Impact of TLR9 and TLR7 gene polymorphisms on prognosis and survival of patients with oral squamous cell carcinoma.

Despite significant efforts in developing new diagnostic and therapeutic modalities, oral squamous cell carcinomas (OSCCs) still exhibit a high recurrence rate, a low five-year survival rate, and an increasing prevalence. Toll-like receptors (TLRs), which initiate and perpetuate immune mechanisms upon activation, have been linked to immune surveillance and the antitumor immune response. The aim of this study was to investigate the association between the polymorphisms of the TLR7 rs3853839 and TLR9 rs187084 genes and OSCC risk, clinicopathological features, and survival. Genotyping was assessed by real-time polymerase chain reaction (PCR) in 95 HPV-negative OSCC patients and 107 age- and sex-matched healthy controls. Patients with lymph node metastases had higher frequencies of the TLR9 rs187084 CC variant genotype compared to the major TT genotype (P = 0.020) and to T-allele carriers (combined TT + CT genotypes, P = 0.015). A higher prevalence of advanced stage III was observed in patients with the TLR9 rs187084 variant CC genotype compared to TT (P = 0.047) and to T-allele carriers (TT + CT, P = 0.037). Kaplan-Meier analysis revealed a lower overall survival rate in patients with the TLR9 rs187084 variant CC genotype compared to TT genotype (P = 0.010, log-rank test) and to T-allele carriers (TT + CT, P = 0.002), though it was not an independent predictor of overall survival. Both TLR9 rs187084 and TLR7 rs3853839 polymorphisms were associated with high alcohol consumption (P = 0.027 and P = 0.001, respectively). The investigated genetic variations were not associated with OSCC susceptibility. The variant CC genotype of the TLR9 rs187084 polymorphism might be a marker of poor survival and tumor progression in OSCC.

Resolution of peri-implant mucositis following standard treatment: A prospective split-mouth study.

BACKGROUND: Peri-implant mucositis (PIM) is a pathological precursor of peri-implantitis, but its pattern of conversion to peri-implantitis is unclear and complicated to diagnose clinically, while none of the available protocols yield complete disease resolution. The aim of this study was the evaluation of PIM responsiveness to standard anti-infective mechanical treatment (AIMT) at clinical and biomarker levels, and estimation of the diagnostic capacity of bone markers as surrogate endpoints and predictors. METHODS: Systemically healthy outpatients presenting one implant exhibiting clinical signs of inflammation confined within the soft tissue (PIM) and one healthy control (HC) implant at a non-adjacent position were included. Clinical parameters and peri-implant crevicular fluid samples were collected baseline and 6 months following mechanical therapy, to assess the levels of RANKL, OPG, and IGFBP2. PIM clustering was performed using machine learning algorithms. RESULTS: Overall, 38 patients met the inclusion criteria. Therapy resulted in the reduction of all clinical and biological indicators, but respective values remained significantly higher compared to HC. Clinical examination noted 30% disease resolution at the 6-month follow-up, while 43% showed no active bone resorption. OPG showed positive prognostic value for treatment outcome, while the clustering based on active bone resorption did not differ in terms of therapeutic effectiveness. CONCLUSION: AIMT is effective in reducing the clinical and biological indicators of PIM, but complete clinical resolution was achieved in only 30% of the cases. Around one third of PIM patients exhibited active bone resorption bellow clinical detectability that was not associated with disease progression and poor treatment responsiveness.

CYP2C19 slow metabolizer phenotype is associated with lower antidepressant efficacy and tolerability.

