Pleasure: The missing link in the regulation of sleep.

Although largely unrecognized by sleep scholars, sleeping is a pleasure. This report aims first, to fill the gap: sleep, like food, water and sex, is a primary reinforcer. The levels of extracellular mesolimbic dopamine show circadian oscillations and mark the "wanting" for pro-homeostatic stimuli. Further, the dopamine levels decrease during waking and are replenished during sleep, in opposition to sleep propensity. The wanting of sleep, therefore, may explain the homeostatic and circadian regulation of sleep. Accordingly, sleep onset occurs when the displeasure of excessive waking is maximal, coinciding with the minimal levels of mesolimbic dopamine. Reciprocally, sleep ends after having replenished the limbic dopamine levels. Given the direct relation between waking and mesolimbic dopamine, sleep must serve primarily to gain an efficient waking. Pleasant sleep (i.e. emotional sleep), can only exist in animals capable of feeling emotions. Therefore, although sleep-like states have been described in invertebrates and primitive vertebrates, the association sleep-pleasure clearly marks a difference between the sleep of homeothermic vertebrates and cool blooded animals.

Short term effectiveness of Pressure Release and Kinesiotaping in Cervical Myofascial Pain caused by sternocleidomastoid muscle: A randomized clinical trial / Efectividad a corto plazo de la liberación por presión y del kinesiotaping en el dolor miofascial cervical causado por el músculo esternocleidomastoideo. Ensayo clínico aleatorizado

Objective: The aim of this study is to evaluate the effectiveness of 2 different therapies, pressure release (PR) and kinesiotaping (KT) for myofascial pain syndrome in the sternocleidomastoid muscle. Methods: Experimental, randomized, controlled, single-blind study. KT was applied for group C, PR to treat group B and placebo to treat group A. The used variables were: Algometry, Numerical Pain Scale (NPS), Questionnaire of Quality of Life SF-12, and Goniometry of cervical complex. Participants were assisted in public hospitals of the Balearic Health Service (Spain), from March 2012 to March 2013. The study includes a sample of 75 patients with cervical myofascial pain syndrome of the sternocleidomastoid muscle. Each patient received three appointments. Each appointment lasted 20 minutes approximately. Results: Questionnaire SF-12 shows that the improvement of the quality of life with KT was 10.32 points (P < 0.001), with PR was 5.0 points (P < 0.05) and the group A with placebo treatment scored 2.20 points (P < 0.05). NPS for KT shows a reduction of pain of 24.00% (P < 0.001), for PR a reduction of 11.20% (P < 0.001), and in group A no significant outcome was found. Algometry shows that the pain is reduced with the KT and the PR significantly. Goniometry of cervical complex improved significantly with KT for all range of mobility. Conclusions: KT and PR are two therapeutic techniques which help to reduce pain, show increased levels in Goniometry (cervical movements) and contribute to improve quality of life. It seems that KT could be more effective than PR

Objetivo: Este trabajo evalúa la eficacia de 2 terapias, la liberación por presión (LP) y el kinesiotaping (KT) para el síndrome de dolor miofascial en el músculo esternocleidomastoideo. Métodos: Estudio experimental, aleatorizado, controlado a simple ciego, en el que se aplicó KT (grupo C), LP (grupo B) y placebo (grupo A). Las variables utilizadas fueron: algometría, escala numérica del dolor, cuestionario de calidad de vida SF-12 y goniometría del complejo cervical. Los participantes fueron atendidos en hospitales públicos del Servicio de Salud de las Islas Baleares (España), desde marzo de 2012 hasta marzo de 2013. El estudio recoge una muestra de 75 pacientes a los que se realizaron 3 visitas de 20 min cada una. Resultados: El SF-12 muestra la mejora de la calidad de vida de 10,32 puntos (p < 0,001) con el KT, de 5,0 puntos (p < 0,05) con la LP y de 2,20 puntos (p < 0,05) con el Grupo A. La escala numérica del dolor señala una reducción del dolor del 24% (p < 0,001) con el KT, del 11,20% (p < 0,001) con la LP, y con el grupo A no se obtienen resultados significativos. La algometría muestra una reducción significativa del dolor con el KT y la LP. La goniometría mejoró significativamente con el KT para todos los rangos. Conclusiones: El KT y la LP son 2 técnicas terapéuticas que ayudan a reducir el dolor, aumentan los rangos de movilidad cervical y contribuyen a mejorar la calidad de vida. Parece ser que el KT podría ser más eficaz que la LP

Effects of the muscarinic agonist pilocarpine on vigilance states and locomotor activity in ring doves.

