Paulo Goberlânio de Barros Silva

Effect of different doses of zoledronic acid in establishing of bisphosphonate-related osteonecrosis

OBJECTIVES To establish osteonecrosis of the jaws in rats treated with different doses of zoledronic acid (ZA). METHODS Male Wistar rats (n=6-7) received three consecutive weekly intravenous ZA infusions at doses of 0.04, 0.20 or 1.00mg/kg ZA or saline (control). Four weeks after the last administration, the animals were submitted to simple extraction of the lower left first molar. An additional dose of ZA was administered seven days later, and the animals were sacrificed 28 days after exodontia. Weight was measured and blood was collected weekly for analysis. The jaw was radiographically and microscopically examined along with the liver, spleen, kidney and stomach. RESULTS All ZA doses showed a higher radiolucent area than the control (p<0.0001), but the dose of 0.04mg/kg did not show BRONJ. Doses of 0.20 and 1.00mg/kg ZA showed histological evidence of bone necrosis (p=0.0004). Anaemia (p<0.0001, r(2)=0.8073) and leucocytosis (p<0.0001, r(2)=0.9699) are seen with an increase of lymphocytes (p<0.0001, r(2)=0.6431) and neutrophils and monocytes (p=0.0218, r(2)=0.8724) in all the animals treated with an increasing dose of ZA. Haemorrhage and ectasia were observed in the spleen (p=0.0004) and stomach (p=0.0168) in a dose-dependent manner, and the animals treated with ZA showed a lower rate of weight gain (p<0.0001). CONCLUSIONS We designed a bisphosphonate-related osteonecrosis of the jaw model that reproduces radiographic and histological parameters and mimics clinical alterations such as leucocytosis, anaemia and idiosyncratic inflammatory post infusion reactions.

Molecular Analysis of Oral Bacteria in Heart Valve of Patients With Cardiovascular Disease by Real-Time Polymerase Chain Reaction.

AbstractStructural deficiencies and functional abnormalities of heart valves represent an important cause of cardiovascular morbidity and mortality, and a number of diseases, such as aortic stenosis, have been recently associated with infectious agents. This study aimed to analyze oral bacteria in dental plaque, saliva, and cardiac valves of patients with cardiovascular disease. Samples of supragingival plaque, subgingival plaque, saliva, and cardiac valve tissue were collected from 42 patients with heart valve disease. Molecular analysis of Streptococcus mutans, Prevotella intermedia, Porphyromonas gingivalis, and Treponema denticola was performed through real-time PCR. The micro-organism most frequently detected in heart valve samples was the S. mutans (89.3%), followed by P. intermedia (19.1%), P. gingivalis (4.2%), and T. denticola (2.1%). The mean decayed, missing, filled teeth (DMFT) was 26.4 ± 6.9 (mean ± SD), and according to the highest score of periodontal disease observed for each patient, periodontal pockets > 4 mm and dental calculus were detected in 43.4% and 34.7% of patients, respectively. In conclusion, oral bacteria, especially S. mutans, were found in the cardiac valve samples of patients with a high rate of caries and gingivitis/periodontitis.

Influence of Educational Level, Stage, and Histological Type on Survival of Oral Cancer in a Brazilian Population: A Retrospective Study of 10 Years Observation

Abstract The mortality rate associated with oral cancer is estimated at approximately 12,300 deaths per year, and the survival rate is only 40% to 50% for diagnosed patients and is closely related to the duration of time between disease perception and its diagnosis and treatment. Socioeconomic risk factors are determinants of the incidence and mortality related to oral cancer. We conducted a retrospective, cross-sectional study of 573 records of patients with oral cancer at Haroldo Juaçaba Hospital – Cancer Institute of Ceará from 2000 to 2009 to evaluate the influence of socioeconomic factors on survival and epidemiological behavior of this neoplasia in a Brazilian population. In this study, patients with oral cancer were males greater than 60 years of age, presented squamous cell carcinoma in the floor of mouth and were characterized by low education levels. A total of 573 lesions were found in oral cavities. Cox proportional hazards regression model showed that the histological type, tumor stage, and low degree of education significantly influenced survival. A lower patient survival rate was correlated with a more advanced stage of disease and a worse prognosis. Squamous cell carcinoma is associated with a higher mortality when compared with other histological types of malign neoplasia.

