First Molars in Permanent Dentition and their Malformations in Various Pathologies: A Review.

Permanent maxillary and mandibular first molars are the first permanent teeth to erupt into the oral cavity along with the mandibular incisors. It serves as an excellent record of maternal and fetal health, reflecting the prenatal, perinatal, and postnatal health and diseases. This review focuses on the molar morphogenesis, molar malformations, their etiopathogenesis, and pathologies causing specific pattern of molar malformations.

Basics of Epigenetics and Role of Epigenetics in Diabetic Complications.

The term "Epigenetics" includes mechanisms by which genetic expression is altered without a change in the underlying DNA sequence. The changes caused by epigenetic mechanisms are inheritable and are one way in direction (irreversible) and also explains why there is differences in genetic expressions of monozygotic twins. The epigenetic mechanisms alter the genetic expressions through DNA methylation, posttranslational modifications (PTMs) of histone, and noncoding RNAs. DNA methylation and histone PTMs cause relaxation or condensation of chromatin units. The epigenetic actions of noncoding RNAs such as microRNAs, small nucleolar RNAs, small interfering RNAs, and long noncoding RNAs act by modifying transcription factors or by degrading target messenger RNAs and their translation factors. Various pathologies and environmental factors cause changes in the cellular epigenetic mechanisms and the epigenetic alterations occurring in diabetes mellitus (DM) are reviewed. DM causes hemodynamic changes and metabolic changes like hyperglycemia and dyslipidemia. These changes induce oxidative stress and activate intracellular signaling and kinases in the target cells. Epigenetic alterations cause chromatin remodeling and altered gene expression leading to inflammation, proliferation, atrophy, hypertrophy, etc.; thereby, diabetic complications such as neuropathy, nephropathy, vasculitis result in the corresponding target organ. When these epigenetic alterations persist for a longer period without intervention, the target cells attain "metabolic memory" meaning that these epigenetic mutations cannot be reversed even after attaining normal blood glucose levels. Thus, epigenetics, an insightful and efficient tool in genomic research, has started crawling into the research arena and needs to reach leaps and bounds for the better understanding of health and diseases.

Cytogenetic analysis of genetic damage in young individuals exposed to chronic mechanical irritation in the lateral border of the tongue due to sharp teeth - a novel study.

BACKGROUND: Chronic inflammation is estimated to contribute to approximately 25% of human cancers. Inflammation can be induced by chronic mechanical irritation which can lead to oral pre-cancer and oral cancer. Though many studies have been conducted to identify the genetic damage in oral cancer or dysplastic stages, no study has been conducted so far on early detection of genetic damage in healthy individuals presenting with sharp teeth in contact with the lateral border of the tongue. OBJECTIVE: The study is aimed at analyzing the genetic damage (micronuclei) in healthy individuals with sharp teeth in contact with the lateral border of the tongue causing chronic mechanical irritation. METHODS: The study group included 75 clinically healthy individuals with sharp teeth in contact with the lateral border of the tongue and 25 clinically healthy individuals with normal teeth in contact with the lateral border of the tongue as a control group. Brush samples of epithelial cells were collected, then spread over clean glass slide and fixed in 100% alcohol, stained with rapid PAP and analyzed under the light microscope. The exfoliated cells were examined to detect micronuclei. RESULTS: Micronuclei frequency was found to be increased in the study group where sharp teeth were in contact with the lateral border of the tongue of healthy individuals without deleterious habits such as usage of tobacco in smoking/smokeless form, areca nut chewing or alcohol consumption. CONCLUSIONS: Cytogenetic analysis is a simple and scantly invasive technique allowing clinicians the early detection of DNA damage in patients with sharp teeth and subsequently preventing carcinogenesis by proper treatment and follow-up.

Molecular Insight into Odontogenesis in Hyperglycemic Environment: A Systematic Review.

