Assessment of the association of myofibroblasts and structural components of the extracellular matrix with histopathological parameters of actinic cheilitis and lower lip squamous cell carcinoma.

BACKGROUND: To evaluate the presence of myofibroblasts (MFs) in the development of lip carcinogenesis, through the correlation of clinical, histomorphometric and immunohistochemical parameters, in actinic cheilitis (ACs) and lower lip squamous cell carcinomas (LLSCCs). METHODS: Samples of ACs, LLSCCs, and control group (CG) were prepared by tissue microarray (TMA) for immunohistochemical TGF-ß, α-SMA, and Ki-67 and histochemical hematoxylin and eosin, picrosirius red, and verhoeff van gieson reactions. Clinical and microscopic data were associated using the Mann-Whitney, Kruskal-Wallis/Dunn, and Spearman correlation tests (SPSS, p < 0.05). RESULTS: ACs showed higher number of α-SMA+ MFs when compared to CG (p = 0.034), and these cells were associated with the vertical expansion of solar elastosis (SE) itself (p = 0.027). Areas of SE had lower deposits of collagen (p < 0.001), immunostaining for TGF-ß (p < 0.001), and higher density of elastic fibers (p < 0.05) when compared to areas without SE. A positive correlation was observed between high-risk epithelial dysplasia (ED) and the proximity of SE to the dysplastic epithelium (p = 0.027). LLSCCs showed a higher number of α-SMA+ MFs about CG (p = 0.034), as well as a reduction in the deposition of total collagen (p = 0.009) in relation to ACs and CG. There was also a negative correlation between the amount of α-SMA+ cells and the accumulation of total collagen (p = 0.041). Collagen and elastic density loss was higher in larger tumors (p = 0.045) with nodal invasion (p = 0.047). CONCLUSIONS: Our findings show the possible role of MFs, collagen fibers, and elastosis areas in the lip carcinogenesis process.

Chemotherapy increases the prevalence of radiotherapy-related trismus in head and neck cancer patients: A systematic review and meta-analysis.

Background: To evaluate the influence of chemotherapy on the prevalence of trismus in irradiated head and neck cancer patients. Material and Methods: This systematic review guided by PRISMA-2020 and registered in PROSPERO (CRD42021255377) screened 963 articles in 7 scientific-databases (PubMed, Lilacs, Livivo, Scopus, Embase, Web of Science, EBSCO) and 3 grey-literature databases (Open Grey, Google Scholar, ProQuest) and eight articles were included for qualitative synthesis, meta-analysis (combined odds ratio, inverse variance method plus random effects), heterogeneity analysis (I² and Tau²), one-of-out evaluation and publication bias analysis (Eggs' and Begg's tests) (RevMan®, p<0.05). The Newcastle-Ottawa Quality Assessment Scale Cohort Studies was used to assess the risk of bias (RoB). The classification assessment, development, and recommendations (GRADE) approach was used to assess the certainty of evidence. Results: The eight articles evaluated 1474 patients treated with chemoradiotherapy and 858 patients treated with radiotherapy. Five articles had low RoB, and three had high RoB. Chemoradiotherapy significantly (p=0.0003) increased the prevalence of trismus (OR=2.55, 95% CI = 1.53-4.23) compared to radiotherapy, with significant (p=0.010) but low heterogeneity (I²=59%;Tau²=0.29). There was no significant risk of publication bias, one-out analysis showed no significant difference between studies, and GRADE showed a moderate level of evidence. Trismus was directly associated to worse quality of life. Conclusions: The incidence of trismus increases when chemotherapy is combined with radiotherapy for head and neck cancer, which negatively impacts the quality of life. Key words:Radiotherapy, Chemoradiotherapy, Head and Neck Neoplasms, Trismus, Quality of Life.

Anti-inflammatory and healing effect of the polysaccharidic extract of Opuntia ficus-indica cladodes in cutaneous excisional wounds in rats.