TNF-alpha expression, evaluation of collagen, and TUNEL of Matricaria recutita L. extract and triamcinolone on oral ulcer in diabetic rats

ABSTRACT Diabetes mellitus (DM) is a disease associated with delayed wound healing of oral ulcers by increased expression of proinflammatory cytokines and cellular apoptosis. Objective to evaluate the influence of Tumor Necrosis Factor alpha (TNF-α) and apoptosis in rats with DM treated with chamomile extract or triamcinolone. Material and Methods Wistar male rats (210.0±4.2 g) were divided into five groups: negative control group (NCG) without diabetes; positive control group (PCG) with DM (alloxan, 45 mg/kg); and groups treated with chamomile extract (normoglycemic= NCG group and diabetic= DCG group) and with triamcinolone (TG). Traumatic ulcers were performed on all animals that received topical triamcinolone, chamomile extract or saline 12/12 hours for ten days. Results On days five and ten the animals were euthanized and the ulcers were analyzed by light microscopy, TUNEL assay, and immunohistochemically (TNF-α). The NCG (p=0.0062), PCG (p=0.0285), NCG (p=0.0041), and DCG (p<0.0001) groups were completely healed on the 10th day, however, there was no healing on the TG (p=0.5127) group. The TNF-α expression showed a significant reduction from the 5th to the 10th day in NCG (p=0.0266) and DCG (p=0.0062). In connective tissue, the TUNEL assay showed a significant reduction in the number of positive cells in NCG (p=0.0273) and CNG (p=0.0469) and in the epithelium only in CDG (p=0.0320). Conclusions Chamomile extract can optimize the healing of traumatic oral ulcers in diabetic rats through the reduction of apoptosis in the epithelium and TNF-α expression.

Antiperoxidative properties of oil mixes of high ratio Omega-9:Omega-6 and low ratio Omega-6:Omega-3 after molar extraction in rats

PURPOSE To evaluate the antioxidant and antiperoxidative effects of oil mixes of high ratio Omega-9:Omega-6 and low ratio Omega-6:Omega-3 in the third day after tooth extraction in rats. METHODS Thirty-two male Wistar rats (270-310 g) were randomly distributed in two groups: Control (n=24) and Test (n=8). Control group was divided into three subgroups (n=8): G1: Sham-Saline; G2: Saline; G3: Isolipid. G1 and G2 animals received NaCl 0.9% while G3 rats were treated with an isolipid mixture (alpha-linolenic acid - ALA) containing -6/-3 oils (8:1 ratio) and-9/-6 (0.4:1 ratio). Test group animals (G4) received oily mixtures (alpha-linolenic acid - ALA, docosahexaenoic acid - DHA, eicosapentaenoic acid - EPA) of -6/-3 (1.4:1 ratio) and -9/-6 (3.4:1 ratio). Saline and oils were administered by gavage during four days before and three days after first mandibular molar extraction. Following, samples (arterial blood and alveolar mucosa) were collected for glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) assays. RESULTS Oil mixes induced a significant decrease in GSH and TBARS tissue and plasma concentrations in the third day post-surgery. CONCLUSION Gavage administration of oil mixes of high ratio Omega-9:Omega-6 and low ratio Omega-6:Omega-3 after molar extraction in rats induces a significant decrease in lipid peroxidation.

The anticonvulsant effect of a polysaccharide-rich extract from Genipa americana leaves is mediated by GABA receptor

