McN-A-343, a muscarinic agonist, reduces inflammation and oxidative stress in an experimental model of ulcerative colitis.

AIM: The aim of the present study was to investigate the anti-inflammatory response mediated of the M1 muscarinic acetylcholine receptor (mAChR) during experimental colitis. MATERIAL AND METHODS: After the induction of 6% acetic acid colitis, mice were treated with McN-A-343 0.5, 1.0, and 1.5 mg/kg or dexamethasone (DEXA, 2.0 mg/kg) or pirenzepine (PIR, 10 mg/kg; M1 mAChR antagonist). Colonic inflammation was assessed by macroscopic and microscopic lesion scores, colonic wet weight, myeloperoxidase (MPO) activity, interleukin-1 beta (IL1-ß) levels and tumor necrosis factor alpha (TNF-α), glutathione (GSH), malondialdehyde (MDA) and nitrate and nitrite (NO3/NO2), mRNA expression of IKKα, nuclear factor kappa beta (NF-kB) and cyclooxygenase-2 (COX-2), as well protein expression of NF-kB and COX-2. RESULTS: Treatment with McN-A-343 at a concentration of 1.5 mg/kg showed a significant reduction in intestinal damage as well as a decrease in wet weight, MPO activity, pro-inflammatory cytokine concentration, markers of oxidative stress and expression of inflammatory mediators. The action of the M1 agonist by the administration of pirenzepine, which promoted the blocking of the mAChR M1-mediated anti-inflammatory response, has also been proven. CONCLUSION: The results suggest that peripheral colonic M1 mAChR is involved in reversing the pro-inflammatory effect of experimentally induced colitis, which may represent a promising therapeutic alternative for patients with ulcerative colitis.

Renal alterations caused by ligature-induced periodontitis persist after ligature removal in rats.

BACKGROUND AND OBJECTIVE: Periodontitis may crosstalk with renal diseases, yet that remains unclear. We investigated whether the renal alterations caused by induced periodontitis are reversible after removal of the ligatures in experimental ligature-induced periodontitis. MATERIAL AND METHODS: Twenty-four female rats were divided into three groups: control (without periodontitis), periodontitis (20 days of ligature-induced periodontitis), and P20-20 (20 days of ligature-induced periodontitis and 20 days after ligature removal). The following periodontal parameters were assessed: gingival bleeding index, probing pocket depth, myeloperoxidase activity, and alveolar bone height. For renal tissues, histopathology, malonaldehyde (MDA) levels, glutathione (GSH) content, and renal weight were evaluated. In the blood, creatinine, uric acid, albumin, total cholesterol, total protein, and glucose levels were assessed. Total protein and creatinine levels in urine were also investigated. RESULTS: Rat renal tissues did not demonstrate reversal of periodontitis-related changes in the P20-20 group in terms of MDA, GSH, and histopathological evaluations when compared to the periodontitis group. Accordingly, only total cholesterol levels were reversible in the P20-20. CONCLUSION: Renal alterations caused by ligature-induced periodontitis persisted even after removal of ligatures in rats.

Alpha-terpineol complexed with beta-cyclodextrin reduces damages caused by periodontitis in rats.

BACKGROUND AND OBJECTIVE: This study aimed to assess the effectiveness of the treatment with alpha-terpineol (αTPN) complexed with beta-cyclodextrin (ßCD) on oral, blood, and hepatic parameters in ligature-induced periodontitis. MATERIAL AND METHODS: Forty female rats were distributed among the following groups: control (vehicle solution), periodontitis (ligature + vehicle solution), 5 mg/kg of αTPN-ßCD (ligature), and 25 mg/kg of αTPN-ßCD (ligature). Compounds were administered daily via intraperitoneal injection over a 20-day period. Periodontitis was induced with the bilateral insertion of ligatures around the first lower molars of each rat. Oral parameters, as well as blood biomarkers, were measured: histopathological assessment of the hepatic tissue was carried out using light and transmission electron microscopy. RESULTS: The treatment with αTPN-ßCD significantly improved several oral parameters and blood biomarkers in comparison with rats with periodontitis. In addition, the treatment with αTPN-ßCD significantly ameliorated the steatosis score and reduced the number of lipid droplets and the amount of foamy cytoplasm in the hepatocytes of rats with periodontitis. CONCLUSION: The results obtained suggest that the treatment with αTPN-ßCD improves several oral and blood parameters in rats with experimental periodontitis. In addition, hepatic alterations caused by periodontitis were ameliorated in the rats treated with αTPN-ßCD.

