Biological and Molecular Docking Evaluation of a Benzylisothiocyanate Semisynthetic Derivative From Moringa oleifera in a Pre-clinical Study of Temporomandibular Joint Pain.

Objective: Moringa oleifera possesses multiple biological effects and the 4-[(4'-O-acetyl-α-L- rhamnosyloxy) benzyl] isothiocyanate accounts for them. Based on the original isothiocyanate molecule we obtained a semisynthetic derivative, named 4-[(2',3',4'-O-triacetyl-α-L-rhamnosyloxy) N-benzyl] hydrazine carbothioamide (MC-H) which was safe and effective in a temporomandibular joint (TMJ) inflammatory hypernociception in rats. Therefore, considering that there is still a gap in the knowledge concerning the mechanisms of action through which the MC-H effects are mediated, this study aimed to investigate the involvement of the adhesion molecules (ICAM-1, CD55), the pathways heme oxygenase-1 (HO-1) and NO/cGMP/PKG/K+ ATP, and the central opioid receptors in the efficacy of the MC-H in a pre-clinical study of TMJ pain. Methods: Molecular docking studies were performed to test the binding performance of MC-H against the ten targets of interest (ICAM-1, CD55, HO-1, iNOS, soluble cGMP, cGMP-dependent protein kinase (PKG), K+ ATP channel, mu (µ), kappa (κ), and delta (δ) opioid receptors). In in vivo studies, male Wistar rats were treated with MC-H 1 µg/kg before TMJ formalin injection and nociception was evaluated. Periarticular tissues were removed to assess ICAM-1 and CD55 protein levels by Western blotting. To investigate the role of HO-1 and NO/cGMP/PKG/K+ ATP pathways, the inhibitors ZnPP-IX, aminoguanidine, ODQ, KT5823, or glibenclamide were used. To study the involvement of opioid receptors, rats were pre-treated (15 min) with an intrathecal injection of non-selective inhibitor naloxone or with CTOP, naltrindole, or norbinaltorphimine. Results: All interactions presented acceptable binding energy values (below -6.0 kcal/mol) which suggest MC-H might strongly bind to its molecular targets. MC-H reduced the protein levels of ICAM-1 and CD55 in periarticular tissues. ZnPP-IX, naloxone, CTOP, and naltrindole reversed the antinociceptive effect of MC-H. Conclusion: MC-H demonstrated antinociceptive and anti-inflammatory effects peripherally by the activation of the HO-1 pathway, as well as through inhibition of the protein levels of adhesion molecules, and centrally by µ and δ opioid receptors.

The Cannabidiol Analog PECS-101 Prevents Chemotherapy-Induced Neuropathic Pain via PPARγ Receptors.

Chemotherapy-induced peripheral neuropathy (CIPN) is the main dose-limiting adverse effect of chemotherapy drugs such as paclitaxel (PTX). PTX causes marked molecular and cellular damage, mainly in the peripheral nervous system, including sensory neurons in the dorsal root ganglia (DRG). Several studies have shown the therapeutic potential of cannabinoids, including cannabidiol (CBD), the major non-psychotomimetic compound found in the Cannabis plant, to treat peripheral neuropathies. Here, we investigated the efficacy of PECS-101 (former HUF-101), a CBD fluorinated analog, on PTX-induced neuropathic pain in mice. PECS-101, administered after the end of treatment with PTX, did not reverse mechanical allodynia. However, PECS-101 (1 mg/kg) administered along with PTX treatment caused a long-lasting relief of the mechanical and cold allodynia. These effects were blocked by a PPARγ, but not CB1 and CB2 receptor antagonists. Notably, the effects of PECS-101 on the relief of PTX-induced mechanical and cold allodynia were not found in macrophage-specific PPARγ-deficient mice. PECS-101 also decreased PTX-induced increase in Tnf, Il6, and Aif1 (Iba-1) gene expression in the DRGs and the loss of intra-epidermal nerve fibers. PECS-101 did not alter motor coordination, produce tolerance, or show abuse potential. In addition, PECS-101 did not interfere with the chemotherapeutic effects of PTX. Thus, PECS-101, a new fluorinated CBD analog, could represent a novel therapeutic alternative to prevent mechanical and cold allodynia induced by PTX potentially through the activation of PPARγ in macrophages.

