An unusual splice defect in the mitofusin 2 gene (MFN2) is associated with degenerative axonopathy in Tyrolean Grey cattle

Tyrolean Grey cattle represent a local breed with a population size of approximately 5000 registered cows. In 2003, a previously unknown neurological disorder was recognized in Tyrolean Grey cattle. The clinical signs of the disorder are similar to those of bovine progressive degenerative myeloencephalopathy (weaver syndrome) in Brown Swiss cattle but occur much earlier in life. The neuropathological investigation of an affected calf showed axonal degeneration in the central nervous system (CNS) and femoral nerve. The pedigrees of the affected calves suggested a monogenic autosomal recessive inheritance. We localized the responsible mutation to a 1.9 Mb interval on chromosome 16 by genome-wide association and haplotype mapping. The MFN2 gene located in this interval encodes mitofusin 2, a mitochondrial membrane protein. A heritable human axonal neuropathy, Charcot-Marie-Tooth disease-2A2 (CMT2A2), is caused by MFN2 mutations. Therefore, we considered MFN2 a positional and functional candidate gene and performed mutation analysis in affected and control Tyrolean Grey cattle. We did not find any non-synonymous variants. However, we identified a perfectly associated silent SNP in the coding region of exon 20 of the MFN2 gene. This SNP is located within a putative exonic splice enhancer (ESE) and the variant allele leads to partial retention of the entire intron 19 and a premature stop codon in the aberrant MFN2 transcript. Thus we have identified a highly unusual splicing defect, where an exonic single base exchange leads to the retention of the preceding intron. This splicing defect represents a potential explanation for the observed degenerative axonopathy. Marker assisted selection can now be used to eliminate degenerative axonopathy from Tyrolean Grey cattle.

Immunohistochemical localization of osteoclastogenic cell mediators in feline tooth resorption and healthy teeth

Tooth resorption is among the most common and most challenging problems in feline dentistry It is a progressive disease eventually leading to tooth loss and often root replacement. The etiology of moth resorption remains obscure and to date no effective therapeutic approach is known. The present study is aimed at assessing the reliability of radiographic imaging and addressing the possible involvement of receptor activator of NF kappa B (RANK), its ligand (RANKL), and osteoprotegerin (OPG) in the process of tooth resorption. Teeth from 8 cats were investigated by means of radiographs and paraffin sections followed by immunolabeling. Six cats were diagnosed with tooth resorption based on histopathologic and radiographic findings. Samples were classified according to a four-stage diagnostic system. Radiologic assessment of tooth resorption correlated very strongly with histopathologic findings. Tooth resorption was accompanied by a strong staining with all three antibodies used, especially with anti-RANK and anti-RANKL antibodies. The presence of OPG and RANKL at the resorption site is indicative of repair attempts by fibroblasts and stromal cells. These findings should be extended by further investigations in order to elucidate the pathophysiologic processes underlying tooth resorption that might lead to prophylactic and/or therapeutic measures. J Vet Dent 27(2); 75 - 83, 2010

Complication and failure rates of fixed dental prostheses in patients treated for periodontal disease

Objectives: To evaluate the biological and technical complication rates of fixed dental prostheses (FDP) with end abutments or cantilever extensions on teeth (FDP-tt/cFDP-tt) on implants (FDP-ii/cFDP-ii) and tooth-implant-supported (FDP-ti/cFDP-ti) in patients treated for chronic periodontitis. Material and methods: From a cohort of 392 patients treated between 1978 and 2002 by graduate students, 199 were re-examined in 2005. Of these, 84 patients had received ceramo-metal FDPs (six groups). Results: At the re-evaluation, the mean age of the patients was 62 years (36.2–83.4). One hundred and seventy-five FDPs were seated (82 FDP-tt, 9 FDP-ii, 20 FDP-ti, 39 cFDP-tt, 15 cFDP-ii, 10 cFDP-ti). The mean observation time was 11.3 years; 21 FDPs were lost, and 46 technical and 50 biological complications occurred. Chances for the survival of the three groups of FDPs with end abutments were very high (risk for failure 2.8%, 0%, 5.6%). The probability to remain without complications and/or failure was 70.3%, 88.9% and 74.7% in FDPs with end abutments, but 49.8–25% only in FDPs with extensions at 10 years. Conclusions: In patients treated for chronic periodontitis and provided with ceramo-metal FDPs, high survival rates, especially for FDPs with end abutments, can be expected. The incidence rates of any negative events were increased drastically in the three groups with extension cFDPs (tt, ii, ti). Strategic decisions in the choice of a particular FDP design and the choice of teeth/implants as abutments appear to influence the risks for complications to be expected with fixed reconstruction. If possible, extensions on tooth abutments should be avoided or used only after a cautious clinical evaluation of all options.

