Salivary Metabolomics of Well and Poorly Controlled Type 1 and Type 2 Diabetes.

Objective: The concentrations of endogenous metabolites in saliva can be altered based on the systemic condition of the hosts and may, in theory, serve as a reflection of systemic disease progression. Hemoglobin A1C is used clinically to measure long-term average glycemic control. The aim of the study was to demonstrate if there were differences in the salivary metabolic profiles between well and poorly controlled type 1 and type 2 subjects with diabetes. Subjects and Methods. Subjects with type 1 and type 2 diabetes were enrolled (n = 40). The subjects were assigned to phenotypic groups based on their current level of A1C: <7 = well-controlled and >7 = poorly controlled. Demographic data, age, gender, and ethnicity, were used to match the two phenotypic groups. Whole saliva samples were collected and immediately stored at -80°C. Samples were spiked using an isotopically labeled internal standard and analyzed by UPLC-TOF-MS using a Waters SYNAPT G2-Si mass spectrometer. Results: Unsupervised principal components analysis (PCA) and orthogonal partial least squares regression discrimination analysis (OPLS-DA) were used to define unique metabolomic profiles associated with well and poorly controlled diabetes based on A1C levels. Conclusion: OPLS-DA demonstrates good separation of well and poorly controlled in both type 1 and type 2 diabetes. This provides evidence for developing saliva-based monitoring tools for diabetes.

Exploring Effectiveness of Computer-Aided Planning in Implant Positioning for a Single Immediate Implant Placement.

The value of computer-aided implant planning using cone-beam computerized tomography (CBCT) for single immediate implants was explored. Eighteen patients requiring extraction of a tooth followed by a single immediate implant were enrolled. Small volume preoperative CBCT scans were used to plan the position of the implant. A taper screwed-type implant was immediately placed into a fresh socket using only the final 1 or 2 drills for osteotomy. Postoperative CBCTs were used for the analysis of actual implant placement positioning. Measurements of the planned and the actual implant position were made with respect to their position relative to the adjacent teeth. Mesio-distal displacements and the facial-lingual deviation of the implant from the planned position were determined. Changes in the angulation of the planned and actual implant position in relation to the clinical crown were also measured. To statistically summarize the results, box plots and 95% CIs for means of paired differences were used. The analysis showed no statistical difference between the planned position and final implant placement position in any measurement. The CBCT scans coupled with the computer-aided implant planning program along with a final 1-to-2 drill protocol may improve the accuracy of single immediate implant placement for taper screwed-type implants.

Immediate placement of a porous-tantalum, trabecular metal-enhanced titanium dental implant with demineralized bone matrix into a socket with deficient buccal bone: a clinical report.

A missing or deficient buccal alveolar bone plate is often an important limiting factor for immediate implant placement. Titanium dental implants enhanced with porous tantalum-based trabecular metal material (PTTM) are designed for osseoincorporation, a combination of vascularized bone ingrowth and osseointegration (bone on-growth). Demineralized bone matrix (DBM) contains growth factors with good handling characteristics. However, the combination of these 2 materials in facial alveolar bone regeneration associated with immediate implant therapy has not been reported. A 65-year-old Asian woman presented with a failing central incisor. Most of the buccal alveolar bone plate of the socket was missing. A PTTM enhanced implant was immediately placed with DBM. Cone beam computed tomography scans 12 months after the insertion of the definitive restoration showed regeneration of buccal alveolar bone. A combination of a PTTM enhanced implant, DBM, and a custom healing abutment may have an advantage in retaining biologically active molecules and form a scaffold for neovascularization and osteogenesis. This treatment protocol may be a viable option for immediate implant therapy in a failed tooth with deficient buccal alveolar bone.

Effects of Antibiotics on Bone and Soft-Tissue Healing Following Immediate Single-Tooth Implant Placement Into Sites With Apical Pathology.

