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. Electrooculogram, self-ratings (Karolinska Sleepiness Scale and Visual Analog Scale for Global Vigor), and tympanic temperature were also recorded. RESULTS: Changes in sleepiness and alertness are paralleled by increases in slow eye movements and theta and delta EEG power. The beginning of the rise of delta, theta, and slow eye movement activity corresponded to the nadir of temperature, peaking at 7:00AM. Cross-correlational analyses showed that changes in slow eye movements were strictly phase locked to those in slow-frequency EEG bands and in subjective measures. The comparison of time intervals that were equivalent with respect to circadian phase confirms the effects of the increased sleepiness on slow eye movement activity and on the other measures. The temporal concordance of the different physiologic and subjective measures is also reflected in the individual time courses. Individual and group analyses converged in indicating that slow eye movements can be considered reliable indexes of sleepiness but only in the eyes-closed condition. CONCLUSIONS: Results suggest that subjective and EEG changes associated with higher sleepiness are paralleled by an increase in slow eye movement activity, but this relationship exists almost exclusively with the eyes closed. Hence, its use in practical and operational contexts seems limited.     

Glutathione levels modulate domoic acid induced apoptosis in mouse cerebellar granule cells.

Exposure of mouse cerebellar granule neurons (CGNs) to domoic acid induced cell death, either by apoptosis or by necrosis, depending on its concentration. Necrotic damage predominated in response to domoic acid above 0.1 microM. In contrast, cell injury with apoptotic features (assessed by Hoechst staining and DNA laddering assay) was evident after exposure to lower concentrations of domoic acid (< or = 0.1 microM). The AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)/kainate receptor antagonist 2,3-dihydroxy-6-nitro-sulfamoylbenzo [f] quinoxaline, but not the N-methyl-D-aspartate receptor antagonist MK-801, prevented domoic acid-induced apoptosis. To evaluate the role of oxidative stress in domoic acid-induced apoptosis, experiments were carried out in CGNs isolated from wild-type mice (Gclm (+/+)) and mice lacking the modifier subunit of glutamate-cysteine ligase, the first and rate-limiting step of glutathione (GSH) biosynthesis (Gclm (-/-)). CGNs from Gclm (-/-) mice have very low levels of GSH and were more sensitive to domoic acid-induced apoptosis and necrosis than Gclm (+/+) CGNs. The antioxidant melatonin (200 microM) and the membrane-permeant GSH delivery agent GSH ethyl ester (2.5 mM) prevented domoic acid-induced apoptosis. Domoic acid increased formation of reactive oxygen species but did not affect intracellular GSH levels. Domoic acid also increased cytosolic and mitochondrial calcium levels, increased oxidative stress in mitochondria, and altered mitochondrial membrane potential, which ultimately caused cytochrome c release, activation of caspase-3, and degradation of poly (ADP-ribose) polymerase. These results indicate that low concentrations of domoic acid cause apoptotic neuronal cell death mediated by oxidative stress.     

Chronic pain in urological diseases: a clinical review

Chronic pain is the central problem in a variety of urological diseases. Pain is an unpleasant sensory and emotional experience associated with either actual or potential tissue damage, or described in terms of such damage. The aim of this research was to update knowledge about the ultrastructural, clinical, psychological and therapeutic aspects of chronic pain in urological diseases, in particular in chronic pelvic syndrome. In this paper we have revisited the most significant and discussed articles published in the last twenty five years, with particular references on the 2008 European Guidelines, searching key words (chronic pelvic pain syndrome, chronic pelvic pain, chronic prostatitis, interstitial cystitis, prostatodynia, urological disease) and data with a high level of evidence. The articles that we have analyzed show that pain is characterized by an initial tissue injury that can lead to sensitization, which is a decrease in the intensity of the stimulus needed to elicit a response by the nerve, involving the peripheral and central nervous systems. The chronic pain state is characterized by loss of inhibitory interneurons, establishment of aberrant excitatory synaptic connections and long-term potentiation of response due to changes in sensitivity of nerve synapses. Stress and hormones might also play a role in central sensitization. Pain also has a cognitive and emotional component. It is very difficult to treat, given the complex nature of the response and the interaction of physiological aspects     

International nursing: the past 25 years and beyond

International nursing has grown substantially in the last 25 years. Once practiced only during war time, with immigrant populations, or in peace time in consultative roles, international nursing is now common, with direct practice, education, consultation, and research collaboration as the roles in which nurses work across borders. A brief history of international nursing, forces that have influenced its growth, and an assessment of its future are discussed.     

