Oxidative Stress and FOXO-1 Relationship in Stage III Periodontitis.

OBJECTIVES: 8-Hydroxideoxyguanosine (8-OHdG) is a marker of oxidative stress, and Forkhead Box-O1 (FOXO1) is a transcription factor and signaling integrator in cell and tissue homeostasis. This study aims to determine FOXO1 and 8-OHdG levels in serum and saliva samples of periodontitis patients and to evaluate their relationship with clinical periodontal parameters. MATERIALS AND METHODS: Twenty healthy individuals, twenty generalized Stage III Grade B periodontitis patients, and nineteen generalized Stage III Grade C periodontitis patients were included in the study. Clinical periodontal parameters (plaque index (PI), probing depth (PD), bleeding on probing (BOP), and clinical attachment level (CAL)) were recorded. Salivary and serum 8-OHdG and FOX-O1 levels were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Clinical periodontal parameters showed a statistically significant increase in periodontitis groups compared to the control group (p < 0.05). 8-OHdG salivary levels were significantly higher in both periodontitis groups compared to the control group. The salivary FOXO1 levels were significantly lower in both periodontitis groups compared to the control group. Salivary FOXO1 level had a low-grade negative correlation with BOP and salivary 8-OHdG level. CONCLUSIONS: While reactive oxygen species increase in periodontal inflammation, low expression of FOXO1, an important transcription factor for antioxidant enzymes, supports that this molecule plays a vital role in tissue destruction, and FOXO1 can be seen as a potential immune modulator. CLINICAL RELEVANCE: The role of FOXO1 in supporting antioxidant defense may suggest that FOXO1 is a candidate target for periodontitis treatment.

Asymmetric and symmetric dimethylarginine gingival crevicular fluid levels in periodontitis.

OBJECTIVE: This study aimed to evaluate the level of ADMA (asymmetric dimethylarginine), SDMA (symmetric dimethylarginine), and IL-1ß (Interleukin-1ß) in gingival crevicular fluid (GCF) from periodontitis patients and control subjects. BACKGROUND: ADMA and SDMA are potentially hazardous non-proteinogenic amino acids that limit nitric oxide (NO) synthesis and have many functions in various human disorders. ADMA causes a structural change in nitric oxide synthase, while SDMA blocks arginine cell uptake. Increased plasma ADMA has been widely recognized as a "trigger" initiating impaired NO bioavailability and vascular dysfunction, which ultimately leads to oxidative stress. METHODS: Twenty-five patients with periodontitis (P) (Stage III, Grade C, n = 25) and 20 control (C) subjects were included in the study. The IL-1ß level of GCF was measured by enzyme immunoassay (ELISA) and ADMA and SDMA by liquid chromatography-mass spectrometry (LC-MS/MS). RESULTS: Periodontitis patients had higher clinical parameters than controls (p < .001). Levels of IL-1ß, ADMA and SDMA GCF were statistically significantly higher in group P than in group C (respectively; p = .003, p < .0001, p < .0001). There was no difference in the ADMA/SDMA ratio (p = .312) between the groups. There were significant positive correlations between clinical periodontal parameters and IL-1ß, ADMA, and SDMA levels (p < .05). ADMA and SDMA levels were significantly correlated with IL-1ß (p < .05). CONCLUSIONS: These findings suggest that ADMA and SDMA may be involved in the pathogenesis of the periodontal disease.

Expression of tight junction proteins in smokers and non-smokers with generalized Stage III periodontitis.

