Evaluation of the antimicrobial efficacy of different nonsteroidal anti-inflammatory drugs alone or in combination with calcium hydroxide intracanal medicament: an in vitro study.

This study explored the antimicrobial effects of ketoprofen, piroxicam, and celecoxib alone or combined with calcium hydroxide (CH) against two strains of Enterococcus faecalis (E. faecalis) and assessed the influence of such combinations on the pH of CH. Minimum inhibitory concentrations (MICs) of the three tested NSAIDs were determined. Tested pastes were placed into wells punched in seeded agar plates and the bacterial inhibition zones were measured. Antibiofilm activity was assessed against 3 weeks of biofilm induced in bovine dentine blocks. The pH of the pastes was measured at four-time intervals. MIC values were 3.12, 25, and 25 mg/ml for ketoprofen, piroxicam, and celecoxib, respectively, and were similar for both bacterial strains except for celecoxib, which showed 8% growth at the highest tested concentration against vancomycin-resistant E. faecalis. Ketoprofen had the largest mean inhibition zone that was comparable to CH. None of the six tested pastes exhibited antibiofilm activity of a significant level in comparison to CH. A noticeable increase in the antibiofilm activity was found when 20% NSAIDs were added to CH while maintaining an alkaline pH. Ketoprofen was found to be the most effective among the tested NSAIDs. Although its effect was comparable to CH, adding ketoprofen at a ratio of 20% resulted in 50% higher antimicrobial action than CH alone. Accordingly, incorporating NSAIDs in inter-appointment dressing has the potential to utilize their anti-inflammatory, local analgesic, and antibacterial actions, which overcome the limitations of CH and improve the outcome of root canal treatment.

Angiotensin(1-7) attenuates tooth movement and regulates alveolar bone response during orthodontic force application in experimental animal model.

BACKGROUND: Renin-angiotensin system and its ACE2/Ang(1-7)/Mas receptor axis regulates skeletal response to multiple physiological and pathological conditions. Recent research suggested a vital role of Ang(1-7) in regulating alveolar bone metabolism and remodeling. In this context, this study evaluated the effects of the Ang(1-7)/Mas receptor axis on orthodontic tooth movement (OTM) and the alveolar bone response to mechanical load. METHODS: A coil spring was placed between the right maxillary first molar and the anterior tooth of Wistar rats to apply bidirectional mechanical force. Ang(1-7) with or without a specific Mas receptor antagonist (A779) was infused using subcutaneous osmotic pumps (200 and 400 ng/kg/min: respectively). Animals were killed after 5 and 14 days from the OTM procedure after the clinical evaluation of tooth movement and mobility. Morphometric analysis of alveolar bone structure was conducted using micro-CT and the histological picture was evaluated after H&E staining. Moreover, collagen fiber distribution was assessed using Picro-Sirius red stain. In addition, bone samples were collected from the pressure and tension sites around the anterior tooth for gene expression analysis. RESULTS: Ang(1-7) infusion suppressed the tooth movement and mobility after 14 days of the orthodontic force application. Additionally, Ang(1-7) infusion preserved the morphometric and histological structure of the alveolar bone at pressure and tension sides. These effects were abolished by adding A779 infusion. Collagen fiber distribution was dysregulated mainly by the A779 Mas receptor blockage. Ang(1-7) affected the bone formation, remodeling- and vascularity-related genes in the pressure and tension sides, suggesting a prominent suppression of osteoclastogenesis. Ang(1-7) also improved osteoblasts-related genes on the tension side, whereas the osteoclasts-related genes were augmented by A779 on the pressure side. CONCLUSION: Collectively, the activation of Ang(1-7)/Mas receptor axis appears to hinder tooth movement and regulates alveolar bone remodeling in response to mechanical force.

Bevacizumab, a vascular endothelial growth factor inhibitor, promotes orthodontic tooth movement in an experimental rat model.