The inter-individual variability in CYP2C19-mediated metabolism may affect the antidepressant treatment. The aim of this study is to evaluate differences in antidepressant efficacy and tolerability between different CYP2C19 metabolizer categories in inpatients suffering from major depressive disorder. The cohort was divided into experimental groups based on CYP2C19 genotype and it contained 24 slow (SMs), 41 normal (NMs), and 37 fast metabolizers (FMs). Efficacy and tolerability were assessed at baseline, and after two and four weeks as a follow-up. The primary efficacy measurement was the change from baseline in Hamilton's Depression Rating Scale (HAMD), while the primary tolerability measurement was the Toronto Side-Effects Scale (TSES) intensity scores at the last visit. The reduction in HAMD score was 36% less pronounced and response rate was exceedingly less prevalent (75% lower) in SMs, compared with NMs. The TSES intensity score was increased in SMs, compared with NMs, by 43% for central nervous system and by 22% for gastrointestinal adverse drug reactions. No significant differences in measured parameters were observed between NMs and FMs. Compared with NM and RM, lower antidepressant efficacy and tolerability was observed in SMs; this association is likely connected with the lower SM capacity to metabolize antidepressant drugs.

Study on the immunopathological effect of titanium particles in peri-implantitis granulation tissue: A case-control study.

OBJECTIVES: To identify titanium particles (TPs) in biopsy specimens harvested from peri-implantitis lesions and secondarily to study the histopathological characteristics in peri-implantitis compared to periodontitis, in order to evaluate whether the presence of TPs could alter respective inflammatory patterns. MATERIAL AND METHODS: Biopsies containing granulation tissue were harvested during routine surgical treatment in 39 peri-implantitis cases and 35 periodontitis controls. Serial sections were obtained using titanium-free microtome blades. The first and last sections of the peri-implantitis specimens were used for identification of TPs by scanning electron microscopy coupled with dispersive X-ray spectrometry. Intermediate sections and periodontitis specimens were processed for descriptive histological study using haematoxylin-eosin staining and for immunohistochemical analysis using CD68, IL-6, Nf-kB and VEGF markers. RESULTS: TPs were identified in all peri-implantitis specimens as free metal bodies interspersed within granulation tissue. However, presence of macrophages or multinucleated giant cells engulfing the TPs were not identified in any specimen. Peri-implantitis granulations were characterized by a chronic inflammatory infiltrate rich in neutrophils. About half of peri-implantitis patients exhibited a subacute infiltrate characterized with lymphocytes interweaved with neutrophils and eosinophils. When compared to periodontitis, peri-implantitis tissues showed higher proportions of macrophages and a more intense neovascularization, based on significantly higher expression of CD68 and VEGF respectively. CONCLUSION: TPs were identified in all peri-implantitis specimens, but without evidencing any foreign body reaction suggestive for direct pathological effects of TPs. The peri-implantitis granulation tissue was characterized by intense neovascularization and presence of a chronic inflammatory infiltrate dominated by plasma cells, neutrophils and macrophages.

Underdiagnosis in Background of Emerging Public Health Challenges Related to Peri-Implant Diseases: An Interventional Split-Mouth Study.

Peri-implant diseases are an emerging public health problem, and it's considered that limitations of standard diagnostics play the role herein. The study objective was the estimation of pathological bone resorption at clinical and biological level in patients with peri-implant mucositis (PIM) and peri-implantitis (PI) before and 6 months after standard treatment and to compare them with healthy controls (HC). The split-mouth interventional study included 60 patients affected with PIM or PI. Patients that also presented at least one more HC were enrolled in the study and underwent standard non-surgical and surgical treatment, respectively. Standard clinical parameters and soluble levels of RANKL were measured in peri-implant crevicular fluid baseline and 6 months following treatment. Clinical parameters and RANKL significantly decreased following treatment in PIM and PI. However, bleeding on probing and probing depth remained significantly increased when compared to HC. RANKL answered requests for biomarker of peri-implant diseases, its baseline levels were significantly increased in PIM and PI, they decreased following treatment and reached HC in peri-implantitis, while in PIM RANKL remained significantly increased. Presence of pathological bone resorption in patients lacked its clinical signs, and respective persistence following treatment suggest the need for biomarker-supported diagnosis for timely diagnosis of peri-implantitis and appropriate orientation of respective management strategies.

