Platelet as a physiological model to investigate apoptotic mechanisms in Alzheimer beta-amyloid peptide production.

Although neuronal apoptosis in Alzheimer's disease is generally interpreted as the consequence of the toxicity of extracellular beta-amyloid (Abeta) peptide aggregates, some experimental results provide evidence that the Abeta overproduction can be the result of a primary neuronal degeneration. As platelets are considered a good model where to study proteolytic processing of the amyloid precursor protein (APP), we exposed platelets to the proapoptotic agent ionomycin and analyzed Abeta40 and Abeta42 levels in the intracellular and extracellular compartments. The activation of apoptotic pathways in platelets has been verified by mitochondrial membrane depolarization, exposure of phosphatidylserine, protease activation and morphological changes.

HCV patients, psychopathology and tryptophan metabolism: analysis of the effects of pegylated interferon plus ribavirin treatment.

Aims: Depression and other psychiatric disorders are frequent in HCV-infected patients, especially during interferon treatment. The molecular mechanism(s) underlying this finding is still unknown but it has been suggested that HCV and/or interferon administration may increase indoleamine 2,3-dioxygenase (IDO) activity, and reduce plasma tryptophan (TRP) levels and brain serotonin synthesis thus leading to psychopathological disorders.

Methods: We studied 89 subjects: (a) 39 patients with chronic hepatitis C virus (HCV) infection and mild liver damage; (b) 39 healthy controls; and (c) 10 patients with chronic hepatitis B virus (HBV) infection.

Poly(ADP-ribose)polymerase 1 (PARP-1) and postischemic brain damage.

Poly(ADP-ribose)polymerases (PARPs) are enzymes that are able to catalyze the transfer of ADP-ribose units from NAD to substrate proteins and are particularly abundant in cell nuclei where they play key roles in the maintenance of genomic integrity, control of cell cycle and gene expression. Brain ischemia overactivates PARPs and PARP-deficient mice or animal treated with PARP inhibitors have a drastically reduced brain damage in various stroke models. PARP 'overactivation' occurs not only in neurons but also in astrocytes, microglial cells, endothelia, and infiltrating leukocytes.

Visceral hypersensitivity and intolerance symptoms in lactose malabsorption.

Lactose malabsorption is not always associated with intolerance symptoms. The factors responsible for symptom onset are not yet completely known. As differences in visceral sensitivity may play a role in the pathogenesis of functional symptoms, we evaluated whether an alteration of visceral sensitivity is present in subjects with lactose intolerance.

Sleep in the human hippocampus: a stereo-EEG study.

Background: There is compelling evidence indicating that sleep plays a crucial role in the consolidation of new declarative, hippocampus-dependent memories. Given the increasing interest in the spatiotemporal relationships between cortical and hippocampal activity during sleep, this study aimed to shed more light on the basic features of human sleep in the hippocampus.

Methodology/principal Findings: We recorded intracerebral stereo-EEG directly from the hippocampus and neocortical sites in five epileptic patients undergoing presurgical evaluations.

[Incidence of thyroid nodules in patients with and without atrial fibrillation].

In one of our previous articles we noted that many patients affected by atrial fibrillation had more thyroid nodules > or = 10mm (38%) than general population (10%). These data are confirmed by a same number of patients without atrial fibrillation admitted to our Department of Internal Medicine. The high incidence of low-T3 syndrome is confirmed too.

[Clinical differences between heart failure versus ischemic patients].

Heart failure represents a very common disease with high mortality, despite therapeutic and preventive measures. In order to evaluate the characteristics of heart failure patients, a case-control study was carried out, comparing sixty heart failure patients versus sixty patients who presented an evident atherosclerotic disease, but not heart failure. Among the differences we found, a higher heart rate, reduced levels of free-triiodothyronine and increased levels of serum uric acid in heart failure patients might directly contribute to its pathophysiology and represent potential therapeutic targets.

High mobility group box 1 protein is released by neural cells upon different stresses and worsens ischemic neurodegeneration in vitro and in vivo.

