Search results for "LER"

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…

Abacavir Induces Arterial Thrombosis in a Murine Model.

2018

Background The purinergic system is known to underlie prothrombotic and proinflammatory vascular programs, making the profile of experimental actions demonstrated by abacavir compatible with thrombogenesis. However, direct evidence of a prothrombotic effect by the drug has been lacking. Methods The present study appraised the effects of abacavir in a well-validated animal model of arterial thrombosis. The role of ATP-P2X7 receptors in the actions of the drug was also assessed, and the actions of recognized vascular-damaging agents and other nucleoside reverse-transcriptase inhibitors (NRTIs) were evaluated and compared to those of abacavir. Results Abacavir dose-dependently promoted thrombu…

Cardiovascular toxicity of abacavir: a clinical controversy in need of a pharmacological explanation.

2017

: There is a long-lasting controversy surrounding an association between abacavir (ABC) and an increased risk of cardiovascular disease in HIV-positive patients. Although differing in their specifics, a number of published cohort studies and clinical trials support such an association, usually relating it to recent exposure to the drug, independently of traditional predisposing factors. However, other clinical trials have failed to reveal such a relation and have pointed to methodological differences to explain discrepancies. Significantly, the controversy has been fueled by the lack of a credible mechanism of action to justify the putative detrimental actions of ABC. There is a myriad of c…

Autism spectrum disorders in children affected by Duchenne muscular dystrophy

2018

Background Duchenne muscular dystrophy (DMD) is the most frequent and severe form of the dystrophinopathies. The literature shows that about 30-40% of DMD subjects have intellectual disability. In males with Duchenne muscular dystrophy, neuropsychiatric disorders have also been observed: attention deficit disorder and hyperactivity, autism spectrum disorders, and obsessive-compulsive disorder. Duchenne muscular dystrophy is not just a muscle disorder, but also a disease that affects the brain. The aim of the present study was to describe a case series of children with Duchenne muscular dystrophy that have also the presence of autism spectrum disorders (ASDs). They have been assessed by mean…

EGFL7 - a potential therapeutic target for multiple sclerosis?

2018

MODULATION OF GRO-ALPHA AND TNF-ALPHA PRODUCTION BY PERIPHERAL BLOOD MONONUCLEAR CELLS TREATED WITH KILLED HELICOBACTER PYLORI.

2007

GRO-alpha seems to play an important role in recruiting and activating neutrophils during Helicobacter pylori infection. In the present study, we examined how treatment with killed H. pylori or/and live H. pylori may differentially influence the in vitro GRO-alpha and TNF-alpha release by peripheral blood mononuclear cells (PBMC). The amounts of TNF-alpha and GRO-alpha produced by PBMC after stimulation with live H. pylori were higher than those produced after stimulation with a combination of killed and live H. pylori and the latter were higher than those produced after stimulation with killed H. pylori. In conclusion, the treatment of peripheral blood mononuclear cells with killed H. pyl…

A Pharmacological Update of Ellagic Acid.

2018

Este artículo se encuentra disponible en la página web de la revista en la siguiente URL: https://www.thieme-connect.com/products/ejournals/pdf/10.1055/a-0633-9492.pdf This is a pre-print of an article published in Ríos, JL., Giner, RM., Marín, M. and Recio, MC. (2018). A pharmacological update of ellagic acid. Planta Medica, vol. 84, n. 15, pp. 1068-1093. The final authenticated version is available online at: https://doi.org/10.1055/a-0633-9492 Este es el pre-print del siguiente artículo Ríos, JL., Giner, RM., Marín, M. and Recio, MC. (2018). A pharmacological update of ellagic acid. Planta Medica, vol. 84, n. 15, pp. 1068-1093 que se ha publicado de forma definitiva en https://doi.org/10…

The emergence of loss of efficacy during antidepressant drug treatment for major depressive disorder: An integrative review of evidence, mechanisms, …

2018

The re-emergence (i.e. ‘breakthrough’) of depressive symptoms despite maintenance treatment of depression with antidepressant drugs is a complex clinical phenomenon referred to as tolerance. Herein we critically appraise evidence from both pre-clinical and clinical studies, focusing on putative mechanisms as well as clinical correlates and implications of the emergence tolerance during antidepressant treatment for major depressive disorder (MDD). It is firstly unclear to what extent this phenotype reflects a pharmacological effect of an antidepressant, is driven by non-adherence, is a marker of latent bipolarity or another comorbidity, a marker of neuroprogression of the underlying disorder…

The more the merrier? Scoring, statistics and animal welfare in experimental autoimmune encephalomyelitis.

2016

Experimental autoimmune encephalomyelitis (EAE) is a frequently used animal model for the investigation of autoimmune processes in the central nervous system. As such, EAE is useful for modelling certain aspects of multiple sclerosis, a human autoimmune disease that leads to demyelination and axonal destruction. It is an important tool for investigating pathobiology, identifying drug targets and testing drug candidates. Even though EAE is routinely used in many laboratories and is often part of the routine assessment of knockouts and transgenes, scoring of the disease course has not become standardized in the community, with at least 83 published scoring variants. Varying scales with diffe…

IL ‐1 signaling is critical for expansion but not generation of autoreactive GM ‐ CSF + Th17 cells

2016

Abstract Interleukin‐1 (IL‐1) is implicated in numerous pathologies, including multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). However, the exact mechanism by which IL‐1 is involved in the generation of pathogenic T cells and in disease development remains largely unknown. We found that following EAE induction, pertussis toxin administration leads to IL‐1 receptor type 1 (IL‐1R1)‐dependent IL‐1β expression by myeloid cells in the draining lymph nodes. This myeloid‐derived IL‐1β did not vitally contribute to the generation and plasticity of Th17 cells, but rather promoted the expansion of a GM‐CSF + Th17 cell subset, thereby enhancing its encephalitog…