Astaxanthin Inhibits Diabetes-Triggered Periodontal Destruction, Ameliorates Oxidative Complications in STZ-Injected Mice, and Recovers Nrf2-Dependent Antioxidant System.

Numerous studies highlight that astaxanthin (ASTX) ameliorates hyperglycemic condition and hyperglycemia-associated chronic complications. While periodontitis and periodontic tissue degradation are also triggered under chronic hyperglycemia, the roles of ASTX on diabetes-associated periodontal destruction and the related mechanisms therein are not yet fully understood. Here, we explored the impacts of supplemental ASTX on periodontal destruction and systemic complications in type I diabetic mice. To induce diabetes, C57BL/6 mice received a single intraperitoneal injection of streptozotocin (STZ; 150 mg/kg), and the hyperglycemic mice were orally administered with ASTX (12.5 mg/kg) (STZ+ASTX group) or vehicle only (STZ group) daily for 60 days. Supplemental ASTX did not improve hyperglycemic condition, but ameliorated excessive water and feed consumptions and lethality in STZ-induced diabetic mice. Compared with the non-diabetic and STZ+ASTX groups, the STZ group exhibited severe periodontal destruction. Oral gavage with ASTX inhibited osteoclastic formation and the expression of receptor activator of nuclear factor (NF)-κB ligand, 8-OHdG, γ-H2AX, cyclooxygenase 2, and interleukin-1ß in the periodontium of STZ-injected mice. Supplemental ASTX not only increased the levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and osteogenic transcription factors in the periodontium, but also recovered circulating lymphocytes and endogenous antioxidant enzyme activity in the blood of STZ-injected mice. Furthermore, the addition of ASTX blocked advanced glycation end products-induced oxidative stress and growth inhibition in human-derived periodontal ligament cells by upregulating the Nrf2 pathway. Together, our results suggest that ASTX does not directly improve hyperglycemia, but ameliorates hyperglycemia-triggered periodontal destruction and oxidative systemic complications in type I diabetes.

Vitamin D and Periodontitis: A Systematic Review and Meta-Analysis.

To explore the vitamin D levels of periodontitis patients in comparison with periodontally healthy ones, and to assess the influence of vitamin D supplementation as an adjunctive during nonsurgical periodontal treatment (NSPT). Five databases (Pubmed, Embase, Scholar, Web of Sciences, and Cochrane Library) were searched until May 2020. Mean difference (MD) meta-analysis with corresponding 95% confidence interval (95% CI) and sensitivity tests via meta-regression were used. We followed Strength of Recommendation Taxonomy (SORT) to appraise the strength and quality of the evidence. Sixteen articles were included, fourteen case-control and two intervention studies, all reporting 25-hydroxyvitamin D (25(OH)D) levels. Compared with the healthy controls, the circulating 25(OH)D levels were significantly lower in chronic periodontitis patients (pooled MD = -6.80, 95% CI: -10.59 to -3.02). Subgroup analysis revealed differences among 25(OH)D measurements, with liquid chromatography-mass spectrometry being the most homogeneous method (pooled MD = -2.05, 95% CI: -3.40 to -0.71). Salivary levels of 25(OH)D showed no differences between groups. Due to the low number of studies, conclusions on aggressive periodontitis and in the effect of vitamin D supplementation after NSPT were not possible to ascribe. Compared with healthy controls, 25(OH)D serum levels are significantly lower in chronic periodontitis patients, with an overall SORT A recommendation. Future studies are needed to clarify the effect of vitamin D supplementation and the biological mechanisms linking vitamin D to the periodontium.

Grape Seed Extract Reduces the Degree of Atherosclerosis in Ligature-Induced Periodontitis in Rats - An Experimental Study.

