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Oral Submucous Fibrosis is a potentially malignant disorder caused by habitual areca nut chewing, which contributes to the dispersion of active alkaloids into subepithelial tissues, stimulating excessive extracellular matrix deposition. Various treatment modalities are available; however, their efficacy in inhibiting fibrosis progression remains limited. Sulforaphane (SFN), an isothiocyanate found abundantly in cruciferous plants, is known to have effective antifibrotic properties. Objective: The present study investigated the antifibrotic effect of SFN via phosphatidylinositol 3 kinase (PI3K), Serine/Threonine Kinase 1 (AKT-1), mammalian target of rapamycin (mTOR) pathway in arecoline (AER) induced fibrosis in human gingival fibroblasts [HGFs]. Material and Methods: MTT assay determined the half-maximal inhibitory concentration of AER and SFN at 24h in the HGF cell line. Expression levels of transforming growth factor ß1 (TGFß1), collagen type 1 alpha 2 (COL1A2), hydroxyproline (HYP), PI3, AKT, mTOR, and nuclear factor erythroid 2­related factor 2 (NRF2) were assessed post-AER and SFN treatment using qPCR and western blot analysis. Results: The findings of the study revealed that AER elicited a stimulatory effect, upregulating TGFß1, COL1A2, HYP, PI3K, AKT, and mTOR and downregulating NRF2 expression. Conversely, SFN treatment significantly upregulated NRF2, inhibiting TGFß1 mediated PI3/AKT/mTOR pathway. Conclusion: These observations suggest that SFN can be used as a promising synergistic antifibrotic agent to combat fibrogenesis via the non-Smad pathway (AU)

Fibrose submucosa oral é uma desordem potencialmente maligna causada pelo habito de mascar a noz da areca, o que contribui para a dispersão de alcalóides ativos nos tecidos subepiteliais, estimulando a deposição excessiva de matriz extracelular. Há várias modalidades terapêuticas, no entanto, com eficácia limitada no controle da progressão da fibrose. O sulforafano (SFN), isotiocianato encontrado abundantemente em plantas crucíferas, é conhecido por suas propriedades antifibróticas. Objetivo: Investigar os efeitos antifibróticos do SFN na via fosfatidilinositol3-quinase (PI3K), via quinase serina/treonina 1 (AKT-1), via do alvo da rapamicina em mamíferos (mTOR), na fibrose induzida por arecolina (AER) em fibroblastos gengivais de humanos (HGFs). Material e Métodos: A meia concentração inibitória mínima de AER e SFN em 24 horas nas células HGFs foi determinada por MTT. Os níveis de expressão de ß1 (TGFß1), colágeno tipo 1 alfa 2 (COL1A2), hidroxiprolina (HYP), PI3K, AKT, mTOR, fator nuclear eritroide 2 relacionado ao fator 2 (NRF2) foram analisados após tratamento com ERA e SFN através de qPCR e western blot. Resultados: O ERA apresentou efeito estimulatório aumentando a expressão de TGFß1, COL1A2, HYP, PI3K, AKT e mTOR e diminuindo a expressão de NRF2. Por outro lado, tratamento com SFN aumentou significativamente a expressão de NRF2, inibindo a liberação de TGFß1 mediada pela via PI3/AKT/mTOR. Conclusão: Esses achados sugerem que o SFN pode ser um agente antifibrótico promissor no combate à fibrogênese decorrente da via não-Smad (AU)

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Electromyography (EMG) is used for the measurement of muscle activity to characterize the nature of muscle contraction in Oral submucous fibrosis (OSMF). Aim: To assess the efficacy of EMG in evaluating masseter muscle activity in the management of OSMF. This review identified 73 records from standard databases which were rigorously screened with eligibility criteria and 3 clinical studies were identified based on our inclusion criteria. The quality of included studies was assessed by the PEDro scale and data was synthesized with detailed characterization. The Risk of Bias assessment among studies was done using the ROBINS-I tool and a meta-analysis could not be done due to high clinical heterogeneity. Our result recommends that EMG be used as an objective prognosis assessment tool by quantifying the management of OSMF irrespective of the intervention applied. However, it is not to be considered the gold standard as of now with limited data pooled and needs to be further assessed with clinical trials. EMG can be advocated as a reliable adjunct assessment for measuring the interventional outcome of OSMF irrespective of treatment modalities.