[Multiple tooth resorption in an Italian greyhound]

An Italian greyhound was presented three times during a two-year period for dental prophylaxis due to periodontal disease. Clinical examination revealed lesions on several teeth. Radiographs revealed extensive resorptive root lesions. On histological examination, the presence of odontoclasts and signs of boney remodeling of the roots confirmed the resorptive nature of the lesions. Given the extent of the lesions, and poor prognosis with conservative treatment alone, teeth affected by the most severe resorption were extracted at each visit using a flap technique combined with alveolar vestibular osteotomy. Dental resorptive lesions are rarely detected in the dog but may be more frequent than previously thought. The routine use of dental radiographs can be used to reveal these lesions in the dog.

A Systematic Review of the Clinical Performance of Tooth-Retained and Implant-Retained Double Crown Prostheses with a Follow-Up of ≥3 Years

Purpose: The objective of this review was to systematically screen the literature for data related to the survival and complication rates observed with dental or implant double crown abutments and removable prostheses under functional loading for at least 3 years. Materials and Methods: A systematic review of the dental literature from January 1966 to December 2009 was performed in electronic databases (PubMed and Embase) as well as by an extensive hand search to investigate the clinical outcomes of double crown reconstructions. Results: From the total of 2412 titles retrieved from the search, 65 were selected for full-text review. Subsequently, 17 papers were included for data extraction. An estimation of the cumulative survival and complication rates was not feasible due to the lack of detailed information. Tooth survival rates for telescopic abutment teeth ranged from 82.5% to 96.5% after an observation period of 3.4 to 6 years, and for tooth-supported double crown retained dentures from 66.7% to 98.6% after an observation period of 6 to 10 years. The survival rates of implants were between 97.9% and 100% and for telescopic-retained removable dental prostheses with two mandibular implants, 100% after 3.0 and 10.4 years. The major biological complications affecting the tooth abutments were gingival inflammation, periodontal disease, and caries. The most frequent technical complications were loss of cementation and loss of facings. Conclusions: The main findings of this review are: (I) double crown tooth abutments and dentures demonstrated a wide range of survival rates. (II) Implant-supported mandibular overdentures demonstrated a favorable long-term prognosis. (III) A greater need for prosthetic maintenance is required for both tooth-supported and implant-supported reconstructions. (IV) Future areas of research would involve designing appropriate longitudinal studies for comparisons of survival and complication rates of different reconstruction designs.

Chlorhexidine and preservation of sound tooth structure in older adults. A placebo-controlled trial

The Trial to Enhance Elderly Teeth Health (TEETH) was designed to test the impact of regular rinsing with a 0.12% chlorhexidine (CHX) solution on tooth loss, and the causes of tooth loss (caries, periodontal disease and trauma) were also investigated. This paper reports on the effectiveness of a 0.12% CHX solution for controlling caries using a tooth surface (coronal and root) survival analysis. A total of 1,101 low income elders in Seattle (United States) and Vancouver (Canada), aged 60-75 years, were recruited for a double-blind clinical trial and assigned to either a CHX (n = 550) or a placebo (n = 551) mouth rinse. Subjects alternated between daily rinsing for 1 month, followed by weekly rinsing for 5 months. All sound coronal and root surfaces at baseline were followed annually for up to 5 years. At each follow-up examination, those tooth surfaces with caries, restored, or extracted were scored as 'carious'. The hazard ratio associated with CHX for a sound surface to become filled, decayed, or extracted was 0.87 for coronal surfaces (95% confidence interval: 0.71-1.14, p = 0.20) and 0.91 for root surfaces (95% confidence interval: 0.73-1.14, p = 0.41). These findings suggest that regular rinsing with CHX does not have a substantial effect on the preservation of sound tooth structure in older adults.

Influence of residual pockets on progression of periodontitis and tooth loss: results after 11 years of maintenance

BACKGROUND: Limited evidence exists on the significance of residual probing pocket depth (PPD) as a predictive parameter for periodontal disease progression and tooth loss. AIM: The aim of this study was to investigate the influence of residual PPD >or=5 mm and bleeding on probing (BOP) after active periodontal therapy (APT) on the progression of periodontitis and tooth loss. MATERIAL AND METHODS: In this retrospective cohort, 172 patients were examined after APT and supportive periodontal therapy (SPT) for 3-27 years (mean 11.3 years). Analyses were conducted using information at site, tooth and patient levels. The association of risk factors with tooth loss and progression of periodontitis was investigated using multilevel logistic regression analysis. RESULTS: The number of residual PPD increased during SPT. Compared with PPDtooth loss with odds ratios of 5.8 and 7.7, respectively, at site and tooth levels. The corresponding odds ratios for PPD=6 mm were 9.3 and 11.0 and for PPD>or=7 mm 37.9 and 64.2, respectively. At patient level, heavy smoking, initial diagnosis, duration of SPT and PPD>or=6 mm were risk factors for disease progression, while PPD>or=6 mm and BOP>or=30% represented a risk for tooth loss. CONCLUSION: Residual PPD>or=6 mm represent an incomplete periodontal treatment outcome and require further therapy.