Brazilian dental students and COVID-19: A survey on knowledge and perceptions.

OBJECTIVE: This study evaluated the knowledge and perceptions of Brazilian dental students about COVID-19 and the undergraduate clinical practice during the COVID-19 outbreak by a self-administered Web-based questionnaire. METHODS: A social network campaign on Instagram was raised to approach the target population. The survey covered demographic and academic profile, general knowledge, preventive measures and perception about COVID-19. Descriptive statistics were used to identify frequencies and distributions of variables, which were compared by type of institution and current year of enrolment using the Chi-square or Fisher's exact tests (α = 0.05). RESULTS: A total of 833 valid responses were received over 10 days. Students were able to identify the incubation period, main symptoms and contagious routes of the disease but struggled in recognising the name of the virus responsible for the pandemic. Hand washing before and after a dental appointment with a patient (97.7%) followed by the use of barriers to protect mucosa (97.2%) were the more frequently recognised measures to prevent COVID-19 spread in the dental office. As for the perception of COVID-19, 73.2% of the dental students perceived the disease as severe, whilst only 11.1% of them thought that COVID-19 is severe only for people presenting risk factors. Dental student's knowledge and perception were associated with the type of institution and year of enrolment. CONCLUSION: In summary, the dental students demonstrated an acceptable general knowledge about COVID-19, but dental schools will need to address gaps in knowledge, preventive measures, and perceptions to ensure a safer return to in person activities.

Information sources of Brazilian undergraduate dental students during the COVID-19 outbreak: a cross-sectional study

Aim: This cross-sectional study aimed to investigate where Brazilian dental students seek information about COVID-19 by a self-administered web-based questionnaire. Methods: A social network campaign on Instagram was raised to approach the target population. The dental students responded to a multiple-response question asking where or with whom they get information about COVID-19. The possible answers were government official websites or health and education institutions websites, TV Programs, professors, social media, scientific articles, health professionals, and family members. The data were analyzed by descriptive statistics, and the frequency distributions of responses were evaluated by gender, age, type of institution, and year of enrollment. Results: A total of 833 valid responses were received. The main source of information used by the dental students were government official websites or health and education institutions websites, which were reported by 739 (88.7%) participants. In the sequence, 477 (57.3%) participants chose health professionals while 468 (56.2%) chose scientific articles as information sources. The use of social media was reported by 451 (54.1%) students, while TV programs were information sources used by 332 (39.9%) students. The least used information sources were professors, reported by 317 (38.1%) students, and family members, chosen only by 65 (7.8%) participants. Conclusion: Brazilian dental students rely on multiple information sources to stay informed about COVID-19, mainly focusing their information-seeking behavior on governmental and health professional's websites

Sulfated polysaccharide from the green marine algae Caulerpa racemosa reduces experimental pain in the rat temporomandibular joint.