OBJECTIVE: This study aims to evaluate the gingival crevicular fluid (GCF) levels of tumor necrosis factor-α (TNF-α), zonula occludens-1 (ZO-1), occludin (Occ), and tricellulin (Tric) in periodontitis, as well as their alterations due to smoking. BACKGROUND: Tight junctions (TJ), which consist of transmembrane and cytoplasmic scaffolding proteins, connect the epithelial cells of the periodontium. Occ, claudins, junctional adhesion molecules, and Tric are transmembrane TJ proteins found at the cell membrane. The transmembrane TJ proteins and the intracellular cytoskeleton are directly linked by cytoplasmic scaffolding proteins such as ZO-1. Although the functions and locations of these molecules have been defined, their behavior in periodontal inflammation is unknown. METHODS: The study included four groups: individuals with periodontal health without smoking (C; n = 31), individuals with generalized Stage III periodontitis without smoking (P; n = 28), individuals with periodontal health while smoking (CS; n = 22), and individuals with generalized Stage III periodontitis while smoking (PS; n = 18). Clinical periodontal parameters were recorded, and enzyme-linked immunosorbent assay (ELISA) was used to examine ZO-1, Occ, Tric, and TNF-α levels in GCF. RESULTS: In the periodontitis groups, clinical parameters were significantly higher (p < .001). The site-specific levels of TNF-α, ZO-1, Tric, and Occ in the P group were statistically higher than those in the other groups (p < .05). TNF-α, probing pocket depth (PPD), and bleeding on probing (BOP) exhibited positive correlations with all TJ proteins (p < .005). CONCLUSIONS: Smoking could potentially affect the levels of epithelial TJ proteins in the GCF, thereby potentially playing a significant role in the pathogenesis of the periodontal disease.

Does smoking influence tryptophan metabolism in periodontal inflammation? A cross-sectional study.

OBJECTIVES: The aim of this study was to identify the effects of smoking and periodontal inflammation on tryptophan-kynurenine metabolism as well as the correlation between these findings and clinical periodontal parameters. BACKGROUND: It has been shown that the tryptophan amino acid's primary catabolic pathway, the kynurenine pathway (KP), may serve as a key biomarker for periodontal disease. Although there are studies investigating the effect of smoking on KYN-TRP metabolism, the effect of smoking on periodontal disease through KP has not been revealed so far. METHODS: The salivary and serum samples were gathered from 24 nonsmoker (NS-P) stage III, grade B generalized periodontitis and 22 smoker (S-P) stage III, grade C generalized periodontitis patients, in addition to 24 nonsmoker (NS-C) and 24 smoker (S-C) periodontally healthy control individuals. Saliva and serum IL-6, kynurenine (KYN), and tryptophan (TRP) values, and KYN/TRP ratio were analyzed by liquid chromatography-mass spectrometry. Clinical periodontal measurements were recorded. RESULTS: Salivary TRP values were significantly higher in both periodontitis groups than control groups (p < .05). Salivary KYN values were highest in NS-P group (p < .05). Salivary KYN values did not differ significantly between periodontitis groups (p = .84). Salivary KYN/TRP ratio was significantly lower in NS-P group compared to other groups (p < .001). Serum TRP value is higher in S-P group than other groups; however, significant difference was found in S-C group (p < .05). Serum KYN values were significantly lower in smokers than nonsmokers. Serum KYN/TRP ratio is higher in NS-P group. NS-P group has the highest salivary IL-6 levels, NS-C group has the lowest values (p < .05). CONCLUSIONS: Our results point out that smoking exacerbates inflammation in the periodontium and increases TRP destruction and decreases IDO activity by suppressing KP in serum. As a result, kynurenine and its metabolites may be significant biomarkers in the link between smoking and periodontal disease.

Wnt signaling in periodontitis.

OBJECTIVE: This study aimed to evaluate the Wnt/ß-catenin signaling pathway activity in gingival samples obtained from patients with periodontitis. MATERIALS AND METHODS: Fifteen patients with stage III grade B (SIIIGB) and eleven with stage III grade C (SIIIGC) periodontitis were included and compared to 15 control subjects. ß-Catenin, Wnt 3a, Wnt 5a, and Wnt 10b expressions were evaluated by Q-PCR. Topographic localization of tissue ß-catenin, Wnt 5a, and Wnt 10b was measured by immunohistochemical analysis. TNF-α was used to assess the inflammatory state of the tissues, while Runx2 was used as a mediator of active destruction. RESULTS: Wnt 3a, Wnt 5a, and Wnt 10b were significantly higher in gingival tissues in both grades of stage 3 periodontitis compared to the control group (p < 0.05). ß-Catenin showed intranuclear staining in connective tissue in periodontitis, while it was confined to intracytoplasmic staining in epithelial tissue and the cell walls in the control group. Wnt5a protein expression was elevated in periodontitis, with the most intense staining observed in the connective tissue of SIIIGC samples. Wnt10b showed the highest density in the connective tissue of patients with periodontitis. CONCLUSIONS: Our findings suggested that periodontal inflammation disrupts the Wnt/ß-catenin signaling pathway. CLINICAL RELEVANCE: Periodontitis disrupts Wnt signaling in periodontal tissues in parallel with tissue inflammation and changes in morphology. This change in Wnt-related signaling pathways that regulate tissue homeostasis in the immunoinflammatory response may shed light on host-induced tissue destruction in the pathogenesis of the periodontal disease.

