N-Methyl-D-Aspartate (NMDA) Receptor Antagonists and Their Pharmacological Implication: A Medicinal Chemistry-Oriented Perspective Outline.

N-methyl-D-aspartate (NMDA) receptors, i.e., inotropic glutamate receptors, are important in synaptic plasticity, brain growth, memory, and learning. The activation of NMDA is done by neurotransmitter glutamate and co-agonist (glycine or D-serine) binding. However, the over-activation of NMDA elevates the intracellular calcium influx, which causes various neurological diseases and disorders. Therefore, to prevent excitotoxicity and neuronal death, inhibition of NMDA must be done using its antagonist. This review delineates the structure of subunits of NMDA and the conformational changes induced after the binding of agonists (glycine and D-serine) and antagonists (ifenprodil, etc.). Additionally, reported NMDA antagonists from different sources, such as synthetic, semisynthetic, and natural resources, are explained by their mechanism of action and pharmacological role. The comprehensive report also addresses the chemical spacing of NMDA inhibitors and in-vivo and in-vitro models to test NMDA antagonists. Since the Blood-Brain Barrier (BBB) is the primary membrane that prevents the penetration of a wide variety of drug molecules, we also elaborate on the medicinal chemistry approach to improve the effectiveness of their antagonists.

Targeting GABA receptors with chalcone derivative compounds, what is the evidence?

INTRODUCTION: In medicinal chemistry, privileged structures have been frequently exploited as a successful template for drug discovery. Common simple scaffolds like chalcone are present in a wide range of naturally occurring chemicals. Chalcone exhibits extensive biological activity and has drawn attention in this context due to its function in the GABA receptor. Epilepsy and GABA receptors are related. It is a chronic neurological condition that affects globally. AREAS COVERED: Numerous neurological disorders, including anxiety and epilepsy, have been related to GABA, the brain's most prevalent inhibitory neurotransmitter. We go through the role of GABA receptors in anxiety and epilepsy in this review. The structure-activity relationship of chalcone and its derivatives on the GABA receptor is covered in our final section. EXPERT OPINION: GABA is a potential therapeutic target for issues associated with the nervous system. We talk about the potential effects of chalcone as a treatment for epilepsy and anxiety on the GABA receptor. Therefore, thorough research is necessary in this regard; the value of in silico tools in developing and enhancing GABA agonists is significant.

Assessment of the effects of hydrogen water on human gingival fibroblast cell culture in patients with chronic periodontitis.

Background: Activated inflammatory cells produce reactive oxygen species (ROS) to eliminate pathogens. Under normal conditions, the pathogens are taken care of, and tissues are repaired. However, in periodontal disease, persistent inflammation causes increased ROS release and impaired healing. Therefore, removal of overproduced ROS using antioxidants is necessary. Hydrogen water has an antioxidative effect on cells and impedes oxidative stress-related disorders. Aim: To study the effect of hydrogen water on cell viability, migration, and its antioxidative potential in fibroblasts obtained from chronic periodontitis patients. Materials and Methods: The gingival tissue samples were obtained from 26 subjects (13 periodontally healthy individuals and 13 chronic periodontitis patients) and processed. The human gingival fibroblasts were cultured and the assays were commenced once adequate growth was detected. The effect of hydrogen water on cell viability was checked by neutral red assay, while the migration potential was assessed by transwell migration assay. The antioxidative potential of hydrogen water was evaluated by CUPRAC assay. Statistical Analysis: Intergroup comparison was done using Mann-Whitney U-test. Intragroup comparison was done using Wilcoxon signed-rank test. Results: Hydrogen water was nontoxic to the fibroblasts at 24 h and 48 h. The intergroup comparison of the cell viability between hydrogen water-treated periodontally healthy gingival fibroblasts (HF) and fibroblasts from patients with chronic periodontitis (CF) showed a statistically significant (P = 0.00) difference at 24 h and 48 h. Hydrogen water also positively influenced the migratory capacity. Hydrogen water-treated fibroblasts obtained from chronic periodontitis patients showed more migration in comparison to the healthy group (P = 0.00). Hydrogen water showed an antioxidative potential. The maximum potential was seen in relation to the fibroblasts obtained from chronic periodontitis patients at 48 h. Conclusion: Hydrogen water was nontoxic, increased the migratory capacity, and showed an antioxidative potential on human fibroblasts obtained from periodontally healthy individuals and patients with chronic periodontitis.

Trios Lidisi Veneer, Transforming Smiles Using an Intraoral Scanner - A Case Report.

INTRODUCTION: The need to perform restorations with a natural appearance is one of the most challenging aspects of dentistry, and reproducing the colour of natural teeth in restorations is a clinical challenge due to the complex optical characteristics of dentition. Various procedures have been advocated in the literature to correct dental anomalies, particularly in the aesthetic region, such as tooth discoloration due to fluorosis or dentition spacing due to changes in tooth shape, such as peg laterals. CLINICAL APPLICATIONS: Veneer are one of the most commonly used treatment modalities in such cases. As the use of ceramics necessitates the use of more opaque restorative materials or different thickness, obtaining adequate results in terms of the final colour of the restoration becomes increasingly difficult. The purpose of this study is to present a clinical case of smile rehabilitation in the anterior region with facets made of lithium disilicate, with the goal of achieving colour uniformity and demonstrating the benefits and achieving smile aesthetics. TAKEAWAY LESSONS: Technological advancement such as intraoral scanner for impression making have significant improved the success of prosthesis. This case report presents conservative and aesthetic procedure in the management of closing the space in maxillary anterior region using lithium disilicate laminate veneers with trios software.