Cholinergic systems play a significant role in regulating a variety of behavioral functions in mammals and birds. The aim of this work is to study the effects of the muscarinic agonist pilocarpine on behavioral states by visual inspection and electroencephalographic recording; also, locomotor activity was continuously recorded by infrared interruption system in ring doves. The current results in birds demonstrated that the muscarinic agonist pilocarpine (1 and 3mg/kg, i.p.) primarily induced theta activity in addition to promote passive waking, while diminished active waking, the EEG slow wave rhythm and REM sleep in ring doves. The locomotor activity recorded continuously in ring doves diminished after pilocarpine treatment, which was in good agreement with the observed reduction of active waking derived of the EEG study. Altogether, the current results are similar to the effects of pilocarpine previously reported in mammals. In conclusion, hippocampal theta rhythm in birds suggests that this rhythm is an ancestral property of hippocampal function and similar cholinergic mechanisms regulate vigilance states and theta generation in mammals and birds.

Effects of serotonergic drugs on locomotor activity and vigilance states in ring doves.

Serotonergic system is implicated on sleep-waking states in mammals. Since studies on serotonin regulation of sleep in birds are scarce, ring dove was chosen as experimental subject in the present work. The role of the neurotransmitter serotonin on vigilance states was studied in ring doves intraperitoneally treated with the 5-HT(1A) agonist 8-OH-DPAT, the 5-HT(1A) antagonist WAY100635 and the inhibitor of serotonin synthesis para-chlorophenylalanine (PCPA) by means of behavioural, electrophysiological and infrared actimetry criteria. 8-OH-DPAT (1 mg/kg) treatment increased locomotor activity, active waking and grooming states and reduced SWS and REM sleep. Pre-treatment with WAY100635 (0.5 mg/kg) prevented the effects induced by 8-OH-DPAT. Serotonin depletion induced by PCPA treatment (two consecutive injections of 300 mg/kg over two consecutive days) reduced locomotor activity, waking and grooming activity while increased both SWS and REM sleep. Moreover, 8-OH-DPAT (0.5 mg/kg) in PCPA treated ring doves produced a notable rise in the locomotor activity, active waking and grooming states, while it decreased sleep. Altogether, the results support the idea that serotonin plays an active role in wakefulness, probably through the activation of 5-HT(1A) receptors that increases wake activities and reduces sleep in ring doves.

Electroencephalogram functional connectivity between rat hippocampus and cortex after pilocarpine treatment.

The muscarinic agonist pilocarpine has been shown to increase the duration and total number of episodes presenting theta rhythm-simultaneously in hippocampus and cortex-in rats during the waking states. Theta waves are suggested to be involved in the flow of information between hippocampus and cortex during memory processes. This work investigates this functional interdependence using the spectral and phase synchronization analysis of the electroencephalogram (EEG) theta band recorded in these brain structures of rats after pilocarpine treatment. Pilocarpine was used at doses devoid of epilepticus-like seizures effects in conscious freely moving rats. The results showed that pilocarpine administration significantly increased the relative theta power during the waking states in the cortex, but not in the hippocampus of rats. Additionally, the EEG coherence between the hippocampal EEG theta band and that arising at the frontal cortex increased after pilocarpine treatment but only during the waking states. This result reveals an increase of the linear correlation between the theta waves of these two brain structures after pilocarpine treatment during the waking states. Moreover, phase synchronization results showed an effective phase locking with non-zero phase difference between hippocampus and frontal cortex theta waves that remained after pilocarpine treatment. Therefore, pilocarpine seems to reinforce the neural transmission waves from the hippocampus toward the cortex during waking. In conclusion, the present EEG study could suggest an effect of the muscarinic cholinergic agonist pilocarpine on the hippocampal-cortical functional connectivity.