Overprescription of antibiotics can cause bacterial resistance problems, leading to life-threatening illnesses and public health crises. Clinicians often believe antibiotics can prevent dental implant failure and postoperative complications. In conjunction with implant surgery, antibiotics are therefore routinely prescribed for all cases. In this double-blind, randomized controlled trial, the effects of antibiotics on the clinical outcomes of immediate implant placement upon replacing a tooth with an apical pathology were examined to compare antibiotics (n = 10) and placebo (n = 10). In each subject, a tooth with a chronic apical lesion was extracted, thoroughly curetted, irrigated, and replaced with single implant with a screw-retained custom provisional abutment/crown. Postoperative pain/discomfort was measured at 1- and 4-week postsurgical follow-up visits using visual analog scales. Facial alveolar bone and soft-tissue changes were measured using pre- and postoperative cone-beam computerized tomography and impressions. We found survival rates of 100% (antibiotics) and 78% (control). However, there was no statistical difference in means for any clinical outcome (t tests with Bonferroni adjustment for multiple testing), except for midfacial soft-tissue changes: 0.43 mm (SD, 0.76) in the antibiotics group and 1.70 mm (SD, 1.06) in the placebo group (t15 = -2.89, P = .011). The average change of the midfacial alveolar plate was 0.62 mm (SD, 0.46) and 1.34 mm (SD, 0.91) for the antibiotic and placebo groups, respectively, which did not significantly differ statistically. No significant correlation (Spearman correlation) existed between the changes in facial alveolar bone and the facial gingival margin. Antibiotics appear to have little effect on immediate implant treatment outcomes.

Immediate Placement and Provisionalization of Implants Into Sites With Periradicular Infection With and Without Antibiotics: An Exploratory Study.

This study explored the necessity of perioperative antibiotics on survival rates of implants immediately placed and provisionalized into sites with infection. Subjects were randomly assigned into antibiotic or placebo groups. Extraction, immediate placement, and provisionalization of an implant were performed. Eight subjects received placebo and five subjects received both a pre- and post-operative antibiotic regimen. One implant from each group failed. Perioperative antibiotic therapy may not be needed in selected immediate implant therapy.

Role of salivary and candidal proteins in denture stomatitis: an exploratory proteomic analysis.

Denture stomatitis, inflammation and redness beneath a denture, affects nearly half of all denture wearers. Candidal organisms, the presence of a denture, saliva, and host immunity are the key etiological factors for the condition. The role of salivary proteins in denture stomatitis is not clear. In this study 30 edentulous subjects wearing a maxillary complete denture were recruited. Unstimulated whole saliva from each subject was collected and pooled into two groups (n = 15 each), healthy and stomatitis (Newton classification II and III). Label-free multidimensional liquid chromatography/tandem mass spectrometry (2D-LC-MS/MS) proteomics on two mass spectrometry platforms were used to determine peptide mass differences between control and stomatitis groups. Cluster analysis and principal component analysis were used to determine the differential expression among the groups. The two proteomic platforms identified 97 and 176 proteins (ANOVA; p < 0.01) differentially expressed among the healthy, type 2 and 3 stomatitis groups. Three proteins including carbonic anhydrase 6, cystatin C, and cystatin SN were found to be the same as previous study. Salivary proteomic profiles of patients with denture stomatitis were found to be uniquely different from controls. Analysis of protein components suggests that certain salivary proteins may predispose some patients to denture stomatitis while others are believed to be involved in the reaction to fungal infection. Analysis of candidal proteins suggests that multiple species of candidal organisms play a role in denture stomatitis.

Systems biology and proteomic analysis of cerebral cavernous malformation.

