Context: Tobacco, the leading preventable cause of death including alcohol and illicit drug abuse, cause morbidity and mortality. Dentists deal with such patients & can/ should intervene, preventing any deleterious habits with apt knowledge and training. Aims: The study assesses the knowledge, attitude and practices amongst dental students to manage patients with tobacco, alcohol and substance abuse in a clinical set up. Methodology: A cross-sectional questionnaire (self-administered 22 items) survey was conducted among 300 dental students (Undergraduates, Interns, Postgraduates) in a dental college, North India to assess their knowledge, attitude and practices regarding substance abuse- tobacco, alcohol and other illicit drugs. Data were analyzed using SPSS version 16.0 and subjected to Chi-square test to determine the significant difference between the dental study groups (p≤ 0.05) Results: There were 37.1% males and 62.9% of females. Final years (33.8%), interns (29.8%) and Post graduates (36.5%) completed the questionnaire. 85.5% Postgraduates, 74.3% final years and 71.9% interns knew where to refer the patients of substance abuse which was statistically significant (p≤ 0.05).A majority (91.1%) of interns prescribe or provide tobacco cessation, followed by 87.1% final years and 78.2% post graduates that were significant values. Conclusions: Although there’s huge awareness on the management of patients with substance abuse habits, only a few practice it on patients correctly. Lack of training and its application due to many barriers have been discussed in detail pointing out the disparity in the number of patients with habit history being screened and to those being managed.
Glutamine, an excitatory neurotransmitter, is necessary for physiological as well as pathological processes. Other than neuronal disorders and/or cancers, glutamate receptors have also been associated with an array of other malignancies. The metabotropic glutamate receptor (mGluR 1–8 [like Groups I, II, and III]) and ionotropic glutamate receptor (iGluR) have been targeted to treat cancers like carcinoma of the lung, breast, prostate, and oral cancer. iGluRs present on N-methyl-D-aspartate (NMDA) and non-NMDA receptors are multisubunit complexes. Since these subunits of NMDA receptors influence the mTOR signaling pathway significantly, their antagonists such as memantine, ifenprodil, or diclozipine are often used in cancer chemotherapy. Non-NMDA receptors such as α-amino 3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) and kainate undergo glutamine to arginine site-specific RNA editing inflicting changes in cancer cell permeability. Thus, the employment of antagonists specific to these receptors would provide an effective anticancer therapeutic approach. Since AMPA receptors and kainate receptors have a crucial role in neural development and other cellular processes, their contribution in tumorigenesis has been mainly recognized in brain tumors although their role in further cancers cannot be ruled out. Delta or orphan receptors are primarily classified based on sequence homology. The effect and activity of antagonists for metabotropic and iGluRs have been pointed out due to their remedial contribution in various tumors. This review also highlights the relation of a range of subunits to cancer and anticancer agents as curatives for future applications and investigations.
9083 Background: Melanoma has long been known to be relatively radio-resistant. GRM1 is a metabotropic glutamate receptor that has been detected in human melanoma cell lines and biopsies. Riluzole (RZ), a glutamate release inhibitor, has been shown to arrest GRM1 positive human melanoma cells in G2/M and sub-G1 phases of the cell cycle. The purpose of this study was to determine if RZ enhances the lethal effects of IR in human melanoma. Methods: ATP luminescence assays were performed. Clonogenic assays were performed and cell survival curves generated. Cell cycle analysis was performed utilizing flow cytometry. Western blot analysis was performed utilizing cleaved PARP and caspase-3 antibodies as markers of apoptosis. Results: Luminescence assays revealed 25uM Riluzole to be the necessary concentration for clonogenic assays. At 2Gy, there was a 48% reduction (p≤0.05) in cell survival in RZ-treated cells. At 4 Gy, there was a 19% reduction (p≤0.05) in cell survival in RZ-treated cells. No differences were seen at 6 and 8 Gy. Cell cycle analysis showed that the combination of IR and RZ was superior to IR alone in increasing the number of cells in sub-G1, which represents apoptotic death. Western blot analysis showed that the combination of IR and RZ showed yielded increased cleaved PARP and caspase-3 activity when compared to IR alone. Conclusions: Riluzole is a FDA approved drug that has long been used in ALS. It is relatively non-toxic and crosses the blood brain barrier. Our data shows that Riluzole in combination with radiation eliminates the radio-resistant shoulder of the C8161 survival curve. RZ and IR, as combination therapy are more lethal than IR or RZ alone in human melanoma, as demonstrated by flow cytometry and WB analysis. This data has promising implications for melanoma patients with brain metastases. No significant financial relationships to disclose.
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