Tumor necrosis factor alpha (TNF-α) blockage reduces acute inflammation and delayed wound healing in oral ulcer of rats.

Oral traumatic ulcers (OTU) are common in dental routine, and the control of proinflammatory cytokines, such as the tumor necrosis factor-alpha (TNF-α), may interfere with OTU repair. Our aim was to evaluate the role of TNF-α in the healing process of OTU in rats. Wistar male rats were divided into six groups: a control-group (treated with 0.1 mL/kg of saline) and five groups treated with anti-TNF-α infliximab (INF) at 1, 3, 5, 7, and 10 mg/kg immediately before OTU production. The animals were weighed (day 0) and euthanized on days 1, 3, 7, 14 and 21 after ulceration. The ulcers were clinically measured, and the mucosa samples were histologically (scores 0-4), histochemically (collagen assay (pircrosirius)), histomorphometrically (cell counting), and immunohistochemically (TNF-α, α-smooth-muscle-actin (α-SMA), monocyte-chemoattractive-protein-1 (MCP-1), interleukin-8 (IL-8), and fibroblast-growth-factor (FGF)) analyzed. The Evans blue assay was used to measure the vascular permeability. ANOVA-1-2-way/Bonferroni, Kruskal-Wallis/Dunn, and correlation analyses were performed (GraphPad Prism 5.0, p < 0.05). High doses of INF reduced the OTU area (p = 0.043), body mass loss (p = 0.023), vascular permeability (p < 0.001), and reduced delayed histologic scores (p < 0.05), polymorphonuclear (p < 0.001) and mononuclear (p < 0.001) cells, blood vessel counting (p = 0.006), and total (p < 0.001), type-I (p = 0.018), and type-III (p < 0.001) collagen. INF treatment reduced TNF-α immunostaining and delayed MPC-1, FGF, and α-SMA expression, with little/none influence in IL-8 immunostaining. TNF-α blockage by INF reduced acute inflammation in OTU but delayed cell migration and wound healing.

Risk factors for renal impairment in patients with hematological cancer receiving antineoplastic treatment.

PURPOSE: Antineoplastic treatments, mainly chemotherapy, affect the kidneys, causing toxicity, and can trigger acute and chronic kidney injuries. This study aimed to analyze the prevalence of renal disorders in patients with oncohematological neoplasms receiving antineoplastic treatment. METHODS: This retrospective cohort study included 75 patients with hematological cancer who underwent chemotherapy between 2012 and 2018 in the Hematology Sector of the Walter Cantídeo University Hospital of the Federal University of Ceará. Sociodemographic and clinical data, blood biochemical assessment findings, and glomerular filtration rate (GFR) were analyzed using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The data were tabulated; transferred to the Statistical Package for the Social Sciences software, version 20.0; and analyzed using Pearson's chi-square test or Fisher's exact test for categorical variables followed by a multinomial logistic regression model (p < 0.05). RESULTS: The prevalence of renal disorders was 52.4% according to the CKD-EPI equation for GFR events. There was a significant association between the decrease in GFRs and the following variables: female sex (p = 0.002), diagnosis of multiple myeloma (p = 0.008), start of treatment within 40 days (p = 0.005), and the following antineoplastic treatments: cyclophosphamide, vincristine, and prednisone (p = 0.026); irarubicin (p = 0.032); azacytidine, dexamethasone, and cyclophosphamide (p < 0.001); zoledronic acid (p < 0.001); and pamidronate (p = 0.012). CALGB 8811 (p < 0.001) was inversely associated with a reduction in the GFR. CONCLUSIONS: The prevalence of renal disorders was high in patients with oncohematological neoplasms receiving antineoplastic treatment. This requires periodic monitoring of the evaluation of renal function since reductions in GFRs were significantly associated with different treatment protocols used.

Risk factors for dysgeusia during chemotherapy for solid tumors: a retrospective cross-sectional study.