UNLABELLED: Cerebral cavernous malformations (CCM) are vascular anomalies caused by mutations in genes encoding KRIT1, OSM and PDCD10 proteins causing hemorrhagic stroke. We examine proteomic change of loss of CCM gene expression. Using human umbilical vein endothelial cells, label-free differential protein expression analysis with multidimensional liquid chromatography/tandem mass spectrometry was applied to three CCM protein knockdown cell lines and two control cell lines: ProteomeXchange identifier PXD000362. Principle component and cluster analyses were used to examine the differentially expressed proteins associated with CCM. The results from the five cell lines revealed 290 and 192 differentially expressed proteins (p < 0.005 and p < 0.001, respectively). Most commonly affected proteins were cytoskeleton-associated proteins, in particular myosin-9. Canonical genetic pathway analysis suggests that CCM may be a result of defective cell-cell interaction through dysregulation of cytoskeletal associated proteins. CONCLUSION: The work explores signaling pathways that may elucidate early detection and novel therapy for CCM.

Role of cytoskeletal proteins in cerebral cavernous malformation signaling pathways: a proteomic analysis.

Three genetic mutations were found to cause cerebral cavernous malformation (CCM), a vascular anomaly predisposing affected individuals to hemorrhagic stroke. These CCM proteins function together as a protein complex in the cell. Loss of expression of each CCM gene results in loss of in vitro endothelial tube formation. Label-free differential protein expression analysis using multidimensional liquid chromatography/tandem mass spectrometry (2D-LC-MS/MS) was applied to explore the proteomic profile for loss of each CCM gene expression in mouse endothelial stem cells (MEES) compared to mock shRNA and no shRNA control cell-lines. Differentially expressed proteins were identified (p < 0.05). 120 proteins were differentially expressed among the cell-lines. Principal component analysis and cluster analysis show the effects of individual knockdown. In all knockdown cell-lines, altered expression of cytoskeletal proteins is the most common. While all CCM mutations result in similar pathology, different CCM mutations have their own distinct pathogenesis in cell signaling.

Development and applications of porous tantalum trabecular metal-enhanced titanium dental implants.

BACKGROUND: Porous tantalum trabecular metal has recently been incorporated in titanium dental implants as a new form of implant surface enhancement. However, there is little information on the applications of this material in implant dentistry. PURPOSE: The purpose of this article is to summarize the contemporary concept on the applications of porous tantalum trabecular metal in implant dentistry. MATERIALS AND METHODS: We therefore review the current literature on the basic science and clinical uses of this material. RESULTS: Porous tantalum metal is used to improve the contact between osseous structure and dental implants and therefore presumably facilitate osseointegration. Success of porous tantalum metal in orthopedic implants led to the incorporation of porous tantalum metal in the design of root-form endosseous titanium implants. The porous tantalum three-dimensional enhancement of titanium dental implant surface allows for combining bone ongrowth together with bone ingrowth, or osseoincorporation. While little is known about the biological aspect of the porous tantalum in the oral cavity, there seems to be several possible advantages of this implant design. This article reviews the biological aspects of porous tantalum-enhanced titanium dental implants, in particular the effects of anatomical consideration and oral environment to implant designs. CONCLUSIONS: We propose here possible clinical situations and applications for this type of dental implant. Advantages and disadvantages of the implants as well as needed future clinical studies are discussed.

Full-mouth rehabilitation for a patient with dentinogenesis imperfecta: a clinical report.

Dentinogenesis imperfecta (DI) is a genetic disorder affecting the structural integrity of the dentin that can result in weakened dentin. The affected teeth, especially posterior teeth, often need to be extracted due to severe wear or fracture. This frequently yields a loss of posterior occlusion and occlusal vertical dimension. Besides wear and fracture, anterior teeth often have an unesthetic appearance because of discoloration. Current treatments of choice, including composite bonding restorations and, more recently, all-ceramic restorations, are typically suggested to preserve the remaining teeth and tooth structure. However, there are a limited number of studies on dental implants in patients with DI. The effectiveness of dentin bonding and dental implants in patients with DI is not known. This clinical report describes a 32-year-old Asian woman with DI who underwent full-mouth rehabilitation. The posterior occlusion, mostly in the molar areas, was restored with dental implants and ceramometal restorations. The anterior teeth and premolars were restored with bonded lithium disilicate glass-ceramic pressed veneers and crowns made with computer-aided design/computer-aided manufacturing. This case demonstrates that restoring functional occlusion and esthetics for a patient with DI can be completed successfully using contemporary implant therapy and adhesive dentistry.