Objective: This study aimed to evaluate the impact of bevacizumab on orthodontic tooth movement (OTM) in Wistar rats. Materials and methods: The OTM model was constructed by placing an orthodontic coil spring between the maxillary first molar and anterior tooth. Bevacizumab (Avastin®; 10 mg/kg twice per week) was started one week before the OTM and continued for 3 weeks. After 1 and 2 weeks, OTM distance and anterior tooth mobility were measured. Thereafter, the maxilla was dissected for micro-CT microarchitectural analysis, followed by histological analysis, and tartrate-resistant acid phosphatase (TRAP) staining. Moreover, the distributions of collagen fibers type-I and -III (Col-I and Col-III) were evaluated using Picro-Sirius red staining. Results: Orthodontic force prompted bone resorption and formation on the pressure and tension sides, respectively. Bevacizumab therapy resulted in a 42% increase of OTM, particularly after 2 weeks. Furthermore, bevacizumab disturbed the morphometric structure at both pressure and tension sites. The histological evaluation indicated about 35-44% fewer osteoblasts in the bevacizumab group, especially at the tension side, whereas the proportion of TRAP-positive osteoclasts at the pressure side was 34-37% higher than the control. The mature Col-I was reduced at the tension site by 33%, whereas the Col-III/Col-I ratio was enhanced by 20-44% at pressure and tension sites, after 2 weeks, in the bevacizumab group. Conclusion: Anti-vascular bevacizumab therapy accentuates OTM in rat model, possibly through the enhancement of bone resorption, at the pressure side, and the reduction of bone formation, at the tension side as well as dysregulation of collagen fibers distribution.

Probiotic Potential of the Marine Isolate Enterococcus faecium EA9 and In Vivo Evaluation of Its Antisepsis Action in Rats.

This study aims to obtain a novel probiotic strain adapted to marine habitats and to assess its antisepsis properties using a cecal ligation and puncture (CLP) model in rodents. The marine Enterococcus faecium EA9 was isolated from marine shrimp samples and evaluated for probiotic potential after phenotypical and molecular identification. In septic animals, hepatic and renal tissues were histologically and biochemically evaluated for inflammation and oxidative stress following the probiotic treatment. Moreover, gene expressions of multiple signaling cascades were determined using RT-PCR. EA9 was identified and genotyped as Enterococcus faecium with a 99.88% identity. EA9 did not exhibit any signs of hemolysis and survived at low pH and elevated concentrations of bile salts. Moreover, EA9 isolate had antibacterial activity against different pathogenic bacteria and could thrive in 6.5% NaCl. Septic animals treated with EA9 had improved liver and kidney functions, lower inflammatory and lipid peroxidation biomarkers, and enhanced antioxidant enzymes. The CLP-induced necrotic histological changes and altered gene expressions of IL-10, IL-1ß, INF-γ, COX-2, SOD-1, SOD-2, HO-1, AKT, mTOR, iNOS, and STAT-3 were abolished by the EA9 probiotic in septic animals. The isolate Enterococcus faecium EA9 represents a promising marine probiotic. The in vivo antisepsis testing of EA9 highlighted its potential and effective therapeutic approach.

Potential Antigenic Candidates for the Development of Peptide-Based Vaccines to Induce Immunization against Helicobacter pylori Infection in BALB/c Mice.

Helicobacter pylori (H. pylori) has been identified as a group-1 definite carcinogen. As of yet, there is no available vaccine for this microorganism. Our study aimed to identify antigenic peptides in H. pylori using an in silico proteomic approach, and to evaluate their effectiveness as potential vaccine candidates. Four different peptide sequences were prioritized using the reverse vaccinology, namely, CagA1, CagA2, VacA, and SabA. Peptides emulsified with Freunde's adjuvant were used to immunize BALB/C mice. Subcutaneously immunized mice were challenged by oral administration of H. pylori. IgG, IgA, IL4, and IL17 were detected in mice sera. Histopathology of the dissected stomach of vaccinated and control mice were assessed using H&E stain. IgG was significantly higher in mice vaccinated with SabA. IL-4 was significantly increased in CagA1, CagA2, VacA, and SabA vaccinated mice compared to the adjuvant group. Additionally, histopathological examination of gastric tissue showed a protective effect in the vaccinated groups compared to adjuvant and PBS groups. Our findings indicate a promising effect of the tested epitopes, particularly the SabA antigen, to induce an immune response against H. pylori.