Temporomandibular disorder is a clinical painful condition in the temporomandibular joint (TMJ) region. The purified sulfated polysaccharide from the green marine algae Caulerpa racemosa (Cr) has provided anti-inflammatory and antinociceptive activity. This study evaluated these effects on a TMJ hypernociception model. Wistar rats (180 - 250 g) were pre-treated (i.v.) with Cr at 0.01, 0.1, or 1 mg/kg or vehicle 30 min before formalin (1.5%/50 µL, i.art.), capsaicin (1.5%/20 µL, i.art.), or serotonin (225 µg/50 µL, i.art.) in the TMJ, and nociceptive behaviors were measured for 45 or 30 min upon inflammatory stimuli. Inflammatory parameters vascular permeability assay, TNF-α, and IL-1ß by ELISA, protein expression of adhesion molecules ICAM-1 and CD55 by Western blot were assessed. The involvement of heme oxygenase-1 (HO-1) and nitric oxide (NO) pathways were assessed by pharmacological inhibition. Cr (1 mg/kg) reduced nociceptive behavior, plasmatic extravasation, TNF-α, and IL-1ß levels, as well as ICAM-1 and CD55 expression in periarticular tissues. Cr antinociceptive effect was not prevented by aminoguanidine, but ZnPP-IX did reduce its antinociceptive effect. Therefore, Cr antinociceptive and anti-inflammatory effects in this experimental model of hypernociception depended on the HO-1 pathway integrity, as well as reducing peripheral inflammatory events, e.g., TNF-α and IL-1ß cytokines levels, ICAM-1 and CD55 expression.

The efficacy of a lectin from Abelmoschus Esculentus depends on central opioid receptor activation to reduce temporomandibular joint hypernociception in rats.

Abelmoschus esculentus is largely cultivated in Northeastern Brazil for medicinal purposes, e.g. inflammatory conditions. This study aimed to evaluate the efficacy of Abelmoschus esculentus lectin (AEL) in reducing formalin-induced temporomandibular joint inflammatory hypernociception in rats. The behavioral experiments were performed in male Wistar rats (180-240 g). Rats were pre-treated (i.v.) with AEL (0.001, 0.01 or 0.1 mg/kg) 30 min before formalin injection (i.art.). To analyze the possible effect of opioid pathways on AEL efficacy, animals were pre-treated with naloxone or CTOP (µ opioid receptor antagonist), naltrindole (δ opioid receptor antagonist) or nor-binaltorphimine (κ opioid receptor antagonist) (i.t.) 15 min before AEL administration followed by intra-TMJ injection of 1.5% formalin. Animals were monitored for a 45-min observation period. TMJ tissue, trigeminal ganglion, and subnucleus caudalis were collected for TNF-α dosage (ELISA). In addition, the vascular permeability was evaluated by Evans Blue extravasation. AEL significantly reduced formalin-induced TMJ inflammatory hypernociception and decreased Evans blue extravasation. It decreased TNF-α levels in the TMJ tissue, trigeminal ganglion, and subnucleus caudalis. AEL antinociceptive effects were not observed in the presence of naltrindole or nor-binaltorphimine, suggesting that AEL efficacy depends on TNF-α inhibition and the activation of δ and κ opioid receptors. AEL has provided prominent analgesic and anti-inflammatory effects in this pre-clinical model of TMJ, supporting its possible use as a pharmacological tool for the management of painful conditions.

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.

Antinociceptive, anti-inflammatory and toxicological evaluation of semi-synthetic molecules obtained from a benzyl-isothiocyanate isolated from Moringa oleifera Lam. in a temporomandibular joint inflammatory hypernociception model in rats.

Inflammation is a key component of many clinical conditions that affect the temporomandibular joint (TMJ) and Moringa oleifera Lam. has been used to treat inflammatory diseases. Here, we evaluated the toxicological effects on mice of a naturally-occurring isothiocyanate from M. oleifera and its seven analogue molecules. Further, the anti-nociceptive and anti-inflammatory effects on a rat model of TMJ inflammatory hypernociception were assessed. The systemic toxicological profile was determined in mice over a 14-day period: MC-1 1 µg/kg; MC-D1 1 µg/kg, MC-D3 100 µg/kg, MC-D6 1 µg/kg, MC-D7 1 µg/kg, MC-D8 1 µg/kg, MC-D9 10 µg/kg, and MC-H 1 µg/kg. The safest molecules were assayed for anti-nociceptive efficacy in the formalin (1.5%, 50 µL) and serotonin (255 mg) induced TMJ inflammatory hypernociception tests. The anti-inflammatory effect was evaluated through the vascular permeability assay using Evans blue. Further, the rota-rod test evaluated any motor impairment. Among the tested molecules, MC-D7, MC-D9, and MC-H were not toxic at the survival rate test, biochemical, and hystological analysis. They reduced the formalin-induced TMJ inflammatory hypernociception, but only MC-H decreased the serotonin-induced TMJ inflammation, suggesting an adrenergic receptor-dependent effect. They diminished the plasmatic extravasation, showing anti-inflammatory activity. At the rota-rod test, no difference was observed in comparison with control groups, reinforcing the hypothesis of anti-nociceptive effetc without motor impairment in animals. The analogues MC-D7, MC-D9, and MC-H were safe at the tested doses and efficient in reducing the formalin-induced TMJ hypernociception in rats. Our next steps include determining their mechanisms of anti-nociceptive action.

