Calotropis procera latex protein reduces inflammation and bone loss in ligature-induced period ontitis in male rats.

OBJECTIVE: Calotropis procera latex protein (CpLP) is a popular anti-inflammatory and therefore we aimed to study its effects on inflammatory bone loss. DESIGN: Male Wistar rats were subjected to a ligature of molars. Groups of rats received intraperitoneally CpLP (0.3 mg/kg, 1 mg/kg, or 3 mg/kg) or saline (0.9% NaCl) one hour before ligature and then daily up to 11 days, compared to naïve. Gingiva was evaluated by myeloperoxidase activity and interleukin-1 beta (IL-1ß) expression by ELISA. Bone resorption was evaluated in the region between the cement-enamel junction and the alveolar bone crest. The histology considered alveolar bone resorption and cementum integrity, leukocyte infiltration, and attachment level, followed by immunohistochemistry bone markers between 1st and 2nd molars. Systemically, the weight of the body and organs, and a leukogram were performed. RESULTS: The periodontitis significantly increased myeloperoxidase activity and the IL-1ß level. The increased bone resorption was histologically corroborated by periodontal destruction, leukocyte influx, and attachment loss, as well as the increasing receptor activator of the nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) ratio, and Tartrate-resistant acid phosphatase (TRAP)+ cells when compared to naïve. CpLP significantly reduced myeloperoxidase activity, level of IL-1ß, alveolar bone resorption, periodontal destruction, leukocyte influx, and attachment loss. The CpLp also reduced the RANKL/OPG ratio and TRAP+ cells, when compared with the saline group, and did not affect the systemic parameters. CONCLUSIONS: CpLP exhibited a periodontal protective effect by reducing inflammation and restricting osteoclastic alveolar bone resorption in this rat model.

Uncaria tomentosa reduces osteoclastic bone loss in vivo.

BACKGROUND: The genus Uncaria (Rubiaceae) has several biological properties significant to human health. However, the mechanisms underlying the protective effect of this plant on bone diseases are uncertain. PURPOSE: The present study investigated the role of Uncaria tomentosa extract (UTE) on alveolar bone loss in rats and on osteoclastogenesis in vitro. MATERIALS: UTE was characterized by an Acquity UPLC (Waters) system, coupled to an Electrospray Ionization (ESI) interface and Quadrupole/Flight Time (QTOF, Waters) Mass Spectrometry system (MS). The effect of UTE treatment for 11 days on the ligature-induced bone loss was assessed focusing on several aspects: macroscopic and histological analysis of bone loss, neutrophil and osteoclast infiltration, and anabolic effect. The effect of UTE on bone marrow cell differentiation to osteoclasts was assessed in vitro. RESULTS: The analysis of UTE by UPLC-ESI-QTOF-MS/MS identified 24 compounds, among pentacyclic or tetracyclic oxindole alkaloids and phenols. The administration of UTE for 11 days on ligature-induced rat attenuated the periodontal attachment loss and alveolar bone resorption. It also diminished neutrophil migration to the gingiva tissue, demonstrated by a lower level of MPO. UTE treatment also decreased the level of RANKL/OPG ratio, the main osteoclast differentiation-related genes, followed by reduced TRAP-positive cell number lining the alveolar bone. Additionally, the level of bone-specific alkaline phosphatase, an anabolic bone marker, was elevated in the plasma of UTE treated rats. Next, we determined a possible direct effect of UTE on osteoclast differentiation in vitro. The incubation of primary osteoclast with UTE decreased RANKL-induced osteoclast differentiation without affecting cell viability. This effect was supported by downregulation of the nuclear factor activated T-cells, cytoplasmic 1 expression, a master regulator of osteoclast differentiation, and other osteoclast-specific activity markers, such as cathepsin K and TRAP. CONCLUSION: UTE exhibited an effective anti-resorptive and anabolic effects, which highlight it as a potential natural product for the treatment of certain osteolytic diseases, such as periodontitis.

Use of antidepressive agents as a possibility in the management of periodontal diseases: A systematic review of experimental studies.