Environment and virulence factors of Vibrio cholerae strains isolated in Argentina.

AIMS: To determine the presence of Vibrio cholerae in different areas of Argentina in three sample types, to determine the composition of planktonic communities in areas at which this pathogen was detected and to characterize the virulence properties and antimicrobial resistance of the recovered environmental isolates. METHODS AND RESULTS: Water and plankton samples were collected in marine, brackish and freshwater environments. Vibrio cholerae non-O1, non-O139 was isolated in 36.1% of the samples analysed. The micro-organism was detected in freshwater but not in marine or brackish samples. No relationship was found between isolation of V. cholerae and presence of any species of plankton. All the isolates presented very similar virulence profiles by PCR, lacking ctxA and tcpA El Tor and containing hlyA (98.7%), rtxA (99.0%), toxR (98.7%) and stn-sto (1.9%). Resistance to ampicillin was found in both Tucumán (21%) and Buenos Aires isolates (45%). CONCLUSIONS: We identified two geographic areas in Argentina where V. cholerae was present: freshwaters of the rivers from Tucumán and the Río de la Plata. SIGNIFICANCE AND IMPACT OF THE STUDY: The identification of V. cholerae strains in the environment, carrying both virulence factors and resistance to antimicrobial agents, highlight the need for a continuous and active surveillance of this pathogen.

Effects of pilocarpine on the cortical and hippocampal theta rhythm in different vigilance states in rats.

It has been suggested that theta rhythm gates the flow of information between the hippocampus and cortex during memory processes. The cholinergic system plays an important role in regulating vigilance states and in generating theta rhythm. This study aims to analyse the effects of the muscarinic agonist pilocarpine (120 and 360 microg, i.c.v.) on hippocampal and frontal cortical theta rhythm during several vigilance states in rats. Pilocarpine injection increased the duration and number of episodes with theta activity, particularly when theta rhythm appeared during waking states in the cortex and hippocampus simultaneously. It seems that the effects of pilocarpine are related to the appearance of cortical theta activity in waking states, and suggest that pilocarpine could modify the transference rate of information from the hippocampus to cortex in rats during wakefulness states, in relation to the postulated effect of cholinergic system modulating memory consolidation.

Comments on evolution of sleep and the palliopallial connectivity in mammals and birds.

This commentary is referred to the review signed by Rattemborg [N.C. Rattenborg, Evolution of slow wave sleep and palliopallial connectivity in mammals and birds. A hypothesis. Brain Res. Bull. 69 (2006) 20-29]. We propose that the review missed important aspects in relation to the characteristics of sleep in poikilotherm vertebrates and in the evolution of sleep. Poikilotherms continuously show an EEG dominated by slow waves, but its highest amplitude appears not during sleep, but during active waking. In addition, they show an arousal reaction which consists in an increase in EEG amplitude and synchrony, opposite to mammals and birds. As a consequence, most of the conclusions proposed in the review should be rejected.

Antioxidant response and oxidative damage in brain cortex after high dose of pilocarpine.

Pilocarpine is a cholinergic agonist capable to induce seizures and an epilepticus-like state in rodents. This status epilepticus (SE) is an useful animal model to study the development and understanding of the neuropathology, behavioural and electroencephalographic alterations of human temporal lobe epilepsy. It has been suggested a relationship between SE and reactive oxygen species (ROS) that can result in seizure-induced neurodegeneration. The aim of this study was to evaluate the existence of oxidative damage and the changes in the antioxidant system in cortex after administration of a high pilocarpine dose. Rats were injected with pilocarpine (350 mg/kg i.p.) or with saline as control and 2h after the animals were sacrificed. Malondialdehyde (MDA) levels, as marker of lipid peroxidation, significantly increased (64%) after pilocarpine treatment evidencing oxidative damage. Antioxidant enzyme activities--catalase (CAT), glutathione peroxidase (GP) and superoxide dismutase (SOD)--significantly increased in response to pilocarpine (28%, 28% and 21%, respectively). GP and Mn-SOD gene expression were induced by pilocarpine treatment. Vitamin E concentration in brain cortex decreased (15%) as result of pilocarpine administration. In conclusion, the high dose of pilocarpine, used in the present study, induces oxidative damage and increases antioxidant enzyme activities and expression in brain cortex. Moreover, increased lipid peroxidation produces the consumption of Vitamin E.