Evaluation of salivary and serum methylated arginine metabolites and nitric oxide synthase in advanced periodontitis patients.

OBJECTIVES: Methylated arginine metabolites and nitric oxide synthase (NOS) play a critical role in regulating endothelial function. The aim of this study was to determine levels of NOS, and methylated arginine metabolites (ADMA, SDMA, homoarginine, arginine, and L-NMMA) and IL-6 in serum and saliva in patients with advanced periodontal diseases and identify their association with clinical parameters. MATERIALS AND METHODS: The study consisted of two groups: healthy individuals (control: n = 24), and generalized Stage III Grade B periodontitis (P: n = 21). Clinical periodontal parameters (probing pocket depth, bleeding on probing, clinical attachment level) were recorded. IL 6 and NOS levels in saliva and serum were analyzed by enzyme-linked immunosorbent assay (ELISA). ADMA, SDMA, homoArg, arginine, and L-NMMA in saliva and serum were analyzed by liquid chromatography-mass spectrometry (LC MS/MS). RESULTS: Clinical parameters were significantly higher in the periodontitis group (p < 0.001). In periodontitis group, NOS, ADMA, and arginine levels in saliva were statistically significantly higher than control group (p < 0.05). Serum levels of SDMA were statistically significantly lower, and IL-6 was statistically significantly higher in P group than C group (p < 0.05). ADMA, NOS, and arginine levels were significantly positive correlated with all clinical periodontal parameters (p < 0.05). CONCLUSIONS: These findings suggest that there is a relationship between severity of periodontal disease and endothelial dysfunction by means of ADMA. Salivary ADMA may be related with periodontal inflammation. CLINICAL RELEVANCE: ADMA levels in periodontal inflammation are associated with endothelial dysfunction. According to the results of our study, periodontal inflammation is effective on both local and systemic methylated arginine metabolites and nitric oxide synthase levels. This may shed light on the relationship between periodontal disease and systemic status.

Influence of periodontal inflammation on tryptophan-kynurenine metabolism: a cross-sectional study.

OBJECTIVES: Kynurenine pathway (KP) is the primary way of degrading tryptophan (TRP) and generates several bioactive metabolites (such as kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3OHKYN)) to regulate biological processes that include host-microbiome signaling and immune cell response. This study is aimed to determine the relationship between periodontal inflammation and tryptophan-kynurenine metabolism and identify their association with periodontal clinical parameters. MATERIALS AND METHODS: Saliva and serum samples were collected from 20 stage III, grade B generalized periodontitis patients, and 20 periodontally healthy control individuals. Samples were analyzed for IL-6, KYN, TRP, KYN/TRP ratio, KYNA, 3OHKYN, picolinic acid (PA), and quinolinic acid (QA) by liquid chromatography-mass spectrometry. Clinical periodontal parameters (plaque index (PI), probing pocket depth (PPD), gingival recession (GR), clinical attachment loss (CAL), and bleeding on probing (BOP)) were recorded. RESULTS: Clinical parameters were significantly higher in the periodontitis group (p < 0.001). Salivary IL-6, TRP, KYN, KYNA, PA, and QA levels were significantly higher and KYN/TRP ratio was significantly lower in periodontitis group than control group (p < 0.05). Serum KYN, KYN/TRP ratio and PA levels were significantly higher in periodontitis group than control group (p < 0.05). PPD, BOP, PI, and CAL had significantly positive correlations with salivary IL-6, TRP, PA, QA, and serum KYN and significantly negative correlations with salivary KYN/TRP ratio. CONCLUSIONS: Our results suggest that periodontal inflammation plays a role in local and systemic tryptophan-kynurenine metabolism. CLINICAL RELEVANCE: Due to their effects on the immune and inflammatory systems, kynurenines may be potential agents for diagnosis and treatment of periodontal diseases.