This study aimed to investigate the anti-inflammatory and wound healing effects of the polysaccharide extract from Opuntia ficus-indica cladodes (TPL-Ofi) using a rat cutaneous wound model. After anaesthesia, four 7-mm-diameter dorsal wounds per animal (n = 6/group for each experimental day of evaluation) were created in female Wistar rats using a surgical punch. The animals were treated topically twice daily with TPL-Ofi (0.01-1%; treated group) or sterile saline (control group) for a period of 21 days. Ulcerated tissue was collected for analysis of histological parameters (inflammation score, number of polymorphonuclear, mononuclear, fibroblast/myofibroblasts and blood vessels), immunohistochemical (fibroblast growth factor 2 [FGF-2]) and oxidative stress markers (myeloperoxidase [MPO] and glutathione [GSH]). After 21 days of treatment, body weight, net organ weight and plasma biochemical levels were measured. TPL-Ofi, containing a total carbohydrate content of 65.5% and uronic acid at 2.8%, reduced oedema on the second day and increased the nociceptive threshold on the second and third days. TPL-Ofi reduced mononuclear infiltrate on the second and MPO activity on the fifth day. TPL-Ofi increased GSH levels on the second day, as well as fibroblast/myofibroblasts counts, neoangiogenesis and FGF-2 levels on the fifth and seventh days. No changes were observed in body weight, net organ weight or toxicology assessment. Topical application of TPL-Ofi exhibited anti-inflammatory and antinociceptive effects, ultimately improving wound healing in cutaneous wounds.

Zoledronate treatment exerts sex-independent effects on bone and dental physicochemical properties in mice jaw necrosis.

INTRODUCTION: Bisphosphonate (BF) therapy is strongly related to the occurrence of medication-related osteonecrosis of the jaw (ONJ). However, no previous study has evaluated if there are sex-related differences on the ONJ establishment together with bone biomechanical alterations, and if they could have a synergy with the ZA treatment. MATERIALS AND METHODS: This study aimed to analyze the physicochemical properties of mineralized tissues in a zoledronate (ZA)-related osteonecrosis mouse model, by a 2 × 2-factorial design, considering sex (female/male) and treatment (ZA/Saline) factors (n = 8/group). After three ZA (1.0 mg/kg) or saline administrations (days 0, 7, 14), the lower left second molar was extracted (day 42). Further ZA administration (day 49) and euthanasia (day 70) were conducted. After confirmation of ZA-induced jaw necrosis (histologic and microtomographic analysis), spectroscopic and mechanical parameters were assessed. RESULTS: ZA-treated groups presented lower bone density due to impaired healing of tooth extraction socket. Sex-related alterations were also observed, with lower bone density in females. Regarding biomechanical parameters, sex and treatment exerted independent influences. ZA, although decreasing flexural modulus and yield stress, increases stiffness mainly due to a higher bone volume. Females show less resistance to higher loads compared to males (considering dimension-independent parameters). Additionally, ZA increases crystallinity in bone and dental structure (p < 0.05). In summary, although strongly related to osteonecrosis occurrence, ZA modifies bone and dental mineral matrix, improving bone mechanical properties. CONCLUSION: Despite sex-dependent differences in bone biomechanics and density, osteonecrosis was established with no sex influence. No synergistic association between sex and treatment factors was observed in this study.

Evaluation of the healing potential of Nile tilapia skin collagen in traumatic oral ulcers in male rats.

OBJECTIVE: To evaluate the healing potential of Nile tilapia skin collagen using a rat model with experimentally induced traumatic oral ulcers. DESIGN: Male Wistar rats were segregated into three experimental groups (n = 8/group/euthanasia day). Ulcers were induced using a dermatological punch on the left buccal mucosa. The rats were then euthanized on days 1, 5, 10, 15, and 20 (ntotal=120 rats). Each group received topical treatment, 2x/day, with 1 % Nile tilapia skin collagen orabase (experimental group), only orabase (negative control), or Oncilom-A® orabase (positive control). Ulcer area, closure percentage, and body mass variation were measured. Slides were prepared for histological analysis, which included Picrosirius red staining (collagen analysis), and immunohistochemistry (platelet endothelial cell adhesion molecule, alpha-smooth muscle actin, and transforming growth factor-beta). RESULTS: On day 15, the experimental and positive control groups displayed smaller ulcer areas, a higher percentage of closure, complete re-epithelialization, superior histological repair scores, and a reduced count of polymorphonuclear cells in comparison to the negative control group (p < 0.05). Additionally, the experimental group exhibited an increased number of blood vessels, total collagen (types I and III) and expression of platelet endothelial cell adhesion molecule, alpha-smooth muscle actin, and transforming growth factor-beta relative to the negative and positive control groups (p < 0.05). By day 20, the experimental group showed a more significant weight gain compared to the other groups (p < 0.0001). CONCLUSIONS: Nile tilapia skin collagen orabase optimizes the healing of traumatic ulcers by stimulating re-epithelialization, angiogenesis, and collagenesis. Transforming growth factor-beta plays a significant role in this process.

