Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Normal development and hypoxic-ischemic changes of glutamate-aspartate transporters (GLAST) and excitatory amino acid transporter type 4 (EAAT4) were demonstrated in the human cerebellum. GLAST-immunoreactive Bergmann's glia and EAAT4-positive Purkinje cells showed a specific distribution and localization, and developed with age in the molecular and Purkinje cell layers. The dendrites and cell bodies of Purkinje cells, which showed EAAT4 immunoreactivity, were ensheathed by GLAST processes. In neonatal hypoxic-ischemic encephalopathy (HIE), GLAST immunoreactivity decreased in the molecular layer and increased in the inner granule cell layer at an early stage, and markedly increased in the Purkinje and inner granule cell layers at a late stage. EAAT4 immunoreactivity decreased with post-ischemic changes of Purkinje cells. GLAST reactivity changed more rapidly than EAAT4 in cases of HIE. These changes of GLAST and EAAT4 may be closely related to the vulnerability of Purkinje cells in hypoxia-ischemia. The glutamate transporter of Bergmann glia may play a more important role in the regulation of the extracellular glutamate concentration in hypoxia and/or ischemia.
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PMID:Expression of two glutamate transporters, GLAST and EAAT4, in the human cerebellum: their correlation in development and neonatal hypoxic-ischemic damage. 963 Feb 35

Neuromyelitis optica is an inflammatory demyelinating disorder of the central nervous system. The discovery of a specific antibody (NMO IgG /aquaporin-4 antibody) in patients with this condition has led to a marked revival of research on the disease. This article summarizes the major advances in neuromyelitis optica, particularly in the last 2 years, and supplements the previous review published in this Journal in 2007. Important among these developments are: the epidemiological studies, which have provided estimates of incidence and prevalence; identification of mutations in the aquaporin-4 gene; improved understanding of the effects of anti-aquaporin-4 antibody on astrocytes; roles of excitatory amino acid transporter type 2 and glutamate; requirement of aquaporin-4 to be in orthogonal arrays to be antigenic; recognition of the presence of aquaporin-4 antibody in patients with cancer and posterior reversible encephalopathy syndrome; possibility of monitoring the disease using the antibody, and the effectiveness of rituximab and mycophenolate in preventing relapses.
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PMID:Neuromyelitis optica - an update: 2007-2009. 2018 70

Transport of the anti-HIV agents across the blood-brain barrier (BBB) is a prerequisite to treat acquired immunodeficiency syndrome (AIDS) related encephalopathy. In the present study, we explored facilitated transport of efavirenz (EFV, a non-nucleoside reverse transcriptase inhibitor) across BBB using phenylalanine anchored solid lipid nanoparticles (PA-SLN). PA (amino acid micro-nutrient) was used as a ligand which facilitated carrier mediated transport (CMT) via l-amino acid transporter i.e. LAT1 to traverse BBB. PA was coupled to SLN via amide linkage using carbodiimide chemistry and coupling was confirmed by comparative infrared spectroscopic analysis. SLNs (SLN and PA-SLN) were nanometric in size (around 150nm) and possessed good entrapment efficiency (around 70%). In vitro drug release revealed controlled release pattern for more than 24h. In vivo studies showed 2-3-folds and 7-8-folds accumulation of PA-SLN in brain as compared to SLN and EFV, respectively. Further, transcytosis studies confirmed capability of PA-SLN to cross BBB i.e. 10-fold higher transcytosis potential as compared to EFV. Fluorescence microscopic imaging reassured enhanced brain localization of PA-SLN. Thus, PA-SLN improved the EFV bioavailability and maintained therapeutic levels in the brain for an extended period of time that can result in significant eradication of the viral load therein. Such nutrient mediated drug targeting could bring forth advances in biocompatible and biodegradable drug delivery systems.
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PMID:Targeting of AIDS related encephalopathy using phenylalanine anchored lipidic nanocarrier. 2598 79