Comparison of linear and volumetric measurements obtained from periodontal defects by using cone beam-CT and micro-CT: an in vitro study.

OBJECTIVES: To assess linear and volumetric measurement accuracy of periodontal defects (class 2 furcation, fenestration, dehiscence, and three-wall intrabony defect) by using CBCT and micro-CT images obtained at different voxel sizes. MATERIAL AND METHODS: We created 66 periodontal defects in human dry mandibles. Images of teeth with defects were taken by Planmeca Promox 3D Max (CBCT) at voxel sizes of 0.2 and 0.075 mm and super-argus PET/CT (micro-CT) at voxel sizes of 0.12 and 0.06 mm. All defects were then linearly (depth, width, and height) and volumetrically measured by 3D-DOCTOR software. Differences between voxels were assessed by Wilcoxon signed rank test. Bland-Altman limits of agreement and ICCs were calculated to assess agreement between the methods. Significance was set at p < 0.05. RESULTS: Volumes measured by micro-CT (0.12-0.06 mm) were higher than those of CBCT (0.2-0.075 mm) measurements regardless of the voxel size. ICC between micro CT and CBCT methods was found to be statistically significant for all types of defects in terms of volume (p < 0.001), height (p < 0.05), width (p < 0.001), and depth measurements (p < 0.001). CONCLUSION: CBCT provides useful information regarding linear and volumetric measurement of periodontal defects in vitro. CLINICAL RELEVANCE: Size and volume of periodontal defects may play an important role in the determination of the most appropriate treatment plan and disease prognosis along with outcome assessment.

Impact of non-surgical periodontal therapy on saliva and serum levels of markers of oxidative stress.

OBJECTIVE: The purpose of this study was to determine the effect of non-surgical periodontal treatment on markers of oxidative stress in saliva and serum in patients with chronic periodontitis. MATERIALS AND METHODS: In total, 25 patients, who were diagnosed with generalized chronic periodontitis (11 females and 14 males), and 26 systemically and periodontally healthy individuals (15 females and 11 males) were included. The plaque index (PI), gingival index (GI), probing pocket depth (PPD), attachment loss (AL), gingival recession (GR), and bleeding on probing (BOP) were recorded at baseline and 6 weeks later. Malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and 4-hydroxy-2-nonenal (4-HNE) were assessed in saliva and serum samples before and after the non-surgical treatment by enzyme-linked immune sorbent assay (ELISA). RESULTS: In the group with chronic periodontitis, all clinical parameters were significantly higher compared to the control group at baseline (p < 0.001). Periodontal treatment reduced plaque, gingival inflammation, and pocket depth significantly (p < 0.001). At baseline, salivary 8-OHdG was significantly higher in chronic periodontitis (p < 0.001) and reduced significantly subsequent to the periodontal treatment (p < 0.001). Salivary MDA and serum 4-HNE were significantly higher in the patients with periodontitis compared to the control group (p < 0.001). Periodontal treatment did not significantly change the levels of 4-HNE and salivary MDA (p = 0.503, p = 0.093). CONCLUSIONS: Salivary 8-OHdG and MDA may be associated with local impact of periodontal disease, while 4-HNE may be associated with systemic impact of chronic periodontitis. CLINICAL RELEVANCE: Clinical intervention in periodontitis may be beneficial for periodontitis patients' systemic oxidative stress control, and using lipidic agents for the use of anti-inflammatory/pro-resolving processes for blocking the actions of arachidonic acid cascade can enable some late therapeutic strategies in order to lead oxidative stress-induced inflammation.

Salivary and serum oxidative stress biomarkers and advanced glycation end products in periodontitis patients with or without diabetes: A cross-sectional study.