Mu and Kappa opioid receptor immunolabeling indicates the prognosis of oropharyngeal squamous cell carcinoma: A cross-sectional observational study.

BACKGROUND: Opioids are the most effective drugs currently available for cancer pain management. The administration of morphine, in addition to its analgesic effect, can alter tumor development. OBJECTIVE: To characterize the immunoexpression of opioid receptors µ and κ in oropharyngeal squamous cell carcinoma, and correlate it with prognostic factors, proliferation markers, and cell death. MATERIALS AND METHODS: A retrospective, cross-sectional observational study was carried out with 50 patients diagnosed at Haroldo Juaçaba Hospital. Sociodemographic, clinicopathological, and overall survival data were collected, and excisional biopsies were taken for immunohistochemistry using tissue microarrays for opioid receptors µ and κ, Ki-67, and caspase-3. Immunolabeling was evaluated and correlated with other variables using Mann-Whitney, Kruskal-Wallis, Spearman correlation, log-rank (Mantel-Cox), and Cox regression tests. RESULTS: Immunoexpression of opioid receptors µ and κ, Ki-67, and caspase-3 was significantly higher in p16+ and p16- primary tumors and lymph node metastases than in surgical resection margins. The overall survival of patients with p16- tumors was 57.53 ± 8.43 months and that of patients with p16+ tumors was slightly higher at 75.92 ± 11.14 months. Multivariate analysis showed that the expression of opioid receptors µ and κ in the nucleus was directly associated with a lower and higher risk of death, respectively. CONCLUSION: We found increased expression of opioid receptors µ and κ in tumor tissues. The nuclear expression of opioid receptors µ and κ influences overall survival and may be a prognostic factor of oropharyngeal squamous cell carcinoma.

Is photobiomodulation effective during maxillary expansion? A systematic review and meta-analysis.

We performed a systematic review on literature associated with meta-analyses to elucidate whether (I) low-level laser therapy (C) compared to placebo accelerates (O) bone neoformation in the region of the midpalatal suture in (P) patients undergoing transverse maxillary expansion. Two reviewers blindly performed targeted searches using the selection criteria (PICOS) in seven major databases and three grey literature databases, employing specific terms and their entrenchments. The RevMan® software (Review Manager, version 5.3, Cochrane Collaboration) was used to adapt the RoB summary illustration to the Cochrane 2.0 tool questions. Meta-analysis was performed using standardized mean difference (SMD) and Cohen's d calculation on random effects, tests for heterogeneity (I2 ) and publication bias (Egger and Begg), and one-of-out sensitivity analysis. GRADE (Grading of Recommendations Assessment, Development and Evaluation) was used for evidence quality analysis. Among the five studies included in the qualitative synthesis, three were included in the meta-analysis. All analysed studies were prospective randomized clinical trials. The risk of bias was such that the Egger (P = .1991) and Begg (P = .024) tests showed no significant risk of publication bias. The meta-analysis showed high heterogeneity (I2  = 81%, P < .00001), and 3 months after the operation, there was no significant difference between the photobiomodulation (PBMT) group and control group (P = .850) or between the subgroups of the periods evaluated after 3 months (P = 0.490). GRADE showed an SMD of 0.62. Photobiomodulation as an adjuvant therapy in patients undergoing transverse maxillary expansion has few benefits and is limited in shape, as it contributes to bone healing in the midpalatal suture region after a period of 3 months.