Heme oxygenase-1/biliverdin/carbon monoxide pathway downregulates hypernociception in rats by a mechanism dependent on cGMP/ATP-sensitive K+ channels.

OBJECTIVE AND DESIGN: To investigate the role of heme oxygenase-1 (HO-1), carbon monoxide (CO), and biliverdin (BVD) in the zymosan-induced TMJ arthritis in rats. MATERIALS AND METHODS: Mechanical threshold was assessed before and 4 h after TMJ arthritis induction in rats. Cell influx, myeloperoxidase activity, and histological changes were measured in the TMJ lavages and tissues. Trigeminal ganglion and periarticular tissues were used for HO-1, TNF-α, and IL-1ß mRNA time course expression and immunohistochemical analyses. Hemin (0.1, 0.3, or 1 mg kg-1), DMDC (0.025, 0.25, or 2.5 µmol kg-1), biliverdin (1, 3, or 10 mg kg-1), or ZnPP-IX (1, 3 or 9 mg kg-1) were injected (s.c.) 60 min before zymosan. ODQ (12.5 µmol kg-1; s.c.) or glibenclamide (10 mg kg-1; i.p.) was administered 1 h and 30 min prior to DMDC (2.5 µmol kg-1; s.c), respectively. RESULTS: Hemin (1 mg kg-1), DMDC (2.5 µmol kg-1), and BVD (10 mg kg-1) reduced hypernociception and leukocyte migration, which ZnPP (3 mg kg-1) enhanced. The effects of DMDC were counteracted by ODQ and glibenclamide. The HO-1, TNF-α, and IL-1ß mRNA expression and immunolabelling increased. CONCLUSIONS: HO-1/BVD/CO pathway activation provides anti-nociceptive and anti-inflammatory effects on the zymosan-induced TMJ hypernociception in rats.

Strontium Ranelate Elevates Expression of Heme Oxygenase-1 and Decreases Alveolar Bone Loss in Rats.

OBJECTIVES: The purpose of this study was to determine the effects of strontium ranelate on ligature-induced periodontitis in rats and assess the putative involvement of heme oxygenase-1 (HO-1) pathway in these effects. MATERIAL AND METHODS: Male Wistar rats underwent nylon ligature placement around maxillary molars and were treated (v.o.) with strontium ranelate (20 or 100 mg/kg) for 7 days. After that, rats were euthanized and histomorphometric/histopathological analyses and RT-PCR for HO-1 expression were performed. RESULTS: Strontium ranelate (20 or 100 mg/kg) prevented bone resorption by 28% and 38%, respectively. Strontium ranelate treatment (100 mg/kg) up-regulated (P < 0.05) heme oxygenase-1 mRNA levels in the gingival tissues in comparison to control groups. CONCLUSIONS: Strontium ranelate prevented periodontal bone loss in experimental periodontitis in rats while heme oxygenase-1 mRNA levels increased after treatment.

Anti-inflammatory and anti-nociceptive effects of strontium ranelate on the zymosan-induced temporomandibular joint inflammatory hypernociception in rats depend on TNF-α inhibition.

