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Aim: The aim of the study was to compare serum ferritin and iron levels and periodontal status in pre- and post-menopausal female patients., Materials and Methods: A total of 108 systemically healthy patients were included in the study, 63 patients in the pre-menopause group and 45 patients in the post-menopause group. The periodontal diagnosis was made according to the new periodontal disease classification of the American Academy of Periodontology and the European Federation of Periodontology Serum Iron (μg/dL) and Serum Ferritin (ng/mL) values were analysed in patients divided into groups according to menopausal status and periodontal status., Result: The mean ferritin in pre-menopausal women (34.96 ± 27.87 ng/mL) was lower than the mean ferritin in post-menopausal women (64.24 ± 36.05 ng/mL), and this difference was found to be statistically significant (P<0.001). There was no statistically significant difference between the averages of iron and ferritin according to periodontal diagnosis in pre-menopausal women (P = 0.200 and P = 0.858). A statistically significant difference was found between serum ferritin averages according to periodontal diagnosis in post-menopausal women (P < 0.001). Serum ferritin at % Interdental bone loss = 0 in Post-M was 33.93 ± 8.65 ng/mL; 47.51 ± 16.17 ng/mL in Stage 1 periodontitis; 72.66 ± 18.12 ng/mL in Stage 2 periodontitis; It was found to be 87.4 ± 47.1 ng/mL in Stage 3-4 periodontitis., Conclusion: Serum ferritin values might vary depending on the presence or severity of periodontitis in post-menopausal women., (© 2024 Australian Dental Association.)

Aim: Cellular oxygen sensing mechanisms have been linked to periodontal condition, and levels of haemoglobin (Hb) (the main carrier of oxygen) can be used as a surrogate measure for hypoxia. We aimed to examine relations between Hb levels and key periodontal health parameters in a general population., Materials and Methods: The population comprised 1711 (47% male) subjects from the Northern Finland Birth Cohort 1966, for whom an oral health examination was carried out at 46 years of age and whose Hb levels were within the Finnish reference values. Relative risks (RRs) were estimated using Poisson regression models., Results: The low-Hb tertile (mean Hb 133 g/L) had healthier anthropometric, metabolic and periodontal health parameters than the high-Hb tertile (mean Hb 151 g/L). Multivariable regression models adjusted for risk factors showed Hb levels to be positively associated with alveolar bone loss (ABL) and periodontal pocket depth (PPD), although the associations were weaker after adjustment for key metabolic parameters and were strongly influenced by smoking status., Conclusions: Hb levels within the normal variation are positively associated with PPD and ABL. The association between Hb levels and periodontal condition appeared to be more complex than had previously been anticipated., (© 2024 The Author(s). Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

The study is aimed to assess the effects of serum vitamin D levels and their relationship to early dental implant failures. A total of 174 implants in 109 patients were placed and serum vitamin D levels were noted on the day of implant placement. Implants were followed up until restoration, approximately 3-6 months later, and any implant failure was reported based on 50% or more bone loss or implant mobility. Eight individuals had an implant fail early and their vitamin D levels had a mean of 42.54 ng/mL compared with the successful patients' levels of 31.92 ng/mL. Although not statistically significant, there was no correlation between patients' low serum vitamin D levels and early implant failure.

We aimed to investigate the effects of chronic stress (CS) on experimental periodontitis (EP) in rats. For this, 28 Wistar rats were divided into four groups: control, ligature-induced experimental periodontitis (EP), chronic stress (CS; by physical restraint model) and CS+EP (association of chronic stress and ligature-induced periodontitis). The experimental period lasted 30 days, including exposure to CS every day and ligature was performed on the 15th experimental day. After 30 days, the animals were submitted to the behavioral test of the elevated plus maze (EPM). Next, rats were euthanized for blood and mandible collection in order to evaluate the oxidative biochemistry (by nitric oxide (NO), reduced-glutathione activity (GSH), and thiobarbituric acid reactive substance levels (TBARS)) and alveolar bone characterization (by morphometric, micro-CT, and immunohistochemistry), respectively. The behavioral parameters evaluated in EPM indicated higher anxiogenic activity in the CS and CS+EP, groups, which is a behavioral reflex of CS. The results showed that CS was able to change the blood oxidative biochemistry in CS and CS+EP groups, decrease GSH activity in the blood, and increase the NO and TBARS concentrations. Thus, CS induces oxidative blood imbalance, which can potentialize or generate morphological, structural, and metabolic damages to the alveolar bone.

This study aimed to explore periodontal and systemic immune response of overweight hosts to periodontitis. Forty C57 BL/6J male mice were divided into high (HF) or low fat (LF) diet groups and fed with the two diets, respectively, for 8 weeks. Each diet group was then divided into periodontitis (P) or control (C) groups (n = 10 per group) for 10-day ligation or sham-ligation. Overweight-related parameters including body weight were measured. Alveolar bone loss (ABL) was morphometrically analyzed and periodontal osteoclasts were stained. Periodontal immune response including leukocyte and macrophage number and inflammatory cytokines were analyzed by histology and quantitative PCR. Serum cytokine and lipid levels were quantified using electrochemiluminescence immunoassays, enzyme-linked immunosorbent assays, and biochemistry. It was found that HF group had 14.4% body weight gain compared with LF group ( P < 0.01). ABL and periodontal osteoclast, leukocyte, and macrophage number were higher in P group than C group regardless of diet ( P < 0.05). ABL and periodontal osteoclast number were not affected by diet regardless of ligation or sham-ligation. Leukocyte and macrophage number and protein level of tumor necrosis factor α (TNF- α ) in periodontium and serum interleukin-6 level were downregulated by HF diet in periodontitis mice ( P < 0.05). Periodontal protein level of TNF- α was highly correlated with serum interleukin-6 and low-density lipoprotein cholesterol levels ( P < 0.01). These findings indicated that impaired immune response occurs both periodontally and systemically in preobesity overweight individuals. Given a well-reported exacerbating effect of obesity on periodontitis, overweight, if let uncontrolled, might place the individuals at potential risk for future periodontal tissue damage.

Background: Diabetes induces long bone loss and aggravation of periodontitis-induced alveolar bone loss. Simvastatin (SIM), which is a lipid-lowering agent is known to have an anabolic effect on bone. Therefore, we investigated effect of SIM on tibial and alveolar bone loss in type 1 diabetic rats with periodontitis., Methods: Rats were divided into control (C), diabetes with periodontitis (DP), and diabetes with periodontitis treated with SIM (DPS) groups. DP and DPS groups were intravenously injected with streptozotocin (50 mg/kg), and C group was injected with citrate buffer. Seven days later (day 0), periodontitis was induced by ligatures of mandibular first molars. DP and DPS groups were orally administered vehicle or SIM (30 mg/kg) from day 0 to days 3, 10, or 20. Alveolar and tibial bone loss was measured using histological and m-CT analysis alone or in combination. Osteoclast number and sclerostin-positive osteocytes in tibiae were evaluated by tartrate-resistant acid phosphatase and immunohistochemical staining, respectively. Glucose, triglyceride (TG), cholesterol (CHO), and low-density lipoprotein (LDL) were evaluated., Results: Consistent with diabetes induction, the DP group showed higher glucose and TG levels at all timepoints and higher CHO levels on day 20 than C group. Compared to the DP group, the DPS group exhibited reduced levels of glucose (day 3), TG (days 10 and 20), CHO, and LDL levels (day 20). Bone loss analysis revealed that the DP group had lower bone volume fraction, bone mineral density, bone surface density, and trabecular number in tibiae than C group at all timepoints. Interestingly, the DPS group exhibited elevation of these indices at early stages compared to the DP group. The DPS group showed reduction of osteoclasts (day 3) and sclerostin-positive osteocytes (days 3 and 20) compared with the DP group. There was no difference in alveolar bone loss between DP and DPS groups., Conclusions: These results suggest that SIM attenuates tibial, but not alveolar bone loss in type 1 diabetic rats with periodontitis. Moreover, attenuation of tibial bone loss by SIM may be related to inhibition of osteoclast formation and reduction of sclerostin expression.