Antidepressant agents have anti-inflammatory functions that could be interesting as adjuvants in periodontal therapy. The aim of the present study was to analyze the effect of antidepressive drugs in the management of periodontal disease. The MEDLINE, Scopus, Embase, LILACS, and SciELO databases were searched. To be included, the studies had to be experimental studies; randomized, controlled; double-blinded; or blinded studies. A total of 565 articles were initially searched, of which five were selected for the systematic review. All studies used rats, and three different drugs were evaluated: tianeptine, venlafaxine, and fluoxetine. Two of these studies evaluated the effect of antidepressive agents in rats submitted to both ligature-induced periodontitis and depression models, showing that depressive rats had greater alveolar bone loss (ABL). Only the venlafaxine study was not able to find any significant ABL reduction in the group that used this antidepressive drug. The other four studies showed statistically-significant differences, favoring the group with the antidepressant agent. Treatments that are able to modulate the brain-neuroendocrine-immune system could be used as an adjuvant to periodontal disease management. However, studies on humans and animals are scarce, limiting the conclusion of a positive effect in the present systematic review.

Severe obstructive sleep apnea treatment with oral appliance: the impact on obstructive, central and mixed events.

PURPOSE: The aim of this study is to evaluate the effectiveness of two types of oral appliance (OA) in the treatment of severe obstructive sleep apnea syndrome (OSAS) and their impact on the reduction of obstructive, central and mixed apneas. METHODS: Forty-eight patients suffering from severe OSAS with a history of non-adherence to positive airway pressure therapy were treated with OA (lingual orthosis and combined orthosis). Polysomnography exams were performed before and after treatment. Computed tomography and cephalometric radiography were requested for all patients to evaluate the titrated position of the OA and the airspace obtained. Statistical tests used the Minitab, version 17, program. The level of statistical significance was 5%. RESULTS: Before treatment, the mean AHI was 56.3 ± 19.1 events/h. It decreased to 8.1 ± 5.2 after the OA titration (p ≤ 0.001). There was a significant reduction in obstructive events from 43.0 ± 20.2 to 7.1 ± 4.6 events/h (p ≤ 0.001). The reduction in central events after OA treatment was also significant (from 5.1 ± 9.3 to 0.8 ± 1.9 events/h; p ≤ 0.001), whereas that in mixed events decreased from 6.4 ± 9.5 to 0.1 ± 0.3 events/h (p ≤ 0.001). The minimum oxygen saturation also showed significant improvement after treatment (p ≤ 0.001). There was no statistically significant difference between both OA with respect to central events (p = 0.22) or mixed events (p = 0.98). CONCLUSION: The treatment was effective in reducing obstructive events which were evaluated through the AHI and minimum oxygen saturation. The oral appliances also normalized central and mixed events among patients with severe OSAS.

Anti-inflammatory and antiresorptive effects of Calendula officinalis on inflammatory bone loss in rats.

OBJECTIVE: The aim of this work was to evaluate the anti-inflammatory and antiresorptive effects of Calendula officinalis (CLO) on alveolar bone loss (ABL) in rats. MATERIAL AND METHODS: Male Wistar rats were subjected to ABL by ligature with nylon thread around the second upper left molar. The contralateral hemimaxillae were used as control. Rats received saline solution (SAL) or CLO (10, 30, or 90 mg/kg) 30 min before ligature and daily until the 11th day. The maxillae were removed and prepared for macroscopic, radiographic, micro-tomographic, histopathologic, histometric analysis, and immunohistochemical localization of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG). The gingival tissues were used to quantify the myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-α), and interleukin-1ß (IL-1ß) concentrations by ELISA. Blood samples were collected for leukogram and to evaluate the bone-specific alkaline phosphatase (BALP) activity and serum levels of aspartate and alanine transaminases (AST/ALT). RESULTS: The bone loss induced by 11 days of ligature induced bone loss, reduced levels of BALP, leukocyte infiltration, increased MPO activity, gingival concentrations of TNF-α and IL-1ß, and RANKL while reduced OPG immunoexpressions in the periodontal tissue and leukocytosis. Of the CLO, 90 mg/kg reduced bone loss, neutrophilia, the levels of pro-inflammatory mediators, and RANKL expression, while it increased OPG immunopositive cells and BALP serum levels, when compared to SAL. CLO did not affect either kidney or liver function, indicated by serum AST/ALT levels. CONCLUSION: The present data suggests that CLO reduced inflammatory bone resorption in experimental periodontitis, which may be mediated by its anti-inflammatory properties and its effects on bone metabolism. CLINICAL RELEVANCE: CLO can be a potential therapeutical adjuvant in the treatment of periodontitis.