High mobility group proteins are chromatin binding factors with key roles in maintenance of nuclear homeostasis. The evidence indicates that extracellularly released high mobility group box 1 (HMGB1) protein behaves as a cytokine, promoting inflammation and participating to the pathogenesis of several disorders in peripheral organs. In this study, we have investigated the expression levels and relocation dynamics of HMGB1 in neural cells, as well as its neuropathological potential.

Differential role of mGlu1 and mGlu5 receptors in rat hippocampal slice models of ischemic tolerance.

Activation of glutamate receptors has been proposed as a key factor in the induction of ischemic tolerance. We used organotypic rat hippocampal slices exposed to 30 min oxygen-glucose deprivation (OGD) to evaluate postischemic pyramidal cell death in the CA1 subregion. In this model, 10 min exposure to OGD 24 h before the exposure to toxic OGD was not lethal and reduced the subsequent OGD neurotoxicity by approximately 53% (ischemic preconditioning).

A key role for poly(ADP-ribose) polymerase-1 activity during human dendritic cell maturation.

Poly(ADP-ribose) (PAR) polymerase (PARP)-1 is a nuclear enzyme regulating protein that functions by targeting PAR chains. Besides its classic role in DNA repair, PARP-1 is emerging as a key transcriptional regulator in different cell types including the immune ones. In this study, we investigated the role of PARP-1 in human dendritic cell (DC) function.

Slow eye movements and subjective estimates of sleepiness predict EEG power changes during sleep deprivation.

Rationale: The aim of the present study was to assess, intraindividually, the relationship among slow eye movements, electroencephalogram (EEG) power, and subjective measures of sleepiness during a 40-hour sleep deprivation comparing 2 experimental conditions: eyes-open and eyes-closed.

Methods: Nineteen normal subjects participated in a sleep-deprivation protocol with recordings of the waking Cz-A1-2 EEG in 36 sessions at 1-hour intervals starting at 10:00 AM. Each session consisted of a 2-minute eyes-closed period, followed by a 4-minute eyes-open period.

Neurophysiological correlates of sleepiness: a combined TMS and EEG study.

Changes of cortical and corticospinal excitability as a function of sleep deprivation have been studied, using EEG power maps and several TMS measures in 33 normal subjects before and after a 40-h sleep deprivation (SD). The effects of SD were independently assessed by subjective and EEG measures of sleepiness, the latter being represented in terms of cortical maps for different frequency bands. Short intracortical facilitation (SICF) and inhibition (SICI) were measured by the paired-pulse TMS technique with different inter-stimulus intervals.

Neurophysiological effects of mobile phone electromagnetic fields on humans: a comprehensive review.

In recent years a growing number of people have begun to use mobile phone technology. This phenomenon has raised questions and doubts about possible effects on users' brains. This literature review focuses on the human electrophysiological and neuro-metabolic effects of mobile phone (MP)-related electromagnetic fields (EMFs) published in the last 10 years.

Amatoxin poisoning: a 15-year retrospective analysis and follow-up evaluation of 105 patients.

Introduction: Fatalities due to mushroom poisonings are increasing worldwide, with more than 90% of deaths resulting from ingestion of amatoxin-containing species.

Methods: A retrospective evaluation of the history and clinical outcome of each patient treated from 1988 to 2002 in the Toxicological Unit of Careggi General Hospital (University of Florence, Italy) for amatoxin poisoning. Data included the biological parameters monitored, the treatment protocols used (intensive fluid and supportive therapy, restitution of the altered coagulation factors, multiple-dose activated charcoal, mannitol, dexamethasone, glutathione, and penicillin G), and outpatient follow-up evaluations.

Relationship between low T3 syndrome and NT-proBNP levels in non-cardiac patients.

Objectives: A low T3 syndrome was described in patients with heart failure (HF), and it appears to be associated with adverse outcome, representing an independent predictor of mortality. However, it is not known if low T3 levels contribute to the pathophysiology of HF. On the other hand, it has been seen that an elevation of brain natriuretic peptides (BNP and NT-proBNP) may represent a warning signal for future cardiovascular disease and may be an early marker of diastolic dysfunction.

Carboxymethyl beta-glucan binds to corneal epithelial cells and increases cell adhesion to laminin and resistance to oxidative stress.