The associations between periodontitis and cardiovascular diseases have been intensely studied in recent years. Oxidative stress is involved in the initiation and both progression of periodontitis and atherosclerosis. Antioxidants can reduce the effects of oxidative stress on inflammatory diseases. Our aim was to measure the effects of a grape seed extract (GSE), rich in antioxidants, on atherosclerosis caused by ligature-induced periodontitis in rats. Thirty male Wistar rats were randomly divided into three groups of 10: control group, periodontitis group, and periodontitis group treated with GSE (GSE group). Periodontitis was induced by placing an orthodontic wire around the cervix of the first mandibular molar and keeping it in place for 4 weeks. On days 1, 7 and 28, blood samples were taken to assess oxidative stress and inflammation markers (malondialdehyde and glutathione - MDA, reduced glutathione - GSH, C reactive protein) and lipids. After 4 weeks, the animals were euthanized, and aortas were collected for histopathologic examination. MDA was significantly higher in Periodontitis group compared to the other groups only at day 7. GSH was significantly increased in the Control and GSE groups on days 1 and 7, compared to Periodontitis group and on day 28 higher in GSE vs. Periodontitis groups. C reactive protein was significantly increased in the Periodontitis group on days 1 and 7 compared to both groups. Cholesterol was significantly decreased in the aortas of GSE group at day 28 compared to the Periodontitis group. Oral administration of a grape seed extract reduces the oxidative stress, inflammation and atherosclerosis in a rat model of ligature-induced periodontitis.

Vitamin D reduces the serum levels of inflammatory cytokines in rat models of periodontitis and chronic obstructive pulmonary disease.

The purpose of this study was to investigate the effects of vitamin D in rat models of chronic obstructive pulmonary disease (COPD) and periodontitis. Animals with both periodontitis and COPD, or with periodontitis only, were established. Once the animal model was established, experimental groups received intraperitoneal injections of 25-hydroxyvitamin D3 (25-OHD3) for 8 weeks, while control groups received refined peanut oil. After sacrifice, inflammatory status was examined in terms of the serum levels of receptor activator of the nuclear factor κB ligand (RANKL), tumor necrosis factor alpha (TNF-α) and interleukins (IL-1 and IL-10), as well as alveolar bone loss, forced expiratory volume (0.20) (FEV 0.20), and the ratio of FEV0.2 to forced vital capacity. The results showed that 25-OHD3 treatment significantly alleviated inflammation by decreasing the serum levels of RANKL, TNF-α and IL-1 and increasing that of IL-10, while reducing alveolar bone loss and slightly improving lung function. These findings suggest that vitamin D supplementation could be a new clinical approach for the treatment of COPD and periodontitis.

The association between periodontal conditions, inflammation, nutritional status and calcium-phosphate metabolism disorders in hemodialysis patients.

OBJECTIVES: To analyze the association between periodontal conditions and inflammation, nutritional status and calcium-phosphate metabolism disorders in hemodialysis (HD) patients. MATERIAL AND METHODS: We analyzed 128 HD patients divided into two groups: dentate (n = 103) and edentulous (n=25). The following items were assessed: baseline characteristics, age at the start and duration of HD, biochemical data: C-reactive protein (CRP), serum albumin, calcium, phosphorus, alkaline phosphatase, parathormone. A single dentist performed a complete dental/periodontal examination, including parameters of oral hygiene and gingival bleeding. RESULTS: One person had healthy periodontium, 62.14% of the patients had gingivitis, and 36.9% had moderate or severe periodontitis. The age at HD onset had a positive impact on periodontal status and negatively correlated with the number of teeth. A positive correlation between age and CRP level and negative correlations between age and serum albumin and phosphorus were found. Pocket depth (PD) was negatively correlated with serum albumin. The number of teeth was negatively correlated with serum CRP. CONCLUSIONS: High prevalence and severity of periodontal disease are observed in hemodialysis patients. There is a high probability that periodontal disease may be present at the early stages of chronic kidney disease (CKD) before the hemodialysis onset.

Tocoyena sellowiana extract decreases bone loss in an experimental model of periodontitis in rats: Putative role for cyclooxygenase-2 and IL-1? inhibition.

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.

The association between periodontal conditions, inflammation, nutritional status and calcium-phosphate metabolism disorders in hemodialysis patients

Abstract Objectives To analyze the association between periodontal conditions and inflammation, nutritional status and calcium-phosphate metabolism disorders in hemodialysis (HD) patients. Material and Methods We analyzed 128 HD patients divided into two groups: dentate (n = 103) and edentulous (n=25). The following items were assessed: baseline characteristics, age at the start and duration of HD, biochemical data: C-reactive protein (CRP), serum albumin, calcium, phosphorus, alkaline phosphatase, parathormone. A single dentist performed a complete dental/periodontal examination, including parameters of oral hygiene and gingival bleeding. Results One person had healthy periodontium, 62.14% of the patients had gingivitis, and 36.9% had moderate or severe periodontitis. The age at HD onset had a positive impact on periodontal status and negatively correlated with the number of teeth. A positive correlation between age and CRP level and negative correlations between age and serum albumin and phosphorus were found. Pocket depth (PD) was negatively correlated with serum albumin. The number of teeth was negatively correlated with serum CRP. Conclusions High prevalence and severity of periodontal disease are observed in hemodialysis patients. There is a high probability that periodontal disease may be present at the early stages of chronic kidney disease (CKD) before the hemodialysis onset.

