An enigmatic pathogenetic mechanism of hypoxia inducible factor - 1/2 alpha in the progression of fibrosis of oral submucous fibrosis and its malignant transformation: A systematic review and meta-analysis.

OBJECTIVE: Oral submucous fibrosis is a frequently reported potentially malignant disorder characterized by fibrosis and a malignant transformation rate of 7-30%. The role of hypoxia-inducible factor-1/2α in malignant transformation mechanisms of oral submucous fibrosis remains uncharted territory owing to a scarcity of studies. Thus the present systematic review and meta-analysis aimed to determine the role of hypoxia-inducible factor-1/2α in the progression of fibrosis of oral submucous fibrosis and its malignant transformation. MATERIAL AND METHODS: Using PubMed, Google Scholar, and Cochrane Library databases, full-text articles that investigated hypoxia-inducible factor-1/2α in oral submucous fibrosis were entailed for review. A modified Newcastle-Ottawa scale was employed to evaluate risk of bias in all articles and Review Manager was utilized for meta-analysis. RESULTS: Eighteen and eight qualified articles respectively were included for qualitative and quantitative data synthesis. Progressive upregulation of hypoxia-inducible factor-1/2α in oral submucous fibrosis is associated with fibrosis-induced carcinogenesis. A Random-effects model uncloaked that oral submucous fibrosis cases with significantly increased expression of hypoxia-inducible factor-1α had an increased associated risk of malignant transformation compared with controls (combined odds ratio 523.83, 95% confidence interval 125.74- 2182.28, p < 0.00001). CONCLUSION: The existing evidence substantiates the notion that hypoxia-inducible factor-1/2α, a fundamental pathogenetic mechanism of progression and malignant transformation of oral submucous fibrosis in the background of fibrosis.

Salivary transforming growth factor beta in oral submucous fibrosis: A diagnostic and predictive marker.

CONTEXT: Growth factors and cytokines like transforming growth factor beta (TGF-ß) play a key role in the pathogenesis of oral submucous fibrosis. AIMS: To elucidate the role of Salivary TGF-ß isoforms as a predictive and diagnostic marker for oral submucous fibrosis. SETTINGS AND DESIGN: A total of 30 OSMF and 10 control patients were included in this study, and their clinic-epidemiological data was recorded. METHODOLOGY: The expression of TGF-ß genes-TGF-ß1, TGF-ß2, TGF-ß3-was studied by a real-time polymerase chain reaction in tissue and saliva. Patients were given medicinal intervention for 12 weeks along with jaw-opening exercises. Expression of salivary TGF-ß genes was studied at 12 weeks. STATISTICAL ANALYSIS USED: SPSS software version 20. RESULT: Expression of salivary TGF beta isoforms in OSMF was more than in the control group. There was an increase in salivary TGF-ß1, ß2, ß3 expressions with increasing clinical grades of OSMF and advancing the stage of the disease. Expression of all the TGF beta isoforms was decreased after treatment with statistically significant results. Statistically significant correlations were found between the mean difference of TGF-ß1 and the mean difference between mouth opening and tongue protrusion. CONCLUSION: Salivary TGF-ß isoforms may be used in diagnosis, risk assessment, and screening of the entire population at risk of OSMF after its clinical validation. However, adequate sample size and segmental assessment of the expression of TGF-ß isoforms are needed for further evaluation.

Prognostic implications of CD-57 expression in oral squamous cell carcinoma cases.

Natural killer (NK) cells are one of the most important effector T -lymphocytes having antitumor effect. Only a few studies are present in the literature, correlating the expression of cluster of differentiation 57 (CD-57) in NK cells in oral squamous cell carcinoma (OSCC). To analyze the effect of the presence of NK cells in the stroma of OSCC and their effect on the tumor progression and prognosis. A retrospective study was performed over 122 OSCC patients who had undergone surgical treatment between 2014 and 16. Wax blocks were obtained and subjected to immunohistochemical (IHC) analysis for CD-57 expression. Patients were followed up for 3 years and 100 cases were finally included in the study and divided into three groups. The association between variable were studied through the Chi-square test, Kruskal-Wallis test, and Mann-Whitney U test. A total of 91% of cases showed positive staining for CD-57. Maximum positive expression (96.6%) was observed in the patients who were alive and without recurrence (Group-II) as compared to dead patients (Group-I) and in well-differentiated squamous cell carcinoma (WDSCC) cases (96.8%) than in poorly differentiated cases. Also, the mean CD-57 positive cells count was found to be highest in Group-II and WDSCC cases. A significant correlation was observed between CD-57 expression and patients' health status. As the expression of CD-57 increased in the tumor stroma of OSCC, the chances for the patient to be alive were increased; therefore, it may serve as a good prognostic marker.