BACKGROUND: Non-invasive methods for periodontitis diagnosis would be a clinically important tool. This cross-sectional study aimed to investigate the association between oxidative stress, glycation, and inflammation markers and periodontal clinical parameters in periodontitis and periodontally healthy patients with type 2 diabetes and corresponding systemically healthy controls. METHODS: Sixty-seven periodontally healthy (DM-H, n = 32) and periodontitis (DM-P, n = 35) patients with type 2 diabetes, and 54 systemically healthy periodontitis (H-P, n = 26) and periodontally healthy (H-H, n = 28) controls were included. Clinical periodontal parameters, body mass index, fasting glucose, hemoglobin A1c (HbA1c), along with saliva and serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE), advanced glycation end products (AGE), AGE receptor (RAGE) and high sensitivity C-reactive protein (hsCRP) levels were recorded and analyzed. RESULTS: Salivary 8-OHdG levels were significantly higher in periodontitis compared to periodontally healthy patients, regardless of systemic status (P < 0.001). Salivary MDA levels were significantly higher in all disease groups compared to H-H group (P ≤ 0.004). Serum AGE levels were significantly higher in diabetic groups than systemically healthy groups (P < 0.001) and in H-P compared to H-H (P < 0.001). Bleeding on probing (BOP) and clinical attachment level (CAL) strongly correlated with salivary 8-OHdG and serum hsCRP (P < 0.001). In systemically healthy patients, salivary 8-OHdG was the most accurate marker to differentiate periodontitis from controls (AUC = 0.84). In diabetics salivary 4-HNE and RAGE were the most accurate (AUC = 0.85 for both). CONCLUSION: Salivary 8-OHdG alone or in combination with 4-HNE, AGE and RAGE for diabetics, and salivary 8-OHdG alone or in combination with MDA and hsCRP for systemically healthy persons, could potentially serve as non-invasive screening marker(s) of periodontitis.

Endocan (ESM-1) levels in gingival crevicular fluid correlate with ICAM-1 and LFA-1 in periodontitis.

Endocan, a 50 kDa soluble proteoglycan, also called endothelial cell-specific molecule-1 (ESM-1), is involved in many major cellular activities and has been reported to be overexpressed in inflammatory conditions. This study aims to determine ESM-1 levels in gingival crevicular fluid (GCF) samples from individuals with periodontitis to determine the correlation between the levels of lymphocyte-function-associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1), and clinical findings of periodontitis. This study enrolled 27 individuals diagnosed with Stage III-Grade C generalized periodontitis and 16 individuals as healthy controls. Bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) were calculated. Enzyme-linked immunosorbent assay (ELISA) test was used for detecting the levels of ESM-1, ICAM-1, and LFA-1 in GCF samples. PPD, BOP, CAL, and GCF volumes were significantly increased in patients with periodontitis in comparison to the control group (p < 0.001). The total amount of ESM-1, ICAM-1, and LFA-1 levels in GCF were increased in the periodontitis group (p < 0.001). ESM-1 level correlated with PPD, BOP, and CAL (p < 0.05). ICAM-1 level correlated with BOP and CAL (p < 0.05). LFA-1 level correlated with PPD and CAL (p < 0.05). Our data indicate that ESM-1, ICAM-1, and LFA-1 levels are increased in GCF of patients with periodontitis. These molecules could be associated with the pathogenesis and progression of periodontal disease.

A disintegrin-like and metalloproteinase with thrombospondin-1 (ADAMTS-1) levels in gingival crevicular fluid correlate with vascular endothelial growth factor-A, hypoxia-inducible factor-1α, and clinical parameters in patients with advanced periodontitis.

BACKGROUND: ADAMTS (a disintegrin-like and metalloproteinase with thrombospondin) are a family of proteinases that are structurally similar to the family of matrix metalloproteinases with critical roles in damage and repair of the extracellular matrix. Their functions are closely related to inflammation, hypoxia, and vascularization. Our aim was to determine levels of ADAMTS-1 in gingival crevicular fluid (GCF) in patients with advanced periodontal diseases and identify their association with hypoxia-inducible factor-1alpha (HIF-1α), vascular endothelial growth factor (VEGF-A), and clinical parameters of periodontitis. METHODS: The study consisted of three groups: healthy individuals (control; n = 20), generalized chronic periodontitis (CP; n = 21), and generalized aggressive periodontitis (GAgP; n = 20). Clinical parameters were measured. Levels of ADAMTS-1, VEGF-A, and HIF-1α in GCF and serum were quantified by enzyme-linked immunosorbent assay (ELISA) and reported as total amounts and concentration. RESULTS: ADAMTS-1 total amount in GCF were significantly higher in patients with CP and GAgP compared with healthy individuals (P < 0.05). HIF-1α total amount in GCF were also higher in periodontitis groups compared with the control group (P < 0.05). GCF total VEGF-A content was significantly higher in the GAgP group compared with the CP and the controls (respectively; P = 0.023, P = 0.003). There was a significant correlation between ADAMTS-1, VEGF-A, and HIF-1α levels in the GCF and clinical periodontal parameters (probing depth [PD], bleeding on probing [BOP], and clinical attachment loss (CAL); P < 0.05). CONCLUSION: ADAMTS-1 may play a role in advanced periodontal disease pathogenesis in correlation with tissue hypoxia and vascularization.