The authors aimed to evaluate the effects of physical exercise on the metabolism and progression of periodontal disease (PD), induced by ligature in diabetic rats induced by high fat diet and streptozotocin (HFD/STZ). Diabetes Mellitus (DM) was induced by four weeks of a hyperlipidic diet associated with a single low-dose of streptozotocin (35 mg/kg/animal). The exercise groups swam for 60 min/day for eight weeks (five times/week). In the last two weeks of exercise, a ligature was placed around the right and left mandibular first molars. The authors determined alveolar bone loss by morphometry. Blood biochemical profile and serum levels of IL-10 and TNF-α were evaluated by colorimetric and enzyme-linked immunosorbent assays (ELISA), respectively. The diabetic animals subjected to exercise showed decreased alveolar bone loss, lower glycemia, triacylglycerols and glycosylated hemoglobin levels than the controls. Total cholesterol and its fractions (High density lipoprotein-HDL-c, Low density lipoprotein-LDL-c and Very low density lipoprotein-VLDL-c) remained similar among the groups. Animals with PD showed higher levels of TNF-α and lower levels of IL-10, when compared to animals without PD. In diabetic animals with PD, physical exercise decreased TNF-α levels and increased IL-10 levels as well as the IL10/TNF-α ratio. In conclusion, eight weeks of physical exercise improved glycemic control and systemic inflammatory profile, and attenuated alveolar bone loss in rats with DM and PD.

Objective: To investigate whether periodontitis, characterized by marginal jawbone loss, precedes the onset of symptoms of rheumatoid arthritis (RA), and to analyze plasma levels of RANKL (a cytokine that is crucial for bone resorption) and anti-citrullinated peptide antibodies (ACPAs) in presymptomatic individuals compared with matched referent controls., Methods: Marginal jawbone loss was measured on dental radiographs of the premolar/molar regions in the jaws in 176 subjects, 93 of whom subsequently developed RA. Among these participating subjects, 46 had documented radiographs predating symptom onset, and 45 cases could be matched to controls, according to sex, age, and smoking status. Plasma RANKL concentrations were analyzed using enzyme-linked immunosorbent assay. A receiver operating characteristic curve was used to define the cutoff value for RANKL positivity., Results: Bone loss was significantly greater in presymptomatic subjects classified as never smokers compared with that in controls, and increasing levels of bone loss were associated with a higher risk of the subsequent development of RA (hazard ratio 1.03, 95% confidence interval 1.01-1.05). No association between jawbone loss and RA was observed in smokers. A significantly greater extent of marginal jawbone loss was detected in RANKL-positive presymptomatic subjects, and even more pronounced jawbone loss was observed in those who were positive for both RANKL and ACPA., Conclusion: Marginal jawbone loss preceded the clinical onset of RA symptoms, but this was observed only in nonsmokers. Moreover, marginal jawbone loss was significantly greater in RANKL-positive presymptomatic subjects compared with RANKL-negative presymptomatic subjects and was highest in presymptomatic subjects positive for both ACPA and RANKL., (© 2017, American College of Rheumatology.)

Recent studies have shown that periodontitis accelerates the progression of obesity-associated metabolic diseases. Thus, we examined the influence of periodontitis on serum biochemical parameters of metabolic disease in a diet-induced obesity (DIO) rat. First, we established the DIO model using ten male rats fed with either basal diet (lean group) or high-fat diet (DIO group) for 12 weeks. Second, to examine the interaction between periodontitis and obesity, we divided 24 DIO rats into the following four groups. (1) Porphyromonas gingivalis (Pg) group was applied with Pg around the maxillary first molar (M1). (2) Ligature group was applied with ligature placement around M1. (3) Ligature/Pg group was treated with both ligature placement and Pg. (4) Control was non-treatment group. Serum biochemical parameters and maxillary histopathology were evaluated at 12 weeks. The DIO model demonstrated significant increases in body weight, serum insulin, alanine aminotransaminase (ALT) levels, and insulin resistance (HOMA-IR) compared to the lean group. In the DIO ligature and ligature/Pg groups, alveolar bone resorption and inflammatory cell infiltration were significantly increased compared to the control. Serum levels of fasting glucose, lactate dehydrogenase, and uric acid were also significantly higher, while the liver damage markers ALT and aspartate aminotransferase were only higher in ligature/Pg group. However, we observed no significant differences between the Pg group and Control. The present study suggested a possibility that periodontitis induced by ligature placement changed serum metabolic parameter regarding organs such as the liver in DIO rat.

Tocoyena sellowiana (Cham. & Schltdl.) K.Schum is one of the most important families of Brazilian medicinal plants. This study aimed to evaluate the effect of Tocoyena sellowiana (Cham. & Schltdl.) K.Schum ethanolic extract in a pre-clinical trial of periodontitis and to investigate possible mechanisms underlying such effects. Periodontitis was induced in Wistar rats by placing a nylon thread ligature around second upper left molars for 11 days. Rats received (per os) Tocoyena sellowiana (0.1, 1 or 10?mg?kg) or vehicle 1?h before ligature and daily until day 11. Macroscopic, histopathological, and COX-2 immunohistochemical analyses were performed to evaluate the periodontium. The gingival tissue was used to quantify the myeloperoxidase (MPO) activity and interleukin (IL)-1? levels by ELISA. Blood samples were collected to evaluate bone-specific alkaline phosphatase (BALP), the dosage of creatinine, aspartate and alanine transaminases. The liver, kidneys, spleen, and body mass variations were also evaluated. Tocoyena sellowiana decreased bone loss, reduced MPO, IL-1? levels as well as COX-2 immunostaining, and increased BALP activity. Moreover, Tocoyena sellowiana did not alter organs nor body weight. Tocoyena sellowiana reduced bone loss in rats and its efficacy was at least partially dependent upon both IL-1? and cyclooxygenase-2 inhibition., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

We report the case of a 14-year-old male with metastatic alveolar rhabdomyosarcoma, presenting with hypercalcaemia (3.89 mmol/l) and elevated parathyroid hormone (PTH) level (10.2 pmol/l). Imaging demonstrated extensive bony lytic damage, with "floating teeth" in the mandible. Normalisation of calcium levels and bony reformation of the mandible occurred following chemotherapy; PTH levels decreased initially but remained above normal levels. Imaging did not demonstrate any evidence of parathyroid abnormality. Tumour ectopic PTH secretion is a very rare cause of hypercalcaemia of malignancy in children. Hypercalcaemia with an elevated PTH, in the absence of parathyroid-related cause, should prompt investigation for underlying malignancy., (© 2017 Wiley Periodicals, Inc.)

Purpose: The aim of this prospective study was to evaluate parathyroid hormone serum level as a potential single factor of bone metabolism around dental implants., Materials and Methods: Parathyroid hormone levels were measured before implantation. Intraoral digital radiographs were taken in standardized conditions in all cases: immediately after implantation, immediately after functional loading, and 3, 6, 9, 12, 18, and 24 months after functional loading. The next phase was to align all radiographs geometrically. Two regions of interest were marked in the bone image: one in the implant neck region and another in the periapical region. Next, the entropy of the microarchitecture of the bone image was calculated, and an analysis of simple regression was performed., Results: The prospective study included 107 patients of both sexes in the age range of 17 to 67 years (mean ± SD: 45.53 ± 12.1 years). A significant relationship was observed between higher levels of parathyroid hormone (but still in the normal range) and the decrease of textural entropy in the alveolar ridge bone at 3, 6, 12, and 18 months after functional loading. However, in the periods immediately after implantation, immediately after functional loading, and 9 and 24 months after functional loading, the relationship was not statistically significant., Conclusion: Assessment of the parathyroid hormone serum level can be considered a useful method to predict bone condition around a dental implant, but not as a single factor.

