Chemical inducers of autophagy that enhance the clearance of mutant proteins in neurodegenerative diseases.

Many of the neurodegenerative diseases that afflict people are caused by intracytoplasmic aggregate-prone proteins. These include Parkinson disease, tauopathies, and polyglutamine expansion diseases such as Huntington disease. In Mendelian forms of these diseases, the mutations generally confer toxic novel functions on the relevant proteins.

Immune neuroendocrine interactions during a fungal infection in immunocompetent or immunosuppressed hosts.

The yeast Candida albicans belongs to the microflora of healthy individuals, although it can infect a variety of tissues ensuing changes in the host's immune status. To evaluate the effect of neuroendocrine input on the early immune response during the fungal infection, we use a 3-day paradigm of chronic varied stress in Wistar rats infected with C. albicans.

Autophagy induction reduces mutant ataxin-3 levels and toxicity in a mouse model of spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 is a neurodegenerative disorder caused by the expansion of the polyglutamine repeat region within the ataxin-3 protein. The mutant protein forms intracellular aggregates in the brain. However, the cellular mechanisms causing toxicity are still poorly understood and there are currently no effective treatments.

GABA transporter lysine 448: a key residue for tricyclic antidepressants interaction.

The effects of three tricyclic antidepressants (TCAs) and two serotonin selective reuptake inhibitors (SSRIs) have been studied with an electrophysiological approach on Xenopus laevis oocytes expressing the rat GABA (gamma-Aminobutyric-acid) transporter rGAT1. All tested TCAs and SSRIs inhibit the GABA-associated current in a dose-dependent way with low but comparable efficacy. The pre-steady-state and uncoupled currents appear substantially unaffected.

Endoplasmic reticulum stress reduces the export from the ER and alters the architecture of post-ER compartments.

In eukaryotic cells several physiologic and pathologic conditions generate the accumulation of unfolded proteins in the endoplasmic reticulum (ER), leading to ER stress. To restore normal function, some ER transmembrane proteins sense the ER stress and activate coordinated signalling pathways collectively called the Unfolded Protein Response (UPR). Little is known on how the UPR relates to post-ER compartments and to the export from the ER of newly synthesized proteins.

1-O-Hexadecyl-2-O-methyl-3-O-(2'-acetamido-2'-deoxy-beta-D-glucopyranosyl)-sn-glycerol (Gln) induces cell death with more autophagosomes which is autophagy-independent.

Autophagic cell death has recently received a great deal of attention. However, a dependence of this type of cell death on the actual process of autophagy has only rarely been proven. Indeed, it is important to differentiate between cell death with an accumulation of autophagosomes and cell death actually caused by excessive or inhibited autophagy.

Methodological considerations for assessing autophagy modulators: a study with calcium phosphate precipitates.

Autophagy has been implicated in various physiological and disease conditions in recent years. A number of small molecule modulators have been identified, both as tools and as potential therapeutics. Despite extensive characterization of autophagy in yeast, mammalian autophagy pathways are not fully understood.

[Music through earphones: an underestimated risk].

Background: The authors studied exposure to the noise generated by digital music listening devices (MP3) as used by young people.

Objectives: to study the level of sound emission of some of these devices at 100%, 75% and 50% volume.

Methods: Using a mannequin, the LeqA, LmaxA, LeqC and the peak in C of nine of the most commonly used devices was measured at levels of sound emission of 100%, 75% and 50%.

Candida albicans-secreted lipase induces injury and steatosis in immune and parenchymal cells.

Virulence depends on opposing reactions between host and pathogen and is intrinsically linked to the host immune status. Virulence factors rely upon microbial attributes that mediate cell damage. While the activity of several Candida albicans hydrolytic enzymes is well characterized, the biological role of lipases is uncertain.

Remifentanil plus low-dose midazolam for outpatient sedation in transesophageal echocardiography.

Background: The search for optimal sedation for transesophageal echocardiography (TEE) continues. We hypothesized that the ultra-short acting opioid remifentanil combined with very low-dose midazolam would provide a better sedation and recovery profile compared to midazolam alone.

Methods: 41 consecutive outpatients scheduled for TEE received either IV midazolam (group M, 2.

Regulation of ERGIC-53 gene transcription in response to endoplasmic reticulum stress.

Accumulation of unfolded proteins within the endoplasmic reticulum (ER) activates the unfolded protein response, also known as the ER stress response. We previously demonstrated that ER stress induces transcription of the ER Golgi intermediate compartment protein ERGIC-53. To investigate the molecular events that regulate unfolded protein response-mediated induction of the gene, we have analyzed the transcriptional regulation of ERGIC-53.

Hepatocellular apoptosis during Candida albicans colonization: involvement of TNF-alpha and infiltrating Fas-L positive lymphocytes.

