Modafinil Administration to Preadolescent Rat Impairs Non-Selective Attention, Frontal Cortex D2 Expression and Mesolimbic GABA Levels.

The misuse of psychostimulants is an increasing behavior among young people, highlighting in some countries the abuse of modafinil (MOD) as a neuropotentiator. However, several clinical trials are investigating MOD as an alternative pharmacological treatment for attentional deficit and hyperactivity disorder (ADHD) in children and adolescents. On the other hand, the early use of psychostimulants and the misdiagnosis rates in ADHD make it crucial to investigate the brain effects of this type of drug in young healthy individuals. The aim of this work was to evaluate the effects of chronic MOD treatment on neurochemicals (γ-aminobutyric acid and glutamate), dopamine receptor 2 (D2) expression and behavior (non-selective attention "NSA") in the mesocorticolimbic system of young healthy Sprague-Dawley rats. Preadolescent male rats were injected with MOD (75 mg/kg, i.p.) or a vehicle for 14 days (from postnatal day 22 to 35). At postnatal day 36, we measured the GLU and GABA contents and their extracellular levels in the nucleus accumbens (NAc). In addition, the GLU and GABA contents were measured in the ventral tegmental area (VTA) and D2 protein levels in the prefrontal cortex (PFC). Chronic use of MOD during adolescence induces behavioral and neurochemical changes associated with the mesocorticolimbic system, such as a reduction in PFC D2 expression, VTA GABA levels and NSA. These results contribute to the understanding of the neurological effects of chronic MOD use on a young healthy brain.

Role of Oxytocin and Vasopressin in Neuropsychiatric Disorders: Therapeutic Potential of Agonists and Antagonists.

Oxytocin (OT) and vasopressin (AVP) are hypothalamic neuropeptides classically associated with their regulatory role in reproduction, water homeostasis, and social behaviors. Interestingly, this role has expanded in recent years and has positioned these neuropeptides as therapeutic targets for various neuropsychiatric diseases such as autism, addiction, schizophrenia, depression, and anxiety disorders. Due to the chemical-physical characteristics of these neuropeptides including short half-life, poor blood-brain barrier penetration, promiscuity for AVP and OT receptors (AVP-R, OT-R), novel ligands have been developed in recent decades. This review summarizes the role of OT and AVP in neuropsychiatric conditions, as well as the findings of different OT-R and AVP-R agonists and antagonists, used both at the preclinical and clinical level. Furthermore, we discuss their possible therapeutic potential for central nervous system (CNS) disorders.

High impulsive choice is accompanied by an increase in dopamine release in rat dorsolateral striatum.

Dopamine neurotransmission has been consistently associated with individual differences in impulsive choice. Clinical and preclinical evidence suggests that low striatal dopamine D2 signaling predisposes to engage in impulsive behaviors. Although dopamine D2 signaling controls dopamine (DA) extracellular levels, the relationship between striatal dopamine extracellular levels and impulsive choice remains poorly understood. Using quantitative microdialysis, we investigated whether extracellular DA levels in rat dorsolateral striatum (DLS) correlates with preference for an immediate small reward or for a delayed larger reward. Rats were tested in a delay-discounting task and classified as high impulsive (HI) or low impulsive (LI) according to the area under the discounting curve (AUC). No-net flux microdialysis experiments, assessing basal DA release, DA-uptake, and DA extracellular concentration (DA Cext), were carried out in dorsolateral striatum (DLS) of urethane-anesthetized rats. Rats classified as HI showed a higher DA release compared with LI rats. Differences in DLS DA-uptake and DA Cext were non-significant. Importantly, a significant negative correlation was observed between AUC and DA release, indicating that the lower the AUC, the higher the DLS DA release. This finding shows that DA release is augmented in the DLS of rats classified as HI, suggesting that a hyper-activated nigro-striatal pathway contributes to impulsive choice.

Priming of GABAergic Long-term Potentiation by Muscarinic Receptors.

