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Sleep is a crucial component of life, characterized by global behavioral and neurochemical inhibition of brain activity. The gold-standard measurement of sleep is polysomnography (PSG). It assesses several organic functions during sleep, embracing brain activity, eyes movements, muscular pattern, and heart rhythm. Despite motor function being reduced during all sleep stages, particular muscular groups remain active, including those involved in respiratory or eye movement control. Polysomnography depends on this residual muscle activity to achieve reliable sleep recordings. Any interference with mechanisms dictating this behavior might impact electrogenic patterns in PSG, therefore, affecting clinical conclusions. There is a lack of knowledge about the association between myofunctional patterns during sleep and the widely prescribed cosmetic procedure of botulinum neurotoxin (BoNT). Considering aesthetical purposes, BoNT injection is often used to minimize facial wrinkles, through a reduction on the tonus of target muscles via cholinergic pathways. This review aimed to raise two important and clinically pertinent questions: (1) would the muscular hypotonicity caused by treatment with BoNT affect PSG patterns?; (2) could this change the way sleep looks like after BoNT-based cosmetic treatment challenging the effective use of standard PSG scoring criteria? A critical review of the literature currently available in the PubMed electronic database was undertaken. This review confirmed the lack of data regarding the possible consequences of the cosmetic use of BoNT on PSG reading and interpretation. We propose putative mechanisms and pathways by which this treatment could have these effects with clinically relevant impact on diagnosis of sleep disturbances. Even though there is little evidence on the relationship between cosmetic use of BoNT and substantial changes on sleep related motor control, it is reasonable to hypothesize that this may impact PSG patterns and its interpretation. As the use of this drug is rising, as well as there is an increase on the prevalence of sleep disturbances needing PSG diagnosis, this should be a relevant subject warranting future research.