Comparative assessment of exfoliated gingival cells in healthy individuals and chronic periodontitis patients with and without tobacco chewing habit: A cytomorphometric study.

Background: Cytomorphometry is the analysis of the morphometry of exfoliated cells. Studies on exfoliated gingival epithelial cells in chronic periodontitis were not evident on the literature search. In the backdrop of this information, we were inspired to conduct a cytomorphometric study. Aim: The aim of the study is to correlate the nuclear area (NA), cytoplasm area (CA), and the nuclear: cytoplasm ratio (N/C) in the gingival cells of healthy individuals, patients with chronic periodontitis, and chronic periodontitis patients who are tobacco chewers. Materials and Methods: Ninety subjects, aged 35-45 years, were categorized into three equal groups of 30 each. Group I had individuals with healthy gingiva, Group II patients with chronic periodontitis without any deleterious habits, while Group III patients with chronic periodontitis and tobacco chewing habit. Exfoliated gingival cells were stained with Papanicolaou stain. Analysis of cells was done using binocular light microscope under ×40 and i-progress® image analyzer software. Results: There was statistically significant increase in CA in all the groups, but NA and N/C ratio did not show any statistical significant difference. When Group II was compared with Group III, we found significant correlation of CA with pocket probing depth and clinical attachment loss (CAL) in Group II. Similarly, we also found a correlation of CA and N/C with pocket depth and CA with CAL in Group III. Conclusion: The results suggest that molecular level changes occur in the cells. Cytomorphometry can be used to analyze the cellular changes in chronic periodontitis patients even before clinical signs manifest. Hence, it can be used as an investigative tool.

Polymer Grafting and its chemical reactions.

Polymer grafting is a technique to improve the morphology, chemical, and physical properties of the polymer. This technique has the potential to improve the existing conduction and properties of polymers other than charge transport; as a result, it enhances the solubility, nano-dimensional morphology, biocompatibility, bio-communication, and other property of parent polymer. A polymer's physicochemical properties can be modified even further by creating a copolymer with another polymer or by grafting. Here in the various chemical approaches for polymer grafting, like free radical, click reaction, amide formation, and alkylation have been discussed with their importance, moreover the process and its importance are covered comprehensively with their scientific explanation. The present review also covers the effectiveness of the graft-to approaches and its application in various fields, which will give reader a glimpse about polymer grafting and its uses.

Assessment of antibacterial effect of hydrogen water on plaque from patients with chronic periodontitis.

BACKGROUND: Periodontitis is an inflammatory disease causing destruction of tissues surrounding the teeth. The primary etiological factor for periodontitis is plaque. An inference could be drawn that an overall reduction in microorganisms halts disease progression. It is desirable to have natural agents with minimal side effects to reduce the microbial load. AIM: The aim of the study is to assess the effect of hydrogen water on microbial count in plaque obtained from chronic periodontitis patients and to determine the antibacterial activity of hydrogen water at various time intervals. MATERIALS AND METHODS: A total of twenty chronic periodontitis patients were included after obtaining approval from the institutional ethical committee. Written informed consent was obtained from all the twenty participants. Plaque samples were collected and exposed to hydrogen water at baseline, 1 min, 2 min 30 s, and 5 min. Samples were then cultured on blood agar and incubated in aerobic and anaerobic conditions. The colony forming units and total bacterial count were recorded after 24-48 h. STATISTICAL ANALYSIS: Intragroup pair-wise comparison was done using Wilcoxon sign-ranked test. RESULTS: Hydrogen water showed antibacterial activity against aerobic and anaerobic organisms associated with chronic periodontitis. There was a statistically significant difference in the number of colony forming units from baseline to 1 and 2.5 min for the aerobic culture and also for baseline to 1, 2.5, and 5 min for the anaerobic culture. CONCLUSION: The data of the present study indicate that hydrogen water has an antibacterial effect on microorganisms associated with chronic periodontitis.

A comparative evaluation of cyclic fatigue resistance for different endodontic NiTi rotary files: An in-vitro study.

AIM: This in-vitro study evaluated and compared the flexural fatigue resistance for Hero Shapers, Hyflex CM, One Shape, Profile Vortex and Protaper Next rotary NiTi files. METHOD AND MATERIALS: Total 25 rotary NiTi files allocated to each experimental group were tested in a simulated constructed apparatus with an angle of curvature 60° & radius of curvature 5 mm. Each experimental file was coated with EDTA gel and was placed in endodomotor handpiece with rubber stopper at support steel cylinder and its end between two shaping steel cylinders on the simulated apparatus. File was then rotated at 400 rpm, 2.5 N/cm torque and simultaneously digital stop watch was started. Time taken (in seconds) until the file got fractured was recorded. RESULTS: Time taken to fracture ranged from 7 to 58 s in different groups. Analysis of variance show a statistically significant intergroup difference (p < 0.001). Tukey HSD test showed the significant differences. The Weibull modulus values ranged from 7.31 to 24.19. CONCLUSION: Cyclic flexural fatigue resistance was observed highest for Grp IV (Hyflex CM) and lowest for Grp I (Hero Shapers). CLINICAL SIGNIFICANCE: Hyflex CM rotary NiTi files can be used in curved root canals as they had superior resistance and long survival time which will be helpful in eliminating one of the reasons for file fracture (due to cyclic flexural fatigue) during the root canal treatment clinically where root canal possesses a sharp bend or curve.