PURPOSE: This study retrospectively analyzed the risk factors for transchemotherapy dysgeusia. METHODS: Before each chemotherapy cycle, patients were routinely evaluated for the presence/severity of dysgeusia based on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale for adverse effects and graded as follows: 0, no change in taste; 1, altered taste with no impact on eating habits; or 2, altered taste with an impact on eating habits. Information from 2 years of evaluations was collected and patient medical records were reviewed to obtain data on chemotherapy cycle, sex, age, body mass index, body surface area, primary tumor, chemotherapy protocol, and history of head and neck radiotherapy. The X2 test and multinomial logistic regression were used for statistical analysis (SPSS 20.0, p < 0.05). RESULTS: Among 7425 total patients, 3047, 2447, and 1931 were evaluated after the first, second, and third chemotherapy cycles, respectively. One-fifth of the patients (19.0%) presented a significant loss of taste, with 1118 (15.0%) showing grade 1 dysgeusia and 442 (6.0%) showing grade 2 dysgeusia. The chemotherapy duration (p < 0.001), female sex (p < 0.001), location of the primary tumor in the uterus (p = 0.008), head and neck (p = 0.012), and testicles (p = 0.011), and use of ifosfamide (p = 0.009), docetaxel (p = 0.001), paclitaxel (p < 0.001), pertuzumab (p = 0.005), bevacizumab (p < 0.001), and dacarbazine (p = 0.002) independently increased the risk of dysgeusia. In head and neck tumors, a previous history of radiotherapy significantly increased the prevalence of dysgeusia (p = 0.017), and the use of cisplatin (p = 0.001) increased this prevalence. CONCLUSION: Cycles of chemotherapy, sex, uterine cancer, head and neck tumors, testicular cancer, ifosfamide, docetaxel, paclitaxel, pertuzumab, bevacizumab, and dacarbazine increase the risk of dysgeusia.

PMS2: a potential prognostic protein marker in oral squamous cell carcinoma / PMS2: un potencial marcador proteico de pronóstico en el carcinoma oral de células escamosas

Background: An increase in oral squamous cell carcinoma (OSCC) cases was observed despite the reduction inexposure to classic risk factors. Although the exact cause of this trend remains unknown, epigenetic factors couldbe contributing to an increased occurrence of these tumors. This study aims to assess the influence of PMS2 pro-tein immunoexpression on the prognosis of patients with OSCC.Material and Methods: This study comprised 76 cases of OSCC treated between 2011 and 2016. Immunohisto-chemical staining for PMS2 was performed. For evaluation, 10 fields per histological section were photographed ata 400x magnification and positively-stained cells were counted with Image J. Mann-Whitney and Kruskal-Wallistests were used to compare the immunolabeling pattern with the clinical-pathological and prognostic characteris-tics. Survival analysis was performed with Chi-square, Long-Rank Mantel-Cox and Cox regression tests (p<0.05).Results: An overexpression of PMS2 was observed in N0/1 tumors and in oral cancers found in unusual locations.In patients ≤60 years of age, high levels of PMS2 (>60%; p=0.041) were associated with low survival (p=0.029).In multivariate analysis, surgery combined with chemotherapy (p=0.030) and high PMS2 immunoexpression(p=0.042) significantly increased the risk of death for ≤60 years old patients Conclusions: The findings of this study indicate that PMS2 can be a potential prognostic protein marker in OSCCpatients 60 years of age and younger.(AU)

Evaluation of a collagen matrix in a mandible defect in rats submitted to the use of bisphosphonates.