Polysaccharide extract of Caesalpinia ferrea (Mart) pods attenuates inflammation and enhances the proliferative phase of rat cutaneous wounds.

Pods of Caesalpinia ferrea, popularly used to treat inflammatory processes, were collected to obtain the polysaccharide-rich extract, presenting anti-inflammatory and antinociceptive effects in acute inflammation models. This study aimed to evaluate the anti-inflammatory, antinociceptive and healing activities of the polysaccharide-rich extract from Caesalpinia ferrea pods (PEp-Cf) in the rat model of cutaneous excisional wound. PEp-Cf (0.025-0.1%) or 0.9% NaCl was topically applied in the wounds at dorsal thoracic region (2×/day) during 21 days for measurement of clinical signs (hyperemia, inflammatory exudate, edema, nociception), wound size, histopathological/histomorphometric, oxidative/inflammatory markers and systemic toxicity. PEp-Cf at 0.1% reduced wound area and increased ulcer contraction [days 2 and 10 (21-78%)]. PEp-Cf reduced clinical signs [days 2 and 5 (2.2-2.8×)] and modulated the healing inflammatory phase via stimulation of epithelialization (days 10 and 14), and inhibition of polymorphonuclears [days 2 and 5 (71-74%)], protein leakage [days 2 and 5 (28-41%)], nitrate [days 2 and 5 (2.2-6×)] and malondialdehyde [days 2 and 5 (46-49%)]. PEp-Cf increased the number of blood vessels [days 5 and 7 (3.1-9.6×)], fibroblasts [days 5 and 7 (2.1-6.4×)] and collagen [days 5 to 14 (1.5-1.8×)]. In conclusion, the topical application of PEp-Cf at 0.1% accelerates the healing process of rat cutaneous wounds via modulation of the inflammatory and proliferative phases, being devoid of systemic alterations.

The anti-inflamatory effect of Andira anthelmia lectin in rats involves inhibition of the prostanoid pathway, TNF-α and lectin domain.

OBJECTIVE: To investigate the effect and mechanisms of Andira anthelmia lectin in rat models of acute inflammation. MATERIAL: AAL anti-inflammatory activity was evaluated in Wistar rat models of paw edema and peritonitis. METHODS: AAL (0.01-1 mg/kg i.v.) was injected 30 min before stimulation with carrageenan and with initial and late phase inflammatory mediators into the animals paw or peritoneum for evaluation of cell migration (optical and intravital microscopy), paw edema (plethysmometry and histopathology); hyperalgesia (analgesimetry). RESULTS: AAL inhibited leukocyte migration induced by carrageenan, mainly neutrophils to the peritoneal fluid, decreasing leukocyte adhesion. In the peritoneal fluid, AAL reduced the gene expression of TNF-α and cyclooxygenase, as well the levels of PGE2. AAL inhibited the paw edema induced by carrageenan, serotonin, histamine, TNF-α, PLA2 and PGE2, but not by L-arginine. In this model, AAL also inhibited mechanical hypernociception induced by TNF-α, PGE2, db-cAMP and capsaicin, and the activity of myeloperoxidase in the paw tissues. CONCLUSION: AAL presents anti-inflammatory effect in acute models of rat inflammation involving the participation of prostaglandins, TNF-α and lectin domain.

Outcomes of Oral and Oropharyngeal Squamous Cell Carcinoma Related to Healthcare Coverage: A Retrospective Cohort Study in Brazil.

We investigated the differences in prognosis according to the type of healthcare coverage of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). This study included 875 medical records. Patients covered by the publicly funded Unified Health System (SUS) had a low educational level, with advanced T stage and delayed treatment initiation. Multivariate analyses revealed an association between T stage (p = .035) and poor prognosis in oral squamous cell carcinoma, and age (p = .029) in oropharyngeal squamous cell carcinoma. Surgical treatment (p = .036) and marital status (p = .015) were considered predictors of better prognosis in OOSCC. Exclusive SUS-dependency can be considered an indirect prognostic factor for OOSCC.