BACKGROUND: Temporomandibular joint (TMJ) disorders show inflammatory components, heavily impacting on quality of life. Strontium ranelate has previously shown anti-inflammatory and antinociceptive effects on other experimental inflammatory pain models. Thus, we aim to investigate the strontium ranelate efficacy in reducing the zymosan-induced inflammatory hypernociception in the TMJ of rats by evaluating the TNF-α, IL-1ß, and hemeoxygenase-1 (HO-1) involvement. METHODS: Wistar rats were treated with strontium ranelate (0.5, 5 or 50 mg/kg, per os) 1 h before zymosan injection (iart). Mechanical threshold was assessed by Von Frey test and synovial lavage was collected for leukocyte counting and myeloperoxidase measurement, joint tissue and trigeminal ganglion were excised for histopathological analysis (H&E) and TNF-α/IL-1ß levels dosage (ELISA). Moreover, rats were pre-treated with ZnPP-IX (3 mg/kg, sc), a specific HO-1 inhibitor, before strontium ranelate administration (0.5 mg/kg, per os), and Evans Blue (5 mg/kg, iv) was administered to assess plasma extravasation. Pre-treatment with indomethacin (5 mg/kg, sc) was used as positive control while the sham group received 0.9% sterile saline (per os and iart). RESULTS: Strontium ranelate did not reduce leukocyte counting, myeloperoxidase activity, Evans Blue extravasation, IL-1ß levels, and TNF-α/IL-1ß immunolabeling; but it increased the nociceptive threshold and reduced TNF-α levels. Additionally, HO-1 inhibition did not change the strontium ranelate effects. CONCLUSION: Strontium ranelate may achieve its antinociceptive effects through the reduction of TNF-α levels in the trigeminal ganglion, but not suppressing IL-1ß expression nor inducing the HO-1 pathway.

Mechanisms involved in antinociception induced by a polysulfated fraction from seaweed Gracilaria cornea in the temporomandibular joint of rats.

Temporomandibular disorder is a common clinical condition involving pain in the temporomandibular joint (TMJ) region. This study assessed the antinociceptive effects of a polysulfated fraction from the red seaweed Gracilaria cornea (Gc-FI) on the formalin-induced TMJ hypernociception in rats and investigated the involvement of different mechanisms. Male Wistar rats were pretreated with injection (sc) of saline or Gc-FI 1h before intra- TMJ injection of formalin to evaluate the nociception. The results showed that pretreatment with Gc-FI significantly reduced formalin-induced nociceptive behavior. Moreover, the antinociceptive effect of the Gc-FI was blocked by naloxone (a non-selective opioid antagonist), suggesting the involvement of opioids selective receptors. Thus, the pretreatment with selective opioids receptors antagonists, reversed the antinociceptive effect of the Gc-FI in the TMJ. The Gc-FI antinociceptive effect depends on the nitric oxide/cyclic GMP/protein kinase G/ATP-sensitive potassium channel (NO/cGMP/PKG/K+ATP) pathway because it was prevented by pretreatment with inhibitors of nitric oxide synthase, guanylate cyclase enzyme, PKG and a K+ATP blocker. In addition, after inhibition with a specific heme oxygenase-1 (HO-1) inhibitor, the antinociceptive effect of the Gc-FI was not observed. Collectively, these data suggest that the antinociceptive effect induced by Gc-FI is mediated by µ/δ/κ-opioid receptors and by activation NO/cGMP/PKG/K+ATP channel pathway, besides of HO-1.

Occurrence and antimicrobial susceptibility of enteric rods and pseudomonads isolated from the dental prostheses biofilm.