Bromelain reduces the non-alcoholic fatty liver disease and periodontal damages caused by ligature-induced periodontitis.

OBJECTIVE: The objective of this research was to evaluate the effects of bromelain (derived from Ananas comosus) upon periodontitis in rats. MATERIALS AND METHODS: Twenty-four rats were separated into groups: control, periodontitis, and bromelain treatment. Bromelain was administered daily by intraperitoneal injection for 20 days. Periodontitis was induced by ligature around the first molars. Oral parameters and blood biomarkers were measured. The histopathological evaluation of the hepatic tissue was performed. Bromelain treatment significantly reduced several oral inflammatory parameters, alveolar bone loss, and blood biomarkers compared to the rats on periodontitis. RESULTS: Treatment with bromelain improved the steatosis score. Bromelain used in ligature-induced periodontitis in rats was able to reduce the oral inflammatory parameters Gingival Bleeding Index (GBI), tooth mobility (TM), probing pocket depth (PPD), malondialdehyde (MDA), alveolar bone height (ABH) and gingival myeloperoxidase (MPO) and blood parameters (cholesterol, triglycerides, alanine aminotransferase, and aspartate aminotransferase). Bromelain treatment reduced the impact of periodontitis, such as the reduction of hepatic steatosis and improvement in the dosages of MDA and GSH. CONCLUSION: Bromelain acts as a potential adjunct in the non-surgical treatment of periodontitis and, consequently, reduces the impact of periodontitis, acting as anti-inflammatory and antioxidant.

Polysaccharides derived from Morinda citrifolia Linn reduce inflammatory markers during experimental colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: There are many reports of pharmacological activities of extracts and fractions of different vegetable-derived products in the scientific literature and in folk medicine. Ethnopharmacological use of these products by various communities continues to be extensively explored, and they account for more than half of all medications used worldwide. Polysaccharides (PLS) extracted from plants such as Morinda Citrifolia Linn present therapeutic potential in treatment of inflammatory bowel diseases (IBD) such as ulcerative colitis (UC). AIM OF THE STUDY: To evaluate the anti-inflammatory action of Noni-PLS against the intestinal damage in UC induced by acetic acid in mice. MATERIALS AND METHODS: In acetic acid-induced colitis, the mice were treated intraperitoneally (ip) with Noni-PLS (0.1, 0.3, and 3.0 mg/kg) or subcutaneously (sc) with dexamethasone (2.0 mg/kg) 30 min before euthanasia to determine the best dose of Noni-PLS with an anti-inflammatory effect in the course of UC. The colonic tissue samples were collected for macroscopic, wet weight, microscopic and biochemical (myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA), nitrate/nitrite (NO3/NO2), cytokines, cyclooxygenase (COX-2) and inducible nitric oxide (iNOS)) analyses. RESULTS: Treatment with Noni-PLS reduced the intestinal damage induced by acetic acid as it reduced macroscopic and microscopic scores and the wet weight of the colon. In addition, MPO activity and levels of GSH, MDA, NO3/NO2, pro-inflammatory cytokines, and COX-2 expression reduced. CONCLUSIONS: This study suggests that Noni-PLS exhibits anti-inflammatory action against intestinal damage by reducing inflammatory cell infiltration, oxidative stress, pro-inflammatory action of cytokines, COX-2 and iNOS expression in the inflamed colon. Noni-PLS shows therapeutic potential against inflammatory disorders like UC.

Evaluation of Biochemical Parameters Present in the Saliva of Patients with Chronic Periodontitis: Results from a Meta-Analysis.

