Search results for "Animal Model"
showing 10 items of 241 documents
Molecular topology as novel strategy for discovery of drugs with aβ lowering and anti-aggregation dual activities for Alzheimer's disease.
2014
Background and Purpose: In this study, we demonstrate the use of Molecular topology (MT) in an Alzheimer's disease (AD) drug discovery program. MT uses and expands upon the principles governing the molecular connectivity theory of numerically characterizing molecular structures, in the present case, active anti-AD drugs/agents, using topological descriptors to build models. Topological characterization has been shown to embody sufficient molecular information to provide strong correlation to therapeutic efficacy. Experimental Approach: We used MT to include multiple bioactive properties that allows for the identification of multifunctional single agent compounds, in this case, the dual func…
Animal Models of Stress - Current Knowledge and Potential Directions
2021
Finding new therapies and new antidepressant agents is of high clinical priority given that many cases of depressive disorder do not respond to conventional monoaminergic antidepressants such as selective serotonin reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors The authors demonstrated that electroacupuncture and fluoxetine, a second-generation antidepressant categorized as a selective serotonin reuptake inhibitor (Perez-Caballero et al , 2014), regulate the expression of key proteins in the calmodulin kinase (CAMK) signaling pathway, which are related to depression in the hippocampi of rats (Takemoto-Kimura et al , 2017;Xie et al , 2019) In a paper on “Sho…
Calcitonin gene related peptide gene expression in collagen-induced arthritis
1995
On a evalue par hybridation in situ semi-quantitative les variations de l'expression genique du peptide lie au gene de la calcitonine (CGRP) dans les motoneurones spinaux et dans les ganglions des racines dorsales (GRD) de rats chez lesquels l'arthrite a ete induite par l'administration de collagene II (AIC). On a examine les effets d'un traitement systemique avec le corticosteroide budesonide sur l'expression basale du CGRP ainsi que sur ses variations dans des conditions d'inflammation. Dans les GRD, l'AIC a induit une augmentation significative des taux d'ARNm du CGRP. Le budesonide a reduit les taux d'ARNm du CGRP constitutif de ces GRD comparativement a ceux des rats temoins non traite…
Lipid profiling following intake of the Omega 3 fatty acid DHA identifies the peroxidized metabolites F-4-Neuroprostanes as the best predictors of at…
2014
International audience; The anti-atherogenic effects of omega 3 fatty acids, namely eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) are well recognized but the impact of dietary intake on bioactive lipid mediat or profiles remains unclear. Such a profiling effort may offer novel targets for future studies into the mechanism of action of omega 3 fatty acids. The present study aimed to determine the impact of DHA supplementation on the profiles of polyunsaturated fatty acids (PUFA) oxygenated metabolites and to investigate their contribution to therosclerosis prevention. A special emphasis was given to the non-enzymatic metabolites knowing the high susceptibility of DHA to free radical…
Glial Promoter Selectivity following AAV-Delivery to the Immature Brain
2013
Recombinant adeno-associated virus (AAV) vectors are versatile tools for gene transfer to the central nervous system (CNS) and proof-of-concept studies in adult rodents have shown that the use of cell type-specific promoters is sufficient to target AAV-mediated transgene expression to glia. However, neurological disorders caused by glial pathology usually have an early onset. Therefore, modelling and treatment of these conditions require expanding the concept of targeted glial transgene expression by promoter selectivity for gene delivery to the immature CNS. Here, we have investigated the AAV-mediated green fluorescent protein (GFP) expression driven by the myelin basic protein (MBP) or gl…
Bleomycin Exerts Ambivalent Antitumor Immune Effect by Triggering Both Immunogenic Cell Death and Proliferation of Regulatory T Cells
2013
International audience; Bleomycin (BLM) is an anticancer drug currently used for the treatment of testis cancer and Hodgkin lymphoma. This drug triggers cancer cell death via its capacity to generate radical oxygen species (ROS). However, the putative contribution of anticancer immune responses to the efficacy of BLM has not been evaluated. We make here the observation that BLM induces immunogenic cell death. In particular, BLM is able to induce ROS-mediated reticulum stress and autophagy, which result in the surface exposure of chaperones, including calreticulin and ERp57, and liberation of HMBG1 and ATP. BLM induces anti-tumor immunity which relies on calreticulin, CD8(+) T cells and inte…
Regulatory T Cells and IL-10 Independently Counterregulate Cytotoxic T Lymphocyte Responses Induced by Transcutaneous Immunization
2011
Background: The imidazoquinoline derivate imiquimod induces inflammatory responses and protection against transplanted tumors when applied to the skin in combination with a cognate peptide epitope (transcutaneous immunization, TCI). Here we investigated the role of regulatory T cells (Treg) and the suppressive cytokine IL-10 in restricting TCI-induced cytotoxic T lymphocyte (CTL) responses. Methodology/Principal Findings: TCI was performed with an ointment containing the TLR7 agonist imiquimod and a CTL epitope was applied to the depilated back skin of C57BL/6 mice. Using specific antibodies and FoxP3-diphteria toxin receptor transgenic (DEREG) mice, we interrogated inhibiting factors after…
Different Representation Procedures Originated from Multivariate Temporal Pattern Analysis of the Behavioral Response to Pain in Wistar Rats Tested i…
2019
Temporal pattern analysis is an advanced multivariate technique able to investigate the structure of behavior by unveiling the existence of statistically significant constraints among the interval length separating events in sequence. If on the one hand, such an approach allows investigating the behavioral response to pain in its most intimate and inner features, on the other hand, due to the meaning of the studies on pain, it is of relevant importance that the results utilize intuitive and easily comprehensible ways of representation. The aim of this paper is to show various procedures useful to represent the results originating from the multivariate T-pattern analysis of the behavioral re…
A novel technique to follow fast PaO2 variations during experimental CPR
2003
An ultrafast responding fluorescent-quenching PO2 probe allows time-resolved, in vivo measurement of PO2. This study describes several validation experiments of this new device in vitro, and reports its first use during cardiopulmonary resuscitation in an animal model of cardiac arrest.The influence of CO2, temperature and motion artefacts on the signal response of the PO2 probe was analysed in vitro by systematic variation of these values. Thereafter, with approval of the Review Board for the care and use of animals, CPR was performed in four pigs. The PaO2 course was recorded continuously at time resolution of80 ms in the abdominal aorta using an uncoated fluorescence-quenching probe (Fox…
Profilin 1 negatively regulates osteoclast migration in postnatal skeletal growth, remodeling, and homeostasis in mice
2019
ABSTRACT Profilin 1 (Pfn1), a regulator of actin polymerization, controls cell movement in a context‐dependent manner. Pfn1 supports the locomotion of most adherent cells by assisting actin‐filament elongation, as has been shown in skeletal progenitor cells in our previous study. However, because Pfn1 has also been known to inhibit migration of certain cells, including T cells, by suppressing branched‐end elongation of actin filaments, we hypothesized that its roles in osteoclasts may be different from that of osteoblasts. By investigating the osteoclasts in culture, we first verified that Pfn1‐knockdown (KD) enhances bone resorption in preosteoclastic RAW264.7 cells, despite having a compa…