Metal hypersensitivity and pro-inflammatory cytokine production in patients with failed orthopedic implants: A case-control study.

Orthopedic implants heal well without complications in most patients but fail for unclear reasons in some individuals. This study determined the relevance of metal hypersensitivity in patients with failed orthopedic implants and those requiring orthopedic implant surgery. The study included 35 patients with failed orthopedic implants and 15 subjects scheduled for orthopedic implant surgery. The production of selected pro-inflammatory cytokines was measured in patients with failed orthopedic implants. Metal hypersensitivity was measured in all subjects using the MELISA® test. Of common metals in orthopedic alloys, the patients with failed orthopedic implants responded most frequently to nickel, chromium, titanium, iron, and molybdenum. Hypersensitivity to metals found in implants was measured in 40% of patients with failed implants. The study also showed that titanium exposure in patients with titanium hypersensitivity might lead to implant failure. Metal hypersensitivity testing should be offered to patients before surgery to minimize the risk of implant failure.

Titanium and Other Metal Hypersensitivity Diagnosed by MELISA® Test: Follow-Up Study.

This study is aimed at proving the clinical benefit of the MELISA® test in the minimization or complete elimination of health problems in patients with confirmed hypersensitivity to metals used for tissue replacements. A group of 305 patients aged 20-75 years with previously proven metal hypersensitivity (initial MELISA® test), mainly to titanium and then to another fifteen metals, was chosen from the database at the Institute of Dental Medicine. From these patients, a final group of 42 patients agreed to participate in the study, 35 of which were female and 7 were male. The patients completed a special questionnaire aimed at information regarding change of health status from their last visit and determining whether the results of the initial MELISA® test and recommendations based on it were beneficial for patients or not. They were clinically examined, and peripheral blood samples were taken to perform follow-up MELISA® tests. Questionnaire data was processed, and the follow-up MELISA® test results were compared with the results of the initial MELISA® tests. For statistical analysis, the Fisher's exact test and paired T-test were used. Thirty-two patients reported that they followed the recommendations based on the results of the initial MELISA® tests, and of these, 30 patients (94%) confirmed significant health improvement. Six patients did not follow the recommendation, and from these, only one patient reported an improvement in his health problems. By comparison of the initial and follow-up MELISA® test results, it can be stated that the hypersensitivity to the given metal decreased or disappeared after the therapeutic interventions performed based on the initial MELISA® test results. The evaluation of the data obtained from patients in this study confirmed a significant clinical benefit of MELISA® test.

The Oral Microbiome in Periodontal Health.

The estimation of oral microbiome (OM) taxonomic composition in periodontally healthy individuals can often be biased because the clinically periodontally healthy subjects for evaluation can already experience dysbiosis. Usually, they are included just based on the absence of clinical signs of periodontitis. Additionally, the age of subjects is used to be higher to correspond well with tested groups of patients with chronic periodontitis, a disorder typically associated with aging. However, the dysbiosis of the OM precedes the clinical signs of the disease by many months or even years. The absence of periodontal pockets thus does not necessarily mean also good periodontal health and the obtained image of "healthy OM" can be distorted.To overcome this bias, we taxonomically characterized the OM in almost a hundred young students of dentistry with precise oral hygiene and no signs of periodontal disease. We compared the results with the OM composition of older periodontally healthy individuals and also a group of patients with severe periodontitis (aggressive periodontitis according to former classification system). The clustering analysis revealed not only two compact clearly separated clusters corresponding to each state of health, but also a group of samples forming an overlap between both well-pronounced states. Additionally, in the cluster of periodontally healthy samples, few outliers with atypical OM and two major stomatotypes could be distinguished, differing in the prevalence and relative abundance of two main bacterial genera: Streptococcus and Veillonella. We hypothesize that the two stomatotypes could represent the microbial succession from periodontal health to starting dysbiosis. The old and young periodontally healthy subjects do not cluster separately but a trend of the OM in older subjects to periodontitis is visible. Several bacterial genera were identified to be typically more abundant in older periodontally healthy subjects.

R/G Value-A Numeric Index of Individual Periodontal Health and Oral Microbiome Dynamics.

The dysbiosis of oral microbiome (OM) precedes the clinical signs of periodontal disease. Its simple measure thus could indicate individuals at risk of periodontitis development; however, such a tool is still missing. Up to now, numerous microbial taxa were associated with periodontal health or periodontitis. The outputs of most studies could, nevertheless, be slightly biased from following two reasons: First, the healthy group is often characterized only by the absence of the disease, but the individuals could already suffer from dysbiosis without any visible signs. Second, the healthy/diseased OM characteristics are frequently determined based on average data obtained for whole groups of periodontally healthy persons versus patients. Especially in smaller sets of tested individuals the typical individual variability can thus complicate the unambiguous assignment of oral taxa to respective state of health. In this work the taxonomic composition of OM was evaluated for 20 periodontally healthy individuals and 15 patients with chronic periodontitis. The narrowed selection set of the most diseased patients (confirmed by clinical parameters) and the most distant group of healthy individuals with the lowest probability of dysbiosis was determined by clustering analysis and used for identification of marker taxa. Based on their representation in each individual oral cavity we proposed the numeric index of periodontal health called R/G value. Its diagnostic potential was further confirmed using independent set of 20 periodontally healthy individuals and 20 patients with periodontitis with 95 percent of samples assigned correctly. We also assessed the individual temporal OM dynamics in periodontal health and we compared it to periodontitis. We revealed that the taxonomic composition of the system changes dynamically but generally it ranges within values typical for periodontal health or transient state, but far from values typical for periodontitis. R/G value tool, formulated from individually evaluated data, allowed us to arrange individual OMs into a continuous series, instead of two distinct groups, thus mimicking the gradual transformation of a virtual person from periodontal health to disease. The application of R/G value index thus represents a very promising diagnostic tool for early prediction of persons at risk of developing periodontal disease.

