Ethanol binge drinking exposure during adolescence displays long-lasting motor dysfunction related to cerebellar neurostructural damage even after long-term withdrawal in female Wistar rats.

Ethanol is one of the psychoactive substances most used by young individuals, usually in an intermittent and episodic manner, also called binge drinking. In the adolescent period, brain structures undergo neuromaturation, which increases the vulnerability to psychotropic substances. Our previous studies have revealed that ethanol binge drinking during adolescence elicits neurobehavioral alterations associated with brain damage. Thus, we explored the persistence of motor function impairment and cerebellum damage in the context of ethanol withdrawal periods (emerging adulthood and adult life) in adolescent female rats. Female Wistar rats (35 days old) received orally 4 cycles of ethanol (3.0 g/kg/day) or distilled water in 3 days on-4 days off paradigm (35th until 58th day of life). Motor behavioral tests (open field, grip strength, beam walking, and rotarod tests) and histological assays (Purkinje's cell density and NeuN-positive cells) were assessed on the 1-, 30-, and 60-days of binge alcohol exposure withdrawal. Our findings demonstrate that the adolescent binge drinking exposure paradigm induced cerebellar cell loss in all stages evaluated, measured through the reduction of Purkinje's cell density and granular layer neurons. The cerebellar tissue alterations were accompanied by behavioral impairments. In the early withdrawal, the reduction of spontaneous movement, incoordination, and unbalance was seen. However, the grip strength reduction was found at long-term withdrawal (60 days of abstinence). The cerebellum morphological changes and the motor alterations persisted until adulthood. These data suggest that binge drinking exposure during adolescence causes motor function impairment associated with cerebellum damage, even following a prolonged withdrawal, in adult life.

Sociodemographic and clinical characterization of cases of 1,103 non-syndromic and 66 syndromic odontogenic keratocyst: a Brazilian multicenter study.

OBJECTIVES: This multicenter study aimed to evaluate cases of non-syndrome and syndromic odontogenic keratocyst, as well as cases of recurrence within these two groups. METHODS: This descriptive, analytical, retrospective cross-sectional study evaluated the sex, age and presence of multiple lesions in 1,169 individuals seen at 10 Brazilian oral and maxillofacial pathology centers. Of these, 1,341 odontogenic keratocysts were analyzed regarding clinical diagnosis, size, site, imaging appearance, signs and symptoms, type of biopsy, treatment, and recurrence. RESULTS: There was a similar distribution by sex. The median age of non-syndromic and syndromic patients was 32 and 17.5 years, respectively. The posterior mandible was the site most affected by small and large lesions in both groups and in recurrent cases. Unilocular lesions were more frequent, also in recurrent cases. Mainly small lesions showed this imaging appearance. Signs and symptoms were absent in most cases. Conservative treatment was the most frequent modality in all age groups, regardless of the patient's condition and recurrence. Recurrences were uncommon. CONCLUSION: This study showed a higher frequency of non-syndromic keratocysts in the population. Clinicopathological features related to the involvement of multiple sites, age, and recurrence may differ between syndromic and non-syndromic cases. Furthermore, we found an association between lesion size and some clinical features and between the time interval to recurrence and the syndromic spectrum. CLINICAL RELEVANCE: To contribute to a better understanding of the distribution and association between clinical, imaging, and sociodemographic characteristics in each spectrum of the lesion.

Proposal of a secure and efficient protocol for a murine oral carcinogenesis model induced by 4-nitroquinoline-1-oxide (4NQO).

An important rat model using the chemical carcinogen 4-nitroquinoline-1-oxide (4NQO) has been described for the study of the process of oral carcinogenesis. This model replicates the gradual progression seen in oral carcinoma patients. However, due to its high level of toxicity, its use in fundamental research is challenging. Here, we propose a secure and efficient modified protocol based on a lower dose of 4NQO concentration as well as an increased water supply and hypercaloric diet, in order to reduce the damage caused to the animals during the process of oral carcinogenesis. Twenty-two male Wistar rats were exposed to 4NQO, evaluated clinically once a week and euthanized at 12 and 20 weeks for histopathological analysis. The protocol involves a staggered dose of 4NQO up to a concentration of 25 ppm, associated with two days of pure water, a 5% glucose solution once a week and a hypercaloric diet. This modified protocol prevents the immediate consequences of the carcinogen. At week 7, all animals displayed clinically evident tongue lesions. From a histological perspective, after 12 weeks of 4NQO exposure, 72.7% of the animals developed epithelial dysplasia and 27.3% developed in situ carcinoma. In the group exposed for 20 weeks, epithelial dysplasia and in situ carcinoma were diagnosed in one case each, whereas invasive carcinoma was diagnosed in 81.8% of the cases. Nonsignificant modification of animal's behavior and weight was observed. This new proposed 4NQO protocol was secure and effective for studying oral carcinogenesis and can be used to conduct lengthy investigations.