Background: The endocrine and the immune system demonstrate a mutual relationship under pathophysiologic conditions. Thyroid hormone plays an important role in the regulation of normal growth and development. Although there is proven bidirectional influence of systemic diseases on periodontium, there are fewer studies on the effect of periodontal therapy on the hormone levels. This study aims to assess the effect of nonsurgical periodontal therapy (NSPT) on serum thyroid stimulating hormone (TSH) levels in hypothyroid patients with periodontal diseases., Materials and Methods: A total of 30 randomly chosen subjects of which 15 known hypothyroidism patients (13 females and 2 males) who were under medication for the same and 15 healthy individuals were enrolled into the study. Clinical parameters and serum TSH levels were recorded at baseline in both the groups, whereas TSH levels were recorded again at 3 months after NSPT in hypothyroid patients. Intergroup comparison was carried out by Tukey Kramer multiple comparisons test and the difference in variables was analyzed using one-way analysis of variance., Results: Mean values of TSH in hypothyroid patients 3.48 ± 1.41 μIU/ml showed significant reduction to 2.31 ± 1.24 μIU/ml (P ≤ 0.05) at 3 months follow up of NSPT. Clinical parameters improved significantly in both the groups after NSPT (P ≤ 0.05). Alveolar bone loss was greater in hypothyroid patients than the control group at baseline., Conclusion: NSPT plays a major role in improving periodontal conditions by reducing inflammatory markers and thereby influencing the thyroid hormone. Thus, immune system serves as an important link between thyroid dysfunction and periodontal diseases.

Objective: To characterize in rice rats: (a) periodontitis (PD) progress with feeding of standard laboratory rat chow (STD) during ages 4-80 weeks; and (b) PD progress with feeding of a high sucrose-casein (H-SC) diet during young adulthood., Methods: One group (N=12) was euthanized at age 4 weeks (Baseline). Four groups (N=8-16) consumed a STD diet from baseline and were necropsied at ages 22, 30, 52, and 80 weeks. Three groups (N=10-16) consumed an H-SC diet from baseline. Two were necropsied at ages 22 and 30 weeks, respectively. The third switched to the STD diet at age 22 weeks and was necropsied at age 30 weeks. All mandibles/maxillae were assessed by histometry for degree of periodontal inflammation (PD Score), alveolar crest height (ACH, mm), and horizontal alveolar bone height (hABH, mm 2 )., Results: In STD diet rats aged ≥30 weeks, all endpoints were worse (P<0.05) than at Baseline. In H-SC diet rats aged ≥22 weeks, all endpoints were worse than at Baseline (P<0.05). At age 22 weeks, all endpoints were worse in the H-SC group than in the STD group (P<0.05). By age 30 weeks, the STD and H-SC groups did not differ., Conclusions: 1) STD diet fed rice rats develop moderate/severe PD by age 30 weeks; 2) an H-SC diet accelerates moderate/severe PD development; and 3) switching to a STD diet does not halt/reverse PD that was accelerated by an H-SC diet. These data further clarify use of the rice rat as a PD model., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Statement of Problem: Continuous bone resorption is the primary reason for complete denture relines. Because resorption rates vary, the frequency at which individuals require relines also varies. Currently, there are no predictors to identify individuals at risk of frequent relines or to guide clinicians in decisions related to relines., Purpose: The purpose of this cross-sectional pilot study was to determine the utility of measuring bone metabolic markers (C-terminal telopeptide, osteocalcin, 25-OH hydroxy vitamin D) to predict the frequency of complete denture relines., Material and Methods: One hundred adult participants with complete dentures (either maxillary, mandibular, or both) participated in 1 dental clinic visit involving a dental examination and brief interview to obtain relevant medical and dental history, information on medication/supplement use, and 1 laboratory blood draw for the measurement of bone metabolic markers. Data were analyzed by using the Pearson correlation, independent Student t test, or analysis of variance (α=.05)., Results: Significant correlations were found between the frequency of relines and C-telopeptide and osteocalcin levels but not with vitamin D or age. No significant associations with reline frequency and other factors (sex, ethnicity, presence or absence of diabetes, use of calcium and vitamin D supplements) were observed., Conclusions: Elevated levels of bone turnover markers in individuals with edentulism were associated with increased frequency of denture relines., (Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Periodontitis is an inflammatory disease characterized by loss of connective tissue and alveolar bone, and osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture. To date, the association between periodontitis and osteoporosis has remained to be fully elucidated. In the present study, an experimental rat model of periodontitis was used to explore the effects of oestrogen deficiency‑induced osteoporosis on the maxillary alveolar bone. Forty‑four female, six‑month‑old Sprague‑Dawley rats were randomly divided into four groups: Control, ligature, ovariectomized (OVX), and OVX + ligature. One month after ovariectomy, rats in the ligature and OVX + ligature groups received ligatures on their first and second maxillary molars for 1 month. Fluorescent labelling was performed prior to sacrificing the animals. At the end of the experiment, the maxillae and serum were collected and subjected to micro‑computed tomography analysis, confocal laser‑scanning microscopic observation, Van Gieson's fuchsin staining, tartrate‑resistant acid phosphatase staining and ELISA. Ligatures slightly reduced the alveolar bone mineral density (BMD) and bone formation rate, but significantly reduced alveolar crest height (ACH). Ovariectomy reduced the alveolar BMD, impaired the trabecular structure, reduced the bone formation rate and increased the serum levels of bone resorption markers. Animals in the OVX + ligature group exhibited a lower alveolar BMD, a poorer trabecular structure, a reduced ACH, a lower bone formation rate and higher serum levels of bone resorption markers compared with those in the control group. The results of the present study showed that ovariectomy enhanced alveolar bone loss and reduced the ACH of rats with experimental periodontitis. Thus, post‑menopausal osteoporosis may influence the progression of periodontitis.

The objective of this study was to assess the effects of oral ingestion of β-glucans isolated from Saccharomyces cereviseae on the metabolic profile, expression of gingival inflammatory markers and amount of alveolar bone loss in diabetic rats with periodontal disease. Diabetes mellitus was induced in 48 Wistar rats by intraperitoneal injection of streptozotocin (80 mg/kg). After confirming the diabetes diagnosis, the animals were treated with β-glucans (by gavage) for 28 days. On the 14th day of this period, periodontal disease was induced using a ligature protocol. β-glucans reduced the amount of alveolar bone loss in animals with periodontal disease in both the diabetic and non-diabetic groups (p < 0.05). β-glucans reduced blood glucose, cholesterol and triacylglycerol levels in diabetic animals, both with and without periodontal disease (p < 0.05). Furthermore, treatment with β-glucans reduced the expression of cyclooxygenase-2 and receptor activator of nuclear factor kappa-B ligand and increased osteoprotegerin expression in animals with diabetes and periodontal disease (p < 0.05). It was concluded that treatment with β-glucans has beneficial metabolic and periodontal effects in diabetic rats with periodontal disease.

Background: The present study aims to investigate the effects of systemic melatonin administration on alveolar bone resorption in experimental periodontitis in rats., Methods: Twenty-four male Sprague-Dawley rats were divided into three groups (control, experimental periodontitis [Ped], and experimental periodontitis treated with melatonin [Mel-Ped]). For periodontitis induction, first molars were ligatured submarginally for 4 weeks. After ligature removal, rats in the Mel-Ped group were treated with a daily single dose of 10 mg/kg body weight melatonin for 15 consecutive days. At the end of the study, intracardiac blood samples and mandible tissues were obtained for histologic, biochemical, and radiographic analysis. Serum markers related to bone turnover, calcium, phosphorus, bone alkaline phosphatase (b-ALP), and terminal C telopeptide of collagen Type I (CTX) were analyzed. Myeloperoxidase levels were determined in gingival tissue homogenates, and receptor activator of nuclear factor-kappa B ligand (RANKL) activation was analyzed in the mandible samples stereologically. Alveolar bone loss was also evaluated radiographically in the mandible samples of each group., Results: Melatonin treatment decreased serum CTX levels and increased b-ALP levels. Serum calcium and phosphorus levels were not statistically different among groups (P >0.05). Alveolar bone resorption and myeloperoxidase activity were statistically higher in the Ped group compared to the Mel-Ped group (P <0.05). Immunohistochemical staining of RANKL and osteoclast activity were significantly lower in the Mel-Ped group compared to the Ped group (P <0.05)., Conclusion: This study reveals that melatonin treatment significantly inhibits regional alveolar bone resorption and contributes to periodontal healing in an experimental periodontitis rat model.

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.

