Search results for "atomic"

Correlation between micro-hardness and mineral content in healthy human enamel

2016

Background Enamel is the hardest and the stiffest tissue in the human body. The enamel undergoes multidirectional stresses, withstands multimillion chewing cycles, all while protecting the internal dentin and pulp from damage due to mechanical overload and exposure to the harsh chemical environment of the mouth. Raman spectroscopy allows to study enamel mineral content in a non-destructive and site-specific way. While Raman spectroscopy has been applied in other studies to assess tooth mineralization, there are no studies that examine the relationship between micro-hardness and mineral content of the untreated enamel. An understanding of this relationship is extremely important in a clinica…

A time based objective evaluation of the erosive effects of various beverages on enamel and cementum of deciduous and permanent teeth

2019

Background Erosion of the teeth is a chronic irreversible process leading to loss of surface enamel and even the dentin, in turn causing sensitivity and pain. Increased consumption of carbonated beverages remains a major cause for dental erosion. However, many of the so called safe beverages that are consumed may also have sufficiently low pH to cause dental erosion. One of the parameters to measure the dental erosion is estimation of hardness and surface roughness. Thus, this study aims to evaluate the difference in hardness and surface roughness of enamel and cementum using three beverages namely (carbonated drink, lime soda, lime juice) in deciduous and permanent teeth. Material and Meth…

beta-Adrenoceptor-mediated Relaxation of Urinary Bladder Muscle in beta 2-Adrenoceptor Knockout Mice

2016

Background and Objective. In order to characterize the β-adrenoceptor (AR) subtypes involved in agonist-stimulated relaxation of murine urinary bladder we studied the effects of (-)-isoprenaline and CL 316,243 on tonic contraction and spontaneous contractions in detrusor strips of wild-type (WT) and β2-AR knockout (β2-AR KO) mice. Materials and Methods. Urinary bladders were isolated from male WT and β2-AR KO mice. β-AR subtype expression was determined with quantitative real-time PCR. Intact muscle strips pre-contracted with KCl (40 mM) were exposed to cumulatively increasing concentrations of (-)-isoprenaline or β3-AR agonist CL 316,243 in the presence and absence of the subtype-selective…

Novel Microglia Depletion Systems: A Genetic Approach Utilizing Conditional Diphtheria Toxin Receptor Expression and a Pharmacological Model Based on…

2019

Microglia are the main population of macrophage residing in the central nervous system (CNS). Depletion experiments gave important insights into the physiology and function of microglia in healthy and diseased CNS. Ablation of microglia can be achieved by application of pharmacological or genetic tools. Here, we describe two approaches to ablate microglia: an efficient genetic model that utilizes DTRMG mouse line that has diphtheria toxin receptor (DTR) expression regulated by the promoter activity of the fractalkine receptor (CX3CR1) gene, and a pharmacological model that utilizes the blocking of macrophage colony-stimulating factor 1 receptor (CSF-1R) with a blocking antibody. Both the ad…

Angiogenic response in an in vitro model of dog microvascular endothelial cells stimulated with antigenic extracts from Dirofilaria immitis adult wor…

2019

Abstract Background Angiogenesis can occur under pathological conditions when stimuli such as inflammation, vascular obstruction or hypoxia exist. These stimuli are present in cardiopulmonary dirofilariosis (Dirofilaria immitis). The aim of this study was to analyze the capacity of D. immitis antigens to modify the expression of angiogenic factors and trigger the formation of pseudocapillaries (tube-like structures) in an in vitro model of endothelial cells. Methods The expression of VEGF-A, sFlt, mEndoglin and sEndoglin in cultures of canine microvascular endothelial cells stimulated with extract of adult worms of D. immitis obtained from an untreated dog (DiSA) and from a dog treated for …

2021

Mutations in TSC1 or TSC2 genes are linked to alterations in neuronal function which ultimately lead to the development of a complex neurological phenotype. Here we review current research on the effects that reduction in TSC1 or TSC2 can produce on the developing neural network. A crucial feature of the disease pathophysiology appears to be an early deviation from typical neurodevelopment, in the form of structural abnormalities. Epileptic seizures are one of the primary early manifestation of the disease in the CNS, followed by intellectual deficits and autism spectrum disorders (ASD). Research using mouse models suggests that morphological brain alterations might arise from the interacti…

Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis

2016

Only a few in vitro assays have been proposed to evaluate the steatotic potential of new drugs. The present study examines the utility of HepaRG cells as a cell-based assay system for screening drug-induced liver steatosis. A high-content screening assay was run to evaluate multiple toxicity-related cell parameters in HepaRG cells exposed to 28 compounds, including drugs reported to cause steatosis through different mechanisms and non-steatotic compounds. Lipid content was the most sensitive parameter for all the steatotic drugs, whereas no effects on lipid levels were produced by non-steatotic compounds. Apart from fat accumulation, increased ROS production and altered mitochondrial membra…

Metabolic activation and drug-induced liver injury:in vitroapproaches for the safety risk assessment of new drugs

2015

Drug-induced liver injury (DILI) is a significant leading cause of hepatic dysfunction, drug failure during clinical trials and post-market withdrawal of approved drugs. Many cases of DILI are unexpected reactions of an idiosyncratic nature that occur in a small group of susceptible individuals. Intensive research efforts have been made to understand better the idiosyncratic DILI and to identify potential risk factors. Metabolic bioactivation of drugs to form reactive metabolites is considered an initiation mechanism for idiosyncratic DILI. Reactive species may interact irreversibly with cell macromolecules (covalent binding, oxidative damage), and alter their structure and activity. This r…

A Multi-Parametric Fluorescent Assay for the Screening and Mechanistic Study of Drug-Induced Steatosis in Liver Cells in Culture.

2017

Human hepatic cells have been used for drug safety risk evaluations throughout early development phases. They provide rapid, cost-effective early feedback to identify drug candidates with potential hepatotoxicity. This unit presents a cell-based assay to evaluate the risk of liver damage associated with steatogenic drugs. Detailed protocols for cell exposure to test compounds and for the assessment of steatosis-related cell parameters (intracellular lipid content, reactive oxygen species production, mitochondrial impairment, and cell death) are provided. A few representative results that illustrate the utility of this procedure for the screening of drug-induced steatosis are shown. © 2017 b…

Upgrading HepG2 cells with adenoviral vectors that encode drug-metabolizing enzymes: application for drug hepatotoxicity testing.

2016

Drug attrition rates due to hepatotoxicity are an important safety issue considered in drug development. The HepG2 hepatoma cell line is currently being used for drug-induced hepatotoxicity evaluations, but its expression of drug-metabolizing enzymes is poor compared with hepatocytes. Different approaches have been proposed to upgrade HepG2 cells for more reliable drug-induced liver injury predictions. Areas covered: We describe the advantages and limitations of HepG2 cells transduced with adenoviral vectors that encode drug-metabolizing enzymes for safety risk assessments of bioactivable compounds. Adenoviral transduction facilitates efficient and controlled delivery of multiple drug-metab…