Growing evidence indicates that GABAergic interneurons play a pivotal role to generate brain oscillation patterns, which are fundamental for the mnemonic processing of the hippocampus. While acetylcholine (ACh) is a powerful modulator of synaptic plasticity and brain function, few studies have been focused on the role of cholinergic signaling in the regulation of GABAergic inhibitory synaptic plasticity. We have previously shown that co-activation of endocannabinoids (CB1R) and muscarinic receptor (mAChR) in hippocampal interneurons can induce activity-dependent GABAergic long-term depression in CA1 pyramidal neurons. Here, using electrophysiological and pharmacological approaches in acute rat hippocampal slices, we show that activation of cholinergic receptors followed by either high-frequency stimulation of Schaeffer collaterals or exogenous activation of metabotropic glutamate receptor (mGluR) induces a robust long-term potentiation at GABAergic synapses (iLTP). These forms of iLTP are blocked by the M1 type of mAChR (MR1) or by the group I of mGluR (mGluR1/5) antagonists. These results suggest the existence of spatiotemporal cooperativity between cholinergic and glutamatergic pathways where activation of mAChR serves as a metaplastic switch making glutamatergic synapses capable to induce long-term potentiation at inhibitory synapses, that may contribute to the modulation of brain mechanisms of learning and memory.

Suppressing bacterial interaction with copper surfaces through graphene and hexagonal-boron nitride coatings.

Understanding biological interaction with graphene and hexagonal-boron nitride (h-BN) membranes has become essential for the incorporation of these unique materials in contact with living organisms. Previous reports show contradictions regarding the bacterial interaction with graphene sheets on metals. Here, we present a comprehensive study of the interaction of bacteria with copper substrates coated with single-layer graphene and h-BN. Our results demonstrate that such graphitic coatings substantially suppress interaction between bacteria and underlying Cu substrates, acting as an effective barrier to prevent physical contact. Bacteria do not "feel" the strong antibacterial effect of Cu, and the substrate does not suffer biocorrosion due to bacteria contact. Effectiveness of these systems as barriers can be understood in terms of graphene and h-BN impermeability to transfer Cu(2+) ions, even when graphene and h-BN domain boundary defects are present. Our results seem to indicate that as-grown graphene and h-BN films could successfully protect metals, preventing their corrosion in biological and medical applications.

Oxytocin and Vasopressin Receptor Gene Polymorphisms: Role in Social and Psychiatric Traits.

Oxytocin (OXT) and arginine-vasopressin (AVP) are two phylogenetically conserved neuropeptides that have been implicated in a wide range of social behaviors. Although a large body of research, ranging from rodents to humans, has reported on the effects of OXT and AVP administration on affiliative and trust behaviors, and has highlighted the genetic contributions of OXT and AVP receptor polymorphisms to both social behaviors and to diseases related to social deficits, the consequences of peptide administration on psychiatric symptoms, and the impact of receptor polymorphisms on receptor function, are still unclear. Despite the exciting advances that these reports have brought to social neuroscience, they remain preliminary and suffer from the problems that are inherent to monogenetic linkage and association studies. As an alternative, some studies are using polygenic approaches, and consider the contributions of other genes and pathways, including those involving DA, 5-HT, and reelin, in addition to OXT and AVP; a handful of report are also using genome-wide association studies. This review summarizes findings on the associations between OXT and AVP receptor polymorphism, social behavior, and psychiatric diseases. In addition, we discuss reports on the interactions of OXT and AVP receptor genes and genes involved in other pathways (such as those of dopamine, serotonin, and reelin), as well as research that has shed some light on the impact of gene polymorphisms on the volume, connectivity, and activation of specific neural structures, differential receptor expression, and plasma levels of the OXT and AVP peptides. We hope that this effort will be helpful for understanding the studies performed so far, and for encouraging the inclusion of other candidate genes not explored to date.

Métodos anticonceptivos ¿Cuáles se utilizan realmente? / Anticonceptive methods What are actually used?