Estimating the Effects of Dental Caries and Its Restorative Treatment on Periodontal Inflammatory and Oxidative Status: A Short Controlled Longitudinal Study.

Dental caries and periodontitis are among the most common health conditions that are currently recognized as growing socio-economic problems relating to their increasing prevalence, negative socio-economic impact, and harmful effects on systemic health. So far, the exact effects of caries and standard restorative materials on periodontal inflammatory and oxidative status are not established. The present study aimed to investigate the effect of caries and its restoration using standard temporary and permanent filling materials on a panel of 16 inflammatory and oxidative markers in gingival crevicular fluid (GCF) of periodontally healthy individuals, 7 (D7) and 30 (D30) days post-restoration, while the intact teeth represented the control. One hundred ninety systemically and periodontally healthy patients with occlusal caries underwent standard cavity preparation and restorations with one of six standard temporary or permanent restorative material according to indication and randomization scheme. Interleukin (IL)-2, IFN- γ, IL-12, IL-17A, IL-13, IL-9, IL-10, IL-6, IL-5, IL-4, IL-22, TNF-α, IL1- ß, thiobarbituric acid reactive substances, superoxide dismutase, and reduced form of glutathione were measured in GCF samples by flowcytometry and spectrophotometry in aid of commercial diagnostic assays. Caries affected teeth exhibited significantly increased IL-1 ß, IL-17, IL-22, and TBARS and decreased IL-9 concentrations compared to healthy controls. Treatment generally resulted in an increased antioxidant capacity with exception of zinc-polycarboxylate cement showing distinctive inflammatory pattern. Comparison of inflammatory and oxidative profiles in temporary and permanent restorations showed material-specific patterning which was particularly expressed in temporary materials plausibly related to greater caries extension. Caries affected teeth exhibited a balanced inflammatory pattern in GCF, with a general tendency of homeostatic re-establishment following treatment. Restorative materials did not provide specific pathological effects, although some material groups did exhibit significantly elevated levels of inflammatory and oxidative markers compared to healthy controls, while the material-specific patterning was observed as well.

Effect of dental caries on periodontal inflammatory status: A split-mouth study.

OBJECTIVE: This controlled split-mouth study aimed to estimate the effect of caries and related treatment on concentrations of interleukin (IL)-2, interferon (IFN)-γ, IL-12, IL-17A, IL-13, IL-10, IL-6, IL-5, IL-4, IL-22, tumor necrosis factor (TNF)-α, and IL1-ß in gingival crevicular fluid (GCF) of caries affected teeth before (B), 7 (7D) and 30 (30D) days post-treatment and to compare them with concentrations from healthy teeth. DESIGN: Study population included 81 systemically and periodontally healthy non-smokers exhibiting at least one shallow occlusal/ inter-proximal caries and one healthy tooth from the same morphologic group at the contralateral position. Following clinical exam, the GCF samples were collected baseline as well as 7D and 30D, while the biomarker measurement was performed using multiplex flowcytometry. RESULTS: Caries affected teeth exhibited significantly higher levels of IFN-γ, IL-1ß, IL-2, IL-4 and IL-6 when compared to healthy teeth. Post-treatment cytokines levels showed general trend of increase when compared to baseline, that was significant for IL-22 and IL-17 at 7D, while IFN-γ was significantly increased at 7D compared to the healthy teeth. At 30D, IFN-γ, TNF-α, IL-17 and IL-4 levels were significantly increased when compared to healthy teeth, while IL-2 levels were significantly higher than baseline levels. CONCLUSION: Considering significantly increased periodontal levels of inflammatory markers in caries affected teeth and in response to performed treatment, it seems that dental caries and related restorative treatment might contribute to periodontal inflammation via additive effects already in early-stage caries.

Is the personalized approach the key to improve clinical diagnosis of peri-implant conditions? The role of bone markers.