The Antifungal and Antibiofilm Activities of Caffeine against Candida albicans on Polymethyl Methacrylate Denture Base Material.

BACKGROUND: In this study, the effect of pure caffeine was established against Candida albicans (C. albicans) using different microbiological techniques. METHODS: Broth microdilution and colony forming units (CFUs) assays were used to detect the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). The Live/Dead fluorescent dyes were implemented to determine the yeast viability. Polymethyl methacrylate acrylic resin (PMMA) discs were prepared to evaluate caffeine's effects against adherent C. albicans using microplate reader, CFUs, and scanning electron microscope (SEM). RESULTS: caffeine's MIC was detected around 30 mg/mL, while the MFC was considered at 60 mg/mL. In an agar-well diffusion test, the inhibition zones were wider in caffeine groups. The Live/Dead viability test verified caffeine's antifungal effects. The optical density of the adherent C. albicans on PMMA discs were lower at 620 nm or 410 nm in caffeine groups. CFU count was also reduced by caffeine treatments. SEM revealed the lower adherent C. albicans count in caffeine groups. The effect of caffeine was dose-dependent at which the 60 mg/mL dose demonstrated the most prominent effect. CONCLUSION: The study reinforced caffeine's antifungal and antibiofilm properties and suggested it as an additive, or even an alternative, disinfectant solution for fungal biofilms on denture surfaces.

Matrix Metalloproteinases in Dental and Periodontal Tissues and Their Current Inhibitors: Developmental, Degradational and Pathological Aspects.

OBJECTIVES: This review article aims to describe some of the roles of Matrix metalloproteinases (MMPs) in enamel, dentine, dental caries, hybrid layer degradation, pulp and periodontal tissues, throwing light on their current inhibitors. The article addresses the potential of MMPs to serve as biomarkers with diagnostic and therapeutic value. DESIGN: The sections of this review discuss MMPs' involvement in developmental, remodeling, degradational and turnover aspects of dental and periodontal tissues as well as their signals in the pathogenesis, progress of different lesions and wound healing of these tissues. The literature was searched for original research articles, review articles and theses. The literature search was conducted in PubMed and MEDLINE for articles published in the last 20 years. RESULTS: 119 published papers, two textbooks and two doctoral theses were selected for preparing the current review. CONCLUSIONS: MMPs are significant proteases, of evident contribution in dental and periapical tissue development, health and disease processes, with promising potential for use as diagnostic and prognostic disease biomarkers. Continuing understanding of their role in pathogenesis and progress of different dental, periapical and periodontal lesions, as well as in dentine-pulp wound healing could be a keystone to future diagnostic and therapeutic regimens.

Caffeine Consumption Influences Lidocaine Action via Pain-Related Voltage-Gated Sodium Channels: An In Vivo Animal Study.

Several factors might influence the duration and efficiency of local anesthesia. This study investigates the effect of habitual caffeine intake on lidocaine action and explores the potential involvement of voltage-gated sodium channels in the interaction effect. Wistar rats were divided into four groups: (i) control (Ctrl), (ii) lidocaine intraplantar injection (LIDO), (iii) habitual caffeine intake (CAF), and (iv) lidocaine intraplantar injection and habitual caffeine intake (LIDO + CAF). Behavioral assessments, consisting of a paw pressure test for mechanical pressure sensation and a paw withdrawal latency test for thermal pain sensation, were performed at 0, 30, 60, and 90 minutes following lidocaine injection and after 10, 11, and 12 weeks of CAF intake. Pressure sensation was significantly reduced in the LIDO + CAF group compared with the control group. Moreover, the LIDO + CAF group exhibited reduced sensation compared to LIDO alone group. The LIDO + CAF combination exerted a synergistic effect at 30 and 60 minutes compared with the control. This synergistic effect was noted at 60 minutes (11 weeks of CAF intake) and at 30 minutes (12 weeks of CAF intake) compared with LIDO alone. Augmented thermal pain-relieving effects were observed in the LIDO + CAF group at all weeks compared to the control group and at 10 weeks compared to LIDO alone group. The molecular analysis of dorsal root ganglia suggested that CAF upregulated the mRNA expression of the Nav1.3, Nav1.7, and Nav1.8 sodium channel subtypes. Chronic caffeine consumption potentiates the local anesthetic action of lidocaine in an experimental animal model through mechanisms that involve the upregulation of voltage-gated sodium channels in the dorsal root ganglia.

