of these patients, 177 were males and 73 were females. RESULTS: Evaluation of patients with gastritis revealed that 66.7% affected with gingivitis, 19.2% with dental erosion on the palatal and lingual aspects of maxillary and mandibular teeth predominantly in the anterior region, 10.1% with periodontitis, 2% with gingival erythema. Among the patients with GERD, 44% of the cases showed dental erosion, 25.5% periodontitis, 9.9% gingivitis, 5.7% gingival erythema, 2.8% palatal erythema, 2.1% gingival ulcers, glossitis 2%, 1.4% floor of the mouth erythema, and 0.7% erythema of the tongue. Patients with ulcerative colitis showed 44.4% of gingival erythema, 33.3% of dental erosions, and 22.2% of gingival ulcers and periodontitis. CONCLUSION: In our study of 250 patients, oral manifestations were observed in 88% of the patients. Both soft tissue and hard tissue changes were evident. There was a high correlation between various GI disease and dental erosion, erythema at various sites of the oral cavity, oral ulcers, gingivitis, periodontitis, and glossitis. Careful evaluation of oral cavity may unveil many GI disorders and help the patient by providing early diagnosis, which further facilitates the prognosis.

The Prosthodontic Pathway for Patients with Anomalies Affecting Tooth Structure.

There are a number of anomalies that affect the structure of the dental hard tissues which impact upon the form, function and aesthetics of the dentition. Understanding the challenges these conditions pose will enable dentists to manage the functional and aesthetic problems with restorative techniques better. This article will present cases that demonstrate the different conditions, the restorative challenges experienced and a variety of restorative treatments in the management of these conditions. Clinical relevance: Awareness of different anomalies affecting tooth structure that may present to the dental practitioner is necessary. Clinicians should appreciate the specific restorative challenges that may arise in treating such patients and the possible treatment options that may be available.

A clinical multicenter study of orofacial features in 26 brazilian patients with different types of mucopolysaccharidosis.

PURPOSE: This study aimed to describe the orofacial features of 26 unrelated Brazilian patients with mucopolysaccharidosis and to verify any possible associations between these findings and specific types of mucopolysaccharidosis. METHODS: Patients were diagnosed with mucopolysaccharidosis and clinically evaluated. Following consent, a clinical assessment form was completed. Facial and intraoral examination was performed by evaluating facial pattern, malocclusions, dental caries, and tooth identification. RESULTS: Midface deficiency, increased lower facial third, anterior open bite, convex profile, macroglossia, gingival enlargement, and spaced arches were the most frequently observed features. These findings did not allow a differential diagnosis among the different types of mucopolysaccharidosis, except for pitting enamel, which significantly associated with mucopolysaccharidosis IVA (P < .001). Open bite was associated with mucopolysaccharidosis types I, II, III, and VI; however, only one patient with mucopolysaccharidosis IVA expressed this feature (P = .043). CONCLUSIONS: Our results suggest that pitted enamel in patients with mucopolysaccharidosis is most likely a feature of mucopolysaccharidosis type IVA; whereas, open bite is rarely observed in these patients. Orofacial features in mucopolysaccharidosis may help pediatric dentists recognize this disorder and minimize the delay between the initial signs/symptoms and diagnosis of the disease. Future studies should focus on the longitudinal manifestations, expression, and severity of mucopolysaccharidosis-associated orofacial anomalies.

The use of micro-computed tomography in the diagnosis of dental and oral disease in rabbits.

BACKGROUND: The aim of this study was to investigate the use of a newly developed micro-computed tomography (micro-CT) system for the diagnosis of oral pathologies in small animals, using the rabbit as a model. The diagnosis of dental diseases in rabbits is usually based on oral endoscopy and radiographic imaging, but detailed pathological diagnosis using these methods is frequently difficult. Micro-CT was used in this study to address this challenge. RESULTS: This study was conducted using 50 privately owned rabbits, presented to our hospital due to loss of appetite or difficulty feeding. Image recording times were 18 s in normal mode and 120 s in fine mode. The animals were maintained in the required position for scanning via the administration of sedatives. Micro-CT captured with a slice thickness of 60-120 mm has excellent spatial resolution, and is suitable for the clinical diagnosis of dental diseases in rabbits weighing 1-3 kg. CONCLUSIONS: Micro-CT can yield more detailed data than radiography or conventional CT. This study determined that this novel imaging modality can be utilized for the accurate assessment of dental and oral diseases in rabbits.

