       Document 0370
 DOCN  M9620370
 TI    [Biochemical studies on AIDS dementia complex--possible contribution of
       quinolinic acid during brain damage]
 DT    9602
 AU    Saito K; Department of Laboratory Medicine, Gifu University School of;
       Medicine.
 SO    Rinsho Byori. 1995 Sep;43(9):891-901. Unique Identifier : AIDSLINE
       MED/96008356
 AB    AIDS dementia complex (ADC) is a complex, progressive neuropsychiatric
       syndrome seen in 60-70% of the patients with AIDS. The structural and
       functional changes associated with ADC may be the result of a variety of
       indirect mechanisms mediated via activated brain cells or/and virus that
       produce neurotoxins including N-methyl-D-aspartate receptor agonist (eg,
       quinolinic acid, glutamate), cytokines, gp 120 and nitric oxide. The
       level of the neurotoxin and kynurenine pathway metabolite, quinolinic
       acid, is increased in the brain and CSF of HIV-1-infected patients, and
       is correlated with quantitative measures of neurologic impairment.
       Importantly, increased CSF and brain levels of QUIN also occur in other
       inflammatory neurologic diseases (bacterial, viral, fungal and parasitic
       infections, meningitis, autoimmune diseases and septicemia), independent
       of HIV-1 infection. Therefore, QUIN and other neuroactive kynurenine
       pathway metabolites may be final common mediators of neurologic
       dysfunction in a broad spectrum of inflammatory neurologic diseases.
       Conversion of L-tryptophan to QUIN has also been demonstrated in vitro
       in both brain tissue following macrophage infiltration, and in
       macrophages stimulated by interferon-gamma or HIV infection. Macrophages
       in vitro have a high capacity to synthesize QUIN following exposure to
       interferon-gamma, tumor necrosis factor-alpha, IL-1 beta and IL-6,
       compared to cells derived from other tissues. Notably, the
       concentrations achieved in the macrophage incubates exceeded the levels
       found in the CNS of HIV-1-infected patients, and exceeded the
       concentrations shown to be neurotoxic in vitro. We hypothesize that
       increased kynurenine pathway metabolism following inflammation reflects
       the presence of macrophages and other reactive cell populations at the
       site of brain infection. Strategies to attenuate the neurotoxic effects
       of kynurenines, such as inhibitors of kynurenine pathway metabolism and
       cytokine antibodies may offer new approaches to therapy.
 DE    Animal  AIDS Dementia Complex/*ETIOLOGY/METABOLISM  Brain/*METABOLISM
       Cytokines/METABOLISM/PHYSIOLOGY  English Abstract  Human
       Kynurenine/METABOLISM  Macrophage Activation  Quinolinic
       Acids/*METABOLISM  JOURNAL ARTICLE  REVIEW  REVIEW, TUTORIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