The Effectiveness of Crataegus orientalis M Bieber. (Hawthorn) Extract Administration in Preventing Alveolar Bone Loss in Rats with Experimental Periodontitis.

The purpose of this animal study was to evaluate the effects of hawthorn (Crataeus orientalis M Bieber.) extract on serum oxidative status and alveolar bone loss in experimental periodontitis. Twenty-seven Wistar rats were assigned to one of the following groups: non- ligated+placebo (saline) (NL, n = 9), ligature only+placebo (saline) (LO, n = 9), and ligature and treated with hawthorn extract in saline (H, n = 9) (100 mg/kg orogastrically, once a day for 11 days). Periodontitis was induced by submerging a 4/0 silk ligature in the sulcus of the mandibular right first molars of rats, and the animals were sacrificed after 11 days. Micro-CT examinations were performed for linear and volumetric parameter assessment of alveolar bone. Periodontal tissues were histopathologically examined to assess the differences among the study groups. Levels of serum total antioxidant status (TAS)/total oxidant status (TOS), and oxidative stress index (OSI) were also analyzed. Alveolar bone loss was significantly reduced by hawthorn administration compared to LO group (p<0.05). The number of inflammatory cells and osteoclasts in the LO group was significantly higher than that of the NL and H groups (p< 0.05). The number of osteoblasts in the LO and H groups was significantly higher than that of the NL group (p<0.05). TOS and OSI levels were significantly reduced in H group compared to LO group (P <0.05) and TAS levels were similar in H and NL group (p< 0.05). Hawthorn extract showed inhibitory effect on periodontal inflammation and alveolar bone loss by regulating TAS, TOS and OSI levels in periodontal disease in rats when administered systemically.

Therapeutic Effects of Melatonin on Alveolar Bone Resorption After Experimental Periodontitis in Rats: A Biochemical and Immunohistochemical Study.

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.

[Clinical and biochemical analysis of ligature-induced periodontitis in rats].

The most common experimental model of periodontitis is a "ligature" model. However due to the complexity connected with performing on rats, modification of existing model is proposed, which differs by fixture of cotton ligature around the central incisor and not around the second molar. The purpose of research - a comparative evaluation of "peroxide" and modified by us, "ligature" models of periodontitis in rats. 2 series of experiments on 36 white Wistar rats were conducted. The animals were divided into two groups: intact rats (control) and rats with a "peroxide" model of periodontitis, which was reproduced by the addition to the diet of rats overoxidized sunflower oil (5% by weight of the feed), daily, for 45 days. "Ligature" model in rats was reproduced by applying a cotton ligature on the central incisor of the upper jaw for 14 days. Elastase activity, malondialdehyde content and catalase activity in the gums and in the blood serum was measured by biochemical methods. The degree of atrophy of the alveolar bone of the mandible was determined by morphometric method. It is found that in both models of periodontitis in rats, changes in the periodontal tissues and in the organism as a whole, is common for periodontal disease in humans. Clinically apparent inflammation of the periodontal tissues is observed, metabolic disorders in the gums, change of biochemical parameters in serum and progressive decline in the alveolar bone are determined. A comparative analysis of the two models showed that the modified "ligature" model of periodontitis in rats has several advantages over the "peroxide" model: shorter term of modeling, more pronounced clinical inflammation of periodontal tissues and faster resorption of alveolar bone.

Docosahexaenoic Acid and Periodontitis in Adults: A Randomized Controlled Trial.