OK-432 sclerotherapy of lymphatic malformation in the head and neck: factors related to outcome.

BACKGROUND: No previous study to the best of our knowledge has examined the multiple factors related to the outcome of OK-432 sclerotherapy of lymphatic malformations. OBJECTIVE: This study aimed to assess factors related to the successful outcome of OK-432 sclerotherapy for lymphatic malformations in the head and neck region. MATERIALS AND METHODS: During a 6-year period, OK-432 sclerotherapy was performed in 26 patients with lymphatic malformations. Several factors related to the efficacy of OK-432 sclerotherapy were evaluated, including the type (macrocystic or microcystic), the maximum lesion diameter, amount and hemorrhagic cytology of the aspirate, degree of aspiration, injected dose of OK-432 and post-therapy inflammation-related symptom. In all cases, ultrasound (US) follow-up was performed. RESULTS: Of the 26 cases, 13 (50%) showed successful elimination of the lymphatic malformations in the follow-up US after the initial session, and all successful cases were of the macrocystic type. The type of lymphatic malformation and the success of OK-432 sclerotherapy were significantly related (P = 0.0149). Of the 16 cases of complete aspiration, 11 (68.8%) showed a successful outcome. Further, of the 17 cases with inflammation-related symptom, 13 (76.5%) showed a successful outcome. While the degree of aspiration and presence of inflammation-related symptom showed a significant relationship with the success of OK-432 sclerotherapy (P < 0.05), no other factors showed a significant relationship. CONCLUSION: The study results suggest that the macrocystic type and complete aspiration of cystic contents were important factors for the success of OK-432 sclerotherapy of lymphatic malformations, and that inflammation-related symptom was a predictor of a successful outcome.

[Oral cavity pathology by renal failure].

The analysis of the scientific literature devoted to organ and tissue changes of oral cavity at the chronic renal insufficiency (CRI)is made. The number of patients in an end-stage of CRI constantly increases and patients receiving renal replacement therapy including hemodialysis, peritoneal dialysis or renal transplantation will comprise an enlarging segment of the dental patient population. Owing to CRI and its treatment there is a set of changes of teeth and oral cavity fabrics which remain even in a end-stage. Renal replacement therapy can affect periodontal tissues including gingival hyperplasia in immune suppressed renal transplantation patients and increased levels of bacterial contamination, gingival inflammation, formation of calculus, and possible increased prevalence and severity of destructive periodontal diseases. Besides, the presence of undiagnosed periodontitis may have significant effects on the medical management of the patients in end-stage of CRI.

Dental anatomy and pathology encountered on routine CT of the head and neck.

OBJECTIVE: Although dental CT is not routinely performed at hospital imaging centers, dental and periodontal disease can be recognized on standard high-resolution CT of the neck and face. These findings can have significant implications with regard to not only dental disease, but also diseases of the sinuses, jaw, and surrounding soft tissues. This article serves to review dental and periodontal anatomy and pathology as well as other regional entities with dental involvement and to discuss the imaging findings. CONCLUSION: Recognition of dental and periodontal disease has the potential to affect management and preclude further complications, thereby preserving the smile, one of the most recognizable and attractive features of the human face and, unfortunately, often disease ridden. Although practicing good oral hygiene and visiting the dentist for regular examinations and cleanings are the most effective ways to prevent disease, some patients do not take these preventative measures. Thus, radiologists play a role in diagnosing dental disease and complications such as chronic periodontitis and abscesses, nonhealing fractures and osteomyelitis, oroantral fistulas, tumoral diseases, osteonecrosis of the jaw, and other conditions.

A review of paediatric oral and maxillofacial pathology.

This review aims to summarise common paediatric oral and maxillofacial pathology. It will focus on lesions that have a particular predilection for children, lesions that impart significant morbidity or rare and important entities which paediatric specialists may be less familiar with. Although the vast majority of pathology encountered will be benign or require minimal intervention, there are also lesions that may require urgent referral to an appropriate specialist, multidisciplinary team care and significant surgery. Recognition and appreciation of the clinicopathological features should facilitate an appreciation that the growth, anatomy, physiology or relationship of the maxillofacial structures may have been altered by the pathological entity or treatment received.