PURPOSE: To assess the effect of a collagen matrix (Mucograft®) on the inflammatory process in a semi-critical experimental defect model in rats treated with bisphosphonates. METHODS: Eighteen Wistar rats were randomly divided into three groups: saline (CG), alendronate (ALD) 5mg/kg (AG) or zoledronic acid (ZA) 0.2mg/kg (ZG). ALD was administered orally for 10 weeks and ZA was administered intravascularly on days 0, 7 and 14 and 49. On day 42, a 2mm defect was created and filled with Mucograft® collagen matrix. The contralateral side was filled with a clot (control side). The animals were euthanized 70 days after the beginning of the experiment and the hemimandibles were radiographically and histologically (counting of empty osteocyte lacunae (%), apoptotic (%) and total osteoclasts, neutrophil and mononuclear inflammatory cells) analyzed. The variables were submitted to ANOVA/Bonferroni and t test (parametric data) (p <0.05, GraphPad Prism 5.0). RESULTS: Significant bone repair occurred in the groups treated with Mucograft®. High number of total inflammatory cells and neutrophils cells were showed in AG (p=0.026 and p=0.035) and AZ groups (p=0.005, p=0.034) on the control sides associated with delayed bone repair and the presence of devitalized bone tissue in AG and ZG on the Mucograft® side. CONCLUSION: Mucograft® collagen matrix attenuated the inflammatory process in a mandible defect in rats submitted to the use of bisphosphonates (AG and ZG).

Evaluation of a collagen matrix in a mandible defect in rats submitted to the use of bisphosphonates

Abstract Purpose: To assess the effect of a collagen matrix (Mucograft®) on the inflammatory process in a semi-critical experimental defect model in rats treated with bisphosphonates. Methods: Eighteen Wistar rats were randomly divided into three groups: saline (CG), alendronate (ALD) 5mg/kg (AG) or zoledronic acid (ZA) 0.2mg/kg (ZG). ALD was administered orally for 10 weeks and ZA was administered intravascularly on days 0, 7 and 14 and 49. On day 42, a 2mm defect was created and filled with Mucograft® collagen matrix. The contralateral side was filled with a clot (control side). The animals were euthanized 70 days after the beginning of the experiment and the hemimandibles were radiographically and histologically (counting of empty osteocyte lacunae (%), apoptotic (%) and total osteoclasts, neutrophil and mononuclear inflammatory cells) analyzed. The variables were submitted to ANOVA/Bonferroni and t test (parametric data) (p <0.05, GraphPad Prism 5.0). Results: Significant bone repair occurred in the groups treated with Mucograft®. High number of total inflammatory cells and neutrophils cells were showed in AG (p=0.026 and p=0.035) and AZ groups (p=0.005, p=0.034) on the control sides associated with delayed bone repair and the presence of devitalized bone tissue in AG and ZG on the Mucograft® side. Conclusion: Mucograft® collagen matrix attenuated the inflammatory process in a mandible defect in rats submitted to the use of bisphosphonates (AG and ZG).

Smoking History Decreases Survival in Patients with Squamous Cell Carcinoma of the Mouth: A Retrospective Study with 15 Years of Follow-up.

Background: The purpose of this study was to evaluate the influence of smoking history on the clinical-pathological, sociodemographic and prognostic characteristics of patients with oral squamous cell carcinoma (SCC). Materials and Methods: A retrospective cohort study was carried out with the records of 136 smokers with SCC and 68 nonsmokers with oral SCC who were diagnosed and treated at Haroldo Juaçaba Hospital (2000-2014). Data on patient sex, age, race, education level, tumor location, tumor size, lymph node involvement, distant metastasis, treatment type, marital status, method of health care access (public or private health systems) and overall survival (15 years) were analyzed by the X² test, Mantel-Cox tests and multinomial and Cox logistic regression models (SPSS 20.0, p <0.05). Results: Smoking history was directly associated with male sex (p <0.001), low levels of education (p = 0.001), tumors of the mouth and palate (p = 0.001), stage T3/4 tumors (p = 0.014), lymph node metastasis (N+) (p = 0.024), palliative treatment (p = 0.024) and receiving health care through the public health system (p = 0.006), with education level being the only independently associated factor (p = 0.039). Lower survival was observed in patients who were smokers (p = 0,002), with low levels of education (p = 0.001), who had stage T3/4 tumors (p = 0.004), with N+ (p = 0.021), and had received palliative treatment (p = 0.002). Age (>65 years old, p = 0.015) and T staging (T3/4, p = 0.033) decreased the survival of SCC patients regardless of the other factors. Conclusions: Smoking history had an independent association with low education level and a history of alcoholism, and survival was negatively associated with older age and larger tumor size, which were more prevalent in smokers.