An Analysis of Xpert Test for Diagnosing Maxillofacial Tuberculosis.

Background: Maxillofacial tuberculosis is a diagnostic challenge for surgeons. The aim of this study was to present a detailed analysis of Xpert test in diagnosing maxillofacial tuberculosis and to analyse the accuracy of Xpert test results for various tissues of maxillofacial region. Materials and Methods: In this cross-sectional study, patients were selected randomly from outpatient department. The patients who had clinical picture and differential diagnosis highly suggestive of maxillofacial tuberculosis were included. Patients were divided into three different groups depending upon the site of involvement. The samples collected from the patients were further subdivided depending upon the type of specimen. Patients were screened first by routine tests, and the negative cases were followed by Xpert test for tuberculosis. Results: A total of 54 patients were enrolled in the study, 13 patients were found to be positive for maxillofacial tuberculosis on routine screening tests for tuberculosis, and 41 tested negative on routine test and were evaluated further through Xpert test. Specimens from bone (n12), soft tissue and skin biopsy (n15) and aspirates from lymph nodes (n14) were obtained and tested. Twenty-one samples were found to be positive, and 20 were negative upon Xpert testing. There was a statistically significant difference seen between the test groups (p < 0.01) with higher frequency of negative results in routine test. The p value for various specimens containing pus, biopsies and aspirates was 0.045, 0.023 and 0.067, respectively. Conclusion: Xpert test is more accurate when compared to routine test for diagnosing maxillofacial tuberculosis. Although accuracy of Xpert test is better for pus and biopsy samples in the specimens from bone and soft tissue, it gives poor accuracy for aspirated cells. The aspirates from lymph nodes were more susceptible for false negative test.

Oncocytoma of the parotid gland: A rare benign tumour.

Oncocytomas are one of the infrequent neoplasms seen in the oral cavity accounting for less than 2% of all neoplasms in the oral cavity with less than 1% chance of malignant transformation. They affect the major salivary glands and have a female predilection. The cognisance of the unique clinical and histopathological features is very important to conclude a confirmatory diagnosis. This paper reviews a case of oncocytoma presented in our department and also elucidates the diagnostic criteria for the same.

Insights of dental postgraduate students and guides toward change in MDS examination pattern: A cross-sectional study.

Introduction: According to the notification dated May 17, 2018, no. DE-14-MDS-2018/2131 published by the Dental Council of India, basic sciences theory examination (Paper-1) will be conducted before the commencement of II-year MDS academic year instead of III-year MDS end. Hence, this study was conducted to assess the opinions regarding this recent change in the curriculum among I MDS students, II MDS students, and their respective postgraduate (PG) guides. Methodology: The study was conducted on 120 participants from three dental colleges. All the participants were interviewed using a pretested, structured questionnaire. The initial part of questionnaire consisted of demographic information of the study participants followed by ten questions targeted to assess the perception toward change in MDS examination pattern. Statistical analysis was performed using SPSS software v20, and Chi-square test was used for comparison of responses among PG students and PG guides. Results: Questions pertaining to the need of allowed to keep term (ATKT), assumption to improved concentration on specialization subjects, and increase in understanding of the subject have received maximum positive response. Negative responses were more for the questions such as hampering of PG curriculum, effect on dissertation selection process, and rendering quality treatment to the patient. Responses to necessity of ATKT and the assumption to better concentrate on specialization subject later differed significantly among the participants. Conclusion: The present study results revealed an overall positive perception toward the change in MDS curriculum pattern among the study participants.

Evaluation of the effect of nonsurgical periodontal therapy on malondialdehyde and 8-hydroxy deoxyguanosine levels in chronic periodontitis.