Periodontitis is a common chronic inflammatory disease initiated by bacteria, resulting in bone resorption, tooth loss, and systemic inflammation. Long-chain omega-3 fatty acids such as docosahexaenoic acid (DHA) reduce periodontitis in animals. We aimed to determine whether DHA supplementation with low-dose aspirin would reduce periodontitis in humans. We conducted a double-blind placebo-controlled parallel trial lasting 3 mo. Fifty-five adults with moderate periodontitis were randomized to 2,000 mg of DHA or identical soy/corn oil capsules. All participants received 81 mg of aspirin but received no other treatments. We analyzed the primary outcome of per-pocket change in pocket depth using mixed models among teeth with pocket depth ≥5 mm. Secondary outcomes assessed with generalized estimating equations included gingival index, plaque index, and bleeding on probing. Gingival crevicular fluid samples were analyzed for changes in high-sensitivity C-reactive protein (hsCRP) and interleukins 6 and 1ß (IL-6 and IL-1ß). Plasma was analyzed for changes in systemic inflammatory markers, including hsCRP. We confirmed adherence with erythrocyte fatty acid measurement. Forty-six participants completed the trial. While similar at baseline, the proportion of DHA in red blood cell plasma membranes increased from 3.6% ± 0.9% to 6.2% ± 1.6% in the intervention group but did not change among controls. DHA supplementation decreased mean pocket depth (-0.29 ± 0.13; p = .03) and gingival index (-0.26 ± 0.13; p = .04). Plaque index and bleeding on probing did not change. Significant adjusted differences were found between DHA and control for both gingival crevicular fluid hsCRP (-5.3 ng/mL, standard error [SE] = 2.4, p = .03) and IL-1ß (-20.1 pg/mL, SE = 8.2, p = .02) but not IL-6 (0.02 pg/mL, SE = 0.71, p = .98) or systemic hsCRP (-1.19 mg/L, SE = 0.90, p = .20). In this randomized controlled trial, aspirin-triggered DHA supplementation significantly improved periodontal outcomes in people with periodontitis, indicating its potential therapeutic efficacy (clinicaltrials.gov NCT01976806).

Plasma polyunsaturated fatty acids and periodontal recovery in Taiwanese with periodontitis: a significant relationship.

BACKGROUND: Plasma levels of polyunsaturated fatty acids (PUFAs) are different before and after periodontal treatment. Asians and Westerners have significantly different baseline levels of plasma PUFAs. However, no Asian study has reported the effects of nonsurgical treatment on the correlation between periodontal condition and plasma levels of PUFAs. We analyzed whether recovery from periodontitis was correlated with the elevation of plasma fatty acids 3 months after the nonsurgical intervention and with no recommended supplements. DESIGN: Thirty-five Taiwanese patients with periodontitis were recruited. Probing pocket depths (PPDs) and clinical attachment levels (CALs) were measured at baseline and 3 months after the nonsurgical treatment. Plasma levels of fatty acids were determined using gas chromatography. Differences and correlations between plasma fatty acid composition and periodontitis severity at baseline and 3 months after treatment were determined. RESULTS: Twenty-six patients completed the study. At the baseline, PPDs were negatively correlated with plasma n-3 PUFAs (r=-0.52, p<0.01), but at 3 months post intervention, periodontitis severity had declined and the weight percentages of n-3 PUFAs, DPA, and DHA were significantly (p=0.019, 0.005, and 0.037, respectively) higher. The recovery percentages of CALs were positively and significantly correlated with plasma ΔPUFAs and the percentage of Δn-3 PUFAs in ΔPUFAs (r=0.42 and 0.45, respectively; p<0.05 for both). CONCLUSIONS: We conclude that a higher weight percentage of n-3 PUFAs in total PUFAs was related to the recovery of CALs 3 months after the nonsurgical periodontal treatment. However, no such relationship was found for PPDs.

Prospective Study of Serum 25-hydroxy Vitamin D and Tooth Loss.