Cardiovascular disease and periodontitis: an update on the associations and risk

BACKGROUND: Associations between periodontitis and cardiovascular diseases have been recognized. MATERIAL AND METHODS: New literature since the last European Workshop on Periodontology has been reviewed. RESULTS: The lack of reliable epidemiological data on disease prevalence makes an assessment of the associations and risks between periodontitis and cardiovascular diseases difficult. Two recent meta-analysis reports have identified associations between periodontitis and cardiovascular diseases (odds ratios: 1.1-2.2). Different surrogate markers for both disease entities, including serum biomarkers, have been investigated. Brachial artery flow-mediated dilatation, and carotid intima media thickness have in some studies been linked to periodontitis. Studies are needed to confirm early results of improvements of such surrogate markers following periodontal therapy. While intensive periodontal therapy may enhance inflammatory responses and impair vascular functions, studies are needed to assess the outcome of periodontal therapies in subjects with confirmed cardiovascular conditions. Tooth eradication may also reduce the systemic inflammatory burden of individuals with severe periodontitis. The role of confounders remain unclear. CONCLUSIONS: Periodontitis may contribute to cardiovascular disease and stroke in susceptible subjects. Properly powered longitudinal case-control and intervention trials are needed to identify how periodontitis and periodontal interventions may have an impact on cardiovascular diseases.

[Periodontitis and cardiovascular disease]

The prevalence of periodontitis and cardiovascular disease (CVD) is high. A mixed infectious biofilm etiology of periodontitis is known but not fully established in CVD. Cofactors; smoking habits, stress, ethnicity, genetics, socioeconomics and age contribute to both diseases. The objectives of this report are to summarize factors in regards to CVD and periodontitis that are clinically relevant. The hypothesis behind a relationship between the two conditions can be founded in (I) shared infections etiology, (II) shared inflammatory response, (III) epidemiological and case-control studies, and (IV) periodontal studies demonstrating improvements of CVD markers. Streptococcus species in the S. mitis group, and S. anginosus group have been identified in periodontitis and are known as pathogens in endocarditis possibly transported from the oral cavity to the heart through bacteremia during dental therapies, and tooth brushing. Other periodontal bacteria such as Porphyromonas gingivalis, Fusobacterium nucleatum and Parvimonas micra are beta-lactamase producing and may contribute to antibiotic resistance (extended spectrum beta-lactamases). Other bacteria in CVD and periodontitis include Staphylococcus aureus, and Pseudomonas aeruginosa. Chlamydia pneumoniae and P. gingivalis lipopolyysaccharide capsels share homology and induce heat-shock protein activity and a cascade of proinflammatory cytokines. Associations between periodontitis and CVD have been presented in many studies when controlling for confounders. Other studies have demonstrated that periodontal therapies increase brachial artery flow rate and reduce serum inflammatory cytokine levels. Thus, physicians caring for subjects at CVD risk should consult with dentists/periodontists. Dentists must improve their medical knowledge and also learn to consult with physicians when treating patients at CVD risk.

Identification of pathogen and host-response markers correlated with periodontal disease

BACKGROUND: Periodontitis is the major cause of tooth loss in adults and is linked to systemic illnesses, such as cardiovascular disease and stroke. The development of rapid point-of-care (POC) chairside diagnostics has the potential for the early detection of periodontal infection and progression to identify incipient disease and reduce health care costs. However, validation of effective diagnostics requires the identification and verification of biomarkers correlated with disease progression. This clinical study sought to determine the ability of putative host- and microbially derived biomarkers to identify periodontal disease status from whole saliva and plaque biofilm. METHODS: One hundred human subjects were equally recruited into a healthy/gingivitis group or a periodontitis population. Whole saliva was collected from all subjects and analyzed using antibody arrays to measure the levels of multiple proinflammatory cytokines and bone resorptive/turnover markers. RESULTS: Salivary biomarker data were correlated to comprehensive clinical, radiographic, and microbial plaque biofilm levels measured by quantitative polymerase chain reaction (qPCR) for the generation of models for periodontal disease identification. Significantly elevated levels of matrix metalloproteinase (MMP)-8 and -9 were found in subjects with advanced periodontitis with Random Forest importance scores of 7.1 and 5.1, respectively. The generation of receiver operating characteristic curves demonstrated that permutations of salivary biomarkers and pathogen biofilm values augmented the prediction of disease category. Multiple combinations of salivary biomarkers (especially MMP-8 and -9 and osteoprotegerin) combined with red-complex anaerobic periodontal pathogens (such as Porphyromonas gingivalis or Treponema denticola) provided highly accurate predictions of periodontal disease category. Elevated salivary MMP-8 and T. denticola biofilm levels displayed robust combinatorial characteristics in predicting periodontal disease severity (area under the curve = 0.88; odds ratio = 24.6; 95% confidence interval: 5.2 to 116.5). CONCLUSIONS: Using qPCR and sensitive immunoassays, we identified host- and bacterially derived biomarkers correlated with periodontal disease. This approach offers significant potential for the discovery of biomarker signatures useful in the development of rapid POC chairside diagnostics for oral and systemic diseases. Studies are ongoing to apply this approach to the longitudinal predictions of disease activity.