Tooth Mobility among Patients visiting a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Periodontitis is a chronic inflammatory disease that results in the destruction of supporting tissue and bone leading to tooth mobility. Tooth mobility if untreated can lead to tooth loss. However, very few studies exist for its assessment. The aim of this study was to find out the prevalence of tooth mobility among patients visiting a tertiary care centre. Methods: This descriptive cross-sectional study was conducted among individuals visiting a tertiary care dental hospital from 1st April to 30th June 2022 after obtaining ethical clearance from the Institutional Review Committee (Reference number: 2202202202). Individuals more than 13 years who gave consent and fulfilled the study criteria were enrolled. Tooth mobility was assessed using Lindhe and Nyman's classification. Proforma also included demographics, simplified oral hygiene index, gingival index, body mass index, and smoking status. Convenience sampling was done. Point estimate and 95% Confidence Interval were calculated. Results: Among 163 patients, 65 (39.88%) patients (32.36-47.40, 95% Confidence Interval) had tooth mobility. Conclusions: The prevalence of tooth mobility was higher than in studies done in similar settings. Keywords: periodontitis; prevalence; tooth mobility.

Lipid Polarization during Cytokinesis.

The plasma membrane of eukaryotic cells is composed of a large number of lipid species that are laterally segregated into functional domains as well as asymmetrically distributed between the outer and inner leaflets. Additionally, the spatial distribution and organization of these lipids dramatically change in response to various cellular states, such as cell division, differentiation, and apoptosis. Division of one cell into two daughter cells is one of the most fundamental requirements for the sustenance of growth in all living organisms. The successful completion of cytokinesis, the final stage of cell division, is critically dependent on the spatial distribution and organization of specific lipids. In this review, we discuss the properties of various lipid species associated with cytokinesis and the mechanisms involved in their polarization, including forward trafficking, endocytic recycling, local synthesis, and cortical flow models. The differences in lipid species requirements and distribution in mitotic vs. male meiotic cells will be discussed. We will concentrate on sphingolipids and phosphatidylinositols because their transbilayer organization and movement may be linked via the cytoskeleton and thus critically regulate various steps of cytokinesis.

Delivery of ceramide phosphoethanolamine lipids to the cleavage furrow through the endocytic pathway is essential for male meiotic cytokinesis.

Cell division, wherein 1 cell divides into 2 daughter cells, is fundamental to all living organisms. Cytokinesis, the final step in cell division, begins with the formation of an actomyosin contractile ring, positioned midway between the segregated chromosomes. Constriction of the ring with concomitant membrane deposition in a specified spatiotemporal manner generates a cleavage furrow that physically separates the cytoplasm. Unique lipids with specific biophysical properties have been shown to localize to intercellular bridges (also called midbody) connecting the 2 dividing cells; however, their biological roles and delivery mechanisms remain largely unknown. In this study, we show that ceramide phosphoethanolamine (CPE), the structural analog of sphingomyelin, has unique acyl chain anchors in Drosophila spermatocytes and is essential for meiotic cytokinesis. The head group of CPE is also important for spermatogenesis. We find that aberrant central spindle and contractile ring behavior but not mislocalization of phosphatidylinositol phosphates (PIPs) at the plasma membrane is responsible for the male meiotic cytokinesis defect in CPE-deficient animals. Further, we demonstrate the enrichment of CPE in multivesicular bodies marked by Rab7, which in turn localize to cleavage furrow. Volume electron microscopy analysis using correlative light and focused ion beam scanning electron microscopy shows that CPE-enriched Rab7 positive endosomes are juxtaposed on contractile ring material. Correlative light and transmission electron microscopy reveal Rab7 positive endosomes as a multivesicular body-like organelle that releases its intraluminal vesicles in the vicinity of ingressing furrows. Genetic ablation of Rab7 or Rab35 or expression of dominant negative Rab11 results in significant meiotic cytokinesis defects. Further, we show that Rab11 function is required for localization of CPE positive endosomes to the cleavage furrow. Our results imply that endosomal delivery of CPE to ingressing membranes is crucial for meiotic cytokinesis.

SSSPTA is essential for serine palmitoyltransferase function during development and hematopoiesis.