Revisiting the evidence of photodynamic therapy for oral potentially malignant disorders and oral squamous cell carcinoma: An overview of systematic reviews.

BACKGROUND: This study summarized the available evidence about the use of photodynamic therapy (PDT) for the management of oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC). METHODS: An overview of systematic reviews was undertaken based on the 2020 PRISMA statement. Electronic searches were performed in five databases. Studies published up to November 2022 were included. Risk of bias was assessed with the AMSTAR 2 tool. RESULTS: A total of 30 studies enrolling 9,245 individuals with OPMD (n = 7,487) or OSCC (n = 1,758) met the selection criteria. All studies examined the efficacy and/or safety of PDT. OPMD were investigated individually in 82.8% of the studies, the most common being oral lichen planus and actinic cheilitis. OSCC was addressed separately in 10.3% of the studies, while only 6.9% evaluated both OPMD and OSCC. Fourteen different types of photosensitizers were described. PDT was used according to the following setting parameters: 417-670 nm, 10-500 mW/cm2, 1.5-200 J/cm2, and 0.5-143 min. Regarding OPMD, leukoerythroplakia showed the best response rates, while oral lichen planus presented a partial or no response in nearly 75% of documented cases. A complete response was observed in 85.9% of OSCC cases, while 14.1% had no resolution. CONCLUSION: Overall, the response to PDT depended on the type of OPMD/OSCC and the parameters used. Although PDT is an emerging candidate for the treatment of OPMD and OSCC, there is heterogeneity of the methodologies used and the clinical data obtained, particularly regarding the follow-up period.

Impact of photobiomodulation in a patient-derived xenograft model of oral squamous cell carcinoma.

BACKGROUND: Photobiomodulation therapy (PBMT) is an effective method for the prevention of oral mucositis. However, the effects of PBMT on oral squamous cell carcinoma (OSCC) have not yet been fully elucidated. This study aimed to evaluate the impact of PBMT in an OSCC-patient-derived xenograft (OSCC-PDX) model. METHODS: BALB/c nude mice with OSCC-PDX models were divided into Control, without PBMT (n = 8); Immediate irradiation, PBMT since one week after tumor implantation (n = 6); and Late irradiation, PBMT after tumors reached 200 mm3 (n = 6). OSCC-PDX were daily irradiated (660 nm; 100 mW; 6 J/cm2 ; 0,2 J/point) for 12 weeks. The tumors were collected and submitted to volumetric, histological, immunohistochemistry, and cell cycle analysis. RESULTS: No significant differences in the volumetric measurements (p = 0.89) and in the histopathological grade (p > 0.05) were detected between the groups. The immunohistochemical analysis of Ki-67 (p = 0.9661); H3K9ac (p = 0.3794); and BMI1 (p = 0.5182), and the evaluation of the cell cycle phases (p > 0.05) by flow cytometry also did not demonstrate significant differences between the irradiated and non-irradiated groups. CONCLUSION: In this study, PBMT did not impact the behavior of OSCC-PDX models. This is an important preclinical outcome regarding safety concerns of the use of PBMT in cancer patients.

Effects of different protocols of defocused high-power laser on the viability and migration of myoblasts-a comparative in vitro study.

The aim of the present study was to analyze for the first time the effect of photobiomodulation therapy (PBMT) using defocused high-power laser (DHPL) in myoblast cell line C2C12 viability and migration and compare them with low-power laser therapy. Cells were divided into 9 groups: Sham irradiation 10% fetal bovine serum (FBS); Sham irradiation 5%FBS; low-power laser 0.1 W; DHPL 810 1 W; DHPL 810 2 W; DHPL 980 1 W; DHPL 980 2 W; DHPL dual 1 W; DHPL dual 2 W. To simulate stress conditions, all groups exposed to irradiation were maintained in DMEM 5% FBS. The impact of therapies on cell viability was assessed through sulforhodamine B assay and on cells migration through scratch assays and time-lapse. Myoblast viability was not modified by PBMT protocols. All PBMT protocols were able to accelerate the scratch closure after 6 and 18 h of the first irradiation (p < 0.001). Also, an increase in migration speed, with a more pronounced effect of DHPL laser using dual-wavelength protocol with 2 W was observed (p < 0.001). In conclusion, the diverse PBMT protocols used in this study accelerated the C2C12 myoblasts migration, with 2-W dual-wavelength outstanding as the most effective protocol tested. Benefits from treating muscle injuries with PBMT appear to be related to its capacity to induce cell migration without notable impact on cell viability.