Carcinogénesis cólica experimental / Experimental colonic carcinogenesis

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Antioxidant response analysis in the brain after pilocarpine treatments.

Cholinergic and gabaergic systems play an important role generating electroencephalographic activity and regulating vigilance states. Pilocarpine is a cholinergic agonist commonly used to induce seizures and an epilepticus-like state in rodents. A relationship between status epilepticus and reactive oxygen species has been also suggested which could result in seizure-induced neurodegeneration. The aim of this study was to evaluate the existence of oxidative damage as well as the antioxidant enzyme response in cortex and hippocampus after the administration of an intraperitoneal (350 mg/kg) and an intracerebroventricular (360 microg, 1 microl) pilocarpine injection in rats. The GABA agonist muscimol (1 mg/kg, i.p.), with described neuroprotective properties, was used as a negative control. Only systemic pilocarpine induced oxidative damage. Malondialdehyde levels, as a marker of lipid peroxidation (LP), increased in both regions (55-56%). Catalase (52-80%) and superoxide dismutase (53-60%) activities also rose in both regions but glutathione peroxidase activity only increased in cortex (45%). Glutathione reductase and caspase-3 activity did not change. In conclusion, systemic pilocarpine produced oxidative brain damage, whereas local pilocarpine brain injection had no effects. Moreover, the enzymatic determinations performed in this study are a good tool to study brain injury in pharmacological manipulations such as the ones used in short recording EEG studies.

Cyclooxygenase-2 inhibition in colon experimental carcinogenesis.

BACKGROUND: An overexpression of cyclooxygenase-2 (COX-2) has been seen in colon tumors; therefore, COX-2 specific inhibitors may be used as preventive agents. The aim of this study was to investigate the effect of both selective and non-selective COX-2 inhibitors on the incidence of colonic tumors in a model of chemical carcinogenesis in the rat. DESIGN: Experimental study with 65 male Sprague-Dawley rats randomly assigned to one of four groups: (a) control (n = 20), with chemical carcinogenesis using 1-2 dimethylhydrazine (1-2 DMH); (b) acetylsalicylic acid (ASA) (n = 15), with chemical carcinogenesis and the addition of ASA at 30 mg/kg; (c) low-dose rofecoxib (n = 15), with chemical carcinogenesis and the addition of rofecoxib at a dose of 1.2 mg/kg; (d) high-dose rofecoxib (n = 15), with carcinogenesis and the addition of rofecoxib at 3 mg/kg. Carcinogenic induction was performed with 1-2 DMH at a weekly dose of 25 mg/kg for 18 weeks. The main parameter evaluated was percentage of neoplastic colonic tissue, which relates tumor surface area to colon surface area. RESULTS: Rofecoxib at a dose of 3 mg/kg significantly reduced chemical colon carcinogenesis in rats (p < 0.01). Rofecoxib in lower doses had the same effect on adenomas (p < 0.05) with no effect on adenocarcinomas. Rofecoxib reduced COX-2 expression in tumoral tissue from adenomas and adenocarcinomas (p < 0.01). CONCLUSIONS: Rofecoxib prevents chemical colon carcinogenesis in the rat, with a reduction of tumoral colonic percentage in adenocarcinomas and tumoral COX-2 expression.