Serine palmitoyltransferase complex (SPT) mediates the first and rate-limiting step in the de novo sphingolipid biosynthetic pathway. The larger subunits SPTLC1 and SPTLC2/SPTLC3 together form the catalytic core while a smaller third subunit either SSSPTA or SSSPTB has been shown to increase the catalytic efficiency and provide substrate specificity for the fatty acyl-CoA substrates. The in vivo biological significance of these smaller subunits in mammals is still unknown. Here, using two null mutants, a conditional null for ssSPTa and a null mutant for ssSPTb, we show that SSSPTA is essential for embryogenesis and mediates much of the known functions of the SPT complex in mammalian hematopoiesis. The ssSPTa null mutants are embryonic lethal at E6.5 much like the Sptlc1 and Sptlc2 null alleles. Mx1-Cre induced deletion of ssSPTa leads to lethality and myelopoietic defect. Chimeric and competitive bone marrow transplantation experiments show that the defect in myelopoiesis is accompanied by an expansion of the Lin-Sca1+c-Kit+ stem and progenitor compartment. Progenitor cells that fail to differentiate along the myeloid lineage display evidence of endoplasmic reticulum stress. On the other hand, ssSPTb null mice are homozygous viable, and analyses of the bone marrow cells show no significant difference in the proliferation and differentiation of the adult hematopoietic compartment. SPTLC1 is an obligatory subunit for the SPT function, and because Sptlc1-/- and ssSPTa-/- mice display similar defects during development and hematopoiesis, we conclude that an SPT complex that includes SSSPTA mediates much of its developmental and hematopoietic functions in a mammalian model.

Sptlc1 is essential for myeloid differentiation and hematopoietic homeostasis.

Serine palmitoyltransferase (SPT) long-chain base subunit 1 (SPTLC1) is 1 of the 2 main catalytic subunits of the SPT complex, which catalyzes the first and rate-limiting step of sphingolipid biosynthesis. Here, we show that Sptlc1 deletion in adult bone marrow (BM) cells results in defective myeloid differentiation. In chimeric mice from noncompetitive BM transplant assays, there was an expansion of the Lin- c-Kit+ Sca-1+ compartment due to increased multipotent progenitor production, but myeloid differentiation was severely compromised. We also show that defective biogenesis of sphingolipids in the endoplasmic reticulum (ER) leads to ER stress that affects myeloid differentiation. Furthermore, we demonstrate that transient accumulation of fatty acid, a substrate for sphingolipid biosynthesis, could be partially responsible for the ER stress. Independently, we find that ER stress in general, such as that induced by the chemical thapsigargin or the fatty acid palmitic acid, compromises myeloid differentiation in culture. These results identify perturbed sphingolipid metabolism as a source of ER stress, which may produce diverse pathological effects related to differential cell-type sensitivity.

Drosophila Sirt2/mammalian SIRT3 deacetylates ATP synthase ß and regulates complex V activity.

Adenosine triphosphate (ATP) synthase ß, the catalytic subunit of mitochondrial complex V, synthesizes ATP. We show that ATP synthase ß is deacetylated by a human nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylase, sirtuin 3, and its Drosophila melanogaster homologue, dSirt2. dsirt2 mutant flies displayed increased acetylation of specific Lys residues in ATP synthase ß and decreased complex V activity. Overexpression of dSirt2 increased complex V activity. Substitution of Lys 259 and Lys 480 with Arg in human ATP synthase ß, mimicking deacetylation, increased complex V activity, whereas substitution with Gln, mimicking acetylation, decreased activity. Mass spectrometry and proteomic experiments from wild-type and dsirt2 mitochondria identified the Drosophila mitochondrial acetylome and revealed dSirt2 as an important regulator of mitochondrial energy metabolism. Additionally, we unravel a ceramide-NAD(+)-sirtuin axis wherein increased ceramide, a sphingolipid known to induce stress responses, resulted in depletion of NAD(+) and consequent decrease in sirtuin activity. These results provide insight into sirtuin-mediated regulation of complex V and reveal a novel link between ceramide and Drosophila acetylome.

Survival response to increased ceramide involves metabolic adaptation through novel regulators of glycolysis and lipolysis.

The sphingolipid ceramide elicits several stress responses, however, organisms survive despite increased ceramide but how they do so is poorly understood. We demonstrate here that the AKT/FOXO pathway regulates survival in increased ceramide environment by metabolic adaptation involving changes in glycolysis and lipolysis through novel downstream targets. We show that ceramide kinase mutants accumulate ceramide and this leads to reduction in energy levels due to compromised oxidative phosphorylation. Mutants show increased activation of Akt and a consequent decrease in FOXO levels. These changes lead to enhanced glycolysis by upregulating the activity of phosphoglyceromutase, enolase, pyruvate kinase, and lactate dehydrogenase to provide energy. A second major consequence of AKT/FOXO reprogramming in the mutants is the increased mobilization of lipid from the gut through novel lipase targets, CG8093 and CG6277 for energy contribution. Ubiquitous reduction of these targets by knockdown experiments results in semi or total lethality of the mutants, demonstrating the importance of activating them. The efficiency of these adaptive mechanisms decreases with age and leads to reduction in adult life span of the mutants. In particular, mutants develop cardiac dysfunction with age, likely reflecting the high energy requirement of a well-functioning heart. The lipases also regulate physiological triacylglycerol homeostasis and are important for energy metabolism since midgut specific reduction of them in wild type flies results in increased sensitivity to starvation and accumulation of triglycerides leading to cardiac defects. The central findings of increased AKT activation, decreased FOXO level and activation of phosphoglyceromutase and pyruvate kinase are also observed in mice heterozygous for ceramide transfer protein suggesting a conserved role of this pathway in mammals. These data reveal novel glycolytic and non-autonomous lipolytic pathways in response to increased ceramide for sustenance of high energy demanding organ functions like the heart.