Diabetes mellitus is an endocrinal disorder affecting worldwide and the disease incidence is rising alarmingly high. The effects of diabetes on tooth development are explored by limited studies and their molecular insights are very rarely studied. This systematic review is aimed to provide the best scientific literature source on the molecular insights into odontogenesis in hyperglycemic environment caused by diabetes mellitus or by maternal diabetes on the offspring. The literature search was conducted on the databases, namely PubMed, PubMed Central, Cochrane, and Scopus. The original studies exploring the alterations in the molecular pathways of odontogenesis in diabetes mellitus were selected. Data were extracted, chosen, and evaluated by two independent researchers. At the end of thorough data search, four articles were eligible for the review. Three articles brought out the molecular pathways involved in the offspring of gestational diabetes through animal models. Fourth article was an in vitro study, which treated the stem cells in hyperglycemic environment and drafted the molecular pathway. The altered molecular pathways in dental epithelial stem cells (DESCs), dental papilla cells (DPCs), and stem cells from apical papilla were studied and empowered with statistical analysis. Thus with this systematic review, we conclude that apurinic/apyrimidinic endonuclease1 downregulation causing deoxyribonucleic acid hypermethylation and Oct4, Nanog gene silencing, activation of toll-like receptor-4/nuclear factor kappa B (TLR4/NF-κB) pathway are involved in suppressing cell proliferation and accelerated apoptosis in DESCs in high glucose environment. DPCs are suppressed from odonto differentiation by activation of TLR4 signaling and resulting inhibition of SMAD1/5/9 phosphorylation in diabetic condition. NF-κB pathway activation causes decreased cell proliferation and enhanced differentiation in apical papilla stem cells in hyperglycemia. Further studies targeting various stages of odontogenesis can reveal more molecular insight.

Immunohistochemical Detection of Nerve Growth Factor (NGF) in Follicular and Plexiform Ameloblastoma - A Novel Study.

BACKGROUND: Ameloblastoma is the second most common odontogenic tumor that holds a unique position among benign tumors due to its locally destructive and invasive nature. The differed tumor biology behind follicular and plexiform ameloblastoma is always an enigma. Nerve growth factor (NGF), a neurotrophin that plays a major role during odontogenesis, could also possibly play a role in the pathogenesis of odontogenic tumors such as ameloblastoma. With this background, the study was aimed to investigate the expression of NGF in follicular and plexiform ameloblastoma. OBJECTIVES: The objectives of this study were to analyze the immunohistochemical expression pattern of NGF in ameloblastoma and to compare the immunohistochemical expression pattern of NGF among the follicular and plexiform histological types of ameloblastoma. MATERIALS AND METHODS: Forty histological sections of ameloblastomas (20 follicular and 20 plexiform) were stained immunohistochemically with anti-human NGF mouse IgG monoclonal antibody and the staining was analyzed statistically. RESULTS: Almost all the 40 ameloblastoma samples (20 follicular and 20 plexiform) showed positive immunoreactivity to NGF. Both peripheral pre-ameloblast-like tall columnar cells and central stellate-reticulum-like cells showed positive reactivity. The pattern of staining was membranous in the immunoreactive cells. The χ2 value for the immunoexpression between follicular and plexiform ameloblastoma was statistically significant with a P value <0.002. A possible mechanism has been proposed after studying the results with the downstream pathways obtained from literature. CONCLUSION: The pattern of expression of NGF is seen in both follicular and plexiform ameloblastoma. But the intensity is more in plexiform than that of follicular ameloblastoma.

Immunohistochemical detection of Tyrosine Kinase receptor (TrK) in follicular and plexiform ameloblastoma - A novel study.

OBJECTIVES: The objective is to analyze the immunohistochemical expression pattern of tyrosine kinase receptor (TrK) in ameloblastoma and to compare the immunohistochemical expression pattern of TrK among the histological types of ameloblastoma, follicular and plexiform patterns. MATERIALS AND METHODS: Forty ameloblastomas (20 follicular and 20 plexiform) were immunostained with anti-human TrK mouse IgG monoclonal antibody, and the pattern of staining is statistically analyzed. RESULTS: Total 20 (4 follicular and 16 plexiform) out of 40 ameloblastomas showed immunoreactivity to TrK. Only the peripheral preameloblast like tall columnar cells showed reactivity, whereas the stellate reticulum like cells is immunonegative. The staining pattern was membranous in the immunoreactive cells. The Chi-square value for the immunoexpression between follicular and plexiform ameloblastoma was statistically significant with a P < 0.005. The results were studied with the downstream pathways from the literature, and a possible mechanism has been proposed. CONCLUSION: The expression pattern of TrK is found to be more in plexiform ameloblastoma than follicular ameloblastoma.