Vacunación; Narcolepsia; Simulación y modelado: en Vacunació; Narcolèpsia; Simulació i modelització Vaccination; Narcolepsy; Simulation and modeling Background & objectives Vaccine safety signals require investigation, which may be done rapidly at the population level using ecological studies, before embarking on hypothesis-testing studies. Incidence rates were used to assess a signal of narcolepsy following AS03-adjuvanted monovalent pandemic H1N1 (pH1N1) influenza vaccination among children and adolescents in Sweden and Finland in 2010. We explored the utility of ecological data to assess incidence of narcolepsy following exposure to pandemic H1N1 virus or vaccination in 10 sites that used different vaccines, adjuvants, and had varying vaccine coverage. Methods We calculated incidence rates of diagnosed narcolepsy for periods defined by influenza virus circulation and vaccination campaign dates, and used Poisson regression to estimate incidence rate ratios (IRRs) comparing the periods during which wild-type virus circulated and after the start of vaccination campaigns vs. the period prior to pH1N1 virus circulation. We used electronic health care data from Sweden, Denmark, the United Kingdom, Canada (3 provinces), Taiwan, Netherlands, and Spain (2 regions) from 2003 to 2013. We investigated interactions between age group and adjuvant in European sites and conducted a simulation study to investigate how vaccine coverage, age, and the interval from onset to diagnosis may impact the ability to detect safety signals. Results Incidence rates of narcolepsy varied by age, continent, and period. Only in Taiwan and Sweden were significant time-period-by-age-group interactions observed. Associations were found for children in Taiwan (following pH1N1 virus circulation) and Sweden (following vaccination). Simulations showed that the individual-level relative risk of narcolepsy was underestimated using ecological methods comparing post- vs. pre-vaccination periods; this effect was attenuated with higher vaccine coverage and a shorter interval from disease onset to diagnosis. Conclusions Ecological methods can be useful for vaccine safety assessment but the results are influenced by diagnostic delay and vaccine coverage. Because ecological methods assess risk at the population level, these methods should be treated as signal-generating methods and drawing conclusions regarding individual-level risk should be avoided. Antecedents i objectius Els senyals de seguretat per les vacunes requereixen una investigació, que es pot fer ràpidament a nivell de població mitjançant estudis ecològics, abans d'iniciar estudis de prova d'hipòtesi. Les taxes d'incidència es van utilitzar per avaluar un senyal de narcolèpsia després de la vacunació contra la influença pandèmica monovalent H1N1 (pH1N1) adjuvant de AS03 en nens i adolescents a Suècia i Finlàndia el 2010. Explorem la utilitat de les dades ecològiques per avaluar la incidència de la narcolèpsia després de l'exposició a la pandèmia H1N1 virus o vacunació en 10 llocs que utilitzaven diferents vacunes, coadjuvants i tenien una cobertura de vacunes variable. Mètodes Es van calcular les taxes d'incidència de la narcolèpsia diagnosticada per períodes definits per la circulació del virus de la influença i les dates de la campanya de vacunació, i es va utilitzar la regressió de Poisson per estimar les taxes de taxa d'incidència (IRR) que comparaven els períodes durant els quals circulava el virus de tipus salvatge i després de començar campanyes de vacunació contra. el període anterior a la circulació del virus PH1N1. Utilitzem dades d'assistència sanitària electrònica de Suècia, Dinamarca, Regne Unit, Canadà (3 províncies), Taiwan, Països Baixos i Espanya (2 regions) de 2003 a 2013. Es van investigar les interaccions entre grups d'edat i adjuvants en llocs europeus i es va dur a terme una estudi de simulació per investigar com la cobertura de la vacuna, l'edat i l'interval des de l'inici fins al diagnòstic poden afectar la capacitat de detectar senyals de seguretat. Resultats Les taxes d'incidència de la narcolepsia variaven segons l'edat, el continent i el període. Només a Taiwan i Suècia es van observar importants interaccions entre grups de temps i edat. Es van trobar associacions per a nens a Taiwan (després de la circulació del virus pH1N1) i de Suècia (després de la vacunació). Les simulacions van demostrar que el risc relatiu de la narcolepsia a nivell individual es subestimava mitjançant mètodes ecològics que comparaven els períodes post-versus pre-vacunació; aquest efecte es va atenuar amb una major cobertura de vacunes i un interval més curt d'inici de la malaltia al diagnòstic. Conclusions Els mètodes ecològics poden ser útils per a l'avaluació de la seguretat de la vacuna, però els resultats estan influïts per la demora diagnòstica i la cobertura de la vacuna. Atès que els mètodes ecològics avaluen el risc a nivell de la població, aquests mètodes han de ser tractats com a mètodes generadors de senyals i s'han d'extreure conclusions sobre el risc individual. Antecedentes y objetivos Las señales de seguridad de la vacuna requieren una investigación, que se puede hacer rápidamente a nivel de la población utilizando estudios ecológicos, antes de emprender estudios de prueba de hipótesis. Las tasas de incidencia se utilizaron para evaluar una señal de narcolepsia después de la vacunación contra la influenza H1N1 (pH1N1) pandovalente con adyuvante AS03 en niños y adolescentes en Suecia y Finlandia en 2010. Exploramos la utilidad de los datos ecológicos para evaluar la incidencia de narcolepsia después de la exposición a H1N1 pandémica virus o vacunación en 10 sitios que utilizaron diferentes vacunas, adyuvantes y tenían una cobertura de vacunas variable. Métodos Calculamos las tasas de incidencia de narcolepsia diagnosticada para los períodos definidos por la circulación del virus de la influenza y las fechas de las campañas de vacunación, y utilizamos la regresión de Poisson para estimar las tasas de incidencia (IRR) comparando los períodos durante los cuales el virus de tipo salvaje circuló y después del inicio de las campañas de vacunación vs. El período anterior a la circulación del virus pH1N1. Utilizamos datos electrónicos de atención médica de Suecia, Dinamarca, Reino Unido, Canadá (3 provincias), Taiwán, Países Bajos y España (2 regiones) desde 2003 hasta 2013. Investigamos las interacciones entre el grupo de edad y el adyuvante en sitios europeos y realizamos una estudio de simulación para investigar cómo la cobertura de la vacuna, la edad y el intervalo desde el inicio hasta el diagnóstico pueden afectar la capacidad de detectar señales de seguridad. Resultados Las tasas de incidencia de narcolepsia variaron según la edad, el continente y el período. Solo en Taiwán y Suecia se observaron interacciones significativas período-tiempo-por-edad. Se encontraron asociaciones para niños en Taiwán (después de la circulación del virus pH1N1) y Suecia (después de la vacunación). Las simulaciones mostraron que el riesgo relativo a nivel individual de narcolepsia se subestimó utilizando métodos ecológicos que comparan los períodos post-vacunación versus pre-vacunación; este efecto se atenuó con una mayor cobertura de la vacuna y un intervalo más corto desde el inicio de la enfermedad hasta el diagnóstico. Conclusiones Los métodos ecológicos pueden ser útiles para la evaluación de la seguridad de la vacuna, pero los resultados están influenciados por el retraso en el diagnóstico y la cobertura de la vacuna. Debido a que los métodos ecológicos evalúan el riesgo a nivel de la población, estos métodos deben tratarse como métodos generadores de señales y deben evitarse conclusiones extraordinarias con respecto al riesgo a nivel individual.