Aim: Homocysteine (Hcy) is implicated in the development of cardiovascular diseases (CVD). The effect of periodontal disease and periodontal therapy on plasma Hcy remains controversial. Hence, in this pilot study we assessed the effect of periodontal disease and non-surgical periodontal therapy (NSPT) on plasma Hcy in systemically healthy Indian subjects., Materials and Methods: Forty participants (30 to 39 years) were enrolled in the study and were divided into two groups based on gingival index, probing depth, and clinical attachment level (CAL): Healthy (control group; n = 20) and Chronic Periodontitis (test group; n = 20). Plasma samples were collected and quantified at baseline and 12 weeks after scaling and root planing (SRP) for Hcy using High Performance Liquid Chromatography with fluorescent detection (HPLC-fld)., Results: Plasma Hcy levels of chronic periodontitis (17.87 ± 1.21 μmol/l) subjects was significantly higher than healthy subjects (9.09 ± 2.11 μmol/l). Post-therapy, the plasma Hcy concentration reduced significantly (11.34 ± 1.87 μmol/l) (p < 0.05)., Conclusion: The rise and descent of plasma Hcy levels with periodontal inflammation and therapy, respectively, indicate a direct relationship of Hcy with chronic periodontitis. NSPT may be employed as an adjunctive Hcy Lowering Therapy, contributing towards primary prevention against CVD's., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Several biologically plausible mechanisms have been proposed to mediate the association between periodontitis and atherosclerotic vascular disease (AVD), including adverse effects on vascular endothelial function. Circulating endothelial progenitor cells (cEPCs) are known to contribute to vascular repair, but limited data are available regarding the relationship between cEPC levels and periodontitis. The aims of this cross-sectional study are to investigate the levels of hemangioblastic and monocytic cEPCs in patients with periodontitis and periodontally healthy controls and to associate cEPC levels with the extent and severity of periodontitis., Methods: A total of 112 individuals (56 patients with periodontitis and 56 periodontally healthy controls, aged 26 to 65 years; mean age: 43 years) were enrolled. All participants underwent a full-mouth periodontal examination and provided a blood sample. Hemangioblastic cEPCs were assessed using flow cytometry, and monocytic cEPCs were identified using immunohistochemistry in cultured peripheral blood mononuclear cells. cEPC levels were analyzed in the entire sample, as well as in a subset of 50 pairs of patients with periodontitis/periodontally healthy controls, matched with respect to age, sex, and menstrual cycle., Results: Levels of hemangioblastic cEPCs were approximately 2.3-fold higher in patients with periodontitis than periodontally healthy controls, after adjustments for age, sex, physical activity, systolic blood pressure, and body mass index (P = 0.001). A non-significant trend for higher levels of monocytic cEPCs in periodontitis was also observed. The levels of hemangioblastic cEPCs were positively associated with the extent of bleeding on probing, probing depth, and clinical attachment loss. Hemangioblastic and monocytic cEPC levels were not correlated (Spearman correlation coefficient 0.03, P = 0.77), suggesting that they represent independent populations of progenitor cells., Conclusion: These findings further support the notion that oral infections have extraoral effects and document that periodontitis is associated with a mobilization of EPCs from the bone marrow, apparently in response to systemic inflammation and endothelial injury.

Objective: To investigate the effect of Lithothamnium sp (LTT) supplement, a calcium-rich alga widely used for mineral reposition, on strain-induced (orthodontic tooth movement [OTM]) and infection-induced bone resorption (periodontal disease [PD]) in mice., Materials and Methods: Mice were divided into two bone resorption models: one with an orthodontic appliance and the other with PD induced by the oral inoculation of Aggregatibacter actinomycetencomitans (Aa). Both groups were fed a regular diet (vehicle), LTT-rich diet (LTT), or calcium-rich diet (CaCO3). Alveolar bone resorption (ABR), the number of osteoclasts, and the levels of tumor necrosis factor α (TNF-α), calcium, and vitamin D3 were evaluated., Results: The number of osteoclasts was reduced in LTT and CaCO3 mice, which led to diminished OTM and infection-induced alveolar bone loss. In addition, LTT- and calcium-treated groups also presented decreased levels of TNF-α in periodontal tissues and increased levels of calcium in serum., Conclusions: These results indicate that the LTT supplement influences ABR, probably due to its calcium content, by affecting osteoclast function and local inflammatory response, thus modulating OTM and PD.

Introduction: We aimed to investigate the relationship between blood profile and histologic findings in both apical periodontitis (AP) and periodontal disease (PD) associated with diabetes., Methods: Wistar rats (N = 80) were assigned to the following 8 groups: control, AP, PD, AP associated with PD, diabetes, diabetes with AP, diabetes with PD, and diabetes with AP and PD. Diabetes mellitus (DM) was induced with streptozotocin, AP was induced by exposure to the oral environment, and PD was induced using periodontal ligature. After 30 days, blood samples were collected, and the rats were euthanized. Subsequently, the maxillae were processed for light microscopy. Hematologic examinations were conducted to determine the total number of erythrocytes and leukocytes, erythrocyte constant, and blood glucose level. One-way analysis of variance and Kruskal-Wallis tests were used for statistical analysis, and the significance was set at P < .05., Results: A significant correlation was found between the histologic findings and blood parameters., Conclusions: In conclusion, diabetes accelerated the development and progression of AP and PD in the rats and caused an increase in the average erythrocyte volume as well as the leukocyte and neutrophil counts. Oral infections increase the total number of leukocytes, the number of neutrophils and lymphocytes, and blood glucose concentrations in DM rats., (Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: Anticardiolipin antibodies (antiCl), present in some patients with autoimmune disease, are associated with thrombosis, fetal loss, and other conditions. A significant proportion of patients with chronic periodontitis (CP) test positive for antiCl, likely because some periodontal pathogens contain antigens homologous to the target antigen of antiCl on the serum protein β-2 glycoprotein-I (β2GPI) and thus can induce antiCl by molecular mimicry. The authors hypothesized that treatment of periodontitis by scaling and root planing (SRP) could therefore decrease serum titers of antiCl in patients with CP., Methods: Thirty patients with CP received complete periodontal examinations at baseline including assessment of probing depth, attachment loss, gingival index, and plaque index. SRP was performed in two sessions at 2-week intervals. Eight weeks later, patients were reexamined. Blood samples were taken at baseline, 2 weeks after the initial therapy appointment, and 8 weeks after the completion of treatment for assessment of immunoglobulin (Ig)G and IgM antiCl levels., Results: All periodontal parameters improved significantly. Consistent with previous observations, five (16.7%) of the 30 patients exhibited elevated levels of IgG or IgM antiCl at baseline. Following treatment, the concentrations of IgG and IgM antiCl remained unchanged for the entire cohort of 30 patients. However, in the five patients with elevated antiCl at baseline, IgM antiCl concentrations decreased significantly (P = 0.0008) owing to therapy, while IgG antiCl did not., Conclusion: The oral microflora is a likely source of antigen inducing antiCl in CP, since IgM antiCl levels can be reduced in the short term with conservative therapy.