BACKGROUND This study aimed to chemically characterize a polysaccharide-rich extract (PRE) obtained from Genipa americana leaves and evaluate its neuroprotective effect in the brain morphology and oxidative markers using mice behavioral models. METHODS Dry powder (5 g) of G. americana leaves were submitted to depigmentation in methanol. PRE was obtained by extraction in NaOH and precipitation with absolute ethanol and characterized by infrared spectroscopy (FTIR) and nuclear magnetic resonance (1H and 13C NMR). Swiss mice (25-35 g) received saline (0.9% NaCl) or PRE (1-27 mg/kg) by intraperitoneal (i.p.) route, 30 min before evaluation in behavioral models (open field, elevated plus maze, sleeping time, tail suspension, forced swimming, seizures induced by pentylenetetrazole-PTZ). Animals brain were dissected and analyzed for histological alterations and oxidative stress. RESULTS FTIR spectrum showed bands around 3417 cm-1 and 2928 cm-1, relative to the vibrational stretching of OH and CH, respectively. 1H NMR spectrum revealed signals at δ 3.85 (methoxyl groups) and δ 2.4 (acetyl) ppm. 13C NMR spectrum revealed signals at δ 108.0 and δ 61.5 ppm, corresponding to C1 and C5 of α-L-arabinofuranosyl residues. PRE presented central inhibitory effect, increasing the latency for PTZ-induced seizures by 63% (9 mg/kg) and 55% (27 mg/kg), and the latency to death by 73% (9 mg/kg) and 72% (27 mg/kg). Both effects were reversed by the association with flumazenil. CONCLUSIONS PRE, containing a heteropolysaccharide, presents antioxidant and anticonvulsant effect in the model of PTZ-induced seizures via gamma-aminobutyric acid (GABA), decreasing the number of hippocampal black neurons.

Anti-inflammatory effect of a fatty acid mixture with high ω-9:ω-6 ratio and low ω-6:ω-3 ratio on rats submitted to dental extraction

OBJECTIVE To evaluate the anti-inflammatory effect of pretreatment for three days with a fatty acid mixture with high ω-9:ω-6 ratio and low ω-6:ω-3 ratio on rats submitted to dental extraction. MATERIAL AND METHODS Thirty-two male Wistar rats (270-310g) were randomly distributed in four groups (n=8/group): the sham control group and the negative control group received saline; the high omega-6/low omega-9 group received isolipid fatty acid with high ω-6:ω-3 ratio and low ω-9:ω-6 ratio; the high omega-3/low omega-6 group received fatty acid with low ω-6:ω-3 ratio and high ω-9:ω-6 ratio. Saline and oils were administered by gavage for 4days before exodontia and 3days after surgery, followed by euthanasia. Masseter edema was evaluated clinically and tissue samples were submitted to osteoclast count (H&E), myeloperoxidase assay, and western blotting (tumor necrosis factor-alpha and interleukin-1beta). RESULTS In the high omega-3/low omega-6 group, a significant decrease was observed in masseter edema (p<0.0001), myeloperoxidase (p<0.0001), osteoclasts (p=0.0001) and TNF-α expression (p<0.0001), but not in IL-1β expression. CONCLUSION The ingestion of fatty acid with high ω-9:ω-6 ratio and low ω-6:ω-3 ratio significantly reduced inflammatory response in rats submitted to dental extraction.

Unusual Occurrence of Tongue Sensorial Disorder after Conservative Surgical Treatment of Lymphoepithelial Cyst

Lymphoepithelial cyst is a rare lesion of the oral cavity, with the mouth floor being the most common site of occurrence. The therapeutic approach of choice is the surgical treatment, which has rare cases of postoperative complications. The aim of this study is to report the case of a 53-year-old patient who came to Dental Service in the Federal University of Ceará complaining of a small nodular lesion (0.5 cm) located in the ventral tongue. Excisional biopsy was performed and the surgical specimen was submitted for anatomopathological analysis, which found that there was an oral lymphoepithelial cyst. The patient returned after seven days for suture removal and reported loss of sensitivity around the ventral tongue. We prescribed Citoneurin for ten days; however, there was not any significant improvement of the sensitivity. Low frequency laser therapy sessions were applied. The only postoperative symptom was dysesthesia, where there is only a sensitivity decrease. Currently, the patient has a postoperative period of 1 year without recurrence of the lesion. Although previous reports have no described tongue sensorineural disorders associated with this lesion, the occurrence of this event may be related to an unexpected anatomical variation of the lingual nerve.

