Search results for "harm"
showing 10 items of 13866 documents
Posttraumatic Propofol Neurotoxicity Is Mediated via the Pro–Brain-Derived Neurotrophic Factor-p75 Neurotrophin Receptor Pathway in Adult Mice*
2016
Objectives:The gamma-aminobutyric acid modulator propofol induces neuronal cell death in healthy immature brains by unbalancing neurotrophin homeostasis via p75 neurotrophin receptor signaling. In adulthood, p75 neurotrophin receptor becomes down-regulated and propofol loses its neurotoxic effect. H
RNA-mediated therapies in myotonic dystrophy
2018
Myotonic dystrophy 1 (DM1) is a multisystemic neuromuscular disease caused by a dominantly inherited 'CTG' repeat expansion in the gene encoding DM Protein Kinase (DMPK). The repeats are transcribed into mRNA, which forms hairpins and binds with high affinity to the Muscleblind-like (MBNL) family of proteins, sequestering them from their normal function. The loss of function of MBNL proteins causes numerous downstream effects, primarily the appearance of nuclear foci, mis-splicing, and ultimately myotonia and other clinical symptoms. Antisense and other RNA-mediated technologies have been applied to target toxic-repeat mRNA transcripts to restore MBNL protein function in DM1 models, such as…
<p>Effects of losartan and atorvastatin on the development of early posttraumatic joint stiffness in a rat model</p>
2019
Background After a trauma, exuberant tissue healing with fibrosis of the joint capsule can lead to posttraumatic joint stiffness (PTJS). Losartan and atorvastatin have both shown their antifibrotic effects in different organ systems. Objective The purpose of this study was the evaluation of the influence of losartan and atorvastatin on the early development of joint contracture. In addition to joint angles, the change in myofibroblast numbers and the distribution of bone sialoprotein (BSP) were assessed. Study design and methods In this randomized and blinded experimental study with 24 rats, losartan and atorvastatin were compared to a placebo. After an initial joint injury, rat knees were …
Myotonic dystrophy: candidate small molecule therapeutics
2017
Myotonic dystrophy type 1 (DM1) is a rare multisystemic neuromuscular disorder caused by expansion of CTG trinucleotide repeats in the noncoding region of the DMPK gene. Mutant DMPK transcripts are toxic and alter gene expression at several levels. Chiefly, the secondary structure formed by CUGs has a strong propensity to capture and retain proteins, like those of the muscleblind-like (MBNL) family. Sequestered MBNL proteins cannot then fulfill their normal functions. Many therapeutic approaches have been explored to reverse these pathological consequences. Here, we review the myriad of small molecules that have been proposed for DM1, including examples obtained from computational rational …
A STAT4 variant increases liver fibrosis risk in Caucasian patients with chronic hepatitis B
2018
Background Host genetic modifiers of the natural history of chronic hepatitis B (CHB) remain poorly understood. Recently, a genome-wide association study (GWAS)-identified polymorphism in the STAT4 gene that contributes to the risk for hepatocellular carcinoma (HCC) was shown to be associated with the full spectrum of hepatitis B virus (HBV) outcomes in Asian patients. However, the functional mechanisms for this effect are unknown and the role of the variant in modulating HBV disease in Caucasians has not been investigated. Aims To determine whether STAT4 genetic variation is associated with liver injury in Caucasian patients with CHB and to investigate potential mechanisms mediating this e…
The role of osteoprotegerin in the crosstalk between vessels and bone: Its potential utility as a marker of cardiometabolic diseases
2018
International audience; Among the numerous molecules that are being studied for their potential utility as biomarkers of cardiovascular diseases, much interest has been shown in the superfamily of tumor necrosis factor (TNF) receptors. Members of this family include osteoprotegerin (OPG) and its ligands, which are receptor activators of nuclear factor κB ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL). These signals may be expressed and regulated, and their functions could be involved in several physiological and pathological processes. The relationship between bone regulatory proteins and vascular biology has attracted attention, and it has been suggested that OPG may medi…
FRI0150 Mtor blockade by rapamycin decreases arthritis and spondylitis development and severity in hla-b27 transgenic rats
2018
Career situation of first and presenting author Student for a master or a PhD. Introduction TNF and IL-17A have been demonstrated as key inflammatory cytokines in Spondyloarthritis (SpA), whereas targeting bone remodeling remains an unmet clinical need in SpA. The mammalian target of rapamycin (mTOR) regulates IL-17 expression and osteogenesis and could therefore be a promising therapeutic target in SpA. Objectives To investigate if blockade of mTOR with rapamycin inhibits the pathological processes in inflammation and bone in SpA. Methods Cytokines were measured by ELISA in the supernatant from SpA patient PBMCs stimulated with anti-CD3/CD28, with various concentrations of rapamycin. SpA F…
HLA-B27-restricted cytotoxic T lymphocyte responses to arthritogenic enterobacteria or self-antigens are dominated by closely related TCRBV gene segm…
1996
Identification of the T-cell receptors (TCR) used by synovial cytotoxic T lymphocytes (CTL) of patients with reactive arthritis (ReA) may be crucial to better understanding the pathogenetic mechanism underlying the HLA-B27 association of spondylarthropathies. The authors, therefore, sequenced 25 TCRB chains from HLA-B27-restricted CD8+ CTL clones and two clonal lines specific for self- or Yersinia enterocolitica antigen isolated from synovial fluids of 3 HLA-B27+ patients with ReA and PBL of one healthy HLA-B27+ individual. Fourteen non-HLA-B27-restricted CTL served as controls. Both autoreactive and Y. enterocolitica specific HLA-B27-restricted CTL used a highly limited set of VB genes wit…
Association of interleukin-10G microsatellite polymorphism with the susceptibility of ankylosing spondylitis
2013
Study suggests an association of IL10.G poly- morphisms with AS which might contribute to the increased or decreased susceptibility to AS. IL10.G8 and G7 microsatellites alleles appear as protective alleles against the development of AS in the German subjects investigated here. Allele IL10.G9 seems to be a risk factor for the development of AS. This protective effect of variant promoter alleles could be related to differences in IL- 10 production, which may be clinically relevant.
Interaction of allopurinol with phenprocoumon in man.
1977
Conditions in two patients on long-term phenprocoumon (Marcumar®) treatment are reported who had signs of phenprocoumon overdosage when given simultaneously allopurinol. The determination of phenprocoumon plasma concentrations in one patient showed that phenprocoumon accumulates for several weeks during treatment with allopurinol. Signs of phenprocoumon overdosage thus can appear long time after starting allopurinol treatment.