Pharmacological Effects of Marine-Derived Enterococcus faecium EA9 against Acute Lung Injury and Inflammation in Cecal Ligated and Punctured Septic Rats.

Microorganisms obtained from the marine environment may represent a potential therapeutic value for multiple diseases. This study explored the possible protective role of marine-derived potential probiotic Enterococcus faecium EA9 (E. faecium) against pulmonary inflammation and oxidative stress using the cecal ligation and puncture (CLP) model of sepsis in Wistar rats. Animals were pretreated with E. faecium for 10 days before either sham or CLP surgeries. Animals were sacrificed 72 hours following the surgical intervention. The histological architecture of lung tissues was evaluated as indicated by the lung injury score. In addition, the extend of pulmonary edema was determined as wet/dry weight ratio. The inflammatory cytokines were estimated in lung tissues, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1ß) using the enzyme-linked-immunosorbent-assay (ELISA) technique. Moreover, markers for lipid peroxidation such as thiobarbituric acid reaction substances (TBARs), and endogenous antioxidants, including reduced glutathione (GSH) were determined in lung tissues. Finally, the enzymatic activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) were assayed in the lungs. Pretreatment with E. faecium markedly attenuated CLP-induced lung injury and pulmonary edema. Markers for inflammation, including TNF-α, IL-6, and IL-1ß were augmented in the lung tissues of CLP animals, while E. faecium ameliorated their augmented levels. E. faecium pretreatment also restored the elevated TBARS levels and the prohibited CAT, SOD, and GPx enzymatic activities in CLP animals. GSH levels were corrected by E. faecium in CLP animals. The inflammatory and lipid peroxidation mediators were positively correlated, while antioxidant enzymatic activities were negatively correlated with CLP-induced lung injury and pulmonary edema. Collectively, marine-derived Enterococcus faecium EA9 might be considered as a prospective therapeutic tool for the management of pulmonary dysfunction associated with sepsis.

The Behavior of Patients with Obsessive-Compulsive Disorder in Dental Clinics.

OBJECTIVES: This review documents published obsessive-compulsive disorder (OCD) cases with dental and oral conditions with potential impact on the dental procedure. The research question was, what are the psychiatric and behavioral features of people with OCD that might affect dental sessions? METHODS: This review followed the PRISMA guidelines (PROSPERO registration No. CRD42020212371). Six databases (PubMed, Scopus, Web of Science, LILACS, Cochrane Library, and PsycINFO) were screened for published clinical studies that report dental patients with obsessions or compulsions behaviors as identified by National Institute of Mental Health (NIMH). Inclusion of the studies was performed according to the eligibility criteria. The quality evaluation was carried out using the Joanna Briggs Institute's (JBI) Critical Appraisal Checklist. The results were qualitatively assessed for synthesis. RESULTS: After elimination of duplication, 530 articles were screened, and 35 articles were evaluated for eligibility. 17 studies met the inclusion criteria (8 case reports, 5 cross-sectional studies, 1 longitudinal cohort study, and 3 case-control studies) and were included in the review. All case reports demonstrated symptoms of obsessions or compulsions such as fear of germs and contamination, aggressive thoughts, having things symmetric in perfect order, excessive cleaning or handwashing, repeatedly checking things, and compulsive counting. OCD-related behavior was assessed in the included clinical investigations using standardized protocols such as Florida Obsessive-Compulsive Inventory, Symptom Checklist-90-Revised, 4-item Corah Dental Anxiety Scale, Diagnostic and Statistical Manual of Mental Disorders, and the Crown Crisp Experimental Index. Quality assessment of the 17 included articles revealed 14 articles with low risk of bias and 3 articles with moderate risk of bias. CONCLUSION: The reported OCD symptoms may implement psychological difficulties during dental procedures without affecting the outcome. Although there was no contraindication for planning or performing dental treatments for a patient with OCD, dental-related procedures and protocols might be modified for successful dental appointments.