OBJECTIVE:: To determine the occurrence and the in vitro antimicrobial susceptibility of enteric rods and pseudomonads from the denture biofilm of 52 subjects at the Center for Dental Specialties of Sobral/ Ceara, Brazil. MATERIAL AND METHODS:: Denture biofilm was collected and samples plated on MacConkey agar. The isolated bacterial colonies were identified using the BBL Crystal enteric/non-fermenter system. Antibiotic bacterial susceptibility was assessed by the disc diffusion method of amoxicillin, amoxicillin/clavulanic acid, doxycycline, tetracycline, tobramycin, imipenem, cefotaxime, and ciprofloxacin. The Minimum Inhibitory Concentration (MIC) of cefotaxime, tobramycin, doxycycline, imipenem, and ciprofloxacin was determined for 40 species by E-test. RESULTS:: 34 subjects (65.4%) harbored enteric rods in their prostheses. Klebsiella pneumoniae (26.5%), Escherichia coli (23.5%), and Enterobacter aerogenes (23.5%) were the most prevalent species. All organisms were susceptible to ciprofloxacin and most species were resistant to amoxicillin or amoxicillin/clavulanic acid, demonstrating variable sensitivity patterns to other antimicrobials. However, the MIC showed the emergence of strains with reduced sensitivity to ciprofloxacin (MIC90≥3 µg/ mL) and cefotaxime (MIC90≥2 µg/mL). CONCLUSION:: The findings show high prevalence of nosocomial diseases-related bacterial species and low susceptibility to antimicrobial drugs. Therefore, these results imply caution against the indiscriminate use of broad spectrum antibiotics in dental practice.

Occurrence and antimicrobial susceptibility of enteric rods and pseudomonads isolated from the dental prostheses biofilm

ABSTRACT Aspiration of oral bacteria leads to cardiac and respiratory infectious diseases and dentures can act as a reservoir for pathogenic microorganisms. Objective: To determine the occurrence and the in vitro antimicrobial susceptibility of enteric rods and pseudomonads from the denture biofilm of 52 subjects at the Center for Dental Specialties of Sobral/ Ceara, Brazil. Material and Methods: Denture biofilm was collected and samples plated on MacConkey agar. The isolated bacterial colonies were identified using the BBL Crystal enteric/non-fermenter system. Antibiotic bacterial susceptibility was assessed by the disc diffusion method of amoxicillin, amoxicillin/clavulanic acid, doxycycline, tetracycline, tobramycin, imipenem, cefotaxime, and ciprofloxacin. The Minimum Inhibitory Concentration (MIC) of cefotaxime, tobramycin, doxycycline, imipenem, and ciprofloxacin was determined for 40 species by E-test. Results: 34 subjects (65.4%) harbored enteric rods in their prostheses. Klebsiella pneumoniae (26.5%), Escherichia coli (23.5%), and Enterobacter aerogenes (23.5%) were the most prevalent species. All organisms were susceptible to ciprofloxacin and most species were resistant to amoxicillin or amoxicillin/clavulanic acid, demonstrating variable sensitivity patterns to other antimicrobials. However, the MIC showed the emergence of strains with reduced sensitivity to ciprofloxacin (MIC90≥3 μg/ mL) and cefotaxime (MIC90≥2 μg/mL). Conclusion: The findings show high prevalence of nosocomial diseases-related bacterial species and low susceptibility to antimicrobial drugs. Therefore, these results imply caution against the indiscriminate use of broad spectrum antibiotics in dental practice.

Inflammatory Cytokines Interleukin-1ß and Tumour Necrosis Factor-α - Novel Biomarkers for the Detection of Periodontal Diseases: a Literature Review.

OBJECTIVES: The article aims to discuss the IL-1ß and TNF-α potential use as salivary biomarkers of periodontal diseases pathogenesis and progression. MATERIAL AND METHODS: This literature review has been registered in PROSPERO database with following number: CRD42016035729. Data investigation was performed on PubMed database as the main source of studies. The following search terms were used: "salivary biomarkers", "periodontal diseases", "TNF-alpha", "Interleukin-1 beta". Clinical trials and animal experimental models of periodontal disease were included in the discussion. In regards to inclusive dates, published studies from January 2006 to December 2015 were considered in this review along with the mentioned inclusion criteria. RESULTS: IL-1ß and TNF-α salivary levels increased in diseased groups, they were associated with onset and disease severity, and their levels reduced in response to periodontal therapy. IL-1ß and TNF-α could be promising biomarkers in the detection of periodontal diseases. CONCLUSIONS: The use of a salivary cytokine-based diagnosis appears to be a screening method capable of diagnosing periodontal diseases in an early fashion, establishing an era of individualized clinical decisions.