BACKGROUND: Study objectives were 1) to estimate diagnostic capacity of clinical parameters, receptor activator of nuclear factor kappa-B (RANKL) and osteoprotegerin (OPG) to diagnose healthy peri-implant condition (HI), peri-implant mucositis (PIM) and peri-implantitis (PIMP) by assessing respective diagnostic accuracy, sensitivity, specificity and diagnostic ranges 2) to develop personalized diagnostic model (PDM) for implant monitoring. METHODS: Split-mouth study included 126 patients and 252 implants (HI = 126, PIM = 57, and PIMP = 69). RANKL and OPG concentrations were estimated in peri-implant crevicular fluid using enzyme-linked immunosorbent assay method and assessed with clinical parameters using routine statistics, while the diagnostic capacity of individual parameters and overall clinical diagnosis were estimated using classifying algorithms. PDM was developed using decision trees. RESULTS: Bleeding on probing (BOP), plaque index, and probing depth (PD) were confirmed reliable discriminants between peri-implant health and disease, while increase in PD (PD > 4 mm) and suppuration were good discriminants amongst PIM/PIMP. Bone turnover markers (BTMs) demonstrated presence of bone resorption in PIM; between comparable diagnostic ranges PIM/PIMP, PIMP was clinically distinguished from PIM in about 60% of patients while 40% remained diagnosed as false negatives. PDM demonstrated highest diagnostic capacity (accuracy: 96.27%, sensitivity: 95.00%, specificity: 100%) and defined HI: BOP ≤0.25%; PIM: BOP >0.25%, PD ≤4.5 mm; PIMP: BOP >0.25%, PD >4.5 mm and RANKL ≤19.9 pg/site; PIM: BOP >0.25%, PD >4.5 mm, and RANKL >19.9 pg/site. CONCLUSIONS: BTMs demonstrated capacity to substantially improve clinical diagnosis of peri-implant conditions. Considering lack of difference in BTMs between PIM/PIMP and cluster of PIM with exceeding BTMs, a more refined definition of peri-implant conditions according to biological characteristics is required for further BTMs validation and appropriate PIMP management.

Influence of Dental Restorations on Oxidative Stress in Gingival Crevicular Fluid.

Biocompatibility of dental materials (DM) can be evaluated by gingival crevicular fluid (GCF) oxidative stress (OS) status. The goal of the study was to ascertain influence of dental caries degree, teeth position, and type and amount of applied DM on GCF OS profile. For this purpose, we tested six DMs that were sealed in one session: amalgam (Amg), composites: Tetric EvoCeram and Beautifil (BF), phosphate cement-zinc phosphate and polycarboxylate cements-zinc polycarboxylate cements, and glass ionomer cement (GIC). The study included 88 dental outpatients. Follow-up was scheduled at 7th and 30th day. Oxidative stress parameters (malondialdehyde (MDA) and glutathione (GSH) levels and total superoxide dismutase (tSOD) activity) were measured before (0th day) and after the treatment (7th and 30th day) in GCF. Control teeth were mirror-positioned healthy teeth. The DM accomplished the following effects (listed in descending order): increase of GSH in GCF was realized by ZPoC > BF > GIC > Amg; tSOD activity increase by ZPoC > BF > Amg; and MDA decrease by ZPoC > ZPhC > Amg > TEC. Dental caries provokes insignificant rise of OS in GCF. ZPoC and ZPhC showed the highest antioxidant effect, contrary to GIC. Restorations with antioxidant properties may reduce gum diseases initiated by caries lesion, what is of great clinical relevance in dentistry.

Association of Cytokine Gene Polymorphism with Peri-implantitis Risk.