Paediatric oral pathology in a Chilean population: a 15-year review.

BACKGROUND: There is only limited information available in Chile regarding the frequency of biopsied oral lesions in paediatric patients. AIM: To determine the frequency of histologically diagnosed lesions in oral pathology specimens from paediatric patients in a Chilean population over a 15-year period. DESIGN: Oral and maxillofacial biopsy records of patients aged 16 years or under were retrieved by visual inspection from the archives of public and private Oral Pathology Health Services in Valdivia, Chile, during the period 1995-2010. Records that contained anatomical site and histopathological diagnoses of the specimen were included. The study population was divided into three age groups according to dentition stage. Oral lesions were classified as inflammatory/reactive, cystic, or tumour/tumour-like. RESULTS: A total of 542 biopsy specimens from children were found. These represented 20.6% of all oral biopsies. The average age was 11.1 years, with female predilection. The most common category of oral lesions was inflammatory/reactive (75.8%), followed by tumour/tumour-like (16.8%) and cystic (7.4%) lesions. The mucocele was the most commonly found lesion, followed by pyogenic granuloma and irritation fibroma, which taken together accounted for 63.8% of all paediatric oral biopsies. The most common localisation for lesions was the lower lip (50.3%). CONCLUSIONS: The vast majority of oral lesions found were predominantly inflammatory/reactive and benign types, although malignant lesions can present themselves in children.

Oral impacts and their association with tooth loss in Sri Lankan adults.

OBJECTIVES: To determine the prevalence of oral impacts and the association between tooth loss and oral impacts in Sri Lankan adults. BASIC RESEARCH DESIGN: A cross-sectional study where the data were collected by means of a pre-tested interviewer administered questionnaire and an oral examination. PARTICIPANTS: 916 > or = 40 year olds from the Colombo district. MAIN OUTCOME MEASURES: Oral impacts were assessed using a validated Sinhalese translation of the Oral Health Impact Profile-14. RESULTS: The prevalence of oral impacts was 27%. The most commonly reported impacts were in the domain of physical pain: "pain" and "uncomfortable to eat". Of the 14 oral impacts, tooth loss was associated with only 6 impacts. According to the multiple logistic regression analysis, the prevalence of oral impacts was independently associated with the number of missing teeth, missing anterior teeth and the number of natural occluding premolar pairs. CONCLUSIONS: The number of missing teeth and the position of teeth were associated with the reporting of oral impacts in this sample of adults. As the position of missing teeth was related to oral impacts, it could be concluded that all missing teeth do not have the same adverse effect on the physical and psychosocial well-being of the subjects.

Classification of patients by the function of dentition, postural, and autonomic nervous systems.

Cluster analysis of the results of studies of the functional status of the dentition postural and autonomic nervous systems in 251 patients (129 men and 122 women) aged 20-60 years was carried out. European stabilometry variant was used. The patients could be distributed into two groups by the results of cluster analysis. By functional parameters, groups 1 and 2 could be defined as patients with decompensated and compensated functional status, respectively. The characteristics of the functional status of patients in the two groups are presented.

Osteomyelitis in a Paleozoic reptile: ancient evidence for bacterial infection and its evolutionary significance.

We report on dental and mandibular pathology in Labidosaurus hamatus, a 275 million-year-old terrestrial reptile from North America and associate it with bacterial infection in an organism that is characterized by reduced tooth replacement. Analysis of the surface and internal mandibular structure using mechanical and CT-scanning techniques permits the reconstruction of events that led to the pathology and the possible death of the individual. The infection probably occurred as a result of prolonged exposure of the dental pulp cavity to oral bacteria, and this exposure was caused by injury to the tooth in an animal that is characterized by reduced tooth replacement cycles. In these early reptiles, the reduction in tooth replacement is an evolutionary innovation associated with strong implantation and increased oral processing. The dental abscess observed in L. hamatus, the oldest known infection in a terrestrial vertebrate, provides clear evidence of the ancient association between terrestrial vertebrates and their oral bacteria.