Update in research and methods in proteomics and bioinformatics.

The 3rd International Conference on Proteomics & Bioinformatics (Proteomics 2013) Philadelphia, PA, USA, 15-17 July 2013 The Third International Conference on Proteomics & Bioinformatics (Proteomics 2013) was sponsored by the OMICS group and was organized in order to strengthen the future of proteomics science by bringing together professionals, researchers and scholars from leading universities across the globe. The main topics of this conference included the integration of novel platforms in data analysis, the use of a systems biology approach, different novel mass spectrometry platforms and biomarker discovery methods. The conference was divided into proteomic methods and research interests. Among these two categories, interactions between methods in proteomics and bioinformatics, as well as other research methodologies, were discussed. Exceptional topics from the keynote forum, oral presentations and the poster session have been highlighted. The topics range from new techniques for analyzing proteomics data, to new models designed to help better understand genetic variations to the differences in the salivary proteomes of HIV-infected patients.

Salivary proteins associated with hyperglycemia in diabetes: a proteomic analysis.

Effective monitoring of glucose levels is necessary for patients to achieve greater control over their diabetes. However, only about a quarter of subjects with diabetes who requires close serum glucose monitoring, regularly check their serum glucose daily. One of the potential barriers to patient compliance is the blood sampling requirement. Saliva and its protein contents can be altered in subjects with diabetes, possibly due to changes in glycemic control. We propose here that salivary proteomes of subjects with diabetes may be different based on their glycemic control as reflected in A1C levels. A total of 153 subjects with type 1 or 2 diabetes were recruited. Subjects in each type of diabetes were divided into 5 groups based on their A1C levels; <7, 7-8, 8-9, 9-10, >10. To examine the global proteomic changes associated with A1C, the proteomic profiling of pooled saliva samples from each group was created using label-free quantitative proteomics. Similar proteomic analysis for individual subjects (N=4, for each group) were then applied to examine proteins that may be less abundant in pooled samples. Principle component analysis (PCA) and cluster analysis (p<0.01 and p<0.001) were used to define the proteomic differences. We, therefore, defined the salivary proteomic changes associated with A1C changes. This study demonstrates that differences exist between salivary proteomic profiles in subjects with diabetes based on the A1C levels.

Elucidating role of salivary proteins in denture stomatitis using a proteomic approach.

Denture stomatitis (DS) is the most common oral pathology among denture wearers, affecting over one-third of this group. DS is usually associated with C. albicans. However, unlike other oral candidiasis, most DS patients have intact host immunity. The presence of a denture alone is usually sufficient for DS. Saliva and its protein contents can theoretically predispose some denture wearers to DS and others resistant toward DS. Here we proposed for the first time to define salivary proteomic profiles of denture wearers with and without DS. SELDI-TOF/MS analysis suggests that there is a proteomic differentiation among control, localized and generalized DS. Based on initial SELDI-TOF/MS profiling, we further used reversed phase liquid chromatography, MALDI-TOF/MS, and LC-MS/MS to characterize the salivary proteins associated with DS. Nineteen proteins based on SELDI-TOF/MS profiling were found including cystatin-SN, statherin, kininogen-1, desmocollin-2, carbonic anhydrase-6, peptidyl-prolyl cis-trans isomerase A like peptides, cystatin C, and several immunoglobulin fragments. The proteomic content gives evidence of the interaction between host tissue, saliva, and candida. Further examination in larger populations of these proteins may help to gain a better understanding of DS pathological processes and improve DS treatments.