4-nitroquinoline-1-oxide (4NQO) induced oral carcinogenesis: A systematic literature review.

OBJECTIVE: Based on a critical review of published studies, we aimed to develop a good practice guide for using 4-nitroquinoline-1-oxide (4NQO) as an inducer of oral carcinogenesis in Wistar rats. DESIGN: A systematic search was performed on Medline Ovid, PubMed, Embase, Web of Science, and Scopus databases. The SYRCLE's risk of bias tool was used to assess the quality of the studies. RESULTS: Thirty-five articles met the selection criteria; 22 (62.9%) of them administered 4NQO systemically in drinking water, with a mean concentration of 30.2 ppm (SD±15.9) and during a mean period of 20.8 (SD±7.8) weeks. The other 13 (37.1%) studies performed topical applications of 4NQO painting the oral mucosa of the animals three times a week (100%) with a mean period of administration of 16.8 (SD±7.0) weeks. Different 4NQO concentrations used for other periods achieved significant tumor development. Most studies didn't perform quantitative clinical analysis, and the histopathological diagnosis/grading criteria varied considerably. CONCLUSIONS: A poor description of solution care, adverse effects, and the number of losses were observed, and the reporting of these features needs to be improved. Suggestions to guide the development of future research are provided.

Oral and Maxillofacial Neuroendocrine Carcinoma: A Systematic Review.

The aim of the present study was to integrate the available data published in the literature on oral and maxillofacial neuroendocrine carcinomas concerning the demographic, clinical and histopathological features of this condition. An electronic search with no publication date restriction was undertaken in April 2021 in four databases. Eligibility criteria included reports published in English having enough data to confirm a definite diagnosis, always showing a neuroendocrine marker. Cases originating in the oropharynx, including base of the tongue and tonsils, were excluded. Outcomes were evaluated by the Kaplan-Meier method along with Cox regression. Twenty-five articles (29 cases) from nine different countries were detected. Mean patient age was 56.3 (± 17.5) years, with a slight male predilection. Symptomatology was present in 72.2% of informed cases. Regarding clinical presentation, a non-ulcerated nodule located in the gingiva with a mean size of 3.4 (± 2.0) cm was most frequently reported. Concomitant metastasis was identified in seven individuals. Histopathologically, most neoplasms were of the small cell type, and immunohistochemistry for both epithelial and neuroendocrine differentiation was used in 65.5% cases. Radical surgery was the treatment of choice in almost all cases, with or without adjuvant therapy. Mean follow-up was 20.5 (± 21.2) months, and only four patients developed recurrences. Eleven (44.0%) individuals died due to the disease. Ulcerated lesions were a prognostic factor. This study provides knowledge that can assist surgeons, oncologists, and oral and maxillofacial pathologists with the diagnosis and management of neuroendocrine carcinomas. Our findings demonstrated that the long-term prognosis of this lesion continues to be poor.

Analysis of referrals to the stomatology service in a Southern Brazilian hospital: a retrospective study.

This paper intends to describe the demand for referrals to the stomatology service requested by the medical teams for inpatients in a reference hospital in the south of Brazil. This research is a retrospective cross-sectional descriptive study focusing on data collection and assessment of information about referrals to the stomatology unit carried out from January 2008 to December 2018. All information was obtained from the hospital management software database, then transferred and analyzed individually for descriptive statistics. A total of 4433 cases were referred to the stomatology team, with an average of 403 cases by year. Hematology/hemato-oncology (37.3%) was the specialty asking for the majority of the referrals, followed by Oncology (20.4%) and Pneumology (8.2%). The mean patients' profile was males (55.5%), receiving a diagnosis of oral mucositis (43.5%), and with the first and second decades of life being the most prevalent ones (34.9%), with a mean age of 34.8±22.3 years. The most common treatment performed by the stomatology team was the photobiomodulation therapy (44.8%). This retrospective study demonstrated the important profile of the stomatological care in hospitalized patients from a specific hospital, especially referred by the hematology/hemato-oncology team. These results evidenced the importance of the stomatology specialty in the hospital environment.