Effect of vitamins C and E on spermatogenesis in mice exposed to cadmium.

Cadmium (Cd) is a potential pollutant of the environment. It manifests cyto-toxic effects in different organs in animals. In the present study, intraperitoneal injection of CdCl(2) (1mg/kg body weight) increased lipid peroxidation in Swiss mice testes indicating oxidative stress during 5th to 8th week of post-treatment . The enzymatic activity of superoxide dismutase (SOD), catalase (CT) and peroxidase (PD) were significantly decreased over the post-treatment phase in Cd-treated mice testes compared to vehicle controls. Further, ascorbic acid content also declined significantly in Cd-exposed mice testes. Following Cd treatment, a marked increase in sperm abnormality percentage and significant decrease in sperm count was observed. The purpose of the present study was to evaluate the effect of vitamins C and E supplementation on Cd-treated mice testes. Therefore, Cd-treated mice groups were injected with vitamins C and E, separately, to assess the effect of the vitamins in combating Cd-induced cytotoxicity and other manifestations. Supplementation of vitamin C (10mg/kg body weight) and vitamin E (100mg/kg body weight) to Cd-induced mice groups declined lipid peroxidation, increased sperm count profile, depressed the percentage of sperm abnormality, increased the activity of antioxidant enzymes mentioned above and also increased the concentration of ascorbic acid to a measurable extent. The role of vitamins in reducing oxidative stress-related effects on spermatogenesis in Cd-treated Swiss mice testes have been reported.

Potential role of vitamins in chromium induced spermatogenesis in Swiss mice.

Chromium (Cr) (VI) compounds are known carcinogens and mutagens. The mechanism of carcinogenicity and mutagenicity caused by chromium(VI) compounds remained unclear for several years. However, in the recent past chromium-induced carcinogenicity and/or mutagenicity was known to happen due to the generation of reactive oxygen species (ROS). In the present context, chromic acid (CrO(3)), a potential Cr(VI) compound could be able to generate reactive oxygen radicals in the testes of Swiss mice as evidenced from significantly higher lipid peroxidation compared to untreated controls. The cytotoxic effects of the compound on the testes are depicted in terms of significantly reduced sperm count level accompanied with increased abnormal sperm population in treated mice. Supplementation of vitamins like Vitamin C and Vitamin E (Vit C and Vit E) to CrO(3) injected mice groups could partially prevent the incidence of abnormal sperm population and increased the sperm count. Of the two vitamins, taken for the study, Vit C happens to be more effective in ameliorating germ cells from degeneration and from mutation to abnormal sperm. Possible antioxidative role of both the vitamins have been studied for significant decrease in lipid peroxidation associated with marked elevation in sperm count level and significant decrease in the percentage of abnormal sperm formation in CrO(3)-treated mice.

Status of antioxidant defense system in chromium-induced Swiss mice tissues.

Based on epidemiological studies, chromium(VI) compounds are considered as more toxic and carcinogenic than chromium(III) compounds. The deleterious effects of chromium(VI) compounds are diversified affecting almost all the organ systems in a wide variety of animals. The present study, describes the cytotoxic effects of chromium trioxide, a well-known chromium(VI) compound in three tissues (liver, kidney, lungs) of male Swiss mice during post-treatment phase (5th-8th week after treatment). Lipid peroxidation, an index of oxidative stress, was determined as thiobarbituric acid-reactive substances (TBA-Rs) in mice tissues dosed with a single intraperitoneal injection of chromium trioxide (1mg/kg body weight). Tissue specific and statistically significant increases in TBA-Rs was observed in chromium-treated mice groups compared to controls in all the weeks of post-treatment. Endogenous ascorbic acid (vit-C) content of tissues which happens to be one of the stable antioxidants, declined significantly due to chromium-induction. Activity of antioxidative enzymes like superoxide dismutase (SOD), catalase (CT) and peroxidase (PD) was significantly inhibited among chromium-injected mice groups compared to respective controls. Protective role of ascorbic acid and the antioxidative enzymes in chromium-induced cytotoxicity in mice is discussed.