ABSTRACT
BACKGROUND AND OBJECTIVE: Adiponectin is produced by adipose cells and is considered an anti-inflammatory molecule. In contrast, C-reactive protein (CRP) has been identified as a hallmark of systemic inflammation and used as a risk marker of cardiovascular disease (CVD). Of interest was the relationship of these two biomarkers to oral health and CVD risk. MATERIAL AND METHODS: This investigation examined these two molecules in serum and unstimulated whole saliva of patients within 48 h of an acute myocardial infarction (AMI) compared to control subjects. We hypothesized a differential response in these biomolecules resulting from the heart attack that would be affected by both the body mass index and oral health characteristics of the individuals. RESULTS: Significantly lower adiponectin levels were observed in the serum of patients with AMI. Serum adiponectin in both groups and salivary adiponectin in patients with AMI decreased with increasing body mass index. Oral health was significantly worse in patients with AMI, and both serum and salivary adiponectin were elevated with better oral health in control subjects. Serum CRP levels were increased in patients with AMI regardless of their oral health, and both serum and salivary CRP were significantly elevated in S-T wave elevated patients with MI. CONCLUSIONS: These initial data provide evidence relating obesity and oral health to salivary and serum analyte levels that occur in association with cardiac events. Relationships have been described between CVD risk and periodontal disease. Additionally, various systemic inflammatory biomarkers appear to reflect both the CVD risk and the extent/severity of periodontitis. Our findings indicated that oral health and obesity contribute to altering levels of these salivary and serum analytes in association with cardiac events. The potential that serum and/or salivary biomarkers could aid in evaluating CVD risk requires knowledge regarding how the oral health of the individual would impact the effectiveness of these biological measures.
Subject(s)
Adiponectin/blood , C-Reactive Protein/analysis , Myocardial Infarction/metabolism , Periodontal Diseases/complications , Saliva/chemistry , Adiponectin/analysis , Biomarkers/analysis , Biomarkers/blood , Body Mass Index , Case-Control Studies , Female , Humans , Male , Middle Aged , Myocardial Infarction/blood , Myocardial Infarction/complications , Obesity/blood , Obesity/metabolism , Oral Health/statistics & numerical data , Periodontal Diseases/blood , Periodontal Diseases/metabolism , Periodontitis/blood , Periodontitis/complications , Periodontitis/metabolismABSTRACT
Fanconi anemia (FA) is caused by mutations of DNA repair genes. The risk of oral squamous cell carcinoma (OSCC) among FA patients is 800-folds higher than in the general population. Early detection of OSCC, preferably at it precursor stage, is critical in FA patients to improve their survival. In an ongoing clinical trial, we are evaluating the effectiveness of the programmable bio-nanochip (p-BNC)-based oral cytology test in diagnosing oral potentially malignant disorders (OPMD) in non-FA patients. We used this test to compare cytomorphometric and molecular biomarkers in OSCC cell lines derived from FA and non-FA patients to brush biopsy samples of a FA patient with OPMD and normal mucosa of healthy volunteers. Our data showed that expression patterns of molecular biomarkers were not notably different between sporadic and FA-OSCC cell lines. The p-BNC assay revealed significant differences in cytometric parameters and biomarker MCM2 expression between cytobrush samples of the FA patient and cytobrush samples of normal oral mucosa obtained from healthy volunteers. Microscopic examination of the FA patient's OPMD confirmed the presence of dysplasia. Our pilot data suggests that the p-BNC brush biopsy test recognized dysplastic oral epithelial cells in a brush biopsy sample of a FA patient.