AIMS: Periodontitis results from the presence of periodontopathogenic bacterial activity in the region of the gingival sulcus promoting tissue degradation and alveolar bone resorption. Biochemical analysis of the saliva can be used as a less invasive method for disease prognosis. This study aimed to evaluate the relationship between biochemical protein levels in the saliva sample of patients with chronic periodontitis and healthy patients. MATERIALS AND METHODS: A literature review was performed using electronic databases (Cochrane Library, Google Scholar, MEDLINE, PubMed, and Web of Science) for studies published before July 2, 2016. The abstracts were evaluated, and the data extraction was performed by two calibrated examiners. The mean difference, and heterogeneity were calculated, and funnel plots were produced. RESULTS: Twenty case-control studies were selected with 2436 patients with chronic periodontitis and 1787 controls. The meta-analysis showed that increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and acid phosphatase (ACP) were all associated with periodontitis (p < 0.05), while blood urea nitrogen (BUN) and osteoprotegerin (OPG) levels did not show statistical differences between cases and controls (p > 0.05). CONCLUSIONS: This meta-analysis evidenced that increased levels of AST, ALT, CK, gama glutamil transferase (GGT), LDH, ALP, and ACP are associated in patients with chronic periodontitis, while BUN and OPG level in saliva did not present differences between groups.

Sulfated polysaccharides from the marine algae Gracilaria caudata prevent tissue damage caused by ligature-induced periodontitis.

Sulfated polysaccharides (PLS) extracted from the marine algae of the genus Gracilaria showed biological activity in different inflammatory models, except for periodontitis. Thus, this study aimed to evaluate the effectiveness of the treatment with PLS from Gracilaria caudata in ligature-induced periodontitis. 40 animals distributed into 5 groups were used (the control group (unligated), the ligated untreated group, and the ligated groups treated with 2.5, 5.0 and 10.0 mg/kg of PLS with intraperitoneal injection, respectively). After 20 days of treatment, the animals were killed and the following parameters were evaluated: Gingival Bleeding Index (GBI), Probing Pocket Depth (PPD), Myeloperoxidase (MPO) activity, Alveolar Bone Loss (ABL) for periodontal tissues; histopathological examination of gingival and liver tissues (Steatosis score); glutathione and malondialdehyde concentrations in the liver, serum levels of alanine aminotransferase and aspartate aminotransferase. The data revealed that treatment with 2.5 mg/kg of PLS showed the best anti-inflammatory effects with reduction of GBI, PPD and MPO activity, as well as oxidative stress and steatosis in liver. Our results indicated that the adjunct treatment with PLS from Gracilaria caudata could prevent the periodontal and hepatic tissue alteration caused by periodontitis.

Topical application of cashew gum or chlorhexidine gel reduces overexpression of proinflammatory genes in experimental periodontitis.

This study aimed to explore the effect of topically administering an orabase gel containing cashew gum (CG), a complex polysaccharide from Anacardium occidentale L., on the transcription of important proinflammatory (COX-2, NOS-2, INF-γ, OSCAR, and MYD88) and anti-inflammatory genes (IL-10, IL-4, and TGFß1) in the gingival tissues of rats with ligature-induced periodontitis, compared to the effect observed upon topically applying a well-known antibiofilm agent (chlorhexidine) under the same experimental conditions. The gene expression profile in the gingival tissues of rats with periodontitis treated with CG did not statistically significantly differ from that observed in the group of animals treated with chlorhexidine. Results showed that CG is able to attenuate general inflammation in the periodontium by reducing the transcription of proinflammatory mediators in a MYD88-independent manner, and not by inducing the expression of anti-inflammatory factors. In conclusion, this study demonstrated that CG and chlorhexidine treatment reduced significantly the gene overexpression (COX-2, NOS-2, INF-γ, OSCAR, and TGFß1) in the model of ligature-induced periodontitis.

Comparative analysis of blood parameters of the erythrocyte lineage between patients with chronic periodontitis and healthy patients: Results obtained from a meta-analysis.

Objective Quantitatively evaluate blood parameters of the erythrocyte lineage in patients with chronic periodontitis and healthy controls by means of a meta-analysis. Material and methods A review of literature was performed in the scientific databases for studies published before September 2016. The abstracts were evaluated and the extraction of data performed by two examiners. The parameters assessed were: hemoglobin levels, number of circulating red blood cells, hematocrit, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration in patients with chronic periodontitis and healthy controls. The calculations were obtained through the statistical software Review Manager version 5.3, with calculation of Mean Difference, heterogeneity (I²) and funnel plot with P < 0.05. Results Nine case/control studies composed the results with 342 patients with chronic periodontitis and 359 healthy controls. There was a significant decrease in hemoglobin levels (MD = -1.60, 95% CI: -2.72, -0.48, P = 0.005) and number of circulating red blood cells (MD = -0.51, 95% CI: -0.78, -0.24, P = 0.0002), hematocrit (MD = -4.41, IC 95%: -7.13, -1.68, P = 0.002), mean corpuscular hemoglobin (MD = -0.80; IC 95%: -1.38, -0,22, P = 0.007) and mean corpuscular hemoglobin concentration (MD = -0.93, IC 95%: -1.63, -0.23, P = 0.009) in patients with chronic periodontitis when compared to healthy controls. No publication bias was found through the funnel plot asymmetry. Conclusion There is an associated of the reduction of hematological parameters (such as levels of hemoglobin and circulating red blood cells, hematocrit, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration) to patients with chronic periodontitis.