Chronic systemic corticosteroid therapy influences the development of pulp necrosis and experimental apical periodontitis, exacerbating the inflammatory process and bone resorption in rats.

AIM: The main aim of the study was to evaluate the inflammatory response and development of apical periodontitis in rats chronically treated with glucocorticoids. METHODOLOGY: Male Wistar rats (Rattus novergicus) were randomly divided into two groups: the experimental group, which was treated with prednisone (5 mg/kg/day) and a control group, which was administered saline solution for 30 days before induction of apical periodontitis, continuing until the day of euthanasia days 0, 7, 14 and 28 after injury induction. The mandibles were subjected to histological evaluation to determine the size of the lesion, was also performed for the presence and absence of pulp necrosis, bone resorption and micro abscesses, and histomorphometric analyses were performed based on the number of polymorphonuclear cells and mononuclear cells. Histochemical analysis was also performed to assess the percentage of collagen fibres and their typification, in addition to immunohistochemistry for the inflammatory markers interleukin IL-1ß, IL-6, TNF-α and TRAP. RESULTS: Despite after 7 days, there was no differences between groups, a significant increase in the root pulp necrosis (p = .001), micro-abscesses (p = .026) and the size of the apical lesion on the 14th day of treatment with prednisone (p = .008). On the same day, there was also an increase in the number of polymorphonuclear cells (p = .042) and cells immunostained for IL-1ß (p = .006), IL-6 (p < .001) and TRAP (p = .002) in animals treated with prednisone. The numbers of mononuclear cells also increase in 28 days (p = .025) and TNF-α ± increases in the prednisone group on the 7th day (p = .041). The prednisone group also showed a decrease in collagen after 14 (both type I [p = .041] and type III [p = .046]) and 28 type III (p = .002) days after the coronary opening. CONCLUSIONS: The glucocorticoids modified the development of experimental apical periodontitis induced in rats, causing an early increase in periapical bone resorption and pulp necrosis. These effects are associated with alterations in cytokine levels, in the inflammatory response and in collagen deposition, in the 14th day after injury induction.

Polymicrobial oral conventionalization model in mice.

The aim of this study is to describe a new polymicrobial oral conventionalization protocol in mice. Oral biofilm samples were collected from wild C57 BL/6 mice (WG), which had not been previously submitted to any experimental procedure. The contents of these samples were used for inoculation in the oral cavity of specific pathogen free (SPF) animals. This inoculation was repeated 3 times. Qualitative cytological analyses were performed in the days 0, 16 and 80 of the experimental protocol, to check the presence or absence of microorganisms, their morphology and staining characteristics on the oral cavity of the animals. At the end of this study, was observed a combination of oral bacterial microbiota of SPF animals and wild animals in the conventionalized group (CONV). Samples collected from CONV mice on day 16, a period in which these animals had been previously inoculated 3 times with wild mouse microbiota, showed a greater amount of Gram-positive cocci, as seen in SPF animals. In addition, Gram-negative cocci were present, although in a much smaller proportion than previously seen in wild mice. On the 80th experimental day, CONV animals showed a predominance of Gram-positive cocci and bacilli. Filamentous bacteria were also seen in this group. The conventionalization of SPF animals using the technique with inoculum from the resident microbiota of wild mice proved to be an effective, low-cost and easily reproducible technique. The conventionalized animals showed the colonization of a microbiota similar to wild animals up to 80 days of experiment.

Streptococcus mutans in atherosclerotic plaque: Molecular and immunohistochemical evaluations.