Habitual caffeine intake affects implant osseointegration: An in vivo study.

OBJECTIVES: This study aimed to evaluate the effect of habitual caffeine (CAF) intake on stability, bone regeneration, and expression of bone markers at the bone-implant interface. BACKGROUND: Studies show that habitual CAF alters bone health and remodeling. Yet, there is no information regarding CAF effects on osseointegration of bone-anchored implants. METHODS: Wistar rats were divided into two groups: one received tap drinking water alone (control) and the other received tap water with CAF (300 mg/L). After 12 weeks, their tibiae received screw-shaped titanium implants. After another 12 weeks, CAF (n = 5) and control (n = 5) animals were sacrificed and the implant stability was evaluated using a removal torque (RTQ) device. Thereafter, the implants were processed for gene expression analysis, and the implantation sites were harvested for histology. Implants with the surrounding bone were dissected en bloc and subjected to micro-computed tomography (micro-CT). RESULTS: The results showed that implants in the CAF group had an 87% significant increase in RTQ compared to the control. Further, micro-CT revealed a higher proportion of mineralized bone filling the implant threads in the CAF group. The molecular analysis indicated higher expression of bone formation (ALP), remodeling (CatK), and vascularization (VEGF) genes in implant-adherent cells in the CAF group. Histology suggested increased vascularity in the tissue surrounding the implant in the CAF group. CONCLUSIONS: Within the limit of this study, it is concluded that habitual CAF intake conveys a positive, promoting effect on long-term osseointegration. Clinical studies are worth pursuing to verify this experimental observation.

Supplementation of Morin Restores the Altered Bone Histomorphometry in Hyperglycemic Rodents via Regulation of Insulin/IGF-1 Signaling.

Pathological mechanisms underlining diabetic bone defects include oxidative damage and insulin/IGF-1 imbalance. Morin is a bioflavonoid with antioxidant and anti-diabetic effects. This study evaluates morin's protective effects against altered bone histomorphometry in diabetic rats through assessing insulin/IGF-1 pathway as a potential mechanism. Diabetic animals were administered two morin doses (15 and 30 mg/kg) for 5 weeks. Different serum hepatic and renal functions tests were assessed. Bone density and histomorphometry in cortical and trabecular tissues were evaluated histologically. The expressions of insulin, c-peptide and IGF-1 were estimated. In addition, the enzymatic activities of the major antioxidant enzymes were determined. Diabetic-associated alterations in serum glucose, aminotransferases, urea and creatinine were attenuated by morin. Diabetic bone cortical and trabecular histomorphometry were impaired with increased fibrosis, osteoclastic functions, osteoid formation and reduced mineralization, which was reversed by morin; particularly the 30 mg/kg dose. Insulin/IGF-1 levels were diminished in diabetic animals, while morin treatment enhanced their levels significantly. Diabetes also triggered systemic oxidative stress noticeably. The higher dose (30 mg/kg) of morin corrected the endogenous antioxidant enzymatic activities in diabetic rats. Findings indicate the potential value of morin supplementation against hyperglycemia-induced skeletal impairments. Activation of insulin/IGF-1 signaling could be the underlining mechanism behind these effects.

Association between Periodontal Disease and Comorbidities in Saudi's Eastern Province.