Chronic treatment with zoledronic acid alters the expression levels of inflammatory, bone, and apoptotic markers and Toll-like receptors 2 and 4 in rat dental pulp.

OBJECTIVE: The aim of this study was to evaluate the immunostaining of inflammatory, apoptotic, and bone markers, as well as Toll-like-receptors (TLRs) 2 and 4 in the dental pulp in rats treated with zoledronic acid (ZA). STUDY DESIGN: We administered 4 intravascular infusions of saline (control group) or 0.20 mg.kg-1 ZA in Wistar rats (n = 6/group). After 70 days, the 3 rights molars (n = 18/group) were microscopically evaluated (presence of ectasic/dilated blood vessels and inflammatory cells). Immunohistochemistry was performed for tartrate resistant acid phosphatase 5 (TRAP; cell counting), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), TLR2, TLR4, receptor activator of nuclear kappa B ligand (RANKL), osteoprotegerin (OPG), and caspase-3 (scored 0-3 in odontoblast and nonodontoblast dental pulp cells). Mann-Whitney and Fisher's exact tests and Spearman's correlation were used (GraphPad Prism 5.0). RESULTS: There was no alteration in ectasic/dilated blood vessels (P = .101) or inflammatory cells (P = .500), but the number of TRAP-positive cells was reduced in the ZA-group (P = .027). In ZA-group odontoblasts, immunostaining for COX-2 (P = .044), TLR4 (P = .003), OPG (P = .035) and caspase-3 (P = .039) increased, and that for RANKL (P = 0.045) decreased. In nonodontoblast dental pulp cells, RANKL immunostaining decreased (P = .009). In the ZA group, the RANKL/OPG ratio decreased in odontoblast (P = .022) and nonodontoblast dental pulp cells (P = .007). IL-6 did not differ between the groups. CONCLUSIONS: ZA increases the expression levels of inflammatory, apoptotic markers, and TLR4 and alters bone makers in the dental pulp of rats.

Experimental model of oral ulcer in mice: Comparing wound healing in three immunologically distinct animal lines.

BACKGROUND: The oral wound healing is dependent of immune participation and the absence or augment of one specific immune profile can delayed wound healing. OBJECTIVES: So, the objective of this study was t evaluate the wound healing of oral traumatic ulcer (OTU) in cheek mucosa of swiss, balb/c and c57bl6J mice. MATERIALS AND METHODS: A total of 144 mice (25-30g) were distributed in three groups: swiss (n = 48), balb/c (n = 48) and c57bl/6j (n = 48). An OTU was performed using a dermatological punch in left cheek mucosa. The animals were euthanized daily (n = 6/group/day by 8 days) for evaluation of the ulcer area, weight loss and histological analysis. RESULTS: There are no differences between ulcer area in three groups; however only swiss group showed total wound healing. Swiss group showed weight loss in 2nd and 3rd days recovering the body mass in 4th day (P < 0.01). Balb/c group showed the greater weight loss (P < 0.05) and c57bl/6j did not show body mass variation (P = 0.258). Histologically swiss group was the only group that showed total reepithelization (P < 0.001). Balb/c (P = 0.022) and c57bl/6j (P < 0.001) showed decrease in histological scores, chronic inflammation on the 8th day. Actinomyces was significantly more observed in surface of OTU of balb/c. CONCLUSION: Balb/c mice showed high infection of OTU surface delaying wound healing, and greater weight loss. C57bl/6J mice showed low infection of OTU, but not healing along the eight days. Only the Swiss mice showed wound healing of OTU.