Salivary Markers for Periodontal and General Diseases.

The determination of biomarkers in saliva is becoming an important part of laboratory diagnostics and the prediction of not only periodontal, but also other tissue and organ diseases. Biomarkers in saliva (e.g., enzymes, protein markers, or oxidative stress markers) can be used for activity determination and for periodontal disease prognosis. Saliva also contains many markers which can predict the risk of certain diseases (e.g., diabetes mellitus, cardiovascular, oncology, endocrinology, and psychiatric diseases). The study of salivary components proteomics clearly shows the relationship of periodontal diseases and diseases of distant systems, organs, or tissues.

C-Reactive Protein in Peripheral Blood of Patients with Chronic and Aggressive Periodontitis, Gingivitis, and Gingival Recessions.

CRP is a plasma protein that reflects a measure of the acute phase response to inflammation and is one of the markers of choice in monitoring this response. CRP can be used for the prediction and early detection of periodontal disease. The aim of this study was to compare and evaluate the systemic levels of CRP in the peripheral blood samples of patients with chronic and aggressive periodontitis, gingivitis, and gingival recessions and compare them with periodontal clinical parameters. All patients (N = 158) were examined prior to the initiation of periodontal treatment. Patients were divided into four groups. Group A consisted of 26 patients with aggressive periodontitis, Group B consisted of 111 patients with chronic periodontitis, Group C consisted of 13 patients with gingivitis, and Group D consisted of 8 patients with gingival recessions. Our study results indicate that CRP levels increase subsequently with the severity of the periodontal disease and that the bleeding on probing index showed much better positive correlation with the CRP levels compared to the pocket depth index in both periodontitis patients groups, especially in aggressive periodontitis patients.

The effect of IL-4 gene polymorphisms on cytokine production in patients with chronic periodontitis and in healthy controls.

Chronic periodontitis (CP) is an inflammatory disease of the teeth-supporting tissues in which genetic predisposition, dental plaque bacteria, and immune mechanisms all play important roles. The aim of this study was to evaluate the occurrence of IL-4 gene polymorphisms in chronic periodontitis and to investigate the association between polymorphisms and cytokines production after bacterial stimulation. Sixty-two subjects (47 CP patients and 15 healthy controls) with detected two polymorphisms in the IL-4 gene (-590C/T and intron 3 VNTR) were examined. Production of cytokines (IL-1α, IL-1ß, IL-4, IL-5, IL-6, IL-10, IL-17, TNFα, INFγ, and VEGF) was studied after in vitro stimulation of isolated peripheral blood by mitogens (Pokeweed mitogen, Concanavalin A), dental plaque bacteria (Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Porphyromonas gingivalis, and Prevotella intermedia), and Heat Shock Protein (HSP) 70 by the Luminex multiplex cytokine analysis system. The results were correlated with IL-4 genotypes in patients with CP and healthy controls. The mononuclear cells isolated from peripheral blood of CP patients with selected IL-4 polymorphisms significantly altered the production of IFNγ, IL-10, IL-1ß, IL-1α, TNFα, and IL-6 after stimulation by HSP 70 or selected bacteria (from P < 0.001 to P < 0.05). IL-4 gene polymorphisms may influence the function of mononuclear cells to produce not only interleukin-4 but also other cytokines, especially in patients with CP.

Porphyromonas gingivalis: major periodontopathic pathogen overview.

Porphyromonas gingivalis is a Gram-negative oral anaerobe that is involved in the pathogenesis of periodontitis and is a member of more than 500 bacterial species that live in the oral cavity. This anaerobic bacterium is a natural member of the oral microbiome, yet it can become highly destructive (termed pathobiont) and proliferate to high cell numbers in periodontal lesions: this is attributed to its arsenal of specialized virulence factors. The purpose of this review is to provide an overview of one of the main periodontal pathogens-Porphyromonas gingivalis. This bacterium, along with Treponema denticola and Tannerella forsythia, constitute the "red complex," a prototype polybacterial pathogenic consortium in periodontitis. This review outlines Porphyromonas gingivalis structure, its metabolism, its ability to colonize the epithelial cells, and its influence upon the host immunity.

Periodontitis as a risk factor of atherosclerosis.

Over the last two decades, the amount of evidence corroborating an association between dental plaque bacteria and coronary diseases that develop as a result of atherosclerosis has increased. These findings have brought a new aspect to the etiology of the disease. There are several mechanisms by which dental plaque bacteria may initiate or worsen atherosclerotic processes: activation of innate immunity, bacteremia related to dental treatment, and direct involvement of mediators activated by dental plaque and involvement of cytokines and heat shock proteins from dental plaque bacteria. There are common predisposing factors which influence both periodontitis and atherosclerosis. Both diseases can be initiated in early childhood, although the first symptoms may not appear until adulthood. The formation of lipid stripes has been reported in 10-year-old children and the increased prevalence of obesity in children and adolescents is a risk factor contributing to lipid stripes development. Endothelium damage caused by the formation of lipid stripes in early childhood may lead to bacteria penetrating into blood circulation after oral cavity procedures for children as well as for patients with aggressive and chronic periodontitis.