Interleukin-1 and tumor necrosis factor-alpha gene polymorphisms in Turkish patients with localized aggressive periodontitis.

Localized aggressive periodontitis (LAgP) is a complex multifactorial periodontal disease to which genetic factors are thought to predispose individuals. Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) are potent immunomodulators and proinflammatory cytokines that have been implicated in the pathogenesis of autoimmune and infectious diseases and proposed to be risk factors for LAgP. Our aim was to investigate IL-1 alpha (+4845), IL-1 beta (+3954), and TNF-alpha (-308) gene polymorphisms in Turkish LAgP patients. We genotyped 31 LAgP patients and 31 healthy controls for IL-1alpha(+4845), IL-1beta(+3954), and TNF-alpha(-308) using standard PCR amplification followed by restriction enzyme digestion and gel electrophoresis. Higher prevalence of heterozygosity for IL-1alpha(+4845) was found in cases (65%) when compared to controls (35%) (P < 0.05). While homozygous allele 1 of IL-1beta(+3954) was the most frequent genotype in cases (62%), no controls were homozygous for this allele (P < 0.001). Homozygous allele 1 was the most common TNF-alpha genotype in both groups, however no significant difference in TNF-alpha genotypes was found between groups. In conclusion, in this Turkish population, susceptibility to LAgP is increased by heterozygosity for allele 1 of IL-1alpha(+4845) or homozygosity for allele 1 of IL-1beta(R+3954). Moreover, IL-1 gene polymorphisms appear to have a role in susceptibility to LAgP, and the above-mentioned genotypes could be an important risk factor for LAgP in the Turkish population.

A Novel Systemic Indicator of Periodontal Tissue Damage: Ischemia Modified Albumin.

BACKGROUND: Ischemia-modified albumin (IMA) is a systemic indicator of inflammatory diseases and is suggested as an oxidative stress marker. OBJECTIVE: To determine the IMA and high-sensitivity C-reactive protein (hsCRP) serum levels for patients with chronic periodontitis (CP) and to evaluate the impact of non-surgical periodontal therapy on serum IMA and hsCRP levels. METHODS: Twenty one systemically healthy patients with CP and 15 systemically and periodontally healthy controls (C) were enrolled in the study. Periodontal pocket depth (PPD), bleeding on probing (BOP) and attachment loss (AL) were recorded at the time of diagnosis and 6 weeks after the nonsurgical periodontal therapy. Blood samples were obtained before and after treatment from all groups, and serum IMA and hsCRP levels were evaluated by ELISA method. RESULTS: All of the clinical findings were found to be elevated in the CP group in comparison to C group (p<0.05). Levels of IMA and hsCRP were higher in the CP group (p<0.05) and decreased after non-surgical periodontal therapy (p<0.05). Positive correlations were determined between PPD, BOP and hsCRP (p<0.05) as well as between PPD, AL, BOP and IMA levels (p<0.01) before treatment. A significant positive correlation was also observed between hsCRP and IMA (p<0.01) before and after treatment. CONCLUSION: IMA is a marker indicating systemic inflammation during periodontal disease, and is significantly reduced as a result of non-surgical periodontal therapy. Therefore, IMA might be suggested as a useful indicator of periodontal disease.