OBJECTIVES: To verify the presence of Streptococcus mutans (S. mutans) in atherosclerotic plaque (AP) using techniques with different sensitivities, correlating with histological changes in plaque and immunoexpression of inflammatory markers. MATERIALS AND METHODS: Thirteen AP samples were subjected to real-time polymerase chain reaction (qRT-PCR), histopathological analyses, histochemical analysis by Giemsa staining (GS), and immunohistochemical analysis for S. mutans, IL-1ß, and TNF-α (streptavidin-biotin-peroxidase method). Ten necropsy samples of healthy vessels were used as controls. RESULTS: All AP samples showed histopathological characteristics of severe atherosclerosis and were positive for S. mutans (100.0%) in qRT-PCR and immunohistochemical analyses. GS showed that Streptococcus sp. colonized the lipid-rich core regions and fibrous tissue, while the control group was negative for Streptococcus sp. IL-1ß and TNF-α were expressed in 100% and 92.3% of the AP tested, respectively. The control samples were positive for S. mutans in qRT-PCR analysis, but negative for S. mutans, IL-1ß, and TNF-α in immunohistochemical analyses. CONCLUSION: The detection of S. mutans in AP and the visualization of Streptococcus sp. suggested a possible association between S. mutans and atherosclerosis. The results obtained from the control samples suggested the presence of DNA fragments or innocuous bacteria that were not associated with tissue alteration. However, future studies are necessary to provide more information.

Rare clear cell odontogenic carcinoma associated with impacted tooth in a young patient: case report and literature review.

Clear cell odontogenic carcinoma (CCOC) is a rare malignant odontogenic tumor. It is characterized by showing, on histopathological examination, clusters of vacuolated and clear tumor cells with epithelial differentiation surrounded by fibrocollagenous stroma and fibroblasts. The present study presents a rare clinical case of mandibular CCOC associated with an impacted tooth in a 26-year-old woman surgically treated with mandibulectomy and reconstruction with iliac crest bone graft. The patient has been followed up for 22 months without signs of recurrence. A search for case report/case series was carried out in the PUBMED database, as well as in the references of relevant previously published literature reviews. Ninety-six publications were identified, totaling 136 distinct cases reported. Female sex was the most affected (63.1%) with 63.3% of cases occurring in patients in the fifth, sixth, or seventh decades of life. The mandible was more affected than the maxilla (74.2%). Association of CCOC with impacted teeth was found in 2.4% of cases, thus rendering it a rare occurrence. The present case report corroborates the results of the survey regarding sex and anatomical location of the tumor; however, it contradicts the findings regarding age predilection. The case described is the fourth known occurrence of tooth impaction associated with the tumor and the first in a female. In conclusion, CCOC should be considered, as well as other malignancies, as a possible diagnosis of maxillary or mandibular intraosseous lesions even in unusual circumstances such as in association with impacted teeth and in young patients.

Effect of continuous and intermittent sodium alendronate oral dosing on post-extraction alveoli healing in rats.

OBJECTIVE: This study aimed to compare alveolar healing after tooth extraction in two experimental rat models using continuous or discontinuous dosing of sodium alendronate (ALN). DESIGN: Forty-eight male Wistar rats were divided into eight experimental groups (n = 6/group) and administered ALN (2.5, 5.0, or 7.5 mg/kg) by gavage, weekly, either intermittently or following a continuous regimen (2.5, 5.0, or 7.5 mg/kg) before tooth extraction. The positive control rats were administered zoledronic acid (ZA; 0.2 mg/kg, intravenous), whereas negative control rats received sterile saline (0.9% NaCl, gavage). RESULTS: Only the ZA-treated animals showed a larger radiolucent extraction site area compared to the saline group (p = 0.007). Small areas of bone tissue filling the alveoli were visualized in the 7.5 mg/kg continuous ALN group and compared with the saline group (p < 0.001). Increased amounts of empty osteocyte lacunae (p < 0.001) and osteoclasts with signs of apoptosis (p = 0.004) were observed in the continuous ALN groups (2.5, 5.0, and 7.5 mg/kg) compared with the saline group. Increased immunolabeling for TNF-α was observed in the 7.5 mg/kg discontinuous ALN group and all continuous ALN groups compared with the saline group (p < 0.001). The number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts was higher in the two continuous ALN groups (5.0 and 7.5 mg/kg) than in the saline group (p < 0.001). CONCLUSIONS: Continuous administration of ALN impaired post-extraction alveolar bone healing in rats; however, discontinuation of ALN administration before tooth extraction allowed for adequate post-dental extraction alveolar healing.