Background: Reactive oxygen species released on stimulation by periodontal pathogens cause oxidation of biomolecules and play significant role in periodontal disease pathogenesis. Aim: This study aimed to evaluate the levels of oxidative by-products malondialdehyde (MDA) and 8-hydroxy deoxyguanosine (8-OHdG) as biomarkers in chronic periodontitis patients compared to healthy as well as before and after nonsurgical periodontal therapy. The correlation between biomarkers and clinical attachment level was also evaluated. Settings and Design: A total of 112 subjects were included in this study. The subjects were divided into two groups (Group I included 56 healthy subjects and Group II constituted 56 chronic periodontitis patients) on the basis of clinical periodontal parameters. Materials and Methods: Group I subjects received no treatment and were evaluated once only for clinical and oxidative stress biomarker parameters. Nonsurgical periodontal therapy was carried out in Group II patients and they were evaluated at baseline and 3 months after therapy. Results: Both salivary and serum levels of MDA and 8-OHdG were found to be increased in chronic periodontitis patients as compared to healthy subjects. After nonsurgical periodontal therapy, the levels of MDA and 8-OHdG significantly reduced. Linear correlation between clinical attachment level and oxidative stress parameters was found to be positive and highly significant. Conclusion: It can be concluded that periodontal therapy is effective in improving the oxidative stress condition.

Development of Topical Gel of Methotrexate Incorporated Ethosomes and Salicylic Acid for the Treatment of Psoriasis.

BACKGROUND: There is an unmet need for optimized drug delivery system of psoriasis therapy because of various issues like adverse reaction, permeation problem associated with convention treatment (oral and topical) available for psoriasis. OBJECTIVE: The goal was to develop an ethosomal gel of methotrexate (MTX)-incorporated ethosomes and salicylic acid (SA) and to evaluate and study its ethosomal gel potential in Imiquimod-induced psoriasis animal model to treat symptoms of psoriasis. METHODS: MTX-SA ethosomal gel was prepared by the cold method given by Touitou et al. and optimized by comparing it with MTX ethosomal gel and drug solution. Particle size, zeta potential, entrapment efficiency, and ex-vivo study were selected as the critical quality checking attributes. Psoriatic Area and Severity Index (PASI) score & histopathological examination were done for checking Antipsoriatic potential of MTX-SA ethosomal gel by using the imiquimod-induced psoriasis model. RESULTS: Optimized MTX-SA exhibited a particle size of 376.04 ± 3.47nm, EE(Entrapment efficiency) of 91.77 ± 0.02%. At the end of 24h, MTX-SA ethosomal gel exhibited a slow and prolonged release of MTX (26.13 ± 1.61% versus 6.97 ± 0.06%) compared to MTX drug solution. It also attributes of 43% retention study as compared to drug solution (13%). Besides, it essentially decreased the PASI score with the recuperation of normalcy of the mice's skin, while the MTX-SA gel displayed indications of gentle hyper and parakeratosis toward the completion of investigation when contrasted with the blank gel. CONCLUSION: The developed MTX-SA ethosomal gel formulation can be a promising alternative to existing MTX formulation in topically treating psoriasis.

Nanocrystalization: An Emerging Technology to Enhance the Bioavailability of Poorly Soluble Drugs.

Most of the active pharmaceutical ingredient used in the management of disease have poor water solubility and offer grueling problems in drug formulation development since low solubility is generally associated with poor dissolution characteristics which leads to poor oral bioavailability. The great challenge for the development of a pharmaceutical product is to create its new formulation and drug delivery system to limit solubility problems of existing drug candidate. Limited drug-loading capacity requires a large amount of carrier material to get appropriate encapsulation of the drug, which is another major challenge in the development of pharmaceutical product which could be resolved by developing nanocrystals (NCs). A significant research in the past few years has been done to develop NCs which helps in the delivery of poorly water soluble drugs via different routes. The technology could continue to thrive as a useful tool in pharmaceutical sciences for the improvement of drug solubility, absorption and bioavailability. Many crystalline compounds have pulled in incredible consideration much of the time, due to their ability to show good physical and chemical properties when contrasted with their amorphous counterparts. Nanocrystals have been proven to show atypical properties compared to the bulk. This review article explores the principles of the important nanocrystallization techniques including NCs characterization and its application.