Versatility of Chitosan-Based Biomaterials and Their Use as Scaffolds for Tissue Regeneration.

Chitosan is a naturally occurring polysaccharide obtained from chitin, present in abundance in the exoskeletons of crustaceans and insects. It has aroused great interest as a biomaterial for tissue engineering on account of its biocompatibility and biodegradation and its affinity for biomolecules. A significant number of research groups have investigated the application of chitosan as scaffolds for tissue regeneration. However, there is a wide variability in terms of physicochemical characteristics of chitosan used in some studies and its combinations with other biomaterials, making it difficult to compare results and standardize its properties. The current systematic review of literature on the use of chitosan for tissue regeneration consisted of a study of 478 articles in the PubMed database, which resulted, after applying inclusion criteria, in the selection of 61 catalogued, critically analysed works. The results demonstrated the effectiveness of chitosan-based biomaterials in 93.4% of the studies reviewed, whether or not combined with cells and growth factors, in the regeneration of various types of tissues in animals. However, the absence of clinical studies in humans, the inadequate experimental designs, and the lack of information concerning chitosan's characteristics limit the reproducibility and relevance of studies and the clinical applicability of chitosan.

Dry Extract of Matricaria recutita L. (Chamomile) Prevents Ligature-Induced Alveolar Bone Resorption in Rats via Inhibition of Tumor Necrosis Factor-α and Interleukin-1ß.

BACKGROUND: Matricaria recutita L. (chamomile) has demonstrated anti-inflammatory activity. Accordingly, the ability of the Matricaria recutita extract (MRE) to inhibit proinflammatory cytokines and its influence on alveolar bone resorption (ABR) in rats. METHODS: Wistar rats were subjected to ABR by ligature with nylon thread in the second upper-left molar, with contralateral hemiarcade as control. Rats received polysorbate TW80 (vehicle) or MRE (10, 30, and 90 mg/kg) 1 hour before ligature and daily until day 11. The periodontium was analyzed by macroscopy, histometry, histopathology, and immunohistochemistry for the receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase (TRAP). The gingival tissue was used to quantify the myeloperoxidase (MPO) activity and tumor necrosis factor (TNF)-α and interleukin (IL)-1ß levels by enzyme-linked immunosorbent assay. Blood samples were collected to evaluate bone-specific alkaline phosphatase (BALP), leukogram, and dosages of aspartate and alanine transaminases, urea, and creatinine. Aspects of liver, kidneys, spleen, and body mass variations were also evaluated. RESULTS: The 11 days of ligature induced bone resorption, low levels of BALP, leukocyte infiltration; increase of MPO, TNF-α, and IL-1ß; immunostaining increase for RANKL and TRAP; reduction of OPG and leukocytosis, which were significantly prevented by MRE, except for the low levels of BALP and the leukocytosis. Additionally, MRE did not alter organs or body weights of rats. CONCLUSION: MRE prevented the inflammation and ABR by reducing TNF-α and IL-1ß, preventing the osteoclast activation via the RANKL-OPG axis, without interfering with bone anabolism.

Relationship between Periodontitis and Rheumatoid Arthritis: Review of the Literature.

Periodontitis (PD) and rheumatoid arthritis (RA) are immunoinflammatory diseases where leukocyte infiltration and inflammatory mediators induce alveolar bone loss, synovitis, and joint destruction, respectively. Thus, we reviewed the relationship between both diseases considering epidemiological aspects, mechanical periodontal treatment, inflammatory mediators, oral microbiota, and antibodies, using the keywords "periodontitis" and "rheumatoid arthritis" in PubMed database between January 2012 and March 2015, resulting in 162 articles. After critical reading based on titles and abstracts and following the inclusion and exclusion criteria, 26 articles were included. In the articles, women over 40 years old, smokers and nonsmokers, mainly constituted the analyzed groups. Eight studies broached the epidemiological relationship with PD and RA. Four trials demonstrated that the periodontal treatment influenced the severity of RA and periodontal clinical parameters. Nine studies were related with bacteria influence in the pathogenesis of RA and the presence of citrullinated proteins, autoantibodies, or rheumatoid factor in patients with PD and RA. Five studies investigated the presence of mediators of inflammation in PD and RA. In summary, the majority of the articles have confirmed that there is a correlation between PD and RA, since both disorders have characteristics in common and result from an imbalance in the immunoinflammatory response.