PURPOSE: To investigate whether polymorphisms of cluster of differentiation 14 (CD14), tumor necrosis factor alpha (TNFα), interleukin (IL)6, IL10, and IL1ra genes are associated with the risk of peri-implantitis susceptibility in patients with dental implants in the Serbian population. MATERIALS AND METHODS: Isolated DNA from the blood was used for IL10-1082, TNFα-308, IL6-174, CD14-159, and interleukin 1 receptor antagonist (IL1ra) genotyping using polymerase chain reaction (PCR)-based methodology. Clinical parameters included: peri-implant pocket depth (PPD), Plaque Index (PI), Gingival Index (GI), bleeding on probing (BOP), and radiologic bone loss. RESULTS: The study included 98 patients with dental implants in function for at least 1 year, divided into peri-implantitis (34) and healthy peri-implant tissue (64) groups. The percentage distribution of smokers was significantly different between patients who developed peri-implantitis and patients with healthy peri-implant tissue (71% vs 42%, respectively) and associated with increased peri-implantitis risk (OR: 3.289, 95% CI: 1.352 to 8.001; P = .007). A positive history of periodontitis was more frequent in the peri-implantitis group (62%) than in the healthy peri-implant tissue (20%) group and associated with increased peri-implantitis risk (OR: 6.337, 95% CI: 2.522 to 15.927; P = .0001). Frequencies of CD14-159, TNFα-308, IL10-1082, and IL6-174 genotypes were significantly different between patients with and without peri-implantitis. However, logistic regression revealed only TNFα-308 polymorphic GA/AA genotypes (OR: 8.890, 95% CI: 2.15 to 36.7; P = .003) and smoking (OR: 6.2, 95% CI: 1.44 to 26.7; P = .014) as independent factors associated with increased peri-implantitis risk, while CD14-159 polymorphic CT/TT genotypes were associated with decreased risk for peri-implantitis (OR: 0.059, 95% CI: 0.009 to 0.355; P = .002). CONCLUSION: The findings suggest that smoking and the presence of TNFα-308 GA/AA genotypes may increase the risk for peri-implantitis, while CD14-159 polymorphic CT/TT genotypes decrease the risk. The results also indicate significant association of CD14-159, TNFα-308, and IL6-174 genotypes and clinical parameters in the Serbian population. However, future studies in larger patient groups are necessary to confirm these observations.

Influence of dental filling material type on the concentration of interleukin 9 in the samples of gingival crevicular fluid.

Background/Aim: Several cytokines and lymphokines (IL1ß, ENA78, IL6, TNFα, IL8 and S100A8) are expressed during dental pulp inflammation. Analysis of gingival crevicu-lar fluid (GCF) offers a non-invasive means of studying gen-eral host response in oral cavity. Although GCF levels of various mediators could reflect the state of inflammation both in dental pulp and gingiva adjacent to a tooth, GCF samples of those without significant gingivitis could be inter-preted as reflection of pulpal process. The aim of this study was to investigate IL9 GCF values in patients with dental car-ies and to assess possible influence of various dental fillings materials on local IL9 production. Methods: The study group included 90 patients, aged 18­70, with inclusion and exclusion criteria in the prospective clinical study. Of the 6 types of material used for the restoration of prepared cavities, 3 were intended for temporary and 3 for definitive restora-tion. According to dental fillings weight, all the participants were divided into 3 groups: those with fillings lighter than 0.50 g, those with 0.50­1.00 g, and those with fillings heavier than 1.00 g. Samples were taken from gingival sulcus using the filter paper technique. Clinical parameters were deter-mined by bleeding index, plaque index (Silness-Lou, 0­3), gingival index (0­3), and gingival sulcus depth. Cytokine con-centrations were assessed using commercially available cy-tomix. Results: According to the weight of dental fillings, there was a clear decreament trend of IL9 values meaning that dental defects greater than 1.00 g of dental filling were associated with lower GCF IL9 concentration. The IL9 val-ues correlated with the degree of gingival index and depth of gingival sulcus, being higher with more advanced gingivitis and more pronounced anatomical changes in the tooth edge. Different filling materials exerted various local IL9 responses. Zink polycarbonate cement and amalgam fillings induced a significant and long-lasting local IL9 decrement, while the use of Tetric EvoCeram and GMA-BISK significantly increased IL9 levels. Conclusion: The obtained results indicate that IL9 GCF could be regarded as a measure of odontoblasts' re-sponse to the extensity of dental caries. The type of material used for dental fillings could profoundly alter biological func-tion of gingival and pulpal cells. Also, the results obtained in this study suggest that some materials could even enhance wound repair by modulating macrophage activation.