Inhibición de la ciclooxigenasa-2 en la carcinogénesis cólica experimental / Cyclooxygenase-2 inhibition in colon experimental carcinogenesis

Introducción: se ha comprobado a nivel clínico y experimentalla existencia de sobreexpresión de la ciclooxigenasa-2 (COX-2)en los tumores de colon, por lo que los inhibidores de dicha enzimapodrían tener un efecto preventivo. El objetivo del estudio esinvestigar el efecto de la inhibición de la ciclooxigenasa en un modelode carcinogénesis cólica farmacológica en la rata.Material y métodos: estudio experimental en 65 ratas Sprague-Dawley macho, asignadas a uno de los grupos: control (n =20), con carcinogénesis farmacológica con 1-2 dimetilhidrazina;grupo ácido acetilsalicílico (n = 15), con carcinogénesis y adiciónde AAS, grupo Inhibidores COX-2 a bajas dosis (n = 15), con carcinogénesisy adición de rofecoxib a dosis de 1,2 mg/kg, y grupoInhibidores COX-2 a altas dosis (n = 15), con carcinogénesis y rofecoxiba dosis de 3 mg/kg. El principal parámetro evaluado es elporcentaje de tejido cólico neoplásico y la expresión de COX-2 enel colon normal y neoplásico.Resultados: el rofecoxib a dosis altas reduce el porcentaje decolon ocupado por adenocarcinomas inducidos (p < 0,01). El rofecoxiba dosis bajas presentó el mismo efecto sobre los adenomas(p < 0,05), sin efecto sobre los adenocarcinomas. La expresiónCOX-2 es superior en los adenocarcinomas frente a losadenomas. El rofecoxib redujo la expresión COX-2 respecto alcontrol y AAS (p < 0,01), tanto en los adenomas como en losadenocarcinomas, no mostrando este efecto sobre el colon normal.Conclusiones: el rofecoxib redujo la carcinogénesis cólica inducidaen ratas, reduciendo la expresión COX-2 en los tumores ydisminuyendo el porcentaje de colon neoplásico

Background: an overexpression of cyclooxygenase-2 (COX-2) has been seen in colon tumors; therefore, COX-2 specific inhibitorsmay be used as preventive agents. The aim of this studywas to investigate the effect of both selective and non-selectiveCOX-2 inhibitors on the incidence of colonic tumors in a model ofchemical carcinogenesis in the rat.Design: experimental study with 65 male Sprague-Dawleyrats randomly assigned to one of four groups: (a) control (n = 20),with chemical carcinogenesis using 1-2 dimethylhydrazine (1-2DMH); (b) acetylsalicylic acid (ASA) (n = 15), with chemical carcinogenesisand the addition of ASA at 30 mg/kg; (c) low-dose rofecoxib(n = 15), with chemical carcinogenesis and the addition ofrofecoxib at a dose of 1.2 mg/kg; (d) high-dose rofecoxib (n = 15),with carcinogenesis and the addition of rofecoxib at 3 mg/kg.Carcinogenic induction was performed with 1-2 DMH at a weeklydose of 25 mg/kg for 18 weeks. The main parameter evaluatedwas percentage of neoplastic colonic tissue, which relates tumorsurface area to colon surface area.Results: rofecoxib at a dose of 3 mg/kg significantly reducedchemical colon carcinogenesis in rats (p < 0.01). Rofecoxibin lower doses had the same effect on adenomas (p < 0.05)with no effect on adenocarcinomas. Rofecoxib reduced COX-2expression in tumoral tissue from adenomas and adenocarcinomas(p < 0.01).Conclusions: rofecoxib prevents chemical colon carcinogenesisin the rat, with a reduction of tumoral colonic percentage inadenocarcinomas and tumoral COX-2 expression

[The work of Santiago Ramón y Cajal in the Revista Trimestral Micrográfica (Trabajos del Laboratorio de Investigaciones Biológicas)]. / La obra de Santiago Ramón y Cajal en Revista Trimestral Micrográfica (Trabajos del Laboratorio de Investigaciones Biológicas).