Salivary gland cancer in Southern Brazil: a prognostic study of 107 cases / Cáncer de glándula salival en el sur de Brasil: un estudio pronóstico de 107 casos

Background: Salivary gland cancers (SGC) represent an uncommon group of heterogeneous tumors. We per-formed a retrospective survey of SGC diagnosed in a reference center for treatment of malignant tumors from thesouth of Brazil aiming to determine the prognostic value of demographic, clinic and pathologic features.Material and Methods: Cases diagnosed as SGC between 2006 and 2016 were retrospectively collected. Medicalrecords were examined to extract demographic, clinic, pathologic and follow-up information.Results: One-hundred and seven cases of SGC were identified. The most common SGC were mucoepidermoidcarcinoma (MEC) (n = 39) followed by adenoid cystic carcinoma (AdCC) (n = 29). Among AdCCs, 55.2% of caseswere classified as cribriform, 27.6% as tubular and 17.2% as solid. The tubular subtype had the highest percentageof cases with perineural invasion (p=0.01). Among MEC, 61.5% of cases were classified as low grade, 15.4% asintermediate grade and 19.9% as high grade. Low grade MEC had the lowest percentage of cases with perineuralinvasion (p=0.04). The 5-year survival for loco-regional control, disease-free survival (DFS) and disease-specificsurvival were 75%, 70% and 84%, respectively. The following features were associated with poor DFS: advanced age (p=0.03), rural residency (p=0.01), being a smoker or former smoker (p=0.01), pain (p=0.03), nodal metastasis(p<0.001), need for chemotherapy (p=0.02), neck dissection (p=0.04), perineural invasion (p=0.01), and being diag-nosed with AdCC compared to MEC (p=0.02).Conclusions: The clinco-demographic and pathologic features identified as prognostic factors reveal the profile ofpatients at increased risk of recurrence and who would benefit from closer follow-up.(AU)

Oral mucositis in childhood cancer patients receiving high-dose methotrexate: Prevalence, relationship with other toxicities and methotrexate elimination.

BACKGROUND: Oral mucositis (OM) is one of the main adverse effects of the chemotherapeutic agent methotrexate (MTX). AIM: To evaluate the relationship of OM with MTX metabolism time and other toxicities in childhood, cancer patients receiving high-dose of methotrexate (HD-MTX). DESIGN: Seventy-seven childhood patients receiving HD-MTX for treatment of leukaemia, osteosarcoma or lymphoma were evaluated. MTX serum level, hepatic and renal function parameters, and presence and intensity of OM were analysed. RESULTS: The patients were submitted to 255 cycles of chemotherapy. OM was diagnosed in 191 (74.9%) cycles. Of these, 119 (46.6%) presented ulcerative lesions. Lymphoma was associated with severe OM (P = .01). OM was associated with higher serum levels of aspartate aminotransferase (P = .006), alanine aminotransferase (P = .04) and creatinine (P = .008). Increase of one unit of total bilirubin and indirect bilirubin associated, respectively, with 11% and 39% higher prevalence of OM. For each increase of one unit of creatinine serum level, it was observed a 37% higher prevalence of OM in patients with lymphoma. No association was found between delayed excretion of MTX and OM development. CONCLUSIONS: OM is a prevalent complication of childhood cancer patients receiving HD-MTX. Renal and hepatic toxicity could be considered risk factors for OM, especially in patients with lymphoma.

Analysis of referrals to the stomatology service in a Southern Brazilian hospital: a retrospective study

Abstract This paper intends to describe the demand for referrals to the stomatology service requested by the medical teams for inpatients in a reference hospital in the south of Brazil. This research is a retrospective cross-sectional descriptive study focusing on data collection and assessment of information about referrals to the stomatology unit carried out from January 2008 to December 2018. All information was obtained from the hospital management software database, then transferred and analyzed individually for descriptive statistics. A total of 4433 cases were referred to the stomatology team, with an average of 403 cases by year. Hematology/hemato-oncology (37.3%) was the specialty asking for the majority of the referrals, followed by Oncology (20.4%) and Pneumology (8.2%). The mean patients' profile was males (55.5%), receiving a diagnosis of oral mucositis (43.5%), and with the first and second decades of life being the most prevalent ones (34.9%), with a mean age of 34.8±22.3 years. The most common treatment performed by the stomatology team was the photobiomodulation therapy (44.8%). This retrospective study demonstrated the important profile of the stomatological care in hospitalized patients from a specific hospital, especially referred by the hematology/hemato-oncology team. These results evidenced the importance of the stomatology specialty in the hospital environment.