The incidence of periodontal diseases is associated with multiple comorbidities that influence a patient's treatment planning. This study evaluates the relation between periodontal disease and multiple comorbidities reported in the Saudi population from the Eastern province. This study was conducted on 190 patients, who visited the periodontology clinics at Imam Abdulrahman Bin Faisal University, Saudi Arabia. Demographic data, smoking habits, past medical and dental histories, blood pressure, random blood glucose, and recent haemoglobin A1c were recorded. A comprehensive periodontal examination included the number of missing teeth, pocket depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and mobility of all teeth except third molars. Radiographic bone loss was measured on standardized full-mouth periapical radiographs. Multivariable regression models were calculated aiming to see the association between different comorbidities and alveolar bone loss with confounders controlled. Out of 190 periodontitis patients, 56 (29.5%) were males and 134 (70.5%) were females. More than half of the patients (60%) were between 26 and 50 years, 30% of them had diabetes, and 18% were smokers. The risk of alveolar bone loss was higher in persons who had diabetes and those who had both diabetes and coronary heart disease than those who did not, although the association was not statistically significant (B = 1.26, 95%CI = -0.30, 2.82, and B = 2.86, 95%CI = -1.25, 6.96, respectively). The risk of alveolar bone loss was significantly higher among persons with diabetes and hypertension (B = 2.82 and 95%CI = 0.89, 4.75). Collectively, the risk of alveolar bone loss in periodontitis patients increases with diabetes in the presence of other comorbidities regardless of smoking or gender.

Renin angiotensin system blockage by losartan neutralize hypercholesterolemia-induced inflammatory and oxidative injuries.

ABSTRACTObjectives: This study explores the protective role of losartan (LT) against oxidative and inflammatory damages in different physiological systems including heart, liver, and kidney tissue in hypercholesterolemic rats.Methods: After induction of hypercholesterolemia by high cholesterol diet for 6 weeks, LT was administered for 4 weeks. In serum, the levels of lipoproteins, aminotransferases, creatine kinases, urea, apoptosis, and inflammatory markers were measured. In cardiac, hepatic, and renal tissues, lipid peroxidation product and GSH as well as antioxidant enzymatic activities were assayed. Finally, histopathological assessment evaluated the structural damage in cardiac, hepatic, and renal tissues.Results: Serum markers of cardiac, hepatic, and renal toxicities including creatine kinases, aminotransferases, and urea were attenuated by LT in hypercholesterolemic animals. Moreover, LT markedly corrected the elevated levels of lipoproteins, apoptosis, and inflammatory biomarkers. Hypercholesterolemia-induced lipid peroxidation, low GSH levels, and diminished activities of antioxidant enzymes were prominently improved in LT treated animals. Histopathological alterations by hypercholesterolemia in heart, liver, and kidney tissues were ameliorated by LT.Conclusion: This study confirmed the pathological enrollment of renin-angiotensin system in hypercholesterolemia-associated metabolic alterations. LT had a significant cardiac, hepatic, and renal protective role against these impairments through down-regulation of oxidative damage, inflammation and necrosis.

Protective Role of Loranthus regularis against Liver Dysfunction, Inflammation, and Oxidative Stress in Streptozotocin Diabetic Rat Model.

Earlier studies revealed the potential therapeutic values of Loranthus regularis (L. regularis). This study evaluated Loranthus regularis (L. regularis) extract systemic antidiabetic effects and benefits against diabetic hepatocellular injuries through antioxidant and anti-inflammatory pathways using the streptozotocin (STZ) model in Wistar albino rats. After diabetes induction, animals were orally treated with L. regularis extract for 4 weeks. Serum levels of glucose, insulin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), total triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were estimated. Furthermore, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), caspase-3, nitric oxide (NO), and prostaglandin E-2 (PGE-2) were estimated in serum. In liver, thiobarbituric acid reactive substances (TBARSs) and reduced glutathione (GSH) as well as the proinflammatory cytokines and enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reeducates (GR), and glutathione-S-transferase (GST) were assayed. Finally, the degree of hepatic tissue damage was evaluated histologically. Treatment of the diabetic rats with L. regularis extract markedly reduced the elevated serum levels of glucose, ALT, AST, TC, TG, LDL, TNF-α, IL-1ß, IL-6, caspase-3, NO, and PGE-2. L. regularis extract also improved serum levels of insulin and HDL. The elevated TBARS, TNF-α, IL-1ß, and IL-6 levels in hepatic tissue of diabetic animals were reduced by L. regularis. Moreover, L. regularis extract significantly restored the diminished hepatic GSH level and enzymatic activities of SOD, CAT, GPx, GR, and GST in diabetic animals. The biochemical protective effects of L. regularis were associated with improved histological hepatocellular integrity and architecture. Taken together, L. regularis has therapeutic effects against diabetic-induced hepatic complications. The restored liver functions and cellular damage might be mediated through free radicals scavenging and proinflammatory cytokine inhibition.