Age estimation by dentin translucency measurement using digital method: An institutional study.

AIMS: The aims of the present study were to measure translucency on sectioned teeth using available computer hardware and software, to correlate dimensions of root dentin translucency with age, and to assess whether translucency is reliable for age estimation. MATERIALS AND METHODS: A pilot study was done on 62 freshly extracted single-rooted permanent teeth from 62 different individuals (35 males and 27 females) and their 250 µm thick sections were prepared by micromotor, carborundum disks, and Arkansas stone. Each tooth section was scanned and the images were opened in the Adobe Photoshop software. Measurement of root dentin translucency (TD length) was done on the scanned image by placing two guides (A and B) along the x-axis of ABFO NO. 2 scale. Unpaired t-test, regression analysis, and Pearson correlation coefficient were used as statistical tools. RESULTS: A linear relationship was observed between TD length and age in the regression analysis. The Pearson correlation analysis showed that there was positive correlation (r = 0.52, P = 0.0001) between TD length and age. However, no significant (P > 0.05) difference was observed in the TD length between male (8.44 ± 2.92 mm) and female (7.80 ± 2.79 mm) samples. CONCLUSION: Translucency of the root dentin increases with age and it can be used as a reliable parameter for the age estimation. The method used here to digitally select and measure translucent root dentin is more refined, better correlated to age, and produce superior age estimation.

Estimation of gingival crevicular blood glucose level for the screening of diabetes mellitus: A simple yet reliable method.

AIM: This study was designed to assess the reliability of blood glucose level estimation in gingival crevicular blood(GCB) for screening diabetes mellitus. MATERIALS AND METHOD: 70 patients were included in study. A randomized, double-blind clinical trial was performed. Among these, 39 patients were diabetic (including 4 patients who were diagnosed during the study) and rest 31 patients were non-diabetic. GCB obtained during routine periodontal examination was analyzed by glucometer to know blood glucose level. The same patient underwent for finger stick blood (FSB) glucose level estimation with glucometer and venous blood (VB) glucose level with standardized laboratory method as per American Diabetes Association Guidelines.1 All the three blood glucose levels were compared. Periodontal parameters were also recorded including gingival index (GI) and probing pocket depth (PPD). RESULTS: A strong positive correlation (r) was observed between glucose levels of GCB with FSB and VB with the values of 0.986 and 0.972 in diabetic group and 0.820 and 0.721 in non-diabetic group. As well, the mean values of GI and PPD were more in diabetic group than non-diabetic group with the statistically significant difference (p < 0.005). CONCLUSION: GCB can be reliably used to measure the blood glucose level as the values were closest to glucose levels estimated by VB. The technique is safe, easy to perform and non-invasive to the patient and can increase the frequency of diagnosing diabetes during routine periodontal therapy.

Clinical evaluation of the role of tulsi and turmeric in the management of oral submucous fibrosis: A pilot, prospective observational study.

The aim of the present study was to investigate the clinical efficacy of herbal medicines (1 gm tulsi and 1 gm turmeric mixed in glycerine base) for the treatment of oral submucous fibrosis (OSMF). Forty-one patients in the age group of 17- 56 years without any systemic complications were included in the study. The patients were treated with medicines, which were to be applied 3-4 times a day. Blood samples were collected before and after treatment to screen for any systemic changes due to these medications. Burning sensation and mouth opening were recorded before and after treatment. Patients were followed up on monthly subsequent visits for three months. Changes in the burning sensation on visual analogue scale (VAS) scale and difference in the mouth opening were analyzed statistically. A statistically significant improvement was seen in both burning sensation and mouth opening. Tulsi and turmeric offers a safe and efficacious combination of natural products available for symptomatic treatment of OSMF.

Evaluation of exfoliative cytology in the diagnosis of oral premalignant and malignant lesions: A cytomorphometric analysis.