CD14 and TNFα single nucleotide polymorphisms are candidates for genetic biomarkers of peri-implantitis.

OBJECTIVES: This study aims to investigate whether CD14-159 C/T and TNFα -308 A/G single nucleotide polymorphisms are associated with peri-implantitis and to evaluate their effects on bone resorption by correlating with local levels of receptor activator nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG). MATERIAL AND METHODS: Study population included 369 Southeastern Europe Caucasians (180 with peri-implantitis and 189 with healthy peri-implant tissues). Genotyping was performed using polymerase chain reaction from the periphery blood samples, while RANKL and OPG were evaluated in peri-implant crevicular fluid specimens using enzyme-linked immunosorbent assay. RESULTS: Analysis of CD14-159 C/T polymorphism showed that genotype of CC nucleic acid combination was associated with peri-implantitis demonstrating a fivefold increased risk in these carriers. Furthermore, for TNFα -308 A/G polymorphisms, it was evidenced that AG genotype was associated with peri-implantitis and a fivefold increased risk in these carriers. Peri-implantitis patients with CC genotype at CD14-159 exhibited significantly higher concentrations of RANKL and relative ratio RANKL/OPG when compared to patients with CT genotype, while concentration of biomarkers between different genotypes at TNFα -308 remained insignificant. CONCLUSION: Within the limitations of the study, we can conclude that CD14-159 C/T and TNFα -308 A/G polymorphisms are associated with peri-implantitis and may present biomarkers for peri-implantitis. CLINICAL RELEVANCE: Investigated genetic markers might serve as precious parameters in clinical practice in course of treatment planning and prognosis, since preventive and treatment approach could be positively shifted and adjusted depending on present genotype.

Estimation of bone loss biomarkers as a diagnostic tool for peri-implantitis.

BACKGROUND: The aims of this study are to estimate the profile of bone loss biomarkers in peri-implant tissues and to identify potential prognostic biomarkers of peri-implantitis. METHODS: Peri-implant crevicular fluid samples collected from 164 participants (52 patients with peri-implantitis, 54 with mucositis, and 58 with healthy peri-implant tissues) were analyzed using enzyme-linked immunosorbent assays to evaluate concentrations of the receptor activator of nuclear factor-κB (RANK), soluble RANK ligand (sRANKL), osteoprotegerin (OPG), cathepsin-K, and sclerostin. RESULTS: Concentrations of RANK, sRANKL, OPG, and sclerostin were significantly increased in patients with peri-implantitis compared with patients with healthy peri-implant tissues. Comparisons between peri-implantitis and mucositis demonstrated significantly higher values of sclerostin in peri-implantitis samples. Comparisons between mucositis and healthy peri-implant tissues showed significantly increased levels of RANK and cathepsin-K in mucositis. CONCLUSION: These results are suggestive of a role of sRANKL, OPG, and sclerostin as prognostic biomarkers in peri-implantitis.

Impact of dental implant insertion method on the peri-implant bone tissue--an experimental study.