Prolonged caffeine intake decreases alveolar bone damage induced by binge-like ethanol consumption in adolescent female rats.

Ethanol consumption has been reported to negatively impact on periodontal disease. In particular, oral cavity disorders occur upon ethanol exposure during adolescence, a life period associated with particular patterns of short and intense ('binge-like') ethanol consumption that is most deleterious to oral health. The hazardous central effects of ethanol have been linked to the overfunction of adenosine receptors, which are antagonized by caffeine, a bioactive substance present in numerous natural nutrients, which can also modify bone metabolism. The aim of this study was to investigate the effects of caffeine on alveolar bone damage induced by an ethanol binge drinking paradigm during adolescence. Female Wistar rats (35 days old; n = 30) were allocated to six groups: control (vehicle), ethanol (3 g/kg/day; 3 days On-4 days Off challenge), caffeine (10 mg/kg/day), caffeine plus ethanol, SCH58261 (0.1 mg/kg/day, an antagonist of A2A receptors), and SCH58261 plus ethanol. Bone micromorphology and vertical bone loss were analyzed by computed microtomography. Our data showed that ethanol binge drinking reduced alveolar bone quality, with repercussion on alveolar bone size. This ethanol-induced alveolar bone deterioration was abrogated upon treatment with caffeine, but not with SCH58261. This shows that caffeine prevented the periodontal disorder caused by ethanol binge drinking during adolescence, an effect that was not mediated by adenosine A2A receptor blockade.

Effects of a mucoadhesive formulation containing Curcuma longa L. on oral wound healing

Introduction: The aim of this study was to investigate the effects of a topical mucoadhesive formulation with Curcuma longa L. extract (MFC) on oral wound healing. Methods: Seventy-two Wistar rats were randomly assigned to 3 groups: Control, Vehicle, and MFC. Traumatic ulcers were made on the dorsum of the tongue with a 3-mm diameter punch. Vehicle and MFC groups received application of the products twice a day, while animals in the control group were cared for in identical conditions but received no product application. Six rats in each group were euthanized at days 3, 5, 10, and 14. Percentage of repair was calculated based on wound area. HE-stained histological sections were obtained for semi-quantitative analysis of re-epithelization and inflammation. Results: Clinical findings revealed that at days 3 and 5, animals from the MFC group exhibited a significantly higher percentage of wound repair. At day 5, animals from this group also demonstrated a significant increase in the degree of re-epithelization and inflammation. Conclusions: MFC is capable of accelerating oral wound repair in an in vivo model by modulating the inflammatory process and stimulating epithelial proliferation. (AU)

Mucoadhesive formulation containing Curcuma longa L. reduces oral mucositis induced by 5-fluorouracil in hamsters.

We explored the effects of a mucoadhesive formulation containing curcuminoid (MFC) from Curcuma longa L. extract on oral mucositis (OM) induced by 5-fluorouracil (5-FU) in hamsters. Seventy-two golden Syrian hamsters were randomly allocated into four groups: control, placebo, chamomilla, and MFC. Animals received an intraperitoneal injection of 5-FU at Days 0 and 2. On Days 3 and 4, the buccal mucosa was scratched. Therapy was initiated on Day 5. Animals received two applications of the substances per day according to the experimental group. Six animals were euthanized on Days 8, 10, and 14. Clinical analysis were performed using photography and histopathological sections of 3 µm were stained by hematoxylin-eosin for semiquantitative analysis of re-epithelization and inflammation. Immunohistochemistry was used for angiogenesis (CD31) and transforming growth factor beta 1 (TGF-ß1) analysis. On Day 5, all groups exhibited OM. Clinical and histopathological findings revealed that on Day 8, both MFC and chamomilla groups exhibited better wound healing. In addition, the MFC group demonstrated lower angiogenesis and TGF-ß1 levels on Day 8 compared with placebo and control groups. Collectively, these findings suggest that MFC has a therapeutic effect on OM, accelerating wound healing through re-epithelization and anti-inflammatory action as modulation of angiogenesis and TGF-ß1 expression.