Vitamin D deficiency and oral diseases (periodontitis, caries, and tooth loss) are highly prevalent in Germany. Previous studies suggested that vitamin D might be a modifiable and protective factor for periodontitis, caries, and tooth loss. However, prospective studies investigating such associations are limited. We explored the association between the concentration of serum 25-hydroxy vitamin D (25OHD) and incidence of tooth loss, progression of clinical attachment loss (CAL) ≥ 3 mm, and progression of restorative and caries status in a population-based longitudinal study. We analyzed data from 1,904 participants from the Study of Health in Pomerania with a five-year follow-up. Generalized estimating equation models were applied to evaluate tooth-specific associations between serum 25OHD and incidence of tooth loss, progression of CAL ≥ 3 mm, and progression of restorative and caries status. Age, sex, education, smoking status, alcohol drinking, waist circumference, dental visit frequency, reasons of dental visit, vitamin D or calcium supplements, and season of blood draw were considered as confounders. Serum 25OHD was inversely associated with incidence of tooth loss. A significant dose-response relationship (p = .0022) was observed across the quintiles of serum 25OHD. After adjusting for multiple confounders, each 10-µg/L increase of serum 25OHD was associated with a 13% decreased risk of tooth loss (risk ratio: 0.87; 95% confidence interval: 0.79, 0.96). The association was attenuated for changes of CAL ≥ 3 mm when adjusting for multiple confounders. No significant association was found between serum 25OHD and caries progression. Vitamin D might be a protective factor for tooth loss. The effect might partially be mediated by its effect on periodontitis.

A short-term evaluation of the relationship between plasma ascorbic acid levels and periodontal disease in systemically healthy and type 2 diabetes mellitus subjects.

BACKGROUND: Deficient ascorbic acid levels (AALs) and Type 2 diabetes mellitus (T2DM) are associated with periodontal disease. This study evaluated the relationship between plasma AAL and periodontitis in systemically healthy and T2DM subjects, which to the best of our knowledge is being reported for the first time. METHODS: One hundred twenty subjects were categorized into four groups of 30 each as group 1: without periodontal disease; group 2: chronic gingivitis; group 3: chronic periodontitis, and group 4: chronic periodontitis and freshly diagnosed T2DM. Plaque index (PlI), sulcus bleeding index (SBI), and probing pocket depths (PPDs) were evaluated. Venous blood was evaluated for plasma AAL spectrophotometrically. Randomized subjects were subgrouped within groups 2-4, to receive either scaling and root planing (SRP) with dietary supplementation (450 mg) of ascorbic acid (AA) for two weeks or only SRP. After two weeks, the clinical parameters were reassessed. Tukey's multiple post hoc procedures and paired t test were used with the level of statistical significance adjusted to p ≤ .05. RESULTS: AAL plasma levels were significantly greater in group 1 than in group 2 (p = .0007) and in group 4 (p = .0003). A significant reduction in the SBI was seen in the subgroups that received dietary supplementation of vitamin C within group 2 (p = .0012) and group 4 (p = .036). CONCLUSIONS: Plasma AAL is below the normal range in systemically healthy subjects with gingivitis and diabetics with periodontitis. Dietary AA supplementation with SRP improves the SBI in subjects with gingivitis and diabetics with periodontitis.

Hydrogen-rich water attenuates experimental periodontitis in a rat model.

AIM: Reactive oxygen species (ROS) contribute to the development of periodontitis. As molecular hydrogen can act as a scavenger of ROS, we examined the effects of treatment with hydrogen-rich water on a rat model of periodontitis. MATERIAL & METHODS: A ligature was placed around the maxillary molars for 4 weeks to induce periodontitis, and the animals were given drinking water with or without hydrogen-rich water. RESULTS: The rats with periodontitis which were treated with pure water showed a time-dependent increase in serum ROS level. Compared with the rats without periodontitis, the periodontitis-induced rats which were given pure water also showed polymorphonuclear leucocyte infiltration and alveolar bone loss at 4 weeks. Hydrogen-rich water intake inhibited an increase in serum ROS level and lowered expression of 8-hydroxydeoxyguanosine and nitrotyrosine in the periodontal tissue at 4 weeks. Such conditions prevented polymorphonuclear leucocyte infiltration and osteoclast differentiation following periodontitis progression. Furthermore, inflammatory signalling pathways, such as mitogen-activated protein kinases, were less activated in periodontal lesions from hydrogen-rich water-treated rats as compared with pure water-treated rats. CONCLUSION: Consuming hydrogen-rich water might be beneficial in suppressing periodontitis progression by decreasing gingival oxidative stress.

Inhibition of peripheral blood neutrophil oxidative burst in periodontitis patients with a homeopathic medication Traumeel S.