Delayed Healing of Tooth Extraction Sockets After Vascular Endothelial Growth Factor Inhibition by Bevacizumab.

PURPOSE: This study aimed to explore the effect of the chemotherapeutic agent bevacizumab on the extraction socket healing process in New Zealand rabbits. MATERIALS AND METHODS: The animals received intraperitoneal bevacizumab treatment for 6 consecutive weeks (3 mg/kg per week). The right mandibular first premolar was extracted in the second week of the experiment, and the jaw bone containing the socket tissues was harvested at the end of the treatment period. The healing of the removed socket was analyzed histologically and radiographically using a micro-computed tomography scan. RESULTS: Quantitative morphometric and histologic assessments of the healing process of the extraction sockets in rabbits showed a marked (P ≤ .05) decrease in the bone volumetric mass after angiogenesis suppression by bevacizumab therapy (n = 5) compared with the control group (n = 5). CONCLUSIONS: The results of this study indicate the physiological significance of angiogenesis in extraction socket healing. Moreover, this study highlights the risks and precautions that should be considered in clinical practice in patients undergoing targeted chemotherapy.

In vivo Assessment of Combined Effects of Glibenclamide and Losartan in Diabetic Rats.

OBJECTIVE: Diabetic complications involve multiple pathological pathways, including hyperglycemia-induced oxidative stress and inflammation. Combination therapy is usually employed to improve treatment outcomes and to lower potential adverse effects. In this study, we evaluated the effects of antidiabetic and antihypertensive agents, glibenclamide (GLI) and losartan (LT), on diabetes mellitus (DM)-associated metabolic changes in rats. MATERIALS AND METHODS: Streptozotocin-induced diabetic animals were orally treated with GLI 5 mg/kg and/or LT 25 mg/kg for 4 weeks. Blood glucose, insulin, aspartate aminotransferase, alanine aminotransferase, urinary creatinine, and urea levels were measured. Serum, liver, and kidney values of inflammatory markers, such as interleukin-1ß, tumor necrosis factor alpha, and interleukin-6 were assessed, along with lipid peroxidation products (e.g., thiobarbituric acid reactive substances), endogenous antioxidants (e.g., glutathione), as well as antioxidant enzyme activities (e.g., catalase, superoxide dismutase, and glutathione peroxidase). Finally, histological changes in liver and kidney tissues were evaluated. RESULTS: DM markedly induced systemic, hepatic, and renal inflammation and lowered antioxidant defense mechanisms. Treatment of diabetic rats with either GLI or LT significantly improved liver and kidney functions and histological structure. Moreover, both medications reduced signs of oxidative stress and inflammation in blood, liver, and kidney samples. Combining GLI and LT showed similar protective potential against systemic, hepatic, and renal oxidative stress and inflammation. CONCLUSION: Adding LT to GLI therapy revealed prospective antioxidant and anti-inflammatory action, while no synergistic or additive effects were observed.

Effects of sunitinib targeted chemotherapy on the osseointegration of titanium implants.

Targeted chemotherapies are novel therapeutic approaches for many malignancies. In contrast to conventional chemotherapies, which are given for a predetermined duration, treatment with targeted chemotherapies like sunitinib is routinely continuous over longer periods, sometimes years. During this prolonged treatment period, patients may need to restore their missing teeth with dental implants. The aim of this study was to examine the effect of the anti-angiogenic substance sunitinib targeted chemotherapy on the osseointegration of titanium implants in a rabbit model. Fourteen white New Zealand rabbits were randomly assigned to two groups of either oral sunitinib at 10 mg/kg twice per week dose for 4 weeks (n = 7) or placebo (n = 7). The first dose was given 2 days before the surgical intervention. Each rabbit received one titanium dental implant in the right distal femoral condyle. Four weeks following implant insertion, rabbits were sacrificed and bone specimens containing the implants were retrieved. Osseointegration of the implants was analyzed using micro-computed tomography and histomorphometric evaluation. Both micro-computed tomography and histomorphometric analysis showed that the osseointegration parameters, including the ratio of bone volume to total volume and bone-implant contact percent for the sunitinib group were significantly lower than those in the control group (P ≤ 0.05). Sunitinib targeted chemotherapy had a negative effect on the osseointegration of titanium implants inserted in a rabbit model.