Effect of Atorvastatin in radiographic density on alveolar bone loss in wistar rats.

The purpose of this study was to evaluate the effect of Atorvastatin (ATV) on alveolar bone loss induced in rats. Periodontitis was induced by ligature placement around the upper second left molar in a total of 24 male Wistar rats (± 200 g). Groups of 6 animals received via oral gavage either saline or ATV (1, 3 and 9 mg/kg) during 11 days. After this time, the animals were sacrificed and their maxillae were removed, defleshed, radiographed by Digora System®, and latter stained to be photographed using a digital camera. Data were analyzed statistically by ANOVA and Bonferroni test at 5% significance level and presented as mean ± SEM. ATV (9 mg/kg) caused a significant increase on gray tone variation of over 48% (118.3 ± 12.0 gray tones) when compared to saline (79.8 ± 6.2 gray tones), indicating greater radiographic density. These data were corroborated by macroscopic findings, where ATV (9 mg/kg) reduced alveolar bone loss by over 47% (p<0.05), when compared to the group of untreated animals (saline). In summary, ATV was able to prevent alveolar bone loss seen on a ligature-induced periodontitis model.

Effect of Atorvastatin in radiographic density on alveolar bone loss in wistar rats

The purpose of this study was to evaluate the effect of Atorvastatin (ATV) on alveolar bone loss induced in rats. Periodontitis was induced by ligature placement around the upper second left molar in a total of 24 male Wistar rats (± 200 g). Groups of 6 animals received via oral gavage either saline or ATV (1, 3 and 9 mg/kg) during 11 days. After this time, the animals were sacrificed and their maxillae were removed, defleshed, radiographed by Digora System®, and latter stained to be photographed using a digital camera. Data were analyzed statistically by ANOVA and Bonferroni test at 5 percent significance level and presented as mean ± SEM. ATV (9 mg/kg) caused a significant increase on gray tone variation of over 48 percent (118.3 ± 12.0 gray tones) when compared to saline (79.8 ± 6.2 gray tones), indicating greater radiographic density. These data were corroborated by macroscopic findings, where ATV (9 mg/kg) reduced alveolar bone loss by over 47 percent (p<0.05), when compared to the group of untreated animals (saline). In summary, ATV was able to prevent alveolar bone loss seen on a ligature-induced periodontitis model.

O objetivo deste estudo foi avaliar o efeito da Atorvastatina (ATV) na perda óssea alveolar induzida em ratos. A periodontite foi induzida através da colocação de ligadura ao redor do segundo molar superior esquerdo de um total de 24 ratos Wistar machos (± 200 g). Grupos de 6 animais receberam por via oral solução Salina a 0,9 por cento ou Atorvastatina (1, 3 e 9 mg/kg), por 11 dias, quando então foram sacrificados e suas maxilas foram removidas, dissecadas, radiografadas através do Sistema Digora System®, e fotografados usando câmara digital. Os dados foram expressos como média ± EPM (ANOVA e teste de Bonferroni). Atorvastatina (9 mg/kg) causou aumento significante de aproximadamente 48 por cento na variação de tons de cinza (ATV 9=118,3 ± 12,0 tons de cinza), indicando maior densidade radiográfica, quando comparada ao controle (solução salina =79,8 ± 6,2 tons de cinza). Estes dados foram corroborados pelos achados macroscópicos, onde Atorvastatina (9 mg/kg) reduziu a perda óssea alveolar em 47 por cento (p<0,05), quando comparado aos animais não tratados (solução salina). Em suma, a Atorvastatina preveniu a perda óssea alveolar vista no modelo de periodontite induzida por ligadura.