A human immunodeficiency virus type 1 (HIV) -seropositive, antiretroviral-naive patient presented with significant cognitive dysfunction. Neuropsychologic, neuroradiologic, immunologic, and virologic studies confirmed HIV-associated dementia (HAD). After 12 weeks of highly active antiretroviral therapy (HAART) with ibuprofen, dramatic improvements were demonstrated in neurologic function and were sustained for ú1 year. HIV-1 RNA in cerebrospinal fluid (CSF) decreased from 10 5 to 10 4 copies/mL after 4 weeks. After 20 weeks of therapy, plasma viremia decreased from 10 6 copies/mL to undetectable (õ96 copies/mL). Assays of neurotoxins (tumor necrosis factor-a, quinolinic acid, and nitric oxide) in plasma and CSF were considerably elevated at presentation and significantly decreased after therapy. Baseline plasma and CSF demonstrated neurotoxic activities in vitro, which also reduced markedly. These data, taken together, support the notion that HAD is a reversible metabolic encephalopathy fueled by viral replication. HAART used with nonsteroidal antiinflammatory agents leads to the suppression of inflammatory neurotoxins and can markedly improve neurologic function in HAD.Human immunodeficiency virus type 1 (HIV)-associated deproteins such as gp120, tat, and nef [18][19][20][21][22]. High levels of these macrophage-produced neurotoxic factors have been found mentia (HAD) is characterized by cognitive and motor impairment in 15%-20% of infected patients [1][2][3][4]. Neurologic defiin the brains and cerebrospinal fluid (CSF) of patients with HAD [23][24][25][26]. These factors produce an encephalopathy with cortical cits have been classified by the American Academy of Neurology, and an algorithm has been developed for mild disand subcortical neuronal damage [27] and induce a breakdown of the blood-brain barrier (BBB) [28, 29]. ease (minor cognitive/motor disorder) or more severe impairment (HAD) [1]. Dementia can occur with few neuropathologic HIV RNA levels in CSF correlate with the presence and severity of cognitive dysfunction [30 -33]. If a central nervous changes or with encephalitis characterized by multinucleated giant cells, astrocytosis, microglial nodules, myelin pallor, and system virus is both necessary and sufficient to induce neurologic impairment, therapy for HAD should of necessity target neuronal loss [5,6]. Of interest, clinical disease is not caused by active HIV replication in neural cells. The virus's target cells HIV. Inhibitors of HIV protease in combination with nucleoside analogue reverse transcriptase (RT) inhibitors can dramatiare mononuclear phagocytes (brain macrophages and microglia) [7,8]. Once infected, these cells become immunoactive and cally reduce levels of plasma viremia [34,35]. Unfortunately, many of these agents are highly plasma protein bound and have produce a variety of neurotoxic secretory products [9]. These include but are not limited to cytokines such as tumor necrosis limited BBB penetration [36]. Zidovudine remains the only drug to date with documented efficacy for H...

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Neuropathologic evaluation of two infants with thanatophoric dysplasia displayed typical gross morphologic characteristics and a distinct pattern of brain malformations, including anomalies of the temporal lobe gyri and hippocampus, neuroglial heterotopias, fiber tract hypoplasia, and dysplasia of deep nuclei. Increased numbers of horizontal cells of Cajal-Retzius were striking in frequency and distribution. The pattern of abnormalities suggests arrest of cerebral cortical ontogeny late in development. As with the mucopolysaccharidoses, a shared common metabolic pathway is a potential mechanism for development of widespread bony and somatic abnormalities and associated central nervous system anomalies.

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These data suggest that resistance exercise plus Cr supplementation may promote gains in strength and FFM in patients with MG.

In an attempt to correlate the ability to activate transcription with affinity for single-stranded DNA, both wild-type and temperature-sensitive pseudorabies virus immediate-early proteins were tested for the ability to bind to single-stranded DNA columns. Wild-type and temperature-sensitive immediate-early proteins bound to nonspecific single-stranded DNA columns with similar affinities at both 0 and 40°C. There did not seem to be a direct correlation between the ability to activate transcription and the ability to bind to single-stranded DNA. To study further the interactions that are involved in binding to single-stranded DNA, we expressed the immediate-early protein in an Escherichia coli expression vector. In this system the expressed immediate-early protein was not phosphorylated, nor could it be complexed with mammalian cell factors. The first trp construct did not express a soluble form of the immediate-early protein, presumably due to the insoluble nature of the trp leader. We deleted a large segment of the trpE gene and found that the immediate-early fusion protein was soluble. We tested this protein for its affinity for single-stranded DNA by passage over single-stranded DNA cellulose columns. The bacterially expressed immediate-early protein bound single-stranded DNA at least as well as did the wild-type protein. Affinity for single-stranded DNA did not appear to be dependent on the phosphorylation state nor on the presence of mammalian cell factors.

Seventeen normal volunteers received either 0.5 mg, 1.5 mg, or 2.5 mg physostigmine i.v. in a placebo-drug-placebo single-blind design. EEG was recorded simultaneously and analyzed by computerized spectral analysis. Eleven healthy elderly volunteers (mean age = 69.1 years) with mild memory impairment were treated with placebo, followed by oral choline chloride (either 8 g/day for 3 weeks, or 16 g/day for 1 week), and then, again, placebo. Recordings of spontaneous EEG and EEG event-related potentials (contingent negative variation) were obtained during both placebo and choline treatments. The larger doses of physostigmine produced an increase in low frequency activity and a slowing of the peak alpha frequency. Oral choline chloride had no effect on the EEG as measured by spectral analysis, but appears to have differential effects on contingent negative variation (CNV) amplitude and reaction time, depending upon the initial CNV amplitude.