Imaging Aspects Of The Mandibular Incisive Canal: A PROSPERO-Registered Systematic Review And Meta-Analysis Of Cone Beam Computed Tomography Studies

PURPOSE This study aimed to perform a systematic review and meta-analysis of the literature on the mandibular incisive canal (MIC) studies using cone beam computed tomography (CBCT). MATERIALS AND METHODS A PROSPERO-registered systematic review (#42017056619) was conducted following the PRISMA statements to summarize current knowledge on the CBCT aspects of the MIC. A search was performed in PubMeds Medline and Scopus databases, without date or language restrictions, using the algorithm {[(Interforaminal region) OR (mandibular incisive channel) OR (mandibular incisive nerve) OR (mental mandible) OR (anterior mandible) (cone beam computed tomography). Also, the references were crosschecked. The Meta-Analysis of Statistics Assessment and Review Instrument and meta-analysis was used to evaluate the selected studies. RESULTS A total of 410 articles were found, and 25 studies were selected after a two-step selection process. The CBCT systems differed regarding field of view (FOV) (large, n = 3; medium, n = 2; small, n = 4; not informed, n = 16) and voxel size (0.15 to 0.4 mm). Geographically, the studies were distributed across four continents (South America, North America, Asia, and Europe), and there was a statistical significance of studies from the American and Asian continents (P < .0001). From 3,421 CBCT exams, the number of female patients was slightly higher than male, and the mean age ranged from 29.8 to 59.1 years. The overall mean prevalence of MIC was 89.6% ± 15.08%, and bilateral occurrence was statistically significant (P < .0001). The studies using a voxel size lower than 0.3 mm showed the highest mean prevalence (93.88%) in comparison with voxel size described as ≥ 0.3 mm (89.33%). Diameter (0.45 to 4.12 mm) and length (6.6 to 40.3 mm) showed great variability among the included studies. CONCLUSION In summary, the results of this systematic review evidenced a high worldwide prevalence of MIC. There was no prevalence of MIC in relation to sex, and its presence was mainly related to adults between the fourth and sixth decades of life. In addition, great heterogeneity of methodologies was observed.

Neutrophils contribute to the pathogenesis of hemorrhagic cystitis induced by ifosfamide

Abstract Ifosfamide (IFO) is an antineoplastic drug that is commonly used to treat gynecological and breast cancers. Hemorrhagic cystitis (HC) is a common side effect associated with IFO injection, which courses with neutrophil accumulation and affects 6–50% of patients depending on dose intensity. Here, we investigated the role of neutrophils in this inflammatory process. Female Swiss mice (n = 8/group) were injected with saline, IFO (400 mg/kg, i.p.), fucoidan (a P‐ and L‐selectins inhibitor, 100 mg/kg, i.v.) or IFO + fucoidan (1–100 mg/kg) alone or combined with mesna (80 mg/kg i.p.). Another group of mice received anti‐Ly6G antibody (500 &mgr;g/mouse, once daily for 2 days) for neutrophil depletion before IFO injection. In another experimental setting, animals received granulocyte colony‐stimulating factor (G‐CSF, 400 &mgr;g/kg), IFO (200 mg/kg), G‐CSF (25–400 &mgr;g/kg, for 5 days) + IFO (200 mg/kg, i.p.) or fucoidan + G‐CSF + IFO. Bladder injury was evaluated 12 h after IFO injection. IFO 400 mg/kg significantly increased visceral hyperalgesia, bladder edema, hemorrhage, vascular permeability, MPO, IL‐1&bgr; and IL‐6 tissue levels, and COX‐2 immunostaining and expression versus the saline group (P < 0.05). Conversely, fucoidan (100 mg/kg) significantly attenuated these parameters compared to IFO‐injected mice (P < 0.05). Additionally, fucoidan potentiated mesna protective effect when compared with IFO + mesna group (P < 0.05). Accordingly, neutrophil depletion with anti‐Ly6G reduced inflammatory parameters and bladder injury compared to IFO (P < 0.05). In contrast, G‐CSF enhanced IFO (200 mg/kg)‐induced HC, which was significantly attenuated by treatment with fucoidan (P < 0.05). Therefore, neutrophils contribute to the pathogenesis of HC. HighlightsNeutrophils contribute to the pathogenesis of hemorrhagic cystitis induced by ifosfamide.Filgastrim (a granulocyte colony stimulating factor) induces neutrophilia.Filgastrim enhances ifosfamide‐induced hemorrhagic cystitis, which is prevented by fucoidan, a P‐ and L‐selectin inhibitor.P‐ and L‐selectins are promising pharmacological targets to inhibit neutrophil migration during hemorrhagic cystitis.