Morphological study of the palatal gingiva of the maxillary first molar in the type 2 diabetes mellitus model rat.

SUMMARY: We studied morphological changes at the maxillary first molar in a model rat for type 2 spontaneous diabetes mellitus (DM), the Goto-Kazizaki (GK) rat, vs. the normal 8-week-old Wistar rat. Serial frontal sections of the gingiva of the maxilla with the bone were prepared from the rats. Image analyses, performed on light micrographs of the hematoxylin-eosin stained specimens, allowed comparison of the thickness of the keratinized, granular, prickle, and basal layers. In addition, the cell population of the granular and prickle layers and the cross-sectional area of the connective tissue beneath the mucosal epithelium were examined. The thickness of the capillary of the maxillary first molar was determined by image analysis of scanning electron micrographs of microvascular corrosion cast specimens. We found that the thickness of the keratinized, granular, and prickle layers was significantly higher in the DM vs. normal group, as were the cell population of the granular and prickle layers. In contrast, the cross-sectional area of the connective tissue beneath the mucosal epithelium, and the thickness of the capillary were significantly lower in the DM vs. normal sections. Therefore, we consider that the DM-associated hyperglycemia causes hypertrophy of the mucosal epithelium, atrophy of the connective tissue beneath the mucosal epithelium, and microangiopathy of the capillary of the palatal gingiva of the maxillary first molar in the GK rat.

Occlusal fissures of the equine cheek tooth: prevalence, location and association with disease in 91 horses referred for dental investigation.

REASON FOR PERFORMING STUDY: Fissures of the occlusal surface of the equine cheek tooth are poorly understood and their association with dental disease is unknown. OBJECTIVE: To describe the prevalence and location of occlusal fissures in the cheek teeth (CT) of a group of horses referred for dental investigation/treatment, and determine association with intercurrent dental disease. METHODS: Digital video recordings of oral endoscopic examinations for all horses referred to the Rossdales Equine Hospital for dental investigation from November 2006 to June 2009 were reviewed. Location of occlusal fissures in relation to both Triadan tooth position and pulpar secondary dentine was recorded; direction of fissure and concurrent involvement of enamel was also documented. The CT location considered at the time of examination to be the primary site/s of disease was correlated with presence of fissures on these teeth. RESULTS: 91 cases meeting the inclusion criteria were identified. Occlusal fissures were documented in 58.2% (53/91) cases, with a total of 227 CT being affected. Fissures were most prevalent mid-arcade. The majority (92.1%) of fissures in maxillary CT were associated with the caudal palatal pulp horn. Fissures in mandibular CT were predominantly associated with the buccal pulp horns (95.7%). There was no significant difference in the median number of CT with fissures in relation to gender. There was no correlation between age (r(2)= 0.01) of horse and number of CT with fissures. A significantly greater number of CT with multiple occlusal fissures was found in mandibular compared to maxillary arcades. No correlation was found between presence of fissures and location of individual CT considered to be primarily responsible for presentation. CONCLUSIONS: Occlusal fissures in this group of animals were common and not correlated to primary site of dental disease. POTENTIAL RELEVANCE: In horses subjected to dental investigation, occlusal fissures of the cheek teeth should not be considered an indicator of tooth compromise. Location and direction of fissure propagation in most cases is inconsistent with occlusal fissures being causally implicated in slab fractures of cheek teeth, although site predilection may indicate a possible association with masticatory forces.

Elodontoma in captive southern red-backed voles (Myodes gapperi).

Five southern red-backed voles (Myodes gapperi) of the first generation of a wild-caught breeding colony were presented with lesions at the maxillary incisors consistent with elodontoma. The affected animals had a history of chronic weight loss, were >16 months of age, and were siblings. Radiographs of the head showed multiglobular to irregularly outlined mineral opacity masses at the apices of the maxillary incisors. On necropsy, maxillary incisor teeth were not grossly visible, and a gingival ulceration was observed at the expected site of eruption. Microscopically, the apical region of the maxillary incisors was thickened or replaced by irregular dental tissue masses consistent with elodontoma. This is the first report to describe elodontoma in red-backed voles.