BACKGROUND: The anti-inflammatory effects of a homeopathic remedy, Traumeel S, have been observed in experimental and clinical studies; however, its antioxidant properties have not been elucidated. The aim of the present study was to evaluate the antioxidant effects of Traumeel S on peripheral blood neutrophils in patients with periodontitis. MATERIAL/METHODS: The study was performed using venous blood of 22 individuals with chronic periodontitis and 21 healthy subjects. The antioxidant effects of Traumeel S on the production of reactive oxygen species by unstimulated and stimulated with unopsonized E. coli neutrophils were investigated using luminol- and lucigenin-dependent chemiluminescence (CL). RESULTS: Polymorphonuclear leukocytes of periodontitis patients produced higher levels (p<0.01) of light output of lucigenin-dependent chemiluminescence and significantly reduced (p<0.01) light output of luminol-dependent chemiluminescence than analogous cells of healthy subjects. Highly diluted (10⁻4 of the stem solution) Traumeel S significantly (by approximately 50%) reduced superoxide-induced oxidation of lucigenin by unstimulated and stimulated with unopsonized E. coli polymorphonuclear leukocytes of periodontitis patients and had a tendency to intensify luminol-dependent chemiluminescence. Preincubation of the unstimulated and stimulated with unopsonized E. coli polymorphonuclear leukocytes of healthy subjects with Traumeel S exerts no inhibitory action on the luminol- and lucigenin-dependent chemiluminescence of the above-mentioned cells. CONCLUSIONS: This study indicates that Traumeel S may significantly reduce production of superoxide anion by unstimulated and stimulated peripheral blood polymorphonuclear neutrophils of periodontitis patients.

Acid-base status and fructose diphosphatase activity in rats exposed to fluoride and induced periodontitis.

This study was conducted to evaluate acid-base status and fructose diphosphatase (FDPase) activity in 40 (4 groups of 10) male Wistar rats. One group of rats was left untreated as control, fed a standard diet, and given distilled water. Periodontitis model induced with 5 mg/kg NH4Cl (group 1), exposed to sodium fluoride (NaF) at the concentration 5 mg/l (group 2), exposed to NaF (5 mg/l) and supplemented with minerals and vitamins (group 3). At the termination of experimental period (30 days) the pH and pCO2 value of arterial blood were analysed. Then, the FDPase activity in the hemogenized heart, kidney liver, mandible, pelvis, and teeth were determined by measuring inorganic phosphate that converts from fructose-1.6-diphosphate and using spectrophotometer at 350 nm. The differences in the acid-base status and FDPase activity in the groups 1 and 2 were statistically significant in comparison with the control and group 3 (P < 0.001). Increased FDPase activities are associated with acid-base status. The minerals and vitamins supplementation proved to restore acid-base balance, reduce toxicity and establish steady enzyme activity, which has not been previously reported.

[Antibiotic therapy in odontogenic infections in children and adolescents: pharmacokinetic/pharmacodynamic analysis]. / Utilización de antimicrobianos en las infecciones odontogénicas en niños y adolescentes: análisis farmacocinético/farmacodinámico (PK/PD).

INTRODUCTION: The objective of this study was to evaluate the efficacy of the most commonly used antimicrobial treatments in odontogenic infections in children and adolescents on the basis of pharmacokinetic/ pharmacodynamic (PK/PD) criteria. METHODS: Unbound drug plasma concentration-time curves were simulated with mean population pharmacokinetic parameters of amoxicillin, co-amoxiclav, cefuroxime axetil, spiramycin, clindamycin, azithromycin, and metronidazole. For drugs showing time-dependent antibacterial killing, the time above MIC90 of the pathogens studied was calculated (T>MIC). For drugs with concentration-dependent bactericidal activity, the area under the concentration-time curve (AUC)/MIC90 ratio was calculated. RESULTS: Adequate efficacy indexes (T>MIC>40%) against all the microorganisms examined with the exception of Veillonella spp. were obtained with co-amoxiclav (80 mg/kg/day). Clindamycin (40 mg/kg/day) obtained adequate PK/PD indexes except for Lactobacillus, Actinobacillus actinomycetemcomitans, penicillin-resistant Peptostreptococcus, and Eikenella corrodens. High-dose amoxicillin yielded unsatisfactory results against many bacterial species. Azithromycin and metronidazole showed inadequate efficacy indexes against the majority of pathogens studied (AUC/MIC90<25). CONCLUSION: When antibiotic therapy is needed for odontogenic infections in children and adolescents, the most active empirical therapeutic choice is co-amoxiclav with high doses of amoxicillin. Clindamycin can be used as an alternative option. These results should be confirmed in clinical trials, in which the PK/PD approach could be useful for the design and assessment of results.