The liver constitutes the first barrier in the control of hematogenous dissemination of Candida albicans of intestinal origin. In rats infected with C. albicans, this organ limits the growth of the yeast and mounts an efficient inflammatory reaction.

Nitric oxide-induced endoplasmic reticulum stress activates the expression of cargo receptor proteins and alters the glycoprotein transport to the Golgi complex.

The endoplasmic reticulum Golgi intermediate compartment 53 protein recycles continuously between the endoplasmic reticulum and the Golgi complex and ensures the anterograde transport of specific glycoproteins with the assistance of the Multiple Clotting Factor Deficiency adaptor protein. Therefore, to analyze the effect of the endoplasmic reticulum stress on the secretory pathway beyond the endoplasmic reticulum, we analyzed the expression of both proteins in J774 macrophages incubated with the nitric oxide donor DETA NONOate or with thapsigargin. Both proteins accumulated progressively, by a transcriptional mechanism, in response to these inducers.

Altered states of consciousness: processed EEG in mental disease.

Due to increasing life expectancy and a rising elderly population in Europe, the incidence of mild cognitive impairment which may predict diseases like Alzheimer's Disease or Vascular Dementia, is rising. Neurophysiological techniques are simple and inexpensive tools for early diagnosis and provide useful and objective correlates of cognitive activity both in normal subjects and patients suffering from the above conditions. Cognitive impairment due to different mental disease is characterized by decreased power and coherence in the alpha/beta band, which suggests functional disconnection among cortical areas, whereas both power and coherence in the delta and theta bands increase as a sign of cortical deafferentation from subcortical structures.

Preoperative use of enoxaparin increases the risk of postoperative bleeding and re-exploration in cardiac surgery patients.

Objective: The purpose of this study was to investigate if the preoperative use of new platelet inhibitors and low-molecular-weight heparins may contribute to bleeding after cardiac surgery.

Design: Retrospective data review.

Setting: University teaching hospital.

Heat shock induces preferential translation of ERGIC-53 and affects its recycling pathway.

ERGIC-53 is a lectin-like transport receptor protein, which recirculates between the ER and the Golgi complex and is required for the intracellular transport of a restricted number of glycoproteins. We show in this article that ERGIC-53 accumulates during the heat shock response. However, at variance with the unfolded protein response, which results in enhanced transcription of ERGIC-53 mRNA, heat shock leads only to enhanced translation of ERGIC-53 mRNA.

[Study on the appropriateness of utilization of dermatological consultants in emergency unit].

The aim of this study is to evaluate the rate of appropriate use of dermatologist consultants, in order to identify its determinants and to define its economic impact. We analysed 1750 dermatological procedures performed in the emergency room of the Azienda Ospedaliera "Maggiore della Carità" in Novara. The 87,64% of the procedures were inappropriate.

Biasing effect of the electromyogram on BIS: a controlled study during high-dose fentanyl induction.

Objective: A biasing effect of the electromyogram (EMG) on the Bispectral Index (BIS) may explain discrepancies in previous studies assessing BIS in the presence of neuromuscular activity. Our aims were: to evaluate variations of BIS in the presence of high EMG activity associated with muscular rigidity after administration of high-dose fentanyl; to compare muscular rigidity, as measured by the EMG variable of the BIS monitor, in patients who were administered two different dosages of fentanyl at induction of cardiac anaesthesia.

Methods: 26 patients undergoing CABG surgery, after premedication with morphine 0.

Low baseline Bispectral Index of the electroencephalogram in patients with dementia.

Unlabelled: The baseline value of the Bispectral Index (BIS) is 96-99 in the awake state. Patients with Alzheimer's disease or vascular dementia may show an increase in slow wave and a decrease in fast wave activity of the electroencephalogram (EEG). BIS is presumed to decrease with EEG slowing.

Coenzyme Q10, exercise lactate and CTG trinucleotide expansion in myotonic dystrophy.

Steinert's myotonic dystrophy (DM) is a genetic autosomal dominant disease and the most frequent muscular dystrophy in adulthood. Although causative mutation is recognized as a CTG trinucleotide expansion on 19q13.3, pathogenic mechanisms of multisystem involvement of DM are still under debate.

Abnormal H-Tfam in a patient harboring a single mtDNA deletion.

We report on a patient suffering from a progressive mitochondrial disorder characterized by ocular myopathy, exercise intolerance, and muscle wasting. Morphological examination of muscle biopsy showed increased variability in fiber size and scattered ragged-red fibers. Analysis of muscle mitochondrial DNA by Southern blot and PCR revealed a heteroplasmic single deletion of 4100 base pairs, located between nucleotide positions 8300 and 12,400.