Lectin from Abelmoschus esculentus reduces zymosan-induced temporomandibular joint inflammatory hypernociception in rats via heme oxygenase-1 pathway integrity and tnf-α and il-1ß suppression.

Temporomandibular joint (TMJ) disorders show inflammatory components, heavily impacting on quality of life. Abelmoschus esculentus is largely cultivated in Northeastern Brazil for medicinal purposes, having it shown anti-inflammatory activity. We evaluated A. esculentus lectin (AEL) efficacy in reducing zymosan-induced temporomandibular joint inflammatory hypernociception in rats along with the mechanism of action through which it exerts anti-inflammatory activity. Animals were pre-treated with AEL (0.01, 0.1 or 1mg/kg) before zymosan (Zy) injection in the TMJ to determine anti-inflammatory activity. To analyse the possible effect of the hemeoxygenase-1 (HO-1) and the nitric oxide (NO) pathways on AEL efficacy, animals were pre-treated with ZnPP-IX (3mg/kg), a specific HO-1 inhibitor, or aminoguanidine (30mg/kg), a selective iNOS inhibitor, before AEL administration. Von Frey test evaluated inflammatory hypernociception, synovial fluid collection was performed to determine leukocyte counting and myeloperoxidase (MPO) activity 6h after Zy injection, and Evans Blue extravasation determined vascular permeability. TMJ tissue was collected for histopathological analysis (H&E) and immunohistochemistry (TNF-α, IL-1ß, HO-1). In addition, TMJ tissue and trigeminal ganglion collection was performed for TNF-α and IL-1ß dosage (ELISA). AEL increased inflammatory nociceptive threshold, reduced leukocyte influx along with MPO activity, leukocyte influx into the synovial membrane, and Evans Blue extravasation. It promoted HO-1 overexpression whilst decreased TNF-α and IL-1ß expression in the TMJ tissue. AEL reduced TNF-α and IL-1ß levels in TMJ tissue and trigeminal ganglion. AEL effects, however, were not observed in the presence of ZnPP-IX. These findings suggest that AEL efficacy depends on TNF-α/IL-1ß inhibition and HO-1 pathway integrity.

Effects of nonsteroidal anti-inflammatory drugs on osseointegration: a review.

The purpose of this study was to review the effects of nonsteroidal anti-inflammatory drugs on osseointegration and determine whether they cause failures in dental implants and whether patients who use them chronically can receive dental implants safely. A bibliographic electronic search was performed using the Cochrane Library, PubMed, and Medline databases, selecting articles published between January 1982 and December 2012. The search included the following keywords, either alone or combined: "nonsteroidal anti-inflammatory drugs," "dental implants," "bone healing," and "osteoprogenitor cells." The inclusion criteria were the following: randomized, double-blind, placebo-controlled clinical studies, in vivo animal model studies of osseointegration, and in vitro studies of the effects of these agents on osteoprogenitor cells. The literature search revealed 360 references. A total of 31 articles met the inclusion criteria, including 2 clinical trials, 20 animal studies, and 9 osteoprogenitor cell studies. The clinical trials revealed that cyclooxygenase-1 (COX-1) inhibitors did not impair osseointegration. The animal studies showed that any drug that is capable of inhibiting COX-2 may impair the osseointegration process. The in vitro studies showed that COX-2 inhibitors are the most potent depressors of osseointegration at the cellular level. Caution must be taken when selecting COX-2 nonsteroidal anti-inflammatory drugs during the postoperative period.