Mismatch Repair Proteins in Oropharyngeal Squamous Cell Carcinoma: A Retrospective Observational Study.

Cases of oropharyngeal squamous cell carcinoma are on the rise and the disease now ranks as the most common human papillomavirus-related cancer. Although risk factors have been extensively discussed in the literature, the role of the DNA mismatch repair system remains unanswered. To evaluate the impact of the DNA mismatch repair (MMR) protein immunostaining on the tumor progression and prognosis of oropharyngeal squamous cell carcinoma (OPSCC). This retrospective observational study comprised 50 cases of OPSCC. Immunohistochemistry for MSH2, MSH6, PMS2, MLH1, Ki67, p16 and caspase-3 was performed. The expression of these proteins was assessed in surgical resection margins, primary tumor (PT), and lymph node metastasis (LNM) of p16+ and p16- OPSCC. Clinical-pathological involvement in immunostaining was evaluated with Kruskal-Wallis/Dunn or Mann-Whitney test, Wilcoxon test and Spearman's correlation. Overall survival (OS) was analyzed with Log-Rank Mantel-Cox and Cox regression. MSH6 and caspase-3 showed high expression in PT (p16+ and p16 -) and in LNM (p16+ and p16-), and high levels of MSH2 were found in LNM (p16+ and p16 -). An imbalance in MutSα also was observed. PMS2 and caspase-3 expression was associated with poor survival in p16- OPSCC and, in multivariate analysis, MSH2, MSH6 and MLH1 had the poorest prognostic impact in p16+ OPSCC. MMR protein immunostaining is involved in OPSCC progression, dissemination and prognosis. The overexpression of MMR proteins as a response to increased DNA mismatch caused by cell proliferation and MSH2, MSH6 and MLH1 proteins might constitute a prognostic marker in p16+ OPSCC.

Dental infection associated with exuberant gingival necrosis in a patient with paroxysmal nocturnal hemoglobinuria: A case report.

Paroxysmal nocturnal hemoglobinuria (PNH) is a hematological disorder that affects hematopoietic stem cells. An association with other hematological diseases, such as hemolytic anemia and neutropenia, is observed with a high occurrence of aplastic anemia. The aim of the present study is to report a case of dental infection in a patient with PNH exhibiting exuberant gingival involvement. A 45-year-old male patient sought the Federal University of Ceara reporting severe toothache associated with tooth 24. Clinical examination revealed that the tooth was associated with an apparent fistula and a yellowish lesion with smooth surface located in the palate. The patient had interrupted the medication to control PNH. Blood transfusion was requested due to deficient hematological parameters. Tooth extraction and excisional biopsy were performed under antibiotic coverage. In the postoperative period, low-level laser therapy (LLLT) was performed. Histopathological examination revealed connective tissue showing extensive necrotic areas, accumulation of basophilic material, numerous cyst-like cavities, and degenerated cells. Histopathological findings were compatible with the initial clinical diagnosis of gingival necrosis. The patient evolved with febrile neutropenia, requiring hospitalization for 1 month. Improvement in the overall health was observed after the administration of antibiotics, eculizumab, and weekly LLLT at the biopsy site.

Galactomannan of Delonix regia seeds reduces nociception and morphological damage in the rat model of osteoarthritis induced by sodium monoiodoacetate.

This study investigated the effects of the protein-free galactomannan obtained from Delonix regia seeds (GM-DR) in an experimental osteoarthritis (OA) model. GM-DR was obtained from water-homogenized endosperms by collection of the supernatant and precipitation with ethanol. The remaining proteins in the galactomannan were removed by alkaline hydrolysis. Weight average molar mass (Mw) of the galactomannan was estimated in 5.8 × 105 g mol-1, presenting mannose:galactose ratio of 2.39:1. Rats received sodium monoiodoacetate (OA groups, 1 mg/25 µL) or saline (sham group) in the right tibio-tarsal joint. GM-DR (30-300 µg) was administered by intra-articular route at days 14 and 21 after OA induction. Hypernociception was evaluated daily by the measurement of the mechanical threshold required to cause joint flexion and paw withdrawal reflex. The 56-day animal groups were euthanized for joint histopahological analysis using the OARSI score system. Lower doses of GM-DR (30 and 100 µg) promoted antinociception from day 15 until the endpoint at day 56. Joint damage was reduced by GM-DR administration (100 µg) in OA-subjected animals, compared to the vehicle-treated OA group (5.9 ± 1.8 vs 19.0 ± 1.8, respectively, p < 0.05). Conclusion: Both antinociception and damage reduction suggest that Delonix regia galactomannan is a promising approach for osteoarthritis therapy.