Aim: To measure glycosylated haemoglobin (HbA1c) in a diabetic model as a means of investigating apical periodontitis and periodontal disease for their effects on both blood glucose concentrations and long-term glycaemic control., Methodology: Wistar rats (n = 80) were assigned to one of eight groups (10 animals/group): control (G1), apical periodontitis (G2), periodontal disease (G3), apical periodontitis and periodontal disease (G4), diabetic (G5), diabetic with apical periodontitis (G6), diabetic with periodontal disease (G7) and diabetic with apical periodontitis and periodontal disease (G8). A diabetic state was induced with streptozotocin. Apical periodontitis was induced by dental exposure to the oral environment. Periodontal disease was induced by periodontal ligature. Blood glucose concentrations were measured at 0, 6, 30 and 60 days. After euthanization, rat maxillae were excised and processed for histopathology and for measurement of HbA1c levels by ion exchange chromatography. Data were tabulated and subject to statistical analysis (P < 0.05)., Results: The inflammatory infiltrate and alveolar bone resorption were more severe in diabetic rats (P < 0.05). Diabetic rats exhibited higher levels of HbA1c independent of apical periodontitis or periodontal disease (P < 0.05). However, the presence of oral infections in diabetic rats was associated with increased blood glucose concentrations (P < 0.05)., Conclusions: Oral infections affect glycaemic conditions in diabetic rats and increase HbA1c levels in normoglycaemic or diabetic rats., (© 2013 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Periodontal disease is a chronic inflammatory disease that results in the breakdown of the tooth-supporting tissues, and can ultimately lead to resorption of the alveolar bone. Recently, several studies have shown a close relationship between increased interleukin-18 (IL-18) levels and the pathogenesis of chronic periodontitis, a major cause of tooth loss. However, it has yet to be shown whether chronic periodontitis results from or causes an increase in IL-18 after bacterial infection. In the present study, we investigated how IL-18 overexpression relates to periodontal disease using IL-18 transgenic (Tg) mice. IL-18Tg and wild-type mice were inoculated intraorally with Porphyromonas (P.) gingivalis, which has been implicated in the etiology of chronic periodontitis. Seventy days after P. gingivalis infection, alveolar bone loss and gingival cytokine levels were assessed using histo-morphological analysis and enzyme-linked immuno-absorbent assay, respectively. Periodontal bone loss was evoked in IL-18Tg mice, but not in wild-type mice. Interestingly, levels of bone-resorptive cytokines, including IL-1α, IL-1β, tumor necrosis factor-α, and IL-6, were unchanged in the gingival tissues of IL-18Tg mice infected with P. gingivalis, although levels of interferon γ (a proinflammatory T-helper 1 cytokine) decreased. RT-PCR analysis showed elevated expression of mRNAs for receptor activator of nuclear factor kappa-B ligand (a key stimulator of osteoclast development and activation) and CD40 ligand (a marker of T cell activation) in the gingiva of IL-18Tg mice infected with P. gingivalis. We conclude that increased IL-18 in the gingival tissues evokes chronic periodontitis after bacterial infection, presumably via a T cell-mediated pathway.

Background: In this study, the relationships between total oxidant status (TOS) and receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) levels and RANKL/OPG ratios in serum and gingival crevicular fluid (GCF) are investigated in patients with chronic (CP) and generalized aggressive (GAgP) periodontitis., Methods: Thirty patients with CP, 30 patients with GAgP, and 28 periodontally healthy controls were included in the study. After clinical measurements and samplings, serum and GCF TOS, RANKL, and OPG levels were determined by a novel automatic colorimetric method and enzyme-linked immunosorbent assays., Results: Serum and GCF TOS, RANKL, and RANKL/OPG values were higher in the periodontitis groups compared with controls, and they were also higher in the GAgP group than the CP group (except serum and GCF RANKL). Furthermore, serum and GCF OPG concentrations were lower in the periodontitis groups than in controls. Strong positive and negative correlations were observed between the periodontal parameters TOS and bone resorption biomarkers., Conclusions: The present results reveal that TOS, RANKL, and RANKL/OPG values are systemically and locally increased in periodontitis and that this increase is more evident in AgP than CP. These findings further suggest that oxidative stress is closely associated with the severity of periodontitis and bone resorption biomarkers.

Periodontitis is characterized by altered host-biofilm interactions that result in irreversible inflammation-mediated alveolar bone loss. Genetic and epigenetic factors that predispose to ineffective control of biofilm composition and maintenance of tissue homeostasis are not fully understood. We elucidated how leukocytes affect the course of periodontitis in Rac-null mice. Mouse models of acute gingivitis and periodontitis were used to assess the early inflammatory response and patterns of chronicity leading to loss of alveolar bone due to inflammation in Rac-null mice. Leukocyte margination was differentially impaired in these mice during attachment in conditional Rac1-null (granulocyte/monocyte lineage) mice and during rolling and attachment in Rac2-null (all blood cells) mice. Inflammatory responses to subgingival ligatures, assessed by changes in peripheral blood differential leukocyte numbers, were altered in Rac-null compared with wild-type mice. In response to persistent subgingival ligature-mediated challenge, Rac-null mice had increased loss of alveolar bone with patterns of resorption characteristic of aggressive forms of periodontitis. These findings were partially explained by higher osteoclastic coverage of the bone-periodontal ligament interface in Rac-null compared with wild-type mice. In conclusion, this study demonstrates that leukocyte defects, such as decreased endothelial margination and tissue recruitment, are rate-limiting steps in the periodontal inflammatory process that lead to more aggressive forms of periodontitis., (Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

To investigate the correlation between postmenopausal osteoporosis (PMO) and the pathogenesis of periodontitis, ovariectomized rats were generated and the experimental periodontitis was induced using a silk ligature. The inflammatory factors and bone metabolic markers were measured in the serum and periodontal tissues of ovariectomized rats using an automatic chemistry analyzer, enzyme-linked immunosorbent assays, and immunohistochemistry. The bone mineral density of whole body, pelvis, and spine was analyzed using dual-energy X-ray absorptiometry and image analysis. All data were analyzed using SPSS 13.0 statistical software. It was found that ovariectomy could upregulate the expression of interleukin- (IL-)6, the receptor activator of nuclear factor- κB ligand (RANKL), and osteoprotegerin (OPG) and downregulate IL-10 expression in periodontal tissues, which resulted in progressive alveolar bone loss in experimental periodontitis. This study indicates that changes of cytokines and bone turnover markers in the periodontal tissues of ovariectomized rats contribute to the damage of periodontal tissues.

The reconstruction of large osseous defects due to periodontitis is a challenge in regenerative therapy. Sclerostin, secreted by osteocytes, is a key physiological inhibitor of osteogenesis. Pharmacologic inhibition of sclerostin using sclerostin-neutralizing monoclonal antibody (Scl-Ab) thus increases bone formation, bone mass and bone strength in models of osteopenia and fracture repair. This study assessed the therapeutic potential of Scl-Ab to stimulate alveolar bone regeneration following experimental periodontitis (EP). Ligature-induced EP was induced in rats to generate localized alveolar bone defects. Following 4 weeks of disease induction, Scl-Ab (+EP) or vehicle (+/- EP) were systemically delivered, twice weekly for up to 6 wks to determine the ability of Scl-Ab to regenerate bone around tooth-supporting osseous defects. 3 and 6 wks after the initiation of Scl-Ab or vehicle treatment, femur and maxillary jawbones were harvested for histology, histomorphometry, and micro-computed tomography (micro-CT) of linear alveolar bone loss (ABL) and volumetric measures of bone support, including bone volume fraction (BVF) and tissue mineral density (TMD). Serum was analyzed to examine bone turnover markers during disease and regenerative therapy. Vehicle + EP animals exhibited maxillary bone loss (BVF, TMD and ABL) at ligature removal and thereafter. 6 weeks of Scl-Ab significantly improved maxillary bone healing, as measured by BVF, TMD and ABL, when compared to vehicle + EP. After 6 weeks of treatment, BVF and TMD values in the Scl-Ab + EP group were similar to those of healthy controls. Serum analysis demonstrated higher levels of bone formation markers osteocalcin and PINP in Scl-Ab treatment groups. Scl-Ab restored alveolar bone mass following experimental periodontitis. These findings warrant further exploration of Scl-Ab therapy in this and other oral bone defect disease scenarios., (© 2013 American Society for Bone and Mineral Research.)