Objetivo: Obtener información acerca de los métodos anticonceptivos utilizados por nuestras usuarias en el momento de la consulta, grado de satisfacción, conocimiento e información recibida respecto al mismo, cumplimiento, embarazos no planificados y otros datos de interés ginecológicos y socio-demográficos. Población, Material y Métodos: Estudio descriptivo, longitudinal y prospectivo basado en los resultados obtenidos de un cuestionario realizado a una muestra de las pacientes (n=87), de entre 16 y 45 años, que acudieron al Servicio de Urgencias Ginecológicas del Hospital General Universitario de Alicante durante el periodo comprendido entre junio 2010 y noviembre de 2011. Resultados: El método anticonceptivo más utilizado por las usuarias encuestadas es el preservativo (88,5%) con un nivel de satisfacción de uso de 6,3, seguido por la píldora ( 75,9% ). El 20,6% (13% ella+ 7,6% familiares y amigos) de las mujeres eligió el método anticonceptivo sin consultar previamente con un profesional sanitario. La edad de inicio de las relaciones coitales fue de 16,9 años. Un 35.6% refería haber tenido al menos un embarazo no planificado y el 70,9% de las mismas refieren haber recurrido a una interrupción legal del embarazo (ILE). El 58,6% (n=51) de las usuarias refieren haber mantenido en alguna ocasión, relaciones sexuales de riesgo. Conclusiones: Consideramos que la educación es el arma principal de la que disponemos los profesionales sanitarios para alcanzar el objetivo que, en esta materia de salud sexual y reproductiva es, evitar embarazos no deseados y que las mujeres y sus parejas puedan disfrutar de una plena y satisfactoria sexualidad a través un adecuado acceso a la planificación familiar (AU)

The aim of this study is to obtain some information about the anticonceptive methods used by our patients in terms of: type, satisfaction, knowledge or information about it, grade of compliance, not desired pregnancy and other data with gynecologist, social or demographic interest. Material and Methods:We conducted a descriptive, prospective and longitudinal study. We ask our patients to complete a questionnaire. A total of 87 women, assisted in the emergency gynecology department at the “Hospital General de Alicante”, participated. Women were aged between 16 and 45 years old, from June 2010 and November 2011. Results: The most employed anticonceptive method among our patients is the preservative (88,5%), which satisfaction level was 6,3 , followed by the contraceptive pill (75,9%). 20,6% of women selected the anticonceptive method without consulting a health worker. Sexual relationships beginning. The mean age of coital debut was 16,9 years old. A 35,6% have had an unplanned pregnancy and a 70,9% a legal abortion. A 58,6% (n = 51) of patients declared a sexual risk behaviour at least once. Conclusion: Education is the most powerful weapon of health workers to achieve the most important objective in sexual matter, to avoid unplanned pregnancies. Women and their partners must enjoy a satisfactory sex life through an adequate upon family planning (AU)

Improvement of human skin cell growth by radiation-induced modifications of a Ge/Ch/Ha scaffold.

Gelatin-/chitosan-/hyaluronan-based biomaterials are used in tissue engineering as cell scaffolds. Three gamma radiation doses (1, 10 and 25 kGy) were applied to scaffolds for sterilization. Microstructural changes of the irradiated polymers were evaluated by using scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). A dose of 25 kGy produced a rough microstructure with a reduction of the porosity (from 99 to 96 %) and pore size (from 160 to 123 µm). Radiation also modified the glass transition temperature between 31.2 and 42.1 °C (1 and 25 kGy respectively). Human skin cells cultivated on scaffolds irradiated with 10 and 25 kGy proliferated at 48 h and secreted transforming growth factor ß3 (TGF-ß3). Doses of 0 kGy (non-irradiated) or 1 kGy did not stimulate TGF-ß3 secretion or cell proliferation. The specific growth rate and lactate production increased proportionally to radiation dose. The use of an appropriate radiation dose improves the cell scaffold properties of biomaterials.

Objective and subjective quality of life in adults with autism spectrum disorders in southern Spain.

Subjective and objective measures of quality of life (QoL) were obtained for adults with autism spectrum disorders (ASDs) living in Andalusia (Spain). Seventy-four families responded to questionnaires about objective QoL indicators such as employment, health, adaptive behaviour and social network, and were asked to act as proxies for subjective QoL measures. Outcome on objective QoL was extremely poor. Social networks were most frequently composed of family members. Community-oriented resources were absent in most cases. For two-thirds of the families, the ability to act as proxies for subjective QoL was seriously limited by the participants' poor social and communicative abilities. The results are indicative of the need for additional support to families of adults with ASD and increased community-based resources. Further conceptualization of indicators and measurement of subjective QoL in individuals with severe disabilities and ASD is also needed in order to include their own perspective in the evaluation of service provision.