BACKGROUND: Many oral squamous cell carcinomas (OSCCs) arise within regions that previously had premalignant lesion. Early diagnosis and prompt treatment of premalignant lesions offers the best hope of improving the prognosis in patients with OSCC. Exfoliative cytology is a simple and non-invasive diagnostic technique that could be used for early detection of oral premalignant and malignant lesions. This study was undertaken to evaluate the quantitative changes in nuclear area (NA), cytoplasmic area (CA) and nuclear-to-cytoplasmic ratio (NA/CA) in cytological buccal smears of oral leukoplakia with dysplasia (OLD) and OSCC patients while comparing with normal healthy mucosa. MATERIALS AND METHODS: A quantitative study was conducted over 90 subjects including 30 cases each of OLD, OSCC and clinically normal oral mucosa. The smears obtained were stained with Papanicolaou (PAP) stain and cytomorphological assessment of the keratinocytes was carried out. The statistical tools included arithmetic mean, standard deviation, Chi-square test, analysis of variance, Tukey multiple comparison. P < 0.001 was considered as significant. RESULTS: The mean NA of keratinocytes in the normal mucosa was 65.47 ± 4.77 µm(2) while for OLD it was 107.97 ± 5.44 µm(2) and 139.02 ± 8.10 µm(2) for that of OSCC. The differences show a statistically significant increment in NA (P < 0.001). There was significant reduction (P < 0.001) in the CA of keratinocytes from OSCC when compared with those from smears of OLD and normal mucosa with the values of 1535.80 ± 79.38 µm(2), 1078.51 ± 56.65 µm(2) and 769.70 ± 38.77 µm(2) respectively. The NA/CA ratio in the smears from normal oral mucosa, OLD and OSCC showed a mean value of 0.043 ± 0.004, 0.100 ± 0.008, 0.181 ± 0.015 respectively with a significant difference among the groups (P < 0.001). CONCLUSION: Evaluation of nuclear and CA of keratinocytes by cytomorphometry can serve as a useful adjunct in the diagnosis and prognosis of a dysplastic lesion which may lead to OSCC.

Immunohistochemical analysis of tenascin expression in different grades of oral submucous fibrosis.

AIM: Tenascin, a glycoprotein, is one of the major constituents of extracellular matrix, which may function in organizing the stroma in normal and pathological conditions. The study aimed to correlate the structural organization of tenascin with the pathological progression of disease from early, moderate and advanced changes in oral submucous fibrosis (OSMF). STUDY DESIGN: A retrospective cross-sectional immunohistochemical (IHC) analysis of OSMF cases was performed. Total 70 slide samples were prepared for the study from 35 formalin-fixed paraffin-embedded tissue blocks with 10 each from histologically proven and graded as early, moderate and advanced OSMF and 5 of normal oral mucosa. The IHC sections were analyzed for the intensity and pattern of tenascin expression at the junction of epithelium and connective tissue (ECJ) and deeper connective tissue (CT), as well as presence or absence of staining around inflammatory cells, fibroblast and endothelial cells using anti-human tenascin. RESULT: Most of the OSMF cases showed retention of antigen at ECJ and in deeper CT. Its expression varied in different grades as well as around inflammatory cells, fibroblast and endothelial cells in same tissue section. Highly significant P values of 0.001 and 0.003 were obtained for tenascin intensity and pattern, respectively, at ECJ in different OSMF grades. In addition, for the expression of tenascin pattern in deeper CT among different OSMF grades, a significant P value of 0.018 was obtained. CONCLUSION: A differential expression of tenascin was observed with the progression of disease. The expression of tenascin as bright and continuous deposition at ECJ in early and moderate stages of OSMF signifies either proliferative organization within the overlying epithelium or an epithelial-mesenchymal interaction. However, a weak immunoreactivity of tenascin at ECJ was observed in advanced stage of OSMF.

Association of Ki-67 antigen and p53 protein at invasive tumor front of oral squamous cell carcinoma.

AIM: Studies reveal that invasive tumor front may be the best field for quantification of proliferative and apoptotic markers. The current study assessed the expression of Ki-67 antigen and p53 protein at invasive tumor front of oral squamous cell carcinoma (OSCC) and correlated the immunostaining with the histologic grades of malignancy. MATERIALS AND METHODS: A total of 80 slides sample was prepared for the study, one each from ten normal oral mucosa cases and two each from 30 OSCC cases. The OSCC patients were biopsied along invasive tumor front, and samples were immunohistochemically analyzed for the expression of both Ki-67 antigen and p53 protein. RESULTS: Of the total 30 OSCC cases, the expression of p53 was found positive in 20 cases (66.6%), while Ki-67 expression was found positive in 21 cases (70%). All the cases in the control group were negative. A higher p53 and Ki-67 expression were seen in OSCC group as compared to normal mucosa. On comparing the control group with various grades of OSCC a statistically significant result was obtained. CONCLUSION: Higher and statistically significant expression was noted for both p53 and Ki-67 antigen. The results emphasize the potential of Ki-67 and p53 as biomarkers of carcinogenesis in OSCC. Ki-67 expression was comparatively higher when compared with p53 except in poorly differentiated squamous cell carcinoma and signifies actively proliferating malignant cells at invasive tumor front.