Mesothelioma registry of the Liguria region. Incidence and occupational etiology in a high risk area

This paper presents the epidemiological analyses based on the first 5 years of activity of the Mesothelioma Registry of Liguria (REM). REM is a population-based cancer registry specialized in the study of both the incidence and etiology of primary pleural and peritoneal mesothelioma in Liguria (Italy). The REM completes normal clinical information with occupational and environmental anamnestic data in order to identify working and living areas at risk for asbestos-related pathologies. The REM started its activity in 1994 describing the incidence of pleural mesothelioma (PM) exclusively in the population resident in the city of Genoa (660,000 inhabitants); since 1996 the REM has studied the entire Liguria Region (1,640,000 inhabitants), where nearly 120 new cases of PM are diagnosed annually (20% are women). In the city of Genoa, between 1986-1987 and 1997-1998, PM crude incidence rate rose from 13.8 to 26.7 per 100,000 males over 40 years old. From 1994 to 1998 the REM registered 495 new patients with histologically (62%) and cytologically (9%) confirmed diagnosis of PM. 54% of them were immunocytohistochemically evaluated. Occupational information has been gathered for 248 subjects, i.e., 61% of cases with sure or probable diagnosis of PM. For 126 patients, occupational asbestos exposure (direct, indirect or only presence in the workplace) was identified on average 40 years before diagnosis. In particular, asbestos exposure was documented in shipyards, docks and cargo handling settings, building trades, iron and steel industries. Interestingly, during the same period (1955-1960), a large fraction of subjects without proved or declared direct asbestos exposure claimed to have worked in the same occupational settings. This suggests a possible unconscious indirect exposure to asbestos fibers in the workplace.     

Antimicrobial peptides: synthesis and antibacterial activity of linear and cyclic drosocin and apidaecin 1b analogues

Drosocin and apidaecin Ib are two insect antimicrobial peptides showing a significant sequence homology and a common mechanism of action, which includes stereoselective elements but is devoid of any pore-forming activity. A substantial difference between the two peptides is the presence in the drosocin sequence of an O-glycosylated threonine residue, which is important for its antimicrobial activity. Through the synthesis of a series of differently glycosylated drosocin analogues, we have shown that the antimicrobial activity against several Gram-negative bacteria appears to be modulated by the sugar moiety (Gal vs GalNAc) and the type of glycosidic linkage (alpha-O-, beta-O-, or alpha-C-). The insertion of a glycosylated threonine residue in the apidaecin Ib sequence improves the sequence homology with drosocin but reduces the antimicrobial activity. To gain information on the possible bioactive conformation of these peptides, we synthesized an unglycosylated cyclic analogue of drosocin, containing an intrachain disulfide bond, and the head-to-tail cyclic analogues of drosocin and apidaecin, as well as their corresponding cyclic dimers. Only the large cyclic dimer of apidaecin partially retained the antimicrobial activity, suggesting that a bending of the peptide chain, in particular in the middle of the molecule, is not a structural element characteristic of the bioactive conformation of drosocin and apidaecin. Experiments aimed at testing the effect of selected drosocin and apidaecin peptides on biological membranes showed that some peptides display a moderate hemolytic activity and that a dissociation between antibacterial activity and cytotoxicity to eukaryotic cells can be achieved in differently glycosylated peptide analogues.     

Radiosensitization of human melanoma cells by ribozyme-mediated inhibition of survivin expression

Survivin is a structurally unique member of the inhibitors of apoptosis protein family and is involved in the control of cell division and inhibition of apoptosis. The notion that survivin is overexpressed in most human tumors but absent in normal adult tissues with only a few exceptions has led to the proposal of survivin as a promising therapeutic target for novel anticancer therapies. In this context, we generated a hammerhead ribozyme targeting the 3' end of the CUA110 triplet in the survivin mRNA. Two human melanoma cell lines (JR8 and M14) overexpressing survivin were stably transfected with the pRc/CMV vector carrying the ribozyme sequence. Two polyclonal cell populations proven to endogenously express ribozyme and characterized by a markedly lower survivin protein level (-60% and -50%, respectively) than JR8 and M14 parental cells were selected for the study. Ribozyme-expressing cells showed a significantly (p<0.01) increased sensitivity to gamma-irradiation (as detected by clonogenic cell survival) compared to JR8 and M14 cells. Moreover, in the JR8 cell line, the extent of radiation-induced apoptosis (in terms of percentage of apoptotic nuclei in cells stained with propidium iodide and level of caspase-3 catalytic activity) was markedly greater in ribozyme-expressing cells than in parental cells. These results demonstrate for the first time that attenuation of survivin expression renders human melanoma cells more susceptible to gamma-irradiation.     

p38 MAP kinase mediates the cell death induced by PrP106-126 in the SH-SY5Y neuroblastoma cells

Prion diseases are neurodegenerative pathologies characterized by the accumulation in the brain of a protease-resistant form of the prion protein (PrP(c)), named PrP(Sc). A synthetic peptide homologous to residues 106-126 of PrP (PrP106-126) maintains many PrP(Sc) characteristics. We investigated the intracellular signaling responsible for the PrP106-126-dependent cell death of SH-SY5Y, a cell line derived from a human neuroblastoma. In this cell line, PrP106-126 induced apoptotic cell death and caused activation of caspase-3, although the blockade of this enzyme did not inhibit cell death. The p38 MAP kinase blockers, SB203580 and PD169316, prevented the apoptotic cell death evoked by PrP106-126 and Western blot analysis revealed that the exposure of the cells to the peptide induced p38 phosphorylation. Taken together, our data suggest that the p38 MAP kinase pathway can mediate the SH-SY5Y cell death induced by PrP106-126.