La electromiografía se ha utilizado para medir la actividad muscular y caracterizar la naturaleza de la contracción muscular. Nuestra revisión sistemática tuvo como objetivo evaluar la eficacia de EMG en la evaluación de la actividad del músculo masetero en el manejo de OSMF. Esta revisión identificó 73 registros de bases de datos estándar que se revisaron rigurosamente con criterios de elegibilidad y se identificaron 3 estudios clínicos según nuestros criterios de inclusión. La calidad de los estudios incluidos se evaluó mediante la implementación de la escala PEDro y los datos se sintetizaron con una caracterización detallada. La evaluación del riesgo de sesgo entre los estudios se realizó mediante la herramienta ROBINS-I y no se pudo realizar un metanálisis debido a la alta heterogeneidad clínica. Nuestro resultado recomienda que la EMG podría utilizarse como una herramienta objetiva de evaluación del pronóstico mediante la cuantificación en el manejo de OSMF independientemente de la intervención aplicada. Sin embargo, no debe considerarse el estándar de oro a partir de ahora con datos agrupados limitados, y debe volver a evaluarse en el futuro después de la disponibilidad de ensayos clínicos extensos. A partir de ahora, la EMG se puede recomendar como un equipo de evaluación complementario confiable para medir el resultado de la intervención de la fibrosis submucosa oral, independientemente de las modalidades de tratamiento.

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This systematic review (SR) with meta-analysis aimed to evaluate the scientific data related to cytogenetic damage in oral exfoliated cells of patients diagnosed with oral potentially malignant disorders (OPMDs). The SR was conducted according to the PRISMA-P guidelines. The PICOS (Participants, Intervention, Comparison, Outcome, and Study Design) strategy was used to answer the question: "Is micronucleus assay in oral exfoliated cells a suitable biomarker for predicting cancer risk in individuals with OPMDs?" The search strategy was performed in the following electronic databases: PubMed, Medline, Scopus and Web of Science. The comparisons were defined as standardized mean difference (SMD), and 95% confidence intervals (CI). The quality of included studies was assessed using the EPHPP (Effective Public Health Practice Project). The GRADE tool was also utilized to assess the quality of evidence of the SR. A total of 110 potentially relevant studies were selected through the search strategy. After screening titles and abstracts, 20 full-text manuscripts were assessed for eligibility and three observational studies were included in the meta-analysis. After reviewing the 20 studies, 13 were considered weak. The meta-analysis data revealed a statistically significant difference in oral micronucleated cells by patients with OPMDs when compared to control (SMD=1.77, 95% CI, 0.36-3.18, p = 0.01), with a Tau2 = 1.97; Chi2 = 66.64, and p < 0.001. Patients with OPMDs had a positive response related to mutagenicity in oral cells compared to control patients. However, SR was not able to validate the micronucleus assay as a putative biomarker in individuals with oral potentially malignant disorders since the majority of studies were considered weak based on high risk of bias.

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Abstract The present study is aimed to formulate steroidal oral mucoadhesive gels of dexamethasone sodium phosphate and betamethasone sodium phosphate. Six gel formulations each of dexamethasone sodium phosphate and betamethasone sodium phosphate prepared using two different polymers carboxymethyl cellulose sodium and hydroxypropyl methylcellulose, in variable proportions. All the formulations subjected for assessment of various physicochemical parameters and mechanical properties. The formulations BSP5 and DSP5, both containing 1.25 % carboxymethyl cellulose sodium, 1.25 % hydroxypropyl methylcellulose, exhibiting mucoadhesive strength of 12.300 ± 0.004 and 12.600 ± 0.01, adhesiveness of 28.04 ± 00 and 30.02 ± 00, cohesiveness of 28.04 ± 00 and 30.02 ± 00, drug release of 86.869 ± 0.380 % and 88.473 ± 0.457 % respectively were considered as promising ones and were further subjected for stability studies and in vivo study in male albino rats. Formulation DSP5 upon oral application for 4 months in arecoline induced oral submucous fibrosis rats, showed more than 80 % reduction in fibrosis as compared with BSP5 which showed nearly 50 % reduction. These results were concluded on the basis of histopathological profile and weight gain among the experimental animals during in vivo study. Hence, DSP5 by minimizing the painful injuries and morbidities justifies being suitable noninvasive model for OSMF treatment.

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ABSTRACT Objective: To evaluate the effectiveness of oil pulling in the management of oral submucous fibrosis (OSMF). Material and Methods: A total of 62 patients clinically and histopathologically diagnosed as OSMF were incorporated in the present study. The subjects are randomly divided equally into two groups, Group A (oil pulling group) and Group B (placebo group). Subjects in Group A were asked to perform OP with sesame oil on an empty stomach in the morning for 3 months and Group B was given placebo capsules for 3 months. Assessment of various clinical parameters was done regularly, and data were analyzed using the Chi-square test. Results: Eighty-two percent had a habit of betel nut chewing, while 18% of the patients had tobacco chewing habits, which were among the main causative factors for OSMF. Clinical improvements in mouth opening, tongue protrusion, difficulty in speech and deglutition, and burning sensation were significant in the Group A. None of the patients reported any discomfort or side effects. The symptoms were not severe in nature and resolved in few days without stopping the therapy. Conclusion: Oil pulling can bring about significant clinical improvements in the symptoms like a mouth opening and tongue protrusion.