BACKGROUND/AIM: The function of dental implants depends on their stability in bone tissue over extended period of time, i.e. on osseointegration. The process through which osseointegration is achieved depends on several factors, surgical insertion method being one of them. The aim of this study was to histopathologically compare the impact of the surgical method of implant insertion on the peri-implant bone tissue. METHODS: The experiment was performed on 9 dogs. Eight weeks following the extraction of lower premolars implants were inserted using the one-stage method on the right mandibular side and two-stage method on the left side. Three months after implantation the animals were sacrificed. Three distinct regions of bone tissue were histopathologically analyzed, the results were scored and compared. RESULTS: In the specimens of one-stage implants increased amount of collagen fibers was found in 5 specimens where tissue necrosis was also observed. Only moderate osteoblastic activity was found in 3 sections. The analysis of bone-to-implant contact region revealed statistically significantly better results regarding the amount of collagen tissue fibers for the implants inserted in the two-stage method (Wa = 59 < 66.5, alpha = 0.05), but necrosis was found in all specimens, and no osteoblastic activity. Histopathological analysis of bone-implant interface of one-stage implants revealed increased amount of collagen fibers in all specimens, moderate osteoblastic activity and neovascularization in 2 specimens. No inflammation was observed. The analysis of two-stage implants revealed a marked increase of collagen fibers in 5 specimens, inflammation and bone necrosis were found in only one specimen. There were no statistically significant differences between the two methods regarding bone-implant interface region. Histopathological analysis of bone tissue adjacent to the one-stage implant revealed moderate increase of collagen tissue in only 1 specimen, moderate increase of osteoblasts and osteocytes in 3 specimens. No necrotic tissue was found. The analyzed specimens of bone adjacent to two-stage implants revealed a moderate increase in the number of osteocytes in 3 and a marked increase in 6 specimens respectively. This difference was statistically significant (Wb = 106.5 > 105, alpha = 0.05). No necrosis and osteoblastic activity were observed. CONCLUSION: Better results were achieved by the two-stage method in bone-to-implant contact region regarding the amount of collagen tissue, while the results were identical regarding the osteoblastic activity and bone tissue necrosis. There was no difference between the methods in the bone-implant interface region. In the bone tissue adjacent to the implant the results were identical regarding the amount of collagen tissue, osteoblastic reaction and bone tissue necrosis, while better results were achieved by the two-stage method regarding the number of osteocytes.

Receptor activator of nuclear factor kappa B (RANK) as a determinant of peri-implantitis.

BACKGROUND/AIM: Peri-implantitis presents inflammatory process that affects soft and hard supporting tissues of osseointegrated implant based on inflammatory osteoclastogenesis. The aim of this study was to investigate whether receptor activator of nuclear factor kappa B (RANK) concentrations in peri-implant crevicular fluid could be associated with clinical parameters that reflect inflammatory nature of peri-implantitis. METHODS: The study included 67 patients, 22 with diagnosed peri-implantitis, 22 persons with healthy peri-implant tissues and 23 patients with periodontitis. Clinical parameters from each patient were recorded and samples of peri-implant/gingival crevicular fluid were collected for the enzyme-linked immunosorbent assay (ELISA) analysis. RESULTS: RANK concentration was significantly increased in samples from the patients with peri-implantitis when compared to healthy implants (p < 0.0001), where the average levels were 9 times higher. At the same time RANK concentration was significantly higher in peri-implantitis than in periodontitis sites (p < 0.0001). In implant patients pocket depths and bleeding on probing values were positively associated with high RANK concentrations (p < 0.0001). CONCLUSION: These results revealed association of increased RANK concentration in samples of peri-implant/gingival crevicular fluid with peri-implant inflammation and suggests that RANK could be a pathologic determinant of peri-implantitis, thereby a potential parameter in assessment of peri-implant tissue inflammation and a potential target in designing treatment strategies.

Bone loss biomarkers associated with peri-implantitis. A cross-sectional study.