Morphological Analysis of Elastic Fibers in Various Grades of Oral Squamous Cell Carcinoma and Epithelial Dysplasia Using Verhoeff-Van Gieson Stain.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy in India. The aggressiveness of OSCC is analyzed not only based on the dysplastic features and tumor infiltration pattern, but also by means of the stromal changes that pave the way for an invasion into the connective tissue. The role of elastic fibers in the progression of OSCC is still unknown because of sparse literature and the masking effect of overlying inflammatory cells and the lower number of elastic fibers in the lamina propria. The present study provides further insight into the qualitative assessment of elastic fibers in various grades of dysplasia and OSCC. OBJECTIVES: To analyze the morphological changes exhibited by the elastic fibers in epithelial dysplasia and OSCC. MATERIALS AND METHODS: Two sections were cut from each of 60 samples of varying grades of OSCC and 60 samples of varying grades of epithelial dysplasia followed by staining with hematoxylin and eosin and Verhoeff-Van Gieson stain. RESULTS: Statistically significant results were obtained for qualitative analysis of elastic fibers. A change in density and orientation to overlying epithelium and tumor islands was seen on progressing from well-differentiated to poorly differentiated OSCC and in progressing grades of dysplasia. CONCLUSION: The uniqueness of this study lies in the exploration of elastic fibers in dysplasia and well-differentiated OSCC, a less explored field. The study of the connective tissue stromal changes can be used as an adjunct to histological grading.

Meta-terminology of Ameloblastoma.

One of the primary tasks of systematic biology is the development of our biological nomenclature and classifications. The key purpose for the development of a standard nomenclature for a disease is the need for a common language for the statement of diagnostic terms and for a means or system whereby diagnosis could be suitably recorded without chaos. Odontogenic tumor nomenclature and classification have confused physicians over the years. Ameloblastoma is one such entity among odontogenic tumors, which has continuously changed to be an evolution of the terms and taxonomy used in literature. In this review, we aim to provide a fundamental basis for the understanding of how the etymology and the position of ameloblastoma in odontogenic tumor classification have evolved over the years.

Ellis-van Creveld.

Ellis-van Creveld (EVC) syndrome is an autosomal recessive disorder that is also known as chondro-ectodermal dysplasia. The common manifestations of this syndrome are short ribs, postaxial polydactyly, growth retardation, and ectodermal and cardiac defects. The present case report is about an 8-year-old boy who had the features of bilateral hexadactyly, knocked knees, cardiac problems, congenital absence of incisors, fused upper and lower labial frenulum, and mulberry molars.

Molecular biology of wound healing.

Wound healing is a dynamic process that involves the integrated action of a number of cell types, the extra cellular matrix, and soluble mediators termed cytokines. In recent years considerable advances have been made in the research, knowledge, and understanding of growth factors. Growth factors are, in essence, proteins that communicate activities to cells. Their function is dependent on the receptor site they attach to. Growth factors were initially named for the type of response generated by them, but newer research has shown that many of these cells may accomplish many different types of response. A growth factor's role in wound repair is a critical component of the successful resolution of a wound. Growth factors help regulate many of the activities involved in healing. The role and function of growth factor is an evolving area of science and offers the potential for treatment alternatives in the future.

Bisphosphonates: An update.

Bisphosphonates are used widely for variety of bone condition, most notably IV bisphosphonates in the treatment of metastic bone lesion and oral bisphosphonates for osteoporosis. They constitute a group of drugs capable of modulating bone turnover and reducing its remodeling when an excessive resorption occurs. In the last few years, due to their extensive use, many cases of complications associated with their use have been published. This paper provides recent knowledge on general characteristics of these drugs and their mechanism of action, pathogenesis, as well as their relevance to dentist.