AIM: This paper is based on a study of Revista Trimestral Micrografica (Trabajos del Laboratorio de Investigaciones Biologicas) between its creation by Santiago Ramon y Cajal in 1896 and his death in 1934. DEVELOPMENT: The journal Revista Trimestral Micrografica was the main way in which Santiago Ramon y Cajal and his school published their work since its creation. Ramon y Cajal created the journal for two main reasons: first, he needed a rapid system to publish his own work; second, the journal could serve to encourage his pupils. The journal published many important reports defending the neuronal theory which expanded the cellular one to include the nervous system.

La obra de Santiago Ramón y Cajal en la Revista Trimestral Micrográfica (Trabajos del Laboratorio de Investigaciones Biológicas) / The work of Santiago Ramón y Cajal in the revista trimestral micrográfica (Trabajos del laboratorio de investigaciones biológicas)

Objetivo. El presente trabajo se basa en el estudio de las publicaciones aparecidas en la Revista Trimestral Micrográfica (RTM) (Trabajos del Laboratorio de Investigaciones Biológicas), desde su creación por Santiago Ramón y Cajal en 1896 hasta su muerte, en 1934. Desarrollo. La RTM, desde su creación, fue el medio principal por el cual el autor y su escuela publicaron sus trabajos. Ramón y Cajal creó dicha revista por dos motivos evidentes: 1. La necesidad de tener una vía rápida de publicación de sus trabajos; 2. La capacidad de alentar el trabajo de sus discípulos. En ella se publicaron la mayoría de trabajos que defendieron la teoría neuronal, lo que permitió extender la teoría celular al sistema nervioso (AU)

Aim. This paper is based on a study of Revista Trimestral Micrográfica (Trabajos del Laboratorio de Investigaciones Biológicas) between its creation by Santiago Ramón y Cajal in 1896 and his death in 1934. Development. The journal Revista Trimestral Micrográfica was the main way in which Santiago Ramón y Cajal and his school published their work since its creation. Ramón y Cajal created the journal for two main reasons: first, he needed a rapid system to publish his own work; second, the journal could serve to encourage his pupils. The journal published many important reports defending the neuronal theory which expanded the cellular one to include the nervous system (AU)

Dualism and uniformism in sleep.

The phenomenological evidence for distinguishing between REM and NREM sleep is overwhelming. However, this difference has only been found thanks to electrophysiological analytical methods, and is practically non existent in phenotypic terms, i.e., observable with the naked eye. It is well accepted that the selective pressure determining evolutionary changes can only work upon phenotypic differences. Hence, it follows that the differences between REM and NREM could not have been selected through evolution and this implies that, in functional terms, both states could be equivalent.

Why we sleep: the evolutionary pathway to the mammalian sleep.

The cause of sleep is a complex question, which needs first, a clear distinction amongst the different meanings of a causal relationship in the study of a given behavior, second, the requisites to be met by a suggested cause, and third, a precise definition of sleep to distinguish behavioral from polygraphic sleep. This review aims at clarifying the meaning of the question and at showing the phylogenetic origin of the mammalian and avian sleep. The phylogenetic appearance of sleep can be approached through a study of the evolution of the vertebrate brain. This began as an undifferentiated dorsal nerve, which was followed by the development of an anterior simplified brain and ended with the formation of the multilayered mammalian neocortex or the avian neostriate. The successive stages in the differentiation of the vertebrate brain produced, at least, two different waking types. The oldest one is the diurnal activity, bound to the light phase of the circadian cycle. Poikilotherms control the waking from the whole brainstem, where their main sensorymotor areas lie. Mammals developed the thalamocortical lines, which displaced the waking up to the cortex after acquiring homeothermy and nocturnal lifestyle. In order to avoid competence between duplicate systems, the early waking type, controlled from the brainstem, was suppressed, and by necessity was turned into inactivity, probably slow wave sleep. On the other hand, the nocturnal rest of poikilotherms most probably resulted in rapid eye movement sleep. The complex structure of the mammalian sleep should thus be considered an evolutionary remnant; the true acquisition of mammals is the cortical waking and not the sleep.