Uniform standards for the recording and scoring of respiratory events during sleep are lacking in Europe, although many centres follow the published recommendations of the American Academy of Sleep Medicine. The aim of this study was to assess the practice for the diagnosis of sleep-disordered breathing throughout Europe. A specially developed questionnaire was sent to representatives of the 31 national sleep societies in the Assembly of National Sleep Societies of the European Sleep Research Society, and a total of 29 countries completed the questionnaire. Polysomnography was considered the primary diagnostic method for sleep apnea diagnosis in 10 (34.5%), whereas polygraphy was used primarily in six (20.7%) European countries. In the remaining 13 countries (44.8%), no preferred methodology was used. Fifteen countries (51.7%) had developed some type of national uniform standards, but these standards varied significantly in terms of scoring criteria, device specifications and quality assurance procedures between countries. Only five countries (17.2%) had published these standards. Most respondents supported the development of uniform recording and scoring criteria for Europe, which might be based partly on the existing American Academy of Sleep Medicine rules, but also take into account differences in European practice when compared to North America. This survey highlights the current varying approaches to the assessment of patients with sleep-disordered breathing throughout Europe and supports the need for the development of practice parameters in the assessment of such patients that would be suited to European clinical practice.

Nervous tissue, central and peripheral, is, as any other, subject to variations in oxygen tension, and to the attack of different xenobiotics; these situations may promote the generation of activated oxygen species of free radical character. Results are presented showing that the content of total glutathione (GSH) in brain is 10-fold that found in the sciatic nerve of the rat (2620 vs. 261 nmol/g wet weight, respectively). The existence of a relatively high superoxide dismutase activity in peripheral nervous tissue, when compared with brain or liver, in combination with the DT-diaphorase activity detected in the sciatic nerve might represent an effective defense mechanism against quinone toxicity, as is also discussed. Nervous tissue, both central and peripheral lack Se-independent GSH peroxidase activity. Finally, the activities of other glutathione-related enzymes studied in the sciatic nerve are very low, when compared with the central nervous tissue, thus suggesting a higher susceptibility of peripheral tissue to oxidative stress damage, since GSH concentration and/or any GSH-related enzymatic activities, e.g. GSH peroxidase or glutathione disulfide reductase, might become limiting.

Procambarus clarkii, the American red crayfish, is used as species for the study of the effect of mercury contamination. The glutathione (GSH) system has been involved in mercury toxicity in different species. This system has been partially characterized in different organs of Procambarus clarkii (Almar et al., Comp. Biochem. Physiol. 89B, 471., 1988), and shown to be sensitive to other heavy metals poisoning (Almar et al., Comp. Biochem. Physiol. 87C, 433, 1987; Almar et al., Biochem. Soc. Trans. 16, 23, 1988). Mercuric chloride treatment with 1/10 of the previously reported LC50 for Procambarus clarkii does not decrease the glutathione content of midgut and green glands since the stoichiometric amount necessary for that is much higher. Some kinetic characteristics of the GSH S‐transferase activity of the cytosolic fraction of the midgut gland (also called hepatopancreas) are presented (pH‐and temperature‐dependence).

Inflammation results in the production of free radicals. In a model of experimental uveitis upon subcutaneous injection of endotoxin to Lewis rats, i.e., endotoxin-induced experimental uveitis (EIU), we have evaluated the status of the antioxidant capacity of ocular tissues. EIU results in a decrease of glutathione (GSH) content and glutathione peroxidase (GPx) activity in whole eye homogenates 24-h after endotoxin administration. Furthermore, an increase in malondialdehyde (MDA) content was observed in these same samples, thus confirming the involvement of oxidative stress in the pathophysiology of the process. In view of the ability of the antioxidant ebselen as GPx enzyme mimic, we tested the effect of the oral treatment with two doses of 100 mg/kg body weight of ebselen (first dose administered at the same time of endotoxin, and the second after 12 h). Ebselen administration normalized the GSH and MDA contents and protected the GPx activity of the EIU rat eyes. The GPx activity in the eye homogenate of the treated rats could be completely acounted for by the ebselen-dependent GPx-like activity, i.e., GPx activity measured in the acidic supernatant of the homogenate after neutralization. Unmodified ebselen was detected in whole eye homogenates, thus it shows for the first time the penetration of ebselen through the blood-aqueous and blood-retina barrier. The results herein may allow the proposal of ebselen as a suitable antiinflammatory agent in ocular tissues.

