Genistein protects against amyloid-beta-induced toxicity in SH-SY5Y cells by regulation of Akt and Tau phosphorylation.

Alzheimer's disease is a neurodegenerative disorder characterized by extracellular deposition of amyloid-β (Aβ) peptide and hyperphosphorylation of Tau protein, which ultimately leads to the formation of intracellular neurofibrillary tangles and cell death. Increasing evidence indicates that genistein, a soy isoflavone, has neuroprotective effects against Aβ-induced toxicity. However, the molecular mechanisms involved in its neuroprotection are not well understood.

Alterations on Na⁺,K⁺-ATPase and acetylcholinesterase activities induced by amyloid-β peptide in rat brain and GM1 ganglioside neuroprotective action.

Alzheimer's disease (AD) is a neurodegenerative disorder whose pathogenesis involves production and aggregation of amyloid-β peptide (Aβ). Aβ-induced toxicity is believed to involve alterations on as Na(+),K(+)-ATPase and acetylcholinesterase (AChE) activities, prior to neuronal death. Drugs able to prevent or to reverse these biochemical changes promote neuroprotection.

Alterations of membrane lipids and in gene expression of ganglioside metabolism in different brain structures in a mouse model of mucopolysaccharidosis type I (MPS I).

Mucopolysaccharidosis I (MPS I) is a congenital disorder caused by the deficiency of α-l-iduronidase (IDUA), with the accumulation of glycosaminoglycans (GAGs) in the CNS. Although GAG toxicity is not fully understood, previous works suggest a GAG-induced alteration in neuronal membrane composition. This study is aimed to evaluate the levels and distribution of gangliosides and cholesterol in different brain regions (cortex, cerebellum, hippocampus and hypothalamus) in a model using IDUA knockout (KO) mice (C57BL/6).

Resveratrol prevents global cerebral ischemia-induced decrease in lipid content.

Objective: The present study was undertaken to evaluate whether resveratrol (RSV) modulates membrane lipid composition, as well as on ganglioside profile in ischemia/reperfusion injury.

Methods: Global cerebral ischemia was induced by four-vessel occlusion for 10 minutes. RSV (30 mg/kg) or vehicle was intraperitoneally administered to rats 7 days prior to ischemia.

Amyloid-β induced toxicity involves ganglioside expression and is sensitive to GM1 neuroprotective action.

The effect of Aβ25-35 peptide, in its fibrillar and non-fibrillar forms, on ganglioside expression in organotypic hippocampal slice cultures was investigated. Gangliosides were endogenously labeled with D-[1-C(14)] galactose and results showed that Aβ25-35 affected ganglioside expression, depending on the peptide aggregation state, that is, fibrillar Aβ25-35 caused an increase in GM3 labeling and a reduction in GD1b labeling, whereas the non-fibrillar form was able to enhance GM1 expression. Interestingly, GM1 exhibited a neuroprotective effect in this organotypic model, since pre-treatment of the hippocampal slices with GM1 10 μM was able to prevent the toxicity triggered by the fibrillar Aβ25-35, when measured by propidium iodide uptake protocol.

Effects of chronic proline administration on lipid contents of rat brain.

In the present work we investigated the effects of chronic proline administration on ganglioside, cholesterol and phospholipid total contents, as well as on ganglioside profile in cerebral cortex, hippocampus, hypothalamus and cerebellum of rats. We also evaluated the ganglioside content and profile in detergent-soluble and resistant microdomains isolated from synaptic membranes obtained from cerebral cortex. Proline solution (hyperprolinemic) or saline (control) were subcutaneously administered to rats from 6th to 28th post-natal day, according to body weight.

Reduction of gangliosides, phospholipids and cholesterol content in cerebral cortex of rats caused by chronic hypermethioninemia.

Neurological dysfunction is observed in patients with severe hypermethioninemia, whose physiopathology is still poorly understood. In the current study we investigated the effect of chronic administration of methionine on the content and species of gangliosides and phospholipids, as well as on the concentration of cholesterol in rat cerebral cortex. Wistar rats received subcutaneous injections of methionine (1.

Phase I study with an autologous tumor cell vaccine for locally advanced or metastatic prostate cancer.

Purpose: To attempt the isolation and primary culture of prostate tumor cells, to use the cultured cells for active immunotherapy, and to evaluate the safety and efficacy in a Phase I clinical trial.

Materials And Methods: Tumor fragments were collected from 50 patients with prostate-specific antigen (PSA) > or = 10 ng/mL, < or = cT2 PCa who underwent radical retropubic prostatectomy (RRP) and 6 patients with metastatic PCa who underwent transurethral resection of the prostate (TURP). Cultured tumor cells were incubated with IFN-fi, irradiated, and cryopreserved.

Health innovation networks to help developing countries address neglected diseases.

Gross inequities in disease burden between developed and developing countries are now the subject of intense global attention. Public and private donors have marshaled resources and created organizational structures to accelerate the development of new health products and to procure and distribute drugs and vaccines for the poor. Despite these encouraging efforts directed primarily from and funded by industrialized countries, sufficiency and sustainability remain enormous challenges because of the sheer magnitude of the problem.