Contemporary practice in forensic odontology.

Forensic odontology plays a major role in the identification of those individuals who cannot be identified visually or by other means. The unique nature of dental anatomy and placement of custom restorations ensure accuracy when the techniques are correctly employed. It is evident that identification of victims in accidents and natural calamities is of utmost importance and is a challenging task. The teeth may also be used as weapons and under certain circumstances; they may provide information regarding the identity of the biter. Dental professionals play a major role in keeping accurate dental records and providing all necessary information so that legal authorities may recognize malpractices, negligence, fraud child abuse and also, identify an individual. In this article, we will discuss such evolvement of the subject.

Prevalence based epidemiological cancer statistics: a brief assessment from different populations in India.

Modern civilization, urbanization, industrialization, changes in daily life, population growth and ageing all have contributed to epidemiological changes in many diseases, including cancer, in India and other countries. Tobacco has been identified as the most important cause of cancer followed by alcohol consumption, dietary practices, inadequate physical activity, infections due to viruses and sexual behavior. The total number of new cancer cases is increasing rapidly, due to growth in size of the population, and an increase in the proportion of elderly persons, as a result of improved life expectancy, following control of communicable diseases. Such changes in the age structure automatically alter the disease pattern associated with ageing and increase the burden of problems such as cancer, cardiovascular and other non-communicable diseases in the society. Knowledge based on epidemiological patterns and trends would be of great help in identifying persons at high risk for the development of a particular cancer. Public education on 'tobacco and its health hazards', recommended dietary guidelines, safe sexual practices, and lifestyle modifications form the scientific basis for planning and organizing prevention, diagnosis and treatment of cancer in a community. Moreover, incorporating screening for cervical, breast and oral cancers into the peripheral health infrastructure can have a significant effect on reducing mortality from these diseases. This paper highlights the incidence and prevalence based epidemiological cancer statistics, its early detection and prevention measures in India.

Determination of sex by radiographic analysis of mental foramen in North Indian population.

AIM: Identification and determination of sex of unknown human skeletal remains has been one of the most challenging tasks for forensic dentistry. The purpose of this study was to determine the gender from the analysis of mental foramen on panoramic radiographs in a north Indian population. MATERIALS AND METHODS: One hundred radiographs were selected for the analysis of mental foramen. Tangents were drawn to the superior and inferior borders of the foramen and perpendiculars were drawn from the tangents to the lower border of the mandible (S-L and I-L). The data obtained were tabulated and subjected to statistical analysis. RESULTS: The average values of S-L and I-L were significantly higher in males than in females, while the distances for the right and left sides of an individual were almost similar in both the male and the females group, and the results were non-significant. CONCLUSION: The distances from the mental foramen to the lower border of the mandible exhibit sexual dimorphism in the north Indian population.

Oral squamous cell carcinomas in age distinct population: a comparison of p53 immunoexpression.

AIMS: The study aimed to assess the diffused expression of p53 protein in patients with OSCC and its association with age at diagnosis (using 50 years as a cut point). STUDY DESIGN: Ten normal oral mucosa and sixty OSCC lesions from age-distinct patient populations were immunohistochemically analyzed for the expression of p53 protein. RESULTS: In OSCC cases, 31 out of total 60 cases (51.67%) showed positive expression for p53 protein and it was more common in older study group (56.67%) than in younger study group (46.67%) but the difference was not statistically significant. Moreover, there was also no significant difference in the p53 indices (percentage of p53 positive cells) between the two study groups (P = 0.827). CONCLUSION: The alteration rates were found to be slightly higher in older patients although not statistically significant.