Association between the rs1143634 polymorphism in interleukin-1B and chronic periodontitis: Results from a meta-analysis composed by 54 case/control studies.

Several factors are involved in the periodontitis with host response through cytokines and as well as with influence of polymorphisms in cytokine genes, however the results remained contradictory. This study aimed at evaluating the rs1143634 polymorphism in interleukin-1B gene, a cytokine gene, and the risk of chronic periodontitis with conducting a meta-analysis focusing in ethnicity. A review in literature was performed in several databases to studies published before June 2017. Data extraction was performed by two calibrated investigators and the calculations of the meta-analysis were obtained through Review Manager version 5.2 statistical software with Odds Ratio (OR) calculation and Funnel plot (P < 0.05) to heterogeneity and the Comprehensive Meta-analysis version 3.3.070 to assessment publication bias by Egger's and Begg's tests. In overall, 54 case/control studies composed the meta-analysis. T allele was significantly associated with patients case (OR = 1.35, 95% CI: 1.24, 1.48, P < 0.00001) in the overall analysis. The stratified evaluation showed the rs1143634 polymorphism had significant association with disease in Caucasian, Asian and mixed population was excepted in African ethnicity (P > 0.05). No publication bias was found in allelic evaluation. This meta-analysis in 9376 participants with 54 case/control studies revealed the rs1143634 polymorphism was associated with elevated risk of chronic periodontitis in overall analysis as well as Caucasian and Asian ethnicities and Mixed population.

Biological Effects of Medicinal Plants on Induced Periodontitis: A Systematic Review.

Objective. The aim of this systematic review was to investigate the advances in the study of medicinal plants and their biologic effects on periodontitis in animal models. Study Design. A systematic search was conducted by three independent researchers, who screened articles published up to March/2016, to identify the studies that contained sufficient and clear information on the association of the medicinal plants and periodontitis in murine models. The searches were performed using PubMed, Cochrane, and Science Direct databases. Results. After a critical analysis of titles and abstracts, 30 studies were finally eligible for analysis. The studies presented a great diversity of the experiment designed regarding the methods of induced periodontitis and the evaluation of the medicinal plants efficacy. None of the studies described the possible toxic effects associated with the administration of the plant material to animals and whether they could prevent damage to organs caused by systemic effect of induced periodontitis. Gel-based formulations containing plant substances are seen as an interesting strategy to treat periodontitis. Conclusions. In this systematic review, the state-of-the-art knowledge on the medicinal plants and the induced periodontitis was critically evaluated and discussed from the experiment designed to the possible clinical application.

Backward masking and the central performance drop.

Kehrer [Spatial Vision 2 (1987) 247] found that texture discrimination performance sometimes peaks in the parafovea rather than at the fovea, and he referred to this phenomenon as the central performance drop (CPD). Kehrer used a backward mask to limit performance and Morikawa [Vision Res. 40 (2000) 3517] argued that in some cases the temporal aspects of the backward mask may be critical to the emergence of the CPD. In one experiment Morikawa showed that the CPD does not emerge when a simultaneous noise-mask (different from the mask used by Kehrer) is used to limit performance. In another experiment Morikawa showed that unmasked texture displays comprising short lines do not elicit the CPD. In both cases, changes in the temporal aspects of the texture displays were accompanied by changes in the spatial structure of the mask or stimulus. For the spatio-temporal theory of the CPD to be sustained one would have to show that noise masks elicit a CPD when used as backward masks and that the short-line textures elicit a CPD when followed by backward masks. Our evidence provides little if any support for either of these predictions. Furthermore, an analysis of a simple filter-rectify-filter model of texture segmentation shows that a greatly attenuated CPD is to be expected when a noise mask is used as a source of spatial noise.