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Background: Oral submucous fibrosis (OSMF) is graded according to various histological factors which include the epithelial changes and the connective tissue changes. These features could be identified in routine Hematoxylin and Eosin (H and E) staining in shades of pink. However, the use of special stains provides a contrast to various connective tissue components thereby aiding in better visualization of these connective tissue changes in advanced OSMF cases. Objective:To compare and evaluate muscle involvement and degeneration in advanced oral submucous fibrosis using three different stains namely, H&E, Van Gieson, and Masson's Trichrome. Material and Methods: 10 Formalin-fixed paraffin-embedded tissue sections of advanced OSMFwere stained using 3 different stains namely Hematoxylin and Eosin (H&E), Van-Gieson, and Masson trichrome. The results obtained were tabulated and statistically analyzed using Kruskal Wallis ANOVA. Results: The hyalinization and fibrosis involving the skeletal muscle were better visualized in Masson's Trichrome but were not statistically significant. The muscle degeneration in deeper areas was better visualized in Masson's trichrome when compared to the H&E and Van Gieson. Conclusion: Hematoxylin and eosin stains all the connective tissue components in various shades of pink, use of special stains bestows contrast between different components of connective tissue, thus improvising grading of OSMF. Masson's trichrome stain can be used as a single adjunct to hematoxylin and eosin stain as changes in the superficial and deeper connective tissue could be ascertained (AU)

Contexto: A fibrose submucosa oral (FSO) é classificada de acordo com vários fatores histológicos que incluem alterações epiteliais e do tecido conjuntivo. Essas características podem ser identificadas na coloração de rotina com Hematoxilina e Eosina (H&E) em tons de rosa. No entanto, o uso de colorações especiais fornece um contraste para vários componentes do tecido conjuntivo, auxiliando assim na melhor visualização dessas alterações do tecido conjuntivo em casos avançados de FSO. Objetivo: Comparar e avaliar o envolvimento e degeneração muscular da fibrose submucosa oral avançada usando três colorações diferentes: H&E, Van Gieson e Tricrômio de Masson. Material e Métodos: 10 seções de tecido fixadas em formalina e embebidas em parafina de FSO avançada foram coradas usando essas três colorações. Os resultados obtidos foram tabulados e analisados estatisticamente por meio do teste de Kruskal Wallis. Resultados: A hialinização e fibrose envolvendo o músculo esquelético foram melhor visualizadas no tricromo de Masson, mas não foram estatisticamente significativas. A degeneração muscular em áreas mais profundas foi melhor visualizada no tricrômico de Masson, quando comparado ao H&E e Van Gieson. Conclusão: Hematoxilina e Eosina coloram todos os componentes do tecido conjuntivo em vários tons de rosa. O uso de colorações especiais confere contraste entre os diferentes componentes do tecido conjuntivo, melhorando assim a avaliação da FSO. A coloração com tricrômio de Masson pode ser usada como um único adjunto para a coloração de Hematoxilina e Eosina, pois assim é possível verificar alterações superficiais e profundas no tecido conjuntivo. (AU)

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ABSTRACT Objective: To evaluate and compare lipid profile level in oral submucous fibrosis (OSMF), oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) patients. Material and Methods: Thirty histopathologically diagnosed subjects each of OL, OSMF, OSCC were recruited along with 30 healthy controls. 5ml of venous blood is collected and estimated using standard diagnostic kits. Results: The mean of Total cholesterol level in controls was 219.03 mg%, in OSCC, OL and OSMF was 142.89 ± 10.21mg%, 155.44 ± 17.63 mg% and 180.60 ± 13.25 mg%, respectively. The mean low-density lipid level in controls was 137.24 mg and in OSCC, OL and OSMF groups were 109.28 ± 2.16 mg%, 126.63 ± 0.85 mg% and 119.15 ± 0.93 mg%, respectively. The mean of high-density lipid level in controls, OSCC, OL and OSMF was 42.87 ± 0.42 mg%, 36.50 ± 2.31 mg%, 21.13 ± 0.77 mg% and 28.37 ± 1.11mg%, respectively. The mean of very low density lipids level in controls, OSCC, OL and OSMF was 30.12 ± 1.51 mg%, 17.24 ± 0.80 mg%, 22.25 ± 0.93 mg% and 25.89 ± 0.43 mg%, respectively. The mean triglyceride level in controls, OSCC, OL and OSMF was 118.80 ± 9.47 mg%, 91.2 ± 3.03 mg%, 105.05 ± 2.96 mg% and 106.19 ± 3.09 mg%, respectively. Conclusion: Lipid profile levels could be early indicators of precancer and cancer.