Background and Objective: Diabetes mellitus is believed to increase the risk and severity of periodontitis. However, less evidence is available on the converse effects of periodontitis on diabetes. The objective of the study was to investigate to what degree experimental periodontitis induced by Porphyromonas gingivalis might influence the onset and severity of diabetes in different mouse models., Material and Methods: Twenty-eight male Tallyho/JngJ mice (type 2 diabetes), 20 male streptozotocin-induced diabetes C57BL/6J mice (type 1 diabetes) and 20 male C57BL/6J mice at 4 wks of age were evenly divided into two groups: periodontal infection and sham infection. Periodontitis was induced by Porphyromonas gingivalis W50 (P. gingivalis) oral inoculation before the development of diabetes. Sham-infected mice received vehicle as control. P. gingivalis in the oral cavity were identified by quantitative polymerase chain reaction. Fasting glucose, body weight and food intake levels were monitored and glucose tolerance tests were performed to assess glucose homeostasis for the onset and progression of diabetes. The level of alveolar bone loss and tumor necrosis factor-alpha were determined in week 20 when mice were killed., Results: Mice in the infection groups developed more alveolar bone loss than those in sham-infection groups (Tallyho p = 0.021; C57-STZ p = 0.014; C57 p = 0.035). Hyperglycemic mice exhibited significantly more bone loss compared to those normal glucose mice (Tallyho vs. C57 p = 0.029; C57-STZ vs. C57 p = 0.024). The level of tumor necrosis factor-alpha was consistent with that of periodontal bone loss and hyperglycemia. There was no significant effect of mouse species on the amount of bone loss at the same level of blood glucose. No statistically significant difference or trend in glucose metabolism was found between the infection and sham-infection group., Conclusion: Diabetes enhanced the risk for periodontal disease induced by P. gingivalis. However, no converse impact was found between this periodontal infection and onset and severity of diabetes in both type 1 and 2 diabetes mice., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: Besides their role in bone metabolism, receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) are also known to be associated with inflammation. We explored associations between the extent/severity of periodontitis and circulating levels of sRANKL and OPG and their ratio using a cross-sectional study design., Subjects & Methods: The extent of periodontal inflammation and tissue destruction and the serum levels of sRANKL (pg/ml) and OPG (pg/ml) were determined in 80 subjects with type 1 diabetes mellitus (T1DM). Plaque-, age-, gender-, smoking-, HbA1c- and body mass index-adjusted associations between periodontal parameters and serum sRANKL, OPG and their ratio were studied using multiple linear regression analysis., Results: Adjusted regression analyses of all the subjects indicated a significant positive association between AL ≥ 4 mm and severity of periodontitis and the level of serum OPG. A major drop in the strength and statistical significance of the above association was observed when the analyses included only non-smokers. Serum sRANKL level and sRANKL/OPG ratio were not associated with periodontitis., Conclusion: Our observations suggest that serum OPG may be an indicator of periodontal tissue destruction in T1DM., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

To explore the role of the IL-23/IL-17 axis in the relationship between periodontitis and coronary heart disease (CHD), 97 subjects were recruited and divided into four groups: (1) CHD + periodontitis, (2) CHD, (3) periodontitus alone, and (4) healthy. The demographic characteristics and periodontal status of all subjects were recorded, and the serum levels of IL-23/IL-17 were detected by enzyme-linked immunoabsorbent assay. Results showed that the serum levels of IL-23/IL-17 in groups 1, 2, and 3 were higher compared with group 4. Group 1 manifested the highest level of serum IL-23/IL-17. A significant positive correlation between IL-23 and IL-17 levels was seen in the three patients groups; groups 1 and 3 also had significant positive correlations with probing depth and attachment loss. The results indicate that there may be an association between periodontitis and CHD, and the IL-23/IL-17 axis may play an important role in the pathologic process of both diseases.

The aim of the present study was to clarify whether there is any correlation between the levels of high-sensitivity C reactive protein (hs-CRP) and stem cell factor (SCF) in serum and gingival crevicular fluid (GCF) of patients with chronic periodontitis (CP) with and without type 2 diabetes mellitus (DM). A total of 40 subjects were divided into 3 groups: 10 periodontally healthy subjects (Group 1), 15 CP patients (Group 2), and 15 type 2 DM patients with CP (Group 3). Levels of hs-CRP and SCF in GCF and serum were quantified using different techniques. The clinical outcomes evaluated were gingival index (GI), probing depth (PD) and clinical attachment level (CAL), and the correlations of the two inflammatory mediators with clinical parameters were evaluated. The levels of these inflammatory mediators increased continuously from group 1 to group 2, and to group 3. The serum levels of both hs-CRP and SCF were correlated with PD in patients with CP (P < 0.05). SCF levels were correlated with PD in Group 3 (P < 0.05). The fact that the levels of hs-CRP and SCF were highest in DM patients with CP suggests that the presence of a systemic condition has a profound effect on the levels of inflammatory mediators, both locally at sites of periodontal disease, and elsewhere.

Periodontitis is a complication of diabetes mellitus, and the two diseases are highly associated with the dysfunction of inflammatory mediators. 25-hydroxyvitamin D(3) (25(OH)D(3)) plays a pivotal role in inflammatory modulation, but little is known about its effects on the progression of diabetic periodontitis and the underlying mechanism. In this paper, we showed that 25(OH)D(3) ameliorated experimental periodontitis in diabetic mice. The intraperitoneal administration of 25(OH)D(3) to streptozotocin-induced diabetic mice reduced fasting glucose and serum TNF-α levels, leading to decreased alveolar bone loss. Western blot analyses of gingival epithelia showed that vitamin D receptor (VDR) and protein tyrosine phosphatase N2 (PTPN2) were upregulated, while the expression of NF-κB and the phosphorylation of Janus family kinase 1 (JAK1) were attenuated upon 25(OH)D(3) treatment. These data may provide an explanation for the therapeutic benefits and anti-inflammatory effects of 25(OH)D(3). Our findings should have important implications for the clinical therapy of diabetic periodontitis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Dyslipidemia increases circulating levels of oxidized low-density lipoprotein (OxLDL) and this may induce alveolar bone loss through toll-like receptor (TLR) 2 and 4. The purpose of this study was to investigate the effects of dyslipidemia on osteoclast differentiation associated with TLR2 and TLR4 in periodontal tissues using a rat dyslipidemia (apolipoprotein E deficient) model., Methods: Levels of plasma OxLDL, and the cholesterol and phospholipid profiles in plasma lipoproteins were compared between apolipoprotein E-deficient rats (16-week-old males) and wild-type (control) rats. In the periodontal tissue, we evaluated the changes in TLR2, TLR4, receptor activator of nuclear factor kappa B ligand (RANKL) and tartrate resistant acid phosphatase (TRAP) expression., Results: Apolipoprotein E-deficient rats showed higher plasma levels of OxLDL than control rats (p<0.05), with higher plasma levels of total cholesterol (p<0.05) and LDL-cholesterol (p<0.05) and lower plasma levels of high-density lipoprotein cholesterol (p<0.05). Their periodontal tissue also exhibited a higher ratio of RANKL-positive cells and a higher number of TRAP-positive osteoclasts than control rats (p<0.05). Furthermore, periodontal gene expression of TLR2, TLR4 and RANKL was higher in apolipoprotein E-deficient rats than in control rats (p<0.05)., Conclusion: These findings underscore the important role for TLR2 and TLR4 in mediating the osteoclast differentiation on alveolar bone response to dyslipidemia.

Background and Objective: Cardiovascular diseases are significantly correlated with chronic periodontitis. The aim of this study was to evaluate bone-loss level, neutrophil migration, CXCL2/CINC-2α, CXCL5/LIX, CCL20/MIP-3α and tumor necrosis factor-α (TNF-α) production, inducible nitric oxide synthase (iNOS) expression and C-reactive protein (CRP) release in spontaneously hypertensive rats (SHRs) and normotensive (WTK) rats after experimental induction of periodontal disease., Material and Methods: Periodontitis was induced by placement of silk yarn ligatures around the first molar counterparts. The levels of CRP, CCL20/MIP-3α and CXCL5/LIX were evaluated in the peripheral blood, and bone-loss level, neutrophil recruitment, the production of myeloperoxidase, CXCL2, CXCL5, CCL20 and TNF-α, and the expression of iNOS were evaluated in the gingival tissue. Histological sections were taken to evaluate and measure bone resorption and neutrophil recruitment in the furcation region., Results: Rats with periodontitis had alveolar bone resorption. SHRs with periodontitis showed marked bone loss and increased neutrophil infiltration in comparison with WTK rats. SHRs with periodontitis showed increased levels of TNF-α and CXCL2, and a slight tendency for increased levels of CXCL5, in the gingival tissue but no increase in the level of CCL20. In SHRs, even without periodontitis, the levels of TNF-α, CXCL2, CXCL5 and CCL20 showed a slight tendency to increase. In the WTK rats, TNF-α, CXCL2 and CXCL5 levels were increased with periodontitis, but the level of CCL20 was not. iNOS was expressed in the gingival tissue of WTK rats and SHRs with periodontitis; however, SHRs appeared to express a higher level of iNOS than did WKT rats. The CRP level was elevated in both types of rats with periodontitis; however, the CRP level was higher in SHRs with periodontitis than in WTK rats with periodontitis., Conclusion: In SHRs, the hypertensive condition per se seems to favor the inflammatory processes that become potentiated with periodontitis, when compared with WKT rats., (© 2012 John Wiley & Sons A/S.)