Effects of selective cyclooxygenase-2 inhibitor and omega-3 fatty acid on serum interleukin-1beta, osteocalcin, and C-reactive protein levels in rats.

BACKGROUND: The aim of this study was to evaluate the effects of selective cyclooxygenase-2 inhibitor, celecoxib, and omega-3 fatty acid on serum levels of interleukin 1-beta (IL-1beta), osteocalcin (OC), and C-reactive protein (CRP) in experimental periodontitis. METHODS: Experimental periodontitis in rats was induced by repeated injection of purified lipopolysaccharide (LPS) derived from Escherichia coli endotoxin. Forty-seven adult male Sprague-Dawley rats were divided into five study groups as follows: saline control, LPS, LPS + celecoxib, LPS + omega-3 fatty acid, and LPS + celecoxib + omega-3 fatty acid. Celecoxib and omega-3 fatty acid were given alone or in combination during 14 days of the experimental study period. At the end of the 2-week protocol, serum samples were obtained, and the rats were sacrificed. Serum samples were analyzed for IL-1beta, OC, and CRP concentrations by enzyme-linked immunosorbent assay. Defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by non-parametric tests. RESULTS: According to the morphometric measurements, the LPS and drug treatment groups showed significantly higher bone loss than the saline control group (P <0.05). Omega-3 fatty acid, both alone and in combination with celecoxib, revealed significantly higher IL-1beta levels than LPS and celecoxib groups (P <0.05). Individual and combined administration of celecoxib and omega-3 fatty acid significantly increased OC levels compared to the LPS group (P <0.05). There were no significant differences in serum CRP levels. CONCLUSIONS: Celecoxib and/or omega-3 fatty acid administration does not significantly influence circulating levels of CRP. The significantly increased serum OC level observed after individual and combination administration suggests that celecoxib and omega-3 fatty acid may influence bone remodeling and thereby inhibit the progression of alveolar bone resorption. However, the failure to observe any significant inhibition of bone loss in celecoxib- and/or omega-3 fatty acid-treated rats compared to the LPS group suggests that their therapeutic effect may be reduced by other factors, such as increases in serum IL-1beta promoting osteoclast activity.

Angiographically confirmed coronary heart disease and periodontal disease in middle-aged males.

BACKGROUND: The aim of this study was to investigate whether an association could be demonstrated between coronary heart disease (CHD) and chronic periodontitis in a population of middle-aged males in Northern Ireland. METHODS: A case-control design was used. Cases were men aged over 40 years with angiographically proven CHD. Controls were age-matched males, with no evidence of CHD, randomly drawn from the same locality as the cases. Each subject had a clinical periodontal examination and completed a detailed sociodemographic questionnaire. High sensitivity C-reactive protein (CRP) was measured in serum by immunoturbidimetry. RESULTS: There were 92 cases (mean age 56.7 years; SD = 6.3) and 79 controls (mean age 58.2 years; SD = 6.7). The CHD cases had an average of three teeth less than the controls (P <0.0001). A higher proportion of sites examined in cases than controls had plaque (P = 0.004), bleeding on probing (P = 0.013), and probing depths of > or = 4 mm (P = 0.006) or > or = 6 mm (P = 0.03). Subjects with > or = 4 mm pocketing in more than 20% of their interproximal sites and those with deep pocketing (> or = 6 mm) were classified as having poor periodontal status. A total of 35 cases (38%), compared to only 13 controls (16%), had a poor periodontal status (P = 0.0017). Men with a poor periodontal condition had higher levels of CRP (median 2.19 mg/l) than those with good periodontal health (median 1.42 mg/l), P = 0.007. After adjusting for smoking, academic achievement, alcohol consumption, unemployment, ability to maintain body weight, regular exercise, ability to relax daily, having a hobby or pastime, plaque, and CRP, logistic regression analysis showed that poor periodontal status was significantly associated with CHD, with an adjusted odds ratio of 3.06 and 95% confidence intervals of 1.02 to 9.17, P = 0.046. CONCLUSIONS: There was an association between coronary heart disease and poor periodontal status in the middle-aged males investigated. This association was independent of diabetes and all other cardiovascular risk factors investigated.