Purpose: Polysaccharides are frequently used as viscoelastic agents to improve pharmacokinetics of ophthalmic preparations. Recently, polysaccharides from yeast cell walls such as beta-glucans have emerged as bioactive molecules endowed with immunomodulatory and cytoprotective properties. In this study, we investigated the effects of carboxymethyl beta-glucan (CMG), a water-soluble derivative of yeast beta-glucan, on cultured rabbit corneal epithelial cells.

Poly(ADP-ribosyl)ation regulates heat shock factor-1 activity and the heat shock response in murine fibroblasts.

Poly(ADP-ribose) polymerase-1 (PARP-1)-dependent poly(ADP-ribose) formation is emerging as a key regulator of transcriptional regulation, even though the targets and underlying molecular mechanisms have not yet been clearly identified. In this study, we gathered information on the role of PARP-1 activity in the heat shock response of mouse fibroblasts. We show that DNA binding of heat shock factor (HSF)-1 was impaired by PARP-1 activity in cellular extracts, and was higher in PARP-1(-/-) than in PARP-1+/+ cells.

Directional information flows between brain hemispheres during presleep wake and early sleep stages.

Neuroscientists' efforts to better understand the underlying processes of human consciousness are growing in a variety of multidisciplinary approaches. Relevant within these are the studies aimed at exploring the physiological substratum of the propagation and reduction of cerebral-namely, corticocortical-communication flows. However, the preferential direction of the information flow between brain hemispheres is as yet largely unknown.

Neither energy collapse nor transcription underlie in vitro neurotoxicity of poly(ADP-ribose) polymerase hyper-activation.

Poly(ADP-ribose)polymerase-1 (PARP-1) overactivation is a key event in neurodegeneration but the underlying molecular mechanisms wait to be unequivocally identified. Energy failure, transcriptional derangement and deadly nucleus-mitochondria cross-talk have been proposed as mechanisms responsible for PARP-1 neurotoxicity. In this study, we sought to determine how these mechanisms contributes to PARP-1-dependent neuronal death.

Modulation of corticospinal excitability by paired associative stimulation: reproducibility of effects and intraindividual reliability.

Objective: Electrical stimulation of the median nerve followed by a magnetic pulse on the primary motor cortex (M1) is effective to cause an increase in the amplitude of motor evoked potential (MEP) registered in the target muscle with the interstimulus interval (ISI) at 25ms (paired associative stimulation, PAS). The aim of this study is to evaluate the reproducibility of PAS with ISI 25 (PAS25), assessed in two separate sessions. Intraindividual reliability of TMS measures was also evaluated.

Pharmacological inhibition of histone deacetylases by suberoylanilide hydroxamic acid specifically alters gene expression and reduces ischemic injury in the mouse brain.

Pharmacological manipulation of gene expression is considered a promising avenue to reduce postischemic brain damage. Histone deacetylases (HDACs) play a central role in epigenetic regulation of transcription, and inhibitors of HDACs are emerging as neuroprotective agents. In this study, we investigated the effect of the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) on histone acetylation in control and ischemic mouse brain.

Low serum tryptophan levels, reduced macrophage IDO activity and high frequency of psychopathology in HCV patients.

Indoleamine 2,3-dioxygenase (IDO), a key enzyme of tryptophan (TRP) metabolism, is induced in various tissues of patients with bacterial and viral infection or with neoplastic diseases. This induction is considered the main cause of the decreased serum TRP levels, the reduced brain serotonin synthesis and the occurrence of psychopathological disorders often detected in patients with chronic infections or different forms of cancer. We studied 89 subjects including: (a) 39 patients with chronic hepatitis C virus (HCV) infection and mild liver damage (b) 40 healthy controls, and (c) 10 patients with chronic hepatitis B virus (HBV) infection.

Kynurenic acid inhibits the release of the neurotrophic fibroblast growth factor (FGF)-1 and enhances proliferation of glia cells, in vitro.

1. Kynurenic (KYNA) and quinolinic (QUIN) acids are neuroactive tryptophan metabolites formed along the kynurenine pathway: the first is considered a non-competitive antagonist and the second an agonist of glutamate receptors of NMDA type. The affinity of these compounds for glutamate receptors is, however, relatively low and does not explain KYNA neuroprotective actions in models of post-ischemic brain damage.