The inflammatory mediators, serum elastase and C-reactive protein (CRP), are associated with an increased risk for coronary heart disease. Thus, the aim of this study is to compare systemic inflammatory mediators in periodontally healthy controls (C), patients with untreated aggressive (AgP) and chronic (ChP) periodontitis. C [periodontal pocket probing depth (PPD)  <3.6 or <5 mm without bleeding (BOP), BOP < 10%], ChP (PDD ≥ 3.6 mm and probing attachment loss ≥5 mm at >30% of sites; age >35 years), and AgP (clinically healthy; PDD ≥ 3.6 mm at >30% of sites, bone loss ≥50% at ≥2 teeth; age ≤35 years) were examined clinically, and the body mass index was assessed. Blood was sampled for assessment of serum levels of elastase, CRP, lipopolysaccharide binding protein (LBP), interleukin (IL) 6, 8, and leukocyte counts. Thirty C, 31 ChP, and 29 AgP were analyzed. Elastase, CRP, LBP, and IL-6 levels were elevated in AgP compared to C (p < 0.013), whereas leukocyte counts and IL-8 were similar. Multiple regression analysis identified AgP (p < 0.001) and education level (p < 0.001) to explain 47% of the variation of elastase. AgP (p = 0.003), African origin (p = 0.006), female sex (p = 0.002), and BMI (p < 0.001) explained 39% of the variation of CRP. Serum elastase and CRP are significantly elevated in AgP compared to C. AgP patients exhibit a stronger systemic inflammatory burden than C patients.

Background and Objective: Loss of clinical attachment and alveolar bone destruction are major symptoms of periodontitis, caused by not only the destructive effect of periodontopathic bacteria but also the overactive response of the host immune system against periodontal pathogens. The details of the participation of the immune system in the onset and progression of periodontitis are unclear. In this study, we attempted to determine whether the host immune system, and in particular the formation of immune complexes, is involved in the periodontal destruction., Material and Methods: We applied ovalbumin or lipopolysaccharide (LPS) as antigens and their specific immunoglobulin G (IgG) antibodies purified from rat serum to rat gingival sulcus alternately. Loss of attachment, alveolar bone destruction and the numbers of inflammatory cells infiltrating the periodontal tissue and osteoclasts on the alveolar bone surface were investigated histometrically. The formation of immune complex was confirmed by immunohistological staining of complement C1qB., Results: Loss of attachment and the presence of C1qB were observed histopathologically in both experimental groups. The group that had been treated with LPS and anti-LPS IgG showed greater loss of attachment. The number of inflammatory cells in the periodontal tissue was increased in both experimental groups, while osteoclasts at the alveolar bone crest were observed only in the group that had been treated with LPS and anti-LPS IgG., Conclusion: In the present study, we showed that the formation of immune complex appears to be involved in the acute phase of periodontal destruction and that the biological activity of antigens is also important., (© 2012 John Wiley & Sons A/S.)

Objectives: Histamine, a potent vasoactive amine, is increased in saliva of periodontitis patients. The present study aimed to further investigate the diagnostic potential of histamine for periodontal disease and assessed smoking, a major risk factor of periodontitis, as a possible influencing factor., Methods: Salivary and serum samples of 106 participants (60 periodontitis patients, 46 controls) were collected. Salivary histamine was determined by a commercially available ELISA kit, and serum C-reactive protein was measured by a routine laboratory test. Cigarettes per day and packyears were assessed as smoking exposure parameters., Results: Statistically significantly increased levels of salivary histamine and serum C-reactive protein were detected between the patient and control group (P = 0.022 and P = 0.001). Salivary histamine levels were significantly higher in smoking compared with non-smoking patients (P < 0.001), and salivary histamine as well as serum C-reactive protein correlated significantly positively with smoking exposure parameters (P < 0.05)., Conclusions: Smoking, an established and common risk factor of periodontitis, was assessed as a possible influencing factor for salivary histamine. Most interestingly, salivary histamine differed highly significantly between smoking and non-smoking periodontitis patients. Our results suggest a possible involvement of histamine in tobacco-exacerbated periodontal disease, but do not suggest salivary histamine as a reliable diagnostic marker for periodontitis., (© 2011 John Wiley & Sons A/S.)

Background: Periodontitis is associated with glycemic control in patients with diabetes. The purpose of this study was to determine if glycosylated hemoglobin is elevated in patients with periodontitis who are non-diabetic adults., Materials and Methods: A total of 36 patients were selected and were divided into test and control groups. Test group included 18 adults without diabetes, but with periodontitis (having at least five teeth with probing depth (PD) ≥5 mm, bleeding on probing (BOP), and clinical attachment loss (>1 mm) on >5 teeth or radiographic bone loss), and the control group included 18 healthy adults (PDs ≤4 mm and BOP ≤15% and no clinical attachment loss). Glycosylated hemoglobin (HbA1c) was assessed in laboratory for these patients. Groups were compared using the t test,kruskal-wallis test, pearsson correlation., Results: Both the groups showed similar HbA1c levels, but there was a marginal increase in levels in the test group (cases), which was not statistically significant (cases- 6.06%, controls-5.8%; P=0.101).There was no significant difference found in the mean HbA1c levels among males and females and among various age groups. Mean BMI among the cases and controls was found to be similar. When inter and intra group comparisons were done according to BMI categories among the cases and controls, we found similar mean HbA1c values., Conclusion: Indians are at a high risk of developing periodontitis and diabetes. These data suggest a possible link between periodontitis and glycemic control in non-diabetic individuals. Periodontal disease may be a potential contributor to development of type 2 diabetes.

Unlabelled: Tumor Necrosis Factor-α(TNF-α), a "major inflammatory cytokine" not only plays an important role in periodontal destruction, but also is extremely toxic to the host. Till date, there are not many studies comparing the levels of TNF-α in GCF and serum and its relationship to periodontal disease. aim: Hence, an attempt is made to estimate the level of TNF-α in GCF and serum, its relationship to periodontal disease, and to explore the possibility of using the level of TNF-α in GCF as a biochemical "marker" of periodontal disease., Materials and Methods: 60 subjects participated in the study and were grouped into control, gingivitis and periodonititis groups. The GCF and serum samples were assayed for TNF-α levels by Enzyme Linked Immunosorbent Assay (ELISA) method., Results: Showed elevated levels of TNF-α in group II and III subjects as compared to healthy controls in both GCF and serum, suggesting an association between periodontal disease and levels of TNF-α., Conclusion: It remains a possibility that the absence or low levels of TNF-α in GCF might indicate a stable lesion and elevated levels might indicate an active site but only longitudinal studies taking into account, the disease "activity" and "inactivity" could suggest the possibility of using TNF-α in GCF as an "Indicator" of periodontal disease.

Background: We examined the extent and severity of radiographic periodontal bone loss in patients with different stages of chronic kidney disease (CKD) and explored a potential dose-response relationship between bone loss and CKD-related biomarkers., Methods: Panoramic radiographs were obtained from 129 CKD patients (78 males and 51 females; mean age: 63.5 years, range: 24 to 91 years), including 63 patients undergoing dialysis for an average of 3.3 years (range: 0.5 to 14 years). Glomerular filtration rate (GFR), dialysis dose, and levels of serum biomarkers were obtained through a hospital database. Interproximal bone loss was assessed as a percentage of root length., Results: Twenty-nine participants were edentulous (23.8% of those on dialysis versus 21.2% of those with residual kidney function; χ(2) test, P = 0.724). The extent of bone loss was higher among dialysis patients (analysis of variance [ANOVA], P = 0.007), but no clear dose-response association between CKD stage and extent was evident. GFR, dialysis dose, and levels of serum biomarkers did not differ between edentulous and dentate individuals, and only serum albumin was lower in patients with extensive bone loss (ANOVA, P = 0.030). After adjusting for dialysis status, the severity of bone loss was positively associated with glucose levels (multiple regression, P = 0.019) and white blood cell count (P = 0.032), whereas the number of teeth present was positively associated with plasma phosphorus (P = 0.008) and negatively with glucose levels (P = 0.011)., Conclusion: Despite a higher extent of bone loss in dialysis patients, the lack of a dose-response association between bone loss and CKD stage or the levels of CKD-related serum biomarkers underscores the complex relationship between the two conditions.