Antinociceptive effect of Lonchocarpus araripensis lectin: activation of L-arginine/NO/cGMP/K+ATP signaling pathway.

OBJECTIVE AND DESIGN: The involvement of nitric oxide pathway in the antinociceptive activity of Lonchocarpus araripensis lectin (LAL) was investigated in the model of carragenan-induced hypernociception. METHODS: Swiss mice received LAL (0.01-10 mg/kg; i.v.) 30 min before s.c. injection of carragenan in the paws. For the involvement of nociceptive pathways, animals were previously treated with the blockers: NOS (L-NAME, aminoguanidine, 7-nitroindazole); soluble guanylyl cyclase (ODQ); channels of ATP-dependent K+ (glibenclamide); L-type Ca2+ (nifedipine), or Ca2+-dependent Cl- (niflumic acid). Participation of lectin domain was evaluated by injection of LAL associated with N-acetyl-glucosamine (GlcNAc). nNOS gene relative expression was evaluated in the paw tissues and nNOS immunostaining in dorsal root ganglia. RESULTS: LAL at all doses inhibited carrageenan-induced hypernociception (4.12 ± 0.58 g), being maximal at 10 mg/kg (3 h: 59%), and reversed by GlcNAc. At this time, LAL effect was reversed by nifedipine (39%), niflumic acid (59%), L-NAME (59%), 7-nitroindazole (44%), ODQ (45%), and glibenclamide (34%), but was unaltered by aminoguanidine. LAL increased (95%) nNOS gene expression in mice paw tissues, but not its immunoexpression in the dorsal root ganglia. CONCLUSION: The antinociceptive effect of Lonchocarpus araripensis lectin involves activation of the L-arginine/NO/GMPc/K+ATP pathway.

Disorders on cardiovascular parameters in rats and in human blood cells caused by Lachesis acrochorda snake venom.

In Colombia, Lachesis acrochorda causes 2-3% of all snake envenomations. The accidents promote a high mortality rate (90%) due to blood and cardiovascular complications. Here, the effects of the snake venom of L. acrochorda (SVLa) were analyzed on human blood cells and on cardiovascular parameters of rats. SVLa induced blood coagulation, as measured by the prothrombin time test, but did not reduce the cell viability of neutrophils and platelets evaluated by the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay and by the lactate dehydrogenase (LDH) enzyme assay. In fact, SVLa increased the absorbance in tests made with platelets subjected to the MTT assay. SVLa induced platelet aggregation whose magnitude was comparable to that of the positive control adenosine diphosphate (ADP), and occurred earlier with increasing SVLa concentration. Acetylsalicylic acid (ASA, a cyclooxygenase inhibitor) or clopidogrel (an ADP receptor blocker) inhibited the aggregating effect of SVLa. Inhibition of SVLa-elicited platelet aggregation also resulted from the treatment with disodium ethylenediaminetetraacetate (Na2-EDTA; metalloproteinase inhibitor) and with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF, serine protease inhibitor). In isolated right atrium of rats, SVLa increased slightly, but significantly, the magnitude of the spontaneous contractions and, in isolated rat aorta, SVLa relaxed KCl- or phenylephrine-induced contractions. In vivo, SVLa induced hypotension and bradycardia in rats, with detection of hemorrhage in pulmonary and renal tissues. Altogether, under experimental conditions, SVLa induced blood coagulation, platelet aggregation, hypotension and bradycardia. Part of the effects presented here may be explained by the presence of snake venom metalloproteinases (SVMPs) and snake venom serine proteases (SVSPs), constituents of SVLa.