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Abstract Objective: To determine the maximum bite force (MBF) in oral submucous fibrosis (OSMF) patients and to compare them with that of healthy subjects. Material and Methods: Twenty patients who were clinically confirmed, as OSMF and 20 healthy controls matched for age, gender, and number of intact functional teeth were included in this study. For each subject, age, gender, weight, height and body mass index (BMI) were recorded. The MBF registration was carried out by the two evaluators, who were previously calibrated. Bite force was measured in the first molar region using a force transducer occlusal force meter for each subject seated at the upright position, with Frankfort's plane nearly parallel to the floor, and no head support. The Student's independent t-test was used to determine the statistical significance in relation to mean height, weight, BMI and the presence of number of intact teeth and MBF between the healthy subjects and OSMF individuals. A comparison of grades of OSMF with all variables was carried out by one-way ANOVA test. Results: No significant difference was found in mean age, mean height, weight, BMI and the presence of the number of intact teeth between healthy individuals and OSMF patients. The mean MBF in healthy subjects was 628.23 ± 24.39 N and 635.47 ± 31.22 N in OSMF patients. Even though the healthy subjects reported a higher MBF than OSMF patients did, the difference was statistically non-significant. With regards to sides, no significant difference was observed in mean MBF in healthy subjects and OSMF patients on the right (p=0.7818) and left side (p=0.6154). Conclusion: The healthy subjects reported higher MBF values than OSMF patients did and the difference was statistically non-significant.

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Objective: To determine the prevalence of Candida species in the saliva of patients with clinically suspected oral potentially malignant disorders (OPMD) and healthy cohorts. Material and Methods: Unstimulated saliva was collected from patients with OPMD (n=100) and age and sex matched healthy subjects (n=170). The samples were inoculated onto Sabouraud Dextrose Agar and incubated for a week. The colonies of the isolates were enumerated using a colony counter. The isolates were identified using standard phenotypic methods. The significance of oral candidal carriage was calculated using Independent T test. Odds and Risk ratio was calculated using Pearson's Chi-square test. Results: Oral candida carriage was present in 51% of patients with OPMD while healthy cohorts had a prevalence of 20.6%. A good statistical significance was observed for the prevalence of oral candidal carriage for patients with OPMD in comparison to healthy cohorts (p=0.013). Significant Odds and risk ratio was observed for the prevalence of Candida species among OPMD. Majority of the isolates in both groups were C. albicans. Colony forming units were high among patients with OPMD. Conclusion: A significant association of oral candidal carriage to oral potentially malignant disorders in comparison to healthy cohorts was observed. Candidal species may be potent risk factor for transition of OPMD to oral Squamous Cell Carcinoma.

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Background: Oral submucous fibrosis (OSMF) is a potentially malignant disorder largely seen in the South-Asian countries where areca nut is found to be the main predisposing factor. Pentoxifylline, a methylxanthine derivative, has vasodilating properties and is believed to increase the vascularity of the mucosal layer. This study was designed to determine the effect of pentoxifylline (Trental) on the clinical progression of oral submucous fibrosis. Aim: The present study was aimed to evaluate the effectiveness of drug pentoxifylline in the management of OSMF and to correlate the clinical parameters evaluated before and after treatment. Methods: Study Design: This investigation was conducted as a case-control study incorporating a Control Group in comparison to a Study Group where pentoxifylline 400 mg was administered 3 times daily, as coated, sustainedrelease tablets for prescribed for 3 months. The stipulated period for the study was 8 months and a total of 80 cases of oral submucous fibrosis (40 test subjects and 40 controls) were included in this study and 100% acquiescence was reported at the end of the test period. Results: Mild dizziness and gastric irritation were the only untoward symptoms reported in 2 of the volunteers in the study group during this trial. These were managed by diet protocols. A review of the patients and controls was done at an interval of every 4 weeks for 3 months. The subjective and objective measurements were recorded. The follow-up data at each visit concerning each other and to base-line values were calibrated using nonparametric tests of the Chi-Square test and Mann-Whitney. Significant comparisons with regard to improvement were recorded as objective criteria of mouth opening (u value =1.137, p = 0.260), tongue protrusion (u value = 0.262, p = 0.794 and cheek flexibility (u value =0.990, p = 0.326). Subjective symptoms of burning sensation of mouth (U value = 2.673, p = 0.008), pain on opening the mouth (U value = 4.320, p < 0.0001), difficulty in swallowing and difficulty in the speech were also recorded. Conclusion: This study showed the effectiveness of pentoxifylline as an additional therapy in the routine management of oral submucous fibrosis.

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