Estimation of serum, salivary immunoglobulin G, immunoglobulin A levels and total protein, hemoglobin in smokeless tobacco chewers and oral submucous fibrosis patients

Background: Oral submucous fibrosis (OSMF) is a debilitating, potentially cancerous oral condition. Although areca nut is the most important causative agent, it is also considered that the disease is immunologically mediated. Aim of the Study: To establish that autoimmunity and nutritional deficiency play a role in the etiopathogenesis of OSMF. Objectives of the Study: To show that serum immunoglobulin markers (immunoglobulin-G [IgG], immunoglobulin-A [IgA]) and nutritional parameters such as total serum protein (TSP), Hemoglobin (Hb) play a role in causing OSMF and also to correlate serum, salivary IgG, IgA levels in OSMF patients. Settings and Design: A case-control study was done with 50 patients (25 patients who were provisionally diagnosed as OSMF - Group I, and 25 patients who were chronic smokeless tobacco chewers and who did not have any intraoral lesion - Group II). Materials and Methods: Five milliliters of blood and saliva were collected from both the groups. Quantitative analysis of serum, and salivary IgG, IgA was done by turbidometric immunoassay. TSP and Hemoglobin (Hb) were estimated by spectrophotometry. Statistical Analysis: Results were analyzed by independent samples t-test and one-way analysis of variance (ANOVA). Results: All patients of OSMF showed significant (P < 0.01) increase in serum IgG, IgA, and salivary IgG levels as compared to smokeless tobacco chewers. The salivary IgA levels showed a significant decrease in OSMF patients (P < 0.05). TSP and Hb levels showed significant (P < 0.01) decrease in OSMF patients as compared to smokeless tobacco chewers. Conclusion: The elevation of immunoglobulin levels supports the concept of autoimmunity. The decrease in TSP and Hb suggests that nutritional deficiency plays a defined role in the occurrence as well as a further progression of OSMF

Inflammation induced insulin resistance is associated with DNA methylation changes in vascular endothelial cells

Vascular insulin resistance manifests in decreased production of nitric oxide subsequently leading to vasoconstriction and atherosclerosis. Inflammatory molecules such as IL-6 are known to induce insulin resistance in vascular endothelial cells. Epigenetic mechanisms including promoter DNA methylation have been demonstrated in development and progression of metabolic disorders and atherosclerosis. However, precise and underlying epigenetic mechanisms governing vascular insulin resistance are not known. Human endothelial cells treated with a) IL-6 and insulin together, b) pretreated with IL-6 and c) hyperinsulinemic conditions induced vascular insulin resistance leading to decreased Akt/eNOS activation and subsequently stabilized STAT3 phosphorylation. In 3D spheroid and matrigel assays, IL-6 abrogated insulin effects on angiogenesis. IL-6 induced insulin resistance was associated with down regulation of DNMT1 and DNMT3B, but not DNMT3A and resulted in decreased enzyme activity leading to global DNA hypomethylation. Protein levels of DNMT1 and DNMT3B were inversely correlated with S-phase of cell cycle. CpG microarray analysis revealed hypomethylation of promoters associated with 199 genes and promoter hypermethylation of 98 genes. Further, methylation status of promoters of genes associated with insulin signaling and angiogenesis such as RPS6KA2, PI3KR2, FoxD3, Exoc7, MAP3K8, ITPKB, EPHA6, IGF1R and FOXC2 were validated by bisulfite sequencing. Differentially methylated CpG sites of four out of five hypomethylated genes harboured putative binding site for HMGB1, a potent inflammatory mediator, suggesting HMGB1 might serve as epigenetic switch facilitating a pro-inflammatory milieu in response to IL-6 in endothelial cells. Our data indicates causal link between IL-6 induced DNMT1 changes and altered gene expression involved in insulin signaling and angiogenesis

Oral gingival metastasis: A diagnostic dilemma

Oral cavity is a rare target for metastasis with an incidence of 1% among all oral cancers. In 24% of such cases, oral metastasis is the first indication of an undiagnosed primary. Metastatic oral malignancies have been reported in the mandible, tongue, and gingiva. Although gingival metastasis has been reported from lung, prostate, rectal carcinoma in men and carcinoma of breast, adrenal glands, and genitalia in females, gingival metastasis from carcinoma of the penis has not been reported. Herein, a case of metastatic gingival carcinoma that developed after extraction of teeth from primary carcinoma of the penis is presented. An extensive literature search revealed no such similar case reports