Aim: To evaluate the associations of serum 25-Hydroxyvitamin D [25(OH)D] levels with periodontal health and chronic obstructive pulmonary disease (COPD)., Material and Methods: We conducted a case-control study of 193 COPD patients and 181 controls. Their periodontal status and lung function were examined, and serum 25(OH)D levels were measured., Results: Mean serum 25(OH)D concentrations were significantly lower in the COPD group than in the controls (32.1 versus 35.8 nmol/l; p = 0.002). Serum 25(OH)D concentrations were positively correlated with lung function among non-smokers and negatively correlated with plaque index (PLI) among former smokers. After adjustment for age, gender, body mass index, season and smoking status, periodontal indexes were significantly associated with serum 25(OH)D concentrations (number of remaining teeth among all groups; probing depth, clinical attachment level, bleeding index, PLI and alveolar bone loss among COPD group). Lower serum 25(OH)D concentrations were significantly associated with an increased risk of COPD among former smokers (Odd ratio 4.11; 95% confidence interval 1.47-11.5; p = 0.007) after adjustment for periodontal indexes and other variables., Conclusions: Lower serum 25(OH)D concentrations were significantly associated with poor periodontal health and an increased risk of COPD., (© 2012 John Wiley & Sons A/S.)

Background and Objectives: The receptor activator of NF-κB ligand-osteoprotegerin (RANKL-OPG) bi-molecular system is the "bottle-neck" regulator of osteoclastogenesis and bone resorption, both in physiological and pathological conditions. This review aims to elaborate the current knowledge on RANKL and OPG in periodontal disease, and to evaluate their diagnostic and prognostic potential as biomarkers of the disease., Materials and Methods: To pursue this aim, electronic and manual searches were performed for identifying clinical and in vivo studies on RANKL and OPG in gingival tissue, gingival crevicular fluid, saliva and blood. Smoking and diabetes mellitus were also considered for their potential effects., Results: Papers fulfilling the inclusion criteria demonstrate that RANKL is up-regulated, whereas OPG is down-regulated in periodontitis, compared to periodontal health, resulting in an increased RANKL/OPG ratio. This ratio is further up-regulated in smokers and diabetics, and is not affected by conventional periodontal treatment., Conclusions: The increased RANKL/OPG ratio may serve as a biomarker that denotes the occurrence of periodontitis, but may not necessarily predict on-going disease activity. Its steadily elevated levels post treatment may indicate that the molecular mechanisms of bone resorption are still active, holding an imminent risk for relapse of the disease. Additional adjunct treatment modalities that would "switch-off" the RANKL/OPG ratio may therefore be required., (© 2011 John Wiley & Sons A/S.)

Background: Visfatin is a pleiotropic mediator that acts as growth factor, cytokine, and enzyme involved in energy including nicotinamide adenine dinucleotide metabolism and was recently demonstrated to exert several proinflammatory functions. The purpose of this study is to determine the presence of visfatin in gingival crevicular fluid (GCF) and serum samples and to find out their association, if any., Methods: At the beginning of the study, 40 individuals (20 males and 20 females; age range: 23 to 53 years) were selected and divided into three groups based on the gingival index, probing depths, clinical attachment levels, and radiologic parameters (bone loss). Group 1 (10 patients with healthy periodontium; age range: 25-36 years), group 2 (15 patients with gingivitis; age range: 25-36 years), and group 3 (15 patients with chronic periodontitis; age range: 23-53 years) GCF (by microcapillary pipettes) and serum (by venipuncture) samples were collected to estimate levels of visfatin using an enzyme-linked immunosorbent assay kit., Results: Mean visfatin concentrations increased in GCF and serum with the severity of disease from healthy to gingivitis to periodontitis groups and differed significantly (P <0.05). However, it was found that GCF values were higher than serum values. The highest to lowest visfatin concentrations were found in groups 3 through 1, respectively. Visfatin in GCF and serum correlated positively with periodontal parameters in the chronic periodontitis group., Conclusions: The results suggest that GCF and serum visfatin concentrations increase with the severity of periodontal disease. Hence, visfatin values were considered an inflammatory marker in periodontal disease in GCF and serum. Visfatin also deserves further consideration as a therapeutic target.

Unlabelled: We recently reported that subantimicrobial-dose doxycycline (SDD) significantly reduced serum bone-resorption biomarkers in subgroups of post-menopausal women. We hypothesize that changes in serum bone biomarkers are associated not only with systemic bone mineral density (BMD) changes, but also with alveolar bone changes over time. One hundred twenty-eight eligible post-menopausal women with periodontitis and systemic osteopenia were randomly assigned to receive SDD or placebo tablets twice daily for two years, adjunctive to periodontal maintenance. Sera were analyzed for bone biomarkers. As expected, two-year changes in a serum bone biomarker were significantly associated with systemic BMD loss at the lumbar spine (osteocalcin, bone-turnover biomarker, p = 0.0002) and femoral neck (osteocalcin p = 0.0025). Two-year changes in serum osteocalcin and serum pyridinoline-crosslink fragment of type I collagen (ICTP; bone-resorption biomarker) were also significantly associated with alveolar bone density loss (p < 0.0001) and alveolar bone height loss (p = 0.0008), respectively. Thus, we have shown that serum bone biomarkers are associated with not only systemic BMD loss, but with alveolar bone loss as well., Clinical Trial Registration Information: Protocol registered at ClinicalTrials.gov, NCT00066027.

Background: Considering that recent studies have demonstrated endothelial dysfunction in subjects with periodontitis and that there is no information about vascular function in coexistence of periodontitis and atherosclerosis, we assessed the impact of oral inoculation with the periodontal pathogen Porphyromonas gingivalis on vascular reactivity in healthy and hypercholesterolemic apolipoprotein E-deficient (ApoE) mice. In vitro preparations of mesenteric arteriolar bed were used to determine the vascular responses to acetylcholine, sodium nitroprusside and phenylephrine (PE)., Results: Alveolar bone resorption, an evidence of periodontitis, was assessed and confirmed in all infected mice. Acetylcholine- and sodium nitroprusside-induced vasorelaxations were similar among all groups. Non-infected ApoE mice were hyperreactive to PE when compared to non-infected healthy mice. P gingivalis infection significantly enhanced the vasoconstriction to PE in both healthy and spontaneous atherosclerotic mice, when compared to their respective controls., Conclusions: This study demonstrates that oral P gingivalis affects the alpha-adrenoceptor-mediated vascular responsiveness in both healthy and spontaneous atherosclerotic mice, reinforcing the association between periodontitis and cardiovascular diseases.

Background: Pentraxins are classic mediators of inflammation and markers of acute-phase reactions. Pentraxin-3 (PTX3) is the first-identified long pentraxin and is believed to be a true independent indicator of disease activity. Although a classic pentraxin, C-reactive protein, and its association with various systemic diseases is well documented in the periodontal literature, there is no data on PTX3 to our knowledge., Methods: Forty participants (20 males and 20 females; age range: 23 to 50 years) were involved in the study. Participants were divided into three groups based on gingival index, probing depth, and clinical attachment level: the healthy group (group 1; n = 10), gingivitis group (group 2; n = 15), and periodontitis group (group 3; n = 15). Gingival crevicular fluid (GCF) and plasma samples collected from each subject were quantified for PTX3 levels using an enzyme-linked immunosorbent assay., Results: In tandem with the disease progression from healthy to gingivitis to periodontitis, the mean PTX3 concentrations increased in GCF and plasma. However, GCF values were higher than plasma values. It was found that PTX3 concentration was highest in group 3 and lowest in group 1. PTX3 concentrations also correlated positively with periodontal parameters., Conclusions: GCF and plasma PTX3 concentrations correlated positively in all groups. However, within the limits of the present study, the differences in plasma PTX3 levels were not found to be statistically significant. Hence, GCF PTX3 values were considered a marker of inflammatory activity in periodontal disease. However, PTX3 deserves further consideration as a therapeutic target. Additional large-scale studies should be carried out to confirm positive correlations.