Endocan (ESM-1) levels in gingival crevicular fluid correlate with ICAM-1 and LFA-1 in periodontitis

Abstract: Endocan, a 50 kDa soluble proteoglycan, also called endothelial cell-specific molecule-1 (ESM-1), is involved in many major cellular activities and has been reported to be overexpressed in inflammatory conditions. This study aims to determine ESM-1 levels in gingival crevicular fluid (GCF) samples from individuals with periodontitis to determine the correlation between the levels of lymphocyte-function-associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1), and clinical findings of periodontitis. This study enrolled 27 individuals diagnosed with Stage III-Grade C generalized periodontitis and 16 individuals as healthy controls. Bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) were calculated. Enzyme-linked immunosorbent assay (ELISA) test was used for detecting the levels of ESM-1, ICAM-1, and LFA-1 in GCF samples. PPD, BOP, CAL, and GCF volumes were significantly increased in patients with periodontitis in comparison to the control group (p < 0.001). The total amount of ESM-1, ICAM-1, and LFA-1 levels in GCF were increased in the periodontitis group (p < 0.001). ESM-1 level correlated with PPD, BOP, and CAL (p < 0.05). ICAM-1 level correlated with BOP and CAL (p < 0.05). LFA-1 level correlated with PPD and CAL (p < 0.05). Our data indicate that ESM-1, ICAM-1, and LFA-1 levels are increased in GCF of patients with periodontitis. These molecules could be associated with the pathogenesis and progression of periodontal disease.

A histopathologic investigation on the effects of electrical stimulation on periodontal tissue regeneration in experimental bony defects in dogs.

BACKGROUND: One endpoint of periodontal therapy is to regenerate the structure lost due to periodontal disease. In the periodontium, gingival epithelium is regenerated by oral epithelium. Underlying connective tissue, periodontal ligament, bone, and cementum are derived from connective tissue. Primitive connective tissue cells may develop into osteoblasts and cementoblasts, which form bone and cementum. Several procedural advances may support these regenerations; however, the regeneration of alveolar bone does not always occur. Therefore, bone stimulating factors are a main topic for periodontal reconstructive research. The present study was designed to examine histopathologically whether the application of an electrical field could demonstrate enhanced alveolar and cementum regeneration and modify tissue factors. METHODS: Seven beagle dogs were used for this experiment. Mandibular left and right sides served as control and experimental sides, respectively, and 4-walled intrabony defects were created bilaterally between the third and fourth premolars. The experimental side was treated with a capacitively coupled electrical field (CCEF) (sinusoidal wave, 60 kHz, and 5 V peak-to-peak), applied for 14 hours per day. The following measurements were performed on the microphotographs: 1) the distance from the cemento-enamel junction to the apical notch (CEJ-AN) and from the crest of newly formed bone (alveolar ridge) to the apical notch (AR-AN); 2) the thickness of new cementum in the apical notch region; and 3) the length of junctional epithelium. The following histopathologic parameters were assessed by a semiquantitative subjective method: 1) inflammatory cell infiltration (ICI); 2) cellular activity of the periodontal ligament; 3) number and morphology of osteoclasts; 4) resorption lacunae; and 5) osteoblastic activity. RESULTS: The results showed that the quantity of new bone fill and the mean value of the thickness of the cementum were significantly higher for the experimental side (P < 0.01). The location of the base of the pocket was positioned more coronally with respect to the apical point of the coronal notch in the experimental side (statistically significant P < 0.01). The length of the junctional epithelium and the number of osteoclasts were higher in the stimulated side than the coronal side; these findings were also statistically significant (P < 0.01). The comparison of the electrically stimulated versus non-stimulated mandibles with the semiquantitative subjective method demonstrated statistically significant differences in defined histopathologic parameters, except for osteoclast morphologies (P > 0.05). CONCLUSIONS: This study demonstrated that the CCEF method has the potential to produce reconstructive effects and bone deposits. Further investigations with respect to the theoretical determination of local field parameters of the periodontal tissue complex, such as permittivity, conductivity, strength of the field electrical stimulation applied to the periodontal field current density, wavelength, and signal frequency appropriate for this field, should be undertaken. Using different electromotive forces alone or in combination with bone graft materials, guided tissue regeneration techniques, and dental implants may achieve a new dimension in periodontal therapy in the near future.

Serum Lp-PLA2: as a novel viewpoint in periodontal treatment of hyperlipidaemics.