In-vivo assessment of the osteo-protective effects of eugenol in alveolar bone tissues.

Estrogen deficiency following menopausal provokes alveolar bone loss, remodeling and inflammation. Eugenol is a phenolic compound with wide dental applications and anti-inflammatory properties. In the present study, the potential protective role of eugenol against alveolar bone deformities was investigated in an ovariectomized (OVX) rodent model. Two doses of eugenol (2.5 and 5 mg/kg/d) were administered to OVX animals for 12 weeks. In Serum, markers of bone metabolism and pro-inflammatory cytokines were estimated using ELISA. Alveolar bone morphometry was analyzed using high-resolution micro-computed tomography (CT). Bone histological analysis (H&E stain) was also performed. Alveolar bone expression of osteoclastogenesis modulating factors, such as osteoprotegerin (OPG), receptor activator of nuclear factor kappa-b ligand (RANKL) and inflammatory mediators, were measured using immunohistochemistry. Eugenol failed to correct elevated body weights and uterine atrophy in OVX rats. The significant elevation of bone metabolic markers and inflammatory cytokines in OVX animals were markedly improved by eugenol treatment, particularly the higher dose. Eugenol treatment considerably attenuated morphometric trabecular alterations of the alveolar bone and improved alveolar resorption and gingival infiltration. Alveolar bone of OVX animals showed augmented expression of RANKL, OPG and inflammatory cytokines, which were corrected by eugenol treatment. Alveolar bone loss and remodeling associated with estrogen insufficiency was ameliorated by eugenol owing to its anti-inflammatory properties, suggesting an extra dental impact for eugenol.

Articaine Versus Lidocaine Concentration in the Palatal Tissues After Supraperiosteal Buccal Infiltration Anesthesia.

PURPOSE: Palatal local anesthetic injection is a painful procedure. Previous studies have reported successful extraction of maxillary teeth using only buccal infiltration of 4% articaine without palatal anesthesia. The aim of the present study was to determine levels of 4% articaine solution in palatal bone and mucosal tissues after buccal injection and compare those levels with 2% lidocaine solution in New Zealand white rabbits. MATERIALS AND METHODS: Eight rabbits received 2 different injections of 0.6 mL of 4% articaine with 1:100,000 epinephrine and 0.6 mL of 2% lidocaine with 1:100,000 epinephrine buccal to the right and left maxillary first molar, respectively, in a split-mouth study design using quantitative syringes. All injections were administered using the buccal infiltration technique without any palatal injection. Ten minutes later, palatal bone and mucosa specimens were collected for analysis. Levels of the 2 local anesthetic agents were measured in palatal tissues using high-performance liquid chromatography (HPLC). RESULTS: HPLC analysis showed markedly higher 4% articaine solution values (0.319 ± 0.037) in palatal mucosal tissues compared with palatal mucosal concentrations of 2% lidocaine solution (0.0839 ± 0.017). In palatal bone, the mean concentration of 2% lidocaine solution was markedly lower than the mean concentration of 4% articaine solution (0.085 ± 0.012 vs 0.155 ± 0.012, respectively). There was no relevant difference between levels of 2% lidocaine in the palatal bone and mucosal tissues. However, the mean concentration of 4% articaine in the palatal mucosa was markedly higher than its concentration in palatal bone. CONCLUSIONS: The buccal vestibule-palatal diffusion of 4% articaine solution with 1:100,000 epinephrine is greater than 2% lidocaine solution with 1:100,000 epinephrine in a rabbit model.