AIM: To investigate the levels of biomarkers associated with osteoclastogenesis in patients suffering peri-implantitis and to compare them with levels in healthy peri-implant sites and severe chronic periodontitis. MATERIAL AND METHODS: Peri-implant/gingival crevicular fluid samples and clinical parameters including: bleeding on probing, modified Plaque Index (PlI), pocket depth and clinical attachment level were collected from 70 patients (23 with peri-implantitis, 25 with healthy peri-implant tissues and 22 with severe chronic periodontitis). The concentrations of sRANKL, RANK and OPG were evaluated using enzyme-linked immunosorbent assays; they were compared between the groups and correlated with the clinical findings. RESULTS: sRANKL (P = 0.01), RANK (P = 0.01) and OPG (P = 0.03) concentrations were significantly higher in peri-implantitis sites when compared to those in healthy implant sites, although differences in the sRANKL/OPG ratio were not statistically significant. In these sites all three markers were significantly correlated with the clinical parameters, with exception of OPG/PI correlation that remained insignificant (P = 0.121). When comparing peri-implantitis and periodontitis findings, RANK was significantly higher in peri-implantitis sites whereas, sRANKL (P = 0.03) and sRANKL/OPG ratio (P = 0.004) were significantly higher in periodontitis sites. Among periodontitis and healthy implant sites the same differences have been observed for both sRANKL (P = 0.000) and sRANKL/OPG ratio (P = 0.000), furthermore RANK was higher in periodontitis sites as well (P = 0.010). CONCLUSION: The findings of this preliminary study on a relatively small sample size suggest that the PICF levels of biomarkers sRANKL, RANK, and OPG are associated with peri-implant tissue destruction and the pattern of these biomarkers differed when compared to periodontitis.

[Impact of dental implant insertion method on the periimplant epithelial seal--experimental study on dogs].

BACKGROUND/AIM: There is a controversial opinion among implantologists on the method of dental implantation that provides more favourable response of soft and bone tissues. The aim of this study was to pathohistologicaly compare the influences of one- and two-phase implant surgical methods on the periimplant epithelial tissues. METHODS: The experiment was performed on 10 dogs. Eight weeks following tooth extractions implants were inserted using one phase method on the right side of the mandible, and two-phase method on the left one. Three months after implantation the animals were sacrificed. Contact regions of epithelial and subepithelial tissues and implants were pathohistologicaly examined, the elements of analysis were scored and compared. RESULTS: Epithelial tissue was not found in the two samples of one-phase implants, while in the remainder of samples the structure of basal membrane was preserved, massive inflammatory infiltrate was found in one, and partial necrosis was found in three samples. Epithelial tissue was not found in the three samples of two-phase implants, in three samples the structure of basal membrane was intact, while in three remained samples the membrane could not be detected; moderate inflammatory infiltrate was found in four samples and massive inflammatory infiltrate in both two remained samples; tissue necrosis, which was observed in the half of the samples, was complete. In subepithelial gingival tissues around one-phase implants the number of blood vessels was increased in three samples, accompanied by the thickening and dilatation of vascular walls, proliferation of blood elements, altered vascular walls and inflammatory cell infiltrate was found in four samples. CONCLUSION: On the base of the analized characteristics of epithelial and subepithelial tissues in contact with dental implants, one-phase method of implantation showed a more favorable tissue response.

Calcium and magnesium content in hard tissues of rats under condition of subchronic lead intoxication.

Lead manifests toxic effects in almost all organs and tissues, especially in: the nervous system, hematopoietic system, kidney and liver. This metal has a special affinity for deposition in hard tissue, i.e., bones and teeth. It is generally believed that the main mechanism of its toxicity relies on its interaction with bioelements, especially with Ca and Mg. This article analyses the influence of Pb poisoning on Ca and Mg content in hard tissues, (mandible, femur, teeth and skull) of female and young rats. Experiments were carried out on 60 female rats, AO breed, and on 80 of their young rats (offspring). Female rats were divided into three groups: the first one was a control group, the second one received 100 mg/kg Pb2+ kg b.wt. per day in drinking water, the third one received 30 mg/kg Pb(2+) kg b.wt. per day in drinking water. Young rats (offspring) were divided into the same respective three groups. Lead, calcium and magnesium content in hard tissues (mandible, femur, teeth-incisors and skull) was determined by flame atomic absorption spectrophotometry in mineralized samples. There was a statistically significant Pb deposition in all analyzed female and young rat hard tissues. Ca and Mg contents were significantly reduced in all female and young rat hard tissues. These results show that Pb poisoning causes a significant reduction in Ca and Mg content in animal hard tissues, which is probably the consequence of competitive antagonism between Pb and Ca and Mg.