BACKGROUND/AIM: To evaluate the effects of periodontal treatment on serum lipoprotein-associated phospholipase A2 (Lp-PLA2) and C-reactive protein (CRP) levels in hyperlipidaemic patients with periodontitis. MATERIALS AND METHODS: The study included 52 hyperlipidaemics and 28 systemically healthy controls (C) with periodontitis. Of the 52 hyperlipidaemics, 29 received a suggested diet (HD), and 23 of them were prescribed statin (HS). Clinical periodontal parameters, serum lipids, Lp-PLA2, and CRP levels were assessed at the baseline and 2 months after the completion of the nonsurgical periodontal treatment (2MPT). Serum parameters were also evaluated 1 week following the periodontal treatment (1WPT). RESULTS: At the baseline, patients in the HS group had a higher percentage of bleeding on probing than those in the C and HD groups. Hyperlipidaemics had higher serum triglyceride levels than the control group at 2MPT compared to the baseline. At 2MPT, the levels of Lp-PLA2 in the HS group were significantly higher compared to the baseline and 1WPT. There were no statistically significant differences in CRP levels between study periods for all groups. CONCLUSION: The periodontal treatment may affect the inflammatory control of hyperlipidaemic patients with periodontitis via increased Lp-PLA2 levels and severity of the impaired lipid metabolism. These findings may be important regarding the therapeutic strategies for hyperlipidaemics with periodontitis.

Evaluation of lipid peroxidation and oxidative DNA damage in patients with periodontitis and hyperlipidemia.

BACKGROUND: The purpose of this study is to determine the serum levels of malondialdehyde (MDA), as a lipid peroxidation marker, and 8-hydroxydeoxyguanosine (8-OHdG), as an oxidative DNA damage marker, in patients with chronic periodontitis (CP) and hyperlipidemia. METHODS: A total of 74 individuals were divided into four age- and sex-matched groups: 18 patients with hyperlipidemia and CP (HLp), 18 periodontally healthy patients with hyperlipidemia (HLh), 19 systemically healthy individuals with CP (Cp), and 19 systemically and periodontally healthy controls (Ch). Clinical periodontal parameters were measured, and serum lipids, MDA, and 8-OHdG levels were assessed in blood samples. RESULTS: 8-OHdG, MDA, probing depth, clinical attachment level, and percentage of sites bleeding on probing (BOP) were significantly higher in the HLp group than the Cp group. In the hyperlipidemic group, BOP was significantly correlated with total cholesterol, the ratio of total cholesterol to high-density lipoprotein cholesterol, and 8-OHdG levels. A significant correlation between 8-OHdG and MDA was also observed in the hyperlipidemia group. CONCLUSIONS: In this study, serum MDA and 8-OHdG were found to be highest in the HLp group. The increased levels of MDA and 8-OHdG in HLp patients may be a result of a harmful oxidative status in association with hyperlipidemia and periodontitis.

Generalized Aggressive Periodontitis in a Patient With Nephrotic Syndrome Associated With Primary Renal Amyloidosis: A Case Report.

INTRODUCTION: Renal amyloidosis may lead to renal disease, and then nephrotic syndrome may develop. To the best of the authors' knowledge, this is the first case report in which a patient presents with generalized aggressive periodontitis (GAgP) and nephrotic syndrome in conjunction with renal amyloidosis. CASE PRESENTATION: An 18-year-old male presented to the periodontology department for generalized gingival recessions. He was diagnosed as having primary renal amyloidosis by his physician. The patient presented with severe gingival inflammation and alveolar bone loss. Biochemical tests were within normal limits except for serum albumin level. No amyloid deposition was found in a gingival biopsy, and the patient was diagnosed as having GAgP. Non-surgical periodontal treatment, in combination with antibiotic treatment, was performed. After 3 years, his systemic and periodontal conditions showed deterioration. CONCLUSIONS: The effects of systemic factors related to nephrotic syndrome in conjunction with renal amyloidosis and deterioration in oral hygiene may play a significant role in the progression of periodontal disease. Even if there is no amyloid deposition in periodontal tissues, clinicians should consider that nephrotic syndrome associated with systemic amyloidosis may provide an important contribution to the periodontal breakdown by the modifying conditions that affect the host response to the accumulation of dental biofilm.