Subject(s)
Carcinoma, Squamous Cell/diagnosis , Cytodiagnosis/instrumentation , Cytodiagnosis/methods , Fanconi Anemia/pathology , Head and Neck Neoplasms/diagnosis , Mouth Neoplasms/diagnosis , Nanostructures/chemistry , Adult , Biomarkers, Tumor/biosynthesis , Biopsy , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Case-Control Studies , Cell Line, Tumor , Cells, Cultured , Fanconi Anemia/metabolism , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/pathology , Humans , Image Cytometry/instrumentation , Image Cytometry/methods , Image Processing, Computer-Assisted/instrumentation , Image Processing, Computer-Assisted/methods , Male , Mouth Mucosa/cytology , Mouth Mucosa/pathology , Mouth Neoplasms/metabolism , Mouth Neoplasms/pathology , Squamous Cell Carcinoma of Head and NeckABSTRACT
The comparative utility of serum and saliva as diagnostic fluids for identifying biomarkers of acute myocardial infarction (AMI) was investigated. The goal was to determine if salivary biomarkers could facilitate a screening diagnosis of AMI, especially in cases of non-ST elevation MI (NSTEMI), since these cases are not readily identified by electrocardiogram (ECG). Serum and unstimulated whole saliva (UWS) collected from 92 AMI patients within 48 hours of chest pain onset and 105 asymptomatic healthy control individuals were assayed for 13 proteins relevant to cardiovascular disease, by Beadlyte technology (Luminex(®)) and enzyme immunoassays. Data were analyzed with concentration cut-points, ECG findings, logistic regression (LR) (adjusted for matching for age, gender, race, smoking, number of teeth, and oral health status), and classification and regression tree (CART) analysis. A sensitivity analysis was conducted by repetition of the CART analysis in 58 cases and 58 controls, each matched by age and gender. Serum biomarkers demonstrated AMI sensitivity and specificity superior to that of saliva, as determined by LR and CART. The predominant discriminators in serum by LR were troponin I (TnI), B-type natriuretic peptide (BNP), and creatine kinase-MB (CK-MB), and TnI and BNP by CART. In saliva, LR identified C-reactive protein (CRP) as the biomarker most predictive of AMI. A combination of smoking tobacco, UWS CRP, CK-MB, sCD40 ligand, gender, and number of teeth identified AMI in the CART decision trees. When ECG findings, salivary biomarkers, and confounders were included, AMI was predicted with 80.0% sensitivity and 100% specificity. These analyses support the potential utility of salivary biomarker measurements used with ECG for the identification of AMI. Thus, saliva-based tests may provide additional diagnostic screening information in the clinical course for patients suspected of having an AMI.
Subject(s)
Biomarkers/analysis , Myocardial Infarction/diagnosis , Saliva/chemistry , Adult , Aged , Biomarkers/blood , C-Reactive Protein/analysis , CD40 Ligand/analysis , Case-Control Studies , Cohort Studies , Creatine Kinase, MB Form/blood , Cross-Sectional Studies , Decision Trees , Dentition , Early Diagnosis , Electrocardiography/methods , Female , Health Status , Humans , Male , Middle Aged , Myocardial Infarction/blood , Natriuretic Peptide, Brain/blood , Oral Health , Salivary Proteins and Peptides/analysis , Sensitivity and Specificity , Sex Factors , Smoking , Troponin I/bloodABSTRACT
A family of diaminobutane core, poly(propylene imine) dendrimers coordinated to Cu(II), DAB-Am(n)-Cu(II)x (n = 4, 8, 16, 32, 64, x = n/2), was studied by means of extended X-ray absorption fine structure (EXAFS) and X-ray absorption near-edge structure (XANES) spectroscopies. The geometry of the dipropylene triamine (dpt)-Cu(II) end-group complexes for all dendrimer generations is reported for the first time and is found to be that of a square-based pyramid with each Cu ion bound to three nitrogen atoms (Cu-N distance approximately 2.03 A) of the dpt end group of the dendrimer. An oxygen atom residing 1.96 A from the Cu ion also occupies the equatorial plane, and the pyramid is completed by an axial oxygen at approximately 2.65 A. In addition, we report for the first time that reduction of the Cu(II)-dendrimer complexes with NaBH4 yields DAB-Am(n)-Cu(0)(cluster) species. Transmission electron microscopy (TEM) studies of the reduced species demonstrate that there is a systematic decrease in the size of the generated Cu clusters with increasing dendrimer generation. Additionally, it was found that the size of the nanoclusters is a function of the n/x ratio of the DAB-Am(n)-Cu(II)x precursor, with highly monodisperse, extremely small nanoclusters (r(cluster) = 8.0 +/- 1.6 A) obtained with n = 64 and x = 16. EXAFS and XANES measurements on the reduced DAB-Am(n)-Cu(0)(cluster) corroborate the TEM data, and provide additional information on the possible encapsulation of the Cu nanoclusters by the dendrimers.