Age-related macular degeneration (AMD) pathogenesis has been related to UV radiation and other factors that may promote increased oxidative damage to the retina. Patients with different AMD grading (n = 25) were compared with an age-matched group of AMD-free subjects (n = 15), both groups older than 60 years. A modification of the AMD grading system is proposed that allows patient grading and not single eye grading. AMD patients showed statistically significant lower serum levels of vitamin E and Zn than AMD-free subjects. Moreover, a negative correlation (Spearman's correlation coefficient r = -0.815, P < 0.001) could be established between AMD grading of both the patients' eyes and serum vitamin E levels. Sun exposure index (SEI) was also compared and found to be significantly higher in the AMD group. The results presented establish the importance of antioxidants in AMD, and set the basis for further studies on adjuvant therapies with antioxidants for AMD. Finally, the results also confirm the pathogenic role of UV radiation in AMD.

The present work tries to establish the antioxidant capacity of the peripheral nervous tissue of the rat, in terms of the enzymatic activities present in this tissue that either prevent the formation of activated species as the semiquinone radical (DT-diaphorase), protect against activated oxygen species (superoxide dismutase, glutathione peroxidase), conjugate natural toxic products or xenobiotics (glutathione S-transferases, especially the activity conjugating 4-hydroxy-nonenal), or complete the glutathione system metabolism (glutathione disulfide reductase, γ-glutamyl transpeptidase). All the activities studied are lower in this tissue than they are in liver, except for γ-glutamyl transpeptidase. The relevance of the results obtained and its possible relationship with different neuropathies is discussed. It is concluded that the peripheral nervous tissue is by far less protected than the liver against oxidative damage.

The major aspects of the glutathione (GSH)-related antioxidant defense of human retina are presented. These include concentration of GSH and activities of some GSH-dependent enzymes: glutathione peroxidase, glutathione disulfide reductase, and glutathione S-transferase toward a broad spectrum substrate 1-chlor-2,4-dinitrobenzene and a toxic product of lipid peroxidation (4-hydroxynonenal). The presence of a relatively high GSH concentration, GSH peroxidase activity, and GSH S-transferase specific activity toward 4-hydroxynonenal in human retina might constitute a central defense mechanism in inflammation-promoted oxidative stress and subsequent lipid peroxidation. The use of different substrates for the determination of the GSH peroxidase activity showed no statistically significant difference, thus suggesting the lack of Se-independent GSH peroxidase in human retina. Large individual variations were obtained for GSH concentration and the different activities tested; the apparent correlation with age of these findings is currently under investigation.

The neurotoxic effects of a single dose of phenytoin (150 mg/kg body weight) alone or 30 min after H7 (a protein kinase C inhibitor) injection (20 mg/kg body weight) were investigated in terms of peripheral neuromuscular function and Na + ,K + -ATPase activity of the sciatic nerve. This intraperitoneal injection of phenytoin induced complete blockade of muscle action potentials in the dorsal segmental muscles of the rat tail evoked by electric stimulation of the caudal nerve and a 40% decrease in the Na + ,K + -ATPase activity of the rat sciatic nerve when compared with control values, measured as the difference between total and ouabain-insensitive ATPase activity. Prior administration of H7 resulted in the complete prevention of both effects. Implication of protein kinase C inhibition in phenytoin neurotoxicity are discussed.

Ebselcn (PZ 5 1 : 2-phenyl1.2-benzisoelenazol-3-( 2H)-one 1 is ii synthetic organoselenium compound with anti-inflammatory activity ( I . 21, which exhibits glutathione peroxidase (GSH-Px)-like activity, catalysing the reduction o f hydrogen peroxide as well as other organic peroxides [3-5]. Its antiinflammatory effect may be mediated by either the GSH-Px activity, the inhibition of leukotriene B4 formation [6], the antioxidant capacity, or a combination of all of them. Many attempts have been made to increase the antioxidant capacity of the myocardium, since free radical generation has been demonstrated in ischaemia-reperfusion damage [7, 81; superoxide dismutase (SOD) and catalase have been used to decrease myocardial reperfusion injury [9]. Moreover, glutathione (GSH) decreases in the myocardium under ischaemic conditions [ 101 and a possible involvement of the myocardial mitochondria1 pool of GSH has also been recently discussed ( I 1 1. This evidence and hypothesis led us to investigate some aspects of the cardiac antioxidant defence, as well as the effect of Ebselen treatment on the peroxidase activity of the myocardium, which are preliminary results necessary for a rationale of the use of Ebselen to prevent or ameliorate ischaemic or reperfusion damage.